Pathogeneis of Fibrosis

Question 1

What is Chronic Liver Disease

Answer 1

Is defined as a disease which causes apoptosis of hepatocytes in association with inflammatory infiltrate of lymphocytes, plasma cells and macrophages.

Question 2

What role do lymphocytes play

Answer 2

The infiltration of lymphocytes can promote an imflammatory state and the rate of fibrosis and apoptosis. The apoptosis is typically portal or periportal. The rate of fibrosis is dependent on the grade of infiltration of the lymphocytes. Begins as interface hepatitis yet can expand into the surrounding parenchyma

Question 3

Describe the stages of fibrosis

Answer 3

Has 4 stages,

1: Enlarged portal tracts, no septa
2: Fibrosis present yet not much linkage between portal tracts
3: 40% of viable hepatocytes remain, symptoms arise, extensive fibrosis and damage as portal to portal damage
4: Cirrhosis, where there are a large network of lobules bordered by collagen

Question 4

How is fibrosis and cirrhosis promoted?

Answer 4

Pathogenesis of Cirrhosis
- There are cells that live within the space between the sinusoid and the hepatocytes called stellate cells
- Their role is to store vitamins, A, C and E
- In inflammation, they come out of quiescent and take on a myofibroblast response
○ Begin to synthesis collagen and lay down to promote fibrosis
○ Scar tissue formation as well
- There will also be remodelling of vasculature supply, may cause ischemia within the liver (parenchyma)

Question 5

What are the three levels of complications with cirrhosis

Answer 5

Parenchymal Liver Failure, Secondary endocrine functions and portal hypertension

Question 6

Describe the symptoms/signs from portal hypertension

Answer 6

Ascites, enlarged spleen, hemroids, oesophageal varices, medusa capute

Question 7

Describe the symptoms/signs from Secondary endocrine functions

Answer 7

Estrogen (spider naviea), gynacomastia and testicular atrophy

Question 8

Describe the symptoms/signs from Parenchymal Liver Failure

Answer 8

Bleeding, toxin build up (hepatic encephalopathy), jaundice, hypoalbumaemia (oedema), portal hypertension, thrombocytopeania (reduced TPO)

Question 9

Mechanism of Portal Hypertension

Answer 9

Destruction or constriction of the sinusoids leading to pressure build up and backflow. This leads to portal hypertension and the attempted return of blood back to systemic circulation via specific anastomis. These are in the rectal arteries, oesophageal arteries and stomach arteries