Metabolic Liver Dz Flashcards
what are secondary causes of hemachromatosis (iron overload)?
alcohol, hep C, NAFLD, transfusions, etc?
inheritance pattern of HHC
AR
this protein facilitates cellular uptake of iron
HFE protein
the HFE protein complexes with the ____ receptor on ____ surface of the enterocyte
transferrin; basolateral
2 different ___ mutations are found in the HFE protein; the worst one is ____
missense; C282Y
crypt-programming model for hereditary hemachromatosis
mutated HFE can’t complex with TfR1, cell senses relative iron deficiency and tells enterocyte to absorb more iron (DMT1 production increases)
hepcidin model for hereditary hemachromatosis
HFE mutation leads to decreased levels of hepcidin production –> inability to downregulate Fe release from enterocytes and macrophages
clinical symptoms of HHC are usually?
asymptomatic or minimal sx
lab findings in HHC
elevated liver tests (ALT), elevated Fe studies (ferritin, serum Fe, saturation)
physical exam findings of HHC
hepatomegaly, “bronzing”
what is the cause of “bronzing” in HHC?
direct iron deposition, increased melanin in dermis
how can HHC lead to diabetes?
pancreatic iron deposition damages islet cells = increased insulin resistance
HHC causes hypogonadism because of?
pituitary and direct testicular iron deposition
cardiomyopathy and conduction disturbances caused by HHC are _____, while arthropathy is ____
reversible with treatment; irreversible
what types of arthropathy are seen in HHC?
pseudogout, squared-off bone ends, hook-like osteophytes
while elevated ____ and ____ are suggestive of HHC, ____ or _____ are diagnostic
transferrin saturation, ferritin; genetic testing for HFE mutation, liver biopsy
what is the tx for HHC?
phlebotomy to remove iron and deplete stores
mutations in ____ lead to Wilson’s dz, a (common/rare) disorder of ____ metabolism
ATP7B; rare; copper
who is affected by Wilson’s? (age)
young patients
which 4 organ systems are predominantly affected in Wilson’s dz?
liver (chronic hepatitis, cirrhosis, fulminant hepatic failure), heme (hemolytic anemia), neuro (psychosis, seizures, ataxia, tremors), renal (tubular acidosis, kidney stones)
what are Kayser-Fleisher rings?
golden-brown pigment deposits around periphery of pupil
diagnostic indicators of Wilson’s
high serum copper, high urine copper, low serum ceruloplasmin, low AP in setting of high bili
management of Wilson’s dz
copper chelation (D-penicillamine, trientine, zinc), liver transplant if bad
dx of alpha-1-antitrypsin deficiency
low A1AT, could also see on liver biopsy with PAS; PiZZ worst phenotype
