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 apex of the lung than at its base. The 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 . 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.
- Definition: movement of air through the respiratory tract into (inspiration) and out of (expiration) the respiratory zone (lungs) to facilitate gas exchange (O2 and CO2)
- Inspiration of air into the conducting zone of the respiratory tree (anatomic dead space): nose → pharynx → larynx → trachea → bronchi → bronchioles → terminal bronchioles
- Air reaches the respiratory zone of the respiratory tree (site of gas exchange): respiratory bronchioles → alveolar ducts → alveoli
- Expiration of air out of the lungs
- See “ ” for details.
Parameters of ventilation
- Respiratory rate (RR): number of breaths per minute
- Tidal volume (VT): the volume of air that is inspired or expired in a single breath
- Minute ventilation (VE)
Physiologic dead space (VD): volume of inspired air that does not participate in gas exchange
- VD is the sum of the anatomic dead space and the alveolar dead space.
- Bohr equation determines the physiologic dead space: VD = VT x (PaCO2 - PeCO2)/(PaCO2)
- In a healthy lung, VD equals the anatomic dead space (normal value: approx. 150 mL/breath).
- Alveolar ventilation (VA)
Normal and pathologic ventilation
|Overview of normal and pathologic ventilation|
|Respiratory rate (RR)|| |
|Bradypnea (< 12/min)||Tachypnea (> 20/min)|
|Tidal volume (VT)||0.5 L/breath||Hyperpnea|
|Minute ventilation (VE)||7.5 L/min||Hypoventilation||Hyperventilation|
Lung volumes depend on age, height, and sex. The values that are listed below are for a healthy young adult.
|Physiological lung volumes|
|Lung volume||Definition||Normal range|
|Total lung capacity (TC, TLC)|| |
|Vital capacity (VC)|| |
|Residual volume (RV)|| || |
|Tidal volume|| || |
|Inspiratory reserve volume (IRV)|| || |
|Inspiratory capacity (IC)|| || |
|Expiratory reserve volume (ERV)|| || |
|Expiratory capacity (EC)|| || |
|Functional residual capacity (FRC)|| |
- Mean pulmonary arterial pressure (mPAP): normal 10–14 mmHg
- Pulmonary capillary pressure: ∼ 8 mmHg
- Pulmonary vascular resistance (PVR): the resistance offered by the pulmonary circulatory system that must be overcome to create blood flow
Pulmonary blood flow
- In healthy individuals the resistance is low and the compliance is high.
- 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
|Characteristics of pulmonary blood flow|
|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 pulmonary circulation can be regulated to match the ventilation of the alveoli in order to optimize gas exchange.
- Ventilation-perfusion ratio (V/Q ratio): the volumetric ratio of air that reaches the alveoli (ventilation) to alveolar blood supply (perfusion) per minute
- If a lung section is perfused but not ventilated, there is a drop in the oxygen concentration in the blood → hypoxic vasoconstriction (Euler-Liljestrand mechanism) → blood shift from poorly ventilated to better ventilated areas
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)
- Increased V/Q ratio (dead space): ventilation of poorly perfused alveoli (if Q = 0 → V/Q ratio = ∞)
- Decreased V/Q ratio (shunt): perfusion of poorly ventilated alveoli (if V = 0 → V/Q ratio = 0)
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 improve PaO2 in patients with airway obstruction, e.g., due to foreign body aspiration.
The main function of the lung is gas exchange (O2 and CO2), which occurs via simple diffusion across the . 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.
Diffusion (gas exchange)
- Diffusion: Vgas = A x Dk x (P1 – P2)/Δx
Factors that affect diffusion
- Air composition
- Solubility of gases (e.g., CO2 > O2 > N2)
- Partial pressure gradient: difference in partial pressures of gases between blood and inhaled air
Alveolar-capillary membrane surface area
- Normal: ∼ 100 m2
- Decreased in emphysema
- Thickness of alveolar-capillary membrane
- Diffusion capacity of the lung for carbon monoxide: measures the amount of CO transferred from the lungs to the blood
Decreased 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). can occur when the surface area of the
|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||160 mmHg (≈ 21%)||104 mmHg (≈ 14%)||116 mmHg (≈ 16%)|
|H2O||3.0 mmHg (≈ 0.5%)||47 mmHg (≈ 6%)||47 mmHg (≈ 6%)|
|CO2||0.3 mmHg (≈ 0.04%)|| |
40 mmHg (≈ 5%)
|28.5 mmHg (≈ 4%)|
|Total of all gases||760 mmHg (= 100%)|
|Partial pressure of O2 and CO2 across the|
|Partial pressure||In the alveoli||In the pulmonary capillaries|
|O2||104 mm Hg||40 mm Hg|
|CO2||40 mm Hg||45 mm Hg|
Inspired air contains more O2, less CO2, and less water vapor than expired air.
Alveolar-arterial gradient (A-a gradient)
- Definition: the difference between the partial pressure of oxygen in the alveoli (A) and the arterial (a) partial pressure of oxygen (normal: 75–100 mm Hg)
- A-a gradient = PAO2 -
- Alveolar gas equation: PAO2 = PiO2 - (PaCO2/R)
- 5–10 mm Hg for a young person breathing room air at sea level
- 15–20 mm Hg in healthy older adult
Causes of increased A-a gradient
- Higher concentration of inhaled oxygen (e.g., goes up to 50–60 mm Hg with 100% O2 in a few minutes)
- Right-to-left shunting
- Fluid in alveoli: e.g., CHF, ARDS, pneumonia
- V/Q mismatch (due to increased dead space or shunting): e.g., pulmonary embolism, pneumothorax, atelectasis, obstructive lung disease, pneumonia, pulmonary edema
- Alveolar hypoventilation: interstitial lung disease, lung fibrosis (usually manifests with ↑ CO2)
An increased A-a gradient may occur in hypoxemia due to shunting, , 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).
