Hepatic Failure

Lecture18 nDr Mohammad Manzoor Mashwani BKMC Mardan

Clinical Syndromes of Liver Diseases

HEPATIC CLINICAL SYNDROMESThe major clinical syndromes of liver disease are: Hepatic failure, Cirrhosis, Portal hypertension, Cholestasis

Definition of Liver FailureLiver failure is the inability of the liver to perform

its normal synthetic and metabolic function as part of normal physiology.

Two forms are recognized, acute and chronic.

80% to 90% of hepatic function must be lost before hepatic failure ensues.

•A course expending as long as 3 months is called subacute failure.

liver has a marked regenerative capacity and a large functional reserve,

Liver Functions1. Manufacture and excretion of BILE.

2. Manufacture of several major plasma proteins such as albumin, fibrinogen and prothrombin.

3. Metabolism of proteins, carbohydrates and lipids.4. Storage of vitamins (A, D and B12) and iron.5. Detoxification of toxic substances such as alcohol

and drugs.

The alterations that cause liver failure fall into three categories:

• 1. Acute liver failure with massive hepatic necrosis• 2. Chronic liver disease• 3. Hepatic dysfunction without covert necrosis

I. Acute Hepatic Failure (ALF)• Acute hepatic failure is defined as "the rapid

development of hepatocellular dysfunction, specifically coagulopathy and mental status changes (encephalopathy ) in a patient without known prior liver disease".

Caused by drugs or fulminant (sudden & severe, thundering) viral hepatitisALF denotes clinical hepatic insufficiency that progresses from onset of symptoms to hepatic encephalopathy within 2 to 3 weeks.

Morphology : Massive hepatic necrosis.

•Hepatotoxic drug reactions

( anaesthetic agents,NSAIDs, anti-depressants), •carbon tetrachloride poisoning, •pregnancy complicated with eclampsia.

II. Chronic hepatic failure (CLF)

• Chronic hepatic failure usually occurs in the context

of cirrhosis.This is the most common route to hepatic failure and is the end point of

relentless (persistent) chronic liver damage ending in cirrhosis.

where the liver fails over months to years

Causes of CLFThe most common causes of chronic liver failure include:

• Hepatitis B• Hepatitis C• Long term alcohol consumption• Cirrhosis• Hemochromatosis (an inherited disorder that causes the body

to absorb and store too much iron)• Malnutrition

chronic active hepatitis, Chronic cholestasis (cholestatic jaundice) Wilson’s disease

III. Hepatic dysfunction without overt necrosis

• Hepatocytes may be viable but unable to perform normal metabolic function,

Causes:Tetracycline toxicity, and Reye syndrome.

.

REYE’S SYNDROME• Reye’s syndrome is defined as an acute postviral syndrome of encephalopathy and

fatty change in the viscera. The syndrome may follow almost any known viral disease but is most common after influenza A or B and varicella. Viral infection may act singly, but more often its effect is modified by certain exogenous factors such as by administration of salicylates, aflatoxins (mycotoxins) and insecticides. These effects cause mitochondrial injury and decreased activity of mitochondrial enzymes in the liver. This eventually leads to rise in blood ammonia and accumulation of triglycerides within hepatocytes. The patients are generally children between 6 months and 15 years of age. Within a week after a viral illness, the child develops intractable vomiting and progressive neurological deterioration due to encephalopathy, eventually leading to stupor, coma and death. Characteristic laboratory findings are elevated blood ammonia, serum transaminases, bilirubin and prolonged prothrombin time.

MORPHOLOGIC FEATURES. Grossly, the liver is enlarged and yellowish-orange.Microscopically, hepatocytes show small droplets of neutral fat in their cytoplasm (microvesicular fat). Similar fatty change

is seen in the renal tubular epithelium and in the cells of skeletal muscles and heart. The brain shows oedema and sometimes focal necrosis of neurons.

The first description of this syndrome was probably made by Najib Khan in Jamshedpur in 1956 (Jamshedpur fever).[

Types ABC• Type A (=acute) describes hepatic encephalopathy

associated with acute liver failure, typically associated with cerebral oedema

• Type B (=bypass) is caused by portal-systemic shunting without associated intrinsic liver disease.

