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PEDIATRICS

COURSE NOTES

Editor:

Conf. Univ. Dr. Mărginean Cristina Oana

List of authors:

Prof. Univ. Dr. Togănel Rodica

Conf. Univ. Dr. Cucerea Manuela

Conf. Univ. Dr. Mărginean Cristina Oana

Șef. Lucr. Dr. Borka Balazs Reka

Șef Lucr. Dr. Duicu Carmen

Asist. Univ. Dr. Chinceșan Mihaela Ioana

Asist. Univ. Dr. Grama Alina Corina

Asist Univ. Dr. Pitea Ana Maria

2013

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CONTENTS

Foreword .................................................................................................................. pag 4

Chapter I. Neonatal Pathology ................................................................................ pag 5

Perinatal asphyxia. New-born resuscitation ................................................................. pag 5

Respiratory distress in new-borns.............................................................................. pag 28

Neonatal infections ................................................................................................... pag 39

Neonatal pathological jaundice ................................................................................. pag 56

HIV-AIDS infections in neonates and children.......................................................... pag 62

Chapter II. Pathology of the Respiratory System .................................................. pag 69

Acute rhynopharyngitis ............................................................................................. pag 69

Acute angina ............................................................................................................ pag 71

Otitis and ostomastoiditis .......................................................................................... pag 74

Acute laryngitis......................................................................................................... pag 83

Epiglotitis ................................................................................................................. pag 80

Acute bronchyolitis ................................................................................................... pag 85

Pneumonias in children ............................................................................................. pag 88

Childhood asthma ................................................................................................... pag 105

Chapter III. Pathology of the Cardiovascular System......................................... pag 114

Congenital heart diseases ....................................................................................... pag 114

Infective endocarditis ............................................................................................. pag 124

Myocarditis ............................................................................................................. pag 128

Pericarditis .............................................................................................................. pag 129

Congestive heart failure .......................................................................................... pag 131

Shocks .................................................................................................................... pag 134

Chapter IV. Colagenoses (Colagenoses, Mesenchymal Diseases, Diseases of Vascular

Collagen, Autoimmune Diseases) ......................................................................... pag 143

Colagenoses – General aspects ............................................................................... pag 143

Acute articular rheumatism .................................................................................... pag 144

Juvenile rheumatoid arthritis .................................................................................. pag 149

Henoch-Schonlein Purpura..................................................................................... pag 154

Kawasaki Disease ................................................................................................... pag 157

Chapter V. Diseases of the Digestive System........................................................ pag 158

Gastro-esophagian reflux ........................................................................................ pag 158

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Gastritis in children................................................................................................. pag 161

Ulcer disease........................................................................................................... pag 165

Malabsorption syndrome (Cystic fibrosis, Celiac Disease) ...................................... pag 167

Food intolerance ..................................................................................................... pag 182

Acute diarrheal disease in infants and children ........................................................ pag 189

Syndrome of acute dehydration ............................................................................... pag 198

Recurrent abdominal pain ....................................................................................... pag 207

Parasites.................................................................................................................. pag 215

Chapter VI. Nutrition and Deficiency Diseases ................................................... pag 221

Malnutrition ........................................................................................................... pag 221

Iron deficiency anemia ........................................................................................... pag 229

Rickets................................................................................................................... pag 233

Tetanus ................................................................................................................... pag 245

Diabetes mellitus.................................................................................................... pag 250

Chpater VII. Renal System................................................................................... pag 266

Urinary infections in children ................................................................................ pag 266

Vesicoureteral reflux............................................................................................... pag 277

Postinfectious glomerulonephritis .......................................................................... pag 279

Nephrotic syndrome................................................................................................ pag 292

Acute kidney injury................................................................................................ pag 302

Chronic kidney disease............................................................................................ pag 304

Chapter VIII. Pathology of the Central Nervous System .................................... pag 308

Acute meningitis .................................................................................................... pag 308

Acute encephalitis ................................................................................................... pag 320

Seizures and epilepsy in children............................................................................. pag 323

CHAPTER IX. Hematology................................................................................. pag 336

Anemia in children – principles of diagnosis ........................................................... pag 336

PTI.......................................................................................................................... pag 338

Hemophilia A.......................................................................................................... pag 342

Chapter X. Pediatric Oncology............................................................................. pag 347

Leukemias............................................................................................................... pag 347

Malignant lymphomas............................................................................................. pag 353

Solid tumors (Neuroblastoma, Nephroblastoma) ..................................................... pag 358

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FOREWORD

The current book is a manual containing basic notions of pediatrics, of importance to

pediatric practice, addressing both medical students and residents and practitioners,

pediatricians, and other physicians eager of clarification of issues encountered in pediatric

medical practice. This third edition of the book has been enriched and up-dated with the latest

news in the field, according to the latest guidelines in pediatric pathology.

The book is divided into ten chapters and includes notions of neonatal pathology,

respiratory, gastrointestinal, cardiac, hematologic and oncologic pathology, pediatric

nephrology, collagenoses in pediatric pathology, neurological diseases, diabetes and

metabolic aspects of the child diseases.

The clear, concise style, employing the absolutely necessary "technical" language,

makes this book attractive and easy to read, the approach and editing of the book,

representing clear evidence of this fact. Mention should be made that this book was designed

by a remarkable collection of primary-care physicians and pediatric specialists, academics at

the University of Medicine and Pharmacy of Tirgu Mures.

By reading it, you gradually come to realize its wealth of information, clarification of

concepts, as well as its accessible style.

Assoc. Prof. Oana Mărginean, PhD

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CHAPTER I – THE NEW BORN

Conf. Univ. Dr. Cucerea Manuela, Conf. Univ. Dr. Mărginean Oana

CHAPTER I – THE NEW BORN

PERINATAL ASPHYXIA

Definition: Perinatal asphyxia is a clinical syndrome determined by insults that cause

reduction in fetal/neonatal oxygenation (hypoxemia), impaired gas exchange (hypoxemia,

hypercarbia) and inadequate tissue perfusion (ischemia). Asphyxia is defined as progressive

hypoxemia and hypercapnea accompanied by the progressive development of metabolic

acidosis that will lead to cellular damage and ultimately death of the newborn. This definition

has replaced the old definition of asphyxia at birth which referred to failure to install

adequate spontaneous respiration within 1-2 minutes after birth and correlated asphyxia with

the Apgar score. The criteria for defining asphyxia by the American Academy of Pediatrics

and American College of Obstetrics and Gynecology (1996) are:

- metabolic or mixed acidosis (pH <7.00, base deficit ≥12 mmol/l) in the cord blood or in

very early neonatal blood samples)

- Apgar scores of 0-3 beyond 5 minutes after birth

- early onset of neonatal neurological manifestations (seizures, hypotonia, coma, hypoxic-

ischemic encephalopathy)

- multiple organ failure (heart, kidney, liver, small intestine).

Thus, we have to distinguish between neonatal depression and birth asphyxia. Depression at

birth is characterized by low Apgar score, without changes in blood gases. Most often, the

time and the main cause of asphyxia remain unknown; it is actually a combination of

antenatal, intrapartum, and postnatal factors.

Pathophysiology of asphyxia. Transition and normal cardiorespiratory adaptation

Birth is a stressful and risky event for the newborn. Placenta-dependent gas exchange should

be replaced immediately after birth by autonomous pulmonary respiration. In the womb, fetal

circulation is characterized by relative hypoxemia (pO2 25-30 mmHg), but the fetus develops

normally since the placenta replaces many functions, thus fetal energy requirements are

reduced. Although there are intrauterine respiratory movements, the fetal lungs are not

functional and they are filled with lung fluid. Under the action of catecholamines sintetized

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and released due to the stress of birth, the newborn adapts to extrauterine life. The factors that

initiate the first postnatal breath are:

1. chest compression that occurs when crossing maternal pelvigenital channel (exerts a

pressure of 60-90 cm H2O) causes removal of 1/3 of lung fluid volume. With the chest

decompression after expulsion, the chest volume increases due to the pleural vacuum

created and air enters the lungs.

Table 1. Etiology and risk factors for perinatal asphyxia

antenatal factorsintrapartum

factorspostpartum

factorsmaternalutero-

placentalfetal

hypertension/toxemia

uterine malformations

congenital anomalies

breech presentation

severe respiratory

distress

hypotension twins

abnormal presentations

(facial, transverse, bregmatic)

apnea spells

heart/lung diseases placenta

praevia

Prematurity/postmaturity

obstetrical maneuvers/forceps

application

patent ductus arteriosus

maternal hemorrhage/anemia

polyhydramniosplacental

detachmentsepticemia

diabetes (preexisting/gestational)

uterine rupture

intrauterine growth restriction

umbilical cord prolapsing critical

congenital heart

malformationsinfectionsplacental infarcts

fetal infections caesarean section

haemolitic anemia/

isoimmunisation

meconium amniotic fluid

2. interruption of fetal-placental circulation stops the oxygen supply (hypoxia), causes

accumulation of CO2 (hypercapnia) and moderate acidosis, determining the stimulation of

chemoreceptors and respiratory center, with the onset of breathing.

3. sensory stimulations (cold air, differences of pressure between the intrauterine and

extrauterine medium, light, noise, newborn handling) excite the respiratory center through

the reflex pathways (nerve endings in the skin).

The lung distension during rhythmic lung ventilation causes the passing of the remaining

lung fluid and its subsequent resorption in pulmonary lymphatic circulation. The increase of

pO2 resulting from the initiation and assumption of gas exchanges by the lungs, will cause

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reduction in the lung resistance by vasodilation in the pulmonary arterioles, that means

dramatic increasing of pulmonary blood flow and redirection of blood to the lungs. The delay

in installation of respiration leads to tissue hypoxia, that could compromise the newborn

survival and normal development of the central nervous system.

With clamping and cutting of the umbilical cord and placenta removal at birth, increasing

systemic pressure occurs, wich means increased pressure in the left ventricle (LV) and left

atrium (LA). Increased pressure in the left heart toghether with increasing of pulmonary

blood flow determine decrease in the right-left shunt through the ductus arteriosus (DA), and

increasing the venous return to the left, to the left atrium. When the LA pressure exceeds the

pressure in the RA, the foramen ovale closes. Decreased shunt through the ductus arteriosus,

and increased pO2 cause its constriction. Oxygen is the most important factor that controls

the DA constriction and closure, especially when its partial pressure is approximately 50

mmHg, through the inhibition of prostaglandin E2 production.

Hypoxemia, hypoxia, asphyxia

Hypoxemia is a reduction of O2 blood transport, leading to the the decrease of pO2.

Hypoxemia decreases O2 content in tissues, resulting tissue hypoxia. Fetal response to

hypoxia involves an increase of the O2 extraction in tissues, a decrease of central nervous

system activity, release of catecholamines, redistribution of blood to vital organs

(centralization of blood circulation), which maintain the energy balance for several hours.

The prolongation of hypoxia will cause the initiation of anaerobic metabolism that will

produce lactic acid and metabolic acidosis. The intrapartum hypoxia is the most important

cause of neonatal asphyxia by altering the placental gas exchange.

Breath is the first vital sign that is affected in O2 deprivation. Decreased oxygenation in the

fetus or newborns leads to a period of rapid irregular breathing attempts, followed by

stopping (apnea), accompanied by decreased heart rate to 100 beats/ minute. Cyanosis is

present and blood pressure is normal or slightly increased. This clinical presentation

corresponds to the primary apnea and the stimulation by introduction of a suction catheter in

the mouth, or tactile stimulations can cause the resumption of breathing and increase the heart

rate. In the old nomenclature, this form of asphyxia was known as blue asphyxia. If nothing is

done and hypoxia continues after primary apnea, breaths become superficial, and after a few

gasps (unexpected sudden inspiration, apneustic type inspiration) the newborn enters in a

period of secondary apnea. (Fig. 1) This is characterized by a pronounced decrease in the

heart rate and blood pressure, marked hypotonia, lack of reactivity to stimuli. The infant will

not respond to stimulation and death will occur unless resuscitation begins immediately.

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Initiation of assisted ventilation with bag and mask is needed to improve tissue perfusion.

Fetal hypoxia can determine both primary and secondary apnea. Both phases can be produced

in utero and they are clinically indistinguishable (in both cases the infant is not breathing and

the heart rate is low), so that any apnea at birth should be treated as secondary apnea, and

resuscitation maneuvers must be initiated in the first minute of life, prior to the assessment of

Apgar score. Heart rate and respiratory response to stimulation can help to estimate the

duration of fetal distress. If the infant does not start to breathe immediately after tactile

stimulation, most likely he/she is in secondary apnea and further tactile stimulation will not

have the desired effect. As a general rule, the higher the fetal distress was prolonged, the

longer the time it will take to normalize vital signs. Delayed resuscitation maneuvers

significantly increase the risk of irreversible brain damage.

Figure 1. Primary and secondary apnea (American Academy of Pediatrics)

The degree of brain damage depends on the severity and duration of hypoxia, which

determines metabolic changes with alteration of cerebral blood flow.

Apgar Score is an objective and a rapid method assessing the clinical status of the newborn

infant at birth, being also a useful index of the response to resuscitation. The score is

estabilished at 1 and 5 minutes of life, and in the case of resuscitation at up to 20-30 minutes

(from 5 to 5 minutes). If neonatal resuscitation is needed, it should be initiated immediately

after birth, before setting the score at 1 minute. Therefore, the Apgar score is not used to

determine the need for resuscitation. The score comprises 5 components: heart rate,

respiratory effort, muscle tone, reflex irritability, and color of the skin, each of which is given

a score of 0, 1, or 2. The score is obtained by summing the score for each of the 5 aspects

evaluated. Apgar score is determined for all infants regardless of their gestational age (GA)

and weight. (Table 2)

Table 2. Apgar Score

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2 1 0

Skin color pink acrocyanosis pale/cyanosis

Heart rate >100 beats/minute <100 beats/minute absent

Respiratory effort effective gasps absent

Muscle tone good weak flaccid

Reflex irritability good weak, grimaces absent

Apgar score values of 10, 9, 8 indicate a clinically good status of the newborn and score

values below 8 indicate disturbances in the newborn adaptation to extrauterine life. A score

below 7 may be the result of immaturity, maternal medications, presence of congenital

malformations. The Apgar score has been used inappropriately to predict specific neurologic

outcome. 1 minute Apgar score does not correlate with subsequent neurological development,

and a 5-minute Apgar score poorly correlates with neurological sequelae. For example, a

score of 0-3 at 5 minutes was associated with a slightly increased risk of cerebral palsy, but

75% of children with cerebral palsy had normal scores at 5 minutes. The risk of neurological

sequelae increases when the Apgar score is below 3 to 10, 15 and 20 minutes.

The incidence of perinatal asphyxia is about 1-1.5% of live births in countries with

advanced perinatal care. The incidence is inversely proportional to gestational age. Perinatal

asphyxia is responsible of 20% of perinatal deaths.

Diagnosis of asphyxia

a. Prenatally diagnosis is achieved by:

1. Cardiotocography: fetal heart rate monitoring (normally between 120-160 beats/minute).

The following can be detected: tachycardia, bradycardia, or early or late decelerations.

2. Non-stress test (NST): recording the fetal heart rate for 30 minutes to of the pregnant

woman in lateral decubitus. Normally, the fetal heart rate changes in response to fetal

movements. The test is considered normal if two or more fetal heart rate accelerations is

are detected for a period of 15 seconds.

3. Stress test (ST) on contractions: the administration of oxytocin or stimulation of the

periumbilical skin stimulates uterine contractions, which in a fetus with hypoxia causes

late heart rate decelerations.

4. Fetal biophysical profile (FBP): is a test that measures five variable parameters: fetal

heart rate (NST), breaths, movements, tone, and amniotic fluid volume. The total score

that can be achieved is 10. FBP is performed after a non-reactive NST test, or after a

suspect ST. Echography is used to measure fetal breathing by detecting fetal chest

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movements. Fetal movements are estimated by detecting movements of separate limbs or

of whole body.

5. Fetal ultrasound: assessment of gestational age, weight, detection of oligoamnios

(associated with fetal distress, pulmonary hypoplasia, urinary tract obstruction) or

polyhydramnios (associated with intestinal atresia), detection of malformations

(hydrocephalus, cardiac, renal)

6. Doppler ultrasound: measurement of blood flow in the umbilical artery and cerebral

arteries

7. Amniocentesis: determiation of fetal karyotype, IgM, hemoglobin, hematocrit,

biochemistry determinations.

b. Postnatal diagnosis

1. Clinical and neurological exam of the newborn: the presence of apnea at birth, low

Apgar score, changing consciousness (hyperexcitability, obtundation, coma), changes in

the other organs and systems (oligo-anuria, dysrhythmia, heart failure).

Clinical presentation: clinical manifestations after hypoxic injury have a very broad

spectrum, from mild to severe. Thus, they can be grouped in postasfixic syndrome, with

multi-organ involvement in severe forms.

the post-hypoxic cardiac damage may clinically translate by in: cardiogenic shock, heart

failure, arrhythmia, hypotension, myocardial ischemia, transient hypertrophic

cardiomyopathy

the post-hypoxic respiratory distress can manifest itself by pulmonary edema, pulmonary

hypertension and pulmonary hemorrhage, meconium aspiration syndrome, respiratory

distress caused by surfactant deficiency

the post-hypoxic kidney damage becomes apparent through transient oligo-anuria, renal

failure, renal vein thrombosis.

the post-hypoxic liver damage causes hepatic necrosis, increased liver enzymes,

cholestatic jaundice, vitamin-K dependent coagulation factor deficiency

the post-hypoxic gastrointestinal damage manifests as ulcerative necrotizing enterocolitis,

especially in prematures

the post-hypoxic haematological dissorders are manifested by the tendency to bleed

through thrombocythemia, disseminated intravascular coagulation. Poliglobuly may be

also present

thermoregulation disorders manifest as hyper/hypothermia

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Post-hypoxic brain impairment is the most serious consequence of perinatal asphyxia.

Cerebral hypoxia is a trigger for hypoxic ischemic encephalopathy (HIE). Initially,

hypercapnia and hypoxia cause redistribution of cardiac output, increasing systemic blood

pressure, playing a role in maintainin the cerebral blood flow. Prolongation of asphyxia

causes loss of cerebrovascular autoregulation, so that the cerebral bllow flow varies

proportionally with the systemic blood pressure; the cerebral circulation becomes passive,

vulnerable to changes pression: risk of ischemia in case of systemic hypotension and risk of

bleeding in case of correction of hypotension. After primary injury, a reperfusion phase

appears and this is followed by a secondary injury phase determined by the action of

resulting macroergic compounds. During reperfusion, hypoxic-ischemic injury triggers a

complex cascade of neurochemical reactions causing neuronal death. The mechanism of

neuronal damage involves circulatory, metabolic, cellular and biochemical factors. Massive

neuronal destructions occur. The clinical picture is that of hypoxic-ischemic encephalopathy

(HIE), the worst consequence being cerebral palsy. Sarnat described three clinical stages of

severity of HIE.

Figure 2. Loss of cerebral autoregulation

Stage I, mild form: it is characterized by irritability, tremor, myoclonus, normal muscle tone,

poor sucking reflex, increased Moro reflex, mydriasis, tachycardia, normal EEG. The

outcome is favorable

Stage II, moderate form: is characterized by lethargy, moderate hypotonia, myoclonus, weak

or absent sucking reflex, incomplete Moro reflex, miosis, bradycardia, abundant secretions,

low voltage EEG. Seizures are present. 20% of children are at risk for subsequent sequelae,

especially when seizures last more than 5 days.

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Stage III, severe form: is characterized by the lack of response to physical stimuli (stupor,

coma), generalized hypotonia, areflexia. Oculomotor disturbances may be present

(nystagmus, ocular immobility), fixed mydriatic pupils or poorly reactive to light. Seizures

appear less frequently than in stage II, they can be generalized and usually resistant to

conventional treatments. The presence of cerebral edema is characterized by bulging

fontanels. Severe respiratory depression may occur with irregular/superficial breaths, severe

pulmonary hypertension, pulmonary hemorrhage or edema, imposing the need for ventilatory

support. Cardiac posthypoxic impairment is evidenced by cardiac arrhythmias, reduced

myocardial contractility, hypotension, severe cardiomegaly, tricuspid regurgitation. Intestinal

lesions initially invisible, is sometimes manifested by peristaltic diminished and delayed

gastric emptying. (Table 3)

Table 3. Clinical staging according to Sarnat & Sarnat 1976

STAGE 1 STAGE 2 STAGE 3

State of consciousness hyperexcitability Lethargy/obnubilation Stupor/coma

Muscular tonus normal hypotonia + hypotonia +++

Myoclonus + + -

Sucking reflex weak weak/absent Absent

Moro reflex strong incomplete Absent

Tonic neck reflex weak exacerbated Absent

Activity of autonomous

system

Generalized

sympathetic

Generalized

parasympathetic

Sympathetic and

parasympathetic

depression

Pupils mydriasis miosis variable, unequal

Heart rate tachycardia bradycardia Variabile

Bronchial secretions reduced abundant Variable

Gastro-intestinal motility normal/reduced increased/diarrhea Variable

Convulsions absent frequent Rare

Duration <24 hours 2-14 days days/weeks

EEG

Normal aspect

(awake)

Initial: microvoltage,

Late: foci

Initial: periodic

suppression

Late: generalized

suppression

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Four phases of symptoms are described in moderate and severe stages. In the first 12 hours

after birth (the initial depression of muscle tone and consciousness), the following prevail:

hypotonia, decreased spontaneous movements, stupor, coma, periodic breathing but

pupillary response to light is intact, seizures in 50% of cases. The period 12-24 hours after

birth is of apparent improvement when a clear improvement in the level of consciousness

occurs, the newborn presenting a hyperalert aspect, being irritable with marked tremor of

stimuli.

Seizures may occur in 15-20% of cases and apnea attacks in 50%. Marked hypotonia in the

legs is predominant in the premature newborn as well as in the pectoral arch of the mature

newborn. The worsening period is described between 24-72 hours after birth, when a

reduction in the level of consciousness occurs, accompanied by severe respiratory distress or

respiratory arrest, oculomotor disturbances, lack of pupillary response to light. Death often

occurs at this stage because of severe intraventricular hemorrhage (premature newborn) or

extensive cortical necrosis (mature newborn).

After 72 hours from birth (period of consciousness disturbance improvement) infants who

survive, present gradual improvement but persistent neurological abnormalities are

characteristic in severely affected patients. Generalized hypotonia and disorders involving

difficulty in sucking and swallowing and therefore feeding, are characteristic.

2. Paraclinic Modifications

Table 4. Paraclinic modifications in HIE

Paraclinic examinations Modifications

Acid-base balance pH<7, PaO2 ↓, PaCO2 ↑

Pulsoximetry SaO2<90%

Blood pressure BP - (Average BP

normal value 30 mmHg)Hypo/hypertension

Glycemia hypoglycemia < 40 mg%,

Calcium hypocalcemia< 7 mg%

Potassemia hyperpotassemia>6 mEq/l

Urea >20 mg%

Creatinine >1 mg%

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TransaminasesAST >140 UI/L

ALT >50 UI/L

Hemoglobin, hematocrit ↓

Thoracic X-ray

Hyaline membrane disease, meconium

aspiration, congenital pneumonia,

cardiomegaly

Tranfontanelar echography, MRI, CTCerebral edema, intraventricular

hemorrhage, leukomalacia

Positive Diagnosis of perinatal asphyxia is based on corroborating:

- historical data (risk factors)

- prenatal diagnosis

- clinical features caused by primary / secondary apnea, Apgar score <3 up

to > 5 minutes of life (neurological, cardiac, renal changes)

- paraclinical modifications

Treatment of perinatal asphyxia

a. Prophylactic treatment

- proper monitoring of pregnancy, early detection of risk pregnancies

- early diagnosis of fetal distress, cesarean section indication

- avoidance of trauma at birth

- proper resuscitation of the newborn in the delivery room

b. Curative treatment

- in the delivery room: correct resuscitation of the newborn

- in ICU

- treatment of complications.

NEONATAL RESUSCITATION

90% of newborns have a normal adaptation to extrauterine life with regular breathing, heart

rate 100 beats / minute, are pink-colored. Children are vigorous and healthy looking. 10% of

the newborns require intervention and/or supportive care at birth, 0.2-0.5% have apnea,

bradycardia, pallor, hypotonia, and below 0.1% are dead but resuscitable (the heart had been

detected 10 minutes before birth). Neonatal resuscitation (NR) is includes all the procedures,

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maneuvers and medical therapy used to help a newborn's transition from the intra- to the

extrauterine life or if the cardiorespiratory failure occurs during the neonatal period.

Newborn resuscitation is an emergency intervention, so it should be performed quickly,

every minute of delay entailing subsequent increased incidence of neurologic sequelae and

neonatal mortality. The neonatal resuscitation guide is designed at national level and

establishes the standards, principles and the fundamental aspects of neonatal resuscitation to

be respected by practicians regardless of the health unit in which they work. The conditions

for adequate resuscitation must avoid heat loss, the trauma and infection of the newborn.

These conditions must be ensured through the existence of a reanimation area (room),

located preferably in the delivery room or in its immediate vicinity. The resuscitation table

will have a radiant heater while aseptic and antiseptic conditions will be rigorous. The

resuscitation area must be equipped with:

- equipment for thermal comfort: radiant heater, sterile linen for wiping the amniotic

fluid

- secretion aspirator and Nelaton sterile probes (disposable) No 5, 6, 8,10 for suction of

mouth and nose secretions

- 0 and 1 blade laryngoscope and endotracheal intubation probes of different sizes

- Ambu resuscitation Balloon (for newborns) with oxygen tank and masks of different

sizes

- drugs: Adrenaline 1/10000, 4.2% Na bicarbonate, volume expanders

- needles, syringes, catheters, gloves, sterile gowns

Neonatal resuscitation implies the existence of a trained staff who know the physiology of

transition to extrauterine life and the resuscitation algorithm. Resuscitation maneuvers must

be gentle and quick. The cycle: assessment-decision-action is continuously followed. The

newborn is assessed, a decision is made and then we operate (for 30 seconds), every action

being followed by a new evaluation in order to assess its effects. Three criteria are used for

rapid assessment of the newborn:

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Figure.3. Neonatal resuscitation equipment

- Heart rate (HR) is determined – stetacustically, through palpation of he femoral artery

pulse or by counting umbilical cord pulsations for 6 seconds and the result is multiplied

by 10 (to obtain the rate / minute).

- Respiratory rate (RR) is assessed by the presence / absence of breath and the breaths

count, and stetacustically by the presence / absence of the vesicular murmur;

- Skin color is assessed by inspection: acrocyanosis, cyanosis, pale, white teguments.

Resuscitation maneuvers represent the Resuscitation ABC

A - Airways - airway patency

B - breath - ensuring breath

C - Circulation - ensuring circulation

Immediately after birth the following questions about the newborn must be answered : Does

the baby scream or breathe? Does he have a good muscle tone? Is the newborn

delivered at term? If you answer YES to these questions (baby at term who breathes, has

good tone) the newborn does not require resuscitation, only supportive routine care. If the

answer is NO to the above questions, the infant needs resuscitation

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1. the newborn

screams/breathes

2. good muscular tone

3. term newborn

Supportive care

1. the newborn does not breathe

2. decreased muscular tone

3. premature newborn

Initiation of resuscitation

steps

Until recently, the resuscitation evaluation was also based on the tegument coloration

criteria. This criterion was abandoned because newborns are often slightly cyanotic during

the first minutes after birth, normal transition lasting several minutes. Term-infants will

require> 10 minutes for the saturation to be > 90%. At birth, it is recommended to attach a

pulse oximeter sensor on the right hand for determining preductal saturation. (Table 5)

Table 5. Normal SaO2 at birth

Minutes after birth SaO2

1 60-65%

2 65-70%

3 70-75%

4 75-80%

5 80-85%

10 85-90%

Resuscitation first steps consist in a series of quick maneuvers to be carried out in all infants,

regardless of birth condition.

1. Ensure airways permeability (A - airways)

It is performed through aspiration of oropharyngeal and nasal secretions (mouth first,

followed by nose). If secretions are in a small amount, aspiration is not necessary. Basically,

aspiration of secretions is made with a sterile, disposable probe. The newborn is placed in

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supine or lateral position, head in slight extension ("sniffing" position) to align the pharynx,

larynx and trachea. The aspiration pressure will be within the 80-100 mmHg range, avoiding

posterior pharyngeal stimulation (vagal response risk with apnea and bradycardia).

Figures.4, 5, 6. Positioning, aspiration

2. Wipe, stimulate, reposition.

Newborn hypothermia increases metabolic rate and hence the need for O2 and energy

substrate. Cold stress increases the risk of hypoglycemia and metabolic acidosis. The child

will be placed immediately under radiant heating, on warm diapers, the skin will be wiped in

sterile diapers, wet sheets being removed and replaced with dry ones. Light tactile

stimulation to the feet and back is performed. Do NOT use water spraying, alternative hot-

cold baths, upside down feet hanging and buttocks kicking. These maneuvers commonly

used once, are now outlawed.

Figure 7, 8. Tactile stimulation (ac.Neonatal Resuscitation, 2013)

These steps should last about 10 seconds (the first 10 seconds of postnatal life), followed by

rapid assessment: coloring, HR, RR, evaluation which decides whether to perform the

resuscitation itself. If the newborn is in apnea, we proceed immediately to the next step:

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3. Breathing initiation (B)- positive pressure ventilation (PPV).

If the newborn is not breathing or gasps, balloon and mask ventilation is initiated. An

Ambu for newborns is used for ventilation (Figure 3), equipped with O2 tank, pressure relief

valves and masks of different shapes and sizes depending on the child's weight. Mask

application must be tight, covering the child’s mouth and nose and avoiding the eyes (may

be harmed). Ventilation is achieved by compressing the balloon with your fingers (Figure 4).

The first blowing pressure should be 30-40 cm H2O, followed by 20-cm H2O so as to avoid

barotrauma. The pace of ventilation must be 40 breaths / min (counting: breathing in-2-3). If

the ventilation is effective, rhythmic rise and fall of the chest is observed, bilateral breath

sounds are audible

Figure 9. Ambu Baloon Figure 10. Ventilation with baloon and mask

Some centers are equipped with modern resucitation devices which can play both the role of

resuscitation balloon and manual ventilator and CPAP machine (ensuring continuous positive

pressure ventilation), i.e. Neopuff T-piece resuscitator (Figure 8, 9). Free flow of 21-100%

O2 concentration can be administered with it.

The most important indicator of PPV success is the heart rate increase, followed by the

appearance of spontaneous breathing and improved coloration. When effective spontaneous

breathing is installed, i.e. HR is> 100 beats / minute, ventilation is interrupted, skin coloration

is monitored and O2 in free flow may be administered until teguments become pink.

20

Figures 11, 12. Neopuff T-piece resuscitator

Figures 13, 14, 15. Administration of O2 in free flow

The old resuscitation protocol included administration of 100% O2. Clinical studies have

shown, however, that there is no difference in terms of neonatal mortality and the risk of

hypoxic-ischemic encephalopathy when using air (21% O2) or 100% O2 in neonatal

resuscitation. [15] According to modern protocols, resuscitation starts with 21% oxygen.

Additional O2 is administered in order to achieve the SpO2 in Table 5. If PPV exceedes 2

minutes, a nasogastric probe must be inserted to avoid stomach distension (which can prevent

lung distension) and the risk of aspiration. The tip of the probe is left open.

21

Figure 16, 17. Measuring the nasogastric probe (nose-year-xiphoid appendix pyramid)

If the HR is <60 beats / minute after 30 seconds of PPV, ventilation is continued and

external cardiac massage is performed. Likewise, oro-tracheal intubation may be

considered.

4. External cardiac massage (ECM)

External cardiac massage ensures circulation, i.e. compresses the heart between the

sternum and spine and pushes blood to the systemic circulation. It can be performed in two

ways: with the two thumbs over one another (the thumb technique) or the index and medius

of the same hand (technique of 2 fingers). The pressure is applied perpendicular to the third

lower sternum (below the internipple line) to avoid the xiphoid appendix, while the rib

frames shall not exceed 1-1.5 cm (1/3 of the anterio-posterior diameter of the chest) in order

to prevent rib fractures and liver damage.

Figurr 18, 19. Techniques of external cardiac massage

ECM is coordinated with ventilation: three simultaneous chest compressions followed by one

balloon insufflation (counting: 1 . 2 . 3 → insufflation, 1 . 2 . 3 → insufflation). Thus, in one

22

minute 30 ventilations will be carried out and 90 chest compressions (if performed at the

same time, the ventilation is ineffective). The cardiac massage will always be accompanied

by ventilation!

After 30-45 seconds of PPV coordinated with ECM, the child is re-assessed. If HR is > 60

beats/min, ECM is stopped and PPV is continued until HR is > 100 beats/ minute.

Subsequently, if there is effective breathing, routine care is continued, possibly free flow O2.

If HR is <60 beats/ minute, PPV and ECM are continued, resorting to endotracheal

intubation and medication.

5. Endotracheal Intubation

Endotracheal intubation may be considered at any stage of the resuscitation, depending on the

resuscitator’s experience. Indications are:

- meconium amniotic fluid, the infant is not vigorous

- a prolonged PPV is anticipated

- PPv with mask and balloon is inefficient

- ECM and adrenalin administration are necessary

- special indications: prematurity, diaphragmatic hernia

The laryngoscope is used for intubation, preferably with cold-light (optic fiber ) and straight

blade no. 0 for premature and no. 1 for the full-term neonate. The intubation probes have

different sizes depending on the newborn’s weight (Table 6)

Table 6. Sizes of endotracheal probes

Weight (w) Gestation age (weeks) Probe size (diameter) mm

<1000 <28 2,5

1000-2000 28-34 3

2000-3000 34-38 3,5

>3000 >38 3,5-4

Intubation probes should have a uniform diameter and should be sterile and disposable. The

tip of the probe shall not exceed the vocal cords by 1-1.5 cm (the probe must be in the

middle, into the trachea, to avoid hyperventilation of one lung and hypoventilation of the

other).

The laryngoscope is inserted on the right side of the tongue and the blade is advancing until

the tip is just below the base of the tongue, emphasizing the glottis and vocal cords, which

23

appear as two vertical strips on both sides of the glottis (the letter V inverted, figure 19,20).

Intubation will be performed within 20 seconds. If we fail within this time span, the baby wil

be ventilated between trials with the balloon and mask. The probe insertion depth is

calculated as follows: 6cm + child weight in kg (eg for a child of 2 kg, the probe will be

inserted 6 +2 = 8 cm).

Endotracheal tube position control will be stetacustic in three places: armpits bilaterally, and

the epigastric region (breath sounds should be equal, symmetrical, bilateral, and there is

absence of air entry into the stomach). Signs of correct position of the probe are:

- chest rises with each breath

- respiratory sounds are perceived on both lung fields

- vapor condensation occurs inside the probe in expiration.

A naso-gastric probe is also placed with intubation. In case of secretions in the

tracheobronchial tree, these can be aspirated with an aspiration probe through the

endotracheal tube.

Figure 20, 21. Orotracheal intubation, vocal cords in inverted letter V aspect shape

6. Medication

The umbilical vein is used for the administration of medication by direct injection or by

catheterization. For some drugs, the endotracheal tube.can be used.

a. Adrenaline is the first drug used in resuscitation

Adrenaline produces peripheral vasoconstriction, increases myocardial contractility and

increases the heart rate. It is sold in vials of 1 ml with a concentration of 1/1000. For neonatal

resuscitation it is used in dilution 1/10000, (1 ml of the diluted 1/1000 is diluted with 9 ml

physiological serum). Adrenaline is not indicated before establishing the ventilation!

24

Dose: 0.1-0.3 ml / kg rapidly of the 1/10000 dilution, intraumbilically, repeated after 3-5

minutes. Adrenaline can be administered endotracheally until the establishment of

intravenous access, the dose being 0.5-1mL/kg of the 1/10000 dilution . After administration,

PPV and ECM are continued. High doses can cause high blood pressure post-resucitation and

cerebral haemorrhage. If HR remains <60 beats/ minute, PPV, ECM, and intubation

effectiveness are verified, and existence of hypovolemia and severe metabolic acidosis are

considered.

b. Volume expander

Volume expander is used if there are signs of hypovolemia (pale skin under ventilation, weak

pulse, capillary recoloring time > 3 seconds) or if hemorrhage occurred during labor or birth.

Administration is through the umbilical vein, at slow pace in 5-10 minutes. The following are

used:

- physiologic serum 10 ml / kg

- Ringer's lactate 10 ml / kg

- 0I Rh negative blood: 10 ml / kg

Signs of volemic re-expansion: pallor mitigation, good pulse, increased blood pressure. If

hypovolemia persists, the volume expander dose is repeated.

c. Sodium bicarbonate

Consequences of prolonged resuscitation are lactic acidosis, decreased cardiac contractility

and pulmonary circulation. However, routine administration of bicarbonate (without

demonstration of acidosis through determination of blood gases) is controversial. Without

adequate ventilation and oxygenation, administration of sodium bicarbonate will not increase

the pH.

Recommended dose: 1-2 mEq / kg slowly iv at a maximum rate of 1 mEq / kg / minute.

Sodium bicarbonate is sold in solutions of 8.4% concentration (molar solution 1 ml = 1

mEq). In neonatal resuscitation a 4.2% solution is used (semimolar: 1 ml = 0.5 mEq) by

diluting the molar solution with physiologic serum.

d. Naloxone is administered to children with respiratory depression from mothers on

narcotics, 4 hours before delivery. Dose: 0.1 mg / kg iv or endotracheally.

e. Atropine and calcium are no longer used in neonatal resuscitation

Resuscitation lasts until effective breathing, pink skin and heart rate over 100 beats / minute.

If the heart rate is absent after 10 minutes of resuscitation, stopping the resuscitation can be

considered. The lack of response to resuscitation may be due to several factors: extreme

prematurity, pneumothorax, congenital pneumonia, diaphragmatic hernia, pulmonary

25

hypoplasia.

After resuscitation, infants are kept under close supervision, usually in a neonatal intensive

care department, to notice and correct various pathological aspects in due time. Several

problems can be detected after resuscitation: pulmonary hypertension, aspiration, pneumonia,

infections, seizures, apnea, hypotension, hypoglycemia, etc.

Resuscitation in meconium aspiration

Meconium amniotic fluid is a sign of fetal distress. Intrauterine hypoxia causes the

elimination of meconium in the amniotic fluid with the possibility of aspiration into the

airways, therefore, obstruction (especially in mature newborns and post-matures) and

installation of a very serious characteristic syndrome. Prophylaxis: meconium amniotic fluid

aspiration from the mouth and nose with the head expulsion to the perineum, before the

shoulders are borne. The newborn is not stimulated. After birth, the trachea is aspirated under

laryngoscopy view, by intubation.

Resuscitation is NOT initiated in the following circumstances:

- GA under 24 weeks, W < 400g

- anencephaly

- confirmed trisomy 13 or 18

2. TREATMENT OF PERINATAL ASPHYXIA IN INTENSIVE CARE

General Measures

- thermal comfort by placing in a servo control incubator

- complex monitoring: HR, RR, blood pressure, O2 saturation by pulse oximetry, urine

output, blood gases, blood glucose

- minimal maneuvers and stimulation

- noninvasive oxygen therapy (CPAP-continuous positive pressure ventilation) or invasive

(IPPV intermittent positive-pressure ventilation)

- total or partial parenteral nutrition 3-5 days

- correction of imbalances:

» Hypoglycemia: administration of glucose intravenously at a rate of 4-6 mg / kg /

min

» Hypocalcemia: administration of Ca gluconate 10% 400mg/kg/day infusion

» Metabolic acidosis: is corrected if EB is above -11. Bicarbonate 4.2% is

administered by slow infusion according to the formula:

NaHCO3 to be admin. = EB x G x0, 3 (mEq)

26

- antibiotics protection: Ampicillin + Gentamicin iv, which is discontinued if cultures are

sterile.

B. Specific measures

Specific measures refer to the treatment of complications of perinatal asphyxia, i.e. the

postasfixic syndrome.

Cerebral Complications: the treatment includes control of cerebral edema through fluid

restriction of 40-60 ml / kg / day, induced mild alkalosis by mild hyperventilation and the

administration of sodium bicarbonate, administration of antioxidants: vitamin C, 100mg/kg,

administration of magnesium sulphate, induction of cephalic end hypothermia; cropping of

seizures with phenobarbital (20mg/kg loading dose, then 4-5 mg / kg / day maintenance dose)

or Phenytoin (20 mg / kg loading dose, 10 mg / kg / day maintenance dose).

Cardiovascular complications: the treatment includes restriction of fluids, dopamine and /

or Dobutamine iv (5-10 mcg / kg / min), Sildenafil (Viagra) for pulmonary hypertension (1-2

mg / kg / dose every 4 hours).

Pulmonary complications: the treatment consists of oxygen therapy, mechanical

ventilation, antibiotics.

Renal complications: the treatment includes restriction of fluid, electrolyte imbalance

compensation, administration of furosemide (1 mg/ kg/ day).

Liver complications: the treatment includes plasma, blood transfusions, vitamin K.

Gastrointestinal complications: the treatment consists of digestive rest, total parenteral

nutrition, antibiotics.

Hematologic complications: the treatment includes plasma, blood transfusions,

exsanguinotransfusion.

Evolution and prognosis

Perinatal asphyxia may increase neonatal morbidity and mortality. HIE stage I mortality rate

is below 1%, 98-100% of infants having a normal neurological development. 20-37% of

children with stage II die or present neurological sequelae. In stage III, mortality is high

(50%) and neurologic disabilities are: severe cerebral palsy, mental retardation, epilepsy,

visual impairment. Accurate estimate of severity of long-term complications is difficult.

Increased risk of cerebral palsy and death is given by:

- lack of spontaneous breathing after 20 to 30 minutes from birth

- seizure (onset within the first 12 hours of life), persistent neurological abnormalities over

7-10 days of life (hypotonia, rigidity), persistence of difficulties in eating

27

Bibliography

1. Morales P, Bustamante D, Espina-Marchant P, Neira-Peña T, Gutiérrez-Hernández MA, Allende-Castro C, Rojas-

Mancilla E. Pathophysiology of perinatal asphyxia: can we predict and improve individual outcomes? EPMA J. 2011

Jun;2(2):211-230.

2. McGuire W. Perinatal asphyxia. Clinical Evidence 2007;11:320, 1-21.

3. American College of Obstetricians and Gynecoclogists. Inappropriate use of the terms fetal distress and birth asphyxia.

ACOG Committee Opinion No 3216. Obstet Gynecol 2005; 106:1469-1470.

4. Sunshine P. Perinatal asphyxia: an overview. In: David K. Stevenson, William E. Benitz eds. Fetal and Neonatal Brain

Injury: Mechanisms, Management and the Risks of Practice, 3rd Edition, 2003, I:1-30.

5. Sharma A, Ford S, Calvert J. Adaptation for life: a review of neonatal physiology. Anaesthesia And Intensive Care

Medicine 2010, Elsevier Ltd. 12:3, 85-90.

6. American Academy of Pediatrics, American Heart Association. Manual de reanimare neonatală - traducere în limba

română, Ed. 6-a, 2013.

7. American Academy of Pediatrics, Committee on Fetus and Newborn, American College of Obstetricians and

Gynecologists and Committee on Obstetric Practice. The Apgar Score. Pediatrics 2006;117;1444-1447.

8. Nelson KB, Ellenberg JH. Apgar scores as predictors of chronic neurologic disability. Pediatrics.1981;68 :36– 44

9. Papile LA. The Apgar score in the 21st century. N Engl J Med. 2001;344:519–520

10. Hansen AR Soul JS. Perinatal Asphyxia and Hypoxic–Ischemic Encephalopathy. In: Cloherty J.P, Eichenwald E.C,

Stark A R, Hansen AR, Eds: Manual of Neonatal Care 7th ed, Lippincott Williams&Wilkins Philadelphia, 2012, 55:711-

729.

11. Manning FA. Antepartum fetal testing: a critical appraisal. Curr Opin Obstet Gynecol. 2009 Aug;21(4):348-52.

12. Manning FA. Fetal Biophysical Profile Score: Theoretical Considerations And Practical Application. In Arthur

Fleischer Ed, Sonography in Obstetrics & Gynecology: Principles and Practice, Seventh Edition, 2011, 23:705-713.

13. Hansen AR Soul JS. Perinatal Asphyxia and Hypoxic–Ischemic Encephalopathy. In: Cloherty J.P, Eichenwald E.C,

Stark A R, Hansen AR, Eds: Manual of Neonatal Care 7th ed, Lippincott Williams&Wilkins Philadelphia, 2012, 55:711-

729.

14. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress: a clinical and encephalographics study. Arch

Neurol 1976;33(10): 696-705.

15. Saugstad O.D, Siddarth R, Soll R, Vento M: Resuscitation of Newborn Infants with 21% or 100% Oxygen: An Updated

Systematic Review and Meta-Analysis, Neonatology 2008; 94:176-182.

16. Asociaţia de Neonatologie din România, Colegiul Medicilor din România, Comisia de Obstetrică şi Ginecologie,

Ministerul Sănătăţii, Comisia Consultativă de Pediatrie şi Neonatologie. Reanimarea neonatală, ghid naţional, 2011,

ISBN 978-973-632-712-4

17. Perlman JM, Wyllie J, Kattwinkel J et al. Neonatal Resuscitation 2010 International Consensus on Cardiopulmonary

Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation.

2010;122:S516-S538

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Village, IL: American Academy of Pediatrics and American Heart Association; 2005

28

RESPIRATORY DISTRESS IN NEONATES

Neonatal respiratory distress is any breathing difficulty in the first 28 postnatal days. The

etiology is varied, involving respiratory, cardiac, neurological, surgical, metabolic, causes.

• Respiratory causes: choanal atresia, hyaline membrane disease, transient tachypnea,

aspiration of amniotic fluid, congenital and postnatal pneumonia, pulmonary

malformations, pneumothorax, pulmonary hemorrhage, persistent pulmonary

hypertension.

• Cardiac causes: Cyanotic congenital heart malformations

• Neurological causes: cerebral edema, intracranial hemorrhage, hypoxic-ischemic

encephalopathy, muscular disorders, phrenic nerve lesions

• Surgical causes: diaphragmatic hernia, esophageal atresia

• Metabolic causes: acidosis, hypoglycemia, hypocalcemia, hypomagnesemia,

hyponatremia.

• Hematologic causes: anemia, poliglobuly, shock.

The clinical picture is dominated by:

1. Tachypnea: respiratory rate is greater than 60 breaths/ minute - up to 120 breaths/ minute

(normal 40-60 breaths/ minute)

2. "Combat breathing" Syndrome

- expiratory grunting: breathing with the partially closed glottis to keep the air in the alveoli

- inter and subcostal retraction, xiphoid retraction: as a result of respiratory effort, due to

accessory respiratory muscle contraction

- flaring of the nares: mechanism of respiratory compensation of the increased upper

airway resistance, nostrils widening to increase the breathed in airflow

- thoracic bulging - increased pulmonary volume

- thoraco-abdominal balance - secondary to diaphragm contraction → abdominal expansion

and thoracic retraction in inhalation, the opposite in exhalation

- apnea is the respiratory pause of over 20 seconds or less but accompanied by cyanosis

and/ or bradycardia.

Distress severity is assessed by the Silverman score:

29

Table 7. Silverman Score

Silverman Score

Respiratory movements

Xiphoid Retraction

Intercostalsretraction

Grunting on exhalation

Flaring of the nares with inhalation

Score 0 present Absent Absent absent absent

Score 1Apnea period

Minimum MinimumAudible on stethoscope

minimum

Score 2Thoraco-abdominal balance

Marked MarkedClearly audible

marked

InterpretationTotal = 0 absent SDR

moderate SDR

severe SDR Total = 4-6

Total = 7-10

The score is obtained by summing up the score for each of the 5 evaluated items. A score of 0

indicates no respiratory distress and a score above 2 means respiratory distress of different

degrees (max 10).

Development of respiratory system

The airway system is a process consisting of 5 phases:

1. embryonic stage: until the 5th week, proximal airway development occurs. Abnormalities

occurring in this period: tracheal agenesis, tracheo-oesophageal fistula.

2. pseudoglandular phase: Week 5 -16. It consists in the development of lower respiratory

ways, which are surrounded by lymphatic vessels and capillaries. First respiratory

movements appear (after weeks 13-15). Diaphragmatic hernia occurs in this period.

3. canalicular phase: weeks 17-24. Development of bronchioles occurs, decrease of the

connective tissue, development of the capillary system. Pulmonary pathways are filled with

lung fluid secreted by type I pneumocytes. Type II alveolar cells involved in surfactant

synthesis appear between weeks 20 to 24.

4. terminal sac stage: weeks 24-37. Pulmonary acinuses develop (subsac and alveoli),

decreased interstitial tissue, expansion of capillary invasion, exponential increase of the

alveolar-capillary barrier.

5. alveolar phase: week 37-3 years. Proliferation and further development of alveoli take

place.

Type I pneumocytes facilitate gas exchange, and the type II secrete and store the surfactant.

This is a phospholipid compound (mix of sphingomyelin and lecithin) that reduces surface

tension in the alveoli, thus ensuring alveoli stability. Surfactant biosynthesis begins after 23-

30

24 weeks of pregnancy, its production increasing after 32-34 weeks and it is in sufficient

amount in term pregnancies.

That is why children born under 24 weeks do not have the necessary equipment to adapt to

extrauterine life, morbidity and mortality of these children being inversely proportional to

gestational age. Lung fluid removal is achieved by chest compression during delivery (30-50

ml) and resorption into the bloodstream and pulmonary lymphatic circuit.

RESPIRATORY DISTRESS THROUGH SURFACTANT DEFICIENCY

Hyaline membrane disease (HMD)

Definition: Infant respiratory distress syndrome (IRDS) through surfactant deficiency

(SDRDS) is a pulmonary impairment that begins at or soon after birth, being characterized

clinically by tachypnea (respiratory rate > 60 breaths / minute), dipneea (inter-, subcostal and

sternal retractions), grunting on exhalation and central cyanosis occurring within 4-6 hours of

life, to achieve maximum severity up to 48 hours after birth and resolution in survivors at 48-

96 hours of life.

IRDS is pathophysiologically defined by low pulmonary compliance and significant

atelectasis at the end of exhalation due to abnormal synthesis (qualitative and / or

quantitative) of surfactant. It is the disease of immature lungs and surfactant deficiency, being

associated with prematurity. Synonyms: idiopathic respiratory distress, respiratory distress

with surfactant deficiency.

The Surfactant: It consists of phospholipids, neutral fat, cholesterol and proteins:

monounsaturated phosphatidylcholine (25%) disaturated phosphatidylcholine (40%),

phosphatidylglycerol (8%), cholesterol (4%), proteins (10%), neutral lipids (5%). Surfactant

synthesis is activated by active fetal cortisol and the exogenous cortisol administered

prenatally.

Functionally, the surfactant lowers the superficial tension at the air-alveoli interface which

allows alveoli expansion in inhalation and stops their colabation at the end of exhalation,

increasing lung compliance. Asphyxia, hypoxemia, hypothermia can inhibit the surfactant

synthesis, therefore the hyaline membrane disease can also occur in the newborn at term.

Chronic intrauterine hypoxia caused by uteroplacental insufficiency has a protective effect,

stimulating the surfactant synthesis (table 8).

31

Table 8. Risk factors for respiratory distress through surfactant deficiency

Factors increasing the risk of HMD Factors decreasing the risk of HMD

Prematurity Delay in intrauterine development

Male gender Female gender

Acute asphyxia Chronic maternal hypertension

Neonatal shock Pregnancy-induced hypertension

Rh Isoimmunisation Intrauterine chronic hypoxia

Neonate of diabetic mother Advanced maternal diabetes

The 2nd twin Mother’s abuse of narcotics

Placental detachment Subacute placental detachment

White (race) Black (race)

Family history of HMD Antenatal administration of steroids

Cesarean delivery Premature rupture of membranes

Pathophysiology: Primary deficiency of surfactant (premature) or secondary (hypoxia,

acidosis) causes atelectasis by increasing the surface tension in the lung alveoli. Atelectasis

causes hypoventilation and change of ventilation perfusion ratio. Alveolar O2 decrease leads

to vasoconstriction, which increases hypoxemia through intrapulmonary shunt (due to

vasoconstriction in poorly ventilated alveoli) and extrapulmonary shunt (ductus arteriosus

and foramen ovale).

Vasoconstriction produces local disorders: alveolar-capillary hyperpermeability, fluid and

plasma proteins extravasation in the alveoli with hyaline membrane formation and interstitial

edema, which increase airway resistance, reduce pulmonary compliance and pulmonary

perfusion and increase the physiological dead space.

Pathologic anatomy: the lung is colabated, has liver consistency, the alveoli are colabated.

The hyaline membrane is composed of fibrin and blood and alveolar cells destroyed in the

alveoli; interstitial edema is present and the muscle tunic of the arteriolar wall is thickened.

Electro-microscopically: alveolar epithelial necrosis and absence of lamellar grain from type

II pneumocytes.

32

Clinical presentation

Onset within the first 10 hours after birth with respiratory distress syndrome of varying

degrees, which is increasing in the next 72 hours. Symptoms:

- Tachypnea: over 60 breaths / minute to compensate for current volume decrease and

increase of residual volume

- inter and subcostal retraction: due to the lung-inflation effort

- exhalation grunting: due to the semi-closed glottis exhalation to maintain end-exhalation

pressure within physiological limits (3-5 cm H2O)

- Nares flaring: due to increased respiratory effort

- Paradoxical breathing: abdomen bulging in inhalation, the diaphragm lowers.

- central cyanosis present in ambient air: bluish coloration of teguments and mucous due

to deficient oxygenation (more than 3-5 g / dl hemoglobin is desaturated)

- Other signs: hypothermia, arterial hypotension, progressive edema, generalized

hypotonia.

Clinical examination: stetacustically: diminished vesicular murmurs; disseminated crepitant

rales are detected in both inspiration and expiration. A heart murmur can be detected due to

patent ductus arteriosus.

Radiological picture: characteristic image from birth, bilateral aspect, air bronchogram with

bronchial image present up to the bronchioles, fine reticulogranular pattern with nodular

opacity given by the collabated alveoli and transparencies given by alveolar ducts. In mild

forms diffuse blurring appears, whereas in severe forms the aspect of matte glass with opacity

and disappearance of cardiac silhouette (fig. nr. 22).

Fig. 22. HMD radiologic aspect before and after surfactant administration

The natural evolution of the disease includes worsening of respiratory damage within 72

33

hours after birth. In some newborns improvement occurs after 72 hours when there is a

regeneration of type II pneumocytes and surfactant synthesis, but in severely affected infants

a rapid deterioration of respiratory function appears, long periods of apnea, vascular collapse,

critical evolution.

Paraclinical examination: blood gases: pO2 <50 mmHg, pCO2> 50 mmHg, pH <7.2, pulse

oximetry: SaO2 <90%.

Required tests: blood count, blood group, Rh, electrolytes, glycemia, urea, creatinine

(necessary to detect metabolic complications) bacteriological examinations: hemocultures,

peripheral cultures (to assess the risk of infection), echocardiography (the differential

diagnosis), transfontanellar ultrasound in dynamics (to evaluate relatively common

neurological complications).

Antenatal diagnosis is achieved by determining the ratio of amniotic fluid lecithin/

sphingomyelin. The normal value is > 2, which is 0 risk of HMD. Values below 1.5 = high

risk of HMD.

Positive diagnosis is made by correlation of history, clinical, radiological and laboratory

data:

- History (risk factors)

- Clinical examination: respiratory distress syndrome occurring within hours after birth

- Radiography: bronchograms appearance of matte glass with air bronchogram

- Blood gas analysis - to assess the IRDS severity.

Differential diagnosis

It is sometimes difficult to perform. It is done with respiratory distresses of other causes:

1. Bacterial pneumonia (streptococcus) - clinical and radiological features may be identical

but gram-positive cocci are detected in the insemination of the maternal cervical canal and

newborn’s gastric aspirate.

2. Transient tachypnea - a visible improvement after birth is described.

3. Aspiration of amniotic fluid - rare in pre-term babies, different radiological appearance

4. Persistent pulmonary hypertension - extremely difficult to differentiate

5. Respiratory distress of cardiac malformations: distress is not severe but hypoxemia is

marked (cyanosis does not improve with O2 administration)

6. Intraventricular hemorrhage: sometimes indistinguishable. The following are obligatory:

examination of CSF obtained by lumbar puncture, transfontanellar ultrasound.

7. Distress from poliglobuly: Htc >60%, intense erythematous and purple teguments

8. Distress from anemia: Hgb less than 13 g%

34

9. Distress from metabolic imbalances: hypoglycemia, hypocalcemia, acidosis.

HMD Treatment

a. Prevention

• prevention of premature birth by administration of tocolytics to pregnant women

• maternal corticosteroids: Betamethasone 12 mg im every 24 hours, 48 hours before

delivery, or 4 doses of 6 mg Dexamethasone every 12 hours. Corticosteroids decrease

HMD severity and reduce the incidence of prematurity complication.

• the neonatologist/pediatrician as part of the perinatal team should collaborate with the

obstetrician to transfer pregnant women with premature delivery imminence to a level III

maternity, according to legislation on maternal-infant care regionalization. Level III

maternity has the specific equipment, medications and the team of specialists needed to

ensure stability and optimal postnatal treatment of the preterm baby.

b. Stabilization in the delivery room

• after the expulsion/ extraction, if possible, it is recommended to delay the umbilical

stump clamping for 30-45 seconds holding the newborn below the mother’s level in order

to allow placento-fetal transfusion

• supplemental oxygen should be administered to all preterm babies with central cyanosis

and / or low peripheral oxygen saturation (SpO2) according to GA and postnatal age.

Oxygen should be administered in the lowest concentration that can maintain a heart rate

of over 100 beats/ minute

• stabilization of the preterm babies with IRDS and spontaneous breathing is done through

administration of continuous positive airway pressure (CPAP) with values of 5-6 cm

H2O using the T-piece resuscitator for alveolar recruitment. This reduces the need for

further MV and surfactant administration.

• in case of preterm babies with IRDS and inefficient spontaneous breathing, administration

of a single balloon inflation is recommended before CPAP initiation.

c. Therapeutic conduct

General measures

- ensure thermal comfort (incubator to monitor skin temperature)

- complex monitoring: respiratory rate, heart rate, blood pressure, temperature, hemoglobin

O2 saturation (Sa O2), diuresis, glycemia, electrolytes, hemoglobin)

- oxygen therapy: heated and humidified O2 should be administered. It can be administered

by the mask, tent, CPAP (continuous positive pressure ventilation by nasal fork) IPPV

assisted ventilation (intermittent positive pressure ventilation) or high frequency (HFV).

35

Oxygen therapy must be conducted so as to maintain PaO2 between 50-70 mmHg in

arterial blood and SaO2 by pulse oximetry is 88%. O2 therapy is carried out with strict

monitoring of blood gases, with rapid decrease in the concentration of the administered

O2, to avoid complications.

- parenteral nutrition, electrolyte and acid-base balancing, fluid restriction in the first days.

It is administered by umbilical or central venous catheter.

- erythrocyte mass transfusions to maintain the hematocrit above 40%

- protection antibiotics: Ampicillin + Gentamicin until we obtain the antibiogram from the

harvested cultures (peripheral or central).

Etiologic treatment

It consists in the administration of exogenous surfactant. Prophylactic surfactant

administration and / or curative in these premature infants decreases morbidity and mortality

risk of IRDS and its complications

a. Prophylactic: administered in the delivery room (within the first 15 minutes of life

after balancing) to all preterm babies with VG < 26 weeks - according to national IRDS

guidelines. Immediate or early extubation is recommended whenever possible (depending on

the clinical condition) as well as CPAP to preterm babies with high risk of IRDS with GA <

30 weeks after prophylactic administration of surfactant (INSURE technique intubation-

surfactant-extubation in CPAP). A modern technique is LISA (less invasive surfactant

administration - administration of surfactant through an endotracheal catheter without

intubation) and MIST (minimally invasive surfactant therapy)

b. diagnosis of HMD. The surfactant can be administered: early curative in the first

two hours of life, in the presence of IRDS signs, if chest radiography excludes other

pathology and increases the FiO2 needed by the premature or: late curative, after 2 hours of

life.

Preparations:

- Curosurf (natural extract of porcine lung). The dose is 100-200 mg / kg

- Survanta (natural extract of bovine lung). The dose of 4 ml / kg. It is administered

endotracheally in divided doses, followed by balloon ventilation through the endotracheal

tube for 30 seconds, between doses. After administration, mechanical ventilation is

established.

- Exosurf (synthetic surfactant). The dose is 5 ml/ kg.

During the administration, SaO2 is monitored by pulse oximetry, chest excursions, tegument

color. The immediate effects of surfactant are: improved oxygenation, increased lung

36

compliance (rapid decrease of the ventilator pressures is necessary to prevent barotrauma)

and improved respiratory distress. Endotracheal tube suctioning is prohibited for 2 hours after

administration. Complications of surfactant administration are: hypoxia, hypotension,

pulmonary hemorrhage, clogging of the intubation probe.

HMD COMPLICATIONS

A. Early:

- Infection: positive cultures

- intraventricular hemorrhage: abnormal tone, seizures

- patent ductus arteriosus: apnea, systolic murmur, cardiomegaly

- pneumothorax, pulmonary emphysema: respiratory status deterioration

- complications of intubation: cardiac arrest, subglottis stenosis

- umbilical artery catheterization complications: embolism, thrombosis, renovascular

hypertension, foot gangrene

- Complications of umbilical vein catheterization: embolism, perforation.

B. Late:

- pulmonary bronchodysplasia: result of mechanical ventilation and oxygen therapy for

long periods of time. Areas of atelectasis and emphysema are evident on x-ray. The

treatment includes administration of diuretics (furosemide 1 mg / kg, spironolactone 2

mg/kg/day) and dexamethasone (0.5 mg / kg / day, and then 0.25 mg / kg / day 1-2

weeks).

- premature retinopathy (retrolental fibroplasia): requires laser correction

- neurological sequelae of varying degrees.

The prognosis depends on: gestational age, present complications, competence of the

neonatal intensive care units.

In recent years, there has been a decrease in HMD mortality through proper monitoring of

premature births, improved quality of care at birth, administration of exogenous surfactant,

assistance of these children in specialized centers. Mortality is correlated with gestational age

and disease complications.

TRANSIENT NEONATALTACHYPNEA (TNT)

Synonyms: delayed lung fluid resorption, type II respiratory distress. Incidence: 1-25%.

Pathogenesis: the lung is filled with pulmonary fluid in intrauterine life. During delivery,

while the fetus passes through the pelvi-genital passage, the thorax is compressed, facilitating

37

the elimination of one third of the lung fluid. The remaining lung fluid is absorbed in the

lymphatic circulation in the first 24 hours after delivery.

The syndrome is secondary to delayed lung fluid resorption, resulting in decreased lung

compliance and current volume (tidal), and increased dead space.

Risk factors: cesarean section, male gender, maternal diabetes.

Clinical presentation: onset within 24 hours with respiratory distress: tachypnea (over 100

breaths / minute), pulling in of the chest/intercostal retraction, grunting sounds on exhalation,

sometimes cyanosis (reversible with O2 administration).

Radiological picture: normal appearance or layout of "wet" lung with perihilar or alveolar

opacities, with occasional pleural fluid blade.

Paraclinic picture: usually normal, without hypoxia, hypercarbia and acidosis

The evolution is favorable in 24 hours.

Differential diagnosis: is difficult to perform with HMD in early stages. Rapid favorable

evolution and no reticulonodular radiological image indicate TNT

The treatment includes thermal comfort and oxygen therapy.

MECONIUM ASPIRATION SYNDROME

Incidence: 5-15% of term or postmature newborns

Predisposing factors postmaturity, fetal distress, SGA (smal for gestational age) neonate

Pathogenesis: intrauterine hypoxia causes the elimination of meconium in the amniotic fluid.

By intrauterine gasping, meconium may be aspirated into the airways antepartum or at the

onset of the first postpartum breaths. Usually, newbornss are dirty or meconium-impregnated.

Aspiration of meconium amniotic fluid produces airway obstruction and chemical

pneumonia.

Obstruction may be total, producingl atelectasis, or partial (with valve effect) resulting in

obstructive emphysema and pneumothorax. These determine the decrease of lung compliance,

disturbance of the ventilation-perfusion ratio triggering: hypoxia, hypercapnia, and metabolic

acidosis.

Clinical picture: is characterized by respiratory distress with tachypnea, expiratory grunting,

intercostal retraction, the barrel chest, cyanosis, crepitant or bronchial disseminated rales in a

newborn with meconium amniotic fluid, requiring resuscitation at birth.

Radiological picture:

Opaque areas with areas of condensation on both pulmonary areas are present, separated by

38

areas of emphysema, increased anterior-posterior diameter, pneumothorax,

pneumomediastinum.

Fig. 3. Meconium aspiration

Treatment

A. prophylactic

- early detection of fetal distress and postmature pregnancies, delivery initiation.

- aspiration of meconium amniotic liquid from the pharynx immediately after the expulsion

of the head to the perineum

B. curative: neonates without asphyxia, with meconium amniotic fluid of low consistency do

not usually require treatment.

• When the meconium has high consistency (pureed peas), tracheal suctioning through

endotracheal intubation is required and avoidance of the newborn stimulation. Massive

aspiration of meconium requires conventional assisted ventilation, sometimes with high

frequency or nitric oxide to fight hipercarbia, hypoxemia and acidosis. For the treatment

of pulmonary hypertension, sildenafil (Viagra, Revatio) is used at a dose of 1-2 mg / kg /

dose, 2-3 days

• antibiotics: for prophylaxis or treatment of superinfection: Ampicillin + Gentamicin is

used initially or a third-generation cephalosporin associated with Amikacin

Complications:

- bacterial infection

- pneumothorax, pneumomediastinum

- persistent pulmonary hypertension.

Evolution: rapid death in massive aspirations; positive evolution for early treatment

Prognosis depends on the degree of neurological damage and pulmonary complications.

References

39

1. Asociaţia de Neonatologie din România, Colegiul Medicilor din România, Comisia de Obstetrică şi Ginecologie,

Ministerul Sănătăţii, Comisia Consultativă de Pediatrie şi Neonatologie. Managementul sindromului de detresă

respiratorie prin deficit de surfactant. Ghid naţional 2011, ISBN 978-973-632-714-8

2. Bhakta KY: Respiratory distress syndrome. In Cloherty JP, Einchenwald EC, Stark AR: Manual of Neonatal Care. 6th

Ed Philadelphia Lippincott Williams and Wilkins 2007; 323-330

3. Cloherty J.P, Eichenwald E.C, Stark A R: Assesment of the Newborn Hystory and Physical Examination of the

Newborn. In: Manual of Neonatal Care, sixth ed, Lippincott Williams&Wilkins Philadelphia, 2008, 59-72, 228- 237,

309-315, 317-323, 518-528.

4. Escobedo M: Moving from experience to evidence: changes in US Neonatal Resuscitation Program based on

International Liaison Committee on Resuscitation Review. J of Perinatol 2008; 28: S35-S40

5. Gomella TL: Hyaline Membrane Disease (Respiratory Distress Syndrome). In Gomella TL: Neonatology:

Management, Procedures, On-call Problems, Disease, and Drugs. 6th Ed Lange Clinical Science 2009; 477-481

6. Gomella TL: Respiratory Management in Gomella TL Neonatology: Management, Procedures, On-call Problems,

Disease, and Drugs. 6th Ed Lange Clinical Science 2009; 48-67

7. Morley CJ: Respiratory distress syndrome. In Polin RA, Yoder MC: Workbook in Practical Neonatology. 4th Ed WB

Saunders Co Philadelphia 2007; 129-150

8. Moss M, Thompson RT: Definitions and clinical risk factors. In Choi AMK: Acute Respiratory Distress Syndrome. 2nd

Ed Informa Healthcare NewYork 2009; 9-201

9. Stoicescu S: Sindromul de detresǎ respiratorie. In Stoicescu S. Boli pulmonare neonatale. Ed Universitară Carol Davila

Bucureşti 2009; 85-100

NEONATAL INFECTIONS

Poor resistance to infections (due to their morpho-functional features), gives the following

features to the new born’s infections :

- increased frequency (> 1%) - tendency of generalization

- poor, atypical symptoms - severe evolution (mortality 20-30%)

Classification is made according to the moment of infection. Thus we have:

- prenatal infections (antepartum)

- intranatal infections (intrapartum)

- postnatal infections (postpartum)

I. MATERNAL-FETAL INFECTIONS

These are infections that occur in newborns under 48 hours old. These are:

- chronic intrauterine infections grouped under the TORCH syndrome

- infections caused by Treponema pallidum, Listeria monocitogenes, varicella-zoster virus

- infections transmitted during labor and delivery - perinatal infections and intrapartum

40

infection (Streptococcus spp., E. coli, Gramm negative germs)

Transmission of infection is by hematogenous way, transplacental (TORCH), by ascending

way (by infected amniotic fluid) or intrapartum, by faeces, secretions, blood (direct contact

or aspiration).

II. NOSOCOMIAL INFECTIONS - HOSPITAL INFECTIONS

Nosocomial infections are infections that occur in the newborn over 3 days old. These

infections can occur from mother, from flora and hospital equipment, and nursing staff.

TORCH Syndrome: T = toxoplasmoza, O = other: HIV, hepatitis, etc, R = rubella, C =

cytomegalovirus, H = herpes simplex.

The incidence of the syndrome is 2.5‰ of live newborns. Intrauterine infections can cause

repeated miscarriages, mortinatality, prematurity, congenital malformations affecting long-

term prognosis.

Pathogenesis: the effect on the concept product depends on gestational age at which the

infection occurs, the virulence of germs and if the infection in mother is primary or recurrent.

Pathogens affect embryogenesis (embryopathy) or cause destruction of tissues already

formed (fetopathy).

Clinical manifestations: most affected infants are asymptomatic in the neonatal period or

present subtle signs, nonspecific, making diagnosis difficult. Other signs: deafness, visual

disorders, motor dysfunction are detectable later, so that these children must have a long term

follow up. Suggestive signs of congenital infections are:

- intrauterine growth retardation - jaundice

- hepatosplenomegaly - microcephaly/ hydrocephalus

- skin lesions - eye injuries

Congenital toxoplasmosis (toxoplasmosis fetopathy)

It is caused by Toxoplasma gondii, an intracellular parasite whose definitive host is the cat.

Transmission to humans is by gastrointestinal way (through food contaminated with cysts, or

through contaminated hands) or transplacental (from mother with acute infection). The

parasite is known to infect the CNS and eyes. Transplacental transmission is reduced when

maternal infection occurs during the first term of pregnancy (14%), but the severity of

infection is higher, often causing abortion; the risk of subsequent sequelae is 40%. In the 3rd

quarter, the transmission rate is 60%, the infection is benign, without increased risk of

sequelae.

The infection causes diffuse or focal meningoencephalitis with cerebral calcifications and

41

loss of cerebral substance, resulting in microcephaly, obstruction of Sylvius aqueduct and

foramen Monro (by calcification), causing hydrocephaly. Eye injuries are chorioretinitis,

iridocyclitis, cataract and microphthalmia. Other alterations are found in the lungs, heart,

kidneys, digestive tract.

Clinical presentation

a. The septicemical form is severe, with multi-organ involvement, fever, hemorrhagic

syndrome, jaundice, hepato-splenomegaly, lymphadenopathy, encephalopathy,

convulsions and rapid death or non-progressive sequelae (hydro-/ microcephaly,

intracranial calcifications fig 23, 24). It occurs in 10% of cases.

Fig 23. MicrophthalmiaFig 24. CT: periventricular

calcifications

b. Attenuated form: with mild symptoms, prolonged jaundice, microcephaly/ hydrocephaly,

chorioretinitis, hypotonia, drowsiness, which may be expressed later by psychomotor

retardation (progressive), seizures, hydrocephaly.

c. Latent form: without clinical manifestations.

Positive diagnosis:

Isolation of the parasite: from body fluids reflects the acute stage of the disease, while

isolation of cysts from tissues obtained by biopsy, is evidence of an old infection.

Prenatal diagnosis: amniocentesis, amniotic fluid and cultures from fetal blood

Postnatal diagnosis:

1. Serology:

• Sabin-Feldman color test determines particularly the IgG, is sensitive and specific

• Indirect fluorescent reaction measures IgG and is widely used in practice. The

antibodies detectable by these reactions appear in 1-2 weeks after infection, reaching high

titers at 6-8 weeks and gradually decrease after a few months. Low titers may persist

throughout life. IgG titer does not correlate with disease severity. A negative result for

42

IgG antibodies excludes previous exposure to T. gondii, except immunocompromised

mothers.

• RIF test (Remington) detects IgM antibodies, being used for the diagnosis of acute

infection. IgM occur within the first 5 days after infection and disappear early. A negative

result virtually excludes recent infection (within the past 6 months). False positives tests

are described (at 60% of pregnant women with positive IgM result, recent infection is not

confirmed).

• ELISA method determines IgM and IgG antibodies. IgM titer is increased over 1000 U/l.

A color or RIF test with titre over 1/1000, a RIF-IgM titres over 1/80 or IgM ELISA over

1/256 signifies a recently acquired infection.

• Polymerase chain reaction (PCR) - quick diagnosis from blood and CSF.

Diagnosis of infection in pregnant women

Pregnant women with positive IgM and negative IgG antibody should be retested every 2

weeks until the occurrence of seroconversion or exclusion of a non-specific IgM response.

RIF-IgM or IgM ELISA are performed, which, if positive, indicate an acute infection. In their

absence, IgG RIF will be done and if the result is over 1/1000, it will be repeated every 3

weeks; if the same values are obtained, it means that infection occurred more than 8 weeks

before and risk for the newborn is reduced. Toxoplasma antigen detection in amniotic fluid

can be made.

Diagnosis of infection in the newborn

Serological tests from cord blood are performed in parallel with those from maternal blood;

detection of significantly increased titer of IgG antibody compared to the maternal, the

presence of IgM and/ or IgA antibody is diagnosis for congenital infection (IgM are present

in only 50-60% of children with congenital toxoplasmosis in the first month of life, and rarely

detected in children born from treated mothers). Serological monitoring should be performed

during the first year of life and the disappearance of IgG during this period practically

excludes congenital infection, mentioning that specific treatment can lead to the reduction or

disappearance of antibodies, but with "serological rebound" at treatment discontinuation.

2. Isolation of the parasite: from placenta, umbilical cord, brain, muscle.

3. Transfontanellar ultrasound, CT: periventricular calcifications are seen, hydrocephaly.

Treatment

Prevention: avoid the cat, insufficiently cooked pork, screening for toxoplasmosis in pregnant

women, treatment.

Treatment: newborn treatment - the most used combination:

43

• Pyrimethamine 2 mg/kg/day the first 2 days, and then 1 mg/kg/day for 6 months, and

then the same dose up to 1 year, 3 days/week.

• Sulfadiazine: 50 mg/ kg / day a year.

• Folic acid 10 mg twice/ week during treatment with pyrimethamine (avoiding bone

marrow depression).

• Corticotherapy Prednisone 1 mg/ kg/ day when there are inflammatory ocular lesions

and increased proteinorachia.

It is recommended to treat hydrocephaly: subcutaneous reservoir, ventriculo-peritoneal shunt.

Congenital rubella (rubella embryopathy)

Incidence: 0.7-7 per 1000 births.

Etiology: rubella virus transmitted transplacental.

Rubella virus can infect the fetus at any time during the course of pregnancy, the infection

being almost certain if the maternal disease occurs in the first term of pregnancy, outlining

the panel of congenital rubella syndrome. Virus excretion by the infected children continues

postnatally; they are contagious up to one year or more after birth. Congenital rubella

serologic diagnosis is made by determining specific IgM and cultures from nasal secretion,

urine and cerebrospinal fluid. Fetal pathology appears when the infection occurred in the first

16 weeks of pregnancy (the first 11: cardiac malformations and deafness, in 11-16 weeks

deafness). The risk for children is 85% in first 2 months of pregnancy, when termination of

pregnancy is recommended, 30% at the third month of pregnancy and 16% in 4-5 months of

pregnancy.

Clinical presentation is variable, depending on the gestational age at the time of exposure to

the infectious agent. Congenital rubella has a wide spectrum of clinical manifestations; in the

classical form, there is a triad: impaired eye (microphthalmia, cataract, glaucoma,

chorioretinitis); hearing impairment (deafness of perception), cardiac malformations. The

generalized form is characterized by the classical triad plus hepatosplenomegaly, cholestatic

jaundice, interstitial pneumonia, meningoencephalitis, lymphadenopathy, thrombocytopenia,

purpura, and evolving microcephaly, mental retardation, behavioral disorders. There An

asymptomatic form is also described (at birth), with late-onset, in the first 5 years, as

encephalopathy.

Positive diagnosis is suspected in newborns from mothers with proven or suspected rubella

during pregnancy, or those with mentioned clinical signs. Serologic diagnosis: specific IgM

antibodies in the newborn, the persistence of specific IgG at 6-12 months of life.

44

Prophylaxis: rubella vaccination in girls 1-18 years (Trimavax, Priorix). Immunoglobulins

do not prevent the disease. The treatment is symptomatic.

Infection with cytomegalovirus (CMV)

Incidence: 1/3000 births.

First cytomegalovirus infection is asymptomatic in 90% of cases. The increased risk of

transplacental transmission is in the first 22 weeks of gestation. Only 10% of the newborns

present clinical infection. There are three clinical forms:

1. Generalized form: hepatosplenomegaly, petechiae, jaundice with increased direct

bilirubin, thrombocytopenia. The following may also be present: microcephaly, intracranial

calcifications, optic atrophy, chorioretinitis; 25% of the symptomatic children die in the first

year of life by hepatic dysfunction, bleeding, DIC phenomena, superimposed bacterial

infection, severe neurologic impairment.

2. Localized form: neonatal hepatitis, thrombocytopenic purpura, neurological impairment.

3. Latent form: asymptomatic but with serological changes.

Pregnant women diagnosis: detection of CMV infection or IgM antibodies.

