The respiratory system consists of a conducting zone (anatomic dead space; i.e., the airways of the mouth, nose, pharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles) and a respiratory zone (lung parenchyma; i.e., respiratory bronchioles, alveolar ducts, alveolar sacs). The conducting zone is composed of nonrespiratory tissue and provides the passage for ventilation of the respiratory zone, where the O2 and CO2 exchange takes place. The respiratory system is furthermore divided into an upper tract (structures from the larynx upwards) and a lower tract (structures below the larynx). The entire respiratory tract down to the bronchioles is covered in ciliated epithelium, which provides immunologic protection by helping clear the airways of, e.g., dust and microorganisms. Hyaline cartilage in the form of C-shaped rings (trachea) and plates (bronchi) provides structural protection and integrity. Gas exchange takes place in the alveoli of the lungs. The right lung consists of 3 lobes (upper, middle, lower), while the left lung consists of 2 lobes (upper, lower) and the lingula, a structure that is homologous to the middle lobe of the right lung. The left lung shares its space with the heart, which it accommodates in the cardiac notch. The development of the lungs begins in the embryonic period and continues until approximately 8 years of age.
- The respiratory tract consists of
- Upper respiratory tract: nasopharynx, larynx
- Lower respiratory tract: trachea, bronchi, bronchioles, lungs
- Formed by a series of cartilages, joined together by annular ligaments.
- Bifurcates at the level of T4 into the left and the right main bronchus (tracheal carina)
- Neighboring structures
- The right main (primary) bronchus divides into 3 lobar bronchi (secondary bronchi).
- The left main (primary) bronchus divides into 2 lobar bronchi (secondary bronchi).
- The lobar bronchi divide further into segmental bronchi (tertiary bronchi).
- Conduction of air in and out of the respiratory tree
- Anatomic dead space (no gas exchange)
- Warms and humidifies air
- Mucociliary clearance: ciliated epithelium transports mucus, bacteria, and dust towards the throat, where it is either swallowed or expelled through the mouth
- Paired organ of the respiratory system
- Located in the
- Surrounded by the
- Hilum of the lung: the point of attachment of the lung to the lung root, which serves as the entry and exit site of the primary bronchi, pulmonary arteries and veins, bronchial arteries and veins, pulmonary nervous plexus, and lymphatics of each lung
- Bronchopulmonary segments
- Lung parenchyma consisting of
|Left lung||Right lung|
|Lobes and bronchopulmonary segments|| || |
- Oxygen and carbon dioxide exchange across blood-air barrier
- phagocytose fine dust particles (< 2 μm)
Only the right lung has a middle lobe. It can be auscultated in the fourth to six intercostal space anteriorly at the midclavicular line!
Each bronchopulmonary segment can be surgically removed without affecting the function of the others.
Vasculature, lymphatics, and innervation
The lungs have a dual blood supply
- Bronchial circulation (part of the systemic circulation)
|Pulmonary trunk|| |
|Left pulmonary artery|| || |
|Right pulmonary artery|| || |
|Bronchial arteries|| |
|Bronchial veins|| |
- Lymphatic vessels drain the entire respiratory tree (lymphatic vessels are not present in the )
- Intrapulmonary nodes → bronchopulmonary nodes → tracheobronchial nodes → paratracheal nodes → bronchomediastinal nodes and trunks → thoracic duct on the left and right lymphatic duct on the right
- Branches accompany the blood vessels and bronchi into the lung.
- Parasympathetic fibers from the vagus nerve (M3 receptors) innervate smooth muscle and glands (bronchoconstriction, increase secretion)
- Sympathetic fibers (act on ß2-receptors): innervate blood vessels, smooth muscle, and glands (bronchodilation, vasoconstriction, decrease secretion)
Trachea and bronchi
- Pseudostratified ciliated columnar epithelium: important for mucociliary clearance
- Cartilage: C-shaped hyaline cartilage rings in the trachea and elastic cartilage plates in the bronchi provide structural support.
- Annular ligaments of trachea: horizontal fibrous bands that join the tracheal cartilage rings together
- Smooth muscle
- Seromucous glands (secrete mucus)
- Bronchioles: simple ciliated columnar epithelium; ; enclosed by smooth muscle
- Terminal bronchioles: simple ciliated cuboidal epithelium; smooth muscle
- Simple cuboidal and squamous epithelium, smooth muscle
- Club cells
- Separated from each other by the interalveolar septum with elastic fibers and capillaries; interalveolar pores connect adjacent alveoli.
- Type I pneumocytes: thin squamous cells that line the alveoli
Type II pneumocytes: cuboidal alveolar cells
- Comprise 5% of the total alveolar area, but 60% of total number of cells
Contain lamellar bodies, which secrete surfactant (surface-activating lipoprotein complex)
- Mainly composed of the phospholipids dipalmitoylphosphatidylcholine (DPPC or lecithin) and phosphatidylglycerol.
