Carriage of O2 Flashcards
what is the importance of Haemoglobin in the carriage of O2?
Despite our ↑ complexity, we still depend upon diffusion for the transfer of gasses (O2 and CO2)
Across lung membranes –> blood –> cell membranes (tissue)
Therefore, there is a high importance of partial pressures (po2 and pco2) as it determines how much these gases move
what 2 ways is oxygen carried in the blood?
Oxygen is carried in the blood in 2 ways:
1. Physically dissolved in the plasma solution
2. Chemically bound to haemoglobin (globular protein) in RBC:
- 4 O2 bind to 1 Hb
- Only the dissolved oxygen molecules exert a ‘partial pressure’
- The chemical combination of O2 with haemoglobin is determined by this partial pressure (PaO2)
How much oxygen is dissolved in physical solution?
We Use Henry’s law to consider how much oxygen will be dissolved for a set partial pressure
α = 0.225 (do not need to know!) - small number for a litre of blood!
what is the relationship between Po2 and dissolved oxygen content of blood?
You can plot the linear relationship between Po2 and dissolved oxygen content of the blood
As ↑ Po2 –> ↑O2 content
At the normal Pao2 (13 kPa) there are 3 mls O2 dissolved per litre of blood
3 mls x 5 L/min (cardiac output at rest) = 15 mls/min delivery of oxygen at rest
This is nowhere near the amount required - body needs at least 250 ml/min to supply V̇O2
We could never deliver even the minimal O2 requirements with dissolved O2 alone - need additional O2 carrying capacity - haemoglobin
what is the structure of haemoglobin?
Made up of 4 polypeptide chains (2α and 2β subunits) which non-covalently bound
1 haem group binds to each of the 4 polypeptide chains (globin) - 1 molecule of haemoglobin
1 molecule of Oxygen (O2) then binds to the iron within a haem group
explain the haemoglobin dissociation curve
We have ~147g of Hb per litre of normal blood
Varies - 150 gL-1 for males & 135 gL-1 for females
Binding of oxygen to haemoglobin:
There are 4 Fe2+ binding sites (haem groups) per Hb molecule
Each haem group has 1 molecule of O2 biding to it.
Haemoglobin express co-operative binding:
- The binding of an O2 to iron makes the binding of a subsequent O2 to the other iron easier.
- Unbinding of an O2 from iron makes subsequent unbinding easier
- Therefore, the binding of oxygen to iron at changing partial pressures is not linear
- Each gram of Hb can bind up to a maximum of 1.34 ml of O2
- Giving an HbO2 capacity of 197 ml of O2L-1 (147 x 1.34)
- Compared to 3 ml of O2 dissolved in each litre of blood
- Therefore, Hb gives the blood a large O2 carrying capacity
- O2 capacity ↓ with ↓ [Hb] (e.g. anaemia)
what does this oxygen- haemoglobin dissociation curve show?
sigmoidal ‘S’ shape
Bottom line: amount of oxygen dissolved in plasma as ↑ Po2
Top line: amount of oxygen bound to Hb as we ↑Po2.
At 13kPA we have full saturation of Hb with O2
define oxygen content
Oxygen content: quantity of O2 in a given sample of blood. i.e. the amount of O2 combined with haemoglobin PLUS the amount dissolved
Varies with PO2 & [Hb]
The higher pO2 and [Hb] is –> high O2 content
define oxygen capacity
Oxygen capacity: maximum quantity of O2 that can combine with haemoglobin in a sample of blood (sum: Total content – dissolved O2)
Determined by [Hb] x 1.34 (ml/O2/g Hb)
Dependent upon [Hb]
Independent of partial pressure of O2 (different to oxygen content!)
define Hb saturation
how is it measured?
Hb saturation: Ratio of the quantity of O2 combined with Hb in a given sample to the O2 capacity of that sample.
