03-11-22 – Gas Transport Flashcards
Learning outcomes
- List the ways by which oxygen is carried in the blood
- Recognise what proportion of oxgyen is carried in each form
- Describe the oxygen-haemoglobin dissociation curve
- Explain the physiological significance of the shape of the curve
- Describe the factors that cause the curve to shift to the right or to the left
- Calculate how much oxygen is carried in the blood
- List the ways by which carbon dioxide is carried in the blood
- Recognise what proportion of carbon dioxide is carried in each form
- Describe the role of the red blood cells in carbon dioxide carriage
- Describe how carbon dioxide is converted to bicarbonate
What is one of the primary functions of the CVS?
Where is CO2 expired?
How are Oxygen and CO2 able to move by diffusion?
Where is Oxygen and CO2 partial pressure high and low?
How does partial pressure change affect diffusion of gas?
What is this principle the basis of?
- One of the primary functions of the cardiovascular systems is to transport O2 from the lungs to all tissues in the body and CO2 from the tissues to the lungs
- The lungs expire this CO2 to the atmosphere
- Oxygen and CO2 can diffuse (passive) as both gases move by diffusion down their partial pressure gradients (also down their concentration gradients)
- Oxygen partial pressure is high in the air, and low in the tissues
- CO2 partial pressure is high in the tissues and low in the air
- These both allow the gases to move down their partial pressure gradient
- If the partial pressure in the liquid becomes greater than in the air, the gas will diffuse out of the liquid, and vice versa, due to gases flowing down partial pressure gradients
- This is the basis for O2 moving into the blood from the lungs, whereas C02 moves out of the blood into the lungs
What 2 ways can oxygen be transported in the blood?
What is the amount of O2 dissolved in blood dependent on?
What formula does Henry’s law state at equilibrium for a given temperature?
How can this be used to calculate the oxygen delivered to tissues form plasma per minute at rest?
How much O2 does our body consume at rest?
What does this system need?
- Oxygen is transported in blood in two ways:
1) Physically dissolved in plasma ~2%
2) Combined with haemoglobin ~98% - Amount of O2 dissolved in plasma depends on its solubility and partial pressure in blood (Recall Henry’s Law)
- Henry’s law states that at equilibrium for a given temperature:
- [O2]Dis = solubility O2 x PO2
- At 37C the solubility of O2 in plasma is poor - only 0.03ml/L/mmHg
- Partial pressure of O2 in arterial blood is ~100 mmHg
- Therefore, only 3ml O2/L of blood can be transported in solution
- Equates to 15ml O2/min delivery to tissues from plasma per minute (as CO is 5L/min at rest)
- At rest, our body consumers 250ml of O2/min at rest, so this system is inadequate and required haemoglobin as an oxygen carrier
What is the structure of normal haemoglobin (HbA) like?
What does each chain have?
How many molecules of O2 can bind to each Hb?
In what state of Haem can oxygen bind?
What other state can it exist in?
What does this lead to the formation of?
How can this be converted back to the other form of Haemoglobin?
How does foetal and adult haemoglobin differ?
How does sickle cell anaemia haemoglobin (HbS) differ?
How does this change red blood cells?
- The structure of normal haemoglobin (HbA) is a tetramer consisting of 2 α (alpha) and 2 β (beta) globin chains
- Each chain has a haem group consisting of a porphyrin ring surrounding an Fe2+ molecule, with the iron being able to bind 1 molecule of O2 (so 4 total molecules of O2 can bind per molecule of Hb)
- O2 can only be bound in Fe2+ (ferrous state)
- If iron oxidised to ferric (3+) state leads to methaemoglobin (~1.5% Hb is in this state)
- Methaemoglobin reductase uses the NADPH chain to reduce metHb back to Hb
- In Fetal haemoglobin (HbF), the β- chains are replaced by γ-chains
- In sickle cell anaemia haemoglobin (HbS), glutamate at position 6 in the β- globin is replaced with a valine.
