Diarrhea : Pathophysiology and Management

Prof.DR.Subijanto,MS,dr,SpA(K)DR.Reza Ranuh,dr,SpA(K)

Alpha Fardah,dr,SpAAndy Darma, SpA

Dept.of Child Health Soetomo Hospital – Medical Faculty Airlangga University

Kuliah Semester VI - 2010

Objectives Understand the pathophysiology Diagnose Comprehensive Management

Annual Under-Five Mortality in Developing Countries

◦ Annual mortality from diarrhea in children less than five years old in developing countries1.8 million deaths

◦ Decreased from 4.5 million deaths in last 20 years

Perinatal problems : 34.7 % Respiratory problems : 27.6 % Diarrhea : 9.4 % Gastrointestinal

disturbance : 4.3 % Unknown : 4.1 % Neurological disease : 3.2 %

4

Household Survey 1992 & 1995National Medical Survey 2001

Respiratory problems : 34.7 % Diarrhea : 27.6 % Neurological disease : 9.4 % Typhoid Fever : 4.3 % Gastrointestinal disturb. : 4.1 % Other infections : 3.2 %

5

Household Survey 1995National Medical Survey 2001

Mortality and Diarrhea (Soetomo Hospital 2008)

0102030405060708090

100

SurviveDead%

Reza Ranuh, 20008

* Approximately 70% of all childhood deaths are associated with one or more of these 5 conditions

Diarrhoea15%

Measles8%

Malaria7%HIV/AIDs

3%

Others49%

Pneumonia18%

Malnutrition*54%

Distribution of 10.5 million deaths among children under 5 years old in all developing countries, 1999

Definition and Pathophysiology

What is Diarrhea ?

Stools of decreased consistency and increased volume due to imbalance of secretion and absorption of water and salts in the intestine

Types of Diarrhea in Developing Countries

Noninfectious (infrequent), e.g., congenital, inflammatory bowel disease

Infectious (predominant), e.g., bacterial, viral, parasitic

Osmotic

Lactase def.Lactose intol.Non absorbablesubstanceOsmotic effectWater retainedLarge volumediarrhea

Excessive secretion of fluid and electrolyteInduced by e.toxin,hormone produced bytumorLarge volume diarrhea

Excessive motilityDecrease transit T surface mucosal contact absorptionLarge volume diarrhea

Secretoric Motile

DIARRHEA

Secretion of Water and Electrolytes

Na+

K+

Cl-

Na+

K+Cl-

Na+

H2OLUMEN

Enterocyte

Enterocyte Tight Junction

K+

Virulence Factors of Enterotoxigenic Coli

Enterotoxigenic E.coli Infection

Rotavirus Infection

Shigella Infection

Shigellosis (Bacillary Dysentery)

Bacterial infection - Shigella sp. Gram (-), facultative, rods◦ Shigella sonnei◦ Shigella dysenteriae◦ Shigella flexneri◦ Shigella boydiiIncubation period:◦ 12 hours to 2 weeks

Usually fever Mild case of Shigellosis

◦ Traveler’s Diarrhea◦ Montezuma’s Revenge◦ Green Apple Two Step

Shigella sonnei

Toxin

Shiga toxin - Kiyoshi Shiga◦ Unusually virulent◦ Bacteria invade intestinal mucosa – produce toxin◦ Severe diarrhea with blood in stool (dysentery)◦ Toxin inhibits Protein Synthesis

Cells lining G.I. tract are shed◦ Up to 20 bowels movements a day

20,000 – 30,000 cases per year in U.S.

5 – 15 deaths

Shigella dysenteriae – more severe - Mortality Rate = 20 %

Salmonellosis (Salmonella Gastroenteritis) Bacterial Infection – Salmonella sp. Salmonella

◦ Gram (-), facultative, non-spore forming rods◦ Found in G.I. Tract of humans and many animals◦ All are considered pathogenic

Taxonomy ◦ Use serotype rather than species◦ Over 2000 serotypes (50 common in U.S.)

