Anaes · Applied cardiovascular & respiratory physiology
Oxygen cascade & hypoxic pulmonary vasoconstriction
Also known as Oxygen cascade · Alveolar gas equation · Alveolar oxygen · Hypoxic pulmonary vasoconstriction · HPV · One-lung ventilation
Oxygen steps down in partial pressure at each stage from the dry inspired air to the mitochondrion — the oxygen cascade — and the lung matches blood flow to that oxygen by a mechanism unique to the pulmonary circulation: hypoxic pulmonary vasoconstriction. The framework rests on five exam-critical ideas: the oxygen cascade falls from about 159 mmHg in dry inspired air at sea level, through 149 in humidified tracheal air, about 100 in alveolar gas, about 95 in arterial blood, about 40 in capillaries, to about 1 to 3 mmHg in the mitochondria; the alveolar gas equation (PAO2 equals FiO2 times the pressure of Patm minus PH2O minus PaCO2 over the respiratory quotient) gives the alveolar oxygen that sets the top of the arterial step; the alveolar-to-arterial difference is normally small (under about 15 mmHg breathing air) and rises with shunt, mismatch and diffusion impairment; hypoxic pulmonary vasoconstriction constricts pulmonary arterioles in response to ALVEOLAR (not mixed venous) hypoxia, diverting perfusion to better-ventilated lung and so defending V/Q matching; and HPV is impaired by volatile anaesthetics, systemic vasodilators and a low systemic vascular resistance, which is the mechanism of hypoxaemia during one-lung ventilation. Built on the alveolar-gas-equation review (Heymer 2026), the lung-isolation study (Brenn 2024), the microRNA-hypoxic-pulmonary-hypertension review (Ma 2026), the high-altitude cardiovascular review (Chacon-Diaz 2026), the respiratory-rate-and-ventilatory-efficiency study (Jung 2026), and the airway-pressure-release-ventilation gas-exchange recommendations (Nieman 2026).
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Red flags
- The alveolar gas equation is PAO2 equals FiO2 times (Patm minus PH2O) minus PaCO2 divided by the respiratory quotient (about 0.8); raising FiO2 and lowering PaCO2 both raise PAO2 — the levers the anaesthetist uses to improve oxygenation.
- Hypoxic pulmonary vasoconstriction responds to ALVEOLAR hypoxia, not mixed venous hypoxia, so it is triggered by poorly ventilated lung (atelectasis, one-lung ventilation) and diverts blood to ventilated alveoli.
- Volatile anaesthetic agents, systemic vasodilators (nitroglycerin, nitroprusside), calcium channel blockers and a low systemic vascular resistance all impair HPV, worsening the hypoxaemia of one-lung ventilation.
- The alveolar-to-arterial gradient is normally under about 15 mmHg breathing room air (under about 50 to 70 on 100 percent oxygen); a raised gradient signals shunt, mismatch or diffusion impairment.
- At altitude the fall in barometric pressure lowers the top of the cascade (inspired PO2), which is why acclimatisation and HPV (chronic hypoxic pulmonary vasoconstriction) become important.
Meet the patient
A 64-year-old smoker is anaesthetised for a right upper lobectomy. The double-lumen tube is placed, the right lung is deflated, and within minutes the SpO2 drops from 99 to 88 percent on FiO2 1.0. The surgeon is mid-dissection and asks you to fix it.[1]
This is the oxygen cascade meeting HPV in the theatre. Every desaturation manoeuvre you know — raise FiO2, check tube position, apply CPAP to the non-ventilated lung, PEEP to the ventilated lung, reduce volatile depth — is an intervention on one step of the cascade or on regional pulmonary blood flow. The question is which lever to pull first.[1]
References6ShowHide
- [1]Heymer J. Alveolar gas equation: a metabolic perspective Intensive Care Med, 2026.PMID 41661294
- [2]Brenn BR, et al. A Comparative Evaluation of Unilateral and Bilateral Sequential Lung Isolation for Vertebral Body Tethering: A Retrospective Propensity Matched Analysis Cureus, 2024.PMID 38854196
- [3]Ma MR, et al. When MicroRNAs meet hypoxic pulmonary hypertension Biomed Pharmacother, 2026.PMID 42166981
- [4]Chacón-Díaz M, Lazo Soldevilla MA, Díaz-Lazo A, et al. The cardiovascular system and high-altitude exposure: from adaptation to disease. Part I Arch Peru Cardiol Cir Cardiovasc, 2026.PMID 42238502
- [5]Jung C, et al. Effects of increasing respiratory rate on ventilatory efficiency and mechanical costs during low-tidal-volume ventilation: a prospective physiological pilot study Ann Intensive Care, 2026.PMID 42306311
- [6]Nieman GF, et al. Expert recommendations for setting and adjusting airway pressure release ventilation based on clinical experience and basic science evidence Front Med (Lausanne), 2026.PMID 41709908