Macrocytic Anemias Lecture Notes

Definition

• Macrocytic anemias are characterized by a higher mean corpuscular volume (MCV), specifically >100 fL (normal is 80-100 fL).

Causes of Macrocytic Anemias

1. Vitamin Deficiencies
   • Vitamin B9 (Folate) Deficiency
   • Vitamin B12 (Cobalamine) Deficiency
2. Alcoholism
3. Liver Disease
4. Drug Use
   • 5-Fluorouracil (5-FU)
   • Methotrexate (folate antagonistic drugs)

Pathophysiology

• Importance of Vitamin B9 and B12:
  • Essential for synthesis of DNA precursors.
  • Required for DNA production and proper cell division.
• Deficiency Impact:
  • Improper DNA synthesis, leading to ineffective cell division.
  • Accumulation of larger, immature cells (megaloblasts).
  • Increased cell size affects both RBCs and WBCs.

Cellular Changes

• RBCs: Larger, immature RBCs (macrocytic RBCs)
• WBCs: Formation of hypersegmented neutrophils (neutrophils with >5 lobes)

Specific Types of Macrocytic Anemias

Megaloblastic Anemia

• Causes: Vitamin B9 and B12 deficiencies.
• Characteristics: Presence of megaloblasts and hypersegmented neutrophils.

Vitamin B9 (Folate) Deficiency

• Sources: Green leafy vegetables, fruits.
• Deficiency Causes:
  • Poor diet
  • Use of certain drugs (e.g., Methotrexate, 5-FU)
• Clinical Findings:
  • Elevated homocysteine levels
  • Normal methylmalonic acid levels
  • Symptoms: Fatigue, pale conjunctiva, glossitis

Vitamin B12 (Cobalamine) Deficiency

• Sources: Animal products (meat, dairy).
• Deficiency Causes:
  • Pure vegan diet
  • Malabsorption syndromes (e.g., Crohn's, ulcerative colitis)
  • Parasitic infections (e.g., Diphyllobothrium latum)
  • Autoimmune conditions (e.g., Pernicious anemia)
• Absorption Mechanism:
  • B12 binds with intrinsic factor (produced by parietal cells in the stomach) and is absorbed in the terminal ileum.
  • Deficiency in intrinsic factor affects absorption.
• Clinical Findings:
  • Elevated homocysteine levels
  • Elevated methylmalonic acid levels
  • Symptoms: Neurological symptoms (due to subacute combined degeneration of the spinal cord), glossitis

Laboratory Findings

• Vitamin B9 Deficiency:
  • Reduced serum folate levels
  • Elevated homocysteine levels
  • Normal methylmalonic acid levels
  • Presence of macrocytic RBCs and hypersegmented neutrophils
• Vitamin B12 Deficiency:
  • Reduced serum B12 levels
  • Elevated homocysteine levels
  • Elevated methylmalonic acid levels
  • Presence of macrocytic RBCs and hypersegmented neutrophils
  • Neurological symptoms due to spinal cord degeneration

Differentiation between B9 and B12 Deficiencies

• Methylmalonic Acid Levels:
  • Elevated in B12 deficiency
  • Normal in B9 deficiency
• Neurological Symptoms:
  • Present in B12 deficiency
  • Absent in B9 deficiency

Summary

• Hypersegmented neutrophils are hallmark for macrocytic (megaloblastic) anemia.
• Both B9 and B12 deficiencies elevate homocysteine levels.
• Methylmalonic acid and neurological symptoms help differentiate between B9 and B12 deficiencies.

Next Steps

• The next topic will cover normocytic anemias.