Unit 6 - Red Cell Structure & Physiology Flashcards
Size of RBC
7-9 um
RBCs can squeeze through small micro vessels as small as ___ in the spleen
3 micrometers
For normal function, the RBC structure must have
1) Intact, functioning membrane
2) Normal internal metabolism
3) No nucleus for repairs
RBC membrane structure components
Lipid Bilayer
Protein layers that transverse lipids
Protein cytoskeleton
Components of the lipid bilayer
Cholesterol
Phospholipids
Phospholipids composed of hydrophobic and hydrophilic parts
Hydrophobic tails - Interior
Hydrophilic heads - exterior
How much cholesterol on lipid bilayer is in proportion to plasma cholesterol
in equilibrium with plasma cholesterol
Components of proteins that transverse the lipid bilayer
Glycophorins
Band 3 protein
Glycophorin types
A, B, C
Three domains of the types of glycophorins
Cytoplasmic - Interior
Hydrophobic - Middle
Extracellular - Exterior
Where is glycophorin C in the membrane of the RBC?
Outside, its heavily glycosylated
What do extracellular glycophorins do
Carry RBC antigens
Negative charge (Zeta potential) that keeps RBCs apart
What does Band 3 protein do
Anion exchange protein 1
Channel for chloride <–> bicarbonate (CO2 exchange)
Components of membrane cytoskeleton
Spectrin
Ankyrin
Actin
Tropomyosin
Bands 4.1, 4.2, 4.9
Where is the RBC Cytoskeleton
Underneath the lipid bilayer
What does the RBC cytoskeleton do
Maintain RBC shape
Pliability to squeeze through capillaries and survive turbulence
What is the main protein of the cytoskeleton
Spectrin
What is spectrum composed of
alpha and beta chains twisted together
What is the shape of spectrin
Arranged in lattice of hexagons to allow it to recoil like a spring
Where is spectrin and what holds it there?
Attached to the bilipid layer by ankyrin and band 4.2
What does ankyrin do
Anchors spectrin
Another name for ankyrin
Band 2.1
What do actin and tropomyosin do
Muscle like filaments that stabilize RBC cytoskeleton
What do Bands 4.1, 4.2, 4.9 do
help with stabilization
Deformability of RBC depends on
1) Biconcave shape
2) Viscosity of internal solution (mostly hgb)
3) Elastic properties of RBC membrane
What does the lipid bilayer rely on for repair?
Plasma lipids
What does an increase of plasma lipids do to RBC
Changes the membrane
What are typical shape changes due to plasma lipids
Codocytes (target)
Acanthocytes (spur)
Anions and water flow freely across the membrane via what structures?
Protein band 3
Water channel protein
What do cations require for permeability?
Cation pump and ATP
What do cation pumps do
Sodium pumped out
Potassium drawn in
What are the main cation pumps in RBC membrane
Na/K
Ca-ATPase
Are calcium and magnesium intracellular or extracellular?
Intracellular
What occurs if the cation pump fails?
Sodium builds up in the cell
Water accumulates in cell
Sphere shape
Hemolysis
What is the cause of cell pump function decreasing
insufficient ATP from insufficient glucose metabolism
Erythrocyte function in addition to O2 and CO2 transport
Membrane permeability to maintain ion balance
Buffer function of hgb via bohr effect
Bicarb formation and dissociation into carbonic acid and hydrogen
Requirements for function of RBC
Energy supply
Membrane integrity
Normal hgb
Pyridine nucleotides (NAD/NADH)
How do RBCs generate ATP?
Glycolysis
What do pyridine nucleotides do
Prevent oxidant injury
Reduce methemoglobin to hemoglobin
Red Cells perform their function without
Nucleus
Mitochondria
Protein synthesis
Red cells are totally dependent on ___ for energy
Plasma glucose
Red cells use oxygen to generate ATP
False, only anaerobic glycolysis
When RBCs are chemically damaged, how are they repaired?
RBC enzymes
Major categories of RBC metabolism
Glycolysis –> ATP
NAD/NADH metabolism to reduce methemoglobin
Leubering Rapoport Shunt
Two different glycolysis pathways for RBC ATP generation
Embden Meyerhoff Pathway
Hexose Monophosphate Shunt
Two NAD/NADH metabolism routes for RBC metabolism
Hexose Monophosphate Shunt
Methemoglobin Reductase Pathway
Anaerobic glycolysis for energy
Embden Meyerhoff Pathway
Hexose Monophosphate Shunt
90% of cellular glucose processed using which pathway?
Embden Meyerhoff Pathway
Glycolytic Pathway (embden meyehoff)
Glucose–>Pyruvate–> Lactate
ATP generated for energy
NADH generated for methemoglobin reduction
Why is NADH important?
Methgb is oxidized hgb when exposed to Oxygen
Methgb can’t carry oxygen so reversal is important
What generates NADH?
G-6PD
5-10% of cell’s glucose processed through
Hexose monophosphate shunt
Hexose monophosphate shunt produces
NADPH2
NADPH function
Converts oxidized glutathione to reduced glutathione
Reduced glutathione neutralizes oxidation
Methemoglobin Reductase Pathway
Enzyme takes NADH and reduces methemoglobin
Diseases/Drugs that interfere with the methemoglobin reductase pathway cause what?
Cyanosis
Leubering Rapoport Shunt
Generates 2,3 DPG
Needed for hgb to exchange oxygen
G6PD deficiency
Glutahtione can’t be generated
Hgb is oxidized
Hgb denatures –> Heinz bodies –> removed by spleen
What inclusion is associated with G6PD deficiency?
Heinz Bodies
What stain allows us to see Heinz bodies
Supravital
How much of hgb is methemoglobin normally
Normal for 2% of hgb to become methgb per day
Without enzyme, how much does methemoglobin build up to?
20-40%
Pyruvate kinase deficiency
Pyruvate can’t be converted to lactate
Less ATP generated
RBC weak (cation pumps)
Hemolytic anemia ensues
WHy do infants get slight anemia after birth?
High RBC counts because Hypoxic in utero
High oxygen after birth –> low EPO
Slight anemia until EPO recovers
Why do males have higher RBC counts
Testosterone magnifies EPO effect
What hormones have an effect of EPO
Thyroid
Pituitary
Adrenals
Chemical signal for senescence to phagocytes
Exposure of phosphatidylserine on RBC surface
Extravascular hemolysis is what percent of normal destruction
90%
Intravascular hemolysis is what percent of normal destruction
10%, old RBCs
Where does most extravascular hemolysis take place
In spleen by phagocytes
also in marrow by phagocytes
Hgb made up of
Heme + Globins
Heme made up of
Iron and protoporphyrin ring
Globins made up of
Amino acids
HEme recyclin
Fe –> Transferrin –> marrow
Porphyrin ring –> bilirubin + urobilinogen
Haptoglobin
Picks up free hemoglobin to prevent loss through kidneys
Where does haptoglobin take hgb
Back to the liver for processing, same as extravascular
What happens if haptoglobin is consumed and there is still excess free hemoglobin
Oxidized to methgb, broken down to heme + globin
Hemopexin
Carries heme to liver for processing
If hemopexin is all used up, what carries heme in its place?
Albumin, forms methemalbumin until hemopexin is produced
IF hemolysis is beyond normal capacity, where is it going to go?
Hemoglobin shows up in urine
Hemosiderinuria
when IV hemolysis sever, iron laden renal tubule cells can slough off
Stain cells in urine sediment with Prussian blue
Better indicator of sever IV hemolysis than hgb in urine