Megaloblastic Anemia

Due to
Vitamin B12 deficiency.
Folic acid deficiency.

Megaloblastic anemia due to B12 deficiency

· Basic features of B12
. dietary vitamin B12
.Animal sources only as meat and dairy
· synthesized in the gut ( not absorbed )
· Daily requirement is 12 mg.
Absorption:
Liberated from food stuffs in the stomach.
§ Bound by intrinsic factor ( synthesized by gastric parietal cell) at an acid PH
§ Absorbed through the terminal ileal mucosa.
Transport:
* Mainly by Transcobalamins.
* Important in nucleic acid synthesis.
Storage:
Primarily hepatic (about 1.5 mg).
Causes of B12 deficiency:
1Dietary (poverty, vegetarians).
2Gastric (pernicious anemia).
-Atrophic gastritis with production of anti parietal and antiin intrinsic factor anti bodies.
-Failure of intrinsic factor production.
-Gastric surgery.
-Achlorhydria
3Intestinal:(sequestration).
a-Blind- loop syndrome
*stricture diverticule's, anastomoses.
* Abnormal gut flora competes for the available B12
b- Diphylobothrium latum infestation which is avid for B12.
C-Post – resection of terminal ileum e.g. chron's disease.
4-Congenital deficiency of transcobalamin (rare).
Pathogenesis :
· B12 deficiency →impaired nucleic acid synthesis →defective nuclear maturation of
cells having high growth rates mainly erythroblasts →Megaloblastic erythropoiesis and
neurological damage.
Laboratory investigations
Hematological:
1Macrocytic anemia (MCV>120 fl).
2Moderate neutropenia may occur.
3Thrombocytopenia.
4Blood film: contains Howel Jolly bodies, oval macrocytes,anisopoikilocytosis,large
hypersegmented neutrophils and giant platelet.
5Bone marrow:
· Hypercellular due to erythroid hyperplasia.
· Megaloblasts : large than normoblasts, with large nuclei, with open stippled chromatin
and nuclear cytoplasmic asynchronism.
· Defective maturation of erythropoiesis.
· Giant metamyelocytes with hypersegmented large polymorphs.
· Atypical megakaryocytes with hypersegmented nuclei.
6 Serum B12 assay:
low level (<160 ng/L).
7Biochemical tests:
a) Increased excretion of methylmalonic acid in urine.
b) Increased serum bilirubin reflecting mild hemolysis & ineffective erythropoiesis
c) High LDH.
8Immunological:
a) Parietal cell antibodies in 80% of patients (not specific).
b) Intrinsic factor antibodies in 60% of patients(more specific).
9Shilling's
test:
· Malabsorotion of B12 corrected by addition of intrinsic factor
· One version is the differential absorption and excretion of B12 with and without
IF, using Co and Co labeled B12.
Other investigations :
Gastric endoscopy , biopsy.