RBC Structure & Function Flashcards
How are RBCs able to transport respiratory gases to/from tissues?
RBCs are capable of traversing the microvascular system without mechanical damage and retain a shape
RBC membrane is highly flexible yet tough
What is the role of cholesterol in the membrane?
Cholesterol won’t form its own membrane so inserts itself into bilayer with with its polar hydroxyl group close to the phospholipid head
membrane [cholesterol] determines membrane SA and fluidity
Increased choleterol = decreased deformability
What is the consequence of excess plasma cholesterol?
Incorporates preferrentially in outer leaflet of RBC membranes
- RBC becomes less deformable
- Remodelled when passing through spleen
- Forms acanthocytes
What determines the membranes strength?
Interactons between membrane and cytoskeletal proteins determine strength and flexibility
What do experiments on humans and rats with liver disease show?
Changes in rbc shape => forms alterations in membrane lipid content
Secondary to plasma lipids changes
Production of abnormal lipoproteins causes increase in [free cholesterol] occur in various types of liver diseases
Where in the membrane are integral membrane proteins?
Extend from outer surface to and traverse entire membrane to inner surface
Describe the structure of RBC membranes
- Semi permeable lipid bilayer with proteins throughout
- Outer hydrophilic porion composed of glycoproteins,
glycolipids, and proteins - Central hydrophobic layer containing proteins,
cholesterol and phospholipids - inner hydrophilic layer of meshlike cytoskeletal proteins
supporting lipid bilayer
How do congenital abnormalities arise in lipid composition?
Increased cholesterol causes acanthocytes which increases blood cholesterol and phospholipids causing target cells
Name the uncharged phospholipids on the outer membrane layer
Phosphatidyl Choline, sphingomyelin and glycolipids
How does the RBCs geometry enable it to withstand structural deterioration?
(SA:Vol) facillitates deformation whilst maintaining a constant SA
What is the composition of red cell membrane?
50% - proteins
40% - lipids
10% - carbohydrates
What are the 2 major integral membrane proteins?
Glycophorins - A,B and C
Band 3 - anion transporter
(other: Na+/K+ ATPase, Aquaporin 1, Surface Receptors e.g. TKAK)
What is the consequence of increased cholesterol in RBCs?
Appear distorted (acanthocytosis) caused by target cells
How is the membranes deformability not cause structural damage to RBC?
Spectrin molecules undergo conformational changes
Some are uncoiled and extended others are compressed and folded
What are the charged phospholipids of the inner layer?
Phosphatidylethanolamine, phosphatidylserine and phosphotidylinositol
How is cholesterol distributed throughout the cell?
Membrane cholesterol exists in free equilibrium with plasma cholesterol
Increasing free plasma cholesterol causes accumulation of cholesterol in RBC membrane
What is the primary function of RBCs?
Transport of respiratory gases to and from tissues
Describe the sturcture and function of Spectrin
Most abundant peripheral protein
composed of α and β chains
RBC membrane integrity - binds with other peripheral proteins to form microfilaments
Controls biconcave shape and deformability
What is the function of glycolipids on cell membranes?
Glycolipids maintain cell membrane stability and facilitate intracellular recognition
Crucial for immune system and connections allowing cells to connect and form tissues
What is the purpose of RBC biconcave shape?
Maximises SA to increase efficiency of oxygen absorption
What is the significnce of microfilaments to RBC structure?
Microfilaments strengthen the membrane protecting it from breaking
What is the significance of maintaining asymmetric distribution of phospholipids in the red cell membrane?
Localisation of PS and phosphoionositides to the inner monolayer has several functional implications
- macrophages recognise & phagocytose red cells
exposing PS on their outer surface
How does the SA:vol effect membrane deformability?
High SA:Vol facilitates large reversible elastic deformation of the RBC allowing it to repeatedly pass through 3um capillaries during microcirculation
How does spectrin interact with other proteins?
Spectrin must be phosphorylated by Protein Kinase requiring ATP
- [ATP] decreases; decreased phosphorylation of spectrin
What is the percentage composition of lipids?
60% - phospholipids
30% - natural lipids (cholesterol)
10% - glycolipids
What is the role of glycophorins?
Account fpr location of RBC antigens
Import negative charge to cell
Reduce interaction with other cells / endothelium
What factors affect the RBC membranes deformability?
- Cytoplasmic viscosity
- Intracellular debris
- Membrane rigidity
- SA:Vol ratio
What are glycolipids?
Lipids with carbohydrates attached via a covalent glycosidic bond
What happens to unphosphorylated spectrin in cell membranes?
Unphosphorylated spectrin no longer binds to actin
Membrane isn’t as elastic
Loss in deformability
Decreased RBC survival time
What is the purpose of localisation of PS on inner layer of red cell membranes?