• Type C (=cirrhosis) occurs in patients with cirrhosis - this type is subdivided in episodic, persistent and minimal encephalopathy

A portosystemic shunt (PSS), also known as a liver shunt, is a bypass of the liver by the body's circulatory system.

Clinical features• Jaundice and cholestasis• Hypoalbuminemia• Hypoglycemia• Palmar erythema• Spider angioma• Hypogonadism• Gynecomastia• Weight loss• Muscle wasting

Early symptoms:NauseaLoss of appetiteFatigueDiarrhea

Serious SymptomsJaundiceBleeding easilySwollen abdomenMental disorientation or confusion (known as hepatic encephalopathy)SleepinessComa

Jaundice usually reflects the severity of liver cell damage since it occurs due to failure of liver cells to metabolise bilirubin. In acute failure such as in viral hepatitis,jaundice nearly parallels the extent of liver cell damage, while in chronic failure such as in cirrhosis jaundice appears late and is usually of mild degree.

Complications of Hepatic Failure• Failure of multiple organ systems• Coagulopathy• Hepatic encephalopathy (Hepatic Coma)• Hepatorenal syndromeHepatic encephalopathy: disturbed consciousness, personality changes, intellectualdeterioration, low slurred speech, flapping tremors, and finally, coma and death.

PrognosisIn chronic liver disease death occurring withinweeks to a few months in about 80% of cases. About 40% of patients with acute liver failure may

recover spontaneously.Liver transplantation in acute or chronic liver failurecan be curative.

Hepatic encephalopathy• Hepatic encephalopathy (also known as

portosystemic encephalopathy) is the occurrence of confusion, altered level of consciousness, and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum. It may ultimately lead to death.

Hepatic encephalopathy may develop rapidly in acute liver failure or insidiously with gradually evolving chronic liver failure from cirrhosis.

In either setting, patients with hepatic encephalopathy show a spectrum of brain dysfunction ranging from subtle behavioral abnormalities to marked confusion and stupor, to deep coma and death.

These changes may progress over hours or days as, for example, in fulminant hepatic failure or gradually in a person with marginal hepatic function from chronic liver disease.

Associated fluctuating neurologic signs include rigidity, hyperreflexia, nonspecific electroencephalographic changes, and, rarely, seizures. Particularly characteristic is asterixis (also called flapping tremor or liver flap),

which is a pattern of nonrhythmic, rapid extensionflexionmovements of the head and extremities, best seenwhen the arms are held in extension with dorsiflexed wrists.

Asterixis- a recurrent flapping tremor of the arms, like the action of a bird's wings, that occurs as a result of a brain condition associated with liver failure

The tremor is caused by abnormal function of the diencephalic motor centers in the brain, which regulate the muscles involved in maintaining position.

The term derives from the Greek a, "not" and stērixis, "fixed position".

Signs & symptoms

•Forgetfulness, •Mild confusion,• Irritability and •Coma.

Disturbed consciousness, personality changes, intellectual deterioration, low slurred speech, flapping tremors, andfinally, coma and death.

• Hyperkinetic circulation. All forms of hepatic failure are associated with a hyperkinetic circulation characterised by peripheral vasodilatation, increased splanchnic blood flow and increased cardiac output. There is increased splenic flow

but reduced renal blood flow resulting in impaired renal cortical perfusion. These changes result in tachycardia, low blood pressure and reduced renal function.

Morphology• In most instances there are only minor morphologic

changes in the brain, such as edema and an

astrocytic reaction.

Two factors seem to be important in the genesis of this disorder:

•1. Severe loss of hepatocellular function•2. Shunting of blood from portal to systemic

circulation around the chronically diseased liver.

In the acute setting, an elevation in blood ammonia,which impairs neuronal function and promotes generalizedbrain edema, seems to be key. In the chronic setting, deranged neurotransmitter production,

particularly in monoaminergic, opioidergic, γ-aminobutyric acid (GABA)-ergic, and endocannabanoid systems, leads to neuronal dysfunction.

