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 . 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): → pharynx → → → → → 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): volume of air that a person breathes per minute (i.e., the product of tidal volume and respiratory rate; VE = VT x RR)
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): volume of gas that reaches the alveoli each minute
- VA = (VT - VD) x RR
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.
|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|
- 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 (R = ΔP / Q)
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
|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
- Ventilation-perfusion ratio: the perfusion of the pulmonary circulation can be regulated to match the ventilation of the alveoli in order to optimize gas exchange
- 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)
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
- Normal V/Q ratio
V/Q mismatch: occurs when either ventilation or perfusion or both change in a way that the two parameters no longer match
- Increased V/Q ratio (dead space): ventilation of poorly perfused alveoli (V/Q = ∞)
- Decreased V/Q ratio (shunt): perfusion of poorly ventilated alveoli
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.
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: Vgas = A x Dk x (P1 – P2)/Δx
Factors that affect diffusion
- Air composition
- Partial pressure gradient: difference in partial pressures of gases between blood and inhaled air
- Solubility of gases (e.g., CO2 > O2 > N2)
- Alveolar-capillary membrane surface area (normal: ∼ 100 m2)
- Thickness of alveolar-capillary membrane (normal: 0.6 μm)
- gas exchange across the blood-air barrier, e.g., in intraparenchymal lung diseases (see for details): may be used to assess
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||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|
|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|
- 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).
- Formula: A-a gradient = PAO2 -
- 5–10 mm Hg for a young person breathing room air at sea level
- 15–20 mm Hg in healthy older adult
A-a gradient increases with
- 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): 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, 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
Perfusion-limited gas exchange: Gas exchange is limited by the rate of blood flow through the pulmonary capillaries.
- Gases can diffuse freely across the blood-air barrier.
- Concentration of gases in the plasma will become equal to the concentration in the alveoli before the end of the capillary.
- An increase in blood flow allows these more distal parts to also participate 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 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.
- 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)
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 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
- 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: 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
Medullary center: creates rhythmic innervation of the respiratory muscles and is influenced by various respiratory stimuli
- Dorsal respiratory group: responsible for inspiration
Ventral respiratory group: responsible for expiration
- Expiration is usually passive, only becoming active during physical exercise
- Pontine center: modifies the activity of the medullary center
- Respiratory stimuli
Hering-Breuer inflation reflex: inhibits inspiration to prevent overinflation of the lungs and alveolar damage
- Mediated by pulmonary stretch receptors and vagal afferents
- 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)
- Hering-Breuer inflation reflex: inhibits inspiration to prevent overinflation of the lungs and alveolar damage
|Pathological breathing patterns||Characteristics||Common causes|
|Biot respirations (cluster breathing)|| |
|Agonal respirations|| |
|Rapid, shallow breathing|| |
- ↑ 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)
Decreased atmospheric O2 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)
- ↑ Pulmonary vascular resistance ( )
- ↑ Hb and hematocrit (due to chronic hypoxia triggering ↑ erythropoietin levels)
- ↑ 2,3-BPG concentration → ↓ Hb affinity to O2
- ↑ Number of mitochondria in cells
Respiratory adaptation in the elderly population
- ↓ Chest wall compliance
- ↑ Lung compliance
- ↓ PaO2 and ↑ A-a gradient
- ↑ V/Q mismatch
- ↓ FVC
- ↑ Susceptibility to aspiration and infections
- Please see for details.