PATHOPHYSIOLOGY OF PATHOPHYSIOLOGY OF ORGAN FAILUREORGAN FAILURE

H.W. ALIDUH.W. ALIDU

hwalidu@uhas.edu.gh

•HEART FAILURE

Notes to heart physiologyNotes to heart physiology

• Essential functions of the heartEssential functions of the heart

• to cover metabolic needs of body tissueto cover metabolic needs of body tissue (oxygen, substrates) by adequate blood (oxygen, substrates) by adequate blood supplysupply

• to receive all blood comming back from the tissue to receive all blood comming back from the tissue to the heartto the heart

• Essential conditions for fulfilling these functionsEssential conditions for fulfilling these functions

• normal structure and functions of the heartnormal structure and functions of the heart

• adequate filling of the heart by bloodadequate filling of the heart by blood

Adaptive mechanisms of the heart to increased load

• Ventricular hypertrophy – increased mass of contractile elements strength

of contraction

• Increased sympathetic adrenergic activity – increased contractility

• Incresed activity of R–A–A system

PreloadPreload

Stretching the myocardial fibers during diastole by Stretching the myocardial fibers during diastole by

increasing end-diastolic volume increasing end-diastolic volume force of contraction force of contraction

during systole = during systole = Starling´s lawStarling´s law

preloadpreload = = diastolic muscle sarcomere length leading to increased diastolic muscle sarcomere length leading to increased tension in muscle before its contraction tension in muscle before its contraction (Fig.2,3)(Fig.2,3)

- venous return to the heart is important venous return to the heart is important end-diastolic end-diastolic volume is influenced

- stretching of the sarcomere maximises the number stretching of the sarcomere maximises the number of actin-myosin bridges responsible for development of actin-myosin bridges responsible for development of forceof force

- - optimal sarcomere length optimal sarcomere length 2.2 2.2 mm

The pressure – volume loop

• It is the relation between ventricular volume and pressure

• This loop provides a convenient framework for understanding

the response of individual left ventricular contractions

to alterations in preload, afterload, and contractility

• It is composed of 4 phases:

- filling of the ventricle

- isovolumic contraction of ventricle

- isotonic contraction of ventricle(ejection of blood)

- isovolumic relaxation of ventricle

It It is expressed as tension which must be developedis expressed as tension which must be developed in in the wall of ventricles during systole to open the the wall of ventricles during systole to open the semilunar valvesemilunar valvess and eject blood to and eject blood to aorta/pulmunary aorta/pulmunary arteryartery

afterloadafterload:: due to - elevation of arterialdue to - elevation of arterial resistance resistance - - ventricular size ventricular size - myocardial hypotrophy- myocardial hypotrophy

afterloadafterload:: due to - due to - arterial arterial resistance resistance - myocardial hypertrophy- myocardial hypertrophy - - ventricular size ventricular size

AfterloadAfterload

Heart failureHeart failure

DefinitionDefinition

It is the pathophysiological process in whichIt is the pathophysiological process in which

the heart as a pump is unable to meetthe heart as a pump is unable to meet

the metabolic requirements of the tissue for the metabolic requirements of the tissue for

oxygen and substrates despite the venousoxygen and substrates despite the venous

returnreturn to heart to heart is either normal or increased is either normal or increased

Explanation of the termsExplanation of the terms

• Myocardial failureMyocardial failure == abnormalities reside in the abnormalities reside in the myocardiummyocardium and lead and lead

to to inability of inability of myocardium myocardium to fulfilling its to fulfilling its function function

• Circulatory failureCirculatory failure = = any abnormality of the circulationany abnormality of the circulation responsible for the inadequacy in bodyresponsible for the inadequacy in body tissuetissue perfusion, e.g. decreased blood volume, perfusion, e.g. decreased blood volume, changeschanges of vascular tone, heart of vascular tone, heart functiones functiones disordersdisorders

• Congestive heart failureCongestive heart failure = clinical syndrome which is = clinical syndrome which is developed developed due to due to accumulation of the blood inaccumulation of the blood in frontfront

of the left or right parts of the of the left or right parts of the

heartheart

General pathomechanisms involved in heart General pathomechanisms involved in heart failure developmentfailure development

Cardiac mechanical dysfunction can developCardiac mechanical dysfunction can develop as as

a a consequence in preload, contractility and afterload consequence in preload, contractility and afterload

disordersdisorders

Disorders of preloadDisorders of preload

preloadpreload length of sarcomere is more than optimal length of sarcomere is more than optimal strength of contractionstrength of contraction

preloadpreload length of sarcomere is well below thelength of sarcomere is well below the optioptimalmal strength of contractionstrength of contraction

