Gas Transport and Exchange Flashcards
What is Dalton’s law
Pressure of a gas mixture is equal to the sum (Σ) of the partial pressures (P) of gases in that mixture
What is Fick’s law?
Molecules diffuse from regions of high concentration to low concentration at a rate proportional to the concentration gradient (P1-P2), the exchange surface area (A) and the diffusion capacity (D) of the gas, and inversely proportional to the thickness of the exchange surface (T)
What is Henry’s Law?
At a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid
What is Boyles law?
At a constant temperature, the volume of a gas is inversely proportional to the pressure of that gas
What is Charles law?
At a constant pressure, the volume of a gas is proportional to the temperature of that gas
Nomenclature
Name the 5 gas Laws and their defenitions?
Inspiratory Gases
If you are giving someone oxygen therapy, you supplement the amount of oxygen in the air
As the patient has a diffusion problem, you need to make the diffusion gradient steeper
Altitude - as you get higher the pressure of the atmosphere decreases but the PROPORTIONS OF THE GASES REMAINS THE SAME
Analogy - they are the same portions of a smaller pie - everything has decreased
Inspiratory Gases
In dry air, you have 21.3 kPa of oxygen
Through the conducting airways there is a slight reduction in PO2 and an increase in PH20
Why is this?
Inspiratory Gases
In dry air, you have 21.3 kPa of oxygen
Through the conducting airways there is a slight reduction in PO2 and an increase in PH20
The increase in PH20 is because the dry air gets warmed, humidified, slowed and mixed as it passes down the respiratory tree
By the time you get to the respiratory airways, you have about 13.5 kPa of oxygen - this is 100% saturation
Oxygen Solubility
You can only dissolve 17 mL of oxygen in your body at 0.34 mL/dL
This is completely inadequate to support life when our VO2 (oxygen consumption) is around 250 mL/min at rest
We can’t rely solely on dissolved oxygen to keep us alive- THATS WHY WE HAVE HAEMOGLOBIN
Haemoglobin
Haemoglobin monomers have a ………. at the centre of the ……………….. ……………. ………… (GREEN BIT) connected to a protein chain (………….), covalently bonded at the proximal …………….. residue
Each haem binds …………. molecule of oxygen
Haemoglobin exists as a …………….. which ….. alpha and …… beta chains - this is normal haemoglobin and is represented as HbA
There is a normal variant of haemoglobin called HbA2 - this has 2 alpha and 2 ……………. chains - this constitutes about 2% of all haemoglobin
Foetal haemoglobin (HbF) is present in trace levels and consists of 2 alpha and 2 ……………. chains
Haemoglobin has a ………….. affinity for oxygen when it is not bound to any oxygen
Eventually, an oxygen molecule will bump into it and bind
When it binds, there will be a ………………..change where the structure relaxes and gets a ………………. affinity for oxygen - then more and more oxygen will bind
There is also a change in the middle of the tetramer - there will be a conformational change which makes the middle a binding site for ……………… - this is a glycolytic by-product
What is 2,3-DPG and what is it directly porportional to?
What effect does 2,3-DPG have on the oxygen in the hameoglobin molecule?
2,3-DPG …………………….. the affinity of haemoglobin for oxygen
Haemoglobin is ………………… - it will change shape depending on what is bound or not bound
Haemoglobin
Haemoglobin monomers have a (Fe2+) at the centre of the tetrapyrrole porphyrin ring connected to a protein chain (globin), covalently bonded at the proximal histamine residue
Each haem binds ONE molecule of oxygen
Haemoglobin exists as a tetramer which 2 alpha and 2 beta chains - this is normal haemoglobin and is represented as HbA
There is a normal variant of haemoglobin called HbA2 - this has 2 alpha and 2 delta chains - this constitutes about 2% of all haemoglobin
Foetal haemoglobin (HbF) is present in trace levels and consists of 2 alpha and 2 gamma chains
Haemoglobin has a low affinity for oxygen when it is not bound to any oxygen
Eventually, an oxygen molecule will bump into it and bind
When it binds, there will be a conformational change where the structure relaxes and gets a greater affinity for oxygen - then more and more oxygen will bind
There is also a change in the middle of the tetramer - there will be a conformational change which makes the middle a binding site for 2,3-DPG - this is a glycolytic by-product
When ATP is being produced in large amounts, more 2,3-DPG is produced so it is reflective of metabolism
When metabolism is higher you want more oxygen so the 2,3-DPG will bind to the haemoglobin and squeeze OUT the oxygen so there is more available for the respiring tissue