- This causes haemoglobin to aggregate, which gives the red blood cells a sickle shape instead of being a concave disk
How does Hb exist in a tensed and relaxed state?
What bonds exist in the tensed state?
What is the consequence of this conformation?
What happens when oxygen binds?
How does the colour of blood change when oxygen binds?
What else does Hb bind?
How does this affect oxygen binding to Hb?
- Deoxygenated Hb exists in a tensed state (T) compared with oxygenated Hb in a relaxed state (R)
- In the tensed state, strong ionic bounds form between the 4 polypeptide chains, causing the chains to be immobile and apart
- The consequence of this is that the Fe lies deeper in the pocket and cannot bind O2
- As O2 binds, the ionic bonds break and the Fe moves to the plane of the porphyrin rings – relaxed state
- The colour of blood changes from dark blue to bright red when oxygen binds to Hb
- Hb also binds 2,3 DPG, which alters the conformation of Hb, decreases the affinity of Hb for oxygen, and causes the release of oxygen from Hb
What is cooperation?
How does this affect the shape of the oxygen dissociation curve?
How many ml of oxygen do we deliver to tissues at rest?
How many molecules of oxygen from haemoglobin do we give up at rest?
What is this important for?
What is the colour change of blood during oxygenation used for?
- Cooperation is when the binding of one O2 molecule to Hb increases the affinity of Hb for binding O2, which makes it easier for the subsequent 3 molecules of O2 to bind
- This leads to the oxygen dissociation curve being very steep, as once the first molecule of O2 binds, the remaining 3 will bind quickly, leading the Hb being full saturated
- At rest, we deliver 47ml of Oxygen per L/min to tissues, so we deliver, 235ml/min to tissues, as CO is 5L/min at rest
- At rest, we are only really giving up about 1 molecule of oxygen from haemoglobin before the Hb returns back to the lungs to become full saturated again
- This means we have a large spare capacity of oxygen in Hb, which is important for exercise
- The colour change rom oxygenation of blood is utilised clinically to measure the O2 saturation of blood using the pulse oximeter
What is O2 capacity?
What does it depend on?
How many ml of oxygen does each g of fully saturated Hb carry?
How can the maximal O2 bound to Hb be calculated from this (in picture)?
How much do we use at rest?
What volume of oxygen is delivered to tissues at rest per minute?
How can % of Hb be calculated (in picture)?
- O2 capacity is amount of O2/L of blood attached to Hb at full saturation
- O2 capacity depends on the Hb concentration in blood
- Each g of Hb, when fully saturated, carries 1.35ml of O2
- The maximal O2 bound to Hb is calculated as 203ml O2/L of blood, but we only use 47ml/L at rest
- This means we deliver 235ml of O2/min to tissues at rest (47mlx5, as CO is 5L/min at rest)
What does a left shift in the oxygen dissociation curve mean?
What 2 types of Hb cause a left shift in the oxygen dissociation curve?
Why is this?
Why is having HbF an adaptive advantage?
Why is it no longer an adaptive advantage after we are born?
How long does it take to convert all HbF to HbA?
What is myoglobin?
Where is it found?
What is it used for?
What happens after myoglobin stores are used?
- A left shift in the oxygen dissociation curve means the affinity of Hb for binding Oxygen is increased, as the PO2 level required to bind oxygen to Hb is decreased
- MyHb and HbF have a left-shifted oxygen dissociation curve
- This is because the gamma chains of HbF have a higher affinity to binding oxygen due to special properties of the 2 gamma chains
- Having HbF is an adaptive advantage, as this left shift in the oxygen dissociation curve allows foetal haemoglobin to take up oxygen at lower PO2 levels that would be found in the placenta
- HbF is no longer an advantage after we are born, as the PO2 level would never be low enough for oxygen to be released from HbF
- It may take up to 2 years to convert all HbF to HbA
- Myoglobin is a dark red pigment found only in muscles
- It acts as a last-ditch small oxygen reserve for severe exertion.