Diagnosis in children: clinical examination and identification of anti-CMV IgM. Other

nonspecific tests: lymphocytosis, hyperbilirubinemia, elevated transaminases.

The most common long-term complication is hearing deficit that occurs in 60% of

symptomatic children and in 5-10% of asymptomatic children. Long term prognosis for

asymptomatic children is good.

Prophylaxis: hygiene in pregnant women, screening.

Treatment is supportive. Certain antiviral agents: Ganciclovir 10-15 mg / kg / day 2 doses,

3-6 wk., Idoxuridine are under study.

Infection with Herpes Simplex Virus

The incidence is 1/2000-1/5000 births per year, involving especially type II virus.

The intrauterine transmission is rare. The newborn may present skin lesions, chorioretinitis,

micro-/ hydrocephaly, neurological sequelae. Most commonly, transmission occurs during

delivery. It can involve the skin, eyes or mouth, CNS or a disseminated form may be present:

thermal instability, apnea, jaundice, hepatomegaly, seizures, DIC. The mortality is high.

Diagnosis: viral cultures, serology.

Prophylactic treatment: indication of caesarean section when there are maternal genital

lesions, newborn isolation; if the mother presents active lesions, we will administer 0.6 ml/kg

45

Ig. standard in the new born; if the mother has primary infection (positive cultures) a

treatment with Ara-A 30 mg/kg/day will be initiated for 10-14 days from the 38th week of

gestation.

Treatment: is represented by supportive therapy, administration of Acyclovir 10

mg/kg/dose, slow infusion every 8 hours for 14 days.

Infection with Varicella-Zoster Virus

Incidence in pregnancy: 1-7/10.000

Clinical manifestations:

• when the infection occurs in the first term, congenital varicella syndrome is found:

intrauterine hypotrophy, skin scarring, limb paralysis and atrophy by necrotizing myelitis,

eye damages (chorioretinitis, microphthalmia, optic atrophy);

• when the infection occurs between the first quarter and last weeks of pregnancy, it has

only serological expression;

• if the onset of maternal chickenpox occurs between 21-5 days before the birth, the

newborn will present benign neonatal varicella (vesicular rash), due to the transfer of

antibodies from mother to fetus; the prognosis is good;

• if the onset of maternal varicella is <4 days before birth and 2 days after birth, the

newborn may present severe neonatal varicella: generalized rash, sometimes polivisceral

lesions (pneumonia, meningitis)

Diagnosis: based on the infectious contact, the clinical and laboratory examinations

(highlighting virus vesicles, positive serology).

Prophylactic treatment: isolation of pregnant women with chickenpox during labor,

isolation of newborns with varicella from other children, but not from mother, specific Ig

administration. Curative treatment: specific antibodies (0.3 ml/kg), supportive care, hygiene

of skin lesions.

Hepatitis infection

The main types of viruses are A, B, C, D and E virus.

Viral hepatitis type A: fecal-oral transmission, rare in newborns. Neonates may be

asymptomatic or may present acute hepatitis.

Diagnosis: detection of antibody.

Treatment: specific anti-A immunoglobulin 0.5 ml im, in the newborn from mother with

hepatitis A in the last two weeks of pregnancy.

46

Viral hepatitis type B is the most serious form of neonatal hepatitis.

Hepatitis B virus causes: specific antigen HBs (surface antigen, indicating acute infection);

HBc antigen (found in infected hepatocytes nucleum); HBe antigen (indicates active

hepatitis). HBs antibodies indicate healing and immunity after hepatitis; HBc antibodies

indicate acute/ chronic infection, HBe-antibodies indicate the resolution of the disease.

Transmission to the newborn:

- vertical: at birth

- transplacentar: rare

- parenteral: blood and blood products, infectious maneuvres

Risk factors:

- maternal infection in the third quarter of pregnancy or one month postpartum (80-90%

risk)

- chronic carrier mother of HBsAg and HBeAg: 80% risk

- mother with HBeAg and HBeAb: low risk: 10-20%

- mother with HBsAg: no risk of transmission to the newborn

Clinical presentation:

- asymptomatic infection: moderately increased transaminases, mild hepatomegaly,

HBsAg positive

- clinical hepatitis: jaundice, hepatomegaly, malaise, elevated transaminases; newborns

become chronic carriers of HBsAg and 1/3 of them progress to chronic hepatitis and

cirrhosis

Prophylactic treatment: compliance with universal precautions for personal, premarital

screening, early washing of babies from HbsAg positive mothers, gentle suction of secretions

to prevent injuries.

If the pregnant woman gets viral hepatitis A close to (or before term), the new born will be

administered Ig standard 0.5 ml/kg, and if mother had hepatitis A 2 weeks before birth, the

new born will be administered 0.15 ml/kg Ig standard.

Standard hepatitis B vaccination (in new borns from mothers AgHBs negative) (EngerixB,

Euvax B, Recombivax HG), first dose at birth: 10µg (0.5 ml) or Recombivax HB 5µg (0.5ml)

at 0-1-6 months or 0-2-6 months, with specific hepatitis B immunoglobulin (Hepatect).

Infants from mothers AgHBs positive are classically immunized, and they will get a dose of

specific Ig for hepatitis B (HBIg) as quickly as possible (the first 12h after birth). Their

immunological status will be supervised at 9 months. If the titer of antiHBs Atb is

>10mIU/ml and AgHBs negative, the infant will get one more vaccination at 0-1-6 months.

47

Fecal-oral or breastfeeding transmission of HBsAg after birth is minimal; breastfeeding is the

mother’s free choice.

Streptococcal infections

Etiology: Streptococcus group B

Transmission: 5-40% of women are carriers of streptococci (vagina, rectum), 50% of the

children are colonized from their mothers; only 1-2% of the children get an obvious infection.

Clinical presentation: The infection has acute onset (in the first week), ½ of the new borns

have signs of infection since birth. It manifests itself as a neonatal sepsis with respiratory

distress, lethargy, low blood pressure, they all have bacterimia; 1/3 - ½ have distress and/or

pneumonia and 1/3 meningitis; 50% die.

The infection with tardive onset appears between 1 week and 3 months of life (the average 3-

4 weeks), meningitis is more frequent, although clinical forms are mild, some of them lead to

coma, status epilepticus, and the element of gravity is neutropenia.

Evolution: More than 50% of the survivors are neurologically affected: late speaking, loss of

hearing, loss of sight, mental retardation, uncontrolled seizures; some late infections such as

osteomyelitis, arthritis, adenitis, might appear.

Treatment: in bacterial sepsis is started with Ampicillin + Gentamicin until the cultures are

known. As a rule, the treatment is continued with Penicillin 450,000 IU/kg IV/day for 10-14

days and in meningitis for 3 weeks.

Prophylaxis: In pregnant women colonized with group B streptococci and which represent

one or more risk factors: premature birth, membrane ruptured for more than 24 hours,

prolonged labor, corioamniotitis, Ampicilin will be administered during delivery. Researchers

try to obtain a specific vaccine.

Congenital Syphilis

Etiology: Treponema Pallidum

The rate of transmission from mother to child is 70% at mothers with primary syphilis, 90%

at mothers with secondary syphilis and 30% at mothers with latent syphilis. In the absence of

the mother’s treatment to the mother, the fetal risk is: 25% risk of fetal death, 25% of

perinatal death and 50% of congenital syphilis in the newborn.

Clinical manifestations:

- confirmed congenital syphilis

48

- presumptive congenital syphilis: any newborn of a mother with untreated or

improperly treated syphilis in pregnancy, any newborn with positive serologic tests

for syphilis, or clinical and radiological signs for syphilis, positive VDRL test from

CSF, FTA-ABS 19S-IgM positive test

Most infants with congenital syphilis are asymptomatic at birth. Precocious congenital

syphilis occurs in the first 2 years of life, symptoms debuting after the third week of life with

general signs: fever, lymphadenopathy (isolated), irritability and triad: rhinitis, palmar-

plantar pemphigus and splenomegaly.

Pemphigus is characteristic (palms and plants); the liquid is very infectious. After breaking of

the vesicles, scabs form. Other skin lesions include: rash, annular or in clusters lesions,

disseminated petechial lesions on buttocks, back, accompanied by cracked or bleeding lesions

of the mucous membranes (nostrils, palate, tongue, anus) . Rhinitis is highly contagious and

is purulent or hemorrhagic. Untreated, the septal cartilage may lead to necrosis resulting in

perforation.

Neurologic involvement: syphilitic meningitis, proteinorahia, polymorphonuclear

pleocytosis, hydrocephaly, optic atrophy, hemiplegia. Eye damage: chorioretinitis, uveitis,

glaucoma, eyelid canker. Lung injury: interstitial pneumonia. Renal impairment: nephrotic

syndrome, glomerulonephritis. Other: myocarditis, pancreatitis, malabsorption.

Radiological abnormalities: osteochondritis, periostitis, osteitis (“yatagan” tibia).

Haematological abnormalities: anemia, leukopenia/ leukocytosis, thrombocytopenia.

Laboratory diagnostic: nonspecific tests: positive VDRL.

Specific tests: FTA-Abs (absorption fluorescent treponemal antibody test) MHA-TP (micro-

hemagglutination test for Treponema). CSF exam: pleocytosis mononuclear proteinorahia,

positive VDRL from CSF.

Treatment:

Neonatal criteria: clinical signs of congenital syphilis, VDRL 4 times higher than of the

mother. Penicillin G is administered 50,000 IU/kg/dose every 12 hours during the first 7 days

of life, then every 8 hours. The duration is 10-14 days.

Monitoring: newborns from positive mothers at birth are followed up clinically and

serologically until the normalization of the tests. Neonates with antibodies transferred from

the mother and those properly treated will have decreasing antibody at 3 months and will be

negative by 6 months. Abnormal CSF examination involves CSF checking until

normalization.

49

INTRANATAL INFECTIONS (Bacterial infections transmitted during labor and birth)

Risk factors: chorioamnionitis, ruptured membranes for over 18 hours, maternal fever over

38º C, urogenital infections, streptococcal or Gramm negative vaginal colonization,

prematurity.

Germs involved: Streptococcus group B, E. coli, Hemophilus influenzae, Klebsiella,

Enterobacter, Pseudomonas, Staphylococcus aureus, Listeria.

Listeria monocytogenes: neonate contamination takes place during birth, but also prenatally

(!).

Clinical manifestations: Early forms, septicemia, late form in 3-5 weeks after birth, located

at meningean level. Features: small white pharynx granulomas and ↑ no. of mononuclears in

the CFS.

Treatment: Ampicillin 200 mg / kg / day in 4 divided doses im Gentamicin 14 days, 21 days

in meningitis.

Chlamydia trachomatis (1970) most freq. cause of sexually transmitted infections

Clinical manifestations: Chlamydia conjunctivitis (inclusions) - 5-14 days incubation;

purulent secretion. (Epithelial inclusions are observed through Giemsa staining of secretions).

Mother-child transmission in 10% of cases also causes pneumonia

Diagnosis - expensive (cell culture, direct immunofluorescence, ELISA, PCR)

Treatment - macrolides (erythromycin, clarithromycin, azithromycin) and tetracycline.

Neisseria gonorrhoeae

Clinical manifestations: gonococcal conjunctivitis. Treatment: 10 days with penicillin G, i.m.

plus ocular instillation (2,500 IU / 1 ml), others recommend 1 % chloramphenicol, sol.,

neomycin, 0.5%, 0.3% gentamycin.

Nongonococcal conjunctivitis. Appears at 24 hours after birth,! NOT to be mistaken for

chemical irritation produced by conjunctival instillation with AgNO3.

Usually, the local treatment is sufficient (instillation into the conjunctival sac).

Some cases require antibiotics - depending on the causing agent, after results of insemination

of conjunctival secretion in various culture media.

ACUTE INFECTIONS IN NEONATES

The most frequent infections are: nn septicemia, nn meningitis, nn pneumonia, nn umbilical

infection and cutaneous. The most severe and feared is septicemia.

50

NEONATAL SEPTICEMIA

Neonatal septicemia (and meningitis) represents a serious clinical context, with

unpredictable evolution. These are determined by various germs, developing a primary

outbreak and the appearance of septic metastases by pathogen migration in general

circulation. Bacteremia is transient downloading of germs in the bloodstream, proven by

positive blood cultures. Incidence: 1-8% from live new borns, one third of them also develop

meningitis.

Predisposing factors:

• immunological immaturity of newborns, the smaller the gestational age is, neonatal

asphyxia, intracranial hemorrhage

• maternal infection: sepsis, bacteremia, urinary tract/ vaginal infections, premature

rupture of membranes for more than 24 hours, difficult birth, maternal toxemia

• nosocomial infections: overcrowding, broken medical circuits, bubbled water and water

from incubators, invasive maneuveres (puncture, catheterization, central venous access),

mechanical ventilation, poor hygiene of staff, misuse of antibiotics.

The admission gate: respiratory, skin, gastrointestinal, umbilical.

Etiology: Group B streptococcus (15-20% of women are colonized), E. coli (the first case in

Romania), Klebsiella, Pseudomonas aeruginosa, Proteus, Salmonella, Candida albicans.

Clinical: no typical symptoms, even fever may be absent.

a. alarm signals (arise from several hours to several days after birth): the newborn who

"doesn`t looks good", pronounced weight loss, vomiting, refusal of food, hypothermia,

spontaneous groan or at handling, “earth-colored” tint of the skin

b. during the state period, there is a syndrome characterized by severe infection: malaise,

impaired thermoregulation, hypotension, changes in the skin (purpura, necrotic lesions,

early, intense jaundice, omphalitis, edema), respiratory disorders (apnea, tachypnea,

respiratory distress), cardio-circulatory collapse (tachycardia/ bradycardia, pale mottled

skin, hypotension, capillary recoloring for more than 3 seconds), digestive signs

(abdominal distension, hepatosplenomegaly, vomiting), signs of meningitis (irritability,

abnormal tone, seizures)

Laboratory examinations

When there is suspicion of sepsis:

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• bacteriological samples from gastric aspirate, blood, urine, CSF, throat, umbilicus, stool,

external auditory canal

• CBC should be taken: leukopenia <5000/mm3, leukocytosis> 33000/mm3, neutrophil

count <1000/mm3, immature neutrophils report/ total neutrophils >0.2, thrombocytopenia;

other tests: ESR >15 mm/h in the first hour of life, positive CRP, impaired coagulation,

metabolic acidosis, hyperbilirubinemia, thoraco-abdominal radiological examinations.

Signs of certainty: positive blood culture, positive CSF culture (with low glicorahia and high

proteinorahia or low CSF glucose, increased CSF proteins).

Prophylactic treatment: screening in all pregnant women, at 35-37 weeks (cultures of

vaginal secretions, urine culture), antibiotic prophylaxis in those with positive cultures.

Treatment: antibiotics are initiated at the time of suspicion, after bacteriological sampling.

Broad-spectrum antibiotics are preferred: Ampicillin 150 mg/kg/ day IV to 12 hours,

Gentamicin 2.5 mg/kg/dose i.v. 12, 18 and 24 hours, depending on gestational age, or a 3rd

generation cephalosporin. In nosocomial infections consider the 4th generation cephalosporin

(Maxepin), Vancomycin, Tienam, Meropenem. Antibiotic treatment is corrected according to

pathogen susceptibility results, treatment duration being 10-14-21 days, especially in cases of

meningeal involvement and 4-6 weeks in osteoarticular impairment

Association of first intention antibiotics according to etiology: Anaerobic - Penicillin, except

Bact. fragillis - chloramphenicol, carbenicillin, cefalosporne, Metronidazole, listeria -

Ampicillin + Gentamicin 14 days Gram neg. enterococci: Ampicillin + aminoglycoside

(Gentamicin, Kanamycin), Pseudomonas, Proteus indole + - carbenicillin, 10-14 days.

Supportive treatment: maintaining thermal comfort (incubator), complex monitoring

(respiratory rate, heart rate, blood pressure, diuresis, oxygen saturation, blood gases, urea,

creatinine), fluid resuscitation (umbilical catheterization).

Treatment of septic shock: plasma, human albumin 5% 10-20 ml/kg, Dopamine/ Dobutamine

5-20 mcg/kg/minute

Immunologic and hematologic treatment: human immunoglobulin 500-1000 mg/kg/dose

every 2 weeks, transfusion of fresh blood, plasma, red blood cell, platelet, exanguino-

transfusion.

Evolution: depends on the gestational age of the newborn, germ involved and the presence of

complications. Mortality is high; septicemia is the 3rd leading cause of death in ICU after

hyaline membrane disease and congenital malformations.

Neonatal Meningitis

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Purulent meningitis is given by a different spectrum than bacterial meningitis of infants over

2 months.

Etiology: Gram neg. Enterobacteriaceae: coli, streptococci gr.B, staphylococci, Listeria,

anaerobic, rarely H. influenzae, meningococcus, pneumococcus

Positive diagnosis: vague symptoms - irritability / lethargy, ± fever, bulging fontanelle (late),

rarely convulsions, vomiting, without signs of meningeal irritation

Fulminant onset with shock and rapid evolution - some signs in the teminal status.

Practical Rules: lumbar puncture is performed in the infant with suspicion of meningitis.

Agiation, irritability, fever - meningitis until confirmation of other diagnosis. Seizures

associated with fever - an indication of LP

Supporting positive diagnosis: LP shows cloudy CSF, l> 10/mm3, germs / smear, cultures +

glicorahia / glycemia <0.5 advocate for diagnosis support. Other foci are looked for (hemo-,

urine cultures)

Tratatamentul antibiotic se adminstreaza 21 zile, I.V.

Treatment: as in the case of sepsis, maximum doses of antibiotics according to antibiogram.

Group B streptococci - penicillin + gentamicin 14 days, then another 7 days Penicillin. Gram

neg. - Difficult (resistant to penicillin, some resistant to Ampicillin, gentamicin penetrates

CSF with difficulty). Moxalactam, other gen.III cephalosporins for. Gram.neg. resistant to

aminoglycosides and Bacteroides (50-100 mg / kg / day, 2 doses), for gen III E.coli -

Cefotaxime 50mg/kg/dose at 12 or 8 h; Ceftazidime, etc.

Antibiotics treatment is administered at 21 days i.v.

General treatment - supportive and symptomatic, seizure control, liquid restriction

(inappropriate ADH secretion) in newborns under 5 days max. liquids: 40ml/kg/day, after 5

days restriction may reach 20ml/kg/day

Discharge criteria: careful neurological assessment upon discharge, but not before 5 fever-

free days, as relapses occur in the third day from antibiotic cessation.

Ulcerative necrotizing enterocolitis

Etiology. It is considered that initially there are ischemic lesions of intestinal mucosa (due to

hypoxia and acidosis). Post-ischemic intestinal stasis and energy substrate provided by

enteral nutrition promotes proliferation of saprophytic or pathogenic gut flora (Enterobacter,

E. coli, Pseudomonas, Salmonella, Staphylococcus epidermidis, Klebsiella, Campylobacter,

enteroviruses), the emergence of intestinal pneumatosis (gas in the intestinal wall) and

perforation and peritonitis with septic disseminations.

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Risk factors: prematurity, asphyxia, acute cardiopulmonary disease, enteral nutrition

(formula milk and hyperosmolar drugs), polycythemia and blood hyperviscosity syndrome,

exanguino-transfusion, umbilical catheterization.

Ulcerative necrotizing enterocolitis is a disease that occurs more frequently in neonatal

intensive care units taking care of children with low gestational age and where invasive

techniques are used for diagnosis and treatment.

Symptoms and diagnosis: ulcerative necrotizing enterocolitis occurs 3-7 days after initiation

of enteral feeding, the most common and early clinical signs (70%) being abdominal

distension (bloating). Also, there is ileus, with absence of intestinal noise, gastric residue that

becomes bloody or bilious (2/3 of cases), bloody stools, ascites, abdominal wall infiltration,

thermal instability, seizures, apnea, bradycardia, and finally signs of shock and DIC. Three

developmental stages are described: stage I (non-specific systemic signs, abdominal

distension, gastric residue, occult stool bleeding), stage II (bloody stools, abdominal wall

edema are added) and stage III (signs of shock).

Laboratory tests: abdominal radiography from AP and lateral incidence points, depending

on the stage of the disease: dilated bowel loops, pneumatosis and air leakage in the portal

system and pneumoperitoneum. CBC: anemia, leukopenia or leukocytosis with left deviation,

thrombocytopenia <50,000. Blood and stool culture analysis are usually positive, and blood

gases show metabolic acidosis. Biochemical determinations (urea, creatinine) are altered.

Hyperkalemia due to enhanced hemolysis is present.

Treatment

- cessation of enteral feeding in order to put the digestive tract to rest (10-14 days)

- continuous naso-gastric suction catheters for intestinal decompression

- strict cardio-respiratory monitoring, pulse oximetry, BP, urine output, fluid intake, stools,

waist circumference measurement

- repeated radiological control, surgical consult

- removal of umbilical catheters, removing potassium infusion

- antibiotics: Ampicillin + Gentamicin IV or Cefotaxime IV (10-14 days), and then

corrected after antibiogram; metronidazole may be considered

- total parenteral nutrition, correction of electrolyte and acid-base imbalances

- supportive care: oxygen therapy, mechanical ventilation, red blood cell transfusions,

plasma, Dopamine infusion

- surgical treatment in case of intestinal perforation

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Prognosis: mortality is 20-40%; complications can occur: short bowel syndrome, subacute

intestinal occlusion caused by strictures and stenoses.

Skin and mucous infections

MONILIASIS - muguet

Etiology-Candida albicans at the passage through the pelvi-genital channel or postnatal

contamination from healthy carrier

Clinical manifestations: oral lesions (jugal, tongue, gums, palate) - small white deposits,

confluent, not detached; rare perianally or disseminated

Certainty diagnosis: - Methylene blue smear. – micelles, spores

Local treatment: Na bicarbonate Sol. 4.2%, 0.5% dequalinum chloride, gentian violet 0.5%

of 3-4x/day, 3-4 days, 4-6 slow oral instillations with Stamicin suspension (100,000 U / ml);

Generally indicated in unfavorable evolution (! Food hygiene, boling the teats) - Treatment

with Stamicin 100,000 U / kg / day 4 times, 7-10 days + gel / suspension Miconazole or

Netamicină - instillation or local applications

BULLOS IMPETIGO (pemfigus)

Staphylococcal etiology

Clinical manifestations: bullous lesions with clear content, in 2-3 days - turbid and then

purulent, successive bursts up to 4 weeks, in good general condition.

Diagnosis by highlighting the content germ

Treatment: isolation, baths with KMnO4 solution 1:10.000, toilet with Rivanol 1%, powder

with sulphonamide antibiotics, ointment in case of crusts; in case of superinfection antibiotics

are administered parenterally

RITTER EXFOLIATIVE DERMATITIS

Etiology: staphylococcal endotoxin

Clinical manifestations: "Scalded skin" syndrome, - B. Ritter and Lyell syndrome,

staphylococcal scarlet fever; similar etiology with toxic shock syndrome. Sudden onset

generalized erythema, epidermal detachment (Nikolsky sign +), large breaking bubbles, toxic

condition

Treatment: local - as impetigo + symptomatics; General penicillinase-resistant penicillin -

Oxacillin 100-200mg/kg/day 4h 7-10 days. Supportive treatment, hydration, maintaining

body temperature.

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Umbilical infections

After sectioning, through devitalization the umbilicus becomes a wonderful culture

environment for germs, being colonized in short time after sectioning through local flora

represented by streptococci and staphylococci.; Represents a gate for tetanos, diphtheria and

erysipelas.

Omphalitis: Inflammation of umbilical ring, it is an inflammatory process characterized

through hyperemia and edema of periumbilical regions, sometimes with a bad smell of the

umbilical blunt.

Etiology: staphilococci, streptococci

Symptomatology:

symptoms of inflammation (fever might be missing) +

manifestations depend - if the umbilical blunt fell or not

Blennorrhea = flowing of the navel cord after the fall.

Umbilicus ulceration =lack of substance covered by pus and tumefied sides.

Granuloma = red bud, juicing

Umbilical phlegmon appears when infection have propagated and also in subcutaneous

cellular tissue

Diagnosis - similar to septicemia

Treatment:

Remove any catheter

Aseptic care of umbilicus and desinfectants (rivanol 1%, hydrogen peroxide, KMnO4)

antibioticotherapy: Penicillin G 100000-200000 UI/kg/day + Oxacillin 100 - 200

mg/kg/day in 4 doses IM 10 - 14 days

outlining with nitrate de Ag in granuloma

Surgical treatment in phlegmon

Local treatment in blennorrhea and ulcerations

PROPHILAXY OF INFECTIONS IN THE NEW BORN

Rules for the prevention of infections in newborns

- depict and treat any infections in pregnant women

- correct birth assistance (maternity, qualified staff, hygiene)

- prophilaxy of pulmonary infection: correct oropharyngean vacuuming immediately after

birth

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- ocular and umbilical prophilaxy

- serious measurements of asepsy and hygiene (in the delviery room, ward, home)

- hand hygiene: frequent washing with water and soap, short nails, avoid rings; most

infections are spread through hands!

- wear lint mask, frequently changed

- detection of germs carrier in medical staff, family

- precoceous isolation and fast treatment of the new born’s infections, starting with

suspicion

- it is forbidden to visit the new born; ill mothers and medical staff are forbidden to have

contact with the new born if they present fever or have respiratory, skin infections or

enterocolitis

PATHOLOGICAL JAUNDICE IN NEW BORNS

Definition: Jaundice is the yellow coloration of teguments and mucosa through increase of

serical blirubin values. Jaudince is evident in new borns at values of 5-7 mg%.

There are three types of jaudince: physiological, pathological and nuclear.

I. Physiological jaundice

Physiological jaundice is a hyperunconjugated (indirect) bilirubinemia in which total

bilirubin is under 12 mg/100ml serum (N < 1.15 mml/l) and conjugated (direct) bilirubin is

under 15% from total bilirubin.

Incidence: it appears in 50-80% in new borns at term and 90% in premature.

Etiology: The causes of physiological jaundice are:

- increased blood volume - short period of life of fetal erythrocytes

- inefficient erythropoiesis - poor hepatic conjugation

- intensification of entero-hepatic circulation

Clinical: Physiological jaundice appears from the 3rd day (after 48h of life) and lasts for 7-10

days in the new born at term and more than 30 days in prematures. Physiological jaundice is

without hepatosplenomegaly.

Treatment:

Prophylactic treatment : precocious breastfeeding (colostrum has purgative effect).

Curative treatment – phototherapy.

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II. Pathological jaundice

Etiology: The pathological jaundice appears in:

- disorders of production

- disorders of metabolism

- disorders of bilirubin excretion

The pathological jaundice appears in the first 24-36 h (precocious jaundice), with a total

bilirubin over 12mg% in new borns at term and more than 15mg/100ml serum in prematures,

or a direct bilirubin over 1.5-2mg%. A jaudince for more than 10 days in new borns at term

and over 2 weeks in prematures defines the prolonged jaundice (table 9, 10, 11).

Table no. 9. Etiology of pathological jaudince

Precocious jaundice Prolonged jaundiceHemolytic disease through Rh and ABO incompatibility

Continues the physiological jaundice.

Hereditary spherocytosisMinkowski -Chauffard disease (anemia with sperocytes + fever)

Appears in intra/ extrahepatic atresy

Citomegalyin prematuresa febrile jaundiceurine sediment with “owl eye" cells

Table no. 10 Causes of indirect hyperbilirubinemia (BiI>85% from BiT)

Excess of production Decrease of Bi-clearance

Feto-maternal Rh/AOB incompatibility

Errors of metabolism: Crigler Najar jaudinceDubin Johnson syndromeRotor-SchiffGilbert syndromeTyrosinosisGalactosemia

Hereditary sperocytosis Prematurity

Hemolytic anemia HypothyroidismPituitary insufficiencyBreastfeeding at mothers with DM

Polycythemia Hepatic hypoperfusion Extravasion/swallowing of blood

Prematurity

Acceleration of entero-hepatic circulation Genetical factors Inhibitors from breast milk (stopping breastfeeding for 48 hours)

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Table no. 11. Causes of direct hyperbilirubinemia (direct bilirubin over 15% from total

bilirubin)

Septicemia Intra-uterine infections- neonatal hepatitis

Coledocian cyst Obstructions of biliary ductus (tumors,

annular pancreas)

Trisomy 18 Galactosemia, thyrosynemia, methyoninemia

Cystic fibrosis Rotor-Schiff syndrome, Dubin Johnson

Sydrome of thickened bile Prolonged total parenteral nutrition

- Atresy of intra/ extrahepatic biliary

ways

Neonatal hemolytic disease is a feto-maternal Rh incompatibility (eritroblastosis) or ABO

incompatibility. The disease appears in the following situations:

- mother is Rh negative and child is Rh positive

- mother has O (I) blood group and child has A (II) or B (III) blood group

The fetus’ red cells produce antibodies in the mother’s blood, which pass into the fetal

circulation and produce hemolysis.

Rh antigenes sensitize during the first pregnancy and in the second pregnancy the hemolysis

and the jaundice appear. More and more severe forms will appear. Sensitization can be

produced even by transfusions or abortions.

A and B antigens are widely spread in nature, that is why, isoimmunization is produced at the

first pregnancy, but it can appear also by heteroimmunization through infections, vaccines

The hemolytic disease in ABO system appears from the first pregnancy. It is more frequent,

but milder than the hemolytic disease in Rh system; it does not affect the intrauterine fetus; it

does not produce severe forms of jaundice at the moment of birth and prenatal diagnosis or

postnatal treatment are not necessary. In this form, mother has O (I) blood group and child

has A (II) or B (III) blood group. Natural agglutinins of those with group A (II) or B (III) are

IgM type, with heavy molecular weight, which do not pass the placenta. Agglutinins of those

with group O (I) - IgM type and IgG – with small molecular weight, cross the placenta.

The physiopathological chain is: hemolysis - hyperbilirubinemia – erythroblastosis (by

compensatory mechanism).

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Clinical signs and symptoms: anemia, jaundice, hepatosplenomegaly, hemorrhagic

manifestations, neurological signs.

Clinical forms:

- Feto-placentary anasarca (fetal hydrops). The new born has: generalized edema, ascitis,

hepatosplenomegaly, paleness, cardiac failure, frequently: dead fetus.

- Hemolytic jaundice: jaundice present at birth: the newborn is apparently normal at birth,

with anemia, but Hgb exceeds 12 mg%, accentuated jaundice, hepatosplenomegaly,

localized edema, bilirubin values over 3-4 mg%.

- Hemolytic anemia: severe anemia at birth, newborn present low Apgar score, Hgb is less

than 12 mg%, bilirubin 3-4 mg%, hepatosplenomegaly.

Laboratory diagnosis

- blood group and Rh in parents and child

- titer of antibodies in pregnant women

- positive Coombs test: presence of antibodies in mother’s serum

- blood test in the new born shows anemia, trombocytopenia

- leukocyte formula: erythroblasts > 25%, reticulocytes > 6%

- indirect bilirubin from umbilical cord > 4 mg%.

Prophylactic treatment

– immunoprophilaxy anti-D (Ig specific)

- in Rh negative women: 300 µg Ig anti-D in the first 72 h after abortion/ birth if the

new born is Rh positive;

- in female gender negative Rh new born from positive Rh mothers.

Curative treatment

In mild and medium forms: phototherapy and Phenobarbital 5-8 mg/day, 3-4 days

In severe forms:

- exanguinotransfusion with double volume (160 ml blood/kg, 85% of the blood

volume is changed)

- integral blood is used with Htc 40-45%, less than 48 h, group O (I) negative Rh or

isogroup with new born blood, but negative Rh

- immediately after phototherapy it is necessary to monitor bilirubin at 6h

- exanguinotransfusion is repeated if bilirubin increases above 1mg/h

- in hydrops or small weight - isovolumetric

- the blood is collected through umbilical artery and transfused through umbilical vein.

Types of jaundice- according to mechanism of production

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- Hemolytic jaundice (prehepatic)

- Hepatic cellular jaundice

- Mechanical jaundice (posthepatic)

A. Hemolytic jaundice (prehepatic)

Signs and symptoms: yellow teguments and mucosa (flavinic jaundice), dark urine,

splenomegaly ± hepatomegaly, hemolysis

Laboratory: increased bilirubin

Treatment: phototherapy, exanguinotransfusion, Phenobarbital

B. Hepatocelular jaundice

Causes:

- septicemia - viral hepatitis

- herpetic disease - listeriosis

- congenital toxoplasmosis - intoxications (tetra, steroids)

- congenital enzymatic deficiencies (Crigler Naijar, Dubin Johnson, Rottor Schiff)

Features:

- yellow-orange teguments and mucosa - hepatomegaly without splenomegaly

- intensely colored urine - acholic feces

Laboratory:

- increased direct and indirect bilirubin

- increased transaminasis and sometimes aldolase, late.

Treatment: specific diets, antibiotics, corticosteroids (in neonatal hepatitis) unspecified

etiology.

C. Mechanic jaundice (posthepatic)

Causes:

- malformations of intra and extra hepatic biliary ways (atresia, agenezis)

- compression of intra and extra hepatic biliary ways (bracket, lymph nodes, tumors)

Features:

- onset: the 2nd week of life - verdinic progressive jaundice

- incresed direct bilirubin - hypercrome urine

- acholic feces - hepatomegaly

- positive hepatic samples

Treatment is surgical - in the first 4-8 weeks

- not faster, due to risk of colestasis syndrome

- not later, because biliary cirrhosis can appear

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III. Nuclear jaundice (hyperbilirubinemic encephalopathy)

- bilirubin over 25 mg% in mature new born, 10 mg% in premature

- the consequence of toxic effect of indirect hyperbilirubinemia (unconjugated,

unbounded to albumin) on CNS

Clinical: jaundice + neurological symptoms (hypotonia, adinamia, difficult sucking,

hypertonia, opistotonus, seizures, apnea crisis)

- indirect bilirubin (unbounded) penetrates the hemato-encephalic barrier in the first 2-4

days of life and it fixes to the basal grey nuclei

- lethal or sublethal evolution (deficiency in CNS development)

Risk factors:

- hemolytical disease - prematurity

- acidosis - asphyxia

- hypoproteinemia - hypoglycemia

Evolution: severe, often death occurs

It can produce chronic encephalopaty:

- ataxia - athetosis

- deafness - mental deficieny

Treatment:

• Phototherapy in risk of increasing bilirubin over bounding capacity of albumin; increased

bilirubin at dangerous levels: premature, extended bruisings, hemolytical disease

• Blood transfusion – indications:

- correct the severe anemia - prevent the nuclear jaundice

- septicemia - DIC

- severe metabolic imbalance

• Exanguinotransfusion (ET): if mother has negative Rh, the following are determined in

the new born: blood test, blood group, Rh, bilirubin, Coombs test.

- ET is recommanded in the first hours after birth if:

» the new born with jaundice, paleness, edema, hepatomegaly, bad general state

» good general state, but Coombs test diectly positive, Hb < 11g% in mature new

borns, < 14g% in premature

» bilirubin from umbilical cord > 4mg% and increasing with 0.5 g/h

» bilirubin 25 mg% in new born at term without asphyxia or 20 mg% in new born at

term with asphyxia

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» bilirubin 18-20 mg% in premature new born without asphyxia or 15 mg% in

premature new born with asphyxia.

ET is repeated when bilirubin increases to values of neurological risk.

Blood transfusion will be done with:

- fresh blood (24h after collection) – in suffering new borns

- irradiated blood – if it got an intrauterine transfusion

- heparin blood

- gluco-citrate blood

HIV-AIDS INFECTION IN NEW-BORNS, NEONATES, AND CHILDREN

Acquired Immunodeficiency Syndrome (AIDS) is an infectious syndrome caused by the

human immunodeficiency virus (HIV) that attacks the body's immune system.

Immune depression caused by the virus favors the development of opportunistic infections.

Etiopathogeny

HIV belongs to the retroviruses class (RNA virus) which has an enzyme (reverse

transcriptase) that converts viral RNA into proviral DNA to be integrated into the host cell

genome.

Unlike other pathogenic viruses (influenza, polio, etc.) that damage cells, retroviruses only

transform them. When these cells will multiply, cellular genome-integrated provirus will

multiply simultaneously.

HIV infection is characterized by a continuous and active retroviral replication associated

with an intense renewal of infected cells (which invalidates the previous model regarding the

existence of a period of latency that would clinically correspond to the asymptomatic phase ).

HIV structure

• (iantigenity)

p24

p18 gp41

p17 gp120

virus identification

ARN chain gp160

(core)

Fig. no. 25. The HIV structure

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The complex genetic structure provides HIV a tremendous genetic diversity. Analysis of

nucleotide sequences of HIV strains reveals extreme genetic variability, virtually there are

NO two similar strains, which is why a vaccine cannot be obtained.

The main targets of HIV are macrophages and T lymphocytes. HIV attaches to CD4 by

gp120 and enters the cell. The most important reservoir of these target cells are lymphoid

tissues, lymph nodes (which are the most important center of viral replication).

After primary infection, viral replication is very intense (p24 ATG): In the first month from 1

million-1 billion copies / ml and an increased number of infected lymphocytes. With the

second month the viral load decreases (up to about 9 months) by 100-1000 times (CD8

cytotoxic), decrease occurring before seroconversion and presence of neutralizing atb.

Without reduction in the viral load, as it happens in the case of malnutrition, tuberculosis and

in infants, development to AIDS is much faster.

In the next period (clinical latency / asymptomatic) viral load remains relatively constant

(infected CD4 lymphocites are replaced until the exhaustion of the regenerative capacity of

the immune system).

In the final stage of HIV infection (AIDS) there is again an increase in the viral load but with

a target cell depletion - 10-20% infected CD4 lymphocites.

It follows that in the early stages of HIV infection, the main factor that limits infection is the

immune system, and finally there is a depletion of target cells.

Natural evolution of HIV infection

Infection

Invading DISSEMINATION Invading of AIDS

regional lymphoid Destruction of lymph nodes tissues lymph nodes

structure

5 years Invasion of other organs

9-10 years

asymptomatic period (in 5% cases in 15 years)

Fig. Nr. 26. The evolution of HIV infection

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Epidemiology

In Romania at the end of 2001 (WHO statistics) the number of HIV-positive was 6500 (2500

adults, 4000 children); in November 2002 -9000 cases. At the end of July 2007 - 15 000 HIV

positive people in Romania. The number of people receiving antiviral therapy - 6500 (70

pregnant women)

The source of infection. The source of infection is represented by infected humans, AIDS

being an infectious disease, not a contagious one. The virus does not resist at temperatures

above 60-64 degrees C or at ordinary disinfectants.

Transmission

Inoculation of infected blood and blood products

Sexually (sperm and the vaginal secretion)

Parent-child transmission can be:

vertical transmission: HIV-positive mothers have HIV antibodies. These antibodies

cross the placenta, so the babies will be HIV positive. Antibodies persist 9-18 months.

Only 15-30% of viral antigens cross the placenta. Thus, in the absence of any intervention

70-85% of babies are protected, not being infected.

transmission during birth / cesarean section: by inoculation of blood or vaginal

secretion

transmission through breast milk is possible, therefore breastfeeding should be

prohibited in HIV mothers. The risk increases to 20-40% for naturally-fed children

(WHO recommends breastfeeding in developing countries where malnutrition is more

dangerous).

Responsiveness to infection. Although some cases meet the conditions for infection,

infection does not occur. It seems that individual genetic factors do not have a leading role,

rather the amount of viral load.

Symptoms, clinical diagnosis

If it is an intrauterine infection, the newborn presents growth retardation, brain anomalies

(most commonly microcephaly), and facial dysmorphism. The infected infant presents the

first symptoms within 3-6 months after birth: major signs or opportunistic or severe recurrent

infections. Major criteria (M) by WHO are: prolonged fever> 1 month, chronic diarrhea> 1

month, weight loss> 10%. Minor criteria are generalized lymphadenopathy (at least 2

regions), oropharyngeal candidiasis, persistent cough> 1 month, generalized dermatitis,

65

serologically confirmed maternal HIV infection. AIDS suspicion= 2M +2 m, in the absence

of other causes of immunosuppression: malnutrition, tuberculosis, tumors.

Laboratory diagnosis

ELISA Test detects Anti-HIV antibodies. It becomes positive at 6-8 weeks after infection.

To avoid false-positive reactions, testing is performed by two different ELISA techniques.

The test is not 100% specific

Western Blot test identifies viral antiproitein antibodies (antibodies directed against viral

envelope, gp120, gp160 and antibodies directed against p18, p24 cores)

Determination of viral antigens - antigens p24

Polymerase chain reaction-identification of the viral genome of blood lymphocytes

Immunity investigation: B lymphocites increase, decrease of T cells (<400/μl shows a

severe defect of immunity), increased immunoglobulin.

Diagnosis of HIV infection in children perinatally exposed is through viral methods; HIV

serology can not be used as a diagnostic test due to the presence of maternal antibodies. In

our country it is recommended that HIV RNA testing should be done in children during the

first 2 days of life, on the 14th day, if the first test was negative; between month 1 and 2 of

life, to the 3rd and 6th month of life.

Etiologic treatment-(antiretroviral therapy)

Zidovudine (AZT, Retrovir) belongs to group A.

It is a nucleoside reverse transcriptase inhibitor, metabolised in the liver. The dose is

according to metabolization (extended in prematures). It produces anemia through medular

inhibition - hemoglobin is checked at birth and at 6 weeks.

Term newborn: 2 mg / kg every 6 hours

Prematures: 2 mg / kg every 12 hours, 2 mg / kg every 8 hours at 2 weeks of life and GA> 30

weeks, 2 mg / kg every 8 hours at 4 weeks and GA <30 weeks.

Lamivudine (3TC) belongs to group B

It has renal metabolization, the dose being proportional to glomerular filtration capacity

maturation in the newborn. It leads to lactic acidosis. Recommended dose: 2 mg / kg every 12

hours. There is recommendation to increase the dose at the age of 4 weeks to 4 mg / kg every

12 hours.

Nevirapine

It is non-nucleoside reverse transcriptase inhibitor with prolonged elimination time in the

newborn. The dose is 2 mg / kg in a single dose after birth, maintaining the plasma levels

increased up to day 7.

66

Schemes of neonatal ARV prophylaxis

Effective prophylaxis reduces the rate of maternal-fetal transmission of HIV to 1-2%. This

requires ARV prophylaxis in both mother and child, obstetrical interventions (scheduled

caesarean) artificial feeding of the child. Depending on the situation, management protocols

for the pregnant woman and the newborn have been employed.

In Romania, according to the Anti-AIDS Commission's recommendations, the interventions

designed to reduce the rate of maternal-fetal transmission of HIV are: artificial infant

feeding; initiation of antiretroviral therapy after the first 6 hours of life with AZT and 3TC

and its continuation for 6 weeks.

Zidovudine (AZT) administered during pregnancy, during labor and post-partum in mother-

child decreased vertical transmission from 25.5% to 8.3% in populations who are not

breastfeeding. At the parent-child pairs receiving combination therapy that included a

protease inhibitor (PI), the transmission rate fell to 0.1 - 1.3%. The protective role of cesarean

section was also demonstrated (intervention performed at 38 weeks of pregnancy).

1. Pregnant woman diagnosed with HIV infection during pregnancy with indication of

ARV therapy: newborns will not be breastfed; initiation of ARV therapy in the first 6

hours of life with AZT and 3TC and continued for 6 weeks.

2. Pregnant woman under antiretroviral therapy when pregnancy occurs: the newborn

will not be breastfed; ARV therapy is initiated in the first 6 hours of life with AZT

and 3TC and continued for six weeks; if the mother's ARV scheme was changed

because of virologic failure, the newborn will receive AZT, 3TC and NVP. If the

pregnant woman is under NVP treatment, the infant will receive the first dose of NVP

at 48-72 hours after birth, and then a daily dose of 2 mg / kg for 7 days followed by a

dose of 4 mg / kg up to 6 weeks; if the pregnant woman received NVP late during

delivery or 1-2 hours before delivery, the newborn will get a dose of 2 mg / kg

immediately after birth, and the next dose should be given after 24-72 hours.

3. Pregnant woman diagnosed with HIV infection in the eighth month of pregnancy: the

newborn baby will not be breastfed; ART therapy is initiated after the first 6 hours of

life with AZT, 3TC, NVP, the infant is considered at high risk of being HIV infected.

The duration of treatment is six weeks

Overall HIV Prevention aims to avoid blood, sperm and vaginal secretions and infected

maternal milk. Junkies, prostitutes (> 90% are infected) and newborns of infected mothers are

considered “high-risk”..

67

Family planning. HIV-positive mothers will be made aware that they can transmit the

infection to the newborn at a 15-30% rate (doctors will not make any "suggestion" only

mother decides to maintain the pregnancy).

Health education. It should be large, well coordinated at the governmental level. It will

include: recommendation to restrict partners, use of condoms (75% of HIV infections occur

through unprotected sexual intercourse); sterilization of needles and instruments for 30 min.

through boiling at 100 degrees C; burning of disposable syringes and needles in

crematoriums.

Mandatory preventive measures have been legislated in our country by testing: in partners,

prenuptially, in women in the first term of pregnancy (may decide to abort or be treated in the

last term of pregnancy), truck drivers and sailors , in persons working abroad for a period of

over 6 months.

Special measures in newborns

• Protective measures at birth: disposable gown, gloves, mask, cap. Ball resuscitation and

suction system should be sterilized after each use, preferably they should be dedicated to

infants from HIV positive mother. Good resuscitation at birth lowers the risk of subsequent

need for laborious procedures of treatment, such infants should be treated as non-invasive as

possible. They can present any postnatal complications: hypoxia at birth, respiratory distress

syndrome, pulmonary hypertension, hypoglycemia.

Measures in the newborns section - isolation room (ideal rooming-in), use gloves to any

contact: changing diapers, suction of secretions; food. Vein puncture should be avoided as

much as possible given the risk of infection and the risk for the staff. Artificial nutrition

formula is recommended for mature infants; for prematures, special formulas (hypercaloric),

administered by continous or intermittent gavage, avoiding parenteral nutrition as much as

possible.

Communication with infectious diseases hospital

It is recommended that laboratory tests regarding existence of HIV infection should take

place in the infectious diseases clinics. The clinic should be informed about the existence of

HIV positive newborn form HIV positive mother; it should establish the ARV prophylaxis

and follow up the child after discharge.

Evolution, prognosis

Severe development invariably developing into AIDS and death.

The prognosis of life expectancy, as well as assessing the treatment effectiveness depends

mainly on the degree of the viral load.

68

References

1. Bopanna SB, Rivera LB, Fowler KB, et al. Intrauterine transmission of cytomegalovirus to infants of women with

preconceptual immunity. N Engl J Med 2001;344(18):1366-1371.

2. Cooper ER, Charurat M, Mofenson L, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1-

infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 2002;29(5):484-494.

3. Benjamin DK, Stoll BJ, Fanaroff AA, et al. Neonatal candidiasis among extremely low birth weight infants: Risk

factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 2006;117(1):84-92.

4. Hyde TB, Hilger TM, Reingold A, et al. Trends in incidence and antimicrobial resistance of early-onset sepsis:

Population-based surveillance in San Francisco and Atlanta. Pediatrics 2002;110(4):690-695.

5. Kliegman RM., Stanton B, St. Geme J, Schor N, Behrman RE. Nelson Textbook of Pediatrics, 19th Edition, 2011

6. John P. Cloherty (Editor), Ann R., Md. Stark (Editor), Ann R. Stark (Editor). Manual of Neonatal Care. 6th Edition,

2008 Lippincott Williams & Wilkins

7. Boucher CA, Coll O, Hernandez M, et al. Vertical HIV-1 transmission correlates with a high maternal viral load at

delivery. J Acquir Immune Defic Syndr Human Retrovirol 1997;14:26-30.

8. Daffos F., Forestier F., Capella Pavloski M., et al. Prenatal management of 746 pregnancies at risk for congenital

toxoplasmosis. N Engl J Med 1988; 318: 271-275.

9. Newell ML. Mechanisms and timing of mother-to-child transmission of HIV-1. AIDS 1998;12:831-837

10. Newell ML, Gray G, Bryson YJ. Prevention of mother-to-child transmission of HIV-1 infection. AIDS 1997;11 (suppl

A): S165-172

11. Njenga S, Ombree JE, Ndinya-Achola, et al. Risk factors for postnatal mother-to-child transmission of HIV in Nairobi.

Conference on Global Strategies for Prevention of HIV Transmission from Mothers to Infants, September 1997,

Washington DC

69

CHAPTER II - RESPIRATORY PATHOLOGY

Conf. Dr. Oana Mărginean, Șef lucr. Dr. Borka Balas Reka

UPPER AIRWAY INFECTIONS IN CHILDREN

ACUTE RHINOPHARYNGITIS

Definition: acute rhinopharyngitis (Rf) is an acute inflammation of the nasal and pharyngeal

mucosa, specific for infants and young children. (Up to the age of 2 years, upper airway

mucosa is immature and an inflammatory process at this level includes not only the throat

and nasal mucosa, but also the paranasal sinuses and the middle ear).

Etiology: can be viral or caused by mycoplasma. More common are mixoviruses (RSV -

respiratory syncytial virus - influenza, parainfluenza), adenoviruses, rhinoviruses and

enteroviruses (Coxsakie A and B).

Predisposing factors:

- Cold and damp, dry air, pollution

- Young age - under 2 years

- Rickets, anemia, malnutrition

Symptoms and diagnosis:

After a short incubation of 48-72 hours the onset is sudden, often with fever over 38 °C,

malaise, capricious appetite and sleep disturbances.

During the acute phase the primary symptoms are nasal obstruction and rhinorrhea, leading

to difficulty in breathing and feeding. After a day of fever and nasal obstruction rhinorrhea

occurs, initially watery, than in 2-3 days becomes opalescent, viscous and sticky. (If the

secretion is purulent or with bloody streaks probably bacterial superinfection occurred).

Secretions can erode the skin or cause coughing and vomiting.

Physical examination: hyperemia of pillars, tonsils and oropharynx, sometimes, with

secretions on the posterior wall of the pharynx.

Laboratory diagnosis is not helpful for the diagnosis (in common practice viral cultures are

not performed).

Differential diagnosis:

- At the onset: with meningitis, especially when seizures occur in addition to fever, or

meningism is present.

70

- During acute phase: with rhinorrhea "a frigore", "secondary" rhinopharyngitis at the

onset of infectious diseases (measles, whooping cough, mumps, mononucleosis, etc.),

sinusitis, nasal foreign body and allergic rhinitis.

Complications:

- Adenoiditis, ethmoiditis, otomastoiditis

- Laringotraheobronchitis, bronchiolitis, pneumonia

- Albuminuria, hematuria

- Diarrhea, dehydration syndrome (due to fever, lack of intake and vomiting)

- Febrile seizures, meningoencephalitis

Healing occurs in 3-4 days (unless bacterial superinfection occurs).

Treatment:

Prophylactic treatment consists of:

- Judicious use of all factors of hardening the body

- Avoiding crowded places and contact with sick people

- Correct triage of children (and attendent) in the communities (nursery, kindergarten).

Curative treatment:

General measures:

- Well ventilated room with constant temperature (l8 -20 °C), humidity (60%)

- Avoiding overheating but without giving up the air cure and daily bath

- In general normal feeding, with more liquids (water, soup, etc.). If feeding difficulty

occurs, fragmented or less frequent meals can be given (gavage is rarely necessary).

Symptomatic treatment:

Fever is treated with antipyretic agents, Paracetamol (Acetaminophen) 50 mg/kg/day PO

from 4 to 4 hours or 125 mg or 250 mg supp. as follows: less than 6 months - 3 x ½ sup. 125

mg/day; 1-3 years - 3 x 1 sup. 125 mg/day; 3-7 years - 2-3 x 1 sup. 250 mg/day.

Nasal obstruction is treated with nasal decongestants and vasoconstrictors. For drainage of

watery secretions the child can be placed in ventral position for 15-20 minutes, especially

before meals. Saline intranasal solution are is used for decongestion followed by aspiration of

the secretion with a vacuum pump.

Topic vasocontrictor solutions: 0.5 % ephedrine or epinephrine 1:20000 (1f 1% epinephrine +

2 f saline solution) for 6 x 2-3 drops/day in each nostril (usually before meals and at

bedtime). Nasal decongestants such xylometazoline, oxymetazoline, phenylephrine are not

approved/suitable for children under the age of 2 years old.

71

Nafazolin (Rinofug) or oil and menthol containing products are not prescribed in infants and

small children. Silver containing disinfectants (0.5 % colargol or 0.5% argirol) can be used 2-

3 x 2-3 drops/day in serous rhinorrhea, but not more than 5 days (they can cause chemical

rhinitis). Skin erosions require protection with creams and ointments (Cutaden, Tetracycline

etc.).

Antibiotic treatment is necessary only if recovery did not occurred occur in 3-4 days (fever,

malaise amended). In preterm, malnourished and disabled (eg. cheilognatopalatoscizis)

infants antibiotic therapy will be introduced from the beginning of the treatment because

superinfection is a rule in these patients. The used antibiotics could be: Amoxicillin susp. 40

mg/kg/day p.o. in 4 doses or Ampicillin susp. 100-200 mg/kg/day PO. or IV. in 4 doses over

a period of 3-5 days. If the clinical evolution after 3-5 days of proper therapy is not favorable,

it is mandatory to carry out an otological examination, a chest x-ray and urinalysis.

ACUTE PHARYNGITIS (acute tonsillitis, acute angina)

Definition: Acute angina/Acute pharyngitis is an inflammatory process in the mucosa of the

pharynx and/or tonsils.

Etiology:

- the most frequent: viruses (adenoviruses, coronaviruses, enteroviruses, rhinoviruses, RSV

respiratory syncytial virus, Epstein-Barr virus - EBV, herpes viruses)

- Group A beta-hemolytic streptococcus (GABHS)

- other agents such as: Streptococcus Group C, Mycoplasma pneumoniae, fusobacterium

ACUTE STREPTOCOCCAL PHARYNGITIS

Epidemiology: Streptococcal pharyngitis produces 37 % of cases of acute pharyngitis in

children older than 5 years. It is uncommon before 2-3 years of age; it has a peak incidence in

the early school years, then it declines in teenagers. It is most common in winter and spring.

The spread of infection is during the acute phase. Symptoms disappear in 24 hours after

starting the antibiotic therapy.

Etiology: Group A beta -hemolytic streptococcus (GABHS)

Clinical manifestations (signs and symptoms)

The onset of streptococcal pharyngitis is rapid with "sore throat" (dysphagia ) and fever in

absence of cough. The incubation period is 2-5 days.

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During acute phase, children present:

- intense erythema of the pharynx (soft palate, palatine tonsils, posterior pharyngx), the

tonsils are enlarged, covered with pus, false membranes, blood-tinged exudates, petechiae

of the soft palate, the uvula may be swollen and red.

- some patients may have headache, myalgia, malaise, depending on etiology

- some children may have scarlatiniform fever, with circumoral pallor, strawberry tongue,

fine maculopapular rash.

- often the anterior cervical lymphnodes are enlarged and painful.

Laboratory testing:

- throat culture, rapid diagnostic test (Rapid diagnostic test - RADT) for GABHS

(carbohydrate antigen test)

- complete blood cell count, acute phase reactants

- ASLO titer is not indicated because it will increase after healing.

Diagnosis

- The throat culture is an imperfect gold standard for diagnosis because false-positive

cultures can occur in children who are GABHS carriers of

- RADT test has a high specificity for GABHS, so if the rapid test is positive, throat culture

is not performed and antibiotic therapy is indicated. If the test is negative, the throat

culture should be done to confirm infection (false negative reactions may exist).

- C- reactive protein is positive if the infection is authentic.

The differential diagnosis includes other acute pharyngitis (with other streptococci,

diphtheria, anaerobs).

Complications of GABHS infection are suppurative and nonsuppurative.

- suppurative complications (infection spread to underlying tissues): cervical

lymphadenitis, peritonsillar abscessus, retrofaringeal abscessus, otitis media, mastoiditis,

sinusitis.

- nonsuppurative complications: acute rheumatic fever, Sydenham's chorea, reactive

arthritis, acute diffuse posstreptococcal glomerulonephritis

Treatment:

1. Antibiotic therapy: Although most streptococcal pharyngitis are resolved without

treatment, antibiotic therapy leads to the disappearance of symptoms in 12 to 24 hours after

initiation and prevents acute rheumatic fever.

Antibiotic treatment is recommended to be initiated immediately in:

- children with symptomatic streptococcal pharyngitis and positive RADT

73

- scarlet fever

- household contact with documented GABHS pharyngitis

- positive past personal history of rheumatic fever or recent history of rheumatic fever

of a family member.

Although multiple antimicrobial agents are effective in GABHS infection, most authors and

guidelines recommend initial treatment with penicillin. The most used antibiotics are:

- Penicillin V (Phenoxymethylpenicilina): 250 mg/dose in children < 27 kg and 500

mg/dose for children > 27 kg in 2 or 3 divided doses for 10 days

- Amoxicillin 50 mg/kg/day in 2 doses, max. 1 g/day 10 days

- Benzathine penicillin (Moldamin): single dose of 600.000 IU i.m. in children < 27 kg

or under 12 years and 1.2 million IU in older children, provides adequate blood

concentration for 10 days

- In case of penicillin allergy:

» Erythromycin 20-40 mg/kg/day in 2-3-4 dose/day

» Azytromicin 12 mg/kg/day 5 days (max 500 mg/day)

» Clarithromycin 15 mg/kg/day in 2 doses/day, 10 days

» Clindamycin 20 mg/kg/day in three doses/day, 10 days

» Cefalorphorins as Cephalexin, Cephadroxil are indicated in case of resistance to

treatment with penicillin.

Follow up throat cultures are not recommended unless symptoms reappear.

Healthy carriers of GABHS involve little risk to their contacts. If necessary, streptococcal

carriers will be treated with clindamycin 20 mg/kg/day in 3 doses 10 days or Cefadroxil 30

mg/kg/day 10 days. 5

2. Symptomatic treatment

- antipyretic and analgesic treatment with Acetaminophen or Ibuprofen

- gargle with salty water, local anesthetic spray

- tablets containing benzocaine, menthol and phenol can relieve local pain.

3. Prophylactic treatment: multivalent streptococcal vaccine. Prophylactic antibiotic

treatment is recommended only to prevent recurrences of rheumatic fever.

Recurrent GABHS pharyngitis

Recurrent streptococcal pharyngitis appears in reinfection with GABHS from a family

member, or can be a sore throat due to another cause in a GABHS carrier. Diagnosis is

established by repeated throat cultures.

74

Treatment is performed with Clindamycin 20-30 mg/kg/day 10 days or

Amoxicillin/clavulanate 40-50 mg/kg/day 10 days or Cefuroxime 20 mg/kg/day PO for 10

days

Tonsillectomy is indicated in order to reduce the incidence of recurrent pharyngitis if the

child had more then seven episodes in the previous year or five in each of the preceding 2

years, in case of peritonsillar abscessus, hypertrophy of the tonsils with significant respiratory

distress, obstructive sleep apnea.

REFERENCES

1. Regoli M, Chiappini E, Bonsignori F, Galli L, de Martino M. Update on the management of acute pharyngitis in

children. Italian Journal of Pediatrics 2011,37:10. http://www.ijponline.net/content/37/1/10

2. http://www.refbooks.msf.org/MSF_Docs/En/Clinical_Guide/CG_en.pdf

3. Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, Martin JM, Van Beneden C. Clinical

Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the

Infectious Diseases Society of America. Clinical Infectious Diseases Advance Access published September 9, 2012

4. Hayden GF, Turner RB. Cap. 373 Acute pharingitis In: Behrman R, Kliegman R, Nelson Waldo, et all eds. Nelson

Textbook of Pediatrics, XIXth ed., Philadelphia, W.B. Sauders Co., 2011

5. Man SC, Nanulescu MV. Pediatrie practică. Cluj Napoca, Risoprint 2006:70-82

ACUTE OTITIS AND OTOMASTOIDITIS

Definition - an inflammatory process of the lining of the middle ear, with a viral or bacterial

cause, which appears consequently, most of the time, after an upper respiratory tract

infection.

Terminology

Acute otitis media (AOM) or suppurative - refers to acute bacterial infection of the middle

ear

Otitis media with effusion (OME) or serous, secretory, or nonsuppurative refers to the fluid

in the uninfected middle ear. OME often precedes the development of AOM or appears

during the healing phase.

I. Epidemiology

Otitis media is the most common bacterial disease in children, with maximum incidence

between 1 and 2 years old children.

II. Etiology

a. Bacterial ( 2/3 of the cases)

- Streptococcus pneumonie (40% of all cases of bacterial otitis)

75

- Nontypeable Haemophilus influenzae (25-30% of cases of acute otitis media)

- Moraxella catarrhalis (in 10-15% of cases)

- Other germs: Streptococcus pyogenes group A, Staphylococcus aureus, Pseudomonas

aeruginosa, Enterobacter cloacae, Mycoplasma pneumonia, etc..

b. Viral: 5-15% of cases; respiratory syncytial virus, parainfluenzae viruses,

adenoviruses and Coxackie viruses

Risk factors with a role in the occurrence of AOM are:

- prematurity, low birth weight - low age

- early onset - positive family history

- abnormalities of the immune system - craniofacial malformations

- Race - Americans, Indigenous Australians Eskimos - allergies

- neuromuscular diseases - nurseries, agglomerations

IV. Clinical manifestations and diagnosis of various clinical forms

The disease usually occurs during the development of upper airway infection that lasts a few

days.

Thus, in the newborn, infant, symptoms are nonspecific, ear pain is manifested by irritability,

agitation, crying, food refusal, change of appetite and sleep; occasionally the child places his

hand on the ear or rubbs his head on the pillow. Sometimes general symptoms are associated:

vomiting, diarrhea or toxic condition, meningeal signs, seizures. The Vacher maneuver

(compression of the tragus) is painful, but the sign is only indicative.

In older children: fever, ear pain and hearing loss.

Ear pain without fever and hearing loss occurs in older children with otitis externa, or those

with dental abscess, temporomandibular joint disorders.

Any infant or young child with fever, without an obvious infectious outbreak, must be

examined for middle ear infection.

Clinical forms

1. Catarrhal otitis media (serous, congestive otitis) is the result of a physical process

secondary to the Eustachian tube obstruction and the negative pressure of the middle ear

which is objectified by the existence of a serous and sterile transudate in the middle ear.

Usually, obstructive catarrh is the result of the inflammation of the rhinopharynx.

The catarrh produces a sensation of pressure in the ear, hearing loss and noise (crackling) in

the ear during swallowing (deglutition) or jaw movements. The baby is agitated because of

the earache. He has a sensation of fullness, pressure in the ear. The existence of the third

relapse within a period of 6 months defines recurrent otitis.

76

2. Suppurative otitis media. The main symptom is otalgia: it is violent, throbbing and

exacerbated by swallowing. The child puts his hand to his ear and screams, places the

affected ear on the pillow, because the heat of the pillow soothes the pain. Deafness, ear noise

and general symptoms may appear, such as: high fever, malaise, vomiting, diarrhea and

sometimes meningism, seizures.

Together with eardrum perforation, the pain diminishes and the fever drops, otorrhea

occuring as the main symptom (which initially is bloody, and then becomes purulent). Often,

it is confused with the resulting liquid after washing the ear. Otoscopic examination reveals

the changes of the eardrum (edematous) or highlights perforation, and tympanometry shows

the immobility of the eardrum. Tympanocentesis performed in newborns in severe forms,

those that do not respond to antibiotic treatment, confirms the diagnosis even in complicated

forms. Typically, there is a hyperleukocytosis

3. Otomastoiditis in infants. Different anatomical conformation and special reactivity of the

infant’s ear cause, at this particular age, the affection of the entire otomastoidian apparatus

simultaneously, and repercussions on the body are more severe.

Otomastoiditis in infants has two forms:

The manifest form occurs in eutrophic infants who have not previously been treated with

antibiotics.

Onset is sudden with high fever, ear symptoms and general intense symptoms (agitation,

sometimes seizures), meningism, diarrhea, vomiting. After eardrum perforation, symptoms

fail and often healing may be spontaneous. Sometimes symptoms do not yield, which

indicates the existence of an antritis which continues to evolve.

Latent otomastoiditis (latent otitis, latent antritis) mostly occurs in malnourished, premature

children with immune deficiencies and other disabilities, or in eutrophics undergoing

inappropriate antibiotic treatment which could not heal them, only masked the symptoms.

The onset is insidious, about 2-3 weeks after a nasopharyngeal infection; presenting with the

symptoms of a general illness: fever (some without fever), toxic facies, pallor, malaise,

agitation or sleepiness, torpor, diarrhea, vomiting and signs of dehydration. This neuro-toxic

syndrome with nervous, digestive and dehydration symptoms contrasts with the few objective

symptoms of otitis (they must be "sought" carefully and repeatedly).

4. Subacute and chronic otitis media. The persistence of negative pressure and sterile

transudation after acute otitis media for a period of 4-8 weeks defines subacute otitis. The

persistence of these conditions over 8 week define chronic otitis.

77

Diagnosis is made by ENT (ORL) examination which at the otoscopic examination shows

thickened, immobile tympanic membrane and indicates the presence of fluid in the middle the

ear. Tympanometry always shows the involvement of the eardrum mobility. In children over

3 years old audiometry can be tried, which highlights hearing loss. Extension of Eustachian

tube dysfunction can lead to the formation of a cholesteatoma.

V. Accurate diagnosis is determined by ENT examination

Investigations

1. Otoscopy: the eardrum intensely congested, eardrum which bulges, sometimes opaque or

perforated, with pus; luminous reflection of the eardrum- diminished or absent

2. Tympanometry: to confirm the diagnosis in some cases

- to follow the development of acute otitis media (facilitates the differentiation between the

quickly and completely healed OMA from OM in which the exudate persists, even

asymptomatically, situation in which the patient must be re-examined)

VI. The differential diagnosis of otitis is done with:

- acute nasopharyngitis, acute adenoiditis, meningo-encephalitis;

- dental pain, temporomandibular joint disorder, ear trauma

Complications: can be classified as:

Intratemporal: tympanic membrane perforation, facial nerve paralysis, acute labyrinthitis,

mastoiditis, chronic otitis media, cholesteatoma, otomastoiditis, chronic suppurative otitis

media, etc.

Intracranial: Meningitis, encephalitis, brain abscess, subdural or supradural abscess,

thrombosis or thrombophlebitis of lateral and sigmoid sinus, hydrocephalus

Systemic: Bacteremia/ septicemia, septic arthritis, parenteral diarrhea

Treatment of otitis

a. In catarrhal otitis media pain painkillers may be recommended (Paracetamol; Ibuprofem),

but not chemotherapy or antibiotics (do not have any proven effect).

b. In suppurative otitis media Amoxicillin is the first choice if the patient received no

Amoxicillin in the last 30 days, if he does not simultaneously associate purulent

conjunctivitis and he is not allergic to penicillin.

In children who received Amoxicillin treatment in the last 30 days, or in which H influenzae

and M catarrahalis B lactamazo + has to be treated, a treatment with Amoxicillin/ clavulanate

will be initiated.

As an alternative: Cefuroxime, Ceftriaxone can be used as well (table 10).

78

Table 10. Antibiotic treatment of AOM with antibiotics in patients with initial treatment

with antibiotics or who evolved unfavorably with symptomatic treatment only during the

first 48-72 hours

Fever > 39C and / or severe ear pain

NO YES

At diagnosis for patients

initially treated with ATB

Amoxicillin 80-90 mg/ kg/

day

Amoxicillin-clavulanate: 90

mg/ kg/ day (amoxicillin)

with 6.4 mg/ kg/ day of

clavulanate

Penicillin allergy: Cefdinir,

cefuroxime, cefpodoxime,

azithromycin, clarithromycin

Penicillin allergy:

Ceftriaxone for 3 days

Unfavorable outcome of

patients only after 48-72

hours of observation

Amoxicillin Amoxicillin-clavulanate

Penicillin allergy: Cefdinir,

cefuroxime, cefpodoxime,

azithromycin, clarithromycin

Penicillin allergy:

Ceftriaxone 1 or 3 days

Unfavorable outcome after

48-72 hours in patients with

initial antibiotic treatment

Amoxicillin Amoxicillin-clavulanat

Penicillin allergy:

Ceftriaxone Ceftriaxone for 3

days; Clindamycin ±

cephalosporin type 3

Penicillin allergy:

In case of failure at the

second antibiotic:

Clindamycin + cephalosporin

type 3

tympanocentesis

ENT re -evaluation

New data show that approximately 83-87% of S. pneumonia isolates are susceptible to 80-90

mg/kg/zi doses of Amoxicillin.

In case of poor outcome under treatment with Amoxicillin tympanocentesis, ENT re-

examination and initiation of treatment with Clindamycin ± will be indicated in order to have

an effect on nontypeable h influenzae and M catarrhalis, such as: Cefdinir, cefixime or

cefuroxime. In proven cases of multidrug-resistant S pneumonia (serotype 19A) including

Clindaicina levofloxacin or linezolid may be used.

Duration of treatment

79

- In children <2 years old and those with severe symptoms: 10 days

- Children 2-5 years old with mild / moderate symptoms of AOM: 7 days

- Children 6 years old with mild / moderate symptoms of AOM: 5-7 days

3. In otomastoiditis in infants the germs which are frequently incriminated are: S pneumonia

and nontypeable H influenzae; while Pseudomonas aeruginosa occurs more frequently in

cases of chronic suppurative otitis media. Broad spectrum iv antibiotic treatment will be

initiated and mastoidectomy will be performed. Depending on the outcome of cultures

antibiotic treatment is continued (preferably "aimed") for 10 days.

4. In subacute and chronic otitis media middle ear ventilation is tried to be improved by

teaching the child to practice the Valsalva's maneuver or a balloon inflation (decongestants,

antihistamines and adenoidectomy have not proved to be effective).

The presence of secretions in the middle ear for more than 12 weeks shows timpanotomia,

with the insertion of a ventilation tube (especially if hearing is affected).

Prophylaxis: The prevention of otitis is complex, characterized by teaching the child to blow

his nose (only one nostril at a time), treating rhino pharyngeal infections correctly and

fighting against multiple factors favoring otitis, vaccination against Streptococcus

pneumoniae and H. influenzae, two of the most common germs involved in the occurrence of

otitis

Bibliography:

1. Muntean I., Mărginean O. Infecții ale căilor respiratorii superioare în Pediatria Tratat, sub redacția Eugen Ciofu și

Carmen Ciofu, ediția 1, Ed Medicală, 2001 , 206-220 (Upper respiratory tract infections in Tediatrics Treaty,

edited by Eugen Ciofu și Carmen Ciofu, 1 edition, Medical Publishing, 2001 , 206-220)

2. Ciofu E, Ciofu C. Penumologie în Esențialul în pediatrie, ediția a 2-a, Ed Medicală Amaltea 2002, 166-256

(Pneumology in The Essential in Pediatrics)

3. Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, et al. The diagnosis and

management of acute otitis media. Pediatrics. 2013 Mar;131(3):e964-99. doi: 10.1542/peds.2012-3488. Epub 2013 Feb

25

4. Kerschner JE. Otitis media in Nelson Textbook of Pediatrics, 19th Edition, Ed Sunders Elsevier, 2007, chapter 632,

2199-2213

5. Falup-Pecurariu O, Bleotu L, Zavarache C, Peled N, Anton O, Robu M, et al. Streptococcus pneumoniae

nasopharyngeal colonization in children in Brasov, Central Romania: high antibiotic resistance and coverage by

conjugate vaccines. Pediatr Infect Dis J. 2011 Jan;30(1):76-8. doi: 10.1097/INF.0b013e3181f42bb6.

6. Falup-Pecurariu O, Leibovitz E, Mercas A, Bleotu L, Zavarache C, Porat N, et al. Pneumococcal acute otitis

media in infants and children in central Romania, 2009-2011: microbiological characteristics and potential coverage by

pneumococcal conjugate vaccines. Int J Infect Dis. 2013 Mar 19. pii: S1201-9712(13)00082-9. doi:

10.1016/j.ijid.2013.02.002.

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7. Leibovitz E, Piglansky L, Raiz S, Press J, Leiberman A, Dagan R. Bacteriologic and clinical efficacy of one day vs.

three day intramuscular ceftriaxone for treatment of nonresponsive acute otitis media in children. Pediatr Infect Dis J.

2000 Nov;19(11):1040-5.

ACUTE LARYNGITIS

Definition: Acute laryngitis is a viral or bacterial infection of the laryngeal mucosa which

can cause distress and / or respiratory failure by laryngeal obstruction.

Classification:

- without respiratory distress - simple acute laryngitis

- with respiratory distress (obstructive laryngitis):

» acute spasmodic laryngitis (stridulous),

» edematous acute laryngitis: subglottis (acute laryngotreheobronchitis),

supraglottic (epiglottitis)

Epidemiology: age of occurrence of acute laryngitis, especially children between 3 months

to 5 years, with a peak at the age of 2.

Etiology

The etiology of most viral laryngitis is of viral origin: influenza viruses, parainfluenza,

adenovirus, respiratory syncytial virus (RSV), measles virus.

Bacterial etiology is rare and is represented by Haemophilus influenzae (common in the past

in epiglottis, rarely now after HiB vaccine introduction), Streptococcus pyogenes,

Streptococcus pneumoniae, Staphylococus aureus. 2,5,10

Clinical forms

I. Simple acute laryngitis (mild clinical form)

Etiology: viral.

Clinical manifestations:

Onset is by acute upper respiratory tract infection (AURTI) with dysphagia, hoarseness,

cough; dyspnea and stridor are missing or are very discrete.

On examination there was only a pharyngeal inflammation, and laryngoscopy may reveal

swelling of the vocal cords and subglottis tissue.

The evolution is benign.

II. Obstructive laryngitis

They are clinically characterized by:

- acute inspiratory stridor - barking cough or with a metallic sound;

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- dysphonia (hoarseness) - inspiratory dyspnoea;

- suprasternal and supraclavicular drafts

II.1. Stridulous laryngitis or spasmodic croup (pseudocroup)

Etiology: virus in some cases, but allergic and psychological factors play an important role,

the pathogenesis is uncertain.

Occurance: age 1-3 years, children with paratrophy or adenoids.

The viral prodrome may be present (acute nasopharyngitis, acute tracheobronchitis).

Clinical manifestations:

The onset is acute, it usually occurs at night, and is preceded by a crisis and hoarseness.

Children will suddenly wake up from sleep and present hoarseness, cough, breathlessness,

respiratory distress, anxiety. The severity of the symptoms is reduced in a few hours. The

child may present some attacks, which will become lighter in the next 1-2 days.

Spasmodic croup treatment is done at home.

Although in the past it was thought that placing the child in the cold night air would improve

spasmodic croup, a Cochrane review has not shown its benefits, on the contrary, the croup

and wheezing worsen in the cold night air.

If the child is in hospital, a nebuliser will be made with racemic epinephrine. 10

II.2. The croup (Edematous subglottis acute laryngitis, acute laryngotracheobronchitis)

Acute laryngotracheobronchitis is an acute inflammatory process where the edema includes

subglottis regions.

Etiology: viral.

Occurance: children aged between 6 months - 3 years.

Clinical manifestations:

The Prodrome is by AURTI with running nose, sore throat, cough, not very high fever by 1-3

days before the onset of obstructive symptoms.

Symptoms of laryngitis are installed progressively, respiratory distress manifesting in 2-3

days. The child has: barking cough, hoarseness, inspiratory stridor, suprasternal and

supraclavicular draft, fever (39-40° C). Symptoms worsen at night, fade in a few days and the

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child cures in a week. Children prefer to stay in bed or slightly raised, they are nervous. Their

general condition is quite good.

Physical examination shows hoarse voice, coryza, inflammation of the throat, mild

tachypnea, rarely nasal wings beat, suprasternal, infrasternal drafts and rib retractions,

continuous stridor hypoxia, cyanosis, pallor. Sometimes severe laryngotracheobronchitis

hardly differs from epiglottis, the latter having an acute onset and a more rapid development.

Paraclinical investigations:

Latero-cervical radiography - indicates narrowing subglottis, labeled "Gothic tower" (the

previous posterior view).

The differential diagnosis of laryngotracheobronchitis is done with: diphtheria, foreign body,

retropharyngeal abscess, angioedema, asthma attack, laryngospasm of tetany, trauma, tumors

or malformations of the larynx, measles and whooping cough.

Complications: otitis media, bronchiolitis, pneumonia, and even more rarely pneumothorax

and mediastinal or subcutaneous emphysema, bacterial tracheitis and toxic shock.

Treatment

a). Most forms of croup are mild so they can be treated at home where a humid atmosphere in

a clean, well-ventilated room is assured

b). In other forms the child’s admission to hospital is ensured and a treatment is given, which

includes:

- ensuring a humid atmosphere and hydration of the child, and, if necessary, even the

administration of O2; 2

- aerosol with classic racemic epinephrine dose: 0,25-0,5 ml racemic epinephrine solution

2,25% - 0,5 ml in 3 ml of normal saline solution, may be repeated every 20 minutes. The

effect of racemic epinephrine is less than 2 hours. Administration of corticosteroids reduces

laryngeal mucosal edema, having an anti-inflammatory effect. Dexamethasone may be

administered IM dose 0.3-0.6 mg/kg/24 hours. Prednisone 2-4 mg/ kg/ hour can be

administered as well;

- intubation, for 2-3 days, may be needed in severe forms of respiratory failure; after

extubation, the child will be observed 1-2 days;

- no antibiotics are administered;

- admission to hospital is recommended in case of progressive stridor, stridor at rest,

espiratory distress, hypoxia, cyanosis, impaired consciousness;

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- racemic adrenaline and Dexamethasone 0.5 mg / kg / dose every 6 hours are useful in the

treatment of croup associated with extubation.

-

II.3. EPIGLOTTITIS (supraglottitis)

Epiglottitis referred to as supraglottitis, is an inflammatory, acute edema of the epiglottis and

hypo-pharynx. Basically, it is a rapidly progressive bacterial cell, that comprises the region

above the vocal cords, leading to the total obstruction of the airways (this is why it is

considered a medical emergency!).

