Megaloblastic anaemia

Introduction, definition, etiology, Vit B12 deficiency ansemia, Folic acid deficiency anaemia, metabolism of Vit.B12 and Folic acid, clinical features, laboratory diagnosis and manangement

1. MEGALOBLASTIC ANAEMIA By: Nityanand Upadhyay Associate Professor Department of MLT Integral University, Lucknow

2. 1. INTRODUCTION 2. DEFINITION 3. PREVALENCE 4. METABOLISM 5. PATHOPHYSIOLOGY 6. ETIOLOGY 7. CLINICAL FEATURES 8. DIAGNOSIS 9. MANAGEMENT LESSION PLAN

3. "anemia" usually refers to a condition in which your blood has a lower than normal number of red blood cells.” “The term  macrocytic  is from Greek words meaning "large cell". A macrocytic class of  anemia  is an  anemia in which the  red blood cells  (erythrocytes) are larger than their normal volume. INTRODUCTION

4. A macrocytic class of  anemia  is an  anemia in which the  red blood cells  (erythrocytes) are larger than their normal volume. i.e MCV>100fl (Normal 82-98fl).

5. I. In a macrocytic anemia, the larger red cells are always associated with insufficient  numbers  of cells and often also insufficient Hb content per cell. II. Both of these factors work to the opposite effect of larger cell size, to finally result in a  total blood hemoglobin concentration  that is less than normal (i.e., anemia).

6. “ Megaloblastic aneamia is characterized by Miacrocytic Blood picture with MCV >100 fl and Megaloblastic Bone Marrow.” “ Megaloblastic anaemia occurs due to Impaired DNA synthesis , due to lack of Vit . B12 and/or Folic Acid . ” DEFINITION (MEGALOBLASIC ANAEMIA)

7. It is second malnutrition Anaemia prevalent in India. In Malnourished Individual . Its frequency is higher in Females, more so in PREGNANCY. PREVALANCE

8. Severity of anaemia is more in . LOWER SOCIO- ECONOMIC GROUP . CHILDREN . PREGNANT WOMEN . ELDERLY

9. 1. Deficiency of Vit . B12: Common in India. 2. Deficiency of Folic acid: Common in India. 3. Multiple Deficiency: Common in India. 4. Pernicious Anaemia : Rare in India. ETIOLOGY

10. Usually of low socio-economic status. The stores folic acid get exhausted due to various etiology like increase demand. Megaloblastic Anaemia appears in 16-18 weeks after depletion of F.A. Stores F.A. last for 2-4 months. 1. FOLIC ACID DEFICIENCY ANAEMIA

11. I. Daily Requirements: 50-250 microgram/day. II. Source of F.A.: . Green leafy vegetables like spinach, lettuce, lemon and Banana. ‘ Heating, baking boiling, frying of food stuffs destroys 90-95% of F.A.”

12. III. Absorption of F.A. Polyglutamates (Food) Monoglatamates Dihydrofolate Tetrahydrofolate THF (FH4)

13. Methyl Tetrahydrofolate (Methyl THF) Absorbed from jejunum and Enters circulation Carried by Plasma To cell where DNA synthesis takes place Monoglutamates to THF(In Intestine)

14. III. Site of Absorption: D uodenum and jejunum. IV.Transportation : Proton-coupled  folate  transporter (PCFT, SLC46A1)

15. The common causes are- 1. Dietary deficiency : . Malnutriton . . Socio-Economically weaker. . Elderly. ETIOLOGY OF F.A. DEFICIENCY ANAEMIA

16. 2. Malabsorption : . Gluten induced enteropathy . . Anticonvulsant Drugs. . Oral Contraceptives. 3. Increased Blood Loss: . Haemodialysis . . Tropical Spure . . Gluten induced enteropathy .

