Macrocytic Anemia 9/27 Flashcards
What tests are done if MCV is low?
Iron studies
Hgb electrophoresis
What tests do you run if MCV is normal?
Check serum creatine and TSH
Bone marrow exam
What do you do if MCV is high?
Check folate and B12 levels
What molecules are required for RBC synthesis? (7)
- EPO
- Proteins for globins
- Iron
- B12 & B6
- Vitamin C
- Folic acid
- TH, estrogen, androgen
In macrocyctic anemia, what will the values of MCH and MCHC be compared to normal?
MCH: ⬆️
MCHC: normal (conc of Hgb is normal)
What is the MCV megaloblastic Macrocytic anemia?
MCV > 110
Severe
What is the MCV of non-megaloblastic?
MCV: 100-110
What are the causes of megaloblastic anemia? (3)
- B12 deficiency
- Folate deficiency
- Drugs
What are the causes on non-megaloblastic anemia? (6)
- Alcoholism
- Liver disease
- Hypothyroidism
- Aplastic anemia
- Hemolysis/acute bleed
- Artifact
- cold agglutin disease
- hyperglycemia (RBC swelling)
What is the shape of RBCs in Macrocytic anemia?
Oval: macro ovalocytes
What is the RBC shape in non-megaloblastic anemia?
ROUND
What part of the cell cycle are B12 and folic acid required for?
DNA synthesis
What is the term for when B12/folic acid deficiency impairs nuclear maturation?
Nuclear cytoplasmic asynchrony: abnormally large erythroid precursors and RBCs
Where is folic acid absorbed and what does it bind to for transportation?
Duodenum & Jejunum
Transported by albumin
What is the metabolic function of folic acid? (2)
- Purine synthesis
2. Conversion of homocysteine to methionine (also requires b12)
Four causes of folic acid deficiency:
- Increased demand: pregnancy, lactation, puberty
- Decreased intake: elderly, low socioeconomic status, alcoholics
- Decreased absorption: acidic foods, drugs (BC, phenytoin), celiac disease, heat
- Metabolic inhibition
How is B12 absorbed?
B12 binds with intrinsic factor (IF), which is synthesized in gastric cells.
Absorption occurs in distal ileum.
What is the name of the protein that transports B12?
TRANSCOBALAMINE II: synthesized in liver, carries b12 to liver, nerves, bone marrow
What could cause impaired absorption of B12? (5)
- IF deficiency due to chronic gastritis
- Malabsorption states
- Intestinal disease (lymphoma, sclerosis)
- Parasite - tapeworm
- Bacterial overgrowth
What folate dependent reaction leads to defective DNA synthesis?
Thymidylate synthesis
What 2 enzymatic reactions is B12 a necessary cofactor for?
- Homocysteine to methionine
- Methylmalonyl CoA to succinyl-CoA
- –> NEUROLOGICAL DEFICIENCIES
What does the stomach secrete to metabolize B12?
Trypsin and stomach acids release B12. IF is released. B12 binds to R-Binding Protein
What happens to B12 in the Jejunum?
PEPSIN releases B12 from R-binding protein.
B12 binds to IF and is carried to ileum, which is where it is absorbed.
How long does it take folate deficiency to develop into megaloblastic anemia? How long for B12?
Folate: 4 months
B12: ~3-5 years
PERNICIOUS ANEMIA is an impaired absorption of B12 leading to deficiency? How?
Decreased secretion of intrinsic factor due to gastric atrophy, loss of parietal cells.
What are 5 other causes of impaired absorption of B12?
- Chronic pancreatitis
- Chron’s disease
- Ileal Sprue
- Fish tapeworm
- Blind loop (intestinal bacterial overgrowth)
How are the levels of methylmalonic acid and homocysteine affected with B12 deficiency? Folate deficiency?
B12: both increased
Folate: only homocysteine increased
What test should be performed to determine the source of B12 deficiency?
Schillings Test
What are the sequence of changes in megaloblastic anemia? (5)
- Vitamin levels ⬇️
- Neutrophil hypersegmentation
- Ovalocytes
- Megaloblastic changes in BM
- Anemia
