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    Hematopoiesis Anemia: Composition of The Blood

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    Ocha24 Tupamahu
    This document discusses hematopoiesis, the production of blood cells, and anemia, a decreased red blood cell count. It describes the components of blood and the process of hematopoiesis where stem cells differentiate into mature blood cells through growth factors. Anemia is then defined and types are listed along with their mechanisms, manifestations, and laboratory findings. Specific production disorders like iron deficiency and vitamin B12/folate deficiency are explained in detail.

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    Hematopoiesis Anemia: Composition of The Blood

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    Ocha24 Tupamahu
    13 views16 pages
    This document discusses hematopoiesis, the production of blood cells, and anemia, a decreased red blood cell count. It describes the components of blood and the process of hematopoiesis where stem cells differentiate into mature blood cells through growth factors. Anemia is then defined and types are listed along with their mechanisms, manifestations, and laboratory findings. Specific production disorders like iron deficiency and vitamin B12/folate deficiency are explained in detail.

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    This document discusses hematopoiesis, the production of blood cells, and anemia, a decreased red blood cell count. It describes the components of blood and the process of hematopoiesis where stem cells differentiate into mature blood cells through growth factors. Anemia is then defined and types are listed along with their mechanisms, manifestations, and laboratory findings. Specific production disorders like iron deficiency and vitamin B12/folate deficiency are explained in detail.

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    13 views16 pages

    Hematopoiesis Anemia: Composition of The Blood

    Uploaded by

    Ocha24 Tupamahu
    This document discusses hematopoiesis, the production of blood cells, and anemia, a decreased red blood cell count. It describes the components of blood and the process of hematopoiesis where stem cells differentiate into mature blood cells through growth factors. Anemia is then defined and types are listed along with their mechanisms, manifestations, and laboratory findings. Specific production disorders like iron deficiency and vitamin B12/folate deficiency are explained in detail.

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    Hematopoiesis

    Anemia

    Composition of the Blood

    1. red blood cells (RBC's or erythrocytes)

    2. white blood cells (or leukocytes)

    3. platelets (or thrombocytes)

    4. plasma
    Hematopoiesis
    • Production and Development of Blood
    Cells
    • Pluripotent Stem Cell
    - Continuous Self-Replication
    - Gives Rise to All Blood Cell
    Lines
    • Growth Factors (Cytokines) - Promote
    Differentiation Into Mature Blood Elements

    Anemia

    Definition - Decreased RBC mass


    Working Definition - Decreased
    Red Blood Cell Count
    Hemoglobin
    Hematocrit
    Red Blood Cell
    • Hemoglobin (Hgb) -
    -Direct Measurement (g/dl)
    • Hematocrit (Hct) -
    - Packed RBC Volume (PV) -
    Manual “Spun” Hematocrit (%)
    - Automated Counters Calculate
    Based on RBC Number and Size

    Red Blood Cell Indices

    • Mean Corpuscular Volume (MCV) - Average


    Size of the RBCs
    • Mean Cell Hemoglobin (MCH) -
    Hgb/RBC
    • Mean Cell Hemoglobin Concentration
    (MCHC) - Hgb/Hct
    • Red Blood Cell Distribution Width (RDW) -
    Index of Size Variation
    Types of Anaemia
     anaemia of B12 deficiency
     anaemia of chronic disease
     anaemia of folate deficiency
     drug-induced immune haemolytic anaemia
     haemolytic anaemia
     haemolytic anaemia due to g6pd deficiency
     idiopathic aplastic anaemia
     idiopathic autoimmune haemolytic anaemia
     immune haemolytic anaemia
     iron deficiency anaemia
     megaloblastic anaemia
     pernicious anaemia
     secondary aplastic anaemia
     sickle cell anaemia

    Mechanisms of Anemia
    Production Disorders:
    • Hematopoietic Cell Damage
    -Drugs, Radiation, Infections, Toxins
    • Factor Deficiency
    -Iron (Heme Synthesis)
    -Vitamin B12 (DNA Synthesis)
    -Folate (DNA Synthesis)
    Mechanisms of Anemia

