Anemia
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Anemia

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    Anemia Anemia Presentation Transcript

    • ANEMIA www.freelivedoctor.com
    • ANEMIA
      • any condition in which the number of red cells , the amount of hemoglobin or the volume of packed red blood cells per unit volume is less than normal.
      • a pathophysiological condition in which the body cannot meet its demands for oxygen.
      www.freelivedoctor.com
    • Blood Reference Values WBC 4,800-10,800/mm 3 RBC M: 4.7-6.1 mil/mm 3 F: 4.2-5.4 mil/mm 3 ( or x 10 6 /  L) Plt 130,000-400,000/mm 3 Hgb M: 14.0-18.0 g/dL F: 12.0-16.0 g/dL Hct M: 42-52% F: 37-47% MCV [= Hct(%) / RBC count(x10 6 /  L)/10] 80-100  3 (or fL) MCH [= Hgb(g/dL) / RBC count(x10 6 /  L)/10] 27-33 pg MCHC [= Hgb(g/dL) / Hct(%)/100] 32-36 g/dL RDW 8.5-11.5 % reticulocyte (absolute number) 40,000-100,000 /  L www.freelivedoctor.com
    • Erythrocyte Indices
      • Hemoglobin (Hgb)
      • Hematocrit (Hct)
      • Mean Corpuscular Volume (MCV)
      • Mean Corpuscular Hemoglobin (MCH)
      • Mean Corpuscular Hemoglobin Concentration (MCHC)
      • Red Cell Distribution Width (RDW)
      • [Packed Cell Volume (PCV)]
      www.freelivedoctor.com
    • RBC “rule of 3’s”
      • For normal erythrocytes:
        • hemoglobin (g/dL)  3 x RBC count (millions)
        • hematocrit (%)  3 x hemoblobin (g/dL)  3%
      • Failure to obey this “rule of 3’s” suggests an abnormality in erythrocytes (sickle cells, etc)
      www.freelivedoctor.com
    • classification of anemia by color
      • hypochromic (decreased color)
        • increased central pallor
      • normochromic (normal color)
        • central pallor ~1/3 of the RBC diameter
      • hyperchromic (increased color)
        • (~spherocytosis)
        • loss of central pallor
      www.freelivedoctor.com
    • anemia
      • M: Hb <13.5 Hct <41
      • F: Hb <12 Hct <36
      www.freelivedoctor.com
    • www.freelivedoctor.com
    • ANEMIA morphologic classification microcytic MCV <80 normocytic MCV 80-100 macrocytic MCV >100 www.freelivedoctor.com
    • ANEMIA classification by volume
      • microcytic anemia (MCV <80)
      • normocytic anemia (MCV 80-100)
      • macrocytic anemia (MCV >100)
      www.freelivedoctor.com
    • ANEMIA classification by volume
      • microcytic anemia (MCV <80)
        • iron deficiency anemia
        • thalassemia syndromes
        • anemia of chronic disease
        • sideroblastic anemia
      www.freelivedoctor.com
    • ANEMIA classification by volume
      • microcytic anemia (MCV <80)
      • normocytic anemia (MCV 80-100)
        • anemia of blood loss
        • hemolytic anemia
      www.freelivedoctor.com
    • ANEMIA classification by volume
      • microcytic anemia (MCV <80)
      • normocytic anemia (MCV 80-100)
      • macrocytic anemia (MCV >100)
        • megaloblastic anemia
      www.freelivedoctor.com
    • ANEMIA classification by volume
      • microcytic anemia (MCV <80)
        • iron deficiency anemia
        • thalassemia syndromes
        • anemia of chronic disease
        • sideroblastic anemia
      • normocytic anemia (MCV 80-100)
        • anemia of blood loss
        • hemolytic anemia
      • macrocytic anemia (MCV >100)
        • megaloblastic anemia
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • a. intrinsic abnormality
          • b. extrinsic abnormality
      • II ↓ RBC production
        • 1. stem cell abnormality
        • 2. erythroblast abnormality
        • 3. unknown/multiple mechanism
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • blood loss
          • a. acute : trauma, massive hemorrhage
          • b. chronic : GI lesion, GYN lesion
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
          • extrinsic abnormality
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
            • acquired memb. defect
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
            • acquired memb. defect
      hereditary spherocytosis hereditary elliptocytosis www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
              • hereditary spherocytosis
              • hereditary elliptocytosis
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
            • acquired memb. defect
      pyruvate kinase def. G6PD def. www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
              • pyruvate kinase def.
