Oxygen is a necessary evil for life. To get any use from the stuff, one must first pluck it from the atmosphere, squeeze it into their bloodstream, slosh it to their organs and somehow plug it into the molecular machinery of life. What could possibly go wrong?
An Important Distinction ⚠️
Hypoxia happens when there is too little oxygen available to maintain normal cellular function. Hypoxia may be global (the whole body) or regional (just one limb/organ) and can be acute or chronic. The feared consequence of hypoxia is death collapse of the electron transport chain.
The most obvious and frequently-encountered cause of cellular hypoxia is hypoxaemia: too little oxygen in the blood (PaO2 ≤ 65mmHg is the accepted definiton). This is where we will begin our sermon.
Hypoxaemia causes hypoxia but not all hypoxia is due to hypoxaemia.
The Causes of Hypoxaemia 😮💨
Low PAO2
Notice the capital A in PAO2? That means we’re talking about the partial pressure1 of oxygen in the aveoli, not the arteries. Too little oxygen in the alveoli means that too little oxygen will diffuse into the alveolar capillaries.
The most straightforward way to reduce PAO2 is by hypoventilation. If you don’t bring enough oxygen into the alveoli, none can get into the blood. Life-threatening hypoxia due to hypoventilation alone is rare, however, because the accompanying respiratory acidosis will kill them first.
The other causes are low barometric pressure (perhaps due to high altitude) and low FiO2 (which you might get from re-breathing in a closed container). We can confidently set these issues aside for now since they are seldom to blame for hypoxiaemia in the hospital.
V’/Q’ Mismatch
V’/Q’ is the ratio of ventilation (V’) to perfusion (Q’) in an alveolus. The “ideal” alveolus runs at a V’/Q’ ratio of approximately one. There are two pathological extremes of V’/Q’ mismatching that lead to hypoxaemia: dead space and shunt.
Dead Space: All V’ and No Q’
Dead space occurs where air flows but no gas exchange takes place. The physiologically normal examples are the trachea and conducting bronchi: all air, with no blood available for gas exchange. Pathological increases in dead space can occur in:
- Poorly-configured mechanical ventilation circuits, which effectively “extend” the trachea with piping and filters
- Very high ventilator pressures, which can squash the alveolar capillaries and prevent perfusion
Shunt: All Q’ and No V’
The converse of dead space is shunt: all blood, no air. Blood from the venous circulation bypasses gas exchange completely, and is shunted into the arterial circulation.
Shunting can happen in the heart itself (an intracardiac shunt) or in the lungs (in intrapulmonary shunt).
Intracardiac | Intrapulmonary |
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|
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The prime example of shunt in the clinical arena is pneumonia. The pus-filled alveolus does not permit gas exchange but continues to take a blood supply. The shunt is further worsened by the fact that pus is vasodilatory, which steals even more blood for the non-exchanging alveolus than it deserves. Supplemental oxygen offers little assistance because the alveoli it lands in are already oxygenating to the maximum extent possible.
Diffusion Limitation
A red blood cell takes about 0.75 seconds to traverse the alveolar capillary bed. In a healthy lung at rest, that red cell only needs about 0.25 seconds to reach equilibrium with the oxygen in the alveolar air. Leaves 0.5 seconds of extra time.
When the oxygen needs more time to equilibrate than the red cell spends in the alveolus, there is a diffusion limitation. There are two things that can upset the apple cart…
- O2 starts moving too slowly across the memrane
- The red cells start whizzing by too quickly
So, what decides the rate of oxygen diffusion? Fick’s law of diffusion has some answers:
\[ \dot{Q}= T \cdot \rho \cdot S \cdot\frac{P_{A_{O_{2}}}-P_{aO_{2}}}{d} \]
And here are the terms:
- Q’ = the rate of solute movement across a membrane (flux)
- T = temperature (in degrees Kelvin)
- ⍴ (say “rho”) = a diffusion coefficient specific to each solute
- S = surface area
- PAO2 = alveolar partial pressure of oxygen
- PaO2 = arterial partial pressure of oxygen
- d = the thickness of the membrane
Fick’s law of diffusion tells us that the rate of diffusion is proportional to the magnitude of the alveolar-arterial O2 gradient and inversely proportional to the thickness of the alveolar basement membrane.
In clinical terms, this tell us that we can speed up diffusion by creating a high alveolar-arterial O2 gradient (by giving them a lot of extra oxygen). We can also aid diffusion by crisping up their alveolar basement membranes with diuretics and antibiotics.
Hypoxia of Other Kinds 🩸
Hypoxaemic hypoxia makes up the bulk of our clinical work. There are, however, a few non-hypoxaemic causes of hypoxia that are worth consideration.
Anaemia
Oxygen is all but insoluble in water blood and we have haemoglobin to thank for pickup up the slack. A big shortage of working haemoglobin means that, despite normal lungs and a working heart, very little oxygen will arrive at the tissues.
Anaemia can be functional (this carbon monoxide poisoning or methaemoglobinaemia) or dilutional (the usual suspect).
Stagnation
Oxygen-rich blood is no use to the peripheral tissues if it can’t go the distance. This effect can be global (e.g. cardiogenic and obstructive shock) or focal (e.g. limb ischaemia).
Cytotoxicity
Oxygen that makes the trip from the atmosphere to the cell faces a final challenge: the mitochondrion. The classic clinical situations where mitochondria are unable to properly utilise oxygen from the cytosol are:
- Sepsis
- Cyanide poisoning
TL;DR 🥱
Hypoxia is lack of oxygen in the tissues.
There are two main types, each with three subtypes:
- Hypoxaemic hypoxia
- Low PAO2
- V/Q mismatch
- Diffusion limitation
- Non-hypoxaemic hypoxia
- Stagnation of blood
- Cytotoxicity
- Anaemia
Parting Thoughts 💭
The above screed attempts to introduce a physiological model of hypoxia. Please don’t get too carried away with it in the clinical world. As a wise intesivist once told me…
If the patient doesn’t have enough oxygen, give them more oxygen.
I think that’ll do for now.
Partial pressures are useful for describing equilibration in mixtures of gasses. The most common example is the atmosphere, which is 21% oxygen by volume. The partial pressure of oxygen is the pressure it would exert if all the other gasses in the atmosphere were removed. ↩