Airways and lungs

Summary

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.

Gross anatomy

Overview

Conducting zone

Large airways

Small airways

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

Function

  • 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

Respiratory zone

Lungs

Left lung Right lung
Lobes and bronchopulmonary segments
Bronchi
  • Left main stem bronchus is longer and more horizontal than the right bronchus
  • Inferior to the left pulmonary artery
Notches

Function

Only the right lung has a middle lobe. It can be auscultated in the fourth to six intercostal space anteriorly at the midclavicular line!

The right main bronchus is wider, shorter, and more vertical than the left main bronchus so aspiration of foreign bodies and aspiration pneumonia are more likely in the right lung!

Each bronchopulmonary segment can be surgically removed without affecting the function of the others.

Vasculature, lymphatics, and innervation

Vasculature

The lungs have a dual blood supply

Pulmonary circulation

Vessels Anatomy Characteristics
Pulmonary trunk
  • Originates in the right ventricle of the heart
  • Divides into the left and right pulmonary arteries → lobar, segmental, and subsegmental arteries
  • Carries deoxygenated blood from the right ventricle to the lungs for oxygenation
Left pulmonary artery
  • Carries deoxygenated blood from the pulmonary trunk to the left lung for gas exchange
Right pulmonary artery
  • Carries deoxygenated blood from the pulmonary trunk to the right lung for gas exchange
Pulmonary veins

Bronchial circulation

Vessels Anatomy Characteristics
Bronchial arteries
  • Supply oxygenated blood to the lung parenchyma, bronchi, and the visceral pleura
Bronchial veins
  • Drain deoxygenated blood from hilar structures and conducting zone structures


Lymphatics

  • Lymphatic vessels drain the entire respiratory tree (lymphatic vessels are not present in the pulmonary alveoli)
  • Intrapulmonary nodes → bronchopulmonary nodes → tracheobronchial nodes → paratracheal nodes → bronchomediastinal nodes and trunks → thoracic duct on the left and right lymphatic duct on the right

Innervation

References:[1][2][3]

Microscopic anatomy

Conducting zone

Respiratory zone

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!

Hemosiderin-laden macrophages are present in alveolar hemorrhage.

References:[4][5][6][7]

Function

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 volumes

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
N2

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.

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

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.

Ventilation

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

Normal and pathologic ventilation

Standard value Abnormally low Abnormally high
Respiratory rate

16–20/min

Bradypnea (< 10/min) Tachypnea (> 20/min)
Tidal volume 0.5 L Hypopnea 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.

Perfusion

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.

Ventilation-perfusion regulation

  • 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

  • Description
    • 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 A-a gradient
  • 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)
  • Pathologic changes:

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).

Respiratory regulation

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
Central
  • Hering–Breuer inflation reflex:
    • Prevents overinflation of the lungs and alveolar damage
    • Mediated by pulmonary stretch receptors and vagal afferents
Chemical
  • pCO2 > 70 mmHg in blood
Unspecific
  • ↑ Blood pressure

A partial CO2 pressure of ≥ 70 mmHg inhibits the respiratory center instead of stimulating it. This is also called CO2 anesthesia!

Through hyperventilation, the partial pressure of CO2 in the blood and thus the respiratory drive can be reduced, which, for example, is used by divers before a dive!

Chest wall dynamics

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) and aging
  • Decreased in: conditions associated with increased lung stiffness (e.g., pulmonary fibrosis, pulmonary edema)

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

Airway resistance

  • Definition: : opposition to airflow through the upper and lower airways caused by the forces of friction (normal: 4 cm H20/L/s)
  • Depends on:
    • 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)

Alveoli

Alveolar macrophages
Medium (3–10 μm) Trachea and/or bronchi Mucociliary escalator
Large (≥ 10 μm) Nasal cavity Nasal vibrissae

References:[8][1]

Function

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.
  • For more information, see learning card on pulmonary physiology.