Important:Important: failing ventricle requires higher end-diastolicfailing ventricle requires higher end-diastolic volume volume

to achieve the same improvement of CO that to achieve the same improvement of CO that

normalnormal

ventricle achievesventricle achieves with lower ventricular with lower ventricular

volumesvolumes Disorders of contractilityDisorders of contractility

In In the the most forms of heart failure the contractility ofmost forms of heart failure the contractility of myocardium myocardium

is decreased (ischemia, hypoxiais decreased (ischemia, hypoxia,, acidosis, acidosis, inflammation, toxins, inflammation, toxins,

metabolic disordersmetabolic disorders...... ) )

Disorders of afterloadDisorders of afterload due to: due to:

• fluid retentionfluid retention in the body in the body

• arterial resistancearterial resistance

• valvular heart diseases ( stenosisvalvular heart diseases ( stenosis ))

Characteristic features of systolic dysfunction

(systolic failure)

• ventricular dilatation

• reducing ventricular contractility (either generalized or localized)

• diminished ejection fraction (i.e., that fraction of end-

diastolic

blood volume ejected from the ventricle during each

systolic

contraction – les then 45%)

• in failing hearts, the LV end-diastolic volume (or

pressure)

may increse as the stroke volume (or CO) decreases

Characteristic features of diastolic dysfunctions(diastolic failure)

• ventricular cavity size is normal or small

• myocardial contractility is normal or hyperdynamic

• ejection fraction is normal (>50%) or supranormal

• ventricle is usually hypertrophied

• ventricle is filling slowly in early diastole (during the period

of passive filling)

end-diastolic ventricular pressure is increased

Causes of heart pump failureCauses of heart pump failure

A. MECHANICAL ABNORMALITIESA. MECHANICAL ABNORMALITIES

1. Increased pressure load1. Increased pressure load

– – ccentral (aortic stenosisentral (aortic stenosis, aortic coarctation..., aortic coarctation...))

–– pperipheral (systemic hypertension)eripheral (systemic hypertension)

2. Increased volume load2. Increased volume load– – valvular regurgitationvalvular regurgitation

– hypervolemia

3. Obstruction to ventricular filling3. Obstruction to ventricular filling –– valvular stenosisvalvular stenosis

–– pericardial restrictionpericardial restriction

B. MYOCARDIAL DAMAGEB. MYOCARDIAL DAMAGE

1. Primary1. Primary

a) a) ccardiomyopathyardiomyopathy

b) b) mmyocarditisyocarditis

c) c) ttoxicity (oxicity (e.g. e.g. alcohol)alcohol)

d) d) mmetabolic abnormalities (etabolic abnormalities (e.g. e.g. hyperthyreoidismhyperthyreoidism))

2. Secondary2. Secondary

a) a) ooxygen deprivation (xygen deprivation (e.g. e.g. coronary heart disease)coronary heart disease)

b) b) iinflammation (nflammation (e.g. e.g. increased metabolic demands)increased metabolic demands)

c) c) cchronic obstructive lung diseasehronic obstructive lung disease

C. ALTERED CARDIAC RHYTHMC. ALTERED CARDIAC RHYTHM

1. 1. vventricular entricular flutter and flutter and fibrilationfibrilation

2. 2. eextreme tachycardiasxtreme tachycardias

3. 3. eextreme bradycardiasxtreme bradycardias

Pathomechanisms involved in heart failurePathomechanisms involved in heart failure

A. Pathomechanisms involved in myocardial failureA. Pathomechanisms involved in myocardial failure

1.1. Damage of cardiomyocytesDamage of cardiomyocytes contractility, contractility,

Consequences:Consequences: defect in ATP production and utilisationdefect in ATP production and utilisation

changes in contractile proteinschanges in contractile proteins

uncoupling of excitation – contraction processuncoupling of excitation – contraction process

number of cardiomyocytesnumber of cardiomyocytes

impairment of relaxation of cardiomyocytes withimpairment of relaxation of cardiomyocytes with decrease decrease compliance of myocardiumcompliance of myocardium

impaired of sympato-adrenal system (SAS) impaired of sympato-adrenal system (SAS) numbernumber of of 11-adrenergic receptors on the surface of -adrenergic receptors on the surface of

cardiomycytescardiomycytes

Chronic heart failure (CHF) is characterized by an imbalance of Chronic heart failure (CHF) is characterized by an imbalance of

neurohumoral adaptive mechanisms with a net results of excessive neurohumoral adaptive mechanisms with a net results of excessive vasoconstriction andvasoconstriction and salt and water retentionsalt and water retention

Catecholamines :Catecholamines : - concentration in blood :- concentration in blood :

