Liver 1

Question 1

What are 3 mechanisms of liver injury and repair?

Answer 1

1. Hepatocyte and parenchymal responses
2. Scar formation and regression
3. Inflammation and immunity

Question 2

In hepatocyte and parenchymal responses, what degenerative but potentially reversible changes are seen?

Answer 2

1. Ballooning Degeneration
2. Steatosis
3. Cholestasis

Question 3

In hepatocyte and parenchymal responses, what is seen in irreversible injury and cell death?

Answer 3

Necrosis
- cell swelling and rupture
Apoptosis
- activation of caspase cascades
- cellular shrinkage and eosinophilia
- spotty necrosis –> confluent necrosis (zonal –> bridging –> submassive –> massive hepatic necrosis)

Question 4

In hepatocyte and parenchymal responses, what is seen in regeneration?

Answer 4

Mitotic replication of hepatocytes
2. Activation of primary stem cell niche (canals of Hering)
3. Ductular Reaction – Stem Cell Activation and hepatocytes reach replicative senescence

Question 5

How does scar formation occur in liver injury?

Answer 5

1. • collapse of underlying reticulin
   • hepatic stellate cells activated and converted into highly fibrogenic myofibroblasts
     – activated by cytokines and chemokines from inflammatory cells, endothelial cells, hepatocytes, bile duct epithelial cells, in response to ECM disruption or direct stimulation from toxins

• portal fibroblasts and ductular reaction (during this there is a epithelial mesenchymal transition which results in more ECM components, myofibroblasts and inflammation produced) also contribute

2. Portal/periportal fibrosis –> portal central and portal portal bridging fibrosis –> cirrhosis
3. Pericellular/perisinusoidal fibrosis
4. Reversal of fibrosis/cirrhosis regression

Question 6

What can be seen in inflammation of liver

Answer 6

Lymphocytes, plasma cells, neutrophils, eosinophils, histiocytes/macrophages
Granulomas
Microabscesses

Question 7

What are the 5 consequences of liver failure?

Answer 7

1. Coagulopathy
2. Hepatic Encephalopathy
3. Cholestasis
4. Hepatorenal, Hepatopulmonary Syndrome
5. Portal HTN

Question 8

What are 3 causes of acute liver failure

Answer 8

Drugs/Toxins
Acute Hep A/B/E
Autoimmune Hepatitis

Question 9

Histologic features of acute liver failure

Answer 9

1. Massive Hepatic Necrosis
   - loss of hepatocytes
   - red blood cell extravasation
   - florid ductular reaction
2. Diffuse injury without obvious cell death (diffuse microvesicular steatosis)

Question 10

What are 3 leading causes of chronic liver failure?

Answer 10

1. Chronic Hep B and C
2. NAFLD
3. Alcoholic Liver Disease

Question 11

Histologic features of chronic liver failure?

Answer 11

Cirrhosis

Question 12

Do all cirrhosis lead to chronic liver failure? Is all end stage chronic liver disease cirrhotic? Is regeneration of cirrhotic liver possible?

Answer 12

No. No. Yes

Question 13

What is liver cirrhosis?

Answer 13

Diffuse transformation of liver into a regenerative parenchymal nodules surrounded by fibrous bands

Accompanied by disturbed vascular architecture (due to variable degrees of vascular (often portosystemic) shunting

Question 14

Mechanisms of scar formation in liver?

Answer 14

1. Dense fibrous tissue forming from a) collapse of underlying reticulin and b) activation of HSCs into highly fibrogenic myofibroblasts

Question 15

What maintains the balance in matrix remodelling?

Answer 15

Question 16

Progression of established to regression of cirrhosis?

Answer 16

1. Broad Septa
2. Large region of extinction containing few small buds of parenchyma
3. Nodules expand against their neighbours
4. Septa are compressed and reabsorbed
5. Large regions of extinction are filled in by expansion of adjacent nodules and new micronodules from buds

Question 17

What are clinical features of cirrhosis? Complication? Common terminal events?

Answer 17

1. 40% asymptomatic until advanced stages
2. Non-specific manifestations: anorexia, weight loss, weakness
3. Advanced Disease: Symptoms and Signs of liver Failure

Hepatocellular Carcinoma

• Hepatic Encephalopathy
• Bleeding fro esophageal varices
• Bacterial infections/sepsis

Question 18

What encompasses the stigmata of chronic liver disease?

Answer 18

1. Cholestasis
   - Jaundice –> Pruritus (due to bile salt deposition), Scleral Icterus
2. Hyperestrogenemia (liver usually inactivates estrogen)
   - Palmar Erythema
   - Spider Angiomas
   - Hypogonadism
   - Gynaecomastia
3. Coagulopathy
4. Portal HTN
   - Ascites
   - Portosystemic Venous Shunts, caput medusae, Anorectal varices
   - Splenomegaly
   - Hepatic Encephalopathy: Asterixis

Question 19

Causes of portal hypertension?

Answer 19

Question 20

Consequences of portal hypertension>

Answer 20

1. Portosystemic shunting of blood = collateral channels = caput medusae, esophageal varices, hemorrhoids OR portosystemic shunting of blood = shunting of ammonia from GIT into general circulation (ammonia not cleared by liver) = hepatic encephalopathy
2. Splenomegaly (can lead to anemia, leukopenia, thrombocytopenia and bleeding as spleen is overactive and sequestes all the blood cells)
3. Ascites
4. Hepatorenal Syndrome

Question 21

Common sites of porto-systemic shunts?

Answer 21

Question 22

What are causes of ascites?

Answer 22

Cirrhosis, CCF, Hypoalbuminaemia, Malignancies

Question 23

What can be found in an ascitic tap if
a) normal
b) infection
c) cancer

Answer 23

a) few mesothelial cells, mononuclear inflammatory cells
b) neutrophils
c) malignant cells (via transdiaphragmatic lymphatics [hydrothorax, R>L]