Lung Function UM1010 Lecture Notes PDF

Lung Function Dr Kathryn Taylor/ slides adapted from Dr Sue Jamieson Lesson Plan Outline various lung volumes and capacities and demonstrate their significance in defining normal or abnormal lung function Flow-volume loops in obstructive and restrictive conditions Pathophysiology of exa...

Lung Function Dr Kathryn Taylor/ slides adapted from Dr Sue Jamieson Lesson Plan Outline various lung volumes and capacities and demonstrate their significance in defining normal or abnormal lung function Flow-volume loops in obstructive and restrictive conditions Pathophysiology of examples of pulmonary disorders - chronic obstructive pulmonary disease (COPD) - asthma - pneumothorax - pulmonary embolism  Pulmonary Ventilation Pulmonary Ventilation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 38, 497-507 Respiratory passages. Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Control of Respiration Cloutier, Michelle M., MD, Respiratory Physiology, 10, 130-144 The three major elements of the respiratory control system. Sensors, including central and peripheral chemoreceptors and pulmonary mechanoreceptors, feed information to the respiratory control center. In turn, the respiratory control center sends... Copyright © 2019 Copyright © 2019 Elsevier Inc. All Rights Reserved. Lung Volumes and capacities  Minute Respiratory Volume The minute respiratory volume is the total amount of new air moved into the respiratory passages each minute. Tidal Volume X Respiratory rate 500 mls X 12 = 6 Litres /min Average minute respiratory volume = 6L/min  A diagram showing respiratory excursions during normal breathing and during maximal inspiration and maximal expiration. Pulmonary Ventilation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 38, 497-507 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved.  Lung volumes and capacities The total volume in the lungs is subdivided into named volumes and capacities Volumes Capacities Do not overlap Subdivisions of the total volume that are the Can not be further divided sum of two or more of the 4 basic lung When added together equal total lung volumes capacity  Volumes  Tidal volume (VT)  Inspiratory Reserve Volume (IRV)  Expiratory Reserve Volume (ERV)  Residual Volume (RV) Capacities Combination of Volumes Inspiratory Capacity (IC) = Functional Residual Capacity (FRC) = Normal values are a function of height, sex, Vital capacity (VC) = age, and to a lesser degree ethnic group. Total Lung Capacity (TLC) = Pulmonary Ventilation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 38, 497-507 A diagram showing respiratory excursions during normal breathing and during maximal inspiration and maximal expiration. Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved.  Volumes  Tidal volume (VT)  Inspiratory Reserve Volume (IRV)  Expiratory Reserve Volume (ERV)  Residual Volume (RV) Capacities Combination of Volumes Inspiratory Capacity (IC) = V T+IRV Functional Residual Capacity (FRC) = ERV+ RV Vital capacity (VC) = IRV+V T+ERV Total Lung Capacity (TLC) = IRV+V T+ERV+RV. Pulmonary Ventilation Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 38, 497-507 A diagram showing respiratory excursions during normal breathing and during maximal inspiration and maximal expiration. Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Relationships between volumes and capacities VC = IRV + VT + ERV VC = IC + ERV TLC = VC + RV TLC = IC + FRC FRC = ERV + RV  Lung volumes recorded by spirometry Note that functional residual capacity FRC and residual volume RV cannot be measured directly with this apparatus alone. IRV and ERV are inspiratory and expiratory reserve volumes respectively 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  Settings: Hospital Pulmonary Function Laboratory Or Physicians Office ( small scale) A practical application of Help in the diagnosis and management of patients with Respiratory pulmonary or cardiac disease Physiology- May be valuable in deciding if a patient can undergo Pulmonary surgery Function Tests May help evaluate a disability Simpler tests may be used in Epidemiological surveys e.g. to assess industrial hazards or prevalence of a disease in a community Rarely used as a definitive diagnosis  