Red blood cell: Structure and function Flashcards
Rbc structure
RBC- unique amongst eukaryotic cells lacks nucleus, mitochondria and ER.
As they lack organelles, it is essential that they maintain their structure
Biconcave, 8 micron cells, to be able to deform & pass through 3 micron capillaries or reticuloendothelial system without fragmentation.
Structural properties are linked to membrane
Function of RBC
Primary function of RBC is transport of respiratory gases to and from the tissues.
To achieves this:
rbc traverse the microvascular system without mechanical damage, and retain a shape which facilitates gaseous exchange.
the red cell membrane should be extremely tough yet highly flexible
Cytoskeletal proteins interaction with the membrane lipid bilayer determines strength and flexibility.
Structure of RBC membrane
A semi-permeable lipid bilayer; with proteins scattered throughout:
an outer hydrophilic portion composed of glycolipids, glycoproteins, and proteins
a central hydrophobic layer containing proteins, cholesterol, and phospholipids
an inner hydrophilic layer of mesh-like cytoskeletal proteins to support lipid bilayer.
RBC Membrane lipids
Asymmetric phospholipid distribution.
Unesterified free cholesterol between.
Uncharged phospholipids of outer layer
(Phosphatidyl choline and Sphingomyelin)
Charged phospholipids of inner layer:
Phosphatidyl ethanolamine
Phosphatidyl serine
Membrane cholesterol exists in free equilibrium with plasma cholesterol:
an increase in free plasma cholesterol results in an accumulation of cholesterol in the RBC membrane.
RBCs with increased cholesterol appear distorted resulting in the formation of acanthocytes.
an increase in cholesterol and phospholipid is a cause of target cells
Why is concentration of cholesterol in rbc important?
The concentration of cholesterol in the membrane is an important determinant of membrane surface area and fluidity:
an increase in membrane cholesterol leads to an increased surface area and decreased deformability.
increased in lipids leads to
acanthocytes (just cholesterol)
increase in both cholesterol and phospholipid causes target cells.
Target cells occur in disproportional increase in SA:V; i.e abnormally high SA (increased SA),
composition of lipids in rbc membrane
Lipids consist of 60% phospholipid, 30% natural lipids (mainly cholesterol) and 10% glycolipids
RBC membrane proteins
Integral membrane proteins
Extend from outer surface and traverse entire membrane to inner surface
• There are 2 major types of integral proteins:
-> Glycophorins A, B, C
Glycophorins give RBCs their negative charge
When suspended in a test tube, blood will take time to settle due to repulsion
When there is an excess of inflammatory proteins, the cells settle quicker as they are
coated in these proteins
Glycophorin A is important for the parasite causing malaria, it uses this protein to enter
the RBC
-> Band 3: anion transporter
These help transfer ions in and out of cell to maintain cell shape
There are several other types of integral proteins as well
Na+/K+ ATPase, Aquaporin 1, surface receptors, e.g. TfR
TfR is transferase receptor found in the innnerpart of the RBC membrane
Peripheral proteins
Limited to cytoplasmic surface of membrane and forms the RBC cytoskeleton
There are many major peripheral proteins
- Spectrin
- Ankyrin
Primarily anchors lipid bilayer to membrane skeleton
Via interaction with spectrin and Band 3 - Protein 4.1
May link the cytoskeleton to the membrane by means of its associations with
glycophorin
Stabilises interaction of spectrin with actin - Actin
Responsible for contraction and relaxation of membrane
Spectrin
The most abundant peripheral protein
Composed of alpha & beta chains
Very important in RBC membrane integrity because it binds with other peripheral proteins to form the cytoskeletal network of microfilaments on the inner surface of RBC membrane
Controls biconcave shape and deformability of cell
Function of membrane
• Provides shape
Provides the optimum surface area to volume ratio for respiratory exchange AND is
essential to deformability
• Provides deformability, elasticity
Allows for passage through micro vessels (capillaries)
• Regulates intracellular cation concentration by use of Na/K ATPase and many other ion channels
Control of Ca2+ is very important
Accumulation of Ca2+ will affect RBC shape
May give a spherical shape
They are quite easily destroye
They may be removed from circulation by the reticuloendothelial system
Separates the contents of the cell from the plasma.
• Acts as the interface between the cell and its environment via membrane surface receptors.
RBC cation pumps
Allows water and electrolytes to exchange via cation pumps.
RBC controls volume and H2O content primarily through control of intracellular concentrations of Na+ and K+ via these cationic pumps which require ATP.
ATP is also required in the Ca++ pump system that prevents excessive intracellular build-up of Ca++.
In ATP depleted cells there is an intracellular build-up of Na+ and Ca++ and a loss of K+ and water. This leads to dehydrated, rigid cells that are culled by the spleen.
Defects in RBC Membrane
Hereditary Spherocytosis
Hereditary Elliptocytosis
Defects in RBC Membrane
Hereditary Spherocytosis
Ankyrin def or abnormalities
A or B spectrin def or abnormalities
Band 3 protein abnormalities
Protein 4.2 abnormalities
Defects in RBC Membrane
Hereditary Elliptocytosis
A or B spectrin mutation – defective spectrin dimer
A or B spectrin mutation – defective spectrin-ankyrin association
Protein 4.1 deficiency or abnormalities
What features allow RBC to withstand life without structural deterioration?
