Macrocytic Anemia

Question 1

Macrocytic Anemia

Answer 1

MCV >100fL: Increased MCH, normal MCHC Megaloblastic: Vitamin B12 deficiency, Folate deficiency, Hematologic neoplasms Non-megaloblastic: Chronic liver disease

Question 2

Megaloblastic Anemia

Answer 2

Delayed nuclear development in comparison to cytoplasmic development. A large, abnormal nRBC Megaloblasts develop as a result of nuclear-cytoplasmic (N:C) asynchrony: Abnormal DNA synthesis most commonly due to Vit B12/Folate deficiencies, Nuclear development is delayed, Cells cannot undergo mitosis and remain large throughout maturation Anemia is caused by the ineffective erythropoiesis from the disrupted DNA synthesis

Question 3

Megaloblastic Anemia Findings

Answer 3

Peripheral smear findings: Megaloblasts very, very rarely; Macroovalocytic RBCs, Poikilocytosis, Inclusions (Pappenheimer bodies, HJ bodies, nRBCs), Hypersegmented neutrophils Lab Findings: Increased - LDH, indirect Bili., Urobilinogen, serum iron, erythropoeitin Decreased - Haptoglobin

Question 4

Folate deficiency

Answer 4

Necessary for DNA synthesis, Becomes active by the action of Vitamin B12, Deficiency (Decreased hematopoiesis, Increased apoptosis, Megaloblastic maturation, May cause birth defects - Spina bifida)

Question 5

Causes of Folate Deficiency

Answer 5

Nutritional deficiency, Anything that requires increased hematopoiesis (Pregnancy, Leukemia, Other types of anemia), Chemotherapy (Methotrexate is an antifolate medication), Alcoholism, Intestinal malabsorption

Question 6

Vitamin B12 Deficiency

Answer 6

Necessary for DNA synthesis (Vitamin B12 is a cofactor for folate function), Fatty acid degradation Robles lead to faulty fatty acid synthesis, causing myelin sheath problems Deficiency: Megaloblastic anemia, Neurological disease which is ONLY PRESENT IN B12, NOT FOLATE DEFICIENCY (Psychotic symptoms, Motor and sensory abnormalities, Defective FA degradation affects myelin sheath of nerves)

Question 7

Causes of Vitamin B12 Deficiency

Answer 7

Nutritional deficiency, Intestinal malabsorption, Intrinsic factor deficiency (Known as pernicious anemia, Intrinsic factor- Produced by gastric parietal cells, Necessary for the absorption of B12- Deficiency often associated with autoimmune diseases)

Question 8

Non-megaloblastic Anemia

Answer 8

Cause of macrocytic development is unknown, but related to an increase in membrane lipids Associated with chronic liver diseases: Alcoholic liver disease, Infectious hepatitis, Biliary cirrhosis, Obstructive jaundice

Question 9

Non-megaloblastic Anemia Characteristics

Answer 9

Shortened RBC life span Hypersplenism is common, Heavy drinking can cause transient hemolysis, Acquired membrane abnormalities

Question 10

Non-megaloblastic Anemia Lab Tests

Answer 10

Macrocytosis, Stomatocytosis, Acanthocytosis, Elevated liver enzymes (To rule out megaloblastic anemia)

Question 11

Megaloblastic Anemia Clinical Presentation

Answer 11

Glossitis in addition to symptoms common to all anemias: Lethargy, weakness, jaundice

Question 12

Pernicious Anemia

Answer 12

Megaloblastic Anemia related to B12 deficiency, patients lack intrinsic factor due to autoimmune gastritis (aquired), can be Congenital (Auto. recessive) and cannot absorb B12 in the gut normally; the Schilling test may be used to differentiate Pernicious Anemia and B12 Deficiency

Question 13

Schilling Test

Answer 13

Given doses of a radioactive form of Vit B12 and urine is checked for the radiolabeled B12. If the levels are normal, the cause is B12 deficiency. If there is a high level of B12 present, the test continues. Intrinsic factor is added to the radiolabelled B12, this is to confrimthat the anemia is due to a lack of intrinsic factor causing poor absorbtion of B12 in the gut.