Normal Erythropoiesis Flashcards
What are RBC’s packed with?
Haemoglobin
What do RBC’s NOT have?
No nucleus or mitochondria.
Also, no DNA/RNA
What does having no DNA/RNA mean?
There is no cell division
What is the life span of an RBC?
120 days
What is the role of the spleen in relation to RBC’s?
It removes fragile old RBC’s from circulation
RBC’s require constant ___________
REPLACEMENT
Via what process does this constant replacement of RBC’s occur?
Erythropoiesis
Where are new RBC’s produced?
In red bone marrow
What are RBC’s produced from?
Pluripotent stem cells
What engulf old RBC’s?
Phagocytic cells of the liver and spleen
Outline the 2 main components of haemoglobin.
- Haem group – made of porphyrin ring, with iron group in the middle.
- Globin – globular protein, made up of amino acids.
What are globular haemoglobin proteins broken down to?
Amino acids which enter the blood stream
What is the haem group (minus iron) converted to?
Bilirubin
What happens to bilirubin?
It is transported to the liver and secreted into bile.
- bilirubin products colour urine and faeces
What happens to iron from the haeme group?
It binds to transferrin in the blood and is recycled.
What is erythrocyte production regulated by?
The HORMONE erythropoietin (EPO).
Where is EPO produced?
In the kidney
What do cells in the kidney sense to increase the production of EPO?
Reduced oxygen-carrying capacity
Why is the fact that mature erythrocytes are shaped as a biconcave disc important?
- Diffusion distance minimised
- Surface area to volume ratio maximised
(This creates a large surface area : volume ratio, meaning more oxygen can get into the Hb effectively.)
What is the membrane of erythrocytes like?
Flexible – can deform to allow cells to squeeze in single file through capillaries
What % of the blood does plasma make up?
55%
What is plasma?
The blood without cells, treated with anticoagulant
What are RBC ion balance and cell volume actively regulated by?
Energy-dependent Na+/K+ ATPases (‘the sodium pump’).
What is the only route for ATP synthesis in RBC’s?
Anaerobic glycolysis – RBC’s have no mitochondria
What is the key fuel in anaerobic glycolysis?
ATP
What state does iron have to be in to bind oxygen?
Fe2+
What keeps iron in its Fe2+ state? Why is this important?
NADH from glycolysis.
- methaemoglobin (HbFe3+) cannot bind O2
What is some glucose metabolised through?
The ‘hexose monophosphate shunt
What does the ‘hexose monophosphate shunt produce?
NADPH, required for maintenance of adequate levels of reduced GLUTATHIONE
When is 2,3 bisphosphoglycerate (2,3 BPG) produced?
When Po2 is reduced – 2,3 BPG releases O2 from Hb
Iron is in its Fe2+ state when the oxygen binds
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NADH is a sacrificial molecule – sacrificing an electron to keep iron in its Fe2+ state
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2,3BPG is a small molecule which can influence the way Hb holds onto oxygen
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What is 2,3 BPG an important bi-product of?
Glycolysis
What is glutathione?
A tripeptide, consisting of glutamate, cysteine and glycine
What does reduced glutathione do?
Combats oxidative stress
What are free radicals?
Highly reactive molecules with unpaired
What do excessive free radicals or inadequate antioxidant defence mechanisms lead to?
Damage of cellular structures and enzymes
What is the main reactive species?
Hydrogen peroxide
The superoxide anion is a very reactive anion
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What does glutathione help protect against?
The toxic effects of reactive oxygen species (free radicals).
- it gives up its hydrogen to make water
What is (reduced) glutathione essential for?
Detoxifying hydrogen peroxide (H2O2), the primary intermediate in oxidative damage
What is needed to produce REDUCED glutathione?
NADPH from the pentose phosphate pathway
In RBC’s, what can lack of reduced glutathione lead to?
Cell damage
Why may a lack of reduced glutathione occur?
As a consequence of glucose-6-phosphate dehydrogenase insufficiency, and hence NADPH deficiency
What enzyme is needed to produce reduced glutathione?
Glutathione reductase
What are required to produce reduced glutathione (GS) from oxidised glutathione (GSSG)?
Glutathione reductase and NADPH and H+.
Why is the presence of reduced glutathione in RBC’s so important? And what would happen if it wasn’t there?
Glutathione prevents the build-up of hydrogen peroxide, minimising oxidative damage.
Inability to maintain reduced glutathione in RBC’s leads to increased accumulation of peroxides, predominantly H2O2, which in turn results in weakening of the cell wall and haemolysis. Accumulation of H2O2 also leads to increased rates of oxidation of haemoglobin (Fe2+) to methaemoglobin (Fe3+) that also weakens the cell wall.
CO2 is carried to the heart in systemic ________ blood, then to the lungs in the __________ _____________.
- Venous
2. Pulmonary artery
What part of haemoglobin does CO2 bind to?
The globin portion – NOT the haem group
What is this CO2 transport facilitated by?
Carbonic anhydrase – an important RBC enzyme. (converts CO2 into bicarbonate)
Bicarbonate is transported into the cells, then gets converted back to CO2
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CO2 produced by tissues is carried to the lungs in three forms. What are these?
- 10% dissolved in solution
- 30% Bound to Hb – carbamino-haemoglobin
- 60% As bicarbonate ion – HCO3-
Describe the structural composition of adult haemoglobin
- 4 globin (protein sub-units) – alpha-2, beta-2
* Each of these contains a single haem molecule
What does each haem group contain?
A porphyrin ring, with a single Fe2+ ion
What can each haem group bind to?
One O2 molecule
When fully saturated, what will 1g Hb bind?
1.34 ml of O2
Describe the haem group.
- Flat molecule. * Fe2+ is collated in the middle.
- Breakdown of the porphyrin ring makes bilirubin.
What does haemoglobin synthesis require?
- Synthesis of globin chains – 4 per molecule of Hb.
- Synthesis of porphyrin ring (haem group).
- Insertion of iron (Fe2+) into haem.
What is foetal Hb made of?
a2y2
What is adult Hb made of?
a2b2
What do allosteric enzymes NOT follow?
Michaelis-Menten kinetics. (i.e. not parabolic-type behaviour).
What type of curve does increasing substrate concentration (oxygen) result in?
A sigmoidal curve (NOT hyperbola
What does this sigmoidal curve indicate?
Co-operative behaviour.
What is ‘co-operativity’?
The influence that the binding of a ligand to one protomer had on the binding of ligand to another protomer in an oligomeric protein
Compared to adult Hb, what does foetal Hb have a i) higher ii) lower affinity for?
i) Oxygen.
ii) 2,3,BPG.
What does foetal Hb facilitate as it has a higher affinity for O2 and a lower affinity for 2,3,BPG?
The transfer of O2 from the mother to the foetus
