Red Blood Cell Structure and function Flashcards
What is the primary function of Red Blood Cells?
• Primary function of RBC is transport of respiratory gases to and from the tissues.
What are the 3 essential factors for RBCs to carry out their function?
- RBC travels 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.
Describe the composition of the RBC 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.
Give an overview of membrane lipids and charged and uncharged phospholipids
• 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
What factors does cholesterol content effect, what happens when you increase the concentration and describe the relationship between plasma cholesterol and membrane cholesterol in RBCs?
- Membrane cholesterol is unesterified and lies between the two layers of the lipid bilayer
- The concentration of cholesterol in the membrane is an important determinant of membrane surface area and fluidity:
- Increase in membrane cholesterol leads to an increased surface area and decreased deformability.
- 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 - High SA
What percentage of the membrane do proteins make up?
50%
What are the two integral membrane proteins and what are there functions?
Integral proteins are;
Glycophorins are the major integral membrane proteins, accounting for location of RBC antigens. They impart –ve charge to cell, reducing interaction with other cells/endothelium. They are all glycophorins are receptors or transport proteins. 3 types: Glycophorins A, B, and C.
Band 3 (acts as anion transport channel). links lipid bilayer to underlying membrane cytoskeleton (ankyrin).
Describe peripheral proteins in RBCs and give examples of 4 of them
• Linked to cytoplasmic surface of membrane and forms the RBC cytoskeleton.
• It is also responsible for deformability properties of the RBC membrane, leading to shape change.
• Major peripheral proteins include:
Spectrin, Ankyrin, Protein 4.1 and Actin
Describe the structure of Spectrins and their function
• 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
What is the function on ankyrin
Attaches lipid bilayer to membrane skeleton via interaction of spectrin and band 3
What is the function of Protein 4.1
attaches cytoskeleton to the membrane by associating with glycophorin and stabilises the interaction of spectrin and actin
What is the function of actin in RBCs?
Responsible for contraction and relaxation of membrane
What are the 4 functions of RBC membrane?
- Provides shape - Provides the optimum surface area to volume ratio for respiratory exchange
- Provides deformability, elasticity allowing for passage through capillaries
- Regulates intracellular cation concentration.
- Acts as the interface between the cell and its environment via membrane surface receptors.
Describe the structure of haemoglobin
• Haemoglobin (Hb) is a globular haemoprotein
haemoproteins are group of specialised 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.
Alpha chain is 141 amino acids long
Beta chain is 146 amino acids
Define prosthetic group
The nonprotein component of a conjugated protein, as the heam group in haemoglobin.
What is the primary function haemoglobin and how long does it take to bond an oxygen molecule to haemoglobin
- Oxygen delivery to the tissues
- One Hb can bind to four O2 molecules
- Less than 0.01 sec required for oxygenation.
What is 2,3-diphosphoglycerate (2,3-DPG), what is its function and what is the body’s primary response to increasing oxygen concentration
- 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.
What does the normal oxygen dissociation curve depend on?
• The normal position of curve depends on: Concentration of 2,3-DPG H+ ion concentration (pH) CO2 in red blood cells Structure of Hb Standard conditions: Temp = 37OC pH = 7.40 BE = 0 • 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.
What are the two inherited disorders from the changes in the structure of Hb?
Thalassaemias and Sickle Cell Disease
What is Haemoglobinopathies?
Haemoglobinopathies are inherited disorders, usually autosomal recessive. Carriers (heterozygotes), with just one abnormal gene, are usually asymptomatic, whereas people who inherit an abnormal gene from both parents (homozygotes) express the disease. In most parts of the UK there is a programme of antenatal and neonatal screening for the most serious variants.
What do metabolic pathways provide energy for in RBCs?
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
What are the four metabolic pathways in RBCs?
- Glycolytic or Embden-Meyerhof Pathway
- Hexose Monophosphate Shunt
- Methaemoglobin reductase Pathway
- Luebering-Rapoport shunt
What is the purpose of the glycolytic pathway in RBCs
- 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
What does the pentose phosphate pathway do?
- 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;
What is the Methaemoglobin Reductase Pathway?
- Maintains iron in the ferrous (Fe++) state.
* In the absence of this enzyme, methaemoglobin accumulates and it cannot carry oxygen