              • G6PD def.
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
            • acquired memb. defect
      Thalassemia sickle cell disease Hb C disease www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
              • Thalassemia
              • sickle cell disease
              • Hb C disease
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
            • acquired memb. defect
      PNH www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
            • acquired memb. defect
              • PNH
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
          • extrinsic abnormality
            • mechanical trauma
            • chemical injury
            • infection
            • immunologic injury
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
          • extrinsic abnormality
            • mechanical trauma (microangiopathic HA)
              • TTP/HUS, DIC
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
          • extrinsic abnormality
            • mechanical trauma
            • chemical injury
              • lead poisoning
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
          • extrinsic abnormality
            • mechanical trauma
            • chemical injury
            • infection
              • malaria
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
          • extrinsic abnormality
            • mechanical trauma
            • chemical injury
            • infection
            • immunologic injury
              • autoimmune hemolytic anemia
              • drug mediated injuries
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
            • acquired memb. defect
          • extrinsic abnormality
            • mechanical trauma
            • chemical injury
            • infection
            • immunologic injury
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
      • II ↓ RBC production
        • 1. stem cell abnormality
        • 2. erythroblast abnormality
        • 3. unknown/multiple mechanism
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
      • II ↓ RBC production
        • stem cell abnormality
          • aplastic anemia
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
      • II ↓ RBC production
        • 1. stem cell abnormality
        • 2. erythroblast abnormality
          • megaloblastic anemia
          • iron deficiency anemia (defective Hb synthesis)
      www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
      • II ↓ RBC production
        • 1. stem cell abnormality
        • 2. erythroblast abnormality
        • 3. unknown/multiple mechanism
          • sideroblastic anemia
      www.freelivedoctor.com
    • Hereditary Spherocytosis
        • intrinsic defect in the membrane cytoskeleton
        • genetic: autosomal dominant
        • pathoetiology: spectrin deficiency -> decreased RBC surface memb. -> loss of biconcavity
        • anemia: moderate anemia
        • normocytic
        • hyperchromic
        • reticulocytosis
        • entrapment of spherocytes in the spleen ( splenomegaly ) ( extravascular hemolysis )
        • increased erythrocyte osmotic fragility
      www.freelivedoctor.com
    • Hereditary Spherocytosis www.freelivedoctor.com
    • Hereditary Spherocytosis
      • Sx: 1. mild to moderate hemolytic anemia
      • 2. splenomegaly
      • 3. marked compensatory erythroid hyperplasia in BM
      • 4. jaundice, pigment cholelithiasis ← ( ↑ bilirubin )
      • 5. increased risk for acute red-cell aplasia due to parvovirus B19 infection
      • Lab: 1. increased osmotic fragility
      • 2. normal MCV with increased MCHC
      • Tx: splenectomy
      www.freelivedoctor.com
    • Hereditary Elliptocytosis
        • intrinsic defect in the membrane cytoskeleton
        • genetic: autosomal dominant
        • pathoetiology: impaired aggregation of spectrin
        • anemia: 90% of pt. are non-anemic
        • non-hypochromic elliptocytes >25% (nl=<15%)
        • Sx: splenomegaly
      www.freelivedoctor.com
    • Embden-Meyerhof glycolytic pathway www.freelivedoctor.com
    • Pyruvate Kinase Deficiency
        • autosomal recessive
        • most common red cell enzyme deficiency involving Embden-Meyerhof glycolytic pathway
        • inability to maintain normal ATP levels
        • mild to moderate hemolysis
        • splenomegaly
        • patients tolerate anemia rather well (  high levels of 2,3-DPG )
        • Dx: - fluorescent spot test
        • - enzyme assay
      www.freelivedoctor.com
    • X www.freelivedoctor.com
    • fluorescent spot test
      • Pyruvate kinase catalyzes the phosphorylation of ADP to ATP with the formation of pyruvate . Pyruvate then reduces any NADH present to NAD with formation of lactate. Loss of florescence of NADH under ultra-violet light is observed as evidence of the presence of pyruvate kinase.