Measured using an oximeter
Expressed as a %
Must calculate/estimate the O2 capacity for the individual
Both Hb Saturation and O2 content measure the amount of oxygen in blood so are interchangeable (swap the y axis – shape remains the same)
(% saturation vs absolute value)
At maximum O2 capacity, Hb is 100% saturated.
in normal situations what would hb saturation look like?
In a normal situation, haemoglobin should be fully saturated at PaO2 (13kpa)
Even at 8 kPa (despite being quite a bit lower than 13 kPa), you still have a relatively high O2 saturation - from below this, falls steeply
50% O2 saturation occurs at ~3.5 kPa = p50 for haemoglobin
p50 can act as a measure if curve is shifting L or R at any point
what are the functional effects of haemoglobin?
explain the association and dissociation part of the curve
Components of haemoglobin dissociation curve:
The Association part of curve = Flat
- The associate part ensures almost complete loading of Hb despite potential small fluctuations in level of Po2 in the lungs
- E.g. you still have 90% saturation even as low as 8 kPa of Po2 (5 kPa less than normal)
- Therefore, even if we have mild respiratory disease* which ↓ alveolar ventilation (↓ PAo2) we will not have much change in saturation of Hb - therefore not much change in oxygen content
*Other factors: decreases in ventilation, V/Q mismatch, shunts
Dissociation part of curve = steep
- The dissociation part of ensures adequate delivery of O2 to tissues whilst still maintaining high arterial Po2
This is important for driving diffusion from blood into cells
- With a small change in Pao2 (at tissues) –> big change in Hb saturation –> large unloading of O2 from Hb into cells
8 kPa🡪 3 kPa you get a 60% desaturation of Hb (compared to 10% for association part)
Oxygen binding affinity of HbA (adult) can be varied, explain the reasons why the Hb dissociation curve is shifted right and left
Hb dissociation curve is shifted right by:
- ↑ Pco2
- ↑ [H+] (making blood more acidic)
the 2 above are due to the Bohr effect
- ↑ temperature
- ↑ 2,3-DPG concentration:
2,3-DPG is a side reaction of glycolysis
It can ↑ with chronic hypoxia (e.g. at altitude)
Also ↓ with acidosis/storage in blood banks (so curve will shift to left)
Hb dissociation curve is shifted left by:
- ↓ of these variables
- p50 can act as a measure if curve is shifting L or R at any point
- Shift to left causes ↓ in P50
- Shift to right causes ↑ in P50
how does metabolism effect the shift in the Hb dissociation curve?
- Pco2, ↑ [H+] + ↑ temperature occurs in tissues due to ↑ metabolism
- E.g. blood passing through legs of cyclist will be facing this environment
- Shifts curve to right
- In tissue where metabolism is ↓, Pco2, [H+] + temperature are not as high
- E.g. blood passing through arms of a cyclist
- Degree by which curve shifts, depends on degree of change in these factors (Pco2, [H+] + temperature)
what is the effect of temperature and the Bohr effect in shifting the Hb dissociation curve?
- The shifting of the curve to the right has little effect upon the ability of blood in lungs to pick up oxygen
- The Flat association part has no change (see image)
The shifting of the curve to the right has a significant effect on tissues:
1. Fixed delivery:
- If curve never shifted its position, you would have fixed delivery of oxygen (saturation = 75%)
2. Autoregulated delivery:
- Because the curve has shifted to right, we can now deliver a greater amount of oxygen (saturation = 40%)
- Therefore, as blood moves into tissue, haemoglobin gives up more than half of oxygen to tissue (<50% saturation at tissue Po2)
- Autoregulated delivery in Tissues: Amount of oxygen delivered to the tissue depends on how far the curve shifts rightward, which depends upon how much Pco2, [H+] and temperature have changed - which depends upon how much metabolism has changed
what does changing ventilation effect?
what factors reduce normal Hb conc?
- Changing ventilation only affects the PaO2.
