Physiology of high altitude Flashcards
Partial pressure O2 at high altitudes
Less
“driving force” to attach O2 to haemoglobin less
Blood in lungs at high altitudes
Less saturated with O2
–> pulmonary hypoxia + hypoxaemia
Ventilation is mainly regulated by
PaCO2
PaCO2 at altitude
Kept constant by body
BUT body becomes hypoxic because of lower partial pressure of O2
Hypoxic drive
Hypoxic drive cannot overcome inhibition by hypercapnic drive
Physiological effects of ascent to altitude are due to
Hypoxia
Physiological effects at high altitude
Low partial pressure of O2 + resulting hypoxaemia will stimulate increased ventilation via hypoxia detectors in carotid bodies
BUT hypoxia-driven ventilation response partially antagonised by more powerful depression of ventilation caused by excess blow off of CO2
–> alkalosis at central chemoreceptors
–> then inhibit the increase in resp. drive
Ventilatory response at high altitude
Inadequate to cope with the low pO2 and a degree of hypoxaemia + hypoxia results
Hypoxic drive from carotid bodies
Weak
Normally only becomes significant at PO2 below about 60mmHg
Hypoxic drive significance
Only significant in low pO2 together with high pCO2
Rapid ascent to 2000m+
Stimulates SNS
Increased resting HR + CO
Mildly increased BP
Rapid ascent 2000m+ after minutes of exposure
PO2 in alveoli is low, so pulmonary circulation reacts to hypoxia with vasoconstriction
–> worsens hypoxaemia
Pulmonary resistance rapid ascent 2000m+
Increases
–> mild pulmonary arterial hypertension
Acclimatisation
Adapting to high altitude
Initial pulmonary arterial hypertension wears off + hypoxia disappears
Acclimatisation from sea level –> 2000m
Rapid
Day or two
Acclimatisation from sea level –> 2000-6000m
Occur in people without respiratory disease
May take few weeks
Fully acclimatised climbers at 6000m
Feel well
Reasonable appetites
Sleep normally
Capable of carrying loads of 20-25kg on easy ground
Above 7000m
Significant hypoxia
Tiredness + lethargy increases
Continuous exercise impossible
Climbing easy slopes painstaking + breathless
Above 7500m
Death zone
Even acclimatised climbers have severe hypoxia + can only remain 2 or 3 days
–> after that body’s major symptoms will have severe physiological damage
Mechanism of Acclimatisation
Metabolic acidosis caused by retention of acid + increased excretion of bicarbonate in kidneys
Increase in erythrocyte number
Reduced pulmonary vascular resistance
Acclimatisation MOA
Low pO2 in inspired air increases rate + depth of breathing
BUT blows off excess CO2 + produces respiratory alkalosis
–> high pH inhibits central chemoreceptors
–> decreased breathing
–> hypoxia
Acclimatisation MOA Pt 2 (kidneys)
Kidneys respond to hypoxaemia by increasing bicarbonate excretion
Decreased excretion of acid
–> metabolic acidosis
Metabolic acidosis counteracts the respiratory alkalosis
–> restores pH to normal
Drive to central chemoreceptors restored –> sustained increase in rate and depth of breathing to restore normoxia
Hypoxia during acclimatisation
Stimulates interstitial cells in kidney to raise EPO
–> increases haematocrit –> increases O2 carrying capacity of blood
Haematocrit maximum
Functional limit to max haematocrit
Increased haematocrit = increased blood viscosity
Higher viscosity –> higher pulmonary vascular resistance –> pulmonary arterial hypertension + right sided heart failure
Pulmonary vascular resistance during acclimatisation
Pulmonary vascular resistance falls
Partially due to reduced hypoxic vasoconstriction response
Partly due to collateral circulations opening up between pulmonary arteries + veins
Increased synthesis of NO in pulmonary endothelium
Causes collateral circulations to open up between pulmonary arteries + veins
Acute Mountain Sickness
First sign that something is wrong
High Altitude Cerebral oedema
Can follow is AMS untreated
Serious neurological condition
Fatal if not treated
High Altitude Pulmonary Oedema
Equally serious to HACE
Can follow on from AMS
AMS signs + symptoms
Headache Poor sleep Tiredness Loss of appetite, nausea, vomiting Dizziness
All scored 0-3 for severity of symptoms –> need score of >3 for AMS diagnosis
Like symptoms of hangover
1500-2000m rapid ascent from sea level AMS
Unlikely in most individuals
Mild illness
2500m rapid ascent from sea level AMS
1 in 5 people have symptoms if ascend within a day
