Anemia due to Decreased RBC Production II

Question 1

dietary sources of vitamin B12

Answer 1

Originally synthesized by bacteria and algae (works it way up the food chain), we eat it through eggs, meat and milk (NO PLANTS). Once ingested, released in the acid environment of stomach. Intrinsic factor (IF) secreted by gastric parietal cells, is a protein carrier and binds VitB12.

Question 2

vitamin B12’s associated site and mechanism of absorption, means of transport and duration and location of storage

Answer 2

Once ingested, released in the acid environment of stomach. Intrinsic factor (IF) secreted by gastric parietal cells, is a protein carrier and binds VitB12. Absorbed in ILEUM and released from IF, bound to transcobalamin binding protein II and transported to liver for storage or to other tissues for use.

Question 3

vitamin B12’s location of storage

Answer 3

6 months of B12 stored in liver, therefore disease doesn’t progress as rapidly.

Question 4

dietary sources of folate

Answer 4

widespread in food: cereals, breads (1/3), fruits and veggies (1/3), meats and fish (1/3). Human milk has enough folate for infants. Overcooking leads to loss of folates from food.

Question 5

folate’s associated site and mechanism of absorption, means of transport and duration and location of storage

Answer 5

Folate absorbed in the JEJUNUM. It is hydrolyzed, reduced and methylated before distribution to tissues or liver for storage (as methyltetrahydrofolate). Liver stores undergo turnover, secretion in the bile and reabsorption (enterohepatic circulation).

Question 6

Describe the findings in the peripheral blood and bone marrow in a patient with B12 or folate deficiency

Answer 6

a. Hematologic Changes: both will show erythroid hyperplasia, cytoplasmic maturation normal, Peripheral blood, Macrocytosis (MCV > 97 fl in adults), Ovalocytes, Hypersegmented nuclei of neutrophils, As anemia progresses, poikilocytes and fragmentation, In severe cases, see neutropenia and thrombocytopenia, ↑ bilirubin (and other evidence of hemolysis, destruction in marrow), Retic index < 1.0. Anemia (may also see neutropenia and thrombocytopenia in severe cases).↑ MCV. Low reticulocyte count and index. ↑ unconjugated bilirubin and LDH.

Question 7

Describe the differences between vitamin B12 deficiency and folate deficiency with respect to their most common causes

Answer 7

Folate: inadequate dietary intake –> megaloblastic anemia
B12: autoimmune disease (#1 cause: pernicious anemia: autoimmune destruction of paretial cells that produce intrinsic factor), intrinsic factor deficiency (congenital, atrophic gastritis, gastrectomy—no paretial cells= no IF), malabsorption (pancreatic insufficiency, bacterial overgrowth, parasites, AIDS), defective transport/storage (transcobalamin II deficiency), metabolic defect

Question 8

Describe the differences between vitamin B12 deficiency and folate deficiency with respect to the presence of neurologic abnormalities

Answer 8

folate: rare
B12: Classical neurologic features: sensory losses first (numbness/tingling), loss of proprioception, ataxia, spasticity, gait disturbances, + Babinski signs, cognitive/emotional changes. Neuro defects may be non-reversible.

Question 9

Describe the differences between vitamin B12 deficiency and folate deficiency with respect to laboratory studies used to make a diagnosis

Answer 9

measurement of serum cobalamin levels and serum or red cell folate levels. Measurement of plasma homocysteine levels has been used as a more sensitive marker. Methylmalonic acid will be ↑ in B12 deficiency ONLY. TO determine etiology of B12 deficiency use Schilling Test.

Question 10

Describe the differences between vitamin B12 deficiency and folate deficiency with respect to time to development

Answer 10

• Pace of folate deficiency is weeks to months (rapid)

- Vit B12 deficiency develops slowly (over years) and is most likely associated with malabsorption

Question 11

Schilling Test

Answer 11

Test: 1 µg of radiolabeled cobalamin given orally, IF produced in stomach binds radiolabeled cobalamin and it is absorbed at terminal ileum. Tagged colabamin is then bound to transcobalamin II and enters blood. A dose of unlabeled colabamin is given IM 2 hrs later, causing some radiolabeled to be excreted via urine (5-35%). If patient isn’t absorbing cobalamin given orally, less radiolabeled cobalamin will be excreted

Question 12

Describe the appropriate therapies for B12 deficiency and folate deficiency.

Answer 12

a. Cobalamin deficiency: IM or SQ injections of B12 (daily for 2 wks, weekly until HCT is normal, then monthly for life).
b. If absorption is normal, oral replacement works.
c. Folate deficiency: 1 mg/day orally or parenterally