RS Physio 3 Lect Combined (PDF) - Respiratory System Lecture Notes

THE RESPIRATORY SYSTEM Lecture I I. OVERVIEW of FUNCTIONS II. INTRODUCTION to VENTILATION Bernard Leung [email protected] HSC1007, AY2023 Meeting ID: 958 3144 3025 Passcode: 728073  Learning O...

THE RESPIRATORY SYSTEM Lecture I I. OVERVIEW of FUNCTIONS II. INTRODUCTION to VENTILATION Bernard Leung [email protected] HSC1007, AY2023 Meeting ID: 958 3144 3025 Passcode: 728073  Learning Objectives Overview of the various components and functions in the respiratory system. How a pleural pressure is generated? How changes in alveolar pressure move air in & out of the lungs? A negative alveolar pressure is created during inspiration for airflow into the lungs. A positive alveolar pressure is created during expiration for airflow out of the lungs.  Respiration Cellular respiration is the intracellular metabolic reactions that use O2 and produce CO2 during ATP production. External respiration is the transfer of O2 and CO2 between the external environment and tissue cells. Respiratory and circulatory system function together to accomplish external respiration. Ch13, Introduction to Human Physiology, 9th Edition, L Sherwood  Functions of the respiratory system Metabolism & acid-base regulation Provides Oxygen to tissues for metabolism Removes Carbon Dioxide & regulates pH (H+ ions) (by-products of cellular metabolism) Clinical Requirements Ventilation in anaesthetised & intensive care patients, ie (paralysed by drugs etc.) Treatment of respiratory diseases eg. asthma, pneumonia, Covid-19. ‘Smokers’ lungs – Emphysema, destruction of alveolar surfaces, inadequate surface area for O2 & CO2 exchange. What else does the respiratory system do? Endocrine functions: activates hormone - Angiotensin II é Fluid retention, fluid intake é Blood pressure & volume Immunological functions: clearance of irritants/particles and potential pathogens (viruses & bacteria) Voice production by larynx (‘voice box’) Route for water loss and heat elimination Schematic diagram showing the circuitry of the cardiovascular system The arrows show the direction of blood flow, (%) of cardiac output Anatomical relationship with heart & major arteries Aorta: blood to rest of body Pulmonary (systemic circulation) trunk with L&R arteries: blood to lungs (pulmonary circulation) R L  Respiratory Airways The respiratory airways conduct air between the atmosphere and the alveoli. – nasal passages ANATOMY – pharynx Gross – Larynx Microscopic Lower Respiratory System FUNCTIONS – trachea Ventilation – right and left bronchi – bronchioles Gas exchange – alveoli Protective mechanisms For Upper/Lower Respiratory structures, please refer to Prof Karthik’s Anatomy notes* * Fundamentals of Anatomy & Physiology, 10th Edition, Martini, Pearson.  Lungs – Ventilation vs Perfusion Resin cast of the human airway tree shows the branching beginning at the trachea. Note the added pulmonary arteries (blue, deoxygenated blood) and veins (red, oxygenated blood) displayed in the left lung.  Functional relationship between Respiratory system & Circulatory system 2. Deoxgenated blood leaves heart via pulmonary arteries to lungs 1. Deoxgenated 5 blood from 3. Oxygenation 1 2 systemic of blood & 4 circulation enters 3R L release of CO2 heart in lungs (alveoli) 4. Oxygenated blood re-enters heart via pulmonary veins ® 5. Distributed to rest of body by aorta & branches  PLEURA: 2 layers Visceral pleura (lines lung) Parietal pleura (outer layer, lines chest wall and diaphragm) R Pleural space Potential space between 2 layers (layers usually in very close contact, glide over each other) Intrapleural fluid found in pleural cavity secreted by surfaces of the pleura lubricates pleural surfaces (5-15ml).  