Hepatic Failure

Lecture 19

• The most severe clinical consenquences of liver disease is hepatic failure . It generally develops as the end point of progressive damage to the liver,

• either insidious destruction of hepatocytes or • repititive discrete waves of parenchymal

damage.

• Less commonly, hepatic failure is the result of sudden and massive destruction of hepatic tissue.

• Whatever the sequence, 80% to 90% of hepatic function must be lost before hepatic failure ensues.

DefinitionLiver 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.

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

• 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

Acute Hepatic Failure• 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".

Acute liver failure with massive hepatic necrosis

• Caused by drugs or fulminant viral hepatitis

• ALF denotes clinical hepatic insufficiency that progresses from onset of symptoms to hepatic encephalopathy within 2 to 3 weeks.

Morphology• The histologic correlate of acute liver failure is

massive hepatic necrosis.

Chronic hepatic failure

• Chronic hepatic failure usually occurs in the

context of cirrhosis.

Chronic liver disease• This is the most common route to hepatic

failure and is the end point of relentless chronic liver damage ending in cirrhosis.

Causes of CLF• The most common causes of chronic liver failure

(where the liver fails over months to years) 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

Hepatic dysfunction without overt necrosis

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

Causes

• Tetracycline toxicity, and • Reye syndrome.

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

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

Early symptoms

• Nausea• Loss of appetite• Fatigue• Diarrhea

Serious Symptoms

• Jaundice• Bleeding easily• Swollen abdomen• Mental disorientation or confusion (known as

hepatic encephalopathy)• Sleepiness• Coma

Complications of Hepatic Failure

• Coagulopathy• Hepatic encephalopathy• Hepatorenal syndrome

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.

Signs & symptoms• Forgetfulness, • mild confusion,• irritability and • coma.

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 semistupor, 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

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

• The development of renal failure without primary abnormalities of the kidneys themselves.

• Kidney function promptly improves if hepatic failure is reversed.

Etiology• Splanchnic vasodilation & • systemic vasoconstriction, leading to severe reduction of renal blood flow.

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.