Respiratory System: Conducting Zone

Respiratory System Overview

• The respiratory system includes the lungs and airways connecting them to the external environment.
• It is divided into the conducting zone and the respiratory zone.
• The conducting zone moves air in and out of the lungs, and the respiratory zone is where gas exchange occurs, lined with alveoli.
• The functions and structures lining the conducting and respiratory zones are different.

Conducting Zone

• Includes the nose, nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles.
• Functions to bring air into/out of the respiratory zone for gas exchange.
• Warms, humidifies, and filters air before it reaches the gas exchange region.
• Progressively bifurcating airways are classified by generation number.
• The trachea, being the zeroth generation, is the main conducting airway.
• The trachea divides into the right and left mainstem bronchi (first generation) which keep dividing into smaller bronchi, up to the 23rd generation.
• Cartilage is present in the walls of the 0th to 10th generations, keeping airways open.
• From the 11th generation, airways depend on transmural pressure to remain open due to no cartilage.
• Its airways are lined with mucus-secreting and ciliated cells to remove inhaled particles.
• Large particles are filtered out in the nose, while smaller particles are captured by mucus and swept upward by rhythmic cilia beating.
• Walls contain smooth muscle, regulated by the autonomic nervous system.
  • Sympathetic adrenergic neurons activate β2 receptors, leading to relaxation and dilation of the airways, also activated by epinephrine and β2-adrenergic agonists like isoproterenol.
  • Parasympathetic cholinergic neurons activate muscarinic receptors, leading to contraction and constriction of the airways.
• Airway diameter changes affect airway resistance/airflow.
• β2-adrenergic agonists (e.g., epinephrine, isoproterenol, albuterol) can be used to dilate airways for asthma treatment.

Respiratory Zone

• Includes structures lined with alveoli involved in gas exchange like respiratory bronchioles, alveolar ducts, and alveolar sacs.
• Respiratory bronchioles possess both cilia and smooth muscle, similar to conducting airways while participating in gas exchange, since alveoli occasionally bud off their walls.
• Alveolar ducts completely contain alveoli and no cilia, and exhibit little smooth muscle.
• Alveolar sacs are the terminal structures, also lined with alveoli.
• Alveoli are pouch-like structures from the respiratory bronchioles, alveolar ducts, and alveolar sacs.
• Each lung contains approximately 300 million alveoli, each ~200 μm in diameter.
• Their thin walls/large surface area allows rapid O₂ and CO₂ diffusion between alveolar gas/pulmonary capillary blood.
• Alveolar walls contain elastic fibers and epithelial cells called type I and type II pneumocytes (alveolar cells).
  • Type II pneumocytes synthesize pulmonary surfactant that reduces surface tension and exhibit regenerative capacity for both pneumocyte types.
• Alveoli contains alveolar macrophages, which are phagocytic cells that keeps alveoli free of dust and debris and migrate to bronchioles to be disposed of via cilia to the pharynx for swallowing/expectoration.

Lung Volumes and Capacities

• Static lung volumes are measured via spirometer.
• During spirometry, the subject sits and breathes into and out of the device, displacing a bell, which is recorded on calibrated paper.
• Tidal Volume (Vt):
  • Volume of air during normal, quiet breathing and is ~500 mL which fills the alveoli plus the volume of air that fills the airways.
• Inspiratory Reserve Volume:
  • The additional volume inspired above tidal volume and equals ~3000 mL
• Expiratory Reserve Volume:
  • The additional volume expired below tidal volume and equals ~1200 mL.
• Residual Volume (RV):
  • Volume of gas remaining after maximal forced expiration
  • Approximately 1200 mL and cannot be measured by spirometry.
• Lung capacities:
  • Inspiratory Capacity (IC):
    • Tidal volume plus inspiratory reserve volume
    • Approximately 3500 mL.
  • Functional Residual Capacity (FRC):
    • Expiratory reserve volume plus RV.
    • Approximately 2400 mL.
    • Volume remaining after a normal tidal volume is expired
    • the equilibrium volume of the lungs.
  • Vital Capacity (VC):
    • Inspiratory capacity plus expiratory reserve volume
    • Approximately 4700 mL.
    • Is the volume that can be expired after maximal inspiration.
    • Increases with body size, is impacted by biological sex, physical conditioning and decreases with age.
  • Total Lung Capacity (TLC):
    • Sum of all lung volumes
    • Equals vital capacity plus the RV or 5900 mL.

Functional Residual Capacity Measurement

• Because Residual Volume (RV) cannot be measured by spirometry, lung capacities including RV, like FRC and TLC, also cannot be measured by spirometry
• the FRC (the volume remaining post normal expiration) is of greatest interest since it is the lungs resting/equilibrium volume.
• The two methods to measure FRC are helium dilution and body plethysmograph.
  • Helium Dilution: The subject breathes a known amount of helium added to the spirometer, which is insoluble in blood, meaning helium concentration equalizes with in the lungs, making it measurable.
  • Body Plethysmograph: Employs Boyle's law, where (P × V = constant) and gas pressure multiplied by gas volume stay constant as long as gas moles and temperature are constant, where volume increase equates to pressure decrease
    • With the subject in a sealed plethysmograph after expiring a normal tidal volume and closing the mouthpiece.
    • The subject tries to breathe, expanding lung volume which decreases lung pressure.
    • The box volume decreases, increasing box pressure, which can be measured to calculate lung perspiratory volume.