Ventilatio Hypoxaemia n and Hypercapnia diffusion Pulmonary Embolism disorders Pulmonary Hypertension COPD Cor Pulmonale Asthma Pulmonar Cystic Fibrosis y Obstructive circulation disorders disorders Respirator y Disorders Disorders of the pleura Interstitial Lung Disease Atelectasis Sarcoidosis Lung Restrictiv inflation e disorder Disorders s When would we assess lung function? Screening for the presence of obstructive and restrictive diseases Evaluating the patient prior to surgery Evaluating the patient's condition for weaning from a ventilator. If the patient on a ventilator can demonstrate a vital capacity (VC) of 10 - 15 ml/Kg of body weight, it is generally thought that there is enough ventilatory reserve to permit (try) weaning and extubation. Documenting the progression of pulmonary disease - restrictive or obstructive Documenting the effectiveness of therapeutic intervention There is a range of pulmonary function tests: Assessment of airways resistance Lung volumes (spirometry) Pulmonary diffusing capacity Arterial blood gases Exercise capacity Lung/chest compliance Pulmonary Function Tests Static lung functions- VOLUMES AND CAPACITIES Static lung volumes measure the maximal effort generated only at the beginning and end of the manoeuvre. Tests based on volume not airflow Dynamic lung function- VOLUME AND VELOCITIES Dynamic lung volumes and flows are assessed during forced inspiration or expiration, or during forced breathing when maximal effort is applied throughout the respiratory manoeuvre. Tests based on time not just volume Static Lung Volumes and capacities  Tests of ventilatory capacity The majority patients with lung disease have abnormal FORCED EXPIRATION It is a simple and informative test of VENTILATORY CAPACITY The FEV 1 is the volume of gas exhaled in 1 sec by a forced expiration from a full inspiration The vital capacity is the TOTAL volume of gas that can be exhaled after a full inspiration.  Printout Spirometry Spirometers vary widely - the ones Screen we use look like this Mouthpiece The general principal is that as air is blown through the turbine, the flow rate is measured and used to calculate the volume Turbine (flow meter) If the details of the participant are entered (age, sex, race, height, weight) then they can be used to calculate the percentage of a normative value  Slow Vital Capacity (SVC or VC) manoeuvre (static) 1. Put on noseclip 2. Inhale maximally 3. Put mouthpiece into mouth 4. Blow out fully, stopping only at maximal exhalation 5. Remove mouthpiece without inhaling through monitor These measurements are useful because they are not limited by constriction of the airways (there is no time restriction for inhalation or exhalation) and do not require a lot of motivation and effort from the patient Forced Vital Capacity (FVC) manoeuvre (dynamic) This is the same as the SVC except that the patient needs to BLOW as HARD and FAST as possible during the exhalation stage You would normally repeat the measure three times, and take the best of the three It is not a comfortable procedure and the patient may need a rest between each attempt A disadvantage of this procedure is that it requires a lot of effort and motivation from the patient; if they are in pain or feel unwell, they may not fully inhale or exhale, or may make little effort. You would normally perform a slow VC in addition to this, if you wanted to assess static volumes and capacities Measurements FEV1 Forced expiratory volume in 1 second This measures how much air you can blow out in 1 second, so reflects the rate of airflow. It can be used to gauge whether the airway is narrowed e.g. in asthma FVC Forced Vital capacity This measures the total volume of air you can blow out after a maximal inhalation It can be used as an independent measure of pulmonary function but it is also used in a ratio with FEV1 Forced Expiratory Volume in 1 second (FEV 1 and Forced Expiratory Ratio (FER) (dynamic) In this procedure, the patient is asked to take a deep breath in and blow out as fast and as far as possible The FEV1 (Forced Expiratory Volume in 1 second) is a measure of the rate of air flow – the higher the value, the faster the flow The FVC (Forced Vital Capacity) is the total volume the patient can exhale