RBC Structure and Function Flashcards
What is the structure of a red blood cell?
RBC- unique amongst eukaryotic cells as it lacks nucleus, mitochondria and ER
It is essentially a ‘bag of haemoglobin’
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
What is the function of RBCs and how do they achieve this?
The primary function of RBC is the transport of respiratory gases to and from the tissues
To achieve 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
Red cell membrane consists of:
50% proteins
40% lipids
10% carbohydrates
What is the structure of a red cell 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
What are the four types of phospholipids in the RBC membrane? How are they distributed?
Sphingomyelin (SM)
Phosphatidylethanolamine (PE)
Phosphatidylserine (PS)
Phosphatidylcholine (PC)
(When PS is expressed on the outer part of the cell that means the cell is preparing to undergo apoptosis)
Unesterified free cholesterol between the phospholipid layers
Uncharged phospholipids of outer layer (Phosphatidylcholine and sphingomyelin)
Charged phospholipids of inner layer:
Phosphatidylethanolamine
Phosphatidylserine
What are the different types of proteins in the RBC membrane?
A. Integral membrane proteins: Extend from outer surface and traverse entire lipid bilayer membrane to inner surface
2 major integral membrane proteins:
Glycophorins: A, B and C- gives a negative charge to a red blood cell preventing them from clumping together
Band 3: anion transporter
Other integral proteins:
Na+/K+ ATPase, Aquaporin 1, surface receptors e.g. TfR
B. Peripheral proteins: Limited to cytoplasmic (inner) surface of membrane and forms the RBC cytoskeleton
Cytoskeleton acts as tough framework to support bilayer
Major peripheral proteins include key roles:
Spectrin, ankyrin, protein 4.1 and actin
What are the roles of major peripheral proteins in RBC membranes? (Spectrin, Ankirin, Protein 4.1 and Actin)
Spectrin:
The most abundant peripheral protein
Composed of alpha & beta chains
Very important in RBC membrane integrity
Binds with other peripheral proteins to form the cytoskeletal network of microfilaments
Controls biconcave shape and deformability of cell
If denatured red cell becomes spherical, loses flexibility
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
Strong cohesion between bilayer and membrane skeleton maintains surface area
What is the role of carbohydrates in RBC membranes and what are some examples found there?
They occur only on the external surface of the cell
The carbohydrate groups are attached to proteins and lipids by a process called glycosylation
They may contain 2-60 monosaccharide units, either branched or straight
The carbohydrate gives a cell identity; the disguising factor for human blood types
Different monosaccharides are found on red cell membrane:
Galactose
Mannose
Fucose
N-acetyl galactosamine
Glucuronic acid
Glucose
Sialic acid
N-acetylglucosamine b
Why are antigens found on the surface of RBCs?
Blood group antigen- antigens found on red cell membrane which determines blood group
Certain blood group antigens are associated with specific membrane structures
Many antigens are proteins: e.g. Rhesus, Duffy, Kidd
Others are carbohydrates; e.g. ABO, Lewis
Others are a combination of glycolipids and proteins
What’s the function of the RBC membrane?
Provides shape- Provides the optimum surface area to volume ratio for respiratory exchange
Provides deformability, elasticity allowing for passage through micro vessels (capillaries)
Regulates intracellular cation concentration
Acts as the interface between the cell and its environment via membrane surface receptors
How can cholesterol influence defects in RBC membrane?
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
What is hereditary spherocytosis?
The cell becomes spherical and loses biconcave shape Ankyrin defect or abnormalities A or B spectrin def or abnormalities Band 3 protein abnormalities Protein 4.2 abnormalities
What is hereditary elliptocytosis?
The cell becomes elliptical and loses biconcave shape
A or B spectrin mutation- defective spectrin dimer
A or B spectrin mutation- defective spectrin-ankyrin association
Protein 4.1 deficiency or abnormalities
What are poikilocytosis and anisocytosis?
Poikilocytosis- when the cells are shaped differently
Anisocytosis- when you see cells that are different sizes
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 the mean cellular haemoglobin concentration:
As MCHC rises, viscosity rises exponentially
What does metabolism do for RBCs and what pathways are key to RBCs?
Metabolism provides 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 include: Glycolytic or Embden-Meyerhof pathway Hexose monophosphate shunt Methaemoglobin reductase pathway Luebering-Rapoport shunt
