Haematology- Red blood cells Flashcards
Describe the structure of a red blood cell
Biconcave
8 microns diameter but pass through 3 microns capillaries
What is the composition of the red cell membrane?
- 50% proteins
- 40% lipids
- 10% carbohydrates
Describe the structure of the red blood cell membrane
Semi- permeable lipid bilayer, with proteins scattered throughout
Has:
- An outer hydrophilic layer
- Central hydrophobic layer
- Inner hydrophilic layer
What is the outer hydrophilic layer composed of?
Glycolipids, glycoproteins, and proteins
What does the central hydrophobic layer contain?
Proteins, cholesterol and phospholipids
What does the inner hydrophobic layer contain?
Mesh-like cytoskeletal proteins to support lipid bilayer
Describe the lipid composition of the red blood cell membrane
- Phospholipids - 60%
- Cholesterol- 30% - unesterfied free cholesterol between 2 layers
- Sphingoloids - 10%
The distribution of phospholipids is asymmetrical. What are the uncharged phospholipids in the outer layer?
- Phosphatidyl choline (PC)
- Sphingomyelin (SM)
What are the charged phospholipids in the inner layer?
- Phosphatidyl ethanolamine (PE)
- Phosphatidyl serine (PS)
What 2 types of proteins are in the red blood cell membrane?
Where are they in the cell membrane?
- Integral membrane proteins - traverse entire lipid bilayer membrane
2- Peripheral proteins- limited to cytoplasmic surface of membrane and forms RBC cytoskeleton
What are the 2 major integral proteins?
- Glycophorins
- Band 3
These are anion transporters
What does the cytoskeleton do for a RBC?
Acts as a tough framework to support the bilayer, and is responsible for deformability (ability of a material to change its shape or size under influence) and maintaining its biconcave shape.
What are the 4 major peripheral proteins?
-Spectrin
-Ankyrin
-Protein 4.1
-Actin
Describe spectrin
Most abundant of peripheral proteins, composed of alpha + beta chains.
Very important in RBC membrane integrity, binds with other peripheral proteins to form cytoskeletal network of microfilaments, responsible for biconcave shaped of RBC
If this becomes denatured, red cells become spherical and lose flexibility
Describe Ankyrin
Family of adaptor protein, interacts with band 3 and spectrin to achieve linkage between bilayer and cytoskeleton
Describe protein 4.1
Major structural element- links cytoskeleton to membrane by means of its associations with glycophorin and stabilises interaction of spectrin with actin
Describe Actin
Abundant protein in cell membrane- responsible for contraction and relaxation of membrane. Allows movement of cell surface enabling cells to migrate, engulf particles and divide.
Where are the carbohydrates on the RBC membrane?
Only on the external surface, attached to proteins and lipids
How do carbohydrates attach to proteins and lipids?
By a process called glycosylation
What does the carbohydrate do for a red blood cell?
Gives the cell identity, the distinguishing factor for human blood types (you know A, B, O, AB), they are what give the blood a group
Where are blood group antigens found?
On red cell membrane and these determine our blood group.
Many antigens are proteins e.g. Rhesus , and these proteins give other info to the red blood cell
Other antigens are carbohydrates e.g. ABO
Describe the structure of Haemoglobin
Globular protein that contains:
- Haemoproteins
- Haem
- Iron
What are haemoproteins?
A group of specialised proteins that contain haem as a tightly bound prosthetic group
What is haem a complex of?
A complex of protoporphyrin (IX) and ferrous iron (Fe2+)
Where is iron in red blood cells?
Iron is held in the centre of haem molecules by bonds to 4 nitrogen of a porphyrin ring (this is a biochemical molecule bound to nitrogen)
What is the main function of haemoglobin?
- To carry oxygen to tissues and return carbon dioxide from tissues
What is the ratio of Hb molecules to number of binding oxygen?
1 Hb molecule binds to 4 O2 molecules
What is the most abundant Hb composition of adult Hb?
2 alpha haem groups and 2 beta haem groups.
This accounts for 96-98% of Hb in blood when in the normal range
What is the less abundant composition of Hb in adult Hb 2? Also known as Hb A2
- Hb is made of 2 alpha haem groups and 2 delta haem groups
- This accounts for 1.5-3.2% of Hb in blood when in the normal range
What is the composition of foetal hameoglobin (HbF)?
- Hb F has 2 alpha haem groups and 2 gamma haem groups.
- This accounts for 0.5-0.8% of Hb in blood when in the normal membrane
How does membrane cholesterol exist in the red cell membrane?
In free equilibrium with plasma cholesterol
What happens if there is an increase in free plasma cholesterol in the RBC membrane?