forcibly The ratio of FEV1 to FVC (FER) is a measure of the patency of the airway –f the value is below 80% it suggests that the airway is constricted  A disorder which restricts the expansion of the lungs May be caused by stiffness of the lungs or chest wall, weakness of the muscles or damaged nerves Examples: Restrictive disorder - Pulmonary fibrosis - Sarcoidosis (an autoimmune immune disease) - Obesity - Muscular dystrophy A disorder in which the airways are narrowed Obstructive Air is exhaled more slowly than normal disorder Residual volume may be higher than normal Examples - Chronic obstructive lung disease (COPD) including chronic bronchitis and emphysema - Asthma - Cystic fibrosis_ West,J,Luks,A.2013.Pulmonary Pathophysiology,Walters Klewer, Philadelphia Researchgate.net Obstructive Respiratory Diseases Make it more difficult to get air out of the lungs. Decrease FVC; Increased TLC, RV, and FRC Restrictive Respiratory Diseases Makes it more difficult to get air into the lungs. They “restrict” inspiration. Decreased VC; Decreased TLC, RV, FRC  The patient sits in a sealed box, breathing from the outside air Whole body plethysmogra The changes in thoracic phy volume during breathing cause changes in the box pressure This can be used to measure any of the lung volumes, but is particularly useful for measuring airways resistance, TLC and RV Although there are normative values for FVC and FEV1, it is difficult to diagnose a problem with these values alone A low FEV1/FVC ratio indicates an obstructive pattern, whereas a normal value indicates either a restrictive or a normal pattern In a restrictive disease, you might expect both to be low, so the ratio could be normal If the FEV1/FVC ratio is normal, a low forced vital capacity value indicates a restrictive pattern, whereas a normal value indicates a normal pattern.  Peak Expiratory Flow Rate (PEFR) (dynamic) Take a deep breath in BLOW as fast and as hard as possible It is not necessary to exhale fully This gives you the maximum flow rate that the person can generate It is dependent upon the diameter of the airway, so can be used to detect airway obstruction This test can be affected by motivation and effort e.g. someone who is tired or in pain may not get a representative result Helium Used to measure residual volume dilution Helium does not cross the barrier between the alveoli and the blood The patient inhales gas of a known concentration from a container of known volume After breathing for several minutes, the concentration of helium in the lungs + container stabilises The concentration of helium can then be used to calculate the volume of the lungs + container (and therefore the TLC) The residual volume can be calculated by subtracting the VC from TLC Flow volume loops Spirogram displays airflow (in L) over time (sec) Flow volume loops displays airflow (in L/second) in relation to lung volume (in L) during maximal inspiration from complete exhalation (residual volume [RV]) and during maximum expiration from complete inhalation (TLC).  Flow-volume loops FEF 25% FEF 25% = forced expiratory flow at 25% of FVC FEF75% - forced expiratory flow at 75% of FVC FEF25-75 = average flow in the mid-section of expiration FEF 75% FEF at 25% - representative of flow in the large to medium air ways FEF at 75% - representative of flow in small airways (lower down in the lungs) FEF 25-75% - expiration not dependent on effort and marker of patency of smaller airways Typical patterns in obstructive and restrictive disorders Obstructive Narrowed airways Reduced peak flow, FEV1 and FER May take longer to reach FVC, measurement may be reduced Restrictive No airway narrowing Restricted inhalation/exhalation Peak flow may be normal FVC and FEV1 reduced FER may be unchanged or even increased West,J,Luks,A.2013.Pulmonary Pathophysiology,Walters Klewer, Philadelphia Researchgate.net Obstructive disorders Flow falls rapidly after the peak, resulting in concave flow- volume loop (remember that air in the larger airways is expired first) The large airways are patent so no obstruction to airflow – peak flow may be normal or reduced Small airways may be obstructed so airflow is significantly reduced later in the exhalation FEF25-75 is reduced and the central