Salmonella arizonae Salmonella brazil Salmonella atlanta Salmonella pakistan Salmonella berlin Salmonella california

Salmonellosis Incubation time 12 – 36 hours Bacteria invade the intestinal mucosa

and multiply May pass thru mucosa into lymphatic or

circulatory system and become systemic Fever, abdominal pain, cramps and

diarrhea

Salmonellosis

1 billion Salmonella per gram of feces Mortality rate < 1 %

◦ Higher in infants and elderly Recovery in a few days

◦ Some may shed bacteria in feces for 6 months

Salmonellosis

Contamination◦ Meats, poultry, eggs, pet reptiles (turtles)

Undercooked or Raw Eggs◦ Hollandaise sauce◦ Cookie batter◦ Caesar salads◦ “Sunny side up” fried eggs

Cholera

Vibrio cholerae - Gram (-) curved rod Endemic in Asia and India Cholera toxin

◦ Secretion of Cl- leads to H2O loss and diarrhea◦ 12 – 20 liters of fluid per day ( 3 – 5 gallons)

Staphylococcal Food Poisoning (Staphylococcal intoxication)

Ingesting an enterotoxin by Staph. aureus Staphylococci

◦ High resistance to heat ◦ Resistant to drying out◦ Resistant to high osmotic pressures◦ Resistant to high salt conc.

◦ Found in nasal passages and hands Contaminate food

Etiology : Virus, Bacterial, Protozoa

Dehydrated Under-Fives with Diarrhea : Bangladesh

Percentage of children less than five years old experiencing dehydration during diarrheal episodes, by enteropathogen, in community-based studies in rural Bangladesh

ISOLATION FREQUENCY OF ENTEROPATHOGENS IN 2000

16%

84%

No. pathogenpositive

No. pathogennegative

Tropical Disease Center Airlangga University 2002

Detection of Enteropathogens in Dept. of Child Health Soetomo Hospital 2000

0

5

10

15

20

25

30

35

40

45

Rotavirus

Rotavirus-DE.coliShigella

Salmonella

V.cholerae

%

Tropical Disease Center Airlangga University 2002

Waterborne Bacteria

Escherichia coli

Vibrio sp.

Waterborne Bacterial Pathogens

Bacteria Reservoir Diseases

Campylobacter sp Human,animal AGI

Pathogenic E. coli[e.g.,EHEC O157:H7]

Human,animal diarrhea, dysentery

Pseudomonas sp. Free-living ear, eye, skin

Salmonella sp. Human,animal AGI, diarrhea

Shigella sp. Human,animal diarrhea, dysentery

Vibrio sp. Human,animal diarrhea, cholera

Helicobacter pylori Human,animal gastritis, ulcers

Legionella Free-living pneumonia

Leptospira sp. Animal,free-living

Protozoal diarrhea

Giardia lamblia and entamoeba histolytica are protozoa associated with diarrhea

Usually acquired traveling to mountainous or recreational water areas, drinking stream or pond water

Giardia sp.*

Waterborne Protozoan Pathogens

Protozoan Reservoir DiseaseCryptosporidium sp. Human,animal Diarrhea

Giardia sp. Human,animal AGI

Entamoeba sp. Human AGI, diarrhea

Naegleria fowleri Free-living PAM (fatal)

Balantidium coli Human,animal AGI, diarrhea

Cyclospora sp. Human,animal diarrhea

Waterborne Protozoans

Cryptosporidium sp.**P. Darben

Rotavirus

Transmission of Rotavirus

Fecal-oral Contaminated water supplies Poor hygiene Food Fomites

Rotavirus: Clinical Syndromes

Childhood gastroenteritis◦ Endemic in tropics◦ Winter in temperate zone

Outbreaks◦ Day care centers◦ Hospitals

Immunocompromised adults

How does Rotavirus cause diarrhea?

