logging in or signing up megaloblastic anemias d_parmar2003 Download Post to : URL : Related Presentations : Let's Connect Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Copy embed code: Embed: Flash iPad Dynamic Copy Does not support media & animations Automatically changes to Flash or non-Flash embed WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 3148 Category: Education License: All Rights Reserved Like it (1) Dislike it (0) Added: March 18, 2011 This Presentation is Public Favorites: 1 Presentation Description No description available. Comments Posting comment... By: rajeevchristian3 (8 month(s) ago) Dr Dipankar, would like to talk to you on this subject. Can you please give your contact no? Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Megaloblastic Anemias: Megaloblastic Anemias DR DEEPANKAR PARMAR KIMS MEDICAL COLLEGE A.P. DR DEEPANKAR PARMARMegaloblastic Anemias: Megaloblastic Anemias Megaloblastic anemias are A subset of macrocytic anemias in which The maturation phase of erythropoiesis in the bone marrow is abnormal, resulting in erythroid precursors that are enlarged and show failure of nuclear maturation (megaloblasts). DR DEEPANKAR PARMAREtiology: Etiology Megaloblastic anemias result from conditions in which nucleic acid synthesis is abnormal , as in Vitamin B12 vitamin B12 reservoirs in the liver are normally sufficient for several years; a decade may pass before vitamin B12 megaloblastic anemia becomes apparent . Folic acid deficiencies DR DEEPANKAR PARMARSlide 4: homocystine methionine Methylcobalamine Cobalamine N- methyl TH4 Methylene TH4 URIDINE THYMIDINE DNA TH4 CH3 DR DEEPANKAR PARMARVitamin B12 and folic acid play roles as cofactors in the conversion of deoxyuridine to deoxythymidine, an essential step in the synthesis of DNA : Vitamin B12 and folic acid play roles as cofactors in the conversion of deoxyuridine to deoxythymidine, an essential step in the synthesis of DNA Lack of either vitamin B12 or folic acid retards DNA synthesis (A). Lack of vitamin B12 leads to abnormal myelin synthesis , possibly via a deficiency of methionine (B). DR DEEPANKAR PARMARSlide 6: . Causes of Megaloblastic Anemia Vitamin B 12 deficiency Inadequate dietary intake: very rare; only in strict vegetarians Failure of absorption due to intrinsic factor deficiency 1 Pernicious anemia Total and subtotal gastrectomy Terminal ileal disease 1 Crohn's disease Strictures and fistulas that bypass the terminal ileum Surgical removal of the terminal ileum Competition for vitamin B 12 by intestinal microorganisms Bacterial overgrowth (blind loop syndromes) Diphyllobothrium latum (fish tapeworm) infection Drugs: para-aminosalicylic acid (antituberculous agent) Congenital deficiency of transcobalamin II (the vitamin B 12 transport protein in blood) DR DEEPANKAR PARMARSlide 7: Folic acid deficiency Inadequate intake Chronic alcoholism Malnutrition Failure of absorption Tropical sprue Other malabsorptive states Increased demand Pregnancy and infancy States of increased DNA synthesis (malignant neoplasms with high rate of cell turnover, erythroid hyperplasia in congenital hemolytic anemias) Drugs with folic acid antagonistic activity Anticancer drugs such as methotrexate Anticonvulsants such as hydantoins DR DEEPANKAR PARMARSlide 8: OTHER CAUSES Arsenic poisoning Nitrous oxide inhalation Some forms of chemotherapy (in addition to folic acid antagonists) Orotic aciduria (a rare condition with abnormal synthesis of purines and pyrimidines) DR DEEPANKAR PARMARPathology: Pathology Red Cell Changes Erythropoiesis changes from normoblastic to megaloblastic. Megaloblasts differ from normoblasts in that they are larger ( increased cytoplasm) and show delayed nuclear maturation but normal cytoplasmic hemoglobinization ( nuclear-cytoplasmic asynchrony) DR DEEPANKAR PARMARSlide 10: Photomicrographs of bone