Physiology of High Altitude

Question 1

How does altitude affect pO2?

Answer 1

pO2 decreases at altitude

Question 2

How does oxygen saturation change at altitude?

Answer 2

At altitude pO2 is decreases and therefore the amount of oxygen available to bind to haemoglobin is reduced, and therefore oxygen saturation is decreased

Question 3

Why do you get hypoxia-driven symptoms at altitude?

Answer 3

Because the body regulates ventilation relative to pCO2 levels, therefore pCO2 levels are maintained but the body becomes hypoxic due to the reduced pO2 at altitude leading to decreased oxygen saturation of Hb

Question 4

How does hypoxia at altitude attempt to increase ventilation rate? Why is this not achieved?

Answer 4

The low pO2 stimulates increased ventilation via the hypoxia chemoreceptors in the carotid body. However, there is a simultaneous powerful depression of excess ventilation as pCO2 levels are normal and therefore hyperventilation is prevented in order to prevent excess CO2 blow-off which would cause respiratory alkalosis.

Question 5

When does the hypoxic drive from the carotid bodies become significant at altitude?

Answer 5

The hypoxic drive produced by the carotid bodies is a relatively weak response and it only really becomes significant when pO2 becomes extremely low, at around 60mmHg and below

Question 6

How does the body respond to a rapid ascent to 2,000m or higher?

Answer 6

This induces increased sympathetic activity. This causes systemic vasoconstriction, increased BP and HR. However, due to the low pO2 there is also vasoconstriction in the pulmonary circulation to redistribute the ventilation perfusion ratio (but this is inappropriate in this scenario) and this therefore worsens the hyperaemia. As a result there is increased pulmonary resistance and this causes pulmonary arterial hypertension.

Question 7

At what altitude would you begin to feel lethargy and tiredness due to the reduced pO2 levels?

Answer 7

7,000m+

Question 8

At what altitude would you only be able to stay for 2/3 days before severe physiological damage was done?

Answer 8

7,500m+, this is known as the death zone.

Question 9

What are the three main mechanisms by which the body acclimatises to altitude?

Answer 9

1) Causing a metabolic acidosis (retains H+ and excretes bicarbonate in the kidney)
2) Increasing erythrocyte numbers
3) Reducing pulmonary vascular resistance

Question 10

Why does the body induce a metabolic acidosis in acclimatisation to altitude?

Answer 10

The prolonged hyperaemia decreases the action of the H+ ATPase in the distal nephron and therefore there is retention of H+ and increased HCO3- excretion in the proximal tubule. This causes a metabolic acidosis which stimulates the central chemoreceptors which cause increased ventilation to form a compensatory respiratory alkalosis (which helps to increase O2 uptake from the decreased atmospheric pO2) and also amplifies hypoxia drive from the carotid body to increase ventilation rate too.

Question 11

What chemoreceptors are affected by metabolic acidosis?

Answer 11

Central chemoreceptors (to stimulate a compensatory hyperventilation/respiratory alkalosis) and the carotid bodies to amplify hypoxic drive

Question 12

How does the body increase EPO production in acclimatisation to altitude?

Answer 12

Hypoxaemia stimulates the interstitial cells of the kidney to increase EPO production in order to increase red cell production and therefore increase the oxygen-carrying capacity of the blood

Question 13

Which cells produce EPO?

Answer 13

Interstitial cells of the kidney

Question 14

Why is there a functional limit as to how much EPO the body can/should produce?

Answer 14

If there is excess EPO production this leads to the increased production of red blood cells, this raises the haematocrit level which increases the viscosity of the blood. This increased viscosity can lead increased pulmonary vascular resistance and can cause pulmonary arterial hypertension and right heart failure.

Question 15

How is pulmonary vascular resistance reduced in acclimatisation to altitude?

Answer 15

The hypoxia-induced pulmonary vasoconstriction is reduced and collateral circulation is produced between the pulmonary arteries and veins. This is thought to be caused by an increase in NO synthesis

Question 16

What causes altitude sickness?

Answer 16

If the ascent is too high, too rapid or there is insufficient time for acclimatisation.

Question 17

What are the three main types of altitude sickness (in order of severity)?

Answer 17

1) Acute mountain sickness (least severe - first sign that something is wrong)
2) High altitude cerebral oedema
3) High altitude pulmonary oedema

Question 18

What are the signs and symptoms of acute mountain sickness?

