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    Anemia of Diminished Erythropoiesis

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    Jared Khoo Er Hau
    This document provides information on anaemias of diminished erythropoiesis. It begins by defining key blood cells and haemopoiesis. It then describes the main types of anaemias of diminished erythropoiesis, including iron deficiency anaemia, megaloblastic anaemia, and aplastic anaemia. For each type, it discusses the etiology, pathogenesis, clinical features, complications, and laboratory findings. The document also provides details on haemoglobin and heme biosynthesis, porphyrias, classification of anaemias, and anaemia of chronic diseases.

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    Anemia of Diminished Erythropoiesis

    Uploaded by

    Jared Khoo Er Hau
    90 views43 pages
    This document provides information on anaemias of diminished erythropoiesis. It begins by defining key blood cells and haemopoiesis. It then describes the main types of anaemias of diminished erythropoiesis, including iron deficiency anaemia, megaloblastic anaemia, and aplastic anaemia. For each type, it discusses the etiology, pathogenesis, clinical features, complications, and laboratory findings. The document also provides details on haemoglobin and heme biosynthesis, porphyrias, classification of anaemias, and anaemia of chronic diseases.

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    Hematology

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    This document provides information on anaemias of diminished erythropoiesis. It begins by defining key blood cells and haemopoiesis. It then describes the main types of anaemias of diminished erythropoiesis, including iron deficiency anaemia, megaloblastic anaemia, and aplastic anaemia. For each type, it discusses the etiology, pathogenesis, clinical features, complications, and laboratory findings. The document also provides details on haemoglobin and heme biosynthesis, porphyrias, classification of anaemias, and anaemia of chronic diseases.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    90 views43 pages

    Anemia of Diminished Erythropoiesis

    Uploaded by

    Jared Khoo Er Hau
    This document provides information on anaemias of diminished erythropoiesis. It begins by defining key blood cells and haemopoiesis. It then describes the main types of anaemias of diminished erythropoiesis, including iron deficiency anaemia, megaloblastic anaemia, and aplastic anaemia. For each type, it discusses the etiology, pathogenesis, clinical features, complications, and laboratory findings. The document also provides details on haemoglobin and heme biosynthesis, porphyrias, classification of anaemias, and anaemia of chronic diseases.

    Copyright:

    © All Rights Reserved
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    of 43

    ANAEMIAS OF DIMINISHED

    ERYTHROPOIESIS
    DR SHWE SIN
    FMHS
    By the end of the lesson, the students should
    be able to :
    Understand the blood cells and haemopoiesis.
    Describe the definition, classifications, clinical
    presentations and complications of anaemia.
    State the definition of anaemia of diminished
    erythropoiesis.
    Describe the aetiology, pathogenesis, clinical features,
    complications and laboratory findings of common
    anaemia of diminished erythropoiesis (e.g Iron Deficiency
    Anaemia, Megaloblastic Anaemia, Aplastic Anaemia etc)
    Describe the pathogenesis of anaemia formation in
    chronic diseases.
    Haemoglobin (Hb) molecule (HbA)
    7
    Hemoglobin biosynthesis
    Heme biosynthesis
    8

    Heme
    The prosthetic group of
    hemoglobin, myoglobin, &
    cytochromes
    A complex of iron and
    protoporphyrin (a
    porphyrin ring)
    Most stable compound
    Synthesis in all tissue
    bone marrow & liver
    Pathway for Heme Biosynthesis
    GLYCINE + Succinyl CoA

    ALA synthase
    Ferrochelatase

    ALA dehydratase

    9
    Control of Heme Biosynthesis
    GLYCINE + SuccinylCoA

    ALA synthase
    Rate limiting step Ferrocheletase
    Heme Inhibit by heavy metal
    Iron storage
    Drugs
    Metabolites
    Glucose
    Steroid
    ALA dehydratase

    (PBG synthase)
    Inhibit by heavy
    metal e.g. Pb++
    elevated ALA
    brain toxicity

    10
    Clinical correlation
    Porphyrias
    11
    1. Acute
    Refers as Vampires disease 2. Cutaneous
    Can be caused by
    Genetic abnormality of enzymes involved in Heme biosynthesis
    Lead poisoning
    Drug, infections, alcohol and hormone such as estrogen
    Clinical presentation:
    Extreme sensitivity to sunlight (sun allergy)
    Problems with nervous systems and muscles
    Constant abdominal pains Does not cause a
    craving for blood
    Receding gum prominent fang like teeth
    Have an averse reaction to garlic
    Reddish to purplish urine
    Anemia/ Increased hair growth/ high blood pressure/ severe vomiting
    and etc
    Not a vampires disease
    12

