Applied Physiology Response to Hypoxia

• Vertical integrative physiology.
• Aviation and high altitude medicine.
• Many conditions/diseases have hypoxic or ischemic components.

• A - alveolar
• a - arterial
• v - venous
• P or p - partial pressure
• C - content
• F - fraction
• I or i - inspired
• E or e - expired
• Q - Cardiac output

• FiO₂ - fraction of inspired air that is oxygen
• CaO₂ - arterial oxygen content
• pO_{2 -} partial pressure of oxygen
• pAO₂ - partial pressure of oxygen in the alveoli

• -Drop in PiO₂
• -The reduced pO2 is transferred all the way down the oxygen cascade.

DO₂ = Q x CaO<sub>2

Systemic Delivery of oxygen = cardiac output x oxygen content of arterial blood.</sub>

When PiO₂ falls, CaO₂ also falls, reducing systemic oxygen delivery.

Q = HR x SV

CaO₂ = ([Hb] x SaO₂ xH) + (PaO₂ x S)

• H = Hufner's constant = 1.39 mL/g
• S = Solubility coefficient
• SaO2 = Solubility coefficient of O = 0.0225 mL/mm Hg

Increase Cardiac Output (Q) via increasing Heart Rate and increasing Stroke Volume

• (DO₂ = Q x CaO₂).
• (Q = HR x SV)

• Restoration of CaO_2.

• Ventilatory Adjustments
• Haematological adjustments

• The Hypoxic ventilatory response
• The Hypercapnic ventilatory response

PACO₂ = k x (VCO₂ / V_A)

Alveolar PCO₂ is inversely proportional to ventilatory rate. I.e. if ventilation doubles the PCO₂ is halved.

PAO₂ = PiO₂ - (PACO₂ / R)

R = indication of the substrates utilised i.e. fatty acids, CHO. Equals about .71 for fats and about 1.0 for CHO. R is a essentially a ratio of amount of CO₂ produced to O_2.

The alveolar ventilation and gas equations explain why hyperventilation works as an adaptation to high altitude. If you double ventilation rate the change in PCO₂ and PAO₂ is halved.

• Sea Level PAO₂ = 150 - (40/0.8) = 100 mm Hg
• Pikes Peak PAO₂ = 150 - (40/0.8) = 50 mm Hg

So PAO₂ (and thus PaO₂) has HALVED.

Sea Level PAO₂ = 150 - (40/0.8) = 100 mm Hg Pikes Peak PAO₂ = 150 - (40/0.8) = 75 mm Hg

Therefore PAO₂ is only reduced by 25% with hyperventilation.

• The Hypoxic ventilatory response (to hyperventilate) is driven by low pO₂.
• The Hypercapnic ventilatory response (also to hyperventilate) is initially driven by high pCO₂.

• Hypoxic - sensors in the carotid and aortic bodies.
• Hypercapnic - sensed by central chemoreceptors in the medulla.

• Normally at sea level this hypocapnia would cause breathing to slow.
• However at altitude the need to correct arterial pO₂ overwhelms the hypocapnic ventilatory response.
• The Resulting condition is HYPERVENTILATION and HYPOCAPNIA. ( Respiratory alkalosis).

pH = pK + log{ [HCO₃^-] / s x PCO₂)

Decrease CO₂ results in an increase in pH.

• By the kidneys - they excrete Bicarbonate.
• Partially compensating for the respiratory alkalosis.