Respiratory Physiology Lecture Notes PDF

Respiratory Physiology Kathryn Taylor Learning Objectives A review of the structure of the respiratory system The mechanics of ventilation The principles of gas exchange in the lungs and factors that affect it Ventilation-perfusion ratio An overview of t...

Respiratory Physiology Kathryn Taylor Learning Objectives A review of the structure of the respiratory system The mechanics of ventilation The principles of gas exchange in the lungs and factors that affect it Ventilation-perfusion ratio An overview of the control of ventilation Breathing and Respiration Respiration is the exchange of gases between the atmosphere, blood, and cells The combination of 3 processes is required for respiration to occur – Ventilation (breathing) – External (pulmonary) respiration – Internal (tissue) respiration The cardiovascular system assists the respiratory system by transporting gases  Overview of respiratory physiology At rest a normal human breathes 12 to 15 times a minute/ 500 mls of Air per breath or 6 to 8 litres per minute are inspired and expired. This air mixes with the gas in the alveoli and by simple diffusion oxygen enters the blood in the pulmonary capillaries while Carbon dioxide enters the alveoli. The Respiratory System  Structures of the Respiratory System Structurally, the components of the respiratory system are divided into 2 parts: 1. Upper respiratory system (nose, pharynx, larynx and associated structures) 2. Lower respiratory system ( trachea, bronchi, and lungs) Functionally, the components of the respiratory system are divided into 2 zones: 1. Conducting zone 2. Respiratory zone Where opportunity creates success Copyright © 2017 John Wiley & Sons, Inc. All rights reserved Upper airway Upper Airway Actual and schematic views of anatomical dead space VD. (a) Corrosion cast preserving the first 10-12 generations of dichotomously branched human airways. Surrounding lung tissue was dissolved with alkali after liquid plastic instilled into the airways had hardened. (b) Diagram of airways that terminate in true alveoli; the estimate of 22-23 generations was first made by Ewald Weibel in 1962. (a): From Fox. Human Physiology, 10th ed.; 2008. (b): FromWest Respiratory Physiology – the Essentials. 6th ed.Williams & Wilkins; 2005. Citation: Chapter 4 Principles of Lung Ventilation and Spirometry, Lechner AJ, Matuschak GM, Brink DS. Respiratory: An Integrated Approach to Disease; 2012. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=1623&sectionid=105763671 Accessed: November 23, 2020 Copyright © 2020 McGraw-Hill Education. All rights reserved Anatomical Dead Space This refers to the part of the airway that is not involved in gas exchange (conducting zone) – average 150ml Volume of fresh gas 500 ml inhaled-(500ML-150ML) X 15 BREATHS /MIN=5,250ml- min-1 Alveolar dead space This refers to alveoli that are ventilated but not perfused – varies depending on circumstances in normal individuals and can be influenced in disease (see later on V:Q relationships Research gate Functions of Conducting Zone (including the nose/mouth/pharynx) Transports air to the lungs Warms, humidifies, filters, and cleans the air – Mucus traps small particles, and cilia move it- Mucociliary escalator away from the lungs. Voice production in the larynx as air passes over the vocal folds The upper airway consists of all structures from the nose to the vocal cords, The lower airway consists of the trachea and the bronchial structures to the alveolus. Main-stem bronchi branch into The tracheobronchial tree is an Nasal breathing is preferential lobar bronchi (three on the right arrangement of branching as; and two on the left) (Generation tubes that begins at the larynx 1. the nose filters particulate 2) that in and matter and plays a major turn branch into segmental ends in the alveoli. role in lung defense bronchi (Generation 3) and an The trachea divides at the 2. the nose humidifies inspired extensive system of ‘carina’ air as a result of the large subsegmental and surface area created by the into the right and left main- smaller bronchi. stem bronchi (Generation 1) nasal septum and the nasal that penetrate the lung turbinates. parenchyma (tissue of the Nose offers higher resistance lung). than mouth- switch to mouth The right main-stem bronchus breathing during excercise is larger than the left, and the angle of the takeoff is less acute. Trachea Functional anatomy of the respiratory tract Lumb, Andrew, MB BS FRCA, Nunn and Lumb's Applied Respiratory Physiology, 1, 1-13.e2 The normal trachea as viewed during a rigid bronchoscopy. The ridges of the cartilage rings are seen anteriorly, and the longitudinal fibres of the trachealis muscle are seen posteriorly, dividing at the carina and continuing down both... Copyright © 2021 Copyright © 2021, Elsevier Limited. All rights reserved. Trachea Respiratory system Respiratory system Bridge, Nick, Master of Health Education, Applied Anatomy & Physiology, Chapter 17, 305-328 Respiratory mucosa. ( Source: Patton KT, Thibodeau GA, editors. Anatomy and physiology, 9 ed. London: Elsevier Health Sciences; 2015.) Copyright © 2020 Copyright 2020 Elsevier Australia. Cellular transition from conducting airway to the alveolus. The epithelial layer transitions from pseudostratified layer with submucosal glands to a cuboidal epithelium and then to a squamous epithelium. The underlying mesynchyme tissue and capillary structure also changes with the airway transition. (Adapted with permission from Fishman AP et al (eds): Fishman’s Pulmonary Diseases and Disorders. 