Metabolic liver disease Flashcards
where is most of the iron in the body? In what form?
65% in hemoglobin. 35% in storage form (either ferritin or aggregates of ferritin called hemosiderin)
where is iron stored?
In Kupffer cells and hepatocytes
transferrin
iron transporter found in plasma. Combines with toxic iron to convert it to storage form (ferrritin)
how does the body balance iron content?
loses 1 mg in dead cells/day. 1mg absorbed/day in diet
cause of primary and secondary hemochromatosis
Autosomal recessive C282Y point mutation on HFE gene. Increased duodenal Fe absorption. Secondary due to chronic transfusions.
Hepcidin: released from? fxn? deficiency? regulated by?
released by liver to degrade ferroportin, thus inhibiting iron release from enterocytes into blood. Hepcidin deficiency leads to iron overload. Regulated by HFE (HFE mutation leads to Fe overload)
what organs are most often damaged in iron overload
liver, skin, pancreas, heart, pituitary, joints
hemochromatosis triad
“bronze diabetes”: DM (pacreas), bronze skin, cirrhosis
alpha 1 AT: function, what are mutant isoforms? what happens in deficiency? What diseases result
protease inhibitor. PiZZ. Synthesized in liver but mutant can’t be secreted to travel to lungs. Accumulates in ER of hepatocytes. Liver disease and emphysema
ceruloplasmin
Cu transport protein
Wilson Disease: Defect? result?
ATP7B copper transporting ATPase (no energy to transport Cu into bile and link it to ceruloplasmin in blood. Cu overload in hepatocytes causing ROS and free copper ions in blood.
what tissues are affected in Wilsons
liver, brain (basal ganglia), cornea, kidneys, joints
Findinds in wilson’s
decreased Ceruloplasmin, Cirrhosis, Corneal deposits (Kayser-Fleischer rings), Carcinoma.
Hemolytic anemia
basal ganglia deterioration (parkinsonism)
Asterixis
Dementia, dyskinesia, dysarthria
tx for wilsons
penicillamine
