The Red Blood Cell

The Red Blood Cell: Structure and Function

• Study focus: RBC (Red Blood Cell) structure and function crucial for survival and health.

RBC Survival and Function

• Critical areas for RBC survival:

  • RBC membrane

  • Hemoglobin structure and function

  • Metabolic pathways

• Defects in any of these components result in impaired RBC survival.

RBC Membrane

• Composition:

  • 40% lipids

  • 52% proteins

  • 8% carbohydrates

• Components:

  • Glycolipids: Contribute to structural integrity.

  • Glycoproteins: Involved in cell recognition and signaling.

  • Proteins: Essential for membrane functionality.

  • Cholesterol: Maintains fluidity.

  • Phospholipids: Form the membrane bilayer.

• Highly elastic; can undergo large shape changes without fragmentation.

Inner Membrane

• Functions:

  • Maintains shape, stability, and deformability/flexibility.

• Types of proteins:

  • Integral membrane proteins: Span the membrane.

  • Peripheral proteins: Associated with the cytoplasmic surface.

Important Membrane Proteins

• Glycophorin:

  • Integral membrane protein that imparts negative charge to RBCs; carries antigens and is involved in transport.

• Spectrin:

  • Flexible, rod-like protein crucial for RBC membrane's structural integrity.

RBC Deformability

• Flexibility essential for oxygen delivery; decreased deformability linked to hemolytic anemias.

• Non-deformability:

  • RBCs are removed by the spleen.

  • Observations: Spherocytes and bite cells can occur, indicating decreased survival.

Membrane Permeability

• Freely permeable to water and anions (e.g., chloride, bicarbonate).

• Relatively impermeable to cations (e.g., sodium, potassium).

• Importance of permeability:

  • Critical for preventing colloid osmotic hemolysis.

  • ATP controls ion entry/exit; depletion leads to excess calcium and sodium with a loss of potassium and water.

Membrane Lipids

• Cholesterol excess makes membranes viscous, reducing fluidity and RBC deformability, affecting survival.

• Associated Conditions:

  • Target cells: Indicative of liver disease.

  • Acanthocytes: Spiny projections related to inherited lipid disorders.

Osmotic Fragility

• Definition: Susceptibility of RBCs to rupture in hypotonic solutions.

• Testing: Evaluates RBC membrane integrity by measuring swelling and bursting in dilute solutions.

• Clinical significance: Used to diagnose various types of hemolytic anemias.

  • Normal RBCs hemolyze in 0.45% NaCl; complete hemolysis at 0.30% NaCl.

  • Increased fragility seen in hereditary spherocytosis (hemolysis at 0.6% NaCl).

  • Decreased fragility in sickle cell and thalassemia (lysates at <0.3% NaCl).

Hemoglobin Structure and Function

• Composition:

  • Consists of globin (4 heme groups)

    • Each heme contains a protoporphyrin ring and ferrous iron (Fe2+).

  • Hemoglobin production requires adequate iron delivery, protoporphyrin synthesis, and globin synthesis.

Iron Delivery and Supply

• Iron delivered in ferric state via transferrin; reduced to ferrous in mitochondria for heme synthesis.

• Excess iron stored as ferritin.

• 2/3 of body iron is bound to heme, crucial for hemoglobin function.

Protoporphyrin Synthesis

• Begins in mitochondria with the formation of delta aminolevulinic acid, influenced by erythropoietin.

• Excess porphyrins result from enzymatic blocks, potentially causing porphyrias.

Globin Synthesis

• Occurs in cytoplasmic ribosomes influenced by genetic inheritance.

• Major types in adults:

  • 95-97% HbA (alpha and beta chains)

  • 2-3% HbA2 (alpha and delta chains)

  • 1-2% fetal HbF (alpha and gamma chains).

Formation of Hemoglobin

• Globin chains link with heme to form hemoglobin (2 alpha, 2 beta chains).

• Synthesis degree affects porphyrin synthesis; iron accumulation leads to sideroblast formation.

Hemoglobin's Function

• Delivers/releases oxygen; reacts with carbon dioxide.

• Binding mechanics:

  • Oxygen loading causes structural changes (expulsion of 2,3 DPG increases affinity for oxygen).

Oxygen Saturation Curve

• Represents hemoglobin’s ability to saturate oxygen.

• Normal P50 = 28 mm Hg; variations depend on factors like pH, 2,3 DPG levels, and temperature.

Abnormal Hemoglobins

• Carboxyhemoglobin: CO binds tightly to heme (200x affinity).

• Methemoglobin: Iron oxidized to ferric state, affecting oxygen transport.

• Sulfhemoglobin: Formed from sulfur drug exposure with irreversible change.

RBC Senescence and Hemolysis

• Lifespan of RBCs: ~120 days; 1% are removed daily by reticuloendothelial system (RES).

• Spleen is instrumental in recognizing and removing aged/damaged RBCs.

The Spleen's Functions

• Functions:

  • Reservoir/storage for platelets and granulocytes.

  • Filtration of RBCs.

  • Immunologic role: Clears encapsulated bacteria.

  • Hematopoietic function.

Risks of Splenectomy

• Increased infection risk, altered immune response, heightened hemolysis, and thrombosis.

• Risk persists even years post-splenectomy.

Extravascular Hemolysis

• 90% occurs outside blood vessels; involves recovery of hemoglobin components.

• Processes:

  • Iron recovery, globin breakdown, conversion of protoporphyrin.

Role of Liver in Extravascular Hemolysis

• Conjugation of bilirubin and its excretion via bile; monitors hemolysis rates.

Intravascular Hemolysis

• 5-10% occurs within blood vessels; haptoglobin captures hemoglobin dimers aiding liver processing.

Hemoglobinuria

• Associated with hemoglobinemia; can change urine color due to oxidation reactions.

Intravascular Hemolysis Details

• Minimal processing leads to hemoglobinemia and urinal changes when haptoglobin is depleted.