RBC Function

Overview of Erythrocyte Function

Primary Function: Oxygen transport from the lungs to the tissues and carbon dioxide transport from the tissues to the lungs
Key Components for Function:
- Hemoglobin (HGB): The oxygen-carrying molecule within the RBC
- RBC Membrane: Provides flexibility and structural integrity
- Metabolic Pathways: Maintain RBC shape, flexibility, and hemoglobin function

Hemoglobin Structure and Function

Structure:
- Tetramer composed of four globin chains (two alpha-like and two beta-like)
- Each globin chain contains a heme molecule
- Each heme molecule contains an iron (Fe2+) atom, which binds to oxygen
Oxygen Binding:
- Each hemoglobin molecule can bind up to four oxygen molecules
- Binding is cooperative, meaning that the binding of one oxygen molecule increases the affinity for subsequent oxygen molecules
Oxygen Dissociation Curve:
- Sigmoidal shape reflects the cooperative binding of oxygen
- P50: The partial pressure of oxygen at which hemoglobin is 50% saturated
  - Increased P50: Indicates decreased oxygen affinity (right shift)
  - Decreased P50: Indicates increased oxygen affinity (left shift)
Factors Affecting Oxygen Affinity:
- pH:
  - Decreased pH (acidosis): Decreases oxygen affinity (Bohr effect)
  - Increased pH (alkalosis): Increases oxygen affinity
- Carbon Dioxide (CO2):
  - Increased CO2: Decreases oxygen affinity (Bohr effect)
  - Decreased CO2: Increases oxygen affinity
- Temperature:
  - Increased temperature: Decreases oxygen affinity
  - Decreased temperature: Increases oxygen affinity
- 2,3-Diphosphoglycerate (2,3-DPG):
  - Increased 2,3-DPG: Decreases oxygen affinity
  - Decreased 2,3-DPG: Increases oxygen affinity

Hemoglobin Variants and Their Functions

Hemoglobin A (HbA):
- α2β2 (two alpha and two beta chains)
- Predominant hemoglobin in adults
Hemoglobin A2 (HbA2):
- α2δ2 (two alpha and two delta chains)
- Minor component in adults
Hemoglobin F (HbF):
- α2γ2 (two alpha and two gamma chains)
- Predominant hemoglobin in fetuses and newborns
- Higher affinity for oxygen than HbA
Abnormal Hemoglobins:
- Hemoglobin S (HbS):
  - Causes sickle cell anemia
  - Polymerizes under low oxygen conditions, leading to sickling of red blood cells
- Hemoglobin C (HbC):
  - Causes mild hemolytic anemia
  - Forms crystals within red blood cells
- Methemoglobin:
  - Iron in the heme molecule is oxidized to the Fe3+ state
  - Cannot bind to oxygen
- Carboxyhemoglobin:
  - Hemoglobin bound to carbon monoxide (CO)
  - Has a much higher affinity for CO than oxygen
  - Impairs oxygen delivery to tissues

Red Blood Cell Membrane

Structure:
- Lipid bilayer with embedded proteins
- Provides flexibility and structural integrity to the red blood cell
Key Membrane Proteins:
- Spectrin:
  - Major component of the cytoskeleton
  - Provides structural support
- Ankyrin:
  - Anchors the cytoskeleton to the cell membrane
- Band 3:
  - Anion exchange protein (exchanges chloride and bicarbonate)
  - Important for CO2 transport
- Glycophorin A:
  - Major sialoglycoprotein
  - Provides a negative charge that prevents RBC aggregation
Membrane Defects:
- Hereditary Spherocytosis:
  - Defects in spectrin, ankyrin, or other membrane proteins
  - Results in spherical-shaped red blood cells that are prone to destruction in the spleen
- Hereditary Elliptocytosis:
  - Defects in spectrin or other membrane proteins
  - Results in elliptical-shaped red blood cells