- norepinephrin – 2-3x norepinephrin – 2-3x higher at the rest than in healthy subjectshigher at the rest than in healthy subjects

- - circulating norepinephrin is increased much more circulating norepinephrin is increased much more during equal load in patients suffering from CHF than during equal load in patients suffering from CHF than in in healthy subjecthealthy subject

- number of beta 1 – adrenergic receptors number of beta 1 – adrenergic receptors sensitivity ofsensitivity of cardiomyocytes to catecholamines cardiomyocytes to catecholamines contractilitycontractility

System rennin – angiotensin – aldosteronSystem rennin – angiotensin – aldosteron

hheart failureeart failure CO CO kidney perfusion kidney perfusion stim stim.. Of Of RAA RAA systemsystem

Important:Important:

Catecholamines and system RAA = compensatory mechanisms

heart function and arterialheart function and arterial BPBP

The role of angiotensin II in development of heart The role of angiotensin II in development of heart failurefailure

vasoconstriction ( in resistant vesels)vasoconstriction ( in resistant vesels)

retention of Na retention of Na blood volume blood volume

releasing of arginin – vasopresin peptide (AVP ) releasing of arginin – vasopresin peptide (AVP ) fromfrom neurohypophysisneurohypophysis

sensitivity of vessel wall to norepinephrinesensitivity of vessel wall to norepinephrine

mitogenic effect on smooth muscles in vessels and mitogenic effect on smooth muscles in vessels and

onon cardiomyocytes cardiomyocytes hypertrophy hypertrophy

constriction of vas efferens ( in glomerulus )constriction of vas efferens ( in glomerulus )

sensation of thirstsensation of thirst

secretion of aldosteron from adrenal glandsecretion of aldosteron from adrenal gland

mesangial conctraction mesangial conctraction glomerular filtration rateglomerular filtration rate

facilitation of norepinephrine releasing from facilitation of norepinephrine releasing from sympatheticsympathetic nerve endingsnerve endings

Pathophysiology of diastolic heart failurePathophysiology of diastolic heart failure

systolic heart failuresystolic heart failure = = failure of ejecting function of the heartfailure of ejecting function of the heart

diastolic heart failurediastolic heart failure = = failure of filling the ventricles,failure of filling the ventricles,

resistanceresistance to filling to filling of ventricles of ventricles

But,But, wwhich of the cardiac cycle ishich of the cardiac cycle is real real diastole ? diastole ?

Diastolic failure is a widely recognized clinical entity

Definition of diastolic heart failureDefinition of diastolic heart failure

It is pathophysiological process characterized by symptoms It is pathophysiological process characterized by symptoms

and signs of congestive heart failure, which is caused byand signs of congestive heart failure, which is caused by

increased filling resistance of ventricles and increased filling resistance of ventricles and iincreasedncreased

intraventricular diastolic pressureintraventricular diastolic pressure

Primary diastolic heart failurePrimary diastolic heart failure

- no signs and symptoms of systolic dysfunctionno signs and symptoms of systolic dysfunction is present is present

-- ! up to 40% ! up to 40% of of patients suffering from heart failure!patients suffering from heart failure!

Secondary diastolic heart failureSecondary diastolic heart failure

- diastolic dysfunction is the consequence of- diastolic dysfunction is the consequence of primary primary systolic systolic dysfunctiondysfunction

Causes and mechanism participating on impairedCauses and mechanism participating on impaired ventricular relaxationventricular relaxation

a)a) physiological changesphysiological changes in chamber relaxation in chamber relaxation due todue to: :

– – prolonged ventricular contraction prolonged ventricular contraction

Relaxation of ventricles is not impairedRelaxation of ventricles is not impaired !

b) pathological changesb) pathological changes inin chamber relaxation chamber relaxation due todue to: : IImpaired relaxation processmpaired relaxation process

delayed relaxation (retarded)delayed relaxation (retarded)

incomplete (slowed) relaxationincomplete (slowed) relaxation

Main causes and mechanisms involved in Main causes and mechanisms involved in pathological remodelation of the heartpathological remodelation of the heart

1.Increased amount and size1.Increased amount and size of myocytesof myocytes == hypertrophyhypertrophy

Due to:Due to: - - volume and/or pressure load volume and/or pressure load (excentric, concentric hypertrophy(excentric, concentric hypertrophy))

- hormonal stimulation of cardiomyocytes by - hormonal stimulation of cardiomyocytes by norepinephrine, angiotenzine IInorepinephrine, angiotenzine II

