Hypoxia
Last updated 22nd August 2022 - Tom Heaton
Hypoxia refers to low oxygen levels in the tissues.
Hypoxaemia refers to low oxygen levels in the (arterial) blood.
There are 4 types of hypoxia:
Hypoxic hypoxia is due to low partial pressures of oxygen in the blood, and thus low hemoglobin saturation, and thus total amount of oxygen.
Anaemic hypoxia arises because there is insufficient haemoglobin to transport oxygen to the tissues.
Ischaemic hypoxia arises because there is inadequate cardiac output to deliver the blood to the tissues.
Histotoxic hypoxia refers to an inability of the tissues to utilise oxygen delivered to it for some reason e.g. cyanide poisoning.
These notes will primarily focus on hypoxic hypoxia.
When considering types of respiratory failure, hypoxaemia can be a feature of all 4 types:
Hypoxaemia refers to low oxygen levels in the (arterial) blood.
There are 4 types of hypoxia:
- Hypoxic hypoxia
- Anaemic hypoxia
- Ischaemic hypoxia
- Histotoxic hypoxia
Hypoxic hypoxia is due to low partial pressures of oxygen in the blood, and thus low hemoglobin saturation, and thus total amount of oxygen.
Anaemic hypoxia arises because there is insufficient haemoglobin to transport oxygen to the tissues.
Ischaemic hypoxia arises because there is inadequate cardiac output to deliver the blood to the tissues.
Histotoxic hypoxia refers to an inability of the tissues to utilise oxygen delivered to it for some reason e.g. cyanide poisoning.
These notes will primarily focus on hypoxic hypoxia.
When considering types of respiratory failure, hypoxaemia can be a feature of all 4 types:
- Acute hypoxaemic
- Ventilatory - hypoxaemia may accompany the hypercapnia
- Post-operative - essentially a subset of type 1
- Hypoperfusion related
Pathophysiology
An understanding of normal respiratory physiology is quite important for this, though will not be explored in great detail here.
The key parts to understand are that oxygen is carried almost exclusively by hemoglobin, at least in terms of the quantities that are clinically relevant - dissolved oxygen is a tiny amount.
This haemoglobin is usually fully saturated in health, carrying the maximum amount of oxygen that it can.
Whilst it is pretty soluble, it is less so that CO2, and so requires a degree of time to diffuse across the thin alveolar membrane and capillary to this Hb.
Both of these factors essentially mean that the blood in the lungs, and the oxygen in the lungs (which will be being inhaled) have to effectively come into contact with each other (or as close as the thin alveolar-capillary gap will allow) to allow oxygenation of the blood.
To really understand oxygen delivery clearly, we can see how much oxygen is transported by blood, the oxygen carrying capacity:
(1.34 x [Hb] x SpO2) + (PaO2 x 0.023)
I think this equation really highlights the proportion that is carried by the haemoglobin.
If you multiply this by the cardiac output, you can see how much oxygen can be delivered to the tissues.
When thinking about this, we can come to a few clear ways in which hypoxaemia can occur:
V/Q mismatching is the most important mechanism as it is the most common.
Here, there is inappropriate matching of the perfusion and ventilation of some lung units.
Lung units that are ventilated but not perfused are termed deadspace, and those that are perfused but not ventilated are physiological shunt.
Deadspace can usually be compensated for but the shunt less so.
This is because this blood is passing through the lungs without coming into contact with oxygen rich alveolar air.
This means it stays desaturated and when it joins the other blood (which has been oxygenated), will essential ‘dilute’ it with oxygen-poor blood.
Because the normal oxygenated blood is, in health, fully saturated, it is unable to compensate and share its oxygen without drifting down from this normal point.
The result is that this physiological shunt results in general hypoxaemia, because the functioning lung units are not fully effectively able to compensate for the deoxygenated blood that misses the contact with lung oxygen.
There are multiple pathological causes of this, primarily of a lung nature, where matching is disturbed by the pathology e.g. pneumonia.
Whilst you may note the beneficial effects of hypoxic pulmonary vasoconstriction here, minimising blood flow where it is not getting oxygenated, this may not be complete enough to have a full effect.
The same mechanism is the case with ‘true shunt’ only here the blood is not even entering the pulmonary circulation, but instead bypassing it.
