Respiratory physiology


The main function of the respiratory system is gas exchange (O2 and CO2). Ventilation is the movement of air through the respiratory tract into (inspiration) and out of (expiration) the respiratory zone (lungs). The physiologic dead space is the volume of inspired air that does not participate in gas exchange. Perfusion of the pulmonary capillaries is closely regulated to match ventilation in order to maximize gas exchange. The ventilation-perfusion ratio is higher in the tip of the lung than at its base. The Euler-Liljestrand mechanism regulates the perfusion of nonventilated alveoli: if a lung section is perfused but not ventilated, there will be a drop in the oxygen concentration in the blood, resulting in hypoxic vasoconstriction. Diseases that affect the perfusion (e.g., pulmonary embolism) or ventilation (e.g., foreign body aspiration) can cause a V/Q mismatch. Gas exchange occurs via simple diffusion across the blood-air barrier. The gases diffuse across the barrier following pressure gradients. In the capillaries, oxygen binds to hemoglobin in erythrocytes or dissolves into the plasma (oxygenation). CO2 diffuses into the alveoli and is exhaled. Central regulation of respiration is provided by the respiratory center located in the reticular formation of the medulla oblongata and pons. Inspiration is an active process driven by the respiratory musculature while expiration is passive at rest, driven by the elastic properties of lung tissue.



Parameters of ventilation

VD is greater than anatomic dead space in diseases with a V/Q mismatch (e.g., pulmonary embolism).

Normal and pathologic ventilation

Normal Decreased Increased
Respiratory rate (RR)


Bradypnea (< 12/min) Tachypnea (> 20/min)
Tidal volume (VT) 0.5 L/breath Hypopnea Hyperpnea
Minute ventilation (VE) 7.5 L/min Hypoventilation Hyperventilation

If alveolar ventilation increases (i.e., hyperventilation), more CO2 is exhaled and the PaCO2 decreases. If alveolar ventilation decreases (i.e. hypoventilation), PaCO2 increases.

Lung volumes

  • Lung volumes depend on age, height, and sex. The values that are listed below are for a healthy young adult.
Lung volume Definition Normal range
Total lung capacity (TC,TLC) Volume of air in the lungs after maximal inhalation TC = VC + RV 6–6.5 L
Vital capacity (VC) Difference in lung volume between maximal exhalation and maximal inhalation (VC = TV + IRV + ERV) 4.5–5 L
Residual volume (RV) Volume of air that remains in the lungs after maximal exhalation 1–1.5 L
Tidal volume (TV) Volume of air that is inhaled and exhaled in a normal breath at rest ∼ 500 mL or 7 mL/kg
Inspiratory reserve volume (IRV) Maximum volume of air that can still be forcibly inhaled following the inhalation of a normal TV 3–3.5 L
Inspiratory capacity (IC) Maximum volume of air that can be inhaled after the exhalation of a normal TV (IRC = IRV + TV) 3.5–4 L
Expiratory reserve volume (ERV) Maximum volume of air that can still be forcibly exhaled after the exhalation of a normal TV 1.5 L
Expiratory capacity (EC) Maximum volume of air that can be exhaled after the inspiration of a normal TV 2 L
Functional residual capacity (FRC) Volume of air that remains in the lungs after the exhalation of a normal TV (FRC = RV + ERV) 2.5–3 L

Residual volume cannot be measured by spirometry. Use full-body plethysmography or a gas dilution test.




Pulmonary blood flow

  • Pulmonary circulation: the blood flow is equivalent to cardiac output (∼ 5 L/min)
  • Distribution of blood flow: depends on the position of the body and is precisely regulated in relation to the ventilation to optimize gas exchange
    • Standing and sitting position: due to gravity, circulation is highest in the lung base
    • Supine position: distribution of the blood is nearly equal throughout the lung
Location Blood flow Pressures
Apical segments Lowest Alveolar pressure > arterial pressure > venous pressure
Middle segments Medium Arterial pressure > alveolar pressure > venous pressure
Basal segments Highest Arterial pressure > venous pressure > alveolar pressure

Regulation of pulmonary blood flow

The apical lung segments have higher O2 partial pressures because the perfusion in these lung segments is lower than the ventilation and thus less O2 diffuses from the alveoli into the bloodstream. Some microorganisms (e.g, M. tuberculosis) favor apical lung segments due to the higher O2 content.

