Airways and lungs

Abstract

Gross anatomy

Overview

Conducting zone

Respiratory zone

Lungs

  • Visceral pleura: covers the lungs
  • Left lung
    • 2 lobes (upper, lower)
    • Contains the lingula
    • The left main bronchus is narrower and less vertical than the right main bronchus, therefore less prone to aspiration.
    • Contains several notches:
  • Right lung
  • Bronchopulmonary segment
    • Consists of:
      • Segmental bronchus
      • Segmental branch of the pulmonary artery
      • Segment of lung tissue surrounded by a connective tissue septum (intersegmental septum)
      • Intersegmental part of the pulmonary vein
    • Left lung has 8–10 segments and right lung has 10 segments

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

Vasculature

Lymphatics

  • Lymphatic vessels drain the whole respiratory tree but 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

  • Pulmonary plexus
    • Branches accompany the blood vessels and bronchi into the lung.
    • Parasympathetic fibers from vagus nerve: innervate smooth muscle and glands (bronchoconstriction, stimulate secretion)
    • Sympathetic fibers (act on ß2-receptors): innervate blood vessels, smooth muscle, and gland (bronchodilation, vasoconstriction, decrease secretion)

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

References:[1]

Microscopic anatomy

Conducting zone

Respiratory zone

  • Respiratory bronchioles:
  • Alveoli :
    • 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 during lung damage
    • Alveolar macrophages: phagocytose foreign materials and initiate the immune response

Pulmonary surfactant produced by type II pneumocytes is essential during breathing. It reduces the surface tension of the thin layer of water that covers the lung epithelium, thereby preventing alveolar collapse at end-expiration and reducing the work of breathing!

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 air 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 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 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 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.

  • 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

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

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

Mechanical work of breathing

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

Embryology

Developmental stage Structural changes Clinical significance

Embryonic period

weeks 0–6

  • Lung bud at the distal end of the respiratory diverticulum develops into:

Pseudoglandular period

weeks 6–16

  • Development of:

Canalicular period

weeks 16–26

  • 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 32 (8 months) – 8 years

  • At birth, only part of the roughly 300 million alveoli in an adult are fully developed.
  • In utero: increased vascular resistance due to aspiration of amniotic fluid
  • Postpartum: inspiration of air leads to a drop in pulmonary vascular resistance

References:[1]

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
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
  • 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.
  • 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.
  • Standring S. Gray's Anatomy: The Anatomical Basis of Clinical Practice. Elsevier Health Sciences; 2015.
last updated 12/12/2018
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