    Complications:
    Coma, Gallstones, Dehydration,
    Kidney failure, Liver failure,
    Respiratory failure , Permanent skin
    damage
    Prophyria is a rare, but
    frightening condition: hard to
    diagnose and has no cure
    13
    ANAEMIA
    Anaemia is defined as a reduction in the
    haemoglobin concentration of the blood below
    normal for age and sex.
    For adult males- <13.5 g/dl
    For adult females- <11.5 g/dl
    2 years to puberty- < 11.0 g/dl
    Newborn infants - < 14.0 g/dl
    Signs and Symptoms
    Shortness of breath particularly on exercise (dyspnoea)
    Weakness
    Lethargy
    Palpitation
    Headache, confusion
    Visual disturbances
    Cardiac failure
    General Signs: Pallor of mucous membrane
    Tachycardia, cardiac murmurs
    Features of heart failure
    Specific Signs : e.g Koilonychia in IDA
    Bone deformities in thalassaemia
    Pallor of conjunctival mucosa and nail
    bed
    Complications:
    Cardiac failure
    Angina pectoris
    Visual disturbances
    Retinal haemorrhage
    Classification of anaemia according to
    red cell morphology

    Classification is based on red cell indices


    Divided into microcytic, normocytic and
    macrocytic anaemias

    Red Cell Indices


    Mean Cell Volume (MCV)
    Mean Cell Haemoglobin (MCH)
    Mean Cell Haemoglobin concentration (MCHC)
    Anemia Inadequate of RBCs

    Inadequate erythropoiesis or haemoglobin synthesis


    Kidney failure and insufficient erythropoietin
    Iron-deficiency anemia
    Pernicious anemia autoimmune attack of stomach tissue leads to inadequate vitamin B12
    absorption
    Hypoplastic anemiaslowing of erythropoiesis
    Aplastic anemiacomplete cessation of erythropoiesis

    Haemorrhagic anemias from bleeding


    Haemolytic anemias from RBC destruction
    I. Hypochromic microcytic anaemia
    Causes: Iron deficiency
    Thalassaemia
    Anaemia of chronic disease (some cases)
    Lead poisoning
    Sideroblastic anaemia
    II. Normocytic normochromic anaemia
    Causes: Many haemolytic anaemias
    Anaemia of chronic diseases (some cases)
    After acute blood loss
    Renal disease
    Bone marrow failure (e.g. post-chemotherapy,
    infiltration by carcinoma etc.)
    III. Macrocytic anaemia
    Causes: 1. Megaloblastic (Vitamin B12 or folate
    deficiency)
    2.Non-megaloblastic (alcohol, liver disease,
    myelodysplasia, aplastic
    anaemia etc.)
    ANISOCYTOSIS AND POIKILOCYTOSIS
    Classification of anaemia according to
    underlying mechanism
    I. Blood Loss:
    Acute: trauma
    Chronic: lesions of GIT, Gynaecologic disturbances
    II. Increased Destruction (Haemolytic Anaemias):
    A. Intrinsic (intracorpuscular) abnormalities
    Hereditary: Membrane abnormalities
    Enzyme deficiencies
    Disorders of haemoglobin
    synthesis
    Acquired: Membrane defect (PNH)
    B. Extrinsic (extracorpuscular) abnormalities
    Antibody mediated: Alloantibodies
    Autoantibodies
    Mechanical trauma to red cells: MAHA
    Infections

    III. Impaired Red Cell Production:


    E.g Iron Deficiency anaemia, Megaloblastic anaemia,
    Aplastic anaemia
    ANAEMIA OF DIMINISHED
    ERYTHROPOIESIS
    Anaemias result from deficiencies of vital
    nutrients necessary for red cell formation (e.g. IDA
    & megaloblastic anaemia) or other causes of
    decreased erythropoiesis (e.g. anaemia of
    chronic diseases, AA) or bone marrow infiltration
    by tumours or inflammatory cells (e.g.
    myelophthisic anaemia).

    1. Iron deficiency anaemia


    2. Megaloblastic anaemia
    3. Anaemia of chronic diseases
    4. Marrow stem cell failure e.g Aplastic anaemia
    I. Iron deficiency anaemia
    Most common cause of anaemia
    Hypochromic microcytic anaemia
    Total body iron- 2 gm for women and 6 gm for men
    Storage form Haemosiderin and ferritin
    Iron transport protein- Transferrin

    Causes of IDA:
    Chronic blood loss (Most common)
    Increased demands (Pregnancy, Infancy etc)
    Malabsorption
    Poor diet

    Pathogenesis:
    Deficient formation of Haem synthesis leading to reduced Hb
    (Anaemia)
    Iron absorption
    Clinical features:
    Features of anaemia (pallor, weakness, listlessness etc)
    Nail changes (Koilonychia or spooning, brittle, thinning & flattening)
    Painless glossitis, angular stomatitis, dysphagia (Oesophageal web)
    Pica (consume non-foodstuffs)

    Peripheral blood film changes:


    Hypochromic microcytic anaemia (Reduced MCV, MCH & MCHC)
    Anisocytosis, poikilocytosis (target cells, pencil-shaped cells)
    Plt count may be increased

