2 MACROCYTIC ANEMIASThese are the anemias in which the RBC have an MCV of greater than 100flThere are 2 groups of macrocytic anemiasMegaloblastic anemiaNon megaloblastic macrocytic anemia
3 Requirements for Red Blood Cell Production ErythropoeitinProteins, required for globin synthesisIronVitamin B12 and folic acidVitamin B6Vitamin CThyroid hormones, estrogens and androgens
4 MEGALOBLASTIC ANEMIAThese are a group of disorders in which the cause the anemia is due to deficiency of vitamin B12 and folic acidThe macrocytes in this condition is usually “oval” - hence they are also called as MACRO OVALOCYTES
5 NON MEGALOBLASTIC MACROCYTIC ANEMIAS These are disorders in which the macrocytosis is not due to vitamin B12 or folic acid deficiencyHere the macrocytes are “ROUND”The conditions in which such round macrocytes are seen areReticulocytosisHypothyroidism / myxedemaMyelodysplastic syndromeScurvy (Vit-C dif)Sideroblastic anemiaLiver disorders
6 MEGALOBLASTIC ANEMIAVitamin B12 and folic acid are important nutrients required in the process of nuclear maturationThey are required during erythropoiesis (during DNA synthesis)These anemias may be caused because of a nutritional deficiency or impaired absorption mainly.
7 MEGALOBLASTIC ANEMIAImpaired DNA synthesis leading to defective cell maturation and cell divisionNuclear maturation delays from the cytoplasmic maturation – NUCLEAR CYTOPLASMIC ASYNCHRONYAbnormally large erythroid precursors and red cells
8 MEGALOPLASTIC ANAEMIA. Affect all marrow elements.Neurologic symptoms (dorsal columns)Ineffective erythropoiesis: High indirect bilirubin Very high LDH
9 Folic Acid: Daily requirement: Transportation: It a vitamin which yellow in colour, water soluble, necessary for the production of the RBC, WBC and platelets.It is not synthesized in the body.It is found in large number of green fresh vegetables, fruits.Daily requirement:The human body needs about µg daily. Absorption:It is absorbed in the Duodenum and Jejunum.Transportation:Weakly bound to albumin.
10 METABOLIC FUNCTION Purine synthesis Conversion of homocysteine to methionine ( which also requires B12 )
12 INCREASED DEMAND Pregnancy Lactation Infancy Puberty and growth period Patients with chronic hemolytic anemiasDisseminated cancer
13 DECREASED INTAKE Elderly Lower socio economic status Chronic alcoholics
14 DECREASED ABSORPTIONAcidic food substances in foods like legumes, beansDrugs like phenytoin, oral contraceptivesCeliac disease which affect the gut absorptionHeat sensitive – more loss during cooking
16 Vitamin B12:This vitamin is synthesized in nature by micro-organism in the intestine of man and animals, but we can not obtain it from the bacteria in our bodies, because it is synthesizing in the large colon after the site of absorption and it is wasted in the faeces in about 5µg/day. So we obtain it from animal food such as liver, kidney, meat and dairy products as milk and cheese.
17 VITAMIN B12 Abundant in animal foods Microorganisms are the ultimate origin of cobalaminIt is stored in liver for many yearsIt is efficiently reabsorbed from bileIt is resistant to cooking and boiling
18 Diary requirements:The human body needs about 1-2 µg daily.Absorption:B12 is combined with glycoprotein called the intrinsic factor (IF), which is synthesized in the gastric cells. The absorption occurs in the distal ileum.Transportation:Transport by a protein synthesized in the liver called Transcobalamine II, which carry vitamin B12 to liver, nerves and bone marrow.
22 IMPAIRED ABSORPTIONINTRINSIC FACTOR DEFICIENCY due to chronic gastritis or antibodies against stomach cells.- PERNICIOUS ANEMIA- GASTRECTOMYMalabsorption statesDiffuse intestinal diseases. Eg., lymphoma, systemic sclerosisCompetitive parasitic uptake – fish tapewormBacterial overgrowth
23 CLINICAL FEATURESPatients develop all general symptoms and signs of the anaemia.Knuckle pigmentationAngular stomatitisAtrophic glossitis- “beefy” tongueNeurological disorders: sever deficiency of the folic acid causes neuropathies diseases.Deficiency during pregnancy causes neural tube defect.
24 PERIPHERAL BLOOD FINDINGS Hemoglobin – decreasedHematocrit – decreasedRBC count – decreased/normalMCV - >100fl ( normal 82-98fl)MCH –increasedMCHC – NORMALReticulocytopenia.Total WBC count – normal / lowPlatelet count – normal/ lowPancytopenia, especially if anaemia is sever.
25 PERIPHERAL SMEAR RBC: Poikilocytosis - tear drops and schistocytes Anisocytosis - oval macrocytes-Macro ovalocytes (macrocytic normochromic)-well hemogloibised, thicker than normal-inclusions like HOWELL JOLLY BODIES, basophilic stippling, Cabot rings
26 PERIPHERAL SMEAR WBC: Normal count or reduced count Hypersegmented neutrophils (>5 lobes)MACRO POLYMORPHO NUCLEAR CELLS (Macropolys)PLATELETS:Normal or decreased
31 BONE MARROW Markedly hypercellular Myeloid : erythroid ratio decreased or reversed. (Normally, there are three myeloid precursors for each erythroid precursor resulting in a 3:1 ratio, known as the M:E (myeloid to erythroid) ratio)Erythropoiesis : MEGALOBLASTIC
32 MEGALOBLAST Abnormally large precursor Deeply basophilic royal blue cytoplasmFine chromatin with prominent nucleoliNuclear cytoplasmic asynchronyAbnormal mitosesMaturation arrest
37 BIOCHEMICAL FINDINGSIncrease in serum unconjugated bilirubin- because of ineffective erythropoiesisIncrease is LDHNormal serum iron and ferritin
38 TESTS FOR FOLATE AND B12 DEFICIENCY Serum folate assayRed cell folate assaySerum B12 assay
39 PERNICIOUS ANEMIA Scandinavian countries more prevalent Disease of elderly – 5th to 8th decadesGenetic predispositionTendency to form antibodies against multiple self antigens
40 PATHOGENESISImmunologically mediated, autoimmune destruction of gastric mucosaCHRONIC ATROPHIC GASTRITIS – marked loss of parietal cellsThree types of antibodies:Type I antibody- 75% - blocks vitamin B12 and IF bindingType II antibody – prevents binding of IF-B12 complex with ileal receptorsType III antibody – 85-90% patients – against specific structures in the parietal cellAssociated with other autoimmune diseases like autoimmune thyroiditis
41 DIAGNOSTIC FEATURES Moderate to severe megaloblastic anemia Leucopenia with hypersegmented neutrophilsMild to moderate thrombocytopeniaMild jaundice due to ineffective erythropoiesis and peripheral hemolysisNeurologic changesLow levels of serum B12Elevated levels of homocysteineStriking reticulocytosis after parenteral administration of vitamin B12Serum antibodies to intrinsic factor