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Biology of Disease CH0576 Respiratory Disorders I Dr Suad Awad [email protected] Room A305 Ellison’s- Ext 3816 1 Lecture Objectives * Identify lung volumes & capacities * Explain effect of relevant pressures in pulmonary ventilation * Discuss causes and consequence of Pneumothorax * Explain the aetiology of obstructive lung disease * Discuss causes and pathological features of Asthma * Explain the basis of pulmonary compliance * Discribe pathological features of Respiratory Distress Syndrome 2 Lecture Outline * Spirometry: Lung Volumes & Capacities * Pneumothorax * Resistance to Airflow * Chronic Obstructive Lung Diseases: Asthma * Pulmonary Compliance: Respiratory Distress Syndrome 3 Lung Volumes & Capacities Classic Spirometer Spirometry: Measure air entering or leaving lung Change in Lung Volume 4 Fig 26-1A- Boron Lung Volumes & Capacities Inspiration: Upward deflection, Expiration: Downward deflection TV= Tidal volume IRV= Inspiratory Reserve Volume Max volume inhaled at end of quiet inspiration ERV= Expiratory Reserve Volume Max volume expired at end of quiet expiration RV= Residual Volume Air remaining in lung after max exp effort Fig 26-1B- Boron RV= Can not be measured 5 by a Spirometer Lung Volumes & Capacities TLC= Total Lung Capacity Sum of all 4 volumes FRC= Functional Residual capacity Sum of ERV + RV Air remaining after quiet expiration IC= Inspiratory Capacity Sum of IRV + TV max inspired volume after a quiet expiration VC= Vital Capacity Sum of IRV + TV + ERV max inspired achievable tidal volume Fig 26-1B- Boron Any capacity that includes the RV can not be measured6 by a Spirometer Lung Volumes & Capacities FEV1 Forced Expiratory Volume in One Second ~ 80% VC in Healthy Young Adults Affected in Pulmonary Disorders with increased Airway resistance Eg Asthma Fig 26-1B- Boron 7 Lung Volumes & Capacities Volumes & Capacities Typical Ranges (L) IRV (Inspiratory Reserve Volume) TV (Tidal Volume) 1.9- 2.5 0.4- 0.5 ERV (Expiratory Reserve Volume) RV (Residual Volume) TLC (Total Lung Capacity) 1.1- 1.5 1.5- 1.9 4.9- 6.4 IC (Inspiratory Capacity) 2.3- 3.0 FRC (Functional Residual Capacity) VC (Vital Capacity) 2.6- 3.4 3.4- 4.5 8 Spirometry: FEV1/VC ratio • FEV1 This is the forced expiratory volume in one second. It reflects airway narrowing and is relatively independent of effort • FVC = the forced vital capacity Normally FEV1 = 70%-80% of the FVC FEV1 and FVC used to differentiate between Obstructive and Restrictive patterns of lung disease 9 Peak Flow Metre • Peak Expiratory Flow Rate (PEFR) is defined as the highest air flow (Vol/time) achieved at the mouth during a forced expiration • It is a measure of the existence and severity of airflow obstruction • The PEFR obtained by a patient is compared to that of a normative standard (use height, age, gender). It is calculated as % of the expected PEFR. 10 Peak Flow Meter Measured by modern Spirometry: Next Lecture 11 FRC Functional Residual Capacity Volume of air remaining in the lungs at the end of a quiet expiration Determined by the lung and chest wall elastic recoils 12 Factors affecting Ispiratory & Expiratory Reserve Volumes * Current Volume The greater the current volume, the less are the reserve volumes * Lung Compliance A measure of how easy to inflate the lungs * Muscle Strength * Comfort * Posture Problems with innervation - muscle weakness Pain (injury) limit desire or ability to make insp efforts Recumbent position = IRV falls- Difficult for diaphragm to move abdominal contents * Flexibility of Skeleton Arthritis, Kyphoscoliosis = Reduce IRV 13 Important Pressures in Pulmonary Ventilation * Atmospheric Pressure - Barometric pressure * Intra-alveolar Pressure - Pressure within the alveoli Fluctuates during breathing cycle: -ve inspiration, +ve expiration * Intrapleural Pressure - Pressure inside the thoracic cavity Less than Barometric P (-ve) 14 Pneumothorax • Occurs when the Intrapleural Pressure equilibrates with atmospheric P. As a result lungs collapse - inherent elastic recoil • Traumatic Pneumothorax - caused by the chest wall being punctured • Spontaneous Pneumothorax 1. Due to a hole in the wall of the lung 2. Congenital defect in connective tissue in alveolar wall 15 Pneumothorax Traumatic COLLAPSED LUNG Spontaneous 16 Pneumothorax 17 Factors Influencing Airflow Through the Lung Airflow (F) depends on: 1. Pressure Gradient PDifference between atmospheric pressure and intra-alveolar pressure. 2. Resistance of Airways (R)Determined by the radii of the airways F is inversely related to R F = P/R 18 Resistance to Airflow F = P/R • Main determinant of resistance to airflow (R) is the RADIUS of the conducting airways • In the healthy lung the radius is relatively large and so R is low • The airways normally offer such a low resistance that only small pressure gradients are needed for adequate airflow into the lung 19 Adjustment of Airway Size • Normally modest changes in airway size, to meet the body’s needs, are achieved through the AUTONOMIC nervous system • In quiet respiration Parasympathetic stimulation promotes bronchiolar smooth muscle contraction causing Bronchoconstriction Maintains muscle tone in airways • Sympathetic stimulation brings about Bronchodilation by bronchiolar smooth muscle, Decreasing airway resistance during exercise, fight or flight situations 20 Pulmonary Diseases Associated with Narrowing of the Airways • Increased Resistance is an extremely important impediment to airflow when airways become narrowed due to disease: CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) • COPD