Dead Space

• Dead space signifies the volume of airways and lungs that do not participate in gas exchange.
• The meaning can be broken down into the anatomic dead space of conducting airways combined with a functional/physiological dead space.
• Anatomic dead space represents the conducting airways volume including the nose/mouth, trachea, bronchi, and bronchioles.
• The volume of conducting equals ~ 150 mL, for example, when a tidal volume of 500 mL is inspired, 150 mL fills the conducting airways, and 350 mL fills the alveoli.
• At the end of expiration, conducting airways contain alveolar air that has already exchanged gases with pulmonary capillary blood.
• During the next inspiration, this alveolar air first enters the alveoli, and the fresh air (350 mL) from inspired tidal volume then enters the alveoli for gas exchange while the remaining tidal volume (150 mL) remains in the conducting airways and is the air that is first expired.
• To sample alveolar air, end-expiratory air must be sampled.
• Physiological dead space signifies both the anatomical dead space in the conducting airways and functional dead space in alveoli.
• Functional dead space signifies ventilated alveoli that do not participate in gas exchange which occurs if there is a ventilation/perfusion defect, in which functional alveoli are not perfused by pulmonary capillary blood.
• Physiological and anatomical dead space are nearly equal in healthy individuals, implying matching alveolar ventilation and perfusion, and only increase if there is ventilation/perfusion defects.
• Physiological dead space to tidal volume ratio is to estimates "wasted" ventilation.
• PhysDeadSpace Volume is calculated by measuring PCO₂ of mixed expired air PECO₂ and (1) CO₂ present in expired air proceeds from CO₂ exchange through functional (ventilated/perfused) alveoli, (2) there is no CO₂ in inspired air, and (3) Physiological dead space alveoli/airways is not functioning.
• If zero physiological dead space, then PECO₂ equals alveolar PCO2 (PaCO2)
• If there exists physiological dead space, then PECO₂ is “diluted” by dead space air, then PECO₂ is less than PACO₂ because of that physiological
• Can over come issues of measurement since alveolar air equilibrates with pulmonary capillary blood (which becomes systemic arterial blood), meaning the PCO₂ of systemic arteriol blood (PaCO2) is equal to the PCO2 of alveolar air (PaCO2).

Alveolar Ventilation Equation

• The alveolar ventilation equation shows the inverse relationship between alveolar ventilation and the partial pressure of carbon dioxide in the alveoli.
• K (constant) denotes 863 mm Hg under BTPS conditions, which includes a body temperature of 310 K, ambient pressure of 760 mm Hg, and gases saturated with water vapor.
• This constant us used if alveolar ventilation and CO2 production are measured in the same units, mL/min.
• Paco2 can be predicted using a rearranged form of the alveolar ventilation equation if the rate of CO₂ production from aerobic metabolism and alveolar ventilation are known.
• Its known due to the hyperbolic relationship between Paco2 and alveolar ventilation where CO₂ production is constant.
• Higher alveolar ventilation will lower Paco2, and vice versa, allowing variations of breathing to affect CO₂ from the bloodstream.
• Alveolar ventilation's inverse relationship occurs since it removes CO₂ from pulmonary capillary blood.
• Breaths intake CO₂ free air that drives CO₂ diffusion from blood into alveolar gas, which is then exhaled.

Alveolar Gas Equation

• The alveolar ventilation equations dependence between alveolar and arterial PCO₂ on alveolar ventilation and predicts alveolar PO₂ relative to alveolar PCO-2, based on respiratory quotient.
• R, the respiratory exchange ratio is usually ignored and respiratory quotient is applied where the correction factor is small.
• Alveolar ventilation equation previously determined ( PCO_2 ) doubles when alveolar ventilation is halved and indicates how alveolar ventilation halves, and what the ( PO_2 ) change will be.
• Respiratory exhange ratio is at 0.8, meaning alveolar ventilation decreasing will cause ( PO_2 ) will be slightly greater than the increase.

Forced Expiratory Volumes (FEV)

• Vital capacity is the maximum expiration volume.
• Forced vital capacity (FVC) can be forcibly expired after full respiration, as shown in diagram
  • FEV1 describes that that can be forcibly expired in the first second.
  • FEV2 refers to the cumulative volume which at 2 seconds
  • FEV3 is the cumulative volume expired in 3 seconds, equating to the vital capacity.
  • FEV4 is not necessary since the entire forceable capacity is generally exhaled within 3 seconds.

