4 - Iron Metabolism and Disorders Flashcards
why does iron need carrier proteins?
ferrous iron is very reactive and will cause oxidative damage to cells
2 carrier proteins for iron
intracellular - ferritin
circulation - transferrin
what is the rate of iron turnover in a day? how much is needed for erythropoiesis?
20-25 mg/d turnover
20 mg/d for erythropoiesis
where is iron absorbed in the GI tract?
duodenum
what channels are used in iron absorption?
divalent metal transporter 1 (DMT1) - lumen to enterocyte
ferroportin 1 - enterocyte to circulation
where are RBCs degraded and by what cell type?
in the spleen by macrophages
what protein is responsible for regulation of iron metabolism and how does it work?
hepcidin - negatively regulates iron absorption in GI and release from macrophages
where is hepcidin synthesized?
hepatocytes
do hepcidin levels increase or decrease with inflammation?
increase
2 general mechanisms of inherited iron overload conditions
hepcidin deficiency or hepcidin resistance
most common form of inherited iron overload and mode of inheritance
classic (type 1) hemochromatosis
autosomal recessive
mechanism of classic hemochromatosis
low hepcidin
juvenile hemochromatosis (type 2)
mutation in hemojuvelin gene or gene for hepcidin > little or no hepcidin
presents in late childhood / early adulthood
how does beta thalassemia lead to iron overload?
ineffective hemoglobin leads to continous erythropoietic signal, which overrides the iron overload signal keeping hepcidin levels low
clinical manifestations of iron overload
cirrhosis, diabetes (may improve w/ tx), joint pain, osteoporosis, restrictive and dilated cardiomyopathy, arrhythmias, heart failure (reversible), increased skin pigmentation, increased risk of liver cancer
first line tests for iron overload
transferrin saturation and serum ferritin
main causes of iron deficiency
chronic blood loss, increased demands (ex growth, pregnancy, EPO), malabsorption, poor diet (mainly in developing countries)
clinical manifestations of iron deficiency anemia
pallor, fatigue, exercise intolerance cardiomegaly pica cognitive impairment defects in leukocyte/lymphocyte fn Plummer Vinson syndrome cerebral vein thrombosis
Plummer Vinson syndrome
occurs in iron deficiency. triad of koilonychia (spooned nails), atrophic glossitis, esophageal web
how can lead poisoning cause iron deficiency?
competition for DMT1 transporter in gut
what should you assume iron deficiency is in an adult male or postmenopausal woman until proven otherwise?
GI blood loss
anemia of inflammation
normocytic (or slightly microcytic) and resistant to iron therapy
due to hepcidin increases (transient)
must treat underlying disease to get rid of it
how does iron metabolism contribute to anemia of chronic kidney disease?
dec kidney fn > dec clearance of hepcidin > inc hepcidin levels > dec iron levels