Etiology. Haemophilus influenzae type B. It is rare, it occurs at any age and it is more

common between the ages of 1-6.

Clinical manifestations:

Onset is sudden, with fever, wheezing, sore throat (dysphagia), shortness of breath, with the

rapid occurance of respiratory obstruction.

The symptomatic progression is so fast, that in a few hours the patient becomes toxic, and

shows difficulties in swallowing and breathing.

During the onset period the child has high fever, malaise (lethargy) and a toxic appearance.

The baby's head is in hyperextension (without any signs of meningeal irritation), and the

child is leaning on his hands with the neck extended and his mouth open while his tongue is

out (the ”tripod position”). He may present inspiratory stridor (spiratory dyspnea with rough,

noisy breathing), associated with more pronounced forms of obstruction, with over- and

substernal draft, supra clavicular and intercostal), cough or hoarseness (hoarseness, muffled

voice; it seems that "it comes from far away”), dysphagia and agitation. Due to the

obstruction, on auscultation, the vesicular murmur is diminished.

Diagnosis: Local examination of the pharynx with the laryngoscope shows a red edematous

epiglottis on the base of the tongue, impaired vocal cord. Examination with a spatula,

laryngoscopy will be performed in a specialized service, because at the hypoxic child,

manipulation in the pharynx, including the use of a tongue depressor can produce a vagal

reflex with possible cardiac arrest.

Paraclinical investigations:

Throat radiography, in lateral incidence, well delimits the epiglottis and the aretino

epiglottis areas (“thumb” sign). The examination will be performed in appropriate conditions,

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with the necessary equipment to perform the required intubation or tracheostomy. Intubation

is maintained for 2-3 days until the disease responds to the antibiotic treatment.

Laboratory investigation shows a leukocytosis of 15-25000/mm3, with a marked neutrophilia.

Bacteremia is present in over 90% of cases.

Complications: pneumonia, cervical lymphadenitis, otitis media, meningitis, septic arthritis,

mediastinal emphysema and pneumothorax (after tracheotomy)

Differential diagnosis:

1. Bacterial tracheitis determined by Staphylococcus aureus, Moraxella catarrhalis,

Corinebacterium diphtheriae, H. influenzae or anaerobic is the most important condition with

which the differential diagnosis is made as it has an increased risk of acute airway

obstruction. It requires tracheostomy, intubation and antibiotic treatment (Vancomycin,

Naficilin, Oxacillin, etc.), plus oxygentherapy.

2. Foreign body aspiration that occurs in young children and is manifested by attacks of

choking, coughing, diaphragm balance.

3. Retrofaringean or peritonsillar abscess can mimic respiratory obstruction.

4. Extrinsic compressions on the airways given by a vascular ring or intrinsic (faryngeal

papilloma, subglottic hemangioma).

5. Angioedema – after anaphylactic reactions, edema after oro-tracheal intubation, tetany,

infectious mononucleosis.

Treatment of epiglottitis

Epiglottitis is a medical emergency and the child should be admitted to the intensive care

unit.

1). It is advisable – that in severe cases – the initial treatment include nasal tracheal

intubation to prevent sudden death. Extubation is done after a few days. Intubation in

epiglottitis has greatly reduced mortality, to nearly zero. Intubation is done in an intensive

care unit.

2). Racemic adrenaline and corticosteroids are ineffective.

3). The antibiotic therapy is aimed for H. influenzae and consists of the administration of

Ceftriaxone 100 mg / kg / day in 2 IM / IV doses, Cefotaxime or Meropenem according to the

antibiogram results from cultures as 10-40% of H. influenzae strains are resistant to

Ampicillin. Antibiotic treatment should be continued for 7-10 days after extubation of the

patient.

85

You can also use Ampicillin 200 mg/ kg/ day iv administered in 3-4 doses, or Amoxicillin

100 mg/ kg/ day in 2-3 doses, orally, for 5 days.

4). Prophylaxis with H. influenzae is made to all family members if the sick child is under 4

years old and he is immunized incompletely or he is under 1 year old and did not receive the

primary vaccination or immunocompromised. Prophylaxis is done with Rifampicin 20 mg/ kg

orally in a single dose for 4 days.

Bibliography

6. Regoli M, Chiappini E, Bonsignori F, Galli L, de Martino M. Update on the management of acute pharyngitis in

children. Italian Journal of Pediatrics 2011,37:10. http://www.ijponline.net/content/37/1/10

7. http://www.refbooks.msf.org/MSF_Docs/En/Clinical_Guide/CG_en.pdf

8. Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, Martin JM, Van Beneden C. Clinical

Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the

Infectious Diseases Society of America. Clinical Infectious Diseases Advance Access published September 9, 2012

9. Hayden GF, Turner RB. Cap. 373 Acute pharingitis In: Behrman R, Kliegman R, Nelson Waldo, et all eds. Nelson

Textbook of Pediatrics, XIXth ed., Philadelphia, W.B. Sauders Co., 2011

10. Man SC, Nanulescu MV. Pediatrie practică. Cluj Napoca, Risoprint 2006:70-82

11. Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the

emergency room. Med Decis Making. 1981;1(3):239-46.

12. McIsaac WJ, White D, Tannenbaum D, Low DE: A clinical score to reduce unnecessary antibiotic use in patients

with sore throat. CMAJ 1998,158(1):75-83.

13. Muntean I., Mărginean O. Infecții ale căilor respiratorii superioare în Pediatria Tratat, sub redacția Eugen Ciofu și

Carmen Ciofu, ediția 1, Ed Medicală, 2001 , 206-220

14. Sun J, Keh-Gong W, Hwang B. Evaluation of the etiologic agents for acute suppurative tonsillitis in children.

Zhonghua Yi Xue Za Zhi (Taipei). 2002;65(5):212-7.

15. Roosevelt GE. Infections Upper Airway. In: Behrman R, Kliegman R, Nelson Waldo, et all eds. Nelson Textbook of

Pediatrics, XIXth ed., Philadelphia, W.B. Sauders Co., 2011

16. Sittel Ch, Koitschev A. Erkrankungen des HNO-Bereichs. In Gortner L, Meyer S, Sitzmann FC. Padiatrie, 4 Auflage,

Dual Reihe 2012:816-18

17. Moore M, Little P. Withdrawn: Humidified air inhalation for treating croup. Cochrane Database Syst Rev. 2011 Jun

15;(6):CD002870. doi: 10.1002/14651858.CD002870.pub3.

ACUTE BRONCHIOLITIS (AB)

Definition: Acute bronchiolitis is a severe inflammation of bronchioles usually due to a viral

infection leading to bronchiolar obstruction.

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Etiology: is viral. The most frequently incriminated is the respiratory syncytial virus (RSV -

up to 80 % of the cases), followed by parainfluenza virus (type 1,3), metapneumovirus, adeno

- and rhinovirus.

Epidemiology: AB occurs most frequently in infants and small children under 2 years of age,

in the cold season (October - March), in small epidemics, more often in boys and in infants of

those young mothers who smoked during pregnancy.

Clinical manifestations:

Symptoms: After a prodrome of 1-2 days with clear rhinorrhea and sneezing, wheezing occurs

with a paroxysmal dry cough, dyspnea, perioral cyanosis and of extremities, tachypnea,

agitation or drowsiness and anorexia. Fever may range from feverish to high fever (38-40°C).

Physical examination is dominated by wheezing, nasal flaring, retraction at the suprasternal

notch, supraclavicular and intercostal spaces, hyperresonant percussion, prolongation of the

expiratory phase of the breathing, fine crackles. Decreased intensity breath sounds suggest an

imminent acute respiratory failure due to nearly complete bronchiolar obstruction.

Patients may have feeding difficulties and some of them could have neurotoxic syndrome

(diarrhea, vomiting, flatulence, lethargy).

Chest X-ray shows pulmonary hyperinflation manifested by:

- increased anteroposterior diameter of the chest

- descent of the diaphragm

- hyperexpansion of lungs

In some cases atelectatic areas can be identified.

Diagnosis of AB: is clinical. In an apparently healthy infant a first episode of wheezing

appears in the context of viral infection.

Laboratory findings:

- Pulseoximetry - to determine the severity degree

- ASTRUP - in case of acute respiratory failure to determine an uncompensated

respiratory acidosis

- Complete blood count: initially may show slight leukopenia or normal leucocyte

value. In case of bacterial superinfection leukocytosis with high neutrophil count will

occur.

- For etiologic diagnosis viral culture may be done from the nasal secretion.

Differential Diagnosis:

- Pneumonia (viral and bacterial)

- Gastro-esophageal Reflux Disease

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- Asthma bronchiale

- Foreign body aspiration

- Cystic fibrosis

- Whooping Cough

Complications: Acute dehydration, acute respiratory failure, otitis media, pneumonia,

recurrent wheezing episodes (occurs in ¾ of patients admitted in the first 2 years of life).

Evolution: In eutrophic children is good. It is reserved in preterm and those with cardiac

malformation, which typically presents complications. Usually AB improves obviously in the

first 3-4 days and heals in 7-10 days. The cough may last up to 3 weeks.

Treatment:

- Adequate hydration (in those with acute respiratory failure oral liquids are

countraindicated)

- Oxygen (in the hospital, if necessary)

- Bronchodilators (unproven effect) - salbutamol 15 mg/kg/dose every 20 minutes, 3 to

4 doses

- Adrenaline: nebulization through mask, 0.3-0.5 ml/kg/dose (1mg/ml adrenaline sol.

with 2-3 ml of saline solution) 2-3 doses, every 20 minutes

- Corticosteroids (controversial efficacy): used in case of neuro-toxic syndrome

- Antibiotics - should not be used routinely, are given in case of bacterial infection

(fever > 38.5°C for 3 days). Amoxicillin/clavulanate or a cephalosporin is preferred.

- Ribavirin is active on RSV. (Aerosols are recommended for children at high risk, such

as premature infants, and with malformations).

Admission is required if:

- Infant under 6 weeks of age

- Presence of risk factors (prematurity, congenital heart defects, immunosuppression)

- Tachypnea > 60/min

- Progressive worsening with apnea attacks

- O2 saturation < 92 %

Prophylaxis: RSV is contagious. Specific anti - RSV immunoglobulins are administered I.V.

in infants under 6 months of age, premature or with multiple diseases. Hospitalized patients

will be isolated because they spread RSV (even for 1-3 weeks after cure).

88

PNEUMONIA

Definition: pneumonia is an acute inflammation of the parenchyma of the lungs (at alvelolar,

interstitial and sometimes simultaneous bronchial level) caused by bacterial, viral, fungal or

parasitic infections, chemical or physical causes (radiation, barotrauma).

Classification of pneumonia:

- Community-acquired pneumonia

- Pneumonia in immunocompromised patients

- Pneumonia - nosocomial infection

Etiology is depend on age (table 11):

Table 11. Ethiology of Pneumonia

AGE PATHOGENS COMMONLY INVOLVED

Neonates Group B Streptococci, Gram negativ bacilli

2 months - 5 years Viruses, Haemophilus influenzae, Streptococcus pneumoniae

2 months - 5 years Staphylococcus aureus/epidermidis, Enterobacteriaceae

5 - 10 years Viruses, Streptococcus pneumoniae

Over 10 yearsViruses, Mycoplasma pneumoniae, Chlamydia pneumoniae;

Streptococcus pneumoniae, Haemophilus influenzae

PNEUMOCOCCAL PNEUMONIA

Streptococcus pneumoniae (Pneumococcus) can be involved in 13-28 % of pneumonia in

children.

Pneumococcal pneumonia recognizes three main clinical and radiological forms according

classic semiology: lobar pneumonia, segmental pneumonia and lobular pneumonia

(bronchopneumonia), the latter tends to be abandoned in the current terminology of lower

respiratory airway infections.

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A. LOBULAR PNEUMONIA (BRONCHOPNEUMONIA) is the most frequent in infants

and toddlers under 2 years. It is characterized by a bronchoalveolitis of the lung lobe

associated with bronchitis (purulent exudate in the bronchi).

Etiology:

- Determining factor is the pneumococcus (Streptococcus pneumoniae).

- Contributing factors are represented by age and deficit of anti-infective defense

mechanisms of the body (prematurity, dystrophy, rickets, anemia, cleft palate, cystic

fibrosis), immunological dysfunction, infectious diseases (measles, whooping cough,

influenza), unbalanced diet and chronic diseases (heart failure, chronic obstructive

pulmonary disease, diabetes mellitus, etc.).

Clinical manifestations and diagnosis:

Onset: More often is slow, insidious, preceded by several days of symptoms of an upper

respiratory tract infection with rhinorrhea, fever, fatigue or cyanosis during feeding,

tachypnea, cough, possibly vomiting, agitation or drowsiness. Rarely, the onset may be

sudden, with fever of 39-40 °C, respiratory distress, sometimes febrile seizures or

meningism.

Later on the course of the illness occur following syndromes:

- Respiratory distress syndrome

- Cardiovascular syndrome

- Toxico-septic syndrome

a. Respiratory distress syndrome includes:

- Tachypnea - is the most consistent clinical sign, expiratory dyspnea, moan

- Inter - and subcostal retractions, nasal flaring

- Cough - initially dry afterwards wet

- Cyanosis - initially perioral later generalized

Physical findings: dullness on percussion and fine crackles exacerbated by coughing and

crying on auscultation. There may have bronchophony and/or tubal respiration.

b. Cardiovascular syndrome occurs in extensive forms due to:

- Direct action of microorganisms or toxins on the myocardium and vessels

- As a consequence of anoxia, hypercapnia and acidosis

It is characterized by: tachypnea, tachycardia, hepatomegaly, edema, cyanosis and

collapse.

90

c. Toxico-septic syndrome is characterized by fever (most common septic type), pallor,

drowsiness, dizziness or agitation, seizures, flatulence, vomiting and diarrhea, sometimes

kidney irrigation impairment (oliguria, albuminuria, hematuria).

Clinical forms:

Majority of clinical forms occurs only with respiratory signs; there are also "silent" forms

which are accidentally discovered on radiologic exam; and also superacute forms. There are

two particular clinical types:

- One, that mimics acute surgical abdomen due to paralytic ileus with abdominal pain,

vomiting, anorexia and flatulence

- One, pseudomeningeal form with headache, vomiting and signs of meningeal

irritation (which usually requires lumbar puncture).

Diagnosis is based on clinical symptoms (fever, chills, tachypnea, wet cough), radiological

examination (pulmonary consolidation) and laboratory findings (leukocytosis with

predominance of neutrophils, elevated CRP, accelerated ESR).

a. Chest radiography indicates the following forms:

- Paravertebral form (paravertebral opacities) more common in premature, newborn and

dystrophic infants

- Disseminated macronodular

- Disseminated micronodular

- Hilio - basal form

- Pseudo - lobar or segmental form, which can simulate lobar pneumonia

b. Laboratory findings:

- Leukocytosis with elevated neutrophil count

- Positive acute phase reactants: accelerated ESR, positive CRP (> 60 mg/l), high

fibrinogen level, increased alpha2 - globulin

- Positive cultures from sputum, pleural fluid, blood (positive in 30% of cases)

- ASTRUP: assess severity of respiratory failure

Differential diagnosis: acute bronchiolitis, acute laryngitis, pulmonary tuberculosis,

interstitial pneumonia, pleuro - pulmonary staphylococcal infection, pulmonary atelectasis

other etiology lobular pneumonia, foreign body aspiration.

Complications:

- Local: pleurisy, pneumothorax, pyopneumothorax, pulmonary suppuration

- General: diarrhea, dehydration, otomastoiditis, febrile seizures, sepsis

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B. LOBAR PNEUMONIA occurs in children older than 2-3 year of age.

Clinical manifestations and diagnosis:

Onset is sudden with: shaking chill, high fever (39-40 °C), stabbing, headache, vomiting,

herpes labialis. Rarely the onset is pseudoapendicular/pseudomeningeal.

Later on the course of the illness occurs frequent cough, initially dry than wet, tachypnea,

polypnea, tachycardia, mild oliguria with albuminuria, fatigue, impaired general condition.

Auscultation of the chest reveal - the pulmonary consolidation syndrome: dullness,

diminished breath sounds, bronhophony, fine crackles.

After approx. 7-10 days fever drops suddenly, the evolution is good in approx. 3-4 weeks.

Chest radiography:

Pulmonary consolidation - homogeneous opacity, triangular, with base to the periphery and

top to the hilum of the lung, sharply demarcated, with subcostal intensity, localized to an

entire lobe or segment of the lung. Rarely is associated with pleural effusion (fig 27).

Fig . 27 - Right lobar pneumonia

Laboratory findings:

- Leukocytosis with elevated neutrophil count

- Positive acute phase reactants: accelerated ESR, positive CRP (> 60 mg/l), increased

fibrinogen level

92

PNEUMONIA with PULMONARY ABSCESS

Etiology:

- Staphylococcus aureus

- Gram negative microorganisms

- Pneumococcus Type 3 (with thick polysaccharide capsule)

A. STAPHYLOCOCCAL PNEUMONIA (Pleuro-pulmonary staphylococcal infection)

Definition: severe, rapid evolution pneumonia caused by Staphylococcus aureus, transmitted

by inhalation or hematological spread.

Clinical manifestations and diagnosis:

Usually starts suddenly with a toxico - septic syndrome with high fever, pallor, agitation or

drowsiness and digestive signs: marked anorexia, vomiting, diarrhea, flatulence. Respiratory

distress syndrome and heart failure can be installed quickly.

Later on the course of the illness (which can be installed in a few hours or days) four clinico-

radiological stages can be distinguished: interstitial, abcedant, pleuretic and bullous.

a. In the interstitial stage toxico - septic syndrome is prevailing with high fever, mottled

skin, circles round the eyes, perioronasal cyanosis, cold extremities and digestive

symptoms, which are more severe, especially persistent flatulence (sometimes up to

ileus). The child has the appearance of "intoxicated " (key clinical features), lethargic

or agitated. Functional respiratory syndrome is manifested by: tachypnea, expiratory

moan, nasal flaring, dyspnea. Sometimes, cardiovascular syndrome is present with

hypotension and tachycardia. Radiological characteristics: pulmonary interstitial

thickening occurs.

b. Abcedant stage: toxico - septic and respiratory syndrome are more intense.

Radiological characteristics: micro- or macronodular opacities, incompletely

delimitated and confluent corresponding to pulmonary microabcesses. These tend to

confluate and empty as vomica. Physical examination reveals: dullness, bronhophony

and crackles. Radiological characteristics: initially aspect of bronchopneumonia with

confluent micro- and macronodular opacities then air-fluid levels.

c. Pleuretic stage: pleuretic syndrome characterized by: dullness, diminuation of tactil

fremitus, decreased breath sounds, decreased respiratory excursions on the affected

93

side. Radiological characteristics: simple pleural thickening or massive pleural

effusion with or without associated pneumothorax.

d. Bullous stage: There is not a proper stage, as bullae may be missing in 20% of cases

or can be added in any other stage. Radiological characteristics: pneumonocele which

can persist for months (fig. 28).

Fig 28 . Right staphylococcal pneumonia

Diagnosis is based on:

- Clinical signs (especially the appearance of "intoxicated" child and abdominal

bloating rebellious to treatment)

- Radiological findings (4 stages)

- Laboratory findings:

o Leukocytosis with elevated neutrophil count, accelerated ESR, positive CRP

(especially important for assessing the clinical progress), intrainfectious

anemia

o Staphylococcus aureus cultures from blood and pleural fluid

o Thoracocentesis: pleural fluid - exudate with polymorphonuclear leucocytes

Evolution: in the early days due to severe toxico-septic syndrome, deaths may occur. The

acute evolution is approx. 2-3 weeks followed by a slow regression period of weeks or

months.

Complications:

- Suppurative: septic arthritis, meningitis, brain abscess, sepsis

94

- Nonsuppurative: pneumothorax, pneumomediastinum

B. PNEUMONIA WITH GRAM-NEGATIVE MICROORGANISMS

Etiology: Klebsiella pneumoniae, Haemophilus influenzae, Psuedomonas aeruginosa,

Proteus, Serattia, rare E. coli, Aerobacter. Frequently are "hospital" germs, nosocomial

infections with resistant bacteria.

Predisposing factors: they occur more frequently in:

- Neonates, premature, malnourished infants and young children, immundepressed

patients with anemia, rickets, hospitalized.

- Malabsorption (cystic fibrosis, celiac disease).

- Immunocompromised patients (leukemia treated with immunosuppressants).

Usually starts slowly, insidiously, through a toxico - septic syndrome with marked digestive

disorders comperative to respiratory syndrome, radiologically with pleural involvement and

typical biological characteristics of bacterial infections.

ATYPICAL PNEUMONIA

It is characterized by:

- Lack of evidence of bacterial etiology

- Without leukocytosis

- Discrepancy between obvious radiological signs and poor pulmonary clinical findings

- Chest radiography: predominantly affecting the basal interstitial lung

- Clinical forms ("common cold", headache, muscle aches, mild fever and cough)

Etiology: frequently viral but other microorganisms may be involved to:

- Viruses with pulmonary tropisms: respiratory syncytial virus, influenza virus,

parainfluenza virus, adenoviruses, rhinoviruses

- Viruses with pulmonary and other tropisms: enteroviruses, hepatitis viruses,

cytomegalovirus, measles, rubella, etc.

- Other mircoorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae, rickettsia,

pararickettsia, Pneumocystis jiroveci (carinii).

95

A. VIRAL PNEUMONIA

Etiology: respiratory syncytial virus (most frequently involved viral agent in infants and

small children).

Clinical manifestations:

The onset is usually sudden, after a short period or concurrently with an acute upper

respiratory tract infection with anorexia, agitation, fever and wheezing.

Later on the course of the illness:

- High fever, respiratory functional syndrome with marked expiratory dyspnea,

irritating cough, inter- and subcotal retraction, nasal flarring, perioral cyanosis.

- Physical findings are poor, often negative, rarely wheezing or crackels can be find.

Diagnosis is based on epidemiological, clinical, radiological and biological findings.

Radiological characteristics: interstitial thickening especially from hilum to the base of the

lung, like "monk locks", sometimes microopacities (difficult to distinguish from lobular

pneumonia) (fig. 29).

Fig . 29 - Interstitial pneumonia

Laboratory findings:

- Possible leukopenia, low ESR (not rule)

- Procalcitonine: to differentiate between viral and bacterial infections ( if ↑ is justified

to use antibiotics)

- Etiological diagnosis - serology: complement binding, hemagglutination, cold

agglutination tests - antibody titer ↑, viral culture (rare)

Differential diagnosis:

96

- Pneumonia with Mycoplasma pneumoniae or Chlamydia

- Pneumocystis jiroveci (carinii) pneumonia

- Bacterial pneumonia

- Acute bronchiolitis

Complications: bacterial superinfections

Evolution: healing in approx. 8-10 days

B. PNEUMONIA with MYCOPLASMA PNEUMONIAE

Occurs more frequently in children older than 5 years and adolescents, in small epidemics,

accounting for 7-40 % of community-acquired pneumonia in children. Incubation lasts 1-3

weeks.

Clinical manifestations:

Onset is pseudoinfluenza like with fever, headache, myalgia, dysphagia.

Later on the course of the illness appears paroxysmal, irritating, initially dry than wet cough,

productive with white or rose-coloured sputum, sometimes dyspnea.

Physical examination of the lung is poor - fine crackles, sometimes wheezing (differential

diagnosis with bacterial pneumonia where wheezing is missing) or bronchial rales can be

identified.

Chest radiography: is nonspecific, changes occur especially unilateral, in the lower lobe of

the lung in 75 % of cases. In the early stage of pneumonia interstitial thickening, reticular

aspect can be seen, later macronodular or segmental opacities occur.

Laboratory findings:

- Serology: antimycoplasma pneumoniae antibodies (IgM remains positive up to 6-12

months after the infection), the presence of cold agglutinins, complement binding

reaction

- Frequently accelerated ESR

- Cultures of sputum or throat culture

Complications are rare: Stevens Johnson syndrome, neurological complications (aseptic

meningitis, meningoencephalitis), hematological complications (thrombocytopenia,

hemolysis), rarely pancreatitis, myocarditis or pericarditis.

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C. PNEUMONIA with PNEUMOCYSTIS JIROVECI (CARINII)

Definition: it is an interstitial plasma cell pneumonitis caused by a parasite, Pneumocystis

jiroveci (formerly Pneumocystis carinii), which occurs in immunocompromised patients: HIV

infected patients, congenital immunodeficiency, malnourished, premature, malignancies,

patients with organ transplants, etc. The incubation period is 3-8 weeks.

Clinical manifestations:

The onset is slow, insidious with marked tachypnea without fever, later gradually associated

dry cough, inter- and subcostal retraction, nasal flaring, cyanosis.

Later on the course of the illness a sever functional respiratory syndrome appears, but the

physical examination is poor or increased breath sounds may occur. Cardiovascular syndrome

may be present with tachycardia, hepatomegaly, edema, restlessness.

Radiological findings: micro- and macronodular diffuse infiltrates occurring, bilateral,

confluent ("sett" aspect) and later both lungs looks as "matt glass".

Accurate diagnosis is established by demonstrating the presens of Pneumocystis jiroveci with

bronchoalveolar fluid lavage.

TREATMENT OF PNEUMONIA

Therapeutic goals of treatment of pneumonia are:

1. Providing vital functions

2. Etiological treatment

3. Hygienic-dietary treatment

Hygienic-dietary reccomandations

- Isolation, room temperature 18 to 21 C, humidity 40 %

- Position in bed: with lift shoulders, position changed every 1-2 hours to avoid stasis, bath

made with 1 hour before meals

- Feeding: will be unchanged if the child is not anorexic or with dyspnoea; may be reduced

or given in divided doses or by gavage. Provide the required amount of liquid, lossed by

sweating and polipnee.

98

Treatment of acute respiratory failure

Desobstruction of upper airways: aspiration of secretions. Respiratory physiotherapy is NOT

useful in patients with severe associated dyspnoea without other pathology. Using of

nasogastric probe will be avoided because of further hampering respiration.

b. Oxygen therapy: improves blood oxygenation, decreases anxiety, labor and respiratory

effort and pulmonary vascular resistance.

Indications of oxigen therapy:

- SaO2 < 92 % if the patient is breathing spontaneously, effitiently

- cyanosis and a "combat for air syndrome " (polipnea, " air hunger ", sweating,

agitation)

- O2 concentration will be 30-100 % to bring pO2 to 60-100 %

- In the tent, face mask: a flow rate of 4 liters/minute, can lead to a saturation of

100% O2

- The optimum level of O2 (if the pressure O2 can not be monitorized) is the flow of

O2 at which cyanosis disappeared plus ¼ of this flow

- Optimal flow of O2 given by nasopharyngeal probe for infant and young child is:

2-4 liters/minute, administered discontinue - before meals and treatments.

- O2 is cold and dry, must be warmed and humidified by bubbling in oxygenator

- Do not use O2 concentration > 40% in preterm infants and newborns because

retrolental fibroplasia can occurring followed by blindness

- Side effects in case of administration of high concentrations O2: tracheobronchial

hypersecretion, fatigue, vomiting, dizziness, epileptic spasms, atelectasis,

pulmonary edema

c. Improve of ventilation:

- Aerosol therapy: provides moisture, allows nebulization of bronchodilators

- Endotracheal intubation and assisted mechanical ventilation are indicated if: pO2

< 50 mmHg, pCO2> 75 mmHg

d. Correction of acidosis: based on ASTRUP parameters.

e. Reduction of O2 consumption at the periphery:

- bed rest, administration of Phenobarbital 3-5 mg/kg/day PO/IM (the goal is to

maintain an O2 saturation > 92% monitored by pulse oximeter)

99

- improving transport O2 if Hb 7 g% with: red blood cell concentrate: 5 ml/kg or

whole blood 10 ml/kg transfusions

Special therapeutic measures:

In pneumonia with hypersecretion: thinning and removal of secretions by:

- Keeping the cough reflex (in case of dry and irritating cough: Codeine 0.3

mg/kg/day, or Calmotusin 3x 4-5 drops/day)

- Postural drainage

- Ensuring the necessary liquids

- Expectorants mucolytics: Bromhexin 3x10 drops under 2 years, 3x15 drops between

2-6 years of age

- Corticosteroids: HHS 10 mg/kg/day, 4-6 x/day, iv; or prednisone 1-2 mg/kg/day, po,

in short courses of 4-7 days (after which period may be cut short without withdrawal).

Corticosteroids have the following effects:

- Suppress tissue response to injury, inhibiting the formation of fibroblasts

- Reduce bronchospasm produced by histamine

- Reduce the inflammatory edema

In pneumonia with bronchospasm: bronchodilators:

Short-acting beta 2 agonists in aerosol:

- Salbutamol (Ventolin) sol. aerosols (5 mg/ml) 0.15 mg/kg/d (up to 5 mg)

- Terbutaline (Bricanyl) sol. aerosols (2.5 mg/ml) 0.15 mg/kg/d

Anticholinergic agents in aerosols:

- Ipratropium bromide (Atrovent) sol. aerosols (0.025 mg/ml)Treatment of

cardiovascular syndrome

- Change the patient's position: trunk elevated

- Reduce the amount of fluid intake

- Place low sodium diet

- Administer cardiac glycosides, diuretics

- In collapse: filling the vascular bed

Treatment of toxico - septic syndrome

I. Antiinfectious treatment

II . Treatment of neuro - toxic symptoms

I. Antiinfectious treatment – etiological treatment: antibiotics (AB), chemotherapy,

antiviral- and antifungal therapy

100

General considerations:

1. Most community aquired pneumonia in children are viral: AB therapy IS NOT

required, only symptomatic treatment will be administered (in case of fever

antipyretics), although in current practice due to the difficult differentiation of the

bacterial and viral pneumonia, and the risk of superinfection of viral pneumonia,

antibiotic therapy is initiated (this usually becomes the roule in newborn and infants

under 6 months of age).

2. Antibiotic treatment is usually empirical because of the difficulty of identification of

the etiological agent.

3. The type antibiotic and method of administration depend on: patient's age, severity of

disease, the involved etiologic agent, the patient's immunological status, regional

sensitivity to antibiotics of bacteria.

Antibiotic treatment:

a. Depending on the severity of the disease:

Mild and moderate forms of the disease (with good digestive tolerance) are treated as an

outpatient with oral antibiotics (PO)

Aminopenicillin (broad-spectrum penicillins)

- Amoxicillin (Ospamox, Standacilin): 20-40 mg/kg/day, 3x/day, suspension or capsule

(is the drug of choice in the age group 2-5 years)

- Amoxicillin - acid clavulanique (Augmentin, Amoxiclav, Bioclavid): 20-40

mg/kg/day calculated for amoxicillin 2x/day suspension, capsules

Cephalosporins - 2nd, 3rd generation

- Cefuroxime (Zinnat): 30 mg/kg/day, 2x/day

- Ceftibuten (Cedax): 9 mg/kg/day, 1x/day

Macrolides:

- Erythromycin (rarely, because of digestive intolerance)

- Azithromycin (Sumamed): 10 mg/kg/day, for 3-5 days 1x/day

- Clarithromycin (Klacid, Fromilid): 15 mg/kg/day, 2x/day

Severe forms - requiring hospitalization; antibiotic will be administered parenterally

(IV,IM )

Criteria for hospitalization:

- Infants under 6 months of age

- If outpatient treatment was inefficient after 48-72 hours

101

- Child has dehydration, hypoxia or significant respiratory failure

- Leukopenia (5000/mm3)

- Unfavorable family or social environment

Aminopenicillin (broad-spectrum penicillins

- Ampicillin 100-200 mg/kg/day, 3-4x/day

Cephalosporins - 2nd, 3rd generation

- Cefuroxime (Kefurox, Cefuroxime, Axycef ): 100-150 mg/kg/day, 2-3x/day

- Ceftriaxone (Rocephin, Ceftriaxone): 50-80 mg/kg/day, 1-2x/day

A. Depending on the most likely etiology at a certain age:

In the newborn:

Streptococcus gr. B: Penicillin G

Gram negative microorganisms: Ampicillin + aminoglycosides (Amikacin, Tobramycin) or

3rd generation cephalosporins (Cetotaxim)

2 months - 5 years: Haemophilus influenzae, Streptococcus pneumoniae (Pneumococcus),

rarely Staphylococcus aureus, and gram-negative bacteria (Klebsiella, Psuedomonas)

Haemophilus influenzae pneumonia: Amoxicillin first choice. In severe forms

Chloramphenicol parenteral Ampicillin or cephalosporins - Ceftriaxone, Cefotaxime

- About 35 % of Haemophilus influenzae strains produce beta - lactamase, theirfore

beta- lactamase resistant antibiotics are required, such as cephalosporins, macrolides

(clarithromycin, azithromycin), amoxicillin/clavulanate

Streptococcus pneumoniae pneumonia (Pneumococcus)

Drugs of first choice: Amoxicillin, Amoxicillin/Clavulanate, Penicillin G (Penicillin - very

seldom used because 25-50 % of pneumococcal strains are resistant)

- In cases with resistance can be given: Cephalosporins, Vancomycin

Staphylococcus pneumonia

- Methicillin-susceptible staphylococci: Oxacillin 200mg/kg/day, Cephalosporins -

2nd, 3rd generation. In case of β - lactam antibiotic allergy - Clindamycin 10-30

mg/kg/day po, in 3 diveded doses.

- Methicillin - resistant staphylococci: Vancomycin 40-60 mg/ kg/day in 3-4 divided

doses

Klebsiella pneumonia

- Aminoglycosides: Amikacin (Pyerami) 15 mg/kg/day 2 diveded doses,

Netilmicin, Tobramycin)

102

- Cephalosporins - 2nd, 3rd generation

- Combination of aminoglycosides with cephalosporins

Pneumonia with Pseudomonas aeruginosa (Pseudomonas)

- See Klebsiella, but use cephalosporins effective on Pseudomonas (ceftazidime,

cefoperazone)

- Carbenicillin, Imipenem

Aspiration pneumonia: etiologic agents incriminated are usually anaerobic germs or

Staphylococcus aureus, Pyogenic streptococci. For anaerobes should be used:

Metronidazole. Clindamycin, Penicillins, Cephalosporins third generation.

Mycoplasma pneumoniae pneumonia:

- Macrolides: Erythromycin, Clarithromycin, Azithromycin

- Alternative: Tetracyclines (after age 8 years), new generation quinolones

Chlamydia pneumoniae pneumonia:

- Macrolides: Erythromycin, Clarithromycin, Azithromycin

- Alternative: Doxycycline

Pneumocystis jiroveci (carinii)

- Trimethoprim/sulfametoxazole (Co-trimoxazole, Biseptol): 20 mg/kg/day

calculated for Trimethoprim, 3x/day, PO for 10-14 (21) days

- Alternative: pentamidine inj. 4 mg/kg/day, 2 weeks.

c.Duration of antibiotic therapy:

- Generally 7-10 (14) days in uncomplicated pneumonia

- Pneumonia complicated with pleural effusion, abscess: requires 14-21 days of

treatment

- Pleuro-pulmonary staphylococcal infection: considered a surgical disease that requires

parenteral treatment three weeks, followed by at least 1-3 weeks oral antibiotics. In

the 3rd- 4th weeks of evolution fibrous connective tissue reaction occurs around the

lesions, which interfering the antibiotic entering in the affected area and

complications may occur: pleural thickening, persistent pleural fluid, pneumothorax,

which requiring surgical treatment (thoracentesis, drainage of abscess, minimum

pleurotomy).

d. Rules of antibiotic therapy:

- In severe forms is recommended, at least initially, antibiotics in iv infusion, and at

shorter intervals of administration

103

- If after 48-72 hours of administration, an antibiotic not prove effective, it will be

changed or will be associated with another antibiotic

- Penicillin G 100.000 IU will be dissolved in 1 ml of normal saline to avoid fibrosis of

quadriceps, when administered IM

- In the event of using two antibiotics, their administration will not be stopped suddenly

at the same time. An antibiotic (usually the most " toxic") will cease sooner.

- Whenever possible, treatment should be conducted on the streight of antibiogramma.

Antiviral treatment (restricted to pneumonia where the causative viral agent is revealed):

Ribavirin (RSV), amantadine (flu), etc.

Antifungal treatment: Pneumonia with Candida albicans (in immunocompromised patients):

Amphotericin B, Flucytosin, Fluconazole (Diflucan)

Prophylaxis:

- Haemophylus influenzae type B vaccine

- Pneumococcal vaccine: immunocompromised children, splenectomised patients,

patients with malformations

- Flu vaccine A, B , C: annual in high-risk children: broncho-pulmonary dysplasia,

lung malformations, congenital heart defects, immunosuppression

Treatment of neuro-toxic symptoms:

- Intravenous corticosteroids: HHS/Methylprednisolone IV

- Administration of 10 g glucose/kg/day

Symptomatic treatment

Antipyretic treatment: over 38.5 °C rectal

- increased fluid intake

- bath with light warm water, prisnitz

- Antipyretics: Paracetamol 10-15 mg/kg 3-4 x/day (oral, supp.), Ibuprofen: 20-40

mg/kg/day, Aspirin 10-15 mg/kg/day (CONTRAINDICATED in varicella, influenza,

INFANTS AND TODDLERS – can cause Reye syndrome)

Fighting flatulence:

- Local warmth on the abdomen

- Rectal probe

104

- Miostin (neostigmine): 0.2-0.3 ml I.M. or S.C

In hypokalemia: administration of potassium

Adjuvant therapy:

- Volume and hydro-electrolytic rebalancing

- Acido-basic rebalancing

- Combat cerebral edema

- Treatment of febrile seizures

- Treatment of digestive disorders: diarrhea, vomiting (Plegomazin: 0.5-1 mg/kg/day)

Maneuvers or surgical procedures: pleural puncture, pleural drainage, exsufflation

pneumothorax, pleurotomy.

References

1. The Management of Community - Acquired Pneumonia in Infants and Children Older Than 3 Months

of Age : Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious

Diseases Society of America , IDSA Guidelines , 2011

2. Samir S. Shah - Current Diagnosis & Treatment of Community - Acquired Pneumonia in Children,

Highlights of the PIDS / IDSA National Guidelines , American Academy of Pediatrics, 2012

3. Jeremy Hull - Community Acquired Pneumonia in Children, Oxford Children's Hospital, UK,

European Respiratory Society, 2012

4. Assessment and Management of Pediatric Community Acquired Pneumonia, Intermountain Healthcare,

2013

5. Guidelines for the Management of Community Acquired Pneumonia in children: update 2011 British

Thoracic Society Community Acquired Pneumonia in Children Guideline Group. - Thorax 2011

6. Shields, M.D. , Bush A , Everard M. L. et al : British Thoracic Society guidelines. Recommendations

for the assessment and management of cough in children. Thorax, 2008, 63

7. Everard ML . - Recurrent Lower Respiratory Tract Infections " - going around in circles, respiratory

medicine style. Paediatric Rev Respir. 2012 Sep, 13 (3):139-43.

8. A. Georgescu, Anca Ioana - Compendiu de pediatrie, ediţia III, Editura ALL, 230-237, 251-255

9. Brand PL , Hoving MF de Groot EP. - Evaluating the child with recurrent lower respiratory tract

Infections . Paediatric Rev Respir . 2012 Sep , 13 (3) :135-8

10. Kliegman, Stanton St . Gems et al. - Nelson Textbook of Pediatrics, 19th Edition, Elsevier Saunders ,

1475-1479

105

CHILDHOOD ASTHMA

Definition: asthma (i.e Bronchial asthma - AB) is a chronic inflammatory condition of the

lung airways characterized by variable airway obstruction (reversible either spontaneously or

with treatment) associated with bronchial hyperresponsiveness to a variety of provocative

exposures.

Etiology: is multifactorial.

- Hereditary predisposition for bronchial hyperreactivity to certain conditions.

- Presence of atopy (respiratory allergy) or the ability to develop serum reagin levels

(Antibodies) IgE, IgG against pneumoallergens (rarely to food allergens).

- AB exacerbation precipitating factors can be: environmental factors - exposure to

allergens:

o dust mites

o pollen, mold, animal dander

o viral infection, chemicals, tobacco smoke

o exercise, emotions, meteorological factors

o aspirin, food additives, endocrine factors, etc.

Avoidance of food and aeroallergens in infants decreases the incidence of atopic dermatitis

in infancy and asthma in high risk children.4

Types of childhood asthma (pathogenic mechanism)

1. Extrinsic or allergic asthma – appears in atopic conditions due to various allergens by

immunoallergic mechanism.

2. Intrinsic asthma (non-allergic, idiopathic) is secondary to disturbances of bronchial

reactivity by changes of chemical mediators, without atopy (IgE values are normal,

absent or moderate eosinophilia - below 10%).

3. Infectious asthma - wheezing episodes are triggered mainly by viral infections.

Subsequently, it can be complicated by other types of asthma.

4. Chronic cough (recurrent, spasmodic). Is a latent form of asthma, a bronchial

hyperreactivity.

5. Effort induced asthma - bronchoconstriction occurs after a prolonged effort over 6

minutes.

6. Aspirin - induced asthma - is an intrinsic asthma associated with nasal polyps and

sinusitis.

106

7. Mixed asthma - the predominance of one of the triggers of the exacerbation.

Diagnosis:

AB clinical suspicion arises when a child presents:

- Frequent episodes of nocturnal cough

- Dyspnea

- Wheezing

especially if it develops or worsens during exercise or the at night, or are is triggered by

exposure to dust, pollen, tobacco smoke, pets, emotions etc.

AB diagnosis is based on:

Medical history: recurrent paroxysmal expiratory dyspnea, nocturnal symptoms, seasonal

exacerbations to allergen exposure, the existence of AB or other atopic manifestations in the

family (allergic rhinitis, atopic dermatitis), etc.

Clinical manifestations:

Key clinical signs suggestive for atopic phenotype include:

- Eczema or atopic dermatitis

- Dry skin

- Ringed eyes

- Conjunctival irritation

- Persistent swelling of the nasal mucosa, rhinorrhea, itchy nose/frequent rubbing of the

nose with the hand and allergic fold on the root of the nose.

Clinical manifestations of asthma:

A. Exacerbation: paroxysmal expiratory dyspnoea reversible either spontaneously or to

bronchodilators. It can be manifested only by spasmodic cough lasting 20-30 minutes during

the night or severe crisis with:

- Expiratory dyspnoea - polipnoea in infants and toddlers, bradipnoea in older children

- Intercostal retraction

- Nasal flaring

- Prolonged expiration, wheezing

- Dry then wet cough

- + / - Cyanosis

Physical examination: anxious child with orthopnoea position (in older children)

- Distended thorax, fixed "in inspiration", hypersonority

- Bronchial rales (ronchi at the beginning of the crisis then crackels)

- Lowering of liver and spleen

107

- Evolution: hours for children, days for infants

B. Status asthmaticus: paroxysm of expiratory dyspnoea lasting over 24 hours, with signs of

severe acute respiratory failure, unresponsive to bronchodilators and associated with hypoxic

encephalopathy (table 12).

Table no. 12 .The symptoms of status asthmaticus

Combat phase - respiratory manifestations

- Marked suprasternal and

intercostal retraction

- Nasal flaring

- Intense expiratory dyspnoea, short

inhalation period

- Cyanosis

- Regular breathing with tachypnea,

then progressively irregular with

short apnea periods short

- Hyperinflation

- Pulmonary hypersonority

- Decreased breath sounds

Phase of bronchoplegia

Respiratory symptoms

- Bronchoconstriction replaced by

bronchodilation

- Shallow, rare breathing

Cardiovascular symptoms

- Tachycardia

- Heart failure

- Initially hypertension, then

hypotension and collapse

Neuropsychiatric manifestations

- Agitation, anxiety

- Drowsiness

- Progressive hyporeactivity

- Coma, seizures

- Cardiopulmonary arrest

C. Intercritical period: the period between exacerbations in which the child may be

completely asymptomatic or presents minimal symptoms (night and/or in the morning

cough). Persistence of clinical manifestations in this period in children with AB represents

elements of sever prognosis. Severe forms of asthma are characterized by intercritical

residual obstruction progressing to chronic respiratory failure which will associate: chest

deformity, cyanosis, clubbing, stature-weight weakness, delayed puberty.

3. Laboratory investigations:

- Blood gas analysis (PaO2, PaCO2 - to assess the severity of exacerbation)

- Chest X-ray: shows hyperinflation, emphysema or atelectatic areas.

108

- Allergy tests: blood eosinophilia, total serum IgE and specific IgE determination, skin

allergy tests

- Pulmonary function testing – spirometry - to confirm bronchial obstruction and its

severity by measuring lung volumes and flows (vital capacity – VC, forced expiratory

volume in one second – FEV1, peak expiratory flow - PEF) allowing monitoring of

spontaneous evolution under treatment. If FEV1 increases with by 12% after

administration of inhaled beta2-agonist, reversibility of bronchial obstruction is

confirmed.

Table no. 13. Classification of asthma severity

Asthma severity Daytime symptoms

Nightime symptoms

FEV1/PEF variability

Intermittent < 1/week ≤ 2/month Normal≥ 80%Variability < 20%

Persistent mild > 1/week (< 1day) > 2/month ≥ 80%Variability: 20% -30%

Persistent moderate

DailyUsing of agonist daily

> 1/week 80-60%Variability: 30%

Persistent severe True out the day, frequent exacerbations

Frequent < 60%Variability > 30%

Fig. no. 30. Evaluation of severity of asthma exacerbation

109

TREATMENT OF ASTHMA

Immediate objectives:

- Bronchodilation

- Repermeabilization of airways

Long-term goals:

- Suppressing the chronic inflammatory process

- Avoiding contact with triggers

Home management of asthma:

- Short-acting beta2-agonists (Salbutamol, Bricanyl, Berotec - spray, spacer): 2 puffs

three times at intervals of 20 minutes, then 1 hour and 4-6 hour respectively. The

following can be administered po: Salbutamol (Ventolin) 0.2-0.3 mg/kg/day divided

into 3 doses.

110

- Corticosteroids: When evolution is unfavorable, if needed, inhalations at intervals of

less than 3-4 hours (PEF as 65-50% of baseline values) are given. Prednisone 1-2

mg/kg/day po in 2 doses or Methylprednisolone (Medrol) 0.5 mg/kg/day in 2 doses.

- Theophylline - 10-15 mg/kg/day po in 2 doses at 12 hours.

Treatment of exacerbations of asthma in emergency room, hospital, intensive care unit: is

a more complex treatment based on careful monitoring of the patient (oxygen, nebulization of

beta2 - agonists, I.V. corticosteroids, anticholinergics - ipatropium bromide (Atrovent)

nebulization, restoration of acid-basic balance, heart failure treatment and mechanical

ventilation (fig. no. 31).

Fig. no. 31. Treatment of exacerbations of asthma in emergency room, hospital, intensive

care unit

111

In case of exacerbation the following should be avoided: sedation, expectorant, high-

volume hydration, chest physiotherapy.

Long-term controller therapy: for management of the chronic inflammatory process and

avoidance of allergens/triggers (table no. 14).

Table no. 14. Long-term control medication according to asthma severity

Asthma severity Controller therapy Symptomatic

treatment (Rescue

medication if needed)

Intermittent - Short-actingbeta2-agonists

Persistent –mild Cromone

Low dose inhaled cortico-steroids:

200-500 mcg/day

Or

Oral leukotriene receptor

antagonists (Singulair -Montelukast)

Short-actingbeta2-agonists (max 4 x

day)

Persistent –moderate Cromolyn

Low/medium dose inhaled

corticosteroids: 500-800 mcg/day

Or

Low dose inhaled corticosteroids +

oral leukotriene receptor antagonists

Or

Inhaled corticosteroids + Long acting

beta2 – agonists

Short-actingbeta2-agonists

Ipatropium bromid

Persistent- severe High-dose inhaled corticosteroids:

800-1200 mcg/day

Or

Low dose inhaled corticosteroid +

Long acting beta2 - agonists

+ Oral corticosteroids

+ IgE antagonists (Omalizumab)

Theophylline retard

Short-actingbeta2-agonists

Ipatropium bromide

112

Long term controller therapy of asthma - "STEP-UP STEP-DOWN" approach, according to

symptom control. Once good asthma control is achieved for at least three months, the

guidelines (GINA 2011) suggest decreasing the dose or number of controller therapy and

moving one step lower to the minimum treatment that maintains control, parallel with close

monitoring of evolution. In case of uncontrolled asthma, the treatment goes up one step to a

higher level, or even in severe cases, will jump two treatment steps (table no 15).

Table no. 15. The controller medication in asthma by steps

Controller medication

STEP 5 STEP 4 + oral corticosteroids

Anti IgE (Omalizumab for children older than 12

years with allergies)

STEP 4 Medium or high dose ICS + Long acting beta2 –

agonists

Or

Medium or high dose ICS + Leukotriene

receptor antagonists

Or

Medium dose ICS + teophyilline retard

STEP 3 Medium or high dose ICS

Or

Low dose ICS + PO Leukotriene receptor

antagonists

Or

Low dose ICS + Long acting beta2 - agonists

Or

Low dose ICS + teophyilline retard

STEP 2 Low dose ICS

Or

Leukotriene receptor antagonists

STEP 1 -

ICS – inhaled corticosteroids

*Global strategy for asthma management and prevention in children 5 years and younger – modified, adapted

113

Elimination, reduction and control of trigger factors: reduces exposure to allergens; it is

composed of avoiding of moisture and dampness, dust, smoke, fresh paint, carpets, curtains,

materials of wool and feathers, aspirin, but also ventilation, dust extraction, air conditioning,

constant temperature (18-20C) and avoiding pets. Food restrictions are only necessary in

well proven cases. Breastfeeding has an important prophylactic role.

Efficacy and success of anti-asthmatic therapy depends also on the education of the child and

family. They need detailed description of the signs and symptoms that indicate an impending

exacerbation, accurate information about allergens and triggers, explaining and checking the

inhalation technique and verifying of the correct monitoring of respiratory parameters.

REFERENCES

1. S.Holgate, H.Bisgaard, L.Bjermer et al. - The Brussels Declaration: the need for change

in asthma management – Eur Respir J, 2008; 32/6

2. Pearce N, Ait-Khaled N, Beasley R. - Worldwide trends in the prevalence of asthma

symptoms: phase III of the International Study of Asthma and Allergies in Childhood

(ISAAC), Thorax 2007; 62,758 - 766

3. J. Bizzintino, N. M. Lee, F. Vang - Association between human rhinovirus C and severity

of acute asthma in children – Eur Respir J., 2011; 37: 1037-42

4. Arshad SH, Bateman B, Matthews SM - Primary prevention of asthma and atopy during

childhood by allergen avoidance in infancy: a randomised controlled study, Thorax.,

2003; 58: 489-93.

5. http://www.sign.ac.uk/pdf/sign101.pdf - British Guideline on the Management of

Asthma 2012

6. http://ginasthma.org/local/uploads/files/GINA_Under5_2009_CorxAug11_1.pdf - Global

strategy for asthma management and prevention in children 5 years and younger

7. http://ginasthma.org/local/uploads/files/GINA_Report_March13.pdf - Global strategy for

asthma management and prevention

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CHAPTER III - CARDIOVASCULAR PATHOLOGY

Prof. Univ. Dr. Togănel Rodica

CONGENITAL HEART DEFECTS (CHD)

Definition Failure of normal cardiac development or of the fetal circulation after birth.

Incidence 7-9/1000 live births.

Causes are unknown in the majority of cases, commonly associated with chromosomal

defects, gene defects, congenital infection (e.g. rubella), teratogenic drugs (e.g. phenytoin,

warfarin, alcohol).

Diagnostic methods The history and physical examination are the keystones for diagnosis

of cardiac problems . A variety of other diagnostic techniques can be employed beyond

besides history and physical examination.

A history of the following may indicate the possibility of CHD: poor weight gain, with a

history of a feeding problem, difficulty in swallowing, fainting attack, respiratory difficulties,

exercise intolerance, with the child assuming a squatting position, intermitent or continuous

cyanosis, history of maternal illness during the first trimester of pregnancy, including rubella,

bleeding, severe anemia, drug ingestion, or other teratogen. The physician should obtain a

complete family history to disclose the presence of CHD, syndromes, or other disorders.

The suspicion of cardiovascular abnormality may be raised initially by specific symptoms,

but more commonly is the discovery of a cardiac murmur. Distinguishing an innocent from a

pathological heart murmur may be difficult. Innocent heart murmurs is are the most common

causes of a heart murmur in children. It arises due to the rapid flow and turbulence of blood

through the great vessels and across normal heart valves. It does not signify the presence of

any underlying cardiac abnormality or any other pathology.

The characteristics of innocent heart murmurs are: systolic in timing, short duration, low

intensity sound, it intensifies with increased cardiac output (e.g. exercise, fever), may change

in intensity with change in posture; no associated cardiac thrill, no radiation, asymptomatic

patient.

Clasification Congenital cardiac malformation may be classified in various ways; a clinical

useful clasification is based on two clinical features: the presence or absence of cyanosis and

the type of pulmonary vascularity as determined by chest X-ray (increased, normal,or

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diminished). CHD can be classified into acyanotic or cyanotic types depending on whether

the predominant presentation is with or without central cyanosis caused by deoxygenated

blood gaining abnormal access to the systemic side of the circulation via the left side of the

heart or the aorta.

Acyanotic CHD: e.g. ventricular septal defect, atrial septal defect, patent ductus arteriousus,

coarctation of the aorta, aortic stenosis.

Cyanotic CHD: e.g.tetralogy of Fallot, transposition of the great arteries, tricuspid atresia,

total anomalous pulmonary drainage.

ATRIAL SEPTAL DEFECT (ASD)

Definition Any opening in the atrial septum is described as an ASD. This definition includes the

secundum atrial defect, septum primum defects and sinus venosus defects.

Prevalence: 5% to 10% of all congenital heart diseases (CHDs). Female preponderance (male-

to-female ratio of 1:2).

Pathology and pathophysiology Three types af atrial septal defects (ASDs) occur in the atrial

septum. Secundum ASD is in the central position of the septum and it is the most common type.

Primum ASD (or partial endocardial cushion defect) is low in the septum and often with deformity

of the mitral or/and tricuspid valve and with persistent atrioventricular canal.(30% of ASDs). Sinus

venosus defect is near the entrance of the superior vena cava (SVC) or inferior vena cava (IVC) to

the right atrium (RA). Partial anomalous pulmonary venous return is common with a sinus venous

defect.

A left-to-right shunt (L-R shunt) is present through the defect, with a volume overload to the RA

and right ventricle (RV) and an increase in pulmonary blood flow.

Clinica manifestations The patients are usually asymptomatic.

A widely split and fixed S2 and a grade 2 to 3/6 systolic ejection murmur at the upper left sternal

border (ULSB) are characteristic of moderate-size ASD. With a large L-R shunt a middiastolic ruble

(resulting from relative tricuspid stenosis [TS]) may be audible at the lower left sternal border

(LLSB). The typical auscultatory findings are usually absent in infant and toddlers, even those with

large defect, because the RV is poorly compliant.

The ECG shows right axis deviation (RAD) (+ 90 to +180 degrees) and mild right ventricular

hypertrophy (RVH) or right bundle branch block (RBBB) with an rsR’ pattern in V1.

Chest x-ray (CXR) films show cardiomegaly (with right atrial enlargement [RAE), increased

pulmonary vascular markings (PVMs), and a prominent main pulmonary artery (MPA) segment.

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Two-dimensional echo shows the position and the size of the defect. Cardiac chateterization is

usually not necessary.

Spontaneous closure of the defect occurs in patients with defects 3 to 8 mm (diagnosed by echo)

before 1 !/2 years of age. An ASD with diameter greater than 8 mm rarely closes spontaneously. The

defect may reduce in size in some patients. If the defect is large and left untreated, pulmonary

hypertension develops in the third and fourth decades of life. Cerebrovascular accident due to

paradoxical embolization through an ASD is possible.

Management Exercise restriction is not required.

Nonsurgical closure of the defect using a catheter-delivered closure device has become a preferred

method, provided the indications are met.

Surgical For patients with primum ASD and sinus venosus defect, and some patients with secundum

ASD for which the device closure is considered inappropriate, surgical closure is indicated when

there is a significant L-R shunt with Qp/Qs of 1,5:1 or greater. Surgery is usually delayed until 2 to 4

years of age, unless congestive heart failure (CHF) develops. Open repair with a mid-sternal incision.

High pulmonary vascular resistance (PVR) (10 units/m2) is a contraindication to surgery.

VENTRICULAR SEPTAL DEFECT

Definition The term ventricular septal defect (VSD) describes an opening in the ventricular

septum. They may occur in isolation or as part of complex malformations. The clinical

features depend on size and location of the defect.

Prevalence. Ventricular septal defect (VSD) is the most common form of CHD, accounting

for 25% of all CHDs. .

Pathology and pathophysiology As a result of the defect, shunting of blood occurs between

the ventricules. When the size of the defect approaches the size of the aortic annulus, flow is

governed by the relative pulmonary and systemic vascular resistances. When the defect is

smaller, blood flows from the left to the right ventricle because of the higher systolic pressure

in the left ventricle.

The ventricular septum consists of all small membranous septum and a large muscular

septum. The muscular septum has three components: the inlet, infundibular, and trabecular

(or simply muscular ) sept. A membranous VSD often involves a varying amount of muscular

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septum adjacent to it (i.e., perimembranous VSD). The perimembranous defect is more

common (70%) than the trabecular, infundibular, or inlet defects.

In VSDs with small to moderate L-R shunt, volume overload is placed on the left atrium

(LA) and the left ventricle (LV) (but not on RV). With large defects the RV is also under

volume and pressure overload, in addition to a greater volume overload on the LA and LV.

Pulmonary blood flow (PBF) is increased to a varying degree depending on the size of the

defect and the pulmonary vascular resistance. With a large VSD, pulmonary hypertension

result. With a long-standing large VSD, pulmonary vascular obstructive disease (PVOD)

develops, with sever pulmonary hypertension and cyanosis resulting from a right-to-left shunt

(R-L shunt). At this stage, surgical correction is nearly impossible

Clinical manifestations. Patients with small VSDs are asymptomatic, with normal growth

and development. With large VSDs, delayed growth and development, repeated pulmonary

infections, CHF, and decreased exercise tolerance are relatively common. With PVOD,

cyanosis and decreased level of activity may result.

With a small VSD, a grade 2 to 5/6 holosystolic murmur maximally audible at the lower left

sternal edge and a systolic thrill may be present. With a large defect, an apical diastolic

rumble is audible, which represents a relative stenosis of the mitral valve due to large

pulmonary venous return to the LA. The S2 may split narrowly, and the intensity of the P2

increases if pulmonary hypertension is present.

ECG findings: Small VSD, normal; moderate VSD, left ventricular hypertrophy (LVH) and

left atrial hypertrophy (LAH) (±); large VSD, biventricular hypertrophy (BVH) and LAH (±);

PVOD, pure RVH.

CXR film reveal cardiomegaly of varying degrees with enlargement of the LA, LV, and

possibly the RV. PVMs are increased. The degree of cardiomegaly and the increase in PVMs

are directly related to the magnitude of the L-R shunt. In PVOD the heart size is no longer

enlarged and the MPA and the hilar pulmonary arteries are notably enlarged, but the

peripheral lungs fields are ischemic.

Two-dimensional echo studies provide accurate diagnosis of the position and size of the

VSD. LA and LV dimensions provide indirect assessment of the magnitude of the shunt.

The Doppler studies of the pulmonary artery (PA), tricuspid regurtation (TR), and the VSD

itself are useful in indirect assessment of RV and PA pressures.

Spontaneous closure occurs in 30% to 40% of all VSD, most often in small trabecular

VSDs. CHF develops in infants with a large VSD but usually not until 6 or 8 weeks of age,

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when the PVR drops below a critical level. PVOD may begin to develop as early as 6 to 12

months of age in patients with large VSD.

Management Medical. Treatment of CHF. No exercise restriction is required in the absence

of pulmonary hypertension, antibiotic prophylaxis.

Surgical. PA banding is rarely performed unless additional lesions make the complete repair

difficult.

Direct closure of the defect is performed under cardiopulmonary bypass and/or deep

hypotermia.

PATENT DUCTUS ARTERIOSUS

Definition Patent ductus arteriosus (PDA) defined the failure of ductus arteriosus to close.

The ductus is functionally closed in about 90% of full term infants by 48 hours of age.

Prevalence 5% to 10% of all CHDs, excluding those in premature infants.

Pathology and pathophysiology There is a persistent postnatal patency of a normal fetal

structure between the PA and the descending aorta. The magnitude of the L-R shunt is

determined by the diameter and the length of the ductus and the level of PVR. With a long-

standing large ductus, pulmonary hypertension and PVOD may develop with an eventual R-L

shunt and cyanosis.

Clinical manifestations Asymptomatic when the ductus is small. When the defect is large

signs of CHF may develop.

A grade 1 to 4/6 continuous (machinery) murmur best audible at the upper left sternal edge.

An apical diastolic rumble is audible with a large shunt PDA. Bounding peripheral pulses

with wide pulse pressure are present with a large shunt PDA.

ECG findings are similar to those to VSD: Normal or LVH in a small to moderate PDA;

BVH in a large PDA; RVH if PVOD develops.

CXR findings are also similar to those of VSD: normal with small shunt PDA. With a large-

shunt PDA, cardiomegaly (with LA and LV enlargement) and increased PVM are present.

With PVOD the heart size is normal, with a marked prominence of the MPA and hilar

vessels.

The PDA can be directly imaged and its hemodynamic significance determined by 2D echo

and color flow Doppler examination. Cardiac catheterization is usually not indicated in

isolated PDA.

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CHF or recurrent pneumonia or both develop if the shunt is large. Spontaneous closure of

PDA usually does not occur in term infants.

Management Medical No exercise restriction is required in the absence of pulmonary

hypertension.

Consider pharmacological closure (e.g. indometacin or ibuprofen).

Catheter closure of the ductus may be employed.

Surgical closure is reserved for those patients in whom nonsurgical technique is not

considered applicable. Ligation and division through left posterolateral thoracotomy. PVOD

is a contraindication to surgery.

COARCTATION OF THE AORTA

Definition Coarctation of the aorta (CoA) is a narrowing of the descending aorta.

Prevalence 8% to 10 % of CHDs, with a male preponderance (2:1). Among patients with

Turner syndrome, 30% have COA.

Pathology and pathophysiology CoA may occur at any point in the descending aorta. In the

majority of cases, it is distal to the origin of the left subclavian artery at the level of ductus

arteriosus.

In CoA a narrowing of the upper thoracic aorta is present. There are two groups of patients

with CoA: one group of patients presenting symptoms early in life and the other group

remaining asymptomatic.

In symptomatic infants with CoA, other cardiac defects (such as aortic hypoplasia, VSD,

PDA and mitral valve anomalies) are often present. These abnomalities may have reduced

antegrade flow through the aorta during fetal life.

In asymptomatic children with CoA, associated anomalies are uncommon. The anterograde

flow through the aorta has resulted in a pressure gradient and stimulated the development of

the collateral circulation during the fetal life.

As many as 85% of patients with CoA have a bicuspid aortic valve.

Clinical features Symptomatic Infants

Signs of CHF (poor feeding, dyspnea) and renal failure (oliguria, anuria) with general

circulatory shock may develop in the first 2 to 6 weeks of life.

A loud gallop is usually present, but heart murmur may be absent with weak and thready

pulses in sick infants.

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The ECG usually shows RVH.

CXR films show a marked cardiomegaly and signs of pulmonary edema or pulmonary

venous congestion.

Two-dimensional echocardiography shows the site and extent of the CoA and other

associated cardiac defects. The Doppler examination reveals a disturbed flow distal to the

CoA, and signs of delayed emptying in the proximal aorta. In symptomatic infants with CoA,

early death from CHF and renal failure is possible.

Management

Medical: Intensive anticongestive measures should be given with fast-acting inotropic agents,

diuretics, and oxygen to stabilize the patient. PGE1 infusion is indicated to reopen the ductus

before any intervention takes place to maintain the systemic circulation.

Balloon angioplasty is controversial, but it can be useful procedure for sick infants;

Surgical repair- Resection and end-to-end anastomosis

Clinical manifestation Asymptomatic Children

These patients are usually asymptomatic except for rare complaints of leg pain.

The pulse in the leg is absent or weak and delayed. Hypertension in the arm or higher blood

pressure (BP) reading in the arm that the thigh may be present. An ejection click resulting

from the bicuspid aortic valve is frequently audible at the apex and/or base. A systolic

ejection murmur grade 2 to 3/6, is audible at the URSB and MSLB and in the left

interscapular area in the back.

The ECG usually shows LVHl.

CXR films show a normal or slightly enlarge heart. Rib notching by collateral vessels may

be seen in the children after about 5 years of age.

Two-dimensional echo shows a discrete, shelflike membrane in the posterolateral aspect of

the descending aorta. The Doppler examination reveals disturbed flow and increased flow

velocity distal to the coarctation. The bicuspid aortic valve is frequently imaged.

Bicuspid aortic valve may cause stenosis and/or regurgitation later in life. If a CoA is left

untreated, LV failure, intracranial hemorrhage, or hypertension encephalopaty may develop

in childhood or adult life.

Management

Medical

Hypertension or hypertensive crisis should be detected and treated

Balloon angioplasty for native CoA is controversial.

A balloon-expandable, stainless-steel stent implanted concurrently with balloon angioplasty.

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Surgical Resection of the coarctation segment and end-to-end anastomosis.

If CoA recurs following either surgery or angioplasty, balloon angioplasty is the procedure of

choice.

TETRALOY OF FALLOT

Definition Tetralogy of Fallot is a cyanotic congenital heart malformation comprising

infundibular pulmonary stenosis, a ventricular septal defect, dextroposition of the aorta such

that the aortic root overrides the crest of ventricular septal defect , and right ventricular

hypertrophy.

Prevalence. 10% of all CHD. It is the most common cyanotic CHD beyond infancy.

Pathology and pathophysiology

The original description of TOF included four abnormalities: a large DSV, RVOT

obstruction, RVH, and an overriding aorta. Systemic venous retour to the right side of the

heart is normal In the presence of pulmonary stenosis, however, the blood is shunted across

the VSD into th aorta and persistent arterial desaturation and cyanosis result. The severity of

cyanosis is dependent on the degree of RV outflow obstruction .

Clinical manifestations

Most patients are symptomatic, with cyanosis, clubbing, dyspnea on exertion, failure to

thrive, squatting, or hypoxic spells.

A right ventricular tap and a systolic thrill at the lower and middle LSB are usually found. A

loud and single S2, and a loud (grade 3 to 5/6) systolic ejection murmur at the middle and

upper LSB are present.

The ECG shows RAD and RVH

CXR films show normal heart size, decreases PVMs, and boot-sharped heart with a concave

MPA segment. Right aortic arch is present in 25% of the cases.

2D echo shows a large subaortic VSD and an overriding of the aorta. The anatomy of the

RVOT, pulmonary valve, and pulmonary arteries can be imaged

Polycythemia is common, but relative iron deficiency state (hypochromic) with normal

hematocrit may be present. Coagulopathies are late complications of a long-standing severe

cyanosis.

Hypoxic spell

Hypoxic of TOF requires recongnition and treatment, as it can lead to serious CNS

complications. It occurs in young infants, with peak incidence between 2 and 4 months of

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age. It is characterized by a paroxysm of hyperpnea (rapid and deep respiration), irritability

and prolonged crying, increasing cyanosis, and decreased intensity of the heart murmur. A

severe spell may lead to limpness, convulsion, cerebrovascular accident, or even death.

Treatment of the hypoxic spell is aimed at breaking the vicious circle. One or more of the

following may be employed in decreasing order of preference:

1. Pick up the infant and hold in a knee-chest position

2. morphine sulfate, 0.1 to 0.2 mg/kg SC or IM, suppresses the respiratory center and

abolishes hyperpnea.

3. Treat acidosis with sodium bicarbonate, 1 mEq/kg IV. This reduces the respiratory

center stimulating effect of acidosis.

4. oxygen inhalation has only limited value, since the problem is a reduced PBF, not the

ability to oxygenate.

5. Propranolol 0.01 to 0.25 mg/kg (average 0.05 mg/kg) in a slow IV push, reduces the

heart rate and may reverse the spell.

Management Medical Hypoxic spells should be recognized and appropriately treated.

Oral propranolol, 2-4 mg/kg/day, may used to prevent hypoxic spells and delay surgery.

Detection and treatment of relative iron deficiency stare. Anemic children are particularly

prone to cerebral accident.

Surgical Palliative procedures are indicated to increase PBF in infants with severe cyanosis

or uncontrollable hypoxic spell on whom the corrective surgery cannot safely be performed,

and in children with hypoplastic PA on whom the corrective surgery is technically difficult.

Different types of S-P shunt have been performed.

The Blalock-Taussig shunt (anastomosis between the subclavian artery and the ipsilateral

PA) may by performed in older infants.

Gore-Tex interposition shunt between the subclavian artery and the ipsilateral PA (modified

Blalock-Taussig shunt) is the procedure of choice in small infants.

Conventional repair surgery: Symptomatic or cyanotic infants with favorable anatomy of the

RVOT and PAS may have primary repair at any time after 3 to 4 months of age.

Asymptomatic and minimally cyanotic children may have repair between age 3 and 24

months, depending on the degree of the annular and pulmonary hypoplasia.

Total repair of the defect is carries out under cardiopulmonary bypass. The procedure

includes patch closure of the VSD, widening of the RVOT resection of the infundibular

muscle tissue, and usually placement of the fabric patch to widen the RVOT.

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COMPLET TRANSPOSITION OF THE GREAT ARTERIES

Definition Transposition of the great arteries (TGA) describes reversal of the anatomic

relation of the great arteries and ventriculoarterial relationship.

Prevalence: TGA constitutes 5% of all CHD. It is more common in boys (3:1).

Pathology and pathophysiology

The aorta arises anteriory from the RV, the pulmonary artery arises posteriory from the LV.

Blood from the right heart goes through the systemic vessels and returns to the right side.

Blood from the left heart goes through the lungs to return to the left side. The end result is

complete separation of the two circuits, with hypoxemic blood circulating in the body and

hyperoxemic blood ciculating in the pulmonary circuit. This anomaly is incompatible with

life unless ASD, PDA or VSD is also present, that permit mixing of the two circulations

The classic complet TGA is called D-transposition, in which the aorta is located anteriorly

and to the right of the PA; When the transposed aorta lies to the left of the PA, it is called L-

transposition.

In neonates with poor mixing of the two circulations, progressive hypoxia and acidosis result

in early death, requiring early intervention. CHF develops in the first week of life in many

patients with this condition.

Clinical manifestations

Cyanosis and signs of CHF (dyspnea, feeding difficulties) develop in the newborn period.

Auscultatory findings are nonspecific.

Sever arterial hypoxemia unresponsive to oxygen inhalation and acidosis are present in

infants with poor mixing. Hypoglicemia and hypocalcemia are occasionally present.

The ECG shows RAD and RVH.

CXR films show cardiomegaly with increased PVMs. An egg-shaped cardiac silhouette with

narrow superior mediastinum is characteristic.

2D echo study is diagnostic. It fails to show a “circle-and-sausage” pattern of the normal

great arteries in the parasternal short axis view. Instead, it shows two circular structure. Other

view reveal the PA arising from the LV and the aorta arising from the RV.

Management

Medical Metabolic acidosis, hypoglicemia, and hypocalcemia should be treated if present

PGE1 infusion is started to raise arterial oxygen saturation by reopening the ductus.

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Administration of oxygen may help raise systemic oxygen saturation by lowering PVR and

increasing PBF, with resulting increase in mixing.

A therapeutic balloon atrial septostomy (Rashkind procedure) may be performed if

immediate surgery is no planned. Treatment of CHF with digitals and diuretics may be

indicated.

Surgical Arterial switch operation (ASO), is the procedure of choice in many cardiac centers.

INFECTIVE ENDOCARDITIS

(SUBACUTE BACTERIAL ENDOCARDITIS)

Definition Infective endocarditis (IE) is an infection of the endocardium and/or heart valves

that involves thrombus formation (vegetation), which may damage the endocardial tissue

and/or valves. Although uncommon in children, it is important to identify and treat IE

because of it significant morbidity and mortality.

Prevalence: IE affects 0.5:1000 to 1:1000 hospital patients, excluding those with

postoperative endocarditis.

Pathogenesis and pathology: IE is the result of a series of complex interactions among

blood-borne pathogens, damaged endothelium, fibrin, and platelets. Most children with IE

have an identifiable risk factor for the disease.

The endocardial surface is initialy injured by shear forces associated with turbulent blood

flow in children with CHD, or indwelling central venous catheters in children without CHD.

At the site of endothelial damage, fibrin, platelets, and occasionally red blood cells are

deposited and initially form a noninfected thrombus.

Transient bacteriemia or fungemia result in adherence of microbial pathogens to the injured

endocardium and thrombus. Subsequent fibrin and platelet deposition over the infected

vegetation result in a protective sheath that isolates the organisms from host defenses and

permits rapid proliferation of the infectious agent.

Two factors are important in the pathogenesis of infective endocarditis: (1) structural

abnormalities of the heart or great arteries with a significant pressure gradient or turbulence,

with resulting endothelial damage and platelet-fibrin thrombus formation, and (2)

bacteriemia, even if transient. Bacteremia frequently results from dental procedures and

chewing with diseased teeth.

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All CHDs (except secundum ASD) and valvular heart disease predispose to endocarditis.

Those with prosthetic heart valve or prosthetic material in the heart are at particularly high

risk for IE. Surgical repair of CHD may reduce but does not eliminate the risk of

endocarditis, with the exception of a simple ASD or PDA. Drug addicts may develop

endocarditis in the absence of known cardiac anomalies.

Vegetation of endocarditis is found usually in the low-pressure side of defect, either around

the defect or on the opposite surface of the defect. For example, vegetations are found in the

PA in PDA or an S-P shunt and in the ventricular surface of the aortic calve and mitral

chordae in AR.

Incolvement of other organs is secondary to embolization or immune-mediated processes.

Microbiology In the past, Streptococcus viridans, enterococci and Staphylococcus aureus

were responsible for over 90% of case. In recent years, this frequency has decreased with a

concomitant increase in cases caused by fungus and HACEK Organisms (Haemophilus,

Actinobacillus, Cardiobacterium, Eikenella, and Kigella)

S.viridans is the most common cause of IE following dental procedures or dental pr

periodontal disease. Enterococcus is the organism most often found after genitourinary or

gastrointestinal surgery or instrumentation. The organism most commonly found is

postoperative endocarditis is the staphylococcus. Fungal endocarditis may occur in sick

neonates, in patients who are on long-term antibiotic or steroid therapy, or after open heart

surgery. HACEK organisms are particularly common in neonates and immunocomplomised

children. Pseudomonas aeruginosa or Serratia marcescens is seen more often is intravenous

drug users.

Clinical manifestations The clinical presentation of IE is variable. It is dependent upon the

extent of the local cardiac disease, degree of involvement of other organ and the causative

agent. Underlying heart defect is present in almost all patients. History of recent dental

procedures, tonsillectomy, or toothache is common. The onset of the illness is insidious, with

fever, fatigue, loss of appetitie, and pallor, myalgi, headache, night sweats.

Heart murmur and fever are almost always present. Splenomegaly is common (70% of

patients).

Skin manifestations (seen in 50% of patient), probably secondary to microemboli, may

include petechiae, Osler nodes (tender red nodes) at the ends of the fingers or toes, Janeway

lesions ( small, painless hemorrhagic areas on the palms or soles), and splinter hemorrhage

(linear hemorrhagic streaks beneath the nails).

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Embolic phenomena to other organs (e.g, pulmonary emboli, seizures and hemiparesis,

hematuria) affect 50% of patients.

Positive blood culture are found in more than 90% of patients is the absence of a recent

antimicrobial therapy. Antimicrobial pretreatment reduces the yield of positive blood culture

to 50% to 60%. Other laboratory findings include anemia, leukocytosis, and increased

erythrocyte sedimentation rate (ESR).

2D echo may actually demonstrate the vegetation. A transesophageal echo study is usually

more productive in demonstrating the vegetation. It is unlikely that vegetation less than 2 mm

in maximum dimension will be image by 2D echo.

Diagnosis: A presumptive diagnosis on infective endocarditis is made when a patient with an

underlying heart lesion has a fever of unknown origin of several days duration and any of the

typical physical findings or laboratory changes is present. The diagnosis of IE is based upon

careful history and physical examination, blood culture and laboratory results, and

echocardiogram.

According to the revised Duke criteria, IE is diagnosed based upon the presence of one of

two pathologic criteria or, more commonly, with certain combination of clinical findings.

Pathologic criteria: one of the following two pathologic criteria are required for the diagnosis

of IE -

- direct evidence of endocarditis based upon histological findings

- positive Gram stain results or cultures of specimens obtained from surgery or autopsy.

Clinical criteria are divided into major and minor findings. The clinical diagnosis of

definitive IE require the presence of either two major criteria, one major and three minor

criteria, or five minor criteria.

Major criteria: blood culture positive for IE; Evidence of endocardial involvement

(echocardiogram positive for IE).

Minor criteria: predisposition, fever, vascular phenomena, immunologic phenomena,

microbiologic evidence.

Management. Three to five blood culture are drawn in succession over 24 or 48 hours,

unless the patients is very ill. In 90% of the cases, the causative agent is recoveres from the

first two culture.

Initial empiric therapy is started with following antibiotics wile awaiting the result of blood

culture

The usual initial regiment is an antistaphyloccal semisyntetic penicillin (nafcilin, oxacilin or

methicilin) and an aminoglycoside (gentamicin

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If a methicilin-resistent S.aureus is suspected, vancomycin should be substitude for the

semisynthetic penicillin.

The final selection of antibiotics depends on the organism isolated and the result of an

antibiotic sensitivity test.

In general, a highly sensitive S.viridans can be successfully treated with IV penicillin for 4

weeks.

The drug of choice for staphylococcal endocarditis is one of the semisynthetic penicillinae-

resistant penicillin, given IV for 4 to 6 weeks. Vancomycin is used in patients allergic to

penicillins.