2,3-DPG DECREASES the affinity of haemoglobin for oxygen
Haemoglobin is ALLOSTERIC - it will change shape depending on what is bound or not bound
ANALOGY
Haemoglobin is a party and oxygen is people
If there is no one at the party, then you wont want to go
As the party becomes bigger, everyone wants to go
A lot of people are wanting to be the last people to arrive at this really good party
This is called ………………………… - it will change its shape and affinity based on how much oxygen is bound
This is called COOPERATIVITY - it will change its shape and affinity based on how much oxygen is bound
- Each ferrous haem molecule can bind one molecule of O2
- Therefore, each haemoglobin molecule can bind 4O2
- If the ferrous iron (Fe2+) is further oxidised to its ferric form (Fe3+), the Hb molecule becomes ……………………………………
- ………………………. does not bind oxygen; ………………………. can cause a functional anaemia (i.e. normal Hct, normal PCV, but impaired O2 capacity)
- ………………………. oxidise Hb into ferric MetHb
- Each ferrous haem molecule can bind one molecule of O2
- Therefore, each haemoglobin molecule can bind 4O2
- If the ferrous iron (Fe2+) is further oxidised to its ferric form (Fe3+), the Hb molecule becomes methaemoglobin (MetHb)
- MetHb does not bind oxygen; methaemoglobinaemia can cause a functional anaemia (i.e. normal Hct, normal PCV, but impaired O2 capacity)
- Nitrites oxidise Hb into ferric MetHb
With the people sat near you, try to think of a reason why a linear oxygen dissociation curve would be not be very good.
The red dotted line at the bottom is for dissolved oxygen which is a very very small amount - this has a linear relationship - the greater the partial pressure of oxygen, the more oxygen is dissolved
Imagine the oxygen dissociation curve for haemoglobin was LINEAR:
The pink bit is the normal physiological range for PaO2 in the lungs (this decreases as you get older)
If the oxygen dissociation curve was linear, we’d get a large variation in oxygenation in the lungs
There is a similar situation in the tissues - there is very little scope for increasing unloading
Haemoglobin, however, has a sigmoid oxygen dissociation curve
This gives us effectively 100% saturation across a big range of alveolar PO2
In the tissues you can go from around 76% to 8% saturated - so there is very high unloading capacity
This ODC changes under different circumstances
What is P50 and what is it a good indicator of?
The curve can be shifted to the RIGHT by things that reflect …………………. ………………… ……………….. such as ……………………
Name 4 things that change during excercise that causes the oxygen dissociation curve to shift to the right?
P50 = the partial pressure of oxygen when haemoglobin is 50% saturated
You figure this out by simply drawing a line across at 50% saturation
P50 is a good indicator of the general shape of the ODC
In this example, if it is more or less than the normal value of 3.3 kPa then we can see how the curve is changing
The curve can be shifted to the RIGHT by things that reflect higher energy consumption such as EXERCISE
When you exercise the following changes take place:
Increase in temperature
Acidosis (due to production of lactic acid and excess CO2)
Hypercapnia (elevated CO2 because there is more cellular metabolism)
Increase in 2,3-DPG
The curve can be shifted to the LEFT when the opposite of the responses to exercise take place:
Decrease in temperature
Alkalosis
Hypocapnia
Decrease in 2,3-DPG
NOTE: the pH is lower in the tissues than in the lungs which helps it unload
What causes the oxygen dissociation curve to move up or down?
What is polycythaemia?
The ODC can also move UP and DOWN
If you are ANAEMIC, you have a lower haemoglobin concentration so here is a reduced amount of oxygen in the blood but the saturation is still the same
NOTE: there are two scale on the y axis - the saturation scale has been adjusted for the different curves - saturation does not change
Pulse oximetry can tell you how saturated the haemoglobin is but wont tell you how much haemoglobin you have
Less haemoglobin = lower oxygen carrying capacity
Polycythaemia = an increase in the packed cell volume (haematocrit) in the blood - it could be due to an increase in the number of red blood cells
As you have more red blood cells, you oxygen carrying capacity increases
You haematocrit (ratio of red blood cells to plasma volume will increase) so your blood will get thicker and the blood will flow slower which will impede oxygen deliver
What effect does CO have on the ODC and why?
State two oveerall effects of CO on haemoglobin?
