MEGALOBLASTIC ANEMIA.pptx

A discussion on Megaloblastic anemia - causes, types, investigations and treatment. referred from standard textbooks of Hematology

1. MEGALOBLASTIC ANEMIA DR TAMIL NILA POST GRADUATE

2. INTRODUCTION DISTINCTIVE CYTOLOGICAL AND FUNCTIONAL ABNORMALITIES IN PERIPHERAL BLOOD AND BONE MARROW CELLS DUE TO IMPAIRED DNA SYNTHESIS

3. ETIOLOGY VITAMIN B12 DEFICIENCY FOLIC ACID DEFICIENCY DRUG INDUCED PERINICIOUS ANEMIA INBORN ERRORS OF METABOLISM

4. VITAMIN B12 DIETARY SOURCE : ANIMAL PRODUCTS ADENOSYL COBALAMIN & HYDROXOCOBALAMIN DAILY REQUIREMENT : 2 – 3 MICROGRAMS/DAY BODY STORES LAST FOR 3 – 5 YEARS COOKING – 10 – 30% LOST STORAGE SITE : LIVER EXCRETED IN BILE ENTEROHEPATIC CIRCULATION

5. FOLIC ACID DIETARY SOURCES – FRUITS & VEGETABLES DAILY REQUIREMENT – 50 MICROGRAMS INCREASED DURING PREGNANCY COOKING : 90% LOST BODY STORES : 5 – 20 MILLIGRAMS STORES LAST FOR 2 – 4 MONTHS

6. ROLE OF VITAMIN B12 & FOLIC ACID IN DNA SYNTHESIS

7. VITAMIN B12 DEFICIENCY CAUSES DIETARY DEFICIENCY - STRICT VEGETARIAN DIET MALABSORPTION - ILEAL RESECTION - BLIND LOOP SYNDROME - IBD - FISH TAPEWORM INFESTATION - BACTERIAL OVERGROWTH - TROPICAL SPRUE - NON-TROPICAL SPRUE • INCREASED REQUIREMENTS - PREGNANCY - DISSEMINATED CANCER • INTRINSIC FACTOR DEFICIENCY - GASTRECTOMY - PERNICIOUS ANEMIA - CONGENITAL ABSENCE OF IF • H2 ANTAGONISTS

8. FOLIC ACID DEFICIENCY CAUSES DIETARY DEFICIENCY UNBALANCED DIET ALCOHOLICS MALNUTRITION IMPAIRED ABSORPTION SPRUE SMALL BOWEL RESECTION/DISEASE ANTICONVULSANTS ORAL CONTRACEPTIVES INTESTINAL SHORT-CIRCUITS INCREASED REQUIREMENTS INFANCY PREGNANCY HEMOLYTIC ANEMIAS MYELOPROLIFERATIVE DISORDERS HEMODIALYSIS

9. DRUG INDUCED SUPPRESSION OF DNA SYNTHESIS FOLATE ANTAGONISTS ALKYLATING AGENTS METABOLIC INHIBITORS OF PURINE SYNTHESIS HYDROXYUREA ACYCLOVIR 6-MERCAPTOPURINE AZATHIOPRINE OF PYRIMIDINE SYNTHESIS 5-FLUOROURACIL, CYTOSINE ARABINOSIDE, AZATYTIDINE ZIDOVUDINE OF COBALAMINE METABOLISM PHENFORMIN, METFORMIN OF DIHYDROFOLATE REDUCTASE: P-AMINOSALICYCLIC ACID HYDROXYUREA CYTARABINE

10. INBORN ERRORS OF METABOLISM DEFECTIVE FOLATE METABOLISM • DEFECTIVE VITAMIN B12 METABOLISM • HEREDITARY OROTIC ACIDURIA • LESCH-NYHAN SYNDROME

11. PATHOPHYSIOLOGY

12. CLINICAL FEATURES ALL AGES ARE SUSCEPTIBLE PALLOR DYSPNOEA & TACHYCARDIA (MOD – SEV) LEMON YELLOW HUE OF SKIN BEEFY RED TONGUE ORAL SORENESS APHTHOUS STOMATITIS NEURAL TUBE DEFECTS INCREASED THROMBOSIS