Geometry of cell; surface area to volume ratio.
facilitates deformation whilst maintaining constant surface area.
Membrane deformability
spectrin molecules undergo reversible change in conformation: some uncoiled and extended, others compressed and folded.
Cytoplasmic viscosity determined by MCHC (mean cell haem conc)
as MCHC rises, viscosity rises exponentially.
Haemoglobin structure
Haemoglobin (Hb) is a globular haemoprotein
haemoproteins are group of specialized proteins that contain haem as a tightly bound prosthetic group.
haem is a complex of protoporphyrin IX and ferrous iron (Fe2+).
Iron held in the centre of haem molecule by bonds to the 4 nitrogen of a porphyrin ring.
Haemoglobin structure
Globin
Globin:
4 polypeptide subunits
2 α-globin chains
2 β-globin chains
adult hameoglobin
globin %
Hb A
structure a2b2
96-98%
Hba2
structure a2d2
1.5-3.2%
HbF
a2Y2
0.5-0.8%
Functions of haemoglobin
Oxygen delivery to the tissues
• One Hb can bind to four O2 molecules
• Less than .01 sec required for oxygenation.
• When oxygenated 2,3-DPG is pushed out; the Β-chains move closer.
• Β-chains are pulled apart when O2 is unloaded, permitting entry of 2,3-DPG resulting in
lower affinity of O2
• Increased amount of 2,3-diphosphoglycerate allows RBCs to release oxygen easily and vice
versa
2,3-diphosphoglycerate (2,3-DPG)
2,3-diphosphoglycerate (2,3-DPG) is a substance made in the red blood cells. It controls the movement of oxygen from red blood cells to body tissues.
The more 2,3-DPG in the cell, the more oxygen is delivered to body tissues. Conversely, the less 2,3-DPG in the cell, the less oxygen is delivered.
Increasing the amount of 2,3-DPG is the body’s primary way of responding to a lack of oxygen.
As Hb molecule loads and unloads O2, the individual globin chains move on each other.
The Beta chains slide on the a1b2 and a2b1 contacts during oxygenation and deoxygenation.
When O2 is unloaded the beta chains are pulled apart, permitting entry of the metabolite 2,3-diphosphoglycerate (2,3-DPG), resulting in lower affinity for O2.
This move is responsible for the sigmoid shape of the O2-dissociation curve
Hb-oxygen dissociation curve
The normal position of curve depends on
Concentration of 2,3-DPG
H+ ion concentration (pH)
CO2 in red blood cells
Structure of Hb (eg fetal hemoglobin does not release oxygen as easily as adult hemoglobin)
Standard conditions:
Temp = 37OC
pH = 7.40
BE = 0
BE
BE stands for Base Excess, and it is a measure of the metabolic acid level. Zero means blood base level is normal which 48mmol/L, or blood pH of 7.4.
For instance, if the patient is acidotic, the base excess will be a negative value; this means acid would have to be taken away to bring the pH to normal. For a base excess of -6 would mean that 6 mEq per litre of base would have to be added to bring the patient’s blood to normal pH (7.4)
What shifts the curve to the right?
Changes in blood pH shift the oxyhemoglobin dissociation curve. An increase in CO2 production by tissue and release into blood results in the generation of hydrogen ions (H+) and a decrease in pH. This shifts the dissociation curve to the right, which has a beneficial effect by aiding in the release of O2 from Hgb for diffusion into tissues. The shift to the right in the dissociation curve is due to the decrease in pH and to a direct effect of CO2 on Hgb
hence increased temp, lower pH, increase 2-3DPG and increase co2 levels
Changes in structure of Hb
Haemoglobinopathies
Inherited disorders of Hb; 2 categories:
Thalassaemias
Sickle Cell Disease
RBC metabolic pathways why?
Metabolism provide energy required for:
Maintenance of cation pumps
Maintenance of RBC integrity and deformability
Maintenance of Hb in reduced state
Maintenance of reduced sulfhydryl groups in Hb and other proteins
Key Metabolic Pathways for the RBC
Glycolytic or Embden-Meyerhof Pathway
Hexose Monophosphate Shunt
Methaemoglobin reductase Pathway
Luebering-Rapoport shunt
Glycolytic Pathway
Glucose is metabolized and generates two molecules of ATP (energy).
Generates 90- 95% of energy needed by RBC’s
Functions in the maintenance of RBC shape, flexibility and the cation pumps
Pentose Phosphate Pathway/Hexose monophosphate shunt
The pentose phosphate shunt provides the reducing power, NADPH
NADPH maintains glutathione in the reduced form (GSH)
RBC uses GSH to protect it from oxidative damage;
Methemoglobin Reductase pathway
Maintains iron in the ferrous (Fe++) state.
In the absence of this enzyme, methaemoglobin accumulates and it cannot carry oxygen
Luebering-Rapoport shunt
Permits the accumulation of 2,3-DPG which is essential for maintaining normal oxygen tension, regulating haemoglobin affinity
