Red Blood Cell Structure and function

Question 1

What is the primary function of Red Blood Cells?

Answer 1

• Primary function of RBC is transport of respiratory gases to and from the tissues.

Question 2

What are the 3 essential factors for RBCs to carry out their function?

Answer 2

• 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.

Question 3

Describe the composition of the RBC cell membrane

Answer 3

• 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.

Question 4

Give an overview of membrane lipids and charged and uncharged phospholipids

Answer 4

• 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

Question 5

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?

Answer 5

• 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

Question 6

What percentage of the membrane do proteins make up?

Answer 6

50%

Question 7

What are the two integral membrane proteins and what are there functions?

Answer 7

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).

Question 8

Describe peripheral proteins in RBCs and give examples of 4 of them

Answer 8

• 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

Question 9

Describe the structure of Spectrins and their function

Answer 9

• 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

Question 10

What is the function on ankyrin

Answer 10

Attaches lipid bilayer to membrane skeleton via interaction of spectrin and band 3

Question 11

What is the function of Protein 4.1

Answer 11

attaches cytoskeleton to the membrane by associating with glycophorin and stabilises the interaction of spectrin and actin

Question 12

What is the function of actin in RBCs?

Answer 12

Responsible for contraction and relaxation of membrane

Question 13

What are the 4 functions of RBC membrane?

Answer 13

• 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.

Question 14

Describe the structure of haemoglobin

Answer 14

• 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

Question 15

Define prosthetic group

Answer 15

The nonprotein component of a conjugated protein, as the heam group in haemoglobin.

Question 16

What is the primary function haemoglobin and how long does it take to bond an oxygen molecule to haemoglobin

Answer 16

• Oxygen delivery to the tissues
• One Hb can bind to four O2 molecules
• Less than 0.01 sec required for oxygenation.

Question 17

What is 2,3-diphosphoglycerate (2,3-DPG), what is its function and what is the body’s primary response to increasing oxygen concentration

Answer 17

• 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.

Question 18

What does the normal oxygen dissociation curve depend on?

Answer 18

•	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.

Question 19

What are the two inherited disorders from the changes in the structure of Hb?

Answer 19

Thalassaemias and Sickle Cell Disease

Question 20

What is Haemoglobinopathies?

Answer 20

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.

Question 21

What do metabolic pathways provide energy for in RBCs?

Answer 21

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

Question 22

What are the four metabolic pathways in RBCs?

Answer 22

• Glycolytic or Embden-Meyerhof Pathway
• Hexose Monophosphate Shunt
• Methaemoglobin reductase Pathway
• Luebering-Rapoport shunt

Question 23

What is the purpose of the glycolytic pathway in RBCs

Answer 23

• 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

Question 24

What does the pentose phosphate pathway do?

Answer 24

• 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;

Question 25

What is the Methaemoglobin Reductase Pathway?

Answer 25

• Maintains iron in the ferrous (Fe++) state.

* In the absence of this enzyme, methaemoglobin accumulates and it cannot carry oxygen