Hemoglobin and Oxygen Affinity

Hemoglobin and Oxygen Binding

• Hemoglobin's affinity for O2 is affected by pH, temperature, and 2,3-diphosphoglycerate (2,3-DPG) concentration in red cells.
• 2,3-DPG and H^+^ compete with O2 for binding to deoxygenated hemoglobin, decreasing the affinity for O2.

Hemoglobin Variants

• Oxidation: Ferrous iron (Fe^2+^) in hemoglobin is converted to ferric iron (Fe^3+^) by exposure to drugs or oxidizing agents, forming methemoglobin.
• Carbon monoxide: Reacts with hemoglobin to form carbon monoxyhemoglobin, displacing O2 and reducing oxygen-carrying capacity.
• Heme is also part of myoglobin, found in red (slow) muscles.

Abnormalities of Hemoglobin Production

• Inherited disorders: Hemoglobinopathies (abnormal polypeptide chains) and thalassemias (decreased or absent chains due to defects in globin genes).
• α thalassemias: Decreased or absent α polypeptides.
• β thal-assemias: Decreased or absent β polypeptides.
• Abnormal hemoglobins: Over 1000 abnormal hemoglobins have been described in humans.

Anemia

• Effects on circulation:
  • Decreased viscosity of blood.
  • Increased work load on the heart (palpitation and tiredness).

Polycythemia

• Increase in RBC production:
  • Primary polycythemia vera (count 7-8 million/mm^3).
  • Secondary polycythemia due to tissue hypoxia (high altitude or chronic smoking).
• Effects on circulation:
  • Increased viscosity of blood, leading to sluggish circulation and thrombosis.
  • Increased work load on the heart, leading to heart failure.

Blood Transfusions and Blood Typing

• ABO blood groups:
  • Type A (30-40%): A/A, A/O, O/A.
  • Type B (10-30%): B/B, B/O, O/B.
  • Type AB (3-5%): A/B or B/A.
  • Type O (40-50%): No A or B.
• Rh group:
  • D antigen: 85% of Caucasians are D-positive, and over 99% of Asians are D-positive.
  • D-negative individuals can develop anti-D antibodies after exposure to D-positive blood.

Hemolytic Disease of the Newborn

• Rh incompatibility: D-negative mother carrying a D-positive fetus, leading to maternal sensitization and potential hemolysis in the fetus.

Platelets (Thrombocytes)

• Small, granulated bodies that aggregate at sites of vascular injury.
• Lack nuclei, and have a half-life of about 4 days.
• Formed by megakaryocytes in the bone marrow.
• Released into circulation, with about 60-75% in circulation and the remainder in the spleen.

White Blood Cells (Leukocytes)

• Agranulocytes:
  • Lymphocytes (25-35%): Involved in immune responses.
  • Monocytes (4-6%): Differentiate to become macrophages, with serious appetites for infectious microbes.
• Granulocytes:
  • Neutrophils (50-70%): Primary responders to infections.
  • Eosinophils (1-3%): Involved in parasitic infections and allergic reactions.
  • Basophils (0.4-1%): Release histamine, causing inflammation, vasodilation, and attraction of WBCs.

Leukopoiesis and Colony Stimulating Factors (CSFs)

• CSFs stimulate bone marrow to increase WBC production.
• Leukocytosis: Increase in WBC count, often due to an increase in one type of WBC.
• Leukopenia: Decrease in WBC count below 4,000.

Corticosteroids and Infection

• Corticosteroids can mask infection by suppressing the inflammatory response and WBC release.
• Masking of infection can lead to undiagnosed spreading of infection.