Physiology Of High Altitude Flashcards
Partial pressure driving o2 uptake at sea level
9.5 kPa
Why is a difference in partial pressure of oxygen needed between alveoli and pulmonary capillaries
Allow o2 to diffuse on capillary blood
Why does partial pressure of o2 decrease between inhalation and reaching alveoli
Addition of water vapour
Mixing w ‘old’ alveolar gas
How does atmospheric partial pressure change as altitude increases
Decreases
Why does oxygen partial pressure decrease with altitude
Decreased atmospheric pressure
What causes gas pressure
Collisions of gas particles + container walls
How does increasing CO2 effect response to hypoxaemia
Increases response
Is PaCO2 high or low at high altitude
Low
Where are receptors detecting hypoxaemia
Carotid bodies
What is the first adaptation to hypoxaemia
Hyperventilation
Is hypoxaemia detected by peripheral or central receptors
Peripheral - carotid bodies
Why do central nervous chemoreceptors depress hypoxaemia driven hyperventilation
Hyperventilation -> excess blow off CO2 -> alkalosis at central chemoreceptors -> depress respiratory drive
How does adaptation to altitude effect central chemoreceptors
Receptors reset to decr depression of hyperventilation
Which nervous system is stimulated by hypoxaemia
Sympathetic
Which response to hypoxaemia is maladaptive
Pulmonary vasoconstriction
Why does pulmonary vasoconstriction occur in hypoxaemia
Ventilation-perfusion matching mechanism due to low alveolar ppO2
Why is pulmonary vasocontriction in response to hypoxaemia maladaptive, and when is it effective
All of lung effected
Effective when only part of lung damaged so perfusion decreases in badly ventilated area
What happens first in high altitude - acclimatisation or adaptation
Adaptation
What is the first step in acclimatisation to hypoxia
Plasma volume gradually decreases 10-25%
Why does plasma volume decrease in acclimatisation to hypoxaemia
Temporarily increases haematocrit
How is RBC production increased in acclimatisation to hypoxaemia
Erythropoietin released from kidney interstitial cells
Why is there a functional limit to haematocrit
Increased haematocrit increases blood viscosity, increasing pulmonary vascular resistance
What does oxygen dissociation curve show
How easily Hb takes up or releases O2
How does acute hyperventilation and respiratory alkalosis shift the oxygen dissociation curve
Left
What molecule is increased when adapting to hypoxaemia to shift oxygen dissociation curve to the right
2,3DPG
Main pH buffer system of the body
Bicarbonate buffer system
Bicarbonate buffer system equation
CO2 + H2O <—> H2CO203 <—> h+ + HCO3-
Where is carbonic anhydrase present
All cells
Is carbonic anhydrase found in plasma
No
What does carbonic anhydrase catalyse
Bidirectional conversion of CO2 + H2O into HCO3 + H+
What ion is plasma pH directly proportional to
HCO3-
What is plasma pH inversely proportional to
pCO2
What pH disturbance does hyperventilation cause
Respiratory alkalosis
How do kidneys respond to respiratory alkalosis
Decrease excretion of protons
Decrease reabsorption of bicarbonate
Increase excretion of bicarbonate
What does renal bicarbonate reabsorption do
Removes filtered bicarbonate from the tubular fluid and reabsorbed it
What happens to protons pumped into kidney tubules in renal bicarbonate reabsorption
React with bicarbonate filtered from blood forming CO2 and water
What happens to CO2 produced in kidney tubules in renal bicarbonate reabsorption
Diffuses back to tubule cell and converted back to bicarbonate
How is proton excretion from the kidneys effected by respiratory alkalosis
Decreased
Where are carbonic anhydrase levels down regulated in response to respiratory alkalosis
Kidney Tubular cells
Kidney tubule lumen
Why is carbonic anhydrase down regulated in kidney tubular cells in response to respiratory alkalosis
Less CO2 converted to bicarbonate and protons -> less protons in tubular cell -> less protons excreted into urine
How are protons excreted from kidney tubular cells to urine
Sodium proton exchange ATPase in luminal wall
How does bicarbonate reabsorption change in response to respiratory alkalosis
Decrease
Where is carbonic anhydrase down regulated to decrease bicarbonate reabsorption
