physiology of high altitude Flashcards
why is blood through the lungs less saturated with O2 at high altitudes?
High altitudes = low partial pressures of oxygen – lower driving force to attach O2 to Hb
what causes the physiological effects of altitude?
hypoxia
how is increased ventilation stimulated by low PaO2?
resulting hypoxaemia stimulates hypoxia detectors in the carotid bodies
what antagonises the hypoxia-driven hyperventilation?
antagonised by the more powerful decrease of ventilation
caused by excess blow off CO2 which causes alkalosis at the central chemoreceptors
which then inhibit the increase in respiratory drive
when is the hypoxic drive from carotid bodies significnt?
in moderate hypoxia (O2 below 60mmHg) and high pCO2
what is moderate hypoxia
O2 below 60mmHg
what type of ascent causes ill effects?
rapid ascent
what does rapid ascent to >2000m cause?
stimulats SNS to increase resting HR and CO and mildly increased BP
how does rapid ascent lead to mild pulmonary arterial hypertension?
low pO2 alveoli
pulmonary circulation reacts to the hypoxia with vasoconstriction
worsens hypoxaemia
pulmonary resistance increases bc the whole pulmonary circulation is increased –> mild pulmonary arterial hypertension
what is acclimatisation?
We adapt to high altitudes – initial pulmonary hypertension wears off and hypoxia disappears
how long does acclimatisation to 2000m take?
rapid
usually within a day or two
how long does acclimatisation from 2000m-6000m take and in who?
will occur in people without respiratory disease - may take a few weeks.
how will fully acclimatised climbers feel at 6000m? what tasks can they carry out?
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
what happens to people at 7000m?
significant hypoxia is present. Feel more tired and lethargic. Continuous exercise becomes impossible. Climbing easy slopes becomes difficult
what heights are considered the death zone?
above 7500m
what happens to even acclimatised climbers in the death zone?
Acclimatised climbers have severe hypoxia and can only remain there for 2-3 days. After that the body’s major systems will show severe physiological damage.
what are the 3 components in the mechanism of acclimatisation?
1) Metabolic acidosis caused by acid retention and increased bicarbonate excretion in the kidneys
2) Increase in erythrocyte number (haematocrit)
3) Reduced pulmonary vascular resistance
what causes respiratory alkalosis during acclimatisation?
- Low pO2 in inspired air stimulates increased rate and depth of breathing
- Blows off excess CO2 respiratory alkalosis
how does metabolic acidosis occur during acclimatisation?
- High pH from resp alkalosis inhibits central chemoreceptors breathing decreases hypoxaemia
- Kidneys response to hypoxaemia by increasing bicarbonate excretion
- Together w decreased acid excretion metabolic acidosis
how is normoxia restored in acclimatisation?
- Metabolic acidosis counteracts the respiratory alkalosis pH restored
- Drive to central chemoreceptors is restored
- Now a sustained increase in rate and depth of breathing – restores normoxia
how is haematocrit increased in acclimatisation?
• Hypoxaemia also stimulates the interstitial cells in the kidney to raise EPO production increases haematocrit increases O2 carrying capacity of the blood
why is there a functional limit to increased haematocrit?
bc increased haematocrit increases blood viscosity –> increases PVR pulmonary arterial hypertension right heart failure
why do athletes train at high altitudes?
Bc acclimitisation increases haematocrit, athletes train at high altitudes. Increase lasts for a few weeks greater aerobic capacity
why does PVR fall during acclimatisation?
o Reduced hypoxic vasoconstriction response
o Collateral circulations opening up between pulmonary arteries and veins
• Change occurs bc of an increased synthesis of NO in the pulmonary endothelium
what happens if the ascent is too high/rapid and there isnt time for acclimatisation?
one or more forms of altitude sickness results;
- acute mountain sickness
- HACE: high altitude cerebral oedema
- HAPE: high altitude pulmonary oedema
what is the first form of altitude sickness that manifests?
acute mountain sickness
what are signs and symptoms of AMS?
Headache (essential for diagnosis) • Poor sleep • Tiredness Loss of appetite, nausea, vomiting • Dizziness (similar to hangover symptoms)
how do you score and diagnose AMS?
All scored 0-3 for severity of symptoms – need score of >3 for AMS diagnosis
how do you treat AMS?
• If mild, rest (no further ascent)
•If more severe then:
o Immediate Descent
o Oxygen
o Acetazolamide 250mg tds (three times daily)
o Dexamethasone 4mg qds, (four times daily) oral or iv
how can you prevent AMS?
- Slow ascent (<300m per day over 3000m)
- Avoid unnecessary exercise
- Acetazolamide 250mg bd at start of climb
what is acetazolamide?
carbonic anhydrase (CA) inhibitor that speeds up the process of acclimatisation
why is carbonic anhydrase in the kidneys important?