Lungs, Pleura, Diaphragm Visceral pleura: covers the 760 mm Hg lungs Parietal pleura: covers the inner thoracic wall Pleural cavity: filled with fluid Diaphragm: separates thorax from abdomen  Pressures Inter-relationships among pressures inside and outside the lungs are important in ventilation. Three pressure considerations: – atmospheric pressure (atm), 760 mmHg at sea level. – intra-alveolar pressure (intrapulmonary pressure), varies with ventilation. – intrapleural pressure, Think of a bicycle pump! 756 mmHg normally less than Atmospheric (-4 mmHg).  Pressures important in ventilation Atmospheric pressure Atmosphere The pressure exerted by the weight 760 mm Hg of the gas in the atmosphere on objects on Earth’s surface = 760 mm Hg at sea level Airways (represents all airways collectively) Intra-alveolar pressure Thoracic wall (represents The pressure within the alveoli entire thoracic cage) = 760 mm Hg when equilibrated with atmospheric pressure 760 mm Hg Pleural sac (space represents pleural cavity) Lungs (represents all alveoli Intrapleural pressure collectively) The pressure within the pleural sac 756 mm Hg The pressure exerted outside the lungs within the thoracic cavity, usually less than atmospheric pressure at 756 mm Hg Ch13, Introduction to Human Physiology, 9th Edition, L Sherwood  Air Movement – Into & Out of the Lungs No Flow Flow In Flow Out Atmospheric pressure (760 mmHg) Volume changes (lung) Pink = Intra-alveolar pressure Blue = Intrapleural pressure Pressure gradient (Patm- Palv) Air flow Ch13, Introduction to Human Physiology, 9th Edition, L Sherwood Intra-alveolar and intrapleural pressure changes throughout the respiratory cycle 1. During inspiration, intra-alveolar pressure is less than atm pressure. 2. During expiration, intra-alveolar pressure is greater than atm pressure. 3. At the end of both inspiration and expiration, intra-alveolar pressure is equal to atm pressure because the alveoli are in direct communication with the atmosphere, and air continues to flow down its pressure gradient until the two pressures equilibrate. 4. Throughout the respiratory cycle, intrapleural pressure is less than intra-alveolar pressure. 5.Thus, a transmural pressure gradient always exists, and the lung is always stretched to some degree, even during expiration. Ch13, Introduction to Human Physiology, 9th Edition, L Sherwood Intra-alveolar and intrapleural pressure changes throughout the respiratory cycle (Intrapleural pressure)* (Transmural pressure) (Intra-alveolar Pressure) The sequence during inspiration results in a fall in intra-alveolar pressure causing air to flow into the lungs. *Intrapleural/pleural; transmural/transpulmonary; Intra-alveolar/alveolar pressures.  PLEURA Pleural space Usually a potential space Can expand if filled with - excess fluid (pleural effusion) lung ie. fluid leaking from capillaries ↑ hydrostatic pressure - excess air (pneumothorax) eg. from puncture of lung (lung also collapses) Disrupts air movement into/out of lungs  Alveoli are sites of Gas exchange Physiologic, or also known as Anatomic Dead Space. Airway Generation Regarding physiological functions, the airway from the trachea to the terminal bronchioles (0-16th division) is called the conducting zone, and the area from the respiratory bronchioles to the alveolar sacs (17–23rd division) is called the transitional and respiratory zone. But this varies within normal healthy population, age & other factors. Transitional/Respiratory zone can start from 15th division onwards, ie, gas exchange!  Alveoli are sites of Gas exchange Alveolar sacs @ end of bronchioles, total of 300-500 million alveoli. Rich supply of vascular supply. Large surface area for gas exchange (≥80 X that of skin, 50-100m2). Alveolus and Surrounding Environment Elastin fiber Alveolar macrophage (Immunity/Foreign Particles) Interstitial fluid Monocyte Type II Alveolar cell (Produce Surfactant) Erythrocyte (RBC) 300 µm Alveolus Pulmonary capillary Type I Alveolar cell Alveolar fluid lining with Pulmonary surfactant 0.5 µm 0.5-µm barrier separating air and blood Ch13, Introduction to Human Physiology, 9th Edition, L Sherwood  RBC O2 Endothelial cell (capillary) 0.5 µm Basement membranes/ interstitial fluid Alveolar CO2 Epithelium Gas exchange occurs by diffusion across thin barrier (~ 0.5µm): from high ® low concentration Contact (travel) time between blood in capillary & alveolus ~ 0.75s: at rest, blood is fully oxygenated by 0.25s.  