This, to some degree, is a normal physiological feature e.g. bronchial blood flow, but major abnormalities can lead to notably hypoxaemia.
In these cases, the hypoxia may be worsened by excess systemic tissue oxygen extraction.
When this is the case, the blood returning to the right heart is more hypoxic than usual (usually only decreased to 70-80% saturated).
However, if this is lower, then it means that shunted blood will have an even strong diluting effect when it arrives in the systemic side.
Optimising factors that may be leading to this high extraction e.g. CVS disturbance, may play a role here.
As noted, diffusion impairment can lead to hypoxia.
Unlike with shunting, there is usually a wide margin for diffusion in health (see West’s Physiology).
Full diffusion occurs in about ¼ to ⅓ of the time needed, as the RBCs pass through the pulmonary capillary.
However, pathology that increases the diffusion distance can start to challenge this ability, increasing the ‘resistance’ to diffusion (as per Fick’s law).
This can be compounded by states where the blood flow through the lungs is shortened e.g. extreme exertion, which reduces the time available for diffusion to occur.
Once blood has inadequate time in the capillaries to get fully oxygenated (resistance to diffuse or faster transit or both) hypoxaemia can result.
We can see in all of this that the PaO2 (the actual tension/partial pressure of oxygen in the blood) is not hugely relevant, instead the saturation of haemoglobin being the most important part.
Whilst this is true, it is important to remember the oxygen saturation curve and its sigmoid shape, describing the relationship between these two factors.
As the PaO2 drops, there is a point where there becomes a more rapid decrease in the haemoglobin saturation.
To be only able to transfer low tensions of oxygen to the circulation is therefore a warning that there is the potential for a rapid decline in oxygen blood content if this gets any worse.
However, it doesn't really add a huge amount of information about the oxygen transport ability of the blood.
The key parts to understand are that oxygen is carried almost exclusively by hemoglobin, at least in terms of the quantities that are clinically relevant - dissolved oxygen is a tiny amount.
This haemoglobin is usually fully saturated in health, carrying the maximum amount of oxygen that it can.
Whilst it is pretty soluble, it is less so that CO2, and so requires a degree of time to diffuse across the thin alveolar membrane and capillary to this Hb.
Both of these factors essentially mean that the blood in the lungs, and the oxygen in the lungs (which will be being inhaled) have to effectively come into contact with each other (or as close as the thin alveolar-capillary gap will allow) to allow oxygenation of the blood.
To really understand oxygen delivery clearly, we can see how much oxygen is transported by blood, the oxygen carrying capacity:
(1.34 x [Hb] x SpO2) + (PaO2 x 0.023)
I think this equation really highlights the proportion that is carried by the haemoglobin.
If you multiply this by the cardiac output, you can see how much oxygen can be delivered to the tissues.
When thinking about this, we can come to a few clear ways in which hypoxaemia can occur:
- Ventilation-perfusion (V/Q) mismatch
- Diffusion impairment
- Alveolar hypoventilation
- True shunt
V/Q mismatching is the most important mechanism as it is the most common.
Here, there is inappropriate matching of the perfusion and ventilation of some lung units.
Lung units that are ventilated but not perfused are termed deadspace, and those that are perfused but not ventilated are physiological shunt.
Deadspace can usually be compensated for but the shunt less so.
This is because this blood is passing through the lungs without coming into contact with oxygen rich alveolar air.
This means it stays desaturated and when it joins the other blood (which has been oxygenated), will essential ‘dilute’ it with oxygen-poor blood.
Because the normal oxygenated blood is, in health, fully saturated, it is unable to compensate and share its oxygen without drifting down from this normal point.
The result is that this physiological shunt results in general hypoxaemia, because the functioning lung units are not fully effectively able to compensate for the deoxygenated blood that misses the contact with lung oxygen.
There are multiple pathological causes of this, primarily of a lung nature, where matching is disturbed by the pathology e.g. pneumonia.
Whilst you may note the beneficial effects of hypoxic pulmonary vasoconstriction here, minimising blood flow where it is not getting oxygenated, this may not be complete enough to have a full effect.
The same mechanism is the case with ‘true shunt’ only here the blood is not even entering the pulmonary circulation, but instead bypassing it.
