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Michael P. Mendez

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date: 05 July 2022

  1. A. Introduction

    1. a. Hypoxemia is a manifestation of an underlying disease process.

    2. b. Hypoxemia is common in hospitalized patients.

    3. c. Patients with hypoxemia always warrant prompt evaluation.

  2. B. Clinical Values

    1. a. Arterial oxygen tension (PaO2). An arterial blood gas analysis is necessary to confirm the presence of hypoxemia. A normal PaO2 at sea level is 80–100 mm Hg.

    2. b. Oxygen (O2) saturation. The arterial O2 saturation is the percentage of oxyhemoglobin in arterial blood. It can be measured by pulse oximetry (indirect) or arterial blood gas analysis (direct).

      Hot Key

      If pulse oximetry has an unreliable waveform, checking an arterial blood gas is important to confirm the PaO2 and arterial O2 saturation. The waveform should have a regular peak and trough and be concordant with the heart rate.

    3. c. Alveolar-to-arterial (A-a) gradient. The A-a gradient helps determine the cause of hypoxemia and provides a rough estimate of how ill a patient is.

      1. i. A normal A-a gradient is less than the patient’s age divided by 4 plus 4. For example, a 24-year-old patient should have an A-a gradient of less than 10 (24/4 = 6; 6 + 4 = 10).

      2. ii. Calculating the A-a gradient is easy using the alveolar gas equation and values from the arterial blood gas report.

        1. 1. First, the alveolar oxygen tension (PaO2) is calculated using the alveolar gas equation:



          Pbarometric = the barometric pressure (760 mm Hg at sea level)

          Pwater = the vapor pressure of water at body temperature (47 mm Hg)

          FiO2 = the fraction of oxygen in the inspired gas (0.21 on room air)

          PaCO2 = the arterial carbon dioxide tension

          Hot Key

          Remember, for the simplified equation to accurately estimate PaO2, the patient must be breathing room air.

          Thus, at sea level, the equation simplifies to:


          The value for Paco2 is obtained from the arterial blood gas report.

    4. 2. To calculate the A-a gradient, subtract the PaO2 (obtained from the arterial blood gas report) from the PaO2 (obtained from the alveolar gas equation):


  3. C. Mechanisms of Hypoxemia. There are five cardinal pathophysiologic mechanisms that cause hypoxemia (Table 17.1).

    Table 17.1 Causes of Hypoxemia

    Pathophysiologic Mechanism

    Clinical Examples

    Ventilation-perfusion (V/Q) mismatch

    Pneumonia, CHF, ARDS, atelectasis, tumor-filled alveoli

    Right-to-left shunting

    Congenital cardiac abnormalities, pulmonary arteriovenous malformation

    Diffusion defects

    Interstitial lung disease, Pneumocystis pneumonia, emphysema


    Cannot breathe: impairment of respiratory mechanics from airway obstruction (e.g., COPD, asthma), neuromuscular dysfunction (poliomyelitis, Guillain-Barré syndrome, myasthenia gravis, ALS), or restriction of the chest wall or lungs (kyphoscoliosis, pulmonary fibrosis)

    Will not breathe: CNS damage, drugs (e.g., opiates and acute alcohol intoxication), obesity hypoventilation syndrome, hypothyroidism

    Low inspired O2 tension

    High altitude

    ALS = amyotrophic lateral sclerosis; ARDS = acute respiratory distress syndrome; CHF = congestive heart failure; CNS = central nervous system; COPD = chronic obstructive pulmonary disease.

    1. a. Ventilation-perfusion (V/Q) mismatch accounts for most cases of hypoxemia. V/Q mismatch occurs when ventilation in a part of the lung is decreased compared with perfusion.

    2. b. Right-to-left shunting occurs when systemic venous blood (PvO2 = 40 mm Hg) enters the left side of the heart without coming in contact with oxygen-rich alveolar air.

      1. i. Right-to-left shunting may result from cardiac abnormalities (e.g., patent foramen ovale, atrial septal defect) or pulmonary abnormalities (e.g., arteriovenous malformations; hepatopulmonary syndrome; consolidated lung with blood, pus or water; or atelectasis [all of which prevent gas exchange]).

      2. ii. A shunt exists whenever ventilation equals zero but perfusion continues.

    3. c. Diffusion defects leading to hypoxemia occur when red blood cell transit time through pulmonary vascular bed decreases (e.g., during exercise). Pathologic causes include interstitial lung diseases (e.g., idiopathic pulmonary fibrosis), environmental lung disease, Pneumocystis pneumonia, and emphysema. In emphysema, loss of alveoli reduces the available surface area for diffusion.

    4. d. Hypoventilation is defined by an elevated PaCO2 with a normal A-a gradient. There are many causes of this abnormality; to find the cause, a systematic approach, starting at the head and working to the lungs, is best.

    5. e. Low inspired oxygen tension. Unless the patient is at a high altitude, this cause can be ruled out.

Suggested Further Readings

Henig NR, Pierson DJ. Mechanisms of hypoxemia. Respir Care Clin N Am 2000;6:501–21. (Classic Article.)Find this resource:

Kane B, Turkington PM, Howard LS, Davison AG, Gibson GJ, O’Driscoll BR. Rebound hypoxaemia after administration of oxygen in an acute exacerbation of chronic obstructive pulmonary disease. BMJ 2011;342:d1557.Find this resource:

Sarkar M, Niranjan N, Banyal PK. Mechanisms of hypoxemia. Lung India 2017;34:47–60.Find this resource:

Tierney LM, Jr., Whooley MA, Saint S. Oxygen saturation: a fifth vital sign? West J Med 1997;166:285–6. (Classic Article.)Find this resource: