Respiratory System: Conducting Zone

Respiratory System Overview

• The respiratory system connects the lungs to the external environment through a series of airways.
• It consists of the conducting zone and the respiratory zone.
• The conducting zone moves air in and out of the lungs.
• The respiratory zone facilitates gas exchange.

Conducting Zone

• Includes the nose, nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles.
• Functions to warm, humidify, and filter air before it reaches the gas exchange region.
• Progressively bifurcating airways are referred to by their generation number.
• The trachea is the zeroth generation and the main conducting airway.
• The trachea divides into the right and left mainstem bronchi (first generation).
• The bronchi continue to divide through 23 generations, culminating in the 23rd generation airways.
• Cartilage is present from the zeroth to the 10th generations of conducting airways to keep them open.
• Airways without cartilage from the 11th generation onward depend on transmural pressure to remain open.
• Mucus-secreting and ciliated cells line conducting airways to remove inhaled particles, with large particles filtered in the nose and small ones captured by mucus and swept upward by cilia.
• The autonomic nervous system regulates the smooth muscle in the walls of the conducting airways
  • Sympathetic adrenergic neurons activate β₂ receptors, causing relaxation and dilation via epinephrine and β₂-adrenergic agonists like isoproterenol.
  • Parasympathetic cholinergic neurons activate muscarinic receptors, leading to contraction and constriction.
• Airway diameter changes affect airway resistance, and β₂-adrenergic agonists such as epinephrine, isoproterenol, and albuterol are used to treat asthma by dilating airways.

Respiratory Zone

• Includes structures lined with alveoli: the respiratory bronchioles, alveolar ducts, and alveolar sacs, facilitating gas exchange.
• Respiratory bronchioles have cilia, smooth muscle, and alveoli for gas exchange.
• Alveolar ducts are completely lined with alveoli with little smooth muscle and no cilia.
• Alveolar sacs are the terminal structures and are also lined with alveoli.
• Alveoli are pouchlike evaginations of the respiratory bronchioles, alveolar ducts, and alveolar sacs
• Each lung contains about 300 million alveoli, each with a diameter of ~200 micrometers.
• Thin alveolar walls and large surface area allow for efficient O₂ and CO₂ diffusion between alveolar gas and pulmonary capillary blood.
• The walls of the alveoli contains elastic fibers and epithelial cells, which includes type I and type II pneumocytes (alveolar cells).
• Type II pneumocytes synthesize pulmonary surfactant to reduce surface tension and have regenerative capacity for both type I and type II pneumocytes.
• Alveoli contain alveolar macrophages, which phagocytize debris because alveoli have no cilia, and macrophages then migrate to the bronchioles where the cilia can transport debris to the pharynx.

Spirometry and Lung Volumes

• Static lung volumes are measured using a spirometer, where the subject breathes in and out, displacing a bell which records the volume on calibrated paper.
• Normal tidal volume is approximately 500 mL, comprising the volume of air that fills the alveoli and airways.
• Inspiratory reserve volume is about 3000 mL.
• Expiratory reserve volume is approximately 1200 mL.
• Residual volume (RV) approximates to 1200 mL and cannot be measured via spirometry.

Lung Capacities

• Lung capacities include two or more lung volumes.
• Inspiratory capacity (IC) is about 3500 mL (tidal volume + inspiratory reserve volume).
• Functional residual capacity (FRC) is about 2400 mL (expiratory reserve volume + RV) and is the equilibrium volume of the lungs.
• Vital capacity (VC) is about 4700 mL (IC + expiratory reserve volume).
• Total lung capacity (TLC) is approximately 5900 mL (vital capacity + RV), including all volumes.
• Vital capacity increases with body size, male gender, physical conditioning, and decreases with age.

Measuring Functional Residual Capacity

• The functional residual capacity (FRC) or the volume remaining in the lungs after a normal expiration, cannot be measured by spirometry, so it uses the helium dilution method or body plethysmograph.
• Helium dilution method requires the helium concentration in the lungs to become equal to that in the spirometer, which can be measured; after a few breaths, the helium concentration is measured.
• The body plethysmograph measures FRC via Boyle's law, which states that for gases at a constant temperature, pressure multiplied by volume is constant (P × V = constant).
• The subject sits in a airtight box and attempts to breathe after expiring a tidal volume after a normal expiration.