2. Increased 2. Increased % % ofof non-myocytnon-myocyticic cells cells iin myocardiumn myocardium and and their their influenceinfluence on structure and function of heart on structure and function of heart

a.a. endothelial cellsendothelial cells – – endothelins :endothelins : mitogenic ability mitogenic ability stimulation growth of smooth muscle cells of vessels, fibroblastsstimulation growth of smooth muscle cells of vessels, fibroblasts

b.b. fibroblastsfibroblasts - - production of kolagens production of kolagens

Symptoms and signs of heart failureSymptoms and signs of heart failure

1.1. forward failure:forward failure: symptoms result from inability of the heart to pump enough symptoms result from inability of the heart to pump enough

blood to the peripheryblood to the periphery (from(from left heart), or to the lungs (from left heart), or to the lungs (from

the right heart)the right heart)

a) forward failure of left heart:a) forward failure of left heart:-- muscle weakness, fatigue, muscle weakness, fatigue, dyspepsia, oliguriadyspepsia, oliguria........

generalgeneral mechanism mechanism:: tissue hypoperfusiontissue hypoperfusion

b) forward failure of right heartb) forward failure of right heart:: - hypoperfusion of the - hypoperfusion of the lungs lungs disorders of gas disorders of gas exchangeexchange

- decreased blood supply decreased blood supply to the left heartto the left heart

2. backward failure:2. backward failure: – symptoms result from inability of the heart to accept symptoms result from inability of the heart to accept

the blood comthe blood commming from periphery and from lungsing from periphery and from lungs

a.a. backward failure of left heart:backward failure of left heart:

– – increased pulmonary capillary pressureincreased pulmonary capillary pressure dyspnoea dyspnoea

and tachypnoea, pulmonary edema (cardiac asthma) and tachypnoea, pulmonary edema (cardiac asthma)

arterial arterial hypoxhypoxemiaemia and hypercapnia and hypercapnia........

b. backward failure of right heart:b. backward failure of right heart:

– increased pressure in increased pressure in systemic systemic venous systemvenous system

peripheral edemas, hepatomegaly, ascites peripheral edemas, hepatomegaly, ascites nocturnalnocturnal diuresisdiuresis........

• RENAL FAILURE

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Age-Related Changes

• Nephrons lost with aging– Reduces kidney mass and GFR

• Less urine concentration– Risk for dehydration

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Assessment

• Color, clarity, amount of urine

• Difficulty initiating urination or changes in stream

• Changes in urinary pattern

• Dysuria, nocturia, hematuria, pyuria

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Assessment• History of urinary problems

• Urinary or abdominal surgeries

• Smoking, alcohol use, number of sexual partners and type of sexual relationship

• Chance of pregnancy

• History of diabetes or other endocrine disorders

• History of kidney stones

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Physical Assessment

• Obtain clean-catch urine specimen– Color, odor, clarity

• Vital signs and skin assessment

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Diagnostic Tests

• Clean-catch urine

• 24-hour urine

• Culture and sensitivity

• BUN, creatinine and creatinine clearance

• CT scan

• Renal scan

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Diagnostic Tests

• Ultrasound

• Bladder scan

• Cystoscopy

• Uroflowmetry

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Renal FailureAcute and Chronic

Renal Obstructive Disorder

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Acute Renal Failure

• Sudden interruption of kidney function resulting from obstruction, reduced circulation, or disease of the renal tissue

• Results in retention of toxins, fluids, and end products of metabolism

• Usually reversible with medical treatment• May progress to end stage renal disease, uremic

syndrome, and death without treatment

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Acute Renal Failure

• Persons at Risks– Major surgery– Major trauma– Receiving nephrotoxic medications– Elderly

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Acute Renal Failure

• Causes– Prerenal

• Hypovolemia, shock, blood loss, embolism, pooling of fluid d/t ascites or burns, cardiovascular disorders, sepsis

– Intrarenal • Nephrotoxic agents, infections, ischemia and blockages,

polycystic kidney disease

– Postrenal • Stones, blood clots, BPH, urethral edema from invasive

procedures

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Acute Renal Failure

• Subjective symptoms– Nausea– Loss of appetite– Headache– Lethargy– Tingling in extremities

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Acute Renal Failure

• Objective symptoms– Oliguric phase –

• vomiting • disorientation, • edema, • ^K+ • decrease Na • ^ BUN and creatinine• Acidosis• uremic breath

• CHF and pulmonary edema

• hypertension caused by hypovolemia, anorexia

• sudden drop in UOP

• convulsions, coma

• changes in bowels

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Acute Renal Failure• Diagnostic tests

– H&P

– BUN, creatinine, sodium, potassium. pH, bicarb. Hgb and Hct

– Urine studies

– US of kidneys

– ABD and renal CT/MRI

– Retrograde pyloegram: is a urologic procedure where the physician injects contrast into the ureter in order to visualize the ureter and kidney.

