What are the key principles of oxygen physiology, including oxygen transport, hemoglobin saturation, and factors affecting oxygen delivery?

Oxygen Physiology: Key Principles

Oxygen Transport in Blood

Oxygen is transported in blood primarily bound to hemoglobin, with only a negligible amount dissolved in plasma. 1 The amount of oxygen carried is expressed as hemoglobin oxygen saturation (SO₂), which represents the percentage of hemoglobin binding sites occupied by oxygen molecules. 1

Normal Oxygen Saturation Values

• Normal arterial oxygen saturation (SaO₂) in healthy adults at sea level ranges from 95–98%. 1 This narrow range indicates that nearly all oxygen-carrying capacity of hemoglobin is utilized under normal conditions. 1

• Normal arterial partial pressure of oxygen (PaO₂) ranges from 80–110 mmHg, varying with age. 2 Young adults (18–24 years) typically have PaO₂ values of 90–111 mmHg, while adults over 64 years range from 68–111 mmHg. 2

• Giving supplemental oxygen to a healthy person with 97% saturation will only increase it to 99–100%, producing minimal increase in oxygen availability to tissues. 1 This reflects the plateau of the oxyhemoglobin dissociation curve at normal saturation levels.

The Oxygen Cascade

Oxygen partial pressure decreases stepwise from atmospheric air (160 mmHg) through the respiratory system to the mitochondria where it is consumed. 3 This cascade includes:

• Alveolar PO₂ falls to approximately 100–120 mmHg because inspired air is humidified and mixes with residual CO₂. 3

• Pulmonary capillary end-PO₂ rises to about 120 mmHg as mixed-venous blood (~45 mmHg) traverses well-ventilated alveoli. 3

• Arterial PO₂ declines to roughly 100 mmHg due to ventilation-perfusion (V/Q) mismatch, physiological shunt, and the non-linear oxyhemoglobin dissociation curve. 3

• Mixed-venous PO₂ is approximately 45 mmHg. 1, 3

Oxygen Delivery (DO₂)

Oxygen delivery to tissues is calculated as: DO₂ = CaO₂ × Q, where CaO₂ is arterial oxygen content and Q is cardiac output. 1, 3, 4 This formula quantifies the total oxygen delivered to tissues per minute.

Components of Oxygen Delivery

• Arterial oxygen content (CaO₂) is determined primarily by hemoglobin concentration and oxygen saturation, with minimal contribution from dissolved oxygen. 1, 3

• Cardiac output is the primary modifiable determinant of oxygen delivery alongside arterial oxygen content. 3, 4

• Supplemental oxygen given to a patient with 90% saturation can increase DO₂ by at most ~10%. 1, 4 In contrast, improving cardiac output or correcting severe anemia increases DO₂ far more effectively than increasing FiO₂ alone. 4

The Oxyhemoglobin Dissociation Curve

The sigmoid-shaped oxyhemoglobin dissociation curve has two protective features: a flat upper portion and a steep lower portion. 1

• The flat upper portion means that marked falls in PaO₂ (down to ~60 mmHg) still maintain near-complete oxygen saturation. 1

• The steep lower portion facilitates continued oxygen delivery to tissues despite rapidly falling saturation, as PO₂ remains relatively preserved. 1

Factors Shifting the Curve

The curve shifts rightward (facilitating oxygen release to tissues) with increases in temperature, PaCO₂, hydrogen ion concentration (low pH), or 2,3-diphosphoglycerate (2,3-DPG). 1 This is known as the Bohr effect. 1

• Chronic hypoxemia increases 2,3-DPG in red blood cells, shifting the curve right and enhancing tissue oxygen delivery. 1

Regulatory Mechanisms

Ventilatory Response

Peripheral chemoreceptors in the carotid bodies detect falling arterial PO₂ (not oxygen content) and stimulate increased ventilation. 1, 3 This response is inversely linear when plotted against oxyhemoglobin saturation but inversely exponential when plotted against arterial PO₂. 1

• Increased ventilation raises alveolar PO₂, particularly improving oxygenation of poorly ventilated lung units. 3

Hypoxic Pulmonary Vasoconstriction

When alveolar PO₂ falls to ~60 mmHg, pulmonary arterioles constrict and redirect blood flow toward better-ventilated regions, optimizing V/Q matching. 1, 3 This mechanism is unique to the lungs. 1

• In contrast, systemic organs (brain, heart, kidneys) vasodilate in response to hypoxia to increase blood flow. 1, 3

Long-Term Adaptations

• Cardiac output can increase within seconds when oxygen levels fall, augmenting oxygen delivery. 3

• The kidneys stimulate erythropoietin production over days to weeks, enhancing red cell mass and oxygen-carrying capacity. 1, 3

Clinical Oxygen Targets

For most acutely ill patients, target SpO₂ of 94–98% to maintain normal physiological range with a safety margin above the critical 90% threshold. 1, 3 This range mirrors normal values for UK adults. 1

• Sudden exposure to SaO₂ levels below 80% can cause impaired mental functioning even in healthy individuals. 1 The brain is the most sensitive organ to hypoxia. 1

• For patients at risk of hypercapnic respiratory failure (COPD, obesity hypoventilation, neuromuscular disease), target SpO₂ of 88–92%. 1, 3 One randomized trial showed significantly lower mortality with titrated oxygen (SpO₂ 88–92%) versus high-concentration oxygen in COPD exacerbations. 1

Limitations of Oxygen Therapy

Oxygen therapy primarily corrects hypoxemia caused by V/Q mismatch but is less effective when hypoxemia results from other causes. 3, 4

Conditions Requiring Additional Interventions

• Anemia (reduced hemoglobin concentration) – Supplemental oxygen provides minimal benefit; transfusion may be needed. 3, 4

• Low cardiac output – Improving hemodynamics is more effective than increasing FiO₂. 1, 4

• Impaired tissue oxygen extraction (e.g., sepsis) – Oxygen therapy alone cannot correct cellular dysfunction. 3, 4

• Carbon monoxide poisoning (blocked hemoglobin binding sites) – High-flow oxygen or hyperbaric therapy required. 3

Common Pitfalls

• Do not rely solely on supplemental oxygen when other physiological disturbances limit oxygen delivery. 1, 4 Address airway obstruction, bronchoconstriction, pulmonary edema, anemia, and low cardiac output directly. 1

• Avoid hyperoxemia (PaO₂ >110 mmHg or SpO₂ >98%), which can cause oxidative stress and potential organ damage. 2 Current guidelines recommend avoiding hyperoxemia, particularly after cardiac arrest. 2

• Remember that normal or high mixed-venous saturation (SvO₂) does NOT exclude tissue hypoxia, particularly in septic patients where oxygen extraction may be impaired. 4