Dead Space

• The dead space refers to lung volume that does not participate in gas exchange, which may be anatomic or physiologic.
• Anatomic dead space: ~150 mL, includes the volume of the conducting airways (nose, mouth, trachea, bronchi, bronchioles), which does not reach the respiratory bronchioles and alveoli.
• Physiologic dead space: the total volume of the lungs that does not participate in gas exchange including the anatomic dead space plus some volume in the alveoli.

Calculating Physiologic Dead Space

• Physiologic dead space is: ventilated alveoli that do not participate in gas exchange secondary to ventilation/perfusion mismatch.
• In normal persons, the physiologic dead space equals the anatomic dead space.
• In pathological situations, physiologic dead space is larger than anatomic dead space in conditions of ventilation/perfusion defect.
• The volume of physiologic dead space is estimated by measuring the partial pressure of CO₂ in mixed expired air and comparing it to CO₂ in the ventilated and perfused alveoli.
• The following assumptions apply to the method of estimating physiologic dead space
  • All CO₂ in expired air comes from ventilated/perfused alveoli
  • There is essentially no CO₂ in inspired air
  • The physiological dead space does not exchange or contribute any CO₂.

Alveolar Ventilation Equation

• The alveolar ventilation equation represents the inverse relationship between alveolar ventilation and the partial pressure of carbon dioxide in the alveoli .
• K = 863 mm Hg, represents the constant under BTPS conditions including a constant body temperature of 310 K, pressure of 760 mm Hg, and saturated gases.
• The constant (K), is used when alveolar ventilation (Va) and CO₂ production are measured in the same units.
• An increase in alveolar ventilation results in a decrease in PaCO₂, and vice versa, creating an inverse relationship.

Alveolar Gas Equation

• The alveolar gas equation helps predict alveolar partial pressure of oxygen , based on the relationship between and carbon dioxide levels.
• When alveolar ventilation is halved, results in doubling and decreasing (the changes are related to the respiratory exchange ratio).

Forced Expiratory Volumes (FEV)

• Vital capacity is the volume that can be expired following a maximal inspiration.
• Forced vital capacity (FVC) is the total volume of air that can be forcibly expired after a maximal inspiration
• FEV₁ is the amount of air forcibly expired in the first second.
• FEV₂ is the cumulative volume expired in 2 seconds
• FEV₃ is the cumulative volume expired in 3 seconds.
• The entire vital capacity can normally be forcibly expired in 3 seconds.

Muscles of Breathing

• Inspiration relies on the diaphragm to increase intrathoracic volume, decreasing intrathoracic pressure and initiating airflow.
• Expiration is passive, driven by the reverse pressure gradient, but expiratory muscles (abdominal and internal intercostal muscles) may be needed during exercise or in certain lung diseases such as asthma.

Lung Compliance

• Compliance describes the distensibility of the lungs and chest wall.
• Compliance measures the change in lung volume for a given change in pressure.
• Compliance of the lungs and chest wall is inversely correlated with their elastic properties (elastance).
• Measuring lung compliance requires simultaneous measurement of lung pressure and volume.
• Lung pressures are always referred to atmospheric pressure, which is considered 'zero'.
• Pressures higher than atmospheric pressure are positive, and pressures lower than atmospheric pressure are negative.
• Transmural pressure is the pressure across a structure, such as the lungs Transpulmonary pressure: the difference between intra-alveolar pressure and intrapleural pressure.