This, to some degree, is a normal physiological feature e.g. bronchial blood flow, but major abnormalities can lead to notably hypoxaemia.
In these cases, the hypoxia may be worsened by excess systemic tissue oxygen extraction.
When this is the case, the blood returning to the right heart is more hypoxic than usual (usually only decreased to 70-80% saturated).
However, if this is lower, then it means that shunted blood will have an even strong diluting effect when it arrives in the systemic side.
Optimising factors that may be leading to this high extraction e.g. CVS disturbance, may play a role here.
As noted, diffusion impairment can lead to hypoxia.
Unlike with shunting, there is usually a wide margin for diffusion in health (see West’s Physiology).
Full diffusion occurs in about ¼ to ⅓ of the time needed, as the RBCs pass through the pulmonary capillary.
However, pathology that increases the diffusion distance can start to challenge this ability, increasing the ‘resistance’ to diffusion (as per Fick’s law).
This can be compounded by states where the blood flow through the lungs is shortened e.g. extreme exertion, which reduces the time available for diffusion to occur.
Once blood has inadequate time in the capillaries to get fully oxygenated (resistance to diffuse or faster transit or both) hypoxaemia can result.
We can see in all of this that the PaO2 (the actual tension/partial pressure of oxygen in the blood) is not hugely relevant, instead the saturation of haemoglobin being the most important part.
Whilst this is true, it is important to remember the oxygen saturation curve and its sigmoid shape, describing the relationship between these two factors.
As the PaO2 drops, there is a point where there becomes a more rapid decrease in the haemoglobin saturation.
To be only able to transfer low tensions of oxygen to the circulation is therefore a warning that there is the potential for a rapid decline in oxygen blood content if this gets any worse.
However, it doesn't really add a huge amount of information about the oxygen transport ability of the blood.
Indices
Assessing the extent of oxygenation problems can be useful.
Some indices that are used include:
Alveolar-arterial oxygen gradient
This is essentially the difference between the (calculated) alveolar oxygen tension (PAO2), and that which is measured in the arterial gas (PaO2).
The alveolar component is calculated using the alveolar gas equation PAO2 = PIO2-(PaCO2/R).
PIO2 is the inspired tension of oxygen, and R is the respiratory quotient.
The normal is 2.5 + (0.21 x age in years)
It is affected by the FiO2 however.
A difference of 10 kPa is a good rule of thumb to remember.
Respiratory Index
This is calculated by dividing the A-a gradient by the FiO2.
This aims to reduce the impact of the FiO2 on the gradient.
Normal is 0.74-0.77 at an FiO2 of 0.21, and 0.80-0.82 with an FiO2 of 1.
Some indices that are used include:
- Alveolar-arterial oxygen gradient
- Respiratory index
- Oxygenation index
Alveolar-arterial oxygen gradient
This is essentially the difference between the (calculated) alveolar oxygen tension (PAO2), and that which is measured in the arterial gas (PaO2).
The alveolar component is calculated using the alveolar gas equation PAO2 = PIO2-(PaCO2/R).
PIO2 is the inspired tension of oxygen, and R is the respiratory quotient.
The normal is 2.5 + (0.21 x age in years)
It is affected by the FiO2 however.
A difference of 10 kPa is a good rule of thumb to remember.
Respiratory Index
This is calculated by dividing the A-a gradient by the FiO2.
This aims to reduce the impact of the FiO2 on the gradient.
Normal is 0.74-0.77 at an FiO2 of 0.21, and 0.80-0.82 with an FiO2 of 1.
Management
The management of hypoxia can be a particular challenge in critical care but there can be some key steps in management.
There will clearly be a difference depending on the clinical status of the patient.
A non-intubated patient is best approached with the standard A to E approach, which will include applying high flow oxygen as a starting point.
In critical care, there is a greater range of management options, and the initial treatment of oxygenation is likely to have failed.
The management can be thought of as having 2 arms:
There will clearly be a difference depending on the clinical status of the patient.
A non-intubated patient is best approached with the standard A to E approach, which will include applying high flow oxygen as a starting point.
In critical care, there is a greater range of management options, and the initial treatment of oxygenation is likely to have failed.