- Reduces alveolar surface tension and thereby prevents the alveoli from collapsing.
- Can also proliferate to replace Type I or Type II pneumocytes following lung damage
- Alveolar macrophages: phagocytose foreign materials and initiate the immune response
Pulmonary surfactant produced by type II pneumocytes reduces the surface tension of the thin layer of water that covers the pulmonary epithelium, thereby preventing alveolar collapse at end-expiration, increasing compliance, and reducing the work of breathing!
are present in alveolar hemorrhage.
The main function of the lung is the absorption of oxygen into the blood and the release of carbon dioxide into the air. For this purpose, the air must first reach the alveoli (see pulmonary function testing for respiratory mechanics). The distribution of air (ventilation) is adjusted to the perfusion of pulmonary vessels so that the gas exchange proceeds evenly. The respiratory center adjusts the breathing to the needs of the entire organism.
|Lung volume||Definition||Normal range|
|Total lung capacity (TC,TLC)||Volume of gas in the lungs after maximal inhalation||6–6.5 L|
|Vital capacity (VC)||Difference in lung volume between maximal exhalation and maximal inhalation||4.5–5 L|
|Residual volume (RV)||Volume of gas that remains in the lungs after maximal exhalation||1–1.5 L|
|Tidal volume (TV)||Volume of gas inhaled into the lungs during a normal resting breath||∼ 500 mL or 7 mL/kg|
|Inspiratory reserve volume (IRV)||Maximum volume of gas that can still be forcibly inhaled following the inhalation of a normal TV||3–3.5 L|
|Inspiratory capacity (IC)||Maximum volume of gas that can be inhaled after the exhalation of a normal TV||3.5–4 L|
|Expiratory reserve volume (ERV)||Maximum volume of gas that can still be forcibly exhaled after the exhalation of a normal TV||1.5 L|
|Expiratory capacity (EC):||Maximum volume of gas that can be exhaled after the inspiration of a normal TV||2 L|
|Functional residual capacity (FRC)||Volume of gas that remains in the lungs after the exhalation of a normal TV||2.5–3 L|
Oxygenation of blood
The main function of the lung is gas exchange. Exchange of O2 and CO2 occurs between walls of alveoli and pulmonary capillaries across the blood-air barrier via simple diffusion. The gases follow pressure gradients, meaning no energy is required for this process. In the capillaries, oxygen binds to hemoglobin in erythrocytes or dissolves into the plasma.
Diffusion of gases depends on:
- Air composition
- Differences in partial pressures of gases between blood and inhaled air
- Partial pressure definition: the pressure of a single gas in a mixture of gases.
- Gas moves from an area where its partial pressure is higher to an area where its partial pressure is lower.
- 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)
|Partial pressure (% 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.
- The diffusion capacity of the lung is decreased in:
Interstitial lung diseases (e.g., pulmonary fibrosis) are marked by inflammatory and fibrotic changes in the alveoli. As a result, the alveolar-capillary membrane is thickened and gas exchange is impaired (reduced diffusion capacity). To determine the diffusion capacity, patients inhale a predefined amount of carbon monoxide (CO), and then the exhaled CO is measured to determine the difference between inhaled and exhaled CO.
|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: PAO2 -
PAO2 = PIO2 - (PaCO2/R)
- PIO2 is the partial pressure of O2 in inspired air (∼150 mm Hg in room air at sea level)
- R is the respiratory quotient; (CO2 produced/O2 consumed) and is typically 0.8
- 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
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 presents 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.
Ventilation refers to the distribution of respiratory air to the different parts of the lung. It is responsible for supplying the alveoli with fresh air for gas exchange. Those sections of the airways that merely conduct air and do not participate in gas exchange are called dead space.
Parameters of ventilation
- Respiratory rate: number of breaths per minute
- Tidal volume: the volume of air that is inspired or expired in a single breath
- Minute ventilation: volume of air that a person breathes per minute (i.e., the product of tidal volume and respiratory rate)
- Alveolar ventilation:
Physiologic dead space
- Definition: volume of inspired air that does not participate in gas exchange
- Physiologic dead space (VD) is the sum of anatomic dead space and alveolar dead space (mainly apex of lung)
- Bohr equation: determines the physiologic dead space: (Tidal volume) x (arterial PCO2 - expired air PCO2)/(arterial PCO2)
- In a healthy lung, VD equals the anatomic dead space (normal value: ∼ 150 mL/breath)
- VD > anatomic dead space in diseases with a (e.g., pulmonary embolism)
Normal and pathologic ventilation
|Standard value||Abnormally low||Abnormally high|
|Respiratory rate|| |
|Bradypnea (< 10/min)||Tachypnea (> 20/min)|
|Tidal volume||0.5 L||Hyperpnea|
|Minute ventilation||7.5 L/min||Hypoventilation||Hyperventilation|
If alveolar ventilation increases, e.g., during hyperventilation, more CO2 is exhaled and the partial pressure of CO2 decreases in blood and in exhaled air. If alveolar ventilation decreases, CO2 concentrations increase in blood and exhaled air.