part of the curve dips due to the reduced airflow FVC may be normal if the condition is not severe – the patient can exhale fully https://www.spirometry.guru/fvc.html Restrictive disorders In restrictive disorders, the patient is unable to inhale and exhale fully, so total lung volume is lower than normal The airways are not narrowed, so the peak flow is not always reduced FEV1 is usually reduced, however the reduction in FVC may result in FER (FEV1/FVC) appearing normal Because there is no airway narrowing, the shape of the flow-volume loop is normal, but the volume expired is reduced Mixed obstructive/restrictive disorders Patients may have mixed disorders (e.g. some forms of COPD), combination of lung disorders and non-pulmonary disorders. PFTs are likely to show characteristics of both e.g. scooped flow-volume loop, lower FVC and FEV1  Restrictive or Obstructive? Answer: OBSTRUCTIVE – low FEV1 (and FVC) and FER; improved by bronchodilator as is forced expiratory time http://internal.medicine.ufl.edu/files/2012/06/5.12.02-How-to-Interpret-Pulmonary-Function-Tests.pdf  Restrictive or Obstructive? Answer: RESTRICTIVE – FER is normal, but both FVC and FEV1 are reduced  Chronic obstructive Pulmonary Disease A disorder that develops over a number of years, usually as result of chronic exposure to pollutants e.g. cigarette smoking, occupational pollution Chronic Bronchitis Emphysema Inflammation of airways Alveolar walls break down Excessive production of sticky Large air spaces within the mucus lungs Coughing and wheeze Lungs become less elastic and more floppy breathlessness Epidemiology Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, causing 3.23 million deaths in 2019. Nearly 90% of COPD deaths in those under 70 years of age occur in low- and middle- income countries (LMIC). COPD is the seventh leading cause of poor health worldwide (measured by disability- adjusted life years) Tobacco smoking accounts for over 70% of COPD cases in high-income countries. In LMIC tobacco smoking accounts for 30–40% of COPD cases, and household air pollution is a major risk factor. https://www.who.int/news-room/fact-sheets/detail/chronic- obstructive-pulmonary-disease-(copd) Pathogenesis of Emphysema Lung Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 13, 495-548 Pathogenesis of emphysema.. Copyright © 2018 Copyright © 2018 by Elsevier Inc. All rights reserved.  What causes emphysema? Normal lung tissue The phagocytes attracted by the inflammatory mediators release enzymes including ELASTASE Elastase breaks down elastin in the alveolar walls Emphysema Reduced elastic recoil of lungs Alveoli and small airways tend to collapse during expiration, resulting in air trapping (results in reduced gas exchange) Breakdown of alveolar walls reduces surface area for diffusion of gases Scar tissue is laid down, which thickens the walls of the small airways causing permanent obstruction  The lungs are normally protected from elastase by α-1 antitrypsin, which is produced in the liver If the degree of inflammation results in more elastase than can be blocked by AAT, then damage to the lungs occurs (i.e. in COPD) α-1 Some people have a defective gene for AAT, and are at a much higher risk of COPD, even if they antitrypsi have never smoked or been exposed to high levels of pollution n (AAT) Smoking or pollution exposure can increase the risk much further AAT defect is an inherited disorder, which required both parents to pass on the defective gene – if an individual has only one defective gene, they do not have the disorder Pulmonary emphysema Lung Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 13, 495- 548 Pulmonary emphysema. There is marked enlargement of the air spaces, with destruction of alveolar septa but without fibrosis. Note the presence of black anthracotic pigment. Copyright © 2018 Copyright © 2018 by Elsevier Inc. All rights reserved.  