liver

Question 1

Progression of liver injury (draw out the diagram)

Answer 1

check

Question 2

Consequences of liver failure

Answer 2

1. Coagulopathy —> inhibits hepatic synthesis function —> easy bruising and bleeding
2. Hepatic encephalopathy —> due to buildup of ammonia, crosses BBB
3. Cholestasis —> impaired bile excretion
4. Hepatorenal/hepatopulmonary syndrome
5. Portal hypertension —> more common in chronic hypertension

Question 3

Reasons for portal hypertension

Answer 3

1. Increased resistance to portal flow at sinusoids
   - Vasoconstriction
   - Scarring/parenchymal nodule formation leading to disrupted blood flow
   - Sinusoidal remodelling, arterial-portal anastomoses (intrahepatic shunting)
2. Increased portal-venous flow due to hyperdynamic circulation
   - increased blood flow through circulation
   - arterial dilation of splanchnic circulation

Question 4

Effects of portal hypertension

Answer 4

1. Ascites —> buildup of fluid in peritoneal space, due to increased pressure in peritoneal capillaries
2. Hepatorenal syndrome —> due to renal vasoconstriction (activation of RAAS)
3. Caput medusae, Hemorrhoids, Esophageal varices —> due to development of collateral channels (portosystemic venous shunts)
4. Hepatic encephalopathy —> buildup of ammonia, crosses BBB
5. Bleeding —> splenomegaly due to back flow of blood into spleen —> thrombocytopenia

Question 5

Define cirrhosis and how does it happen?

Answer 5

Diffuse transformation of liver into regenerative parenchymal nodules surrounded by fibrous bands (scarring) and variable degrees of vascular shrinkage
Balance between deposition of matrix by activated hepatic stellate cells (HSCs) and resorption due to matrix metalloproteinases (MMPs)

Question 6

Symptoms of acute hepatitis

Answer 6

1. Jaundice
2. Dark coloured urine
3. Fever
4. Fatigue
5. Poor appetite
6. Nausea and vomiting
7. Abdominal pain

Question 7

What types of hepatitis cause chronic and acute liver failure?

Answer 7

Acute: HAV, HBV, HDV (HEV in pregnancy)
Chronic: HCV +/- HBV (HAV, HEV does not cause unless immunocompromised)

Question 8

How does drug and toxin-induced liver injury occur? What hepatotoxins cause acute and chronic liver disease?

Answer 8

1. Direct toxicity
2. Conversion of xenobiotic to active toxin
3. Immune-mediated mechanisms
   Acute liver disease: acetaminophen
   Chronic liver disease: alcohol

Question 9

How does cirrhosis develop from alcoholic liver disease? Draw out the diagram

Answer 9

check

Question 10

What can alcoholic liver disease give rise to?

Answer 10

1. Steatosis (fatty change of the liver)
2. Alcoholic hepatitis
3. Progressive steatofibrosis
4. Marked derangement of vascular perfusion

AST: ALT = 2:1

Question 11

Pathogenesis of liver fibrosis (due to alcoholic liver disease)

Answer 11

1. Increased lipid biosynthesis (increased NADPH)
2. Acetaldehyde-induced liver peroxidation
3. Increased hypoxia and oxidative stress (ROS)

Question 12

Pathogenesis of non-alcoholic fatty liver disease

Answer 12

2-hit model
1. Insulin resistance —> dysfunctional lipid metabolism + increased production of inflammatory cytokines
2. Oxidative injury —> liver cell necrosis —> fat laden cells are highly sensitive to lipid peroxidation products

Question 13

Risk factors for hepatocellular carcinoma

Answer 13

• Viral infections (HBV, HCV)
• Toxins (aflatoxin, alcohol)
• Metabolic diseases
• NAFLD associated with metabolic syndromes

Question 14

Ways of Hep B infection

Answer 14

• IVDA (needle sharing)
• Sexual transmission
• Needlestick injury
• Infected mother to fetus during childbirth