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Handout # 7

MICROCYTIC ANEMIAS
Pathogenesis
Decreased Hb synthesis --> Heme synthesis in iron stores --> liver synthesis of transferrin --> TIBC

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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

Anemia of chronic inflammation (ACD)

Decreased Hb synthesis: Iron blocked in macrophages iron stores --> liver synthesis of transferrin --> TIBC

Hb rarely < 9 gm/dL

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.

Decreased Hb Synthesis: defect in heme synthesis Iron overload in mitochondria

Alcoholism:MCC owing to alcohol being a mitochondrial poison Pyridoxine (B6) deficiency: INH therapy in TB Pb poisoning MDS

Handout # 7

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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

Beta thal minor: Increase in HbA2 and HbF

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

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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

Macrocytic anemias (MCV >100) Causes Clinical findings


Alcoholism: MCC (not beer - rich in Glossitis (not present in beer folate) drinking alcoholics) Poor diet: diet poor in vegetables, goat's milk Pregnancy/Lactation:utilization of folate; only 3-4 months supply in liver. Drugs: block dihydrofolate reductase methotrexate, trimethoprim block intestinal conjugase & conversion of polyglutamates to monoglutamates phenytoin block jejunal reabsorption of monoglutamate birth control pills, alcohol Pernicious Anemia (PA) MCC of B12 deficiency; autoimmune destruction of parietal cells in body/fundus; no intrinsic factor, no acid Pure vegan diet: B12 only in animal products Terminal ilieal disease: site of IFB12 complex resorption; Crohn's disease Fish Tapewprm Chronic Pancreatitis: Can not cleave off R factor from R factor-B12 complex (R factor from saliva protects B12 from acid destruction) Bacterial overgrowth Patient: sallow, waxy complexion, elderly womon of Scandinavian origin Glossitis: smooth sore tongue, atrophy of papilla Autoimmune disease: PA MCC of B12 deficiency Atrophic gastritis of body and fundus antiparietal cell/IF ab destroy parietal cells achlorhydria predisposes to cancer (adenocarcinoma) Malabsorption: loss of stem cell in GI tract Neurologic disease: decreased vibratory sensation and proprioception (posterior column disease) UMN signs (lateral corticospinal tract disease) Dementia, psychosis

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

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