Lecture on Macrocytic Anemia

Introduction

• Discussion on macrocytic anemia as part of clinical medicine.
• Anemia defined by low hemoglobin levels:
  • Males: <13 g/dL
  • Females: <12 g/dL
• Mean Corpuscular Volume (MCV) determines type of anemia:
  • <80: Microcytic
  • 80-100: Normocytic

  • 100: Macrocytic

Types of Macrocytic Anemia

Megaloblastic vs. Non-Megaloblastic

• Megaloblastic Anemia: Presence of hypersegmented neutrophils due to impaired DNA synthesis.
• Non-Megaloblastic Anemia: Absence of hypersegmented neutrophils, not related to DNA synthesis.

Megaloblastic Anemia

• Involves the red bone marrow producing large red blood cells and hypersegmented neutrophils.
• Causes include deficiencies in Vitamin B12 and Folate, leading to impaired DNA synthesis and abnormal cell maturation.
• Pathophysiology involves increased apoptosis of immature red blood cells in bone marrow and spleen.

Non-Megaloblastic Anemia

• Causes include alcohol use, liver disease (cirrhosis), hypothyroidism, myelodysplastic syndrome, and reticulocytosis.
• Alterations in bone marrow or lipid metabolism affect red blood cell membrane shape.
• Similar apoptosis process but with normal polymorphonuclear leukocytes.

Biochemistry of Megaloblastic Anemia

• DNA synthesis depends on B12 and Folate:
  • Proper nucleotide formation requires B12 and methylene tetrahydrofolate.
  • Deficiencies impair thymidine synthesis, affecting DNA replication.
• B12 converts homocysteine to methionine; deficiency increases homocysteine, affecting cardiovascular health.

Causes of Vitamin B12 and Folate Deficiency

Vitamin B12 Deficiency

• Causes:
  • Strict vegan diets (low intake).
  • Stomach issues like atrophic gastritis or gastrectomy (low intrinsic factor).
  • Pernicious anemia (autoimmune destruction of parietal cells or intrinsic factor).
  • Pancreatic insufficiency (lack of proteases to separate B12 from proteins).
  • Intestinal absorption issues due to Crohn's or celiac disease.
  • Bacterial overgrowth or tapeworms consuming B12.
• Neurological complications include subacute combined degeneration and neuropsychiatric disturbances.
• Increased risk of cardiovascular issues due to elevated homocysteine.

Folate Deficiency

• Causes:
  • Severe alcoholism leading to poor dietary intake.
  • Medication interference (e.g., phenytoin) or disease conditions (e.g., Crohn's, celiac).
  • Methotrexate or trimethoprim-sulfamethoxazole inhibiting folate metabolism.
  • Increased demand during pregnancy or hemolysis.
• Associated with increased cardiovascular risks and neural tube defects in pregnancy.

Diagnosis and Differentiation

• Blood tests: CBC, reticulocyte index, B12, and folate levels.
• Presence of hypersegmented neutrophils indicates megaloblastic anemia.
• Schilling test for absorption issues in B12 deficiency.

Treatment

• Blood transfusion guidelines:
  • Hemoglobin <7 g/dL in stable patients; <8 g/dL with pre-existing cardiac conditions.
  • Considerations for hemorrhagic shock.
• B12 deficiency: Oral intake for dietary issues, IM B12 for absorption issues or neurological symptoms.
• Folate deficiency: Oral supplementation.
• Avoid treating macrocytic anemia with folate alone; include B12 to prevent neurological damage.

Summary

• Understanding the pathophysiology and causes of macrocytic anemia is crucial for effective diagnosis and treatment.
• Differentiate between megaloblastic and non-megaloblastic anemias to guide appropriate therapy strategies.