Enterococcus cause endocarditid usually requires a combination of IV penicillin or ampicillin

for 4 weeks and IV gentamicin for 2 weeks

HACEK organisms may have become resistant to ampicilin. A third-generation

cephalosporin, such as ceftriaxone, is generally recommended.

Amphotericin B is the most effective agent for most fungal infections.

Operative intervention may be necessary before the antibiotic therapy is complete if the

clinical situation warrants (e.g., progressive CHF, significant malfunction of prosthetic

valves, persistently positive blood cultures after 2 weeks therapy). Bacteriologic relapse after

an appropriate course of therapy also calls for operative intervention.

Prevention: Endocarditis prophylaxis is indicated only for certain cardiac conditions and

procedures: prosthetic cardiac valve, previous infective endocarditis, CHD, cardiac

transplantation

The antibiotic prophylaxis is given orally 1 hour before a procedure. It should not be started

several days before the procedure. Parenteral antibiotics are given within 30 minutes of

starting procedure.

for dental ( all dental procedures that involve manipulation of gingival tissue of the

periapical region of teeth or perforation of the oral mucosa), respiratory tract (for procedures

that involve incision or biopsy of respiratori mucosa, such as tonsillectomy and

adenoidectomy), or esophageal procedure are directed against Streptococcus viridans; for

genitourinary (GU) and gastrointestinal (GI) procedure (in patients with infected GI or GU

tract) are directed against Enterococcus faecalis (enterococci).

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MYOCARDITIS

Myocarditis is an inflammation or degeneration of the heart muscle, usually secondary to

systemic infection

Etiology: myocarditis may be caused by an infectious agent, immune-mediate process,

collagen disease, or toxic agent. A cell-mediated immunology reaction, not merely

myocardial damage from viral replicatiom, appears important in viral myocarditis.

Infections: Viruses are probably the most common cause of myocarditis; adenovirus,

coxsackie viruses and echoviruses are the most common agents. Many other viruses (such as

poliomyelitis, mumps, measles, rubella, cytomegalovirus, HIV, arboviruses, adenovirus, and

influenza) can cause myocarditis. Rarely, bacteria, rickettsia, fungi, protozoa and parasites

are the causative agents.

Immune mediated disease: cut rheumatic fever, Kawasaki disease

Collagen vascular disease toxic myocarditis (drug ingestion, diphtheria exotoxin, and anoxic

agents)

Clinical manifestations

History of an upper respiratory infection may be present in older children. The onset of

illness may be sudden in neonates and small infants, causing anorexia, vomiting, lethargy and

occasionally circulatory shock.

The presentation depends on the patient’s age and the acute or chronic nature of the infection.

Typical cardiovascular examination includes: weak pulses, tachycardia, gallop rhythm distant

hear sound

The ECG may show any one or combination of the following: low QRS voltage, ST-T

changes ,prolongation of the QT interval, and arrhythmias, especially premature contractions.

Cardiomegaly on CXR films is the most important clinical signs in myocarditis

Echo studies reveal cardiac chamber enlargement and impaired LV function, often regional.

Occasionally, increased wall thickness and LV thrombi are found.

Cardiac troponin levels (-I and -T) and myocardial enzyme (creatine kinase [CK], MB

isoenzyme of CK[CK-MB]) may be elevated. Troponin levels may be more sensitive than the

cardiac enzyme. The normal value of cardiac troponin I in children is 2 ng/ml or less.

Radionuclide scanning (after administration of gallium 67 or technetium 99m pyrophosphate)

may identify inflammatory and necrotic changes characteristic of myocarditis. Myocarditis

can be confirmed by an endomyocardial biopsy.

Myocarditis may be a precursor to idiopathic dilated cardiomyopathy in certain patients.

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Management

Treatment is directed at the underlying cause at controling symptoms of congestive heart

failure.

Bed rest and limitation of activities are recommended during the acute phase (because

exercise intensifies the damage from myocarditis in experimental animals).

Anticongestive measures include rapid-acting diuretics (e.g., furosemide or ethacrynic acid),

rapid acting inotropic agents (e.g., isoproterenol, dobutamin, dopamine), administration of

oxygen, and bed rest.

Digoxin may be given cautiously, using half of the usual digitalizing dose, as some patients

with myocarditis are exquisitely sensitive to it. An ACE inhibitor (e.g., captopril) may be

benefical in the acute obese.

Arrhythmias should be treated aggressively and may require the use of IV amiodarone.

Beneficial effects of high dose γ-globulin (2g/kg over 24 hours) have recently been reported

(with better survival an batter LV function by echo). A high dose of γ-globulin have been

reported to be effective in myocarditis secondary to Kawasaki disease.

The role of corticosteroids is unclear except for the treatment as sever rheumatic carditis.

PERICARDITIS

Inflammation of the pericardium may be primary, or a manifestation of more generalized

illness.

Etiology Viral infection is probably the most common cause, particularly in infancy.

Acut rheumatic fever is also a cause of pericarditis

Bacterial infection (purulent pericarditis). Commonly encountered are S.aureus,

Streptococcus pneumoniae, Haemophylus influenzae, Neisseria meningitis, and streptococci.

Tuberculosis (an occasional cause of constrictive pericarditis with insidious onset). Heart

surgery (postpericardiotomy syndrome). Collagen disease such as rheumatoid arthritis. A

complication of oncologic disease or its therapy including radiation. Uremia (uremic

pericarditis)

Pathophysiology Pathogenesis of symptoms and signs of pericardial effusion is determined

by two factors: speed of fluid accumulation and competence of the myocardium. A rapid

accumulation of a large amount of fluids or a slow accumulation of a small amount of fluids

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in the presence of myocarditis can produce circulatory embarrassment. Slow accumulation of

a large amount of fluid may be well tolerated if the myocardium is intact.

With the development of pericardial tamponade, several compensatory mechanism are

called on: systemic and pulmonary venous constriction (to improve diastolic filing), an

increase in the SVR (to raise falling blood pressure), and tachycardia (to improve cardiac

output).

Clinical manifestations

The patients may have a history of upper respiratory tract infection. Precordial pain with

occasional radiation to the shoulder and neck may be presenting complaint. The pain may be

relieved by leaning forward and made worse by supine position or deep inspiration.

Pericardial friction rub is the cardinal physical sign. In children with purulent pericarditis,

septic fever (38o ti 41o C), tachycardia, chest pain, and dyspnea are almost always present.

Signs of cardiac tamponade may be present (distance heart sounds, tachycardia, pulsus

paradoxus, hepatomegaly, venous distension, and occasional hypotension with peripheral

vasoconstriction).

The ECG may show a low-voltage QRS complex, ST segment shift, and T wave inversion.

CXR films may show a varying degree of cardiomegaly. Water battle-shaped heart and

increased pulmonary venous markings are seen with large effusion.

Echo is the most useful tool in establishing the diagnosis of pericardial effusion and in

detecting cardiac tamponade.

Management

Pericardiocentesis or surgical drainage to identify the cause of the pericarditic is mandatory,

especially when purulent or tuberculosis disease is suspected.

Salicylates may be administrated for precordial pain in nonbacterial pericarditis and

rheumatic fever. Costicosteroid therapy may be indicated for children with severe rheumatic

carditis or postpericardiotomy syndrome.

For cardiac tamponade, urgent decompression by surgical drainage or pericardiocentesis is

indicated

Urgent surgical drainage is indicated when purulent pericarditis is suspected. Purulent

pericarditis is treated with an IV antibiotic therapy for 4 to 6 weeks.

Constrictive pericarditis

A fibrotic, thickened, and adherent pericardium restricts diastolic filling of the heart.

Although rare in children, it may be associated with earlier idiopathic or viral pericarditis,

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tuberculosis, incomplete drainage of purulent pericarditis, hemopericardium, mediastinal

irradiation, neoplasic infiltration, or connective tissue disorders.

Diagnosis of constrictive pericarditis is suggested by the following clinical finding:

signs of elevate jugular venous pressure; hepatomegaly with ascites and systemic edema;

diastolic pericardial knock; calcification of the pericardium, enlargement of the SVC and the

A, and pleural effusion on CXR films; low QRS voltage, T wave inversion or flattening,

LAH, and atrial fibrillation on the ECG.

An M-mode echo may reveal two parallel lines representing the thickened visceral

and parietal pericardia or multiply dense echoes. Also, 2D echo show an immobile and dense

appearance of the pericardium

The treatment for constrictive pericarditis is complete resection of the pericardium;

symptomatic improvement occurs in 75% of the patients.

CONGESTIVE HEART FAILURE

Definition Hear failure is a clinical condition that results from impairment of the ventricle to

fill with or eject blood.

Pathophysiology and Etiology: Congestive heart failure (CHF) may result from congenital

or acquired heart diseases with volume and/or pressure overload or from myocardial

insufficiency.

CHD is the most common cause of CHF in children. The time of onset of CHF varies rather

predictably with the type of the defect.

The underlying pathophysiology mechanisms that lead to compromise of cardiac stroke

volume and heart failure include: increase afterload (pressure work), increased preload

(volume work), myocardial abnormalities, arrhythmias.

Ventricular pump dysfunction results in reduced ventricular contractility that lead to impaired

ejection of blood from the ventricle (cardiomyopathy, myocarditis, arrhythmias).

Volume overload with preserved ventricular contractility ( increased preload) resulting in

CHD is due to CHD with significant left-to-right shunt, or less commonly, valvular

insufficiency.

Pressure overload is due to CHD with severe ventricular outflow obstruction that impedes

ejection of blood from the hear resulting in inadequate cardiac output.

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Clinical manifestations. The diagnosis of CHF relies on several sources of clinical findings,

including history, physical examination, and CXR film. Cardiomegaly is almost always

present on CXR film.

Poor feeding of recent onset, tachypnea, poor weight gain, and cool sweat on the forehead

suggest CHF in infants. In older children, shortness of breath, especially with activities, easy

fatigability, puffy eyelids, or swollen feet may be presenting complaints. Physical findings

can be divided by pathophysiologic subgroups.

1. Compensatory responses to impaired cardiac function: Tachycardia, gallop rhythm, weak

and thready pulse and cardiomegaly; CXR films are more reliable than physical examination

in demonstrating cardiomegaly. Signs of increased sympathetic discharges (growth failure,

perspiration, and cold wet skin.)

2. Signs of pulmonary venous congestion (left-side failure) include tachypnea, dyspnea or

exertion (poor feeding in small infants), orthopnea in older children, and wheezing and

pulmonary crackles.

3. Signs of systemic venous congestion (right side failure) include hepatomegaly and puffy

eyelids. Distended neck vein and ankle edema are nor seen in infants.

Cardiomegaly on CXR films is almost always present.

The electrocardiogram may be helpful in determine the cause. Sinus tachycardia is common.

Echocardiography can confirm the presence of chamber enlargement or impaired LV

function and determine the cause of CHF.

Management Elimination or correction of predisposing factors (e.g, fever, anemia, infection)

and treatment of underlying causes (hypertension, arrhythmias, or thyrotoxicosis), general

supportive measures and control of heart failure by inotropic agents, diuretics, afterload

reducing agents are the treatment goals.

Pharmacologic therapy: Improvement in symptoms can be achieved by inotropic agents,

diuretics, digoxin, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II

receptor blockers (ARBs).

Prolongation of patient survival has been documented with beta-blockers, ACE inhibitors,

ARBs, and aldosterone antagonists. Improvement in LV function and reversal of LV

dilatation, LV remodeling with chronic use of ACE inhibitors, ARBs, and aldosterone

antagonists.

Rapidly acting inotropic agents (dopamine, dobutamine, milrinone) are used in critical ill

infants and children with CHF, in those with renal dysfunction; rapidly acting catecholamines

with a short duration of action are preferable to digoxin

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Diuretics decrease preload by promoting natriuresis and provide relief of volume overload

symptoms. Patients with CHF often improve rapidly after a dose of fast-acting diuretic, such

as furosemide or acid ethacrynic. Side effects of diuretic therapy include hypokalemia, and

hypochloremic alkalosis; both may increase the likelihood of digitalis toxicity. Diuretic

almost always are used with inotropic agents.

Digoxin has a positive inotropic effect, a negative chronotropic effect that slow atrial

conduction, and vagotonic properties. Digoxin is used in all noncritical patients. The use of

digoxin is contraindicated in CHF caused by hypertrophic cardiomyopathy, complete heart

block, or cardiac tamponade. Therapeutic ranges of serum digoxin levels for treating CHF

are 0.8 to 2 ng/ml, levels obtained during the first 3 to 5 days after digitalization. A serum

digoxin level greater than 2 ng/ml is likely associated with toxicity if the clinical findings

suggest digital toxicity.

Afterload-reducing agents are popular because they can increase cardiac output without

increasing myocardial oxygen consumption. Reducing the afterload tends to augment the

stroke volume without change in the contractile state of the heart and therefore without

increasing myocardial oxygen consumption. These agents are usually used in conjunction

with digitalis glycosides and diuretics. In addition to myocardial dysfunction, patients with

CHF from large L-R shunts (such as VSD, AV canal, PDA) have been shown to benefit from

captopril. Angiotensin-converting enzyme inhibitors (captopril, enalapril) are accepted as an

important component of CHF therapy in children.

Beta-blockers counteract the maladaptive effects of chronic sympathic activation of the

myocardium. In adults with CHF they improve patient survival, reverse LV remodeling and

decrease myocardial fibrosis.

Nonpharmacologic interventions for advanced heart failure: positive pressure ventilation,

mechanical circulatory support in end-stage heart failure and heart transplantation.

Nonpharmacologic therapy for chronic heart failure. Nutrition- caloric intake and growth

should be carefully assessed. Some children may need a daily intake greater than 120kcal/hg

for optimal growth because of increased metabolic demands. In order to provide adequate

caloric intake, intermittent or continuous nasogastric or gastrostomy tube feeds may be

required. In addition, salt and fluid restriction is recommended in children with severe CHF

to reduce volume overload.

For patients with structural heart disease with preserved pump function, surgical or catheter-

based interventions are used to correct the underlying defects causinh CHF.

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SHOCK

Definition. It is a plurietiologic, multipathogenetic clinical syndrome, characterized

haemodynamically by reduction in the tissue blood flow below a certain critical level

necessary for the normal metabolic processes. Therefore, the shock is determined mainly by

tissue perfusion deficit, independent of blood pressure value and can evolve with normal

blood pressure and a normal or increased cardiac activity.

Etiopathogenic classification of shock- table no. 16:

HYPOVOLEMIC SHOCK decreased intravascular volume with decreased venous return and preload

Water and electrolyte loss: diarrhea, vomiting, diabetes insipidus, renal losses, burns

Hemorrhage: internal, posttrauma, post surgery Plasma loss: burns, nephrotic syndrome, peritonitis

DISTRIBUTION SHOCK secondary to alteration of vascular tone through vasoplegia → marked decrease in the BP

Anaphylaxis: antibiotics, vaccines, blood products, local anesthetics, insect bites, food

neurological injuries: head trauma, spinal cord injury early stage of septic shock: meningococcal

septicemia, staphylococcal, gram negative flora drugs: barbiturates, phenotiazidics, tranquilizers,

antihypertensivesCARDIOGENIC SHOCK congenital or acquired heart disease

MCC: hypoplastic left heart syndrome Primary cardiomyopathy: obstructive, degenerative acquired cardiomyopathy: infectious, toxic,

irradiation Congestive heart failure After cardiovascular surgery dysrhythmias obstruction: cardiac tamponade

SEPTIC SHOCK occurs initially through vasogenic mechanism subsequently associated with hypovolemic and cardiogenic mechanism

etiology: different depending on the age and immune mechanism competence

Newborn: beta-hemolytic streptococci gr. B, Enterobacteriaceae, Listeria monocytogenes, Staphylococcus aureus

Infant: H. influenzae, Streptococcus pneumoniae, Staphylococcus aureus

Child: Streptococcus pneumoniae, Neisseria meningitidis, S. aureus

immunocompromised patients: S aureus,

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Pseudomonadaceae, Enterobacteriaceae, Candida albicans

DISSOCIATIVE SHOCK severe anemia carbon monoxide poisoning methemoglobinemia

PathophysiologyIn all pathogenetic forms of shock, cardiac output is inadequate for the tissue needs due to

mismatches between the vascular bed and the blood volume.

• hypovolemic shock: vascular bed is normal, but low volemia

• cardiogenic shock: the circulating blood volume is low, while the vascular bed is

normal. Cardiac output is affected either due to ineffective diastolic filling (in the

context of dysrhythmias) or as a result of the serious compromise of myocardial

contractility (myocarditis or cardiomyopathy).

In cardiogenic shock, as a particular form of shock in pediatrics due to myocardial

insufficiency, venous stasis occurs with increased risk of acute pulmonary edema,

with systemic venous stasis, with increased central venous pressure (PVC).

Cardiogenic shock is a form of increased PVC shock – congestive shock, and

therefore therapy will be conducted so that the patient will need only fluid and

electrolyte as maintenance, providing basic needs and treatment target remains the use

of vasoactive substances and inotropic medication.

• vasogenic shock: total blood volume is normal, but the vascular bed capacity

is increased

These details are useful for therapeutic conduct.

Links involved in the pathophysiology of shock are:

• reduced effective circulating volume

• pump failure

• hemodynamic disturbances in the microcirculation

• decreased venous return

• metabolic disorders

There are three stages in the shock evolution:

• compensated stage: homeostatic mechanisms act to maintain perfusion of vital organs;

blood pressure, urine output and cardiac function are normal

- consequence of inadequate cardiac tissue needs leads to the onset of two

compensatory mechanisms needed to ensure proper circulation at myocardial

and cerebral levels:

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a) centralization-by vasoconstriction in the kidney (oligoanuria

appears), mesenteric territory, liver, muscle, skin (vasoconstriction in the skin,

it is a cold shock) and is made through adrenaline, noradrenaline, renin and

angiotensin

b) penetration of interstitial fluid in the vascular bed - occurs due to

reduced hydrostatic pressure at capilary level.

• decompensated stage: diminishes compensatory mechanisms

- If the shock-triggering cause persists, inadequate irrigation of tissues and inadequate

intake of oxygen in the cessl will cause vasoconstriction with vasodilatation replacement

(vasoplegia), increased capillary permeability (fluid moves to interstitium), activation of

disseminated coagulation with microthrombi formation in different organs and significant

reduction of the contraction ability of the heart. These changes announce decompensated

shock and are triggered by hypoxemia, acidosis, increased permeability of the digestive tube

to endotoxins, excessive formation of free radicals, activation of kinin pathways.

• Final stage: compensatory mechanisms are compromised, evolution is progressive to exitus

Clinical presentation

General Signs: drowsiness, pale and cold teguments (except for septic shock), dry, often

cyanotic lips, sometimes nasal flare.

Neurological signs: dizziness to the stage of coma, general sensitivity diminished to coma,

diminished tendon reflexes

Cardiovascular signs:

- in the first phase of shock vasoconstriction predominates: tachycardia, blood pressure can

be normal due to increased peripheral vascular resistance;

- In final stages: deafness of heart sounds, tachycardia, abrupt fall in the blood pressure,

filiform pulse, colabation of shallow veins, cyanosis of extremities, mottled skin;

- when shock is associated with heart failure: jugular venous turgor

Respiratory signs:

- Initial phase: tachypnea, caused by stimulation of respiratory centers and by metabolic

acidosis. Hyperventilation causes increased CO2 elimination, stimulates vasoconstriction

(especially venous), improving venous return.

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- In final stages: lung structural alterations with alveolar hypoventilation, hypoxemia and

hypercapnia: PaO2 <65mmHg, PaCO2:> 50mmHg

Digestive Signs: Although the shock causes digestive mucosal lesions, gastrointestinal

bleeding rarely presents digestive hemorrhages. Hepatocellular lesions: early alteration of

coagulation factors, cholestasis syndrome.

Renal Signs

- In the initial stages: signs of acute functional renal failure: oliguria, anuria, in relation to the

degree of renal ischemia

- In the late stages: acute renal organic failure: acute tubular necrosis

Diagnostic explorations table no. 17:

Blood Urine Other investigations CBC ionogram glycemia urea, creatinine Astrup lactic acid BT, BD procalcitonin amilazemia GOT, GPT, GGT hemostasis: PT and

aPTT hemoculture

urine summary urine culture

Thoracic X-ray thoracic, abdominal,

cerebral CT Marrow MRI coproculture toxicologic tests ECG ecocardiography

Invasive investigations:

- Invasive blood pressure monitoring

- Determination of PVC (catheter placement in an intrathoracic vein, normal values:

4-8 cm water). Determination of PVC provides information on right atrial venous return

(preload), and the cardiac contractility. A high PVC shows either a relative hypervolemia or

cardiac decompensation, or both. In such situations administration of fluids is not

recommended, rather cardiac tonics in order to increase the cardiac output.

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Table no. 18. Medical monitoring

Clinical Admission 10 min

30min hourly o Paraclinical

FC HLCFR ASTRUPSaO2 Serum ionogramBP Urea, creatineDiuresis GlycemiaCaplillary reload time

Neurologic status Rectal, skin temperature

Diagnosis :

Diagnosis of the state of shock and the evolutionary phase (compensated,

uncompensated, final) is defined by clinical criteria and listed diagnostic explorations and

etiopathogenetic form on the clinical context in which the shock installed.

Early diagnosis of shock requires a high degree of suspicion and knowledge of the

conditions that predispose children to shock. The child’s age can provide the diagnosis key in

conditions such as congenital heart disease, cardiac surgery, immunodeficiency states,

ingestion of certain substances or recent traumatic history raise the suspicion of shock in

children.

Treatment

The treatment is applied according to the etiology of shock and its evolutionary stage

and consists of a complex of therapeutic measures aimed at:

- Removal of the shock-producing factor

- Pathogenetic chain termination by removal of main pathogenetic factors

- Correction of metabolic disorders

In the first hour from the onset of shock, emergency measures to be taken are:

- Ensuring higher permeability of superior air pathways

- O2 administration by mask or in some cases assisted ventilation (positive pressure

ventilation)

- Installation of catheter for PVC monitoring

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- vascular access should be rapidly established, if intravenous approach fails, then

intraosseous approach is indicated. Vascular access makes it possible to correct volemia

through fluid volume expansion.

1. Treatment of hypovolemic shock:

a. volemia correction through fluid administration:

i crystalloid solution (9%0 NaCl or mixture of NaCl 9%0 and 5% glucose 0),

20ml/kgb in the shock with acute dehydration

ii. isogroup blood, izoRH, 10-20ml/kgb in acute dehydration

iii. fresh plasma: 10-20ml/kgb if any sign of CID

iv. colloidal solutions: dextran, albumin, 20ml/kgb

b correction of acidosis and hypocalcaemia:

i antiacid solution: Na bicarbonate, THAM if pH <7.2, the amount of 1-

2mEq/kgb or the formula: base deficit x W (kg) x 0.3, administering half the

amount resulting from the calculation , mixing equal parts with sol.of Dextrose

5% in a period of 2 hours

ii. hypocalcemia: CaCl2 10% 10-20mg/kgb slowly infused (Do not mix Na

bicarbonate)

The amount of liquids and the rhythm of administration are determined by

clinical criteria (BP, pulse, recoloring, appearance of rales, gallop rhythm,

hepatomegaly, increased respiratory effort), and more precisely, according to

the monitoring of PVC.

c. Other therapeutic measures:

i management of hypoxia by oxygen therapy

ii. maintaining the patient temperature around 36.5 to 37.2 degrees C

iii. management of neurological signs by improving cerebral perfusion

iv. prevention and treatment of CID by coagulation factors (fresh blood, fresh plasma),

heparin 25UI/kgb/h when coagulation factor intake does not affect CID

After volume expansion, fluid administration continues for the correction of losses produced

after initiation of rebalancing and physiological needs.

1. Treatment of distribution shock :

Treatment of anaphylactic shock :

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i. applying tourniquets where allergen inoculation occurred at limb level

through sc, im injection, insect bites (applied above the inoculation site

)

ii. placing the patient in Trendelemburg position to prevent ischemia and

irreversible brain damage

iii. Adrenaline - of choice in anaphylactic shock , sc, im , iv

administration in doses of 0.1 mg / kgb (max 0.35 ml ) of solution 1:

1000 it can be repeated at 20min. If allergen inoculation was by

injection or insect bites, first administration is in place of inoculation to

restrain antigen resorption and release of chemical mediators . If after

repeated administration of Adrenaline, BP does not increase,

Noradrenaline can be administered.

iv . volume liquids: colloidal solutions , if after the initial adrenaline ,

followed by Noradrenaline, BP does not increase

v. Oxygen

vi . Miofilin ( 5-6mg/kgb ) - in cases with severe bronchoconstriction ,

where bronchospasm has not responded to the administration of

adrenaline and hydrocortisone hemisuccinate

vii . Antihistamines - with secondary importance in anaphylactic shock

( Claritin , Ketotifen , Romergan , Feniramin , Tavegyl )

viii .tracheostomy – in case of asphyxia in patients with acute laryngeal

edema , followed or not by mechanical ventilation

2. Septic shock treatment :

i. antibiotice conform antibiogramei germenilor izolaţi prin hemoculturi,

uroculturi sau culturi din alte produse biologice

ii. antibiotics according to the antibiogram of germs isolated by blood

cultures, urine cultures and cultures of other biological products

iii. volume expansion according to PVC (whole blood, colloid and

crystalloid solutions)

iv. vasoactive-inotropics where fluid administration does not correct BP;

Dopamine, Norepinephrine, isoproterenol

v. Oxygen-therapy

vi. corticosteroids – when adrenergic function is impaired when, as in the

Waterhouse-Friderichsen syndrome

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vii. Naloxone, an antagonist of epinephrine effective in septic shock

viii. correction of acidosis: Na bicarbonate

ix. Surgery: removal of the source of infection (where surgical approach is

possible), but only after 24 hours of intensive treatment

3. Treatment of cardiogenic shock : addresses the essential pathogenetic links of

cardiogenic shock: pump failure, hypovolemia and changes in vascular resistance

a. fluid infusion: to control volume expansion (counterindicated in hypervolemic

form with PVC> 20cmH2O). NaCl9%0 5ml/kg bis indicated in 30min or

colloids. Fluid administration is mandatory in cases of cardiogenic shock with

acute pulmonary edema associated with PVC <5cmH2O, noting that volume

overload should be avoided

b. Vasoactive inotropics - indicated after volume expansion, if the deficit of tissue

perfusion is maintained or signs of heart failure are present, except for

dysrhythmia or tamponade.

Dopamine is the agent of first choice, natural precursor of adrenaline, with

Vasomotor effects that vary by dose: low doses 1-6 mcg / kg / min, have an effect on

beta and delta receptors, causing renal and mesenteric vasodilation and reduce

afterload . Middle doses of 6-12 mcg / kg / min, have an effect on beta receptors,

increasing the capacity of contraction of the heart, and high doses> 12 mcg / kg / min

have an effect on alpha-and beta receptors, maximum inotropic and peripheral

vasoconstrictor effect, in which case association of vasodilator medication is

recommended.

Other vasoactive inotropic agents: Dobutamine, Isoproterenol,

Epinephrine, Norepinephrine, Na nitroprusside, Nitroglycerin

c. α-adrenergic blockers-indicated in cases evolving with intense vasoconstriction

and increased total peripheral resistance, or the administration of Dopamine is

not followed by signs of improvement in tissue perfusion. Phentolamine

(Regitine) at a dose of 0.5-1mg / kgb/24ore iv infusion. If the shock condition

persists or worsens under Phentolamine treatment, Epinephrine is added.

d. Digitalis-management involves risks to children electrolyte disturbances, heart

failure, acid-base disorders, compromised renal function. Along with medication

administration, acidosis, hypoxia, diselectrolitemia, anemia, are corrected.

4. Support treatment

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a. coagulation abnormalities: may increase hypoperfusion regardless shock

etiology. Monitoring of prothrombin time, partial thromboplastin time, platelets

is necessary. Therapy is aimed at correcting specific coagulation factors. The use

of vitamin K, fresh plasma and platelet transfusion corrects most coagulation

imbalances.

b. gastrointestinal complications: hemorrhages and ileus. Ileus, resulting from

fluid and electrolyte disorders, produce abdominal distension with impaired

respiration. Gastrointestinal bleeding can be prevented by administration of

antacids and / or H2 receptor blockers (omeprazole).

c. Renal support: to prevent acute renal insufficiency, increased circulating

volume, diuretics (mannitol, furosemide). 3-5microg/kgb/min doses of

Dobutamine increase renal flow with beneficial effect in the prevention of acute

renal failure in shock.

d. respiratory support: increasing the amount of oxygen, tracheal intubation

opportunity to improve hypoventilation and hypoxia

Shock treatment is multifactorial. Therapy should be assessed for each stage and

for each type of shock

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CHAPTER IV – COLAGENOSES

Asist. Univ. dr. Grama Alina Corina, Conf. Univ. Dr. Mărginean Oana

INTRODUCTION

Definition: chronic diseases including a heterogeneous group of clinical and pathologic states

that share inflammatory structural changes of the connective tissue throughout the body,

mainly in the blood vessel walls.

There are multiple collagenous diseases: Systemic lupus erythematosus, scleroderma,

Periarterita nodosa, juvenile idiopathic arthritis, Acute articular rheumatism, Vasculitis:

Henoch Sconlein purpura, Wegener granulomatosis, Churg-Strauss Syndrome; Polyarteritis

nodosa, Kawasaki disease, Takayasu arteritis.

Etiology: unknown.

Pathogeny: probably due to body background in each of these conditions there is an

inadequate response to infection, stress and hormonal changes, conducting to the production

of autoantibodies and immune complex formation.

- trigger causes remain a mystery

- primary pathologic immune event initiating the inflammatory vascular disease cannot

be identified in most of the cases

- proinflammatory cytokines involved in the immunologic process include: gamma

interferon, IL 1,2,6,8, tumor necrosis factor (TNF), platelet-growth factor (PDGF),

and the involved cells are macrophages, neutrophils, endothelial cells, Ly T, B, NK,

fibroblasts, smooth muscle cells, platelets

- vascular endothelium has an important role in: hemostatic equilibrium, achieving

vascular tone, vascular inflammatory reactions.

Immuno-pathological mechanisms characterize each type of collagenosis differently:

- formation of pathogenic immune complexes: Henoch Sconlein purpura vasculitis

associated with collagen diseases,

- production of endothelial anticell antibodies: Kawasaki disease,

- production of anti-neutrophil citoplasmic antibodies (ANCA): Churg-Strauss

syndrome, Wegener's granulomatosis,

- pathogenic response of Ly T (CD4 +) and granuloma formation: Kawasaki disease,

Takayasu arteritis, Wegener's granulomatosis.

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Positive diagnosis of colagenosis is difficult to establish because there are specific clinical

and laboratory criteria. Polymorphic profiles exist in colagenoses and any organ can actually

be affected in any type of colagenosis.

Clinical symptoms are uncharacteristic, realizing various profiles with fever, leukocytosis,

accelerated erythrocyte sedimentation rate, arthralgia, rash. The diagnosis should always be

done by excluding other conditions that could present the same symptoms.

Laboratory

1. Routine tests:

- blood count - ESR

- C-reactive protein - Creatinine, Urea

- liver and muscle enzymes (SGPT, SGOT, CPK, aldolase)

- Protein electrophoresis - Urine test

- Test for occult bleeding - Chest Rx, chest CT, MRI

2. Serologic tests:

- Immunoglobulins - rheumatoid factor

- LE Cells - AAN's

- immune complexes - Complement and complement fractions

- Cryoglobulins - Tests for hepatitis B, C, CMV, EBV

- "gold standard": ANCA-c (proteinase 3), ANCA-p (myeloperoxidase)

3. Analytical tests for determining proinflammatory factors – endothelial products

- Il-1,2,6,8, TNF

- VCAM-1 (vascular adhesion molecule)

- ICAM-1 (intercellular adhesion molecule)

- MCP-1 (monocyte chemotactic protein)

- E Selectin

4. Other tests: Angiography, Ultrasound, skin biopsy, scintigraphy with Th / Tc

ACUTE ARTICULAR RHEUMATISM

(AAR, rheumatic fever, Bouillaud rheumatism)

Definition : Systemic inflammatory disease of the connective tissue that occurs as a result of

an infection with group A beta-hemolytic streptococci, mainly affecting the heart, joints and

nervous system, with recurrent development in bursts and self-limited character.

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Etiology: the causative agent is the beta-hemolytic Streptococcus group A :

• Obligatory faringian location (premonitory angina followed by a period of asymptomatic

latency, lasting 1-5 weeks)

• Not all serotypes can cause the disease

• The most common serotypes isolated from AAR patients: Type M (1,3,5,6,14,18,19,24)

• Streptococcal skin infection is NOT associated with AAR

• The epidemic of streptococcal pharyngitis in communities (schools, boarding schools)

can cause AAR peaks.

Predisposing factors:

- background (there is a familial predisposition)

- season (most commonly occurs in winter and spring)

- climate (temperate zone)

- living conditions (overcrowding, socioeconomic standard: it is considered "a poverty-

specific disease")

Pathogeny

The link between Streptococcus group A beta-hemolytic infection in the upper respiratory

tract and cardiac and joint lesion production is still unclear.

Cytotoxicity theory

- Enzymes (streptolysin O) can produce injuries on experimental models: animals

- Can not explain the latency between infection and organ damage

Immunological theory is supported by :

- High antigenicity on streptococcus surface

- Reproduction of the experimental model by using antigens (protein M1, M5, M6,

M19)

Morphopathology: evolving inflammatory AAR process has four phases: Mucoid, fibrinoid

stage, granulomatous and scarring phase.

Clinical manifestations:

• Onset

- Sudden - febrile arthritis or

- Insidious: asthenia, fever, pallor, malaise, weight loss

• The state period is characterized by presence of isolated or various combinations of the

following five major symptoms:

1. Arthritis (polyarthritis)

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- often febrile, migratory, asymmetric

- includes large joints: knee, ankle, elbow, radio-carpal, shoulder

- celsiene signs are present: redness, swelling

- pressure and movement pain, improving on local heating

- it is not accompanied by radiographic changes and leaves no sequelae.

2. Carditis

Essential for the diagnosis:

- occurrence of an organic murmur (apical systolic, diastolic basal, apical mezodiastolic)

- friction or pericardial effusion, radiologically-confirmed cardiomegaly, endocarditis,

myocarditis, pericarditis, generally pancarditis

- common symptoms

» tachycardia » deafness of heart sounds

» cardiomegaly » congestive heart failure: acute pulmonary edema

Consequences: Progressive valve disease.

3. Coreea (Coreea minor, Sydenham disease)

- more common in girls, at about 3 months after streptococcal infection

- remitted within weeks, sometimes years

- emotional lability, abnormal behavior, mental instability

- lack of movement coordination

- reduced school performance

- facial grimacing exarcebate by stress and disappear in sleep

- requires neurological examination

4. Leiner marginated erythema

- is a nonpruriginous erythema, with severe lesions with circular edges and clear central

area

- appears on the trunk and limbs, never on the face

- can occur in waves, over a period of weeks and exacerbates with heat.

5. Meynet’s subcutaneous nodules (rheumatic)

- hard, mobile, painless, nodules

- placed on the elbows, back of the hands and feet

- up to 2 cm in size

- are fugitive

Laboratory: evidence of streptococcal infection is required

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- ASLO - positive a few weeks after streptococcal infection

- ESR, C-reactive protein, alpha-2-globulin - certify inflammation of conjunctive tissue

- Blood count - no diagnostic value

- chest Rx

- EKG, echocardiogram

Positive diagnosis : based on amended Jones criteria (table.no.16)

Table 19 Allen Jones criteria

Major criteria (M) Minor criteria (m)

Evidence of

streptococcal infection -

obligatory criterion (O)

Carditis

Poly (arthritis)

Coreea

Marginated erythema

Subcutanous nodules

Fever

Arthralgia

Presence of acute phase Reactants

(ESR, CRP)

Prolonged PR interval on the ECG

Scarlet fever history

Positive throat swab

Positive ASLO

Positive diagnosis is based on:

2M + O

1M + 2m + O

When neither of the above equations is the case but there are minor criteria and evidence of

streptococcal infections, we have minor post-streptococcal syndrome (MPSS).

Differential diagnosis:

a. When arthritis is present:

- rheumatoid Arthritis

- Reactive arthritis (Shigella, Salmonella, Yersinia)

- Serum disease (history data are important)

- Siklemia (rare in our country)

- Malignancies (osteosarcoma, acute lymphoblastic leukemia)

- SLE

- Lyme disease (borreliosis)

- Gonococcal infection (in older sexually-active children)

b. When differential carditis is made by:

- viral myocarditis - viral pericarditis

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- infective endocarditis - Kawasaki disease

- MCC - mitral valve prolapse

c. Coreea imposes differential diagnosis with the following diseases:

- Coreea Huntigton - Wilson disease

- SLE - cerebral palsy, brain tumors

- tics - hyperreactivity

- encephalitis

Evolution: AAR is a self-limited disease, flare-ups heal spontaneously in 8-12 weeks,

actually within the treatment period.

Treatment:

1. Absolute rest in bed 2 to 3 weeks, followed by another 2-3 weeks of relative rest

- in case of articular forms, school activity will be resumed

- in cardiac forms, rest is extended to 8-12 weeks and school activity will begin after 16

weeks

2. Careful cardiologic monitorization

3. Antibiotherapy after the diagnosis is made and streptococcal infection is confirmed :

- Penicillin G 1.2-1.8 million U/ day injection at 6 hours, for 10 days

- Erythromycin, 40 mg/ kg/ day po at 6 hours, Clarithromycin 15 mg/ kg/ day, 2 doses

for 10 days (in case of an allergy to penicillin)

- a single dose of benzathine penicillin i.m.

4. Anti-inflammatories: salicylates and cortisone

- Aspirin 100 mg / kg / day divided into 4 doses for 7 days, and 75 mg / kg / day for 4

weeks

- Patients with carditis and/or cardiomegaly will be treated with cortisone

Prednisone 2 mg / kg / day divided into 4 doses for 2-3 weeks, then

a. Withdrawal: 5 mg/24h at 2-3 days

b. At this point will be associated with aspirin at a dose of 75 mg / kg / day divided

into 4 doses for 6 weeks

c. In congestive heart failure: fluid restriction, digoxin, diuretics, oxygen.

5. Coreea treatment – symptomatic

- Fenobarbital 2-3 mg/kg/dose at 8 h po

- Haloperidol 1 mg/kg/24h, divided in 2-3 doses

- Diazepam 0,1-0,5 mg/kg/day in 3-4 doses

6. SPSM treatment

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- Anti-infective treatment with penicillin is identical to AAR

- Treatment with aspirin is enough for 4 weeks

- Streptococcus prophylaxis lasts 1 year.

7. Prophylactic treatment

a. Prophylaxis of the first AAR attack:

- correct treatment of scarlet fever

- correct treatment of streptococcal angina

b. Prophylaxis of AAR relapses (American Academy of Pediatrics, Red Book, 2006) aimed

at preventing streptococcus and lasts at least 5 years after acute flare-up:

Benzatinpenicilin im 1x/month

- AAR with confirmed carditis, ecocardiography without heart valve lesions, 10 years

- AAR residual valvular lesions with heart ecocardiography confirmation, until the

patient is 40 years old.

JUVENILE RHEUMATOID ARTHRITIS (JRA)

Definition: chronic inflammatory disease of the connective tissue, of unknown etiology,

occurring frequently in childhood (<16 years), clinically characterized by painful and

swelling joints, functional impotence, ± extraarticular systemic manifestations, lasting ≥ 6

weeks and pathologically by chronic infiltrative-proliferative inflammation of the chronic

synovitis type. Option for the current JRA name is the result of consensus reached in 1997 at

the ILAR Congress (International League Against Rheumatism) from Duban (South African

Republic).

Disease etiology is unknown.

Pathogeny: we can speak of a specific immunological susceptibility and the existence of

trigger factors :

- External trigger: viruses - EBV, parvovirus B19, rubella, bacteria - Listeria

monocytogenes, some types of Mycoplasma

- Host hyper-reactivity to its own antigens

- LyT Hyper-reactivity to bacterial infections

- Genetic predisposition : HLA-DR4 (polyarthritis), HLA-DR5, HLA-DR8 (oligoarthritis)

Aspects of the inflammatory process are manifested through :

- congestion, edema on the internal surface of the synovium, necrosis and fibrosis of

the superficial synovial layer

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- granulation tissue, multiplication and increase in volume of synovial cells

- subchondral osteolysis, resulting in: destruction of cartilage, ankylosis and joint

deformities.

Clinical manifestations:

The onset may be:

Insidious (common): articular manifestations (especially small joints of the limbs,

numbness, swelling of soft parts, morning joint stiffness) and general : asthenia,

fatigue, low grade fever

superacute (especially in infants and small children) : affected general condition,

fever

atypical (rarely) : arthralgia with local inflammatory signs, often monoarticular

arthralgia

Juvenile rheumatoid arthritis diagnosis during the onset can sometimes be extremely difficult

because of the initial symptomatic polymorphism.

Clinical forms:

I. Systemic form (Still's disease) more frequent in males and young ages (1-3 years)

characteristic: discrepancy between general extra-articular manifestations and scarcity of

articular ones (occurring late)

• General manifestations :

- prolonged fever, septic aspect responding to cortisone treatment

- erythematous rash - nonpruritic maculopapular elements in various locations, except

the face, fugitive nature

- Koebner phenomenon: new lesions appearing in minor superficial injuries or after

bath

- moderate adeno-hepato-splenomegaly

- pleuritis, pericarditis, myocarditis, encephalitis

- neurological symptoms (seizures, psychotic disorders)

• Joint manifestations (polyarthritis) may occur 4-6 months after the onset of the general

ones, making it difficult to diagnose the disease in the early stages (joint-radiocarpal,

tibiotarsal, knee)

II. Pauciarticular form (oligoarticular)

- affects 1-4 large joints (knees, ankles, hands, hip), asymmetric, moderate severity

- general signs (fever, hepatoslenomegaly) if existing, they are not severe

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- major evolutionary risk is represented by the chronic iridocyclitis

- monoarticular impairment raises issues of DD with bacterial arthritis

III. Polyarticular form :

- articular manifestations that occur early in any joint (≥ 5 joints affected) except

vertebral dorso-lumbar joints

- morning stiffness, important joint deformity

- presence of rheumatic nodules on the extensor of the elbow

- rare extra-articular manifestations

- FR positive and FR negative forms (forms are either HIV (+) or HIV (-) on the

onset and do not change in the course of the disease)

IV. Enthesitis-associated arthritis :

- occurs more frequently in boys over 8 years old, 50% of cases being HLA-B27 positive

- Arthritis affects large joints (hips, knees, shoulders), lumbar spine, sacroiliac joints

- associated with enthesitis

- eye impairment occurs in 10% of cases, being of acute type - Previous acute uveitis

V. Psoriatic form

- in 5% of cases, patients may develop: arthritis, psoriasis, dactylitis, nail abnormalities.

Laboratory and paraclinic examinations:

- CBC: hypochromic anemia, leukocytosis, thrombocytosis

- Acute phase reactants: ESR, CRP, fibrinogen, alpha 2 globulin - especially in systemic

forms

- Rheumatoid factor present in HIV-positive polyarticular forms

- Antinuclear antibodies (ANA)

- Seropositivity is associated with chronic uveitis.

- Other examinations :

• bone radiography: osteoporosis, periostitis, periarticular soft tissue swelling

subsequently subchondral erosions, joint space narrowing (stages I-IV of articular

manifestations)

• joint puncture + cytology, biochemistry and immunologic examination of the joint

fluid (rarely indicate and contribute to septic arthritis DD)

Positive diagnosis :

based on clinical findings, laboratory data and exclusion of other diseases (required AAR

and Lupus erithematosus)

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the following criteria are used in the absence of specific tests:

- time!!!- Persistence of mono / polyarthritis > 6 weeks (3 months, according to other

specialists) if other diseases had been excluded;

- leukocytosis, anemia, elevated ESR, positive acute phase reactants (fibrinogen, CRP)

nonobligatory;

- presence of "rheumatoid factor" (anti-γ-globulin autoantibodies emphasized through

Latex and Waler-Rose test), present especially in polyarticular forms, with prognostic

role (HIV forms - most severe);

- presence of antinuclear antibodies, especially in cases of chronic iridocyclitis

- synovial fluid extracted by puncture is yellow-green, turbid, of low viscosity with 10-

50.000/mm3 leukocytes (about 75% polymorphonuclear)

- initial X-ray examination shows edematous soft tissues, osteoporosis without erosive

joint changes

Differential diagnosis with other arthritis :

- Reactive arthritis : acute nonsuppurative inflammatory arthropathy, sterile, appears

after a distant infection in people with a certain genetic predisposition: digestive

infection with Salmonella, Shigella, Yersinia or genital infections – Chlamydia

- Osteomyelitis

- Autoimmune hepatitis

- Lyme disease (borreliosis)

- Legg-Calve-Perthes Disease

- Inflammatory bowel disease

- Acute lymphoblastic leukemia, TBC

- Lupus erithematosus, Schonlein Henoch purpura

- Joint Injuries

Treatment: The proposed objective is to achieve medication-based remission with minimal

risk of adverse effects; multidisciplinary team!!!

1. Hygienic-dietary treatment:

- normocaloric, normoglucidic, normoprotidic diet

- in case of corticotherapy: further restriction of sodium and supplement of protein,

potassium, calcium and vitamin D3

- physical exercises as tolerated by the patient.

2. Etiologic treatment – not known

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3. Pathogenic treatment

• NSAIDs 4-6 weeks: Aspirin, Ibuprofen, Diclofenac, Indomethacin, Piroxicam

(attention to adverse effects) ± intraarticular triamcinolone hexacetonid

• steroidal anti-inflammatory only in systemic forms, chronic iridocyclitis and

NSAIDs-resistant forms

• Methotrexate (MTX) - 10-15 mg/m2/week administered orally or parenterally, the

therapeutic benefit is evident after 3-4 weeks, maximum response is achieved only

after 3-6 months of treatment

• Cyclosporin A is used in the systemic forms of JIA that are resistant to MTX

treatment

• Etanercept (Enbrel)

- antagonist of tumor necrosis factor produced by recombinant DNA technology is

indicated in severe forms of systemic JIA / polyarticular refractory to MTX

treatment or in the presence of corticosteroid-related toxicity with prolonged

administration of high doses

- 0.4 mg / kg sc 2 times/ week, alone or in combination with MTX

- response is observed in 2 weeks - 80% of children with polyarticular onset have

favorable response

- demonstrate outstanding benefits

- the only approved biologic agent and covered by a national program of CNAS,

Etanercept does not guarantee remission in all cases

4. Balneophysiotherapy and kinesitherapy – important as an adjunct to preserve joint

movement, maintain joint force

5. Surgical: in pauciarticular forms not responding to conservative therapy

6. Psychotherapy: as optimal as possible integration of the patient in his environment,

social security in order to ensure compliance to treatment.

Evolution is unpredictable, with exacerbations and remissions for many years :

- polyarticular forms have prolonged development, HIV forms are frequently

accompanied by disability, the sero-negative can have better evolution;

- oligoarticular forms in children under 6 years will develop chronic uveitis;

- systemic forms are difficult to control.

Complications: rare but severe - ankylosing joints, growth retardation, skeletal deformities,

cecity (due to chronic iridocyclitis), psychological complications

Prognosis – factors of reserved prognosis :

154

- active systemic disease at 6 months after onset

- polyarticular onset or development

- female

- positive Rheumatoid factor, positive antinuclear antibodies

- tenosynovitis, subcutaneous nodules

- early impairment of small joints of the hands and feet

- rapid emergence of joint erosion.

Bibliography :

1. Arion C., Dinu B. Boli inflamatorii sistemice în Ciofu E., Ciofu Carmen – Pediatria Tratat, Ed. Medicală, Bucureşti,

2001, p. 948-971

2. Man Sorin C., Nanulescu Mircea V. – Pediatrie practică, Ed. Risoprint, Cluj-Napoca, 2006, p. 513-530

3. Militaru Andreea - Artrita juvenilă idiopatică în Nanulescu M. - Protocoale de diagnostic și tratament în pediatrie,

Ed. Medicală Amaltea, București, 2013, p. 321-326

4. Miller L. Michael, James T. Cassidy – Rheumatic Diseases of Childhood în Kliegman R.M., Behrman R.E., Jenson

H.B. et al (eds) - Nelson Textbook of Pediatrics, 18 th edition, Saunders Elsevier, Philadelphia, 2007, p. 995-1052

5. Miller L. Michael - Approach to the Child with Joint Pain, but Normal Physical Examination, 2006

6. Muntean I. - Vademecum de Pediatrie, Ed. Medicală, București, 2007, p. 375-388

7. Popescu V. – Algoritm diagnostic și terapeutic în pediatrie, vol I, Ed. Medicală Amaltea, București, 1999, p. 715-

724

8. Popescu V. – Algoritm diagnostic și terapeutic în pediatrie, vol II, Ed. Medicală Amaltea, București, 1999, p. 690-

702

SCHӦNLEIN-HENOCH PURPURA

Definition: immune vasculitis, with peak incidence between 4-15 years, with skin, joint,

abdominal and renal determinations by affecting small arterioles and capillaries.

Etiology: Unknown; the disease may occur secondary to a bacterial infection (streptococcal),

viral (measles, hepatitis), after some foods (milk, eggs, chocolate), drugs (penicillin, aspirin),

stinging insects.

Pathogeny: generalized vasculitis of arterioles and capillaries with <2 mm diameter,

produced by immunological mechanisms similar to those of collagenoses (in lupus

erythematosus and periarterita nodosa only arterioles are affected).

Clinical manifestations: the onset may be slow or acute in 50%, by fever or low grade

fever, headache, malaise, abdominal pain. State period is marked by four different clinical

manifestations (skin, joints, abdominal, renal) that may either occur all or in various

combinations.

1. Skin manifestations

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- urticariform petechial maculopapular layout with hemorrhagic center not disappearing

under pressure (hemorrhagic purpura)

- hemorrhagic center can be the size of a pin to that of a pea and evolve gradually from red

to pale

- purpura is present in all cases, symmetrically on extremities, especially on ankles and

buttocks, around the knee joints and external faces of the limbs

- purpura is "palpable" as opposed to the ITP

2. Joint manifestations: appear in 2/3 of the patients and affect one or more joints

- ankle and knee joints are most commonly affected as polyarthralgias

- the joint may be swollen, warm and painful to movement (arthritis), sometimes with

synovial collection

- joint symptoms usually disappear within a few days

3. Abdominal manifestations (Henoch form)

- abdominal cramps

- vomiting

- occult bleeding or melena

- sometimes haematemesis; due to edema and bleeding in the gut wall, invagination or

bowel perforation may sometimes occur

4. Renal manifestations: occur in 20-50% of cases and are crucial for prognosis;

- may occur in the first week of illness or late

- micro or macroscopic hematuria ± cylindruria

- proteinuria

- rarely, oliguria, edema, nitrogen retention, hypertension and nephrotic syndrome

A. Laboratory

- leukocytosis, accelerated erythrocyte sedimentation rate, posthaemorrhagic

anemia

- changes in urinary disorders: hematuria, albuminuria, leucocyturia

- occult hemorrhages in stool

- hypoalbuminaemia in severe forms

- β-hemolytic streptococcal (+) in throat swab, incresed ASLO

- tourniquet test (+) in 25% of cases

B. Positive diagnosis: is based on clinical manifestations in conjunction with normal

hemostasis tests.

C. Differential diagnosis

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- purpura may be mistaken for that of ITP but in this case the platelet count is low

- joint manifestations will differ from those in the AAR, JRA

- abdominal pain requires differential diagnosis with other causes of acute abdomen

(cecal colic, invagination, intestinal perforation)

- renal manifestations will differ from those of AGN (acute glomerulonephritis),

especially the poststreptococic type

D. Treatment

Hygienic dietary measures

- Bed rest and regular, light food - 3-6 weeks while the disease heals; if renal

manifestations prevail, AGN diet is adopted.

- If the β-hemolytic streptococcus is present in the pharyngeal exudate or ASLO titre is

increased, penicillin G 50-100000 U / kg / day is administered for 10 days.

Treatment

Most cases receive only symptomatic treatment:

- for edema, fever, rash

- Arthritis - Aspirin 100 mg / kg (alleviates joint phenomena)

- antihistamines

- capilarotrofic

- sedatives

Corticotherapy:

- In renal forms, especially when hematuria is persistent, low doses of heparin and

prednisone are administered for 3 weeks

- When abdominal colics are in the foreground, a short cure (about 7 days) of

prednisone (1-2 mg / kg / day) is administered; prednisone reduces swelling and the

intestinal hemorrhage and thus prevents intestinal invagination.

Immunosuppressive therapy: in case of persistent nephritis

Anticoagulants and immunosuppressives: in installed purpuric nephropathy

Evolution and prognosis: in most cases the evolution is favorable, the disease heals within

3-6 weeks. There are cases with 1-3 episodes of purpura; the disease can evolve with periods

of remissions and exacerbations.

In some cases the disease can take months and years.

Overall prognosis is excellent; one third of the cases have a recurrence within the first 6

weeks. Prognosis depends on renal involvement; sometimes cases may develop for months or

years leading to chronic glomerulonephritis.

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KAWASAKI DISEASE (KD)

Synonyms: cutaneous-mucous lymphadenopathy syndrome, infantile polyarteritis nodosa

Definition: febrile vasculitis affecting the coronary vessels with propensity.

KD is found worldwide. Asian populations are at increased risk of developing the disease.

The peak incidence is between 9-12 months, and 50% of cases occur under the age of 2 years.

Epidemiology:

Japan: incidence: 100/100.000/year children under 5 years; bimodal seasonality: January and

June

Taiwan: Incidence: 66/100.000/year children under 5 years

USA: Incidence 17-18/100.000 children under 5 years

UK: Incidence: 5.5 / 100,000 children under 5 years

Diagnostic criteria

Fever lasting for at least five days (100%), plus four of the five criteria listed below:

1. Bilateral bulbar conjunctival congestion (85%)

2. Changes of buccopharyngeal mucosa, raspberry tongue (90%)

3. Skin changes of the extremities (palmar erythema / edema, desquamation of fingertips)

4. Rash on the trunk

5. Unilateral cervical lymphadenopathy non suppurating

Severe cardiac impairment is manifested by:

• Myocarditis (50%)

• Pericarditis - in the acute phase

• Coronary aneurysms that occur in the 2nd and 3rd week with rupture risk on Ø> 8 mm

• KD should be considered as differential diagnosis when are existing:

• Fever for several days + rash + serous conjunctivitis in a child under the age of 1 year

There is a possibility of error diagnosis in the following situations:

- a rash from antibiotics

- a sterile pyuria after partial treatment for UTI

- CSF with pleocytosis for a typical viral meningitis.

Treatment:

- association of steroids if fever persists after 2 doses of IVIG

- Infliximab (Remicade-monoclonal antibody against TNF)

- plasmapheresis

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CHAPTER V - DISEASES OF THE DIGESTIVE SYSTEM

Conf. Univ. Dr. Mărginean Oana, Asist. Univ. Dr. Pitea Ana Maria

GASTROESOPHAGEAL REFLUX

Definition: repeated flow (passage) of the gastric contents into the esophagus

• regurgitation

– the flow of the stomach content into the pharynx/the oral cavity sometimes protrudes,

generally without any effort

– vomiting

– pharyngeal receptor stimulation triggered by gastric contents

• rumination

– remastication/redeglutition of the regurgitated gastric contents in the mouth

Etiopathogeny: GERD is common (1/500 live births) in the first months of life: 30 - 40% of

the infants present regurgitation (small amount) and more frequently the premature and

dismature ones.

Infant reflux becomes evident in a few months with a peak at 4 months, resolving to 12-24

months.

Genetic predisposition associated with oesophagitis, hiatus hernia syndrome Barrett

adenocarcinoma. It is an autosomal dominant transmission, localized on chromosome 13q14.

Pathogenic mechanisms

1. Lower esophageal sphincter incompetence (LES) which maintains a pressure of 15-40

mmHg (gastric pressure: 6-10mmHg); pressure changes causes reflux.

2. Extension of esophageal clearance: hiatal hernia, malposition of the cardia and

gastric tuberosity, causes a prolonged peristaltic and even aspiration of gastric contents.

3. Delayed gastric emptying, found in acid levels after meals which are rich in lipids.

GERD once installed maintains the lower esophageal sphincter incompetence,

determining motor failure mechanisms and a prolonged contact of the esophageal mucosa

with the gastric pepsin, bile salts, and the pancreatic proteolytic enzymes; while the

esophageal mucosa erodes, causing peptic esophagitis.

Clinical symptoms

Newborn and infants, 80-90% of cases, regurgitation and vomiting occur (the bloody ones

are a sign of esophagitis); commonly associated with respiratory symptoms: bouts of apnea,

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recurrent cough, nocturnal wheezing, bronchospasm and can be wrongly labeled as asthmatic,

obstructive bronchitis. Infants are irritable, anorexics, have colic, do not gain weight, they

show distrophy, in small infants sudden death may occur.

Food refusal in infants appears to be associated with GERD.

In older children GERD is rarely manifested by epigastric pain, heartburn (dominant

symptoms), dysphagia, vomiting, chronic, recurrent pneumonia (vacuum), areas of gastric

metaplasia (Barrett epithelium) or peptic stricture asymptomatic post oesophagitis.

Occasionally both infants and preschool children present contortions of the neck or head and

opisthotonus posture, which can be mistakenly interpreted as seizures or neurological

distress. This is called Sandifer’s syndrome.

The following can be associated with reflux: otitis media, sinusitis, lymphoid hyperplasia,

nodules of the vocal cords, laryngeal edema.

Diagnosis

Laboratory investigations

1. Radiography (esogastric) with a contrast substance provides information about esogastric

junction: hiatal hernia, Hiss obtuse angle, stenoses, and compressions

2. Oesophageal manometry evaluates the pressure of LES.

3. Scintigraphy with technetium (Tc99) allows visualization of the bile reflux, flow in the

bronchial tree and esophageal clearance.

4. Esophageal pH monitoring is done using an electrode placed in the esophagus,

determining the esophageal pH for 16-24 hours (n = 5-7, the stomach has a pH = 2); in

GERD esophageal pH is less than 4. The number and duration of flows will be recorded. In

GERD there are 2 flows/hour with a pH below 4 the slumping being present in more than 5%

during the determination.

5. Esophageal endoscopy (with flexible fiberscopes) allows the visualization of the lesions of

the esophagus and collection of biopsy material for histological diagnosis (there are four

degrees of peptic oesophagitis), diagnosis of hiatal hernia, and diagnosis of the

complications: esophageal stenosis.

6. Intraluminal impedance is difficult to perform, helps in the diagnosis of nonacidic reflux.

7. Laringotraheobronhoscopia assesses signs associated with GERD, posterior inflammation

of the larynx and the vocal cords, highlighting silent aspiration.

8. Ultrasonography (> 3 slumpings/20min of examination) and oesophageal scintigraphy

Differential diagnosis is made with:

- recurrent wheezing - asthma

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- apnea attacks - gastritis

- neurological suffering, seizures - acute laryngitis

- infections, allergies - cystic fibrosis

Complications: oesophagitis, Barrett's esophagus, esophageal stricture, haematemesis,

aspiration pneumonia, anemia.

Treatment

1. Hygienic-dietary in infants

A. Dietary treatment

- changing the preparation of milk powder (HA, hydrolysed)

- substantial increases of meals with milk

a. with nutritional value: rice flour; a dose 5-15 g/100ml milk

b. no nutritional value: carob seed flour, pectin- cellulose

B. Postural therapy

• prone anti-Trendelenburg

• supine anti-Trendelenburg

• position change

2. Medicamentary

- motility disorder control - reducing the frequency of slumpings (β receptor agonist of

GABA) - Baclofen 0.6 mg/ kg, 3-4 doses/ day

Prokinetic (acetylcholine), increases oesophageal peristalsis and LES tonus, accelerates

gastric and duodenal emptying:

- Metoclopramide 0,1 mg/kg before meals, Cisapride: 0,2 mg/kg/day - 3 doses - 20-30`

before meals.

- Erythromycin 5-10 mg/ kg/ day ± Ranitidine 5-10 mg/ kg/ day - 3 intakes before

meals, 1 month.

- Domperidom (Motilium) has fewer adverse effects on the CNS, but has similar side

effects as Cisapride (intravenously administration of QT prolongation): children: 0.8-

1 mg/ kg/ day in 3-4 doses, 15-30 minutes before meals, adults: 10-20 mg/ dose, 30

minutes prior to meals and at bedtime

Inhibitors of H2 – receptors in mild and medium forms of oesophagitis at least for three

weeks: Ranitidine 5 mg/ kg/ day - 2 doses, Famotidina 1 to 1.5 mg/ kg/ day - 2 doses.

Proton pump inhibitors in case of severe oesophagitis: Omeprazole (Losec, Ultop), Controloc

(Pantoprazole) 0.7 mg/ kg/ day - single dose - 4 weeks (8 weeks).

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In older children and adolescents, with frequent recurrence, the medication should be

continued for another 6 months -a single small dose.

Sucralfate – for mucosa healing.

Respond poorly to drug therapy: children under 18 months old if there is hiatus hernia or

neurological disabilities.

3. Surgery - indications: persistent oesophagitis at 6-8 weeks of medical treatment

oesophageal stricture, persistent vomiting, malnutrition, seizures, apnea, chronic lung disease

or lack of response to medical treatment for 2-3 months.

Evolution and prognosis

In mild to medium forms it occurs through dietary and medicinal healing. In complicated

cases (aspiration pneumonia, anemia) the evolution is extended.

The prognosis is good.

GASTRITIS IN CHILDREN

Definition: inflammatory processes in the gastric mucosa, with histopathological arguments,

commonly associated with peptic ulcer and duodenitis.

Etiopathogenical classification

• infectious

- bacterial: H.pylori, H. heilmannii

- viral: CMV (b.Menetriere), v.herpetic

- fungi, parasites

• non-infectious, immune

- eosinophilic gastritis

- gastritis in Henoch-Schonlein

- gastritis in celiac disease

• idiopathic

- gastritis in Crohn's disease

- collagenous gastritis

• reactive

- by bile reflux

- medicines, toxic

- mucosal prolapse, gavage probe

• vascular

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- from portal hypertension

• metabolic diseases

- chronic granulomatous disease

Contributing factors: alcohol, smoking, fast chewing - poor teeth, too cold or too hot food,

food abuse.

Pathogenesis - imbalance between aggressive factors and mechanisms of defense. Among

aggressive factors we mention acid secretion, pepsin secretion, stress, aspirin, NSAIDs, H.

pylori and among defense mechanisms of the mucosa: mucus and bicarbonate secretion,

mucosal blood flow, prostaglandins (PG) (which stimulates other mechanisms).

Clinical symptoms

Onset can be fast, characterized by nausea and vomiting, or slow, non-ulcer dyspepsia (NUD)

without endoscopic signs, epigastric pain, rhythmed by food intake, as in UDS (ulcer

dyspepsia syndrome), rarely diffuse or periumbilical, frequent nausea, consequence of bile

salts, pancreatic ferments (by duodeno-gastric reflux), food, bilious, bloody vomiting

(hematemesis is relatively characteristic of H. pylori); anorexia, regurgitation and heartburn,

bloating, constipation or diarrhea completes the picture NUD - functional dyspepsia.

Positive diagnosis

Measuring acidity, gastric barium examinations are inconclusive. The positive diagnosis

system requires the criteria of the Sydney system (1994).

Endoscopic criteria: erythematous-exudative gastritis, erosive, atrophic, bleeding, reflux or

folds hypertrophy.

Histological criteria: acute gastritis, chronic, special (eosinophilic, lymphocytic,

granulomatous); in acute forms the infiltration is with neutrophils, when in chronic forms is

lymphoid.

Differential diagnosis

Clinical - other causes of recurrent abdominal pain.

HELICOBACTER PYLORI GASTRITIS

Nobel Prize for Medicine in 2005.

When the infection occurs an ulcerous or non-ulcerous dyspepsia syndrome appears and as it

becomes chronic the symptoms alleviate.

Most infections are asymptomatic. Slow infection of the gastric mucosa begins in childhood,

with an annual rate of infectivity of 1%, showing the origin of childhood infection

prevalence.

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The phenomenon of "cohorts" is known: infection of 20 years is about 20%, at 50 is 50%.

Maximum prevalence is at the age of 3-4; 10-20% of children have IgG, IgA positive (H.

pylori colonization). H.p. is the most frequent cause of gastritis, ulcersIn 1994 WHO situates

the infection in group I carcinogen; gastric cancer is the second leading cause of cancer

death. The incidence of gastritis in children is 1% in developed countries, 10% in developing

countries.

Current assumptions

The etiology of gastroduodenal diseases include environmental factors, genetic

predisposition consisting of genetic susceptibility to infection and DNA repair mechanisms

related to carcinogenesis, respectively host polymorphism - CZP2C19 and MDR1 genes

that influence the pharmacokinetics and efficacy of treatment with proton pump inhibitors.

The source of infection is the human being (and possibly cats). The route of transmission is

the fluid one. The weight of infection in urban areas is 70%, the water in the system is

infected; bacteria live 16 hours in the water, mostly in cold water, a possible role have

carbonated juices.

Contamination may be oral-oral or fecal-oral, the infection is more common in countries with

lower socio-economic conditions (congestion, local children).

Diagnosis

1. Biopsy – bioptic fragment analysis sampled with scopes.

Histologically the spiral H. pylori microorganism can be identified by Warthon - Starry

argentic staining (very sensitive and specific), modified Giemsa staining, acridine orange

staining and cresyl violet.

Rapid urease test identification of H. P. from the gastric mucosa specimens from different

urea; the colour change occurs in 30 minutes; with a turn in 24 hours if the number of

bacteria is low.

Tests for infection deceleration:

2. Urea breath test labeled with C13, C14. Principle: urease produced by H. P. catalyzes the

hydrolysis of urea into NH3 and CO2 (2 samples of 20 in 20 min.), rapidly normalized after

resolution of infection, evaluating the effectiveness of treatment, tests that detect the presence

of specific Ig remain positive up to 6 months.

3. Serological tests detect antibodies

Elisa - IgG, IgA serum. IgG serum has a specificity below 50% in children under the age of

7, similar with the specificity in adults after the age of 12.

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4. Determination of specific IgG in saliva has a specificity of 82%, sensitivity 93%, varying

according to the used reagents.

5. Immunoassay determination of Atg from stool (HpSA) (H. pylori stool antigen test)

with polyclonal antibody, or recently - monoclonal ones, is a non-invasive method, with a

sensitivity of 91-98% and specificity of 83 - 100%.

6. Immunological tests PCR and DNA- enzymes: PCR with amplification - detected by gel

electrophoresis the use of colorimetric detection, a faster method, which may be automated.

Treatment

The best diet in acute forms is abstinence from any food for 12 to 24 hours, if hardly bear

hunger - tea, juices, soups are allowed, on the second day one can try toast, cottage cheese,

grated apple, rice, and then gradually introduce vegetables, meat and other, after tolerance.

Medications

The North American Society of Pediatric Gastroenterology and Nutrition (2000) recommends

combinations.

- Amoxicillin 50 mg/ kg/ day in 2 doses + Clarithromycin 15 mg/ kg/ day - 14 days + 2

doses of proton pump inhibitors (omeprazole, pantoprazole) 0.7 to 1 mg/ kg/ day - 2

doses - 1 month.

- Amoxicillin 50 mg/ kg/ day - 2 doses + Metronidazole 20 mg/ kg/ day - 2 doses - 14

days + proton pump inhibitors (Omeprazole, pantoprazole) 0.7 to 1 mg/ kg/ day - 2

doses - 1 month.

- Clarithromycin 15 mg/ kg/ day - 2 doses + Metronidazole 20 mg/ kg/ day - 14 days + 2

doses of proton pump inhibitors (Omeprazole, pantoprazole) 0.7 to 1 mg/ kg/ day - 2

doses - 1 month.

The scheme has good results in the eradication of the infection (80%). Some schemes use:

Clarithromycin, Erythromycin, Tetracycline.

Anti-infective therapy is associated with antisecretory for 3-8 weeks:

a). Proton pump inhibitors: Omeprazole 0.7 mgkg/ day - single dose after lunch

b). H2 receptor inhibitors: Ranitidine 5 mg/ kg/ day or Nizatidine -2 doses (Axid) 2-3 mg/ kg/

day - 2 doses, Cimetidine 5 mg/ kg/ day after meals; Famotidina 1-1.5 mg/ kg/ day - single

dose.

The treatment of other gastritis

Objective: to maintain the pH above 4 with antacids and antisecretory.

In gastroesophageal reflux prokinetics are administered.

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Estimation of healing is done after two months, usually after treatment clinical and

histological recovery

Prognosis - favorable.

Prophylaxis: general rules of food hygiene, avoiding alcohol and smoking, and in future

vaccination of children for H. pylori.

ULCER DISEASE (peptic ulcer)

Definition: the gastric or duodenal location of a loss of substance (solution of continuity) at

the level of mucosa. Clinically we encounter the dyspeptic ulcer syndrome with food

rhythmicity and seasonal periodicity.

The etiology is multifactorial.

Hereditary factors: 1/3 of children have degree I, II relatives who have suffered or suffer from

ulcers.

Infectious factor ("rarely - ulcer without H. pylori "); eradication of the bacteria decrease

recidivism (60-70% to 1-2%); H. pylori is present in 70% of cases in gastric ulcer and over

90% in the duodenal one.

The stress factor: Cushing stress ulcer by CNS injury, Curling’s ulcer in burns, emotional

ulcer

Ulcerogenic drugs: aspirin, NSAIDs, corticosteroids.

Contributing factors: food abuse, tobacco, coffee, alcohol excess.

Pathogenesis: (see gastritis).

Clinical symptoms

In newborn hematemesis, melena, perforation are the first signs; usually there is sepsis,

severe respiratory distress.

Between the ages of 1-6 the primary symptom is vomiting, pain - especially in the

periumbilical region, abdominal discomfort (irritable bowel syndrome or functional

dyspepsia), and gastrointestinal bleedings are relatively common.

Over the age of 6 the triad appears: abdominal pain, vomiting, gastrointestinal bleeding, most

commonly after 12 years.

The onset may be sudden or insidious (approximately in equal proportions).

Duration: in this stage the dyspeptic ulcer syndrome occurs (DUS) in 2/3 of cases, rhymed

nutrition pain, shortly after in gastric ulcer, approximately 3 hours after meals and at night in

duodenal ulcer. The intensity of the pain is variable (cramp, colic) and it is located in the

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epigastric region with radiation to the hypochondrium, septic iliac (confusion with

appendicitis!); the painful episode is followed by calmness, repeatable in spring (very rarely

in children it may occur in autumn). Sometimes the pain is diffuse or periumbilical and it is

associated with a feeling of fullness, heartburn, malaise, neuro-vegetative disorders. In case

of sudden onset gastrointestinal bleedings and perforations are common. Patients diagnosed

with peptic ulcer rarely present abdominal pain given by the perforation itself or symptoms of

a secondary pancreatitis may be present to a posterior penetrating ulcer.

The pains are often dull, than become sharp and are associated with heartburn. The pain may

last from minutes to hours, and can evolve with exacerbations or remissions lasting weeks or

months. Nocturnal pain occurs mostly in older children. Positive history with aspirin was

detected in 33% of cases.

Positive diagnosis

Highlighting ulcer niche at the radiological examination- has lost importance.

Endoscopic examination with the fibroscope: ¾ of duodenal ulcers are situated on the

anterior wall of the duodenal bulb; in over one third of the cases in the sampled biopsy H.

pylori is found.

The ulcer crater often presents gray-whitish debris and it is brownish-if there is bleeding. The

bottom of the ulcer is round, with straight-edges - benign ulcer. Ulcers can be round, oval,

oblong or linear.

Differential diagnosis

It is made in other causes of acute or chronic abdomen pain

Complications: hematemesis, melena, perforation, pyloric stenosis (very rare in childhood).

Treatment

1. Dietetic in acute phases, initially – milk, then vegetable soups, boiled egg, toast, later meat

and other foods; diet has lost its importance.

Prohibitions: alcohol, coffee, carbonated water, smoking.

2. Medicamentary

- Alkalines Ulcerotrat, Trisilicalm, Dicarbocalm, Gelusil, Maalox, Alumag. Pain

killers- an hour after eating (acid secretion is the highest, the effect takes about 3h, on

the "empty stomach" the effect is 30 min., together with the antisecretory maintains a

pH above 4.

- Anti-infective therapy - As with gastritis, for the eradication of H. pylori one of the

three schemes is used

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- Antisecretory: Omeprazole 20 mg/ day 1 caps/ day (children 0.7 mg/ kg/ day) 4 weeks

in duodenal ulcer, 8 weeks in the gastric one; Ranitidine 5 mg/ kg/ day - 2 doses;

Nizatidine (Axid) 2-3 mg/ kg/ day - 2 doses; Famotidine 1-1.5 mg/ kg/ day as a single

dose during meals, 4-8 weeks (rarely 8-12 weeks); Cimetidine 5 mg/ kg/ day after

meals, with the disadvantage that inhibits the liver enzyme (cytochrome).

- Cytoprotective agents Sucralfate has good results in some forms.

- Other agents: parasympathetic (Scobutil), anticholinergics (Metoclopramide) sedative

agents used to treat specific basic diseases (burns, head trauma, sepsis)

3. Surgery is indicated in complications or failure of medical treatment.

Evolution and prognosis can record relapses, but the overall prognosis is good.

It is possible that a gastric cancer at the age of 40-50 be the continuation of a gastritis or a

gastric ulcer from childhood.

THE MALABSORPTION SYNDROME

Definition. The syndrome encompasses a wide range of digestive disorders (>100) that have

as a common feature, the inability to supply the body (partially or completely) with trofins,

vitamins, minerals and water.

(The classification in malabsorption and maldigestion sundromes is not a current one, their

confusion being proven).

The consequences of the syndrome are of deficiency, having various nutritional and

metabolic effects.

The syndrome comprises, roughly, the following mechanisms:

1. Intraluminal digestion (modification of motor and gastric secretory function;

pancreatic insufficiency; hepatobiliary disorders; short bowel; intestinal

dysbiosis).

2. Intestinal absorption.

3. Blood or lymphatic transport

4. Exudate and intestinal motility.

5. Synthesis and altered catabolism of food principles

6. Unknown mechanism.

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CYSTIC FIBROSIS (Cystic fibrosis – C/F; Mucoviscidosis; Cystic fibrosis of the

pancreas)

It is a chronic disease characterized by airway obstruction and chronic infections and

maldigestion; it is an autosomal recessive genetic disease characterized by the dysfunction of

the exocrine gland epithelium, with a high frequency: 1 case/ 2000 births. It is more common

in white people of northern Europe, North America, Australia and New Zeeland.

The etiopathogeny – the C/F gene located on the long arm of chromosome 7 (the largest

gene), it is the gene that codifies the synthesis of membrane glycoproteins, called

“Transmembrane conductance regulator of C/ F” (CFTR), is placed at the apical poles of

secreting or resorptive cells, facilitates transmembrane transport of Cl-, 40 mutations, which

may affect the gene..

Abnormal CFTR determines an excess of Cl- şi Na+ at the level of the glands of various

organs, the secretory epithelium of the mucous glands becomes waterproof for Cl- ions (then

Na+, K+ and water) resulting in viscous fluids.

A particular situation is represented at the level of the serous glands (sweat and salivary

glands), the resorptive ducts being affected; the epithelium is impermeable for Cl- ions, the

final sweat will contain high amounts of Cl- (secondary to Na+), the water content being

normal.

Types of C/F: without exocrine pancreatic insufficiency and with exocrine pancreatic

insufficiency (85%).

Pathophysiology: bronchial mucous gland hyperplasia, cystic pancreatic ducts surrounded

by fibrous tissues, aspect of biliary cirrhosis and other changes that cause pluriorganic

sufferings.

According to the alteration mechanism of the CFTR protein function there are:

Class I mutations, that determine the synthesis of some defective, unstable CFTR

proteins, with little or no function

Class II mutations, because of which the protein would be incompletely glycosylated

(immature), without the correct spatial conformation, undetected at the cell surface;

the most frequent mutation (70%) F 508: deletion of three base pairs from exon 10

of the gene ausing loss of phenylalanine at position 508 of the primary sequence of

CFTR.

Class III mutations, CFTR proteins having defective adjustments

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Class IV mutations, the conductivity of the formed CFTR proteins being affected in

the apical membrane.

Class V mutations – reduced production of CFTR.

Class VI mutations – stressed turnover on the cells surface

Class I-III mutations cause severe diseases with reduced survival, whereas Class IV-VI

mutations determine mean forms of diseases.

Many hypotheses have tried to explain how CFTR dysfunction acts in order to determine

clinical phenotypes. The most plausible are the assumptions that highlight the inability to

secrete salt and secondary to secrete water in the presence of excessive salt and water uptake.

In CF high intake of Na through altered CF cells is associated with increased conductance

amiloride sensitive - Na in the apical pole of the membrane and increasing the locus Na-K-

ATPase in the basal pole side of the membrane.AMPc mediates at the level of the apical pole

(luminal) of the Cl- secretion membrane associated with CFTR that does not work in the

epithelium of patients with CF, but an alternative way of Ca2 + - Cl- conductance is present

in normal cells with CF as well. CF cells have a limited ability to secrete Cl and absorb

excess Na limiting the water available to hydrate secretions.

The proposed mechanism is explained by insufficient water at the level of the airways in

order to hydrate secretions. Dehydrated secretions become more viscous and elastic and are

more difficult to clean by muco-ciliary activity and other mechanisms. In addition CFTR

dysfunction alters the microclimate with low concentrations of HCO3- and a more acid pH,

which alters the rheology of the mucus and makes the low mucociliary clearance worse. The

result is the stagnation of the secretions in the airways, starting with the smallest ones –

bronchiole, airway obstruction and then superinfections with Staphylococcus aureus,

Pseudomonas aeruginosa and Burkholderia cepacia. This causes bronchiolitis, then, over

time the accumulation of mucus in the higher airways leads to bronchitis. With time mucus

superinfects - bacterial invasion. Bronchioles obstruction, bronchiectasis, emphysematous

bubbles or subpleurale, pneumothorax, hemoptysis (by dilating the bronchial arteries) appear.

