Hematology Chapter 2: The Red Blood Cell: Structure and Function

What are the three crucial areas for normal red blood cell survival and function?

The RBC membrane, hemoglobin structure and function, and metabolic pathways.

What is the structure of the red blood cell membrane as viewed by transmission electron microscopy?

A trilaminar structure with a dark-light-dark band arrangement, consisting of an outer hydrophilic layer, a central hydrophobic layer, and an inner hydrophilic layer.

What is the role of the RBC membrane cytoskeleton?

It strengthens the lipid bilayer and maintains the shape, stability, deformability, and flexibility of the RBC.

What are integral membrane proteins in the RBC membrane?

Proteins that extend from the outer surface and traverse the entire membrane to the inner cytoplasmic side.

What is the major integral membrane protein in red blood cells?

Glycophorin, which represents 20% of the total RBC membrane protein and contains approximately 60% carbohydrate.

What is the most abundant peripheral protein in the RBC membrane cytoskeleton?

Spectrin, comprising 25% to 30% of the total membrane protein and 75% of the peripheral protein.

How does ATP depletion affect spectrin and RBC survival?

It leads to decreased phosphorylation of spectrin, reducing deformability and RBC survival.

What are the three properties crucial for RBC membrane deformability?

Cytoskeletal proteins, processes controlling intracellular ion and water handling, and membrane surface-to-volume ratio.

What is the permeability characteristic of the RBC membrane?

It is freely permeable to water and anions (Cl- and HCO3-) but relatively impermeable to cations (Na+ and K+).

What is the role of the calcium-ATPase pump in red blood cells?

It actively pumps Ca2+ from the interior of the RBC into the plasma, preventing excessive intracellular calcium buildup.

What happens to RBCs when they are ATP-depleted?

Excess intracellular calcium and sodium accumulate, leading to potassium and water loss, resulting in a dehydrated, rigid RBC.

What are the main components of red blood cell membrane lipids?

A bilayer of phospholipids, unesterified cholesterol, and glycolipids present in equimolar quantities.

What is the significance of cholesterol in the RBC membrane?

Cholesterol comprises 25% of the RBC membrane lipid and affects membrane viscosity and morphology.

What is hemoglobin composed of?

A conjugated globular protein consisting of globin (two pairs of polypeptide chains) and four heme groups.

What is required for the synthesis of hemoglobin?

Adequate iron delivery, synthesis of protoporphyrins, and globin synthesis.

How is iron delivered to RBC precursors?

By the protein carrier transferrin.

What is the major rate-limiting step in heme biosynthesis?

The formation of delta-aminolevulinic acid from glycine and succinyl coenzyme A (CoA).

What are porphyrinogens?

Unstable intermediates of heme synthesis that are readily oxidized to form stable porphyrins.

What are the types of hemoglobin present in normal adults?

95% to 97% HbA, 2% to 3% HbA2, and 1% to 2% HbF.

What is the function of calmodulin in RBCs?

It is speculated to control calcium-ATPase pumps, preventing excessive intracellular calcium buildup.

What morphological changes can occur in RBCs due to cholesterol accumulation?

Target cells and acanthocytes (RBCs with irregular, spiny projections).

What is the effect of reduced surface-to-volume ratio in RBCs?

It can lead to the formation of spherocytes.

What is the relationship between RBC ion leaks and ATP-fueled pumps?

RBC ion leaks are balanced by sodium and potassium pumps that require ATP.

What is the relationship between globin synthesis and porphyrin synthesis?

The rate of globin synthesis is directly related to the rate of porphyrin synthesis; if globin synthesis is impaired, protoporphyrin synthesis is reduced.

What happens to iron when globin or protoporphyrin synthesis is impaired?

Iron accumulates in the RBC cytoplasm as ferritin aggregates.

What is a sideroblast?

An iron-laden, nucleated RBC; the anucleated form is called a siderocyte when stained with Prussian blue.

What is a ringed sideroblast?

A diagnostic feature indicating impaired protoporphyrin synthesis, characterized by iron encrustation around the nucleus of the RBC precursor.

What is the primary function of hemoglobin?

To deliver and release oxygen to tissues and facilitate carbon dioxide excretion.

How does 2,3-biphosphoglycerate (2,3-BPG) affect hemoglobin's affinity for oxygen?

It lowers hemoglobin's affinity for oxygen, facilitating oxygen unloading.

What is the tense (T) form of hemoglobin?

The conformation of deoxyhemoglobin with a lower affinity for oxygen, caused by the binding of 2,3-BPG.

What occurs when hemoglobin loads oxygen?

Salt bridges are broken, alpha chains are pulled together, and 2,3-BPG is expelled, resulting in a relaxed form with higher oxygen affinity.

What is the hemoglobin-oxygen dissociation curve?

A sigmoid curve that illustrates the relationship between oxygen tension and hemoglobin's oxygen binding and dissociation.

What does a rightward shift in the hemoglobin-oxygen dissociation curve indicate?

Increased levels of 2,3-BPG, resulting in decreased affinity for oxygen and increased oxygen delivery to tissues.

What is carboxyhemoglobin?

A form of hemoglobin where oxygen molecules are replaced by carbon monoxide, which binds 200 times tighter than oxygen.

What is methemoglobin?

Hemoglobin with oxidized iron in the ferric state, which can form due to oxidant stress or enzyme deficiency.

What is sulfhemoglobin?

A form of hemoglobin that cannot carry oxygen, formed from sulfur-containing drugs or chronic constipation.

How can carboxyhemoglobin and methemoglobin be reverted to oxyhemoglobin?

Carboxyhemoglobin can be treated with oxygen inhalation, while methemoglobin can be treated with strong reducing substances.

What metabolic pathway generates 90% of ATP needed for RBC survival?

The Embden-Meyerhof glycolytic pathway.

What is the role of the hexose monophosphate (HMP) shunt in RBC metabolism?

It produces NADPH from NADP+, contributing to RBC metabolism.

What is the Leubering-Rapoport shunt's significance?

It causes an accumulation of 2,3-BPG, affecting hemoglobin's affinity for oxygen.

What is the lifespan of a red blood cell (RBC)?

Approximately 120 days.

What system removes senescent RBCs from circulation?

The reticuloendothelial system (RES) or mononuclear phagocytic system (MPS).

What role does phosphatidylserine play in RBC senescence?

It mediates the recognition of senescent RBCs, signaling for phagocytosis.

What is the primary mechanism of extravascular hemolysis?

Phagocytosis of senescent RBCs by RES cells and digestion by lysosomes.

What happens during intravascular hemolysis?

RBCs rupture, releasing hemoglobin directly into the bloodstream.

What is haptoglobin's function?

To bind free hemoglobin in the plasma, preventing its loss through the kidneys.

What occurs when haptoglobin is depleted?

Unbound hemoglobin dimers appear in the plasma (hemoglobinemia) and can lead to hemoglobinuria.

What happens to free hemoglobin that is not processed by the kidneys?

It is oxidized to methemoglobin and further degraded, with metheme groups released.

What is the role of hemopexin in hemoglobin metabolism?

To bind free metheme and transport it to the liver for catabolism.