- It has no effect upon the position (shift left/right) or shape of Hb dissociation curve
- It just tells you where you are on that curve
Factors that reduce normal Hb concentration - reduce O2 capacity: - Dietary (e.g. iron deficient)
- Reduced RBC count (anaemia)
- CO poisoning
how does anaemia reduce O2 capacity of blood?
- Normally the max. oxygen content is 200 ml.L-1,
- But in case of anaemia –> ↓ [Hb] –> Reduced oxygen capacity/content by 50%
- However, there is no change in the shape or position of the saturation curve - capacity is low, but your ability to deliver oxygen is unaffected (at least in resting to mild exercise)
- If we plotted partial pressure against oxygen saturation, at 13kpa - 100% saturated Hb
- i.e. when you lose Hb you reduce the capacity of blood to carry oxygen but Hb itself is not changed.
- BUT changing the shape of the saturation curve affects the delivery of oxygen
- This is done by affecting haemoglobin on a chemical level
- This is almost always bad
why is Anaemia not fatal but CO poisoning is?
- In both anaemia and CO poisoning, you have a 50% O2 capacity
- However, CO poisoning is fatal when anaemia is not.
- This is because anaemia does not change the shape of the curve (stays sigmoidal) whereas CO does (rectangular hyperbola)
- CO poisoning = brown line
- Anaemia = blue dotted line
Consider oxygen delivery:
- The height of the blue boxes shows the volume of oxygen that needs to be unloaded and delivered to tissues.
- In order to deliver sufficient oxygen, Po2 in tissues must drop to a level indicated on graph by dot + arrow (lower boundary of blue box)
- In a normal person PO2 needs to drop to 5kpa
- In anaemia, patient PO2 needs to drop to 4kpa
- In CO poisoning O2 is only released from Hb when the Po2 is fatally low (1kpa), at which point tissues are dying.
- This is due to the shape of Hb curve
what is foetal Hb made up of?
explain its affinity to 2,3-DPG
- Made up of 2α + 2γ chains
- Without the interaction of other factors it has a slightly less affinity for O2 than HbA
- BUT it has considerably less affinity for 2,3-DPG than HbA - therefore it is shifted to the left of HbA dissociation curve.
- Therefore, overall foetal Hb has higher affinity for O2 than HbA
- So at all levels of Po2, oxygen will move from maternal blood into foetal blood, (in placenta)
- This shows the importance of 2,3-DPG in placing the position of the curve
- 2,3-DPG is generally constant across the body.
- Changes in Pco2, pH, temperature are transient (their levels vary across the body) - these factors therefore mostly set p50.
- In the absence of 2,3-DPG, the p50 of normal adult Hb is shifted from 3.5 kPa to just 0.1 kPa (virtually a straight vertical line - so O2 not given up in tissues)
what is Myoglobin?
function?
*Not haemoglobin!
- It is stores oxygen in the muscle.
- This oxygen can then be used at onset of exercise to temporarily supply muscle until further blood flow arrives
- Has only 1 haem group
- Produces a hyperbolic rather than sigmoidal curve.
- The curve is also left shifted relative to haemoglobin
=> No Bohr effect
- p50 = 1 kPa there myoglobin is 100% saturated at 2.5 kPa
- Easily saturated
- It doesn’t let go of oxygen until Po2 is very low
- Therefore, when you begin exercise if your muscle O2 delivery through blood flow to your muscles is not sufficient the muscle becomes hypoxic so O2 is released from myoglobin to give the muscle the O2 is requires until the blood flow can catch up.
How much O2 is dissolved in plasma when 100% O2 is breathed e.g. via a facemask?
PB = 101kpa
PH20 = 6.26kpa
Paco2 = 5kpa
R = 0.8
PIo2 = (PB – PH20) x (% oxygen)
PIo2 = (101 – 6.26) x 100 = 94.74kpa
PAo2 = 94.74 – (5/0.8) = 88.49kpa
88.49 x 0.225 = 19.91ml/L
Loss of 2,3DPG would:
Answer = E
