This document provides an overview of liver failure, including its causes, types, and pathophysiology. It discusses the major causes of acute and chronic liver failure. Acute liver failure can result from drug or toxin damage, viral hepatitis, or the end stage of chronic liver disease leading to cirrhosis. Chronic liver failure is usually the end result of chronic hepatitis or liver disease progressing to cirrhosis. The document describes the pathophysiology behind several clinical manifestations of liver failure, including hepatic encephalopathy, hepatorenal syndrome, and hepatopulmonary syndrome. It also discusses the mechanisms leading to ascites in liver failure patients.

1. Tutorial
Pathophysiology of Liver Failure
1/9/2019

2. Learning Objectives
By the end of this tutorial you should be able to:
• List the major causes of Acute Liver Failure
• List the major causes of Chronic Liver Failure
• Describe the types of Liver Failure
• Describe pathophysiology of sign and symptoms of Liver Failure
• Identify Hepatic Encephalopathy
• Identify Hepatorenal Syndrome
• Identify Hepatopulmonary Syndrome

3. 3
Liver Failure (LF) or Hepatic Failure (HF)
About 80 to 90% loss of hepatic functional capacity results in LF
Types:
Acute liver failure associated with encephalopathy within 6 months
after the initial diagnosis
Fulminant liver failure when encephalopathy develops within 2 weeks
of the onset of jaundice
Sub-fulminant liver failure when encephalopathy develops within 3
months of onset of jaundice
Chronic liver failure, end result of chronic hepatitis or chronic liver
disease, leads to cirrhosis
Hepatic dysfunction without apparent liver necrosis

4. LIVER FAILURE
Acute liver failure, due to massive liver necrosis caused by
Drug or toxin induced; direct toxic damage to hepatocytes or combination of
toxicity and inflammation with immune-mediated hepatocyte destruction e.g
acetaminophen, halothane, rifampin, isoniazid, antidepressant monoamine
oxidase inhibitors, CCL4, and mushroom poisoning (Amanita phalloides)
Viral Hepatitis; A, B & E infection accounts for 4-8% but not with HCV infection
Chronic liver disease
Most common route to LF; chronic hepatitis ending in cirrhosis
Hepatic dysfunction without necrosis
Hepatocytes may be viable but unable to perform normal function, seen in
Reye syndrome, tetracycline toxicity, and acute fatty liver of pregnancy

5. Pathologic Basis of Clinical Manifestation of LF
Hypoalbuminemia; Peripheral edema and ascites
Hyperammonemia; Cerebral dysfunction (encephalopathy)
Mercaptans formation; action of GIT bacteria on methionine, causes Fetor
hepaticus (body odor "sweet and sour“)
Impaired estrogen metabolism; Hyperestrogenemia, leads to hypogonadism
and gynecomastia in male
Reflection of local vasodilation-palmar erythema and spider angioma (a
central, pulsating, dilated arteriole from which small vessels radiate)
Impaired hepatic synthesis of clotting factors II, VII, IX & X; Bleeding
tendency in GIT Intestinal absorption of blood, metabolic load on liver,
worsens extent of LF
Highly susceptible to failure of multiple organ system; respiratory failure with
pneumonia and sepsis combine with renal failure

6. Hepatic encephalopathy
• Disorder of neurotransmission in CNS and neuromuscular system
associated with elevated blood ammonia levels
• Disturb consciousness, confusion, deep coma and death
• Flapping tremors
• Encephalopathy reversible if acute onset, in the chronic setting neuronal
dysfunction

7. Hepatorenal syndrome
Renal failure in severe CLD due to decrease glomerular filtration because of;
• Sodium and water retention
• Due to decreased renal perfusion pressure secondary to systemic
vasodilation
• Activation of renal SNS with vasoconstriction of afferent renal arteriole
• Increased synthesis of renal vasoactive mediators

8. Portopulmonary Hypertension or Hepatopulmonary Syndrome
Abnormal intrapulmonary vascular dilatation in combination with increased
pulmonary blood flow results in shunting of blood which leads to;
• Ventilation-perfusion mismatch
• Reduced oxygen diffusion
• Severe arterial hypoxemia
• Dyspnea
• Cyanosis

9. Ascites
The pathogenesis of ascites involves following mechanisms:
• Increased movement of intravascular fluid into the extravascular space of
Disse, caused by sinusoidal hypertension and hypoalbuminemia
• Renal retention of sodium and water due to secondary hyperaldosteronism