Innervation & musculature of airways Trachea & bronchi: mainly cartilage, little smooth muscle Bronchioles up to terminal bronchioles: mainly smooth muscle Bronchi & bronchioles can constrict & dilate: smooth muscles innervated by - autonomic nervous system (sympathetic - brochodilation & parasympathetic - bronchoconstriction) Asthma - excessive bronchoconstriction b2-adrenergic receptor agonist bronchodilator that relaxes the smooth muscle in the airways which allows air to flow in and out of the lungs more easily.  Protective mechanisms of airways Protection of respiratory epithelium (mucosa) Humidification of air in upper passages Mucous secretion Protection of lungs Mucociliary trapping of foreign matter Ciliary escalator Alveolar macrophages Airway reflexes eg. cough, sneeze, epiglottis closes glottis during swallowing  cilia epithelial cell globlet cell (secretes mucus) Mucus moves away from lungs Epithelium of upper airways to trachea, bronchi & bronchioles have cilia Epithelium is also covered by mucus Cilia beat to move particles away from lung (ciliary escalator) - macrophages ingest small particles which reach lung Defective ciliary movements may lead to lung infections  SUMMARY: FUNCTIONS of RESPIRATORY SYSTEM Gas exchange - Pulmonary circulation brings blood from rest of body to lungs for gas exchange - & back to heart to be distributed via the systemic circulation - Gas exchange occurs between blood in alveolar capillaries & air in alveoli Immunological & other protective functions Endocrine functions (ie angiotensin II) Voice production, water/heat lost  Break & Couple of MCQs Q1. When the diaphragm contracts, it moves inferiorly, causing _____. (a) a decrease in the volume of the thoracic cavity. (b) an increase in the volume of the thoracic cavity. (c) increased pressure in the thoracic cavity. (d) intra-pulmonary pressure remains the same. Q2. Respiratory zone of the airways where gas exchange first take place at which division? (a) 5 (b) 10 (c) 15 (d) 19  PART II: INTRODUCTION TO VENTILATION How does: Air (O2) get from the atmosphere into alveoli to reach capillary blood? Waste (CO2) get expelled from blood through lungs? Ventilation ALVEOLI Perfusion (air) Diffusion (blood) (membranes)  INTRODUCTION TO VENTILATION Ventilation Movement of air into & out of respiratory tract Does the ‘fresh air’ reach the alveoli? R L Does the ‘waste air’ leave the lungs effectively?  INTRODUCTION TO VENTILATION How do lungs move air in & out? Air is drawn in (inspired) & expelled (expired) by movements of the chest wall & lungs Chest wall: skeleton (ribs, sternum, clavicles) & muscles (diaphragm, intercostal muscles) clavicle ribs sternum intercostal muscles diaphragm  Respiratory Skeleton Muscle Activity During Inspiration and Expiration Before inspiration Inspiration External intercostal muscles (relaxed) Elevation of ribs causes sternum to move upward and outward, Sternum which increases front-to-back dimension of thoracic cavity Diaphragm Contraction of (relaxed) diaphragm Contraction of external intercostal Lowering of diaphragm on muscles causes elevation of ribs, contraction increases vertical which increases side-to-side dimension of thoracic cavity dimension of thoracic cavity  INTRODUCTION TO VENTILATION Lungs & chest wall are elastic structures Can expand ® form bigger volume ® pressure in lungs ↓ ® Intrapleural pressure? SIT Internal Can recoil ® form smaller volume PRINCIPAL MOVEMENTS FOR RESPIRATION IN ALL 3 DIMENSIONS ® pressure in lungs ↑ Increased A-P diameter Increased transverse diameter Prof Karthik’s Lecture lung Pump & Bucket handle movements Increased vertical diameter Picture courtesy: Gray’s Anatomy for students, 3rd Edition, Elsevier Ltd. Pleural Pleura cavity Diaphragm Inspiration: Quiet Expiration: Chest cavity expands: Chest cavity recoils: intrathoracic volume ↑ volume ↓ (diaphragm & inspiratory (diaphragm & inspiratory chest wall muscles contract) chest wall muscles relax) Pressures in thorax & Pressures in thorax & pleural cavity ↓ pleural cavity ↑ Lungs expand: air flows in Lungs recoil: air flows out ACTIVE PASSIVE When ventilation is stimulated eg.in exercise Other muscles are recruited (intercostals, abdominals) ® enhance movement of chest wall: Stronger inspiratory efforts Stronger expiratory efforts ► ↑ lung volumes further ► ↓ lung volumes further ► ↑ air drawn into lungs ► ↑ air expelled from lungs per unit time per unit time ACTIVE ACTIVE How do lungs move air in & out??? Ventilation: Not all inspired air undergoes gas exchange with blood - must reach alveoli! Volume of air that does not exchange with blood: Physiologic Dead Space (Anatomic Dead Space: airways up to respiratory bronchioles just short of R L alveoli) Vol. of air that reaches alveoli / min: Alveolar Ventilation Ventilation: Not all inspired air undergoes gas exchange with blood - must reach alveoli! Vol. of air that reaches alveoli / min: Alveolar Ventilation = (Tidal volume – Anatomic dead space) X Breaths per min R L  INTRODUCTION TO VENTILATION SUMMARY Ventilation is effected by changes in thoracic volumes & pressures Integrity of lungs & pleura, muscles & innervation, rib cage Alveolar ventilation is crucial Inspired air ► reach alveoli ► deliver O2 to blood Expired air (with CO2) ► expelled from alveoli  Learning Objectives Overview of the various components and functions in the respiratory system. How a pleural pressure is generated? How changes in alveolar pressure move air in & out of the lungs? A negative alveolar pressure is created during inspiration for airflow into the lungs. A positive alveolar pressure is created during expiration for airflow out of the lungs.  References The Respiratory System: Ch23, Fundamentals of Anatomy & Physiology, 10th Edition, Martini. Ch13, Introduction to Human Physiology, 9th Edition, L Sherwood. https://hstalks.com.singaporetech.remotexs.co/t/5068/introduction-to-the- respiratory-system/?biosci (approx. 32mins via SIT library). Visible Body – Launch A&P App Visible Body – Respiratory System, Ch34-37 Visible Body – Practice MCQs THE RESPIRATORY SYSTEM Lecture II I. GAS EXCHANGE by DIFFUSION II. PERFUSION of LUNGS III. VENTILATION VOLUMES IV. CONTROL of RESPIRATION Bernard Leung [email protected] HSC1007, AY2024 Meeting ID: 956 7013 2553 Passcode: 375090  Learning Objectives The concept of ventilation and gas exchange by diffusion. How partial pressure drives the diffusion of O2 and CO2? Factors that influences the rates of gas transfer across the alveolar membrane. Basic concept of ventilation and perfusion. Ventilation terminology and different lung volume measurements. Control of Respiration.  EFFECTIVE OXYGENATION & CO2 REMOVAL IN LUNGS depend on… I. Ventilation & Gas exchange by Diffusion § Do lungs get enough ‘fresh air’ at each breath cycle? § Does the ‘fresh air’ reach the alveoli? § At the alveoli, can the ‘fresh air’ R L DIFFUSE effectively across to the capillary blood? § After gas exchange, can the ‘stale air’ leave the lungs effectively? EFFECTIVE OXYGENATION & CO2 REMOVAL IN LUNGS depend on… II. Perfusion of lungs § Does blood coming from the heart reach the alveoli? § Are all alveoli perfused by blood? 