Week 1 - B - Normal Erythrocytes - Erythropoiesis/EPO, Erythrocyte Metabolsim (glycolysis), Pathways, Glutathionine, Co2, HbA&F Flashcards
Describe the properties of mature red blood cells? What are they also known as?
They are biconcave in shape They have no nucleus or mitochondria and no DNA or RNA - therefore no cell division can occur They live for roughly 120 days and are packed with haemoglobin Mature RBCs are also known as erythrocytes
What organ removes fragile RBCs from circulation? What is the constant production of new red blood cells known as? WHere are new red blood cells produced from?
The spleen moves fragile red blood cells out of circulation Erythropoesis is the formation of new red blood cells - production of the cells occurs in the bone marrow and they are produced from pluripotent cells
When does the red blood cell lose its nucleus?
It loses its nucleus before entering the blood stream to become a reticulocyte (loses its nucleus once it becomes a late normoblast) The proerythroblast is what the RBC poduction comes from - this is a committed cell which means it can only make a certain final cell
Phagocytic cells of the liver and spleen engulf old RBCs Globular haemoglobin proteins are broken down to amino acids which enter the blood stream WHat happens to the haem group of haemoglobin?
The haem group is broken down to biliverdin by haem oxygenase which is broken down to bilirubin to form bilirubin by biliverdin reductase The iron part of the haem group is recycled
Bilirubin is transported to the liver and secreted into bile Bilirubin breakdown products colour urine and faeces What does bilirubin bind to in the blood to reach the liver for conjugation? What does iron bind to when it is sent into the blood to be recycled?
Bilirubin binds to albumin to be transported to the liver Iron binds to transferrin when being transported through the blood
Erythrocyte production is regulated by which hormone? Where is this hormone produced?
Erythrocyte production is regulated by the hormone erythropoetin (EPO) which is produced by the interstitial fibroblasts in the kidneys
What is EPO produced in response to?
Erythropoeitn is an important hormone made in the kidney that is important in regulating erythropoiesis EPO is released in response to low oxygen levels in the blood and is released into the blood
Once EPO is released into the blood, what does it do? Erythropoietin ( EPO ) is a lineage-specific hematopoietic growth factor required for survival, proliferation and differentiation of committed erythroid progenitor cells
EPO once released into the blood travels into the bone marrow to bind to receptors on the progenitor red cells that then activates the JAK-STAT pathway which causes the development of red blood cells
Describe the change in the appearance of the red cell from proerythroblast to erythrocyte? Proerythroblast (the committed cell) is derived from the common myeloid progenitor cells What are the CMP cells derived from?
The proeryhtoblast is very blue (lots of RNA) with an open nucleus It then begins to proliferate/differentiate becoming more red as Hb is formed and the nucleus condenses- eventually the cell enucleates forming a reticulocyte which is released into the blood - & becomes an eryhtrocyte after a couple of days
The mature red blood cell is a biconcave disc in shape, describe its dimensions roughly? Is the membrane flexible or rigid?
Roughly: 8 nanometers in diameter 2 nanometers thickness at edge 1 nanometer thickness at centre This is so the surface to volume ratio is maximised The membrane is flexible - it can deform to squeeze cells through capillaries eg nephritic syndrome
What is the liquid in which red blood cells are suspended known as? What percentage of total blood volume does it make up?
The liquid in which red blood cells is suspended is known as plasma Plasma makes up 55% of the total blood volume
What percentage of the total blood volume do white blood cells and platelets make up?
White blood cells + platelets make up <1% of the total blood volume
Blood fractionation is the process of fractionating whole blood, or separating it into its component parts. How is this typically carried out?
This is typically done by centrifuging the blood. A centrifuge causes the substances that are more dense to move to the bottom of the cyclinder and subjects that are less move to the top
After put through a centrifuge, the components of blood are spearated, how does this look in the test tube?
Top layer = plasma (accounts for 55% of total blood volume) Buffy coat layer = white blood cells + platelets (accounts for <1% of total blood volume) Red blood cells (erythrocytes) = are packed at the bottom of the centrifuge
- * When put through a centrifuge all the red cells will go to the bottom because they are far denser, the white cells would form a thin buffer coat on top with the plasma being at the top
- * The only way of determining whether seomne was anaemic or not would be by carrying this out in a centrifuge in the old days
What is is the fraction of the total volume for which the red blood cells make up known as?
This would be the haematocrit
RBC ion balance and cell volume are actively regulated by energy-dependent Na+/K+ ATPases (‘the sodium (potassium) pump’) What is required for this pump? Which ions enter and which leave the cell?
The sodium potassium pump taking place in the red blood cell to regulate ion balance and cell volume requires ATP 3 sodium are pumped out of the red blood cell and 2 potassium are pumped in (this is an active transport system by ATP as both ions are being pumped against their concentration gradient)
What is the purpose of the Na+ K+ ATP ase pump?
This is in place to regulate the cell ion balance but also to prevent the cell from swelling and therefore regulating its volume 3 sodium and pumped out of the cell and 2 potassium are pumped in
Red blood cells have no mitochondria and therefore how do they make ATP?
Red blood cells make ATP via glycolysis (anaerobic respiration)
Defects in ATP synthesis are associated with loss of cell volume, increased RBC rigidity, decreased survival What is it produced from glycolysis that helps to keep iron in the Fe2++ state? Why is this important?
NADH from glycolysis helps keep iron in Fe2+ state by giving up its own electron This is important as methaemaglobin (HbFe3+++) cannot bind oxygen and Fe3+ is toxic if transported unbound
There are three important linked pathways involved in red blood cells glycolysis What is the important pathway known as that generates ATP (energy) and NADH (to help reduce Fe3+ (metHb) to Fe2+ (Hb)) Why is this pathway important? What is the difference between ferric and ferrous?