- After Myoglobin stores are used, anaerobic respiration takes place
What 4 factors affect the affinity of Hb for O2?
How do they each do this?
How do they each affect the oxygen dissociation curve (in picture)?
What do left and right shifts of oxygen dissociation curve mean for O2 affinity of Hb?
When might you see these shifts?
- 4 factors affect the affinity of Hb for O2:
1) CO2
2) H+
3) 2,3 DPG
4) Temperature - They each do this by affecting the globins
- A left shift of the oxygen dissociation curve means the O2 affinity of Hb is high, as Hb is moved to a high affinity relaxed state
- This happens in the pulmonary capillaries of the lungs, where it is important for Hb to bind O2
- A right shift of the oxygen dissociation curve means the O2 affinity of Hb is low, as Hb is moved to a low affinity tensed state
- This happens in the systemic capillaries of the tissues, where it is important for Hb to release O2
What is respiratory acidosis a response to?
What was the observation of Bohr?
What is the Bohr effect?
What are the 2 components of respiratory acidosis?
Which component accounts for most of the Bohr effect?
- Respiratory acidosis is your body’s response to having too much carbon dioxide (CO2) in your lungs
- Bohr observed that respiratory acidosis shifted the Hb-O2 dissociation curve to right
- The Bohr effect states Haemoglobin’s oxygen binding affinity is inversely related both to acidity and to the concentration of carbon dioxide
- This respiratory acidosis has two components:
1) Increase in PCO2 (increased CO2 blood concentration - Hypercapnia)
2) Decrease in pH (more acidic) - decreased ratio of arterial bicarbonate to arterial pCO2 (acidic), which results in a decrease in the pH of the blood - Changes in pH account for most of Bohr effect, with changes in PCO2 being a small portion of the Bohr effect
How does temperature affect the O2 binding of Hb?
What are 2 ways metabolic acidosis can occur?
How does decreased pH from metabolic acidosis affect the oxygen dissociation curve?
What does Hb act as for H+?
How does H+ concentration affect the structure and affinity for O2 of Hb?
- Temperature affects the O2 binding capacity of Hb by affecting Hb structure
- Metabolic acidosis develops when:
1) There is too much acid is produced in the body
2) Kidneys cannot remove enough acid from the body - Decreased pH from metabolic acidosis leads to a right-shift of the oxygen dissociation curve
- Hb is a good buffer for H+
- As [H+] increases, conformational change in Hb structure and O2 affinity reduces, leading to a right-shift in the oxygen dissociation curve and oxygen being released from Hb
How does increased PCO2 affect Hb structure?
What does this form?
How does affect Oxygen binding affinity in Hb?
How does this affect the oxygen dissociation curve?
- PCO2 increases leads to Hb buffering CO2 through CO2 combining with unprotonated amino group on Hb, forming carbamino groups
- This leads to the formation of carbamino haemoglobin
- This destabilises Hb, so oxygen is released more easily
- This leads to a small right shift of the oxygen dissociation curve
What do RBCs not have?
What do decreasing PO2 levels in RBCs stimulate in RBCs?
How does 2,3 DPG interact with Beta chains of Hb?
How do increased 2,3 DPG levels affect the oxygen dissociation curve?
How does 2,3 DPG interact with gamma chains of HbF?
What does this allow HbF to do?
- RBCs don’t have mitochondria, meaning they only undergo glycolysis, not aerobic respiration
- Decreasing PO2 levels in RBCs stimulate glycolysis in RBCs, resulting in increased levels of 2,3 DPG (as 2,3 DPG is a by-product of glycolysis)
- 2,3-DPG interacts with β chains, destabilising interaction of O2 with Hb
- This disrupts the structure of Hb, leading to oxygen being released more easily
- Increased 2,3 DPG levels lead to a small right-shift of the oxygen dissociation curve
- 2,3 DPG can bind less well to the gamma chains of HbF
- This means increased 2,3 DPG levels won’t bring about the same effects in HbF as seen in HbA
- This allows HbF to hold onto oxygen, and to bind oxygen at lower PO2 levels, like those that would be found in the placenta
What 3 things can also bind to and relax Hb?