• Carbonic anhydrase in PCT of kidney is vital for renal absorption of bicarbonate
what does inhibition of carbonic anhydrase cause?
causes increased bicarbonate excretion metabolic acidosis that compensates for respiratory alkalosis caused by hyperventilation at altitude
what part of the body filters bicarbonate? where is it reabsorbed?
glomerulus
reabsorbed mainly in the PCT
what ion is bicarbonate reabsorption linked to?
sodium
explain the action of acetazolamide
- Blocks conversion of bicarbonate to CO2 in the lumen so filtered bicarbonate stays in the tubule and is lost in the urine
- Bc CA is blocked inside the cell, CO2 from the blood can’t be converted to bicarbonate.
- So no H+ is available for the Na+/H+ ATP-ase – H+ aren’t pumped into the urine Na+ isn’t reabsorbed
- Na+ is excreted in the urine instead of protons
what is the net effect of acetazolamide?
bicarbonate & sodium are lost in urine - not reabsorbed. The urine becomes alkaline and the blood becomes more acidic –> metabolic acidosis
what do high doses of acetazolamide cause?
inhibit CA in RBCs; blocks transport of CO2 from tissues to lungs - decreases loss of CO2 in lungs, tends to counteract excessive loss of CO2 from the body by hyperventilation
what are symptoms of high altitude cerebral oedema?
- Ataxia – key symptom!
- Nausea/vomiting
- Hallucination or disorientation
- Confusion
- Reduced conscious level
- Coma – can lead to unconsciousness and death within 12hrs from onset of symptoms, but normally takes 1-2 days to develop
why is a HACE coma so dangerous? how long does it take to develop?
can lead to unconsciousness and death within 12hrs from onset of symptoms, but normally takes 1-2 days to develop
when should treatment be started for HACE?
at first sign of ataxia
how should HACE be treated?
• Descend immediately - but a PAC (portable altitude chamber) bag will often be used first if available
• Acetazolamide - reduces formation of CSF so reduces intracranial pressure
• Oxygen – 2-4L/min oxygen
• Dexamethasone (Diamox) – corticosteroid widely used as an anti-inflammatory med. Prevents brain swelling.
o 8mg given as first dose
o 4mg then given every 6 hours orally or intravenously (prevents brain swelling)
why is acetazolamide used to treat HACE?
reduces formation of CSF so reduces intracranial pressure
what is dexamethasone?
corticosteroid widely used as an anti-inflammatory med. Prevents brain swelling.
what does of Diamox should be given to treat HACE?
o 8mg given as first dose
o 4mg then given every 6 hours orally or intravenously (prevents brain swelling)
why does HACE occur?
- In hypoxaemia ATP supply in nerve cells decreases and Na+ pumps run down
- Na+ leaks into nerve cells draws in water brain cells swell increased ICP cerebral veins blocked
- Cerebral circulation fails hypoxia gets worse oxygen-deprived neurons are squashed and start to die
what are signs and symptoms of high altitude pulmonary oedema?
- Dyspnoea
- Reduced exercise tolerance
- Dry cough
- Blood stained sputum
- Crackles on auscultation of chest
why does high altitude pulmonary oedema occur?
- Hypoxic pulmonary vasoconstriction that occurs initially on ascent normally decreases with acclimatisation
- If it doesn’t occur then pulmonary arterial hypertension can develop
- Raised arterial and capillary pressure leads to fluid leaving the blood and entering the alveoli pulmonary oedema
- Worsens already compromised gas exchange
- Increases hypoxia and increases constriction vicious cycle occurs
what is the treatment for HAPE?
- Descend immediately
- Sit patient upright
- Oxygen
- Nifedipine (calcium channel blocker) 20mg qds orally
- Hyperbaric chamber
- Sildenafil* (Viagra) – inhibits altitude-induced hypoxaemia and pulmonary hypertension
what is Nifedipine and what is its effect?
(calcium channel blocker) helps block pulmonary artery constriction - reduces PAH.qw
how does a hyperbaric chamber help?
increases PaO2 to improve oxygenation of blood and also reduce hypoxic vasoconstricton
what is the effect of Sildenafil?
pulmonary hypoxic vasoconstriction bc of lack of NO being released from the pulmonary endothelium
o Slows down the breakdown of cyclic GMP (vasodilator produced by NO)
o Increasing cGMP levels with Viagra relaxes pulmonary arteries, stops PAH and improves blood oxygenation
what is the difference between HACE and HAPE in terms of symptoms?
HACE is AMS with CNS symptoms
HAPE is AMS with pulmonary symptoms