This is known as Embden-Myerhof Pathway (basically anaerobic glycolysis pathway) This pathway is important as oxygen iron in the heme group will not be Fe3+ (its ferric state) and will instead by Fe2+ (its ferrous state) and therefore can bind oxygen FerrIC is toxIC - Fe3+ Ferrous is Fe2+ - not toxic
In the glycolysis reaction, glucose-6-phophate is usually converted to fructose-6-phosphate Some glucose is metabolised through a pathway known as the ‘hexose monophosphate shunt’ What happens in this pathway?
In the hexose monophophatase shunt - glucose-6-phosphate gives up a hydrogen via an enzyme to regenerate NADPH which is regenerates glutathionine, which is a key molecule which helps prevent oxidative stress
When NADP+ is reduced to NADPH by glucose 6 phosphate dehydrogenase converting G6P to hexose monophosphate and therefore providing the hydrogen ion, what is the enzyme that uses the reduced NADPH to convert GSSG (oxidised glutathionine) to GSH (reduced glutathionine)?
This would be glutathionine reductase
Describe all three linked pathways?
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Glutathionine is a tripeptide consisiting of glutamate, cysteine and glyciene Is it reduced or oxidised glutathionine that combats oxidative stress? What pat of the glutathionine contains the sulfur hydride part?
It is reduced glutathionine (GSH) that combats oxidative stress Cysteine is the part of the glutathionine that contains the SH
Glutathione helps protect against the toxic effects of reactive oxygen species (free radicals) (Reduced) glutathione is essential to detoxify hydrogen peroxide (H2O2), the primary intermediate in oxidative damage What is the only source of glutathionine for erthrocytes? (GSH)
Hexose monophosphatase pathway NADPH from the hexose monophosphates shunt is essential for the formation of glutathionine as well as
The enzyme glucose-6-phosphate dehydrogenase is important as without this enzyme, NADP+ would not be able to be reduced to NADPH when G6P is oxidised (to form hexose monophosphates) and therefore the concentration of gluathionine would be majorly reduced resulting in oxidative damage to the red blood cells
The inability to maintain reduced glutathione in RBCs leads to increased accumulation of peroxides, predominantly H2O2, that in turn results in a weakening of the cell wall and concomitant haemolysis. Accumulation of H2O2 also leads to increased rates of oxidation of haemoglobin (Fe2+) to methaemoglobin (Fe3+) that also weakens the cell wall. Ferric haeme cannot bind O2.
What is the enzyme that converts hydrogen peroxide to molecules of water?
- Glutathionine peroxidase
- G6PD converst the G6P to hexose monophosphates, resulting in the reducing of NADP+ to NADPH from which GSSG can be reduced to GSH by the enzyme glutathionine reductase.
- Glutathionine peroxidase used reduced glutathionine to convert hydrogen peroxidase to 2 water molecules
WHat is the ion channel that allows for bicarbonate ions to enter the lungs so that CO2 can be blown off?
This would be the Chloride/Bicarbonate ion exchange channel Red colour is arterial phase Darker red is venous phase Follow each of the colours separately
How many oxygen molecules (O2) can each haem bind? 4 globin (protein) sub-units, each containing a single haem molecule Haem group contains a single Fe2+ ion When fully saturated, 1g Hb will bind what volume of oxygen?
Each haem group binds one O2 molecule and each haem group contains one Fe2+ ion When fully saturated, each haem group will bind 1.34 ml of oxygen
What causes the oxyhaemoglobin curve to shift to the left or right? Three things shift to the right Two things shift to the left
Shift to the left -
- * Decreased 2,3 BPG
- * Decreased CO2 (causes increase pH)
- * Decreased temp
Shift to the right -
- * Increased 2,3 BPG
- * Increased CO2 (causes decreased pH)
- * INcreased temp
What is the effect known as where there is a decreased affinity of Hb for oxygen due to an increase in CO2? How does this work?
This is the Bohr effect and it shifts the oxgen dissociation curve to the right The increase in CO2 causes a decrease in pH In low pH, this affects the Hb ability to hold on to oxygen and therefore Hb releases more O2
Clinically, what pressures are very important in the oxygen dissociation curve? They account for venous and arterial pressures
Venous pressure - 5.3kPa Arterial pressure - 13.3kPa Arterial blood gases remember range the arterial partial pressure of O2 form - 10.5 to 13.5 kPa
Why does foetal haemoglobin have a higher affinity for oxygen than adult?
The γ globins in HbF have a reduced affinity for 2,3BPG Because the γ subunit has fewer positive charges than the (adult) β subunit, 2,3-BPG is less electrostatically bound to HbF compared to HbA This lowered affinity facilitates the movement of O2 from mother 2feotus
- What type of respiration occurs in glycolysis? WHat is formed?
- What is the ion channel to pump ions to stop swelling in the red blood cells?
- What else is produced by the Embden-Myerhof pathway?
- What is the main reactive oxygen species?
- What is the ion channel that allows CO2 to be blown off?
- * Anaerobic respiration takes place in glycolysis -net gain of 2ATP
- * The ion channel that stops swelling in RBCs is the Na+/K+/ATPase ion channel
- * ATP and NADH are formed from glycolysis - NADH important for the Embden-Myerhof pathway as it can reduce Fe3+ to Fe2+
- * Main reactive oxygen species is hydrogen peroxide - glutathionine peroxidase converts this to water
- * The ion channel that allows blowing of CO2 is the chloride/bicarbonate channel
