High Altitude and Ventilation

In this post we'll be talking about the effects of high altitude on ventilation, including stuff like mountain sickness.

Describe the ∆ PB at high altitude (HA)

As you are probably aware, barometric pressure (PB) decreases as altitude increases. Barometric pressure drops by half with every 5500m increase in altitude. Generally "high altitude" is classified as 1500-3000m, very high altitude as 3000-5000m and extreme altitude as greater than 5000m.

Understand the stress of HA
Describe the effect of HA on gas exchange

Since the barometric pressure is lower at high altitudes, so too is the partial pressure of oxygen. This means that there is a reduced pressure gradient, and therefore a reduced "driving pressure" for oxygen as you go up. Saturation of haemoglobin also decreases with altitude, so you have even less oxygen in the blood than usual. Heart rate can also increase with altitude, leaving less time for the blood in the pulmonary capillaries to equilibrate with the air. All of these factors combined can lead to hypoxemia (low blood oxygen) and hypoxia at high altitudes.

The alveolar gas equation was also brought up in these slides. The alveolar gas equation, as you may recall, is PAO2 = PIO2 - (PACO2/RQ), where PAO2 is the partial pressure of alveolar oxygen, PIO2 is the partial pressure of inspired oxygen, PAO2 is the partial pressure of alveolar carbon dioxide and RQ is the respiratory quotient (usually around 0.8). On the summit of Mt Everest, the barometric pressure is around 253mmHg, giving a PIO2 of around (253-47)*0.21 = 43mmHg. Plugging this into our equation, along with a "normal" PACO2 of 40mmHg, gives us 43 - (40/0.8) = -7 mmHg. But how can this be? Well, turns out that PACO2 is much lower than 40mmHg at high altitudes due to hyperventilation, as I'll discuss later.

Discuss short- & long term acclimatisation

Acclimatisation to high altitudes depends on several factors: the severity of hypoxic stress (which depends on altitude), the rate of onset of hypoxia (which depends on how quickly you're going up) and individual factors such as genetics. We can look at acclimatisation in both the short and long term. Let's look at the short term first:

Short-term acclimatisation

When we are hypoxic, the peripheral chemoreceptors pick this up and stimulate respiratory centres in the medulla. These centres stimulate an increase in ventilation, which results in a decrease in PACO2 (which is why PACO2 is often lower at high altitudes). A low PACO2 then suppresses the respiratory centres in the medulla, keeping things somewhat in check. Overall, though, ventilation increases by around 1.65 times.

If hypoxia is prolonged, carotid bodies increase their sensitivity to PO2, sending even more signals to the medulla to increase ventilation. Furthermore, the kidneys will eventually start to increase their secretion of bicarbonate ion, balancing out the decrease in PACO2 (and hence stopping low PACO2 from suppressing the medulla). This leads to a roughly 5x increase in ventilation.

Aside from ventilation changes, low PO2 can also cause vasodilation in the systemic circulation. Cardiac output can also increase. This leads to an increase in pulmonary blood flow and sustained oxygen delivery to the tissues.

The problem with short-term acclimatisation is that these processes tend to be very energy-hungry. Thankfully there are also long-term acclimatisation processes!

Long-term acclimatisation

Over a long time, HIF (hypoxia-induced factor) and EPO (erythropoietin) can cause polycytaemia, or an increase in red blood cells. This increases haematocrit and haemoglobin, and therefore oxygen-carrying capacity as well. Polycytaemia raises the O2-Hb dissociation curve (as the extra haemoglobin means that there is more oxygen in the blood at a given partial pressure of blood oxygen), but this all comes at a cost. Polycytaemia causes the blood to become more viscous (resistant to flow), increasing the workload for the heart.

The diffusing capacity of the lung can also increase. Normal diffusing capacity is around 21mL/mmHg/min, but this can increase 2-3 times with acclimatisation. This increase occurs due to an increase in pulmonary arterial blood pressure, pulmonary capillary blood volume and lung air volume.

The cells themselves can acclimatise to high altitudes. They do this by increasing their amounts of mitochondria and oxidative enzymes.

Angiogenesis, or development of new blood vessels, is another important method of acclimatisation. When there is sufficient oxygen, HIF (hypoxia-inducible factor) gets hydroxylated and degraded. When oxygen is low, however, HIF can translocate into the nucleus, where it can upregulate vascular endothelial growth factor, fibroblast growth factor and angiogenin. These factors can lead to increased angiogenesis.

Discuss mountain sickness & treatments

Mountain sickness is, well, sickness from climbing mountains (due to the increase in altitude). Some of the more severe problems at high altitude include high altitude pulmonary oedema and high altitude cerebral oedema.

High altitude pulmonary oedema occurs when hypoxia causes uneven pulmonary vasoconstriction, so that some vessels get hardly any blood and others get way too much. The vessels that get way too much blood get an increase in capillary pressure, causing damage to the capillary wall and oedema. Inflammatory mediators may also be produced, further contributing to oedema.

High altitude cerebral oedema occurs when hypoxia causes brain vasodilation, increased sympathetic activity and the production of factors such as cytokines that increase the permeability of the blood-brain barrier. All of these factors combined can lead to increased capillary pressure in the brain, which leads to leakage and therefore oedema. Symptoms of high altitude cerebral oedema include severe disorientation, seizures and coma.

Now, back to mountain sickness. Mountain sickness can be classified as acute (from climbing a mountain or whatever) or chronic (from living in a high place for a while). Symptoms of acute mountain sickness include headache, dizziness, sleep disturbance, nausea and loss of judgement. Symptoms of chronic mountain sickness, also known as Monge's disease, include the symptoms of acute mountain sickness, as well as pulmonary oedema and heart failure. Heart failure can occur due to polycytaemia (which, as mentioned before, puts extra work on the heart), as well as the increase in blood pressure due to pulmonary artery constriction (as occurs during hypoxia). The right ventricle is usually most likely to be affected, as that's the ventricle that pumps blood to the lungs.

The #1 treatment for mountain sickness is pretty logical: descend to a lower altitude. If that's not possible due to bad weather, you can use a Gamow bag, which is a bag that can be filled to a pressure higher than what you'd be getting on the mountain. In a similar vein, you can use supplemental oxygen. Another treatment option is removal of excess red blood cells via phlebotomy. There are also some drugs that can be used to help: acetazolamide increases ventilation by increasing bicarbonate secretion (this makes the blood more acidic, which increases the drive to breathe) and vasodilators such as nifedipine and sildenafil can help decrease pulmonary hypertension. Steroids, such as dexamethasone, can also aid in treatment.