4 - Iron Metabolism and Disorders

Question 1

why does iron need carrier proteins?

Answer 1

ferrous iron is very reactive and will cause oxidative damage to cells

Question 2

2 carrier proteins for iron

Answer 2

intracellular - ferritin

circulation - transferrin

Question 3

what is the rate of iron turnover in a day? how much is needed for erythropoiesis?

Answer 3

20-25 mg/d turnover

20 mg/d for erythropoiesis

Question 4

where is iron absorbed in the GI tract?

Answer 4

duodenum

Question 5

what channels are used in iron absorption?

Answer 5

divalent metal transporter 1 (DMT1) - lumen to enterocyte

ferroportin 1 - enterocyte to circulation

Question 6

where are RBCs degraded and by what cell type?

Answer 6

in the spleen by macrophages

Question 7

what protein is responsible for regulation of iron metabolism and how does it work?

Answer 7

hepcidin - negatively regulates iron absorption in GI and release from macrophages

Question 8

where is hepcidin synthesized?

Answer 8

hepatocytes

Question 9

do hepcidin levels increase or decrease with inflammation?

Answer 9

increase

Question 10

2 general mechanisms of inherited iron overload conditions

Answer 10

hepcidin deficiency or hepcidin resistance

Question 11

most common form of inherited iron overload and mode of inheritance

Answer 11

classic (type 1) hemochromatosis

autosomal recessive

Question 12

mechanism of classic hemochromatosis

Answer 12

low hepcidin

Question 13

juvenile hemochromatosis (type 2)

Answer 13

mutation in hemojuvelin gene or gene for hepcidin > little or no hepcidin
presents in late childhood / early adulthood

Question 14

how does beta thalassemia lead to iron overload?

Answer 14

ineffective hemoglobin leads to continous erythropoietic signal, which overrides the iron overload signal keeping hepcidin levels low

Question 15

clinical manifestations of iron overload

Answer 15

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

Question 16

first line tests for iron overload

Answer 16

transferrin saturation and serum ferritin

Question 17

main causes of iron deficiency

Answer 17

chronic blood loss, increased demands (ex growth, pregnancy, EPO), malabsorption, poor diet (mainly in developing countries)

Question 18

clinical manifestations of iron deficiency anemia

Answer 18

pallor, fatigue, exercise intolerance
cardiomegaly
pica
cognitive impairment
defects in leukocyte/lymphocyte fn
Plummer Vinson syndrome
cerebral vein thrombosis

Question 19

Plummer Vinson syndrome

Answer 19

occurs in iron deficiency. triad of koilonychia (spooned nails), atrophic glossitis, esophageal web

Question 20

how can lead poisoning cause iron deficiency?

Answer 20

competition for DMT1 transporter in gut

Question 21

what should you assume iron deficiency is in an adult male or postmenopausal woman until proven otherwise?

Answer 21

GI blood loss

Question 22

anemia of inflammation

Answer 22

normocytic (or slightly microcytic) and resistant to iron therapy
due to hepcidin increases (transient)
must treat underlying disease to get rid of it

Question 23

how does iron metabolism contribute to anemia of chronic kidney disease?

Answer 23

dec kidney fn > dec clearance of hepcidin > inc hepcidin levels > dec iron levels