Since the entire blood volume of the body must pass through the lungs, the pulmonary circulation corresponds to the cardiac output. The distribution of the blood on the lung sections, however, has a great influence on the oxygenation of the blood. Therefore, it is precisely controlled by special reflexes such as the Euler-Liljestrand mechanism.
- Pulmonary blood flow: corresponds to cardiac output (∼ 5 L / min)
- Distribution of blood flow: circulation is highest in the lung base due to gravity
- Mean pulmonary arterial pressure (mPAP): normal 10–14 mmHg
- Pulmonary capillary pressure: ∼ 8 mmHg
- 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 ventilation-perfusion ratio is higher in the lung tip than in the lung base → O2 partial pressures are higher in the lung peak than in the lung base
Ventilation-perfusion mismatch (V/Q) mismatch
- An imbalance between the total lung ventilation (airflow; V) and total lung perfusion (blood flow; Q).
- Most common cause of hypoxemia
- Characterized by an increased
Normal V/Q ratio
- 0.8 (ranges from 3 at the apex (V > Q) to 0.6 at the base (Q > V) since lung bases are better ventilated and perfused than the apices in an upright person)
- Ideal is a V/Q ratio of 1
Two types of V/Q mismatch:
- Dead space: ventilation of poorly perfused alveoli (V > Q)
- Shunt: perfusion of poorly ventilated alveoli (V < Q)
- Decreased V/Q ratio (↑ shunt): in decreased ventilation (e.g., in pneumonia, atelectasis, cystic fibrosis, pulmonary edema)
- Increased V/Q ratio (↑ dead space): in decreased perfusion (e.g., in pulmonary embolism, cardiovascular shock)
- V/Q = 0: in airway obstruction (e.g., foreign body aspiration)
- V/Q = infinity: in blood flow obstruction (e.g., pulmonary embolism)
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).
Regulation of respiration takes place centrally in the so-called respiratory center located at the base of the medulla in the formatio reticularis. It causes rhythmic innervation of the respiratory muscles and is influenced by various respiratory stimuli.
- Strongest respiratory drive under normal conditions: increased pCO2
- Highest respiratory drive in chronic hypercapnia (e.g., in COPD): low pO2; (respiratory center develops a tolerance for increased pCO2)
|Respiratory stimuli||Stimulation of the central inspiratory drive||Inhibition of the central inspiratory drive|
Resting expiratory position ( )
- Thorax pulls outward and lungs pull inward (due to the passive elastic recoil of the lungs)
- Alveolar pressure = atmospheric pressure (state zero)
- Intrapleural pressure is negative (to keep lungs expanded and prevent atelectasis)
- 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) and aging
- Decreased in: conditions associated with increased lung stiffness (e.g., pulmonary fibrosis, pulmonary edema)
- Definition: : opposition to airflow through the upper and lower airways caused by the forces of friction
- Diameter of the airways → the smaller the diameter, the greater the resistance
- Velocity of airflow (laminar < turbulent)
- 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 > small airways)
- Greatest in: segmental bronchi
- Increased in: forced expiration, obstructive lung diseases (e.g., asthma, COPD)
- Decreased in: exercise
Pulmonary clearance of inhaled particles
Inhaled particles within the respiratory tree are cleared by different means depending on their size.
|Particle size||Deposit into||Clearance via|
|Small (< 3 μm)|| |
|Medium (3–10 μm)||Trachea and/or bronchi||Mucociliary escalator|
|Large (≥ 10 μm)||Nasal cavity||Nasal vibrissae|
|Developmental stage||Description||Clinical significance|
| || |
| || |
Week 36–8 years
| || |
|Pathological breathing patterns||Characteristics||Common causes|
|Kussmaul respirations|| |
Consistent very deep breathing at a normal or increased rate (to eliminate excess CO2)
|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.|| |
|Rapid, shallow breathing||Rapid, shallow breaths with low tidal volume.|
Lung physiology during exercise
- Increased depth and rate of ventilation
- Despite hyperventilation, PaCO2 and PaO2 remain normal
- Increase in pulmonary blood flow
- Vasodilation of apical pulmonary capillaries → decreased V/Q ratio in the apical region and evening out of the V/Q ratio throughout the lung
- Oxygen diffusion, which is perfusion-limited in the resting state, becomes diffusion-limited