Embryology

Developmental stage Description Clinical significance

Embryonic period

Weeks 4–7

  • Lung bud at the distal end of the respiratory diverticulum develops into:
    • Trachea
    • Bronchial buds → mainstem bronchi, secondary bronchi, tertiary bronchi

Pseudoglandular period

Weeks 5–17

Canalicular period

Weeks 16–25

  • Errors lead to pulmonary hypoplasia or respiratory distress syndrome
  • Surfactant production begins at 20–22 weeks' gestation; mature levels are reached at 35 weeks' gestation.

Saccular period

Weeks 26–birth

  • Development of: alveolar ducts and thin-walled alveoli (separated by primary septa)
  • Fetus is able to survive and breathe outside the uterus from about 24–25 weeks of gestation with intensive care.

Alveolar period

Week 36–8 years

  • Between birth and adulthood, alveoli increase in number but not in size
    • At birth approx. 150 million alveoli
    • In adults: approx 300 million alveoli
  • In utero: increased vascular resistance due to aspiration of amniotic fluid
  • Postpartum: inspiration of air leads to a drop in pulmonary vascular resistance

References:[9][10][11][12]

Clinical significance

Pathological breathing patterns

Pathological breathing patterns Characteristics Common causes
Kussmaul respirations

Consistent very deep breathing at a normal or increased rate (to eliminate excess CO2)

Cheyne–Stokes respiration

Cyclic, spindle-shaped (crescendo-decrescendo) breathing with intermittent periods of hypoventilation/apnea.

Biot respirations ("cluster breathing") Irregular breathing followed by regular or irregular periods of apnea.
  • Intracranial pressure
  • Brain damage (e.g., trauma, stroke)
  • Opioid use
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 Rapid, shallow breaths with low tidal volume.

Lung physiology during exercise

  • Increased depth and rate of ventilation
  • 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

References:[13]

  • 1. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
  • 2. Chung KW. Gross Anatomy. Baltimore, MD: Lippincott Williams & Wilkins; 2005.
  • 3. Celis EA. Lung Anatomy. In: Mosenifar Z. Lung Anatomy. New York, NY: WebMD. https://emedicine.medscape.com/article/1884995. Updated December 7, 2017. Accessed December 15, 2018.
  • 4. Faculty of Biological Sciences, University of Leeds. Functions of the Respiratory Portion. https://www.histology.leeds.ac.uk/respiratory/respiratory.php. Accessed December 15, 2018.
  • 5. Kalsheker N, Stockley RA. Alpha-1-Antitrypsin Deficiency: Biology, Diagnosis, Clinical Significance, and Emerging Therapies. Academic Press; 2017.
  • 6. Kuhn C, Senior RM. The role of elastases in the development of emphysema. Lung. 1978; 155(1): pp. 185–197. doi: 10.1007/bf02730693.
  • 7. Weiss ST. Chronic Obstructive Pulmonary Disease: Risk Factors and Risk Reduction. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/chronic-obstructive-pulmonary-disease-risk-factors-and-risk-reduction. Last updated August 22, 2018. Accessed December 29, 2018.
  • 8. Theodore AC. Oxygenation and Mechanisms of Hypoxemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/oxygenation-and-mechanisms-of-hypoxemia. Last updated April 12, 2016. Accessed January 7, 2016.
  • 9. Reuter S, Moser C, Baack M. Respiratory distress in the newborn. Pediatr Rev. 2014; 35(10): pp. 417–429. doi: 10.1542/pir.35-10-417.
  • 10. Le T, Bhushan V,‎ Sochat M, Chavda Y, Abrams J, Kalani M, Kallianos K, Vaidyanathan V. First Aid for the USMLE Step 1 2019. New York, NY: McGraw-Hill Medical.
  • 11. Human Embryology. 18.1 Phases of Lung Development. http://www.embryology.ch/anglais/rrespiratory/phasen06.html. Updated January 1, 2018. Accessed December 15, 2018.
  • 12. Hislop AA, Wigglesworth JS, Desai R. Alveolar development in the human fetus and infant. Early Hum Dev. 1986; 13(1): pp. 1–11. doi: 10.1016/0378-3782(86)90092-7.
  • 13. 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.
  • Standring S. Gray's Anatomy: The Anatomical Basis of Clinical Practice. Elsevier Health Sciences; 2016.
  • Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill Education; 2015.
last updated 08/08/2019
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