13. NEUROLOGICAL MANIFESTATIONS SUBACUTE COMBINED DEMYELINATION OF POSTEROLATERAL COLUMNS OF SPINAL CORD POOR GAIT & MEMORY LOSS SEVERE DISRUPTION IN GAIT LOSS OF POSITION SENSE BLINDNESS PSYCHIATRIC DISTURBANCE

14. CBC REPORT RETICULOCYTE COUNT DECREASED PANCYTOPENIA BIZARRE FORMS & MEGATHROMBOCYTES PLT FUNCTION IS IMPAIRED INCREASED : MCV, MCH & RDW MCHC NORMAL

15. PERIPHERAL SMEAR

16. HOWELL JOLLY BODIES, BASOPHILIC STIPPLING, CABOT RINGS, BASOPHILIC RBC

17. BONE MARROW ASPIRATION MARKED ERYTHROID HYPERPLASIA RESULTING IN A REVERSAL OF M : E RATIO INCREASED. MEGALOBLASTS SHOW SIEVE LIKE NUCLEAR CHROMATIN BEST APPRECIATED IN POLYCHROMATOPHILIC STAGE

18. BONE MARROW ASPIRATION PREPONDERANTLY EARLY MEGALOBLASTS WITH OPEN NUCLEAR CHROMATIN INTERMEDIATE -AND LATE MEGALOBLASTS ARE FEWER MATURATION ARREST

19. BONE MARROW ASPIRATION EARLY MEGALOBLASTS WITH LARGER SIZE SIEVE LIKE NUCLEAR CHROMATIN AND BASOPHILIC CYTOPLASM NUCLEAR CYTOPLASMIC ASYNCHRONY

20. BONE MARROW - DYSERYTHROPOIESIS LATE NORMOBLAST WITH FEATURES OF IRREGULAR HB HOWEL JOLLY BODIES MARKED BASOPHILIC STIPPLING

21. BONE MARROW DYSERYTHROPOIESIS ERYTHROID HYPERPLASIA WITH MITOTIC FIGURES

22. BONE MARROW MYELOPOIESIS GIANT BAND FORMS GIANT METAMYELOCYTES IRREGULAR NUCLEAR SHAPE ABNORMAL STAINING CHARACTER

23. BONE MARROW MEGAKARYOPOIESIS ABNORMAL OPEN NUCLEAR CHROMATIN COMPLEX NUCLEAR LOBULAR HYPERSEGMENTATION MEGALOBLASTOSIS IS PRESENT

24. BMA – PERL’S STAIN INCREASED IRON STORES IN THE BONE MARROW

25. BONE MARROW TREPHINE BIOPSY ERYTHROID HYPERPLASIA PREPONDERANCE OF EARLY MEGALOBLASTS UNIFORM SIZE DELICATE NUCLEAR MEMBRANE VESICULAR NUCLEI 1— 3 LINEAR NUCLEOLI FREQUENT MITOSIS

26. DIMORPHIC ANEMIA – PERIPHERAL SMEAR

27. BMA – DIMORPHIC ANEMIA LATE MICRONORMOBLASTS – IDA EARLY MEGALOBLASTS – VIT B12 DEFICIENCY GIANT METAMYELOCYTES

28. PERINICIOUS ANEMIA CLINICAL MANIFESTATIONS LIGHT BLUE/ GREY EYES PREMATURE GREYING OF HAIR DIARRHOEA BILATERAL SYMMETRIC TINGLING GLOVE & STOCKING PARASTHESIA

29. NON MEGALOBLASTIC MACROCYTOSIS MCV : 100 – 110 FL LOW RDW NORMOBLASTIC MARROW MACROCYTOSIS WITHOUT ANEMIA NEWBORNS INFANTS PREGNANCY CAUSES LIVER DISEASE ALCOHOLISM COPD HEMOLYTIC ANEMIA POSTHEMORRHAGIC ANEMIA ZIDOVUDINE THERAPY ACUTE LEUKEMIA