Compliance of the Lungs

• The pressure-volume loops help illustrates compliance of an isolated lung in a jar, emulating changes in intrapleural pressure using a vacuum pump.
• In an air-filled lung experiment, both the airways and alveoli are exposed to atmospheric conditions (this equate alveolar pressure with atmospheric pressure).
• The lung expands and its volume increases when external pressure is reduced, but it encounters increasing resistance at higher volumes, reducing is compliance and flattening the curve.
• Volume is greater expiration than during inspiration, which means the compliance is higher during expiration, a phenomenon known as hysteresis.
• Compliance is typically measured on the expiration limb of the curve due to complexities in inspiration with maximum expansion.
• The inspiration and expiration limbs differ because of the surface tension at the liquid-air interface in the air-filled lung, due to intermolecular attractive forces driving surface tension.
• Surfactant reduces surface tension and increases lung compliance.
  • During inspiration, liquid molecules are closely packed, so surfactant reduces surface tension as lung surface area increases.
  • During expiration, liquid molecules are diminished, so increasing surfactant densities continues to increase compliance.
• The effect of surface tension is seen from repeat experiments with the same outcome.
• The chest wall also has compliance that can be demonstrated via a pneumothorax.
• Normally, intrapleural space maintains negative pressure via the lungs, which are naturally collapsing (elastic recoil), and the chest wall, which tends to spring outward. This creates the vacuum.

Disorders Affecting Lung Compliance

• Pneumothorax happens where intrapleural pressure suddenly equates to atmospheric pressure because a sharp object punctures the intrapleural space.
• Airway pressure equals zero at FRC.
• Diseases of lung compliance can alter these pressure volume relationship curves.
  • Emphysema (increased lung compliance): The destruction of elastic fibers leads to increased lung compliance, higher lung volumes, and barrel-shaped chests.
  • Fibrosis (decreased lung compliance): Fibrosis decreases lung compliance, resulting in lower FRC levels.

Surface Tension of Alveoli

• Surface tension is a challenge to keep alveoli due to the their small size.
• Alveoli are lined with fluid and molecules exhibit strong cohesive forces (meaning greater attraction of their liquid molecules than air).
• This drives surface tension to decrease surface area, causing alveoli to generate contractile forces
• Surfactant counteracts this process

Law of Laplace for Spheres

• The formula for the law of Laplace is used to give the surface tension value in an alveoli
• It explains that the pressure causing an alveolus to collapse relates to its surface tension and inversely it's radius.
• Surfactant, produced by type II alveolar cells, decreases surface tension by disrupting cohesive forces between liquid molecules.
• Dipalmitoyl phosphatidylcholine (DPPC) the primary component of surfactant facilitates it amphipathic natures, disrupting their cohesive forces
• Lack of surfactant causes neonatal respiratory distress syndrome, common in premature infants lacking surfactant. There is increased surface tension and collapsing pressures in the alveoli.

Airflow, Pressure and Resistance

• Airflow, pressure, and resistance are analogous to blood flow, pressures, and resistance in the cardiovascular system.
• Airflow (Q) is directly proportional to the pressure difference (ΔP) and inversely proportional to resistance (R).
• Airway resistance is also affected by the radius and compliance of the lungs, as measured by Poiseuille's law.

Airway Resistance

• Increased airway diameter leads to lower airway resistance.
• Airway diameter is primarily affected by the smooth muscle.
• Smooth muscles of the airway walls are innervated by the autonomic nervous system.
• Constriction results from parasympathetic cholinergic nerve fibers
• Dilation results from sympathetic adrenergic nerve fibers.
• Sympathetic adrenergic nerve fibers stimulate B₂ receptors.

Bronchoconstrictors

• Histamine, several leukotrienes as well as increased volume, or viscosity increases airway resistance.
• Compensatory bronchoconstriction is an adaptive mechanism when ventilated alveoli aren't perfused, causing those areas to increase PAO₂ and decrease PACO₂ levels.
• Parasympathetic stimulation causes constriction that increases with muscarinic agonists, but decreases with muscarinic antagonists.
• Sympathetic causes relaxation that decreases using B₂ receptors.

Breathing Cycle

• The breathing cycle can be described by volumes of air moved, as well as intrapleural and alveolar pressures during rest, inspiration, and expiration.
• During inspiration, the diaphragm contracts, which causes expansion.
• Lung pressures drop during inspiration.