Hematologic Alterations: Anemia

Anemia

• Definition:
  • Decreased total number of circulating erythrocytes.
  • Decreased quality or quantity of hemoglobin.
• Causes: (individual or combined)
  • Impaired erythrocyte production.
  • Increased erythrocyte destruction.
  • Blood loss.

Anemia Classification

• Terminology: Based on erythrocyte assessment.
  • Changes in morphology.
    • -cytic: changes in cell size.
    • -chromic: changes in hemoglobin content (color saturation).

Overall Effects of Anemia

• Reduced oxygen carrying capacity of the blood leads to hypoxia.
• Compensatory mechanisms:
  • Increase in preload, heart rate, and stroke volume.
  • Decrease in afterload.
  • Increased cardiac output to maintain adequate tissue oxygenation.

Clinical Manifestations of Anemia

Macrocytic (Megaloblastic) Anemias - Pathophysiology

• Vitamin deficiencies (B12 or Folate).
• Defective erythrocyte precursor DNA synthesis.
• Unusually large stem cells in bone marrow produce large erythrocytes (red blood cell -RBCs) without the usual pale center. Increased cell size $(\uparrow)$
• Hemoglobin is normal with well-saturated red color.
• Types:
  • Pernicious anemia
  • Folate deficiency anemia

Pernicious Anemia – Vitamin B12

• Most common megaloblastic anemia.
• Deficiency of Vitamin B12.
• Common over age 50.
• Pathophysiology
  • Absence of Intrinsic Factor (IF) (gastric parietal cells).
  • $(\downarrow)$ IF binding with dietary B12.
  • $(\downarrow)$ small intestine absorption of B12.
  • Defective DNA synthesis in erythrocytes.
• Causes:
  • Chronic atrophic gastritis (autoimmune) – Type A
  • Genetic
  • Other endocrine autoimmune disorders
  • Excessive damage to gastric mucosa
  • Alcohol, caffeine, smoking
  • Gastrectomy (partial/full)
  • Helicobacter pylori gastritis - Type B
• Unique Clinical Manifestations:
  • Insidious onset – B12 liver storage.
  • Severe at time of diagnosis.

Folate Deficiency Anemia

• Pathophysiology
  • $(\downarrow)$ RBC production and maturation:
    • Altered DNA synthesis → Megaloblastic cells with clumped nuclear chromatin.
    • Apoptosis of erythrocytes during late stage of erythropoesis
• Complications:
  • Pregnancy - Neural tube defects
  • $(\uparrow)$ Circulating homocysteine → atherosclerosis
  • Colorectal cancers
• Unique Clinical Manifestations:
  • Ulcerations of lips, mouth, buccal mucosa

Microcytic Anemia

• Characteristics
  • Erythrocytes:
    • Small
    • Reduced hemoglobin. Decreased cell size $(\downarrow)$
  • Caused by disorders of:
    • Iron metabolism
    • Synthesis of hemoglobin components:
      • Heme (porphyrin) - pigment
      • Globin - protein

Iron-deficiency Anemia

• Most common anemia worldwide.
• Causes:
  • Inadequate dietary intake
    • Infants, small children, adolescents, pregnant women
  • Chronic blood loss
    • GI bleeding
    • Pathologic
    • Medication-induced (ASA, NSAIDS)
    • Menorrhagia
  • Impaired GI absorption
    • Decreased gastric acid production – proton pump inhibitors – Omeprozole
  • Lead poisoning

Iron-deficiency Anemia - Pathophysiology

• Depletion of iron stores.
  • Inadequate iron intake
  • Excessive blood loss
• Less iron in the bone marrow leads to decreased hemoglobin synthesis.
• Metabolic dysfunction
  • Insufficient iron delivery to bone marrow
  • Impaired iron use by bone marrow
• Result is decreased hemoglobin synthesis
• Pathophysiology Stages:
  • Stage 1:
    • Depletion of iron stores
    • Serum ferritin level drops
    • Normal – Hgb normal
  • Stage 2:
    • Ferritin depletion
    • $(\downarrow)$ Transportation of iron to bone marrow
    • Serum iron level drops
    • Iron-deficiency erythropoiesis
    • $(\downarrow)$ Hgb production
  • Stage 3:
    • Iron-deficient RBC in circulation outnumber mature RBC
    • Iron stores depleted
    • Erythrocytes are hypochromic and microcytic
    • $(\downarrow\downarrow\downarrow)$ Hgb production
    • Signs/symptoms of iron-deficiency anemia

Iron-deficiency Anemia - Clinical Manifestations

• Early:
  • Fatigue
  • Weakness
  • Shortness of breath
• Progressive:
  • Epithelial tissue changes (nails)
  • Glossitis
  • Dysphagia
  • Hyposalivation
  • Esophageal web development