Haemoglobin has a much greater affinity for carbon monoxide than oxygen
Haemoglobin binding to carbon monoxide will reduce the amount of haemoglobin available to bind to oxygen
ADDITIONAL POINT: if two of the chains in haemoglobin are bound to CO and the other two are bound to oxygen, then the two that are bound to oxygen will hold on to the oxygen tighter and will be less willing to release the oxygen at respiring tissue
OVERALL EFFECT OF CARBON MONOXIDE:
Increase Affinity
Decrease Capacity
Effect of Carbon Monoxide on ODC:
Downward and Leftward Shift
Oxygen Dissociation Curve for Myoglobin and Foetal Haemoglobia
Sketch an ODC with Myoglobin and Foetal Haemoglobia and normal haemoglobin?
Why has Fetal haemoglobin got a higher affinity?
What is myoglobin?
Foetal haemoglobin has high affinity because it needs to steal oxygen from the mother’s blood
Although it is NOT a haemoglobin variant, myoglobin is a monomeric protein which has a hyperbolic ODC
It is a protein in muscle which holds on to oxygen - it is there for a rainy day when the muscle needs oxygen rapidly
There is also methaemoglobin which is where the ferrous Fe2+ ion becomes ferric Fe3+
Haemoglobin with Fe3+ CANNOT bind to oxygen
We all have a small proportion of methaemoglobin
INTERESTING FACT: After a few weeks, mince meat will become grey because anything that binds oxygen will go from the Fe2+ state to the oxidised Fe3+ state which no longer binds oxygen and so we lose the red colour
Oxygen Transport
The blood that’s arriving is NOT deoxygenated - it has around 75% oxygen bound
Instead of thinking of it as ‘deoxygenated blood’ think of it as mixed venous blood
The mixed venous blood arriving at the exchange surface has a PO2 of around 5.3 kPa
There is lots of oxygen in the alveolus which will diffuse through the exchange surface into the blood
There is also a diffusion gradient in the red cell
The plasma concentration of oxygen is higher than the intraerythrocytic partial pressure so the oxygen will move into the red cell
When the oxygen moves in it will occupy the final binding spot in the haemoglobin and the haemoglobin will be 100% saturated
What is oxygen flux?
When the blood reaches the tissues it will be around 97% saturated not 100%- why??
Oxygen Transport at the Tissues
When the blood reaches the tissues it will be around 97% saturated
THE BLOOD WILL BE DILUTED BY THE BRONCHIAL CIRCULATION
The pulmonary system has two circulations - it has it’s own blood supply to keep it alive and it has the pulmonary blood supply for oxygenation of blood
The circulation keeping the lung tissue alive drains back into the pulmonary vein before returning to the left atrium
At the tissues the following changes take place:
Concentration of Oxygen:
20.3 - 15.1 mL/dL
Saturation of Oxygen:
97 - 75%
Oxygen Flux = the overall amount of oxygen being deposited
In this case the oxygen flux is = -5 mL/dL
There are 50 decilitres in the body so 5 x 50 = 250
REMEMBER: 1 DECILITRE = 100 MILLILITRES
The resting volume of oxygen consumed is 250 mL of oxygen per minute - the numbers all add up
Carbon Dioxide Transport
Carbon dioxide will diffuse into the blood stream
Carbon dioxide is much more …………….. than oxygen so it dissolves in the plasma more happily
Once in the plasma, the CO2 might bump into some water and it will turn into ………….. …………..
Carbonic acid then dissociates into a ………….. and ………………………. - this is a VERY SLOW reaction because there aren’t any enzymes
CO2 also moves into the red blood cells where there are enzymes
Inside the red cell, bicarbonate is produced from carbon dioxide at a rate 5000 times greater than in the plasma
So the red blood cell plays a major role in moving CO2
………….. ………….. catalyses this reaction
Carbon Dioxide Transport
Carbon dioxide will diffuse into the blood stream
Carbon dioxide is much more soluble than oxygen so it dissolves in the plasma more happily
Once in the plasma, the CO2 might bump into some water and it will turn into Carbonic Acid (H2CO3)
Carbonic acid then dissociates into a proton and bicarbonate (HCO3-) - this is a VERY SLOW reaction because there aren’t any enzymes
CO2 also moves into the red blood cells where there are enzymes
Inside the red cell, bicarbonate is produced from carbon dioxide at a rate 5000 times greater than in the plasma
So the red blood cell plays a major role in moving CO2
CARBONIC ANHYDRASE catalyses this reaction
Inside the red blood cell, the carbonic acid will dissociate into ……………. and a …………….
The bicarbonate will diffuse out into the plasma via the ……………. ……………. and a ……………. ion will move in
Because an anion is moving out (HCO3-), we need to bring an anion in to maintain ……………. .. ………….. across the membrane
This inwards movement of chloride via the AE1 transporter is called the ……………. …………….