marrow films stained by May-Grünwald-Giemsa. A: Megaloblasts; B: Normoblasts for comparison. DR DEEPANKAR PARMARSlide 11: Photomicrograph of bone marrow film stained by May-Grünwald-Giemsa showing giant metamyelocytes DR DEEPANKAR PARMARSlide 12: DR DEEPANKAR PARMARSlide 13: Comparison of normoblasts ( left ) and megaloblasts ( right ). The megaloblasts are larger, have relatively immature nuclei with finely reticulated chromatin, and have an abundant basophilic cytoplasm. DR DEEPANKAR PARMARThe peripheral blood smear shows: The peripheral blood smear shows Macrocytosis (large red cells with elevated MCV) and Marked variation in size (anisocytosis) and shape (poikilocytosis) Oval forms (macro-ovalocytes) are prominent, and Howell-Jolly bodies , consisting of nuclear debris, are occasionally seen. Megaloblastic anemias are therefore macrocytic anemias if morphologic classification is used. DR DEEPANKAR PARMARSlide 15: DR DEEPANKAR PARMARNeutrophil Changes: Neutrophil Changes The delay in nuclear maturation is also seen in other lineages Neutrophil precursors in the bone marrow show marked enlargement; giant metamyelocytes . In the peripheral blood , neutrophils show hypersegmented nuclei, with many cells showing more than 5 nuclear lobes DR DEEPANKAR PARMARSlide 17: Here is a hypersegmented neutrophil that is present with megaloblastic anemias. There are 8 lobes instead of the usual 3 or 4. DR DEEPANKAR PARMARSlide 18: This hypersegmented neutrophil is present along with macro-ovalocytes in a case of pernicious anemia. Compare the size of the RBC's to the lymphocyte at the lower left center. DR DEEPANKAR PARMARChanges in Other Cells in the Body: Changes in Other Cells in the Body The abnormality in DNA synthesis affects many other cells in the body, notably those that have a high rate of cell turnover. These include the intestinal mucosa and other epithelia , which show cell enlargement and nuclear abnormalities. DR DEEPANKAR PARMARBONE MARROW: BONE MARROW Delayed maturation leads to accumulation of erythrocyte precursor cells . The bone marrow is hypercellular and contains large numbers of megaloblasts ; As a result of intramedullary hemolysis or ineffective erythropoiesis, Many megaloblasts undergo destruction in the bone marrow before maturation, aggravating the anemia and producing mild elevation of serum bilirubin and lactate dehydrogenase (LDH isoenzymes 1 and 2). DR DEEPANKAR PARMARClinical Features & Diagnosis: Clinical Features & Diagnosis Present with symptoms of severe anemia . Megaloblastic anemia should be suspected upon finding in the peripheral blood. macrocytic anemia with hypersegmented neutrophils Bone marrow examination is necessary for confirmation and shows megaloblastic erythropoiesis. DR DEEPANKAR PARMARSlide 22: There are two principal forms of megaloblastic anemia: folate deficiency , which has several underlying causes vitamin B12 deficiency , again with several causes, including pernicious anemia. DR DEEPANKAR PARMARSlide 23: The megaloblastic anemia of folate deficiency is identical to that of vitamin B12 deficiency; Administration of folic acid may thus mask (partially correct) the anemia of vitamin B12 deficiency , and vice versa; However, folic acid administration does not correct the neurologic effects of B12 deficiency . For this reason, it is important to exclude vitamin B12 deficiency before treating megaloblastic anemia with folate. DR DEEPANKAR PARMARSlide 24: D/D of Folic Acid and Vitamin B 12 Deficiency Anemias. Vitamin B 12 Deficiency Folate Deficiency Megaloblastic anemia + + Peripheral blood features Identical Subacute combined degeneration + – Serum vitamin B 12 1 Low Normal Serum folate 1 Normal Low Red cell folate Normal Low Response to vitamin B 12 by injection 2 + – Vitamin B 12 absorption test (Schilling) Abnormal 3 Normal Antiparietal or intrinsic factor