Kidney tubular cells
Kidney Tubular lumen
Why is carbonate anhydrase decreased in kidney tubular lumen in response to respiratory alkalosis
Less bicarbonate converted to CO2 in tubule
What causes decreased pulmonary vascular resistance in acclimatisation to hypoxia
Reduced initial hypoxic vasoconstriction response
Collateral circulations open between pulmonary arteries and veins
How does pulmonary resistance change in hypoxia at high altitude
Initially - increase
Once acclimatised - decrease
What genetic aspects impact hypoxia acclimatisation
Activity of carbonic anhydrase
Ability to make NO
Ability to make 2,3-DPG
What causes AMS, HACE, and HAPE
Too rapid or high ascent without time for acclimatisation
Acute mountain sickness AMS
First sign of illness due to hypoxia
What conditions can follow on from acute mountain sickness
HACE high altitude cerebral oedema
HAPE Hugh altitude pulmonary oedema
Acute mountain sickness symptoms
Headache
Insomnia
Fatigue
Anorexia
Nausea
Vomiting
Dizziness
Lightheadedness
Which symptom is required for an acute mountain sickness diagnosis
Headache
What signs are found in a physical exam of a patient with acute mountain sickness
Usually none
What is needed for a diagnosis of acute mountain sickness
Headache
Symptoms score >3
How likely is AMS after a rapid ascent to 1500-2000m above sea level
Unlikely
How likely is ams after a rapid ascent to 2500m above sea level
Fairly likely - 1 in 5 people
How likely is AMS after a rapid descent to 5000m above sea level
Extremely likely
Mild AMS treatment
Rest
stop ascending
Severe AMS treatment
Immediate descent
Oxygen
Acetazolamide
Dexamethasone
AMS prevention
Slow ascent
Avoid unnecessary exercise
Acetazolamide prophylaxis
What is Acetazolamide
Carbonic anhydrase inhibitor
How does Acetazolamide treat AMS
Speeds up carbonic anhydrase activity decrease occurring in acclimatisation
How does high doses of Acetazolamide decrease loss of CO2 from hyperventilation
Inhibits carbonic anhydrase in RBCs decreasing transport of CO2 to lungs
Dexamethasone
Corticosteroid to prevent brain swelling and inflammation
How can Dexamethasone be administered
Orally
Intramuscular
Intravenous
High altitude cerebral oedema symptoms
Worsening headache
Photophobia
Hallucinations
Vomiting
Difficulty speaking
Confusion
Signs of high altitude cerebral oedema
Truncus ataxia
Altered consciousness
Seizures
Coma
How does HACE happen
ATP supply decreases -> sodium pumps run down -> Na leaks into nerve cells -> water follows causing swelling + intracranial pressure incr -> cerebral veins blocked -> neurons die -> dead neurons release ions and fluids worsening oedema
What raises intracranial pressure in HACE
Sodium leaks into brain cells bring water with it
HACE treatment
Descend immediately
Dexamethasone
Acetazolamide
Oxygen
Hyperbaric oxygen treatment
How does Acetazolamide treat HACE
Reduces cerebrospinal fluid volume decreasing intracranial pressure
HAPE symptoms
Dyspnoea
Decr exercise tolerance
Dry cough
Haemoptysis
Orthopnoea
Dyspnoea
Breathlessness
Haemoptysis
Coughing up blood
Orthopnoea
Dyspnoea when lying flat
HAPE signs
Tachypnoea
Tachycardia
Fever
Rales on chest auscultation
Mental status changes
Rales
Diffuse crackles in chest on auscultation
What causes HAPE
Initial hypoxic pulmonary vasoconstriction doesn’t decrease -> pulmonary arterial hypertension -> fluid moves from blood to alveoli -> pulmonary oedema -> worsens hypoxia and vasoconstriction
How does HAPE form a vicious cycle
Pulmonary oedema further worsens gas exchange causing more hypoxia which causes more vasoconstriction and more hypoxia
HAPE treatment
Descend immediately
Sit patient upright
Oxygen
Acetazolamide
Dexamethasone
Nifedipine
Hyperbaric o2 chamber
Sildenafil
Nifedipine
Calcium channel blocker
How do nifedipine and Sildenafil help HAPE
Relax smooth muscle decreasing vascular resistance
Sildenafil
Increases cGMP levels and decreases intracellular calcium -> relax smooth muscle
VIAGRA
Long term adaptations to hypoxia
Incr erythropoietin
Incr Hb
Incr capillary density
Adaptations to hypoxia
Incr 2,3-DPG
hyperventilation
Decr renal bicarbonate reabsorption
Decr renal proton excretion
