Physiology of high altitude

Question 1

how does hypoxia and hypoxemia result at high altitudes

Answer 1

• At high altitudes the partial pressure of oxygen in the atmosphere is less, and so the ‘driving force’ to attach oxygen to haemoglobin is less. Blood passing through the lungs is less saturated with oxygen than normal. Pulmonary hypoxia and hypoxemia results.

Question 2

define hypoxemia

Answer 2

low concentration of oxygen in the blood

Question 3

what is the drive to breath mainly caused by

Answer 3

• The hypoxic drive from carotid bodies is weak and normally only becomes significant at PO2 below 60mmHg, ie during moderate hypoxia
• Hypoxic drive is only significant in low pO2 in the presence of high pCO2
• but main drive for ventilation is regulated by paCO2

Question 4

what are the physiological effects of ascent to altitude due to

Answer 4

hypoxia

Question 5

what antagonises the hypoxic driven hyperventilation response

Answer 5

• this hypoxia-driven hyperventilation response is partially antagonised by the depression of ventilation caused by excess blow off of CO2 resulting in alkalosis at the central chemoreceptors, which then inhibit the increase in respiratory drive.
• Thus the ventilatory response is inadequate to cope with the low pO2 and a degree of hypoxaemia and hypoxia results.

Question 6

when do we suffer ill effects of altitude

Answer 6

We suffer ill effects with a rapid ascent to high altitude (over 2000 m)
- can cope well if the ascent is gradual as there is time to acclimatise to to the height

Question 7

why do we get ill with rapid ascent to high altitude to 2000m or more

Answer 7

• the sympathetic nervous system is triggered
• this causes increased resting heart rate and therefore cardiac output increases and so does blood pressure
• the partial pressure of oxygen in the alveoli is low at a high altitude
• this causes global hypoxia in the lungs which leads to global vasoconstriction due to the ventilation perfusion mismatch
• this pulmonary resistance increases and results in mild pulmonary artery hypertension
• this causes a decrease in cardiac output

Question 8

what happens in acclimatisation

Answer 8

We acclimatise (adapt) to high altitude This means that the initial pulmonary arterial hypertension wears off and the hypoxia disappears.

Question 9

how long does acclimatisation take at…
2000m
2000-6000m

Answer 9

Acclimatisation (from sea level) to 2000m is rapid, usually within a day or two.

Acclimatisation to altitudes 2000-6000m will occur in people without respiratory disease, although it may take a few weeks.

Question 10

describe the limit to acclimatisation

Answer 10

At 6000m fully acclimatised climbers may expect to feel well, have reasonable appetites, sleep normally and be capable of carrying loads of 20-25 kilos on easy ground.

Above 7000m,: significant hypoxia is present, the feeling of tiredness and lethargy increases, continuous exercise becomes impossible and climbing even easy slopes becomes a painstaking, breathless achievement.

Regions above 7500 meters are referred to as the death zone: Even acclimatised climbers have severe hypoxia and can only remain there for two or three days. After that the body’s major systems will start to show severe physiological damage. Unless they have oxygen

Question 11

name 3 things that happen in acclimatisation

Answer 11

1) A metabolic acidosis caused by retention of acid and increased excretion of bicarbonate in the kidneys
2) An increase in erythrocyte number (haematocrit)
3) Reduced pulmonary vascular resistance.

Question 12

why does the body generate a metabolic acidosis during acclimatisation

Answer 12

1) Initially the low pO2 in the inspired air stimulates an increased rate and depth of breathing.
- However this blows off excess CO2 and produces a respiratory alkalosis.
- The high pH inhibits central chemoreceptors so the breathing decreases, resulting in hypoxaemia.
2) The kidneys respond to this hypoxaemia by increasing excretion of bicarbonate.
- This, together with decreased acid excretion produces a metabolic acidosis.
- This metabolic acidosis counteracts the respiratory alkalosis and restores the pH to normal.
- The drive to the the central chemoreceptors is restored:
- There is a now a sustained increase in rate and depth of breathing to restore normoxia.

Question 13

why is there an raised erythrotopien production in acclimatisation

Answer 13

2) During acclimatisation the hypoxaemia also stimulates the interstitial cells in the kidney to raise erythropoeitin production.
- This increases the haematocrit and thus helps to increase the oxygen carrying capacity of the blood.

