The Red Blood Cell: Structure and Function

Define the toxic levels for abnormal hemoglobins of clinical importance.

carboxyhemoglobin: 5.0 g% methemoglobin: 1.5 g% sulfhemoglobin: 0.5 g%

List the steps in the extravascular breakdown of senescent RBCs.

hemoglobin molecules are disassembled, the iron is returned to the erythroid precursors in the marrow, globin is broken down into amino acids and redirected to the amino acid pool of the body, the protoporphyrin ring is disassembled, its alpha carbon is exhaled as carbon monoxide, biliverdin is converted to bilirubin and carried to the liver, it is conjugated in the liver and excreted into the intestines, it is converted into urobilinogen and excreted in the stool

List the major lipid components of the red cell membrane.

phospholipids, glycolipids, and cholesterol

List the areas of red cell metabolism that are crucial to normal red cell survival and function.

the RBC membrane, hemoglobin structure and function, metabolic pathways

Describe the assembly of the protoporphyrin ring.

A protoporphyrin ring is made up of four pyrrole rings linked by methine bridges. Four methyl, two vinyl, and two propionate side chains are attached.

Define "shift to the left" in relation to the hemoglobin-oxygen dissociation curve.

A shift to the left of the hemoglobin-oxygen dissociation curve results in an increase in hemoglobin-oxygen affinity and a decrease in oxygen delivery to the tissues.

Define "shift to the right" in relation to the hemoglobin-oxygen dissociation curve.

A shift to the right of the hemoglobin-oxygen dissociation curve results in a decrease in the affinity of hemoglobin for the oxygen molecule and an increase in oxygen delivery to the tissues.

Define the primary function of hemoglobin.

Hemoglobin is the iron-containing pigment of the red blood cells that functions to carry oxygen from the lungs to the tissues.

List the steps in the intravascular breakdown of senescent RBCs.

RBCs rupture and release hemoglobin into the bloodstream, hemoglobin is carried to the liver where it is broken down the same way as in extravascular hemolysis

Describe hemoglobin function.

The primary function of hemoglobin is delivery and release of oxygen to the tissues and facilitation of carbon dioxide excretion.

List the abnormalities that may lead to a change in RBC structure and name the associated RBC morphology.

cholesterol accumulation in the RBC membrane: target cells abetalipoproteinemia with cholesterol accumulation: acanthocytes LCAT deficiency with cholesterol accumulation: hemolysis with red cell fragmentation decreased phosphorylated spectrin or altered spectrin: bite cells and spherocytes

List the two most important red blood cell (RBC) membrane proteins and describe their function and the characteristics of deformability and permeability.

glycophorin: the principal integral blood cell protein, containing 60% carbohydrate and giving the red cell its negative charge spectrin: a large molecule, found in the inner surface of the RBC membrane, that is responsible for the biconcave shape of the red cell as well as for its deformability

List the proteins that carry the following components in circulation: iron, hemoglobin dimers, metheme, and bilirubin.

iron: transferrin hemoglobin dimers: haptoglobin metheme: hemopexin bilirubin: albumin

List the structural components of normal hemoglobin.

two alpha chains, two non-alpha globin chains, and four heme groups (iron plus a protoporphyrin ring)

List the globin chains found in HbA, HbA₂, and HbF, and their respective concentrations (%) found in vivo.

HbA (2 alpha, 2 beta): 95-97% HbA₂ (2 alpha, 2 delta): 2-3% HbF (2 alpha, 2 gamma): 1-2% Hb Portland (2 zeta, 2 gamma): 0% Hb Gower 2 (2 alpha, 2 epsilon): 0% Hb Gower 1 (2 zeta, 2 epsilon): 0%

List the various metabolic pathways involved in red cell metabolism, stating the specific function of each one.

Embden-Meyerhof glycolytic pathway: generates 90% of the ATP needed by RBCs; the metabolism of glucose results in the net generation of two molecules of ATP hexose monophosphate shunt: metabolizes 5-10% of glucose; produces NADPH, which protects the RBC from oxidative injury methemoglobin reductase pathway: converts methemoglobin (nonfunctional, resulting from reduction of ferrous iron to ferric) back into hemoglobin Leubering-Rapaport shunt: causes an accumulation of 2,3-DPG, which is important because of its profound effect on the affinity of hemoglobin for oxygen

Define P₅₀ and state normal in vivo levels.

P₅₀: the partial pressure of oxygen or oxygen tension at which the hemoglobin molecule is 50% saturated with oxygen under standard in-vitro conditions of temperature and pH The P₅₀ of normal blood is 26 to 30 mm Hg.

Describe the chemical composition of the red cell membrane in terms of percentage of lipids, proteins, and carbohydrates.

The chemical composition of the membrane mass is approximately 40% lipids, 52% proteins, and 8% carbohydrates.

Describe hemoglobin function in terms of the oxygen dissociation curve.

The dissociation and binding of oxygen by hemoglobin exhibit a sigmoid-curve relationship to the oxygen tension (PO₂) of its environment,known as the hemoglobin-oxygen dissociation curve.

List the criteria for normal hemoglobin synthesis.

adequate iron delivery and supply, adequate synthesis of protoporphyrins (the precursor of heme), and adequate globin synthesis