Paranasal sinuses are uneven filled with secretions leading to polypoid lesions (polyps

around maxillary and ethmoid sinuses).

Similar changes occur at the level of the pancreatic ducts – usually small ones, occasionally

cystic. In 85-90% of the cases lesions progress to replace acini with fibrous tissue and fat,

calcifications, resulting in most cases in exocrine pancreatic insufficiency, sometimes an

endocrine one.

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At the level of the intestinal tract the modifications are minimal, possibly destines glands

with mucus secretion. Changes at the level of the biliary tracts lead to the obstruction of the

intrahepatic bile ducts with the onset of focal biliary cirrhosis (30-70% of cases).

The obstruction of the uterine cervical glands can lead to endocervisitis, and at males the

obstruction of the ependymal ducts can occur of the vas deferens, seminal ones, with

secondary infertility.

Clinical symptoms

1. Respiratory symptoms: occur early in 90% of the cases/ in infancy. The onset is

characterized by monoliform, dry cough, leading to confusion with pertussis, then productive

sputum, often like bronchitis; while evolving to hyperinflation, peribronchitis, bronchiectasis,

atelectasis (right upper lobe), low hematosis ventilation reduction with chronic respiratory

failure and death may occur.

Complications: pneumothorax and hemoptysis, late bronchiectasis and chronic respiratory

insufficiency; infection is frequent (viscous mucus, aderent being adherent culture medium

especially for. Staphylococcus and Pseudomonas, B. cepacia encountered in over 90% of

cases), lung colonization and rapid deterioration of the respiratory functions; the infection

worsens the obstruction and favors the infection (a vicious circle is created). Non tubercular

cystic fibrosis is the most common chronic disease in children.

2. Digestive symptoms:

Meconium ileus (15 - 20%), not removing the meconium 24-48 hours after birth causes

symptoms of intestinal obstruction, with flatulence, air-liquid images; the normal meconium

is rich in carbohydrates, but in cystic fibrosis has a high content of protein and is viscous.

Drug treatment consists of the administration of gastrografin (a contrast agent with increased

osmotic pressure), or N-acetylcysteine for dissolving. Surgery is temporary ileostomy (with

poor results).

Malabsorption is another digestive symptom, given by the exocrine pancreatic insufficiency

at birth which occurs after 6 months by chronic diarrhea and malnutrition; the viscous mucus

obstructs the pancreatic ducts, and in the absence of the pancreatic juice, the digestion

disorder of lipids and proteins occur; malabsorption: steatorrhea, azotorrhea,

hypoproteinemia, hypocholesterolemia, malabsorption of fat soluble vitamins A, D, E, K,

with clinical consequences: edema, impaired night vision, rickets, haemorrhages. The

children are weak, malnourished, with a "voracious" appetite. The abdomen is distended, the

stools are steatorrheic (celiac differentiation!).

Rectal prolapse (2%) is a pathognomonic sign in children under 2 years old.

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3. Hydroelectrolyte disorders may occur when patients sweat excessively (fever, high heat),

causing hypernatremic dehydration or hypochloremic alkalosis.

4. Other symptoms: pansinusitis, slowed growth, intussusception, subocclusions, sterility,

biliary cirrhosis.

Positive diagnosis

It shall be based on clinical symptoms and sweat test.

Suspicion arises in a child with chronic digestive distress, recurrent respiratory infections or a

child under 2 years old with rectal prolapse.

The sweat test allows Cl-and Na + dosing from the collected sweat after iontophoresis with

pilocarpine; values over 60 mEq/ L at two consecutive tests are suggestive, and under age 3 -

over 40 mEq/ L).

Diagnosis of pancreatic insufficiency requires a stool test, which detects undigested muscle

fibers, neutral fat and a duodenal tubing showing a reduced viscous pancreatic secretion, with

no pancreatic enzymes (trypsin, lipase, amylase, chymotrypsin) when the secretion is

analyzed. For endocrine pancreatic insufficiency the oral glucose tolerance test is

recommended in children over the age of 10.

Other modifications: hipolipemia with hypocholesterolemia, hypoproteinemia, malabsorption

of fat-soluble vitamins (A, D, E, K) and of vitamin B12, Zn, Se, Fe deficiency, hyponatremia

and hypochloremia in sweating.

Genetic screening allows diagnosis of pathological CFTR mutations on both chromosomes.

Tests for 30-96 mutations of CFTR are done.

Chest radiography highlights the hyperinflation, pulmonary infiltrations, cysts,

bronchiectasis, pneumothorax, etc.

The study of lung function by assessing residual volume, functional residual capacity is

recommended after the age of 4-6.

Evaluation of microbial superinfection (S. aureu, P. aeruginosa, B. cepacia or Mycoplasma)

is useful for making the correct treatment according to the antibiogram and to preserve the

correct lung function. If children do not expectorate bronchoscopy is recommended.

Detection before birth: trophoblast biopsy study (week 10), determining the activity of

intestinal enzymes in the amniotic fluid (week 18).

Neonatal diagnosis between the 5th day and the first two months of life: demonstration of an

increased level of immunoreactive trypsin in blood.

Differential diagnosis

a) Digestive symptoms will differ from intestinal obstruction and other malabsorptions

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b). Pulmonary symptoms require differential diagnosis with pertussis, bronchitis, pneumonia,

asthma, bronchiectasis, tuberculosis, foreign body.

Treatment

The goals of the treatment are:

1. Monitoring

2. Pulmonary therapy

3. Digestive therapy

1. Monitoring and follow-up every 1-3 months. Sputum examination or throat swab is

recommended after each episode of cough and treatment according to the antibiogram. A

multidisciplinary assessment is required: pulmonologist, gastroenterologist, dietician, and

psychologist. Adequate hydration is recommended (oral or intravenous) in order to minimize

the complications associated with a viscous mucus. Scopul The goal of therapy is to ensure a

stable condition as long as possible.

2. Pulmonary therapy:

a. Inhaler treatment is used to deliver medication and adequate hydration of the lower

airways. Bronchodilators, corticosteroids and mucolytics are used:

Mucolytics: N. ACC - Fluimukan, f 3 ml solution, with good effects (FEV> 50%), 1-3

ml/ session - 2-3 times/ day. N ACC is toxic to the ciliated epithelium and repeated

administrations will be avoided.

Bronchodilators for patients who respond to the treatment: Albuterol 0,1-0,2

mg/kg/day (2-3x), Metropoterenol, Terbutalină, Teofilină, etc.

Recombinant human deoxyribonuclease (2.5 mg) administered daily as a single dose

improves lung function, decreases the number of pulmonary exacerbations, promoting

well-being in patients with moderate disease (Pulmozyne). The treatment is

administered continuously ≥ 12 months.

Nebulization with a hypertonic saline solution (7%), being hyperosmolar rehydrates

the mucus, and the pericilliary film, improving muco-ciliary clearance. DNA from

neutrophils destruction increases the viscosity of the sputum slowing down the

removal of the mucus, 2.5 ml/ day/ session, minimum 6 months.

Antibiotics in aerosols (tobramycin) in case of airway colonization with P. aeruginosa

b. Therapy for airway clearance (chest physiotherapy) consists of percussion combined with

postural drainage, forced expiratory in young children who do not cooperate, chest percussion

and vibration application (1-4 hours/day)

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c. Antibiotic treatment - aimed at controlling progression and lung infections. Treatment with

antibiotics may be given orally, in aerosol and IV.

Oral antibiotic therapy is administered to eradicate antibiotic agents isolated from respiratory

cultures as S. aureus, H. influenzae, P. aeruginosa, B. cepacia, gram-negative Mycoplasma.

Staphylococcus and H. influentzae can easily be eradicated per os, but Pseudomonas requires

prolonged treatment over 2 weeks, with the maximum dose. For S. aureus the following can

be used: Dicloxacillin 25-50 mg/ kg/ day in 4 doses, Linezolid 20 mg/ kg/ day in 2 doses,

Clindamycin 10-30 mg/ kg/ day in 3-4 doses, Amoxicillin/ Clavulanic 25-45 mg/ kg/ day in 2

doses; for H. influentzae Amoxicillin 50-100 mg/ kg/ day in 2-3 doses; for Pseudomonal -

Ciprofloxacin or other quinolones 20-30 mg/ kg/ day in 2-3 divided doses; for B. cepacia

Trimetroprin 8-10 mg/ kg/ day in 2-4 doses., empirical macrolide as Azithromycin 10 mg/ kg/

day, on day 1 and 5 mg/ kg/ on days 2-5 or Erythromycin, or Clarithromycin, macrolides that

reduce the virulence of P. aeruginosa.

Inhaled antibiotics are administered for P. aeruginosa and other gram-negative germs, which

are resistant to oral antibiotics.

In the aerosol, antibiotics such as Tobramycin (300 mg 2 times/ day), Colistin (75-150 mg in

aerosols, 2-4 times/ day) or Gentamicin can be used. With this inhaled therapy the P.

aeruginosa density decreases in sputum and hospitalizations are reduced. Intravenous

antibiotic therapy is given to patients with progressive pulmonary and persistent disease, for a

period of 7-14 days. Suitable for P. aeruginosa: Tobramycin 8-12 mg/ kg/ day 1-3 doses,

Amikacin 15-30 mg/ kg/ day in 2-3 doses, Ticarcillin 400 mg/ kg/ day in 4 doses, Piperacillin

300 -400 mg/ kg/ day in four doses, Meropenem 60-120 mg/ kg/ day in 3 doses, Imipenem

45-100 mg/ kg/ day in 3-4 doses, for Staphylococcus Vancomycin 40 mg/ kg/ day in 3 -4

doses, Nafcillin 100-200 mg/ kg/ day in 4-6 doses, and for B. cepacia Meropenem 60-120

mg/ kg/ day in 3 doses. For Pseudomonas a combination of two antibiotics eg tobramycin +

piperacillin) and for staphylococcus another antibiotic is usually used. (Initial doses are

higher, and if the patient's progress is good, the doses are adjusted.

d. Anti-inflammatory treatment: glucocorticoids in bronchopulmonary aspergillosis, 2 mg/

kg/ day, NSAIDs have the same effects as steroids, with fewer side effects: Ibuprofen,

Piroxicam; Pentoxifylline and fish oil preparations are useful.

e. Endoscopy and bronchial lavage especially in the case of atelectasis or obstructive mucus.

Antibiotics such as Tobramycin or Gentamicin can be instilled directly.

f. Potential Therapies: Gene mutation therapies (PTC 124 can suppress codon termination)

3. Fighting digestive disorders - correcting digestive disorders;

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The diet will be rich in proteins, glucagons, poorer in lipids with 1 g ClNa supplement under

2 years and 2 g over 2 years, in summer and in case of fever, with vitamins (A, D, E , K), zinc

(risk of enteropathic acrodermatitis)

Pancreatic extracts are required at every meal, individualized, 4-12 tablets/ day in order to

obtain 1-2 stools/ day. Infants need 2000-4000 U lipases/ meal administered with apple juice.

Pancreatic enzymes will not exceed 200 units lipase/ kg/ meal.

Evolution and prognosis

The evolution is constantly overshadowed by infections.

The prognosis is reserved, depends on the lungs (95% of deaths occur in bronchopulmonary

damage). The average life expectancy has increased to 35 years.

Prevention: an early detection.

The test for the assessment of albumin content of meconium (N = 0-5 mg%); in cystic

fibrosis the value is of 20-80 mg%. The downside is the possibility of false-positive reactions

(in premature infants); the test is positive when the color is green instead of yellow.

The determination of circulating immunoreactive trypsin: in blood the quantity of trypsin is

little (inactive) and increases with increasing pressure in the pancreatic ducts A screening

may be made concurrently with the detection of phenylketonuria and hypothyroidism.

Determination of potential differences in the nasal mucosa.

Genetic tests for highlighting mutations.

GLUTEN-SENSITIVE ENTEROPATHY (CELIAC DISEASE, CELIACHIA)

Frequency of celiac disease (CD) is estimated at 1-2500 inhabitants, and in Northern Europe

1/500 inhabitants. It seems, however, that the incidence is higher. The iceberg theory was

entertained, according to which CD is 0.5-1% of the general population as the disease is not

properly diagnosed and therefore, in to one diagnosed case, correspond other 5-10

undiagnosed ones.

Definition: CD is a systemic disease, immune mediated, triggered by sensitization to gluten

in the flour and prolamin in the barley, oats and rye, with clinical manifestations - due to

gluten sensitization and CD specific-antibodies (Autoantibodies transglutaminasis TG2,

antiendomisium EMA, Antibodies against deaminated gliadin peptides – DGP) Patients have

haplotypes HLA-DQ2 or HLA-DQ8 and enteropathy

Etiology is multifactorial, with high genetic predisposition

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Children with celiac disease have hypersensitivity to gluten proteins of some

cereals (wheat, rye, barley, oat)

In patients with celiac disease, T lymphocytes have been determined in the

thin intestine, which recognize the gliadin peptides in HLA DQ2 or HLA

DQ8 context

The TG2 atb determination as major auto-antigens in celiac disease led to the

recognition of the autoimmune nature of the disease

The disease is very rare in rice consumers, the risk being much lower in those

naturally fed.

Predisposing factors: infections, stress, hunger.

Pathogenesis:

The celiac enteropathy is the result of the immune-mediated lesion on the mucosa of

the bowel

The physiopathological cascade of events begins with alteration of barrier function of

the bowel mucosa

zonulin override (an intestinal peptide), has a role in the increased intestinal

permeability to the gliadin peptides in patients with CD

tissue transglutaminasis is present in lamina propria , an enzyme that catalyzes the

cross linking of the proteins, deamidated peptides of the gliadin, increasing their

affinity for HLA molecules located on the membrane of the antigen-presenting cells

(APC) (macrophages)

HLA molecules form “a ditch" where the peptide can be specifically connected – the

intestinal T lymphocytes are activated

T lymphocytes release pro-inflammatory cytokins (interferon γ, TNF α) which

determine enterocytes damages, increased proliferation in the intestinal crypts and

severe lesion of the arhitecture of the intestinal mucosa (atrophy)

Cascade of events

intraluminal digestion of gliadin peptides and release of toxic epitopes;

intraluminal release of zonulin dependent gliadin (circle);

opening fine intercellular junction secondary to zonulin action followed by passage of

toxic gliadin fragments in the submucosa;

tissue transglutaminase(star) -mediated gliadin deamidation followed by engagement

to HLA DQ2/DQ8 located on the surface of antigen presenting cells (APC);

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antigen presentation to T lymphocytes;

presentation to B lymphocytes;

generation AGA-producing plasma cells (antigliadin antibodies) and EDA / tTG atb

(anti endomisium / anti transglutaminase);

killer T cell activation and increased production of cytokines, which leads to damage

of the intestinal mucosa.

Symptoms

The onset in classic forms is at 6-18 months, in a few weeks/ months after the introduction of

pasta in the diet.Atypical forms can appear at any age.

Clinically, children are weak, pale, anemic, and irritable, with hypotonic muscles, distended

abdomen, hepato-splenomegaly, “fused” buttocks, stopped growth and weaknesses: rickets,

osteoporosis, and anemia.

Because the atypical form is more frequent than the classical form the working team

ESPGHAN has decided to use for symptomatology: gastrointestinal signs and symptoms and

extra intestinal signs and symptoms: anemia, neuropatia , decrease of bone density

increased risk of fractures and so on

Gastrointestinal manifestations (clasic symptomatology):

chronic diarrhea (50% of the cases) . Features at a young age are stools which

are: abundant, pasty, fatty, with a characteristic odor (steatorrhea) and during

acute diarrhea they become watery, frothy. Infections, stress and starvation

cause episodes of acute diarrhea, the so-called "celiac crisis", where quick

dehydration occurs which can lead to collapse.

recurrent abdominal pains

abdominal distension (here comes the name of the disease)

anorexia

chronic constipation

loss of weight

vomiting

flatulence

height and weight retardation

Extraintestinal manifestations (more often):

malnutrition

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deficiency signs: iron deficiency anemia or other types of anemia,

osteoporosis (decreased bone density), rickets, delayed puberty, amenorrhea,

irritability, chronic tiredness

transaminases increase

herpetiformis dermatitis

dental dystrophy

aphthous stomatitis

chronic hepatitis

neuropathy

arthralgia

After the age of 5-6 years 50% of cases begin with extradigestive symptoms: dermatitis

herpetiformis, iron deficiency anemia, dental dystrophy, osteoporosis, chronic hepatitis and

others.

In adolescents, young adults the latent disease can be met with weight loss and diarrhea, only

with fatigue, abdominal pain, bloating, anemia or Duhring-Brock dermatitis herpetiformis.

Clinical forms:

classic form with characteristic symptoms

latent form (which seems to be more common than the classic form with atypical

symptoms - fatigue, adinamia, anemia, neuropathy, decreased bone density, increased

fracture risk, etc.)

The silent form with CD positive antibody , positive HLA, histopathological changes

compatible with CD, but without signs and symptoms which justify a celiac disease

suspicion

Latent form: positive HLA , but without enteropathy in a patients who had suffered

once of sensitive gluten enteropathy.

Potential form: has specific anti CD antibodies has positive HLA, but without

histopathological changes in the duodenal biopsy

CD Associated diseases are:

associated conditions (after AHRQ – Healthcare Research and Quality):

High prevalence of the disease in the relatives of the patient with celiac

disease (10-20%)

Children with DM type I (the prevalence is 3-12%)

Autoimmune thyroiditis (up to 7%)

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Chromosomal aberrations (Down syndrome 3-12%, Turner syndrome,

Williams syndrome - up to 9%)

IgA nephropathy

selective IgA deficiency (10-20 times more increased prevalence)

Autoimmune hepatitis (12-13%)

Juvenile chronic arthritis

Therefore, patients with classic symptoms and those with extraintestinal manifestations

and related diseases will be tested for CD.

Laboratory:

Serological tests: anti TG2, EMA antibodies or anti DGP (antigliadin peptide). For

the interpretatation of the antibodies results, we must consider: if the total level of

IgA in serum is (< 0,2 g/L), the diagnosis will be set according to antibodies type

IgG . Deficienţa de IgA,este boală asociată cu o incidenţa crescută a celiakiei.

Atc anti TG2 and/ or EMA are associated with a high probability of celiac disease,

having a specificity of 98-100%. Anti TG2 antibodies with high values of > 10 times

are associated to vilositary atrophy. Therefore, when anti TG2 Atb are done of routine

and when they are 10 times the normal value, duodenal biopsy is no longer performed

but genetic testing is recommended. DGP antibodies (deamidated gliadin peptides)

have high specificity and sensitivity similar to IgA tTG IgA EmA and therefore are

used as screening. The best diagnostic test is anti-TG2 atb+ DGP atb (combined).

HLA tests - major antigens of histocompatibility HLA-DQ2 and HLA-DQ8 are useful

to exclude celiac diseases. These examinations are recommendedwhen specific Atb

for celiac disease are negative, but histopathological there are medium changes in the

bowel mucosa, when there is great suspicion of celiac disease, antibodies are

intensively positive,and the biopsy is negative, in patients belonging to the group at

risk

The genetical susceptibility for celiac disease is given by HLA class II, DQA and

DQB, genes situated on the short arm of the 6th chromosome. More than 95 % of the

patients with celiac disease are heterodymer HLA-DQ2 (cis [encoded by HLA-DR3-

DQA105:01-DQB102:01], or trans [encoded by HLA-DR11-DQA105:05 DQB1

03:01 /DR7-DQA102:01 DQB1 02:02]) and approximately 5% heterodymer HLA-

DQ8 (encoded by DQA10301-DQB10302). The expression of HLA –DQ2 or

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HLA-DQ8 molecules is necessary, but not enough (30-40% of the white population

have these haplotypes, but only 1% get the disease).

The biopsy will be multiple and they are taken through superior digestive endoscopy

(from D III). Biopsies by suction capsule can be made. Histopathological changes

described by Marsh are:

Marsh I – infiltrative lesion; normal structure of the intestinal mucosa; -

lymphocytic inflammatory infiltrated in the villi epithelium (> 30 lymphocytes

at 100 enterocytes)

Marsh II – hyperplastic lesion; increased intraepithelial lymphocytic

inflammatory infiltrated; crypts widening , crypts depth

Marsh III – the destructive lesion is present

Marsh III a – partial villi atrophy, villi shortening, inflammatory infiltrated

Marsh III b – subtotal villi atrophy; clear villi atrophy, but villi can be

recognized; crypts widening and rich inflammatory infiltrated are associated

Marsh III c – total villi atrophy; almost total absence of villi; hyperplasic and

inflammatory lesions

Other investigations:

Anemia (serum iron under 50%in the context of malabsorption),

decreased coagulation factors,

hypoproteinemia, Ca + + and P +3 low serum (osteoporosis)

• Zn + + low, which causes "blunt taste" and loss of appetite.

Microscopic examination of the stool will highlight the unabsorbed fatty acids

(not neutral fats such as in cystic fibrosis). Determination of the fecal fat (3 days)

shows a fecal excretion over 15% in infants and above 8%.in children.

Biopsy is not recommended ed if TG2 atb are over 10 times the normal value. In other cases

biopsy is mandatory. Biopsy should be repeated after the introduction of gluten. Assessment

of therapeutic efficacy is made by serological tests

Positive Diagnosis

Presumptive diagnosis is based on symptoms and serological tests, HLA testing, duodenal

biopsy.

Differential diagnosis

It is necessary with cystic fibrosis and celiachiform syndrome which occurs in the case of

giardiasis, and long antibiotherapy (5-10% of cases with transient intolerance to gluten).

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ESPGHAN proposes the following diagnostic algorithms in CD children:

Fig.no. Algorithm of diagnosis In children and adolescents with signs and symptoms

suggestive of celiac disease

Fig. no. Algorithm of diagnosis in children and adolescents without signs and symptoms of

celiac disease

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Treatment

The basis of the treatment is a gluten-free regime; the following will be excluded from the

diet: wheat flour, barley, oats, rye and derivatives. Rice, corn flour, potato and millet will be

used. There is also gluten-free flour. The regime will be easily hipercaloric (+25%), with an

intake of protein and vegetable oils.

Under diet: the symptoms disappear within 1-2 weeks, histologic lesions (variable after the

degree of villous atrophy) disappear within 2 months - 5 years or more.

Additional vitamin intake is required: vitamins A, B, C, D, E, folic acid, iron and calcium.

In celiac disease crises Prednison 1-2 mg/kg/day is administered, rapid rehydration is

initiated (to avoid anhidremic collapse).

Evolution and prognosis

The evolution is long, with crises. The prognosis is reserved. Untreated, in these patients, the

incidence of lymphomas and adenocarcinomas of the intestine are greatly increased.

The "detoxification" of the gluten is tried by changing a nucleotide from the DNA chain in

the grain of wheat and creating a vaccine and also genetic modulation.

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FOOD INTOLERANCE

DISACCHARIDE INTOLERANCE

Defition: an autosomal recessive metabolic disease, resulting from the mutation of the

specific gene (from chromosome 2, resulting in the inability of the enterocytes to synthesize

lactase.

Can be of an infantile type - congenital alactasia- of two types

true – very rare, 32 cases published in the literature up to this date

false - "physiological" intolerance that occurs in infants

The second type is the adult type by a posttranslational defect in the synthesis of the

enzyme.

Clinical picture: there are some common and some particular elements of the disease.

The common elements are diarrhea and deficiency syndrome (in chronic forms).

Diarrhea is the main symptom; the child has 4-10 watery, frothy, yellowish stools/ day, which

are eliminated in an explosive way, and associated with perianal skin irritation and intertrigo.

The onset of diarrhea depends on the etiopathogenical shape.

It has a chronic/ recurrent character correlated with milk nutrition; disappears when milk is

excluded from the daily diet and reappears when milk is reintroduced. It can also present:

abdominal cramps, gurgling, flatulence and vomiting.

Deficiency Syndrome occurs in children who, without specifying the diagnosis, are still on

milk diet; the diarrhea becomes chronic, children present somatic deficiency, weight curve is

downward, height gain slowed or stopped, anemia, multi vitamin deficiencies.

The diagnosis is suggested by: pediatric clinical symptoms disappear after a steady diet of

removing lactose over a period of at least 2 weeks, with recurrence of symptoms when

reintroducing the lactose.

Laboratory:

• determination of pH in the stool: acid pH, below 5.5 (even up to 3.8).

• microscopic examination of the stool highlights incompletely digested food scraps from

all food sectors

• test for reducing substances in the stool is positive

• oral lactose loading test is pathological: flat curve of the glucose appears and diarrhea,

cramps, gurgling may be associated

• oral glucose loading test is normal

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• expiratory test of the hydrogen is positive. In order to perform the test a 2g/kg lactose is

used, the test has a better performance if is performed after a 6-hour post; false-negative

tests may occur, especially after antibiotic treatment (hydrogen is metabolized by bacteria

to methane).

• radiological examination of the digestive tract involving lactose or barium sulfate is not

indicated in children. In adult, radiolgically the The Preger triad appears: shortened

intestinal transit time, distended jejunal loops, imprecisely defined outline due to enteral

hypersecretion

• determination of lactase activity in jejunal mucosa biopsies: its absence is seen in a

genetic form – with a neo-natal onset and low values in other forms.

• histological examination of intestinal mucosa reveals a normal aspect in the genetic form

and it is altered specifically to the causing disease as acquired.

1. Primary genetic lactase deficiency - infantile type (Alactasia)

It is an exceptionally rare disease, has an early onset, AR transmission described in a few

cases (32), with homozygous mutations (Y1390X named Fin) in 84% of cases and

heterozygous mutations (S166 fsx1722, S 218 fsx 224, Q268H and G 1363 S) in the rest of

the cases.

Symptoms appear a few days after birth, after breast feeding or formula containing lactose.

The selective, persistent, severe character, with acid and liquid diarrhea, flatulence, leads to

severe malnutrition.

Children are hungry, rarely present vomiting; some may have hypercalcemia and

nephrocalcinosis by metabolic acidosis and/or increase of calcium absorption after

administration of lactose. At the appearance of suspicion a lactose-free diet is started, and in

case the effects are positive the diagnosis is supported.

In order to confirm the diagnosis it is necessary to emphasize the deficit lactase activity in the

jejunal mucosa biopsy with normal morphology of the jejunal mucosa and molecular genetic

tests- to strengthen the diagnosis

Treatment

The treatment consists of a strict lactose-free regime, with adequate preparations: lactose-free

Nan, Lactopriv, Pregomin, Isomil, older children will receive additional lactase with

preparations containing enzyme - Lact-Aid, Lactase; lifelong treatment.

2. Primary genetic lactase deficiency - adult type (Hypolactasia) (Late-onset)

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It is very common in humans, with different prevalence: 10-90% by geographic area and

race (5-12% at white population, up to 70% in U.S. blacks). The disease is rare in northern

Europe, as in some tribes in Africa and India where10-20% occur.

It is a post-translational defect in the synthesis of the enzyme, which becomes apparent in all

mammals after weaning. Lactase deficiency in this form is installed progressively after

infancy, clinical onset may be after 3-5 years or in adolescence, and intolerance symptoms

may develop in adolescence or adulthood. Enzyme deficiency is only partial, sometimes

allows milk consumption in small quantities (1-1½ glasses), the diarrhea installing only after

the consumption of large quantities of milk.

Symptoms occur after milk consumption: abdominal discomfort (colic), flatulence, low

consistency stools, diarrhea. It is believed that 30-40% of children with DAR may present

lactase deficiency.

Treatment

Corresponding decrease in milk intake of individual tolerance, delactosed milk consumption,

lactase replacement therapy: Lact-Aid solution, Administration of calcium (for bone

mineralization) is important in these patients, noting an increased incidence of osteoporosis

secondary to milk avoidance.

Daily intake of calcium-fortified fruits (oranges) is recommended, vegetables and milk

without lactose and consumption of yogurt containing Lacto-bacillus bulgaricus and

Streptococcus thermophilus cultures producing lactose digestion.

Lactobacillus acidophilus has lactase activity and is available in sweet acidified milk, with

similar taste to milk.

3. (Secondary) Acquired lactase deficiency

It is secondary to some acute illnesses, usually an acute enterocolitis, or secondary to chronic

disease development: EGS, CF, lambliasis, b. Brohn, bowel resections, severe malnutrition,

drug enteropathies.

Pathogenetic mechanisms:

- reducing the number of enterocytes in diseases that are accompanied with villous

atrophy (EGS) or patients with jejunal resection and

- the reduction of the enzymatic synthesis of the enterocytes, due to cellular metabolic

suffering (in inflammatory bowel diseases, FC).

Diagnosis

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Includes common criteria and variable-onset (especially in infants, not after birth), it has a

transient, non-selective nature (associated with other disaccharide deficiencies), jejunal

morphology specific to the underlying disease.

Treatment

Dietary treatment with hypo-allergenic milk or a lactose free one and a substitution treatment

with lactase preparations (Lact-Aid, Lactrase, etc), are required for a variable period,

depending on the causing disease.

ALLERGIES AND FOOD INTOLERANCES

Definition

There are sensibilizations of the mucous membranes at one/ more food components, more

frequent sensibilizations associated with gastrointestinal manifestations are given by cow's

milk protein or soy products.

Intolerance (allergy) to cow-milk (CM) proteins (CMPI)

It is characterized by a group of acute "allergic" or chronic manifestations, malabsorption

syndrome produced by CM protein sensitization. Cow's milk contains 20 proteins, 5 of which

have proven antigenic properties: β-lactoglobulin, α-lactalbumin, casein, bovine

seroglobulina and bovine serumalbumina.

Clinical symptoms:

Digestive manifestations dominate the picture: brutal, explosive, bloody diarrhea or

abundant, soft, coarse stools with vomiting.

The acute symptoms appear after eating, often a shock emerges, hypotonia, disorders of

consciousness, gray pale, peribuccal cyanosis; ymptoms disappear within a few hours,

reappear after feeding.

The chronic form is insidious, diagnosed late, the rarer being the forms prone to paralytic

ileus, necrotising enterocolitis, exudative enteropathy, colic symptoms: inflammatory

proctocolitis in newborn, hemorrhagic colitis.

Extradigestive manifestations are varied with:

- anaphylactic shock,

- rare respiratory manifestations: asthmatic bronchitis, pulmonary infiltrates, allergic

rhinitis,

- dermatological symptoms: eczema, hives, Quinke swelling, dermatitis herpetiformis or

- controversial symptoms, such as sudden infant death, severe insomnia, myocardial

infarction, nephrotic syndrome.

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Diagnosis

It is based on the disappearance of symptoms after exclusion of CM and recurrence in 48

hours after milk reintroduction, after eliminating other causes of digestive disorders.

It is useful for diagnosis:

- the presence of red blood, Charcot-Leyden crystals, leukocytes in the stool,

- loss of plasma proteins in exudative enteropathy,

- increase of the level of anti-milk serum antibodies

- lymphoblastic transformation test (involvement of cellular immunity)

- intestinal malabsorption research

Treatment

- is essentially dietetic, through CM exclusion, its derivatives and foods containing it

- the use of soy formulas (Humana SL, Nutry-Soy, Lactopriv),

- synthetic formulas and

- supplementing the diet with meat (beef, chicken), vegetable oil, glucose for caloric

intake

- good results are obtained by refilling with mother milk

- in severe forms parenteral supine then elemental diet or APT.

Primary prophylaxis is to promote natural feeding

Soy protein intolerance

May be isolated or associated to CMPI.

Clinically

The onset occurs in the moment of introduction of a soy food.

Symptoms: watery diarrhea, vomiting, anaphylactic shock.

Laboratory: hyposideremic hypochromic anemia, hypoproteinemia, acid pH of the stool and

unsteady blood in stool may occur

Treatment: exclusion of soy proteins from the diet.

Eosinophilic gastroenteritis

It is a rare disease; represented by sensitization to food.

Clinically children present abdominal pain, vomiting, diarrhea after ingestion of certain food.

Associated atopic symptoms as rhinitis, asthma, and eosinophilia can be observed, suggesting

the allergic base of the disease. Protein loss can be produced determining decreased albumin

and Ig.serum

The diagnosis is suggested by:

- recurrent symptoms,

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- eosinophilia,

- endoscopy with biopsy (gastric and duodenal lesions, eosinophilic congestion of the

lamina propria, shortening of villi, bleeding, muscular involution determining

strictures)

- and changes of the serous until ascites

Evolution

It is often chronic sometimes with severe, exacerbations; elimination of the incriminated food

can help, but most patients require systemic corticosteroids.

Food allergy

Sensitization reactions after food ingestion are based on immune mechanisms, differ from

commonly occurring adverse reactions and are given by food toxins and non-immune factors,

through pharmacological and biochemical mechanisms.

Etiology

Involved allergens are different with age.

Atg sources at infants are LV, cereals, citrus, bananas, vegetables, meat – poultry and beef.

Atg sources in older children: eggs, chocolate, strawberries, walnuts, peanuts, fish, pork and

shellfish.

Hypersensitivity phenomena can alleviate when advancing in age.

Clinical symptoms

Symptoms of allergic reactions to foods are: urticaria, angioedema, gastrointestinal disorders,

severe asthma attack, even anaphylactic shock.

The response to an allergen can be immediate, after a few minutes or delayed (2 hours).

In case of late manifestations, problems of differential diagnosis with non-allergic reactions

may occur.

Syndromes associated with hypersensitivity to food:

Angioedema often accompanied by urticaria, is manifested as a swelling of the lips and

periorbital mild arthralgia, malaise, in severe cases swelling of the tongue, pharynx, larynx,

with joint swelling and death by suffocation.

Anaphylaxis is an immediate reaction with dizziness, pallor, paraesthesia, generalized

pruritus, palpitation, tachycardia, syncope, signs of pulmonary edema, severe asthma attack,

and vascular collapse.

Gastrointestinal intolerance presents symptoms attributed to "allergy" but the basic

mechanisms are unclear: nausea, flatulence, bloating, abdominal discomfort, diarrhea; in

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severe cases incoercible vomiting occurs, colic, bloody diarrhea, dehydration, these repeated

episodes causing dystrophy and growth retardation.

It is unclear whether the “tension – asthenia” syndrome is associated with an allergic

mechanism; nervousness, insomnia, fatigue, pallor, ringed eyes, vague abdominal pain,

headache, atopic symptoms to abundantly ingested food, (eggs, LV, cereals, chocolate, pork)

may occur.Allergic rhinitis, asthma, atopic dermatitis and urticaria may be signs of allergic

reactions to food as well.

Laboratory

- eosinophilia is observed in the fecal mucus and blood

- skin tests present strongly positive reactions which may have an aetiological

significance but negative reactions DO NOT exclude an allergy

- serological tests have about the same value

- food challenge tests are rarely used, only in less severe forms.

The treatment consists of:

- removing foods that cause allegric reactions and ensuring an appropriate nutritional

intake.

- administration of breast milk up to the age of 1

- late introduction of solid foods

- using goat milk (!anemia), meals based on soybeans, avoiding the food that triggers

the allergy up to 8-10 years, later being reintroduced carefully, under supervision

- if allergic symptoms may occur upon reintroduction, these foods will be avoided

forever

Prophylactic treatment

Na cromoglycate (Nalcron), Ketotifen po in extended cures (variable results) can be used,

lowering the frequency and intensity of reactions.

Symptomatic and etiopathogenic treatment

It is based on the symptoms.

Prognosis

It is good if the foods can be identified and are no longer given.

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ACUTE DIARRHEA OF INFANTS AND SMALL CHILDREN

Definition

Acute gastroenteritis (AGE) is defined by softening stools and/ or an increase in discharges

(≥ 3 in 24 hours), with or without fever and vomiting. The diarrhea lasts less than 7 days, but

no more than 14 days. However, a change in stool consistency in relation to the consistency

of previus stools is more predictive for diarrhea than the number of stools, especially in the

first month of life (ESPGAN definition).

We have to mention that in the first 3 months of life infants have more stools depending on

the type of food they are given.

Persistent diarrhea is defined as diarrhea episodes that begin as acute ones and last 14 days.

These episodes represent 3-20% of the diarrheal episodes in children under 5 years and up to

50% of the total episodes of diarrhea.

Epidemiology

The incidence of diarrhea varies between 0.5 - 1.9 episodes/ child/ year in children aged

under 3 years in Europe.’

Etiology

- viral - the most frequent agents – rotavirus 10-35% (with the highest incidence in the

cold season – (from october until May), norovirus, adenovirus

- bacterial – the most frequent agents Campylobacter jejuni (4-12%) and Salmonella spp

(5-8%), more rarely E. Coli (EPEC, ETECT, EHEC, EAggEC), Yersinia, Shigella,

cholera. Bacterial diarrhea occur mostly in summer, with two peaks in May-June and

September-October.

- parasitic – Giardia lamblia and Cryptosoridium in immunocompromised children,

Entamoeba hystolitica, Trichiuris trichiura, Strongyloides stercoralis (rarely).

If AGE occurs at a higher incidence than expected, we may speak about an epidemic

diarrhea.

Age-related etiology is presented in the following table:

Table ccc Acute diarrhea etiology

< 1 year 1-4 years > 5 years

Rotavirus Rotavirus Campylobacter

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Norovirus

Adenovirus

Salmonella

Norovirus

Adenovirus

Salmonella

Campylobacter

Yersinia

Salmonella

Rotavirus

Table cccc Risk factors for severe and/or persistent diarrhea:

Severe diarrhea Persistent diarrhea

The severity of the diarrhea, linked to the

degree of dehydration and vomiting

Loss of appetite, fever, vomiting and

mucus in stools

SDA in infants less than 6 months old

associated with rotavirus infection (most

severe pathogen of infant diarrhea)

Under 6 months old Under 6 months old

Rotavirus, norovirus, astrovirus,

enteroagregative E. Coli in industrialized

countries

Poor socio-economic conditions

(developing countries)

Poor socio-economic conditions

(developing countries)

Collectivity (care centers)

Congenital or acquired immune

deficiencies (HIV) favor persistent

diarrheal episodes, (opportunistic agent -

Crystosporidium parvum)

1. Predisposing factors

2. ex constitutione: newborn, small, premature baby, diatheses (lymphocytic, exudative

allergic).

3. Ex curatione: personal hygiene, house, season, the use of hardening factors such as water,

sun, air, vaccination, etc.

Pathogenesis. The pathogenesis and severity of the bacterial diarrhea depends on the

production of bacterial toxins (Salonella, Bacillus cereus), which produce secretory diarrhea

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(cholera, E. Coli, Salmonella, Shigella), cytotoxins (Shigella, S. Aureus, C. difficile, E. Coli,

C, jejuni), and are invasive germs or multiply in food.

Enteropathogens agents can lead, at the level of the intestinal mucosa, either to an

inflammatory response or to a non- inflammatory response.

The non-inflammatory response – by enterotoxins (ie "exudative" noninvasive because

germs do not penetrate the mucosa and do not damage it) or superficial adhesion/ invasion

produces diarrhea by increasing the adenyl-cic from the intestinal mucosa and thus cAMP٭

increases, inhibits the absorption of NaCl, but have no effect on the glucose pump - Na,

leading to an increased secretion of water and electrolytes (Na+, K+, Cl-, bicarbonate). The

cytoskeleton rearrangement is affected by altering the flow of water and electrolytes. This

type is found in cholera, being produced by E. coli (ETEC, EPEC, LT, ST), Clostridium

perfringens, Bacilus cereus, S. Aureus, Rotavirus, Giardia lamblia as well.

a. The inflammatory response is caused by bacteria directly invading the bowel or

sometimes cytotoxins with penetration into the lumen of fluids, proteins, cells

(erythrocytes, leukocytes): E. Coli (EIEC, EHEC), Campylobacter, ş.a. An alteration of

the cell morphology is produced with the decrease of the glucose-Na pump function and

NaCl absorption. For example ETEC colonizes and adheres to intestinal enterocytes at the

level of the fimbriae and induce the hypersecretion of fluids and electrolytes by toxins 1

and 2.

b. Mechanism of penetration – acts at the level of the distal small bowel, causes enteric

fever, the appearance of leukocytes in feces. The diarrhea caused by this mechanism is

given by Salmonella typhi, Yersinia, Campylobacter fetus. Salmonella behaves somewhat

differently in newborns and infants. Some types penetrate the epithelium until the “lamina

propria” where they produce inflammation (therefore oral antibiotics are ineffective) but

easily penetrate blood and lymphatic vessels, leading to septicemia.

Symptoms. The onset of the disease is made by a prodrome, in which the infant presents:

anorexia, stagnant growth rate, and behavioral changes (malaise, restlessness, sleep patterns

change), and in some change in stool appearance and nappy rash.

High fever, blood in the stool, abdominal pain, CNS symptoms suggest a bacterial etiology

(shigella, salmonella), and vomiting and respiratory withdrawal symptoms suggests the

etiology of a viral disease. However, in AGE with rotavirus more severe forms of the illness,

vomiting and dehydration can be met.

During the state period the triad usually occurs: anorexia, diarrhea and vomiting.

Vomiting, which is not mandatory, is more frequent, when it occurs

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Stools, more frequent in numbers, 3-5/day are aqueous (lasă leaves large halo on the diaper)

of fermentation (light yellow, airy with a sour, acidic smell). Rarely may be muco-coarse,

semi consistent ones

Some children present abdominal colics as well, (“rub their heels”), flatulence. The growth

rate decreases. If nothing is done, the symptoms of acute dehydration may install.

Fever may be absent, or may be the consequence of dehydration. Infants with 6 to 10 stools/

day are not in danger of dehydration if intake is adequate. Those with more than 10 stools/

day are at risk of dehydration even in case of an adequate intake. Premature infants, severely

malnourished ones and other handicapped infants do not have usually fever.

Clinical forms

1. Etiologically unlabeled, nonspecific acute diarrhea: insidious or brutal onset, with

prodrome of anorexia, behavioural changes, weight stagnation, nappy rash., vomiting,

thirst fever

2. Acute enter-infectious diarrhea

- bacillary dysentery (shigelloza) - sudden onset with fever, chills, sensory disorders,

convulsions, colic, tenesmus, pathological stools.

- Salmonellosis: gastroenteritis form and enteric fever

- acute diarrhea with E. Coli - high fever, vomiting, dehydration, metabolic acidosis,

watery, smelling, acid green, explosive stools.

3. Acute viral diarrhea, gastroenteritis - occurs during winter, it is given by rotavirus The

onset is sudden, with fever, vomiting, watery diarrhea, myalgia, rush, respiratory catarrh.

4. Parenteral diarrhea - "dyspepsia" secondary ITU, otitis, pneumonia. It is resolved after

the treatment of the underlying disease.

Positive diagnosis

It is based on clinical signs and simple laboratory tests.

a) Stool test which highlights only constant pathogenic specific bacteria; has the

disadvantage that it is obtained late (~ 72 h). Remains the primary means of

determining the etiology for entero-bacteria (Vibrio cholerae, Salmonella, Shigella, E.

coli, Proteus, Pseudomonas). In 50-80% of BDA in infants, stool test remains negative

(viral etiol.).

b) The pH of the stool is normally 5-8, and a pH below 5 shows an intolerance to glucose

c) The virological examination of the stool is useful for diagnosis, although it is less

accessible; special kits are sold for rotaviruses.

d) Fecal examination may reveal the causative agent in parasitic diarrhea.

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e) Fecal examination consists of highlighting leukocytes in stool using methylene blue

stain; normally there are no leukocytes in the stool; 0 leukocytes/ field in infants are

allowed. Leukocytes can appear in the stool in bacterial infections.

f) Immunoassay tests: ELISA, ROTALEX

g) The Gregersen reaction allows highlighting occult bleeding (product harvested after 72

h of food without meat)

h) Blood count, Ionogram, microASTRUP; Biochemistry: urea, creatinine

i) Bacteriological examination from products other than stools

If the diarrhea persists more than two weeks, and stool cultures are negative, radiographic

examinations and endoscopy should be carried out for harvesting biopsy material.

Differential diagnosis is carried out with:

- osmotic diarrhea (much sugar in the diet), is a "false diarrhea"

- food abuse (especially cold drinks, spicy or fatty food),

- food poisoning,

- acute exogenous poisoning,

- intussusception,

- perforated Meckel diverticulum,

- parenteral diarrhea,

- acute episodes of diarrhea in the case of:

» malabsorption

» malnutrition

» allergy (in particular cow's milk protein intolerance)

» prolonged therapy with antibiotics

Evolution and complications. Most infectious diarrhea are self-limiting; they heal in about

two weeks, the period for rebuilding intestinal mucosa, of the enterocytes. It is very important

to assess the degree of dehydration (mild, moderate or severe) associated to diarrhea in order

to provide appropriate treatment.

The child will consult a doctor if he/she has > 8 diarrheal episodes/ day, persistent vomiting,

severe underlying disease, age < 2 months.

The child will be admitted to hospital if he/she has: shock, severe dehydration (> 9% of body

weight), neurological changes, incoercible vomiting, failure to rehydrate with ORS, suspicion

of impaired operation.

Another possible evolution are recurrences. We are talking about a chronic evolution, usually

after 2-3 weeks of poor outcome in treatment.

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Two complications are more common as children are smaller:

- acute severe dehydration syndrome ascending to collapse and

- septicemia, by generalized infection.

The prognosis is favorable.

Treatment of acute diarrhea

Basic measures are- adequate diet selection, oral rehydration, enteral nutrition,

supplementation with micronutrients (zinc) and additional therapies such as adjuvant therapy

and probiotics. Drug therapy and parenteral rehydration are reserved for severe cases.

1. Dietary treatment

Oral rehydration

The first line of treatment in AGE is oral rehydration with ORS solution. The one

recommended by WHO is that with 75 mmol/l Na, but the one recommended by ESPGHAN

is the hypoosmolar one with 60 mmol/l Na. It is the therapy of choice and it is sufficient in

diarrhea produced by Vibrio cholerae, but also in the non choleric one. Hypoosmolar solution

reduces the volume of stools, vomiting, and decreases the need for intravenous fluid

supplements. ORS solution with rice can be administered as well respectiv;it is recommended

to ORS solutions with probiotics.

Its indications: acute diarrhea, SDA gr. I and II without vomiting, in the presence of

peristalsis.

Way of administration

In the first 3-4 h 10 ml/ kg/ hour is given in the mild forms and 20 ml/kg/hour in medium

forms, or 50 ml/kg during the first 4 h in mild forms and 80-100 ml/kg during the first 6 h in

medium forms.

Rehydration with administration of 50 ml ORS will be continued for each modified stool

under the age of 2, and 100 ml ORS for each modified stool for children over 2, until

recovery, or 20-50 ml/ kg after 3-4 hours.

Oral Rehydration Solutions administration rules:

1. Chilled or frozenoral rehydration solution (ORS) is tolerated

2. Give ORS with a spoon rather than with a bottle

3. Consider adding flavor to ORS

4. Gelified ORS, if available, is more palatable

5. Adding honey to ORS may be of benefit

Nutritional interventions

Breast-fed infants will continue to receive breast milk.

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The maintanance of natural feeding is recommended and rapid return to age-appropriate

nutrition in order to prevent villous atrophy and damage of the luminal enzyme production.

In children with mild or moderate dehydration normal diet is recommended after 4-6 hours

from the onset of rehydration. In these cases there is no need to dilute the formula. Most

children can continue eating the formula with a normal amount of lactose, the lactose-free

formula benefits compared to the standard ones are negligible. Soy-based formulas or

hydrolyzed protein ones are indicated only in the first 2 months of life.

The BRAT diet (bread, rice, apple, toast) is not recommended and sweetened juices should

not be used.

When the rehydration is complete, appropriate nutrition will be resumed continuing the

administration of rehydration solutions in order to compensate any loss due to vomiting or

stools and for maintenance.

Restrictive diets should be avoided during acute diarrheal episodes. Breastfeeding will

continue "on demand" even during oral rehydration. Infants too weak to be able to consume

will receive milk or formula through nasogastric tube. Usually lactose formulas are well

tolerated. If there is clinically significant lactose malabsorption, a lactose-free formula can be

used. Alternative strategies to reduce the lactose content in children with extended diarrhea

include the adding of different cereals in the milk or replacing milk with fermented products

(yogurt).

It was seen that there were no differences between early and late refeeding as regards

unscheduled intravenous fluid therapy, vomiting, persistent diarrhea, duration of

hospitalization, total stool output, percentage of weight gain at 24 hours or at resolution of

illness, and hyponatremia. In addition, early refeeding was associated with a shorter duration

of diarrhea.

In several European and non European countries, attempts have been made to find a food to

counteract diarrhea. In other words, is there something that can help resolve this problem

sooner in children with AGE? Various foods have been tested for their antidiarrheal effect.

These include yoghurt, staple foods, cereal-milk mixtures, solid foods, and more recently,

amylase digestive starch. Although some studies found evidence of a limited advantage for

selected nutrients, there is no agreement about whether a particular food can be useful in the

treatment of diarrhea. Consequently, this approach is not included in the treatment of

gastroenteritis.

Rehydration in a hospital setting

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When oral rehydration is not feasible, rehydration by the nasogastric route or IV route should

be considered. The nasogastric route is as effective if not better than IV rehydration.

Nasogastric rehydration is associated with significantly fewer severe adverse events and a

shorter hospital stay compared with IV therapy and is successful in most cases. In particular,

its use is associated to prompt rehydration, reduced number of hospitalizations, better

replacement of bicarbonates, reduced number of episodes of diarrhea and vomiting, and

overall a better gain of weight at discharge.

Adjuvant and symptomatic therapy

a). Probiotics

Probiotics may be an effective adjunct to the management of diarrhea. Available data suggest

the use of probiotic strains with proven efficacy and in appropriate doses for the management

of children with AGE as a adjunct to rehydration therapy: Lactobacillus GG, Saccharomyces

boulardii.

• Lactobacillus GG:

- reduces duration of diarrhea

- highly effective for rotavirus AGE

- reduces the risk of diarrhea at 48 and 168 h

- no studied effects on fecal output

• Saccharomyces boulardii

- reduces duration of diarrhea

- reduces number of evacuations

- reduces the risk of diarrhea at 48, 144 and 168 h

- no studied effects on fecal output

b). Adsorbers

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An extract of clay is given (Smecta) 1,5 g (½ sachet) 1-3 x/day in foods for infants and 1-2

sachets/ in children over 1 year. You can also use Hidrasec 2 x ½ sachet/ day <1 year and 2-3

x 1/day in children> 1 year.

Recadodril can be used in the management of AGE.

c). Zinc supplementation

There is evidence that zinc supplementation in children reduces the duration and severity of

the diarrhea. WHO and UNICEF recommended for children in areas of risk the administration

of oral zinc preparations for 10-14 days during and after diarrhea (10 mg/ day less than six

months and 20mg/day over 6 months).

d) Collapse is to be controlled by rehydration in severe cases.

e) Vomiting - Plegomazin 1-2 mg/ kg/ day or Phenobarbital 5-10 mg/ kg im. Ondansetron

may be used - non-toxic effective antiemetic - a sublingual dose or 1 effervescent tb. (8-15

kg: 2 mg, 15-30 kg: 4 mg over 30 kg: 8mg). Beware because Ondansetron may increase the

QT interval on ECG, risk of death

f) Fever is to be fought by physical methods and administration of the well- known

antithermics (Paracetamol).

g) Flatulence is fought by local heat, rectal probe or 0,2-0,3 ml Miostin S.C. or I.M. de 1-2 x.

In some situations K are given, bloating being a symptom of hypokalemia.

h) Motility inhibitors (loperamide) – controversial, ESGHAN, not recommended

2. Drug treatment

Eutrophic infants, in mild/ medium forms of the disease, do not require medication, the oral

rehydration being sufficient. Most infectious diarrhea is self-limiting. In most cases of BDA,

antibiotic treatment is NOT necessary, as the etiology is a viral one (50-80%), even in the

presence of bacterial etiology, the antibiotic treatment may not be beneficial, producing side

effects. Antibiotic therapy is indicated in patients infected with a pathogen agent, agent that

acts through an invasive mechanism, if the patients presents fever, severe colicky abdominal

pain, stool with blood or pus, digestive occult bleeding (Gregersen positive reaction),

leukocytes in stool, in new born and in lambliasis. It is especially recommended in

shigellosis, salmonellosis, forms of dysentery with Champilobacter gastroenteritis

The following can be administered:

- Furazolidone 8-10 mg/ kg/ day in three doses for 3-5-7 days

- Biseptol 6-8 mg/ kg/ day in 2 doses, 3-5-7 days

The most commonly used oral antibiotics are:

- Ampicillin 100-200 mg/ kg/ day in 4 doses for 3-5 days

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- Amoxicillin 50 mg/ kg/ day in four doses over 3-5 days

- Colimicina 125,000 u/ kg/ day in 4 doses for 3-5 days

- Negamicina (Neomicyna) 100 mg/ kg/ day in four doses over 3-5 days

- Ciprofloxacin 15 mg/ kg/ day in 2-3 doses/ day for 5-7 days (especially in infections

with salmonella and invasive shigelle)

In the traveler's diarrhea, for Clostridium difficile the following medication is recommended:

Vancomicyn 40 mg/ kg/ day in 4 doses, 10 days

Metronidazole 15 mg/ kg/ day in 3 doses, 10 days

and for Entamoeba histolytica

- Metronidazole 45 mg/ kg/ day in 3 doses, 10 days

At present, effective antibiotic agents for shigellosis include third-generation

cephalosporines, azithromycin, nalidixic acid, and fluoroquinolones. Trimethoprim-

sulfamethoxazole and ampicillin, which were the classical antibiotics for Shigella, should be

considered only if the strain isolated is susceptible to those specific antibiotics.

In BDA short-term administration of these drugs is recommended (in order to avoid

resistance), the antibiotic is chosen until DST arrival based on the experience of the

physician, in severe cases concomitant therapy is administered.

Prolonged antibiotic treatment will be associated with B vitamins, mycostatics (Stamicin

50,000 IU/ kg/ day) and vitamin K (1 mg/ kg/ week).

ACUTE DEHYDRATION SYNDROME (ADS)

The syndrome produced by the loss of water and electrolytes is called acute dehydration

syndrome. A body, the younger, the more water it contains. Water represents a large

percentage of body weight, so: in prematures 80%, in newborns 78%, in infants 65%, while

in adults 60%.

Water distribution throughout the fluid sectors is as follows:

● in infants:

65% 25% Extracellular sector (E.C.S.) 5% compartment (plasma compartment

20% compartment

(interstitial comp.)

40% Intracellular sector (I.C.S.)

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● after the age of 1 year, fluid distribution by sector is similar to adults:

60% 20% E.C.S. 5% plasma compartment

15% interstitial compartment

40% I.C.S.

(There is also a transcellular compartment made up by L.C.R., synovial, pleural, pericardial,

intestinal fluid with a lower practical role and which is taken into consideration only in case

of ileus, massive pleural effusion , etc.) A rapid weight loss (24-36 hours) and 1% of body

weight means a loss of water. Water, however, does not circulate"freely" in the body, but as

an ionic solution (linked by electrolytes) and much less in the form of colloidal solutions

(linked by proteins).

Therefore, any loss of water means as well loss of electrolytes. Dehydration means not only

loss of water, but a hydro- electrolyte disorder as well (hydromineral).

Given the peculiarities of the hydromineral metabolism in infants and toddlers (low resistance

to thirst, more lively exchange of water, etc.) dehydration retention of water and electrolytes

(edema)( in the pathology of the adult) prevail.

Causes

1. Determining causes: insufficient intake (thirst, starvation); exaggerations in removing

water and electrolytes by physiological methods: a. intestinal (diarrhea, vomiting), b. skin

(abundant sweating), c. pulmonary (polipnee) and/ or reducing intake (anorexia, intolerance,

abolition in swallowing); other diseases: renal, endocrine, medications causing polyuria

(diuretics, lithium salts, hypokalemia, hypercalciuria).

2. Favoring causes: young age, constitutional diatheses, prematurity, rickets and dystrophy,

diabetes.

Diagnosis

The syndrome has two aspects, a clinical and a pathophysiological one.

From a clinical point of view, there are three degrees of ADS, stages of severity and also

developmental stages

ADS gr. I - mild dehydration

In infant (description model) represents a weight loss up to 5% of the total body weight, the

child is more anxious/ drowsy, more apathetic/ agitated, thirsty, his lips and the tongue - "are

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somehow" drier, minor symptoms, usually go unnoticed, the only objective sign is the fact

that the tongue loses its shininess.

ADS gr. II - medium dehydration

Losing weight is between 5-10% of the total body weight, with the same symptoms as in

ADS gr. I, but more pronounced, agitation, drowsiness, fried lips, dry tongue; decreased

turgor occurs in addition (persistent), sunken (depressed) fontanelle (if still open).

ADS gr. III - severe dehydration

It is a weight loss of more than 10% of the total body weight, symptoms from ADS gr. II are

more pronounced, further (memotehnic one/ more C’s): C - disorders of consciousness

(restlessness, drowsiness, torpor, sleepiness) - up to coma, C – collapse or C – convulsions. It

is enough to have signs of dehydration and 1 C for a severe dehydration. Some authors call it

"syndrome" only ADS gr.III (emergency). Toxicosis is an ADS gr. III of a digestive origin.

Infants and toddlers, at losses of over 15% evolve rapidly to death (an adult can withstand the

loss of abou 27%). High risk categories are malnourished premature, small babies (under 3

months). Fat children are more hydrolyzed (fat is poor in water). Depending on the particular

hydro-mineral metabolism, rates of water loss are lower: mild dehydration - up to 3%,

medium dehydration 3-8%, severe dehydrationmore than 8%.

At adolescents and in adults, a 3, 6 up to 9% is allowed.

Table CCCC Clinical dehydration scale

Characteristics 0 1 2

General

appearancenormal

thirsty, restless, or lethargic but

irritable when touched

drowsy, limp, cold, or

sweaty, comatose or not

Eyes normal slightly sunken very sunken

Mucous

membranesmoist Sticky dry

Tears tears Decreased absent

Score of 1= no dehydration

Score of 1 to 4= mild/moderate dehydration

Score of 5 to 8= sever dehydration

(Bailey B, Acad Emerg Med 2010)

From the pathophysiological point of view three forms are recognized, based on water

movements that attract major changes in ions: Na + (the ion of the extracellular space), K+

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(the ion of the intracellular space). It disrupts the acid-base balance, Cl- concentration,

bicarbonate (the concentration varies inversely on the anion column), and of H+.

Table zzzz Changes in ions

Cations+ (B) Anions- (Ac) Total

Na+ 140 mEq/l Cl- 110mEq/l ↑ - acidosis

K+ 5 mEq/l HCO3- 25 mEq/l ↑- alkalosis

and Ca++, Mg++... SO4-... 310 mEq/l

The sodium is the main electrolyte of the extracellular space, the basic element of the

pathophysiological classification of dehydration. There are 3 forms.

1. Hypernatremic Dehydration (hypertonic, intracellular)

The plasma sodium is above 150 mEq/L (N = 140 mEq/L), the body loses proportionately

more water than Na +, children are febrile, thirsty, the skin and mucous membranes are dry

(~hot), wrinkled tongue, H-irritability, agitation prevails, the pulse is more rapid, the TA is

relatively normal for a long time, signs of water loss are predominant intracellularly and for a

while the plasma compartment of E.C.S is relatively well preserved, shown by the pulse and

TA; usually hyperglycemia occurs (poor utilization of glucose by dehydrated cells), or

hypocalcemia (the cause is unclear). It is estimated that this form represents ~ 20% of total

dehydrations.

Causes: the use of inappropriate infusion concentrates to restore dehydration, a renal

concentrating defect with the loss of free water. The excess of glucose, urea or mannitol can

cause the same problems as the excess Na +.

2. Hyponatremic dehydration

The plasma sodium is below 130 mEq/L, is as hypotonic, extracellular form, the body loses

proportionately more water than Na +. Children are afebrile, refusing food and water, the skin

is wet, cold, decreased turgor, apathy, drowsiness prevail, to coma, the pulse is rapid (without

fever), low TA, frequently progresses to collapse. In this form we meet water loss symptoms,

predominantly extracellular ones; the plasma and interstitial compartment suffers faster and

more intense, frequently occurring seizures (hyponatremia) and cerebral edema. Represents

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5% of total dehydration, is the most "noisy form”, fastly connected to the plasma

compartment, therefore some admit small percentages in this form - 3, 6, 9%.

Causes: incorrectly replaced enteral losses, only with water, tea, fruit juice, i.v. correction of

the loss of "free water", the solution of glucose or solutions with a low Na+ content.

3. Isotonic/isonatremic dehydration

The plasma sodium is relatively normal (130-150 mEq/L), the body loses evenly water and

Na +, the clinical signs of dehydration are as hypotonic ones, with dry skin and mucous, the

turgor is not so low. It represents about 75% of the dehydration, the majority begin with

isotones, almost all body fluids (exception saliva, tears) being isotonic with plasma (fluid

homeostasis).

Assessment of dehydration:

- capillary refill time (> 2 seconds)

- skin turgor

- respiratory rate

These are the three best individual examination signs for assessment of dehydration.

Treatment

Etiological treatment – treatment of the condition which led to dehydration: acute diarrhea,

vomiting, pneumonia, etc..

Pathogenic treatament of the ADS. The pathogenic treatment should be initiated always in the

presence of ADS, being in front of a state of hypovolemic shock. The main purpose is to

preserve functional the plasma compartment, volemia (relatively stable compartment and

absolutely necessary to the homeostasis of the body).

In practice dehydration treatment is confused with rehydration, replacement of lost water and

electrolytes.

There are two methods for rehydration: oral (per os) and parenteral (i.v.)

Oral rehydration - see BDA

Indications: ADS gr. I and II without vomiting, with peristalsis

Parenteral rehydration

Indications: ADS gr. III, ADS gr. I+II with continuous vomiting and if the patient can not

receive oral treatment (stomatitis, burning, and so on).

Venous access is difficult in the newborn and infant, peripheral veins are collapsed.

Other avenues of approach are the superior longitudinal sinus (if the fontanelle is open), tibial

bone puncture, discovery of the cephalic vein in the arm; infusion line installed will be kept

for 24 hours.

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Parenteral rehydration methods:

A. Standard rehydration

The method comprises administering electrolyte solutions (Ringer, Ringer's lactate, Starter,

and others), n order to correct electrolyte and acid-base disturbances during 24-48 hours.

B. Directed rehydration

Method of fineness; applied if standard rehydration fails.

Correction of electrolyte and acid-base disorders is based on data obtained by flamfotometry

(plasma and urinary ionograma), microASTRUP parameters.

A. The standard method

A.1. Calculation of current needs (maintenance ratio)

A.1.1. Water needs, resulting in energy metabolism:

- between 3-10 kg body weight …………...100 kcal/kg

- between 10-20 body weight ……………1000 kcal + 50 kcal for each kg > 10

kg

- > 20 kg ……………………………..1500 kcal + 20 kcal for each kg > 20 kg.

Because for 100 metabolized kcal 100 ml water is needed, the above formula also applies

to determine current needs of water.

A simplified formula (Chicoine, Ayotte) according to age:

- under the age of 1: 90 ml/kg/day

- over the age of 1: (85 ml – 3a)/kg/day, a = age in years

A.1.2. Current needs of electrolytes, resulting also from energy metabolism, respectively loss

of electrolyte to 100 metabolized kcal, thus:

Table xxxxxx Loss of electrolyte

Way Water Na (mmol) K (mmol)

Perspiration 15 0 0

Sweating 40 0,1 0,2

Feces 5 0,1 0,2

Urine 65 3,0 2,0

Total 125 ml 3,2 mmol 2,4 mmol

Considering that 15 ml of water comes from the intermediary metabolism, the following ratio

is toi be taken into consideration: 100 ml water + 3 mmol Na + 2 mmol K.

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Reported per liter, the current needs of electrolytes are:

1000 ml + 30 mmol Na + 20 mmol K

Fanconi's solution (1/5 normal saline solution + 4/5 glucose 5%) covers the current

necessities of Na, making 30 mmol Na/L and 30 mmol Cl/L (plus an energy intake by those

40 g glucose/1 L).

A.2. Deficit calculationcitului (of losses)

A.2.1. Water loss. It results from the percentage of weight loss (by weighing). If someone lost

"on scale" 1 kg, it means he lost 1 liter of water. If he has not been previously weighed,

assessment is made by clinical appearance, respectively ADS gr. III over 10%, ADS gr. II: 5-

10%; ADS gr.I: 3-5%.

A.2.2. The loss of electrolytes. It is calculated using Darow-Viallate’s scheme so: at 100 ml

of water lost by various means, the following electrolytes are lost:

Way Na (mmol) Cl (mmol) K (mmol)

Vomiting 10 10 2

Diarrhea 6 6 6

Sweating (fever) 2 2 2

If losses occur in several ways, an average is made in the first place. (i.e. 100 ml is lost due to

vomiting and diarrhea, meaning 10 + 6 = 16/2 = 8 mmol Na).

Standard methods take into account some mandatory rules. In addition to current needs the

following must be known:

a). The duration of dehydration (affects, in time,the hydro sectors)

The duration of dehydration % ECS loss % ICS loss

< 2 days 75% 25%

> 7 days 50% 50%

2-7 days 60% 40%

b). The composition of hydro sectors (it is very different)

- ECS: Na = 140 mEq/L; K = 5 mEq/L

- ICS: Na = 10 mEq/L; K = 160 mEq/L

Principles of parenteral rehydration:

- Fast filling and completion of the circulating volume with an isotonic solution with

LEC (normal saline solution, Ringer, Ringer-lactate, Starter)

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- Replacing deficit and current needs of water and electrolyte with a solution made

according to the severity and type of dehydration (hypo, hyper, isotonic) solution

which is administered 24-48 hours.

- Concomitant administration of both the deficit and the current needs of water and

electrolytes, as far as oral administration is not optimal.

• The first stage is to combat hypovolemic shock (collapse), because dehydration decreases

the volume of ECS leading to the decrease of the tissue perfusion with impaired renal

function, compensatory tachycardia and lactic acidosis.

In the decrease of circulating volume, the child responds by tachycardia, keeping TA before

dehydration. Therefore, a significant decline or a TA crash is a sign of collapse.

20 ml/kg i.v. (PEV) crystalline solutions (normal saline solution, Ringer sol., etc) or plasma

substitutes (dextrans, products of gelatin, 5-10% of human albumin) are is urgently

administered “in bolus” and it is repeated, if needed, until restoring the blood volume

(maximum is 60 ml/ kg).

If circulation is not restored after the administration of 40 ml/kg isotonic solution, the

existence of a sepsis, cardiogenic shock or occult bleeding must be infered.

In anhidremic shock (as well as in the haemorrhagic one) the loss of the interstitial

extracellular fluid must be taken into account (LEC), the one that passes intravascularly

(where the colloid osmotic pressure is higher, especially due to glucose which increases after

bleeding).

In intensive care the relationship between the plasma/ interstitial compartment is taken into

consideration, respectively 1:3 and therefore, 3-4 times more fluid should be administered

than lost blood.

• The next step is to restore the LEC administering in the first 8 hours: ½ of water and

electrolytes lost, and the other ½ in the next 16 hours. Simultaneously content

maintenance is administered as well.

B. Conducted rehydration

It requires the cognition of the plasma and urinary ionogram (so “the outputs”) in order to

redress the electrolytes and the parameters of the microAstrup method in order tp correct

acid-base imbalances.

Plasma ionogram

(normal value)Urinary ionogram Astrup parameters

Na = 140 mEq/L Na = 110-1180 mEq/L pH = 7,35 – 7,45

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K = 5 mEq/L K = 35 – 55 mEq/L pCO2 = 46 mmHg (in

arterial blood = 40 mmHg)

Ca = 7-10 mEq/L BS = 25-28 mEq/L

Mg = 7-8 mEq/L BE = ± 2,3

Cl = 110 mEq/L (pO2 = 40 mmHg; arterial

= 100 mmHg – oximetry is

obtained not by Astrup).

PO4 = 25-30 mEq/L

SO4 = 20-30 mEq/L

The general formula

mEq administration. = (Cd – Ca) x 0,3 (0,6) x G

Cd = the desired figure (n)

Ca = current figure (of the apparatus)

0,3 =the coefficient of the extracellular space

0,6 = distribution factor for Na (differs for K, HCO3)

Acid-base disorder diagnosis

The

disorder

pH

(BE)pCO2

BS

(RA)Renal compensation

Pulmonary

compensation

Metabolic

acidosis

Acidic urine

NH4 HCO3 reabsorption

rapid, ample v.

pCO2

Respiratory

acidosis

Idem –

Metabolic

alkalosis

alkaline urine

NHA HCO3 reabsorption

superficial, rare v.

CO2

Respiratory

alkalosis

Idem –

Legend:

BE = excesul de baze; RA = alkaline reserve; v = vantilation, * = compensation.

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RECURRENT ABDOMINAL PAIN (RAP)

Definitions

Apley and Naish in 1958 defined recurrent abdominal pain (RAP) as a “ syndrome

characterized by intermittent episodes of abdominal pain, with variable duration and

intensity, occurred over a period of at least 3 months, without any identifiable cause or which

interferes with the child's daily activities”. Occasional, transient pains, which do not disrupt

the normal activity of a child are excluded from RAP. RAP has a duration of a few minutes

up to 1-3 hours (80%) and over 24 hours (10%). With time the criteria were modified, the

term recurrent was replaced with chronic or functional pain.

Chronic abdominal pain is one of the most common symptoms that occur in childhood and

adolescence, with a prevalence of 1-19% and represents 2-4% of cases of going to the

pediatrician. It is characterized by continuous, chronic abdominal pain, recurrent with quiet

periods which are short and rare, the pain not being well localized and changing the child's

daily activities. Chronic abdominal pain is functional and organic.

Today the terms of recurrent or chronic abdominal pain were abandoned and were replaced

with the term “ pain-related functional gastrointestinal disorders” (FGIDs).

In 1999 in Rome an expert group of pediatricians gastroenterologists have made an attempt to

establish criteria for the diagnosis of FGIDs named as Roma II criteria. On this occasion the

classification of RAP in children in 4 groups of FGIDs did not have support to sustain a

classification. However, there are 4 groups of FGIDs: functional dyspepsia (FD), irritable

bowel syndrome (IBS), functional abdominal pain (FAP) and abdominal migraine.

Subsequent studies have expanded, so that in 2006 s- diagnostic criteria for FGIDs were

revised and updated, and they are known as pediatric Rome III criteria. Thus due to the high

variability and phenotypic presentation of children with FGIDs, the category of functional

abdominal pain from the previous classification was divided into two separate problems,

namely: childhood functional abdominal pain and childhood functional abdominal pain

syndrome (FAPS). In addition the duration of symptoms was changed from 2 to 3 months.

The new classification is shown in the following table.

Classification of functional abdominal pain according to the Rome III criteria

Functional dyspepsia (FD)

Persistent or recurrent pain or discomfort centered in the upper abdomen (above the

umbilicus)

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Not relieved by defecation or associated with the onset of a change in stool frequency

or stool form (i.e., not irritable bowel syndrome)

No evidence of an inflammatory, anatomic, metabolic or neoplastic process

that explains the subject’s symptoms

Criteria fulfilled at least once per week, at least two months prior to diagnosis

Irritable Bowel Syndrome (IBS)

Abdominal discomfort (uncomfortable sensation not described as pain) or pain

associated with two or more of the following, at least 25% of the time:

a) Improvement with defecation

b) Onset associated with a change in frequency of stool

c) Onset associated with a change in form (appearance) of stool

Criteria fulfilled at least once per week, at least two months prior to diagnosis

Symptoms, which through cumulation, support the diagnosis of irritable bowel are: 1.

abnormal stools (four or more times/ day and two or less/ week), 2. abnormal aspect of the

stool (coarse/ consistent or unformed/ watery diarrhea), 3. abnormal discharge (tension,

urgency, feeling of incomplete discharge), 4. mucus and 5. bloating or feeling of abdominal

distension.

Abdominal migraine

Paroxysmal episodes of intense, acute periumbilical pain that lasts for 1 hour or more

Intervening periods of usual health lasting weeks to months

The pain interferes with normal activities

The pain is associated with 2 of the following:

a) Anorexia

b) Nausea

c) Vomiting

d) Headache

e) Photophobia

f) Pallor

All the above criteria must be included and performed more than twice in the last 12

months

Functional Abdominal Pain

Episodic or continuous abdominal pain

Insu�cient criteria for other FGIDs

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Must satisfy criteria for functional abdominal pain and have at least 25% of the time

one or more of the following:

1. some loss of daily functioning

2. additional somatic symptoms such as headache, limb pain, or di�culty sleeping

Criteria fulfilled at least once per week for at least 2 months prior to diagnosis

* No evidence of an inflammatory, anatomic, metabolic, or neoplastic process

that explains the subject’s symptoms

Epidemiology

The incidence of recurrent abdominal pain (RAP) ranged from 0.3 to 19%, with an average of

8.4%. The disease is very rare, under the age of 3. It is more common in schoolchildren and

adolescents. There are two peaks of age that develop recurrent abdominal pain, that is: first

peak around the age of 5 and the second one at 8 – 10 years. In the prepubertal period there is

gender equality and in adolescence the ratio F/ M = 2/1.

Pathophysiological mechanisms

The exact etiology and pathogenesis of the pain is known.

Since 1987 it is known that pain is perceived and stored since the fetal period. CNS

immaturity at birth and incomplete myelination do not let pain to be perceived less because

the algo conductive paths are not affected. Children perceive pain as adults, but perception

increases depending on the stage of cognitive development.

Visceral pain perception performs a complex relationship between the peripheral and the

central nervous system. The enteric nervous system (ENS) is organized into two major

plexuses which provide the intrinsic innervation of the bowel: Auerbach’s myenteric plexus,

located between the outer longitudinal layer and the inner circular muscle layer and

Meissner's submucosal plexus; there is a functional fusion between them forming a mini-

brain, “intestinal brain ". ENS can work individually; he receives impulses from the CNS of

which is bound by related and efferent fibers. SNC continuously integrates information from

the gastrointestinal tract with information from other organs or from the environment; CNS

initiates appropriate responses, which explains the gastrointestinal response to stress or

emerging clinical manifestations (cyclical vomiting, diarrhea, etc.). ENS and brain use

multiple excitatory type neurotransmitters: acetylcholine, P substance, nitric oxide, ATP,

vasoactive intestinal peptide - VIP, cholecystokinin, etc. So at this age "the gastrointestinal

tract is the resonance box of the whole body."

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There are some "ailments", negative emotions (psycho-emotional factors) that the child

perceives as RAP. The pathogenesis of functional painful disorders involves the relationship

between altered gastrointestinal motility and changes in visceral sensations– visceral

hyperalgesia.

The symptoms for altered motility are: diarrhea, constipation, abdominal distension, and

those for hypersensitivity to pain and discomfort..

Factors that are incriminated in the pathogenesis of abdominal pain syndrome include:

- visceral hypersensitivity,

- altered central modulation of pain sensations

- genetic factors - children with irritable bowel syndrome (IBS) have parents with

functional gastrointestinal disorders

- Serotonin - the key mediator in modulating visceral sensitivity and motility.

- inflammation - role in the pathogenesis of IBS

- stress and psychological factors (depression, hypochondriasis, hysteria), or behavioral

disorders (school phobia, pain by imitation).

- Dysmotility

- aerophagia

Clinical symptoms: about 50% occur daily, 30% have a painful episode/ week, 20% have

one episode/ month.

Characteristics of pain:

Organic pain is precisely localized, constant and radiates; if the baby wakes up from sleep it

means the pain is organic; when the pains are generalized, the child especially perceives them

in flanks. It occurs in 8-27% of the cases. The presence of fever, accelerated ESR, weight loss

lead toward organic pain.

Functional pain (inorganic) is usually diffuse and localized around the navel (60%) and then

epigastric (26%) or in other places; it can associate headache, nausea, vomiting, and

constipation. Sometimes painful crisis can be connected with psycho-emotional events (tests,

theses, festivals, school fights, “Monday morning colic”); even sexual feelings in puberty can

be translated into RAP. The pain may have the form of a colic (50%), dull (30%) or cramps

(20%).

The diagnosis of functional abdominal pain

Because the exact etiology and pathogenesis of the abdominal pain is unknown, there are no

specific markers for the diagnosis of functional abdominal pain.

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Because most of the time abdominal pain does not have an organic cause, it is important to

make a minimum investigation at the beginning that will be extended depending on the

serevrity of the case.

The diagnostic algorithm of functional abdominal pain is presented in the chart below:

Algorithm for evaluation of children with recurrent abdominal pain

Chronic abdominal pain

History and physical examination

The presence of some alarm signals

1. Involuntary weight loss2. Growth retardation3. Delayed puberty4. Significant vomiting5. Diarrhea6. Gastrointestinal bleeding7. Extraintestinal symptoms8. Unexplained fever9. Family history of IBD10. Right iliac fossa pain11. Abnormalities on physical

examination

Yes

Additional examinations

No

Criteria for constipation YesTreatment of constipation

No

Diagnosis related to pain of functional gastrointestinal disordersDiagnostic tests

1. Complete CBC2. ESR3. Metabolism examination4. Investigations for celiac5. Urinalysis6. Parasitological examination7. Tests for H. Pylori (atg.

from stool, respiratory and urea test,)

8. Lactose test

Modified tests

Yes

Additional investigations

No

Initiation of appropriate treatment

Subtype diagnostic - Rome III criteria

Isolated pain: Functional abdominal painWith associated spt: Functional abdominal pain

syndromeWith alteration of the peristaltic: Irritable Bowel

SyndromeParoxysms.: abdominal migraine

In the diagnosis of FGIDs the following are important:

History and physical examination of the patient: In most cases, the abdominal pain is

functional, being organic only 8-27% of the cases. History will be done thoroughly, focusing

on the characteristics of pain, detection of psychological and emotional factors; in children

with an "irritable bowel” atopic, colopatic or neurotic family history is always detected. The

Irritable Bowel Syndrome” has symptoms according to age: colic in infants, nonspecific

diarrhea in children between 1-5 years old, RAP Between the ages 5-13, diarrhea-

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constipation alternating in adolescents and abdominal pain with diarrhea and/ or constipation

in adults.