0.5µm capillary § At the alveoli, does the rate of blood flow CO2 give sufficient time O2 for gas exchange? alveolus  GAS EXCHANGE @ ALVEOLI: FACTORS AFFECTING Diffusion across alveolar-capillary barrier – Factors influencing efficiency of diffusion: Partial pressures of gases Thickness of barrier Surface area Blood Flow – Rate of blood flow through alveoli – Perfusion of alveoli  GAS EXCHANGE @ ALVEOLI: DIFFUSION ~ a little maths! Diffusion of gas is from areas of high partial pressure ® low Partial pressure of a gas (Dalton’s Law) : Pressure that gas exerts in a mixture of gases - proportional to % of gas in mixture If gas = O2, and the mixture = dry air @ sea level Then pO2 (partial press. of O2) in air = 0.21 (21% of air is O2) X 760mmHg (total air pressure @ sea level) https://www.youtube.com/watch?v=6qnSsV2syUE Gas Exchange and Partial Pressures, Animation  Partial Pressure and % of Respiratory Gases at Sea Level (Barometric Pressure PB=760 mmHg) ie, 160/760 = 21% ie, 150/760 = 20% Respiratory Zone 600/760 = 79% 47/760 = 6% Gas Exchange 563/760 = 74% (Alveolar Ventilation) (Anatomic Dead Space) Alveolar Ventilation = (Tidal volume – Anatomic dead space) x Breaths per minute Tidal Vol (500ml) – Anatomic Dead Space (150ml) x 12 breaths/min = 4,200ml (4.2L)  GAS EXCHANGE @ ALVEOLI: DIFFUSION Diffusion of gas is from areas of high partial pressure ® low Gas potentially diffuses until partial pressures are equalised in areas High partial pressure low partial pressure Equal partial pressure Diffusion stops Diffusion of oxygen if partial pressure @ alveoli equal capillary blood?  GAS EXCHANGE @ ALVEOLI: DIFFUSION Alveolar Basement Capillary epithelium membranes endothelium capillary CO2 O2 alveolus Diffusion: Gases diffuse down partial pressure (concentration) gradients across epithelial barriers Overview of Respiratory Processes and Partial Pressures in Respiration (For your info!) Pulmonary Venous Admixture - before reaching the left atria, mixing of non- reoxygenated blood with reoxygenated blood distal to the alveoli in the pulmonary veins, reaching the atria with an arterial PO2 of 95 mmHg.  O2 DISSOCIATION CURVE O2@dissociation pH 7.4, 37 curve oC, PCO 40mmHg 2 (pH7.4, 37 degrees Celsius, pCO2 40mmHg) 20 100% O2 concentration for Hb 98% O2 saturation of Hb 16 of 15g/dL (ml/dL) O2-Hb End of pulmonary 12 dissociation capillaries: curve 50% PO2 ~ 8 100mmHg, 4 Dissolved O2 Hb 98*% 0 0% saturated with O2 0 50 100 Rest as dissolved PO2 (mmHg) oxygen! *Most textbook refer to as 97.5% Saturation of Hb  GAS EXCHANGE @ ALVEOLI: DIFFUSION Surface area for diffusion capillary CO2 O2 alveolus Diffusion across many perfused alveoli in both lungs Reduced area for diffusion in eg.? Consequences for gas exchange?  GAS EXCHANGE @ ALVEOLI: RATE OF BLOOD FLOW capillary CO2 O2 alveolus Alveolar gases take time to diffuse & equilibrate with blood Different gases diffuse / equilibrate @ different rates Rate of blood flow across alveolus can change eg. ↑↑↑ in severe exercise: enough time for gas exchange (diffusion)?  GAS EXCHANGE @ ALVEOLI: BLOOD FLOW through ALVEOLI (PERFUSION) capillary CO2 O2 alveolus Gas exchange occurs when blood perfuses capillary Blood flow ceases ® no gas exchange (eg. pulmonary embolism: blood clot in pulmonary artery) Sherwood Human Physiology, Table 13-5, p470.  PERFUSION OF LUNGS Pulmonary circulation route Right Ventricle (RV) ® Main pulmonary artery (PA) branches successively into several pulmonary arteries (accompany bronchioles) PA Arterioles ® LA Capillary bed around alveoli RV Small pulmonary veins ® Large pulmonary veins ® Left Atrium (LA)  PERFUSION OF LUNGS Low pressure system vs. high pressure systemic circulation Pulmonary artery pressure >25/15 mmHg vs Systemic arterial pressure 120/80 mmHg High volume system: lungs receive whole of cardiac output at all times Distribution of blood flow in lungs is not uniform Pulmonary Circulation has Unique Hemodynamic Features Unlike the systemic circulation, the pulmonary circulation is a low- pressure and low resistance system. Pulmonary circulation is characterized as normally dilated, whereas the systemic circulation is characterized as normally constricted. Pressures are given in mm Hg; a bar over the number indicates mean pressure. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. Comparison of Systemic vs Pulmonary BP Just a quick visual guide – FYI only! Guyton & Hall Medical Physiology, Ch14, Elsevier.  