RBC Structure and Function

The red cell membrane is crucial for function and survival, exhibiting high elasticity and deformability, which allows the RBC to change shape during circulation. It's a semipermeable lipid bilayer with a meshlike cytoskeleton, maintaining strength, shape, and allowing molecular movement.

Membrane Composition

Composed of 52%52\% proteins, 40%40\% lipids, and 8%8\% carbohydrates. It includes integral proteins (like Glycophorin) spanning the membrane and peripheral proteins (like Spectrin) on the cytoplasmic surface.

RBC Membrane Proteins

  • Glycophorin: Integral protein, contributes to negative charge, and prevents RBC aggregation.

  • Spectrin: Peripheral protein, major component of the cytoskeleton, essential for deformability, and anchors to the membrane via ankyrin.

RBC Cytoskeleton

Spectrin forms long, filamentous proteins that provide structural support, maintain the biconcave shape, protect against shear forces, and are integral to deformability.

Deformability

Key determinants are cytoskeletal integrity, intracellular ion/water handling, and membrane surface-to-volume ratio. It's vital for capillary travel and oxygen delivery, with loss of ATP or increased Ca²⁺ reducing it.

Permeability

Freely permeable to water, Cl⁻, and HCO₃⁻, but relatively impermeable to Na⁺, K⁺, and Ca²⁺, which is maintained by ATP-dependent pumps.

Membrane Lipids

Composed of a bilayer of phospholipids and cholesterol. Glycolipids in the outer bilayer form RBC antigens, while cholesterol (

Hemoglobin

Responsible for O₂ transport to tissues and CO₂ transport to lungs, occupying 33%33\% of RBC volume. Synthesis occurs during pronormoblast to reticulocyte stages. Hemoglobin is a tetramer with 44 globin chains (α,β,γ,δ,ε,ζ\alpha, \beta, \gamma, \delta, \varepsilon, \zeta) and 44 heme groups.

Hemoglobin Structure

Adult Hb types: HbA=α<em>2β</em>2HbA = \alpha<em>2\beta</em>2 and HbA2=α<em>2δ</em>2HbA2 = \alpha<em>2\delta</em>2. Fetal Hb: HbF=α<em>2γ</em>2HbF = \alpha<em>2\gamma</em>2. Embryonic forms include Hb Gower 1, Gower 2, and Portland.

Hemoglobin Synthesis

Requires adequate iron delivery (for heme), protoporphyrin synthesis (heme precursor requiring Fe²⁺ and vitamin B6), and globin synthesis (protein chains).

Iron Delivery and Supply

Iron is delivered by transferrin, used for heme synthesis, and stored as ferritin (primary) and hemosiderin. Absorption is 1−2 mg/day1-2\,\text{mg/day} from a 10−15 mg/day10-15\,\text{mg/day} dietary intake.

Iron Metabolism and Storage

Most iron from senescent RBCs is taken up by splenic macrophages. Serum ferritin reflects iron stores.

Protoporphyrin Synthesis

Begins in mitochondria, involves δALAδ\text{ALA} as the rate-limiting step, and requires vitamin B6. Blockages can lead to porphyrias.

Globin Synthesis

Occurs on RBC cytoplasmic ribosomes, with genes on chromosomes 1111 and 1616.

Hemoglobin Function and Dissociation Curve

Transports O₂ and CO₂. The Hb-O₂ dissociation curve shows % saturation vs PO₂. A left shift (higher O₂ affinity) reduces O₂ delivery, caused by higher pH, lower temperature, or decreased CO₂. A right shift (lower O₂ affinity) enhances O₂ delivery, caused by acidosis, higher temperature, or increased 2,3-BPG.

Abnormal Hemoglobins

  • Carboxyhemoglobin: CO binds heme with very high affinity, causing hypoxia.

  • Methemoglobin: Iron in ferric (Fe³⁺) state, treated with reducing agents.

  • Sulfhemoglobin: Sulfur incorporation into heme, irreversible.

RBC Metabolism

Mature RBCs rely mainly on anaerobic glycolysis. The Methemoglobin reductase pathway maintains heme in the ferrous state.

RBC Senescence and Hemolysis

RBCs have a lifespan of ≈120 days\approx 120\,\text{days} and are primarily removed by RES macrophages (spleen). Hemolysis can be extravascular (most common, recycling Hb, producing bilirubin) or intravascular (Hb released into plasma, binds haptoglobin; can lead to hemoglobinemia/uria if haptoglobin is depleted). Lab tests indicate hemolysis via bilirubin, urobilinogen, and haptoglobin levels.

Notes on RBC Pathophysiology (Contextual)

Porphyrias result from protoporphyrin/heme synthesis blockages, and sideroblasts indicate issues with iron deposition or heme synthesis.