What is the CO binding affinity of Hb like?
How does this effect maximal O2 capacity?
How does CO affect the oxygen dissociation curve?
- 3 things that can also bind to and relax Hb:
1) CO
2) NO
3) H2S - CO has a 200-fold greater affinity for Hb than O2
- Maximal O2 capacity falls to extent that CO binds
- O2 capacity is amount of O2/L of blood attached to Hb at full saturation
- CO also increases O2 affinity of Hb and shifts dissociation curve to left
- This leads to Hb does not release O2 when it gets to tissue, leading to hypoxia
How much CO2 does metabolism generate a minute?
How does solubility of CO2 in plasma compare to that of O2?
What are 2 ways CO2 is transported in the blood?
- Metabolism generates 200 ml CO2/min at rest
- Solubility of CO2 in plasma is 20 times that of O2
- CO2 is transported in blood in two main ways:
1) In plasma
* Physically dissolved
* Combined with plasma proteins or as bicarbonate (HCO3-) ions
2) In red blood cells
* In physical solution
* Combined with Hb or as bicarbonate ions
Describe the 6 steps of CO2 travelling in the plasma or red blood cells from tissues?
What are the 3 fates of CO2 exiting tissues?
What % of CO2 ends up as each?
- 6 Steps of CO2 travelling in the plasma or red blood cells from tissues:
1) CO2 exits tissue cells by going through endothelial capillary cells and entering the plasma
2) Some CO2 is dissolved in the plasma, while some enters red blood cells going through the capillaries
3) When CO2 enters the RBC, is it combined with water and converted to HCO3- (bicarbonate) and H+ ions
4) HCO3- is goes from the RBC to the plasma via HCO3- and Cl- exchanger
5) H+ binds to the haemoglobin in the RBC and enhances O2 release by decreasing pH and right-shifting the oxygen dissociation curve
6) Protonated haemoglobin becomes a substrate for carbamino formations, leading to carbaminohaemoglobin formation, which also increases oxygen release from Hb
- 3 fates of CO2 exiting tissues:
1) HCO3- (70% of CO2)
2) CO2 dissolved in plasma (10%)
3) Carbaminohaemoglobin (20%)
How does CO2 release in lungs compare to CO2 transport in tissues (previous card)?
What 5 things happen during CO2 release in the tissue?
- In CO2 transport in lungs, the complete opposites happens from CO2 transport in tissues (previous card)
- 5 things that happen during CO2 transport in the lungs:
1) Partial Pressure gradients for O2 and CO2 reverse
2) High PO2 causes H+ to dissociate from Hb
3) H+ and HCO3- combine to form CO2 and H2O
4) HCO3- from blood plasma re-enters RBCs from the HCO3- and Cl- exchanger and combines with H+ to form H2CO3 (carbonic acid) which dissociates to release CO2 and H2O
5) The dissolved CO2 in the blood plasma and the CO2 formed from these reactions in RBCs enters the lungs and is breathed out
What do the CO2 dissociation curves demonstrate?
What 3 things does carriage of CO2 in blood depend on?
What is the relationship between PO2 and PCO2 in physiological ranges?
What is the Haldane effect?
When does Hb CO2 carrying capacity rise and fall?
- The CO2 dissociation curves demonstrates how changes in PCO2 affect total CO2 blood content
- 3 things carriage of CO2 in blood depends on:
1) PCO2
2) Plasma pH
3) PO2 - There is a near linear relationship between PCO2 and PO2 in physiological range
- The Haldane effect is upshift of the CO2 dissociation curve with decreasing PO2
- As blood enters systemic capillaries and Hb releases O2, Hb CO2 carrying capacity rises
- As blood enters pulmonary capillaries and Hb binds O2, Hb CO2 carrying capacity falls and blood dumps CO2