- Results in an accumulation of cholesterol in RBC membrane
What happens to the structure of the RBC membrane when there’s increased cholesterol?
- They become acanthocytes- these are dense, shrunken, and irregularly shaped red blood cells with spikes on the outside.
What are target cells (codocytes)?
Erythrocytes (RBC) with an increased cell membrane:volume ratio
They look like a target, as in a target for shooting arrows.
What causes target cells (codocytes) ?
An increase in cholesterol and phospholipid is a cause of target cells.
They can also result from a decrease in intracellular haemoglobin
Describe hereditary spherocytosis and how it causes damage to the cell membrane
-An inherited blood disorder in which red blood cells are very round and have trouble changing their shape.
This makes moving through small blood vessels difficult, therefore the red blood cells stay in the spleen longer, causing harm to the cells’ membrane.
What are the causes of spherocytosis?
Why do they cause spherocytosis?
- Ankyrin deficiency or abnormalities - this leads to a decrease in spectrin assembly on the membrane, causing a loss in the biconcave shape
- Alpha or beta deficiency or abnormalities
- Protein 4.1 abnormalities - this will affect the binding of the other peripheral proteins that maintain the cytoskeleton of the red blood cell
- Band 3 protein abnormalities - prevents the linking of band 3 and spectrin, inhibiting the maintenance of the biconcave structure
Describe hereditary elliptocytosis
What does the spleen do to these red blood cells?
- Red blood cells are elliptically shaped (elongated, oval shape). These can be called elliptocytes.
- The spleen captures and eliminates these abnormal elliptocytes, resulting in hemolytic anemia (this is when the red blood cells are being destroyed faster than they’re being produced.
What are haemoglobinopathies?
Medical term for a group of inherited blood disorders involving Hb
What are 2 haemoglobinopathies?
(Haemoglobin disorders)
1- Thalassaemias - results in no production or too little production of haemoglobin, causing anaemia
2- Sickle cell disease- Hb is abnormal shape, resulting in RBC to be rigid and shaped like a ‘C’ or sickle
What is microcytosis?
Presence in blood of significant numbers of erythrocytes that are SMALLER than normal
What is macrocytosis?
Condition where red blood cells are LARGER than normal
What is anisocytosis?
Presence of red blood cells of VARYING SIZES
What is poikilocytosis?
Presence of red blood cells of VARYING SHAPES
How do red blood cells generate energy?
Through anaerobic oxidation of glucose via glycolysis via the glycolytic pathway
What other way can red blood cells produce energy?
Via the hexose monophosphate shunt (HMS) (or can be called pentose phosphate pathway)
Why must red blood cells generate ATP?
- To survive the 120 days it needs to live
- To maintain red cell shape and deformability
- To regulate intracellular cation conc. via cation pumps (Na/K pump)
What are disorders of the glycolytic pathway and what is the result of this?
- Pyruvate Kinase (PK) deficiency
- ATP is depleted, cells lose large amount of potassium and water, become dehydrated and rigid
- This causes chronic, non-spherocytic haemolytic anaemia.
What does NADPH do?
- Protects the RBC from oxidative damage, maintains glutathione (a redox active, small molecule critical to cellular and organism health) in reduced state (GSH)
What are disorders of HMS and what are the results of this?
- Generation of NADPH and GSH impaired
- This causes acute haemolysis on exposure to oxidant stress- oxidative drugs, fava (broad) beans or infections.
- Hb precipitation- Heinz bodies- This occurs from oxidative injury resulting in denatured (oxidised), precipitated haemoglobin that tends to adher to the inner surface of RBC membranes.
- G6PD deficiency- this is the most common enzymopathy (genetic disorders affecting cellular metabolism). This deficiency means the body doesn’t have enough G6PD enzyme, so red blood cells break down faster than they usually would, resulting in haemolytic anemia.
What is meant by precipitation?
A process where soluble antigens bind with their specific antibody, resulting in the formation of an insoluble precipitate.
How does the lipid bilayer binding to the cytoskeleton help a RBC?
- Helps maintain flexible biconcave shape with ability to deform
- Biconcave shape also provides optimum SA:V ratio for gas exchange
How does having proteins traverse throughout the lipid bilayer benefit RBC?
These proteins serve as transporters of anions, water and glucose
How does the RBC having no nucleus or mitochondria and just having Hb benefit it?
- Hb allows the RBC to perform its primary function:
Bind to O2 to form oxyhaemoglobin and transport oxygen from lungs to tissues
Binds to CO2 to form carbominohaemoglobin (HbCO2) and transport carbon dioxide from tissues
What are the purposes of the 2 main metabolic pathways of the blood?
- Generates ATP to maintain intracellular cation concentration and cell shape
- NADPH and GSH to protect against stress and Hb precipitation
