Systems Pathology: Liver Failure

Question 0

Hepatocyte location related to function

Answer 0

Centrilobular hepatocytes (acinar zone 3)-> supplied by oxygen depleted blood-> low oxidase activity, high esterase activity -> most vulnerable to damage by hypoxia or poor perfusion
-> esterases make metabolic intermediates-> vulnerable to toxins such as paracetamol 
Peripheral hepatocytes (acinar zone1)-> oxygenated blood-> low esterase activity -> resist perfusion damage and toxin damage
Differential susceptibility to toxins

Question 1

Functions of liver

Answer 1

Carb metabolism 
Fat metabolism 
Protein synthesis and catabolism
Bile synthesis
Storage
Detoxification

Question 2

Responses of liver to injury

Answer 2

Fatty change-> metabolic stress and alcohol
Choleostasis
Inflammation
Fibrosis
Regeneration 
Neoplasia

Question 3

Choleostasis

Answer 3

Bile plugs caliculi
Caused by conditions that cause hyperbilirubinemia
Raised serum alkaline phosphatase
Intra hepatic-> diseases effecting bile secretion
Extra hepatic-> blockage of bile ducts outside the liver

Question 4

Acute liver failure causes

Answer 4

Acute liver damage-> severe necrosis
Systemic shock as part of multi organ failure-> necrosis
Declining chronic liver disease
80% of patients die

Question 5

Liver cell necrosis

Answer 5

Liver necrosis

• > release of Transaminases-> lab test
• > failure of bilirubin metabolism-> jaundice
• > failure to detoxify nitrogenous compounds-> encephalopathy
• > failure to synthesis factors II,VII,IX,X-> bleeding
• > shock with low GFR-> renal failure

Question 6

Chronic liver disease causes

Answer 6

Chronic hepatitis-> inflammation of liver persisting more than 6 months
Hep B,C,D
Autoimmune
Drug metabolic disease
Cirrhosis-> nodules of regeneration separated by fibrosis

Question 7

Chronic hepatitis pathology

Answer 7

Liver cell necrosis and inflammation-> piecemal necrosis-> necrosis of the cells next to the portal tract connective tissue
-> bridging necrosis-> extensive necrosis that bridges between central veins or portal tracts
Fibrosis-> regeneration is distorted by fibrosis-> growth factors produced as part of the inflam response-> portal expansion, periportal, bridges between portal triads

Question 8

Grading of chronic hepatitis

Answer 8

Necrosis and inflammation are given a grade
0-> none or minimal
1-> portal and lobular inflammation
2-> mild periportal necrosis, focal necrotic cells in lobules with acidophilus bodies
3-> moderate necrosis of periportal, lobular severe focal cell damage
4-> severe necrosis of periportal, damage includes necrosis or liver cells that bridge portal tracts

Question 9

Staging of liver fibrosis

Answer 9

0- none
1 enlarged fibrotic portal tracts
2 fibrosis extends to periportal areas
3 fibrosis extends in to septa but no distortion of liver architecture
4 fibrosis associated with architectural distortion corresponding to cirrhosis

Question 10

Cirrhosis

Answer 10

Chronic hepatitis and alcoholic liver disease can progress to cirrhosis
-> long standing liver cell destruction
Also biliary obstruction
Fibrosis
Nodules of regenerate hepatocytes
Distorted liver architecture
Irreversible
-> liver failure and portal hypertension -> ascites
Reduced hepatocyte function-> decreased blood clotting decreased bile etc
Reduced immune competence
Increased risk of carcinoma
Increased risk of portal view thrombosis

Question 11

Alcoholic hepatitis

Answer 11

Fatty change-> fat accumulates in hepatocytes, reversible
Necrosis-> focal reversible intitally 
Hyaline
Ballooned cell
Fibrosis-> cirrhosis

Question 12

Portal hypertension

Answer 12

Caused by obstruction of blood flow in the portal system
Back pressure-> Splenomegally, ascites
New Porto-systemic anastomoses-> varicose venous channels
-> oesophageal varices
Cirrhosis, portal tract fibrosis, idiopathic, poly cystic disease

Question 13

Chronic liver disease destabilisation

Answer 13

Alcohol binge
Constipation, dehydration
Infection
GI bleed