Question 14

what is the negative part to an increased erytropotien production in acclimatisation

Answer 14

There is a functional limit to the maximum haematocrit as an increased haematocrit increases the blood viscosity. A higher viscosity increases the pulmonary vascular resistance and can lead to pulmonary arterial hypertension and right heart failure.

Question 15

why do athelets go to high altitudes to train

Answer 15

. Because acclimatisation increases haematocrit, many athletes will go to high altitudes to train; this increases their haematocrit; this increase will last for a few weeks after they return to low altitude, and will give them greater aerobic capacity.

Question 16

why does pulmonary vascular resistance decrease during acclimitsiation

Answer 16

During acclimatisation the pulmonary vascular resistance falls.

• This is partly due to a reduced hypoxic vasoconstriction response and partly due to collateral circulations opening up between pulmonary arteries and veins.
• The mechanism mediating this change is believed to be an increased synthesis of nitric oxide in the pulmonary endothelium

Question 17

when does acute mountain sickness arise

Answer 17

• If the ascent is too rapid or too high, there is not time for acclimatisation and one or more forms of altitude sickness result

Question 18

name three types of acute mountain sickness

Answer 18

• AMS: Acute Mountain Sickness. The first sign that something is wrong. If you ignore this that you can progress to the next two conditions
• HACE: High Altitude Cerebral Edema. Can follow on from AMS if not treated. A serious neurological condition; fatal if not treated
• HAPE: High Altitude Pulmonary Edema. Equally serious pulmonary condition which can follow on from AMS.

Question 19

what are the signs and symptoms of acute mountain sickness

Answer 19

• Headache (essential for diagnosis) – due to constriction of blood vessels
• Poor sleep
• Tiredness
• Loss of appetite, nausea, vomiting – due to constriction of blood vessels in the brainstem
• Dizziness – due to constriction of blood vessels of the vestibuli nuclei in the blood vessel and pons
(all scored 0-3 for severity of symptoms)

• need a score of greater than 3 for a diagnosis of MAS

Question 20

at what height does AMS occur after a rapid ascent from sea level

Answer 20

• 1500-2000m: mild illness possible but unlikely in most individuals. (Denver Colorado with 600,000 population is at ~1600m)
• 2500m: About 1 in 5 people have some symptoms of AMS if they ascend from sea level within a day to 2500 meters. However, most people will acclimatize within a day or so. (worldwide, 40m people live above 2,500m)
• 5000m: Everyone will become temporarily ill if they ascend within a few hours to 5000m (eg in an airoplane). Acclimatisation will occur but can takes several days or more.

Question 21

what is the treatment of AMS

Answer 21

A) If mild, rest (no further ascent !)
B) If more severe then:
1. Immediate Descent
2. Oxygen
3. Acetazolamide 250mg tds (three times daily)
4. Dexamethasone 4mg qds, (four times daily) oral or iv – steroid that can prevent brain swelling due to hypoxia,

Question 22

how do you prevent onset of AMS

Answer 22

1. Slow ascent (<300m per day over 3000m)
2. Avoid unnecessary exercise
3. Acetazolamide 250mg bd at start of climb – decreases metabolic acidosis

Question 23

what is acetazolamide (Diamox)

Answer 23

• drug used to prevent and treat AMS

- Acetazolamide is a carbonic anhydrase (CA) inhibitor

Question 24

how does acetazolamide work

Answer 24

• Acetazolamide is a carbonic anhydrase (CA) inhibitor.
• Inhibition of CA activity causes increased bicarbonate excretion producing a metabolic acidosis that compensates for the respiratory alkalosis caused by the hyperventilation at altitude.
• this happens normally by acetazolamide just speeds up the process
• With acetazolamide, the conversion of bicarbonate to CO2 in the lumen is blocked and so the filtered bicarbonate stays in the tubule and is lost in the urine.

Question 25

what does acclimitisation do to bicarbonate

Answer 25

• bicarbonate is filtered in the glomerulus but normally all of it is reabsorbed, mainly in the proximal tubule.
• Acclimatisation is essentially a process of reducing this reabsorption

Question 26

descirbe how bicarbonate is not excreted and remains in the body

Answer 26

A) CO2 diffuses from blood into proximal tubule cells where it is converted into bicarbonate and protons by carbonic anhydrase (CA) inside the cells.

• The protons formed are ejected into the tubular lumen by a Na+/H+ exchange ATP-ase.
• Result: sodium is reabsorbed from tubular fluid and protons ejected into tubular fluid. Bicarbonate collects in cell

B) The excreted protons react with bicarbonate in the lumen.

