2. EVALUACIÓN DEL ESTADO AMBIENTAL ACTUAL
2.2. Elementos de evaluación
The RBC membrane is impermeable to cations Na1, K1, and Ca21. It is permeable to water and the anions bicarbonate (HCO32) and chloride (Cl2), which freely exchange between plasma and RBC cytoplasm.49 Aquaporin 1 (Table 9-5) is a transmembrane protein that forms pores or channels whose
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surface charges create inward water flow in response to internal osmotic changes.
The ATP–dependent cation pumps Na1ATPase and K1ATPase (Table 9-5) regulate the concentrations of Na1 and K1, maintaining intracellular-to-extracellular ratios of 1:12 and 25:1, respectively.50,51 Ca21ATPase extrudes calcium, maintaining low intracellular levels of 5 to 10 mmol/L. Calmodulin, a cytoplasmic Ca21 -binding protein, controls the function of Ca21-ATPase.52 These enzymes, in addition to aquaporin, maintain osmotic balance.
The cation pumps consume 15% of RBC ATP production.
ATP loss or pump damage permits Ca21 and Na1 influx, with water following osmotically. The cell swells, becomes spheroid, and eventually ruptures. This phenomenon is called colloid osmotic hemolysis.
Sickle cell disease provides an example of increased cation permeability. When crystallized sickle hemoglobin deforms the cell membranes, internal levels of Na1, K1, and especially Ca21 rise, which results in hemolysis.52
• Glucose enters the RBC with no energy expenditure via the trans-membrane protein Glut-1.
• The anaerobic Embden-Meyerhof pathway (EMP) metabolizes glucose to pyruvate, consuming two ATP molecules. The EMP subsequently generates four ATP molecules per glucose molecule, a net gain of two.
• The hexose-monophosphate pathway (HMP) pathway aerobically converts glucose to pentose and generates NADPH. NADPH reduces glutathione. Reduced glutathione reduces peroxides and protects proteins, lipids, and heme iron from oxidation.
• The methemoglobin reductase pathway converts ferric heme iron (valence 31 iron, methemoglobin) to reduced ferrous (valence 21 form), which binds O2.
• The Rapoport-Luebering pathway generates 2,3-BPG and enhances O2 delivery to tissues.
• The RBC membrane is a lipid bilayer whose hydrophobic compo-nents are sequestered from aqueous plasma and cytoplasm. The membrane provides a semipermeable barrier separating plasma from cytoplasm and maintaining an osmotic differential.
• RBC membrane phospholipids are asymmetrically distributed.
Phosphatidylcholine and sphingomyelin predominate in the outer layer; phosphatidylserine and phosphatidylethanolamine form most of the inner layer.
• Enzymatic plasma to membrane exchange maintains RBC membrane cholesterol.
• Acanthocytosis and target cells are associated with abnormalities in the concentration or distribution of membrane cholesterol and phospholipids.
• RBC transmembrane proteins channel ions, water, and glucose and anchor cell membrane receptors. They also provide the
vertical support connecting the lipid bilayer to the underlying cytoskeleton to maintain membrane integrity.
• RBC cytoplasm K1 concentration is higher than plasma K1, whereas Na1 and Ca21 concentrations are lower. Disequilibria are maintained by membrane enzymes K1-ATPase, Na1-ATPase, and Ca21-ATPase. Pump failure leads to Na1 and water influx, cell swelling, and lysis.
• The shape and flexibility of the RBC, which are essential to its function, depend on the cytoskeleton. The cytoskeleton is derived from a group of peripheral proteins on the interior of the lipid membrane. The major structural proteins are a- and b-spectrin, which are bound together and connected to transmembrane pro- teins by ankyrin, actin, protein 4.1, adducin, tropomodulin, dema-tin, and band 3. Cytoskeletal proteins provide the horizontal or lateral support for the membrane.
• Hereditary spherocytosis arises from defects in proteins that pro-vide vertical support for the membrane. Hereditary elliptocytosis is due to defects in cytoskeletal proteins that provide horizontal support for the membrane.
• Membrane proteins are extracted using sodium dodecyl sulfate, separated using polyacrylamide gel electrophoresis, and stained with Coomassie blue. They are numbered from the point of appli-cation; lower numbers correlate to high protein molecular weight and lower net charge.
Now that you have completed this chapter, go back and read again the case study at the beginning and respond to the questions presented.
SUMMARY
REVIEW QUESTIONS
Answers can be found in the Appendix.
1. Which RBC process does not require energy?
a. Oxygen transport
b. Cytoskeletal protein deformability
c. Preventing the peroxidation of proteins and lipids d. Maintaining cytoplasm cationic electrochemical gradients
2. What pathway anaerobically generates energy in the form of ATP?
a. Hexose monophosphate pathway b. Rapoport-Luebering pathway c. Embden-Meyerhof pathway d. 2,3-BPG pathway
122
PART II Blood Cell Production, Structure, and Function 3. Which is true concerning 2,3-BPG?a. The least abundant of RBC organophosphates b. Enhances O2 release from hemoglobin c. Source of RBC glucose
d. Source of RBC ATP
4. To survive, the RBC must detoxify peroxides. What hexose-monophosphate shunt product(s) accomplishes detoxification?
a. ATP b. 2,3-BPG
c. Pyruvic and lactic acid
d. NADPH and reduced glutathione
5. Which of the following helps maintain RBC shape?
a. Membrane phospholipids b. Cytoskeletal proteins c. GPI anchor
d. Glycocalyx
6. The glycolipids of the RBC membrane:
a. Provide flexibility.
b. Carry RBC antigens.
c. Constitute ion channels.
d. Attach the cytoskeleton to the lipid layer.
7. RBC membranes block passage of most large molecules such as proteins, but allow passage of small molecules such as the cations Na1, K1, and Ca11. What is the term for this membrane property?
a. Semipermeable b. Deformable c. Intangible d. Flexible
8. RBC membrane phospholipids are arranged:
a. In a hexagonal lattice.
b. In chains beneath a protein exoskeleton.
c. In two layers whose composition is asymmetric.
d. So that hydrophobic portions are facing the plasma.
9. RBC membrane cholesterol is replenished from the:
a. Plasma.
b. Mitochondria.
c. Cytoplasm.
d. EMB pathway.
10. The hemoglobin iron ion may become oxidized to the 13 valence state by several pathological mechanisms. What portion of the Embden-Meyerhof pathway reduces iron to the physiologic 12 valence state?
a. Methemoglobin reductase pathway b. Hexose monophosphate pathway c. Rapoport-Luebering pathway d. The 2,3-BPG shunt
11. Which of the following is an example of a transmembrane or integral membrane protein? of the transmembrane and cytoskeletal RBC membrane proteins may be seen as:
a. Shape changes.
b. Methemoglobin increase.
c. Reduced hemoglobin content.
d. Enzyme pathway deficiencies.
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