Sideroblastic Anemia Flashcards
An anemia caused by a defect in protoporphyrin synthesis…
Sideroblastic anemia
Why does defective protoporphyrin synthesis lead to microcytic anemia?
There is a decrease in the amount of protoporphyrin→ decreased amount of protoporphyrin and Fe binding to form heme→ decreased heme→ decreased Hb→ microcytic anemia
In protoporphyrin synthesis, what enzyme converts succinyl CoA to aminolevulinic acid (ALA)?
Aminolevulinic acid synthetase (ALAS)
RATE LIMITING STEP
What cofactor is used to convert succinyl CoA to aminolevulinic acid (ALA)?
Vitamin B6
What is the rate-limiting step for protoporphyrin synthesis?
succinyl CoA to aminolevulinic acid (ALA) by ALAS and Vit B6 cofactor
What enzyme is used for the conversion of aminolevulinic acid (ALA) to porphobilinogen?
Aminolevulinic acid dehydrogenase (ALAD)
What enzyme attaches protoporphyrin to iron to form heme?
Ferrochelatase
Where does the final reaction of heme synthesis (protoporphyrin to iron forming heme) occur?
Mitochondria
Why do ringed sideroblasts form in sideroblastic anemia?
This is due to the buildup of iron that enters the mitochondria to attach with protoporphyrin to form heme. Without protoporphytin, Iron is unable to bind and heme is unable to form. The iron build-up in the mitochondria and forms the distinctive ring seen under microscopy.
What step of protoporphyrin synthesis is involved in the congenital form of sideroblastic anemia?
ALAS—conversion of succinyl CoA to aminolevulinic acid (ALA)
The RATE LIMITING STEP
What are the 3 most common causes of acquired sideroblastic anemia?
Alcoholism
Lead poisoning
Vitamin B6 deficiency
Why does alcoholism cause sideroblastic microcytic anemia?
The ETOH causes mitochondrial poisoning
What is the mechanism by which lead poisoning causes sideroblastic microcytic anemia?
Inhibits ALAD and ferrochelatase within the protoporphyrin synthesis pathway
A patient is being treated with isoniazid for his tuberculosis and presents with sideroblastic microcytic anemia. What is the most likely cause of this patient sideroblastic anemia?
Vitamin B6 deficiency caused by the isoniazid treatment
With respect to ferritin, TIBC, serum iron and % saturation of iron, what are the findings on laboratory studies of patients who present with sideroblastic anemia?
Ferritin—increased
TIBC—decreased
Serum iron—Increased
% saturation—increased
Iron-overloaded state