antibodies in serum ± – DR DEEPANKAR PARMARPernicious (Addisonian) Anemia: Pernicious (Addisonian) Anemia Pernicious anemia is a form of megaloblastic anemia due to vitamin B12 deficiency. Pernicious anemia occurs predominantly after the age of 50 years , slightly more often in males than in females. DR DEEPANKAR PARMARPathogenesis: Pathogenesis An autoimmune disease , caused by immunologic destruction of the gastric mucosa. The mucosa of the body and fundus of the stomach is characterized by lymphocytic infiltration and progressive loss of parietal cells (chronic atrophic gastritis). This process is associated with failure of secretion of acid and intrinsic factor. Achlorhydria is invariably present in these patients. In the absence of intrinsic factor , vitamin B12 absorption is drastically reduced. DR DEEPANKAR PARMARThe exact mechanism of immune destruction is not fully known: The exact mechanism of immune destruction is not fully known Three types of autoantibodies are demonstrated in both serum and gastric juice : (1) About 75% of patients have an antibody that blocks vitamin B12 binding to intrinsic factor (blocking antibody); (2) About 50% have an antibody that binds with the intrinsic factor-vitamin B12 complex, interfering with the binding of the complex to ileal mucosal receptors, a prerequisite for vitamin B12 absorption; and (3) About 90% of patients have antibodies against gastric parietal cells. DR DEEPANKAR PARMARSlide 28: DR DEEPANKAR PARMARSlide 29: Gastric histology in pernicious anemia. ( Left) Normal fundus . The thick mucosa is packed with gastric glands composed mostly of chief cells and parietal cells. The mucus-secreting cells are concentrated in the necks of the glands. ( Right) Fundus in pernicious anemia. Gastric glands in the atrophic mucosa are sparse and consist mainly of mucus-secreting cells. The mucosa is densely infiltrated by lymphocytes. DR DEEPANKAR PARMARNeurologic changes are due to demyelination by uncertain mechanisms.: Neurologic changes are due to demyelination by uncertain mechanisms. The most characteristic neurologic abnormality in pernicious anemia is subacute combined degeneration of the spinal cord , characterized by demyelination of the posterior and lateral columns of the cord. This leads to paresthesia, loss of position and vibration sense, weakness, ataxia, and finally spasticity. Peripheral neuropathy is due to segmental demyelination of nerves. These neurologic changes do not occur in patients with folic acid deficiency. DR DEEPANKAR PARMARSlide 31: Degeneration of spinal cord in combined system disease. DR DEEPANKAR PARMARDIAGNOSIS: DIAGNOSIS Clinical picture Macrocytic blood picture Megaloblastic bone marrow Low serum Vit B 12 Positive serum intrinsic factor antobody test Schilling’s test Elevated serum gastrin level DR DEEPANKAR PARMARFOLIC ACID DEFECIENCY: FOLIC ACID DEFECIENCY DR DEEPANKAR PARMARClinical Features: Clinical Features Includes all the nonspecific manifestations of megaloblastic anemia plus the following specific features: (1) a history and laboratory studies indicating folate deficiency, (2) absence of the neurologic signs of cobalamin deficiency and (3) a full response to physiologic doses of folate . DR DEEPANKAR PARMARLaboratory Features: Laboratory Features The earliest indicator of folate deficiency is a low serum folate . A better indicator of the tissue folate status is the red cell folate , which remains relatively unchanged while a red cell is circulating and thus reflects folate turnover over the preceding 2 to 3 months. However, red cell folate also is low in more than 50 percent of patients with cobalamin-deficient megaloblastic anemia, therefore, it cannot be used to distinguish between these two deficiencies. DR DEEPANKAR PARMARSlide 36: END DR DEEPANKAR PARMAR You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.