Macrocytic anemia: B12 & folate

1. Macrocytic anemia: B12 & folate

2. Macrocytosis

3. Practical approach to Macrocytosis • History for alcohol, liver • CBC and blood film for evidence of marrow disease • Reticulocyte count • B12/Folate levels • Liver function, TSH • Bone marrow exam if cause in doubt and you really want to know

4. Low Hb=Anemia MCV Low=microcytic High=macrocytic Normal=normocytic Ferritin Measure B12 + folate Fe deficient Fe normal Normal Low - Establish cause Establish cause Obvious cause Cause not obvious Consider bone marrow Anemia of chronic disease or hemoglobinopathy Reticulocyte count Anemia of chronic disease Renal failure Marrow failure low Hemolysis or blood loss high

5. Vitamin B12 and folate All you need to know is contained in the following list

6. Both vitamin B12 and folate deficiency cause an identical megaloblastic anemia • Vitamin B12 deficiency causes demyelination in the spinal cord and peripheral nerves • It takes about 3 months to run out of folic acid, and 3 years to run out of vitamin B12 • Folate is in meat and vegetables (foliage) and is absorbed from the jejunum • Vitamin B12 is only in foods of animal origin; its absorption from the terminal ileum requires a specific binding protein called intrinsic factor • Folate deficiency results from poor diet, malabsorption or increased requirements • Vitamin B12 deficiency is commonly the result of Pernicious Anemia • Pernicious Anemia results from an autoimmune attack on gastric parietal cells causing achlorhydria and Intrinsic Factor deficiency • Low vitamin B12 levels are common in the elderly and usually do not cause anemia: they should be managed with oral vitamin B12 replacement • Deficiency of vitamin B12 and folic acid can be diagnosed by measuring serum levels; homocysteine and methylmalonic acid levels may help • Folate can be replaced orally. Vitamin B12 is traditionally given parenterally, but high dose oral therapy also works for Pernicious Anemia • Increasing dietary folate intake in a population lowers its average level of serum homocysteine: the daily dose for a maximum effect is 400 mcg • Neural tube defects can be prevented by using folate supplements in women intending to become pregnant

7. Biochemical Introduction

12. Both vitamin B12 and folate deficiency cause an identical megaloblastic anemia

13. Normal

14. oval macrocytes

15. hypersegmented polymorph

16. Normal marrow cells

17. Normal marrow cells

18. Megaloblastic marrow cells

19. Megaloblastic marrow cells giant metamyelocyte

20. 2. Vitamin B12 deficiency causes demyelination in the spinal cord and peripheral nerves

22. It takes about 3 months to run out of folic acid, and 3 years to run out of vitamin B12 • Folate is in meat and vegetables (foliage) and is absorbed from the jejunum

23. Victor Herbert 1927-2002 Louis Sullivan (b. 1933)

24. Vitamin B12 is only in foods of animal origin; its absorption from the terminal ileum requires a specific binding protein called intrinsic factor

26. George R Minot 1885-1950 William Murphy 1892-1987 George H Whipple 1878-1976 The Nobel Prize in Physiology or Medicine 1934

28. Blood, 1948, 3 (1).: 8-21.

31. Castle, who slept in a room next door to the Thorndike ward kitchen, resolutely fed himself 300 grams of raw beef patties every morning while in fasting state and after one hour induced regurgitation by pharyngeal stimulation. The captured semiliquid contents were adjusted to pH 2.5 to 3.5 with HCl and incubated for six hours at body temperature, after which the liquefied material was passed through a fine sieve and neutralized before introduction via Rehfuss tube into the stomach of the unwitting patient. Patients who were unresponsive to beef muscle alone (or to gastric juice alone) showed brisk reticulocyte responses when this sour admixture of predigested beef muscle was administered. Observations on the etiologic relationship of achylia gastrica to pernicious anemia. I. The effect of the administration to patients with pernicious anemia of beef muscle after incubation with normal human gastric juice. Am. J. Med. Sci. 1929, 178:748-63.

32. Folate deficiency results from poor diet, malabsorption or increased requirements

33. Vitamin B12 deficiency is commonly the result of Pernicious Anemia • Pernicious Anemia results from an autoimmune attack on gastric parietal cells causing achlorhydria and Intrinsic Factor deficiency

35. Other causes of Vitamin B12 deficiency • Elderly persons ("food vitamin B12 malabsorption") • Inadequate intake • vegans • Absorption defects • Congenital • Gastrectomy • Bowel abnormalities • blind loop syndrome, tropical sprue, fish tapeworm

36. Low vitamin B12 levels are common in the elderly and usually do not cause anemia: they should be managed with oral vitamin B12 replacement

37. Deficiency of vitamin B12 and folic acid can be diagnosed by measuring serum levels; homocysteine and methylmalonic acid levels may help

39. Folate can be replaced orally. Vitamin B12 is traditionally given parenterally, but high dose oral therapy also works for Pernicious Anemia

40. Increasing dietary folate intake in a population lowers its average level of serum homocysteine: the daily dose for a maximum effect is 400 mcg

41. Neural tube defects can be prevented by using folate supplements in women intending to become pregnant