Keeping PS on inner layer allows cells to survive the frequent encounters with macrophages of the reticuloendothelial system (esp. in the spleen)
What is the consequence of mutations in peripheral proteins?
Mutations in cytoskeletal proteins Spectrin and Protein 4.1 weakens horizontal linkage decreasing membrane mechanical stability causing hereditary eliptocytosis (He)
What are the RBCs membrane functions?
- Maintain cell volume
- Maintain Na+/K+ content
- Maintain osmotic fragility
- Ca2+ homeostasis
- Anion exchange
What is the role of Actin?
Contraction and relaxation of membrane
Strong cohesion between bilayer and membrane
Skeleton maintains surface area
Name some of the major peripheral proteins
Spectrin, Ankyrin, Protein 4.1, Actin
What is the link between RBC membrane and its structure
They have a flexible membrane with a high SA:Vol
What is the function of red cell membranes?
Provides shape
- Provides optimum SA:Vol ratio for respiratory exchange
Provides deformability / elasticity
- Allows passage through microvessels
Regulates intracellular cation concentration
What is the specific function of Protein 4.1?
Links cytoskeleton to membrane by means of its associations with glycoproteins
Stabilises Spectrin and Actin interaction
What are glycophorins?
All glycophorins are recptors or transport proteins
3 types: A, B and C
What is the consequence of abnormalities in peripheral proteins?
Defects of Band 3, Ankyrin or Protein 4.1 leads to destabilisation of overlying lipid bilayer and release of lipid in microvessels causing:
Hereditary ellipocytosis
Hereditary Spherocystosis
Describe the structure of red blood cells
Contain no nucleus, mitochondria or endoplasmic reticulum Biconcave shape (8um) Able to deform and pass through 3um capillaries or reticuloendothelial system without fragmentation
How does the cytoplasmic viscosity regulate RBC structure?
Determined by MCHC - as MCHC rises, viscosity rises exponentially
What are peripheral proteins?
Proteins limited to the cytoplasmic surface of the membrane forming the RBC cytoskeleton
How does an increase in plasma cholesterol effect membrane cholesterol?
An increaes in plasma cholesterol causes an increase in membrane cholesterol
=> leads to Acanthocytes
What is the role of Band 3?
Acts as an anion transporter channel
Links lipid bilayer to underlying membrane cytoskeleton (ankyrin)
Describe the Pentose Phosphate Pathway
Alternative to glycolysis
Generates NADPH and pentoses
NADPH maintains gultathione in reduced form (GSH)
RBC uses GSH to protect itself from oxidative damage
What is haemoglobin?
Hb is a globular protein
What is the role of Peripheral proteins?
- Provide rigid support & stability to bilayer
- Deformability properties for RBC
- Leads to shape change
What is a prosthetic group?
The non protein components of a conjugated protein
What does metabolism provide energy for?
- Cation pumps maintenance
- Hb maintenance in reduced state
- Reduced sulphydryl and other proteins in Hb
maintenance - RBC integrity and deformability maintenance
What are haemoproteins?
A group of specialised proteins that contain a haem group tightly bound as a prosthetic group
What is the structure of Haemoglobin?
Made of 4 polypeptide chains
2 α globin chanis and 2 β chains
What is the structure of haem?
Haem is a complex of Protoporphyrin IX and Ferrous Iron Fe2+
Iron is held in the centre of haem molecules by bonds to the 4 nitrogens of the porphyrin ring
What is the Leubering Rapoport Shunt?
A biochemical pathway in mature erythrocytes involving the formation of 2,3-DPG
What is the fnction of 2,3-DPG?
Essential for maintaining normal oxygen tension, regulating HB affinity
- regulates oxygen release from Hb and delivery to
tissues
What is the role of the Hexose monophosphate shunt?
Used for NADPH production from NADP
What happens to the methaemoglobin reductase pathway in the absence of the methaemoglobin reductase enzyme?
Methaemoglobin accumulates and can’t carry oxygen
List 2 integral proteins in red cell membranes
- Glycophorins
- Band 3
What are the key metabolic pathways for RBCs?
Glycolytic Pathway
Hexose Monophosphate Shunt
Methaemoglobin Reductase Pathway
Luebering Rapoport Shunt
Describe the methaemoglobin reductase pathway
Membrane Na+/K+ ATPase used
Produces NADPH needed by methaemoglobin reductase enzyme
Maintains iron in Ferrous state
Describe the glycolytic pathway?
- Glucose metabolised in a series of reactions forming
lactate - Generates 2 ATP for every 1 glucose molecule used
Generates 90% of energy needed by RBCs
ATP provides energy for maintenance of RBC cell volume, shape, flexibility and cation pumps
