ePathoPlusPage

Home

Lectures

Features

Plus

 

ANEMIA

Outline
A. Erythropoiesis
    1. Pathway for maturation of rbc from stem cell

    2. factors affecting maturation in bone marrow
        a. Vit B12

        b. folic acid

        c. formation of Hgb

            heme = made up porphyrin and Fe, 4 hemes combine with one  globin = hemoglobin (globin made up of 4 large polypeptide chains,   2 alpha and 2 beta)

        d. trace elements

    3. iron metabolism

B. M= IT
    a. M = size of rbc mass (in avg man = 25 x 10 which = 3% lean body mass)

    b. I = input of new rbc from bone marrow (in avg man = 0.8% of M)

    c. T = time representing rbc life span (120 days)

    d. one definition of anemia is when M is < normal, can be the result of  decreased I or decreased T or combination of both (anemia can also exist if rbc are inefficient in delivery of oxygen)

C. Anemia Secondary to Blood Loss
    a. Acute - avg adult has a blood volume of 6000ml., they can loose 500 cc without serious or lasting effects, > 1000 cc = serious condition

    b. Chronic
        1. most common cause of iron deficiency anemia
        2. Causes
            unsuspected GI tract malignancy

            slowly bleeding peptic ulcer

            hemorrhages

D. Anemia Secondary to Bone Marrow Dysfunction
    a. Aplastic Anemia (usually characterized by decrease in all blood producing elements: leukopenia, thrombocytopenia and anemia.  N.B. pancytopenia is one term which combines all three preceding terms)    

        1. Causes

Idiopathic (50% of time)

                    exposure to antineoplastic drugs or radiation

                    exposure to other drugs (e.g. chloramphenicol, sulfonamides, benzene)

                    metabolic or toxic bone marrow suppression secondary to other diseases (e.g. chronic infection, renal failure ,

                    neoplastic disease

            b. syngeneic- marrow from identical twin

            c. allogenic- marrow from matched donor

    b. Sideroblastic Anemia (impaired production of erythrocytes due to impaired porphyrin synthesis, a microcytic and/or hypochromic anemia)
        1. Causes
            toxic agents (e.g alcohol, lead, isoniazid)

            genetic - rare, sex linked, responds to tx with pyridoxine

            idiopathic- generally refractory to tx with pyridoxine

    c. Iron Deficiency Anemia ( a microcytic and/or hypochromic anemia)

1.. avg adult body has approx. 4 grams of Fe of which 3 grams is in Hgb,500 mg- 1 gram in Fe stores in liver and bone marrow and remainder stored in tissues and enzyme systems. Avg daily loss of   iron is about 1.5 mg which is compensated for from diet

        2. Causes
                blood loss

                gastrointestinal (malabsorption)

                gynecologic

                urinary tract (rare), paroxysmal nocturnal hemoglobinemia

   3. Severe clinical manifestations = koilonychia (brittel and spoon shaped nails), smooth, shiny, bright red tongue and cheilosis (corners of mouth crack and become red and painful)

    d. Vit B12 and Folic Acid Deficiency Anemias (megaloblastic or macrocytic anemias)   

            1. pernicious anemia= deficiency of intrinsic factor due to failure of   parietal cells), high expression in norther european whites, may be genetically determined but not expressed until 4th decade of life

            2. chronic alcoholism is leading cause of folic acid deficiency

E. Anemias Secondary to Destruction of Erythrocytes (Hemolytic Anemias)
    a. Spherocytosis (membrane abnormally leads to osmotic swelling of rbc with increased susceptibility for removal by spleen, Ca and Na pumps are ineffective)

        1. autosomal dominant trait

    b. G6PD deficiency (lack of G6PD leads to direct oxidation of hemoglobin to methemoglobin with subsequent hemolysis)

        1. number of genetic variants, African variant is found in 10% of American Blacks, usually this form is mildly expressed and not associated with chronic hemolytic anemia unless exposed to antioxidant drugs

    c. Sickle Cell Disease (qualitative defect in hemoglobin)

        1. distinguish from Sickle cell trait (those with trait are heterozygous,  do not have disease but are carriers, those with disease are  homozygous for mutation in gene that codes for adult hemoglobin)

        2. mutation in gene that codes for adult hemoglobin (get what is called HgbS, instead of normal HgbA) . 

        3. HgBS - a single amino acid is substituted for another in one of the polypeptide chains- leads to sickling of rbc when oxygen tension in tissue decreases

        4. Clinical picture

                    anemia    

                    pain, especially in bones, joints, back (may be localized o  migratory)

                    growth and sexual maturation may be delayed

                    increased susceptibility to infections

                    hepatosplenomegaly

                    enlarged heart (cardiomegaly)

                    sickle cell crises, may be either

                            thrombotic

                            aplastic

    d. Thalassemia (quantitative defect in hemoglobin, al)so a microcytic and   hypochromic anemia)
        1. characterized by decreased synthesis of one of the globin chains

            a. defect in beta chain = beta thalssemia

            b. defect in alpha chain = alpha thalssemia

    2. Thalassemia Major and Thalassemia Minor
        a. Major is homozygous, minor is heterozygous and carrier

        b. normally minor causes mild anemia but needs to be watched
            during pregnancy

    3. hemosiderosis= deposition of iron in tissues- leads to cardiac failure

F. Polycythemia (increased rbc mass)

    a. relative polycythemia - HCT rises because of loss of blood volume)

    b. secondary polycythemia - results from increased erythropoietin due to  increased altitude, or conditions that increase hypoxia such as chronic heart and lung disease or smoking

    c. polycythemia vera- proliferative dx of bone marrow