Pathology of the GI Tract- Liver and Gallbladder (3)

Question 1

what is the most common morphologic pattern of drug or toxin induced liver injury?

Answer 1

necrosis of perivenular hepatocytes (zone 3) is the typical feature of drug-induced liver injury

Question 2

what is the most common culprit for idiosyncratic reactions, which are the most common form of drug-induced liver injury ?

Answer 2

antimicrobial drugs

Question 3

what are the three forms of alcohol related liver disease?

Answer 3

steatosis, steatohepatitis, and steatofibrosis/cirrhosis

Question 4

how does steatosis present?

Answer 4

hepatomegaly with minimal symptoms, mildly elevated bilirubin and alk phos

Question 5

how does steatohepatitis present?

Answer 5

tender hepatomegaly, +/- cholestasis, hyperbilirubinemia, AST:ALT 2:1 levels, elevated alk phos

Question 6

how does steatofibrosis/cirrhosis present?

Answer 6

labs reveal hepatic dysfunction if enough liver tissue left, hypoproteinemia, coag abnormalities

Question 7

what is NAFLD strongly associated with?

Answer 7

insulin resistance

Question 8

what is a patient with NASH at risk for developing?

Answer 8

NASH cirrhosis or HCC

Question 9

where does fibrosis of the liver typically develop?

Answer 9

around the central vein

Question 10

how does pediatric NAFLD differ from adult NAFLD?

Answer 10

typically children show more diffuse steatosis and portal (rather than central) fibrosis, and ballooned hepatocytes may not be present

Question 11

how does NAFLD present?

Answer 11

it is typically asymptomatic except for signs and symptoms of metabolic syndrome

Question 12

what is hemochromatosis caused by?

Answer 12

excessive iron absorption

Question 13

what is occurring in hereditary hemochromatosis?

Answer 13

regulation of intestinal absorption of dietary iron is abnormal

Question 14

what is the main regulator of iron absorption?

Answer 14

hepcidin

Question 15

what gene encodes for hepcidin?

Answer 15

HAMP gene

Question 16

where is hepcidin produced?

Answer 16

the liver

Question 17

the adult form of hemochromatosis is usually caused by mutations of what gene?

Answer 17

HFE gene

Question 18

what is the most common HFE mutation?

Answer 18

a cysteine-to-tyrosine substitution at amino acid 282

Question 19

which population of people is the HFE mutation most common?

Answer 19

caucasian populations of european origin

Question 20

what are the principal manifestations of hemochromatosis?

Answer 20

hepatomegaly, abdominal pain, abnormal skin pigmentation, deranged glucose homeostasis or DM, cardiac dysfunction, and atypical arthritis

Question 21

how is hemochromatosis diagnosed?

Answer 21

very high levels of serum iron and ferritin and liver biopsy or genetic testing screening of family members of probands is important

Question 22

what stain shows hemochromatosis on histology slides?

Answer 22

prussian-blue stain

Question 23

what could be the final outcome of hemochromatosis?

Answer 23

cirrhosis or cardiac disease; hepatocellular carcinoma

Question 24

what is wilson disease?

Answer 24

an autosomal recessive disorder caused by mutation of the ATP7B gene resulting in impaired copper excretion into bile and a failure to incorporate copper into ceruloplasmin

Question 25

what are the manifestations of wilson disease?

Answer 25

accumulation of toxic levels of copper in many tissues and organs (liver, brain, and eye); hemolytic anemia

Question 26

what is the age of onset of wilson disease?

Answer 26

6 to 40 years of age

Question 27

how is the biochemical diagnosis of wilson disease made?

Answer 27

decreased serum ceruloplasmin, increased hepatic copper content, and increased urinary excretion of copper

Question 28

how does a patient with wilson disease present?

Answer 28

some with acute or chronic liver disease, some may have neurologic involvement (movement disorders or psychiatric symptoms) or hemolytic anemia

Question 29

what happens when copper is deposited into Descemet's membrane of the cornea?

Answer 29

it presents as Kayser-Fleischer rings

Question 30

what is alpha-1-antitrypsin deficiency?

Answer 30

an autosomal recessive disorder of protein folding marked by very low levels of circulating alpha-1 antitrypsin

Question 31

what is the function of alpha-1-antitrypsin?

Answer 31

it inhibits proteases (particularly neutrophil elastase)

Question 32

what does alpha-1-antitrypsin deficiency lead to?

Answer 32

pulmonary emphysema and it causes liver disease as a consequence of hepatocellular accumulation of the misfolded protein

Question 33

what is the most common clinically significant mutation leading to alpha-1-antitrypsin deficiency?

Answer 33

PiZ

Question 34

when is alpha-1-antitrypsin deficiency diagnosed?

Answer 34

because of it's early presentation with liver disease, alpha 1 AT deficiency is the most commonly diagnosed inherited hepatic disorder in infants and children

Question 35

what type of mutation leads to alpha-1 AT deficiency?

Answer 35

a point mutation (glu342-->Lys342)

Question 36

what are the histologic features associated with alpha-1 AT deficiency?

Answer 36

cytoplasmic globular inclusions in hepatocytes

Question 37

what are the 3 clinical presentations of alpha-1 AT deficiency?

Answer 37

neonatal hepatitis with cholestatic jaundice; adolescence (hepatitis, cirrhosis, or lung disease); middle to late life (cirrhosis +/- HCC)