4th ed. New York: McGraw-Hill; 2008.) Citation: Chapter 34 Introduction to Pulmonary Structure & Mechanics, Barrett KE, Barman SM, Brooks HL, Yuan JJ. Ganong's Review of Medical Physiology, 26e; 2019. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=2525&sectionid=204297523 Accessed: November 23, 2020 Copyright © 2020 McGraw-Hill Education. All rights reserved Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Bronchus Respiratory System : Function and Structure Cloutier, Michelle M., MD, Respiratory Physiology, 1, 1-14 Scanning electron micrograph of airway, showing the ciliated, pseudostratified, columnar epithelium of a bronchus. Each cilium is connected to a basal body (BB), which collectively appears at the base of the cilia (C) as a dark band. Goblet cells (GC) and basal cells (BC), the potential precursors of the ciliated cells, are shown. CT, connective tissue. From Berne RM, Levy ML, Koeppen BM, Stanton BA (eds.). Physiology , 5th ed. St. Louis: Mosby; 2004. Copyright © 2019 Copyright © 2019 Elsevier Inc. All Rights Reserved. Alveolar structure Oxygen and carbon dioxide moves via simple diffusion and the blood gas barrier is extremely thin and has a surface area of between 50- 100 square metres. This large surface area is acheived by wrapping capillaries around an enormous number of alveoli (air sacs). Alveolar Tissue  Surface tension This is the attraction between molecules at a gas/liquid interface that tends to pull those molecules together In a spherical structure such as an alveolus, this increases the pressure within the alveolus – the smaller the alveolus, the greater the pressure This means that smaller alveoli have more tendency to collapse than larger ones SURFACTANT reduces the surface Clinical relevance - example tension, and is essential to enable the Neonatal RDS – Respiratory distress syndrome is expansion of alveoli related to surfactant deficiency Ventilation Primary principle of ventilation. Put simply, air moves down its pressure gradient—that is, it always moves from an area of high pressure to an area of lower pressure. To achieve inspiration, the higher pressure must be outside the body. PATTON, KEVIN T., PhD, Anatomy and Physiology, Adapted International Edition, 36, 824-84 Copyright © 2019 © 2019, Elsevier Limited. All rights reserved. Boyles Law Boyles Law  Boyle’s Law Pressure changes that drive inhalation and exhalation are governed, in part, by Boyle’s Law – The volume of a gas varies inversely with its pressure What this means for the lungs, is that when the volume of the thorax is decreased by the ribs falling and the diaphragm rising, the air in the lungs is put under pressure and the result is flow of air i.e. exhalation And the opposite during inhalation Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. Inspiration and expiration Copyright © 2014 John Wiley & Sons, Inc. All rights reserved Mechanics of breathing Inspiration is active; expiration is passive at rest The diaphragm is the most important muscle of inspiration; it is Supplied by phrenic nerves that originate at C3, 4, 5 During exercise expiration is active and the abdominal muscles contract Muscles and movement in respiration. A) An idealized diagram of respiratory muscles surrounding the rib cage. The diaphragm and intercostals play prominent roles in respiration. B) and C) Radiograph of chest in full expiration (B) and full inspiration (C). The dashed white line in C is an outline of the lungs in full expiration. Note the difference in intrathoracic volume. (For (A) Reproduced with permission from Fishman AP et al (eds): Fishman’s Pulmonary Diseases and Disorders. 