MEGALOBLASTIC ANAEMIA VIT B12 DEFICIENCY
CAUSES OF MEGALOBLASTIC ANAEMIA VIT B12 DEFICIENCY FOLATE DEFICIENCY ABNORMALITIES OF VIT B12 OR FOLATE METABOLISM DEFECTS OF DNA SYNTHESIS:
Congenital enzyme deficiencies Acquired enzyme defienciencies
In Western countries, severe deficiency is usually by pernicious anaemia. Less commonly, it may caused by veganism in which the diet lacks B12, gastrectomy or small intestinal lesions. The deficiency takes at least 2 years to develop when there is severe malabsorption of B12 from diet. Nitrous oxide, however, may rapidly inactivate body B12
VIT B12 DEFICIENCY Low dietary intake (strict vegetarian) Absorption:
Pernicious A / Gastrectomy- malabsorption syndromes- terminal ileal disorder Congenital deficiency of intrinsic factor (IF)/ transcobalamin II
In small gut: Vit B12 binds IF which is synthesized by the gastric parietal cells
The IF-B12 complex can then bind to a specific surface receptor for IF, cubilin, which then binds to a second protein, amnionless which directs endocytosis of the cubilin IF-B12 complex in the distal ileum
Vit B12 is then absorbed & IF is destroyed
Vit B12- absorbed in portal blood = becomes attached to the plasmabinding protein- transcobalamic---which delivers B12 to bone marrow (BM) and other tissues
PERNIOUS ANAEMIA AUTOIMMUNE DISEASE CHARACTERIZED BY ATROPHY OF THE GASTRIC MUCOSA RESULTING = failure of the IF production & hence failure of B12 absorption
CLINICAL FEATURES OF VIT B12 DEFICIENCY •
FATIGUE, HEADACHE, PALPITATION, ANGINA, PALLOR, TACHYCARDIA
3.
SKIN HAS A LEMON YELLOW (MILD JAUNDICED) = excess breakdown of haemoglobin resulting from increased ineffective erythropoiesis in BM
5.
GLOSSITIS (a beefy-red sore tongue) & ANGULAR STOMATITIS
7.
PURPURA & BLEEDING TENDENCY DUE TO THROMBOCYTOPENIA
9.
SEVERE VIT B12 DEFICIENCY ANAEMIA= Progressive neuropathy affecting the sensory nerves & posterior & lateral columns
LAB FINDINGS Serum B12 low MCV>95 fl (severe 120-140 fl) Macrocytes- typically oval in shape Reticulocyte count decreased Total WC & platelet count may moderately reduced Neutrophils show hypersegmented nuclei( with 6/> lobes) BM= hypercellularity & erythroblasts are large Serum unconjugated bilirubin & LDH raised as result of marrow cell breakdown
Hypersegmented Neutrophils Multilobed polymorphonuclear neutrophils are characteristically found in megaloblastic anaemia which is usually consequent on deficiency of either vitamin B12 or folic acid. In normal people, not more than 3% of neutrophils have more than five lobes; in megaloblastic anaemia the average lobe count is increased and neutrophils with 6, 7, or 8 lobes may be seen. This film also shows macrocytosis, anisocytosis and poikilocytosis
Schiling Test – used to distinguish malabsorption from inadequate diet. A Schilling 24-hour urine test is done to evaluate whether vitamin B12 is being absorbed by the body. It is usually done when the results of a vitamin B12 blood test are low. A Schilling test may be given in two parts. Part one measures the amount of vitamin B12 passed in urine after a known amount of the vitamin tagged with a radioactive substance is swallowed. If the intestines absorb vitamin B12 normally, a certain amount of the vitamin (up to 25% of the amount swallowed) will be passed in the urine. If the intestines cannot absorb the vitamin normally, very little or no vitamin B12 will be present in the urine.
TREATMENT Hydroxylocobalamine