Laboratory tests include:

- CBC

- Hepatic analyses: transaminases, bilirubin, GGT, LDH

- Renal analyses: creatinine, urea, uric acid

- Amylase

- ESR

- Urinalysis and urine culture

- Stool analyses, including the detection of occult blood in the stool and fecal exam

- Total protein, protein electrophoresis

- atc IgE and IgG – for diagnosing food allergies

- atc. Anti endomisium, anti-reticulin (celiakie)

- Serological tests for the detection of Helicobacter pylori

- Abdominal ultrasound

- Digestive and inferior endoscopy

- Esophageal pH meter

- Barium transit

The differential diagnosis of chronic recurrent abdominal pain is made between the

following conditions, which represent the most common causes of recurrent abdominal pain:

- Functional abnormalities

Functional abdominal pain

Functional abdominal pain syndrome

Irritable bowel syndrome

Functional dyspepsia

Abdominal migraine

Aerophagia

- Gastrointestinal tract

Gastro-oesophageal reflux disease

Helicobacter pylori gastritis

Peptic ulcer

Esophagitis

Lactose intolerance

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Celiac disease

Parasitic infestation (Gyardia, Blastocystis hominis)

inflammatory bowel disease

Meckel diverticulum

Intestinal malrotation with intermittent volvulus

Chronic appendicitis

- Gall bladder, liver and pancreas

Cholelithiasis

Choledochal cyst

Hepatitis

Liver abscess

Recurrent pancreatitis

- Genitourinary Tract

Urinary tract infection

Hydronephrosis

Urolithiasis

Dysmenorrhea

Pelvic inflammatory disease

- Various Causes

Gilbert’s syndrome

Family Mediterranean Fever

Malignancies

Sickle cell

Lead poisoning

Vasculitis (especially Sconlein-Henoch)

Angioedema

Acute intermittent porphyria

Treatment

The treatment includes education, identification and modification of psychological factors

and stress, dietary therapy, drug therapy

1. Education is very important in the treatment of children with chronic functional abdominal

pain.The patient will be given the necessary empathy and will be explained to him and to his

family that the so-called functional abdominal pain is the most common cause of RAP. It

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requires a normal lifestyle, with a regular school activity, the child's involvement in

extracurricular activities, normal sleep schedule.

Identification of stress factors and provision of appropriate psychological support

Cognitive behavioral therapy and hypnotherapy (especially in IBS) is very important.

2. Dietary treatment:

- fibers (cereals) – especially in constipation decreasing the intestinal transit time

- avoiding lactose (lactose intolerance)

- elimination diet – on the basis of the suspected food allergy. In food allergy Sodium

cromoglycate 60 mg/ kg/ day plays an essential role

- Probiotics have a role in preventing the growth of pathological bacterial flora and

maintaining the integrity of the mucosal barrier. Biotics, Enterol 2 x 1 caps/ day

Ecoflorina 2 x 1 vial/ day

3. Medication useful for modulating gastrointestinal motor function, neurohormonal response

to stress, cytokines involved in the inflammatory process.These include:

- H2 blockage – Famotidine in patients with functional affections

- Serotonergic agents: Pizotifen, Citalopram, alosetron, Tegaserod.

Only the first two have been used in limited batches in children and decreased the

frequency of painful episodes/ day. Controlled studies are still needed in order to

include them into treatment.

- Tricyclic antidepressants used in the past, today only in adults (Amitriptyline,

Nortriptyline, Clomipramine, Imipramine)

- Tranquilizers and antispasmodic: Oxifenonium (parasympatholytics synthesis) 3 x ½

-1 tablet./ day for school children, combats smooth muscle spasm of the

gastrointestinal tract, urogenital and biliary tract; Propantheline (anticholinergic,

antispasmodic, antisecretory); benzodiazepines (minor tranquillizers such as

diazepam, oxazepam, alprazepam the last one is a disinhibitor, administered in case of

anxiety

- Antihistamines: Hydroxyzine for 1 week - good results in the regulation of sleep;

- Neuroleptics: Thioridazine and Levomepromazine - weak action (sedatives),

Chlorpromazine (Largactil) average action and Haloperidol with strong action

(antipsychotic).

- Complementary therapy: peppermint oil (relaxes smooth muscles of the

gastrointestinal tract), ginger – useful for patients with nausea, dyspepsia, diarrhea.

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- For organic cases - specific treatment of the underlying disease: giardiasis, ITU, renal

calculus, gastritis, peptic ulcer, colitis, Meckel’s diverticulum, hernias of the

abdominal wall, perforation of the hymen.

- In the irritable bowel syndrome fats are reduced in the diet, cold liquids are

prohibited, the is enriched with dietary fibers, in association with medication:

Loperamide: 4 x 1 mg (½ tb/ day) between 4-9 years, 3 days; 4 x 2 mg (1 tb/day) over

9 years, for 5 days, in "spastic colon" in order to stimulate motility - Cisapride

(Prepulsid), dopamine antagonists in children over 12 years of 3 x 10 mg (3 x 1 tb/

day) 6 weeks (4 weeks in non-ulcer dyspepsia).

PARASITES

Parasitic infections of the gastrointestinal tract occur in all geographic regions of the world

and cause substantial morbidity in children.

Below only the most important and most common parasites in children are presented.

PROTOZOA

Giardiasis (Giardiasis, Lambliasis)

Giardiasis is an infection caused by the parasite Giardia lamblia which is found in the normal

duodenum and jejunum.

Fecal-oral transmission makes this parasite to be frequent in units where there are children;

but it is also common among healthcare workers (25% of the cases)

Symptoms are extremely varied, and can also be manifested by diarrhea with an insidious

onset, steatorrhea, irritability with weight loss, recurrent abdominal pain. In 25-30% of cases

it is asymptomatic.

Positive diagnosis is made by:

- Highlighting cysts in stool. In one infected case the cystic form is found in the stool in

a percentage of 30%, so the examination of the stool will be repeated at least 3 times,

which increases the chance of detection to 50%. In heavy infections mobile

trophozoites can be observed in the freshly emitted stool. Poor highlighting of the

cysts is due to their irregular excretion.

- Highlighting the vegetative form from the duodenal juice. Highlighting of

trophozoites helps to put the accurate diagnosis, however, infants and young children

hardly bear the duodenal survey. The entero-test is more acceptable.

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- Serological tests are sometimes used as well: indirect immunofluorescence and

immunoassay analysis - IgM.

The differential diagnosis is done with other causes of chronic abdominal pain and

celiachiform syndrome.

Treatment

1. Atebrina (Mepacrin) 1 tablet. = 0.100 g;. 6 mg/kg/day (max. = 0,3 g), divided into 2

to 3 daily doses for 6 days (cause yellow coloration of the whites).

2. Metronidazole 1 tablet = 0.250 g, 20 mg/ kg/ day (max = 1 g), divided in 2-3 daily

doses for 7-8 days.

3. Tinidazol (Tinidazole, Tinigyn) 1 tablet = 0,500 g, 50 mg/kg/day (max. = 2 g) in a

single dose, 80% of cases resolved. Some people prefer it as a consolidation

treatment after using Atebrina or Metronidazole over a period of 2-3 days and

divided into 2-3 doses.

4. In infants and young children a combination of erythromycin + furazolidone is used.

- Erythromycin 20 mg/ kg/ day administered 30 minutes before meals,

- Furazolidon 5 mg/ kg/ day after meals. This combination is given for 5 days (10

days).

This treatment is well tolerated but it is only effective in a percentage of 40% therefore,

usually, the treatment needs to be repeated after 6 weeks.

Another scheme uses only Furazolidone 8 mg/kg/day in 3 divided doses for 10 days. (The

results are good provided that food is properly chewed).

5. Ornidazol (Tiber). Dose: children under 1 year 2 x ¼ tablet./ day, 1 - 6 years 2 x ½

tablet./ day, 7-12 years 2 x ¾ tablet./ day, in the morning and in the evening after

meals, for 5-10 days.

6. Albendazole 400 mg/ day in a single dose from 5 to 7 days.

Because giardiasis is associated with oidium albicans, Stamicina or yogurt will be associated

to the basic treatment.

Infection control will be done after 6 weeks, period considered necessary to eliminate drugs

and remultiplication of the parasite, not a mandatory control.

A single treatment is recommended to be done.

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NEMATODES

Strongiloidosis

Strongiloidosis is caused by the parasite Strongiloides which has two forms: a parasitic one

and one with a free life.

The route of entry is dermal, from here through the blood vessels reaches the pulmonary

capillaries where produces alveolar hemorrhage and bronchopneumonia and affects the

gastrointestinal system as well causing villous atrophy. From here through the lymphatic

system may disseminate anywhere in the body.

Clinical symptoms

Many patients may be asymptomatic.

Patients become rapidly symptomatic after penetration of the skin presenting: local skin

reaction, respiratory symptoms: cough, wheezing, pulmonary infiltrates, watery diarrhea,

abdominal cramps, urticarial rash, occasional bowel obstruction, sepsis, meningitis, etc.

Diagnosis

- Hypereosinophilia > 500 cells/μl

- Detection of larva migrans in the stool, sputum, jejunal biopsy

- Positive serology (> 80% of cases)

Treatment

- Ivermectin 150-200 mg/ kg single dose, repeated after 1 week. Or

- Ivermectin 200 μg/kg/day for 3 days.

TRICHINELLA SPIRALIS

Trichinella spiralis occurs in communities where infected pork is consumed.

After ingestion of infected meat, the cysts release their larvae in the stomach which reach

maturity in 5 – 10 days in the small intestine. Mature females create new larvae which

penetrate through the intestinal wall and migrate at the level of the striated muscles and rarely

at the level of the brain and heart.

Clinical symptoms

They appear only in heavily infested people and consist of: abdominal colic, watery and

bloody diarrhea, vomiting, dehydration. In the stage of larval invasion facial or periorbital

edema, myalgia, lymphadenopathy satellite, swelling of the salivary glands, fever can occur.

Heart rhythm disorders, neurological symptoms meningoencephalitis can occur as well.

The diagnosis is based on the symptoms, elevated LDH and CPK, muscle biopsy (at 3-4

weeks after infection), serological reactions

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Treatment

Mebendazole 200 mg x 2/ day or Thiabendazole 2 x/ day for 10 days.

ASCARIASIS

Ascaris lumbricoides infestation occurs through ingestion transmitted by dirty fingers, dirty

eggs, water or food contaminated. After ingestion the eggs reach the duodenum where they

transform into rhabdoid larva, then they get into the port system and liver, then the lungs (by

venous or lymphatic way).

The clinical picture

Most patients are asymptomatic. The disease becomes manifest in massive infestation.

Children may present somatic and neuropsychiatric retard, pulmonary symptoms -

pneumonia (by the migrating parasite), digestive symptoms: abdominal pain, nausea,

vomiting, flatulence, diarrhea, intestinal obstruction, hepatobiliary and pancreatic symptoms.

Diagnosis

- Elimination of the parasite

- Ultrasound or endoscopy with retrograde cholangiopancreatography.

Treatment

- Albendazole in a single dose of 200 mg/day in children of 2 to 5 years old and

400 mg/day in children> 5 years old or

- Decaris (Levamizol) 5 mg/ kg in a single dose.

ENTEROBIASIS (OXYURIS)

Enterobius vermicularis infests the human being by ingestion of the embryonated eggs. Eggs

are disintegrated in the stomach and migrate to the cecum. They have sizes less than 1 cm and

they are white. During the night the females migrate to the perianal region where they lay

their eggs.

The clinical picture

The disease may develop asymptomatically, but children may present nocturnal anal pruritus,

agitation, insomnia, weight loss, scratches.

Diagnosis:

- Highlighting the adult worms in the stool or detecting their eggs

Treatment

- Albendazole 200 mg/ day in children under 5 years old and 400 mg/ day for children

over 5 years old as a single dose

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- Mebendazole 2 x 100 mg/ day for 3 days

- Pyrantel pamoate or piperazine

VISCERAL LARVA MIGRANS (TOXOCARIASIS)

Toxocara infestation occurs in young children, 1-4 years old, if living in close contact with

dogs and cats. Soil contamination with feces of dogs and cats contributes to the spread of the

infestation. Infection in humans occurs by ingestion of parasite eggs. After ingestion the eggs

give rise to larvae which penetrate the wall of the digestive tract and migrate to the liver,

lung, brain, kidneys, heart, eyes.

Clinical symptoms: fever, cough, wheezing, severe respiratory failure, seizures, abdominal

pain, hepatomegaly, skin rash, lymphadenopathy. The ocular form may occur as well

characterized by decreased visual acuity, strabismus, etc.

Diagnosis: Increased eosinophilia confirmed by serological reactions – ELISA tests, specific

atc.

Treatment

- Thiabendazole 25 - 50 mg/ kg/ day for 5-days or

- Albendazole 2 x 400 mg/ day for 5-days

- In the location of the eye: Prednisone 2 mg/ kg/ day until symptoms improve.

CESTODES

ECHINOCOCCOSIS (HYDATID DISEASE)

The disease caused by Echinococcus granulosus is endemic in regions characterized by

intensive rearing of sheep, goats and cattle.

The adult worm is localized in the small intestine of some organisms which are the definitive

hosts of the parasite (dog, cat, wolf), and in the larva state (hydatid cyst) is found in the

viscera of some ruminants (sheep, cattle, goats) or of mammals (pig) that are intermediate

hosts. By ingesting parasite viscera by the definitive hostsof the parasite in their small

intestine scolexs are released which are anchored to the intestinal or duodenal mucosa and

adult worms are developed, which after maturing produce eggs that are eliminated through

faeces.

The clinical picture: the disease may develop long asymptomatically for a long time due to

the slow growth of the cyst (for years). It is manifested clinically by large hydatid or broken

cysts when the patient may present irregular hepatomegaly, portal hypertension (rarely),

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allergic manifestations, chest pain, dyspnoea, cough or signs of intracranial haemorrhage and

focal neurological signs in cerebral localization

Diagnosis

Eo ↑, TST Cassoni positive, monoclonal atc

Treatment

- Surgical removal of the cyst

- Postoperative treatment with albendazole aimed to destroy possible small hydatid

cysts, undetectable clinically or through laboratory investigations

- If the cyst cannot be treated surgically 10-15 mg/ kg/ day of Albendazole is

administered divided in three doses during 3 months

- In disseminated forms and in peritoneal echinococcosis, Albendazole is recommended

in 4-6 cures each one for 4 weeks with intervals of 2 weeks between them.

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CHAPTER VI - NUTRITION AND DEFICIENCY DISEASES

Conf. Univ. Dr. Mărginean Oana, Asist. Univ. Dr. Pitea Ana Maria, Asist.

Univ. Dr. Chinceșan Mihaela, Asist. Univ. Dr. Grama Alina

MALNUTRITION DISTROPHY PROTEIN-ENERGETIC MALNUTRITION MPE

Definition: Chronic nutritional disorder

The body incapacity to cover quantitative and/or qualitative – the needs (caloric, nitrous) by

lack of intake or the impossibility of the digestive tube to accept, process or absorb the food

properly.

Etiopathogeny

I Determinant causes

a) “ex alimentatione”

dietary mistakes - hypocaloric diets desequilibrum

b) “ex infectione”- all infections ↓ digestive tolerance

more “dangerous”

o infections of the digestive tube

o repeated infections – different causes

c) “e morbo”- chronic diseases

malformations

enzymopathies

malabsorption

parasitosis

II. Favoring causes

a) ex constitutione”:

constitutional diathesis

hydrolability

b) “ex curatione” - care conditions

Etiology - multifactorial (a single cause can be rarely incriminated)

Etiological factors determines process of (starvation). The center of pathogeny is caloric and

proteic insufficiency.

Insufficient caloric intake: org. cons. glucides (reserve ~1% from weight), then lipids (in

absence of glucides they burn with formation of cetonik corps, so uneconomical)

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Prolongued fast determines protein burn (autophagy).

Insufficient protein intake

The absence unique source of nitrogen results in “burnt”of proteins themselves.

The aim is energetic, in the plastic detrimental, with negative nitrogen balance.

To burn 1 g lipids , 2 g glucides are needed.

Caloric and proteic insufficiencies once with the gluconeogenesis initiation

Many synthesis are stopped:

decrease of digestive enzymes determines decrease digestive tolerance

antibodies synthesis leads to low antimicrobian defense, so without any

defense, the body is exposed to many affections which, in these conditions,

evolve more prolonged and more severe

Positive diagnosis

Positive diagnosis is based on clinical symptoms and support of anthropometric

measurements.

I. Anthropometric measurements

Anthropometric indicators based on body (physical) measurements are height or size

(nutritional index), weight, thorax perimeter, cranial perimeter (useful in the first 2 years of

life), abdominal circumference, buttock circumference, mean arm circumference, skin fold,

abdominal fold, tricipital fold and others (related to age and sex of the individual), with the

advantage of being inexpensive and non-invasive.

Three of the most commonly used indicators for infants and children are weight for

height (WFH weight for height), height for age (height for age HFA) and weight for age

(weight for age WFA) which can be obtained by comparing the indicators core, weight,

height and age, separately by gender, with reference data for children "healthy". The

following can be used:

Weighted index (WI) (= actual weight / ideal weight), normally between 0.9-1.2. If at

WI over 1.2 we have obesity, below 0.9 we have dystrophy (first degree dystrophy:

0.90 to 0.75 in II degree dystrophy: 0.75 to 0.60, and III degree: below 0.60).

Weight deficit (IP) (DP) = Ideal W – Real W x 100

Ideal W I degree = < 25%

II degree = 25 – 40%

III degree = > 40%

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Body Mass Index (IMC, sau BMI - Body Mass Index) W/H2 (normal 18,00 - 25,00

kg/m2).

By comparing the results of measurements of similar individuals (in terms of age and

sex), anthropometric indices are converted to reference data. There are three ways to express

these comparisons:

a. z-score (standard deviation score): the difference between the value for an individual

and the mean of the reference population of the same age or height, divided by the

standard deviation of the reference population.

b. The percentage of median: ratio of the measured or observed value in an individual

and the mean reference data for the population of the same sex, and age or height.

c. percentile: an individual's position on a given reference distribution, determined by

what percentage of the reference group, the person overlaps with or exceedes.

Other indicators: waist (nutritional index) head circumference (in the first 2 years)

abdominal fold, tricipital fold, etc.

There are several ways to define malnutrition in children. In the past Gomez

classification wa used, which employed only weight for height, a classification used today

only for didactic reasons and which classified malnutritition into: Ist degree - mild

malnutrition (WFA 70-90%), medium – II degree (WFA 60-74%), severe -. III degree (WFA

<60%)

II. Clinical symptoms

Clinical - infant, small child - 3 degrees (didactic)

Malnutrition, I degree

normal aspect

decreased adipose tissue on the belly and thorax

the weight curve increases slower

digestive tolerance – relatively good

good resistence to infections

Malnutrition II degree

the child is pale, anemic

cellular tissue is dissapeared on the belly and thorax and diminished on the face and

limbs

stationary weight curve decrease slow or “gradually”

low digestive tolerance (often diarrhea)

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decreased rezistence to infections (pyoderma, otitis)

symptoms specific to the metabolism of starvation: hyipotermia and bradycardia

Malnutrition IIIrd degree

grey color (dirty)

cellular tissue is dissapeared (Bichat bubble too)

face has aged aspect (simian, volterian)

the skin seems too large - “tobacco sack” (buttocks)

persistent turgor, weight curve - collapsed

digestive tolerance very decreased, the child does not tolerate the ration of

maintenance

hypoglicemia, hyperinsulinism (starvation)

very low rezistence to infections: frequent infections (pneumonia, septicemy, TBC),

biological reactions which are not interpretable, impossible vaccinations

neuromental retard

Malnutrition IIIrd degree – particular clinical forms:

kwashiorkor

marasm

marasmic kwashiorkor

a). Kwashiorkor (“red child”)

protein nutrition

can get the normal ration of calories

proteins absent, often replaced by flour

the edematous form appears in big child, extremely rare in us

associates anemia, distended abdomen, undigested food/feces

areas of skin depigmentated and hyperpigmentated

thin, frail hair

apathy, irritability – frequent emotional disorders

b). Marasm

insufficient nutritional intake (not only proteic)

proteic-energetical malnutrition (proteic-caloric)

can appear in infant too

clinical – severe cachexia with emaciere

melting muscle and subcutaneous tissue

hypotonia

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crying/characteristic groaning

frequent form in our patients

high share in the infants’mortality

c). Kwashiorkor marasmic

characteristic to marasm

plus edemas

Antropometric measurements - MPE 3 degrees

Weight index (I.P.) = G. real /G ideal

Ist degree.: 0,89 – 0,76 W = weight in kg

II degree: 0,75 – 0,61

III degree: under 0,60

Weight deficiency

(DP) = ( ideal W – real W x 100)/ ideal W

MPE degrees after anthropometry:

I = < 25%

II = 25 – 40%

III = > 40%

Other index :

waist (nutritional index)

cranial perimeter (in the first 2 years)

abdominal crease, tricipital, and so on

Degree of weakness and height retard is made after Waterloo classification:

Waterloo classification

evaluates the state of nutrition

distinguish weakness as acute sign of MPE compared to stop of the growth as sign of

chronic malnutrition and reflected through a Height for age decrease

W for waist > 80% W for waist < 80%

Waist for age > 90% Normal wasting

Waist for age < 90% Height retard wasting with height retard

WHO classification uses:

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- z score for WFH (Wasting), defining acute malnutrition which can be moderate (z score -3

≤ z <-2) or severe (z score <-3) or

- z-score for HFA - defining chronic malnutrition - can be moderate (z score -3 ≤ z <-2) or

severe (z score <-3)

To assess nutritional status MUAC, TSF can be used with high accuracy, which, associated

with proteinemia (albumin) well define the nutritional profile of the child.

Evolution of weight curve (the degrees of MPE which are known are valid)

stage I: passes unnoticed, the child has normal aspect

stage II: diminished turgor, signs of starvation appear (hypotermia, bradycardia)

stage III: subnutrition involves the immune system, so MPE is accompanied by

infection (diarrhea, pneumonia, TBC...)

Laboratory – biological balance

Hgb, Htc, erithrocytes number, constant E

dehydration’s degree

anemia (Fe/folic acid, B12, hemolysis)

Glucose - hypoglycemia

Electrolytes (Na, K, Mg, pH, Cl, CO3HNa)

hyponatremia and dehydration’s type

hypokalemia, alkalosis, acidosis

T protein, transferrin – grade of proteic deficiency

Creatinine – renal function

Number of. L, PCR, serology - bacterial/ viral infections

Coprologic examination- presence of parasites

Hypoalbuminemia

present in all 3 forms of MPE

not only in edematous forms

Socio-economic conditions common in all forms

poverty

ignorance

„taboo” foods

Malnourished mothers who do not have breast milk

Unsanitary housing

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Prophilactic treatment

Avoid the factors which lead to malnutrition

Encourage breastfeeding

Avoid dietary imbalances

evicţia infecţiilor (călire, including vaccinations)

Measurements to improve the social conditions, environment

The treatment objectives are:

Improve energy, protein and micronutrient intake

Promote weight gain for catch-up growth

Correct any nutritional deficiencies

Encourage adequate oral intake to meet nutritional requirements

Support parents through dietary changes

Commence enteral support if oral intake is insufficient

Monitor, monitor.

Curative treatment

team (doctor, dietetician, social nurse)

aim: avoid rehospitalism

rule: correct rehydration, progressive feeding restart

nutritional rehabilitee ~ a month

mpe production needs months

complete recovery – the same

undernourishment acts at least 4 months before to influence length growth

Rehydration

i.v. – good experience with the Starter solution

i.v./oral max. 60 ml/kg – the first 2-3 days (the volume of myocard is ↓)

↑: 80 - 100 ml zilele 5-7

↑ progresively to cover the total hydric necessitiesle (120 - 150 ml/kg/day)

Caloric intake

ensure 60 – 80 kcal/kg/day – the first 3 days

then 100 kcal/kg/day in the next 4 days

In the first week do not administrate solid foods

The 2nd week ↑ progresively at 150 – 200 kcal/day

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Breast milk- important – for the intake of IgA

After the first week, the protein intake of 9% is ensured

then 12% (from the whole energetical intake) as long as it exists in the formulas for

infants

Proteins

will↑ gradually in nutrition

4 g/kg/day – daily supervising of the renal function

(35 – 40 kcal for each gram of protein)

Carbohydrates

• glucose (10 – 15 g/kg/zi)

• fructose (7-8 g/kg/zi)

• Polimers of glucose (dextrin - maltose)

• total/partial formulas without lactose (monosaccharides and polimers of glucose)

• Tolerance to lactose improves slowly (weekly), restored - after 3-4 months

Lipids

administrate 0,5 g/kg/day

Up to 4-5 g/kg/day

exploratory with vegetal oil, dietetic pp. degresate, parţial degresate

carnitina from preparations favors the transfer TG with long chain through

mitochondrial membrane

Minerals, oligoelements (zinc, iron, iodine) - additional 6 weeks. Are essential in restoring

the growth rate

Vitamins-administered at least 3 months. Vitamin A and Vitamin D are important in the

recovery phase.

Syndrom of renutrition

Severe hypophosphatemia - the first week of realimentare

Body reserve of P, Mg, K are decreased (intracel.)

With food intake, glucides determines insulinic response which forces the

intracellular absorbtion of P, Mg, K resulting in decrese of plasmatic (daily

measurement in the first week)

low P plasmatic 0,5 mmlo/L may determine:

shivering - rhabdomyolysis

cardio-vascular insufficiency - arrhythmia

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convulsions - consience’s alteration

death

Criteria of care and treatment efficiency

normal intestinal transit

reluarea weight gain after 2-3 weeks

Nutritional rehabilitee after a month

Immune recovery at 25 – 30 days

clinical recovery at 6 – 8 weeks

Evolution is favorable, with exception : rare cases of enzymopathy or malformations

Prognosis

Reserved in MPE IIIrd degree

in the period of infant and if prolonged

they are 2-3 cm smaller in waist than their others at the same age

do not have psycho-intelectual performances

less resistant to diseases

IRON DEFICIENCY ANEMIA

Etiology: iron deficiency develops especially in childhood periods of rapid growth, such as

infancy and puberty.

• Obstetrical and neonatal causes:

- maternal iron deficiency

- gemelarity, prematurity

- intrauterine hypotrophy

- fetal-maternal transfusion

- neonatal bleeding

• Dietary causes:

- extended exclusively lactate feeding

- insufficient intake of dietary iron

• Disorders of intestinal iron absorption:

- chronic enteropathy: celiac disease, cow's milk protein intolerance

• Gastrointestinal blood loss:

- intestinal parasites

- chronic occult bleeding secondary to aspirin treatment

- peptic esophagitis

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- gastritis, gastric ulcer

- meckel diverticulum

- intestinal polyposis

• Extra-digestive blood loss:

- menometrorrhagia

- pulmonary hemosiderosis

- recurrent bleeding in children with hemostasis disorders

- repeated blood harvesting in small infants

Effects of iron deficiency manifest throughout the body:

• On tissues:

- anorexia

- atrophic glossitis

- gastric hypoacidity

- exudative enteropathy

- malabsorption syndrome

- decreased activity of intestinal enzymes

• On CNS:

- irritability, abnormal behavior

- fatigue

- delayed psychomotor development

- decreased attention, reduced cognitive performance

- poor school performance

- headache

• On the cardiovascular system:

- tachicardia

- cardiomegaly

• On the musculoskeletal system

- decreased muscle activity

- decreased exercise performance

Clinical manifestations: occurs most often in the age of 6-24 months; usually the child is fed

exclusively on milk.

Symptoms: moderate anemia is frequently asymptomatic; irritability, anorexia, fatigue appear

as iron deficiency increases.

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Signs: on clinical examination, the child with iron deficiency anemia is fat and pale, often

presents tachycardia and systolic murmur. In severe forms (Hg <3 g / dl) or complications

requiring intensive cardiovascular activity, congestive heart failure occurs.

Diagnosis

• Laboratory tests:

- CBC

- morphological examination of erythrocytes (May-Grunwald-Giemsa smear)

- erythrocyte indices: MCV, MCH, MCHC

- iron levels (serum iron) – low

- ferritin

- total iron binding capacity (TIBC) – increased

- coefficient of saturation of transferrin - low

• Other tests (rarely necessary):

- protein diagram

- highlighting stool blood (Gregersen reaction)

- myelogram

Differential diagnosis: with other microcytic, hypochromic, anemias.

• Hemoglobinopathies: beta-thalassemia minor: hypochromic microcytic anemia with

reticulocytosis hypersideremia, erythrocytes with basophilic stippling, shaped

erythrocytes; diagnosis is indicated by hemoglobin electrophoresis.

• Lead poisoning: erythrocytes with basophilic stippling

• Infectious and chronic inflammation anemia: red cells are normochromic and normo-

or microcytic; serum iron is low, TIBC is low; normal or high ferritin being an acute

phase protein.

• Sideroblastic anemia (sideroacrestic) idiopathic or secondary: presence of iron excess

in macrophages and increased sideroblasts.

• Congenital atransferrinemia: severe microcytic hypochromic anemia, with neonatal

onset and almost complete absence of plasma iron

Treatment

Prophylactic treatment

Prophylactic treatment begins with proper nutrition during the mother's pregnancy (elemental

Fe content of 10-15 mg/ day) and supplementary iron therapy in the last 3 months of

pregnancy.

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The premature child is considered to have iron deficiency since it is born with low iron

stores. Prophylactic treatment of iron deficiency anemia in premature children starts at the

age of 4 weeks with 1-2 mg elemental Fe / kg / day 2-3 months.

Food diversification is important in preventing iron deficiency anemia. Iron-fortified cereals

and milk prevent iron deficiency anemia in high-risk infants and young children.

Curative treatment

1. Oral administration of iron: dose of 6 mg / kg / day elemental iron (up to 10 mg), divided

into 2-3 doses, 30 minutes before meals or between meals, with citrus juice, or vitamin C,

which promotes the absorption. We prefer simple iron soluble salts (sulphate, ferrous

fumarate). Iron is administered to normalize blood count, then the same dose is continued

for a further 2 -3 months to replenish iron reserves.

It is important to consume iron-rich foods (meat, liver, eggs, fruits, vegetables) and

reduce the amount of milk to 500 ml / day.

2. Parenteral administration of iron is rarely indicated and is reserved for special situations.

Indications:

a. Low digestive tolerance (diarrhea, vomiting)

b. Low iron absorption

c. Chronic losses

The formula for total administered iron mg:

mg parenteral iron = (ideal Hb - actual Hb) x 80 x 3.4 x 1.5 / 100

- 80 = blood volume in ml / kg

- 3.4 = mg iron necessary to increase Hb by 1 g

- 1.5 = correction factor to ensure completion of iron deposits

There are dextran iron or polymaltose iron ampoules (ampoules of 100 mg elemental iron).

Parenteral iron (i.v. / i.m.) is administered every 2-3 days, in 2-4 doses. In infants not more

than 50 mg / dose and in young children not more than 100 mg / dose should be used.

3. Red cell transfusion: is indicated only in severe iron deficiency anemia (Hb <4-5 g / dl)

with cardiovascular decompensation and / or severe infections. Izogroup izoRh red blood

cells mass is used, at a dose of 3-5 ml / kg / day.

Evolution and prognosis: are favorable, provided generating causes are removed. Mild

forms have a tendency of self-correction on proper diet. Lack of response to iron therapy

raises questions about the accuracy of diagnosis, compliance with therapeutic indications or

the existence of associated diseases (malabsorption, intestinal parasites).

233

DEFFICIENT RACHITISM – RICKETS

(common, vitamin-D sensitive)

Definition

Osteodistrophy deficiency

Lack of bone mineralization => Lack of vitamin D

Affects growing bones => bones deformation

osteomalacia affects the bones which do not grow

Etiopatogeny

Lack of vit. D

dietary

lack of exposure to UV rays- sun

“Plasmatic stockage” of vit. D

reflects the reserves

decreases in deficiency

Calcitriol - main role in intestinal absorption of Ca

Vit. D: >40 metabolits - actions incompletely known

Receptors for calcitriol

lung

endocrine organs

hematoformatoare organs

other tissues

Daily need

Infant:

400 – 800 u.i./day.

infant’s nutrition is poor in vit. D

exposure to sun is not enough

Lack of vitamin D

↓ abs. Ca => hipocalcemia

h-Ca stimulates secretion of PTH => Hyperreactional paratiroidism

consequences:

↓ renal reabsorption of phosphorus => hyperphosphaturia and hypophosphatemia

↑ intestinal abs. of Ca and ↓ renal elimination

fixes calcium in bones

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Through these pathogenic links

hypocalcemia can be corrected

“tribut” is paid by the bone through reabsorption or bone modifications

Decisive factors

The deficiency of vit. D from food

normal nutrition ensures 15%

Insufficient exposure to sun

ensures 85% of the necessity of vit. D

Vit. D – main role in homeostasis Ca and P

intestinal absorption of Ca and P

renal absorption of P

the increase of Ca, P deposits at the level of the bones ( hydroxiapatity formation)

Vit. D interferes in other processes:

Participate to synthesis ATP muscular, basic element of contr. musculare (rachitic

= hipoton)

favors the absence of Iron and Co at the level of intestines (anemia of rachit)

When vitamin D is lacking=> slow metabolic process, favoring the metabolites

accumulation → acidosis →↑ pres. osmotic intracel. → attract the water (pasty

aspect of rachitic children)

Favoring factors

Small age (3 months - 2 years)

Fast growth (premature,twins, vigorous children)

Nutritional Factors - inadequate diets

Artificial nutrition (cow milk is poor in vit. D)

Consume dairy products which are not enriched with vit. D

Vegetarian diet

Food rich in flour (fitaţi), oxalate, P

Total parenteral nutrition

Life conditions

temperate climate - october-april, r.U.V. ↓

poluted environment - towns – the powders filtrate r.U.V.

exposure to sun

Skin Pigmentation

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limits the skin syntheses

Affections which prevent hydroxilation

hepatic

renal

Affections which prevent intestinal absorption

cystic fibrosis

celiachia

biliary atrezy

Medicines

cortisone

anticonvulsivants

iron pp

heparin

chelatoare

Maternal factor

Many pregnant women (season, life style) – weak exposure to sun → lack of

vitamin D

Their new born – small reserve of vitamin D (or Ø)

A lot of new born have decreased conc of vit. D (Calcidiol) in winter or at the

beginning of spring

N.B.! Associate the favoring factors!!

Diagnosis

clinical signs

biological aspects

radiological elements

Clinical description

Onset

Not characteristic

It can pass unnoticed

irascibility

anxiety

capricious apetite

agitation

sweat (nape)

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reduced sleep

Period of state

bone modifications

term. II - head

term. III - thorax

term. IV – limbs

cranian

Craniotabes (precoceous 3-6 months)

parietal softening

occipital softening

clogging

sensation “ping-pong ball”

Teeth

tardive eruption

enamel hypoplazia

carii dentare

in tardive forms – affect definitive teeth

Forehead and head

high forehead (olimpian)

cap natiform

brahicefalie (occipit turtit)

plagicephaly (turtit postero-lateral)

suturile do not close on time

fontanel remains open for a long time

Thorax

deformations

“torace in funnel”

“in careen”

"chondrocostal rosary” (osteoid) - at the level of the axial ant.lines

“Harisson ditches”

submammary ditches

at diaphragm insertion

thorax base splay

the spine

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Different degrees of scoliozis

lordoze

cifosis (reductible)

Basin

tight – future distocice births (in ♀)

Limbs

hands

“rachitic bracelets”

epiphysis tumefied

visible thickening

or palpable thickening of distal extremities of radiusului

development of demineralized bone tissue

Lower limbs

Changes which appear after the child walks

o coxa vara

o coxa valga

o genu varum (O - paranthesis)

o genu valgum (X - mai rarely)

Other modifications in rachitism

rachitic Nanism – today it is very rare

laxe ligaments– large movements

hypotone Muscles – motor retard

big abdomen - “ batracian”

hepato-splenomegaly

anemia - paleness

Other extra bone modifications

infant- as manifestations of tetanie

convulsions

laringospasm

Sweats a lot

hipotony

la respiratory muscles → ventilation disorders and bronchopulmonary infections

(rachitic pulmonul )

proeminent abdomen

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late motor development

big child and adolescent

Similar to adult’s osteomalacia

artralgia

astenia

Tiredness at walking

Hypocrom anemia (rachitic anemia )

90% of rachitic children are anemic too

Clinical forms

Rickets of premature

precoceous

severe

favors the severe pulmonary complications

Common rickets

- florid – severe form

- medium – common form

- frust

Tardive rickets - 6-7 years, puberty

Common florid rickets

severe form

tetanic convulsions

craniotabes present

or crisis of tetany

Common medium rickets - common form

Common rough rickets- minor symptoms

late walking

open fontanels

late teeth appearance

“soft and sweats a lot” (neck)

rtg.of the hand - salutară

Tardive rickets

Favored by skin pigmentation

Insufficient sun exposure

Foods deficient in Calcium (milk, yoghurt,cow cheese) for a long time.

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practically – extremely rare, a calcium deficiency

In adolescents who say that they have bone pains, especially the lower limbs (and do

not suffer of renal or intestinal affections) – let’s think about R.C.!

Laboratory

Hipocalcemia - 50% of the cases

Without correlation with the intensity of bone manifestations

< 6 months show infraclinic rachitism (with discrete radiological manifestations)

intercurences (gastroenteritis) aggravates the Ca deficiency

calcemia can be normal (Ca = 2,42-2,60 mmol/L)

calciuria – practically nule

Hypophosphatemia

P normal = 1,56-2,10 mmol/L

Maybe the most important analyze

Precocious sign (before clinical signs)

phosphaturia a little bit increased

Serical alc phosphatases

Always increased > 40-100 U.I

Osteoblastic activity in the context of calcium deficiency

normal > 10-20 UB or 50-350 UI/l

Period of recovery: normal phosphatemia, Ca appears in urine

PTH

normal 4-8 mg/ml

secondary

o hyperparatiroidia

o hyperphosphaturia

o hyperaminoaciduria

lack of calcium in urine (r. Sulcowitch negative)

Plasmatic:

H-Mg.ziemia

citremia ↓

25-HO-vit. D: 10-30 ng/ml

↓ = ↓ stocks or metabolism anomalies

1,25-(HO)2-vit. D: 40 pg/ml

Urinary

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hyperaminoaciduria (H-paratiroidism reactional prevents the renal reabsorbtion of aa)

Sulkovich reaction

evidence the urinary calcium

after high doses of vitamin D, calciuria ↑

reaction +

interrupt the vitamin treatment

Biochemical - 3 evolutive stages

Stage I

hypocalcemia

normophosphatemia

fosf. alcaline slightly increased

Stage II

normocalcemia

hypofosfatemia

increased fosf. alcaline

Stage III

hypocalcemia

hypophosphatemia

ALP a lot increased

Radiology useful Rtg. knee, hand

Modifications at 2-3 weeks since the onset

Hand rtg.:

Enlarge of the diaphyzo-epiphyseal space

Enlarge of metaphysis with metaphyso-epiphyseal line deleted, laced

cortical extended to epiphysis through 2 “rachitic spur”

diaphysis extremity with cup aspect

Delayed ossification of nuclei - size ↓ than their age, demineralized, with

imprecise outline

More demineralized structure of diafizei

periosteum "duplicated" through calcification Ø

Rtg. pursuit is indispensable to confirm recovery

after 2-3 weeks of treatment appears a new line of metaphysar calcification

Positive diagnosis

Anamnesis: food, sun exposure, prophilaxy with vitamin D

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Clinical signs

Laboratory: phosphats decreased, ALP increased

Confirmation

bone Rtg (characteristic lesions)

Differential diagnosis

R. vitamin D resistent pseudocarential

autosomal-recesive

appears after 1 year

clinical signs like R.C.

treatment with vitamin D is inefficient, neces. D ↑↑ vit.D

forms through deficiency of 1-alfa-hidroxilasis, and others

cellular resistance to calcitriol

hypoglicemie (renal incapacity of hidroxilation)

R. hypophosphatemic

transmitere X-linkate transmission

very decreased phosphatemia

normal calcemia

treatment with vitamin D is not enough

R. from malabsorption, tubulopathies, hepatic/ renal insufficiency

All have a clinical and biological evocative context

rarely needs a differential diagnosis of:

craniotabes TO bone softening in premature

rachitic nanism ≠ other nanisme

Hypomagneziemic rachitism

defined as R.C. in which it is

hypomagneziemia (n = 1,5-2 mg%)

moderate hypocalcemia

decreased alkaline phosphatases

o in RC are increased

adm. of Mg - 8 mg/kg/day for 1-2 months in this form of rachitism, has good results

Prophilaxy

Romania - compulsory 6 years

Pregnant woman in IIIrd term - 1000 u/day oral- 2 drops Vit.D2 ol.

New born

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Will get from the 7th day- 1 drop/day , it does not matter how it will be fed

In the first 7 days vit.D can not metabolyze

The infant and child under 2 years

Needs 2 drops/day (1000 u.i.)

Except the warm months (may-september) if the child is correctly exposed to sun

and the weather is sunny - gets 1 drop/day

Premature,twins,underweight, malnutrited, those from areas intensively

polluted, with poor environmental conditions or with anticonvulsivant

treatment

Need 2 drops/day

In cold season 3 drops/day

in special medical or family situations

vit. D2/ D3 - injections I.M. - 200.000 u.i. at 6-8 weeks, totally 1.200.000 UI in

the first year of life – efficient for most children

Children over 2 years

It is good to get 1-2 drops of Vit.D in cold season, until school period

Add calcium

Only in premature and children who get less than 400 ml milk/day

Recommended dose - 50 mg/kg/day Ca elemental (500 mg gluconate of calcium

– 1 f gluconate Ca 10%)

Profilaxy RC

It does not mean only administration of vit.D

equally important, or maybe the measures of body hardening are more important

o Sun exposure

o Correct nutrition – rich in meat, eggs

Treatment

Hygieno-dietetic treatment

Correct nutrition

Breastfeeding at least 3 months

Correct diversification (aport de vit. D, Ca)

Adequate life style - aired

Heliomarine cure > 1 year

Sunny , aired room

Body heardening - bathing, frections, shower, massage, gymnastics

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Shoes with flexible sole

Curative treatment

Recommended in infants with

clinical signs

radiological

and biological signs of florid rachitism

3 therapeutically schemes are recommended and accepted in our country

Scheme I

the most used

oral adm.of vit. D: 2.000-5.000 u.i.

means 4-10 drops./day

for 1-2 months

then it will be introduced in a scheme of prophilaxy

Scheme II

- 3 doses i.m. de 100.000 UI D2/ D3

- adm. at 3 days

- a total of 300.000 UI, in a week

- after 30 days – a new adm. - 200.000 UI i.m.

- then vit. D in prophylaxis doses

Scheme III

adm. Of a single dose of 600.000 UI D3,

after 30 days continue with a prophylactic dose

if it is possible, it is recommended a daily dose of 0,5-2 mg 1,25

hidroxicolecalcipherol - 4 weeks

Calcitherapy

2-3 days before administration of vit. D

D.: 40-50 mg/kg/day as Ca gluconic, lactic, effervescent, and so on

sol. Ca gluconic 10% - in tea, soup, juice

adm. I.V. of Ca – necessary only in crisis of tetany

if the nutrition is deficient in calcium, it can be prescribed for 1-4 weeks

Supplementary administration of vitamin A and C

↓ renal eliminations of Ca

Pharmaceutic preparations

fish oil

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fish liver oil

different combinations vit. A + D2/D3 + fluor

Vigantol, Vigantoletten, Vigorsan, Sterogyl, AT 10, Rocaltrol, Halycitrol, Calcipat

D3, Zymaflour

Heliomarine cure

Rules of the treatment with vit. D

splited treatment po – the most efficient

pp vit. D3 - hidrosoluble - abs.good

adm. During meals

stop 2 weeks before a helio-marine diet (recommended after 1 year)

some forms need administration of Mg

vaccination antipolio - only po; diarrhea not CI adm. vit. D

prolonged anticonvulsivant and corticotherapy - vit. D during treatment

↓ doses when pp enriched with vit. D is administred

Evolution and prognosis

After vitaminotherapy, the biological parameters are normalized thus:

3-4 days calcemia

2-3 weeks fosfatemia and plasmatic PTH

6-8 weeks alkaline phosphatases (their normalization confirm the “biological

recovery” of RC)

“Radiological recovery”

starts after 2-4 weeks of treatment

normalization of metaphyze and epifizelor is made after 3 months

appears the „line of doliu”

the deformations of the long bones are corrected very slowly, under the effect of bone

remodelation (4-5 years)

some sechele will be corrected with gymnastics,

others - exceptional – orthopedic correction

Recovery

"spontaneous" or through treatment with vitamins

Mild forms – recovery in a few weeks, Ø sechele

Complete recovery when the bone structure is restaurated

recovery “with defect" – deformations which disappear in months/ years since

treatment is started.

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Evolution

under treatment - favorable

without treatment – threatened by infections

good prognosis

some bone deformations - definitive

others need ortopedic treatment > v. 3-5 years (exceptional)

dispensarization 3 years from healing

Hypervitaminosis D - Intoxication with vit. D

Manifestations:

- rebel anorexia - vomiting

- dehydration - constipation

- azotate retention - hypercalcemia

- hypercalciuria > 5 mg/kg/24h -

is rare - should stop the administration

no exposure to UV rays - no foods rich in Ca

hospitalization in severe cases - corticotherapy

TETANY

Definition: Hyperexcitability state, neuromuscular produced by the modification of the main

ions concentration, clinically manifested through muscular spasms and seizure.

Etiology

formula of excitability Na+ K+ OH- / Ca++Mg++H+

hyperexcitability is produced through denominator reduction (more frequent - Ca++)

can be precipitated by the coexistence of a hyper-K-thousands or alkalosis

Clinical forms

tetany from rachitism

tetany-other origins

new born’s tetany

Tetany from rachitism

85% of the children with tetany are rachitic

Appears mostly in cases fruste

In sunny months or after administration of vitamin D

246

in the period of R.C recovery .

When there is certain hypocalcaemia

• deposit of Ca in the bones

Tetany-other origins

new born , from difficult births (diencephalic dysfunctions, mezencephalic)

intestinal affections: CF, EGS

severe nephropathies

respiratory alkalosis (after vomiting, exaggerated intake of bicarbonate, citrate,

phosphates)

hyperproteinemia

hyperpotasemia

hypomagnezemia

Clinical manifestations of tetany

spasmophilia (latent form)

hiperexcitabilitatea neuromuscular hyper excitability manifests only when it is

caused

Tetany itself (the form manifests)

Spasmofilia (latent form)

Tests of mechanical provocation:

The Trousseau sign

applied on the cuff of the measuring device TA on the arm

it is pumped at a pressure a little over TA max.

let it 3 minutes

positive test when appears“mamos hand”

The Chvostek sign

with a finger we percuss at the half distance between the tragus and oral comisura

the test is positive when it produces the contraction of orbicular m. of the lips, of

nose’s wing or the whole hemifeţe

he most faithful sign

appears the earliest

it is the last which gives up

Weiss sign

we percuss with a finger the exterior angle of the eyes

the test is positive at contraction of orbicular m. of the eyelashes

247

Lust sign

we percuss fibula’s head

the test is positive when abduction and dorsal flexion of the leg is produced

EKG

elongation of the QT interval, T ample, sharp

EMG

On the normal line appear “accidents” which are repeated at short intervals

(“doublets”)

Laboratory

Ca seric ↓ (< 7 mg% or 2,25 mmol/L)

indirect, shows ↓ Ca++ ionic, the fraction which caused the symptoms (n = 3-3,5

mg%)

Tetany itself

Intercurrent infections, mainly acute, ↓ Ca plasmatic => spasmophilia changes in tetany

Clinical signs

Tonico-clonic sizures

more often generalized

duration 15 sec. – 15 min

recurrent

symetric, unpainful

days - weeks

Carpo-pedal spasm

the hand gets the aspect of “mamos hand”

the leg gets the aspect of “ equin leg”

Muscle contractions

at the limb’s radix

does not produce spasms

lips contraction - the mouth in “fish mouth”

Muscle hypertonicity

surprinde in a hypotonic rachitic patient!

the muscular contractions and hypertonicity are symmetric

sometimes painful

can associate paresthesia

Laryngospasmul

248

spasm of the glottis (of adductorilor laringelui)

wheezzing inspiration, prolonged, uncomfortable, followed by short breathing

modifications, jerky, then apnea

children are agitated, with the neck in hyperextension, cyanotic face, dilated nostrils

apnea is defeated and then a whizzing breathing appears again

the accesses last for a few minutes and repeat many times a day

Visceral spasms

makes gastric T.

cardiac T.

bronchotetany

pharynx spasms

diaphragm spasms

New borns’ s tetany

In the first 2 months of life, due to a transitory hypoparatiroidism => neonatal

hypocalcemia

2 forms:

early hypocalcemia

late hypocalcemia

Early Hypocalcemia

• in the first 36-48 h of life

• often crisis of apnea or letargy

• rare convulsions, hypertonicity, laringospasm

Favoring factors:

prematurity

asphyxia, acidosis

difficult, prolonged birth

the child of a diabetic mother

Late Hypocalcemia

• after feeding

• iatrogenic

• more often between the 5-10th day of life up to 6 weeks

• in new born at term, artificially fed (LV, LP =rich in P, while LM is poor in P)

• immature glomerular filtration ↑ P seric faţă de Ca =>↓ raport Ca/P (n = 2/1)

249

• insufficient paratiroidele can not compensate the situation => T

Clinical symptoms in new born

atypical, cheating

nutritional difficulties

vomiting

crisis of apnea

even lethargy instead of convulsions

Positve diagnosis

in both forms - value ↓ of calcemia

Diferential diagnosis

• epilepsy

• tetanus

• laryngitis striduloasă (pseudocroup)

• tetany-other origins: hipoMg, hiperK, hypoproteinemia, alcalosis

Tetanies treatment

General measuress

ensure a quiet atmosphere

not many manipulations

airways permeability, O2

Emergency treatment

In all clinical forms – adm. of

Ca gluconic 10% 2ml/kg I.V. slow

Ca gluconic repeated after 15 min.

Fast adm. => a too large quantity of Ca++ in the atriul dr. – would inhibit the

sinusal nodule => bradicardie, bloc sau stop cardiac

Paravenous adm. or I.M. leads to necrosis and calcifications

The dose can be adm. ulterior every 6 hours up to “cuparea” of all symptoms

in practice – in a child with convulsions or laringospasm, adm.:

Diazepam 0,3 mg/kg I.V., repeated after 20-30 min.

If the convulsions do not Ø - Ca gluconic IV

If convulsions last – hypertonic Glucose 20% 2 ml/kg I.V. (logical treatment

based on the more frequent etiology of convulsions, but inefficient in case of

hypocalcemia)

In late hypocalcemia

250

“interest” is to keep P in the intestine through administration of Ca salts in excess

(gluconate, carbonate, lactate) => fosfat de Ca neabsorbabil

adm. 2-3 g/day disolved in milk, 7-10 days

In tetany from rachitism

after emergency treatment, therapeutically doses of Ca and vit. D are

administrated

Evolution

Characteristic – tends to relapse

The disease can remain latent for a long time

Manifests only in case of precipitant factors

Mainly injections

Prognosis is good.

DIABETES MELLITUS (DM)

Definition: Diabetes mellitus is a chronic metabolic disease caused by a relative or absolute

deficiency of insulin which causes the body's inability to use glucose as an energy source.

Absence, destruction or loss of Langerhans islet beta cells cause an absolute deficiency of

insulin, which triggers type 1 diabetes (insulin-dependent diabetes - IDD).

Epidemiology: The geographical distribution of the disease varies, the world's highest rates

of incidence being found in Northern Europe (Finland, Sweden, Norway).

Low incidence of IDD are found in Asian and African populations, in Australia, New

Zealand, Central Europe.

In Romania: The risk of IDD in children in Romania is low and it remains relatively

constant during adolescence. IDD incidence in children of 0-14 years is 5.5 cases/100000

inhabitants / year. In our country, the prevalence of known cases of the disease is considered

of 3.2%. In recent years, the incidence of type 1 diabetes nearly doubled in all countries,

which advocates for significant intervention of environmental factors.

- Gender: similar trend for both sexes

- Age: The incidence rate increases with age until mid-puberty, followed by a decline

after puberty. Onset in the first year of life, although uncommon, can occur and should

be investigated in any infant or young child with unexplained or evocative symptoms.

Etiopathogeny:

251

Currently there are multiple arguments to support the theory that diabetes is the result of the

combined action of main factors:

Genetic factors - HLA antigens common in patients with diabetes: HLA B8, B15, B18

and HLA DR3, HLA-DR4

Immunological factors -selfdestructive factors of beta islet cells

- Islet cell antibody (ICA), which can be noticed in the patients’ blood several years

before clinical manifestations of the disease and are present in 60-80% of newly

diagnosed patients.

- Anti-insulin antibodies (AIA), which are present before the onset of insulin

treatment and can be evidenced in almost 100% of patients in whom the disease is

manifest before the age of 5 years.

- Antibodies to glutamic acid decarboxylase (GADA) - their appearance precedes

the clinical manifestations of the disease by a few years.

Environment factors – triggers

- Viral factors: the urlian, mumps, rubella, Coxsackie viruses, varicella-zoster,

cytomegalovirus

- Dietary factors: consumption of cow's milk introduced early in the diet, intake of

foods containing nitrosamines, chemicals found in smoked foods and some water

supply networks

- Chemical and toxic agents: aloxan, streptozotocin

Pathophysiology:

The main pathophysiologic link is the inadequate insulin activity or inability to use normal

peripheral glucose. Defining clinical manifestations are: hyperglycemia, glycosuria, ketosis,

ketonemia, ketonuria, metabolic acidosis, dehydration. Insulin deficiency causes a decrease in

the uptake of glucose in tissues, resulting in the occurrence of hyperglycemia (glucose> 200

mg / dL or 11 mmol / l).

Glycosuria occurs when the renal glucose threshold is exceeded (blood glucose> 180 mg /

dl). The kidneys can not reabsorb the excess of glucose load, causing glycosuria, osmotic

diuresis, thirst and dehydration (hyponatremia, hypokalemia). A particular type of

dehydration is installed - hypertonic with hyponatremia, hyperglycemia-induced

hyperosmolarity.

Ketonemia resulting from increased degradation of fats and fatty acids with increased

elimination of urine - ketonuria.

252

Metabolic acidosis occurs through keto-acid excess and decreased bicarbonate buffer,

innitially being compensated by decreased PaCO2 - acidotic polypneea, and when the

possibilities for compensation are exceeded, decompensated metabolic acidosis installs.

Other metabolic changes:

- increased degradation of fats and proteins leads to the production of ketones and weight

loss

- decreased triglycerides formation occurs and increased mobilization of free fatty acids

from peripheral adipose tissue

- protein production is reduced, amino acids use for gluconeogenesis in the liver increases.

Disruption of protein metabolism explains somatic growth disorder and cachexia found in

decompensated juvenile diabetes.

Classification of Diabetes mellitus (Clinical Practice Consensus Guidelines - ISPAD):

1. DM type 1 or insulin-dependent diabetes – usually sets in under the age of 25 years and

can be frequently complicated by diabetic ketoacidosis.

2. Type 2 diabetes or non-insulin dependent - usually starts after the age of 30 years, and is

characterized by hyperglycemia and insulin resistance; ketoacidosis is rare.

3. Adult type diabetes of the young (MODY - maturity-onset diabetes of the young) is an

inherited form of diabetes caused by autosomal dominant transmission of defective

pancreatic β cell function. Depending on the location of the genetic mutation, several

types have been described. Disease severity can vary considerably from one type to

another, but most often MODY acts like a mild form of type 1 diabetes.

4. Secondary forms of diabetes - in which the trigger is known

diseases of the exocrine pancreas: pancreatitis, trauma, cystic fibrosis, cancer

endocrinopathies: acromegaly, Cushing syndrome, pheochromocytoma,

hyperthyroidism

genetic syndromes: Down, Klinefelter, Turner, Prader Willi syndrome, porphyria

drugs, toxic substances: glucocorticoids, thyroid hormones, thiazide

infections: congenital rubella, cytomegalovirus, others.

5. Gestational diabetes – with onset or diagnosed during pregnancy

Clinical presentation

Onset:

253

1. Acute or rapid onset - occurs in small children in 4% of cases. Symptoms of a rapid onset

within 2-3 days: coma / pre-coma, thirst, abdominal pain (50% of cases), quickly installed

exicosis without vomiting and diarrhea;

2. Intermediary onset - is the most common (80-90% of cases), within 2-4 up to 6-8 weeks,

with the following suggestive signs: polyuria, polydipsia, polyphagia, weight loss,

fatigue, loss of concentration, vomiting abdominal pain;

3. Slow (extended) onset - rarely found (6% of cases), in older children and adolescents.

Sign evolution develops in months or even a year or two. Characteristic signs: thirst,

progressive polyuria, progressive weight loss (5-10 kg), decreased exercise capacity,

hunger or appetite, itching, secondary dermatitis or pyoderma.

Physical examination may reveal issues associated with other autoimmune

endocrinopathies, with a higher incidence in children with DID (thyroid disease with

symptoms of hypo-or hyperactivity and possibly palpable goiter). Cataracts may occur

commonly in girls, with a long prodrome of mild hyperglycemia. Necrobiosis lipoidica often

appears on the front of the leg as well delineated red atrophic areas.

Laboratory diagnosis:

Table X Investigations for DM

Mandatory investigationsSupplementary

investigations

Investigations for diagnosis

of complications and

treatment monitoring

fasting glucose > 126 mg% (7

mmol / l)

↓

glycemic profile

glycosuria

cetonuria

DM suspicion?

↓

Oral glucose tolerance test (OGTT)

HbA1c (n = 4.5 to 5.4%)

Insulinemia

C peptide

pancreatic beta cell

antibodies

Anti-islet antibodies

HLA

Leukocytosis: infection,

metabolic stress

Lipids: triglycerides, free

fatty acids, cholesterol

Ionogram, pH

T3, T4, TSH, antithyroid Atb

Microalbuminuria – annually

(indicator for risk of diabetic

nephropathy)

Diagnosis criteria (According to ISPAD 2011)

- specific symptoms (polyuria, polydipsia, polyphagia, blurred vision, weight loss) +

glucose> 200 mg / dl

254

- fasting plasma glucose > 126 mg / dl

- 2-hour OGTT-glucose > 200 mg / dL (1.75 g / kg max 75 g)

- HbA1c ≥ 6.5

• In the presence of obvious, intense, clinical symptoms, random screening of blood sugar,

anytime during the day, with a value > 200 mg / dl (11 mmol / l), and a fasting blood

glucose > 126 mg / dl (7 mmol / l) certifies diagnosis; transient hyperglycemias are

excluded during acute and stress diseases.

• In the absence of symptoms, the physician must confirm these results on different days.

• Glycemia can be determined by the capillary method, the strip or the blood glucose

meters; these are conventional techniques for daily monitoring of diabetes control.

• Glycosuria - a positive test for glycosuria is suggestive, but not certain for the diagnosis

of DID. The diagnosis should be confirmed by a combination of high glycemia and

possibly ketonuria.

• Ketonuria - confirms lipolysis and gluconeogenesis, which is normal during periods of

fasting.

• Hyperglycemia with marked glycosuria and ketonuria = marker of insulin deficiency and

possibly diabetic acidocetosis.

Oral glucose tolerance test is performed if blood glycemia levels are not indicative. A value

of fasting blood glycemia is obtained, and then glucose is administered orally in 250 ml of

water: children under 3 years - 2g/kg, 3-10 years - 1.75 g / kg (maximum 50 g) over 10 years

- maximum 75 g; blood glycemia is again determined at 2 hours (table. ..)

Table.. Diagnosis criteria for glucose intolerance and DM

Interpretation

Diagnosis criteria

Glucose

Fasting at 2 hours

Normal values < 110 mg% < 140 mg%

Decrease of glucose tolerance 110-126 mg% 140-200 mg%

DM ≥ 126 mg% ≥ 200 mg%

255

Stages of type 1 diabetes

I. Pre-diabetes - no clinical manifestations, antibodies may be revealed (ICA, IAA, GADA)

II. Low tolerance to glucides

III. Remission "honeymoon" phase - occurs at a variable interval after the start of insulin

treatment and is due to remaining pancreatic ß cell hyperfunction in their attempt to produce

enough insulin to compensate the hyperglycemia.

IV. Manifest tipe 1 DM - during the remission phase, continues destruction of pancreatic ß

cells and eventually leads to the total lack of endogenous insulin, total diabetes being

installed.

Differential diagnosis

Table... Differential diagnosis

Mainly with Initial coma Clinical signsWith other

glycosuria

• diabetes insipidus

• pancreatitis

• hyperthyroidism

• pheochromocytoma

• Cushing sdr

• Genetic sdr: Down,

Turner, etc.

• transient blood

sugar

» stress: burns,

trauma, infections

» medications:

corticosteroids,

thiazide

• poisoning with

salicylates

• meningoencephaliti

s - neurological

brain: edema/

infectious vascular

rupture

• hyperosmolar coma

• hypoglycemic coma

• hyperglycaemic

coma

• acute abdomen

• encephalitis

• other ketosis

• severe dehydration

in infants

(toxicosis)

• metabolic acidosis

in hereditary

metabolism

diseases

• renal diabetes

• chronic

tubulopathy

• poisoning with

Pb, Hg

• haemoglobinuria

• myoglobinuria

• pyelonephritis

• galactozuria,

fructozuria,

pentozuria,

zaharozuria

Treatment:

Objectives:

- immediate: so that the child could have a normal life and avoid hypo- and hyper-

glycaemia,

256

- long-term: ensuring normal growth and development, psychosocial and vocational

integration, prevention of chronic complications.

Means :

1. insulin therapy

2. nutrition (diet)

3. exercise

4. medical education

5. self blood glucose control

1. Insulin therapy – is always necessary in the treatment of insulin-dependent DM, its

absence being fatal (table X)

Insulin analogues (other than the chemical structure of human insulin by 1-2 amino acids) can

be short and long-term acting.

They could provide a predictable pattern of action and may eventually replace traditional

forms.

Combinations of intermediate and fast-acting insulin are available in a variety of

concentrations varying around the world from the mixture 10/90 (10% IR and 90% isophane)

to the 50/50 mixture. Premixed insulins are Humulin M and Mixtard (table X)

Table X Pre-mixed insulins

Insulin typeRatio

Rapid insulin Semi-slow insulin

Pre-mixed Insulins

(fast + semi-slow

acting)

Mixtard 10 Actrapid 10% Insulatard 90%

Mixtard 20 Actrapid 20% Insulatard 80%

Mixtard 30 Actrapid 30% Insulatard 70%

Mixtard 50 Actrapid 50% Insulatard 50%

Humulin M2 Humulin R 20% Humulin R 80%

Humulin M3 Humulin R 30% Humulin R 70%

257

Table X Insulin preparations from Romania (according to V. Șerban 2007)

Product Composition Onset

(min)

Maximum

result (h)

Duration

(h)

Presentation

I. Insulin analogues with rapid action

Clear solution

1. Humalog

(Eli Lily)

Lispro insulin 5-15 1-2 3,5-4 Cartridges

(3 ml)

2. Novo Rapid

(Novo

Nordisk)

Aspart insulin 10-20 1-3 3-5 Cartridges

(3 ml)

FlexPen- pen

3. Apidra

(Sanofi-

Aventis)

Insulin glulisin 5-15 1-2 3-4 Cartridges

(3 ml)

Product Composition Onset

(min)

Maximum

result (h)

Duration

(h)

Presentation

II.Insulin with short or regular action or human soluble

Clear solution

1. Actrapid HM

(Novo Nordisk)

Human insulin

Recombined

DNA

30 2-4 Maximum

8

Vials (10 ml)

Cartridges

(3 ml)

Novolet-pen

2. Humulin R

(Eli Lily)

Human insulin

Recombined

DNA

30-60 2-4 6-8 Vials 10 ml

Cartridges

(3 ml)

3. Insuman Rapid

(Sanofi-

Aventis)

Human insulin

Recombined

DNA

15-20 1-4 7-9 Vials (10 ml)

Cartridges

(3 ml)

OpiSet-pen

Product Composition Onset

(min)

Maximum

result (h)

Duration

(h)

Presentation

258

III.Insulins with intermediary action

Turbid solution

1. Insulatard HM

(Novo Nordisk)

NPH

(Izofan)

90 4-12 16-20 Vials (10 ml)

Cartridges

(3 ml)

Novolet-pen

2. Humulin N

(Eli Lily)

NPH

(Izofan)

60-120 4-10 16-20 Vials 10 ml

Cartridges

(3 ml)

3. Insuman bazal

(Sanofi-Aventis)

NPH

(Izofan)

45-60 4-10 16-20 Vials (10 ml)

Cartridges

(3 ml)

OpiSet-pen

Product Composition Onset

(min)

Maximum

result (h)

Duration

(h)

Presentation

IV.Insulin analogues with long-lasting action

Clear solution

1 Lantus

(sanofi-Aventis)

Diarginine

glycine

(glargine)

120 - 24 Vials (10 ml)

Cartridges

(3 ml)

OpiSet-pen

2. Levemir

(Novo-Nordisk)

60-

120

- Maximum

4

Cartridge (3 ml)

FlexPen-pen

Insulin is administered in the subcutaneous tissue as 2-4 injections daily or, intravenously in

crisis. Rapid insulin therapy regime before meals and intermediate-acting insulin at bedtime

has become a widely used scheme. Insulin doses will be adjusted according to the child's

individual needs and varies according to the stage of diabetes development:

259

Table X Insulin Doses

Insulin needs 1 UI/kg/zi

Onset period 0,5-1,5 UI/ kg/day

Remission period (”honeymoom“) 0,5 UI/kg/day

perioada de stare – state period

- small children, school children (pre-puberty)

- puberty

- post puberty

1 UI/kg/day

1 UI/kg/day, to 1,5-2 UI/kg/dayi

0,8-1 UI/kg/day

acute diseases, accidents, operations Higher doses of rapid insulin

Complications of insulin therapy:

• Somogyi phenomenon – as a result of hypoglycaemia during the night, due to release of

hormone antagonists, hyperglycemia occurs in the morning

• Dawn phenomenon: in the morning between 5-8:00 because of low tissue sensitivity to

insulin, hyperglycemia occurs (without prior nocturnal hypoglycaemia)

• allergic manifestations - local reactions may occur (redness, rash, burning, itching) at the

injection site; they are spontaneously remitted in a few days

• emergence of anti-insulin antibodies

• lipodystrophy - due to inadequate technique or lack of rotation of the injection site

• hypoglycemia - suddenly installs in minutes; is manifested by pallor, sweating, trembling,

intense hunger, tachycardia, drowsiness.

Causes of hypoglycemia: too large dose of insulin, exercising too intensely, skipping a meal.

The treatment consists in administration of fast-absorbing glucydes orally if the patient is

conscious or intramuscular glucagon, glucose solution I.V., respectively, if the patient has

lost consciousness.

2. Diet

Daily caloric intake should be ensured according to universal recommendations, as follows:

• 50-55% carbohydrates

• 30-35% lipids (the ratio mono, polyunsaturated vegetal fats / animal saturated fat = 1)

• 10-15% proteins

Caloric needs (cal/day) = 1000 + 100 x age (years)

Number of recommended meals : 3 main meals + 3 snacksOverall percentage distribution of

caloric intake and carbohydrates in meals:

260

Breakfast 20%

Lunch 30%

Dinner 20%

Snacks of 10 % each (at 10, 16, 22 o’clock).

The meal plan must be tailored to family habits, the school program, and insulin therapy

should be adjusted; the diet aims to balance food intake with insulin intake as well as physical

activity and get a blood sugar as much as possible within the reference range, eliminating

extremes such as hypoglycemia and hyperglycemia. Adequate intake of complex

carbohydrates (cereals) is important in the evening before bedtime in order to eliminate

nocturnal hypoglycemia.

3. Physical activity

Physical activity is a major indication for glycemic control improvement in diabetic patients,

with certain precautions. Children with diabetes should not be exempt from physical

education classes at school – minimum 30-60 minutes of daily moderate exercise are

necessary. If it is unbalanced, the child will be exempt from sports until the glycemic balance

is restored.

Recommendations

• glycemic selfcontrol before, during and after exercise;

• sugar should always be carried along;

• progressive increase in intensity and duration of physical exercise;

• in the first three hours preceding effort, slow absorption carbohydrates should be eaten to

saturate muscle and liver glycogen reserves;

• in case of prolonged effort children should drink sweet drinks (water with 6-8% glucose)

before exercise, during exercise and after exercise, a general recommendation is to

consume 15 g of glucydes every 40 minutes of sport;

• glycemic control before bedtime following an exercise is important in order to prevent

nocturnal hypoglycemia;

• dose reduction of insulin acting during or immediately after exercise;

• avoid injecting insulin in an area subject to physical effort.

Complications

261

Table X DM complications

Acute complications Chronic complicationsAssociated autoimmune

diseases

Hypoglycaemia

Hyperglycemia

Diabetic ketoacidosis

Nutritional (Nobécourt sdr.,

Mauriac sdr.)

Metabolic – dyslipidemias

Degenerative:

1. vascular:

- Diabetic retinopathy

- Diabetic nephropathy and

hypertension

- Diabetic neuropathy

- Atherosclerosis,

cardiomyopathy

2. Lipodystrophy and

hypertrophy at injection site

3.limitation or joint mobility.

• Hypothyroidism

• Hyperthyroidism

• Addison's disease

• Celiac disease

• Necrobiosis lipoidica

Diabetic ketoacidosis - can be a life-threatening emergency - the cause is the imbalance

between insulin requirements and intake, and may be encountered at the:

- onset (inaugural ketoacidosis)

- increased insulin requirements - intercurrent infections, surgery, trauma with

progressive onset

- omission of insulin therapy or low dose administration.

Clinical presentation:

The onset is gradual: thirst, polyuria, loss of appetite, abdominal pain, polypnea, lack of

dynamism;

The state period:

Digestive symptoms (ketosis): loss of appetite, vomiting, abdominal pain

Respiratory symptoms (acidosis) polypnea, hyperpnea - Kussmaul breathing

Neurological symptoms: lack of dynamism, drowsiness, sensory obnubilation, psycho-motor

agitation, coma

Acute dehydration syndrome with diuresis (glycosuria causes osmotic diuresis), collapse

262

Particular clinical signs: acetone odor of breath (rotten apples) - halitosis acetonaemia

Diagnostic explorations :

- hyperglycemia> 200 mg / dl

- glycosuria, ketonuria

- Astrup parameters (metabolic acidosis pH <7.3, HCO3 <15 mmol / L)

- ionogram, urea, creatinine

- CBC (haemoconcentration by dehydration)

- bacteriological tests (blood cultures, urine culture, throat and ear secretion)

- EKG, SaO2

Complications:

• cerebral edema, hemorrhage, thrombosis

• metabolic disorders: hypokalemia, hyperkalemia, hypoglycemia

• infections: septicemia

• aspiration pneumonia, pulmonary edema, adult type respiratory distress syndrome

• heart failure, cardiac arrhythmias, thrombosis in large vessels

• pneumomediastinum, subcutaneous emphysema

• Pancreatitis, intestinal necrosis

• Renal failure.

Treatment : figure....

Childhood and adolescence are a time of intensive education and treatment can prevent or

delay the onset and progression of complications. Retinopathy causes vision loss and

blindness. Diabetic nephropathy causes hypertension and renal failure. Neuropathy causes

pain, numbness, muscle weakness and autonomic dysfunction. Macrovascular disease causes

heart disease, stroke and peripheral vascular disease with limb loss.

1. Good glycemic control reduces the risk of installation and progression of vascular

complications

2. Blood pressure measured annually (< 95th percentile for age)

3. Patients with diabetes should not smoke

4. Eye fundus examination should be performed immediately after the diagnosis of diabetes

- for early detection of cataract and refractive errors requiring treatment. Eye fundus

examination should be performed by a physician experienced in diabetic eye examination.

Subsequently eye fundus examination is performed once / year.

5. Screening for retinopathy and nephropathy (microalbuminuria) should be performed from

the age of 11 years and for 2 years after diagnosis.

263

6. Lipid profile - performed at diagnosis of diabetes in patients aged> 12 years. If the values

are within normal limits, then it should be repeated every 5 years.

7. Neurological examination - for the diagnosis of peripheral and autonomous neuropathy -

after the age of 11 years and for 2 years after diagnosis.

Forensic dangers, traps :

- diabetes is easy to miss in infants or pre-school children. In case of doubt, urine

glucose and glycemia are checked.

- ketoacidosis may manifest as respiratory distress (dyspnea).

- inappropriate or excessive treatment of hypoglycaemia can lead to serious

consequences.

- omission of systematic analysis of complications, particularly in the kidney and eye.

264

Chronic complications

Positive DiagnosisKETOACIDOSIS

DIABETIC

HistoryPolyuriaPolydipsiaWeight lossAbdominal painsVomitingWeakness

ParaclinicalHyperglicemiaKetonuriaMetabolic acidosis

Clinical signsDehidrationKussmaul breathHalitosis acetonaemmiaObnubilation

ResuscitationRespiratory tract ± nazogastric probeOxigenotherapyNaCl 0,9% : 10-20 ml/kgin 1-2 h, repeated if necessary, without exceeding

iv Treatment Liquid need is adjusted in 48 hNa Cl 0,9%EKG (T wave modifications) : add KClNaHCO3 at pH < 6,9

Shock (weak peripheric puls)Obnubilation/Coma Deshidration > 5%

HyperventilationVomitingNo shock

Minim deshidrationDigestive tolerance

Treatment Insulin scOral hidration

Insulin 0,1 U/kg/h at 1-2 h after initiation of hidration

MonitoringGlucoseIngesta-excretaNeurologic status Ionogram

Acidosis persists Glucose > 250 mg %Glucose < 250 mg %

Neurological deteriorationHeadacheIrritabilityOmnubilation

ReevaluationCalculation of iv liquidsInsulinSepsis ?

iv Treatment NaCl 0,9% (glucose > 250 mg %)Glucose 5 % (glucose < 250 mg %)

ExclusionHypoglycemiaCerebral edema

ImprovementGood general condition

Oral hydratation

TreatmentManitol 0,5-1g/kgLiquid restrictionIntensive therapy

Insulina sc

Unsuccessfultreatment

Fig.... Management ofDiabetic ketoacidosisAcc. to ISPAD 2011

265

Prognosis :

• DM generally has a low immediate morbidity, except for severe ketoacidosis or

hypoglycemia.

• Mortality is low, but can occur in ketoacidotic coma.

• The risk of complications is related to diabetes control.

• With good care, patients have the prospect of living a normal, healthy life.

• insulin pumps and pancreas transplantation may improve prognosis.

Bibliography

1. American Diabetes association – Standards of Medical Care in Diabetes 2013. Diabetes Care, vol 36,

Supp 1, jan 2013, p. S11-S66, care.diabetes.journals.org

2. Ghidul ISPAD 2011 pentru managementul Diabetului zaharat de tip 1 la copil și adolescent -

International Diabetes Federation, global IDF/ISPAD guideline for diabetes in childhood and

adolescence, ISBN 2-930229-72-1, 2011

3. Man Sorin C., Nanulescu Mircea V. – Pediatrie practică, Ed. Risoprint, Cluj-Napoca, 2006, ISBN

973-751-131, p. 448-472

4. Micle Ioana – Diabetul zaharat al copilului și adolescentului în Georgescu A. Ciofu E - Ghiduri și

protocoale în Pediatrie, Ed. Medicală Amaltea, București, 2008, p. 77-109

5. Mihai Cristina Maria, Catrinoiu Doina. Ghidul de tratament al copilului şi adolescentului cu diabet

zaharat, Ed. Universitară „Carol Davila”, Bucureşti, 2008, ISBN : 978-973-708-328-9

6. Moraru Dan, Evelina Moraru, Carmen Oltean, Laura Bozomitu, Bogdan A. Stana. Recent Data on

Type 1 Diabetes Mellitus in Children. Revista Română de Pediatrie – Vol. LVII, Nr. 3, 2008, p. 214-

227

7. Popa I, Velea I. - Cap. Diabetul zaharat în Ciofu E., Ciofu Carmen – Pediatria Tratat, Ed. Medicală,

Bucureşti, 2001, p. 1304-1320

8. Ramin Alemzadeh, David T. Wyatt - Diabetes Mellitus in Children în Kliegman R.M., Behrman R.E.,

Jenson H.B. et al (eds) - Nelson Textbook of Pediatrics, 18 th edition, Saunders Elsevier, Philadelphia,

2007, p. 2404-2433

9. Șerban V – Diabetul zaharat de tip 1 al copilului și tânărului – Ghid practic, Ed. Marineasa,

Timișoara, 2007

10. Velea I., Corina Paul. – Diabetul zaharat în Nanulescu M. - Protocoale de diagnostic și tratament în

pediatrie, Ed. Medicală Amaltea, București, 2013, p. 212-224

266

CHAPTER VII - RENOURINARY SYSTEM DISORDERS

Șef lucr. Dr. Duicu Carmen

URINARY TRACT INFECTIONS (UTI)

Definition

UTI are defined as an inflammatory bacterial processes of the urinary tract and/or renal gap,

characterized by localizing symptoms or systemic features and significant bacteriuria.( the

American Academy of Pediatrics (AAP) criteria for the diagnosis of UTI in children 2-24

months are the presence of pyuria and/or bacteriuria on urinalysis and of at least 50,000

colony-forming units (CFU) per mL of a uropathogen from the quantitative culture of a

properly collected urine specimen)

Term includes localizations such as cystitis, pyelitis, pyelonephritis, with hard delimitation in

children.

Precise estimates of rates of UTI are difficult to ascertain, because of asymptomatic forms

that may lead a minus in diagnosis, while the improper method of collection of a urine

sample may cause excess in UTI diagnosis.