    Survival Disorders:
    • Blood Loss - External or

    Internal
    • Red blood Cell Destruction

    -Hemolytic Anemias

    Anemia
    Manifestations - Cause & Chronicity
    Nonspecific Signs and Symptoms
    • Weakness, Malaise, Fatigue
    • CNS hypoxia - Headaches, Faintness, Dimness
    of Vision
    • Skin Pallor, Thinning and Inelasticity
    • Nail Brittleness
    • Angina Pectoralis (if ASCVD)
    Production Disorder - Iron
    Deficiency
    • Most Common Nutritional Deficiency
    • Required in Hemoglobin Synthesis
    Heme + Globin Chains = Hemoglobin
    • Occurs in RBC Cytoplasm ⇒
    Hypochromic Microcytic Anemia

    Iron Metabolism

    • Iron is Absorbed Primarily in Duodenum


    - 25% of Heme-Bound Iron (Red Meat)
    - 1-2% of Non-Heme Iron
    • Body Losses of Iron are Limited
    - 1-2 mg/Day By Epithelial Cell Shedding
    • Mucosal Block - Maintains Balance
    Transferrin
    • Transport Protein For Iron In Blood
    • Fully Saturated Transferrin = TIBC
    300 - 350ug/dl Fe
    • Normal Transferrin - 1/3 Filled With Iron
    100 - 120ug/dl Fe (Serum Iron)

    Iron Storage

    Ferritin - Protein Iron Complex


    *Found In All Tissues
    *BM, Liver (Transferrin)
    *Spleen (RBC Breakdown)

    Hemosiderin - Breakdown Product of


    Ferritin
    Development of Iron Deficiency
    • Depletion of Stores
    ⇓ Serum Ferritin
    ⇓ Stainable BM Iron

    ↑ TIBC)
    ⇑ Transferrin (↑ ⇓ Serum Fe

    ⇓ Transferrin Saturation
    • ⇓ Hemoglobin, Myoglobin, Fe Proteins

    Iron Deficiency Anemia Laboratory Findings

    • Hypochromic Microcytic Anemia


    ↓ RBC Count, ↓ MCV)
    (↓
    • ↓ Serum Ferritin Levels
    • ↓ Transferrin Saturation
    ↓ Serum Fe, ↑ Transferrin)
    (↓
    Causes of Iron Deficiency
    • External Blood Loss - Most Common
    Female Genital Tract
    Gastrointestinal Tract
    • ↑ Demand - Infancy, Pregnancy
    • Dietary Deficiency - Rare
    (Vegetarian Diets)
    • Intestinal Malabsorption Syndrome

    Iron Deficiency
    Clinical Manifestations

    • Anemia - Non-Specific Findings


    • Koilonychia
    • Plummer-Vinson Syndrome
    -Hypochromic Microcytic Anemia
    -Atrophic Glossitis
    -Esophageal Webs (Dysphagia)
    Production Disorder -
    Vitamin B12 or Folate Deficiency

    Megaloblastic Anemias
    • Impaired DNA Synthesis (Nucleus)
    • Function - Transfer of Carbon Groups
    • Affects All Rapidly Dividing Cells
    -Mouth - Atrophic Glossitis
    -GI tract - Intestinal Malabsorption

    Megaloblastic Anemia
    Peripheral Blood

    • RBCs - Large Oval Macroovalocytes


    - MCV > 100u3
    • Anemia Due To Ineffective Hematopoiesis
    - Autohemolysis of Megaloblasts
    (Circulating Large RBCs Destroyed)
    • Hypersegmented Neutrophils
    • Thrombocytopenia, Neutropenia (Severe)
    Vitamin B12 Deficiency - Cause

    Western World - Pernicious Anemia


    • Autoimmune Disorder

    -Autoantibodies to IF and Parietal Cells


    -Chronic Atrophic Gastritis
    -Achlorhydria - Absent HCL
     ⇑ Incidence of Other Autoimmune Disorders

