Metabolic Liver Dz

Question 1

what are secondary causes of hemachromatosis (iron overload)?

Answer 1

alcohol, hep C, NAFLD, transfusions, etc?

Question 2

inheritance pattern of HHC

Answer 2

AR

Question 3

this protein facilitates cellular uptake of iron

Answer 3

HFE protein

Question 4

the HFE protein complexes with the ____ receptor on ____ surface of the enterocyte

Answer 4

transferrin; basolateral

Question 5

2 different ___ mutations are found in the HFE protein; the worst one is ____

Answer 5

missense; C282Y

Question 6

crypt-programming model for hereditary hemachromatosis

Answer 6

mutated HFE can’t complex with TfR1, cell senses relative iron deficiency and tells enterocyte to absorb more iron (DMT1 production increases)

Question 7

hepcidin model for hereditary hemachromatosis

Answer 7

HFE mutation leads to decreased levels of hepcidin production –> inability to downregulate Fe release from enterocytes and macrophages

Question 8

clinical symptoms of HHC are usually?

Answer 8

asymptomatic or minimal sx

Question 9

lab findings in HHC

Answer 9

elevated liver tests (ALT), elevated Fe studies (ferritin, serum Fe, saturation)

Question 10

physical exam findings of HHC

Answer 10

hepatomegaly, “bronzing”

Question 11

what is the cause of “bronzing” in HHC?

Answer 11

direct iron deposition, increased melanin in dermis

Question 12

how can HHC lead to diabetes?

Answer 12

pancreatic iron deposition damages islet cells = increased insulin resistance

Question 13

HHC causes hypogonadism because of?

Answer 13

pituitary and direct testicular iron deposition

Question 14

cardiomyopathy and conduction disturbances caused by HHC are _____, while arthropathy is ____

Answer 14

reversible with treatment; irreversible

Question 15

what types of arthropathy are seen in HHC?

Answer 15

pseudogout, squared-off bone ends, hook-like osteophytes

Question 16

while elevated ____ and ____ are suggestive of HHC, ____ or _____ are diagnostic

Answer 16

transferrin saturation, ferritin; genetic testing for HFE mutation, liver biopsy

Question 17

what is the tx for HHC?

Answer 17

phlebotomy to remove iron and deplete stores

Question 18

mutations in ____ lead to Wilson’s dz, a (common/rare) disorder of ____ metabolism

Answer 18

ATP7B; rare; copper

Question 19

who is affected by Wilson’s? (age)

Answer 19

young patients

Question 20

which 4 organ systems are predominantly affected in Wilson’s dz?

Answer 20

liver (chronic hepatitis, cirrhosis, fulminant hepatic failure), heme (hemolytic anemia), neuro (psychosis, seizures, ataxia, tremors), renal (tubular acidosis, kidney stones)

Question 21

what are Kayser-Fleisher rings?

Answer 21

golden-brown pigment deposits around periphery of pupil

Question 22

diagnostic indicators of Wilson’s

Answer 22

high serum copper, high urine copper, low serum ceruloplasmin, low AP in setting of high bili

Question 23

management of Wilson’s dz

Answer 23

copper chelation (D-penicillamine, trientine, zinc), liver transplant if bad

Question 24

dx of alpha-1-antitrypsin deficiency

Answer 24

low A1AT, could also see on liver biopsy with PAS; PiZZ worst phenotype