Iron Overload Syndromes Flashcards
What are the two major categories of Iron Overload syndromes?
- Hereditary hemochromatosis
- Secondary iron overload
What occurs in hereditary hemochromatosis?
Toxic accumulationin parenchymal cells, particularly of the liver, heart, and pancreas
What are the clinical hallmarks of hereditary hemochromatosis?
- Cirrhosis
- Diabetes
- Skin pigmentation
- Cardian failure
Inheritance of hereditary hemochromatosis?
Autosomal recessive
What vitamin deficiency makes iron absorption difficult?
Vitamin C deficiency
Protein that facilitiates cellular iron transport? Carrier export protein? Transport in the serum?
- Ferroportin
- Hephastin
- Transferrin
Primary iron storage protein?
Ferritin
What is the product of ferritin degradation?
Hemosiderin
Most important regulator of plasma iron?
Hepcidin
Gene involved with hereditary hemochromatosis?
HFE gene on chromosome 6
Two hypotheses of hereditary hemochromatosis?
- Mutant HFE protein cannot promote iron uptake. Therefore, duodenal crypt cells sense an iron deficiency and upregulate DMT-1 and ferroportin expression which increases absorption of dietary iron
- Hepcidin protein downregulates iron release by enterocytes and macrophages
What is juvenile hemochromatosis?
Mutation in hemojuvelin causing rapid and severe progression of tissue damage
What appears to play the central role in hemochromatosis?
Hepcidin
Complications of hemochromatosis?
- Liver always affected resulting eventually in cirrhosis
- Skin - pigmentation
- Pancreas - Diabetes
- Heart - congestive HF
- Endocrine - deposition in pituitary, adrenal, thyroid, parathryoid
- Joint - arthropathy
With what conditions do patients have massive iron overload?
- Sickle Cell
- Hemolytic anemias
- Thalassemia major
- Anemias w/ ineffective erythropoesis
