Respiratory Physiology Pulmonary Mechanisms 2024-2025 PDF

CB Respiratory Physiology Pulmonary Mechanisms physiology division 2024-2025  Pulmonary Mechanisms Aim To explain what is meant by lung compliance To explain the factors influencing ventilation of the lungs Objectives By the end of this lecture and associated Spl and p...

CB Respiratory Physiology Pulmonary Mechanisms physiology division 2024-2025  Pulmonary Mechanisms Aim To explain what is meant by lung compliance To explain the factors influencing ventilation of the lungs Objectives By the end of this lecture and associated Spl and practical sessions you should be able to: List and describe the forces acting on the lungs and chest wall Explain how changes in alveolar and intrapleural pressures cause lung inflation and deflation. Describe the importance and cause of surface tension in the lung Describe the conditions that affect lung compliance Describe the effects of surfactant, and its lack, on respiratory function Describe the major site and control of airway resistance Explain how the lungs are affected by diseases such as emphysema and fibrosis when volume decreases molecules get closer together --> pressure increases NEWGIZA UNIVERSITY Mechanics of Breathing Air inflow and outflow between lungs & atmosphere occurs due to PRESSURE GRADIENT created by the following sequence: 1- changes in size of thoracic cage (by expansion & contraction) → 2- Followed by changes in lung size (because its connection to chest wall via pleura) 3- which creates a pressure gradient between the alveoli and the atmospheric air 4- leading to air inflow / outflow  NEWGIZA UNIVERSITY FORCES FOR PULMONARY VENTILATION Air flow in & out of lung occurs when there is a pressure gradient between alveoli & atmosphere Air moves from an area of high pressure to an area of low pressure by DIFFUSION It is determined by the equation F = P / R  Flow is directly proportional to pressure gradient ( P) & inversely proportional to the resistance (R)  NEWGIZA UNIVERSITY Thoracic Pressures relationship 1- Atmospheric pressure (PB) between these 2 causes It is 760 mmHg at sea level. inflow/outflow of air To compare respiratory pressures to it, it is considered to be zero = “zero reference pressure”. 2- Intra-alveolar (Intra-pulmonary) pressure (PA): inside lungs 3- Intra-pleural (Intra- thoracic)between parietal and visceral pressure (Ppl): outside lungs pleura 4- Trans-pulmonary (trans-mural) pressure (PA – Ppl) 5- Transthoracic pressure (PA –PB) difference bet. atm. and  NEWGIZA UNIVERSITY 2- INTRA-ALVEOLAR PRESSURE Definiton: It is the pressure inside alveoli It is influenced by changes in lung volume Boyle’s Law: It describes the relationship between Pressure & volume It states: If volume of container  → pressure exerted by gas  → & vice versa Normal values of Intraalveolar NEWGIZA UNIVERSITY Pressure (Palv or PA): period in- - At rest: With glottis wide open & no air between flowing in or out = zero mmHg (=PB) breaths ---> equal to 760 same as atm. At MID inspiration: Chest Expansion: pressure drops to - 1 mmHg less than atm. by 1 --> 759 → creates pressure gradient between alveoli & atmosphere (transthoracic pressure) → air flows into alveoli At end of inspiration: 0 mmHg (=PB) At MID expiration : Recoil of Chest: pressure rises to + 1 mmHg → creates pressure gradient between alveoli & atmosphere → air flows out At end of expiration: 0 mmHg (=PB)  pneumothorax--> hole in wall of pleura--> suction --> air moves into plueral cavity 3. Intrapleural Pressure (Pip or PPL) NEWGIZA UNIVERSITY Definiton: pressure inside the narrow space between the visceral and parietal layers of pleura. Under normal conditions, Pip is always negative (sub-atmospheric) Cause of Negativity: Continuous tendency of lungs and chest wall to recoil In opposite directions [lungs tends to recoil inwards & chest wall tends to expand outwards] creates a vacuum in the sealed pleural space suction In turn, this negative Pip is responsible for preventing the lungs from collapsing and the chest wall from springing out Elastic properties of lungs and chest NEWGIZA UNIVERSITY wall (CW) Lungs and chest wall