23 - Metabolic Liver Disorders & Tumors

Question 1

genotype of alpha 1 antitrypsin def

Answer 1

PiZZ (PiMM is normal)

Question 2

clinical course of alpha 1 antritypsin def

Answer 2

variable - can present from childhood to adulthood
can cause fibrosis, chronic hepatitis or cirrhosis
can also cause pulm emphysema (but not usually in same pts w/ liver probs)

Question 3

% of alpha 1 antitrypsin pts (homozygous) that develop clinical dz

Answer 3

10%

Question 4

how does alpha 1 antitrypsin def cause liver damage?

Answer 4

builds up in cells (can’t go from ER > golgi)

triggers autophagocytic response > mitochondrial dysfunction > hepatocyte injury

Question 5

gene mutated in Wilson’s dz

Answer 5

ATP7B (transmembrane copper ATPase)

Question 6

ceruloplasmin

Answer 6

copper carrying protein in blood

will have dec levels in Wilson’s dz due to inhibition of secretion

Question 7

pathogenesis of Wilson’s dz

Answer 7

impaired incorporation of Cu into ceruloplasmin > inhib of ceruloplasmin secretion > dec Cu transport into bile > accumulation

Question 8

tx of Wilson’s dz

Answer 8

penicillamine

Question 9

which lab test is a bad measure for Wilson’s dz?

Answer 9

serum copper - can be nl, low or high, so tells you nothing.

Question 10

MC gene mutated for hereditary hemochromatosis

Answer 10

HFE gene - usually C282Y mutation

Question 11

pathogenesis of hereditary hemochromatosis

Answer 11

dec hepcidin expression > excessive iron absorption in gut > tissue toxicity from iron overload

Question 12

how much iron accumulation does it take to get sx?

Answer 12

~20g (hemochromatosis pts net .5-1 g/yr)

Question 13

sx of hemochromatosis

Answer 13

general weakness, hepatomegaly, arthralgia, DM, arrhythmias/cardiomyopathy, skin pigmentation, amenorrhea/impotence/loss of libido, cirrhosis

Question 14

MCC chronic liver test elevation

Answer 14

nonalcoholic fatty liver disease

Question 15

histologic features of steatohepatitis

Answer 15

steatosis, ballooning degen, Mallory Denk bodies (Mallory hyaline), lobular neutrophils, nonspecific portal and lobular inflammation, fibrosis around terminal hepatic veins and perisinusoidal fibrosis “chicken wire”

Question 16

MC benign tumor in liver

Answer 16

hemangioma

Question 17

focal nodular hyperplasia

Answer 17

usually in women 20-50yo
usually asymptomatic, no malignant potential
hepatocytes and ductules present, vascular etiology w/ regen

Question 18

hepatic adenoma

Answer 18

women of childbearing age
OCP is risk factor (strength and duration), also anabolic steroid use in men, androgens given for Fanconi’s/aplastic anemia, glycogenosis

moderate risk for hemoperitoneum, so larger ones resected. rare for malignant transformation to occur

Question 19

largest risk factor worldwide for HCC

Answer 19

hep B carriage

Question 20

risk factors for HCC

Answer 20

hep B/C
aflatoxins - toxic product of aspergillus
long term use of androgens
cirrhosis
G6PD def
congenital malformations - ex biliary atresia

Question 21

where does HCC metastasize to?

Answer 21

other places in liver / porta hepatis
LNs
lung
bone

Question 22

who survives HCC?

Answer 22

mostly only people w/ non-advanced disease who can have complete resection of tumor
noncirrhotics&raquo_space; cirrhotics

Question 23

fibrolamellar carcinoma

Answer 23

usually in children/ young adults
no cirrhosis or assoc w/ viral hepatitis
normal serum AFP
inc vit B12 binding proteins

prognosis much better than usual HCC

Question 24

cholangiocarcinoma causes

Answer 24

thorotrast (used in radiographic exam of biliary tract in past)
parasites - clonorchis, etc
hepatolithiasis
primary sclerosing cholangitis
congenital hepatic fibrosis, other congenital liver problems
cystic dilatation of bile ducts
cirrhosis inc risk (although most cases are in non-cirrhotics)
chronic hep C

Question 25

properties of cholangiocarcinoma

Answer 25

adenoCA
doesnt make bile
mucin pos, AFP neg
often k-ras mutations

Question 26

prognosis for cholangiocarcinoma

Answer 26

bad
most diagnosed late in course
mean survival <2 yrs
most dead in 6 mo

Question 27

angiosarcoma risk factors

Answer 27

thorotrast (old contrast)
PVC
arsenicals
androgen therapy

Question 28

prognosis/metastasis of angiosarcoma

Answer 28

very aggressive, most die in a year

goes to lungs, pleura, LNs, bone

Question 29

MC malignant tumor found in liver

Answer 29

metastasis (usually colon, lung, breast)