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Acute Renal Failure• Medical treatment

– Hemodialysis• Subclavian approach• Femoral approach

– Peritoneal dialysis– Continous renal replacement therapy (CRRT):

The concept behind continuous renal replacement techniques is to dialyse patients in a more physiologic way, slowly, over 24 hours, just like the kidney

• Can be done continuously• Does not require dialysate: the fluid and solutes in a dialysis

process that flow through the dialyzer, do not pass through the membrane, and are discarded along with removed toxic substances after leaving the dialyzer.

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Acute Renal Failure

• Nursing Diagnosis-– imbalanced fluid volume= excess

– Altered electrolyte balance

– Altered cardiac output

– Impaired tissue perfusion: renal

– Anxiety

– Imbalanced nutrition

– Risk for infection

– Fatigue

– Knowledge deficit

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Acute Renal Failure

• Plan-– Promote recovery of optimal kidney function.– Maintain normal fluid and electrolyte balance.– Decrease anxiety.– Increase knowledge.

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Acute Renal Failure

• Nursing interventions– Monitor I/O, including all

body fluids– Monitor lab results– Watch hyperkalemia

symptoms: malaise, anorexia, or muscle weakness, EKG changes

– watch for hyperglycemia or hypoglycemia if receiving TPN or insulin infusions

– Maintain nutrition

– Safety measures

– Mouth care

– Daily weights

– Assess for signs of heart failure

– Skin integrity problems

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• Kidney failure causes hypoglycemia in three separate ways. The kidneys help to generate new glucose from amino acids (called gluconeogenesis). Gluconeogenesis is impaired in kidney failure. Also, insulin circulates for a longer period of time and is cleared slowly when kidney function is poor. The third important reason is that kidney failure reduces the appetite and consequently, oral intake

of food.

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Chronic Renal Failure• Results from gradual, progressive loss of renal

function• Occasionally results from rapid progression of

acute renal failure• Symptoms occur when 75% of function is lost but

considered chronic if 90-95% loss of function• Dialysis is necessary D/T accumulation or uremic

toxins, which produce changes in major organs

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Chronic Renal Failure

• Subjective symptoms are relatively same as acute• Objective symptoms

– Renal• Hyponaturmia• Dry mouth• Poor skin turgor• Confusion, salt overload, accumulation of K with muscle

weakness• Fluid overload and metabolic acidosis• Proteinuria, glycosuria• Urine = RBC’s, WBC’s, and casts

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Chronic Renal Failure

• Objective symptoms– GI

• Stomatitis

• Ulcers

• Pancreatitis

• Uremic fetor (Ammonia breath odour)

• Vomiting

• constipation

– Respiratory• ^ chance of infection

• Pulmonary edema

• Pleural friction rub and effusion

• Dyspnea

• Kussmaul’s respirations

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is a deep and labored breathing is a deep and labored breathing pattern often associated with severe pattern often associated with severe metabolic acidosis, particularly metabolic acidosis, particularly diabetic ketoacidosis (DKA) but also diabetic ketoacidosis (DKA) but also

renal failurerenal failure..

Chronic Renal Failure

• Objective symptoms– Endocrine

• Stunted growth in children

• Amenorrhea

• Male impotence

• ^ aldosterone secretion

• Impaired glucose levels R/T impaired CHO metabolism

• Thyroid and parathyroid abnormalities

– Hemopoietic• Anemia

• Decrease in RBC survival time

• Blood loss from dialysis and GI bleed

• Platelet deficits

• Bleeding and clotting disorders – purpura and hemorrhage from body orifices , ecchymoses

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Chronic Renal Failure

• Objective symptoms– Skeletal

• Muscle and bone pain

• Bone demineralization

• Pathological fractures

• Blood vessel calcifications in myocardium, joints, eyes, and brain

– Skin• Yellow-bronze skin

with pallor

• Puritus

• Purpura

• Uremic frost

• Thin, brittle nails

• Dry, brittle hair, and may have color changes and alopecia

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Uremic frost: Uremic frost: A clinical finding in severe chronic renal failure, in A clinical finding in severe chronic renal failure, in which the concentration of urea is markedly increased in sweat, which the concentration of urea is markedly increased in sweat, causing precipitation of crystallised urea in the skincausing precipitation of crystallised urea in the skin

Chronic Renal Failure• Lab findings

– BUN – indicator of glomerular filtration rate and is affected by the breakdown of protein. Normal is 10-20mg/dL. When reaches 70 = dialysis

– Serum creatinine – waste product of skeletal muscle breakdown and is a better indicator of kidney function. Normal is 0.5-1.5 mg/dL. When reaches 10 x normal, it is time for dialysis