During exercise, the increased cardiac output from the right ventricle increases pulmonary circulatory pressure, which then opens apical blood vessels that were initially collapsed. This allows for perfusion in that region, thereby reducing dead space (V/Q ratio ≈ 1).

Ventilation-perfusion mismatch (V/Q mismatch)

Administering 100% O2 improves PaO2 in patients with increased V/Q ratio due to pulmonary embolism (i.e. increased physiological dead space due to blood flow obstruction). It does not, however, improve PaO2 in patients with airway obstruction, e.g., due to foreign body aspiration.


Gas exchange


The main function of the lung is gas exchange (O2 and CO2), which occurs via simple diffusion across the blood-air barrier. The gases diffuse across the barrier following pressure gradients, meaning no energy is required for this process. In the capillaries, oxygen binds to hemoglobin in erythrocytes or dissolves into the plasma (oxygenation). CO2 diffuses into the alveoli and is exhaled.

Decreased diffusion capacity can occur when the surface area of the blood-air barrier is reduced (e.g., emphysema), the diffusion distance is increased (e.g., interstitial lung disease, pulmonary fibrosis, pulmonary edema), or the capacity to transport gases in blood is reduced (e.g., anemia).

Partial pressures

Partial pressure during the respiratory cycle (% of total gas composition)
Gases In inspired air In alveoli In expired air

593 mmHg (≈ 79%)

573 mmHg (≈ 75%) 593 mmHg (≈ 79%)
O2 150 mmHg (≈ 21%) 104 mmHg (≈ 14%) 116 mmHg (≈ 16%)
H2O 3.0 mmHg (≈ 0.04%) 47 mmHg (≈ 6%) 47 mmHg (≈ 6%)
CO2 0.3 mmHg (≈ 0.004%)

40 mmHg (≈ 5%)

28.5 mmHg (≈ 4%)
Total of all gases 760 mmHg (= 100%)

Inspired air contains more O2, less CO2, and less water vapor than expired air.

Partial pressure of O2 and CO2 across the blood-air barrier
In the alveoli In the pulmonary capillaries
Partial pressure of O2 104 mm Hg 40 mm Hg
Partial pressure of CO2 40 mm Hg 45 mm Hg

Alveolar-arterial gradient (A-a gradient)

An increased A-a gradient may occur in hypoxemia due to shunting, ventilation-perfusion mismatch, or impaired gas diffusion across the alveoli due to fibrosis or edema. The A-a gradient remains normal with hypoventilation due to CNS and neuromuscular disorders (no diffusion defect) and in high altitude (despite a lower fraction of inhaled O2). Patients with hypoventilation (e.g., due to a drug overdose) usually present with increased CO2.

Types of gas exchange

At rest, gas exchange is perfusion-limited, meaning it is limited by the rate of blood flow through the pulmonary capillaries; during strenuous exercise and in certain pathological conditions that affect the blood-air barrier (e.g., emphysema), gas exchange is limited by the diffusion rate of the gas across the blood-air barrier.


Lung and chest wall compliance

Lung compliance

  • Definition: the ability of the lungs to distend under pressure
  • Measurement: change in volume of the lung per unit change in pressure (C = ΔV/ΔP)
  • Increased in: emphysema (lungs fill easier), aging
  • Decreased in: conditions associated with increased lung stiffness (e.g., pulmonary fibrosis, pulmonary edema, pneumoconioses, ARDS)

Surfactant reduces the surface tension in the alveoli and thus increases the compliance of the lungs.

In old age, lung compliance increases due to loss of elastic recoil, while chest wall compliance decreases because the chest wall stiffens.

