Megaloblastic Anaemia
Definition: A group of haematological disorders characterized by distinctive morphological appearance of the developing erythroid cells in the marrow. Causes include: B12 or folate deficiency ( in the vast majority ). Abnormalities of B12 and folate metabolism. Abnormalities of DNA synthesis.Causes of megaloblastic anaemia
Cobalamin deficiency or abnormalities of cobalamin metabolism Folate deficiency or abnormalities of folate metabolism Therapy with antifolate drugs (methotrexate) Independent of either cobalamin or folate deficiency & refractory to cobalamin & folate therapy:Some cases of AML or MDS Therapy with drugs interfering with synthesis of DNA(cytosine arabinoside,hydroxyurea,6mercaptopurine,azidothymidine).
Gonad is also affected & sterility is common in patients with either deficiency. Maternal folate deficiency has been implicated as a cause of prematurity,folic acid supplement at the time of conception & in the first 12 weeks of pregnancy reduce the incidence of neural tube defects & most of the protective effect can be achieved by taking folic acid 0.4mg daily Reduced 5,10MTHFR caused by common c677t polymorphism in the MTHF gene also cause NTD and even cleft palate. High serum homocystein lead to thrombotic disease ,dementia and Alzheimer disease..
Haematological features Anemia , Increase MCV Peripheral blood: RBCs: macrocytosis, characteristically oval in shape with marked red cell distortion ( anisopoikilocytosis ). WBCs: usually reduced in number with hypersegmented neutrophiles Pancytopenia ( usual in severe cases ).
Bone marrow changes Hypercellular BM. Erythroid hyperplasia. Megaloblastic maturation: Large erythroid cells. Predominance of early stages. Nuclear-cytoplasmic dissociation. Marked dyserythropoiesis Granulopoiesis: Giant forms(giant metamyelocytes or stab cells) Thrombopoiesis: hyperpolyploid megakaryocttes(normally mega. Contain up to 32 n.). Incseased marrow iron.
Sources and requirementsFoods of animal origin, plant origin foods are devoid of B12Daily requirements 1 – 3 μg.Stores ( mainly in the liver ) 2- 3 mg.Stored B12 is sufficient for 3-4 years if supplies are cut off completely.
Absorption of B12 Minor amounts are absorbed passively ( 1%). The normal mechanism is through combination with gastric intrinsic factor ( IF ), absorption is through special receptors at the terminal ileum. B12 is carried to target organs by special proteins known as transcobalamins ( I, II and III ).
Causes of B12 deficiency Dietary deficiency: Vegetarians ( mainly Hindus ) Infants born to B12 deficient mothers. Malabsorption: Nutritional vegans Malabsorption pernicious anemia Gastric congenital IF deficiency Functional abnormality Total or partial gastrectomy
Intestinal Intestinal stagnant loop syndrome Jujinal diverticulosis Iloecaecal fistula Anatomical blind loop Intestinal stricture etc. Ileal resection Crohn’s disease Selective Malabsorptionvit Tropical sprue TCII deficiency Fish tape worm
Folate DeficiencySources and requirements:Unlike B12 folates are present in both plant and animal origin foods.Daily requirements are about 100 μgBody stores, mainly in the liver are about 10 mg.Stores are sufficient for about 4 months.
Absorption and transport of folates. Absorption is from upper intestinal tract, the exact mechanism is not known whether it is an active or facilitated diffusion. In the plasma about 2/3 are free and 1/3 loosely attached to albumin, mostly in the form of methyl tetra hydro folate.
Causes of folate deficiency Dietary deficiency: Neglected adult,poor, alcoholics and psychiatric patients. Infants with kwashiorkor, scurvy, prematurity,repeated infections and those fed on goat milk.
Malabsorption :Gluten enteropathy.As a congenital defect “ selective folate malabsorption “.Drugs as salazopyrine and.Excess utilization:Pregnancy.(requirement 200-300Mg & to400Mg)Prematurity.Chronic haematological diseases.Inflammatory diseasesChronic dialysis & congestive heart failure.Antifolate drugs: antiepileptic, alcohol, methotrexate, trimethoprim.