– Creatinine clearance is best determent of kidney function (GFR). Must be a 12-24 hour urine collection. Normal is > 100 ml/min

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Chronic Renal Failure

• Ca– With disease in the kidney, the enzyme for utilization

of Vit D is absent– Ca absorption depends upon Vit D– Body moves Ca out of the bone to compensate and with

that Ca comes phosphate bound to it.– Normal Ca level is 4.5-5.5 mEq/L– Hypocalcemia = tetany

• Treat with calcium with Vit D and phosphate• Avoid antacids with magnesium

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Chronic Renal Failure

• Other abnormal findings– Metabolic acidosis– Fluid imbalance– Insulin resistance– Anemia– Immunoligical problems

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Chronic Renal Failure

• Nursing diagnosis– Excess fluid volume– Imbalanced nutrition– Ineffective coping– Risk for infection– Risk for injury

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Chronic Renal Failure

• Nursing care– Frequent monitoring – Hydration and output– Cardiovascular

function– Respiratory status– E-lytes– Nutrition– Mental status– Emotional well being

– Ensure proper medication regimen

– Skin care

– Bleeding problems

– Care of the shunt

– Education to client and family

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Chronic Renal Failure Treatment

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Chronic Renal Failure

• Medical treatment• IV glucose and insulin• Na bicarb, Ca, Vit D, phosphate binders• Fluid restriction, diuretics• Iron supplements, blood, erythropoietin• High carbs, low protein• Dialysis - After all other methods have failed

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Hemodialysis

• 3-4 times a week

• Takes 2-4 hours

• Machine filters

blood and

returns it to

body

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Chronic Renal Failure

• Hemodialysis– Vascular access

• Temporary – subclavian or femoral

• Permanent – shunt, in arm– Care post insertion

– Can be done rapidly– Takes about 4 hours– Done 3 x a week

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Nursing Considerations• Make sure the dressing remains intact• Do not push or pull on the catheter• Do not disconnect any of the catheters• Always transport the patient and

bags/catheters as one piece• Never inject anything into catheter

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Chronic Renal Failure

• Transplant– Must find donor– Waiting period long– Good survival rate – 1 year 95-97%– Must take immunosuppressant’s for life– Rejection

• Watch for fever, elevated B/P, and pain over site of new kidney

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End-Stage Renal Disease

• Slow, insidious process

• Final stage is end-stage renal disease

• Increasing in incidence

• Diabetic nephropathy and hypertension are leading causes in U.S.

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End-Stage Renal Disease

• Nephrons destroyed by disease process

• Remaining nephrons hypertrophy and have increased workload– Can compensate for a while

• Renal insufficiency develops

• Further insult leads to ESRD– Uremia develops

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End-Stage Renal Disease - Manifestations

• Often not identified until uremia develops• Nausea

• Apathy

• Weakness

• Fatigue

• Confusion

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Obstruction disorders

Causes of Obstruction

•Tumor

•Stones

•Congenital structural defects

•Fibrosis

•Treatment with radiation in pelvis

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Complication of Obstruction

• If untreated, permanent damage can occur within 48 hours

• Renal failure– Retention of

• Nitrogenous wastes (urea, creatinine, uric acid)

• Electrolytes (K, Na, Cl, and Phosphorus)

• Acid base balance impaired

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Renal Calculi• Called nephrolithiasis or urolithiasis• Most commonly develop in the renal pelvis but

can be anywhere in the urinary tract• Vary in size –from very large to tiny• Can be 1 stone or many stones• May stay in kidney or travel into the ureter• Can damage the urinary tract• May cause hydronephrosis• More common in white males 30-50 years of age

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Renal Calculi• Predisposing factors

– Dehydration– Prolonged immobilization– Infection – Obstruction– Anything which causes the urine to be alkaline– Metabolic factors

• Excessive intake of calcium, calcium based antacids or Vit D• Hyperthyroidism• Elevated uric acid

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Renal Calculi- Manifestations

• Kidney/Pelvis– May be asymptomatic– Dull, aching flank pain

• Ureter– Acute severe flank pain, may radiate– Nausea/vomiting– Pallor– Hematuria

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Renal Calculi- Manifestations

• Bladder– May be asymptomatic– Dull suprapubic pain– Hematuria

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Renal Calculi

• Diagnostic procedures– Urinalysis – 24 hour urine– Renal CT– Kidney ultrasound– Cystoscopy with retrograde pyleogram

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Renal Calculi• Treatment

– Most are passed without intervention– May need cysto with basket retrieval – Lithotripsy : Extracorporeal shock wave lithotripsy

(ESWL) is the non-invasive treatment of kidney stones (urinary calculosis) and biliary calculi (stones in the gallbladder or in the liver) using an acoustic pulse.