Types of gas exchange
Perfusion-limited gas exchange: Gas exchange is limited by the rate of blood flow through the pulmonary capillaries.
- Gases (e.g., O2, CO2, N2O) can diffuse freely across the blood-air barrier.
- The concentration of gases in the plasma will become equal to the concentration in the alveoli before the blood reaches the end of the capillary.
- An increase in blood flow causes an increase in gas exchange .
- Occurrence: under normal conditions (i.e., at rest)
- Diffusion-limited gas exchange: Gas exchange is limited by the diffusion rate of the gas (e.g., O2, CO) across the blood-air barrier.
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
- 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)
Chest wall dynamics
Resting expiratory position ( )
- Thorax pulls outward and lungs pull inward (due to the passive elastic recoil of the lungs).
- Alveolar and airway pressure = atmospheric pressure (state zero)
- Intrapleural pressure is negative (to keep the lungs expanded and prevent atelectasis).
- Definition: opposition to airflow through the upper and lower airways caused by the forces of friction during inspiration and expiration (normal: 2–3 cm H2O/L/s) 
- Diameter of the airways: The smaller the diameter, the greater the resistance.
- Velocity of airflow ( < )
Viscosity of the gas breathed
- Viscosity creates friction.
- The higher the viscosity, the higher the resistance.
- Number of parallel pathways
- Increased in: forced expiration, obstructive lung diseases (e.g., asthma, COPD)
- Decreased in: exercise
Definition: the energy used to overcome elastic recoil and airway resistance by the respiratory muscles for respiration (expressed in J/L) 
- Elastic recoil
- Increases with ↑ lung compression (e.g., due to ↑ intraabdominal pressure, pleural disease, mediastinal mass), ↑ flow rate (e.g., due to ↑ respiratory rate), and ↓ airway diameter (e.g., due to bronchospasm)
- Influenced by, e.g., tissue resistance (e.g., chest wall/lung resistance) and airway resistance
- In physics, work (W) is defined as the product of force (F) and distance (d) and is measured in joules: W = F × d
- In respiratory physiology, W is more specifically defined as the product of pressure (P) and volume (V): W = P × V
- Normal value: ∼ 0.35 J/L (in a healthy person at rest) 
- Regulation 
- Changes in WOB due to respiratory condition 
- Function: creates rhythmic innervation of the respiratory muscles and is influenced by various respiratory stimuli
- Dorsal respiratory group
Ventral respiratory group
- Responsible for expiration
- Expiration is usually passive, only becoming active during physical exercise.
Pontine center 
- Function: modifies the activity of the medullary center
- Controls the intensity of breathing
- Promotes deep gasping inspiration (apneusis) by stimulation of the dorsal respiratory group and inhibition of the
- Controls the respiratory rate and pattern of breathing
- Limits or delays inspiration
- Respiratory stimuli
- Hering-Breuer inflation reflex
- Diving reflex: immersion of the head triggers peripheral vasoconstriction, redirection of blood to the heart and brain, and slowed pulse rate, which optimizes respiration
- Spinal cord responses: recruitment of additional respiratory muscles (e.g., to compensate hypoventilation) via stimulation of motor neurons by the respiratory center
- Upper airway responses (e.g., coughing, sneezing)
|Causes of oxygen deprivation|
|Hypoxemia|| || |
Pathological breathing patterns
|Characteristics of pathological breathing patterns |
|Pathological breathing patterns||Characteristics||Common causes|
|Biot respirations (cluster breathing)|| |
|Agonal respirations|| |
|Rapid, shallow breathing|| |
Respiratory adaptation to exercise
- ↑ O2 consumption and ↑ CO2 production lead to ↑ depth and rate of ventilation (hyperventilation).
- ↑ HR and ↑ SV → ↑ cardiac output → ↑ pulmonary blood flow
- ↓ Arterial pH (due to lactic acidosis)
- Rightward shift of the oxygen dissociation curve
- Oxygen diffusion becomes diffusion-limited (in resting state it is perfusion-limited).
- ↑ V/Q ratio (from base to apex) → V/Q ratio is more evenly distributed throughout the lung during exercise than at rest
Respiratory adaptation to high altitude
Decreased atmospheric oxygen (PiO2) at high altitudes triggers various adaptation mechanisms; in the respiratory system. Insufficient adaptation to the high altitude results in .
- ↓ PaO2 → ↑ ventilation rate (stimulated by hypoxemia) → ↓ PaCO2 and ↑ arterial pH (respiratory alkalosis)
- ↑ Renal HCO3- excretion (to compensate for respiratory alkalosis)
- ↑ ( ): chronic hypoxia → pulmonary vasoconstriction → → right ventricular hypertrophy
- ↑ Hb and hematocrit (due to chronic hypoxia triggering ↑ erythropoietin levels)
- ↑ 2,3-BPG concentration → ↓ Hb affinity to O2 → rightward shift of the oxygen dissociation curve
- ↑ Number of mitochondria in cells
Respiratory adaptation in the elderly population
- ↓ PaO2 and ↑ A-a gradient
- ↑ V/Q mismatch
- ↓ FVC
- ↑ Susceptibility to aspiration and infections
- See “” for details.