Injures intestinal epithelium◦ Malabsorption

Increases secretion by epithelium

Rotavirus Clinical Syndromes

Asymptomatic carriers

Diarrheal illness◦ 2-3 day incubation

period◦ diarrhea, vomiting,

fever 3-7 days◦ high infectivity

Complications◦ dehydration◦ chronic diarrhea◦ dissemination◦ NEC

Diagnostic and Evaluation

Diagnostic Evaluation

1. History2. Physical examination

Assessment: History

Etiology Patogenesis (course of disease) Patofisiologi Patology (injury mucosa)

Physical examination Vital sign Dehydration Imbalance electrolyte Imbalance acid-base Mucosal injury Accompanying disease

Type of Dehydration

1. Isotonic (affect ECF ,Na = 135meq /l)2. Hypotonic( loss in ECF 2 correct ICF, Na = less than

135meq/l )3. Hypertonic ( sever loss in ICF ,Na = more than 150meq/l

0

10

20

30

40

50

60

Age

Neonatus

Infant

Toddler

Child

%

Reza Ranuh, 20008

Age Distribution

Dehydration Status

0

10

20

30

40

50

60

Dehydration Status

Non Dehydration

Mild

Moderate

Severe

%

Reza Ranuh, Soetomo Hospital 2008

Serum Electrolyte Inbalance

0

10

20

30

40

50

60

70

Hypo NaHyper NaNormal NaHypo KHyper KNormal K

%

Reza Ranuh, Soetomo Hospital 2008

Nutrition Status

0

5

10

15

20

25

30

35

40

45

Nutrition Status

Wellnourished Over Nourished Under Nutrition Severe Malnutrition

Reza Ranuh, Soetomo Hospital 2008

%

0

10

20

30

40

50

60

70

80

2004 2005 2006 2007 2008

with

without

Diarrhea and Accompanying Diseases 2004-2008

%

Reza Ranuh, Soetomo Hospital 2008

Distribution of Accompanying Diseases

0

10

20

30

40

50

60

70

Accompanying Diseases

Without Accompanying dis Bronchopnemonia Febrile convulsion

Under Nutrition Marasmic Kwarsiorkor Others

%

Reza Ranuh, Soetomo Hospital 2008

Complications of Diarrhea

Acute diarrhea may cause severe dehydration and electrolyte imbalance

Infants, young children, and the elderly are most at risk for dehydration

Children less than 2 yrs of age often have complications that require hospitalization

Physical Signs of Dehydration

Signs & Sympt. Mild Moderate Severe

General Thirsty, allert,restless

Thirsty, irritable,Or drowsy

Dowsy – limp, skin cold/sweaty

Radial pulse Normal rate Rapid and weak Rapid, feeble

Respiration Normal Deep Deep and rapid

Anterior font Normal Sunken Very sunken

Skin turgor Pinch retracts immediately

Retracts slowly Poor

Eyes Normal Sunken Grossly sunken

Tears Present Absent Absent

Mucous memb. Moist Dry Very dry

Urine flow Normal Dark & decreased

Oliguria/anuria

Management Diarrhea

New Recommendations on the Management of Diarrhoea

New Recommendations on the Management of Diarrhoea

Global Diarrhoea Treatment Policy

Treatment of dehydration with ORS solution (or with an intravenous electrolyte solution in cases of severe dehydration)

Provide children with 20mg per day of zinc for 10-14 days

Continue feeding or increase breastfeeding during, and increase feeding after the diarrhoeal episode

Use antibiotics only when appropriate (i.e. bloody diarrhoea and cholera) and abstain from administering anti-diarrhoeal drugs (including probiotics)

Advise mothers on danger signs and on compliance with the treatments

WHO/UNICEF. Joint statement on the clinical management of acute diarrhoea. 2004.

Mengganti cairan dan elektrolit yang hilang. Rumatan. Mengganti on going abnormal losses. Tergantung individu.

