Anemia

• RBC development

  1. Begin in bone marrow

  2. Mature in blood

  3. Evolve through 4 stages
• Proerythroblasts

  Earliest stage of RBCs, lack hemoglobin
• Erythroblasts


  Next stage of RBCs, gain hemoglobin
• Reticulocytes

  Immature erythrocytes, enter systemic circulation
• Erythrocytes

  Fully mature RBCs
• Factors required for RBC development

  • Healthy bone marrow
  • Erythropoietin
  • Iron for hemoglobin
  • Vitamin B12
  • Folic acid
• If any of these factors is absent or amiss, anemia will result
• Iron

  Essential for hemoglobin, myoglobin, and iron-containing enzymes
• Iron cycle

  1. Uptake in intestine

  2. Storage as ferritin or binding to transferrin

  3. Uptake by bone marrow, liver, muscle, other tissues

  4. Recycling from catabolized RBCs
• Excretion of iron is minimal, only 1 mg per day
• Iron uptake is regulated to prevent excessive buildup
• Iron requirements

  • High for infants, children, pregnant women
  • Low for adult men (8 mg/day)
  • Higher for adult women (15-18 mg/day)
• Iron deficiency

  Imbalance between iron uptake and demand, usually due to increased demand
• Iron deficiency causes anemia, developmental problems, impaired cognition
• Hallmarks of iron deficiency anemia

  • Microcytic, hypochromic erythrocytes
  • Absence of hemosiderin in bone marrow
• Laboratory tests for iron deficiency anemia

  • Reduced RBC count
  • Reduced reticulocyte hemoglobin
  • Reduced hemoglobin and hematocrit
  • Reduced serum iron
  • Increased serum iron-binding capacity
• Ferrous salts

  Iron salts that are more readily absorbed than ferric salts
• Ferrous iron salts

  • Ferrous sulfate
  • Ferrous gluconate
  • Ferrous fumarate
  • Ferrous aspartate
• Ferrous sulfate


  Treatment of choice for iron deficiency anemia
• Antacids, tetracyclines, and high doses of ascorbic acid can affect iron absorption
• Carbonyl iron

  Elemental iron in microparticles, good bioavailability, reduced toxicity risk
• Iron deficiency treatment

  1. Identify cause

  2. Increase hemoglobin and RBC production

  3. Oral iron preferred, parenteral iron if oral fails

  4. Continue treatment until hemoglobin normalizes, then dietary iron may be sufficient
• Combining oral and parenteral iron can lead to toxicity
• Vitamin B12 deficiency

  Causes anemia and nervous system damage
• Intrinsic factor

  Required for efficient absorption of vitamin B12
• Vitamin B12 deficiency is usually due to impaired absorption, not dietary insufficiency
• Pernicious anemia is caused by lack of intrinsic factor
• Vitamin B12 is essential for DNA synthesis and cell growth and division
• Intrinsic factor

  A compound secreted by parietal cells of the stomach that is required for the absorption of vitamin B12
• Vitamin B12 absorption

  1. Vitamin B12 forms a complex with intrinsic factor

  2. Complex interacts with receptors on intestinal wall

  3. Complex dissociates after absorption

  4. Free B12 binds to transcobalamin II for transport
• In the absence of intrinsic factor, absorption of vitamin B12 is greatly reduced, but 1% can still be absorbed by passive diffusion
• Causes of poor vitamin B12 absorption

  • Regional enteritis
  • Celiac disease
  • Antibodies against B12-intrinsic factor complex
  • Bariatric surgery
  • Reduced stomach acid secretion
• Pernicious anemia


  The syndrome resulting from lack of intrinsic factor
• Vitamin B12 deficiency

  Causes megaloblastic or macrocytic anemia
• Folic acid can reverse the hematologic effects of B12 deficiency but not the neurologic deficits
• Folic acid should not be used alone to treat B12 deficiency as it can mask the deficiency and allow neurologic damage to progress
• Folic acid deficiency

  Causes megaloblastic anemia identical to B12 deficiency
• Folic acid can be activated through an alternate pathway that does not require vitamin B12
• Enterohepatic recirculation of folate

  Folate is excreted into the intestine, reabsorbed, and returned to the liver, helping to maintain folate stores
• Causes of folic acid deficiency

  • Poor diet, especially in alcohol abuse
  • Intestinal malabsorption diseases
  • Increased requirements in pregnancy, lactation, hemodialysis, hemolytic anemias
  • Certain drugs