– Lithotomy: is a surgical method for removal of calculi, stones formed inside certain hollow organs, such as the bladder and kidneys (urinary calculus) and gallbladder (gallstones), that cannot exit naturally through the urethra, ureter or biliary duct

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•LIVER FAILURE

Bilirubin Metabolism: Summary

JAUNDICE/ICTERUS IN ADULTS

• The reference range of bilirubin in adults is up to 17.1 µmol/l

• Jaundice is characterized by the yellowish colouration of the tissues due to retention of pigments

• Experienced physicians discern when blood [bilirubin] is about 35 µmol/l

• It becomes overt when levels are about 55-70 µmol/l

• Jaundice is a symptom of an underlying disease

• JAUNDICE - may be due to (1) pre-hepatic,

(2) hepato-cellular

(3) post-hepatic

Pre-hepatic Jaundice

it may be due to haemytic or non-haemolytic causes Haemolytic jaundice may be due to acquired (malaria) or

congenital(G6PD deficiency) causes It may also be due to ineffective erythropoiesis (pernicious

anaemia) or right sided congestive cardiac failure Non haemolytic jaundice is usually of congenital origin e.g

Criggler-Najjar and Gilberts’syndrome

Hepatocellular Jaundice

• This may be due to defects in conjugation of bilirubin or defects in its hepatic uptake

• Defects in conjugation may result from diffuse hepatic injury which may occur in the following:

• Acute, subacute, chronic and fulminant hepatitis

• Effects of drugs or toxins such as paracetamol, alcohol, CCl4 and halothane

Intra-hepatic cholestasis

• This may occur in subacute or chronic hepatitis

• It may also be due to the effects of drugs such as 17 α-alkylated steroids e.g methyltestosterone or norethisterone

• Phenothiazine e.g chlorpromazine

POST-HEPATIC JAUNDICE

• This is usually due to mechanical obstruction of the biliary tree as a result of:

• Gallstones

• Carcinoma of the head of the pancreas

• Scarring from infection

Laboratory investigation• Usually, the following examinations are taken:

- FBC (haemolysis)

-serum aminotransferase (AST,ALT)

- Serology for hepatitis including HCAb,HBsAg, HBcAb

- ALP: if elevated or if an obstruction is suspected, images of the bile ducts should be obtained.

- GGT

- Fractionated bilirubin

Laboratory differential diagnosis of jaundice

Hemolytic Cholestatic Hepatocellular

Features Bilirubin usually <75µmol/L

No bilirubin in urine

Reticulocytosis

Hemoglobin ↓

Haptoglobin ↓

LDH may ↑

Bilirubin ↑ ↑ ↑

Bilirubin in urine

ALP more than 3x normal range

AST, ALT,LDH

usually modestly ↑

AST, ALT ↑ ↑

Bilirubin ↑later

Bilirubin in urine

ALP ↑ later

INHERITED HYPERBILIRUBINAEMIA

• This may be classified into unconjugated and conjugated types

• The congenital unconjugated hyperbilirubinaemias are Gilberts and Criggler-Najjar Syndromes

• The congenital conjugated hyperbilirubinaemias are Dubin Johnson and Rotor Syndromes

GILBERT’S SYNDROME

• This is a heterogenous condition

• It is characterized by the defective uptake of bilirubin by the hepatocytes

• There may be an associated reduction in the life span of the erythrocytes

• Their serum [bilirubin] is usually between 20-40 µmol/l and rarely exceeds 80 µmol/l

• Their serum bilirubin levels may rise during intercurrent illness or during fasting

• It may present at any age but it commonly presents in the second decade of life.

Crigler-Najjar Syndrome• This is characterized by the deficiency of

hepatic glucuronyl transferase

• Two types of the condition have been described

• Type I is characterized by a marked deficiency of the enzyme which may lead to death from kernicterus at infancy

• Kernicterus i.e. abnormal accumulation of bile pigment in the brain

• Type II is characterized by a partial deficiency of the defective enzyme

• The serum [bilirubin] may be reduced by drugs which induce hepatic enzyme synthesis e.g phenobarbitone

• Crigler-najjar Syndrome usually presents at birth

Dubin- Johnson Syndrome

• This is a rare and benign condition which is characterized by defective excretion of bilirubin but not bile salts

• It is associated with a slightly raised serum conjugated [bilirubin]

• Affected subjects present with bilirubinuria but the Alkaline Phosphatase is normal

• There may be hepatomegaly

• The liver of affected persons has orange-yellow granules

• the liver of subjects is usually dark brown

Rotor Syndrome

• This is also characterized by defective excretion of conjugated bilirubin into the biliary tree

