Respiratory System: Conducting Zone

Respiratory System Overview

• The respiratory system facilitates connection of the lungs to the external atmosphere via a series of airways.
• It is divided into the conducting zone and respiratory zone.
• The conducting and respiratory zones differ in structure and function.

Conducting Zone

• Encompasses the nose, nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles.
• Structures warm, humidify and filter air.
• Critical gas exchange region.
• Progressively bifurcating airways are classified by their generation number.
• The trachea represents the zeroth generation as the main conducting airway.
• The trachea divides into the right and left mainstem bronchi (first generation), then continues to divide through 23 generations, culminating in the 23rd generation airways.
• Cartilage is present in the walls of the 0th-10th generations which keeps airways open.
• Cartilage is absent starting with the 11th generation and patency depends on a favorable transmural pressure.
• Mucus-secreting and ciliated cells line conducting airways in order to remove inhaled particles.
• Large particles are filtered by the nose.
• Small particles are captured and swept upwards by cilia.
• Autonomic nervous system regulates smooth muscle in conducting airway walls.
• Sympathetic adrenergic neurons activate β₂ receptors, resulting in bronchial smooth muscle relaxation and airway dilation and are also influenced by epinephrine and β₂-adrenergic agonists.
• Parasympathetic cholinergic neurons activate muscarinic receptors, leading to airway contraction.
• Airway diameter changes affect airway resistance and airflow.
• β₂-adrenergic agonists (epinephrine, isoproterenol, albuterol) are used to treat asthma by dilating airways.

Respiratory Zone

• Includes structures lined with alveoli that are involved in gas exchange; respiratory bronchioles, alveolar ducts and alveolar sacs.
• Respiratory bronchioles serve as transitional structures because they have cilia and smooth muscle and also participate in gas exchange due to alveoli budding off their walls.
• Alveolar ducts are completely lined with alveoli, contain no cilia and very little smooth muscle.
• Alveolar sacs are terminal structures.
• Alveoli are pouch like structures found in the respiratory bronchioles, alveolar ducts, and alveolar sacs.
• Each human lung contains around 300 million alveoli with ~200 μm diameter.
• Thin alveolar walls containing elastic fibers and epithelial cells (type I and type II pneumocytes) and large surface area enable efficient oxygen and carbon dioxide diffusion between alveolar gas and pulmonary capillary blood
• Type II pneumocytes synthesize pulmonary surfactant which reduces surface tension and have regenerative capacity for type I and type II pneumocytes.
• Alveolar macrophages phagocytize and clear debris.
• Macrophages migrate to the bronchioles, cilia transport debris to the pharynx where it is either swallowed or expectorated.

Lung Volumes and Capacities

• Static lung volumes are measured using spirometry.
• The subject breathes into and out of a spirometer, and the displaced volume is recorded.
• Tidal volume (Vt) is the normal volume (~500 mL) inspired and expired during quiet breathing, including air that fills both alveoli and conducting airways.
• Inspiratory reserve volume: additional volume (~3000 mL) possible above tidal volume is called the inspiratory reserve volume.
• Expiratory reserve volume: additional volume (~1200 mL) possible below tidal volume.
• Residual volume (RV) is gas volume (~1200 mL) remaining in the lungs after maximal forced expiration.
• RV cannot be measured via spirometry.
• Inspiratory capacity (IC) is the sum of tidal volume and inspiratory reserve volume (~3500 mL).
• Functional residual capacity (FRC) is the sum of expiratory reserve volume and residual volume (~2400 mL) and signifies the volume remaining after normal tidal volume expiration
• FRC can be considered the equilibrium volume of the lungs
• Vital capacity (VC) is the sum of inspiratory capacity and expiratory reserve volume (~4700 mL).
• It correlates with body size, gender, physical conditioning and decreases with age.
• Total lung capacity (TLC) includes all lung volumes, calculated as the sum of vital capacity and residual volume (~5900 mL).
• Because RV cannot be measured by spirometry, lung capacities that include the RV (FRC and TLC) cannot be measured via spirometry.
• FRC is the lung capacities not measurable by spirometry of greatest interest since it is the resting volume.
• Helium dilution and body plethysmography are ways to measure FRC.

Helium Dilution Method

• The subject breathes a known amount of helium, which has been added to the spirometer
• After a few breaths the helium concentration in the lungs equalizes to that of the spirometer since helium is insoluble in blood.
• The amount of helium added to the spirometer is then used to "back calculate" the lung volume that the helium was distributed in.
• The lung volume being calculated is the FRC if the measurement is made following a normal tidal volume expiration.