      www.freelivedoctor.com phosphoenol pyruvate pyruvate lactate PK ADP ATP *NADH NAD
    • www.freelivedoctor.com
    • G6PD Deficiency
        • Pathophysiology: decreased half life of G6PD
        • increased vulnerability to oxidative denaturation due to limited
        • generation of NADPH (older RBCs are preferentially destroyed)
        • Genetics:
        • high genetic heterogeneity
        • x-linked recessive (  full expression in male hemizygote)
        • Sx:
        • hemolysis after exposure to oxidant stress
        • - drugs: primaquine, chloroquine, sulfonamides, nitrofurantoins
        • - infections: viral hepatitis, pneumonia, typhoid fever
        • “ favism” : hemolysis after ingestion of fava beans (Mediterranean type)
        • Lab:
        • - poikilocytes, some spherocytes
        • - Heinz bodies : precipitates of denatured hemoglobin material
        • - “bite cells”
      www.freelivedoctor.com
    • G6PD Deficiency bite cell Heinz bodies www.freelivedoctor.com
    • ANEMIA pathophysiologic classification
      • I RBC loss
        • 1. blood loss
        • 2. ↑ RBC destruction
          • intrinsic abnormality
            • membrane disorder
            • enzyme disorder
            • Hgb synthesis disorder
              • Thalassemia
              • sickle cell disease
              • Hb C disease
      www.freelivedoctor.com
    • hemoglobin molecule two  chains two  chains four  -globin genes two  -globin genes www.freelivedoctor.com
    • globin genes www.freelivedoctor.com CH16 CH11
    • Thalassemia Syndromes
        • heterogeneous hemolytic disorders characterized by quantitative abnormalities of hemoglobin synthesis
        • genetic defect in globin production
        • selective depression or absence of a- or b- chain of hemoglobin
        • broad spectrum of presentation
        • predominantly seen in persons of Mediterranean , African and Asian ancestry
        • α -thalassemia : α -chain deficiency due to gene deletion
        • β -thalassemia : β -chain deficiency due to point mutation (Cooley’s anemia)
      www.freelivedoctor.com
    • Thalassemia Syndromes pathophysiology
        • Two (2) pathological mechanisms to contribute to develop anemia
        • 1. inadequate Hgb formation  low MCHC, hypochromasia
        • 2. relative excess of unaffected Hgb chain
        •  aggregation and precipitation of excess chain
        •  damage to the cell membrane
        •  loss of K+ and impaired DNA synthesis
        •  apoptosis of RBCs in BM (“ ineffective erythropoiesis ”)
      www.freelivedoctor.com
    • Thalassemia Syndromes pathophysiology
        • ineffective erythropoiesis
        • +  severe erythroid hyperplasia
        • hemolysis excess absorption of iron
        • severe iron overload
      www.freelivedoctor.com
    • α -thalassemia  1  2  /  normal  1  2  /   + -thal heterozygote (mild)  1  2  /   0 -thal heterozygote (moderate) www.freelivedoctor.com
    • α -thalassemia  1  2  /   + -thal homozygote (moderate)  1  2  /   0 -thal x  + -thal (severe)  1  2  /   0 -thal homozygote (lethal) www.freelivedoctor.com
    • β -thalassemia
      • clinical classification of β thal is based on the severity of the anemia (based on the type of genetic defect and gene dosage )
      • β + -> some β chain production
      • β 0 -> no β chain production
      • clinical manifestation
      • homozygous ( β + / β + or β 0 / β 0 ) severe
      • heterozygous ( β + / β or β 0 / β ) mild
      www.freelivedoctor.com
    • β -thalassemia promoter gene mutation: 75-80% reduction of transcription rate (  + thal) chain termination mutation: premature termination of mRNA translation (  0 thal) splicing mutation: aberrant splicing (  0 &  + thal) most common cause of thal www.freelivedoctor.com
    • “ Thalassemia Major”
        • homozygous β + / β + or β 0 / β 0
        • severe anemia at 6 to 9 months of age requiring blood transfusion
            • death at early age, if not transfused