are elastic structures, each having a relaxation volume where it is neither compressed nor stretched - Relaxation volume of lung = 1 L - Relaxation volume of CW = 5 L At birth, lungs expand & are stretched and chest wall is compressed (like a spring) At end of normal expiration (FRC) when respiratory muscles are relaxed, ❖ the outward elastic recoil of chest wall BALANCES the inward elastic recoil of lungs ❖ Volume of LUNGS + CW = 2.3 L Thus, Lungs are stretched & tend to recoil CW is compressed & tends to expand If chest is punctured→ negative IPP is lost: lungs collapse & chest wall expands (snap back)  NEWGIZA UNIVERSITY Values of Intrapleural Pressure With normal breathing: At the END of normal expiration: Functional Residual Capacity  Pip is – 3 mmHg (– 5 cmH2O ) At the END of normal inspiration: Inspiratory Capacity Expansion of chest wall makes IPP more negative  Pip reaches – 6 mmHg (– 7.5 cmH2O ) With forced breathing: During forced inspiration with glottis closed: Mueller’s Experiment: Inspiratory Reserve Volume  Pip may reach -30 to -40 mmHg During forced expiration with glottis closed: Valsalva’s Experiment: Expiratory Reserve Volume  Pip may reach +50 mmHg  NEWGIZA UNIVERSITY Measurement of IPP: by intra-esophageal balloon  NEWGIZA UNIVERSITY Functions of Intrapleural Pressure 1- Keeps alveoli open which 2- Helps venous return helps lung expansion during inspiration  NEWGIZA UNIVERSITY 4- Transpulmonary (Transmural) Pressure Definiton: It is pressure difference between intra- alveolar & intrapleural pressures, i.e., difference between pressure inside & outside the lungs) It is the distending pressure of the lungs How? During inspiration, chest wall expansion makes IPP more negative, thus transpulmonary pressure increases leading to lung distension It opposes recoil tendency of lungs Transmural Pr. (PTM) = (Palv - Pip) At end of expiration: = 0 – (– 3) = 3 mmHg (or 5 cm H2O) At end of inspiration: = 0 – (– 6) = 6 mmHg (or 7.5 cm H2O) ▪ The DISTENDING PRESSURE P = 3 mmHg OR 2.5 cmH2O  NEWGIZA UNIVERSITY PULMONARY PRESSURES DURING RESPIRATORY CYCLE  PNEUMOTHORAX NEWGIZA UNIVERSITY Definiton: It is the presence of air in the pleural sac Types: 1. Open = external pneumothorax: - Air from outside fills intrapleural opens from parietal space (E.g. Stab or bullet wounds ) pleura 2. Closed = internal pneumothorax: - Air from lung enters interpleural space Due to rupture of an alveolus (E.g. severe cough or TB) opens visceral pleura Effects of Pneumothorax: IPP negativity lost: 1- Lung collapses & chest wall expands 2. Mediastinum & trachea shift towards the healthy lung  NEWGIZA UNIVERSITY X-Ray of extensive right side pneumothorax normal lung collapsed lung  NEWGIZA UNIVERSITY Recoil tendency of lungs & chest wall Recoil tendency of lungs and chest wall: is the ability to return (snap back) to their original relaxation volume after removal of the external force Causes of recoil tendency of chest wall: Elastic properties of chest wall (muscles, tendons & ligaments) Causes of recoil tendency of lungs: 1/3: Elastic properties of lungs (elastin & collagen in lung parenchyma) 2/3: Surface tension of fluid lining alveoli Water molecules facing alveolar air (at air-water interface) are attracted to each other (hydrogen bonds), which try to collapse alveoli [Fortunately, the type II epithelial cells of the alveoli continually secrete a molecule called surfactant that solves this problem] oily layer --> lines alveoli above fluid  NEWGIZA UNIVERSITY Surfactant & Surface Tension Definition: Surfactant is a surface-active agent which spreads over the fluid lining the alveoli reducing its surface tension. How? lipid layer separating fluid from air → transforms air- water interface into: air-lipid -water interface Secreted: from Type II alveolar epithelial cells Structure: mixture of secrete surfactant 1-phospholipids:DPPC dipalmitoyl-lecithin 2- apoproteins & 3- calcium (spread lipid layer) dipalmitoyl-lecithin+ apoprotiens+3-calcium Function: Reduces Surface Tension & collapsing pressure: 1- facilitate lung expansion (& reduce work of breathing needed) during inspiration 2- prevent alveolar collapse (esp during expiration when alveoli become smaller (HOW?) 3- prevent pulmonary edema  NEWGIZA UNIVERSITY Law of Laplace: Explains Surface tension of a sphere (alveolus) (P = 2T /r ) P = collapsing pressure T = surface Tension r = radius According to Laplace Law: If surface tension was equal in all alveoli, smaller alveoli will pressure is too high have higher collapsing pressure, and may causes collapse at the end of expiration rupturing of alveoli However, surfactant prevents smaller alveoli from collapsing during expiration. HOW? as an alveolus becomes smaller during expiration, surfactant molecules move closer together, reducing surface tension still further, and thus, decreasing the collapsing pressure.  NEWGIZA UNIVERSITY Infant respiratory distress syndrome (IRDS): Occurs in premature infants because of the lack of surfactant (24-35 wks) The infant exhibits difficulty inflating the lungs, atelectasis (lung collapse) when surfactant and hypoxia inc lecithin inc Generally, a lecithin : sphyngomyelin ratio greater than 2:1 in amniotic fluid reflects mature levels of surfactant Thus in IRDS, the ratio is < 2:1 ▪ Gas diffusion decrease ▪ V/Q drop ▪ Compliance decreases and work of breathing increases  Airway Resistance [Raw] NEWGIZA UNIVERSITY ❖ Air flow: is directly proportional to pressure gradient and inversely proportional to airway resistance [Raw] F = P/R ❖ Airway resistance : Definition: the opposition to airflow caused by friction with the airways It is a measure of: change in pressure required for a unit change in flow (R= P/F) It is determined by : A- Type of Air flow : laminar or turbulent B- Radius of airways  NEWGIZA UNIVERSITY A- Types of Air Flow A. Laminar Flow: In small airways, air flows with low velocity, low resistance, streamline flow in parallel lines less friction B. Turbulent Flow: In large airways, air flows with high velocity, high resistance, turbulent flow. Airway Resistance increases when air flow is turbulent: e.g in bronchoconstriction (asthma) or in rapid breathing (exercise). Turbulence can be heard clinically by noisy breath sounds or wheezing V.V.V.I NEWGIZA UNIVERSITY B- Radius of airway is a primary determinant for Airway Resistance: (Raw) can be calculated by Ohm’s Law & Poiseuille’s Law (same laws applied for blood flow) Flow (V) = P / R radius^4  NEWGIZA UNIVERSITY Primary determinant of Raw : Radius of Airways (Total cross sectional Area) Airway resistance is inversely related to Radius raised to power of 4 Thus, we might expect the small airways (terminal bronchioles) to offer the highest resistance to air flow. However, they do not because of their: 1) huge number& large cross-sectional area & 2) parallel arrangement (laminar flow)→ combined resistances is low because they add as reciprocals  NEWGIZA UNIVERSITY Primary determinant of Raw : (cont-) Radius of Airways (Total cross sectional Area) ❖ 40 – 50 % of airway resistance is located in upper respiratory tract (nose, pharynx & larynx) ❖ In the tracheobronchial tree (below the larynx): the highest resistance (80%) lies in Medium-sized bronchi (4 – 8 th generation) due to their: 1) smallest number & cross sectional area and 2) turbulent flow. ❖ However, in disease states (asthma&COPD) terminal bronchioles are the major site of airway resistance, because they are easily occluded (small diameter) Factors affecting Airway Diameter NEWGIZA UNIVERSITY A- Physical Factors: Due to lack of cartilaginous support, the Small Airways are kept distended by: 1. Negative Intrapleural pressure is the major factor keeping small airways, just as it keeps alveoli, open. 2. Radial traction: elastic recoil in the alveoli surrounding airways, help to keeping airways open by pulling them outwards in all directions With INSPIRATION: IPP becomes more negative, → increases recoil tendency of alveoli → distending the alveoli → increasing the radial traction of surrounding alveoli on airways → distending small airways and decreasing airway resistance With EXPIRATION, the opposite occurs  NEWGIZA UNIVERSITY B- Nervous & Chemical Factors: 1- Sympathetic 2 Adrenergic stimulation: cause bronchodilatation 2- Parasympathetic cholinergic (Vagal) stimulation: cause bronchoconstriction and increase mucous secretion. Thus, 2 agonists (eg. Salbutamol) and anticholinergics (eg. Tiotropium, ipratropium) can dilate airways and are constituents of inhalers for asthma attacks. 