Chest wall dynamics


Airway resistance

  • Definition: opposition to airflow through the upper and lower airways caused by the forces of friction during inspiration and expiration
  • Depends on
    • Diameter of the airways: The smaller the diameter, the greater the resistance.
    • Velocity of airflow (laminar flow < turbulent flow)
    • Viscosity of the gas breathed: viscosity creates friction; the higher the viscosity, the higher the resistance
    • Number of parallel pathways: resistance reduces at each generation of branching; resistance in large and medium-sized airways is greater than in small airways
  • Increased in: forced expiration, obstructive lung diseases (e.g., asthma, COPD)
  • Decreased in: exercise

Airway resistance is lowest in the small airways due to a large number of parallel bronchioles, while the highest airway resistance is in the larger airways (trachea, bronchi).

Respiratory regulation

Respiratory center

Regulation of respiration takes place centrally in the respiratory center located in the reticular formation of the medulla oblongata and pons.

  • Medullary center: creates rhythmic innervation of the respiratory muscles and is influenced by various respiratory stimuli
  • Pontine center: modifies the activity of the medullary center
    • Apneustic center: controls the intensity of breathing (e.g., promotes deep; gasping inspiration (apneusis) by stimulation of the dorsal respiratory group and inhibition of the pneumotaxic center
    • Pneumotaxic center: controls the respiratory rate and pattern of breathing; limits or delays inspiration


A chronically elevated pCO2 ≥ 70 mmHg (e.g., in COPD) inhibits the respiratory center instead of stimulating it.

Hyperventilation can reduce the PaCO2 and thus the respiratory drive; this technique is used, for example, by divers before a dive!

Pathological breathing patterns

Pathological breathing patterns Characteristics Common causes
Kussmaul breathing
  • Hyperventilation with a deep, labored, breathing pattern (to eliminate excess CO2)
Cheyne-Stokes respiration
  • Cyclic, crescendo-decrescendo pattern of breathing with intermittent periods of apnea
Biot respirations (cluster breathing)
  • Irregular breathing followed by regular or irregular periods of apnea.
Agonal respirations
  • Labored breaths, gasping, myoclonus and grunting, often prior to terminal apnea and death; can last seconds to hours.
  • Cardiocirculatory arrest
Rapid, shallow breathing


Respiratory adaptation

Respiratory adaptation to exercise

  • ↑ Depth and rate of ventilation (hyperventilation)
  • ↑ O2 consumption
  • ↑ CO2 production
  • ↑ Pulmonary blood flow (cardiac output)
  • V/Q ratio has a more even distribution throughout the lung than at rest.
  • Oxygen diffusion becomes diffusion-limited (in resting state it is perfusion-limited).
  • ↓ Arterial pH (due to lactic acidosis)

Respiratory adaptation to high altitude

Decreased atmospheric O2 at high altitudes triggers various adaptation mechanisms in the respiratory system. Insufficient adaptation to the high altitude results in altitude sickness.

Respiratory adaptation in the elderly population


  • 1. Hall JE. Guyton and Hall Textbook of Medical Physiology. Philadelphia, PA: Elsevier; 2016.
  • 2. Kaplan. USMLE Step 1 Lecture Notes 2016: Physiology. Kaplan Publishing; 2015.
  • 3. Costanzo LS. Physiology Board review series. Lippincott Williams & Wilkins; 2014.
  • 4. Whited, Graham. Stat Pearls - Abnormal Respirations. StatPearls. 2019. pmid: 29262235.
  • 5. Dutschmann, Dick. Pontine Mechanisms of Respiratory Control. Comprehensive Physiology. 2012; 2(4): pp. 2443–2469. doi: 10.1002/cphy.c100015.
  • 6. Alraiyes AH, Thompson P, Thammasitboon S. Biot's respiration in a chronic opioid user: Improved with adaptive-servo ventilation. Am J Respir Crit Care Med. 2011; 183. doi: 10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a5279.
  • Le T, Bhushan V. First Aid for the USMLE Step 1 2020. New York, NY: McGraw-Hill Professional Publishing; 2020.
last updated 08/11/2020
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