Lecture 5: Oxygen in the blood Flashcards
Whats the solubility coefficient of oxygen?
0.01 mmol/L/kPa (at 37 degrees)
Not very soluble in water
How much oxygen is dissolved in arterial blood?
0.13 mmol/L
At PaO2 of 13.3 kPa
(13.3 x 0.01)
Why can’t we rely on dissolved oxygen only?
Cardiac output would have to be really high, as we need 12 mmol of oxygen per minute so we would need to pump 92 L/min around the body
What is the average cardiac output for a healthy person?
4.5-5 L
Why does oxygen binding need to be reversible?
- oxygen must be able to associate with the carrier at the lungs
- dissociate from carrier at tissues to supply them with oxygen
What is the structure of Hb?
Tetramer, which binds 4 oxygen molecules
- haem molecule on each chain
- haem molecule has iron at its centre
- molecular oxygen combines reversibly with iron
What are the 2 states of Hb?
T state (tense): low affinity for oxygen, difficult for oxygen to bind R state (relaxed): high affinity for oxygen, easy for oxygen to bind
What determines whether Hb is in the T or R state?
Partial pressure of oxygen
- when pO2 is low, Hb is tense
- when pO2 is high, Hb is relaxed
What is positive coorperativity?
As each oxygen binds, Hb becomes more relaxed and binding of the next oxygen molecule is easier
(opposite is true: oxygen leaving Hb makes it more tense and therefore more likely that another oxygen will dissociate)
Does the oxygen dissociation curve tell us how much Hb a person has?
It does not tell us about the amount of Hb a person has
Does saturation of Hb change in anaemia?
No, they are fully saturated, there is just less Hb.
-but O2 content will be lower so not enough oxygen present in the blood
Describe the oxygen dissociation graph:
Y axis: -Hb saturation % -oxygen conc mL/100mL X axis: -kPa (pO2)
Sigmoidal curve:
- initially, there is a shallow relationship with b/w the pO2 and binding. It is very hard for oxygen to bind to the Hb
- as some oxygen binds, this facilitates further binding (steep part of curve)
- curve steepens as pO2 rises
- curve flattens as saturation is reached
What information can we get from an oxygen dissociation curve?
- see how much oxygen will be bound or given up when moving from one partial pressure to another
- work out the difference in % saturations between 2 pO2 values
- p50: PP of oxygen where Hb is 50% saturated
Give some important partial pressures of oxygen on the Hb dissociation curve:
-Hb saturated above 9-10 kPa
-virtually unsaturated below 1 kPa
-half saturated at 3.5-4 kPa
(saturation changes greatly over a narrow range)
What are the different zones on the Hb dissociation curve?
Zone A: wide range of safe partial pressure of oxygen
Zone B: even small drops in partial pressure of oxygen are dangerous- tissue hypoxia as delivery to tissues is compromised
How do we define respiratory failure in terms of oxygen?
When the arterial partial pressure of oxygen falls below 8 kPa
What is the average Hb concentration for oxygen?
2.2 kPa
Each Hb carries 4 molecules
=8.8 mmol/L (average)
What does tissue pO2 depend on?
How metabolically active the tissue is
- usually 5 kPa
- Hb saturation drops to 65% (given off 35% of oxygen)
- at this low saturation, Hb is tense and doesn’t want to bind oxygen
What is spare capacity of Hb?
In mixed venous blood over half the oxygen is still bound: 6kPa
(in case we find ourselves in a situation where we need to extract more oxygen)
How low can tissue pO2 get?
-capillaries supplying the tissues can’t fall below 3kPa
-need a partial pressure gradient
-higher the capillary density, the lower the pO2 can fall as it doesn’t have far to diffuse
(very metabolically active tissues have a higher capillary density/high altitudes will have a higher capilarry density)
What is the Bohr effect?
-acidic conditions shift dissociation curve to the right, so it has less affinity for oxygen: promotes the T state (metabolically active tissues have a low pH)
How does the temperature effect the oxygen dissociation curve?
High temp shift curve to the right, so there is less affinity for oxygen
-as metabolically active tissues have high temperatures
What is the most metabolically active tissue?
The heart
-it removes the most oxygen from the blood
Where does maximum unloading of oxygen occur?`
-in tissues where pO2 can fall to a low level
-conditions where increased metabolic activity results in a more acidic environment and higher temp
-in tissues with a high capillary density where partial pressure gradient of oxygen can be very small
Here up to 70% of bound oxygen can be given up (on average 30% of oxygen is extracted from blood)
What is 2,3-BPG and its effect on the dissociation curve?
Metabolically active substance, which is an intermediate of RBC glycolysis normally rapidly consumed
- in hypoxia, RBC production of 2,3-BPG increases
- this shifts the curve to the right so there will be more unloading of oxygen which is helpful in hypoxic conditions
In who is 2,3-BPG increased?
-people with anaemia
-people who live in a high altitude
(2,3-BPG are decreased slightly in blood bank blood so in someone critically ill you want to get them as fresh blood as possibleso the 2,3-BPG isn’t as decreased)
How does carbon monoxide affect oxygen delivery to tissues?
- reacts with Hb to form COHb
- CO has 200x affinity for Hb than oxygen, causing reduced oxygen transport and total oxygen content
- CO increases affinity of unaffected subunits for oxygen so they hold onto oxygen: shifts curve to the left, leading to reduced oxygen release to peripheral tissue
When is carbon monoxide levels fatal?
If HbCO is >50%
-children are at increased riskas they breath faster so get more CO in
What are the symptoms of carbon monoxide poisoning?
-headache
-nausea
-vomiting
-slurred speech
-confusion
Initially may not have many resp symptoms as PaO2 is normal
What is the difference between hypoxia and hypoaemia?
Hypoxaemia: low PaO2 in arterial blood (reflects the dissolved oxygen, not bound to Hb)
Hypoxia: low oxygen levels in body or tissues
If PAO2 levels are low what do you experience?
If pO2 levels in the alveoli are low, not all the Hb will be saturated so you get both hypoxia and hypoxaemia
How does shock cause peripheral hypoxia?
Reduce blood flow via peripheral vasoconstriction
Give some examples where oxygen is being used up faster that it is being delivered?
- peripheral artery disease (arteries are narrowed)
- raynaud’s
- congestive heart failure with low cardiac output
What is cyanosis?
Blue colouration due to unsaturated Hb
- as deoxygenated Hb is less red than oxygenated Hb
- can be peripheral due to poor circulation
- can be central cyanosis due to poorly saturated blood in the systemic circulation (mouth/tongue/lips/mucous membranes)
Why is cyanosis difficult to detect?
-hard to see in poor lighting
-harder to see if your skin colour is darker (look at fingernails)
-wearing shoes
Therefore you need to be looking for it
What is pulse oximetry?
Detects levels of Hb saturation (non-invasive)
- detect difference in absorption of light between oxygenated and deoxygenated Hb (more blue)
- only detects pulsatile arterial blood levels (not in tissues/non-pulsatile venous blood)
What is the disadvantages of pulse oximetry?
- regular 2 wave pulse oximeter can’t detect COHb, so will report normal saturation
- can’t give information about Hb levels but it gives the saturation
What other tests can you do as well as a pulse oximetry?
ABG (arterial blood gas)
-painful
-does not detect CO
-some ABG’s calculate pO2 from dissociation curve
Detects oxygen levels, electrolytes and acid/base balance