PERFUSION OF LUNGS Distribution of blood flow in lungs: Influenced by - gravity (hence posture) (eg. upright: more blood flow at bottom) - muscular tone of arterioles distension: pulmonary arterioles have less muscular walls vs. systemic arterioles ® can distend more easily with increased blood flow vasoconstriction: less blood flows through capillaries Ventilation and Perfusion Ratios of the Lungs  Local controls to match airflow and blood flow of the lung Large Air-flow/Small blood flow ie, Apex of the Lungs Sherwood Human Physiology, 9th Ed, Ch13.  Local controls to match airflow and blood flow of the lung Large Blood Flow/Small Air-flow (Base of the Lungs) Sherwood Human Physiology, 9th Ed, Ch13.  LIMITATIONS OF RESPIRATORY RESPONSES IN DISEASE Reduced alveolar ventilation: ↓ Tidal volume &/ or ↑ Dead space What disease conditions may cause ↓ tidal volume Restriction of lung or chest wall movements (ie, Pain) eg. loss of lung elasticity by fibrosis (‘scarring’) of alveolar walls ↑ dead space?  SUMMARY OF GAS EXCHANGE & PERFUSION In order for gas exchange to occur: - Fresh air must reach the alveoli: ventilation (alveolar ventilation vs dead space) - Alveoli must be perfused by blood - Diffusion at alveoli should be efficient (partial gas pressure, rate of blood flow, diffusion barrier & surface area)  SUMMARY OF PARTS I & II: GAS EXCHANGE & PERFUSION Special properties of pulmonary circulation - Low pressure, high volume system (100% cardiac output) - Gravity-dependent - Blood flow through capillaries can be regulated by arteriolar tone Time for a Break!  PART III. VENTILATION TERMINOLOGY Not all air taken in undergoes gas exchange: Dead Space (usually mainly = air in conducting airways) More forceful inspiration & expiration (vs. normal quiet breathing) are possible Various volumes of air can move in & out of lungs: defined by different terms AT REST Tidal volume (TV; VT) – Volume of air entering lungs @ each resting breath (or exiting lungs on passive expiration) Inspiratory reserve volume (IRV) - Extra air entering lungs with RV maximal inspiration (on top of TV) Expiratory reserve volume (ERV) ERV - Extra air expelled from lungs with TV maximum expiration (after passive IRV expiration) Residual volume (RV) - Volume of air left in lungs after maximum expiration  VENTILATION VOLUMES: normal range of values vary with size, age & physical fitness of person Men (Ave Litre per Women breath) RV: 1.2 1.1 ERV: 1.0 0.7 TV: 0.5 0.5 IRV: 3.3 1.9 Total: Total: 6 4.2 VENTILATION VOLUMES can change Tidal volume (TV; VT) Volume of air that moves into lungs with each inspiration (or exits with each expiration) during a respiratory cycle RV Depends on eg. activity ERV Resting VT < Exercising VT TV IRV Exercising VT recruits other lung volumes (IRV,ERV)  VENTILATION VOLUMES can change Ability to ventilate depends on properties of chest wall & lungs & other factors which affect breathing Some egs. Chest wall : Muscle power? Skeletal deformities? RV Lungs: Resistance to airflow? Areas of ‘stiffness’ ERV (loss of elasticity)? Areas of Vital collapse? TV capacity Others: Abdominal IRV movement restricted eg. pain?  Minute ventilation: TV X Respiratory rate (breaths/ minute) What is the normal range of minute ventilation in the adult human at rest? TV ~ 0.5L, respiratory rate = ? Breaths /min Hence minute vent. = ? L /min During exercise? Some deviations from ‘normal’ ventilation Hyperventilation: ↑ ventilation Hypoventilation: ↓ ventilation Tachypnoea: ↑ rate of respiration Dyspnoea: distressful sensation of breathing  ALVEOLAR VENTILATION Not all air breathed in gets to alveoli VD Alveolar ventilation (VA): volume of air that reaches alveoli / minute RV ERV VA (L/min) = [ TV - VD ] TV (VT;tidal volume) (dead space) IRV X Respiratory rate (breaths per minute)  SUMMARY OF PART III. VENTILATION Alveolar ventilation is key to gas exchange in the lungs Control of Respiration  CO2 TRANSPORT IN BLOOD Carbamino Hb (23%) Red blood