Red Blood Cell Metabolism

Key Metabolic Pathways:
- Glycolysis (Embden-Meyerhof Pathway):
  - Provides ATP for maintaining cell shape, membrane integrity, and ion transport
  - Deficiency in pyruvate kinase (PK) can lead to hemolytic anemia
- Pentose Phosphate Pathway (Hexose Monophosphate Shunt):
  - Produces NADPH, which protects against oxidative damage
  - Deficiency in glucose-6-phosphate dehydrogenase (G6PD) can lead to hemolytic anemia
- Methemoglobin Reductase Pathway:
  - Maintains iron in the reduced (Fe2+) state
  - Deficiency can lead to methemoglobinemia
- Rapport-Luebering Shunt:
  - Produces 2,3-DPG, which regulates hemoglobin’s oxygen affinity

Carbon Dioxide Transport

Mechanisms:
- Dissolved CO2 in Plasma:
  - Small amount of CO2 is transported in the plasma
- Carbaminohemoglobin:
  - CO2 binds to hemoglobin
- Bicarbonate (HCO3-):
  - Most CO2 is transported as bicarbonate
  - CO2 enters red blood cells and is converted to carbonic acid (H2CO3) by carbonic anhydrase
  - Carbonic acid dissociates into H+ and HCO3-
  - HCO3- is exchanged for chloride (Cl-) via the anion exchange protein (Band 3) (chloride shift)

Red Blood Cell Destruction (Senescence)

Process:
- As red blood cells age, they become less flexible and more susceptible to damage
- Senescent red blood cells are removed from the circulation by macrophages in the spleen
Hemoglobin Breakdown:
- Hemoglobin is broken down into globin, iron, and porphyrin
- Globin is broken down into amino acids
- Iron is recycled or stored
- Porphyrin is converted to bilirubin, which is then excreted in the bile
Clinical Significance:
- Increased red blood cell destruction (hemolysis) can lead to anemia and elevated bilirubin levels

Assessment of Erythrocyte Function

Hemoglobin (HGB):
- Measures the amount of hemoglobin in the blood
Hematocrit (HCT):
- Measures the percentage of blood volume occupied by red blood cells
Red Blood Cell Count (RBC):
- Measures the number of red blood cells in a volume of blood
Mean Corpuscular Volume (MCV):
- Measures the average size of red blood cells
Peripheral Blood Smear:
- Evaluates the morphology (size, shape, color) of red blood cells
- Can identify abnormalities such as:
  - Spherocytes
  - Elliptocytes
  - Sickle cells
  - Target cells
Reticulocyte Count:
- Measures the percentage or absolute number of reticulocytes in the blood
- Indicates the rate of red blood cell production by the bone marrow
Hemoglobin Electrophoresis:
- Separates and identifies different types of hemoglobin
- Used to diagnose hemoglobinopathies (e.g., sickle cell anemia, thalassemia)
Direct Antiglobulin Test (DAT):
- Detects antibodies or complement proteins on the surface of red blood cells
- Used to diagnose autoimmune hemolytic anemia
Osmotic Fragility Test:
- Measures the resistance of red blood cells to hemolysis in hypotonic solutions
- Used to diagnose hereditary spherocytosis
Glucose-6-Phosphate Dehydrogenase (G6PD) Assay:
- Measures the activity of the G6PD enzyme
- Used to diagnose G6PD deficiency
Pyruvate Kinase (PK) Assay:
- Measures the activity of the PK enzyme
- Used to diagnose PK deficiency
Haptoglobin:
- Protein that binds free hemoglobin released into the plasma
- Decreased in hemolytic anemia
Lactate Dehydrogenase (LDH):
- Enzyme released from damaged cells
- Elevated in hemolytic anemia
Unconjugated Bilirubin:
- Product of heme breakdown
- Elevated in hemolytic anemia

Key Terms

Hemoglobin: Oxygen-carrying protein in red blood cells
Heme: Iron-containing porphyrin ring
Globin: Protein chains that make up hemoglobin
Oxygen Affinity: The strength of binding between hemoglobin and oxygen
2,3-DPG: Regulates hemoglobin’s oxygen affinity
Reticulocyte: Immature red blood cell
Anemia: Deficiency of red blood cells or hemoglobin
Hemolysis: Destruction of red blood cells
Spherocyte: Spherical-shaped red blood cell
Elliptocyte: Elliptical-shaped red blood cell

RBC Production

RBC Destruction