Chapter 4: Megaloblastic Anemias (macrocytic anemias) Flashcards
What are macrocytic anemias?
Anemias in which cells have a MCV greater than 95.
What is megaloblastic anemia?
Anemia characterized by cells with nuclei that are immature compared with the cytoplasm.
What is the underlying cause of megaloblastic anemia?
Megaloblastic anemia is usually caused by defective DNA synthesis. (commonly the result of B12 or folate deficiency.
What is cobalamin (55)?
Cobalamin is Vitamin B12.
Where is B12 created (55)?
B12 is created by microorganisms.
What is the structure of B12 (55)?
B12 (cobalamin) is composed of a cobalt atom at the center of a corrin ring
How is B12 absorbed(56)?
B12 binds to intrinsic factor (IF) forming a complex that binds the receptor cubilin. the new complex then binds a second protein called amnionless which then endocytoses the B12.
What happens to B12 in the blood stream (56)?
B12 in the blood stream binds to either transcobalamin or haptocorrin. However, only transcobalamin is able to deliver B12 to the bone marrow.
What binds more B12 haptocorrin or transcobalamin (57)?
Haptocorrin binds most of the B12.
What are the two biochemical functions of B12 (57)?
(1) B12 is a cofactor for methionine synthase in the synthesis of methionine
(2) B12 helps to convert methylmalonyl CoA to succinyl CoA.
How is B12 deficiency tested for (57)?
levels of homocysteine or methylmalonic acid are assayed.
How is Folate absorbed(58)?
Folate is converted to THF to be absorbed by enterocytes. The enterocytes then convert THF to folate polyglutamates.
What is the function of folate(58)?
Folate functions in single carbon unit transfer. (synthesis of glycine or purine etc.)
Why does folate deficiency cause megaloblastic anemia(58)?
Folate deficiency causes megaloblastic anemia because folate is necessary for the synthesis of thymidylate (a precursor of thymine).
How is dihydrofolate converted to tetrahydrofolate during thymidylate synthesis(59)?
It is converted by dihydrofolate reductase?
What drugs inhibit dihydrofolate reductase(59)?
(1) Methotrexate (antineoplastic)
(2) pyrimethamine (anti malarial)
(3) Trimethoprim (antimicrobial)
What are the most common causes of B12 deficiency in western culture (59)?
(1) Addisonian pernicious anemia
(2) Veganism (it is found in meat)
(3) Gastrectomy or small intestinal lesions.
(4) Nitrous oxide may inactivate B12.
What causes pernicious anemia(59)?
Pernicious anemia is caused by an autoimmune attack that causes atrophy of the gastric mucosa. (commonly initiated by helicobacter pylori infection)
What is the epidemiology of pernicious anemia(59)?
(1)Pernicious anemia is most common in females. (2)Peak age of onset is 60. (3) Occurs most in northern europeans. (4) 2-3% of patients develop carcinoma of the stomach.
What antibodies are present in pernicious anemia(60)?
(1) Parietal cell antibodies (against H/K ATPase) (90%) (also occurs in 16% for normal people over 60)
(2) Type 1 blocking antibody against IF (50%)
(3) Type 2 precipitating antibody against IF.
How long does it take for B12 deficiency to take effect (60)?
it takes 2 years for B12 stores to be depleted.
What are some secondary causes of B12 deficiency (60)?
(1) Congenital defect in B12 absorption complex
(2) inadequate intake
(3) atrophic gastritis (without IF antibodies) (helicobacter pylori)
What causes folate deficiency (60)?
Folate deficiency occurs when intake is not adequate for the level of folate utilization. Increased utilizaiton (pregnancy) or inadequate diet may be the cause.
What are the primary clinical features often seen in Megaloblastic anemia (60)?
Insidious with progressive onset
(1) Mild jaundice
(2) Glossitis
(3) Angular stomatitis
(4) Mild malabsorption and weight loss (epithelial abnormality)
(5) melanin pigmentation