        • severe erythrophagocytosis and extramedullary hematopoiesis
        •  hepatosplenomegaly
        • marked red marrow expansion  “Crew-Cut” sign
        • hemosiderosis
        • heart disease 2º to hemochromatosis is the major cause of death in older patients
      www.freelivedoctor.com
    • “ Thalassemia Major” www.freelivedoctor.com
    • “ Thalassemia Major”
        • Dx:
        • anemia work up
        • hemoglobin electrophoresis  no or very low HbA
        • markedly elevated HbF
        • DNA analysis
        • Rx:
        • blood transfusion with iron chelators
          • improvement of anemia
          • suppression of secondary features related to excessive erythropoiesis
        • BM transplantation
      www.freelivedoctor.com
    • “ Thalassemia Minor”
        • much more common than Thalassemia major
        • heterozygous b + /b or b 0 /b
        • peripheral smear: hypochromia, microcytosis, basophilic stippling, target cells
        • may be resistant against falciparum malaria
        • usually asymptomatic or mild anemia (microcytic anemia)
        • DDx: iron deficiency anemia
              • serum iron
              • total iron binding capacity
              • serum ferritin
      www.freelivedoctor.com
    • www.freelivedoctor.com
    • www.freelivedoctor.com
    • www.freelivedoctor.com
    • www.freelivedoctor.com
    • www.freelivedoctor.com
    • www.freelivedoctor.com
    • Sickle Cell Disease
        • prototype of hereditary hemoglobinopathies
        • structurally abnormal hemoglobin from a point mutation
      www.freelivedoctor.com
    • Sickle Cell Disease
        • - severe anemia  generalized growth and developmental impairment
        • - vaso-occlusive complications
        • - painful crisis: bones, lungs, liver, brain, spleen, penis
        • - acute chest syndrome
        • - aplastic crisis
        • - sequestration crisis (splenic hyperplasia  pooling of blood)
        • - chronic hyperbilirubinemia
        • - increased susceptibility to infection  septicemia, meningitis
        • (encapsulated bacteria)
        • Dx: clinical findings
        • peripheral blood smear
        • hemoglobin analysis
      www.freelivedoctor.com
    • Sickle Cell Trait
        • - heterozygous (Ss) Hb S -- 30-40%
        • - approx. 10% of American blacks
        • - normal peripheral blood count and RBC life span
        • - rare sickling with low oxygen tension, low pH
        • (local ischemia, high altitude, pneumonia, etc.)
      www.freelivedoctor.com
    • Paroxysmal Nocturnal Hemoglobinuria (PNH)
        • an acquired clonal disorder of stem cells, and results from a somatic mutation in phosphatidylinositol glycan A (PIGA) gene that is essential for the synthesis of the glycosylphosphatidylinositol (GPI) anchor protein of the membrane, and makes RBCs very sensitive to complement-mediated cell lysis due to the deficiency of proteins that regulate complement activity
      GPI-linked complement reg. Proteins CD55 (DAF) CD59 CD8 binding protein www.freelivedoctor.com
    • Paroxysmal Nocturnal Hemoglobinuria (PNH)
        • clinical:
        • - chronic hemolysis without dramatic hemoglobinuria (75%)
        • - paroxysmal and nocturnal intravascular hemolysis (25%)
        • - venous thromboses in hepatic, portal or cerebral veins
      www.freelivedoctor.com
    • TTP / HUS
        • Thrombotic Thrombocytopenic Purpura (TTP)
        • Hemolytic Uremic Syndrome (HUS)
        • - widespread formation of hyaline thrombi in microcirculation
        • - endothelial injury and activation of intravascular thrombosis seem to be the initiating mechanisms
        • - may have diverse causes
        • - verotoxins ( E.coli O157:H7)
        • - viral infection
      www.freelivedoctor.com
    • TTP / HUS
        • TTP (Thrombotic Thrombocytopenic Purpura)
        • adult female with pentad
        • 1. Fever
        • 2. Thrombocytopenia
        • 3. Microangiopathic hemolytic anemia