cell + Hb HHb (buffers pH) Carbonic Hb Cl- shift anhydrase + maintains CO2 + H2O ® H2CO3 ® H+ + HCO3- electrical neutrality CO2 Dissolved HCO3 - Cl- CO2 (7%) (~70%) plasma diffusion CO2 (higher PCO2) tissue  Chemoreceptor Control Peripheral Chemoreceptors Carotid body & Aortic bodies O2 & H+ sensor medulla Blood Pressure Baroreceptor  Chemical Control of Breathing PCO2 – main respiratory regulator – mainly affect on central chemoreceptors – CO2 can pass blood-brain barrier – H+ cannot pass the barrier [H+] – monitored by carotid & aortic bodies PO2 – monitored by carotid & aortic bodies – arterial PO2< 60 mmHg to stimulate peripheral chemoreceptors  Influence of Chemical Factors on Respiration Sherwood Human Physiology Ch13 Chemoreceptor Response to Changes in PCO2 Martini Anatomy & Physiology Ch23, Fig23-26.  Learning Objectives The concept of ventilation and gas exchange by diffusion. How partial pressure drives the diffusion of O2 and CO2? Factors that influences the rates of gas transfer across the alveolar membrane. Basic concept of ventilation and perfusion. Ventilation terminology and different lung volume measurements. Control of Respiration. THE RESPIRATORY SYSTEM Lecture III I. GAS EXCHANGE @ ALVEOLI: Closer Inspection – what can go wrong? II. WORK OF BREATHING III. GAS TRANSPORT Bernard Leung [email protected] HSC1007, AY2024 Meeting ID: 956 9797 5243 Passcode: 986493  Learning Objectives Describe how alveolar area and membrane thickness affect gas diffusion in health and disease. Explain how lung elastic recoil affects lung compliance. Surfactant and alveolar inter-dependence in maintaining alveolar stability. Factors affecting airway resistance, and how spirometry measures lung volumes and airflow in patients. The mechanisms by which O2 and CO2 are transported by the blood. Changes in O2 and CO2 balance during exercise. Ventilation and Perfusion Ratios of the Lungs From Yesterday’s Lecture Local control mechanisms attempt to match Ventilation & Perfusion 2016 Pearson Education, Inc. Movement of O2 and CO2 across the alveolar - capillary membrane is by diffusion. Gases move across the blood - gas interface (alveolar - capillary membrane) by diffusion. 0.25 second to Equilibrate PAO2, partial pressure of alveolar oxygen. PACO2, partial pressure of alveolar carbon dioxide. GAS EXCHANGE AT ALVEOLI Amount of gas taken up/released by capillaries depends on local factors @ alveoli: Diffusion & Blood Flow  DIFFUSION of GASES: Factors influencing - Difference in partial pressure of gas between alveoli & blood – Diffuses from higher ® lower partial pressure – ↑ Difference in pressure ® faster diffusion Diffusion barrier (alveolar-capillary thickness, 0.5µM) – Thicker barrier ® slower diffusion Area available for diffusion – Smaller area ® less area for diffusion Diffusion properties of gas eg. solubility – More soluble in blood ® diffuse faster (CO2 > O2) ABNORMAL DIFFUSION ↓ difference in partial pressure of gas ® ↓ diffusion (eg. ↓PO2 in alveolus @ high altitude, >10,000 feet)* Abnormal thickening of alveolar-capillary barrier ® ↓ diffusion O2 CO2 (eg. fibrosis, edema) Alveolar- CO2 ↓ alveolar volume / capillary ↓ no. of functional alveoli ® ↓ barrier area for diffusion (eg. pneumonia) *Sea level = 760mmHg (PAO2 100mmHg); 10,000 feet = 523mmHg (PAO2 73mmHg).  GAS EXCHANGE AT ALVEOLI Amount of gas taken up/released by capillaries depends on local factors @ alveoli: Diffusion versus Blood Flow blood flow ↓↓: gas exchange ↓ - eg. blood clot in pulmonary arteries (embolism) blood flow ↑↑: gas exchange may also ↓ - due to less time for gas to equilibrate – exercise - especially in diseased alveoli with thickened membranes  PO2 of blood normally reaches alveolar PO2 by 0.25s (1/3 of its way along capillary) Severe exercise can ↓ transit time of blood cell in capillary to 1/3 (0.25s) ® less time for gas to equilibrate 40 Thick alveolar- capillary barrier Time of blood cell in capillary (sec)  II. WORK OF