What causes chronic Smoke and dust particles stick to surface of airways bronchitis? Dilation of blood Tissue becomes capillaries red and hot Damaged cells release inflammatory Swelling Increased leakiness of Escape of blood mediators capillary walls plasma and airway narrowing Increased Increased number and mucus Leukocytes (white blood cells) activity of goblet cells production attracted by mediators squeeze through leaky capillary walls Other types of Phagocytic leukocytes leukocytes increase engulf foreign particles inflammation Schematic representation of overlap between chronic obstructive lung diseases Lung Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 13, 495-548. Copyright © 2018 Copyright © 2018 by Elsevier Inc. All rights reserved. Schematic diagram of the effect of smoking on airway inflammation and structural components of alveolar walls—the latter by altering the relationship between elastase and α 1-antitrypsin (also called α1-protease inhibitor). Chronic obstructive pulmonary disease Weinberger, Steven E., MD, MACP, FRCP, Principles of Pulmonary Medicine, 6, 88  Schematic diagram of radial traction exerted by alveolar walls (represented as springs), acting to keep the airways open. A, Normal situation. B, Loss of radial traction as seen in emphysema. Chronic obstructive pulmonary disease Weinberger, Steven E., MD, MACP, FRCP, Principles of Pulmonary Medicine, 6, 88-106 Copyright © 2024 Copyright © 2024 by Elsevier, Inc. All rights reserved. Bullous emphysema Lung Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 13, 495-548 Bullous emphysema with large apical and subpleural bullae. (From the Teaching Collection of the Department of Pathology, University of Texas Southwestern Medical School, Dallas, Texas.) Copyright © 2018 Copyright © 2018 by Elsevier Inc. All rights reserved. Emphysema Respiratory System Disorders Hubert, Robert J., BS, Gould's Pathophysiology for the Health Professions, Chapter 13, 272-324 Emphysema. A, Normal alveolus. B, Emphysema. C, Air trapping. D,Upper micrograph, Normal adult lung. Lower micrograph, Pulmonary emphysema with characteristic dilated airspaces. (Courtesy of R.W. Shaw, MD, North York General Hospital, Toronto, Ont... Copyright © 2018 Copyright © 2018, 2014, 2011, 2006, 2002, 1997 by Saunders, an imprint of Elsevier Inc. Definition of Asthma Asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment. https://www.ncbi.nlm.nih.gov/books/NBK7223/ :https://cks.nice.org.uk/topics/asthma/background- information/prevalence/ Video : https://www.nhs.uk/conditions/asthma/ Asthma affects more than 300 million people worldwide including 11.6% of children aged 6 to 7 years. In the UK, over 8 million people, or approximately 12% of the population, have been diagnosed with asthma. However, some may have grown out of the condition, and 5.4 million people are receiving asthma treatment. Approximately 160,000 people in the UK are diagnosed with asthma each year, however, incidence rates went down by around 10% between 2008 and 2012. The incidence of asthma is higher in children than in adults. In early childhood, asthma is more common in boys than in girls, but by adulthood, the sex ratio is reversed. Asthma accounts for 2-3% of primary care consultations, 60,000 hospital admissions, and 200,000 bed days per year in the UK. Occupational asthma may account for 9–15% of adult-onset asthma. It is reported to be the most common industrial lung disease in the developed world. [Olin, 2014; BTS/SIGN, 2019; Mukherjee et al, 2016; British Lung Foundation, 2018] Hygiene hypothesis 4 fold increase in incidence in Western society One explanation for this trend is the hygiene hypothesis, where a lack of exposure to infectious organisms (and possibly nonpathogenic microorganisms as well) in early childhood results in defects in immune tolerance and subsequent hyperreactivity to immune stimuli later in life. https://cks.nice.org.uk/topics/asthma/background-information/prevalence/  Asthma Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or early in the morning. The hallmarks of asthma are intermittent, reversible airway obstruction; chronic bronchial inflammation with eosinophils; bronchial smooth muscle cell hypertrophy and hyperreactivity; and increased mucus secretion. Sometimes trivial stimuli are sufficient to trigger attacks in patients, because of airway hyperreactivity. Major factors contributing to the development of asthma include genetic predisposition to type I hypersensitivity (atopy), acute and chronic airway inflammation, and bronchial hyperresponsiveness to a variety of stimuli. What are the