• The liver of affected subjects does not have orange-yellow granules

NEONATAL JAUNDICE• The refernce range of bilirubin in neonates is 8-

67 µmol/l

• In the first week of a neonates life, there may be a physiological hyperbilirubinaemia

• The serum [bilirubin] may rise to as high as 200 µmol/l and is usually prolonged in preterm neonates

Pathophysiology of neonatal jaundice• Neonatal jaundice results due to the following

phenomena:

Increased breakdown of fetal erythrocytes. This is the result of Increased breakdown of fetal erythrocytes. This is the result of the shortened lifespan of fetal erythrocytes and the higher the shortened lifespan of fetal erythrocytes and the higher erythrocyte mass in neonates. erythrocyte mass in neonates.

Hepatic excretory capacity is low both because of low Hepatic excretory capacity is low both because of low concentrations of the binding protein ligandin in the hepatocytes concentrations of the binding protein ligandin in the hepatocytes and because of low activity of glucuronyl transferase, the enzyme and because of low activity of glucuronyl transferase, the enzyme responsible for binding bilirubin to glucuronic acid.responsible for binding bilirubin to glucuronic acid.

CAUSES OF NEONATAL JAUNDICE• Haemolytic disease e.g blood group

incompatibilty and G6PD deficiency

• Immaturity of the hepatic processes for uptake and excretion of bilirubin

• Interference with hepatic transport functions by drugs e.g progeterone or steroids with progesterone-like activity

• Biliary atresia may lead to cholestatic jaundice

• Neonatal hyperbilirubinaemia may be aggravated by:

• Acid-Base disturbances

• Hypoxia

• hypoglycaemia

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Treatment options for Treatment options for

neonatal jaundiceneonatal jaundice

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Risk factors for jaundice JAUNDICE• J - jaundice within first 24 hrs of life• A - a sibling who was jaundiced as neonate • U - unrecognized hemolysis• N – non-optimal sucking/nursing• D - deficiency of G6PD• I - infection• C – cephalhematoma /bruising• E - East Asian/North Indian

Acute Liver Disease

• This may be caused by:

• Poisoning

• Infection

• Inadequate perfusion

Poisoning

• This may result from:

• Paracetamol

• Carbon tetrachloride

• Some plant and fungal toxins e.g amanita phalloides

• Toxins or drugs which give rise to hepatocellular damage in some individuals

Infection

• Both bacteria and viruses may give rise to infective hepatitis

• Viral hepatitis may be associated with viral infections such as infectious mononucleosis (Epstein Barr virus), rubella and cytomegalovirus

• Clinically, viral hepatitis is usually associated with infection by the hepatitis viruses

• Alcoholic hepatitis may also result from extensive alcohol abuse

• It is usually characterized by ↑MCV, hypertriglyceridaemia, hyperuricaemia, ↑GGT as well as moderate increases in aminotransferases and bilirubin

Inadequate Perfusion

• This may result from:

• Severe anaemia

• Trauma

• Dehydration which will result in hypovolaemia

Outcome of acute Liver damage

• Acute liver damage may progress in three ways as follows:

• It may resolve (majority of cases)

• It may progress to acute hepatic failure

• It may lead to chronic hepatic damage

Chronic Liver Disease

• This may be caused by the following:

• Alcoholic fatty liver

• Chronic active hepatitis

• Primary biliary cirrhosis

Chronic active Hepatitis

• This may be caused by active hepatocellular destruction with episodes of relapses and remisssions

• It may occur at any age but is most common in women

• It may be:

• Associated with viral infections such as HBV or HCV or may be induced by drugs

Outcome of Chronic Liver disease

• The outcome of chronic liver disease is Cirrhosis of the Liver

• Cirrhosis is characterized by the shrinking of the liver with the disorganization of its architecture

• The remaining hepatocellular tissue develop fibrosis

• Ascites due to reduced albumin syntheiss which may result in hypovolaemia and hypotension

• Bleeding tendencies due to reduced synthesis of clotting factors

• Terminal liver failure

• The major complaints in cirrhosis may be:

• Difficulty in coping with food especially fatty foods

• Reduced capacity to metabolise drugs

• Pruritis due to disruption of the biliary architecture and failure to excrete bile acids which accumulate in skin

• Reduced immunological response leading to increased susceptibilty to infections

Hepatic Failure• It is characterized by the following:

• Electrolyte imbalance, plasma sodium and calcium may be reduced

• There may be severe metabolic acid-base disturbances and hypoglycaemia

• ↑ blood nitrogen due to renal impairment

• ↑ bilirubin, Alkaline Phosphatase AST and ALT

• ↓ blood urea, serum albumin and clotting factors

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