Prinsip Terapi Cairan

65

Composition of the New ORS - 2004

NaCl 2.6 g Na Citrate 2.9

g KCl 1.5

g Glucose 13.5

g

Na+ 75 mEq/l K+ 20 mEq/l Citrate 10 mmol/l Cl- 65 mEq/l Glucose 75 mmol/l

Osmolar. 245 mmol/l

Reduced Osmolarity ORS Solution

Stool output is reduced by 25 to 30%

Vomiting is reduced by 30%, and

The need for unscheduled IV fluids is reduced by more than 35%

The Molecular process of ORT

CONCLUSION

A group of experts recommended that:

a single ORS solution be used and that this ORS solution contain 75 mEq/l of sodium and 75 mmol/l of glucose, and have a total osmolarity of 245 mOsmol/l;

this reduced osmolarity ORS be used in place of standard ORS for treatment of adults with cholera.

Plan Degree of dehydration

Estimation of fluid

Type of solution

Route of treatment

A Normovolemia 10-20 ml/kg/diarrhea

ORS oral

B Moderate 6-9%

Mild

70ml/kg/3h

50ml/kg/3h

HSD/ORS

HSD/ORS

Iv/intra gastric

Oral/iv/intragastric

C Severe 30ml/kg/1h Ringer Lactate

iv

Pediatric Fluid Rehydration (iso-hyponatremia)

Bronchopnemonia, Severe Malnutrition; Neo/<3 Mo : D10%0,18 NaCl : severe : 30ml/kg/2h ; Mild :70ml/kg/6h

Hypernatremia : HSD 320ml/kh/48h

Pediatric Standard Therapy of Soetomo Hospital 2008

Pediatric Fluid Therapy Principles

Maintenance H2O needs:

Weight in Kg H2O fluid needs1-10 100cc /kg /day11-20

1000+50cc/kg/day> 20 1500 +

20cc/kg/day Add 12 % for every 0C

73

Severe Malnutrition

Do not use the IV route for rehydration except in cases of shock

ReSoMal 5ml/kg/30 minutes for first 2 hrs ; then 5-10 ml/kg/h for the next 4-10 hrs

ReSoMal : 37.5mmol Na, 40mmol K and 3 mmol Mg per litre

Severe Malnutrition

Severe Malnutrition

Severe Malnutrition

Low

Inter-mediate

High

~33% of the world’s population live in countries with a high risk

of zinc deficiency

Zinc Defiency

Low

Inter-mediate

High

Zinc for the Treatment of DiarrhoeaResearch Findings

20% reduction in duration of acute diarrhoea Significant reduction in diarrhoea severity 24% reduction in duration of persistent

diarrhoea 42% reduction in treatment failure or death

in persistent diarrhoea

Additional Preventive Aspects of Zinc Treatment

Zinc supplementation for 10-14 has longer term effects on childhood illnesses in the 2-3 months after treatment

34% reduction in prevalence of diarrhoea 26% reduction in incidence of pneumonia Zinc Dose : < 6 Mo (10mg) for 10 days > 6 Mo (20 mg)

Zinc Investigators’ Collaborative Group. Pediatrics. 1999.

Mechanisms of Action of ZINC

"Booster" effect on immune function: Zinc is the main-cofactor of immune function enzymes

Anti-Secretory effect: Zinc acts as a K channel blocker of cAMP mediated chlorine secretion, leading to increased absorption of Na+ et reduced secretion of Cl

Anti-oxydative effect: maintenance of tissue integrity

Useful action Harmful action

Synthesis of vitamins

Digestion and

absorption

Prevention of

Infection

Stimulation of

immunity

Microbes

Intestinalputrefaction

Microbialtoxin

CarcinogenicRelated substance

Pathogen

Bacteriodes

Eubacterium

Anaerobic Streptococcus

Bifidobacterium

Enterococcus

Escherichia

Lactobacillus

Veillonella

Clostridium

Staphylococcus

Proteus

Pseudomonas

Pengaruh Flora normal

Bifidobacteria – E.coli

0

0.5

1

1.5

2

2.5

3

3.5

4

days

Diarrhea Hospitalization

Control Probiotic

Diarrhea : Student t test ; t = -7.778 ; df = 98 ; p = 0.001 ( significant )