30. ALCOHOLIC’S PS & BM

31. INVESTIGATIONS INCREASED HYPERHOMOCYSTEINEMIA FIGLU LEVELS IN URINE SERUM IRON FERRITIN SERUM BILIRUBIN METHYLMALONIC ACIDURIA ( > 300 MG/DAY) SERUM LDH1 (LDH1>LDH2) SERUM GASTRIN GASTRIC JUICE pH(>6) REDUCED SERUM VITAMIN B12 LEVELS (<150 PG/ML) SERUM FOLIC ACID LEVELS RED CELL FOLATE LEVELS INTRINSIC FACTOR S. HOLOTRANSCOBALAMIN

32. THE SCHILLING TEST FASTING PATIENT ORAL DOSE 1 MICROGRAM RADIOACTIVE VIT B12 2 HRS LATER – 1000 MCG UNLABELLED IM INJ VIT B12 1/3 RD OF RADIOACTIVE B12 WASHED OUT IN URINE IN NEXT 24 HRS INTERPRETATION ON B12 EXCRETION NORMAL SUBJECTS > 10% PERINICIOUS ANEMIA < 5% ATROPHIC GASTRITIS <10% FURTHER TESTING WITH INTRINSIC FACTOR INTERPRETATION IMPROVES – PERINICIOUS ANEMIA NO CHANGE – MALABSORPTION

33. GASTRIC BIOPSY LOSS OF GASTRIC GLANDS AND PARIETAL CELLS INFILTRATION BY LYMPHOCYTES IN LAMINA PROPRIA GLANDULAR EPITHELIAL CELLS ARE REPLACED BY GOBLET SECRETING CELLS -INTESTINALIZATION OF STOMACH

34. DUODENAL BIOPSY TOTAL VILLOUS ATROPHY CRYPT HYPERPLASIA LYMPHOPLASMACYTIC INFILTRATE DECREASE IN GOBLET CELLS INTRAEPITHELIAL LYMPHOCYTES

35. APPROACH B12 DEFICIENCY FOLATE DEFICIENCY COMBINED SERUM B12 LOW NORMAL LOW (30%) LOW SERUM FOLIC ACID NORMAL (50%) LOW LOW RED CELL FOLATE LOW LOW LOW HOMOCYSTEINE HIGH HIGH HIGH METHYL MALONIC ACID HIGH (FOLATE TRAP) LOW LOW

36. B12 VS FOLIC ACID THERAPY FA DEFICIENCY – NOT CORRECTED BY B12 ALONE B12 DEFICIENCY IS CORRECTED BY FOLIC ACID THERAPY IN B12 DEFICIENCY, MEGALOBLASTIC ARREST – DEFECT IN FOLATE UTILIZATION

37. PRINCIPLES OF TREATMENT ORAL SUPPLEMENTS CRYSTALLINE B12 2 MG PER DAY FOLIC ACID 1 – 2 MG PER DAY IRON PARENTRAL SUPPLEMENTS B12 1000 MCG IM PER WEEK X 8 WEEKS 1000 MCG PER MONTH PROPHYLAXIS AGAINST THROMBOEMBOLISM NEUROLOGICAL COMPLICATIONS MENTAL DETERIORATION PREVENT NEURAL TUBE DEFECTS

38. RESPONSE TO THERAPY - PS POLYCHROMASIA HYPERSEGMENTED NEUTROPHILS DISAPPEAR IN 2 WEEKS

39. RESPONSE TO THERAPY - RC RETICULOCYTE INCREASES ON DAY 2 DAY 5 PEAKS

40. RESPONSE TO THERAPY - BM NORMOBLASTIC MARROW IN 12 – 48 HRS EFFECTIVE ERYTHROPOIESIS GIANT BAND FORMS AND METAMYELOCYTES PRESIST FOT 2 – 4 DAYS

41. RESPONSE TO THERAPY FALL IN LDH1 FALL IN S.BILIRUBIN HB RISES AT THE RATE OF 1GM DL PER WEEK FULL CORRECTION BY 2 MONTHS

42. REFERENCES DE GRUCHY'S CLINICAL HAEMATOLOGY IN MEDICAL PRACTICE DACIE AND LEWIS PRACTICAL HAEMATOLOGY ATLAS AND TEXT OF HEMATOLOGY – DR TEJINDER SINGH ESSENTIALS OF HEMATOLOGY – SHIRISH M KAWTHALKAR HEMATOLOGY CMC NOTES ROSAI & ACKERMAN’S SURGICAL PATHOLOGY ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE

43. THANK YOU