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Lecture 10

Macrocytic Anemia

Definition of Macrocytosis MCV>100 femtoliters (fL)
What is the bioche mical significance of megablastic anemia? This type of anemia indicates defective synthesis of DNA.
What are the morphologic findings in blood and marrow tissue in megaloblastic anemia? (1) Oval macrocytes (2) Hypersegmented PMN (3) Pancytopenia (4) "Giant" bands
Describe the mechanism of megaloblasic anemia due to folate deficiency. Anemia is a result of defective de novo DNA synthesis. With folate deficiency, dUTOP accumulates replacing dTTP in newly synthesized DNA. The faulty sequences are excised but repiar is not possible due to the lack of dTTP.
What is the importance of vitamin B12 in folate metabolism? Vitamin B12 is indirectly required for the conversion of folate to a form required for the synthesis of thymidylate.
How is vitamin B12 absorbed? In the stomach, vit B12 dissociated from food and binds to R protein. In the duodenum, B12 is released from R protein and binds to intrinsic factor (IF). The B12-IF complex binds to membrane receptors in the ileum.
What cells produce intrinsic factor (IF)? Gastric parietal cells
How is absorbed B12 transported in the plasma? Vitamin B12 is transported in the plasma by binding to transcobalamin II (TCII)
Where is trancobalamin II produced? (1) Liver (2) Macrophages (3) Endothelial cells
What biochemical processes is cobalamin essential for? (1) Conversion of homocysteine to methionine (2) Conversion of methylmalonyl-CoA to succinyl-CoA
What is the dietary source of cobalamin? Certain bacteria and animal muscle/organs
What is the most common cause of Vit B12 deficiency? Intrinsic factor deficiency
What conditions cause intrinsic factor deficiency? Pernicious anemia, Gastrectomy, Destruction of gastric mucosa, Anti-IF antibody in gastric juice
(T or F) A poor diet is a very common cause of Vitamin B12 deficiency anemia. False. A poor diet is a very rare cause of Vitamin B12 deficiency anemia.
What portion of the small bowel would result in Vitamin B12 deficiency? Ileum
An autoimmune disease in which parietal cell antibodies against gastric H+/K+ ATPase result in the destruction of gastric parietal cells, resulting in achlorhydria and decreased or absent intrinsic factor secretion. Pernicious Anemia
What is the effect on methylalonic acid and homocysteine in Vitamin B12 deificiency? Methylmalonic acid and homocysteine are elevated.
What chemical blocks hepatic release of folate into bile? Alcohol
What form is folate present in food? Polyglutamate form
What is the methylfolate trap hypothesis? It is a hypothesis that explains how B12 deficiency causes folate deficiency. Cobalamin is needed to convert N5-metyl-FH4 to FH4 (tetrahydrofolate). Colbalamin is a one carbon unit acceptor. In colabalmin deficiency, folate is trapped as N5-methyl-FH4.
What is the formate starvation hypothesis? Explains how B12 deficiency results in folate deficiency, based on the concept that only formylated folate can be conjugated. Lack of methionine decreases formate levels, resulting in impaired formylation of FH4, thus no conjugation to N5,10-methylene FH4
What are the dietary sources of folate? Green leafy vegetables, fruit, dairy products, yeast and animal livers.
What is the most common cause of folate deficiency? Poor diet (ex: alcoholism, infancy, dialysis)
What portion of the small bowel is folate absorbed? Jejunum
What is the daily requirement of cobalamins? 1 microgram
What is the daily requirement of folate? 100 micrograms
How long does the body's storage of folate last? The body stores a small amount that lasts for a few months.
How long does the body's storage of cobalamins last? The body stores a large amount that lasts for years.
What is a major complication of vitamin B12 deficiency? Irreversible neruological damage characterized as progressive neuropathy affecting both sensory and motor functions.
Will folate administration correct the neurologic deficits resulting from vitamin B12 deficiency? No. Folate administration only correct hematologic abnormalites of Vitamin B12 deficiency, but not the neurological deficits.
What conditions can result in both folate and cobalamin deficiency? Myeloma, pregnancy, and technetium/gallium scans.
What is the most likely cause of megaloblastic anemia if the Schillings test results for abnormally low, but normal after intrsinic factor administration? Prenicious anemia
Created by: UVAPATH4