megalobastic A by Abdulmanan Haneef .pptx

MA

1. Megaloblastic Anemia It is a red blood cell disorder due to the inhibition of DNA synthesis during erythropieosis which is characterized by the presence of distinctive morphologic appearance of the developing red cell in bone marrow By Dr haneef

2. Etiology of the megaloblastic anemia Vit B12 deficiency Folate deficiency Drugs Myelodysplastic syndrome Acute leukemia

3. ■DIETARY SOURCES AND REQUIREMENTS Only Source for human food of animal origin Meat,fish,dairy products Normal Western diet daily 5-30mcg coblamine Adult daily loses (1-3mcg)(0,1%body store) daily requirements are also about 1–3 μ g. Body stores are of the order of 2–3 mg, sufficient for 3–4 years if supplies are completely cut off

4. Obsorption of cobalamine Tow mechanism exists for cobalamine obsorption 3:enterohepatic circulation 1:One is passive, occurring equally through buccal, duodenal, and ileal mucosa; it is rapid but extremely inefficient, with <1% of an oral dose being absorbed by this process. 2:The normal physiologic mechanism is active; it occurs through the ileum and is efficient for small (a few micrograms) oral doses of cobalamin, and it is mediated by gastric intrinsic factor (IF).

5. Dietary sources and requirements of folate Legumes,nuts,whole grains,cereals,yeast Green vegetables,broccoli , asparagus,okra ,cauliflower Orange,carrots and cantaloupes Requirements and storage Total-body folate in the adult is ∼10 mg, with the liver containing the largest store. Daily adult requirements are ∼100 μ g, and so stores are sufficient for only 3–4 months in normal adults, and severe folate deficiency may develop rapidly.

6. Cobalamine deficiency Malabsorption (chilling test(radioactive B12-urine)) Inadequate intake ( vegan,poverty,infant Pernicious anemia(RH A,Autoimmune) Gastric biopsy ( Atropy,parietal cell replaced by mucus cells and increase cD4 Serology (IF ig G Ab 1) provent IF - cobalamine Type 2 provent IF – illeal muc Partial cell Ab a and b subunit H-k Atpase

7. Cont … 4:IF deficiency or non functional 5:Gastrectomy 6:intestinal stagnant loop syndrome (fecal organisms colonization)Tnx diverticulosis ,anastomosis , Crohns 7:illeal resaction more then 1,2m 8:topical sprue 9:fish tapeworm infestation 10:gluten induced enteropathy 11:chronic pancreatitis 12:zollinger Ellison syndrome 13:Drug metformine decl TC1 14:Radiation

8. Folate deficiency Nutritional deficiency Malobsorption Excessive Utilization ( fetus,pregnancy ,prematurity) Hemolytic disorders Inflammatory diseases ( appetite,demand ) Long term dialysis CHF Congenital Drug

9. Clinical manifestations Anorexia SOB Paleness of skin Wight lose Tachycardia

10. Neurological manifestations Degeneratio of spinal N ,CN( cervical,thoracic )( post,lateral ) Psychotic symptoms Dementia Depression Cognitive impairment Anosmia Lose taste Paresthesia,muscle weakness,difficulty in waking Loses proproception,vibration sensation , ataxia,hyper reflexes Postural hypotension Impotence Incontenance Children(poor brain development,convulsions , leathery,coma )

11. GI manifestations Glositis Angular cheiolosis Diarrhea Constipation Rapid division (RT,GI,GU)

12. Pregnancy Prematurity (folate) Fetal loss Neural tube defect Cleft plate (1 st 12week 400mcg reduce risk 70%) Increase risk anti epileptics and anti folate drugs)

13. Cardiovascular Disease: Children with severe homocystinuria (blood levels ≥100 μ mol/L) due to deficiency of one of three enzymes (methionine synthase, MTHFR, or cystathionine synthase; Fig. 99-1) have vascular disease, for example, ischemic heart disease, cerebrovascular disease, or pulmonary embolus Malignancy :ALL

14. DX CBC(low HB ,High MCV) Peripheral smear (Oval macrocyte,anisocytosis , poikilocytosis , hypersegmated Neutrophil more then five Necluar lobe Leukopenia >1,5 Thrombocytopenia rare <40 RC normal or low

15. Cont… S cobalamine level(118-148). Symptoms <74 S methylmalonate and homocysteine S folic acid LDH Bilrubin

16. Treatment 1;It is usually possible to establish which of the two deficiencies, folate or cobalamin, is the cause of the anemia and to treat only with the appropriate vitamin 2;patients who enter the hospital severely ill, however, it may be necessary to treat with both vitamin 3;Transfusion is usually unnecessary and inadvisable. If it is essential, packed red cells should be given slowly, one or two units only, with the usual treatment for heart failure if present 4;Occasionally, an excessive rise in platelets occurs after 1–2 weeks of therapy. Antiplatelet therapy, for example, aspirin, should be considered if the platelet count rises to >800 × 109/L.

17. Cont… 1;Initially, patients with vitamin B12 deficiency are usually treated with parenteral therapy. Intramuscular or subcutaneous injections of 100–1000 mcg of vitamin B12 are adequate for each dose (with the higher dose recommended initially). 2;Replacement is usually given daily for the first week, weekly for the next month, and then monthly for life Sublingual or oral 1mg /day 3; A brisk reticulocytosis occurs in 5–7 days, and the hematologic picture normalizes in 2 months. CNS symptoms and signs are potentially reversible if they have been present for less than 6 months. 4;Hypokalemia may complicate the first several days of therapy, particularly if the anemia is severe.

18. Cont.. Folic acid deficiency is treated with daily oral folic acid (1 mg). reticulocytosis in 5–7 days, and total correction of hematologic abnormalities within 2 months.

19. MEGALOBLASTIC ANEMIA NOT DUE TO COBALAMIN OR FOLATE DEFICIENCY OR ALTERED METABOLISM This may occur with many antimetabolic drugs (e.g., hydroxyurea , cytosine arabinoside , 6-mercaptopurine ) that inhibit DNA re plication.

20. References Harrison’s Current

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