3- Chemical factors that constict airways 1- Histamine: allergy (bronchial asthma) 2- Leukotrienes: inflammation (bronchitis) 3- Environmental factors, eg. Plant pollens 4- Decrease CO2 in airways (CO2 in airways is a bronchodilator) Causes of ↑airway resistance and NEWGIZA UNIVERSITY difficult expiration in obstructive lung diseases 1- Emphysema In a person with Emphysema, forced expiration may cause the airways to collapse How? In emphysema, loss of elastic recoil → ↓ radial traction → ↓ diameter of small airways → ↑airway resistance → require forced expiration to exhale → leading to premature closure of airways → air trapping  NEWGIZA UNIVERSITY 2- Bronchial Asthma Inflammatory disease characterized by attacks of broncho-constriction due to: 1- hyperresponsiveness of bronchial smooth muscles to allergic stimuli → brochospasm 2- thickening and edema of bronchial walls 3- increased production of mucous ↑airway resistance→ ↓dynamic compliance → ↑ work of breathing Airway resistance is increased especially during forced expiration due to premature closure of airway → difficult to exhale quickly FEV1/FVC markedly reduced Treated by bronchodilator inhaler (β2 agonist)  NEWGIZA UNIVERSITY Clinical Assessment of Airway Resistance Spirometry for measuring: FEV1/FVC Peak flow meter for measuring: Peak expiratory flow rate (PEFR), is the maximum speed of air flow achieved during a forced expiration starting from the level of maximal lung inflation Challenge Tests (Bronchoprovocation): These tests are done by intentionally exposing the airways to a trigger and then measuring how sensitive (“hyperresponsive”) the airways are by spirometry. Airway sensitivity is a sign of asthma. The most common types of challenges or stimuli are: direct (methacholine) and indirect (exercise) stimuli.  Compliance and Work of Breathing  NEWGIZA UNIVERSITY PULMONARY COMPLIANCE (C) Compliance is a measure of distensibility (expandability = stretchability) of lungs and chest wall depending on their elasticity Compliance is the ratio between the change in volume per unit change in transmural pressure (= PTM) V change in vol C= P Compliance (C) is RECIPROCAL to / opposed by : Elastance (E) Elastance : (Elastic recoil = stiffness = resistance to expansion) : depends on the amount of elastic tissue & surface tension Elastance = 1/ compliance E = 1/C [Compare trying to inflate baloon / paper bag]  NEWGIZA UNIVERSITY Calculation of Compliance Compliance (C) = ∆V/∆P = tidal volume / transpulmonary (IPP) pressure = 500 ml / 2.5 cmH2O (7.5- 5)= 2.5 = 200 ml /cmH2O = 0.2 L / cmH2O Compliance of lung alone = 200 ml (0.2 L) Compliance of chest wall alone = 200 ml (0.2L) Compliance of lungs & chest wall together = 100 ml (0.1L) (baloon inside balloon) Total elastance (resistance) = lung R + chest wall R 1/C = 1/C lungs + 1/C chest wall = 1/200 + 1/200 = 2/200 = 1/100 = 0.1 L  NEWGIZA UNIVERSITY Procedure of measuring Compliance Subject performs maximal inspiration then exhales slowly We measure pressure-volume relationship, and the compliance that is measured depends on how the test is performed. If the lung is deflated in very small steps, and the lung volume allowed to stabilize after each step, with no airflow, the recorded graph gives: STATIC LUNG COMPILANCE. If measurements are made during actual breathing and airflow, it gives: DYNAMIC COMPILANCE of lungs and chest wall together  NEWGIZA UNIVERSITY Static Lung Compliance Curve volume a3la a7san Notice that the curve is S-shaped: Highest compliance is at lung volume around FRC and lowest compliance is at Low & high lung volumes Notice that the curve recorded during inflation is different from that recorded during deflation. This shape is called hysteresis Notice that there is a larger volume change with every pressure change during deflation i.e. slope is steeper, → compliance is higher during expiation Why? During expiration, surfactant