    Vitamin B12 Deficiency


    Additional Causes:
    • Inadequate Diet - Rare (>20yr Stores)
    -Foods Containing Animal Protein
    -Microorganisms Synthesize
    -Stored in Liver, Reabsorbed in Bile
    • Gastrectomy, Ileal Resection
    • Malabsorption States, Gastric Atrophy
    • Diphyllobothrium Latum - Fish Tapeworm
    Megaloblastic Anemia - Bone Marrow

    Nuclear- Cytoplasmic Asynchrony:


    • Erythroid Series (Hallmark Changes)

    -Megaloblasts
    -Erythroid Hyperplasia
    • Myeloid Series

    • Megakaryocytic Series - (Infrequent)

    Vitamin B12 Deficiency


    • Clinical - Similar to Folate Deficiency But
    Demyelinating Neurologic Disorder
    - Affects Both Sensory and Motor Tracts
    - Lack of Correlation With Anemia
    • Parenteral B12 - Improves Anemia,
    +/- Resolution of Neurologic Symptoms
    • Caution! Anemia of B12 Deficiency Also
    Improves With Folate Supplementation
    Vitamin B12 Deficiency
    Laboratory Findings:
     Low Serum Vitamin B12 Levels
     Normal RBC Folate Levels
     Abnormal Schilling Test - Impaired
    Absorption of Radioactive Vitamin B12
    Correctable by Addition of IF
     Anti-Intrinsic Factor Antibodies (Anti-
    Parietal Antibodies Less Sensitive)

    Causes of Folate Deficiency

    • Dietary Deprivation
    - Widely Distributed in Foods
    (Uncooked Vegetables, Fruits, Liver)
    - Limited Body Stores (Wks-Months)
    - Chronic Alcoholics, Elderly, Indigent
    • Malabsorption (Upper 1/3 Intestine)
    - Intestinal Disease (Sprue, Celiac Dx)
    - Chronic Drugs (Dilantin)
    Folate Deficiency
    • Increased Requirements - Pregnancy
    • Impaired Utilization - Folic Acid
    Antagonists (Chemotherapy Drugs)
    Laboratory Findings:
    • Red Blood Cell Folate - Reflects Tissue
    Content of Folate Throughout Body
    • Serum Folate - Levels Fluctuate Based on
    Recent Intake, Do Not Reflect Stores

    Anemia of Chronic Disease


    • Normochromic Normocytic Anemia
    (or Hypochromic Microcytic)
    • Chronic Disorders (Inflammation or
    Tissue Necrosis)
    -Chronic Microbial Illnesses
    -Chronic Immune Disorders
    -Neoplasms
    • Often ↓ TIBC, ↑ Ferritin
    Anemia of Chronic Disease
    Defect
    Storage Iron
    IL-1
    TNF α
    γ IFN
    Erythroid Precursors
    (Insufficient Erythropoietin)

    Hematopoietic Cell Damage


    Aplastic Anemia
    Bone Marrow Aplasia (Lack of Cells)
    • Failure of Multipotent Stem Cell

    - T-cell Mediated Suppression or


    - Genetic Damage
    • Bone Marrow - Markedly Hypocellular

    • Peripheral Blood - Pancytopenia

    - Normochromic Normocytic RBCs


    Aplastic Anemia

    Causes of Stem Cell Failure


    • Idiopathic (>50%) - Poor Prognosis
    Especially If < 40 Years Old
    • Whole Body Irradiation
    • Viral Infections - Most Common
    After Non-A/Non-B Hepatitis
    • Chemical Agents and Drugs - Reversible
    and Non-Reversible

    Myelophthisic Anemia

    BM Replacement ⇒ BM failure:
     Metastatic Carcinoma Most Common

     Destruction By Non-Neoplastic Process is

    Less Common i.e. Fibrosis, Infection


     Peripheral Blood Cytopenias, Immature

    Circulating Cells

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