4th ed. New York: McGraw-Hill; 2008; (B, C) Reproduced with permission from Comroe JH Jr: Physiology of Respiration, 2nd ed., Year Book; 1975.) Citation: Chapter 34 Introduction to Pulmonary Structure & Mechanics, Barrett KE, Barman SM, Brooks HL, Yuan JJ. Ganong's Review of Medical Physiology, 26e; 2019. Available at: https://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=204297546&gbosContainerID=0&gbosid=0&groupID=0&sectionId=204297523&multimediaId=undefined Accessed: September 14, 2021 Ventilation – at rest Inhalation Exhalation Muscles of Respiration Muscles of respiration. Diagram of the anatomy of the major respiratory muscles. Left side, inspiratory muscles; right side, expiratory muscles. Kaminsky D. The Netter Collection of Medical Illustrations: Respiratory System, vol. 3, 2nd ed. Copyright © 2019 Copyright © 2019 Elsevier Inc. All Rights Reserved. Overview of the Respiratory System : Function and Structure Cloutier, Michelle M., MD, Respiratory Physiology, 1, 1-14 West,J,Luks,A.2013.Pulmonary Pathophysiology,Walters Klewer, Philadelphia Movements of the thoracic wall during inhalation and exhalation in the anterior (A) and axial superior (B) views. C. Thoracic wall movements during respiration. The bucket and water-pump handle are analogies for the movement of the rib cage when acted upon by respiratory muscles. Citation: CHAPTER 3 Lungs, Morton DA, Foreman K, Albertine KH. The Big Picture: Gross Anatomy, 2e; 2019. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=2478&sectionid=202020215 Accessed: September 14, 2021 Copyright © 2021 McGraw-Hill Education. All rights reserved Pulmonary pressure Transpleural pressure The pressure difference across the lungs; the difference between the pressure at the airway opening and the pressure on the visceral pleural surface (i.e., pressure at the airway opening – pleural pressure).  SEM Alveoli Alveoli must remain open to participate in gas exchange - the alveoli are interconnected with elastic tissue so inflation of one alveoli helps to expand the adjacent alveoli. Factors affecting gas exchange FICKS LAW Anything that affects diffusion will affect gas exchanges; factors that affect diffusion include: Surface area Diffusion gradient Diffusion distance (i.e. thickness of membrane) The blood gas barrier is extremely thin- 0.2-0.3Um and large surface area of 50-100m2 Distance of diffusion Increased if there is fluid in the Normally very short in lungs (e.g. in pneumonia) or healthy lungs (0.2 – 0.4 µm) mucus in the lungs (e.g. cystic fibrosis) OTHER FACTORS AFFECTING PULMONARY VENTILATION Lung Compliance The ease with which the lungs and thoracic wall can be expanded Defined as the change in lung volume per change in transpulmonary pressure: ΔV/ΔP Will be reduced by conditions that make lung tissue stiffer e.g. pulmonary fibrosis OTHER FACTORS AFFECTING PULMONARY VENTILATION Elasticity The lungs contain elastic tissue that stretches on inhalation During exhalation the elastic tissue recoils, which aids the flow of air out of the lungs Disorders that cause loss of elasticity (e.g. Emphysema) can affect ventilation Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. Gas exchange between the alveoli and pulmonary capillaries Bridge, Nick, Master of Health Education, Applied Anatomy & Physiology, Chapter 17, 305-328 Gas exchange between the alveoli and pulmonary capillaries. ( Source: Patton KT, Thibodeau GA, editors. Anatomy and physiology, 9 ed. London: Elsevier Health Sciences; 2015.) Copyright © 2020 Copyright 2020 Elsevier Australia Structure of the normal alveolus Structure of the normal alveolus. The type I cell, with its long thin cytoplasmic processes, lines most of the alveolar surface, whereas the cuboidal type II cell, which is more numerous, occupies only about 7% of the alveolar surface. Capillaries (C) with red blood cells (RBC) are also shown. A, alveolar surface; IS, interstitial space; L, lamellar body, source of surfactant. Modified from Weinberger S, Cockrill, BA, Mandel J. Principles of Pulmonary Medicine , 5th ed. Philadelphia: W.B. Saunders; 2008. Transmission electron micrograph of a pulmonary capillary in cross section Transmission electron micrograph of a pulmonary capillary in cross section. Alveoli (Alv) are on either side of the capillary that is shown with a red blood cell (RBC). The diffusion pathway for oxygen and carbon dioxide (arrow) consists of the areas numbered 2, 3, and 4, which are the alveolar–capillary barrier, plasma, and erythrocyte, respectively. BM, basement membrane; C, capillary; EN, capillary endothelial cell (note its large nucleus); EP, alveolar epithelial cell; FB, fibroblast process; IN, interstitial space. Reproduced with permission from Weibel ER. Morphometric estimation of pulmonary diffusion capacity, I. Model & method. Respir Physiol. 1970;11:54–75. Pulmonary circulation The lung has two separate circulations. The pulmonary circulation brings deoxygenated blood from the right ventricle to the gas-exchanging units. The bronchial circulation arises from the aorta and nourishes the lung parenchyma. The circulation to the lung is unique in its dual circulation and in its ability to accommodate large volumes of blood at low pressure. During EXTERNAL RESPIRATION oxygen diffuses from the alveoli into the pulmonary capillaries, carbon dioxide in the opposite direction During INTERNAL RESPIRATION oxygen diffuses from the systemic capillaries into the tissues, and carbon dioxide in the opposite direction Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. Summary Other functions include acid–base balance, host defense and metabolism, and the handling of bioactive materials. 