become more concentrated thus ↓ surface tension and ↑compliance Hysteresis is thus caused by the additional pressure required during inflation to overcome surface tension forces  NEWGIZA UNIVERSITY Surface tension is Main Cause of Hysteresis #inspiration and expiration complicate are not the same #compliance of deflation is better than inflation ❖Significance of surface tension can be studied by comparing the lung compliance when filled with air to that filled with saline ❖Experiment: An excised cat lung is inflated by saline instead of air (i.e., no air-fluid interface → no surface tension) → the lung becomes much more compliant (maximally inflated by much less pressure ) and hysteresis is almost abolished mas2ol 3an 2/3 men el recoil This shows that surface tension is a major force that resists lung inflation and that it is also the main cause of the observed hysteresis  CONDITIONS AFFECTING STATIC LUNG COMPLIANCE N E W G I Z A U N I V E R S I T Y 1- Elastic tissue(1/3) 2- Surface tension(2/3) fibrosis(restricted disease)--> compliance a2al #compliance a7san--> less elastic tissue Abnormally LOW Compliance: Restrictive lung diseases: - lung congestion or fibrosis: (lungs are stiffer & more difficult to inflate) Surfactant deficiency : RDS or pulmonary edema (surface tension increase and lungs are difficult to inflate) Clinical Significance: Stiff lungs → difficulty to get air into lungs Abnormally HIGH Compliance: Old age : lungs lose their elasticity Emphysema: lungs lose their elasticity → tendency of lungs to recoil decrease < tendency of the chest wall to expand → Lung compliance is increased and the patient’s chest becomes barrel-shaped, reflecting this higher volume Clinical significance: Poor elastic recoil → difficulty to get air out of lungs (air trapping) NEWGIZA UNIVERSITY  NEWGIZA UNIVERSITY CONDITIONS AFFECTING CHEST WALL COMPLIANCE (Elastic properties of thorax including muscles, tendons&connective tissue) Decreased in the following abnormalities: Bone deformities (kyphosis or scoliosis) Neuromuscular disorders Morbid Obesity Pleural effusion Severe burns (tightening skin) Crush injuries Increased in atheletes  Dynamic Lung Compliance NEWGIZA UNIVERSITY It is the lung compliance measured during actual air flow, i.e. during continuous non-interrupted breathing cycle (tidal volume breathing) Thus, dynamic compliance is affected by Airway frictional resistance Dynamic compliance is decreased by ↑↑frictional resistance to airflow: 1- Bronchoconstriction → ↓radius of airways, e.g. bronchial asthma, cholinergic stimulation. 2- Rapid breathing (rapid air flow) → ↑turbulence. e.g. During heavy exercise #know if disease increases work of breathing and which work of breathing Work of Breathing: NEWGIZA UNIVERSITY The work / effort done / energy expended by the respiratory muscles for P-V changes Compliance/Elastic Tissue resistance Airway resistance Work (65%) Work (7%) Work (28%) Work required to expand Work required to Work required to the lungs against its overcome the resistance overcome airway elastic forces of non elastic viscous resistance during tissue of chest wall movement of air into the lungs Increased in ↓ Lung Increased in ↓chest wall Increased in ↑airway Compliance, e.g. Compliance, e.g. resistance e.g. a. Lung fibrosis a. Kyphoscoliosis a. Bronchial asthma b. lung edema b. muscle disease b. Exercise c. ↓↓surfactant c. Cholinergic stimulation #just reading NEWGIZA UNIVERSITY How to illustrate Work of breathing on dynamic P-V curve ? Work = Force x Distance = Pressure x Volume 1- Compliance (elastic) work (65%): 2- Non-Elastic work (35%): Tissue resistance work (7%): Airway resistance work (28%):  NEWGIZA UNIVERSITY Sum up NEWGIZA UNIVERSITY Further reading Human Physiology Vander, Sherman & Luciano 9th Ed pp 481-489 Human Physiology Pocock & Richards 3rd Ed pp 331-332 Medical Sciences. Naish, Revest, Syndercombe-Court Chpt. 13. Review of Medical Physiology. Ganong F, 23rd Ed sec VII Textbook of Medical Physiology, Guyton AC and Hall JE, 12th Ed unit VII Core conditions Asthma Chronic Obstructive Pulmonary Disease Interstitial lung disease Pneumothorax Respiratory Failure