Hospitalization : Student t test ; t = -7.33 ; df = 98 ; p = 0.001 ( significant )

Duration Diarrhea and Hospitalization

Conclusion on Probiotics

Probiotics may be efficacious in shortening diarrhoea, however

There is not enough evidence from community-based studies, and from developing countries to make any global recommendation for use of probiotics in the management of diarrhoea

89

Penyebab(1)

Antibiotika Terpilih(2)

Pilihan Lain

Kolera Tetraksiklin Anak diatas 7 thn 50

mg/kg/hr dibagi 4 dosis untuk 2 hari.

Furasolidon Anak 5 mg/kg/hr dibagi 4

dosis untuk 3 hari

Shigella2 Trimetoprim (TMP) dan Sulfametoksasol (SMX) Anak –TMP 10 mg/kg/hr

dan SMX 50 mg/kg/hr

Asam nalikdisat Anak –55 mg/kg/hr dibagi

4 dosis selama 5 hari

Trimetoprim (TMP)Sulfametoksasol (SMX) 4Semua umur – TMP 8 mg/kg/hr

AmebiasisUsus akut

Metronidasol

Anak – 30 mg/kg/hr selama 5 – 10 hari

Pada kasus yang berat : injeksi intra muskuler, dalam dehidro emetin hidrokhlorida1 – 1,5 mg/kg (maks 90 mg) s.d. 5 hari tergantung reaksi (untuk semua umur)

Giardiasis Metronidasol

Anak –15 mg/kg/hr selama 5 hari

Kuinakrin

Anak – 7 mg/hr dosis terbagi dalam dosis terbagi – 5 hari

Obat antimikroba yang digunakan

Global Diarrhoea Treatment Policy Treatment of dehydration with ORS solution (or with an

intravenous electrolyte solution in cases of severe dehydration)

Provide children with 20mg per day of zinc for 10-14 days Continue feeding or increase breastfeeding during, and

increase feeding after the diarrhoeal episode Use antibiotics only when appropriate (i.e. bloody diarrhoea

and cholera) and abstain from administering anti-diarrhoeal drugs (including probiotics)

Advise mothers on danger signs and on compliance with the treatments

WHO/UNICEF. Joint statement on the clinical management of acute diarrhoea. 2004.

New Recommendations on the Management of Diarrhoea

Risk Factors, Transmission and

Prevention

Seasonality in Developing Countries

Bacterial diarrheas usually peak in hot months

Viral diarrheas may have some peak in cooler months, but transmission continues year round

Seasonality of Diarrhea in East of Java 2003

0

10

20

30

40

50

60

70

80

90

100

J an Peb Maret April Mei Juni Juli Agust Sept Okt Nop Des

Transmission of Infectious Agents Causing Diarrhea

◦ “Fecal–oral”viaFood◦ Water◦ Hands

Infectious Dose Affects Transmission

Low infectious dose(e.g., shigella, giardia, rotavirus, cryptosporidium) can be transmitted by person-to-person contact

High infectious dose(e.g., salmonella, E. coli,vibrios) usually transmitted by water or food

Preventive Interventions for Diarrhea Mortality

Breastfeeding and complementary feeding Improving food safety, water, sanitation, and

hygiene Vitamin A Zinc Measles immunization Future—specific vaccines, e.g., for rotavirus,

ETEC (enterotoxigenic Escherichia coli), shigella Rotavirus vaccination

Risk Factors for Childhood Diarrhea

Suboptimal breastfeeding Contaminated complementary foods Poor quality of water Poor sanitation and hygiene Malnutrition and micronutrient deficiencies - vitamin A deficiency

- zinc deficiency