4. Cirrhosis and hepatic failure

What is cirrhosis?

When there is a chronic state of inflammation and hepatocyte destruction - and the hepatocytes are damaged to the point where its no longer reversible

- cirrhosis will happen

What are the most important causes of cirrhosis?

- Hepatitis infection

- Alcoholic liver disease

- Non-alcoholic liver disease (NAFLD)

What is alcoholic liver disease?

Chronic and progressive liver disease caused by long term excessive alcohol consumption

Stages of alcoholic liver disease?

1. Hepatocellular steatosis

2. Steatohepatitis

3. Steatohepatitis with fibrosis

4. Cirrhosis

Hepatocellular steatosis?

Fat accumulates in the hepatocytes

- spreads outward from the central veins

Why do hepatocellular steatosis happen?

Alcohol dehydrogenase generates so much NADH from ethanol, that lipid synthesis is favoured by the metabolism

What does the liver macroscopically look like during steatosis?

- Big (4-6kg)

- Soft

- Yellow

- Greasy

Steatohepatitis? what are the changes?

Inflammation of the liver associated with excess fat

- Hepatocyte ballooning

- Malory-Denk bodies

- Neutrophil infiltration

What is hepatocyte ballooning?

Single or scattered foci of hepatocytes undergo swelling and necrosis

What is Mallory-Denk bodies?

Eosinophilic inclusion bodies in degenerating hepatocytes

- consist of damaged intermediate filaments

Neutrophil infiltration?

Neutrophils accumulate around the degenerating hepatocytes

- especially around the Mallory-Denk bodies

Steatohepatitis with fibrosis?

A distinctive pattern of fibrosis occurs with fatty liver disease

- appears first as central vein sclerosis, and spreads outwards, encircling individual or small clusters of hepatocytes

Morphology of alcoholic hepatitis?

The area around the central veins are most susceptible to toxic injury

- because the generation of acetaldehyde and free radicals is the biggest here

What are the causes of alcoholic hepatitis?

Toxic products and metabolites from alcohol metabolism

- acetaldehyde

- reactive oxygen species

- cytokines

What is non-alcoholic fatty liver disease?

The development of a fatty liver resulting from excessive quantities of fats being deposited, from causes that exclude alcohol

- associated with insulin resistance and metabolic syndrome

What is metabolic syndrome?

Medical term for a combination of HT, obesity, dyslipidemia, and insulin resistance.

- increased risk of heart disease and stroke

Pathomechanism of NAFLD?

Insulin resistance results in the accumulation of triglycerides in hepatocytes

- fat loaded hepatocytes are very sensitive to lipid peroxidation products generated by oxidative stress, which can damage mitochondria and plasma membranes

- eventually leads to apoptosis of the hepatocytes

Gross morphology of a cirrhotic liver?

Brown, hard, shrunken organ

- composed of cirrhotic nodules

Microscopical morphology of cirrhosis?

Histology shows pseudolobules separated by fibrosis

How can the pseudolobules be distinguished form hepatic lobules?

Can be distinguished from hepatic lobules by the fact that they dont have a central vein

Clinical manifestations of cirrhosis?

- Elevated serum aminotransferases (ALT and AST)

- Hyperbilirubinemia

- Hypoproteinaemia

- Anaemia

Types of cirrhosis?

- Micronodular cirrhosis

- Macronodular cirrhosis

- Pigment cirrhosis

- Biliary cirrhosis

Micronodular cirrhosis?

Most commonly the result of chronic alcohol abuse

Macronodular cirrhosis?

Caused by chronic viral hepatitis or other infections

Pigment cirrhosis?

Caused by hemochromatosis (iron accumulation) or Wilsons disease (copper accumulation)

Biliary cirrhosis?

Caused by damage to the biliary tree

What is hepatic failure?

The condition where the liver is unable to perform its normal liver functions

- because of the damage to the liver parenchyme

How can we categorize the complications of hepatic failure?

- Parenchymal decompensation, due to decreased function of the parenchyme

- Vascular decompensation, due to congestion of the portal circulation

Types of parenchymal decompensation?

- Hypoproteinaemia

- Hyperbilirubinaemia

- Increased levels of estrogen

- Hepatorenal syndrome

- Hepatopulmonary syndrome

- Hepatic encephalopathy

What is hepatorenal syndrome?

End-stage cirrhosis causes a rapid onset of irreversible renal failure without evidence for an alternative diagnosis

What is hepatic encephalopathy?

Brain dysfunction and damage caused by increased ammonia in the blood, resulting from severe liver disease

Vascular decompensation?

- Portal hypertension

- Ascites

- Esophageal varices

- Caput medusa

- Splenomegaly

- Malabsorption