RBC Structure and Function

Vocabulary flashcards covering RBC membrane structure, hemoglobin synthesis and function, metabolism, and senescence from the lecture notes.

Trilaminar RBC membrane structure

Membrane composed of a semipermeable lipid bilayer with a mesh-like cytoskeleton; proteins reinforce the bilayer, provide shape, deformability, and selective transport.

Lipid bilayer

Two-layer sheet of phospholipids with cholesterol and interspersed proteins forming the RBC outer boundary.

Cytoskeleton

Protein network under the membrane that strengthens the bilayer, maintains cell shape, and supports deformability.

Integral membrane protein

Proteins that extend across the membrane (e.g., glycophorin) and contribute to structure and function.

Peripheral membrane protein

Proteins attached to the cytoplasmic surface (e.g., spectrin) forming the cytoskeletal framework.

Glycophorin

Integral membrane protein (~20% of membrane proteins) with heavy carbohydrate content; sialic acid gives negative charge to prevent RBC adhesion.

Spectrin

Peripheral cytoskeletal protein; major component of the RBC skeleton; forms microfilaments and, with ankyrin, stabilizes the membrane.

Ankyrin

Anchoring protein that links spectrin to band 3 and other membrane components.

Band 3

Integral protein involved in Cl−/HCO3− exchange and cytoskeleton anchoring; important for membrane integrity.

RBC membrane deformability

Ability of RBCs to change shape to traverse capillaries; depends on cytoskeleton, ion/water handling, and surface-to-volume ratio; ATP loss reduces deformability.

Membrane permeability

Membrane freely permeable to water, Cl−, and HCO3−; relatively impermeable to Na+, K+, Ca2+; relies on ATP pumps to maintain gradients.

ATP-dependent pumps

Energy-driven ion pumps that maintain gradients and cell volume; loss of ATP reduces deformability and increases rigidity.

Embden–Meyerhof pathway

Primary glycolytic pathway in mature RBCs; generates ATP for membrane maintenance and function.

Methemoglobin reductase pathway

Methemoglobin reductase system keeps hemoglobin iron in the ferrous state to prevent methemoglobin formation.

Hemoglobin structure

Tetrameric protein with four globin chains and four heme groups; occupies about 33% of RBC volume and 95% of dry weight.

Heme

Iron-containing porphyrin ring bound to each globin chain; binds O2 and is central to Hb function.

Globin chains

Six globin polypeptide chains (α, β, γ, δ, ε, ζ) encoded on chromosomes 11 and 16; combine to form Hb types.

HbA

Adult hemoglobin: α2β2 tetramer.

HbA2

Adult hemoglobin: α2δ2 tetramer.

HbF

Fetal hemoglobin: α2γ2 tetramer; higher O2 affinity than HbA.

Gower 1

Embryonic Hb: ζ2ε2 tetramer.

Gower 2

Embryonic Hb: α2ε2 tetramer.

Delta-ALA

Delta-aminolevulinic acid; rate-limiting step in heme synthesis; formed in mitochondria from glycine and succinyl-CoA; requires vitamin B6.

Protoporphyrin

Porphyrin ring precursor that becomes heme after incorporation of iron.

Porphyrinogens

Intermediates in heme synthesis that are oxidized to porphyrins.

Porphyrias

Metabolic disorders due to defects in porphyrin synthesis leading to excess porphyrins.

Iron delivery and transferrin

Iron delivered as Fe3+ bound to transferrin to RBC precursors; reduced to Fe2+ in mitochondria for heme synthesis.

Ferritin

Primary iron storage protein; stores iron in ferric form for quick mobilization.

Hemosiderin

Iron-storage complex less readily available for use; forms when ferritin capacity is exceeded.

Globin synthesis

Globin chains synthesized on RBC cytoplasmic ribosomes; six chains produced; genes on chromosomes 11 and 16.

Globin genes on chromosomes 11 and 16

Locations of β-like (chromosome 11) and α-like (chromosome 16) globin gene clusters.

HbA: α2β2

Adult HbA composition: two alpha and two beta chains.

HbA2: α2δ2

Adult HbA2 composition: two alpha and two delta chains.

HbF: α2γ2

Fetal Hb composition: two alpha and two gamma chains.

Embryonic Hb Gower 1 and Gower 2

Embryonic Hb types: Gower 1 (ζ2ε2) and Gower 2 (α2ε2).

Hemoglobin function

Primary role is transporting oxygen to tissues and carbon dioxide to lungs.

Oxyhemoglobin

Hemoglobin bound to oxygen.

Deoxyhemoglobin

Hemoglobin without bound oxygen.

Oxygen dissociation curve

Relationship between Hb saturation and PO2; shifts reflect changes in affinity and delivery.

Curve shifts (left and right)

Left shift: increased Hb affinity (improved O2 loading, reduced delivery); Right shift: decreased Hb affinity (enhanced O2 delivery).

Right shift

Decrease in Hb affinity for O2; caused by higher CO2, lower pH, higher temperature, and other factors; increases tissue O2 delivery.

Left shift

Increase in Hb affinity for O2; caused by higher pH, lower temperature, and certain Hb variants; reduces tissue O2 delivery.

Abnormal hemoglobins

Carboxyhemoglobin, methemoglobin, and sulfhemoglobin; each affects oxygen carrying capacity and may require distinct management.

Carboxyhemoglobin

CO bound to heme with high affinity; impairs O2 delivery; treated supportively.

Methemoglobin

Iron in ferric (Fe3+) state; reduces O2 carrying capacity; treated with reducers.

Sulfhemoglobin

Hemoglobin bound to sulfur-containing compounds; not easily converted back; removal of RBCs may be required.

Haptoglobin

Protein that binds free hemoglobin in plasma during intravascular hemolysis and delivers it to the liver.

Hemopexin

Protein that binds free heme released from Hb and transports it to the liver.

RES (reticuloendothelial system)

Macrophage system that removes aged/damaged RBCs; primary site is the spleen.

Extravascular hemolysis

Destruction of RBCs outside the bloodstream, typically by macrophages in the RES.

Intravascular hemolysis

Destruction of RBCs within the bloodstream; free Hb appears in plasma and urine.

Ring sideroblasts

Nucleated RBCs with iron-laden mitochondria around the nucleus; seen in sideroblastic anemia; visualized with Prussian blue.

Siderocytes

Anucleated RBCs with iron-containing inclusions (Pappenheimer bodies).