The management can be thought of as having 2 arms:
- Optimising oxygen delivery
- Reducing oxygen demand
Optimising Oxygen Delivery
Optimising oxygen delivery involves focusing on the steps in the chain of delivering oxygen from the concentrated pipeline/cylinder to the arterial blood of the patient.
An approach can be:
Airway
An airway issue is not uncommon and needs rapid correction.
This can include assessment of the full circuit for problems.
Problems may include:
Patient
This may be related to the patients pathology or physiology
Positioning the patient can be a key factor for improving their physiology/pathology.
Again, drawing on respiratory physiology, we can identify that the superior parts of the lungs (in relation to gravity) ventilate better, and that blood flow is also partly affected by garvity (hydrostatic pressure).
Proning is one well recognised approach to this, where the primarily collapsed and poorly ventilated bases are suddenly superior, allowing them to be better ventilated.
This covered in more detail elsewhere.
Ventilation
This will primarily relate to optimising the ventilation mode and values to achieve the best gas exchange conditions for blood oxygenation.
An understanding of the causes of (and a primary likely cause in your patient) of hypoxia.
In many cases, the most common cause is that of V/Q mismatching - the blood passing through the lungs, and the ventilation of alveoli, are not appropriately matched to each other.
Ventilation strategies will therefore often focus on improving this.
A key parameter for this is to increase mean airway pressure.
An approach can be:
- Optimise airway
- Optimise patient
- Optimise ventilation
Airway
An airway issue is not uncommon and needs rapid correction.
This can include assessment of the full circuit for problems.
Problems may include:
- Tube displacement
- Endobronchial
- Extubation
- Tube blockade
- Kinked
- Biting
- Debri e.g. mucus
- Circuit malfunction
- Disconnection
- Gas failure
Patient
This may be related to the patients pathology or physiology
- Resistance to ventilator
- Inadequate sedation
- Inadequate muscle relaxation
- Inappropriate ventilation mode
- Airway resistance
- Bronchospasm
- Mucus plugging
- ‘Lung’ pathology
- Atelectasis
- Pneumonia
- Pneumothorax
Positioning the patient can be a key factor for improving their physiology/pathology.
Again, drawing on respiratory physiology, we can identify that the superior parts of the lungs (in relation to gravity) ventilate better, and that blood flow is also partly affected by garvity (hydrostatic pressure).
Proning is one well recognised approach to this, where the primarily collapsed and poorly ventilated bases are suddenly superior, allowing them to be better ventilated.
This covered in more detail elsewhere.
Ventilation
This will primarily relate to optimising the ventilation mode and values to achieve the best gas exchange conditions for blood oxygenation.
An understanding of the causes of (and a primary likely cause in your patient) of hypoxia.
In many cases, the most common cause is that of V/Q mismatching - the blood passing through the lungs, and the ventilation of alveoli, are not appropriately matched to each other.
Ventilation strategies will therefore often focus on improving this.
A key parameter for this is to increase mean airway pressure.
- Increase FiO2
- Increase mean airway pressure
- Increase PEEP
- Increase inspiratory time
- Recruitment maneuvers
Reducing Oxygen Demand
This may be a less obvious management option, but may be possible in certain conditions, and indeed very relevant in others.
This essentially involves reducing the metabolic activity that is requiring oxygen.
Options include:
This essentially involves reducing the metabolic activity that is requiring oxygen.
Options include:
- Treating pyrexia
- Active cooling
- Reducing work of breathing e.g. treating bronchospasm
- Sedation
- Neuromuscular blockade
Links & References
- Al-Shaikh, B. Stacey, S. Essentials of anaesthetic equipment (3rd ed). Churchill Livingstone Elsevier. 2007
- Dornan, R. Principles of IPPV. e-LFH. 2016.
- Gould, T. Ventilation - Basic modes 1. e-LFH. 2016.
- Gould, T. Ventilation - Basic modes 2. e-LFH. 2016.
- Anaesthesia UK. Ventilation. http://www.frca.co.uk/SectionContents.aspx?sectionid=172
- The Intensive Care Foundation. Handbook of mechanical ventilation: a user's guide. 2015.
- Hypoxia. LITFL- Part One. http://www.partone.lifeinthefastlane.com/hypoxia.html
- Nickson, C. Improving oxygenation in ARDS. 2019. LITFL. https://litfl.com/improving-oxygenation-in-ards/