    Laboratory findings:
    Serum iron- Reduced
    Serum ferritin- Reduced
    Transferrin saturation- Low
    Total iron-binding capacity (TIBC)- Increased
    Koilonychia
    IDA (Peripheral blood film)

    IDA Normal Blood Film


    II. Megaloblastic anaemia
    Caused by deficiencies of folate or vitamin B12
    Macrocytic anaemia
    Both vitamins are co- enzymes & required for DNA
    synthesis (Purine & thymidine)

    Vit B12 absorption process:


    Dietary Vit B12 bind R-binders or cobalophilins in
    saliva then Vit B12 release at duodenum
    then bind with intrinsic factor (IF) produced by parietal
    cells absorption at ileum
    Pathogenesis:
    Both Vitamin B12 & folic are coenzymes required for DNA
    synthesis deficiency leads to disturbances in
    derangement of DNA synthesis delayed nuclear
    maturation and cell division enlarged erythroid
    precursors (megaloblasts) because of nuclear-
    cytoplasmic asychrony abnormal large red cells
    (macrocytes)
    Other myeloid lineages are affected
    hypersegmented neutrophils
    Because of all three cell lineages affected
    Pancytopenia
    Causes of Vit B12 deficiency:
    Pernicious anaemia due to deficiency of intrinsic factor (IF)
    Nutritional deficiency
    Malabsorption
    Strict vegetarians
    Following gastrectomy
    Excess loss
    Drugs

    Causes of folate deficiency:


    Nutritional deficiency
    Malabsorption
    Following gastrectomy
    Excess loss
    Drugs
    Clinical Features:
    Glossitis (red tongue)
    Angular stomatitis
    Mild jaundice
    Neuropathy- Demyelinating disorder (Vit B12 only) (Subacute
    combine degeneration of spinal cord) leading to symmetric
    numbness, tingling and burning in feet or hands, unsteadiness
    of gait & loss of position sense

    Peripheral blood film changes:


    Hypochromic macrocytic anaemia
    Hypersegmented neutrophils
    Pancytopenia
    Glossitis & Angular stomatitis
    Megaloblastic anaemia (Peripheral blood film)
    III. Anaemia of chronic diseases
    It occurs in variety of chronic inflammatory disorders:
    - Chronic microbial infections (OM, bacterial
    endocarditis & lung abscess)
    - Chronic immune disorders (SLE, RA, regional enteritis)
    - Neoplasms (Hodgkin lymphoma, Ca breast, Ca lung)

    Pathogenesis:
    Chronic inflammation pro-inflammatory cytokines
    sequestration of iron in mononuclear phagocytes
    anaemia (but increased storage iron)
    Result in reduced serum iron, reduced total iron binding capacity but
    high serum ferritin

    Peripheral blood film findings:


    Normochromic normocytic anaemia
    IV. Anaemia due to marrow failure
    Aplastic Anaemia
    Multipotent myeloid stem cells are suppressed leading to
    bone marrow failure (hypocellularity) and pancytopenia
    Associated with reticulocytopenia (decrease reticulocyte
    count)

    Pathogenesis:
    Aplasia of bone marrow due to fault in remaining stem
    cells or immune reaction
    Causes of aplastic anaemia:
    I. Primary
    1) Congenital (e.g. Fanconi type)
    2) Idiopathic
    II. Secondary
    1) Ionizing radiation
    2) Chemicals (e.g. Benzene, organophosphates)
    3) Drugs (e.g cyclophoshpamide, chloramphenicol,
    sulphonamides)
    4) Virus (e.g. Viral hepatitis, EBV)
    Peripheral blood film findings:
    Anaemia (NNA)
    Leucopenia
    Thrombocytopenia
    Reticulocyte count- low (Normal- 0.5-2.5 %)
    No abnormal cells in peripheral blood

    Bone marrow findings:


    Hypocellular marrow with increased fat
    Myelophthisic Anaemia
    Extensive replacement of marrow by tumors or other
    lesions
    Most commonly associated with metastatic Ca breast,
    lungs, prostate or advanced TB

    Peripheral blood film findings:


    Leukoerythroblastic (LE) pictures- immature granulocytic
    and erythrocytic precursors seen
    Tear-drop rbc can be seen
    LABORATORY FINDINGS IN ANAEMIA
    Haemoglobin (Hb) concentration Reduced
    Red cell indices MCV Reduced or normal or
    increased
    MCH- Reduced or normal
    MCHC- Reduced
    WBC count Normal or reduced or increased
    Platelet count Normal or reduced or increased
    Reticulocyte count Increased or reduced
    Blood film examination
    It is essential in all cases
    Checked for abnormal red cell morphology or red cell
    inclusions.
    Also assessed for white cell abnormalities and platelet
    number and presence or absence of abnormal cells
    REFERENCES
    Essential Haematology (A.V. Hoffbrand and P.A.H.Moss),
    6th Edition
    Robbins Basic Pathology, 9th Edition

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