Physiology of high altitude Flashcards
What is air like at high altitude?
- PO2 is less
- lower driving force to attach oxygen to haemoglobin
- blood passing through lungs is less saturated with oxygen
- results in pulmonary hypoxia and hypoxaemia
Why does increased ventilation not resolve hypoxia and hypoxaemia at high altitudes?
Low PO2 and hypoxaemia detected by carotid bodies = increased ventilation
Excess blow off of CO2 = alkalosis detected by central chemoreceptors = inhibit increase in respiratory drive
Therefore 2 mechanisms are opposite and ventilatory response is inadequate
How significant is the hypoxic drive?
Very weak, only significant when PO2 below 60mmHg and when pCO2 is high
What is the initial response to a rapid ascent in altitude?
SNS stimulation -> increased HR and CO and BP
Low PAO2 -> pulmonary circulation vasoconstriction -> worsening hypoxaemia -> pulmonary resistance increase -> mild pulmonary arterial hypertension
What is acclimatisation?
Adapt to high altitude
- initial pulmonary arterial hypertension wears off and hypoxia disappears
What are the limits to acclimatisation?
> 7500m is referred to as the death zone
acclimatised climbers have severe hypoxia and can only remain there for 2 or 3 days
body’s major systems will then start to show severe physiological damage
What 3 things happen during acclimatisation?
1) metabolic acidosis as acid retention and increased bicarbonate excretion
2) increase in erythrocyte number, haematocrit increase
3) reduced pulmonary vascular resisatnce
What are the physiological changes during acclimatisation?
- low pO2 stimulates increased breathing rate and depth which blows excess CO2 off = respiratory alkalosis, high pH inhibits central chemoreceptors so breathing rate decreases = hypoxaemia
- kidneys respond to hypoxaemia by bicarbonate excretion and this with acid excretion = metabolic acidosis counteracting resp alkalosis restoring pH and drive to central chemoreceptors = sustained increase in rate and depth of breathing restoring normoxia
- hypoxaemia also stimulates interstitial cells in kidney to raise EPO = increased haematocrit and oxygen carrying capacity of blood
- fall in pulmonary vascular resistance, due to reduced hypoxic vasoconstriction and collateral circulation opening (NO effect in pulmonary endothelium)
Why do athletes train in high altitudes?
To increase their haematocrit - increase lasts for a week weeks after they return to low altitude giving them greater aerobic capacity
What is altitude sickness?
- not enough time for acclimatisation and ascent is too rapid or too high
you get: - acute mountain sickness: first sign
- High altitude cerebral edema: if AMS not treated, serious neurological condition, fatal if not treated
- High altitude pulmonary edema: equally serious pulmonary condition following AMS
What are some signs and symptoms of AMS?
headache, poor sleep, tiredness, loss of appetite/nausea/vomiting, dizziness
(alcohol hangover like symptoms)
scored 0-3 for severity
need >3 score for diagnosis of AMS
At what height does AMS occur after rapid ascent?
> 5000m everyone will get it, acclimatisation will take several days or more
2500-5000 - 1 in 5, most acclimatise in a day or so
How is AMS treated?
- if mild - rest and no further ascent
- if more severe:
immediate descent
oxygen
acetazolamide
dexamethasone
How is AMS prevented?
slow descent
avoid unnecessary exercise
acetazolamide
What does acetazolamide do?
carbonic anhydrase inhibitor
conversion of bicarbonate back to CO2 is blocked so filtered bicarbonate is just lost in the urine instead of reabsorbed
no protons produced inside the tubular cells so none pumped out via the sodium hydrogen pump into the urine meaning sodium is not reabsorbed either
this means the urine is less acidic as more bicarb gets excreted instead of reabsorbed and H+ does not get excreted as cannot be ejected via pump
- hence acetazolamide increases retention of acid in the body instead accelerating respiration
- high doses of it also inhibits CA in RBCs blocking CO2 transport from tissues to lungs decreasing lung loss of CO2
How is bicarbonate reabsorbed?
Gets filtered in the glomerulus and then reabsorbed in the PCT
- CO2 from blood diffuses into the PCT cells around the kidney and react with water to get converted to H2CO3 by carbonic anhydrase and then broken down into H+ and HCO3-
- H+ protons get ejected into the PCT cell lumen via the sodium/proton exchange transporter while sodium gets reabsorbed
- HCO3 that has been filtered out into the PCT lumen then react with the excreted protons to get converted back to carbon dioxide and water by carbonic anhydrase
- CO2 diffuses back into the tubule cell joining the blood CO2
- bicarbonate and sodium is reabsorbed and more protons are excreted than bicarbonate ions
What are some symptoms of high altitude cerebral oedema?
ataxia Nausea/vomiting Hallucination or disorientation Confusion Reduced conscious level Coma
Why does HACE occur?
hypoxaemia = decrease ATP supply in nerve cells = sodium pumps run down = sodium leaks into nerve cell = pulls water with it and brain swells = intracranial pressure raised = cerebral veins blocked = cerebral circulation fails = hypoxia worsens = neurones die as oxygen starved
How is HACE treated?
1) immediately descend
2) Acetazolamide - reduces CSF formation so intracranial pressure reduced
3) oxygen
3) dexamethasone
5) hyperbaric chamber
What are some signs and symptoms of HAPE?
Dyspnoea Reduced exercise tolerance Dry cough Blood stained sputum Crackles on auscultation of chest
Why does HAPE occur?
hypoxic pulmonary vasoconstriction doesn’t decrease with acclimatisation = pulmonary arterial hypertension = fluid leaves blood and enters alveoli = gas exchange worsened even more = hypoxia increased and constriction increased = viscous cycle
How is HAPE treated?
1) immediately descend
2) sit upright
3) oxygen
4) nifedipine (CCB) - blocks constriction of pulmonary arteries and so reduces PAH
5( hyperbaric chamber) - increases partial pressure of oxygen to improve oxygenation of blood and reduces hypoxic vasoconstriction
6) Viagra (sildenafil) - inhibits altitude induced hypoxaemia and pulmonary hypertension, increases cGMP levels which is the vasodilator produced by NO so pulmonary arteries relaxed improving oxygenation of blood
What is the key symptomatic difference between HACE and HAPE?
HACE - AMS with CNS symptoms
HAPE - AMS with pulmonary symptoms