Frequency increases with age. It is generally more common in females. During the first year

of life, the male: female ratio is 2.8-5.4: 1, appearing even forms of urosepsis. There are

differences in frequency related to age and sex, so in newborns and in infants symptomatic

UTI is 3 times more common in males than females. After this age it is more common in

females (2.8%). The risk of relapse is proportional to the previous ITU. After the first UTI,

60-80% of girls will develop a second UTI within 10 months.

After 1 year of age there is a striking female preponderence, with a male: female ratio of

1:10; while at school age it is 30 times higher in girls than in boys.

Ethiology

UTIs are caused mainly by colonic bacteria, with a predominence of Gram-negative

organisms: Eserichia coli ( more than 80% of childhood UTIs), Enterobacter (5-10%),

Proteus, Klebsiella and Pseudomonas; the gram-positive organisms: Staphylococcus (is

usually considered a contaminant, but it can cause illness), Enteroccocus fecalis, Group B

Streptocuccus; other bacteria: Chlamydia trachomatis. Viral infections, particularly

adenovirus, also may occur, especially as a cause of cystitis.

267

More recently Mycoplasma homminis and Ureaplasma urealyticum are involved in the

etiology of UTIs; the bacteria being responsible for urogenital tract infection, sexual

transmited disease.

Risk factors for UTIs:

Female gender- ♀ shorter urethra < 2 cm, opened in the anatomic contaminated area

Obstructive uropathy- congenital/aquired anomalies,vesicoureteral reflux,

ureteropelvic junction(UPJ) obstruction, kidney stones, kidney dysplasia,

hydronephrosis, polycystic kidney disease, etc

stasis constipation, pregnancy, neuropathic bladder

vesicoureteral reflux (in 20-70% of the children with UTIs) → stasis; infection can

cause retrograde flow

race – Caucasian children incidence↑ vs. afro-americans

other causes: Wiping from back to front in females, toilet training, urethral

instrumentation, genital infections , Sexual activity, Pinworm infestation, high blood

pressure, diabetes mellitus, cirrhosis, hypogammaglobulinemia, failure to thrive, etc

Voiding dysfunction

Uncircumcised male

Anatomic abnormality (labial adhesion)

Tight clothing (underwear)

Factors related to the causative organisms:

nefritigene strains of E. coli with capsular polysaccharide surface antigens (K1,

K2, K3, K12, K13) resistance to opsonization, phagocytosis and bactericidal

activity of serum

virulence strains of E. coli fimbriae, P fimbriae (are more likely to cause

pyelonephritis)

Epithelial receptors – influence the adherence

Endotoxins of the germs

Pathogenesis

Virtually all UTIs are ascending infections. The bacteria arise from fecal flora, colonize the

perineum, and enter the bladder via the urethra. In uncircumcised boys, the bacterial

pathogens arise from the flora beneath the prepuce. Rarely, renal infection may occur by

hematogenous spread, as in endocarditis or in some neonates. If bacteria ascend from the

bladder to the kidney, acute pyelonephritis may occur.

268

Classification

Depending on symptoms and location:

- Symptomatic: upper UTI (pyelonephritis - DMSA scan) or lower UTI (cystitis)

- Asymptomatic: asymptomatic bacteriuria (most common in girls)

Depending on the presence of complications:

-uncomplicated

-complicated (hypertension, sepsis)

Depending on evolution: acute UTI; recurrent UTIs (unresolved or reinfection), persitent UTI

(chronic).

Functional: with or without renal failure

Clinical manifestation

The history and clinical course of a UTI vary with the patient's age and the specific diagnosis.

No one specific sign or symptom can be used to identify UTI in infants and children.

Neonates and infants up to age 2 months who have pyelonephritis usually do not have

symptoms localized to the urinary tract. UTI is discovered as part of an evaluation for

neonatal sepsis. Neonates with UTI may display the following symptoms: fever, jaundice,

failure to thrive, poor feeding, vomiting, irritability, etc

Infants and children aged 2 months to 2 years: symptoms are nonspecific, usually they

present with systemic features such as: poor feeding, high fever, vomiting, strong-smelling

urine, abdominal pain or tenderness, irritability, malaise, etc

Children aged 2-6 years:Preschoolers with UTI can display the following symptoms:

gastrointestinal signs, such as vomiting and diarrhoea, abdominal pain, fever, strong-smelling

urine, cloudy urine, enuresis, urinary symptoms (dysuria, urgency, frequency)

Children older than 6 years and adolescents.School-aged children with UTI can display the

following symptoms: fever, vomiting, abdominal pain, flank/back pain, strong-smelling

urine, urinary symptoms (dysuria, urgency, frequent voiding), enuresis, incontinence;

suprapubic, abdominal or lumbar pain may appear with or without fever.

Physical examination. It is mandatory to look for phimosis, labial adhesion, signs of

pyelonephritis, epididymo-orchitis, and stigmata of spina bifida, e.g. hairy patch on the sacral

skin. The absence of fever does not exclude the presence of an infective process.

Physical examination findings in pediatric patients with UTI can be summarized as follows:

Costovertebral angle tenderness

Abdominal tenderness to palpation

Suprapubic tenderness to palpation

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Palpable bladder

Dribbling, poor stream, or straining to void

Clinical evaluation includes: physical exam, blood pressure measurement, genitalia exam,

lumbar sacral region exam.

Laboratory tests

The definitive diagnosis of infection in children requires a positive urine culture. Urine must

be obtained under bacteriologically reliable conditions when undertaking a urine specimen

culture. A positive urine culture is defined as the presence of more than 100,000 cfu/mL of

one pathogen. The urine specimen may be difficult to obtain in a child less than 4 years old

and different methods are advised since there is a high risk of contamination.

If the culture shows 100,000 colonies of a single pathogen, or if there are 10,000

colonies and the child is symptomatic, the child is considered to have UTI.

The American Academy of Pediatrics (AAP) criteria for the diagnosis of urinary tract

infection (UTI) in children 2-24 months are the presence of pyuria and/or bacteriuria on

urinalysis and the presence of at least 50,000 colony-forming units (CFU) per mL of a

uropathogen from the quantitative culture of a properly collected urine specimen. In neonates

younger than 2 months of age, criteria include the presence of lower amounts of a single

pathogen (10,000-50,000 CFU/mL).

Collection of the urine:

Midstream urine collection is possible and reliable in older children with sphincteric control.

Suprapubic bladder aspiration is the most sensitive method, even though urine may be

obtained in 23-99% of cases.

Bladder catheterization is also a most sensitive method, even though there is the risk of

introduction of nosocomial pathogens.

Plastic bag attached to the genitalia Prospective studies showed a high incidence of false-

positive results, ranging from 85-99%.

Quantification of bacteriuria

The final concentration of bacteria in urine is directly related to the method of collection,

diuresis, method of storage and transport of the specimen. Promp plating of the urine sample

is important, because if the urine sits at room temperaturefor more than 60 min, overgroth of

a minor contaminant may suggest a UTI when the urine may not, in fact, be infected.

Refrigeration (40C), for maximum 24 hours, is a reliable method of storing the urine until it

can be cultured.

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A urinalysis shoul be performed from the same specimen that was cultured.

The presence of pyuria (more than 5 leucocytes per field) and bacteriuria in a fresh urine

sample will reinforce the clinical diagnosis of UTI.

Pyuria (leucocytes in the urine, > 5 leucocytes/ power field) suggest infection, but infection

can occur in the absence of pyuria, consequently this finding is more confirmatory than

diagnostic. Conversely, pyuria can be present without UTI.

Nitrites and leucocyte esterase ussually are positive in infected urine.

Whide blood cell casts in urinary sediment suggest renal involvment.

If the child is asymptomatic and the urinalysis result is normal, it is unlikly that there is a

UTI. However, if the child is symptomatic, a UTI is possible, even if the urinalysis result is

negative !!!

Gram staining:

Other analyses: Urinary sediment , complet blood count, reactants of acute phase (ESR,

CRP); renal function: urea, creatinine; electrolytes, immunogram, proteinogram, glycemia,

blood culture – pyelonephritis, sepsis in new born with UTI

Table x. Criteria of UTI in children (according to European Association of Urology

Guideline):

Urine specimen from

suprapubic

bladder puncture

Urine specimen from

bladder

catheterization

Urine specimen from

midstream

void

Any number of cfu/mL (at

least 10

identical colonies)

> 1,000-50,000 cfu/mL > 104 cfu/mL with symptoms

> 105 cfu/mL without

symptoms

Bacteriuria without pyuria may be found:

in bacterial contamination

in colonization (asymptomatic bacteriuria)

when collecting a specimen before the onset of an inflammatory reaction.

In such cases, it is advisable to repeat the urinalysis after 24 hours to clarify the

situation

Pyuria without bacteriuria may be due to:

incomplete antimicrobial treatment of UTI

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urolithiasis and foreign bodies

infections caused by Mycobacterium tuberculosis and other fastidious bacteria, e.g.

Chlamydia trachomatis.

Imaging studies

- the goal of imaging studies in children with a UTI is to identify anatomic

abnormalities that predispose to infection

- are mandatory from the first episode(ultrasonography for all children with UTI !)

- the gender does not matter

Indications:

- All newborns

- Recurrent UTI

- pyelonephritis

1. renal ultrasound: reveals malformations, hydronephrosis, renal duplicity,

ureterocele, UPJ obstructions, kidney stones, obstructive uropathy, etc. In acute

pyelonephritis: enlarged kidney, loss of corticomedullary differentiation, increased

renal echogenicity

2. Voiding cystourethrogram (VCUG) is performed to detect vesicoureteral reflux. Is

recommended after upper UTI, recurrent UTI or when renal sonogram shows a

significant abnormality: hydronephrosis, disparity of renal length, bladder wall

thickening, bladder obstruction: posterior urethral avlve.

3. Renal scanning with DMSA (dimercaptosuccinic acid)- static and dynamic (with

DTPA + furosemid). DMSA scan demonstrate renal focal abnormalities, renal scars,

determine differential renal function

4. Nativ Renal X-ray : for radio-opacue calculi /stones

5. Intravenous pyelography: has been replaced by renal ultrasound and DMSA scan;

give informations about: size, shape of the kidney, pyelocaliceal system,

ureters,urinary bladder

6. urodinamic investigations (uroflowmetry)

- Assessment of lower urinary tract

- Bladder function - storage, transport, emptiness

7. Pelvic exam

Diagnosis has the next steps:

Establish the diagnosis of ITU

Etiologic diagnosis

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localization (upper/ lower UTI)

presence of risk factors

UTI rebound upon the renal function

Clinical forms:

1. Acute pyelonephritis (upper UTI) Clinic: abdominal or flank pain, malaise, nausea,

vomiting, sometimes diarrhea. In newborn, nonspecific symptoms: decreased appetite,

irritability, weight loss, prolonged jaundice, etc. Involvment of the renal parenchima =

acute pyelonephritis, whereas if there is no parenchymal involvment= pyelitis.

2. Pyonephrosis: accumulation of purulent material in the renal pelvis and renal

collecting system with obstructive hydronephrosis. Symptomatologia-result similar to

that of acute pyelonephritis.

3. Renal abscess is established by the hematogenous spread of the infection pathway in

other dynamic sites without genitourinary tract or by extension a high ITU. Clinic:

signs of severe pyelonephritis, fever, pain in the flanks, leukocytosis and occasionally

sepsis. The diagnosis is ultrasound.

4. Cystitis (lower UTI) - bladder involvement - and those can be viral (adenovirus).

Symptoms: dysuria, urgency micturition, pollakiuria, suprapubic pain, urinary

incontinence, smelly urine, hyperchrome.

5. Asymptomatic bacteriuria - is defined by positive urine culture in the absence of

any symptoms of urinary infection. Occurs more frequently in women at preschool

and school age groups. Incidence is declines with increasing age. It does not cause

kidney damage.

Positive diagnosis

Significant bacteriuria

piuria

Evidence the germs

Other analyzes

Diferential diagnosis

I. Between upper and lower UTI

II. urethrites (irritative- soap), vaginitis,vulvovaginites, traumas, sphincter- detrusor

dissinergy (which produces incontinence)

III. other causes of enuresis/ voiding disfunction

IV. pneumonia, gastroenteritis, apendicitis, pelvic inflammations- with symptoms similar

to acute pyelophritis with general manifestations

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Complications

septicemia (new born, urinary malformations)

Renal scars (→ HBP, ↑risk of CRF)

calculogenezis

chronic pyelonephritis

Hospital Admission Criteria:

Hospitalization is necessary for the following patients with UTI:

Patients who are toxemic or septic

Patients with signs of urinary obstruction or significant underlying disease

Patients unable to tolerate adequate oral fluids or medications

Infants younger than 2 months with febrile UTI (presumed pyelonephritis)

All infants younger than 1 month with suspected UTI, even if not febrile

Treatment

General treatment

1. Hygiene

Wipe in the correct direction, from front to back, after using the bathroom

Clean the bladder area first when washing to prevent contamination with bacteria from other

parts of the body.

Take showers and avoid prolonged baths.

Use tampons for periods. Tampons are advised during the menstrual period rather than

sanitary napkins or pads because they keep the bladder opening area drier than a sanitary pad,

thereby limiting bacterial overgrowth.

Extremely effective is avoiding long intervals between urinating. Try to empty the bladder at

least every 4 hours during the day while awake, even if the need or urge to void is absent.

When feeling the need to empty the bladder, do not try to “hold it” until a more convenient

time or place.

2.Clothing: Cotton underwear for general use is suggested.

3. Diet: Empty the bladder at least every 4 hours. Drink more water and consider drinking

cranberry juice (or taking cranberry pills). It cannot harm. Start with 1 extra glass with each

meal. If the urine appears any darker than a very pale yellow, this means not enough liquid is

being ingested; increase the fluid intake.

4. Activities:

make sure to empty the bladder frequently and drink plenty of water and other fluids.

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Take special precautions after sexual activity; such activity may also increase risk because it

can introduce bacteria into the bladder area. The bladder should be emptied after intercourse;

drink 2 extra glasses of water.

- Combat/treat constipation

- Urine acidification (1-2 tb. Vit. C 200) ↓ germs proliferation

(Not – if it gets aminoglicozids, which has a better action in the alkaline environment)

II. Medicines

parenteral treatment (I.V.) with antibiotics

Indications

Febrile cases

complications (urinary malformations, renal abces)

New born, infants and children under 2 years old

Reduced compliance

Gastric intolerance: nausea, vomiting, diarrhea

It can be used:

Aminoglycoside antibiotic- parenteral route

Amikacin (Pierami, Amikin): 15 mg/kgc/day, 2 (3) doses I.V./I.M.

Netilmicin (Netromycin): 6-7,5 mg/kgc/day, in 2 (3) doses I.V./I.M.

Tobramycin (Nebcin, Brulamycin): 5 mg/kgc/day, in 3 doses I.V./I.M.

Gentamicin: 7,5 mg/kg/day, in 3 doses, I.V./I.M., it will be given only if

there is no other treatment option (because of nephrotoxicity and ototoxicity)

Cephalosporins - i.v.

Ceftriaxon (Cefort, Rocephin): 75 -100 mg/kgc/day, 1 dose.

Cefuroxim (Axetine): (50)-100 mg/kgc/day, in 2-3 doses

Cefotaxim (Cefotax): 150 mg/kgc/day, in 3-4 doses

Ceftazidim (Ceftami): 100–150 mg/kg/day, in 3 doses

In acute febrile infection sugestive of pyelonephritis, a 10 to 14- day cours of antibiotics

capable of reaching significant tissue level is preferable. Children who are dehydrated, are

vomiting, or unable to drink fluids, newborns and infants or in whom urosespis is a

possibility shoult be attmited to the hospital for intravenous antibiotiv therapy and

rehidrattion. Parenteral antibiotics may be used with daily follow-up until the patient is

afebrile for 24 hours.

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Complete 10-14 days of therapy with an oral antibiotic that is active against the infecting

bacteria. For a safety period of 24-36 hours, parenteral therapy should be administered. When

the child becomes afebrile and is able to take fluids, he/she may be given an oral agent to

complete the 10-14 days of treatment, which may be continued on an outpatient basis.

b. Oral treatment is recommanded in the other cases.

Aminopenicillins:

amoxicillin/clavulanate (Augmentin Bis, Amoxiklav susp 457mg/5ml: 40-50 mg/kgc/day

in 2 doses

Sulphonamides:

sulfamethoxazole-trimethoprim (SMZ-TMP). ( Sumetrolim, Epitrim, Biseptol, Bactrim):

6-12 mg/kgc/day TMP and 30-60 mg/kg/day SMZ in 2 doses

Sulfisoxazole 120–150 mg/kg/day in 4 doses

Cephalosporins:

Third generation

Cefixime ( Eficef, Suprax,etc ) 8 mg/kg/day in 1-2 dose PO

Cefpodoxime 10 mg/kg/day in 2 doses PO

Ceftibuten (Cedax): 9 mg/kgc/day in 1 dose P.O.

Second generation:

Cefuroxim axetil (Zinnat, Axycef susp 125mg/5ml sau cp a 250mg, 500mg) 20-

30mg/kgc/day in 2 doses

Cefprozil (Cefzil,Procef, Cronocef) 30 mg/kg/day in 2 doses

Cefaclor (Ceclor, Cefaclor, Ceclodyne): 20 mg/kgc/day in 3 doses P.O.

First Generation:

Cefalexin (Keflex, Ospexin): 25-50 mg/kgc/day in 2-4 doses P.O.

Cefadroxil (Cexyl susp 250mg/5ml) 25mg/kg/day in 2 doses P.O.

A simple UTI is considered to be a low-risk infection in children. The duration of treatment

in uncomplicated UTIs treated orally should be 5-7 days.

Nitrofurantoin 5-7 mg/kg/24 hr in 3 to 4 divided doses, reomended just in lower UTIs (! It

does not achive significant renal tissue levels).

in forms with resistant germs (ex Pseudomonas) treatment is based on the culture sensibility

Meronem (Meropenem) 10-20 mg/kg/dose every la 8 hous, I.V.

Imipenem (Tienam) 15 mg/kg/dose, every 6 hours, I.V.

Ciprofloxacin,Norfloxacin, Levofloxacin 15 mg/kgc/day in 2 doses P.O./IV

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Ceftazidim (Ceftamil) 100–150 mg/kg/day, in 3 doses

Ticarcilina (Timentin) 300mgmg/kg/day in 3 doses I.V

Prevention of reccurent UTI- is recomanded in case of:

- Reccurent UTIs

- Abnormal renal ultrasound in neonates

- Bladder catheterization

- After an episod of acute pyelonephritis (upper UTI): for 4 to 6 weeks until the

imagistic studies are completed or if there are risk factors

In case of renal anomalies (obstructive uropathy, vesicuretheral reflux, etc ) prophylaxis is

recomended until the abnormality is solved by medical or surgical treatment. Sometimes it is

necessary life long. If there is an increased risk of pyelonephritis, e.g. VUR, and recurrent

UTI, low-dose antibiotic prophylaxis is recommended. It may also be used after an acute

episode of UTI until the diagnostic work-up is completed.

For prophilaxis it may be used:

sulfamethoxazole-trimethoprim (SMZ-TMP).: 2 mg/kgc/day (TMP), single dose-

evening

Nitrofurantoin: 1-2 mg/kgc/day, 1 dose- evening

Nalidixic Acid (Negram, Nalixid, etc): 20 mg/kgc/day in 1-2 doses

Cephalexin, Cefaclor: 10 mg/kgc/day, 1 doses- evening

Augmentin Bis: 10 mg/kgc/day, 1 dose evening (amoxicilina)

In simple UTIs we may reccomand:

- Urinary antiseptics (Uricol, Urisan, Urinal, Cystenal, etc)

- Cranberry products

- Immunotherapy with Uro-Vaxom 1 cps/day P.O. , a 3 months cours.

III.Surgical treatment is recommended in case of congenital kidney anomalies, kidney

stones, etc.

Evolution: with adequate treatment is favorable. We can not predict the recurrency, but we

may prevent them.

Without treatment, acute pyelonephritis may lead to renal scars and kidney damage

Prognosis: is good, depends on diagnosis precocity and treatment.

Chronic pyelonephritis is an important ethiologic factor in chronic kidney disease (CKD).

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VESICOURETERAL REFLUX (VUR)

Retrograde flow of urine from bladder to the ureter and renal pe4lvis is referred as

vesicoureteral reflux.

It can be unilateral or bilateral.

VUR represents the main cause of UTI in children (it is found in 15-70% of patients with

UTIs, depending on age).

Classification:

1. Based on grading of the reflux

Voiding cystourethrography (VCUG) is the criterion standard in diagnosis of VUR, providing

precise anatomic detail and allows grading of the reflux. The International Classification

System for VUR is as follows:

Grade I - Reflux into nondilated ureter

Grade II - Reflux into renal pelvis and calyces without dilation

Grade III - Reflux with mild to moderate dilation and minimal blunting of fornices

Grade IV - Reflux with moderate ureteral tortuosity and dilation of pelvis and calyces

Grade V - Reflux with gross dilation of ureter, pelvis, and calyces, loss of papillary

impressions, and ureteral tortuosity

Fig ccc. International grading system for vesicoureteral reflux (From International reflux

Study Comittee, Pediatrics 1981;67:392-400)

2. Based on ethiology:

- Primary: congenital incompetence of the valvular mechanism of the vesicoureteral

junction or associated with other malformations of the ureterovesical junction

(ureteral duplication, ureterocele with duplication, ureteral ectopia, etc)

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- Secondary to: increased intravesical pressure(neuropathic bladder, posterior

urthral valve, etc); inflammatory processes (foreign bodies, vesical calculi, etc);

surgical procedures involving the ureterovesical junction

Types of refluxes:

- Reflux occuring during bladder filling= low pressure or passive reflux: a

permanent retrograde flow of urine →statis→ chronic pyelonephritis→ reflux

nephropathy→ CKD

- Reflux during voiding is tremed as high-pressure or active reflux

Clinical manifestation:

- clinical UTI

- hydronephrosis, often prenatally identified using ultrasonography.: VCUG: VUR

in 40%

- voiding disfunction/ enuresis

- renal insufficiency:

- hypertension

Diagnosis: based on VCUG

Signs of poor outcome: UTI reccurency despite prophylaxis, hypertension, proteinuria and

CKD

Treatment: the goals are to prevent pyelonephrities, renal injury and other complications of

reflux

- medical treatment: antimicrobial prophylaxis

- surgical therapy:endoscopic antireflux techniques (Deflux), open surgical

techniques for children who fail medical therapy (development of new renal

scars, failure of reflux to resolve, a low chance to resolve: grade V VUR,

reccurent UTI despite appropiate antibiotic prophylaxis, etc)

Follow-up:

- periodic urinalysis: initially monthly, then at 3 or 6 month; immediately in case of

febrile illness)

- Assessment of renal function – once a year: urea, creatinine, proteinuria

- annual BP measurement

- imaging studies- reassessment (ultrasound, VCUG, DMSA scan)

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ACUTE GLOMERULONEPHRITIES (AGN)

Acute glomerulonephrities (GN) comprises a specific set of renal diseases in which an

immunologic mechanism triggers inflammation and proliferation of glomerular tissue that

can result in damage to the basement membrane, mesangium, or capillary endothelium.

Acute GN involves both structural changes and functional changes.

Hyalinization or sclerosis indicates irreversible injury.

These structural changes can be focal, diffuse or segmental, or global.

Functional changes include proteinuria, hematuria, reduction in GFR (ie, oligoanuria), and

active urine sediment with red bloob cells (RBCs) and RBC casts. The decreased glomerular

filtration rate (GFR) and avid distal nephron salt and water retention result in expansion of

intravascular volume, edema, and, frequently, systemic hypertension.

Etiology:

-most frequent postinfections:

- bacterial infections: frequent Streptococcus group A; pneumococcus,

Staphylococcus, etc

- viral infections: Epstein-Barr virus, parvovirus B19, CMV, coxsackie, rubella,

mumps, Hepatitis B, etc

- parasites: Plasmodium malariae, Plasmodium falciparum, Schistosoma mansoni,

Toxoplasma gondii, Filaria

- secondary GN: Henoch-Schonlein purpura, systemic lupus erythematosus (SLE),

bacterial endocarditis, Goodpasture syndrome

- toxic or allergic factors: drugs, vaccine, etc

Evaluation

1. Anamnesis:

- Case history: acute streptococcal tonsillitis (1-2 weeks previously), pyodermitis/

impetigo (3 weeks previously), vetriculoperitoneal shunt

- Family history: hematuria/ renal failure ± deathness = Alport syndrome

Autoimmune diseases: SLE, etc

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2. History (table 2)

Macroscopic hematuria:

- Painless, Dark brown-colored urine; with the same

aspect during micturition

- GN

Post upper respiratory tract infection, macroscopic

hematuria during acute episode, otherwise microscopic

hematuria

1-3 days: IgA nephropathy(Berger

disease)

Post acute tonsillitis/ pyodermitis; edema, HBP,

hematuria, oliguria

7-10 days: postinfectious GN

(recurency- less reliably)

Concomitent with an upper resiratory tract infection, a

positive case history of glomerular disease; anemia+

hyperazotemia from begining, high blood pressure

(HBP)

Acute phase of chronic GN

Edema, weight gain Nephrotic

syndrome/glomerulonephrities;

Chronic renal failure

Edema, hematuria, Diminished urine output (300-150

ml/m2/day), HBP

AGN (acute glomerulonephrities)

Rash (95-100%), Palpable purpura, particularly on the

buttocks and legs , Gastrointestinal symptoms, arthritis

(big joints)

Henoch Schonlein Purpura (HSP)

Glomerulonephities, hemolitic anaemia,

trombocytopenia, purpura

Hemolitic uremic syndrome

+ case history , hematuria, proteinuria, HBP, fever,

hepatosplenomegaly, arthritis, purpura; + blood culture

Shunt nephritis

HBP, nepfromegalia, renal insufficiency, familal history

of hematuria

ADPKD(Autosomal Dominant

Polycystic Kidney Disease)

Fever, arthritis (small joints), rash, females SLE

Hematuria, proteinuria, dry cough +/-hemoptysis, HBP,

chronic renal failure

Goodpasture sdr

Clinical manifestations of endocarditis+

micro/macroscopic hematuria, proteinuria, + blood

culture

Acute/subacute bacterial

endocarditis

281

3. Clinical characteristics:

Skin :

- pallor: haemolytic uraemic syndrome (HUS), systemic lupus erythematosus ,

glomerulonephritis

- Rash : Henoch- Schonlein purpura , SLE, HUS , other vasculitis ,

fat

- Swelling : nephrotic syndrome , glomerulonephritis, acute/chronic renal failure

Osteoarticular system

- Arthritis: Henoch- Schonlein purpura , SLE

Cardiovascular System

- HBP,

- Tachycardia, gallop rhythm

- Turgid jugular vein, venous pulsation at this level

- Murmurs : bacterial endocarditis

Respiratory System : tachypnea ( secondary to fluid overload )

- acute pulmonary edema signs ( polipnea , orthopnea , cough with frothy sputum ,

rodents, anxiety, sweating, cyanosis, stetacustic: pulmonary crackles )

Digestive System :

Oral and nasal bleeding at this level: ANCA + vasculitis ( Wegner granulomatosis )

abdomen :

- Nephromegalia : parenchymal nephropathy

- Hepato + / - splenomegaly : systemic disease , shunt nephritis

- marked abdominal pain: HSP

Nervous system and sense organs :

- Ocular abnormalities and / or hearing : Allport syndrome

- Signs of acute cerebral edema (Amaurosis fugax = transient monocular or binocular

visual loss), headache, vomiting, seizures, coma ) :AGN

4. Labs tests

The first line/intention:

Urinalysis with sediment:! RBCs- dysmorphic, erythrocyte casts, hyaline and granular

casts

Proteinuria/24 hours: moderate / significant (gold standard), or report protein / creatinine

and urinary albumin / creatinine urine from urinary spot

± at family members (Alport sdr.)

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- ! nonselective protinuria

2. Blood: Complete CBC, urea, creatinine, ionogram, protein,! Serum complement

levels: CH50,C3, C4; antistreptolysin O (ASO), anti-DNAse B, antistreptokinase, anti-

NADase, antihyaluronidase antibody

Later stage: acute phase reactions, immunogram, CIC, antinuclear antibody, anti-DNA

antibody, ANCA, anti-GBM antibody, serology for EBV and hepatitis B and C; renal

ultrasound, renal biopsy (light microscopy and immunofluorescence)

Other investigations: ASTRUP, EKG, fundus examination

Acute nephritic syndrome is the most serious and potentially devastating form of the various

renal syndromes.

GLOMERULONEPHRITIS ASSOCIATED WITH INFECTIONS

Most often, at least in children, acute nephritic syndrome is secondary to acute postinfectious

glomerulonephritis.

Definition: = immune inflammatory processes involving the renal glomeruli with exudative

and proliferative lesions of the glomerular capillary. When damage of glomeruli is uniform,

we speak about diffuse acute glomerulonephritis.

Glomerular lesions in acute GN are the result of glomerular deposition or in situ formation of

immune complexes. On gross appearance, the kidneys may be enlarged up to 50%.

Histopathologic changes include swelling of the glomerular tufts and infiltration with

polymorphonucleocytes. Immunofluorescence reveals deposition of immunoglobulins and

complement.

Ethiology:- see above

Postinfectious GN can occur at any age but usually develops in children. Most cases occur in

patients aged 5-15 years; only 10% occur in patients older than 40 years. Outbreaks of PSGN

are common in children aged 6-10 years. Acute nephritis may occur at any age, including

infancy.

Acute GN predominantly affects males (2:1 male-to-female ratio). Postinfectious GN has no

predilection for any racial or ethnic group. A higher incidence (related to poor hygiene) may

be observed in some socioeconomic groups.

Nephritic syndrome is defined by the presence of characteristic clinical manifestations and

laboratory findings.

1. Oliguria/oligoanuria. Diminished urine output: 300-150 ml/m2/day, (urine

output <1ml/kg/day in infants; <0.5ml/kg/day in children) .

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2. Edema (peripheral or periorbital) are soft, white. It is reported in approximately 85% of

pediatric patients; edema may be mild (involving only the face) to severe, bordering on a

nephrotic appearance.

3. Hypertension and cardiovascular overload. HBP is due to increased peripheral resistance

(due to arterial vasoconstriction produced as a result of increased secretion of renin) and

vascular overload.

Overloading the circulation may be evidenced by hepatomegaly, jugular vein turgit, gallop

rhythm, to pulmonary edema .

4. Hematuria . It can be macro- or microscopic. It appear as a dark coloured urine, reddish

brown like beer; like meat or tea-colored washings concentrated .

Urinary sediment contain RBCs, RBC casts, hyaline and granular casts.

5. Proteinuria. As the volume and concentration of urine depends on liquids ingestion and

renal function is more accurate to determin proteinuria in urine collected within 24 hours.

Normal is less than 100 mg/24 h .

In AGN proteinuria varies between 300 mg 1-2g / 24h .

• 100-500 mg/24 - mild proteinuria

• 500-2000 mg/24 h - moderate proteinuria

• 2000 mg/24 - massive proteinuria

6. Azotemia is the result of reduced glomerular filtration rate leading to increased blood urea

nitrogen, creatinine, uric acid , phosphates , etc.

7. Anemia is mild, normochromic with Hgb 9-11 g/dl .

8. Electrolyte and acid-base disorders :

-hyperkalemia resulting from a reduction in urinary excretion of K + concomitent with the

ingestion and contribution of cellular catabolism .

-metabolic acidosis - installed with reduced urine output and becomes obvious when severe

oliguria is present.

Pathology

There are some common signs in most forms of AGN. Glomeruli are enlarged, some

capillaries are blocked, capillary edema and polymorphonuclear infiltration, mesangial

edema, cellular proliferation of one or more types of glomerular cells (endothelial, mesangial

and epithelial).

Sometimes can be found the gap infiltrated with mononuclear or polymorphonuclear.

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ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS (APSGN)

Definition: It is a self-limiting complication of poststreptococcal infections, an upper

respiratory tract or a skin infection with a nephritogenic strain group A -hemolytic

streptococci. It is a proliferative glomerulonephritis that occurs with increased frequency in

boys between 5-15 years.

- Is the main cause of acute nephritic syndrome (80% of cases).

APSGN is characterized by:

• Clinical: an acute nephritic syndrome

• Etiology: group A hemolytic Streptococcus

• pathogenesis: mediated by circulating immune complexes

• pathological: diffuse endocapillary proliferative glomerulonephritis with numerous

polynuclear cells and the presence of humps on the external side of GBM

• evolution is usually favorable, with complete resolution and healing, with restitutio ad

integrum for 95% of children with APSGN

• The most common (60-95% of the child AGN) and typical form of AGN

Etiology:

a). nephritogenic strains of group A beta-hemolytic streptococci: serotype 12 ( throat

infection (pharyngitis)) and serotype 49 (skin infection (impetigo) ).

Between streptococcal infection and apparent disease onset there is an asymptomatic latency

period (5-14 days), or more rarely with uncharacteristic symptoms (fatigue, low grade fever,

anorexia).

b). rarely- Group C streptococci, have been responsible for recent epidemics of APSGN (eg,

Streptococcus zooepidemicus).

Favoring factors:

a) age: childhood and adolescence, most common 5-15 years

b) sex: male predominance (male-to-female ratio 2:1)

c) cold and wet climate (autumn and winter)

d) in communities with densely populated dwellings that have poor hygienic conditions with

a high incidence of malnutrition, anemia, and intestinal parasites.

e) immunological status of the patient

Pathogenesis

Most forms of acute poststreptococcal glomerulonephritis (APSGN) are mediated by an

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immunologic process. Cellular and humoral immunity is important in the pathogenesis of this

disease, and humoral immunity particularly in APSGN.

An immune complex–mediated mechanism is the most widely proposed mechanism leading

to the development of APSGN. In most circumstances, glomerular inflammation begins with

an antigen-antibody reaction, either direct antibody binding to an antigen expressed or

trapped in the glomerulus, or the localization of a circulating complex in the kidney.

This incites injury by activating one or more systems of inflammatory mediators: the

complement cascade, coagulation factors, cytokines, growth factors, and others. The

inflammation is marked by proliferation of resident glomerular cells and infiltration by

lymphocytes or neutrophils.

Complement activation from both serum profiles and immunofluorescence patterns for

glomerular deposits indicates that C3 activation in APSGN is predominantly via the

alternative pathway. The immune deposits consist of immunoglobulin G (IgG), C3,

properdin, and C5.

Physiopathogeny

The glomerular inflammation and expansion impairs the microcirculation, reducing the

glomerular filtration rate (GFR) and usually resulting in an increase in BUN and creatinine.

This reduction in GFR, in turn, leads to the retention of salt and water, causing fluid overload.

The degree of fluid overload in AGN can vary considerably. In severe situations, it can be

manifest by life-threatening hypertension and pulmonary edema. Indeed, hypertensive

encephalopathy may be the presenting complaint in some children with AGN.

Streptococcal infection

Immune complex formation+ deposide in GBM

Complement system acivated low serum complement

Immune injuries

Cellular proliferation GBM fracture

Capillary lumen narrowed hematuria

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proteinuria

Glomerular blood flow decreased

Oliguria GFR distal Na reasorption

Retention of water and Na

Blood volume

Edema

hypertension

Fig 2. Physipathology of APSGN

Clinical manifestation

The typical patient develops an acute nephritic syndrome 1-2 week after an antecedet

streptococcal pharyngitis or 3-6 week after a streptococcal pyoderma. Sometimes within the

physiacl exam we may detect angina or other streptococcal infections.

a. The onset may be:

- Acute onset after infection, with acute oliguria, edema, macroscopic hemtauria, HBP

- an insidious or slow (common) with: anorexia, asthenia, pallor, low back discomfort, eyelid

edema, tonsillitis, fever, headache, vomiting, abdominal pain, urine: proteinuria and

hematuria ( dysuria, pollakiuria)

- a dramatic (more rarely) by one of the acute complications: acute cerebral edema

(amaurosis, headache, vomiting, seizures, coma) or pulmonary edema.

- frequent atypical onset (diagnosis errors!)

Period of state: in typical forms is dominated by the 4 cardinal syndromes of the disease:

1. Syndrome of hydro-saline retention (edematous, hidropigen)

discrete/moderate edema – soft, white, on the eyelids and face

More pronounced in the morning

Lead to weight gain

Sometimes noticed only in diuresis resumption → ↓ weight

2. Urinary syndrome

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oliguria < 300 ml/m2/24h

Macroscopic hematuria (meat wash)

laboratory

a. specific gravity normal or mild decreased (>1020)

b. Moderate nonselective proteinuria (0,5-1g/24h), later selective

c. glomerular hematuria (dysmorphic hematuria)

d. Erytrocite casts but also hialin or granulous casts

3. Hypertensive syndrome and cardiovascular overloading

The acute phase of the disease is characterized by frequent and sudden

changes in BP that requires frequent monitoring (every 4-6 hours). It is a sistolo-diastolic

HBP.

Signs of cardio-vascular overloading:

a.tachicardy, gallop rithm, cardiomegaly

b. Venous stasis (jugular turgescence, jugular pulsations, CVP ↑)

c. hepatomegaly, hepatojugular reflux

d. Severe forms - mimic APE

4. Syndrome of nitrogen retention characterized by: urea > 40 mg%, uric acid

>4 mg%, creatinine > 1,2 mg%

Specific symptoms as malaise, lethargy, abdominal or flank pain, fever are common.

The acute phase generally resolves within 6-8 weeks.

Although urinary protein excretion and hypertension usually normalize by 4-6 weeks after the

onset, persistent microscopic hematurea may persist for 1-2 years after the initial

presentation.

Diagnosis:

1. urinalysis → RBC , RBC casts, proteinuria, polymorphnuclear leukocytes.

2. There may be mild normochromic anemia due to hemodilution and low-grade

hemolysis.

3. C3 is usually ↓ in acute phase and return to normal level after 6-8 weeks.

4. The diagnosis is confirmed by the clear evidence of invasive streptococcal infections

:

a. positive throat culture may support diagnosis or represent carrier state.

b. A rising antibody titer to streptococcal antigens confirms a recent streptococcal

infection. These include :

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• ASO titer is commonly ↑ after pharyngeal infection but rarely ↑ after

streptococcal skin infection.

• The best single antibody titer to document cutaneous infection is the

deoxyribo- nuclease (DNAase) B antigen.

• The streptozyme test is alternative study which detects antibodies to

streptolysin O, DNAase B, hyaluronidase, & streptokinase using a slide

agglutination test.

5. increased ESR, α2 and γ globuline

6. urinary protein electrophoresis – initially nonselective, in convalescence – selective

proteinuria

7. The electrolyte profile is usually normal; hyperkalemia and metabolic acidosis are only

present in patients with significant renal functional impairment. The same applies to

hyperphosphatemia.

8. EKG: signs of overloading left ventricle

9. FO – papillar edema, retinal vessels stasis

10. Circulating immune complexes (CIC) ↑

11. ANCA, antinuclear antibodies, anti-DNA antibodies, anti-GBM antibodies, serology

for EBV and hepatitis B and C – differential diagnosis

12. Renal biopsy should be considered :

a) In the early stages:

- Short latency period

- Severe anuria

- Rapid unfavorable outcome/ acute renal failure

- HBP 2 weeks

- Low GFR 2 weeks

- normal level of C3

- Absence of evidence of streptococcal infections, ASO- insignificant titre

- Non-renal manifestations

b) convalescence period:

- Low GFR 4 weeks

- Hypocomplementemia 12 weeks

- Persistent proteinuria 6 months

- Persistent microscopic hematuria 18 months

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Positive diagnosis is sustained by clinical description and laboratory data .

1. There is no signs of systemic disease associated with typical cluster.

2. Evidence of streptococcal disease (positive throat culture or skin infection, evaluation of

antibody titers in both acute and convalescent).

3. Serum complement levels: C3 decreased in the acute phase, normal C4; C3 values return to

normal in 6-8 weeks.

4. Improvement of symptoms in the first week of illness: resumtion of diuresis, normalization

of BP, decreased nitrogen retention.

5. Normalization of urinary sediment: the disappearance of macroscopic hematuria in 2-3

weeks, 3-6 months disappearance of proteinuria, microscopic hematuria disappearance during

the first year.

Differential diagnosis:

-other causes of hematuria

1. GN during infection - intrainfectious onset, Alb-uria, Complementemia-N., no

edema, without HTA, renal function-N., self-limited disease

2. hemolitic-uremic syndrome – hemorrhagic nephritis Renal failure

3. UTI – bacteriuria and leucocyturia

4. Secondary GN -systemic diseases (SLE, PN)

5. Acute exarcebation of chronic glomerulonephritis- previous nephropathy, viral uppert

respiratory tract infection, anemia, azotemia from the onset, C level N/↑, renal biopsy

6. other hematuria (trauma, lithiasis, anticoagulant)

7. pielonephritis/viral hemorrhagic cystitis

8. nephritis from purpura Schonlein Henoch

9. nephrotic syndrome – massive P-uria, monstrous edema , H-lipemia, hAlb.

10. AGN with CIC - non-streptococcal

11. Acute glomerulonephritis following other infections like staphylococci, streptococcus

pneumonia, Gram negative bacteria, bacterial endocarditis

Clinical course

Spontaneous improvement typically begins within 1 week with resolution of edema in 5-10

days and hypertension in 2-3 week, but urinalysis may be abnormal (persistent microscopic

hematuria) for 1-2 year after the initial presentation. Creatinine improves in 1 week and

become normal in 3-4 weeks, albuminuria may last a few months. C3 levels normalized in 6-

8 weeks.

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Figure 2. Natural history of acute post-streptococcal glomerulonephritis

Complications:

Hypertension : seen in 60% of cases and may lead to hypertensive encephalopathy in

10%.

Acute renal dysfunction : hyperkalemia, hyperphosphatemia, hypocalcemia, acidosis,

seizure, uremia.

Heart failure.

Prevention

� Early systemic antibiotic treatment for streptococcal throat and skin infection does not

eliminate the risk of glomerulonephritis.

� Family members of the patient should be cultured for group A β-hemolytic streptococci

and treated if culture is positive.

Treatment:

Treatment of APSGN is largely that of supportive care. Usually, patients undergo a

spontaneous diuresis within 7 to 10 days after the onset of their illness - strict monitoring –

nephrotic chart + fluid restriction until dieresis is restored

Management is directed at treating the acute effects of renal insufficiency and hypertension.

General measures (Hygieno-dietetic treatment):

Bed rest: only indicated during the oliguric phase (1st week). Relative rest 2-4 weeks,

without violent physical activity for 1 year; then normal activity

Diet :

3-6 wks / 2wks

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high carbohydrates diet to provide adequate calories, min. caloric 300-400kcal/m2/day

through oral or i.v. glucose solution

and low protein and salts during oliguric phase and with complications as severe

hypertension and marked vascular congestion

without NaCl, restriction of K

initially-proteins restriction; they will be introduced >7-10 days- vegetals

Fluid balance : During the oliguric phase, measurement of the daily urinary output is

important. The total daily fluid intake should be equal to the urinary output + insensible

water loss; liquid restrictions - 500ml/m2/day + diuresis of the previous day,

Specific measures :

a)etiologic: although a 10-day course of systemic antibiotic therapy with penicillin is

recomended to limit the spread of the nephrogenic organisms, antibiotic therapy does not

affect the natural history of glomerulonephritis.

Penicillin 50.000-100.000UI/Kgcorp/day, im, 4 doses, 10 days

Eryttromycin 30-50mg/kgbody/day po

Moldamin for prophilaxy 600 000 < 12 years, 1 200 000 > 12 years weekly p.la ext.

b). Control of hypertension : decrease Na+ intake, diuretics, Ca+2 channel antagonists,

vasodilators, & angiotensin converting enzyme inhibitors. [ captopril 0.5-1 mg/kg/day,

hydralazine 1-2 mg/kg/day, propronalol 1-2 mg/kg/day, the dose of each drug is divided 3-4

times ].

c). Control of edema: In most cases, edema subsides spontaneously at the end of 1st week and

with the onset of diuresis. Reduced fluid and salt intake during the 1st week is usually

important. In more severe cases, negativeve fluid balance is required. Diuretics as furocemide

may be used.

d). Treatment of complications :

1. Severe hypertension (hypertensive crisis) : Na+ nitroprusside infusion (0.5-10

microgram/kg/minute), Labetalol infusion (0.25-3 mg/kg/hour), Esmolol infusion

(150-300 microgram/kg/minute).

2. Heart failure.

3. Renal failure.

Antihypertensives are usually not necessary after the child leaves the hospital, although mild

hypertension may persist for as many as 6 weeks. The medications that can be used span the

entire range of antihypertensives, such as vasodilators (eg, hydralazine), calcium channel-

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blocking agents (eg, long-acting nifedipine, amlodipine), or angiotensin-converting enzyme

(ACE) inhibitors (eg, enalapril).

Carefully monitor blood pressure (BP) for at least 1 week after the drug is discontinued to

ensure that rebound hypertension does not occur.

Long-term follow-up for a patient following acute poststreptococcal glomerulonephritis

(APSGN) primarily consists of blood pressure measurements and urine examinations for

protein and blood.

In general, examinations are performed at 4- to 6-week intervals for the first 6 months and at

3- to 6-month intervals thereafter, until both hematuria and proteinuria have been absent and

the blood pressure has been normal for 1 year. Documenting that the low C3 has returned to

normal after 8-10 weeks may be useful.

Prognosis

Fortunately, most cases of AGN in children are either self-limited or amenable to therapy

although there may be devastating complications of the illness during the acute phase. Less

commonly, what begins as an apparent AGN may presage the development of a chronic

process, which ultimately may progress into irreversible end-stage renal disease (ESRD).

APSGN – excellent prognosis

Complete recovery occurs in > 95% of patients

Decission upon recovery assert after 1-2 years from the onset

5-10% - progressive evolution, persistent

Mortality rate in the acute phase can be avoided by appropriate treatment of acute

renal failure, heart failure, & hypertension.

Infrequently, the acute phase may be severe & may → chronic renal insufficiency.

Recurrences are extremely rare.

NEPHROTIC SYNDROME (NS)

Nephrotic syndrome is primarily a pediatric disorder and is 15 times more common in

children than adults.

Definitions:

Nephrotic syndrome, or nephrosis, is defined by the presence of nephrotic-range proteinuria,

edema, hyperlipidemia, and hypoalbuminemia.

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Nephrotic-range proteinuria in children is defined as protein excretion of more than 40

mg/m2/h or a first-morning urine protein/creatinine of 2-3 mg/mg creatinine or greater and

correlates with results from 24-hour urine collection.

Remission: marked reduction in proteinuria; urinary protein excretion < 4 mg/m2/hour or

urine dipstix nil/trace for 3 consecutive days.

Relapse: recurrence of massive proteinuria; urinary protein excretion > 40 mg/m2/hour or

urine dipstix ++ or more for 3 consecutive days.

Frequent relapses: Two or more relapses within 6 months of initial response or four or more

relapses within any 12 month period.

Steroid dependent NS: Two consecutive relapses occurring during the period of steroid

taper or within 14 days of its cessation.

Steroid sensitive NS: Normalization of proteinuria within 4 weeks after start of standard

initial therapy with daily oral predinisolone (patients who enter remission in response to

corticosteroid treatment alone)

Steroid resistance NS: Failure to achieve remission in spite of 6-8 weeks of standard

corticosteroid treatment.

The annual incidence of NS in most countries is estimated to range from 2-7 new cases per

100.000 children. There is a male preponderance among young children, at a ratio of 2:1 to

females.

Etiology:

Most children (90%) with NS have a form of idiopathic NS. Causes of idiopathic NS include

minimal change disease (85%), mesangial proliferation (5%), and focal segmental

glomerulosclerosis (FSGS) (10%). The remaining 10% of children with NS have secondary

NS related to systemic or glomerular disease such as membranous nephrotahy or

membranoproliferative glomerulonephrities.

Table 3. Causes of nephritic syndrome

Genetic Primary or Idiopathic - no

known aetiology

Secondary

Congenital NS

Infantile NS

Genetic

Minimal change disease

(MCD)

Focal Segmental

• Systemic disease

- Systemic lupus erythematosus

(SLE)

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syndromes

etc

Glomerulosclerosis (FSGS)

Membranous nephropathy

- Henoch-Scholein Purpura (HSP)

- Diabetes mellitus (DM)

• Infections

- Post-infectious GN

- Hepatitis B, C; HIV

- Syphilis, Malaria, Toxoplasmosis

• Drugs: D-penicilamin, gold,

mercury, heroin, nonsteroidal anti-

inflammatory, interferon, ACEIs, etc

• Toxins and allergen food

allergens, bee sting

• Associated with malignant

disease

- lymphoma, leukemia

Minimal Change Nephrotic Syndrome (MCNS)

- also known as: pure NS, lipoid nephrosis

In MCNS (85% of cases of NS in children), the glomeruli appear normal or show a minimal

increase in mesangial cells and matrix. Findings on immunofluorescence microscopy are

typically negative, and electron microscopy simply reveals effacement of the epithelial foot

processes. More than 95% of children with minimal change disease respond to corticosteroid

therapy.

It is called “pure” because are present elements that define the syndrome: proteinuria,

hypoalbuminemia, hyperlipemia, while hematuria, hyperazotemia and hypertension (the 3 H)

are absent (the 3 H are present in “impure” NS form).

Pathophysiology

The hallmark of INS is massive proteinuria, leading to decreased circulating albumin levels.

The initiating event that produces proteinuria remains unknown. However, strong evidence

suggests that INS, at least in part, has an immune pathogenesis.

The glomerular filtration barrier consists of the fenestrated capillary endothelium, the

extracellular basement membrane, and the intercalated podocyte foot processes, connected by

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35-45 nm slit diaphragms. Nephrotic syndrome is associated with the biopsy finding of fusion

(effacement) of podocyte foot processes.

Figure 3. Epithelial cell injury and destruction of the basement membrane as a result of

immune complex in the glomerulus. (Kumar et al. Kidney and Its Collecting System in

Robbins Basic Pathology. 9th edition, Elsevier, 2012)

Normally, the basement cell membrane does not filter large molecules such as albumin

(70,000 kD), which is present in urine if the membrane is damaged.The underlying

abnormality in nephrotic syndrome is an increase in permeability of the glomerular capillary

wall, wich leads to massive proteinuria and hypoalbuminemia.

In MCNS it is possible that T-cell dysfunction leads to alteration of cytokines, which causes a

loss of negatively charged glycoproteins within the glomerular capillary wall.

In its normal state, the glomerular basement membrane is negatively charged because of the

presence of various polyanions along this surface, such as heparan sulfate, chondroitin

sulfate, and sialic acid. This negative charge acts as a deterrent to filtration of negatively

charged proteins, such as albumin. Children with MCNS have been reported to have

decreased anionic charges in the glomerular basement membrane.

In addition to the traditional immunological theories of INS pathogenesis, it has become clear

in recent years that INS is a podocytopathy. Podocytes also possess glucocorticoid receptors,

which can lead to stabilization of the podocyte cytoskeleton and inhibit apoptosis.

Cyclosporine, another important treatment for INS, can act directly on the podocyte by

inhibiting phosphorylation of the podocyte protein synaptopodin, which plays an important

role in the maintenance of the glomerular basement membrane.

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In most instances, massive urinary protein loss leads to hypoalbuminemia, which cause a

decrease in the plasma oncotic pressure and transudation of fluid from the intravascular

compartment to the interstitial space, followed by intravascular volume depletion. The

reduction in intravascular volume decreases renal perfusion pressure, activating the RAAS,

which stimulates tubular reasorbtion of sodium and also stimulates the release of antidiuretic

hormone, which enhance the reasorbtion of watter in collectin duct.

INS is accompanied by disordered lipid metabolism. The traditional explanation for

hyperlipidemia in INS was the increased synthesis of lipoproteins that accompany increased

hepatic albumin synthesis due to hypoalbuminemia. Elevations in triglyceride levels occur

with severe hypoalbuminemia. Low and very low-density lipoproteins are responsible for the

transport of cholesterol and triglycerides. There is also an increase in the hepatic synthesis of

cholesterol.

Clinical manifestation

INS is more common in males than in females (2:1), and most commonly appears between

the ages of 2 and 6 years.

Puffiness around the eyes, characteristically in the morning.

Pitting edema over the legs.

Pitting edema is the presenting symptom in about 95% of children with nephrotic syndrome.

It is typically found in the lower extremities, face and periorbital regions, scrotum or labia,

and abdomen (ascites). Generalized edema throughout the body is known as anasarca.

The onset may be: sudden (more often) or insidious

Other signs and symptoms of nephrotic syndrome may include the following:

Respiratory tract infection - a history of a respiratory tract infection immediately

preceding the onset of nephrotic syndrome is frequent

Anorexia, irritability, abdominal pain, diarrhea- are common

Microscopic hematuria- in 23% of cases

Symptoms of infection - such as fever, lethargy, irritability, or abdominal pain due to

sepsis or peritonitis

Hypotension and signs of shock - can be present in children presenting with sepsis

Hypertension (rare)

Respiratory distress /Dyspnea- due to either massive ascites and thoracic compression or

frank pulmonary edema, effusions, or due to diaphragmatic compression with ascites.

Tachypnea - to compensate for mechanical restriction to breathing

Seizure - due to cerebral thrombosis

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Hepatomegalia, umbilical herina, rectal prolaps

In time the signs of malnutrition will appear

When the following signs appear : hematuria, hypertension, hyperazotemia, we discuss about

nephritis-nephrosis and a kidney biopsy is recommended.

Differential diagnosis:

allergic edema

protein-losing enteropathy (urine and cholesterol - normal)

hepatic failure: chirrosis, hepatitis, etc; jaundice, dilated veins over umbilicus (caput

medusae), encephalopathy, etc, anomalies in the liver function tests

congestiv heart failure: cardiomegalia, murmurs, location and colour of edema

acute or chronic glomerulonephritis (APSGN, Membrano-prolipherative GN)

protein malnutrition

Pure NS/Impure NS

Secondary NS

Laboratory evaluation

The diagnosis of NS is confirmed by the triad of generalized edema, proteinuria, albuminuria

and hypoalbuminemia (serum albumin <2,5g/dl), although hypercholesterolemia is also

commonly present.

In order to establish the presence of nephrotic syndrome, laboratory tests should confirm the

existence of (1) nephrotic-range proteinuria, (2) hypoalbuminemia, and (3) hyperlipidemia.

- hypoproteinemia: < 6g% - ↓ Alb < 2,4g% (n:4g% ); seric protein electrophoresis:

disproteinemia, ↓ Alb and γglobulines; ↑α and β glob.( lipoproteic fractions); a

decreased A/G ratio (a decreased A/G ratio, consider the following: Neoplasm,

infectious disease including AIDS, Intestinal disease, Liver disease, Renal disease,

The cachexic patient, CHF)

- erythrocyte sedimentation rate (ESR) is increased due to increased fibrinogen & other

plasma contents and because of disproteinemia, increased fibrinogen (n: 0,200 -

0,400g%) and no of platelets↑

- lipid profile: hyperlipemia > 1g and hypercholeterolemia > 250mg; specifically elevated

LDL, usually with concomitantly elevated VLDL

- ureea and creatinin may be increased in 1/3 of the cases (transient)

- immunogram: decreased plasmaIgG levels (secondary to urinary loss)

- plasma Ionogram: hypokalemia, Na normal values

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- URINE: froty, sometime opalescent aspect

- Nephrotic range proteinuria; proteinuria is "selective" for albumin (ie, > 85%

albumin)( tested by urine protein electrophoresis)

- Urine sediment examination: granular casts ; Viewed by polarizer, the oval fat bodies

and fatty casts cause a "Maltese cross" appearance

-Other tests: Complete blood count (CBC), Metabolic panel - levels of serum electrolytes,

calcium, phosphorus, and ionized calcium, as well as of blood urea nitrogen (BUN) and

creatinine ; Testing for HIV, hepatitis B and C; Complement studies (C3, C4), Antinuclear

antibody (ANA), anti–double-stranded DNA antibody (in selected patients), genetic tests.

Renal Biopsy

For childhood nephrotic syndrome, a renal biopsy is indicated for the following:

Congenital nephrotic syndrome

Children older than 8 years at onset

Steroid resistance

Frequent relapses or steroid dependency

Significant nephritic manifestations

Positive diagnosis: clinical manifestation and lab test

Complications of INS include:

Edema

Hyperlipidemia-atherosclerosis

Thrombosis- hypercoagulable state due to urinary losses of antithrombin,

thrombocytosis fibrinogen ↑ and number ↑ of platelets (renal vein thrombosis, deep

vein thrombosis, and pulmonary embolism are the most frequently encountered TEC

in children)

Infection (spontaneous bacterial peritonitis- the most coomon; sepsis, cellulitis)

Acute kidney failure (rare) due to hypovolemia

anemia and rickets are associated -↓ transferin and ferritin; and the proteins which

binds Ca (calcium levels should be adjusted based on the albumin level and ionized

calcium levels should be checked)

Hypothyroidism: deficiency of the thyroglobulin transport protein thyroxin due to

decreased thyroid binding globulin.

Proetin malnutrition: this occurs when the amount of protein that is lost in the urine is

greater than that ingested, this leads to a negative nitrogen balance

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Growth retardation: can occur in cases of relapse or resistance to therapy. Causes of

growth retardation are protein deficiency from the loss of protein in urine, anorexia

(reduced protein intake), and steroid therapy (catabolism).

Vitamin D deficiency can occur. Vitamin D binding protein is lost.

Cushing's Syndrome

Medication adverse effects (steroids, diuretics, albumin, steroid-sparing agents).

Treatment

1. Diet and activity

The diet in patients with nephrotic syndrome should provide adequate energy (caloric) intake

and adequate protein (1-2 g/kg/d). A diet with no added salt will help to limit fluid overload.

Fluid restriction per se is not required.

There are no activity restrictions for patients with nephrotic syndrome. Ongoing activity,

rather than bedrest, will reduce the risk of blood clots.

School attendance– as soon as possible, also under corticotherapy or immunosupressors

2. Pathogenic treatment

The management of steroid-sensitive nephrotic syndrome in children aged 1–18 years

according to KDIGO:

Initial treatment: Oral prednisone, starting as a daily dose of 60 mg/m2/day or 2

mg/kg/day (maximum, 60 mg/day) for 4–6 weeks. After 4–6 weeks, switch to 40

mg/m2 or 1.5 mg/kg (maximum, 40 mg) on alternate days for 2–5 months with

tapering, with a minimum total duration of treatment of 12 weeks.

Treatment of infrequent relapse (1 relapse in 6 months or 1–3 relapses in 12 months):

Administer initial treatment dose (60 mg/m2/day or 2 mg/kg/day) until urinary protein

is negative for 3 days. After urine is negative for protein for 3 days, change

prednisone to 40 mg/m2 or 1.5 mg/kg (maximum, 40 mg) on alternate days for 4

weeks, then stop or taper dose.

Treatment of frequent relapse (2 relapses in 6 months or ≥4 relapses in 12 months):

Continue infrequent relapse treatment for 3 months at lowest dose to maintain

remission or use corticosteroid-sparing agents, including alkylating agents,

levamisole, calcineurin inhibitors, mycophenolate mofetil.

immunosuppressive medication, other than steroid and immunomodulators are

indicated in:

o corticoresistant NS

o Side effects to corticosteroid treatment

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o Frequent relapses

3. Simptomatic treatment

- For edema: diuretics are needed. Furosemide (1 mg/kg/d) and spironolactone (2

mg/kg/d) will help when fluid retention is severe, provided no signs of renal failure or

volume contraction are evident.

- achieving a satisfactory diuresis is difficult when the patient's serum albumin level is

less than 1.5 g/dL. Albumin in a dose of 1 g/kg may be given, followed by

intravenous furosemide.

- Hyperlipidemia- lipid-lowering agents: It is administrated for the consequences upon

the cord and vessels(hyperlipemia accelerates the glomerulosclerosis)

- In case of infection: antibiotherapy, and not for rutine

- in preventing thromboembolic complications: An antiplatelet drug (antiaggregant)

- angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor

blockers. These may reduce proteinuria by reducing the systemic blood pressure, by

reducing intraglomerular pressure, and also by direct action on podocytes.

- Supplemental calcium and vitamin D may attenuate bone loss.

- Painful abdominal crisis:

- Corect the hidroelectrolyte imbalances

- Maybe paracentesis

- Severe renal insufficiency - unusual – needs peritoneal dialysis, hemodialysis

Long-term follow-up

Follow-up care in patients with nephrotic syndrome includes immunization, treatment of

relapses of steroid-responsive nephrotic syndromes, monitoring for steroid toxicity, and

monitoring of diuretic and angiotensin antagonist regimens.

Routine immunizations should be delayed until the patient is free of relapses and has been off

immunosuppression for 3-6 months.

Transmissible diseases and vaccins - special problems: *measles or chickenpox – specific

immunoglobulines

*vaccination antipolio and BCG only after remission, imediately after Ø corticotherapy, at 6

months after Ø imunosupressors

Monitoring for steroid toxicity every 3 months in the outpatient clinic is necessary to help

detect adverse effects and to record growth in children.

A yearly checkup is necessary to help detect cataracts.

Prognosis

301

Pediatric nephrotic syndrome is a chronic illness characterized by relapses and remissions,

which can extend throughout childhood.

Evolution is good in those who had a good response to initial corticotherapy (> 90% of the

cases)

The prognosis for patients with minimal-change nephropathy is good.

Most children respond to steroid therapy; still, about 50% of children have 1 or 2 relapses

within 5 years and approximately 20% of them continue to relapse 10 years after diagnosis.

Only 25-30% of children never have a relapse after the initial episode. Approximately 5% of

patients who initially respond to steroids become steroid-resistant.

Recurrences can not be prevented.

In some cases- relapses at > 5 -10 years from the apparent recovery

Fig 4. NS prognosis

302

Fig5. Proposed algorithm for SRNS treatment (expert meeting, Londra 2005)

ACUTE KIDNEY INJURY (AKI)

Acute kidney injury (AKI) (previously called acute renal failure), is defined as an abrupt or

rapid decline in renal filtration function. This condition is usually marked by a rise in serum

creatinine concentration or by azotemia (a rise in blood urea nitrogen [BUN] concentration).

AKI is a clinical and biological syndrome that result to the sudden decrease in renal function,

impaired renal function, ruling out normal clearout substances such as blood urea, creatinine,

potassium, and on the other hand uremia and electrolyte disorders causing numerous

symptoms such as pulmonary edema, hypervolemia, hypertension, heart failure, cardiac

arrhythmias, pericarditis, lethargy, vomiting, seizures, coma, etc..

AKI may be classified into 3 general categories, as follows:

Prerenal - As an adaptive response to severe volume depletion and hypotension, with

structurally intact nephrons

SRNS - FSGS

Gene testing Rule out other undelying diseses leading to FSGS

Positive for mutation in podocin, WT1, CD2AP,

TRPC6,etc

Not done/ not availablenedisponibil /Negative

Careful watching, antiproteinuric treatment

with ACE-inhibitors, angiotensin receptor

blocker

kidney transplantation

Trial with Cyclosporin + concomitant Prednison

for at least 6 monthsNo respons

Respons

Continue cyclosporine as lang-term treatment

(years)

303

Intrinsic - In response to cytotoxic, ischemic, or inflammatory insults to the kidney,

with structural and functional damage (acute tubular necrosis, glomerulonephritis, APSGN,

HUS, renal artery/vein trombosis, drugs, etc)

Postrenal - From obstruction to the passage of urine (ureteric obstruction, urethral

obstruction, etc)

Clinic:

- decrease circulating volume (pallor, pulse, BP, neurological, etc.)

- state of hydration (dehydration, hyperhydration)

- assessment of vital signs (tachypnea, hypo / hypertension, tachycardia)

- neurological assessment – mandatory

- Fever, rash, petechiae, purpura, ecchymosis, abdominal collections, pleural effusion,

pericardial

- lower/upper gastrointestinal bleading

Lab tests

Complete blood count (CBC), peripheral smear,

Serum biochemistries: urea, creatinine, uric acid, ASTRUP, electolytes, blood

glucose, cystatin C, amylase, lipase, creatinine clearance

Urine output, specific gravity, Urine analysis with microscopy, urine sediment, Urine

electrolytes

Immunology: Complement levels, Antinuclear antibody (ANA), Antineutrophil

cytoplasmic antibody (ANCA), Anti-glomerular basement membrane (anti-GBM) antibody,

Hepatitis B and C virus studies, Antistreptolysin (ASO)

Imaging studies: chest x-ray, abdominal ultrasound, nuclear scanning: 99m Tc-

diethylenetriamine penta-acetic acid (99m Tc-DTPA), angiography, NO i.v urography

Diagnosis:

- oliguria (<0.5 ml / kg / hr or 500 ml / 1.73m2/day)

- increased serum creatinine

- decreased creatinine clearance

Complications:

- Common (acute pulmonary edema, congestive heart failure, uremic pericarditis,

hypertension + acute cerebral edema, coma, convulsions, lower/upper gastrointestinal

bleading, polyuria, hyperkalemia, Hypo/ hyper phosphatemia, hypoCalcemia, decompensated

metabolic acidosis, infection, death)

304

- MSOF (respiratory failure, heart failure, liver failure, pancreatitis,uremic pericarditis,

uremic coma)

Treatment:

- the current treatment for AKI is mainly supportive

- Maintenance of volume homeostasis and correction of biochemical abnormalities remain

the primary goals of treatment

-Dietary changes are an important facet of AKI treatment. Restriction of salt and fluid

becomes crucial in the management of oliguric renal failure. K and Ph: restriction or dietary

supplementation and IV replacement

- sometime - renal replacement therapy, dialysis-required in approx 20% of cases of AKI

Prognosis

The prognosis of AKI is highly dependent on the underlying etiology of the AKI.

CHRONIC KIDNEY DISEASE (CKD)

Chronic kidney disease is characterized by an irreversible deterioration of renal function that

gradually progresses to end-stage renal disease (ESRD).

CKD is a clinical syndrome with multiple etiology, with a slow onset; pathophysiology

characterized by the inability of the kidneys to ensure normal function due to organ damage,

bilateral or located at a single kidney in conditions of unique congenital or surgical kidney,

with irreversible changes by death in years.

It is characterized by a decreased glomerular filtration rate (GFR), as defined by a GFR of

less than 75 mL/min per 1.73 m2

Etiology

Obstructive uropathy, Hypoplastic or dysplastic kidneys, Reflux nephropathy

Focal segmental glomerulosclerosis as a variant of childhood nephritic syndrome

Polycystic kidney disease,

Secondary GN,

Vascular nephropaties (HUS, HBP, DM, renal vein trombosis, etc)

The frequency of chronic kidney disease increases with age and is much more common in

adults than children. Among children, chronic kidney disease is more common in children

older than 6 years than in those younger than 6 years.

Once chronic kidney disease (CKD) occurs, progression to end-stage renal disease (ESRD)

appears certain.

305

Children with chronic kidney disease and their families should receive education about the

importance of compliance with secondary preventative measures, natural disease progression,

prescribed medications (highlighting their potential benefits and adverse effects), diet, and

types of long-term renal replacement modalities.

Clinical manifestation

Unexplained anemia or short stature is sometimes the only presentation in a child with

chronic kidney disease (CKD). A high index of suspicion is required for early diagnosis.

Chronic kidney disease (CKD) is asymptomatic in its earliest stages (stage I and stage II),

although urinalysis findings or blood pressure may be abnormal. As chronic kidney disease

progresses to more advanced stages, signs and symptoms greatly increase. Signs of acute

disease may appear in the context of intercurrent infections or acute dehydration syndrome .

1. Growth failure: occurs in 50 % of cases of CKD and is particularly serious if renal failure

is installed before the age of 2 years.

2 . Chronic anemia. Anemia that not respond to treatment with preparations containing iron

may indicate a chronic anemia

.Urinary : polyuria / polydipsia , oliguria / anuria , enuresis, UTI, stones

Gastroenterology- nausea, vomiting , stomatitis , gingivitis , gastritis,

colitis, anorexia: uremia , pancreatic insufficiency, pain , hepatitis B , C

Respiratory system : uremic lung, acute lung disease, pleural efusions

Cardio-vascular: hypertension, infectious and / or uremic pericarditis, uremic /

metabolic cardiomyopathy, cardiac arrhythmias, heart failure,LVH, APE,

atherosclerosis

Neurological: poor school performance, unexplained headache, uremic

encephalopathy , somnolence, dizziness, seizure, uremic coma, ACE, ICH, stroke,

hypertensive encephalopathy

Hematologic: normochromic - normocytic anemia , thrombocytopenia /

thrombasthenia ,

moderate leukocytosis, etc

Neuropathy : asterixis, paresthesia, restless legs, muscle syndrome, carpal Tunnel

Metabolic: fluid overload / dehydration, malnutrition, hyperlipoproteinemia ,

carbohydrates intolerance, hypothermia

Other events: endocrine, dermatological, ocular, musclular.

306

Clinical and biological assessment:

BP measurement- use an appropriate cuff for (age, arm size)

Biochemical: complete blood cell (CBC) , urea, serum creatinine, serum sodium,

potassium, calcium, phosphorus, bicarbonate, alkaline phosphatase, parathyroid hormone

(PTH), and cholesterol and fractionated lipid levels, renal osteodystrophia -

hyperparathyroidism (Ca, P, Ca x P, hypocalcemia, PTH ↑, ↑ APh), endocrine

dysfunction,etc

Urine: specific gravity (urine-concentrating capacity). Urine microscopy (red blood

cells (RBCs), white blood cells (WBCs), and casts), proteinuria and albuminuria analysis,

cystatin C- the plasma cystatin C concentration may correlate more closely with the GFR

than with the PCr, urinary electolytes

Imaging studies such as ultrasonography and radionuclide studie, x-ray (bone,

heart,lung), i.v.Urography /VCUG, renal tomography

kidney biopsy

Diagnosis based on plasma creatinine concentration (PCr), proteinuria, blood pressure, GFR,

urinary sediment, renal ultrasound

Differential Diagnoses

Acute Renal Failure

Chronic Glomerulonephritis

Diabetic Nephropathy

Nephrosclerosis

Rapidly Progressive Glomerulonephritis

Treatment of chronic kidney disease should include the following:

Specific therapy based on diagnosis

Evaluation and management of reversible causes of renal dysfunction

Prevention and treatment of complications of decreased kidney function (eg, anemia,

bone disease, cardiovascular manifestations, hypertension, growth failure)

Evaluation and management of comorbid conditions

Slowing the loss of kidney function

Preparation for kidney failure therapy

Replacement of kidney function with dialysis and transplantation if signs and

symptoms of uremia are present

Management of complications

307

Prognosis

About 70% of children with chronic kidney disease develop ESRD by age 20 years.

Children with ESRD have a 10-year survival rate of about 80% and an age-specific mortality

rate of about 30 times that seen in children without ESRD.

The most common cause of death in these children is cardiovascular disease, followed by

infection.

References:

2. Bălgrădean Mihaela. Rinichiul în patologia copilului. Vol 1. Ed Universitară Carol davila, București 2011

3. Coman I., Stanca DV., Miu N., Bizo A. Infecțiile de tract urinar la copil. Abordare nefro-urologică. Ed

Medicală Universitară Iuliu Hațieganu Cluj-Napoca 2003

4. Elie V, Fakhoury M, Deschênes G, Jacqz-Aigrain E. Physiopathology of idiopathic nephrotic syndrome:

lessons from glucocorticoids and epigenetic perspectives. Pediatr Nephrol. Aug 2012; 27(8):1249-56.

5. Gbadegesin R, Smoyer W.E. Nephrotic syndrome in Comprehensive Pediatric Nephrology, Ed Mosby

Elsevier 2008, 205-218

6. KDIGO CLINICAL PRACTICE GUIDELINE FOR GLOMERULONEPHRITIS 2011

7. Lombel RM, Gipson DS, Hodson EM. Treatment of steroid-sensitive nephrotic syndrome: new guidelines

from KDIGO. Pediatr Nephrol. Mar 2013; 28(3):415-26

8. Man Sorin C, Nanulescu Mircea V. Pediatrie Practică, Risoprint Cluj-Napoca, 2006, 311-316

9. Nanulescu Mircea. Aparatul reno-urinar în Protocoale de diagnostic și tratament în pediatrie. Ed medicală

Amaltea 2012, 108-119

10. Davis ID, Avner ED. Nephrology In Nelson. Textbook of pediatrics. Ed Saunders Elsevier, 18th edition

2007, 2163-2219

11. Niuadet Patrick. Nephritic syndrome in Comprehensive Pediatric Nephrology, Ed Mosby Elsevier 2008,

195-204

12. Schrier RW, Wang W, Poole B, Mitra A. Acute renal failure: definitions, diagnosis, pathogenesis, and

therapy. J Clin Invest. Jul 2004; 114(1):5-14.

13. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and

Management.Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the

Initial UTI in Febrile Infants and Children 2 to 24 Months. Pediatrics Vol. 128 No. 3 September 1, 2011 pp.

595 -610 (doi: 10.1542/peds.2011-1330)

14. Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria.

N Engl J Med. Mar 30 2006; 354(13):1387-401.

15. Welch Thomas R. An Approach to the Child with Acute Glomerulonephritis. International Journal of

Pediatrics Volume 2012, Article ID 426192, 3 pages, doi:10.1155/2012/426192

16. White Brett. Diagnosis and Treatment of Urinary Tract Infections in Children.Am Fam Physician. 2011

Feb;83(4):409-415.

308

CHAPTER VIII – CENTRAL NERVOUS SYSTEM DISEASES

Conf. Univ. Dr. Mărginean Oana, Asist. Univ. Dr. Grama Alina

MENINGITIS

Definition: Meningitis is an inflammatory disease of the protective membrane that covers the

brain and spinal cord, known collectively as the meninges. The inflammation can be caused

by infection with viruses, bacteria or other microorganisms, and less commonly by non-

infectious agents. Meningitis can be life-threatening because of the proximity of the

inflammation to the brain and spinal cord; therefore, the condition is classified as a medical

emergency.

Meningean syndrome = all clinical manifestations due to meninges damage.

The etiology varies according to age:

Age Etiology of bacterial meningitis

0-1 month Streptococcus agalactiae (streptococul betahemolitic group B)

Escherichia coli

Other Enterobacteriaceae

Listeria monocytogenes

1-3 months Streptococcus agalactiae

Streptococcus pneumoniae

Haemophilus influenzae

Listeria monocytogenes

3months-5 years Haemophilus influenzae

Neisseria meningitidis

Streptococcus pneumoniae

> 5years Streptococcus pneumoniae

Neisseria meningitidis

Staphylococus aureus

Streptococi

Haemophilus influenzae (rarely)

309

Other causative pathogenic agents (chlamydia, mycoplasmas, protozoa, fungi) occur

especially in patients with a history of compromised biological background, with poor

immunological mechanisms.

Contributing factors :

- anatomical abnormalities and surgical procedures (post-neurosurgery)

- inflammatory diseases of the cephalic extremity (mastoiditis, pansinusitis)

- endocranial lesions with CSF circulation disorders (brain abscess, subdural empyema,

hydrocephalus)

- neurological trauma and skull base fracture

- various immunodeficiency syndromes (asplenia, hypogammaglobulinemia,

myeloproliferative diseases, immunosuppressive, rheumatic diseases)

Physiopathology :

Microorganisms can reach the central nervous system in three ways:

- through the bloodstream - from a primary infection outbreak

- contiguous from a parameningian infectious outbreak (sinus, otic, dental)

- direct sowing of CSF by cranio-cerebral injury and rarely iatrogenic.

In newborns, the infection occurs due to "harvesting" the germ from the mother during birth.

In infants, who are susceptible to infection with Gram-negative enteric bacteria, the large

intestine is the pathogen source. Colonization of the nasopharynx is the starting point for

meningitis in older children. In meningitis pathogeny, increased intracranial pressure,

cerebral edema, and increased volume of CSF occur:

Diagnosis algorithm:

A. History :

Prodromal signs, changing the general condition, headache, nausea, vomiting, agitation,

seizures, and fever are crucial signs. In newborns, attention may be drawn by an abnormal

sleepiness or irritability, shrill screams, toxic state.

B. Clinical evaluation :

The clinical features of bacterial meningitis vary with age, etiology, predisposing factors,

disease duration prior to making clinical examinations and individual response to infection.

(table XX)

Table XX Clinical features of bacterial meningitis

Age Symptoms and signs Bear in mind

310

newborn Malaise

Apnea, respiratory distress

Hypotonia, short scream

Vomiting, diarrhea, jaundice, flatulence

Hypothermia / hyperthermia

Shock

Petechiae, purpura, pustules

Anterior fontanelle sometimes bulges -

usually late sign

Rarely present, even if the

infection is severe:

Neck stiffness

Kernig sign

Brudzinski sign

infant, child Symptoms of meningeal irritation :

- Neck stiffness

- Kernig sign (when bending the trunk,

bends the knees)

- Brudzinski sign (when bending the

head bends the knees)

Fever

Seizures (more common in infants,

usually generalized)

Cutaneous hyperesthesia, reducing

ROT, paresis / paralysis

Increased intracranial pressure :

bulging fontanelle, bradycardia,

headache, vomiting, photophobia

Encephalitic symptoms: drowsiness,

agitation, coma (meningoencephalitis)

Manifestations from other organs :

diarrhea, purpura, etc.

Signs and symptoms of

meningitis under 18 months

are not specific despite the

disease severity!!!

In older children, the

symptoms are clearer from

the onset: symptoms of

meningean irritation,

headache, photophobia,

vomiting, "gun cock"

position

C. Paraclinical examinations

1. Confirmation of the diagnosis of meningitis is based on CSF examination (table...), for

which lumbar puncture should be performed in all patients who are suspected of meningitis;

it is contraindicated in certain situations (table. Xx)

311

a. Gram staining is a simple and rapid diagnosis method of bacterial meningitis. Although it

has an 80% sensitivity, its advantage is the rapid performance.

b. Other tests of CSF that can make the difference between a viral and a bacterial

meningitis, include determination of endotoxin, C-reactive protein, fibronectin, and

lactate concentration. Tests for the determination of antigens are expensive and are not

routinely used.