Body Plethysmograph

• The body plethysmograph employs a variant of Boyle's law (P x V = constant, at constant temperature and number of gas moles).
• Upon expiring a normal tidal volume, the subject attempts to breathe against a closed mouthpiece.
• Lung volume increases and pressure decreases as the subject attempts to inspire.
• Volume in the box decreases alongside pressure increase, because the subject is sitting in a large airtight box called a plethysmograph.
• The increase in pressure in the box measured is then used to calculate perspiratory volume in the lungs, and thereby the FRC.

Dead Space

• Dead space refers to the volume of airways/lungs where no gas exchange occurs.
• It includes both anatomical and physiological dead space.
• Anatomic dead space is the volume of the conducting airways (nose, mouth, trachea, bronchi, bronchioles; does not include respiratory bronchioles and alveoli), which is approximately 150 mL.
• A tidal volume of 500 mL will have 150 mL of air filling the conducting airways and 350mL filling the alveoli
• At the end of expiration the conducting airways are filled with alveolar air.
• During the next inspiration that alveolar air enters the alveoli first, followed by fresh tidal air (350 mL inspiratory volume) and the remainder stays in the conducting airways to later be expired.
• Physiologic dead space is the total lung volume not participating in gas exchange.
• Physiologic dead space = Anatomic dead space + functional dead space in the alveoli.
• Functional dead space are ventilated alveoli that do not participate in gas exchange mostly caused by ventilation/perfusion defects.
• In normal persons, physiologic dead space is approximately equal to anatomic dead space.
• When a ventilation/perfusion defect is present, the physiologic dead space can increase above the anatomic dead space.
• Partial pressure of CO₂ (Pco₂) of mixed expired air (PeCO₂) and the following assumptions are used to estimate the volume of the physiologic dead space:
  • It has to be assumed that all CO₂ in expired air comes from CO₂ exchange in ventilated/perfused alveoli
  • There is very little CO₂ in inspired air
  • Functionless alveoli/airways neither exchange nor contribute CO₂
• The alveolar Pco2 (PaCO2) will equal PeCO2 if the physiologic dead space is zero.
• PeCO2 will be less than PaCO2 by a dilution factor if at least one physiologic dead space is present.
• The volume of physiologic dead space can be measured by comparing PeCO2 and PaCO2.
• Alveolar air equilibrates with pulmonary capillary blood; therefore, alveolar air cannot be directly sampled and the Pco2 of Systemic arterial blood will be equal to the Pco2 of alveolar air.

Alveolar Ventilation Equation

• Alveolar ventilation (Va) is inversely related to the partial pressure of carbon dioxide in the alveoli (PaCO2).
• Constant K is defined as 863 mm Hg under BTPS (body temperature of 310 K, ambient pressure of 760 mm Hg, gases saturated with water vapor) conditions.
• When both Va and CO2 production(V̇co2) are measured in same units (mL/min), the constant is used.
• Paco2 can using a rearranged form of the alveolar ventiliation equation with aerobic CO2 production, and alveolar ventiliation.
• The rate of CO2 clearance from the bloodstreem depends on this inverse relationship.
• In the pulmonary capillary, CO2 always seeks balance with alveolar gas.
• Arterial PCO2 (Pa CO2​) equilibrates with alveolar arterial P CO2.
• The alveolar ventilation equation shows that by introducing CO2- free air each breath, CO2 is able to diffuse into the space.
• Enhancing this removal process is achieved vis increased ventilation, lowering both alveolar and arterial P CO2.

Alveolar Gas Equation

• Describes dependence of alveolar/arterial PCO₂ on alveolar ventilation.
• Predicts alveolar PO₂ based on alveolar PCO₂.
• Correction factor = small value usually ignored.
• During the steady state, the respiratory quotient equals the respiratory exchange rate.
• When alveolar ventilation is halved, less CO₂ removed from the alveoli means (PCO₂) will double.
• Halving alveolar ventilation will decrease (PO₂), meaning less O₂ is getting into the alveoli.
• Because the normal value for the respiratory exchange ratio is 0.8, when alveolar ventilation is halved, the decrease in (PO₂) will be slightly greater than the increase in (PCO₂).
• To summarize, V halved = (PCO₂) doubled (PO₂) is slightly more than halved.
• If the the respiratory quotient and respiratory exchange ratio are 0.6 rather than 0.8, then ( PO_2 ) would decrease relative to (PCO_2)

Forced Expiratory Volumes

• 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
• The volume of air that can be forcibly expired in the first second is called FEV1
• Likewise, the cumulative volume expired in 2 seconds is called FEV2 and the cumulative volume expired in 3 seconds is called FEV3.
• Normally, the entire vital capacity can be forcibly expired in 3 seconds, so there is no need for 'FEV4.'