BREATHING How hard do respiratory muscles work to move air in & out of lungs? How easily can chest wall & lungs stretch? Compliance How much resistance is there to air movement in respiratory passages? Airway resistance Other states that trigger increased respiratory efforts? eg. exercise  WORK of BREATHING: COMPLIANCE OF LUNGS & CHEST WALL How easily air flows in depends on stretchability of lungs & chest wall Compliance: measure of stretchability = Change in lung volume /unit change in airway pressure (ΔV/ΔP)  WORK of BREATHING: COMPLIANCE OF LUNGS & CHEST WALL How easily air flows in depends on stretchability of lungs & chest wall Compliance: measure of stretchability = Change in lung volume /unit change in airway pressure (ΔV/ΔP) ↓compliance: ↓ stretchability & ↑ work of breathing (eg. ↓ compliance of lung tissues due to fibrosis; lack of surfactant; oedema of alveolar walls)  COMPLIANCE OF LUNGS Major determinant: surface tension of alveoli Alveoli lined by liquid film® generate surface tension (T) Attractive forces between adjacent liquid molecules pull alveolar surface together Surface tension causes alveoli to contract ®↑ pressure (P) within alveoli Smaller alveoli: higher pressure (↓r, ↑P) ® empty into bigger alv. ↓r : ↑P P (pressure in sphere) µ T (surface tension)/ r (radius)  Alveoli – Not the same size! Alveoli Respiratory bronchiole Branch of pulmonary artery uct ar d Alveoli Alveolar eol sac A lv Alveolar sac Alveolar duct (a) LM X 42 (b)  COMPLIANCE OF LUNGS Millions of Smaller alveoli have tendency to smaller & collapse! bigger alveoli How to improve stretchability (compliance)? Reduce T ® reduce P ® ↑ compliance P (pressure in sphere) µ T (surface tension)/ r (radius)  COMPLIANCE OF LUNGS Surfactant can ↓ alveolar surface tension (T): Mixture of phospholipids, capillary lipids & proteins Lines inner surfaces of Alveolar alveolar epithelium epithelium ↓ surface tension of alveoli Lack of surfactant in Type II cell premature babies ® (produce alveoli collapse surfactant) Infant respiratory distress syndrome in newborn.  Surfactant Promotes Alveolar Stability at Low Lung Volumes Calculation Not Necessary to Remember! (A) If surface tension remains constant (50 dyne/cm), alveoli that are interconnected but differ in diameter become unstable and cannot coexist. Pressure in the smaller alveolus is greater than that in the larger alveolus, which causes air from the smaller alveolus to empty into the larger alveolus. At low lung volumes, the smaller alveoli tend to collapse. (B) Surfactant lowers surface tension proportionately more in the smaller alveolus. As a result, pressures in the two alveoli are equal, and alveoli of different diameters can coexist. WORK of BREATHING:AIRWAY RESISTANCE Resistance to flow of air (trachea, bronchi, bronchioles) ↑ resistance by narrowing of airways due to: - contraction of smooth muscle of bronchioles (bronchoconstriction) - ↓ lung volume - mucus accumulation ® ↑ work of breathing (to draw air into lungs) Stimulants Mediated by Bronchoconstriction Irritants eg. Parasympathetic ↑ sensitivity: asthma smoke; cold air nerves Bronchodilation Drugs: Sympathetic b2 adrenergic mediators agonists (epinephrine on b2 adrenergic receptors) Sherwood Human Physiology, 9th Edition, Ch13.  SUMMARY OF PART II: WORK OF BREATHING Work of breathing is influenced by: – Compliance of lungs & chest wall Importance of surfactant in stabilising alveoli – Airway resistance Altered by changes in airway caliber (constriction/dilation)  Measuring Lung Volumes & Air Flow Rates by SPIROMETRY Men (Ave Litre per Women breath) RV: 1.2 1.1 ERV: 1.0 0.7 TV: 0.5 0.5 IRV: 3.3 1.9 Total: Total: 6 4.2  Measuring forced lung volumes & air flow rates by SPIROMETRY Forced expiratory volumes: FEV1: forced expiratory volume of air exhaled in 1 sec after full inspiration, approx 80% (0.8) of Vital Capacity FVC: forced vital capacity – total volume expired forcefully after full inspiration ie, Asthma = FEV1/FVC