Chapter 18: Liver

Question 1

3 main types of hepatic failure

Answer 1

• acute liver failure (encephalopathy within 6 months of onset; including fulminant liver failure which is within 2 weeks)
• chronic liver disease leading to cirrhosis
• hepatic dysfunction without necrosis as in fatty liver of pregnancy

Question 2

Definition of cirrhosis

Answer 2

• bridging fibrous septa (portal to portal or portal to lobular)
• parenchymal nodules resulting from hepatocyte regeneration and scarring
• disruption of architecture of entire liver

Question 3

Posthepatic causes of portal hypertension

Answer 3

• right heart failure
• constrictive pericarditis
• hepatic vein outflow obstruction

Question 4

Pathophysiology of cirrhosis

Answer 4

• increased resistance to blood flow at the level of the sinusoids due to contraction of smooth muscle cells and myofibroblasts, and disruption of blood flow due to scarring
• increased portal venous flow due to hyperdynamic circulation, particularly from increased slanchnic arterial blood flow

Question 5

Basic causes of jaundice

Answer 5

• bilirubin overproduction
• hepatitis
• obstruction of biliary flow

Question 6

What is UGT1A1?

Answer 6

• uridine diphosphate (UDP)-glucuronyl transferase that conjugates bilirubin the liver
• mutations cause hereditary unconjugated hyperbilirubinemia (Crigler-Najjar and Gilbert syndome)

Question 7

Causes of jaundice

Answer 7

• excess extrahepatic production of bilirubin
• reduced hepatic uptake of bilirubin
• impaired conjugation of bilirubin
• decreased hepatocellular excretion of conjugated bilirubin
• impaired bile flow

Question 8

Dubin-Johnson syndrome

Answer 8

• autosomal recessive defect in hepatic excretion of bilirubin
• excess conjugated bilirubin

Question 9

Causes of cholestasis

Answer 9

• intra or extrahepatic obstruction of bile channels

- defects in hepatocyte bile secretion

Question 10

What is the supposed underlying pathogenesis of autoimmune hepatitis?

Answer 10

• T cell-mediated autoimmunity
• IFN-gamma produced by CD4 cells causes hepatic damage, as do CD8 cells
• may be triggered by viral infections or drugs

Question 11

What are the deleterious effects of alcohol on the liver?

Answer 11

• steatosis
• dysfunction of mitochondrial and cellular membranes
• hypoxia
• oxidative stress

Question 12

What organs accumulate iron in hemochromatosis?

Answer 12

Liver, pancreas, joints, heart, other endocrine organs

Question 13

How is iron toxic to the host?

Answer 13

• lipid peroxidation as iron catalyzes free radical reactions
• stimulation of collagen formation by activation of hepatic stellate cells
• interaction of ROS and iron with DNA, leading to cell injury or HCC

Question 14

What is the main regulator of hepatic iron absorption?

Answer 14

Hepcidin; functions to lower plasma iron levels such that its absence causes iron overload

Question 15

What mutations cause hemochromatosis?

Answer 15

-mutations in hepcidin, hemojuvelin, TfR2 and HFE, all of which decrease hepcidin expression

Question 16

What are the two most common HFE mutations?

Answer 16

• C282Y (low penetrance)

- H63D (milder)

Question 17

What is the underlying problem in Wilson’s disease

Answer 17

• AR mutation of ATP7B (chr 13) resulting in impaired copper excretion and a failure to incorporate copper into ceruloplasmin
• Serum shows increased urinary excretion of copper and decreased serum ceruloplasmin

Question 18

What antibodies are found in PSC patients?

Answer 18

• ANA
• anti-smooth muscle
• RF
• pANCA but not against MPO but rather against a nuclear envelope protein

Question 19

What are causes of hepatic vein outflow obstruction?

Answer 19

• Budd Chiari syndrome (HV thrombosis)

- Sinusoidal obstructive syndrome (VOD; bush tea, post BMT)

Question 20

What is the pattern of fibrosis in cardiac sclerosis?

Answer 20

-centrilobular fibrosis; rarely meets the true criteria for cirrhosis

Question 21

What are associations with hepatic vein thrombosis and what is Budd Chiari syndrome?

Answer 21

-associations: myeloproliferative disorders, coagulation disorders, APL syndrome, intraabdominal cancer
Triad: liver enlargement, pain and ascites

Question 22

What is the histology of sinusoidal obstruction syndrome?

Answer 22

• obliteration of hepatic vein radicles
• acute disease shows centrilobular congestion
• later, perivenular fibrosis often with total obliteration of the venule

Question 23

What features on liver biopsy suggest extrahepatic biliary atresia?

Answer 23

• bile ductular proliferation
• portal tract edema and fibrosis
• cholestasis