18-3: Drug, Alcohol, and Metabolic Diseases

Question 1

which zone of the lobule is most susceptible to necrosis due to toxic substances

Answer 1

central zone of the lobule -> necrosis of perivenular hepatocytes (zone 3)

Question 2

with idiosyncratic reactions, which agent is most common in causing liver damage?

Answer 2

antimicrobials

Question 3

what percentage of alcoholics develop cirrhosis?

Answer 3

10-15 percent so drink on friends.

Question 4

What P450 enzyme isoform is prevalent in metabolizing alcohol?

Answer 4

CYP2E1

Question 5

describe clinical features of steatosis

Answer 5

hepatomegaly with minimal symptoms, mildly elevated bilirubin and alk phos

Question 6

describe clinical features of steatohepatitis

Answer 6

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

Question 7

describe clinical features of steatofibrosis/cirrhosis

Answer 7

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

Question 8

What diseases of the liver are diseases of purely metabolism

Answer 8

NAFLD
Hemochromatosis
Wilson disease
Alpha 1 antitrypsin deficiency

Question 9

What is the most common cause of chronic liver disease in the US

Answer 9

NAFLD

Question 10

Define NAFLD

Answer 10

presence of hepatic steatosis in individuals who do not consume alcohol and who do not have another cause of secondary hepatic fat accumulation

-histologically associated with metabolic syndrome

Question 11

how does pediatric NAFLD differ from adult NAFLD

Answer 11

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

Question 12

what causes hemocromatosis

Answer 12

excessive iron absorption

Question 13

how does excess iron damage the liver?

Answer 13

1) lipid peroxidation
2) stimulation of collagen by stellate cells
3) interaction of ROS with DNA -> HCC

Question 14

defect in what gene is responsible for hemochromatosis

Answer 14

HFE gene. Cystine-to-tyrosine 282

confined to caucasian

Question 15

what are the principle manifestations of hemochromatosis

Answer 15

hepatomegaly 
abd pain
abnormal skin pigmentation
deranged glucose or DM 
Cardiac dysfunction

Question 16

describe wilson disease

Answer 16

AR disorder caused by mutation of the ATP7B gene

impaired copper excretion into bile and failure to incorporate cu into ceruloplasmin.

Question 17

what is the age of onset for wilson disease

Answer 17

6-40 y/o with average being 11.4 years

Question 18

what are some clinical features of wilson disease

Answer 18

neurologic movement disorders
hemolytic anemia
acute and chronic liver disease

Question 19

how do a1AT deficiency affect the liver

Answer 19

accumulation of misfolded protein in liver

Question 20

what is the usual function of a1AT

Answer 20

inhibition of proteases (elastase, cathepsin G, proteinase 3) released by neutrophils at sites of inflammation

Question 21

what is the most common clinically significant mutation associated with a1AT?

Answer 21

PiZ

PiZAT sounds like Pizza. shut up I know yall’s fat asses get it

Question 22

what about the clinical progression of a1AT makes it the most commonly diagnosed inherited hepatic disorder in children

Answer 22

early presentation

Question 23

Order the mutation alleles from least to most severe in a1-Antitrypsin deficiency

Answer 23

MM
SM
ZM
SZ
ZZ