subclassifications of Asthma? Asthma - subclassifications Atopic Asthma This is the most common type of asthma and is a classic example of type I IgE–mediated hypersensitivity reaction Often triggered by allergens, dust, pollen- often preceded by eczema, urticaria, rhinitis, evidence of allergen sensitization Non-Atopic Asthma- common trigger - Resp virus- no allergen sensitization Drug-Induced Asthma- eg. Asprin Occupational Asthma e.g. triggered by fumes, dust, chemicals Sub classifications of Asthma Atopic Asthma (Revision Slide) This is the most common type of asthma and is a classic example of type I IgE–mediated hypersensitivity reaction It usually begins in childhood. A positive family history of atopy and/or asthma is common, and the onset of asthmatic attacks is often preceded by allergic rhinitis, urticaria, or eczema. Attacks may be triggered by allergens in dust, pollen, animal dander, or food, or by infections. A skin test with the offending antigen results in an immediate wheal-and-flare reaction. Non-Atopic Asthma Patients with nonatopic forms of asthma do not have evidence of allergen sensitization, and skin test results usually are negative. A positive family history of asthma is less common. Respiratory infections due to viruses (e.g., rhinovirus, parainfluenza virus) and inhaled air pollutants (e.g., sulfur dioxide, ozone, nitrogen dioxide) are common triggers. It is thought that virus-induced inflammation of the respiratory mucosa lowers the threshold of the subepithelial vagal receptors to irritants. Although the connections are not well understood, the ultimate humoral and cellular mediators of airway obstruction (e.g., eosinophils) are common to both atopic and nonatopic variants of asthma, so they are treated in a similar way. Drug-Induced Asthma Several pharmacologic agents provoke asthma, aspirin being the most striking example. Patients with aspirin sensitivity present with recurrent rhinitis, nasal polyps, urticaria, and bronchospasm. The precise pathogenesis is unknown but is likely to involve some abnormality in prostaglandin metabolism stemming from inhibition of cyclooxygenase by aspirin. Occupational Asthma Occupational asthma may be triggered by fumes (epoxy resins, plastics), organic and chemical dusts (wood, cotton, platinum), gases (toluene), and other chemicals. Asthma attacks usually develop after repeated exposure to the inciting antigen(s). Pathophysiology of Asthma Lissauer, Tom, MB, BChir, FRCPCH, Illustrated Textbook of Paediatrics, 17, 299-322 Pathophysiology of asthma. Copyright © 2022 © 2022, Elsevier Limited. All rights reserved.  Figure A shows the location of the lungs and airways in the body. Figure B shows a cross- section of a normal airway. Figure C shows a cross- section of an airway during asthma symptoms. Sinyor B, Concepcion Perez L. Pathophysiology Of Asthma. [Updated 2023 Jun 24]. Asthma Death — more than 1,200 people died of asthma in the UK in 2014 [ British Lung Foundation, 2018]. Annually, asthma causes an estimated 250,000 deaths worldwide [Olin, 2014]. Histopathologic features of bronchial asthma. Atopic bronchial asthma results from repeated immediate hypersensitivity reactions in the lungs with chronic late- phase reactions. A cross-section of a normal bronchus (A) and a cross-section of a bronchus with pathology. Schematic Diagram of Events in Pathogenesis of Antigen-Induced Asthma. A hypothetical series of complex interactions is shown, focusing on bronchoconstriction, mucus secretion, and airway inflammation. Ag, antigen; IgE, immunoglobulin E. Schematic Diagram of Events in Pathogenesis of Antigen-Induced Asthma. A hypothetical series of complex interactions is shown, focusing on bronchoconstriction, mucus secretion, and airway inflammation. Ag, Weinberger, Steven E., MD, MACP, FRCP, antigen; IgE, Principles of Pulmonary Medicine, 5, 69- immunoglobulin E. 87  Lung Kumar, Vinay, MBBS, MD, FRCPath, Robbins Asthma Basic Pathology, Chapter 13, 495-548 (A and B) Comparison of a normal airway and an airway involved by asthma. Copyright © 2018 Copyright © 2018 by Elsevier Inc. All rights reserved. The classic atopic form is associated with excessive type 2 helper T (T H 2) cell activation. Cytokines produced by T H 2 cells account for most of the features of atopic asthma—IL-4 and IL-13 stimulate IgE production, IL-5 activates eosinophils, and IL-13 also stimulates mucus production. IgE coats submucosal mast cells, which on exposure to allergen release their granule contents and secrete cytokines and other mediators. Mast cell– derived mediators produce two waves of reaction: an early (immediate) phase and a late.  