1.4-RBC-Physiology

FUNCTIONS OF RBC

Two Complex Functions of RBC:

  1. Gas Transport: This critical function involves the transport of oxygen from the lungs to body tissues and carbon dioxide from tissues back to the lungs for expiration. Hemoglobin within RBCs binds to oxygen in the lungs, facilitating its delivery to hypoxic tissues. Additionally, it transports carbon dioxide back, where it is converted to bicarbonate for easier elimination.

  2. Buffering of Blood: RBCs play an important role in maintaining the acid-base balance of blood, which is essential for normal metabolic functions. The normal pH of blood ranges from 7.35 to 7.45. Hemoglobin not only carries gases but also helps regulate pH levels by binding and releasing hydrogen ions (H⁺), playing a vital role in stabilizing blood acidity. Other physiological systems that contribute to acid-base balance include:

    • Kidneys (Metabolic): By excreting hydrogen ions and reabsorbing bicarbonate.

    • Lungs (Respiratory): Through the regulation of carbon dioxide levels by helping with its elimination during respiration.

CHARACTERISTICS OF NORMAL RBC

  • Shape and Size:

    • Biconcave disc: The unique biconcave shape increases the surface area to volume ratio, enhancing gas diffusion.

    • Average Volume: Approximately 90 fL.

    • Diameter: Ranges from 6-8 µm.

    • Thickness: About 1.5-2.5 µm.

    • Average Surface Area: Approximately 140 µm².

  • Inclusions: There should be no inclusions in healthy RBCs, as their presence can compromise stability and functionality.

  • Life Span: Healthy RBCs typically have a lifespan of about 120 days (range: 90-120 days), after which they are sequestered in the spleen. Aging RBCs lose their deformability, transitioning from a discoid shape to a spheritic shape, negatively impacting their function.

  • Deformability: The ability of RBCs to bend and stretch is crucial for navigating narrow capillaries. Factors influencing RBC deformability include:

    • Biconcave Geometry: Aids in flexibility.

    • Elastic Membrane: Ensures recovery of shape.

    • Cytoplasmic Viscosity: Affects how easily they can change shape.

    • Unique deformability in comparison to platelets and leukocytes is vital for effective circulation.

FACTORS CAUSING LOSS OF DEFORMABILITY

  • Thalassemia: A genetic disorder resulting from gene deletions, significantly altering the shape and function of RBCs.

  • Sickle Cell Anemia: Caused by a defect in hemoglobin synthesis due to a substitution mutation in the beta globin chain, resulting in hemoglobin S (Hb S). This leads to crystallization, causing RBCs to assume a sickle shape, further resulting in hemolytic anemia due to increased RBC destruction. This distortion (poikilocytosis) significantly impairs oxygen delivery.

  • Oxidative Stress: RBCs require that hemoglobin remains in a reduced state for optimal function. Oxidized hemoglobin can lead to stress resulting in cell lysis; hence, antioxidants play a critical role in RBC health.

RBC MEMBRANE STRUCTURE

  • Proteins:

    • Transmembrane Proteins (Integral Proteins): Traverse lipid bilayers, playing essential roles in transport and signaling. Examples include:

      • CD47: A marker that helps RBCs evade immune detection.

      • Band 3: Involved in anion exchange (Cl−/HCO3−).

      • Rh proteins: Important for blood typing and Rh factor.

    • Peripheral Proteins: Attach to the cytoplasmic side of the membrane for stability; mutations may lead to conditions like hereditary spherocytosis.

    • Key proteins include Spectrin, Ankyrin, Protein band 4.1, and Protein band 4.2, which provide structural integrity and assist in maintaining shape.

HEMOGLOBIN SYNTHESIS

  • Process: Begins in the rubriblast stage and completes at the reticulocyte stage, where RNA remnants can still be found.

    • Comprises two essential components:

      • Heme Synthesis: Occurs in mitochondria, initiated by the combination of Glycine and Succinyl CoA to form heme. Enzyme deficiencies here can lead to disorders like porphyria.

      • Globin Synthesis: The production of globin chains that combine with heme to form functional hemoglobin.

PATHWAYS FOR ENERGY PRODUCTION

  • RBCs generate energy primarily through two pathways:

    1. Embden Meyerhof Pathway (EMP): The dominant pathway for ATP production in RBCs.

    2. Rapoport Luebering Pathway: Essential for producing 2,3 BPG, which regulates oxygen transport and release in response to tissue demands.

GAS TRANSPORT AND BUFFERING EFFECTS BY HGB MOLECULE

  • Bohr Effect and Haldane Effect: Explain the relationship between oxygen and carbon dioxide transport in blood, allowing for efficient gas exchange.

  • Buffering Blood Acidity: Hemoglobin plays a key role in maintaining blood pH through its capacity to buffer excess hydrogen ions during conditions of acidosis, helping to stabilize pH levels in response to carbon dioxide concentrations.

OXYGEN DISSOCIATION CURVE

  • This curve illustrates how hemoglobin's affinity for oxygen relates to the partial pressure of oxygen (PO2). The P50 value indicates the oxygen saturation level at which hemoglobin is 50% saturated with oxygen.

    • Curve Shifts:

      • Right Shift: Indicative of increased oxygen release; occurs under conditions of acidosis and elevated CO2 levels.

      • Left Shift: Indicates decreased P50 and reduced oxygen release; usually seen in alkalosis or increased pH conditions.

MYOGLOBIN

  • Functions primarily as an oxygen reservoir within muscle tissues, allowing for sustained aerobic metabolism during physical exertion.