Metabolic/ Storage Diseases of Liver Flashcards
alpha 1-antitrypsin deficiency
autosomal recessive
mutation the is most pathological in alpha-1-antitrypsin deficiency
Pi ZZ variant: glutamine to lysine at position 342
A1AT deficiency - presentation in newborns/children
- liver related complications (more than adults)
- sx: neonatal jaundice, hepatomegaly, FTT, acute liver failure
- elevated liver enzymes in 25%
A1AT deficiency - adult presentation
- varying, but lung > liver
- greater risk of cirrhosis and HCC
- usually pts w/ cirrhosis or lier involvement have another identifiable cause of liver disease
- COPD and emphysema
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less common manifestation of A1AT deficiency: necrotizing panniculitis - painful necrosis of subq fat
(can also get anti-proteinase-3-positive vasculilits)
why might you see high or normal levels of A1AT in pts who truly have A1AT deficiency?
can be elevated in inflammation (acute phase reactant)
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A1AT deficiency
tx for A1AT deficiency - liver
liver transplant = cure
smoking cessation!
b/c this is the only place that alpha-1 antitrypsin is made
what problems are related to deficieny in each of these:
- C1 inhibitor
- antithrombin III
- alpha-1-antichymotrypsin
- C1 inhibitor: angioedema
- antithrombin III: thrombosis
- alpha-1-antichymotrypsin: COPD
function of hepcidin
expressed in hepatocytes, secreted into circulation
binds ferroportin (macrophages and basolateral side of enterocytes) –> more internalization and degradation of ferroportin, which INHIBITS iron export –> less iron in circ
how is iron regulated?
circulating iron detected by enterocytes –> stim hepcidin formation –> hepcidin effects ferroportin in enterocytes and macrophages –> more ferroportin internalized –> less iron absorbed and available
HFE protein
found on hepatocytes
sensor of circulating iron
features of HFE iron overload
- impaired synthesis or function of hepcidin
- lots of iron in plasma –> elevated transferrin saturation
- normal erythropoiesis
- responds to phlebotomy
features of non-HFE iron overload
- not assoc w/ hepcidin function or level
- transferrin sat slightly high or LOW
- iron in RES and cells (not plasma
- phlebotomy doesn’t help
hereditary hemochromatosis pathogenesis
mutation in HFE –> decreased hepcidin –> increased iron absorption and levels –> increased transferrin saturation –> deposition of iron in liver, heart, spleen and endocrine organs