Initial trigger leads to the release of inflammatory mediators, and activation and migration of other inflammatory cells The inflammatory reaction is a T- helper type 2 (TH2) lymphocytic response Cd4+ lymphocytes secrete IL-4, Il-5,IL-13, TNF alpha, ltb-4, a product of the lipoxygenase pathway, as well as mast cell tryptase. This TH2 response is important in the initiation and prolongation of the inflammatory cascade The early-phase reaction is dominated by bronchoconstriction, increased mucus production, and vasodilation. Bronchoconstriction is triggered by mediators released from mast cells, including histamine, prostaglandin D2, and leukotrienes LTC4, D4, and E4, and also by reflex neural pathways. The late-phase reaction is inflammatory in nature. Inflammatory mediators stimulate epithelial cells to produce chemokines (including eotaxin, a potent chemoattractant and activator of eosinophils) that promote the recruitment of T H 2 cells, eosinophils, and other leukocytes, thus amplifying an inflammatory reaction that is initiated by resident immune cells. Mediators and treatment of asthma Allergy Abbas, Abul K., MBBS, Cellular and Molecular Immunology, Chapter 20, 459-479 Mediators and treatment of asthma. Mast cell– derived leukotrienes and platelet-activating factor (PAF) are thought to be the major mediators of acute bronchoconstriction. Therapy is targeted at reducing mast cell activation with anti–immunoglobuli... Copyright © 2022 Copyright © 2022 by Elsevier Inc. All rights reserved. Summary -Triggers Infections Allergic triggers Air pollution Exercise Occupations Drugs -asprin Other conditions – churg-strauss, aspergillosis, GORD Causes Many factors have been linked to an increased risk of developing asthma, although it is often difficult to find a single, direct cause. genetic predisposition Asthma is more likely if other family members also have asthma – particularly a close relative, such as a parent or sibling. Asthma is more likely in people who have other allergic conditions, such as eczema and rhinitis (hay fever). Atopic individual Urbanization is associated with increased asthma prevalence, probably due to multiple lifestyle factors. Events in early life affect the developing lungs and can increase the risk of asthma. These include low birth weight, prematurity, exposure to tobacco smoke and other sources of air pollution, as well as viral respiratory infections. Exposure to a range of environmental allergens and irritants are also thought to increase the risk of asthma, including indoor and outdoor air pollution, house dust mites, moulds, and occupational exposure to chemicals, fumes or dust. Children and adults who are overweight or obese are at a greater risk of asthma. Treatment Asthma cannot be cured but there are several treatments available. The most common treatment is to use an inhaler, which delivers medication directly to the lungs. Inhalers can help control the disease and enable people with asthma to enjoy a normal, active life. There are two main types of inhaler: bronchodilators (such as salbutamol), that open the air passages and relieve symptoms; and steroids (such as beclometasone) that reduce inflammation in the air passages, which improves asthma symptoms and reduces the risk of severe asthma attacks and death. People with asthma may need to use their inhaler every day. Their treatment will depend on the frequency of symptoms and the types of inhalers available.  