Most ppl will acclimatise within a day or so
5000m rapid ascent from sea level AMS
Everyone temporarily ill if ascend within few hours to 5000m (e.g. plane)
Acclimatisation can take several days or more
AMS Treatment Mild
Rest
No further ascent
AMS Treatment Severe
Immediate descent
O2
Acetazolamide 250mg (3x day)
Dexamethasone 4mg (4x daily) oral or IV
AMS Prevention
Slow ascent- <300m per day over 3000m
Avoid unnecessary exercise
Acetazolamide 250mg 2x day at start of climb
Acetazolamide (Diamox)
Carbonic anhydrase inhibitor
Carbonic anhydrase
In proximal tubule of kidney
Vital for renal reabsorption of bicarbonate
Acetazolamide MOA
Inhibits CA activity
Increases bicarbonate excretion –> metabolic acidosis
Compensates for the respiratory alkalosis caused by the hyperventilation at altitude
Acetazolamide MOA compared to normal
Kidneys produce metabolic acidosis anyway as part of acclimatisation
–> Diamox speeds up process
Bicarbonate reabsorption Pt 1
CO2 diffuses from blood into proximal tubule cells
Converted into carbonic acid (H2CO3) by Carbonic Anhydrase A inside the cells
H2CO3 –> H+ and HCO3-
Protons formed are ejected into tubular lumen by a Na+/H+ exchange ATPase
–> sodium reabsorbed from tubular fluid + protons ejected into it
–> bicarbonate collects in cell
Bicarbonate reabsorption Pt 2
Excreted protons react with bicarbonate which has been filtered by glomerulus
The two ions are converted to CO2 + water by CA lining the tubule
CO2 diffuses back into tubule cell where converted back into carbonic acid (H2CO3)
–> bicarbonate is reabsorbed from tubule into tubular cells
Bicarbonate reabsorption part 3
CO2 that has diffused back into cell then converted back to H2CO3 by CA inside tubular cells
H2CO3 –> H+ and HCO3-
Protons pumped out to continue the reabsorption cycle
HCO3- transferred from tubular cells back into blood
Acetazolamide
Conversion of HCO3- to CO2 in lumen is blocked
–> filtered bicarbonate is lost in urine
CA blocked inside cell
CO2 from blood can’t be converted to HCO3-
- -> no H+ available for the Na+/H+ ATP-ase
- -> protons not pumped into urine + Na+ not reabsorbed
- -> Na+ excreted in urine instead of H+
Acetazolamide net effect
Bicarbonate + Na+ lost in urine
Urine becomes alkaline
Blood becomes more acid
High levels of acetazolamide
Also inhibit CA in erythrocytes
Blocks transport of CO2 from tissues –> lungs
–> decreases loss of CO2 in lungs
–> counteracts excessive loss of CO2 from body by hyperventilation
High altitude cerebral oedma (HACE) Symptoms
Can follow AMS if AMS left untreated Ataxia Nausea/vomiting Hallucination or disorientation Confusion Reduced conscious level Coma
HACE MOA
In hypoxaemia, supply of ATP in nerve cells decreases + sodium pumps run down
Sodium leaks into nerve cell –> pulls water with it + brain swells
Raises ICP + blocks cerebral veins
Cerebral circulation fails, hypoxia gets worse + neurones die (starved of O2 + squished)
HACE treatment
Descend immediately
Acetazolamide (reduces formation of CSF so decreases ICP)
O2
Dexamethasone 8mg then 4mg 4x day orally or IV (prevents brain swelling)
Hyperbaric chamber
High altitude pulmonary oedema (HAPE) sings + symptoms
Dyspnoea Reduced exercise tolerance Dry cough Blood stained sputum Crackles on chest ausculation
HAPE MOA
Hypoxic pulmonary vasoconstriction normally decreases with acclimatization
–> if doesn’t occur, pulmonary arterial hypertension can develop
Raised arterial + capillary pressure –> fluid leaving blood + entering alveoli
–> worsens already compromised gas exchange
–> increases hypoxia + constriction
–> VISCIOUS CYCLE
HAPE treatment
Descend immediately
Sit patient upright
O2
Nifedipine (Ca channel blocker) 20mg 4x day
Hyperbaric chamber
Viagra (inhibits altitude-induced hypoxaemia + pulmonary hypertension)
Nifedipine
Blocks constriction of pulmonary arteries
–> reduces PAH
Hyperbaric chamber
Increases partial pressure of O2 to improve oxygenation of blood
Reduces hypoxic vasoconstriction
Viagra
Slows down breakdown of cyclic GMP, which is the vasodilator produced by NO
Increases cGMP levels relaxes pulmonary arteries, stops PAH + improves O2 oxygenation
Pulmonary hypoxic vasoconstriction
Due to lack of NO being released from pulmonary endothelium
HACE + HAPE symptoms
HACE= AMS with CNS symptoms HAPE= AMS with pulmonary symptoms