The genesis of CNS manifestations in liver disease is by toxic products not metabolised by the diseased liver. The toxic products may be ammonia and other nitrogenous substances from intestinal bacteria which reach the systemic circulation without detoxification in the damaged liver and thus damage the brain..

Hepatic encephalopathy West Haven Criteria

• Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction

• Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behaviour

• Grade 3 - Somnolence to semi stupor, but responsive to verbal stimuli; confusion; gross disorientation

• Grade 4 - Coma (unresponsive to verbal or noxious stimuli)

Other signs & symptoms• Jaundice, • Ascites, • Peripheral oedema. • Tendon reflexes exaggerated, • Babinski's sign positive• Foetor hepaticus

Hepatic encephalopathy- Causes• Liver failure, • Large amount of protein consumption,• GIT bleeding, • Renal failure, • Constipation, • Hyponatremia,• Hypokalemia,• Alkalosis, • Hypoxia,• Dehydration, • Sedatives, narcotics, alcohol intoxication,• Surgery,

• Unknown (2o-3o%).

Hepatorenal syndrome• Patients of (both acute and chronic) hepatic failure who

develop renal failure as well, in the absence of clinical, laboratory or morphologic evidence of other causes of renal dysfunction.

• Hepatorenal syndrome develops in about 10%cases of acute and chronic liver diseases. Kidney function promptly improves (reversible ) if

hepatic failure is reversed.

Etiology• Splanchnic vasodilation & • systemic vasoconstriction,

leading to severe reduction of renal blood flow.The pathogenesis of the syndrome is poorly understood but appears to be initiated by effective reduction of the renal blood flow (effective hypovolaemia) as a consequence of systemic vasodilatation and pooling of bloodin portal circulation.

Clinical features • Drop in urine output, associated with rising blood

urea nitrogen and creatinine values.

• The renal failure may hasten death in the patient with acute fulminant or advanced chronic hepatic disease.

• Alternatively, borderline renal insufficiency may persist for weeks to months.

The acute renal failure is usually associated with oliguria and uraemia butwith good tubular function.

Hepatopulmonary syndrome. The pulmonary changes in chronic hepatic failure

such as in cirrhosis consist of pulmonary vasodilatation with intra-pulmonary arteriovenous shunting. This results in ventilation-perfusion

inequality that may lead to impaired pulmonary function, clubbing of fingers and sometimes cyanosis.

Coagulation defects Impaired synthesis of a number of coagulation

factors by the diseased liver may result incoagulation disorders. These include disseminated

intravascular coagulation (consumption coagulopathy), thrombocytopenia and presence of fibrin degradation products in the blood.

Ascites and oedemaChronic liver failure due to cirrhosis may result in

portal hypertension and ascites.Decreased synthesis of albumin by the liver resulting

in hypoproteinaemia and consequent fall in plasma oncotic pressure, increased hydrostatic pressure due to portal hypertension and secondary hyperaldosteronism, contribute to the development of ascites and oedema in these patients.

Endocrine changes The changes are more common in alcoholic cirrhosis

in active reproductive life. In the male, the changes are towards feminisation such as gynaecomastia and hypogonadism. In the female, the changes are less towards masculinisation but atrophy of gonads and breasts occurs. The underlying mechanism appears to be changed end-organ sensitiveness to sex hormones in cirrhosis.

Skin changes In alcoholic cirrhosis ‘arterial spiders’ having

radiating small vessels from a central arteriole are frequent in the vascular region drained by superior vena cava such as in the neck, face, forearms and dorsum of hands.

• Less frequently, palmar erythema, especially in the hypothenar and thenar eminences and on the pulps of the fingers, is observed in chronic liver disease.

Foetor hepaticus A sweetish pungent smell of the breathis found in severe cases of acute and chronic

hepatocellular diseases. It appears to be of intestinal origin, possibly due to failure of the liver to detoxify sulfur-containing substances absorbed from the gut.