A chronic inflammatory condition of the airways Asthma Inflammation causes airways hyperresponsiveness Increased sensitivity to stimuli causes airway narrowing The response is reversible by bronchodilator drugs Exercise-induced asthma A small number of patients are never able to blow reproducible flow-volume loops Due to exercise-induced asthma. The forced manoeuvre of the FVC can cause an asthma attack in reactive patients. The results of every following flow- volume loop will be worse than the previous trial. Red =1 st manoeuvre  Infection Biggest risk factor is a Allergens genetic predisposition for an allergic Exercise response mediated by irritants the antibody IgE Histamine and Mediators released from leukotrienes mast cells and certain types of white blood cells Inflammation of Broncho- mucosa lining constriction airways (swelling) (smooth muscle) Excess mucus production  Mucus production Airway swelling Airway smooth Reduced ventilation muscle contraction Asthma Reduced surface area for gas exchange Reduced perfusion Hypoxaemia and Hypercapnia Too little oxygen in the blood Too much carbon dioxide in the blood Normal values - Partial pressure of oxygen Normal values - Partial (PaO2): 75 to 100 mm Hg (10.5 pressure of carbon dioxide to 13.5 kPa) (PaCO2): 38 to 42 mm Hg (5.1 to 5.6 kPa) Reduced ventilation Reduced surface area for gas exchange Reduced perfusion of the lungs Factors contributing to hypoxaemia and/or hypercapnia in disease Mucus production Airway swelling Air trapping Reduced ventilation Airway collapse Chronic Reduced surface Breakdown of alveolar Obstructive lung area for gas walls Air trapping exchange disease Reduced perfusion Pulmonary Embolism Pulmonary embolism occurs when thrombi form in large veins and travel to the lungs, become lodged and occlude pulmonary circulation. Pathogenesis: often arise from deep veins of lower extremities but can originate from upper extremities, right side of heart and pelvic veins. Venous thrombi tend to form due to 3 important conditions: Virchow’s triad Stasis of blood Alterations in blood coagulation system Abnormalities of the vessel( intimal injury) Pulmonary Embolism May be limited due to pain Reduced ventilation Pulmonary Reduced surface embolism area for gas exchange Reduced perfusion Reduced blood flow to area of lung with blockage Pulmonary Embolism Diagnosis Different sized emboli occur : small, medium, massive Diagnosis can be made using a CT pulmonary angiogram or a ventilation perfusion scan Restricted blood flow can damage part of the lung, often haemorrhage and atelectasis, alveolar structures remain viable ( rarely infarction/ unless Pneumothorax May be limited due to pain Part of lung collapsed Reduced ventilation so not ventilated Reduced surface Pneumothorax area for gas Part of lung collapsed exchange May be reduced Reduced perfusion blood flow to affected area Reduced cardiac output Pneumothorax When air enters the intrapleural space pneumothorax occurs and lung collapses Normal pressure outside the lung is sub atmospheric ; introduction of air into the intrapleural space raises the pressure to atmospheric and the lung collapses inward Both the chest wall and thoracic cage have elastic properties and under equilibrium the chest wall is pulled inward and the lung is pulled outwards  Age-related changes to the respiratory system Generalised loss of neurological and muscular function results in reduced Reduction in muscle effectiveness of cough reflex mass and power Reduced muscle power means that measurements involving an element of force (FVC, and FEV1) are reduced Compliance of lung tissue increases with gradual breakdown of elastic elements Changes in pulmonary Compliance of the chest wall decreases due to stiffening of intercostal muscles compliance and kyphosis - this is more important than the changes to lung compliance in reducing lung function Alveolar surface are decreases with age due to gradual breakdown of alveoli Reduction in Diffusion distance increases due to thickening of the alveolar walls diffusing capacity Small airways collapse due to loss of elasticity, reducing surface area Reduction in sensitivity of peripheral and central chemoreceptor function Decline in control of (reduction in hypoxic response of 51% and hypercapnic response 41% by age 73 breathing (Lewis, nd)) Reduction in central integration system function http://www.heart-health-for-life.com/improving-lung-function.html Learning Outcomes UM1010 Basic methods of assessing lung function by spirometry Outline Interpretation of lung function tests and how this relates to disease Lung volumes and capacities Some uses and limitations of tests