23 - Metabolic Liver Disorders & Tumors Flashcards
genotype of alpha 1 antitrypsin def
PiZZ (PiMM is normal)
clinical course of alpha 1 antritypsin def
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)
% of alpha 1 antitrypsin pts (homozygous) that develop clinical dz
10%
how does alpha 1 antitrypsin def cause liver damage?
builds up in cells (can’t go from ER > golgi)
triggers autophagocytic response > mitochondrial dysfunction > hepatocyte injury
gene mutated in Wilson’s dz
ATP7B (transmembrane copper ATPase)
ceruloplasmin
copper carrying protein in blood
will have dec levels in Wilson’s dz due to inhibition of secretion
pathogenesis of Wilson’s dz
impaired incorporation of Cu into ceruloplasmin > inhib of ceruloplasmin secretion > dec Cu transport into bile > accumulation
tx of Wilson’s dz
penicillamine
which lab test is a bad measure for Wilson’s dz?
serum copper - can be nl, low or high, so tells you nothing.
MC gene mutated for hereditary hemochromatosis
HFE gene - usually C282Y mutation
pathogenesis of hereditary hemochromatosis
dec hepcidin expression > excessive iron absorption in gut > tissue toxicity from iron overload
how much iron accumulation does it take to get sx?
~20g (hemochromatosis pts net .5-1 g/yr)
sx of hemochromatosis
general weakness, hepatomegaly, arthralgia, DM, arrhythmias/cardiomyopathy, skin pigmentation, amenorrhea/impotence/loss of libido, cirrhosis
MCC chronic liver test elevation
nonalcoholic fatty liver disease
histologic features of steatohepatitis
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”
MC benign tumor in liver
hemangioma
focal nodular hyperplasia
usually in women 20-50yo
usually asymptomatic, no malignant potential
hepatocytes and ductules present, vascular etiology w/ regen
hepatic adenoma
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
largest risk factor worldwide for HCC
hep B carriage
risk factors for HCC
hep B/C
aflatoxins - toxic product of aspergillus
long term use of androgens
cirrhosis
G6PD def
congenital malformations - ex biliary atresia
where does HCC metastasize to?
other places in liver / porta hepatis
LNs
lung
bone
who survives HCC?
mostly only people w/ non-advanced disease who can have complete resection of tumor
noncirrhotics»_space; cirrhotics
fibrolamellar carcinoma
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
cholangiocarcinoma causes
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
properties of cholangiocarcinoma
adenoCA
doesnt make bile
mucin pos, AFP neg
often k-ras mutations
prognosis for cholangiocarcinoma
bad
most diagnosed late in course
mean survival <2 yrs
most dead in 6 mo
angiosarcoma risk factors
thorotrast (old contrast)
PVC
arsenicals
androgen therapy
prognosis/metastasis of angiosarcoma
very aggressive, most die in a year
goes to lungs, pleura, LNs, bone
MC malignant tumor found in liver
metastasis (usually colon, lung, breast)