17. 4. Increased Demands: . Infancy . Lactation . Adolescence . Pregnancy . Malignancy . Hyperplastic Bone Marrow

18. Vegetarians are likely to develop B12 deficiency anemia due to Vit.B12( Cynocobalamine ) is mainly present in Animal Products. More common in India due to more population are VEGETARIANS. Develop due to deficiency of Vit . B12. II. VITAMIN B12 DEFICIENCY ANAEMIA

19. The stores of Vit.B12 are sufficient for 2-3 years. In case of dietary deficiency of Vit.B12, its takes 2-4 years to manifest Anaemia . 1. Daily Requirement: 2-3 Microgram/ day. 2. Resources: Animal products , including fish, meat, poultry,  eggs ,  milk , and  milk  products

20. Intrinsic factor (IF) is essential for absorption of Vit.B12. IF is secrteted by parietal cells of gastric mucosa. 1. Cobalamine combines with R-binder (Secreted in saliva) in stomach. 2. In duodenum R-binder is digested and Vit . B12 combines with IF. ABSORPTION OF Vit . B12

21. 3. In terminal ileum , Vit.B12 is absorbed and IF is destroyed in epithelial cells. 4. After absorption Vit.B12 is carried into plasma by TRANSCOBALAMINE II and transported throughout the body including Bone Marrow. => Disease in Stomach and Ileum affect Vit.B12 absorption.

22. A. Decrease Intake: i . Dietary deficiency ii. Vegetarians B. Impaired Absorption: i . IF deficiency ii. Fish tapeworm infestation ETIOLOGY OF Vit . B12 DEFICIENCY

23. iii. Small bowel bacterial overgrowth iv. Drugs- Metformin C. Increased Demand: i . Pregnancy ii. Disseminated Cancer

24. ROLE OF Vit.B12 & FA IN BIOSYNTHESIS OF DNA

25. Fatigue Glossitis Pallor Tingling Dizziness Thrombosis Headache CLINICAL FEATURES

26. Numbness Glossitis : tongue swelling or soreness Cold hands and feet fast or irregular heartbeat

27. A. Haematological : 1. Hb : 5-10gm/dl. ( in sever anaemia Hb = as low as 03 gm/dl). 2. Haematocrit : 13-30% . 3. Absolute values: MCV = >100 fl MCH = Increase MCHC= Normal DIAGNOSIS

28. 4. Blood Picture: . Moderate degree of ANISOPOIKELOCYTOSIS with few Tear drop cells. .Red cells are MACROOVALOCYTES with few NUCLEATED RBC,s . . Basophilic stippling . Cabot Ring . Howel jolly bodies.

29. 5. Reticulocyte count: 2-3%. 6. WBC: Leukopenia . 7. DLC: Hypersegmented Neutrophils (6-10 Nuclear lobes). 8. Platelets count: Thrombocytopenia. 9. Pancytopenia : 10-20% of cases. ( Hypersegmented Neutrophils are Common features of Megaloblastic Anaemia )

30. B. Bone marrow Examination: 1. Cellularity : Hypercellular . 2. Erythropoisis : Erythroid hyperplasia, Megaloblastic Erythropoisis .

31. 3. Myeloopoisis : Demonstration of larger Myeloid cells specially GIANT METAMYELOCYTE and GIANT BAND FORMS. 4. Megakaryopoisis : Hypoplasia . 5. Bone marrow Iron: Increased.

32. C. Others Examination: 1. Serum Vit.B12: Decrease in Vit.B12 deficiency cases. 2. S. Folate level : Decrease in folate deficiency cases. 3. Serum methyle malonic acid: Increases in Vit.B12 deficiency cases.

33. 4. FIGLU in urine: Formiminoglutamate is an intermediate product in conversion Histidine to Glutamate and is excreated in Folic acid deficiency. 5. Schilling Test of Vit.B12:

34. 1. Oral Vit.B12 Therapy: 100 microgram to 1000 microgram are availables . 2. Parenteral Iron Therapy: 1mg injection of Hydroxycobalamine is given every week for 5 week. 3 . Folic Acid: 1-5 mg tablets are available. MANAGEMENT

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