Mechanics of Breathing

• Diaphragm is the most important muscle
• Diaphragm contracts, the abdominal contents pushed downwards, the ribs lifted upward, the intrathoracic volume is increased, the intrathoracic pressure is lowered, and flow of air into the lungs is initiated.
• Increase breathing frequency/tidal volume and external intercostal/accessory muscles may be used for vigorous inspiration.

Muscles of Expiration

• Expiration normally is a passive process
• Reverse pressure gradient between the lungs and the atmosphere is created to drive air.
• During exercise/diseases which increase aiway resistance, the abdominal muscles compress while the diaphragm lift up/the internal intercostal muscles pull downward.

Compliance

• System compliance described by distensibility.
• Lung/chest wall compliance of primary interest measured by volume changes by pressure change relationship.
• Compliance of the lungs/chest wall is inversely related to their elastic qualities/elastance.
• Thick rubber band = more elastic tissure = hard to stretch and is less distensible/compliant
• The greater amount of elastic tissue equates a greater tendency to 'snap back/elastic recoil force decreasing compliance.
• Lung compliance requires simultaneous measurement of lung pressure and volume. Transmural pressure = pressure across a pressure. Transpulmonary pressure = intrapleural pressure and intra-alveolar pressure difference.

Compliance of the Lungs

• Isolated lung pressure volume relationship demonstrates where the lung is excised inside a jar that mimics intrapleural pressue
• Vacuum pressue stimulates intrapleural change altering the outlide volume and measuring using a spirometer
• Isolated lung inflated with negatie outside pressue and deflated by reducing that negatie outside pressure
• Sequnce = pressure-volume loop/pressure volume loop's slopes are compliance slopes.
• Air/airways during the experiment are equally exposed to conditions.
• Lung volume increases if the external pressure is reduced.
• Decreased compliance on the pressure-volume loop is caused by the lungs encounter increased resistnace from the alveoli becoming more full/stiffer.
• Reaching full expansiion shifts the curve due to compliance decreasing caused by volume reduction and external pressure being less negative.

Hysteresis

• Hysteresis = inspiration/expiration differences in pressure volume slopes related to compliance variety between inspiration and expiration.
• During the same external pressure, lung volume and complience = greater expriation during both.
• Inpsiration limb is more complex and has reduced compliance at top expansion.
• Lung complience curve differences are becasue of surface tension and amount of elastic tissue influenced curves
• The attractive forces between liquid molecuels are greated due to surface tensions
• Inpsiration's liquid molecuels are close/intermolecular forces are strongest/more forces must be overcomed.
• Phosphilipid creates surface tension (surfactant) and increasing lung compliance helps the process.
• Lung's surface acre and surfactant spread less effectively in its initial expansion, decreasing compliance and flattening curve due to low surfactant density/high surface tension.
• Increase surfactant desnity, slope/enhnace the compliance, and decrease surface tension is surfactant density due as expansion continues.
• Lungs are easier to overcome during expiration because there is high lung volume with diminished intermolecular forces.
• The initial part of the expriation is flat due lowered suractan density. Surface tension's effects are eliminated vis saline, inspiration/expiation can achieve uniform results.
• Pneumothorax demonstrates chest wall.
• Normally, the intrapleural space must have a negative pressure (less than atmosphere), but with pneumotherax that no lnger exisits and lungs tend to collapse, and chest walls spring out.
• The 'spring' of the chest wall is contained by by negative intrapleural pressure, so by elimiatiing this the chest wall will spring up.

Pressure-Volume Curves for the Lungs, Chest Wall, and Combined Lung

• Deriving these pressure vlume vurves for: for the chest wall, combined lung and chest wall = deducting the lung curve and combined syste's.
• Hysteresis gets eliminated from the lung while trained subject used volume-controlled procedure using their breathing while spriometer closes and relaxaing their respiratiory muscles/the measuremnts of all the pressure.
• Airway pressures = static volumes for both. Function Residual Capacity (FRC) = airwy preessure is zero.
• If Volume < FRC, airway pressures = negative and lung volumes lowered/decraeased pessurre, but conversely > FRC, pressures become positive and volume expansions / increased pressure.
• The curves are described by compliance, chest and lung are about equally compiant
• Compliance of combined system = < than either.

Functional Residual Capacity

• Using FRC you can graph at compared voulume less than/greater than FRC for interrpetatations: airwy pressure = atmospheric pressure that matches both want to either collapse ro expand.
• Volume becomes < system FRC if forced expiration used to reduce collapsed lugs/increase chest.
• Volumes is also > from lung volumes being more elevated during spriometier and lung collapes is smaller vs chest expansion. Thus smaller collapsing force from the lungs smaller results pressure being negative.
• Diseases alter lung relationship and affect how volume related to chest/wall.