312

Table...Interpretation of CSF results in meningitis (infants and children)

Normal Bacterial Viral TuberculosisBacterial partially

treated

Macroscopic Clear Turbid Opalescent/clear Clear Variable

Cytorahia

(cells/mm3)≤ 5

100-60000

(usually >1000)

10-1000

(usually < 300)

< 1000

(usually 50-100)

1-10000

(usually 200-5000)

Predominant

Cells

Mononuclear

(≤1PMN/mm3)PMN >50%

Initially PMN, then

mononuclearInitially PMN, then lymphocytes

PMN or

mononuclear

Proteinorahia

(mg/dl)< 40

↑↑

(usually 100-500)

N/↑

(usually 40-200)

↑↑

(usually 100-500)

↑

(usually >100)

Glycorahia

(% of Glycemia)> 60 ↓ N ↓/N ↓/N

Gram Smear Negative Usually positive NegativeNegative (Ziehl-Nielsen smear can

be positive)Can be negative

Bacterial

culturesSterile Usually positive Sterile

Sterile (M.tuberculosis cultures

can be positive)Can be sterile

* in newborns normal values are: cytorahia ≤ 30; predominant cells ≤ 40% PMN; proteinorahia < 170; glycorahia > 50

313

314

Table XX Indications and contraindications of lumbar puncture

Indications :

Bacteremia in newborns

Septicemia (especially in infants)

Seizures associated with fever and age <18 months

Complex febrile seizures

Children with fever associated with lethargy, hypotonia, irritability, decreased

appetite, vomiting, shock, dehydration, without satisfactory explanation

Classic manifestations of meningitis: fever, headache, stiff neck

Coma or neurological changes without explanation

Skin lesions of meningococcemia

Facial cellulitis in small children or cellulitis regardless of location in infants

Absolute contraindications

Poor cardiorespiratory status

Significant intracranial hypertension

Brain abscess, subdural empyema

Relative contraindications

Severe coagulopathy

Thrombocytopenia (<50.000/mm3)

Malformation of the lumbar spine or spinal cord

Skin infection at the puncture site

2. Other examinations :

- Blood count, differential leucocyte count, platelet

- ESR, PCR

- Ionogram (Na, K, Ca, Ph)

- Urea, creatinine

- Transaminases

- Exploration of hemostasis: APTT, Quick time, degradation of fibrinogen / fibrin

- Determination of blood gases (acid-base balance)

- Fasting plasma glucose (FPG) important compared to glicorahia

- Serum protein electrophoresis, immunogram

- Urine examination

315

- Cultures of blood, urine, stool, purpuric lesions, abscesses, secretory otitis, pharynx

- Eye fundus, sinus Rx, mastoids, lung Rx

- transfontanellar ultrasound in infants

- EEG shows diffuse involvement of the brain, but it does not help in locating the cause of

injury

- CT or MRI are indicated to diagnose the cause of outbreak signs

- interdisciplinary consultation - neurology, infectious diseases

Differential diagnosis:

1. Meningism – there are signs of meningeal irritation (neck stiffness frequently) and

increased CSF pressure, but no other changes in CSF appear; in infections located outside the

CNS infections (flu, pneumonia, scarlet fever, dysentery) and subarachnoid hemorrhage

2. Meningeal reaction - where there is a meningeal clinical syndrome and mild changes

in CSF: increased cytology (40-50 elem/mm3), slight increase in the CSF albumins, the

presence of red blood cells; no germs of the disease in the CSF, element of differential

diagnosis with a real meningitis.

3. Other causes of neck stiffness:

Cervical lymphadenitis

Retrofaringean abscess

Intracranial hemorrhage or tumor

Cervical Trauma

Juvenile Idiopathic Arthritis

Spinal Abnormalities

Torticolis

Tetanus

4. Other causes of headache and vomiting: sunstroke

5. Medulloblastoma and leukemic infiltration, where glycorahia is low

Treatment :

I. Hygienic-dietary and electrolytic treatment :

Food po if the sensors are clear; absolute digestive rest if the patient vomits, has seizures

or altered sensors (risk of aspiration);

In case of dehydration, deficit recovery will be made with isotonic fluids; for maintenance

needs, hypotonic fluids are administered evenly over 24 hours (1500ml/m2/day);

316

in case of sepsis, Waterhouse-Friederichson syndrome - dehydration and shock treatment

is installed, with volume-expanders (crystalloid / colloid), if necessary with hemodynamic

monitoring.

II. Antibiotic treatment: empirical treatment of meningitis must take into account the most

common etiology for age and possible resistance to the incriminated microorganism

Table XX Types of recommended antibiotic therapy for bacterial meningitis

Type of bacteria Antibiotic to be chosenDuration of

treatment

Gram colouring

Coci

Gram positive

Gram negative

Vancomicin + CFS large spectrum

(cefotaxime/ceftriaxone)

Penicilin G

Bacili

Gram positive

Gram negative

Ampicilin + AMG (Gentamicin)

CFS large spectrum

On cultures

S. pneumoniaePenicilin G or Vancomicina, Meropenem

+ CFS large spectrum (ceftriaxone)10-14 days

Streptococ agalactiaePenicilin G + Gentamicin

or Ampicilina + Gentamicin

14-21 days (in

newborns)

H. influenzae Ceftriaxone/ Cefotaxime 10-14 days

N. meningitidis Penicilin G 7-10 days

L. monocytogenes Ampicilin + Gentamicin 14-21 days

EnterobacteriaceaeCFS large spectrum (cefotaxime/

ceftriaxone) + Gentamicin21 days

Pseudomonas aeruginosa,

AcinetobacterCeftazidime + AMG (Gentamicin) 21 days

!!! Treatment duration should be individualized according to the clinical and microbiological

response

317

Table ... Antibiotic posology in bacterial meningitis*

Antibiotic Newborn Infants and children

0-7 days 8-28 days

Ampicilin 100-150 (3) 150-200 (4) 200-300 (4)

Cefotaxim 100-150 (2) 150-200 (3-4) 200 (4)

Ceftriaxon Is avoided Is avoided 80-100 (2)

Ceftazidim 60 (2) 90 (3) 125-150 (3)

Gentamicin 5 (2) 7,5 (3) 7,5 (3)

Amikacin 15-20 (2) 20-30 (3) 20-30 (3)

Penicilin G 150 000 UI (3) 200 000 UI (4) 300 000 UI (4-6)

Vancomicin** 20-30 (2-3) 30-40 (3) 40 (4)

Meropenem 60-120 (3)

*the dose is expressed in mg/kb/day, and for Penicilin G in UI/kg/day (the no of doses/day in

brackets) **administered in 1 hour EVP

III. Treatment of complications and neurologic manifestations :

Medical treatment of intracranial hypertension :

- hyperventilation - effects of cerebral vasoconstriction cuased by hypocapnia lead to

decreased cerebral blood flow and intracranial hypertension decrease

- hypertonic solution (Mannitol) is usually effective in reducing intracranial

hypertension

- Treatment of seizures :

- Diazepam 0.2 to 05 mg / kg / dose intravenously which can be repeated every 15

minutes

- Phenobarbital 15-20 mg / kg / dose ± endotracheal intubation

- metabolic imbalances should be found and treated!

IV. Dexametazone

• absolute indication in H. influenzae meningitis, is adminstered in a dose of 0.15 mg /

kg body / dose iv every 6 hours for 4 days

• relative indication in children over 6 weeks with meningococcal or pneumococcal

bacterial meningitis

V. Imunotherapy : in some forms of meningitis (Streptococcus agalactiae in neonates) iv

immunoglobulin can be administered

VI. Monitorization :

318

A. Acute phase:

1. Vital Signs: heart rate, respiratory frequency, blood pressure, hydration status, weight

2. Neurological signs: pupillary reflexes, sensors, muscle strength, cranial nerves, cranial

perimeter measurement (infants 1x/day) every 4 h during the first 72 hours, afterwards

1x/day

3. Laboratory: Hb, leukocytes, platelets, serum ionogram, fibrinogen, APTT, Quick T,

creatinine, urine summary

4. lumbar puncture

- Indications of repetition: in newborns with no response or poor response after 48-72

hours of treatment

- CSF signs of improvement: emergence of mononuclei, glycorahia growth, Gram

smear shows no germs, sterile culture

B. Afterwards :

1. audiological evaluation 1 month after discharge

2. psychological assessment

3. neurologic rating

VII. Prophylaxy :

Chemical prophylaxy

of contactsInclusion criteria Regimen

Hemofilus influenzae

- Family members (if there is

at least one child < 4 years

in the family)

- groups (nursery,

kindergarten)

- supervising personnel (if in

the community ≥ 2 cases

occurred within 2 months)

Rifampicina po : 20

mg/kg/day (max 600

mg/day), in single dose

4 days

Neiseria meningitidis

- Family members

- Contacts in groups

- Persons who come into

contact with oral secretions

of the case

Rifampicina po : 20

mg/kg/day (max 600

mg/day), in 2 doses, 2 days

or

Ceftriaxon im :

125 mg in children < 12

319

years

250 mg in children > 12

years, adults, single dose

Complications :

A. Acute

1. Neurologic

- Convulsions - Paralysis of cranial nerves

- Cerebral hernia - Loculation of the meningeal suppurative process

- Subdural empyema - Subdural effusion (up to 50%)

- Cerebral abscess - Cortical vein or cortical venous sinuses thrombosis

- SIADH (syndrom of inappropriate antidiuretic hormone secretion)

2. Systemic

Apnea • Disseminated Intravascular Coagulation

Toxi-infectious shock • Hypoglycemia

Pneumonia, endocarditis, pericarditis, septic arthritis

B. Chronic (seqelae)

1. Mental retardation

2. Convulsion

3. Delayed speech

4. Hearing loss

5. Visual disturbances

6. Behavioral disorders

7. Motor deficits

8. Hydrocephalus

9. Central diabetes insipidus

Prognosis – The reserved prognosis factors:

- age < 6 months - poor nutritional status

- late sterilization of CSF - over 106 bacterial colonies / ml CSF

- glycorahia < 20 mg/dl - coma

- SIADH - signs of outbreak on hospital admission

- delayed / inadequate antibiotic therapy - cerebral infarction

- toxic and septic shock - disseminated intravascular coagulation

- E. coli or Pseudomonas aeruginosa meningitis

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- recurrent seizures lasting > 4 days after therapy initiation

ACUTE ENCEPHALITIS

Definition: Encephalitis is an acute inflammation of the CNS caused by multiple etiological

agents, (particularly viruses) and different pathogenic mechanisms, characterized clinically

by an infectious syndrome associated with neuropsychic pain, sometimes with self-limited

evolution, but generally unpredictable.

Etiology:

1. Viral encephalitis - are the most common and important encephalitises:

a) Primary: with identified virus (arboviruses, rubella virus, influenza and parainfluenza,

mumps v., rabies v.) or unidentified virus;

b) Secondary:

- to general viral diseases (measles, influenza, chickenpox, infectious mononucleosis,

adenoviruses)

- post-vaccination (BCG vaccination, measles, polio, smallpox)

2. Non-viral encephalitis caused by rickettsiae, Mycoplasma pneumoniae, bacteria: TB,

spirochete: syphilis, listeriasis, protosoa: Toxoplasma gondii, fungi, echinococcosis,

cysticercosis

Positive diagnosis :

1. History - plays an important role in specifying encephalitis diagnosis and frequently it

can orient towards its etiology.

a. Presence of acute viral infections like: measles, rubella, varicella or anti-rabies, anti-

measles vaccination in the recent history can guide to the diagnosis of postinfection

encephalitis;

b. The presence of other cases of encephalitis with epidemic aspect in the patient’s region

has special value for primitive viral encephalitis.

2. Clinical features :

• The incubation period ranges ≤ 7 days up to 2-3 weeks

• usually sudden onset with high fever, impaired general condition, headache, chills,

nausea; in infants: unexplained crying, colicky abdominal pain, vomiting

• There are signs of general infection

• Further disease progresses with intense headache, irritability, anorexia, vomiting,

indicating cerebral edema

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• Signs of encephalus impairment: mental disorders - obnubilation, disorientation,

slurred speech, hallucinations, encephalitic cry, psychomotor agitation or drowsiness,

coma of varying degrees

• Signs cerebral trunk impairment: cranial nerve palsies, hemiplegia, bulbar paralytic

syndromes with swallowing and respiratory disorders

• Meningeal signs: positive Babinski sign, neck stiffness, changes in tendon reflexes

• Characteristic: Very short intervals variability of symptoms and progressive

enlargement of cerebral edema with impaired brain functions in different areas

3. Paraclinical examinations

Haematological exploration does not bring useful information, blood count is usually

normal, and acute phase reactants are missing

Eye fundus examination to exclude intracranial hypertension syndrome

Lumbar puncture with CSF examination

- clear CSF, hypertensive

- slightly elevated albuminorahia and glycorahia

- tens-hundreds of elements/mm3 pleocytosis (with predominance of lymphocytes)

- bacteriological examination for possible bacterial etiology

- tissue culture seeding for a possible viral etiology (expensive)

- serological determinations for early identification of viral and bacterial antigens

(by immunofluorescence), as well as dosage of specific Atb.

- viral cultures of CSF, throat swab, stool, and research specific Atb. such as IgM in

the blood and CSF

- EEG, transfontanelar Eco, cranial CT

Differential diagnosis :

- metabolic encephalopathies: hypoglycemic, uremic, hepatic; those of inborn

errors of carbohydrates or proteins metabolism

- toxic encephalopathies: from drug intoxication, ethanol, insecticides, Reye sdr

- subarahnoidine hemorrhages caused by arteriovenous malformation of the brain

or brain aneurysms

- intracranial expansive processes: tumors, abscesses

- status epilepticus, heatstroke

- neuro-psychiatric diseases: hysteria, schizophrenia

- general infectious diseases of various etiologies

322

- bacterial cerebral embolism, secondary to subacute endocarditis

Treatment : intensive, precocious

A. General measures :

• bed rest, hospitalization

• hygiene of the skin and mucous membranes, latch position, suctioning of

tracheobronchial secretions, ensurance of bowel and urine output, permanent

surveillance

• ensurance of sufficient intake of calories and protein, hydration and feeding (by

parenteral or nasogastric tube)

B. Etyologic treatment :

• Acyclovir - herpetic virus, gancyclovir – cytomegalovirus, interferon and

izoprinozina

• specific human IgG (anti-measles, antiherpetic, antiurlian, anti varicella- Zoster)

• gamma globulin intravenously

• Encephalitis of non-viral etiology benefit from chemotherapy and antibiotics

according to the sensitivity of the causative germ

C. Pathogenic treatment : is crucial due to the lack of etiologic treatment

• corticotherapy is applied early: hydrocortisone hemisuccinate 10-20 mg / kb / day iv

2-3 days, continued with Prednisone 1-2 mg / kg / day po for 1-2 months, depending

on the clinical evolution

• to reduce cerebral edema, hypertonic solutions: Mannitol 20% 1,5-2 g / kg / day in

endovenous perfusion repeated every 4-6 hours, 33% hypertonic glucose, furosemide

1-3 mg / kg / day iv or i.m.

• patient sedation with Phenobarbital 5-8 mg / kg / day po or i.m. in 3-4 doses, with or

without Diazepam 0.3 mg / kg / dose for convulsion cropping

• hydro-electrolitic and acid-base balancing

• decompressive lumbar puncture in cases of convulsions or marked agitation

• vitamin therapy and neurotrophic medication: Vitamin C, B1, B2, B6, B12, Piracetam

• antibiotics (Meropenem, Imipenem, CFS Generation III) are indicated if bacterial

superinfection occurred or there is a high risk of superinfection (profound/prolongued

coma, assisted ventilation).

Complications :

323

- neuro-psychological and varied motor sequelae (motor incoordination, convulsion

syndrome, sensory deficits, behavioral disorders, spastic paralysis, hydrocephalus,

mental retardation, loss of motor acquisition, deterioration of school performance)

- cardiovascular, lung, liver, eyes, etc.

Prophylaxy :

- Combating arthropods-bearing and other main vectors (mosquitoes, ticks)

- Vaccination of high risk population

- Early diagnosis and appropriate and rapid treatment of such infection.

Bibliography :

1. Baghiu Maria Despina – Caiete de Semiologie Pediatrică, Ed. University Press, Târgu-Mureș, 2012, p. 53-

56

2. Iagăru Rozina, Ceaușu E. – Boli infecțioase bacteriene și virale la copil în Ciofu E., Ciofu Carmen –

Pediatria Tratat, Ed. Medicală, Bucureşti, 2001, p. 1492-1502, 1542-1547

3. Lazăr C. – Sindromul de hipertensiune intracraniană în Nanulescu M. - Protocoale de diagnostic și

tratament în pediatrie, Ed. Medicală Amaltea, București, 2013, p. 271-276

4. Man Sorin C., Nanulescu Mircea V. – Pediatrie practică, Ed. Risoprint, Cluj-Napoca, 2006, p. 577-589

5. Muntean I. – Vademecum de Pediatrie, Ed. Medicală, București, 2007, p. 442-447

6. Popescu V. – Algoritm diagnostic și terapeutic în pediatrie, vol I, Ed. Medicală Amaltea, București, 1999,

p. 485

7. Popescu V. – Algoritm diagnostic și terapeutic în pediatrie, vol II, Ed. Medicală Amaltea, București,

1999, p. 372-378

8. Prober G. Charles - Central Nervous System Infections în Kliegman R.M., Behrman R.E., Jenson H.B. et

al (eds) - Nelson Textbook of Pediatrics, 18 th edition, Saunders Elsevier, Philadelphia, 2007, p. 2513-2523

SEIZURES

SEIZURES (PAROXISTIC DISORDERS)

Definition: seizures are a series of involuntary, tonic, clonic, tonico-clonic muscle

contractions, partial or generalized, with or without loss of consciousness, representing a

symptom and NOT a disease.

Classification

- non epileptic = the normal brain reaction to noxes; they disappear when the cause is

removed

- epileptic = pathologic cerebral reactivity through neural epileptogenic lesions, having

a recurrent character

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Etiological classification

1. Acute seizures (non recurrent, non epileptic, occasional)

a) febrile

b) metabolic - hCa, hNa, hMg, HNa, hG, hCu

c) neuroinfections - meningitis, encephalitis, abscess, malaria, typhoid fever, cavernous

sinus, thrombophlebitis

d) cerebral hemorrhage - obstetrical trauma, hemorrhagic disease of newborns,

aneurysms, subdural hematoma

e) toxic - drugs, tetanus, Shigella, Salmonella

f) brain tumors

g) anoxia

h) acute cerebral edema

i) Various - porphyria, SLE

2.Chronic seizures (recurrent, epileptic)

a) Idiopathic epilepsy (primary, cryptogenic, genuine)

- Hereditary

- Acquired

b) organic epilepsy (secondary, symptomatic)

- Posttraumatic (brain tissue rupture)

- Posthaemorrhagic (intra-postnatal, haemorrhagic disease)

- Postanoxic (severe neonatal asphyxia)

- Postinfectious (meningitis, encephalitis, abscess, thrombophlebitis)

- Postintoxication (nuclear jaundice, Pb, As)

- Degenerative (idiopathic atrophy, encephalitis)

- Congenital (cerebral aplasia, porencephaly, holoprosencephaly)

- Parasitosis (cysticercosis, toxoplasmosis)

- Post-hypoglycemia sequelae

c) Sensory epilepsy

- reading, light, music, sound

- touching

- sensorially self-induced

Positive diagnosis

History

325

- infection, trauma, poisoning, anticonvulsive medication (inadequate dosage, lack of

treatment)

- History, pregnancy, birth, perinatal period

Physical examination

- fever

- dysmorphia, microcephaly/ macrocrania, hypo-/hypertelorism

- fontanelle, noise at cranial percussion, hemangiomas

- depigmented areas, stains, hematoma

- nervous - meningeal irritation, motor disorders

Paraclinical

a. blood pressure

b. Lumbar puncture and CSF examination – mandatory under the age of 2 years

c. Eye fundus examination- hemorrhage, chorioretinitis, choroidal tubercles, retinitis

pigmentosa, macular cherry spot, angioma, papilloedema

d. cranial radiography - fractures, ICH signs

e. EEG (electroencephalogram) - 8-10 days postcritic

f. Biological - Ca, Ph, alkaline phosphatase, Mg, Glucose, ionogram, Astrup, urea,

enzymes, hemoculture, karyotype

g. Computer tomography - brain tumors, structural abnormalities, cerebral edema,

hemorrhage

Differential diagnosis

1. Syncope - at pain, the sight of blood

2. Sobbing spasm - 6-18 months, neurotic constitution - excessive anxiety of the mother

or of the family environment

3. Narcolepsy - sudden episodic fall in sleep

4. Bouts of vertigo - 1 ½ - 2 ½ years – sudden stop from work

5. Spasm mutans - 4-12 months - head shaking in neglected infants

6. Sleep disorders

7. Paroxistic visceral manifestations

8. Nocturnal ambulatory automatism – Sleepwalking

9. night pavor - crying / screaming in deep sleep with vegetative reactions: tachycardia,

tachypnea, mydriasis, cold sweat; reactive perturbations within the instinctual

reactive and vegetative sphere

10. Nocturnal verbal automatism – somnilocvia

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11. Masticatory automatisms – bruxism

12. Paroxistic visceral manifestations

13. Abdominal epileptic seizures: hyperreactivity + neurovegetative dystonia

14. recurrent idiopathic ketosis

15. Bouts of headache

FEVERISH SEIZURES (FS)

• Convulsive syndrome: characterized by paroxysmal seizures of central origin, translated

by seizures triggered by disordered sudden and violent activity of brain neurons.

• Febrile seizures (hyperpiretic) – convulsive episodes during a febrile extracerebral

illness in a child <5 years, previously normal neurologically and who had not had

convulsions, and if he had, these have always occurred because of high temperature.

Etiology

– Without an identifiable cause - occurs in 4% of children

Heredity - "threshold", a predisposition to febrile seizures, however ,> 30% of children with

FS have at least one relative with seizures

Fever - > 38 C is considered to act as a natural contaminant on the CNS

Age (3 months / 6 years) - mostly under 3 years

Infections - FS are more freq. in ear, urinary and respiratory infections,

Pathogenesis

• by anoxia and

• decreased intake of glucose in the CNS

=> convulsive seizure = response of a normal brain to cerebral aggression

Clinical description - overlaid the epileptic description

• Typical forms (simple feverish seizures)

- A feverish child loses consciousness

- a generalized tonic contracture occurs

- overlapping clones

- gradually decrease in number

- crisis ends with a new contracture

- a position of muscle resolution (relaxation) follows, then sleep

- duration less than 20 minutes, usually shorter

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- changes occur in crisis: ↑ pulse, ↑ BP, mydriasis, glandular hypersecretion (sweating,

salivation), skin redness, cyanosis (hypoxia and ↓ venous return)

- in some cases - the emission of urine and faeces

- post-crisis - more sleepy, lower motility and tone

• Atypical forms (complex seizures):

- various aspects: tonic seizures

- unilateral hypotonic crises

- crisis longer than 20 minutes

- partial

- always with worse prognosis than typical forms

Laboratory

Lumbar puncture (LP)- normal CSF

- LP is mandatory for depletoric effect, diagnosis and it is not dangerous

• EEG post - critical (after 10 - 14 days)

- no paroxysmal abnormalities

- similar aspect in crisis to the epilepsy

- the peak wave abnormalities places convulsions in the category of complex seizures

Main diagnosis criteria for feverish seizures:

- occur in connection with ↑ temperature> 38 C

- fever is not related to an acute disease of the CNS (meningitis, encephalitis)

- the child does not have a history of neurological disorders (pre-, peri-, postnatal)

Secondary criteria for feverish seizures:

- crisis lasts < 20 minutes

- does not realize the state of convulsive malaise

- clinically: widespread crisis

- age of onset of the first FS - under 3 years

- EEG reveals no pathological abnormalities at 10-14 days after the crisis

Dfferential diagnosis :

- epileptic seizures, other convulsions

- meningitis, encephalitis

- hypocalcemic seizures, hypoglycemia, dehydration (hypo-Na), intoxications

(organophosphorus)

Treatment

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I. Crisis treatment: - common to all seizures

General measures: silence, head on one side, airways permebealization, O2 administration,

spontaneous recovery may occur.

Medicines: Diazepam iv if the crisis> 3 min - 0.3 mg / kg, repeated 2-3 times, t ½ ~ 15 min.

If the vein cannot be approached quickly- 0.5 mg / kg ir without prior enema (max. 20 mg)

reaches anticonvulsant dose in 4 min. (vs. 20-30 min. at i.m. administration)

Desitin - Diazepam rectal - tube - 5 mg <15 kg and 10 mg> 15 kg, repeated every 2-4 h (in

status epilepticus after 10-15 min. + Glucose + thiamine, vitamin B6); in the absence of

Diazepam, Phenobarbital 10 mg / kg im – this will be mentioned on the referral since in the

case of Diazepam administration there is a risk of respiratory arrest or hypo BP.

Diazepam is not associated with any other drug due to frequent incompatibility.

Fighting fever – physically

- Tylenol 50 mg / kg / day in 3-4 divided doses p.o. or rectally

- Ibuprofen 20-30 mg / kg / day in 3-4 divided doses p.o. or rectally, over the age of 2

months

II. Post-crisis treatment

Indicated only in recurrent febrile seizures (3-5 FS / year).

Phenobarbital administration of 3-5 mg / kg / day po, - 2 times daily (last 1h before bedtime)

Prophylactic treatment is administered to prevent relapses and is recommended only in case

of frequent relapses in patients with altered EEG. EEG is performed at 7-10 days post-crisis

(immediate EEG is unjustified).

Alternative:

t> 38 C – administration of Diazepam i.r. and anti-pyretic (5 years)

Na valproate 20-40 mg / kg / day continuously for children under 3 years

Evolution and prognosis

Immediate evolution - good

- Treated correctly – no sign of complications

- 40% – relapses

Late prognosis - reserved

- Approximately 5% ( 2% at 5 years, 7% at 25 years) will develop a secondary epilepsy

(residual)

- Follow-p – for 6 months from the FS.

- Prognosis depends on many factors

329

Table xxx Risk factors for recurrence of febrile seizures

Major risk factors

Duration of fever < 24 hr

Fever 38-390C

Minor risk factors

Family history of febrile seizures

Family history of epilepsy

Complex febrile seizure

Day care

Male gender

Lower serum sodium

Table xx - Risk factors for occurrence of subsequent epilepsy

Risk factor Risk for subsequent epilepsy

Simple febrile seizure 1%

Neurodevelopmental abnormalities 33%

Focal complex febrile seizure 29%

Family history of epilepsy 18%

Fever < 1 hr before febrile seizure 11%

Complex febrile seizure, any type 6%

Recurrent febrile seizure 4%

330

• History• Exam• Manage acute febrile seizure and acute illness (first aid,

midazolam, diazepam, diagnostic tests) as needed.• Determine risk factors for recurrence and estimate risk of

recurrence of the febrile seizures

Counsel parents about risk of recurrence and how to provide

first aid and manage fever

Determine risk factors for later epilepsy

Low riskNo therapy or

investigations are necessary

Intermediate or high risk1. Consider EEG and imaging2. Consider intermitent oral diazepam or,

in exceptional cases that recur, continuous therapy

Figure xxx – Management of febrile seizures

Criteria of unfavorable prognosis are:

• Small age (under 1 year)

• Severity of crisis

• Frequency of recurrencesof recurrences

CHRONIC RECURRENT SEIZURES (EPILEPSY)

Epilepsy

• Recurrent paroxysms which manifest suddenly with modifications of motor, sensorial,

psychic function and characteristic EEG modifications;

• convulsive attack (ictus) can be clinically presented

- as a convulsion

- minor motor movements

- a certain sensation

- momentary stop of activity

- impaired consciousness (not always)

Etiology

• 80% of the cases - unknown (primary, idiopathic, crypto genetic, essential epilepsy)

331

• 20% - secondary epilepsy, symptomatic, organic

Secondary epilepsy:

• congenital metabolic disease and degenerative (fenilcetonuria)

• Cerebral diseases (vascular, tumors, congenital anomalies)

• traumatisms (at birth, anorexia) or anoxia?

• infections (encephalitis, meningitis)

• intoxications (lead) (plumb)

Classification:

Chronic seizures – depending on EEG signs

- partial

- generalized

Simple partial seizures:

• focal (localized epileptogenic focus) usually motor without loss/alteration of

consciousness

• adverse – eyes and head turn in opposite position of the focal lesion

Partially complex seizures:

• Psychomotor or of temporal lobe

- start as focal, accompanied by sensorial, behavioral, psychomotor, vegetative or

psychic manifestations and generalize secondarily – associated with alteration/ loss

of consciousness – they manifest as a grand-mal crisis with aura (in idiopathic

epilepsy there is no aura and loss of consciousness is primary)

- the behavioral or affectivity changes can be subtle and difficult to attribute to

epilepsy.

- focus in the frontal lobe

These are adverse or jacksonian seizures, with local motor symptoms (face, hand, leg) which

spread to other muscles. They start suddenly, but do not affect the consciousness, determining

only obnubilation. If they generalize => loss of consciousness

• Focal parietal - rare

- they manifest as sensitive jacksonian seizures (paresthesic, painful), with short

duration and no alteration of consciousness

• Occipital focal epilepsy

332

They present visual hallucinations (colored points); macro-, microsomia, cecity; their EEG

diagnosis is difficult since it is only suggestively in crisis, 20% from epileptic children have

normal intercritical EEG

GENERALIZED SEIZURES

Tonic-clonic convulsions (grand-mal - GM)

• Classical epileptic seizures (described at FS)

• There is a prodromal phase, of discomfort which can precede the seizure with ~ hours

(it should be distinguished from aura)

• If they start with sensorial or motor aura – indicate the cortical focus and will be

classified as complex partial seizures with secondary generalization

• focal EEG modifications

• no aura in grand-mal.

Petit-mal epilepsy – primary generalized forms - 5-15 years

PM absence

- Short crises, below 10-20'', with no sudden loss of consciousness

- The attack can be repeated more times a day – precipitated by H-ventilation and

strong light

- without aura or remission, ± localized automatisms

- EEG complex discharges of peak-wave of 3 cycles/sec.: bilateral, symmetrical,

synchronical

- Myoclonic PM

• Short-term loss of consciousness

• Myoclonic diskinesia of the face or axorizomelic muscles

• symmetrical/ asymetrical myoclonus

• recede with the crisis

• EEG – discharging of peak wave: bilateral, symmetrical, synchronous, with different

rhythm in different patients

f ppoli-wave bilateral, , syncr

- Amiotonic-akinetic PM

• Sudden loss of consciousness

• Cancelling of the muscle tone

• collapse, no other motor manifestations

• below 1 minute

333

• EEG - discharging of slow sinusoidal, ample waves, on all the derivations: bilateral,

synchronic, symmetrical verysyncron

- Enuretic or encompretic PM

• They can transform into GM crisis or temporal epilepsy

Infantile myoclonic encephalopathy with hypsarrhythmia - infantile spasml – the West

disease

- Severe affection, appears at 5-6 months

- 3 major manifestations

- Muscle spasms – arms and head flexion

Mental degradation

characteristic EEG - hypsarrhythmia – total degradation of the route -

hypervolted beta, delta waves

Epileptic encephalopathy with variant PM - B. Lennox – Gastaut

- Severe affection but with low incidence

- Varied epileptic manifestations

- muscular atony with body or head falling on the chest – no consciousness

modification – most frequently (necessaryforo diagnosis)

- Can be atypical tonic, psychomotor, myoclonic PM, GM crisis,

- specific EEG (petit-mal variant) - complex peak-wave of 1,5-2,5 cycles/sec.

EPILEPTIC STATUS

• Succession of convulsive crises which last more than 20 min., repeated without

consciousness recovery

• GM, PM or focal type

• Can reappear spontaneously, often favored by infections, traumatisms, metabolic

disorders, intoxications, usually appear at lack of anticonvulsive treatment

• Life-threatening through hypoglycemia, hypoxia, acidosis, high BP and ICH,

hyperpyrexia

EEG – shows activity of neuronal disorder

It is the main element in the classification of convulsions

334

correct classification is crucial in finding the right treatment

• In partial convulsions (simple or complex), the electrical line indicates the epileptogen

focus

• grand-mal crisis- highly volted peaks

• Crisis of absence – peak or slow wave at 3 cycle/s on a normal basic rhythm

• myoclons- multifocal peaks at 2-4 cycle/s.

• infantile spasm (West Dis.) – hypsarrhythmia with irregular peaks or waves

General treatment

• Keep the vital functions (dezobstruation, O2, intubation, cardiac massage)

• DZ - 0,2-0,3 mg/kg i.v. slowly, repeatable 2-3x or i.r. 0,5 mg/kg, max. 20 mg

(plasmatic anticonvulsivant conc. in 4 minutes)

• Fight the main causes (metabolic)

• succession (after blood collection for laboratory tests):

- sol. G 20% 2 ml/kgc i.v

- sol. gluconic Ca 10% 1-2 ml/kgc i.v. slowly

- sol. SO4Mg 25% 0,2 ml/kgc i.m (!)

- Piridoxin 50-100 mg/ dose i.v.

Treatment of bad convulsive state

a) Maintain the vital functions

- monitoring, control hypoxia - bladder catheterization

- venous way - combat hyperpyrexia and acidosis

- treat ICH - corect the metabolic disorders

- emergency anticonvulsive treatment

b) Stop the seizures

• Diazepam 0,3 mg/kg/D i.v. slow or PEV in SF solution

• Fenitoin - 10-12 mg/kg, i.v (Ø conv. in 5-10 min.)

• Phenobarbital 5-7 mg/kg i.v./i.m. (Ø conv. în 20 min.; !associated with DZ depresses

respiration)

• Paraldehid 4%, 2-4 ml/kg i.r.

• Xilin 5-10 mg/kg/h i.v. – EKG monitoring

• Na Valproate 30-50 mg/kg i.r.

• Total anesthesia and curing

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• Antitermics in febrile convulsions

• in CF

Post-crisis Treatment

- Phenobarbital 3-5 (6) mg / day, po, 2 doses, the last before bedtime in recurrent

prolonged, focal seizures,

- Na valproate or 0.3 mg / kg / day - 2 doses po

- Prophylactic treatment 3-4 years follow-up

- Gradually decrease the dose for 2 months, then stopping treatment

Follow-up of epileptic patients

• Periodic clinical control+ EEG every 6 months or when needed

• If the patient does not have crisis for 3-5 years, medication is stopped

• Compulsory follow-up

• Orientation towards jobs without danger of traumatisms, accidents

• In adolescent s– epilepsy has good prognosis, but the treatment will last (more than 2-

3 years)

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CHAPTER IX – HEMATOLOGY

Asist. Univ. Dr. Chinceșan Mihaela

ANEMIA IN CHILDREN – PRINCIPLES OF DIAGNOSIS

Definition: Anemia is defined by decrease in the number of circulating red blood cells

associated with parallel decreases in hematocrit and hemoglobin concentration. It is not an

independent disease, rather a symptom of a particular disease.

Criteria of hospital admission:

Any severe anemia with Hb <6 g / dl, regardless of age

Newborns with Hb <13 g / dl, infants under 6 months with Hb <8 g / dl and clinical signs

Positive diagnosis of the type of anemia is made through: history, physical examination and

laboratory data.

A. History

- detection of possible sources of bleeding, occult blood loss

- duration of symptoms

- existence of recent or repeated infections

- amendment of the type of infant feeding, consumption of meat, milk, iron

deficiency anemia under treatment (curative / preventive), consumption of beans

(G6PD deficiency anemia)

- drugs intake: Chloramphenicol

- neonatal pathology: prolonged jaundice, hemolytic disease, prematurity, twins

- ethnic group

- family history of anemia

B. Physical examination: complete; BP is measured and heart rate is monitored

Symptoms: lethargy, fatigue, dyspnea

Signs:

- Pallor (elective areas of evaluation: pinna, lips, sclera, oral mucosa, palms, plants, nail

bed)

- Jaundice (hemolysis)

- Active bleeding, petechiae

- Adenomegalia

- Hepato-splenomegaly

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- Bone abnormalities; dysmorphia

- Stool with altered appearance

C. Laboratory

- complete blood count with peripheral smear

- reticulocyte count (> 2% if bone marrow functions normally)

- MCV (mean corpuscular volume)

- total bilirubin and direct and indirect fractions

- urea, creatinine, ionogram, sideremia

- blood group

- urine test

- stool test for occult bleeding

• Hypochromic microcytic anemia: MCV <70 fl under 5 years <75 fl 5 years

Additional tests: ferritin, hemoglobin electrophoresis to rule out a hemoglobinopathy.

Iron deficiency anemia is investigated according to the protocol for iron deficiency anemia.

• Normocytic normochromic anemia: MCV between 70-90 fl

If serum bilirubin is increased and is associated with reticulocytosis – these suggest a

haemolytic anemia.

• Macrocytic anemia: MCV> 90 fl

Is rare in child pathology and suggests vitamin B 12 and / or folic acid deficiency secondary

to malabsorption.

Normal valuesof red blood cells in the period 0-18 years of age are shown in Table I.

Table I - Erythrocyte values according to age (average, lower limit of normal –

lower limit is given by two standard deviations below the mean)

Age

Hemoglobin (%) Hematocrit (%) MCV (fl)

AverageInferior

limitAverage

Inferior

limitAverage

Inferior

limit

1-3 days 18.5 14.5 56 45 108 95

1 month 14.0 10.0 43 31 104 85

2 months 11.5 9.0 35 28 96 77

3-6 months 11.5 9.5 35 29 91 74

6 months-2 12.0 11.0 36 33 78 70

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years

2-6 years 12.5 11.5 37 34 81 75

6-12 years 13.5 11.5 40 35 86 77

12-18 years

females

14.0 12.0 41 36 90 78

12-18 years

males

14.5 13.0 43 37 88 78

IMMUNE THROMBOCYTOPENIC PURPURA (ITP; IDIOPATHIC PT;

WERLHOFF DISEASE)

Definition: purpuric syndrome caused by low platelet count (below 100.000/mm3) due to

peripheral damage by immunological mechanisms, which exceeds the capacity of normal

compensatory thrombocytopoiesis, hematologically translated by thrombocytopenia with

megakaryocytosis.

Etiologic classification

Idiopathic (primary): 5 -10 %

Secondary

- postinfectious (EBV, CMV infection, varicella, rubella, measles, tuberculosis, HIV)

- after vaccination

- collagen diseases

- lymphoproliferative syndromes

- solid tumors

- medicines:

» antibiotics: ampicillin, gentamicin, penicillin, rifampicin, trimethoprim,

vancomycin, sulfamethoxazole

» NSAIDs: acetaminophen, aspirin, gold salts, phenylbutazone

» other: digoxin, allopurinol, carbamazepine, cimetidine, diazepam

» heparin, spironolactone, morphine

- pregnancy

- other (hemophilia A, Hashimoto thyroiditis, sarcoidosis)

339

Epidemiology: in up to 90% of the cases, the immunological nature of the disease can be

proven. It mostly occurs in children aged 2-8 years and adolescents, often 2-3 weeks after an

intercurrent infection and has an increased seasonal incidence (March to October).

Pathogeny: The disease is caused by immunological mechanisms (antiplatelet and

antimegakarocytic antibodies) where the spleen plays a role in removing the sensitized

platelets and acts as a source of antiplatelet antibodies. In 30% of cases other organs,

particularly the liver, may be involved as well.

Clinical manifestations: The onset may be gradual or insidious (more frequently chronic

ITP). During the state period, mucocutaneous purpura and visceral bleeding appear. Bleeding

is spontaneous and prolonged; there is no serious bleeding and the overall condition is good.

- skin purpura: the skin petechiae and bruising appear in minimal traumas or

spontaneously, especially in exposed areas (legs), giving the appearance of

"bludgeoned child " or leopard skin

- mucosal bleeding: epistaxis, gingival bleeding, haemorrhagic bullae, endo oral

purpura = wet purpura

- visceral bleeding: meningo-cerebral hemorrhage is the most feared

- puberty menorrhagia: may be the only manifestation

- splenomegaly; adenomegaly - rarely

Clinical elements of severity:

- association in the onset or during the evolution of a diffuse purpura on the

abdomen

- oral bleeding bubbles

- hematuria

- retinal hemorrhage - may herald impending meningocerebral hemorrhage.

Laboratory

- complete blood count: Thrombocytopenia <100.000/mm3

- prolonged bleeding time, normal clotting time

- PTT and PT

- Coombs test

» antiplatelet antibodies

» immune complexes fixed on platelets

» marrow examination: pronounced megakaryopoiesis, with deviation to

the left of the megakaryogram.

Typical aspect for ITP:

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• Tr <50.000/mm³ Hb > 10 to 11 g%

• WBC: 4000-5000/mm ³ Granulocytes: 1500-2000 / mm³

• Peripheral smear of normal appearance

Positive diagnosis is based on the following criteria:

- clinical criteria: cutaneous and mucosal petechiae purpura, no adeno-

hepatosplenomegaly

- peripheral haematological and bone marrow criterion: isolated thrombocytopenia;

normal or increased number of megakaryocytes in the bone marrow, with deviation to

the left of the megakaryogram

- exclusion of other causes of excessive platelet destruction

- immunological criterion (optional): antiplatelet antibodies or immune complexes

fixed on platelets

Differential diagnosis:

1. Schonlein-Henoch Purpura – the number of platelets is normal

2. Other thrombocytopenias:

- congenital bone marrow production deficiency : Fanconi anemia, TAR syndrome,

osteopetrosis, thrombocytopenia of metabolic diseases

- acquired bone marrow production deficiency: aplastic anemia, leukemia,

lymphoma, infections, medications, toxic substances.

- excessive destruction: immunological; trombocytoliytic (post-vaccination, viral

infection, drug); splenic sequestration (congestive splenomegaly); excessive

consumption (DIC, hemolytic syndrome) mechanical destruction (prosthetic heart

valves).

Treatment

General measures: Being a self-limited disease, most patients with ITP are doing well

without medication. Bed rest, avoidance of trauma, injections and vaccinations at least 18-24

months as well as drugs that interfere with platelet function (NSAIDs, Aspirin) are important.

1. Initial treatment

• Corticotherapy: various schemes; inhibits platelet phagocytosis by splenic macrophages;

enhances capillary resistance and inhibits antibody synthesis.

- Prednisone 1-2 mg / kg / day po in three divided doses for 14-21 days, with gradual

reduction and discontinuation in 4-6 weeks

- Prednisone 4 mg / kg / day po divided into three doses for 7 days, with progressive

reduction and remission in 3 weeks

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- Methylprednisolone 30 mg / kg / day iv for 3-4 days.

Depending on the response to corticosteroids, there are ITP corticosensibile forms,

corticosteroid dependent or corticoresistant forms.

• Immunoglobulin intravenously:

- 400 mg / kg / day 4 consecutive days or 1-2 g / kg / day for 2 consecutive days

• Red cell mass: only in severe forms, with life-threatening bleeding.

• Emergency plasmapheresis or splenectomy may be necessary in patients refractory to

first-line treatments mentioned above.

2. Treatment of refractory forms

• Immunosuppressive therapy:

» Azathioprine (Imuran) 1-2 mg / kg / day

» 6-Mercaptopurine 1.5-2.5 mg / kg / day

» Cyclophosphamide 1-2 mg / kg / day

» Vincristine 1.5 mg / m² / week

• Interferon

• Cyclosporine

• Monoclonal macrophage antibodies (Rituximab)

Splenectomy is indicated only after the age of 4 years, in chronic forms, after at least 12

months of evolution and appropriate preparation (pneumococcal polysaccharide,

meningococcal and antihemophylus vaccines). Splenectomy is effective in 70-80% of cases;

in 20-30% may not be effective if the platelets are sequestered and destroyed in the liver and /

or bone marrow.

Complications

- cerebral hemorrhage in 1% of cases

- fatal hemorrhages

- infectious complications after splenectomy

- viral infection after therapy with blood products or immunoglobulins

Evolution and prognosis

The prognosis is generally favorable. ITP is an evolving self-limited benign disease in 80-

90% of cases. In 10-20% of cases chronicity risk exists, especially in over 10 year-old girls,

with lack of response in the first 3 weeks of disease development.

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HEMOPHILIA

Definition: Haemophilia is a hereditary coagulopathy characterized by low levels of blood

coagulation factor VIII (haemophilia A), IX (Hemophilia B) and XI (Hemophilia C).

Haemophilia A is four times more common than haemophilia B.

Pathophysiology: Coagulation factors VIII and IX are important in the formation of

thrombin. When an injury occurs, a primary thrombus is produced that will then be woven by

fibrin filaments. Haemophilia is characterized by delayed abnormal thrombus formation.

Deep hemorrhage (intra-articular, intramuscular) is characteristic in hemophilia. The

thrombus is brittle and recurrent bleeding is frequent.

Figure I. Coagulation cascade

Etiopathogeny: The defective gene is located on chromosome X, and X-linked transmission

is recessive, so women carriers transmit the disease and it manifests in boys.

Figure II. X-linked transmission

◊ Female carrier ◊ Affected male

-50% risk of daughter carriers -All daughters are carriers

-50% risk of boys with hemophilia - No boy will be affected

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Epidemiology: Haemophilia A is the most common hereditary coagulopathy, its prevalence

being 10-20/100.000 newborn males. Hemophilia A occurs in 85% of haemophilia patients

and haemophilia B just in 15%.

Severity: Is assessed by the level of the factor affecting the patient's blood:

- severe form: factor VIII less than 1%

» severe bleeding either spontaneously or with minimal traum

- average form: factor VIII between 1-5%

» bleeding from minor or moderate trauma

- mild form: factor VIII > 5%

» late diagnosis, bleeding from surgery or major trauma.

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Clinical manifestations:

Haemophilia A is rarely revealed in the neonatal period; 2% of neonates with hemophilia

have cerebral hemorrhage and 30% bleed profusely during circumcision. Most commonly,

the diagnosis is made only at the age of 1-5 years, first signs of the disease often occurring

during tooth eruption or walking, when small accidents involve bleeding.

Bleeding characteristics:

• Caused hemorrhage (minor trauma, injection, puncture)

• Appearance of "spontaneous" bleeding in very low concentrations of factor VIII

• Prolonged duration of outward bleeding without tendency of spontaneous stopping

• Profound hemorrhage localization : intracavitary, intratissular, intravisceral

• No petechial lesions

The most common bleeding manifestations are:

• Hemarthrosis: large joints - knees, elbows, ankles, hips, shoulders

• Bruising and superficial subcutaneous or intramuscular hematoma (buttocks

muscles, deltoids, pectorals) and profound (ilio-psoas muscle, retroperitoneal)

• Epistaxis, "open" buccal and lingual bleeding wounds, bruise / cut skin wounds

• Hematuria

• Meningocerebral hemorrhage - life-threatening

• Gastrointestinal bleeding

Laboratory

• normal bleeding time (BT)

• extended clotting time (CT)

• normal platelets, leukocytes and erythrocytes

• normal Quick Time (PT)

• prolonged activated partial thromboplastin time (APTT)

• low factor VIII level

Hemophilia cannot be diagnosed without the coagulogram !!

Positive diagnosis: In a male patient is based on personal history, present or absent family

history of bleeding in conjunction with clinical and laboratory manifestations (deep or

externalized bleeding) are suggestive.

Differential diagnosis

- Haemophilia through factor IX deficiency (Hemophilia B) or XI (Hemophilia C): the

thromboplastin generation test

- ITP: petechiae and bruises that occur spontaneously; decreased platelets

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- Acute leukemia: characteristic clinical and hematologic features

Treatment

Prophilactic treatment

- genetic counseling

- counterindication of im injections and Aspirin

- lifestyle that avoids trauma and aggressive sports; choosing a profession that will not

expose to accidents and injuries

- prophylactic treatment with factor VIII three times a week at a dose of 20-40 U / kg

iv.

Curative treatment: consists in substitution of the deficient factor. The treatment begins

when bleeding occurs, within the first hour of bleeding. The hemorrhage is difficult to control

when the replacement therapy is delayed.

Factor VIII dose = % x G (kg) / 2

% = the value at which we want to increase the factor VIII level in the patient’s blood and it

depends on the location and severity of bleeding (bleeding from the mouth 30-40%; joint or

muscle bleeding 40-60%; hematuria 40-50%; cerebral hemorrhage 100%). The half-life of factor

VIII is 12 hours, therefore, the calculated dose is administered twice a day i.v. (every 12 hours).

Factor VIII products:

Factor VIII recombinant

Factor VIII concentrate extracted from human plasma

Cryoprecipitate (a bag of cryoprecipitate contains about 100 U of factor VIII)

Fresh frozen plasma 10 to 15 ml / kg / dose

Adjuvant therapy: In mild bleeding or lesions, application of ice, local pressure are useful;

local agents (Gelaspon, thrombin sponges); in mucosal bleeding antifibrinolytic therapy is

used (epsilon-aminocaproic acid, tranexamic acid).

Complications

- disease-linked: joint ankylosis, nerve compression, muscle contractions and

retractions

- the advent of anti factor VIII inhibitors

- viral infections by administration of inappropriate products (HIV, Hepatitis A, B, C,

CMV, EBV, parvovirus, etc.)

Prognosis: is favorable in a correctly followed up patient. Childhood trauma are more

frequent; after the age of 15 bleeding tendency decreases. With chronic replacement therapy

at a young age, the quality of life increases.

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References:

1. Arceci Robert J, Hann Ian M, Smith Owen P. Pediatric hematology, 3th edition. Blackwell Publishing,

2006

2. Baghiu Maria Despina, Horvath Adriennne. Hematologie, oncologie şi endocrinologie pediatrică. Note de

curs pentru medici rezidenţi. Litografia UMF Târgu Mureş, 2007

3. Lanzkowsky P. Manual of Pediatric Hematology and Oncology, 4th edition. Elsevier, 2005

4. Man Sorin C, Nanulescu Mircea V. Pediatrie practică. Ed.Risoprint Cluj-Napoca, 2006

5. Muntean I şi colab. Vademecum de pediatrie. Ed.Medicală Bucureşti, 2007

6. Schwartz M.William, Bell Louis M, Bingham Peter M. et al. 5-Minute Pediatric Consult, 5th edition.

Lippincott Williams & Wilkins, 2008

7. Şerban Margit, Ioniţă Hortensia, Poenaru D, Ritli L.O viaţă cu hemofilie. Ed. Brumar Timişoara, 2009

8. Şerban Margit, Schramm W. Hemostazeologie clinic. Ed.Brumar Timişoara, 2001

347

CHAPTER X – ONCOLOGY

Asist. Univ. Dr. Chinceșan Mihaela

LEUKEMIAS

Although rare in childhood, malignancies are the 2nd leading cause of death, following

accidents. Leukemia is the most common malignancy in children, followed by brain tumors

and lymphomas. The incidence is 3.5 cases / year / 100,000 children under 15 years.

Classification

1. Acute leukemias:

- Acute lymphoblastic leukemia (80%)

- Acute myeloblastic leukemia (20%)

2 . Chronic leukemias:

- Chronic granulocytic leukemia (1%).

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

Epidemiology: Acute lymphoblastic leukemia occurs more frequently in boys at the age of

2-5 years.

Etiology:

Environment Factors:

- ionizing radiation - after the atomic bomb (Japan) - increased incidence of ALL

- toxic chemicals: benzene, pesticides, herbicides

- alcohol

- medicines: alkylating substances, Leukeran, Cyclophosphamide

- diagnostic irradiation in pregnant women increases by 5 times the risk of leukemia in

the fetus during the first term

Viral infections:

- Epstein-Barr virus can produce mature B-cell ALL (FAB L3)

- T lymphotropic human virus may cause T-cell ALL

- HIV (or secondary immunodeficiency) predisposes to malignancy

Immunodeficiencies:

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- Primary: Bruton agammaglobulinemia, Wiskott-Aldrich sdr., ataxia telangiectasia,

congenital neutropenia, etc.

- Secondary: HIV infection, chemotherapy treatments, cortisone treatments

Chromosomal abnormalities and other genetic diseases:

- Down Sdr.(trisomy 21) - leukemias are 10-18 times more common

- Neurofibromatosis

- Fanconi Anemia (pronounced chromosomal fragility)

- in families with ALL children - 2-3 times higher risk to other children than in the

general population

- monozygotic twins - 25% risk of the twin to develop leukemia

Pathogeny

Through malignant transformation of a lymphoid precursor, a malignant clone forms that will

be able of infinite self-replication. At least two sequential mutations in genes that check cell

proliferation are necessary in order to produce leukemia. Malignant transformation and clonal

proliferation may occur at different stages of lymphoid differentiation (maturation).

Clinical manifestations

Signs and symptoms may rarely occur suddenly, within a few days, but most commonly the

onset is insidious, taking a few weeks or months. The clinical picture is given by the fact that

the bone marrow is infiltrated with lymphoblasts and production of normal cellular elements

disappears, blastic extramedullary infiltrations appearing as well.

Marrow infiltration with lymphoblasts determine:

• Anemia: pallor, fatigue, dizziness

• Neutropenia: fever, infections

• Thrombocytopenia: bleeding skin and mucosa

Extramedullary leukemic infiltrations:

- Adenomegaly - Hepato-splenomegaly

- Bone pain - Renal infiltrations

- Pericarditis - Infiltration of the myocardium

(cardiomyopathy)

- Pleurisy - Mediastinal tumor (in ALL with T cells)

- Testicular impairment - CNS symptoms: headache, vomiting, seizures

- Skin signs - Eye infiltration

Laboratory

Blood count highlights three major events:

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- aregenerative normochromic, normocytic anemia

- thrombocytopenia (<100.000/mm ³)

- leukocyte abnormalities: leukemia-form (Leukocytes > 10.000/mm ³)

» subleukemic form (Leukocytes 5-10.000/mm ³)

» aleukemic-form (Lekocytes <5.000/mm ³)

Peripheral smear: monomorphic lymphoblasts give a monomorphic character to the

peripheral smear

Bone marrow: marrow examination shows decreasing numbers of normal hematopoietic

series and their replacement with pathological lymphoblasts morphologically similar to those

in the periphery. The presence of lymphoblasts, higher or equal to 25% in the bone marrow

establishes the ALL diagnosis.

- Morphological examination of the bone marrow: lymphoblasts are classified based on

morphological aspect into 3 types (FAB classification): L1, L2, L3. In terms of prognosis,

L1 has the best prognosis, L2 poorer and L3 corresponds to mature B cell with the

poorest prognosis.

- Cytochemical examination: the lymphoblast is PAS (periodic acid Schiff) positive and

peroxidase negative

- Immunologic examination of the blasts is performed with monoclonal antibodies.

Lymphoblasts may be B and T cell line at various stages of differentiation. Markers for

cell line B: CD 19, CD20, CD21, CD24 and T cell lines are: CD1, CD2, CD3, CD4, CD5,

CD7, CD8.

- Cytogenetic examination: Changes in the number or structure of chromosomes are

observed in the malignant transformed cells. Of the changes in number (ploidy),

hiperployd forms have better prognosis and of the structural changes, deletions,

translocations, duplications. Some translocations have favorable prognosis, t (12, 21),

other unfavorable t (8, 14), t (9, 22), t (4, 11).

- Changes in molecular genetics: gene rearrangements can be observed.

CSF examination: in case of meningeal damage, there are changes in the cerebrospinal fluid:

increased cellularity, increased proteinorahia, low glicorahia; CSF smear shows

lymphoblasts.

Laboratory in tumor lysis syndrome: increased LDH, uric acid, phosphorus and calcium.

Imagistic explorations

- Chest Rx: widening of mediastinum or tumor mass and / or adenomegaly.

- Long bones X-ray: osteoporosis and vertebral body deformity.

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- Abdominal ultrasound: nephromegaly, abdominal lymphadenopathy, hepato-

splenomegaly.

Eye fundus examination: papilledema, retinal hemorrhages, tortuous vessels (CNS disease)

Brain MRI / CT: brain infiltration (CNS disease)

Differential diagnosis

• Histologically benign diseases

- Rheumatoid Arthritis - Infectious mononucleosis

- Pertussis - ITP

- Aplastic Anemia - Acute infectious lymphocytosis

• Malignancies

- Neuroblastoma

- Retinoblastoma

- Rhabdomyosarcoma

• Other: hypereosinophilic syndrome

Prognostic factors

• Favorable prognosis

- age 1-6 years

- females

- initial number of leukocytes <20.000/mm3

- rapid response to corticosteroids (Day 8- absolute number of lymphoblasts in

peripheral blood <1.000/mm3)

- complete remission on day 33

- L1 morphology according to FAB classification

- pre-B immunology

- absence of Philadelphia chromosome and other adverse translocations

• Unfavourable prognosis

- age <1 year or> 6 years

- males (testicular relapse, at ALL more frequently with Tcells)

- poor response to corticosteroid therapy (day 8 number of blasts> 1.000/mm3 in

peripheral blood)

- lack of remission on day 33

- immunology: ALL with B mature cells, ALL with T cells, presence of Philadelphia

chromosome t (9, 22)

- cytogenetics: hypoploidy, euploidy

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- CNS symptoms in the onset

- poor nutrition

Treatment: is done in specialized centers according to treatment protocols and proper

stratification of patients into risk groups. Intensity of treatment depends on leukemia

malignancy; chemotherapy and supportive treatment is applied in parallel.

The goal of the treatment: treating the patient with minimal risk of drug specific acute

toxicity and late complications and achieving long term total remission (disappearance of

signs and symptoms, normal blood count and peripheral smear, <5% lymphoblasts in the

bone marrow).

Treatment principles:

Induction: induction treatment lasts two months, the aim being to achieve total

remission. It includes the following medication: high-dose prednisone and cytostatics:

asparaginase, citozinarabinozide, cyclophosphamide, daunorubicin, purinethol,

vincristine, intrathecal methotrexate.

Consolidation/ intensification treatment: lasts two months, aiming to further

decrease the number of lymphoblasts in the body. It includes chemotherapy that is

different than in the induction: high-dose methotrexate IV, intrathecal methotrexate,

purinethol p.o.

Re-induction treatment: lasts 6 weeks and is similar to induction with some

modifications in order to eradicate minimal residual disease.

Maintenance treatment: lasts 2-2.5 years, so that all the treatment takes just three

years, calculated from the first day of treatment. It includes purinethol po once daily

and methotrexate po once/ week, with re-induction twice a month with a dose of

vincristine po, and prednisone 5 days po; at 3-4 months intrathecal methotrexate is

administered for CNS prophylaxis.

Cranial irradiation: is indicated in all cases of high and medium risk of CNS

symptoms in the onset or T-cell leukemia and is applied at the beginning of the

maintenance treatment.

Allogeneic bone marrow transplantation: is indicated in high-risk forms and

relapses, if remission can be achieved again.

Support treatment:

Isolation of the patient to protect him from infection: compliance with the rules of

hygiene

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Appropriate diet: hypo-sodic diet during corticosteroid therapy, avoiding salads, raw

food, salami, etc., during severe marrow aplasia; otherwise, varied, balanced diet.

Prophylaxis of infections that are frequent and severe in immunocompromised

patients:

- carinii pneumonia prophylaxis with Biseptol 6-8 mg / kg / day, 3 days / week

throughout cancer therapy.

- chickenpox can be fatal, so avoid contact with chickenpox patients; in case of

contact: high-dose acyclovir, 14 to 28 days po. In case of chickenpox, specific

anti-chickenpox Ig and acyclovir are administered i.v. Vaccination (live

attenuated varicella vaccine) is absolutely counter-indicated in immune-

compromised patients (may cause chickenpox).

- any acute bacterial infection is treated vigorously with broad-spectrum antibiotics

in high dose intravenously.

Management of transfusion:

- anemia is adjusted to Hgb <8 g%, except in septicemia, where red blood cell

mass is administered in Hgb values <10 g%.

- thrombocytopenia is adjusted to Tr <10.000/mm3 or at any value if the patient

bleeds - standard platelet mass is administered/ obtained through cytapheresis.

- Fresh frozen plasma may be administered for hemostasis disorders or CID.

- Administration of granulocyte-monocyte colony stimulating factors:

in the case of severe neutropenia (<500/mm3) associated with infection, the aim

being to shorten the neutropenic period.

Prognosis: total remission can be achieved in 75% of the patients; 25% die from

complications or cytostatic drug resistance. 30% of patients may present BM or extra-

medullar relapse (testicle, CNS). The occurrence of relapses implies a poor prognosis,

especially if they appear under chemotherapy or within the first 6 months after treatment

(early relapses); late relapse prognosis is more favorable.

Complications

Complications caused by the underlying disease:

- DIC with cerebral hemorrhage

- acute renal tumor through the lysis syndrome

- leukemic infiltration of the brain that can cause seizures, intracranial hypertension

- mediastinal compression

Treatment-induced complications:

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Corticotherapy: osteoporosis, hypokalemia, psychosis, ulcers, cataracts, iatrogenic

diabetes, cardiomyopathy, Cushingoid appearance, muscle weakness, high blood

pressure.

Early chemotherapy-induced complications: infections of any type, anemia, anorexia,

nausea, vomiting, mucositis, alopecia, peripheral neuropathy, myopathies, hemostasis

disorders.

Late cytostatic- induced complications: mental disorders,learning difficulties,

infertility, endocrine disorders (most commonly hypothyroidism), the appearance of

the second tumor (even after 10 to 15 years), cardiomyopathy, liver fibrosis,

psychosocial disorders (isolation).

Patient follow-up

- during treatment every week, or every 4 weeks depending on treatment

- follow up care continue even after the end of chemotherapy, for at

- least 5 years, preferably throughtout lifetime.

MALIGNANT LYMPHOMA

HODGKIN LYMPHOMA

Epidemiology:

The disease occurs more frequently in two age groups: at the age of 20 and 50 years; in

childhood it is more common over the age of 5 years. Boys are more prone to the disease than

girls. A relationship between infection with Epstein-Barr virus (EBV) and Hodgkin's disease

occurrence was established, the presence of EBV genome embedded in the DNA of Reed-

Sternberg cells and positive serology for anti EBV Ab.

Biology:

Reed-Sternberg cells are formed from malignant transformation of activated B-cells.

Malignant transformation is triggered by a genetic abnormality or external environmental

factors. Malignant giant Reed-Sternberg cell produces cytokines that act like growth factors

on Reed-Sternberg cells and other cells (lymphocytes B, T, eosinophils, granulocytes).

Histology:

Malignant cells form <1% of the tumor cell population, the rest being represented by

inflammatory infiltrate with histiocytes, plasma cells, lymphocytes, eosinophils, neutrophils

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and fibrosis, caused by the action of cytokines secreted by tumor cells. In diagnosis

development, Reed-Sternberg cell, inflammatory infiltration and fibrosis must be present.

Reed-Sternberg cells may be present in other malignancies (sarcoma, non-Hodgkin

lymphoma, carcinoma) and in non-malignant diseases (infectious mononucleosis).

Histological types of lymphoma

- Lymphocytic predominance: occurs in 10-15% of patients and has the best prognosis. It

is characterized by a benign inflammatory infiltrate, and if the few Reed-Sternberg cells

are not found, it may be mistaken for reactive lymphocytic hyperplasia.

- Mixed cellularity: occurs in 25-30% of patients, especially under the age of 10 years;

usually patients present to the doctor in advanced stages.

- Lymphocytic depletion: rare in childhood, is the form with the most severe prognosis;

Develops bone and bone marrow metastases. It is characterized histologically by the

paucity of lymphocytic infiltrate and presence of more Reed-Sternberg cells.

- Nodular sclerosis: occurs in 40% of younger children and 70% of adolescents. Reed-

Sternberg cells are difficult to highlight.

Clinical features

- Volume increase of lymph nodes: latero-cervical or supra-clavicular nodes are

frequent, of firm consistency; sometimes node conglomerates; mediastinal lymph

nodes causing compression signs: rare irritative cough, dyspnoea, face edema, face

cyanosis. Rarely, the disease begins with the swelling of axillary or inguinal lymph

nodes.

- Splenomegaly, frequently

General signs - may be present: fatigue, weight loss, anorexia.

Subjective signs - "B symptoms" - have worse prognosis and are used in staging: fever, night

sweats, loss of > 10% of body weight in the last 6 months

- itching, sometimes just excoriations from scratching

- extranodal implications: bone marrow, liver, CNS (10-15%)

- bone and lung implications: rarely

Laboratory

Blood count: leukocytosis, neutrophilia, lymphopenia (in advanced cases), eosinophilia,

monocytosis, moderate microcytic anemia with hypersideremia

ESR may be increased and may be an element of evolution and prognosis

Liver function tests – modified in cases of hepatic involvement

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LDH (lactic dehydrogenase), cupremia and ferritin are increased and are markers for

evolution and prognosis

Node biopsy: essential in the diagnosis

Chest Rx: hilar lymphadenopathy or mediastinal masses

Thoracic and abdominal CT: show node, pulmonary, hepatic and splenic involvement.

Bone marrow examination: shows marrow involvement in advanced cases

Bone scan: shows bone involvement in advanced cases

PET / CT exam (positron emission tomography combined with CT) allows accurate staging

of the disease and response assessment to treatment

Ann – Arbor Staging

Stage I: damage to a single lymph node region or a single extra-lymphatic organ

Stage II: 2 or more lymph node regions on the same side of the diaphragm, or

extra-lymphatic organ + ganglion on the same side of the diaphragm

Stage III: impaired lymph node region on both sides of the diaphragm ± spleen

(IIIS) ± extralymphatic organ (IIIES)

Stage IV: disseminated disease (liver, skin, bone, bone marrow).

Differential diagnosis

Lymphadenopathy should be distinguished from

- inflammatory origin: tuberculosis, toxoplasmosis, infectious mononucleosis

- Non-Hodgkin Lymphoma

- Metastases: nasopharingeal carcinoma, sarcoma of soft parts

Mediastinal tumor: differs from normal thymus

Treatment

• Chemotheropy

» ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)

» COPP (cyclophosphamide, oncovin, prednisone, procarbazine)

Radiotherapy: Hodgkin lymphoma is sensitive to radiotherapy

Autologous stem cell transplantation, bone marrow transplantation: indicated in relapses

after further chemotherapy

Prognosis: survival over five years is possible in 90% of cases; in stage IV - 65%.

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NON-HODGKIN LYMPHOMA

Epidemiology:

5-7% of child malignancies; is rarer in children than in adults; the incidence increases with

age. Burkitt lymphoma from Africa is known as endemic whereas forms from other

geographic regions are known as sporadic. Epstein-Barr virus infection is attributed a role in

the etiology of endemic Burkitt lymphoma (BL).

Classification

» B-cell Lymphomas

» T-cell Lymphomas

In precursor tumors, thymus is affected especially in the T-cell lymphoblastic lymphoma.

Burkitt lymphoma (BL), Burkitt-like, and large B-cell (LBCL) are mature B-cell lymphoma;

lymphoblastic lymphoma (LL) is in particular a pre-T cell lymphoma and anaplastic

lymphoma with large cells (ALCL) derive from T cells or natural killer (NK).

Clinical features: varies depending on the histological type. Usually it has extra-nodal

location. B-cell lymphomas are in the abdominal cavity and T-cell lymphomas in the thorax.

General signs (fever, weight loss) are rarely encountered.

Sporadic Burkitt Lymphoma:

- abdominal location: abdominal pain, vomiting, diarrhea, abdominal distention,

palpable abdominal mass, ascites, hepatosplenomegaly

- frequently invades the retroperitoneal structures (pancreas, kidney)

- frequent ovary infiltration

- nasopharingeal location - rarely (unilateral tonsillar hypertrophy) or paranasal sinuses

- skin and mediastinal location - extremely rare

- lymphomatous infiltration of the breast - in pre-pubertal girls and breast-feeding

mothers

Endemic Burkitt lymphoma: common in Africa, affecting mostly the jawbone

Lymphoblastic lymphoma:

- pre-T LL: mediastinal mass

- pleurisy, pericarditis

- superior vena cava syndrome (pain, dysphagia, dyspnea, orthopnea, swelling of

the neck, face and upper limbs)

- CNS damage -10% of cases

Laboratory

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- node biopsy: essential for diagnosis - complete blood count

- assessment of liver and kidney function; LDH - ionogram

- infectious profile: anti HIV Atb, hepatitis A and B, C, CMV, varicella

- CSF examination: CNS involvement - BM test

- chest Rx and CT - abdominal ultrasound

- bone scan - PET / CT

Diagnosis: based on histopathological examination with CD45 positivity (LCA = leucocyte

common antigen) the haematological origin of the tumor may be proved

Staging

Stage I

A single extranodal tumor or single node region, except for the abdomen and

mediastinum

Stage II

Single extranodal tumor with regional lymph node involvement;

On the same side of the diaphragm: 2 or more lymph node regions, 2 extranodal tumors

with nodal involvement

Completely resectable primary gastrointestinal tumor, ± nodal involvement

Stage III

On both sides of the diaphragm: 2 extranodal tumors, two or more lymph node

regions

All primary chest tumors (mediastinal, pleura, thymus)

All abdominal tumors are extended, inoperable

All of primary tumors are para-spinal or epidural

Stage IV

CNS or BM symptoms (> 25%)

Differential diagnosis

- localized infectious adenopathies

- mediastinal and abdominal masses: neuroblastoma, Wilms tumor

- bone tumors in case of primary bone location

- brain tumors if HIC phenomena or paralysis of cranial nerves appear.

Treatment

Emergency treatment: is often necessary since the tumors grow rapidly; the symptoms are

caused by compression of organs or metabolic disturbances. Mediastinal tumors cause

tracheal compression, pericarditis, pericardial tamponade, superior vena cava compression.

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Abdominal tumors cause intestinal obstruction, ureteral compression, bleeding and severe

metabolic disorders: tumor lysis syndrome and acute renal failure. CNS location can produce

convulsions, paraplegia, paralysis of cranial nerves, meningeal irritation.

Chemotherapy: because of many complications that can occur at the beginning of treatment,

it begins in an intensive care unit, even if the patient's condition is satisfactory.

- Lymphoblastic lymphoma: chemotherapy according to protocols for lymphoblastic

ALL

- Burkitt lymphoma (BL): treatment is shorter and more intensive - cytotoxic blocks

administered every two weeks

- Large B-cell lymphoma (ALCL) – identical with LB treatment

Supportive hematologic treatment: identical to ALL support therapy

Prognosis: depends on the stage of disease, histological and genetic appearance; 3 years

survival in stage I and II - 90-95% in stage III - 86% in stage IV - 75%.

SOLID TUMORS

NEUROBLASTOMA

Epidemiology:

8% of child malignancies; 28-39% of newborn malignancies; average age of neuroblastoma

diagnosis - 2 years, 90% of cases are diagnosed under 5 years; higher frequency in males and

in white patients. Evolution is unique and can present spontaneous regression, especially in

infants in stages 1 and 4S of the disease.

Etiology: unknown.

- risk factors: intrauterine exposure to alcohol, drugs, hormones, hair dyes

- association with other neural crest cell disorders: neurofibromatosis, B.Hirschprung

Syndrome, DiGeorge Syndrome, Beckwith-Wiedemann Syndrome.

- Neuroblastoma cells: chromosomal changes (deletion of the short arm of chromosome

1), in advanced forms and unfavorable prognosis

- amplification of n-myc proto-oncogenes (oncogene located on the short arm of

chromosome 2) indicates poor prognosis.

Clinical features: appears to be a tumor on the sympathetic chain; the symptoms are

polymorphic, according to symptom location and neuroendocrine symptomatology of the

tumor.

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1. Simptoms given by the tumor mass

- abdominal location: localized abdominal pain, abdominal distension, constipation,

palpable abdominal tumor exceeding midline

- chest location: dyspnoea, cough, or discovered by chance

- cervical location: severe dyspnea, difficult swallowing, Horner syndrome (miosis,

enophthalmos, palpebral ptosis, iris heterochromia of the affected side)

- pelvic location: difficulty in defecation and urination

- paramedular and intramedular locations: pain in the spine, sphincter dysfunction, gait

disturbances, paresis (due to compression)

2. Paraneoplastic syndrome

- symptoms due to hypersecretion of catecholamines: hypertension, tachycardia, fever,

sweating, paleness, headache, increased urinary excretion of degradation products:

Vanilmandelic acid, homovanillic acid

- symptoms due to hypersecretion of intestinal vasoactive peptide: diarrhea

unresponsive to treatment, abdominal distention, hypokalemia

- acute myoclonic encephalopathy (rare): myoclonus, opsoclonus (sudden movements

of the eyes), trunk ataxia, head restlessness

- manifestations due to metastatic locations: adenopathy, hepatomegaly, brain

metastases, bone marrow, skin (bluish skin nodules only in babies)

- nonspecific signs: lethargy, anorexia, pallor, weight loss, abdominal pain, irritability

Laboratory

- CBC: anemia and thrombocytosis; cytopenia in case of medullar metastasis

- serum ferritin, LDH, ESR, neuron specific enolase - usually high

- Vanil-mandelic acid (VMA) of 24-hour urine – high

- aspirate / bone marrow biopsy – metastasis bilaterally: tumor cells similar to

lymphoblasts in nest locations

- chest radiography: mass in the posterior mediastinum: calcifications in the tumor

(pathognomonic for neuroblastoma)

- abdominal ultrasound

- thorax, abdomen, pelvis CT: extension of the tumor, metastases, calcifications

MRI: para-vertebral tumor; bone metastases

bone scintigraphy (MIBG, Tc-99): bone metastases

PET / CT

Positive diagnosis

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Obligatory elements for positive diagnosis (INSS recommendation)

- presence of neuroblasts in primary tumor with characteristic histologic picture

- in the bone marrow: neuroblast nests and / or high level of blood catecholamine or urine

metabolites

Staging

Stage I: localized tumor, completely resectable.

Stage IIA: localized tumor with incomplete resection, ipsia and controlateral lymph nodes are

microscopically negative.

Stage IIB: localized tumor with complete or partial resection, positive ipsilateral node and

negative controlateral node.

Stage III: inoperable tumor beyond the midline with or without lymph node involvement.

Stage IV: distant metastases: in the removed lymphnodes, liver, bone, bone marrow, skin and

other organs.

Stage IVS: localized primary tumor (Ist or IInd degree) with metastases in the skin, liver,

bone marrow in children under 1 year of age.

Differential diagnosis

- other abdominal masses: Wilms tumors, ovarian germ tumors, rabdomiosarcoamas,

lymphomas

- fecaloma from constipation

- intestinal duplication

Treatment

Surgical excision: the localized disease: curative excision; in metastatic disease: "second

look" surgery

Chemotherapy: preoperative and postoperative

Autologous bone marrow transplantation: stage IV and age over 1 year; n-myc gene

amplification irrespective of the stage

Radiotherapy

Pprognosis: according to stage, genetic and age modifications; survival in patients under one

year of age: 75% and only 25% in patients over one year.

NEPHROBLASTOMA (WILMS TUMOR)

Epidemiology:

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The most common malignant renal tumor that occurs only in childhood, most commonly in

the age group of 1-5 years; 5-6% of child malignancies, with an incidence of 1: 10,000 in

newborns and equal frequency in both sexes. In 10% of cases it is bilateral. It is commonly

associated with aniridia and genitourinary malformations.

Etiology: unknown; cases occur mostly in young children with genetic anomalies or

familial predisposition, but there are sporadic forms as well. It is a mixt embryonic kidney

neoplasm formed of 3 components: blastemal, stromal and epithelial. The gene responsible

for Wilms tumor is located on chromosome 11.

Clinical features

- abdominal tumor located on a flank; it does not exceed the midline, and is not

breathing-mobile

- abdominal pain, vomiting

- fever, weight loss

- micro / macroscopic hematuria, rarely dysuria, polyuria

- moderate hypertension in 75% of cases (through increased release of renin by the

kidney tumor or compressed kidney tissue)

- metastases are produced by local extension or by hematogenous way: tumor invasion

of the renal vein and inferior vena cava; heart, lung; liver.

Laboratory

- Blood count: anemia - Urine test: ± haematuria, urinary tract infection

- LDH, elevated ESR - Urea, creatinine - usually normal

- Cytogenetic exam

- Histopathology: favorable histology (90%), unfavorable histology (anaplastic and

sarcoma with clear cells) (10%).

- Abdominal ultrasound: highlights renal tumor; possibly liver metastases, in the

inferior vena cava or lymph nodes

- AP and LL chest Rx: presence of metastases

- Abdominal CT: evidence of Wilms tumor as heterogeneous mass, with intratumoral

necrosis ± contrast

- Bone scan, MRI and / or head CT: for head or bone metastases in forms with

unfavorable histology

Differential diagnosis

- Non-neoplastic renal masses: hidronefrotic kidney, polycystic kidney, renal

hematoma

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- Neuroblastoma: tumor mass that displaces the kidney, exceeds the median line;

increased AVM

- Hepatoblastoma, lymphomas

- Splenomegaly

- intestinal tumor

Staging of Wilms tumor

Stage I: completely resectable intrarenal tumor

Stage II: The tumor destroys the renal capsule; peri-renal extension but completely

resectable. Regional lymph nodes are negative

Stage III: macroscopic or microscopic residue after tumor removal,

tumor-infiltrated regional lymph nodes

Stage IV: presence of distant metastases (hematogenous) in the lungs, brain, bone, liver.

Stage V: bilateral tumor.

Treatment

Surgical treatment: formation resection in an oncologic surgical department; if the inferior

vena cava is invaded, chemotherapy and then resection are performed

Chemotherapy: preoperative and postoperative

Radiotherapy: for stages III and IV and forms with unfavorable histology

Prognosis: depends on the initial tumor staging, histological type and treatment; the chance

of survival in 90% of cases.

References:

1. Baghiu Maria Despina, Horvath Adriennne. Hematologie, oncologie şi endocrinologie pediatrică. Note de

curs pentru medici rezidenţi. Litografia UMF Târgu Mureş, 2007

2. Lanzkowsky P. Manual of Pediatric Hematology and Oncology, 4th edition. Elsevier, 2005

3. Muntean I şi colab. Vademecum de pediatrie. Ed.Medicală Bucureşti, 2007

4. Pinkerton Ross, Shankar A.G, Matthay Katherine. Evidence-based pediatric oncology. 2th edition;

Blackwell Publishing, 2007