• The two ions are converted to CO2 & water by carbonic anhydrase lining the tubule.
• The CO2 formed diffuses back into the cell where it is converted back to carbonic acid, generating more protons to exchange with sodium

C) The CO2 that has diffused back into the cell is then converted back to bicarbonate and protons by more carbonic anhydrase present inside the tubular cell.

• The protons are pumped out to continue the reabsorption cycle.
• End result: The filtered bicarbonate & sodium are transferred from the tubular cells back into the blood.

Question 27

what is a side effect of acetazolamide

Answer 27

• can cause the excretion of sodium ions
• therefore the urine can become more alkaline and the blood can become more acidic

this is because
- As CA is blocked inside the cell as well, CO2 from the blood cannot be converted to bicarbonate. So no protons are available for the Na+/H+ ATP-ase; the result is that protons are not pumped into the urine and sodium is not reabsorbed. Sodium ions are excreted in the urine instead of protons.

• take salt tablets to fix this

Question 28

what does HACE stand for

Answer 28

high altitidue cerebral oedema

Question 29

what are the symptoms of HACE

Answer 29

1. Ataxia – effects co-ordination, balance and speech
2. Nausea/vomiting
3. Hallucination or disorientation – due to cortical hypoxia
4. Confusion – due to cortical hypoxia
5. Reduced conscious level- due to cortical hypoxia
6. Coma
   - Key symptom is ataxia, important if you are climbing a mountain

Question 30

what is the treamtnet of HACE

Answer 30

1. Descend immediately
2. Acetazolamide (reduces formation of CSF so reduces intracranial pressure) – given every 12 hours and 2-3 litres/minute oxygen
3. Oxygen
4. Dexamethasone 8mg then 4mg every six hours orally or intravenously (prevents brain swelling)
5. Hyperbaric chamber (portable hyperbaric

Question 31

what is dexamethasone

Answer 31

corticosteroid widely used as an anti-inflammatory medicine

Question 32

why does HACE occur

Answer 32

• In hypoxaemia the supply of ATP in nerve cells decreases and the sodium pumps run down.
• Sodium leaks into the nerve cell, it pulls water with it and the brain cells swell.
• This raises intracranial pressure (icp) and blocks cerebral veins.
• The cerebral circulation fails, hypoxia gets worse and the neurones, starved of oxygen and squashed together, start to die.

Question 33

how quickly does a coma develop with HACE

Answer 33

Coma from HACE can lead to unconsciousness and death within 12 hours from the onset of symptoms, but normally takes 1-2 days to develop.

Question 34

what does HAPE stand for

Answer 34

High Altitude Pulmonary Edema

Question 35

what are the signs and symptoms of HAPE

Answer 35

1. Dyspnoea
2. Reduced exercise tolerance
3. Dry cough
4. Blood stained sputum
5. Crackles on auscultation of chest

Question 36

why does HAPE happen

Answer 36

• The hypoxic pulmonary vasoconstriction that occurs initially on ascent to altitude normally decreases with acclimatization.
• If this does not occur pulmonary arterial hypertension can develop.
• The raised arterial and capillary pressure leads to fluid leaving the blood and entering the alveoli causing pulmonary oedema.
• This worsens the already compromised gas exchange.
• This increases the hypoxia and increases the constriction and a vicious circle occurs

Question 37

what is the treatment of HAPE

Answer 37

1. Descend immediately
2. Sit patient upright
3. Oxygen
4. Nifedipine (calcium channel blocker) 20mg qds orally
5. Hyperbaric chamber
6. Sildenafil* (Viagra)

Question 38

what is the action of nifedipine

Answer 38

(calcium channel blocker) helps block the constriction of the pulmonary arteries and thus reduces PAH.

Question 39

what is the action of a hyperbaric chamber

Answer 39

increases partial pressure of oxygen to improve oxygenation of blood and also reduce hypoxic vasoconstricton

Question 40

what is the action of sildenafil

Answer 40

pulmonary hypoxic vasoconstriction is due to a lack of nitric oxide being released from the pulmonary endothelium.

Sildenafil slows down the breakdown of cyclic GMP, which is the vasodilator produced by nitric oxide.

Increasing cyclic GMP levels with viagra relaxes the pulmonary arteries, stops PAH and improves oxygenation of blood