        • 4. Transient neurologic deficits
        • 5. Renal failure
        • HUS (Hemolytic Uremic Syndrome)
        • child with acute renal failure
        • microangiopathic hemolytic anemia
        • thrombocytopenia
        • no neurologic symptoms
      www.freelivedoctor.com
    • Disseminated Intravascular Coagulation (DIC)
        • - an acute, subacute, or chronic thrombohemorrhagic disorder occurring as a secondary complication in a variety of diseases
        • - activation of clotting system resulting in wide spread formation of microthrombi throughout the microcirculation
        • - as a consequence, causing consumption of platelets, fibrin and coagulation factors, and activation of thrombolytic mechanism
        • Two major triggering mechanisms
        • 1. release of tissue factor or thromboplastic substance
        • 2. widespread endothelial injury
      www.freelivedoctor.com
    • Disseminated Intravascular Coagulation (DIC)
        • Pathology:- wide spread thrombi
        • (brain, heart, lungs, kidneys, adrenals, spleen , liver)
        • - microinfarcts
        • Clinical: - ~50% associated with obstetric complications
        • - ~30% with carcinomatosis
        • - microangiopathic anemia
        • - dyspnea, cyanosis
        • - convulsions, coma
        • - oliguria, acute renal failure
        • - shock, circulatory failure
      www.freelivedoctor.com
    • Lead Poisoning
        • - inhibition of 5’-nucleotidase and sodium-potassium pump
        •  decreased RBC survival
        • - intestinal absorption of Pb is enhanced by def. of calcium, iron or zinc
        • - blood accumulates 5-10% of absorbed Pb
        • - Pb clearance:
        • from blood  rapidly cleared
        • from bone  slow (half-life = 30 yrs)
        • Lab: basophilic stippling
      www.freelivedoctor.com
    • Malaria
        • - intracellular protozoan parasite ( Plasmodium )
        • P.falciparum : worldwide infection affecting 100 million people
        • 1 to 1.5 million deaths each year
        • other malaria parasites:
        • P.vivax
        • P.ovale
        • P.malariae
      www.freelivedoctor.com
    • Immunohemolytic Anemia
        • several subtypes
        • (1) warm antibody type
        • (2) cold agglutinin type
        • (3) cold hemolysin
      www.freelivedoctor.com
    • Immunohemolytic Anemia
        • (1) warm antibody type
        • - 80 to 90% of autoimmune hemolytic anemia
        • - lg G antibody
        • - coating RBC with anti-Rh Ab and complement
        • - RBCs are ultimately destroyed by splenic macrophages
        • clinical: - intermittent hemolysis
        • - moderate splenomegaly
        • - unpredictable clinical course
        • etiology:
        • a. idiopathic disease
        • b. secondary disorder
        • - lymphoma (lymphocytic lymphoma)
        • - leukemia (chronic lymphocytic leukemia)
        • - autoimmune disorders (SLE, collagen vascular diseases)
        • - viral infections
        • - drugs: penicillin, cephalosporin (hapten)
        • α -methyldopa (autoantibody)
      www.freelivedoctor.com
    • Immunohemolytic Anemia
        • (2) cold agglutinin type
        • - 10 to 20% of autoimmune hemolytic anemia
        • - Ig M type antibody
        • - complement-coated RBC will be removed by liver Kupffer cells
        • etiology:
        • a. acute: - mycoplasma
        • - infectious mononucleosis
        • b. chronic: - idiopathic
        • - lymphoma
      www.freelivedoctor.com
    • Immunohemolytic Anemia
        • (3) cold hemolysis
        • paroxysmal cold hemoglobinuria
        • - caused by IgG bind to RBCs at low temp and fix complement
        • - acute intermittent massive hemolysis after exposure to cold
        • - complement dependent hemolysis
        • - caused by IgG against P blood group antigen
        • - IgG-Ab (Donath-Landsteiner Ab) binds to RBC and fix complement at cold temp and then complement activation when temp is elevated.
