Hypoxia

Last post for PHYL3002!

Define hypoxia, hypoxemia and cyanosis.

• Hypoxia: Low oxygen content.
• Hypoxemia: Low partial pressure of oxygen in the arteries.
• Cyanosis: Discolouration of the skin due to unsaturated haemoglobin.

List the main types of hypoxia

Hypoxia can be divided into peripheral and central hypoxia. Peripheral hypoxia only affects some tissues, whereas central hypoxia affects the whole body. Peripheral hypoxia can be ischaemic (due to poor perfusion of tissue, as might happen if you tie a tourniquet too tightly), histotoxic (due to mitochondrial failure, as happens in cyanide poisoning) or in heavy exercise (oxygen supplies are depleted, causing muscle to switch to anaerobic metabolism).

Explain why there is no hypoxemia in anaemic hypoxia

Anaemia can cause hypoxia without causing hypoxemia. In anaemia, there are fewer red blood cells, and therefore less haemoglobin for oxygen to bind to. Therefore, the total oxygen concentration (oxygen dissolved in arterial blood + oxygen bound to haemoglobin) is less overall, resulting in hypoxia. Anaemia, however, does not cause oxygen dissolved in arterial blood to decrease, and therefore does not cause hypoxemia.

Identify the five causes of hypoxemia
Explain the changes in gases cause by the five types of hypoxemia

The five causes of hypoxemia are as follows:

1. Low PiO2 (partial pressure of inspired oxygen, such as in high altitudes)
2. Hypoventilation
3. Diffusion limitation (i.e. issues in gases diffusing across the alveolar wall)
4. R-L shunt (i.e. mixing of deoxygenated and oxygenated blood, as occurs in several congenital heart defects)
5. V'/Q' mismatch (the most common cause of hypoxemia)

Now let's go over each one in turn!

Low PiO2

As mentioned, this can occur at high altitudes. It can also occur due to occupational hazards (e.g. a nitrogen gas leak that displaces oxygen).

Hypoventilation

Hypoventilation = ventilation insufficient to meet respiratory demands. This can have several causes, including but not limited to the following:

• Asphyxiation- no ventilation due to a physical obstruction (strangling etc.)
• Failure of respiratory drive- can be due to CNS damage or certain drugs
• Failure of respiratory muscle- can be due to a neuromuscular disease such as muscular dystrophy
• Failure of lung ventilation- due to a restrictive or obstructive lung disease
• Drowning- as I will explain...

The effect of drowning depends on whether you are drowning in salt or fresh water. (Okay, the overall result- death- is still the same, but the path to death is a bit different.) Also most patients who die by drowning actually die by laryngospasm rather than by the water itself, but let's ignore that for now.

If you are drowning in fresh water, your blood will have a higher osmolarity than the fluid in the alveoli, so water is drawn into the blood. This causes cells to swell and then lyse. Lysed cells release a lot of potassium, so the potassium concentration of the blood goes up (which can lead to arrhythmias, heart failure etc.). Concentrations of other solutes, such as sodium, chlorine and proteins, will decrease as they have become diluted by the extra water.

If you are drowning in salt water, your blood will have a lower osmolarity than the fluid in the alveoli, so even more water is drawn into the alveoli. Therefore, salt water drowning is harder to save someone from than fresh water drowning. Since fluid is being lost from the blood, the blood is more concentrated, and so concentrations of sodium, chloride, magnesium, proteins etc. all increase.

Hypoventilation decreases oxygen concentrations and increases carbon dioxide concentrations. (This is in contrast to V'/Q' mismatch, diffusion limitation and R-L shunt, all of which cause hypoxia with little to no hypercapnia.) Therefore, hypoventilation can be distinguished from V'/Q' mismatch by use of the alveolar gas equation, but I will explain that later.

Diffusion limitation

Diffusion limitation essentially occurs to problems with gases diffusing (due to a thickened alveolar membrane etc.). This can be detected by measuring the diffusion capacity of carbon monoxide, as mentioned here. Diffusion limitation causes hypoxia with little to no hypercapnia.

R-L shunt

In a R-L shunt, there is mixture of deoxygenated and oxygenated blood. This occurs when venous blood does not get exchanged with air. There are two types of shunts: anatomical shunts, where blood fails to pass through alveoli, and physiological shunts, where air fails to get to alveoli. A normal healthy lung will have around 2% shunt, half of which is accounted for by bronchial circulation. When there is too much shunt, however, this can be problematic.

Shunt can be diagnosed by giving the patient 100% oxygen. Since 100% oxygen causes PAO2 (remember, capital A = alveolar) to increase to around 650mmHg, a normal healthy person will also have a massive increase in PaO2 (lowercase a = arteriolar). When there is a shunt involved, there is no improvement in PaO2 as the shunted blood is not exposed to the high PAO2. R-L shunt causes hypoxia with little to no hypercapnia.

V'/Q' mismatch

See earlier post: Gas Exchange and V'/Q' Ratio. Note that this is the most common cause of hypoxemia. It causes hypoxia with little to no hypercapnia.

Calculate the AaDO2 from blood gases

Since hypoventilation is the only cause of hypoxemia that causes an increase in PaCO2, it can be distinguished by using the alveolar gas equation. If you don't remember from 2nd year, the alveolar gas equation is as follows:

PAO2 = PiO2 - (PACO2/RQ)

where PAO2 is alveolar partial pressure of O2, PiO2 is inspired partial pressure of O2, PACO2 is alveolar partial pressure of CO2 and RQ is respiratory quotient, which in turn is V'CO2/V'O2 (i.e. moles of CO2 produced per moles of O2 consumed). RQ is 1 for a pure carbohydrate diet, around 0.7 for a pure fat diet, and around 0.8 for a normal Western diet.

Since we can't actually measure alveolar gases directly, we assume that they are similar to arterial gases (which they are if gas exchange is normal). Therefore, we can substitute PAO2 for PaO2 and PACO2 for PaCO2 in the above equation. PiO2 is something we can easily measure, and for RQ we can estimate 0.8 (I don't know if there are better ways to measure it though). By substituting our measured PaCO2 into the equation, we can find a theoretical PaO2, which we can then compare to the real PaO2 to find the AaDO2 (Alveolar-arterial difference in oxygen). If AaDO2 is less than 15mmHg, then hypoventilation is the cause of the hypoxemia.

Maybe this will make more sense with an example! Let's say that we have a patient with a PaO2 of 68mmHg and a PaCO2 of 50mmHg. To test whether or not they are hypoventilating, we can substitute the PaCO2 into the alveolar gas equation, find the theoretical PaO2 and compare it with the real PaO2. This gives us the following:

PAO2 = PiO2 - (PACO2/RQ)
PaO2 (theoretical) = 0.21*(760-47) - (50/0.8)
PaO2 (theoretical) = 149.73 - 62.5
PaO2 (theoretical) = 87.23mmHg

AaDO2 = PaO2 (theoretical) - PaO2 (actual)
AaDO2 = 87.23 - 68
AaDO2 = 19.23mmHg

In this case, AaDO2 is more than 15mmHg, so hypoventilation is not the cause of this patient's hypoxemia. In this case, we would have to do extra tests- a 100% oxygen test to rule out shunt and a DLCO test to rule out diffusion capacity issues. If both of those tests come back negative, then the patient has V'/Q' mismatch. Note that hypoxemia due to shunts or diffusion capacity issues are quite rare.