Answer 18

HEADACHE, poor sleep, fatigue, loss of appetite, nausea, vomiting and dizziness

Question 19

Why is acetazolamide used in the treatment of mountain sickness (MoA)?

Answer 19

Acetazolamide is a carbonic anhydrase inhibitor that can act as a diuretic. It acts to increase sodium excretion and reduce H+ excretion and therefore leads to increase water loss. However, this increased H+ retention can also cause a metabolic acidosis which helps to speed up acclimatisation as it will cause activation of central chemoreceptors and amplification of the action of hypoxia-sensing carotid bodies to cause an increased ventilation rate which can act to compensate for the reduced atmospheric pO2 levels.

Question 20

What is the cause of acute mountain sickness?

Answer 20

Ascending too quickly

Question 21

Describe the treatment of acute mountain sickness.

Answer 21

> If the condition is mild, rest and ascend no further
If the AMS is more severe then descend, provide oxygen, provide acetazolamide 250mg td (speeds up acclimatisation by causing metabolic acidosis) and give dexamethasone qd

Question 22

How can acute mountain sickness be prevented?

Answer 22

With a slow ascent (<300m per day over 3,000m), avoid unnecessary exercise and take acetazolamide bd

Question 23

What are thy symptoms of high altitude cerebral oedema?

Answer 23

Ataxia (loss of full control of body movements), nausea, vomiting, hallucination, confusion, reduced conscious level, coma.

Question 24

Explain the pathophysiology behind high altitude cerebral oedema

Answer 24

In hyperaemia there is insufficient blood supply to the brain to supply it’s metabolic requirements, and therefore the sodium pumps can’t function and sodium can leak back into the nerve cell which can cause brain cells to swell, increase intracranial pressure and block the cerebral veins. Eventually these neurones/glial cells will begin to die.

Question 25

How is high altitude cerebral oedema treated?

Answer 25

• Descend immediately
• Acetazolamide (reduces the formation of CSF reduces intracranial pressure)
• Provide oxygen
• Dexamathasone – 8mg then 4mg 4 times a day to prevent brain swelling
• Hyperbaric chamber

Question 26

What are the signs and symptoms of high altitude pulmonary oedema?

Answer 26

Dyspnoea, reduced exercise tolerance, dry cough, blood-stained sputum, crackles on chest auscultation

Question 27

Explain the pathophysiology of high altitude pulmonary oedema

Answer 27

If the initial hypoxic pulmonary vasoconstriction doesn’t resolve with acclimatisation, then pulmonary arterial hypertension can develop leading to fluid leaving the blood and entering the alveoli. This worsens the already compromised gas exchange –> increased hypoxia –> increased constriction –> cycle continues.

Question 28

Describe the treatment of high altitude pulmonary oedema

Answer 28

• Descend immediately
• Sit patient upright
• Provide oxygen
• Nifedipine (calcium channel blocker) – 20mg 4 times a day orally, this helps to inhibit the constriction of the pulmonary arteries vasodilation decreased pulmonary arterial pressure
• Hyperbaric chamber – this increases the partial pressure of oxygen and there helps in improving the oxygenation of the blood and also helps to reduce the hypoxic vasoconstriction
• Viagra – inhibits altitiude-induced hypoxaemia and pulmonary hypertension; it slows down the breakdown of cGMP (the vasodilator produced by NO) which leads to relaxation of the pulmonary arteries improves

Question 29

What is nifedipine and why is it used in the treatment of high altitude pulmonary oedema?

Answer 29

This is a calcium channel blocker that prevents calcium entry into the smooth muscle of blood vessels and therefore acts to produce vasodilation, especially in the pulmonary arteries in order to decrease pulmonary arterial pressure and subsequently prevent the oedema formation

Question 30

Why is viagra used in the treatment of high altitude pulmonary oedema?

Answer 30

Viagra slows down the breakdown of cGMP (the vasodilator that is produced by action of NO and therefore this leads to pulmonary arterial vasodilation which improves the symptoms of oedema (as pulmonary oedema reduces)

Question 31

How may acetazolamide administration also prevent excessive loss of carbon dioxide in hyperventilation at altitude?

Answer 31

High doses will inhibit the carbonic anhydrase in red blood cells, and this will block the transport of carbon dioxide from the tissues to the lungs and therefore will decrease the amount of carbon dioxide in the lungs