        • mostly seen after infection: mycoplasmal pneumonia
        • measles
        • mumps
      www.freelivedoctor.com
    • Drug-Mediated Injury
        • (1) autoantibody induction
        • α -methyldopa  Ig G antibody
        • (2) immune complex formation (drug-Ab complex)
        • quinidine  Ig M complex
        •  complement-mediated lysis
        • (3) hapten formation (drug-RBC membrane protein complex)
        • penicillin
      www.freelivedoctor.com
    • Aplastic Anemia
        • - pancytopenia characterized by
        • (1) anemia
        • (2) neutropenia
        • (3) thrombocytopenia
        • - failure or suppression of multipotent myeloid stem cells causes inadequate production or release of the differentiated cell lines
        • Etiology:
        • - 65% idiopathic
        • - chemicals/drugs
        • (benzene, chloramphenicol, alkylating agents, antimetabolite)
        • - whole body irradiation
        • - viral hepatitis
      www.freelivedoctor.com
    • Aplastic Anemia
        • Pathology: markedly hypoplastic bone marrow
        • Clinical: - may occur at any age
        • - variable initial manifestations
        • (depending on the affected cell line)
        • - no splenomegaly
        • - normocytic and normochromic RBCs
        • - no reticulocytosis
        • Dx: bone marrow biopsy
        • hypocellular due to stem cell failure
      www.freelivedoctor.com
    • Megaloblastic Anemia
        • A group of disorders characterized by a reduced rate of DNA synthesis
        • The dyssynchrony in nuclear (DNA) and cytoplasmic (RNA) development is the morphologic hallmark of this type of disorder, since RNA synthesis, RNA processing and protein synthesis are unaffected.
      www.freelivedoctor.com
    • Vitamin B12 / Folate Deficiency
      • Vitamin B12 (cobalamin) -- a vital ingredient for DNA synthesis and Krebs cycle
      Methylcobalamin a coenzyme for tetrahydrofolate (FH 4 ) www.freelivedoctor.com
    • Vitamin B12 Absorption Vit B12: absorbed in ileum (with intrinsic factor) Intrinsic factor www.freelivedoctor.com
    • Vitamin B12 / Folate Deficiency
        • Lab:
        • Blood: - macro-ovalocytes, giant hypersegmented PMNs (no giant platelets)
        • - pancytopenia
        • - elevated MCV
        • - anisocytosis
        • - poikilocytosis
        • BM: - hyperplastic
        • -  myeloid : erythroid ratio
        • - megaloblasts
        • - giant metamyelocytes
        • - autohemolysis ( -> ↑ serum bilirubin, ↑ LDH)
      www.freelivedoctor.com
    • Vitamin B12 Deficiency
      • etiology:
      • dietary deficiency ---- rare
          • strict vegetarians)
      • decreased absorption
        • decreased intrinsic factor
          • gastrectomy
          • pernicious anemia
        • pancreatic insufficiency
        • intestinal malabsorption
          • parasites (fish tapeworm [ Diphyllobothrium latum ])
          • bacteria (blind-loop syndrome)
          • ileal Crohn’s disease
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    • Vitamin B12 Deficiency
      • Sx:
      • weakness ← anemia (megaloblastic anemia)
      • sore (“beefy”) tongue ← generalized epithelial atrophy
      • demyelination of spinal cord (posterior and lateral portions) (subacute combined spinal degeneration)
        • loss of vibration and position senses ← posterior tracts loss
        • arm and leg dystaxia ← dorsal spinocerebellar tracts loss
        • spastic paralysis ← corticospinal tracts loss
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    • Vitamin B12 Deficiency
      • Lab:
      • low serum B12 level
      • increased serum homocysteine
      • increased methylmalonic acid in urine
      • Dx: Schilling test
      • oral radioactive B12 -> 2 hrs later -> parenteral large flushing dose of non-labeled B12 -> measure urine for radioactive B12
      • nl: >7% of radio-labeled B12 excreted in 24-hr urine
      • abnormal (lacking IF): less than 7% of B12 excreted
      • Tx: intramuscular vitamin B12
      • -> increase in reticulocytes in 5 days
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    • folate deficiency
      • etiology:
      • dietary deficiency (folate def. takes only months to develop)
        • “ tea and toast” diet (elderly individuals)
        • chronic alcoholics
      • decreased absorption
        • intestinal malabsorption (folate is absorbed in upper intestine)
      • increased requirement
        • pregnancy (folate def in pregnancy -> neural tube defects)
        • infancy
      • folate antagonists
        • chemotherapy (i.e. methotrexate)
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    • folate deficiency
