Recommended
More Related Content
Similar to MEGALOBLASTIC ANEMIA.pptx
Similar to MEGALOBLASTIC ANEMIA.pptx (20)
More from Tamil Mahizhenthi
More from Tamil Mahizhenthi (15)
Recently uploaded
Recently uploaded (20)
MEGALOBLASTIC ANEMIA.pptx
- 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. COBALAMIN GETS RELEASED FROM FOOD B12 BINDS WITH GASTRIC R BINDER (TCI OR HAPTOCORRIN) COBALAMIN & R BINDER SEPARATE IN THE DUODENUM R BINDER DIGESTED IF + B12 COMBINE & REACH TERMINAL ILEUM
- 6. B12 RECEPTORS IN ILEUM TAKE UP B12-IF COMPLEX IF DESTROYED IN CYTOPLASM B12 + TRANSCOBALAMIN II B12 – TCII TAKEN TO BONE MARROW WITHIN 1 HOUR TAKEN TO ALL CELLS OF THE BODY
- 8. 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
- 10. ROLE OF VITAMIN B12 & FOLIC ACID IN DNA SYNTHESIS
- 11. 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
- 12. 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
- 13. 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
- 14. INBORN ERRORS OF METABOLISM • DEFECTIVE FOLATE METABOLISM • DEFECTIVE VITAMIN B12 METABOLISM • HEREDITARY OROTIC ACIDURIA • LESCH-NYHAN SYNDROME
- 15. PATHOPHYSIOLOGY B12 & FA REQUIRED FOR THYMIDINE & PURINE SYNTHESIS IF DEFICIENT, DNA SYNTHESIS RETARDED CYTOPLASMIC SYNTHESIS GOES ON CELL KEEPS ENLARGING INTRAMEDULLARY DEATH OF HEMATOPOIETIC PRECURSORS INEFFECTIVE HEMOPOIESIS PANCYTOPENIA
- 16. 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
- 17. 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
- 18. CBC REPORT • RETICULOCYTE COUNT DECREASED • PANCYTOPENIA • BIZARRE FORMS & MEGATHROMBOCYTES • PLT FUNCTION IS IMPAIRED • INCREASED : MCV, MCH & RDW • MCHC NORMAL
- 19. PERIPHERAL SMEAR
- 20. HOWELL JOLLY BODIES, BASOPHILIC STIPPLING, CABOT RINGS, BASOPHILIC RBC
- 21. 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
- 22. BONE MARROW ASPIRATION PREPONDERANTLY EARLY MEGALOBLASTS WITH OPEN NUCLEAR CHROMATIN INTERMEDIATE -AND LATE MEGALOBLASTS ARE FEWER MATURATION ARREST
- 23. BONE MARROW ASPIRATION EARLY MEGALOBLASTS WITH LARGER SIZE SIEVE LIKE NUCLEAR CHROMATIN AND BASOPHILIC CYTOPLASM NUCLEAR CYTOPLASMIC ASYNCHRONY
- 24. BONE MARROW - DYSERYTHROPOIESIS LATE NORMOBLAST WITH FEATURES OF IRREGULAR HB HOWEL JOLLY BODIES MARKED BASOPHILIC STIPPLING
- 25. BONE MARROW DYSERYTHROPOIESIS ERYTHROID HYPERPLASIA WITH MITOTIC FIGURES
- 26. BONE MARROW MYELOPOIESIS • GIANT BAND FORMS • GIANT METAMYELOCYTES • IRREGULAR NUCLEAR SHAPE • ABNORMAL STAINING CHARACTER
- 27. BONE MARROW MEGAKARYOPOIESIS • ABNORMAL OPEN NUCLEAR CHROMATIN • COMPLEX NUCLEAR LOBULAR HYPERSEGMENTATION • MEGALOBLASTOSIS IS PRESENT
- 28. BMA – PERL’S STAIN INCREASED IRON STORES IN THE BONE MARROW
- 29. BONE MARROW TREPHINE BIOPSY • ERYTHROID HYPERPLASIA • PREPONDERANCE OF EARLY MEGALOBLASTS • UNIFORM SIZE • DELICATE NUCLEAR MEMBRANE • VESICULAR NUCLEI • 1— 3 LINEAR NUCLEOLI • FREQUENT MITOSIS
- 30. DIMORPHIC ANEMIA – PERIPHERAL SMEAR
- 31. BMA – DIMORPHIC ANEMIA • LATE MICRONORMOBLASTS – IDA • EARLY MEGALOBLASTS – VIT B12 DEFICIENCY • GIANT METAMYELOCYTES
- 32. PERINICIOUS ANEMIA • CLINICAL MANIFESTATIONS • LIGHT BLUE/ GREY EYES • PREMATURE GREYING OF HAIR • DIARRHOEA • BILATERAL SYMMETRIC TINGLING • GLOVE & STOCKING PARASTHESIA
- 33. 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
- 34. ALCOHOLIC’S PS & BM
- 35. 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
- 36. THE SCHILLING TEST • FASTING PATIENT • ORAL DOSE 1 MICROGRAM RADIOACTIVE VIT B12 • 2 HRS LATER – 1000 MCG UNLABELLED IM INJ VIT B12 • 1/3RD 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
- 37. 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
- 38. DUODENAL BIOPSY • TOTAL VILLOUS ATROPHY • CRYPT HYPERPLASIA • LYMPHOPLASMACYTIC INFILTRATE • DECREASE IN GOBLET CELLS • INTRAEPITHELIAL LYMPHOCYTES
- 39. 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
- 40. 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
- 41. 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
- 42. RESPONSE TO THERAPY - PS • POLYCHROMASIA • HYPERSEGMENTED NEUTROPHILS DISAPPEAR IN 2 WEEKS
- 43. RESPONSE TO THERAPY - RC RETICULOCYTE INCREASES ON DAY 2 DAY 5 PEAKS
- 44. RESPONSE TO THERAPY - BM • NORMOBLASTIC MARROW IN 12 – 48 HRS • EFFECTIVE ERYTHROPOIESIS • GIANT BAND FORMS AND METAMYELOCYTES PRESIST FOT 2 – 4 DAYS
- 45. 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
- 46. 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
- 47. THANK YOU