Megaloblastic anemia

Megaloblastic anaemia is a red blood cell disorder due to the inhibition of DNA synthesis during erythropioesis.
Mitotically, the inhibition of the DNA synthesis impaires the progression of the cell cycle development from G2 to (M) stage.

1. MEGANOBLASTIC ANEMIA PRESENTED BY ASOGWA UKAMAKA DEPT. OF MEDICAL LABORATORY SCIENCE FEDERAL MEDICAL CENTRE MAKURDI 03/08/2015 Asogwa Uka 1

2. Megaloblastic Anemia Outline Definition Etiology of megaloblastic anemia Pathophysiology Clinical presentation of megaloblastic anemia Laboratory Diagnosis Sources of Vitamin B12 and Folic Acid 03/08/2015 Asogwa Uka 2

3. Definition 03/08/2015 Asogwa Uka 3 Megaloblastic anaemia is a red blood cell disorder due to the inhibition of DNA synthesis during erythropioesis. Mitotically, the inhibition of the DNA synthesis impaires the progression of the cell cycle development from G2 to (M) stage.

4. Etiology of megaloblastic anemias Vitamin B12 or Cobalamin deficiency. Folic acid deficiency a and b deficiency. 03/08/2015 Asogwa Uka 4

5. VITAMIN B12 DEFICIENCY Inadequate intake : This is common among pure vegetarians, old and bed ridden patients Inability to absorb vitamin B12 : after gastric surgery, lack of hydrochloric acid in gastric juice, lack of intrinsic factor due to auto antibodies to parietal cells. Competition for intestinal vit.B12 : Competitive absorption of the vitamin by fish tape worm ( Diphyllobothrium latum ) and bacteria overgrowth in blind-loop syndrome, intestinal stasis. Drugs Inhibition : Metformin , Proton pump inhibitors 03/08/2015 Asogwa Uka 5

6. FOLATE DEFICIENCY Inadequate intake: a poor diet Old and bed ridden patients ICU patients. over cooked food especially vegetable Increased requirements pregnancy and lactating mothers. Growing infants Hemolytic anemic patients. Drugs Folic acid antagonists: Methotrexate Chronic alcoholism : It inhibits folic acid absorption. It increases folate excretion through the urine Inability to absorb folic acid: Following gastric surgery, chronic diarrhoea . 03/08/2015 Asogwa Uka 6

7. Pathophysiology When vitamin B12 or folate is deficient, thymidine synthase function is impaired and DNA synthesis is interrupted but RNA synthesis remains unimpaired. The inability to synthesize DNA leads to ineffectual erythropoiesis resulting in excess hemoglobin and enlarged erythroid precursors being produced. The developing red cell has difficulty in undergoing cell division but RNA continues to be translated and transcribed into protein leading to growth of the cytoplasm while the nucleus lags behind. Often one or more cell division are skipped leading to a larger than normal cell. There is often erythroid hyperplasia in the marrow but most of these immature cells die before reaching maturity leading to - elevated Lactate Dehydrogenase (LDH) and hyperbilirunemia . 03/08/2015 Asogwa Uka 7

8. Megaloblastic precursor cells versus Normoblastic precursor 03/08/2015 Asogwa Uka 8 Fig.1a. Megaloblastic precursors, showing the asynchrony between the nucleus and the chromatin; the cytoplasm of most cells is extremely basophilic . Fig.1b.Normoblastic erythropoiesis with a polychromatophilic normoblast ( arrow ).

9. CLINICAL PRESENTATION Anaemia symptoms Neurological symptoms Gastro- intestinal complain Symptoms of Anemia weakness, palpitation, fatigue, light- headedness ,,shortness of breath, premature graying of hair, jaundice and pallor. Severe pallor and slight jaundice combine to produce a telltale lemon-yellow skin in patient with megaloblastic anemia . 03/08/2015 Asogwa Uka 9

10. 03/08/2015 Asogwa Uka 10 Fig 2a,b “Lemon yellow” pallor Fg .2d Neura tube defects e.g . Spina Bifida Clinical signs in pictures

11. Neurological symptoms The syndrome usually begins with paraesthesia (numbness and tingling) in the feet and fingers, difficulties in balance and walking . Vitamin B12 deficiency causes a demyelinization of the peripheral nerves, the spinal cord, and the brain , resulting in more severe neurological symptoms. When it affects the spinal cord it causes spastic ataxia( stiffness of the muscles with uncoordinated movement). At the brain it results in dementia, psychotic depression and paranoid schizophrenia. This has been termed “ megaloblastic madness .” 03/08/2015 Asogwa Uka 11

12. Gastro- intestinal complains : symptom include loss of appetite, glossitis (red, sore, smooth tongue) and diarrhoea 03/08/2015 Asogwa Uka 12

13. Laboratory diagnosis of megaloblastic anemias Full Blood Count ( FBC): ↓ Hb / Hct , ↑ MCV, ↓ retics , ↓WBC, ↓ Plts , macroovalocytosis , anisocytosis , poikilocytosis , hypersegmentation of granulocytes. Also there may be variable thrombocytopenia. Bone marrow smear : Bone marrow examination reveals myeloid cell changes (giant bands, metamyelocytes and hypertsegmentation ) and megakariocytes are decreased and show abnormal morphology. 03/08/2015 Asogwa Uka 13

14. Fig. 3a. Peripheral smear from a patient with megaloblastic anemia . Note the hypersegmented neutrophils and the macro- ovalocytes . Fig. 3b Megaloblastosis (Giant Band Forms in Bone Marrow) 03/08/2015 Asogwa Uka 14

15. Biochemistry Test: hyperbilirubinemia ↑lactate dehrogenase (LDH) Schilling test : The Schilling test is used to determine whether there is faulty absorption of vitamin B12. 03/08/2015 Asogwa Uka 15

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17. Sources of Vitamin B12 and Folic Acid Vitamin B12 • Meat, liver, kidney, clams, fish • Eggs, cheese, and other dairy products Folic Acid • Green leafy vegetables • Broccoli • Fruit • Whole grains • Dairy products 03/08/2015 Asogwa Uka 17

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