      • Sx:
      • megaloblastic anemia
      • no neurologic degeneration
      • Lab:
      • low serum folate level
      • increased serum homocysteine
      • Tx: folate
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    • Iron Deficiency Anemia
      • Iron: absorbed in duodenum
      • When iron loss exceeds its intake for a long time, iron storage decreases and insufficient amount of iron is available for hemoglobin production
      • Iron deficiency anemia develops in sequence of stages:
      • 1. Iron Depletion
      • 2. Iron Deficient Erythropoiesis
      • 3. Iron Deficiency Anemia
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    • Iron Deficiency Anemia
      • Clinical:
      • - general fatigue
      • - SOB
      • - spoon nails (koilonychia)
      • - smooth, sore tongue
      • - epithelial atrophy
      • - pica (eating unusual things [e.g., dirt])
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    • Iron Deficiency Anemia
        • Lab:
        • Blood: - normochromic-normocytic
        •  microcytosis, anisocytosis, poikilocytosis, hypochromia
        • - decreased reticulocytes
        • - low MCV
        • - relatively low Hgb, Hct
        • Marrow: no iron storage
        • normoblastic hyperplasia
        •  smaller normoblast with deficient Hgb
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    • Iron Deficiency Anemia
        • Serum iron (nl = 50-160 mg/dL) : low
        • Serum iron-binding capacity (nl = 250-400 mg/L) : increased
        • % saturation of TIBC (nl = 20-55%) : <15%
        • Serum ferritin (nl = 12-300 mg/L) : low
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    • sideroblastic anemia
      • due to altered production of heme (defect in protoporphyrin production)
      • associated with ring sideroblasts in bone marrow
      • peripheral blood: may show dismorphic RBCs
      • lab: increased serum iron ferritin free erythrocyte protoporphyrin (FEP) % saturation of TIBC decreased TIBC
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    • Sideroblastic Anemia
        • a heterogeneous group of disorders associated with various defects in the porphyrin biosynthetic pathway
            • porphyrn biosynthesis defects
            • diminished heme synthesis
            • increased cellular iron uptake
        • characterized by the association of anemia with presence of ringed sideroblast (a normoblast containing excessive deposits of iron within mitochondria) in bone marrow
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    • Sideroblastic Anemia
        • Sub-types:
        • Hereditary Sideroblastic Anemias
        • hereditary sex-linked
        • inheritance undetermined
        • Acquired Sideroblastic Anemias
        • primary (idiopathic) sideroblastic anemia
        • secondary (drug- or toxin-induced) sideroblastic anemia
        • anti TB drugs (isoniazid, cycloserine, pyrazinamide)
        • lead poisoning
        • chloramphenicol
        • ethanol
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    • Sideroblastic Anemia www.freelivedoctor.com
    • Sideroblastic Anemia
        • clinical: characterized by hypochromic, often microcytic, red cells in the blood usually mixed with normochromic cells
          • hypochromic anemia
          • hyperferremia
          • increased transferrin saturation
        • Lab: serum iron: increased
        • TIBC: decreased
        • % saturation: greatly elevated
        • bone marrow: - markedly increased iron storage
        • - erythroid hyperplasia
        • - increased sideroblasts
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    • anemia work-up
      • M: Hb <13.5 Hct <41
      • F: Hb <12 Hct <36
      • [check MCV]
      • MCV <80 = microcytic
        • Fe deficiency
        • thalassemia
        • anemia of chronic disease
        • sideroblastic anemia
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    • anemia work-up
      • MCV >100 = macrocytic
        • megaloblastic anemia
          • VitB12 deficiency
          • folate deficiency
        • alcoholic liver disease
      • MCV 80-100 = normocytic
      • [chech reticulocyte count]
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    • anemia work-up
      • low reticulocyte:
        • - marrow failure - leukemia/metastasis
        • - aplastic anemia - renal failure
        • myelofibrosis - anemia of chronic disease
      • high reticulocyte:
        • sickle cell anemia - autoimmune hemolytic anemia
        • G6PD deficiency - hereditary sphelocytosis
        • paroxysmal nocturnal hemoglobiuria
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