1. The principal function of the respiratory system is gas exchange. 2. Gas exchange occurs in the alveolar–capillary unit, the basic physiologic unit of the lung. 3. The bronchopulmonary segment is the segment of the lung supplied by a segmental bronchus. It is the functional anatomic unit of the lung. 4. The alveolar surface is lined by type I and type II cells. The thin cytoplasm of the type I cell is ideal for optimal gas diffusion, whereas the type II cell is important for the production of surfactant, which decreases the surface tension of the alveolus. Ventilation –Perfusion coupling Perfusion-blood flow reaching alveoli Ventilation-amount of gas reaching alveoli Ventilation and perfusion would need to be matched (coupled) for efficient gas exchange However, there are regional variations due to the effect of gravity and air flow Ventilation –perfusion ratio The ventilation – perfusion ratio varies throughout the lungs Normal V-Q ratio for the whole lungs is 0.8 In the upright lung: Apices – receive more ventilation than perfusion (high ventilation/perfusion ratio), > 0.8 Bases – more perfusion than ventilation (low ventilation/perfusion ratio) < 0.8 Distribution of blood flow in the lungs of an upright person Due to gravity, blood flow is greater at the base than at the apex of the lungs Distribution of ventilation throughout the lungs in an upright person Ventilation increases from the top to the bottom of the lungs The effect of gravity on the lung tissue means that the intrapleural pressure is greater at the base – there is less difference between the pressure in the atmosphere and that in the lungs This means that between breaths they are not as expanded as the alveoli at the apex, so they have a greater capacity to expand during inhalation The alveoli at the base therefore get a greater proportion of the tidal volume Ventilation and Perfusion Factors that decrease V-Q ratio Decreased ventilation (or increased perfusion) Chronic bronchitis (bronchospasm, inflammation, airway obstruction) Asthma (bronchoconstriction, excess mucus) Pulmonary oedema (fluid build up in the lungs) Pulmonary fibrosis (decreases compliance This means that although there is blood passing the alveoli, gas exchange is limited due to limited refreshing of the alveolar air; blood oxygen level will fall and blood carbon dioxide level will rise Factors that increase V-Q ratio Increased ventilation or decreased perfusion Pulmonary embolism: a blood clot in the lungs may block lung blood vessels, resulting in limited perfusion to an area that is being ventilated effectively ; the overall V-Q ratio will therefore increase. In COPD, patients have a high ventilation rate but poor perfusion due to damage to the alveoli; the level of ventilation is relatively high and V-Q ratio will increase This means that although there is plenty of air getting into the alveoli, oxygen is not getting into the blood and carbon dioxide is not getting out effectively , as the relative level of blood flow is too small. Control of Breathing The normal automatic The cortex can override these process of breathing centre’s if voluntary control is originates in impulses that desired come from the Brainstem Breathing Patterns and Respiratory Movements Eupnea -normal breathing Apnea - no breathing Dyspnea - laboured breathing Tachypnea - rapid breathing Costal breathing - breathing by rib movement only Diaphragmatic breathing - breathing by diaphragmatic movement only Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. Control of Respiration Respiration is controlled by both central carbon dioxide sensors and peripheral carbon dioxide and Hypercapnia oxygen chemoreceptors. – A slight increase in PCO2 (and thus H+) – Stimulates central chemoreceptors and peripheral (carotid) chemoreceptors Hypoxia – Oxygen deficiency at the tissue level – Caused by a low PO2 in arterial blood due to high altitude, airway obstruction or fluid in the lungs – Stimulates peripheral (carotid) chemoreceptors Copyright © 2017 John Wiley & Sons, Inc. All rights reserved  Lung Receptors Pulmonary stretch receptors( slowly adapting) lie within airway smooth muscle. Discharge in response to distension in lung Activity sustained with lung inflation Impulses travel in vagus nerve via large myelinated fibres. Main reflex effect of stimulating these receptors is a slowing of respiratory frequency. HERING-BREUER inflation reflex. Provides self regulatory negative feedback mechanism Inflation inhibits further inspiratory muscle activity Deflation initiates inspiratory activity. Central and Peripheral chemoreceptors