Mechanics of Breathing

• The important muscle for inspiration is the diaphragm, which upon contraction, the abdominal contents are pushed downward and the ribs are lifted upward.
• Exercising will utilize the external intercostal muscles and accessory muscles for more vigorous inspiration.
• Expiration is usually a passive process where air out through the lungs through the reversing pressure gradient.
• In specific diseases and exercise and diseases, expiratory muscles will aid the expiratory process like abdominal muscles (compress cavity and push diaphragm) and internal intercostal muscles (pull ribs downward).
• Compliance measures the distensibility of a system
• Compliance is how volume changes when pressure changes.
• Lung compliance measures the lung volume change for each pressure change.
• Lung compliance versus chest and wall are inversely correlated with elastic capacities like elastance
  • The more elastic 'tissue' the more compliant.
  • The thicker the rubber hand, the more elastic and difficult to stretch due to low compliance.
• Measuring lung compliance measures the lungs at a certain volume, like pressure in the alveoli and outside of them.
• Transmural pressure is across structure, like transpulmonary pressure as intra alveolar minus intrapleural
• Lung pressures equal to atmospheric pressure is zero; if higher, it is positive; if lower, it's negative.

Lung Compliance

• The pressure-volume plot shows how the pressure outside the lungs is varied to simulate intrapleural pressures, where variation equates to volume.
• Vacuum with atmosphere equating alveolar with atmospheric.
• Vacuum reduced results in negative pressure in the lung, increasing volume which flattens as alveoli volumes increasing resistance at higher volumes decreases compliance. External pressure will then decrease as the lung volumes decrease/
• Slopes will between volume increase of lungs between inspiratory and expiration indicates how lung compliance varies and is called the hysteresis.

Surface Tension of Alveoli

• Volume slopes show the lung relationship shows varying compliance where the liquid/gas surface differs for filled lungs
• Filled lungs exhibit intermolecular forces that are stronger at the molecule level compared to liquid air interfaces between air and liquid
• Inspiration limb, the liquid molecules closely packed, and intermolecular forces will overcome these as lungs inflate, resulting in reduced surfactant density and high surface tension with flattened curves.
• Expiration limb molecules are not breaking forces because the surface area is removed more quickly than surface linings, where lung compliances increases
• Saline will cause liquid inspiration/expiration lanes to be same due to liquid air surface tensions

Pneumothorax

• The point of using a air outside of the lung to describe how pneumothorax affects lung compliance is an example of how the system is compliant.
• Normally a negative pressure is needed to cause elastic and expand forces so the intrapleural is always open.
• Without the forces, the lungs can collapse but are constrained the chest wall, leading to springs-like behaviour.
• Air in pleural cavity will generate increased pressure, which will collapse lungs and cause external chest cavity to spring out

Functional Residual Capacity (FRC), Lung Collapsing

• Functional Reserve Capacity in the lungs. At this point is is labelled as zero since atmospheric equates to pressure
• If the forces were uneven then elastic forces would move. However, since the combined lung and chest-wall are equilibrium it it does not
• Lungs are have reduced volumes, hence the collapsing elastic volume of lungs is is lessened since force on chest is expanded since the combined lungs want to expand.
• if the volume is more inflated, or exceed FRC, then elastic increases and the expanding force is reduced in the combined lung and chest since it it wants to collapse

Compliancy Diseases

• Changes in lung compliance due to disease.
  • Emphysema (increased lung compliance): loss of elastic fibers in the lungs. The collapse of lungs can not resist
  • Fibrosis (decreased lung compliance): stiffening of the lung tissues (restrictive). Since its more effort for chest to expand it may decrease the opposing pressure
  • Alveolar radius' affect on force, surfactant is needed so they wont be too strong or prone to collapse.

Alveoli Tension

• Liquid air surface tensions are too high force needed for alveoli open, so the air sacs are the same shape as well.
• Tension on the the liquid and gas needs to maintain their shape and is is described by the law of laplace since the spherical the higher the sphere.
• Larger spheres will less pressure, while the smaller ones will face higher pressure, but due to surface area, liquid inside need surfectenant to stop alveoli from bursting
• Law of LaPlace describes how more fluid collapses causes pressure is created, the alveoli radius will inverse depending on the liquid on it. Since, without the surfactant, small alveoli will collapse (atelectasis). With surfactant air helps maintain open air via reduce pressure
• Type II alveolar cells from DPPC reduce surface tension, they repel and attract while the hydro ends repel/attract which stops the tension and maintains
• Surfactant increase lungs compliance, reducing the lungs, which are more prone to ventilation, as well as allows surface tension adjustments for both the expanded and surfactant ventilation.
• Premature infants are at risk due to absence of surfactant, increasing the likely for exchange and and making breathing difficult.
• analogy for air flow is blood vessels/pressure, as well as resistence is related.

Respiration

• Q= deltaP/R is used to describe airflow which is affected by pressure and resistance from resistance in the airways
• During rest at the equilibrium atmospheric pressure is always used, while during inspiration, diaphragms allow for decreased pressure which establishes a pressure gradient needed for air flow.
• Airway resistence acts like cardiovascular resistence dependent on poisuille law, but during rest are affected by
  • Air molecules, length, resistence
• Resistnace to radial is dependent on the radials radius diameter change.
• parallel arrangement smallest airways exhibit the highest resistance vessels. If parallel, total resistence is is dependent on diameter and the air of inspired volume

Overview of the respiratory system, focusing on the conducting zone. Includes the nose, nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles. Functions to bring air into/out of the respiratory zone for gas exchange.