What is oxygen physiology?

Oxygen Physiology Overview

Oxygen physiology describes how oxygen moves from inspired air through the lungs into the bloodstream, binds to hemoglobin, gets delivered to tissues via cardiac output, and ultimately reaches mitochondria for cellular energy production—a process known as the oxygen cascade. 1

Oxygen Transport in Blood

Oxygen is transported in two forms: a negligible amount dissolved in plasma and the majority bound to hemoglobin molecules. 2

• The amount of oxygen carried is expressed as oxygen saturation (SO₂), representing how saturated circulating hemoglobin is with oxygen. 2
• Normal arterial oxygen saturation (SaO₂) in healthy adults at sea level ranges from 95–98%. 2
• At this normal range, almost all oxygen-carrying capacity of hemoglobin is already utilized, meaning supplemental oxygen in healthy individuals only increases saturation minimally (from ~97% to 99–100%), producing very small increases in oxygen availability to tissues. 2

The Oxygen Cascade

The oxygen cascade describes the stepwise decline in oxygen partial pressure from atmospheric air (~150 mmHg) down to mitochondria (single digits). 1, 3

Key pressure points along the cascade:

• Alveolar PO₂: Falls to approximately 100–120 mmHg due to humidification and mixing with residual CO₂. 1
• Pulmonary capillary end-PO₂: Rises to 120 mmHg as mixed-venous blood (45 mmHg) traverses well-ventilated alveoli. 1
• Arterial PO₂: Declines to roughly 100 mmHg (range 90–110 mmHg in young adults) due to ventilation-perfusion (V/Q) mismatch, physiological shunt, and the non-linear oxyhemoglobin dissociation curve. 1
• Mixed-venous PO₂: Approximately 45 mmHg. 1

Determinants of Oxygen Delivery

Oxygen delivery (DO₂) equals arterial oxygen content (CaO₂) multiplied by cardiac output. 1

• CaO₂ is determined by: hemoglobin concentration, oxygen saturation, and dissolved O₂ (negligible). 1
• Tissue PO₂ is governed by: cardiac output, arterial oxygen content, and tissue oxygen consumption—with cardiac output and CaO₂ being the primary modifiable determinants. 1

Compensatory Mechanisms

The body employs multiple mechanisms to maintain adequate tissue oxygenation when oxygen levels fall:

Ventilatory Response

• Peripheral chemoreceptors in the carotid bodies detect falling arterial PO₂ (not oxygen content) and stimulate increased ventilation. 1
• Increased ventilation raises alveolar PO₂, particularly improving oxygenation of poorly ventilated lung units. 1

Hypoxic Pulmonary Vasoconstriction (HPV)

• When alveolar PO₂ falls to ~60 mmHg, pulmonary arterioles constrict and redirect blood flow toward better-ventilated regions, optimizing V/Q matching. 1, 4
• This is unique to the pulmonary circulation—the only vascular bed that constricts in response to hypoxia. 4
• In contrast, systemic organs (brain, heart, kidneys) vasodilate in response to hypoxia to increase blood flow. 1, 5

Cardiovascular and Hematologic Adaptations

• Cardiac output can increase within seconds when oxygen levels fall, augmenting oxygen delivery. 1
• The kidneys stimulate erythropoietin production over days to weeks, enhancing red-cell mass and oxygen-carrying capacity. 1, 5

Critical Thresholds and Organ Vulnerability

Sudden exposure to SaO₂ levels below 80% causes impaired mental functioning even in healthy individuals. 2

• The brain is the most sensitive organ to hypoxia, but other organs in critically ill patients may be vulnerable to hypoxic tissue injury at oxygen levels above this range. 2
• Most experts emphasize keeping SaO₂ above 90% for acutely ill patients. 2

Clinical Oxygen Targets

For most acutely ill patients, target SpO₂ of 94–98% to stay within the normal physiological range while providing a safety margin above the critical 90% threshold. 1

• For patients at risk of hypercapnic respiratory failure (COPD, obesity hypoventilation, neuromuscular disease), target SpO₂ of 88–92%. 1

Limitations of Supplemental Oxygen

Supplemental oxygen primarily corrects hypoxemia caused by V/Q mismatch. 1

Oxygen therapy is less effective when hypoxemia results from:

• Anemia (reduced hemoglobin concentration) 1
• Carbon monoxide poisoning (blocked hemoglobin binding sites) 1
• Low cardiac output 1
• Impaired tissue oxygen extraction (e.g., sepsis) 1

Management should address these underlying factors directly rather than relying solely on supplemental oxygen. 1

Important Clinical Pitfall

In COPD exacerbations, supplemental oxygen can release HPV, potentially worsening V/Q mismatch—oxygen corrects hypoxemia but paradoxically worsens V/Q balance. 4 This explains why controlled oxygen therapy with lower saturation targets (88–92%) is critical in these patients to avoid CO₂ retention while still preventing dangerous hypoxemia.