Peripheral chemoreceptors Located in the carotid and aortic bodies Respond to decreased arterial PO2 and increased PCO2 and H+ Central chemoreceptors : Rapidly responding Located near ventral surface of medulla Sensitive to PCO2 but not PO2 of blood Respond to the change of pH of the ECF/CSF when CO2 diffuses out of the cerebral capillaries Control of Respiration Control of respiration involves a basic rhythm generated by the brainstem that is modified by multiple neural inputs. Control of breathing The pons and medulla generate a normal cyclic pattern of respiration. This pattern is altered by HOMEOSTATIC and ADAPTIVE reflexes. Control of Respiration Control of Respiration Cloutier, Michelle M., MD, Respiratory Physiology, 10, 130-144 Dorsal view of the location of the pontine and medullary respiratory neurons. DRG, dorsal respiratory group; E, expiratory; I, inspiratory; Iα and Iβ, two populations of inspiratory neurons in the DRG inhibited and excited, respectively, by lung i... Copyright © 2019 Copyright © 2019 Elsevier Inc. All Rights Reserved. Control of Respiration Control of Respiration Cloutier, Michelle M., MD, Respiratory Physiology, 10, 130-144 Neural signalling of inspiratory motor neurons involves one inspiratory and two expiratory phases. Inspiration is abrupt, followed by a steady ramp-like increase in neuron firing rate. At the end of inspiration, there is an off-switch event, result... Copyright © 2019 Copyright © 2019 Elsevier Inc. All Rights Reserved.  Central control is modified Respiratory control by peripheral centre chemoreceptors Set points for O2, CO2 pH Chemoreceptors (carotid body) Respiratory muscles If 2 of these happen at the same time, the effect is more than additive Increased PCO2 and/or Stimulus reduced decreased PO2 Increased frequency and depth of breathing During quiet breathing During forceful breathing Respiratory system Bridge, Nick, Master of Health Education, Applied Anatomy & Physiology, Chapter 17, 305-328 Control of breathing. ( Source: Patton KT, Thibodeau GA, editors. Anatomy and physiology, 9 ed. London: Elsevier Health Sciences; 2015.) Copyright © 2020 Copyright 2020 Elsevier Australia. Summary Other influences on control of breathing Voluntary control Useful for communication e.g. speaking, but limited in extent Ventilation can be increased or reduced due to Other CNS areas emotion; also transient effects such as gasping, e.g. for emotion sobbing etc Information from motor cortex related to level of effort Motor cortex e.g. involved in exercise feeds into respiratory control centre during exercise Additional functions of the lungs Additional functions of the lungs The lungs can inactivate vasoactive substances such as Bradykinin. Convert angiotensin I to Angiotensin II. Act as a blood reservoir. Heparin producing cells are abundant in the capillaries where small clots may be trapped. Immunological surveillance and repair Acid Base balance Covid 19 Some additional reading – for interest only -  Covid-19 Stage 1 Asymptomatic, likely binds to epithelium in nasal cavity and replicates.ACE2 is main receptor Stage 2 Upper airway and conducting airway ;propagates down respiratory tract along conducting airways. Stage 3 20 % infected patients will proceed to Stage 3. Virus now reaches gas exchange units of lung and infects alveolar Type II cells in preference to Type I. This leads to apoptosis of cells, diffuse alveolar damage with fibrin rich hyaline membranes. Aberrant wound healing may lead to more severe scarring and fibrosis than other forms of ARDS. European Respiratory Journal 2020 55: 2000607; DOI: 10.1183/13993003.00607-2020  Pathophysiology “Autopsy studies have revealed that patients who died of respiratory failure had evidence of exudative diffuse alveolar damage with massive capillary congestion, often accompanied by microthrombi. Hyaline membrane formation and pneumocyte atypical hyperplasia are common. Pulmonary artery obstruction by thrombotic material at both the macroscopic and microscopic levels has been identified. Patients also had signs of generalised thrombotic microangiopathy. Severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes has been noted. Other findings include bronchopneumonia, pulmonary embolism, alveolar haemorrhage, and vasculitis. Significant new blood vessel growth through intussusceptive angiogenesis distinguishes the pulmonary pathology of COVID-19 from severe influenza infection.” https://bestpractice.bmj.com/topics/en-gb/3000201/aetiology  Acute Respiratory Distress Syndrome ARDS can be triggered by: an infection such as pneumonia and severe flu blood poisoning (sepsis) a severe chest injury inhaling vomit, smoke or toxic chemicals near drowning acute pancreatitis – a serious condition where the pancreas becomes inflamed over a short period of time an adverse reaction to a blood transfusion British lung foundation