Blood Composition, Plasma Proteins, and Red Blood Cell Physiology

Composition of Blood

• After centrifugation, whole blood separates into three visible layers:
  • Bottom, dark‐red layer: Hematocrit (packed red blood cells, a.k.a. erythrocytes).
  • Average proportion ≈ $45\%$ of total blood volume (sex- and individual-dependent).
  • Quantitatively described by $\text{Hematocrit}=\dfrac{\text{Volume of RBCs}}{\text{Total Blood Volume}}\times 100\%$.
  • Middle, thin whitish layer: Buffy coat (leukocytes + platelets).
  • Makes up <$1\%$ of blood.
  • Top, straw-yellow layer: Plasma.
  • Accounts for ≈ $55\%$ of blood.

Plasma

• Definition: Fluid ECM (extracellular matrix) in which blood cells are suspended.
• Composition by mass/volume:
  • $92\%$ water → solvent, thermal buffer, transport medium.
  • $7\%$ plasma proteins → create colloid osmotic pressure (COP) that retains fluid within vasculature.
  • $\approx 1\%$ assorted solutes (nutrients, ions, gases, hormones, metabolic wastes).
• Biomolecules present:
  • Amino acids, lipids (cholesterol, triglycerides, phospholipids), glucose, vitamins.
  • Electrolytes: $\text{Na}^+$, $\text{K}^+$, $\text{Ca}^{2+}$, $\text{Cl}^-$, $\text{HCO}_3^-$, etc.

Plasma Proteins & Their Significance

• Albumin (most abundant)
  • Synthesized by liver; major contributor to COP.
  • Serves as a nonspecific carrier for hydrophobic molecules (e.g., steroid hormones, free fatty acids, bilirubin, certain drugs).
• Immunoglobulins (antibodies)
  • Produced by plasma cells; central in adaptive immunity.
• Fibrinogen & Plasminogen (clotting precursors)
  • Fibrinogen → fibrin (forms clot meshwork).
  • Plasminogen → plasmin (dissolves clots); balance essential to hemostasis.
• All plasma proteins collectively sustain COP, aiding in fluid balance between plasma & interstitial space (link to Starling forces discussed previously).

Cellular Components (Formed Elements)

1. Red Blood Cells (RBCs, Erythrocytes)

• Shape: Biconcave disc ("doughnut" without a complete hole) → high surface area/volume for gas diffusion; flexibility for capillary transit.
• Intracellular architecture:
  • Anucleate & mitochondria-free → maximizes room for hemoglobin & prevents O$_2$ consumption.
  • Packed with glycolytic enzymes → produce ATP via anaerobic glycolysis.
• Numbers & capacity:
  • ≈ $250\,000\,000$ hemoglobin (Hb) molecules per RBC.
  • Each Hb binds $4$ O$<em>2$ → ≈ $1\times10^9$ O$</em>2$ molecules/RBC.
• Function hierarchy:
  1. Primary: Transport O$_2$ from lungs → tissues.
  2. Secondary: Carry ~$20\%$ of CO$_2$ back to lungs; act as acid–base buffer (Hb can bind $\text{H}^+$).
• Production: Erythropoiesis (in red bone marrow).
  • Trigger: Tissue hypoxia → kidneys release erythropoietin (EPO).
  • Feedback ensures RBC count matches O$_2$ demand.

2. White Blood Cells (Leukocytes)

• <$1\%$ of blood volume (reside mostly in tissues).
• Immunological roles (to be detailed in later lecture).

3. Platelets (Thrombocytes)

• Cytoplasmic fragments from megakaryocytes.
• Essential for primary hemostasis & clot formation (future lecture topic).

Hemoglobin (Hb) – Structure & Binding

• Globular protein comprising 4 polypeptide chains (globins).
• Each chain houses a heme group with central $\text{Fe}^{2+}$.
  • O$_2$ binds reversibly to iron in the heme.
• Stoichiometry: $\text{Hb} + 4\,\text{O}<em>2 \rightleftharpoons \text{Hb}\,(\text{O}</em>2)_4$.
• CO binding, pH sensitivity, & cooperative binding will be explored in subsequent physiology modules.

Directionality of Gas Transport

• Oxygen path: Lungs → Heart (systemic arterial blood) → Tissues.
• Carbon dioxide path: Tissues → Heart (venous blood) → Lungs → Exhalation.
• Mitochondria-free RBCs ensure delivered O$_2$ is not metabolically consumed en route.

Metabolic Considerations in RBCs

• ATP generation exclusively via anaerobic glycolysis.
  • Prevents intracellular O$_2$ utilization.
  • Produces lactate, which diffuses into plasma.
• Contains enzymes (e.g., carbonic anhydrase) facilitating CO$<em>2$ transport as $\text{HCO}</em>3^-$.

Clinical & Real-World Connections

• Hematocrit is routinely measured to evaluate anemia, polycythemia, dehydration.
• Erythropoietin (EPO) therapy supports patients with renal failure; illicit EPO use in sports constitutes blood doping.
• Plasma protein deficits (e.g., hypoalbuminemia in liver disease) ↓ COP → edema.
• Hydroxyurea, transfusions, & gene therapy target RBC disorders (sickle-cell, thalassemia).
• Platelet & plasma transfusions apply principles of formed‐element & protein functionality during trauma/surgery.

Key Numerical Recap (All from Transcript)

• Plasma: $55\%$ of total blood.
• Hematocrit (RBC fraction): ≈ $45\%$.
• Buffy coat: <$1\%$.
• Plasma composition: $92\%$ water, $7\%$ proteins.
• RBC content: $\approx 250\times10^6$ Hb molecules → $\approx 1\times10^9$ O$_2$ molecules/RBC.

Take-Home Principles

• Blood is a specialized connective tissue consisting of plasma (fluid matrix) + formed elements (cells/platelets).
• Plasma proteins govern oncotic pressure, transport, immunity, and hemostasis.
• RBC design is an evolutionary trade-off: maximal gas carriage vs. forfeiting organelles.
• Hormonal feedback (EPO) aligns oxygen delivery capacity with metabolic need.
• Understanding the basic composition lays groundwork for deeper dives into immunology, coagulation, and cardiovascular physiology to follow.