Diseases of Lung Compliance

• Emphysema
• COPD losses elastic, raising volume, and lowering colapsisng forces while new interxection created to meet balanced opposing torces.
• Fubrosis
• Restritictive, leads to lowers and elevated collapsing forces and new intersecitons.

Aveloli

• There is a challenge from keeping them open due to surface tension effects; they exhibit molecules that have cohesion when they are together.
• Alveoli will have smaller shap becasue attraction is greater vs gas molecuwle inside them, but this tension to tend will pull the liquid serfeac into smaller shape. The surface tension is sphere shaped and sphere law of laplace is described mathmatically by
• The pressure causing an aveouli is affected by tension with fluids proportionally. Inverse relationshi mean lagrger volume and smaller alveoli get higher collapsing pressures.
• With surfactant smaller elvolie become prone to cellpase, which would affect exchange of small areas.

Surfactant

• Surfactant is a mixture of phospholipds and reduces surface tension, thiss allowing smaller aveloi to have the answer for the collapse
• When these is an present with no surfactant from Alveoli, atelectasis occurs, this can lead non exchange of gas and lead to newborn issues.
• This tension from amphiphatic traits, makes these molecuels hydrophobic will cause collapse. DPPC repels repels the hydrophillic
• Surfactant adds pressure and decrases surfcae tension and compliance, aiding expension to inhlaation
• During breathing its used to keep even alveaolar sizes.
• Without surfactants alveolar inflation can't happen and uniform expansion can't be achieved.

Neonatal Respiratory Distress Syndrome

• The bsence of surfactant is a majpr concern when theya re not getting enough production of the fetus. Small aveolo will collapse due to tension from the low exchange of hypoxic air.
• Flow, Pressure, Resistance : analgous of cardio systme and dynamics are goverened as follows

Air Flow

• (Q) is directly proportional to the pressure difference (ΔP) between the mouth or nose and the alveoli and it is inversely proportional to the resistance of the airways (R)
• The pressure difference is the driving force—without a pressure difference, air flow will not occur
• Alveolar pressure equals atmospheric pressure at rest and during inspiration, the diaphragm contracts to increase lung volume which drives air flow to the lungs.

Airway Resistnace

• Airway resistance (Q = ΔP/R) is inversely proportional with Poiseuille law helps explain its relationship
• Airway r depends on its dependency . This can increase and decease based on radius.
• Resistance levels get higher for smallest areway. Vessels are parrel to resist collective amount can reach a superion number if that get blood.

Changes in Airway Resistance

• Relationship = resistance/airway diameter in 4 power relationship. Changes in airway diameter change resistance/airflow. In
• Autonomic nervous system fibres innervate smooth msucle conducting lead to constircuting/dictlation.
• Paralsympthetic stimulates can reduce/constrict airflow by blocking or using various agonists
• Sympathetic b2 stimulate can relax msucle and increase diameter through different agonists
• Alveoili that over inflate can result reduced resitance from high lung area that is partially counteracting the airway.
• Histamine, viscositiy, other can affect all the dynamics.
• Viscoistiy levels depend on the poisuille relationship for the impact , increased level due to deep sea/decreae with low level gas = lead to resistance decras.

Compensation

• Adaptability of alveolar resistance is used to blood in the pulpinalry and cause cause gas exchange not allowe
• Results values are inspired can cause constricting and cause air flows for regions can occur.

Breathing Cycle

• Breathing cycles consists rest, inspiration, expiration phases from lung. graphcial elements shown with lungs, intrapleual and alevloar pressure.
• Rest = equilibriem state that no moving is involved. pressure are refereed too are at atmpshere when we do not involve breathing
• Intraplueral state is negative.
• The lung tends to collapse, the transmurral pressure keeps structire together
• Inspiraton's volume rises and pressure is decareased because law, drives the gradient. continues untill there is equalization during the end cycle and airflow eases
• Pressure because more evelated with pulls frocefully againat lung volume

Expiration

• Expriation = pasive process.

Positive Alveolar Pressure

• Forcefully pushing against the volume. Volume that is epxpired = vt. all returns to rest state for cycke
• Deliberaltey and foree breathed during process . muscel expiraotry helps keep these alwea positive

Normal Lungs

• All volumes and lung/arteral pressures much eleavte than epxpated, transumsal pressure gets positive for the volume and gradents are forced fully. Persons with emphysema that have high comliance and raise and reverse, with the pursed lip helps keeps preessure and preevnt collapse.