The movement of chloride into the red blood cell draws ……………. with it
Water was being used to react with carbon dioxide and it, in effect, moves out because half of the water is in bicarbonate so if water didn’t move in with chloride, the cell would dehydrate and get smaller
Carbon dioxide will also bind to …………….
Carbon dioxide will bind to the ……………. end of the proteins forming …………………………………………
If the concentration of proton increases inside the red blood cells then the red blood cell pH will decrease
We need to mop up these excess protons and the proteins make good buffers
Some of the amino acids are negatively charged and are really good proton acceptors - histidine is particularly good
When you get to the lungs, the processes will reverse to unload CO2
Inside the red blood cell, the carbonic acid will dissociate into bicarbonate and a proton
The bicarbonate will diffuse out into the plasma via the AE1 transporter and a chloride ion will move in
Because an anion is moving out (HCO3-), we need to bring an anion in to maintain chemical electroneutrality across the membrane
This inwards movement of chloride via the AE1 transporter is called the CHLORIDE SHIFT
The movement of chloride into the red blood cell draws water with it
Water was being used to react with carbon dioxide and it, in effect, moves out because half of the water is in bicarbonate so if water didn’t move in with chloride, the cell would dehydrate and get smaller
Carbon dioxide will also bind to proteins
Carbon dioxide will bind to the amine end of the proteins forming CARBAMINOHAEMOGLOBIN (HbCO2)
If the concentration of proton increases inside the red blood cells then the red blood cell pH will decrease
We need to mop up these excess protons and the proteins make good buffers
Some of the amino acids are negatively charged and are really good proton acceptors - histidine is particularly good
When you get to the lungs, the processes will reverse to unload CO2
Define respiratory membrane?
What is the pulmonary transit time?
Pulmonary Transit Time
Blood arrive in the lungs and gas exchange doesn’t take place until it reaches the respiratory membrane
Respiratory Membrane = areas where the alveolar cells and endothelial cells of the capillaries are close enough for exchange to take place
REMEMBER: rate of diffusion is inversely proportional to thickness so only when the membranes are close enough will exchange take place
The green area is where gas exchange takes place - this is pulmonary transit time
The pulmonary transit time is around 0.75 s - the blood cells are only in contact with the respiratory membrane for this short time
By 0.25 s, all of the gas exchange is complete (at rest)
When exercising, cardiac output increases and pulmonary blood flow increases and the lines get stretched rightwards - however, there is still time to reoxygenate the blood
CO2 is much more willing to cross through the membranes so it exchanges much faster
What is the Haldane effect?
Carbon Dioxide Dissociation Curve
Haldane Effect = describes how the amount of carbon dioxide that binds to the amine end of the haemoglobin protein chains changes depending on how much oxygen is bound - this is another allosteric behaviour
This is just referring to the green part of the graph - the carbon dioxide that’s bound in carbaminohaemoglobin form
Usually when the oxygen saturation is 100% (immediately after the alveoli) we don’t want to be binding CO2 and so at this point, carbon dioxide will not bind to the amine end of the proteins
When we get to the tissues we start unloading oxygen and the protein chains on the haemoglobin become more receptive to binding CO2
A = arterial blood
B = mixed venous blood
Carbon dioxide binding to haemoglobin:
100% - 0
95% - there’s a little bit binding
75-0% - greater binding
Ventilation Perfusion Matching/Mismatching
The blood flow to the lung is NOT homogenous
It takes less effort for the heart to push through the lower resistance circuit at the bottom because it isn’t pumping against gravity
Less blood perfuses the apex of the lung because of the RESISTANCE OF GRAVITY
Regarding ALVEOLI - there is a similar relationship - there is better ventilation at the BOTTOM compared to the top
In other words, the base of the lung gets a lot more perfusion and ventilation
There are different ratios of ventilation to perfusion in different parts of the lung
Differences in V/Q:
Base - tend towards ZERO
Apex - tend towards INFINITY
Where the two lines cross in the V/Q graph, the ventilation is equal to perfusion and hence the ratio is 1
Based on the differences in V/Q matching, zones can be attributed to different parts of the lung:
Zone 1: Alveolar Pressure > Arterial Pressure > Venous Pressure
Zone 2: Arterial Pressure > Alveolar Pressure > Venous Pressure
Zone 3: Arterial Pressure > Venous Pressure > Alveolar Pressure
NOTE: arterial pressure will always be greater than venous pressure or the blood would flow backwards
dO QUESTIONS AT HE END OF HIS LECTURE
