Lecture 8 Flashcards
What are the 3 main components to RBC survival?
RBC membrane
Hemoglobin structure and function
Cellular metabolism
Red Cell Membrane
semipermeable lipid bilayer supported by a protein mesh-like cytoskeleton structure
Phospholipids, the main lipid components
Proteins that extend from the outer surface and span the entire membrane
Glycophorin
the principal RBC glycoprotein (20% of the total membrane protein)
Four glycophorin (4) types : A, B, C, D
What does glycophorin do?
carry the RBC antigens
serve as receptors, or transport proteins
anchor the plasma membrane envelop to the cytoskeleton network
Are lipids distributed equally throughout the 2 layers of the membrane?
No they are not
RBC Lipid Bilayer: Outer layer
rich in glycolipids and choline phospholipids
sphingomyelin and phosphatidlycholine
RBC Lipid bilayer: Inner layer
rich in phosphatidlyserine, phosphatidylethanolamine (known as amino phospholipids), and phosphotidylinositol
Biochemical composition of RBC membrane
52 percent protein
40 percent lipid
8 percent carbohydrate
Normal lifespan of RBC
120 days
What is a critical role in cell membrane
deformability and permeability
What is freely permeable in a cell membrane?
Water
Anions (HCO3- and Cl-)
occurs through a large number of exchange channels
What isn’t freely permeable in an RBC membrane?
Cations (Na and K)
erythrocyte intracellular-to-extracellular ratios for sodium and potassium
1:12 (Na), respectively
25:1 (K), respectively
How many pumps control the passive influx of Na and K?
300 cationic pumps
What is needed for the cationic pumps for Na and K?
Needs energy like ATP
Also needs ATPase, a membrane enzyme
What element is also actively transported from the interior of the RBC?
Calcium (C++)
through the energy-dependent calcium-ATPase cationic pump
Calmodulin
cytoplasmic calcium-binding protein
speculated to control calcium-ATPase pumps
preventing excessive intracellular calcium buildup
What happens with build of calcium?
shape changes and loss of deformability
permeability properties of the RBC membrane
crucial to preventing colloid osmotic hemolysis
controlling the volume of the red cell
What is the proper Osmotic pressure for RBCs?
300 mOs- considered Isotonic
What are the other Osmotic pressures?
100 mOs- Hypotonic (Bloated)
500 mOs- Hypertonic (Shriveled)
The energy required for active transport and maintenance of membrane electrochemical gradients is provided by what?
ATP
What is the metabolic Pathway of ATP for RBCs?
Anaerobic, because the function of the red cell is to deliver oxygen, not to consume it
How must energy be made in RBC? Why?
generated almost exclusively through the breakdown of glucose
Because mature erythrocytes have no nucleus and no mitochondria apparatus
What is done in RBC metabolism to maintain hemoglobin function?
divided among the anaerobic glycolytic pathway and three ancillary pathways
For the sake of RBC structure and O2 transport
What is the main metabolic pathway of RBCs?
Glycolysis- Ninety percent of the ATP needed by RBCs is generated
What is the remaining ATP made from?
The remaining 10% ATP is provided by the pentose phosphate pathway
methemoglobin reductase
another important pathway
are important in maintaining hemoglobin in a reduced functional state
necessary to maintain the heme iron of hemoglobin in the ferrous (Fe++) functional state
Methemoglobin
form of the oxygen-carrying hemoglobin, in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous)
Can’t carry O2
NADH
enzyme responsible for converting methemoglobin back to hemoglobin
What happens when NADH is low?
Methemoglobin accumulates
loss of oxygen transport capabilities
Luebering-Rapaport shunt
permits the accumulation of another important red cell organic phosphate, 2,3-diphosphoglycerate (2,3-DPG)
2,3-diphosphoglycerate (2,3-DPG)
Found in one-to-one molar relationship with hemoglobin, representing approximately 5 mM
profound effect on the affinity of hemoglobin for oxygen
What is essential for Hemoglobin Synthesis?
Adequate iron delivery and supply
Adequate synthesis of protoporphyrins (the precursor of heme)
Adequate globin synthesis
What is the most common Hemoglobin?
HbA, 92 to 95 percent of the hemoglobin
HbA composition
two alpha and two beta chains
HbA1c
3 to 5 percent of the hemoglobin
Made of 2 alpha chains and 2 glucose chains
HbA2
2 alpha and delta chains
2-3% of the hemoglobin
HbF
Fetal Hemoglobin
1 to 2 percent of the hemoglobin
two alpha and two gamma
What is hemoglobin’s main function?
gas transport: oxygen delivery to the tissues and carbon dioxide (CO2) excretion
What is essential about 2,3-DPG?
most important controls of hemoglobin affinity for oxygen
Tense v Relaxed forms of hemoglobin
Tense has a low affinity
Relaxed has a high affinity
How is the dissociation and binding of oxygen by hemoglobin represented
a sigmoid-curve relationship
The normal position of the oxygen dissociation curve depends on three different ligands normally found within the red cell
H+ ions
CO2
organic phosphates (2,3-DPG)
Of the three ligands for O2 dissociation curve, which is most important?
2,3-DPG
shift to the right of curve
In situations such as hypoxia
an decrease in hemoglobin-oxygen affinity and an increase in oxygen delivery to the tissues
mediated by increased levels of 2,3-DPG
Aside from Hypoxia how can a right shift help?
a patient who is suffering from an anemia
making the RBCs, although few in number, more efficient
patients may be able to tolerate anemia
shift to the left of curve
an increase in hemoglobin-oxygen affinity and a decrease in oxygen delivery to the tissues
Reasons for left shift
Alkalosis
increased quantities of abnormal hemoglobin’s, such as methemoglobin and carboxyhemoglobin
increased quantities of hemoglobin F; or multiple transfusions of 2,3-DPG
RED CELL PRESERVATION
provide viable and functional blood components for patients needing blood transfusion
How is RBC preservation done?
focused on maintaining red cell viability during storage and lengthening red cell posttransfusion survival
RBC Deformability
Loss of ATP
increase in deposition of membrane calcium
causing an increase in membrane rigidity and loss of pliability
RBC Deformability: signs
“spherocytes” (cells with a reduced surface-to-volume ratio)
“bite cells” removal of a portion of membrane
