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MICROCYTIC ANEMIAS
Pathogenesis
Decreased Hb synthesis --> Heme synthesis in iron stores --> liver synthesis of transferrin --> TIBC
Win 07
Anemias characteristics
Iron deficiency Anemia Most Common anemia MCV: microcytic (<80) Key findings: microcytic hypochromic RBCs Thrombocytosis in chronic cases
Causese
Bleeding: MC overall cause (usually GI bleed) Prematurity Newborns: Bleeding Meckel's diverticulum 6 months-2years of age: nutritional: milk baby Child: bleeding Meckel's Pregancy Female < 50 years: menorrhagia Male < 50 years: duodenal ulcer Male/female > 50 yrs: GI bleed; R/O colon Ca Chronic inflammation: Microbial, rheumatoid arthritis Malignancy: ACD is the most common anemia
Clinical Findins
Spoon nails = Koilnychia Plummer Vinson syndrome: esophageal web, achlorhydria, glossitits, intestinal malabsorption
Decreased Hb synthesis: Iron blocked in macrophages iron stores --> liver synthesis of transferrin --> TIBC
Alpha thalassemia MCV: microcytic Reticulocyte count: <2% in mild >3% in severe types
Decreased globin chain synthesis But, ,, chain syntheses are normal Hence, HbA (2/2), HbA2 (2/2)and HbF(2/2) are all reduced
1 gene deletion: silent carrier Asians 2 gene deletion: thalassemia trait: African Americans African American (-/-): one gene deletion on each chromosome. Asian:(/--): both deletions of same chromosome. 3 gene deletion: HbH disease (HbH=4-globin chians); Hemolytic anemia 4 gene deletion: Hb Bart's disease (Hb Bart's = 4 globin chains); spontaneous abortions (hydrops fetalis); incidence of choriocarcinoma Beat thal minor: mild protective effect against falciparum malaria Beta thal major (Cooley's anemia) : hemolytic anemia Herditary persistence of HbF: variant of beta thal noted in African Americans. Absent beta and delta chain synthesis alpha and gamma chains unite to form HbF, which persists into adult life no anemia Child: eating old lead based paint Adult: working in a battery factory, drinking moonshine, using lead glazed pottery,sniffing gasoline African Americans, Italians, Greeks Terms: minor, intermedia and major connote degree of severity Severe thalassemia does not manifest at birth since (gamma globin chians predominate; HbF) first manifestation occurs at 6-9 months of age
Beta thalassemia: MCV: microcytic Tear drop cells and Target cells Reticulocyte count: <2% in mild >3% in severe types
Decreased beta globin chain synthesis on chromosome 11 Point mutation producing splicing defect is the most common defect But, ,, chain syntheses are normal. Hence, decreased synthesis of HbA (2/2). increased synthesis of HbA2 (2/2)and HbF(2/2). 0 = No beta globin chain synthesis + = some beta globin chain synthesis Decreased Hb synthesis Pb denatures enzymes: ferrochelatase ALA dehydrase ribonuclease: can not degrade ribosomes --> Coarse basophilic stippling Iron overload: Fe enters mitochondria and cannot exit --> Fe stores--> Liver synthesis of transferrin--> TIBC
Sideroblastic Anemia: Lead Poisoning: MCV : microcytic Reticulocyte count: often > 3% due to mild hemolytic component Key finding: Coarse Basophilic stippling : prominent ribosomes Ringed sideroblasts in BM Sideroblastic Anemia: MCV : microcytic Reticulocyte count: <2% Key finding: Siderocytes: called Pappenheimer bodies, Common in iron overload disease such as hemosiderosis Ringed Sideroblasts: in the BM, present in all sideroblastic anemias
Abnormal craving (pica) for paint and plaster Lead colic: severe abdominal pain Peripheral neuropathy: wrist drop (radial nerve), claw hand (ulnar nerve. Encephalopathy: cerebral edema, convulsions learning disability. Bone: Pb deposited in epiphysis (visoble on X ray- Pb line) Proximal renal tubular acidosis: Pb denatures proximal tubular cells.
Alcoholism:MCC owing to alcohol being a mitochondrial poison Pyridoxine (B6) deficiency: INH therapy in TB Pb poisoning MDS
Handout # 7
Win 07
Laboratory Findings
Serum Iron : decreased TIBC : increased % saturation: decreased Serum ferritin: decreased RDW : increased MCHC: decreased
Serum Iron : decreased TIBC : decreased % saturation: decreased Serum ferritin: increased RDW : normal MCHC: decreased Iron Studies: normal in the mild variants RBC count: normal to increased Hb Electrophoresis: Alpha thal minor (1 or 2 gene deletions): normal Alpha thalassemia (3 gene deletions): HbH increased Alpha thalassemia (4 gene deletions) Hb Bart's increased
Blood Pb levels: best screen and confirmatory test. Urine delta ALA: increased Serum iron: increased TIBC: decreased % saturation: increased Serum ferritin: increased Bone radiographs: deposits in the epiphysis
Serum iron: increased TIBC: decreased %saturation: increased Serum ferritin: increased Bone marrow: ringrd sideroblasts required for diagnosis
Handout # 8
Anemia characteristics
Folate deficiency MC macrocytic anemia MCV: macrocytic Reticulocute count:<2% Key findings: PS: macroovalocytes hypersegmented neutrophils pancytopenia BM: megaloblastic BM giant metamyelocytes
Pathogenesis
Defect in DNA synthesis Nuclear maturation defect: nucleus remain large No defect in proprionate metabolism: no CNS disease
B12 deficiency MCV: macrocytic Reticulocute count:<2% Key findings: PS: macroovalocytes hypersegmented neutrophils pancytopenia BM: megaloblastic BM giant metamyelocytes
Defect in DNA synthesis Nuclear maturation defect: nucleus remain large Proprionate metabolism: odd chain fatty acid metabolism Propionyl CoA --> Methylmalonyl CoA --> Succinyl CoA. Deficiency of B12 increases propionate: produces demyelination of CNS (posterior column and lateral corticospinal tracts)
Handout # 8
Laboratory tests
Serum folate: low RBC folate: low Serum homocysteine: increased Urine FIGLu: increased Serum LDH: increased
Serum B12: decreased Serum Homocysteine: increased Urine methylmalonic acid: increased Schilling test: abnormal Correction with IF: PA Corection with antibiotics: bacterial overgrowth Correction with pancreatic extract: chronic pancreatitis No correction with any of the above: terminal ilieal disease