is a group of lung diseases including Chronic Bronchitis, Asthma and Emphysema • COPD is characterised by Increased Airway Resistance 21 Chronic Obstructive Pulmonary Disease * Sufferers have to work harder to breathe • F = P/R When resistance is increased, a larger pressure gradient is needed to maintain a normal airflow. e.g. If resistance is doubled by narrowing of airway lumens, P must be doubled through increased respiratory muscle workload • Expiration is more difficult to accomplish than inspiration giving rise to the characteristic ‘WHEEZE’ as air is forced out of narrow airway 22 Chronic Obstructive Lung Diseases (COPDs) Aetiology: • Group of diseases in which there is a chronic limitation to airflow • Flow is reduced for one of two reasons: 1. Narrowing of the Airways causing increased resistance - Asthma, Chronic Bronchitis 2. Loss of Elastic Recoil - Reduction in the outflow pressure - Emphysema 23 Asthma • Asthma is the Greek word for ‘Breathless’ or ‘to breathe opened mouthed’ • It is caused by Chronic Inflammatory Responses in the airways • This leads to REVERSIBLE airway obstruction. • It is characterised by breathlessness and wheezing caused by generalised narrowing of intrapulmonary airways 24 Causes of Asthma Asthma is a heterogeneous disease triggered by a variety of inciting agents (Genetic + Environ) • Extrinsic Factors Caused by Type I hypersensitivity reactions on exposure to extrinsic allergen (pollen, perfume, dust mite, others?) • Intrinsic Factors Non-immune trigger mechanism e.g. hormonal, stress, exercise 25 Asthma There are three main features of asthma: Remember: (F = P/R) 1. Muscle Spasm – Bronchospasm (Narrowing of airway lumen- increased airway R) 2. Mucus Plugging- (air trapping in distal bronchioles- increased RV, and relevant volume & capacities; eg? ) 3. Mucosal Oedema- (Narrowing of lumen- increased R- increased pressure- increased work for respiratory muscles) 26 Pathological Features of Asthma * Mucosal Oedema - Inflammatory cell infiltration (Eosinophils 5%-50%) - Basement membrane thickening - Goblet cell and submucosal gland hyperplasia - Hypertrophy and hyperplasia of the smooth muscle in the bronchial wall These events lead to - Airway Obstruction Bronchial Muscle Constriction Airway Congestion 27 Early phase response in asthma Dust mite, pollen Other?? SM spasm followed By inflammation Lamina propria Histamine induces SM contraction Through H1 Rs 28 Late phase response in asthma Eosinophill Infiltration, (MBP, ECP) Loss of Epithelial Cells Increased mucus secretion Edema SM Hypersensitivity (histamine), Infiltration of Basophils & Neutrophils 29 Pathological Features of Asthma 30 Bronchioles in Asthma 31 Features of Asthma in Status Asthmatics • Lungs are Overdistended - Due to trapped air • May be small areas of Atelectasis • The most striking feature is the blocking of bronchi and bronchioles with thick mucus plugs • The mucus plugs contain - Whorls of shed epithelium - Eosinophils - Charcot - Leyden Crystals 32 Charcot Leyden Crystals Crystallised Lysophospolipase Enzyme produced By Eosinophils Up to 50 m length Normally colourless Stains reddish by trichrome Indicative of a disease involving eosinophilic inflammation & proliferation 33 Asthma - Clinical Course • Severe Dyspnoea with wheezing • Hyperinflation of lungs, with air trapped distal to the bronchi which are constricted and full of mucus (which volumes & capacities are affected?) • This leads to Hypercapnia, acidosis and hypoxia • Asthma tends to be severely debilitating rather than lethal 34 COMPLIANCE • A factor influencing the pressure gradient P in the lung is the ELASTIC behaviour of the lung • This affects alveolar and lung volume, and therefore the pressure gradient needed to inflate lung • COMPLIANCE refers to how much effort is required to stretch or distend the lungs • Specifically Compliance is a measure of the change in lung volume due to a given change in transmural pressure (The Force That Stretches the Lung) C = V/ P 35 COMPLIANCE • A HIGHLY compliant lung stretches further for a given increase in pressure than does a LESS compliant lung (eg inflating a very flexible Vs stiff balloon) • A LESS compliant lung will require MORE Effort (P) to produce a given degree of inflation • A POORLY compliant lung is referred to as a ‘STIFF LUNG’ • Compliance is reduced in pulmonary diseases e.g. FIBROSIS of the lung 36 Factors Affecting Pulmonary Compliance Pulmonary compliance depends on various factors: 1. Highly Elastic Connective Tissue 2. Alveolar Surface Tension:- due to a thin liquid film lining each alveolus. It resists any force that increases surface area (thus OPPOSES expansion) 3. Pulmonary Surfactant:- Surface Active Agent - detergent ! produced by TYPE II alveolar cells, decreases surface 37 tension (70 dynes/cm Vs 25 dynes/cm) Pulmonary Compliance 38 Effect of Pulmonary Surfactant • It REDUCES the surface tension and contributes to lung stability • It acts by interspersing water molecules lining the alveolus, which reduces surface tension Benefits of Reducing Surface Tension: a) Increases pulmonary compliance - thus reducing the effort needed to inflate the lungs b) It stabilises the alveoli so they do not collapse at end of expiration 39 Newborn Respiratory Distress Syndrome • Surfactant produced by 34th wk gestation * Premature infants- Deficiency in lung surfactant leads to Newborn Respiratory Distress Syndrome • Very strenuous inspiratory efforts are required to overcome the high surface tension in the alveoli The lungs are Poorly Compliant • It may require transmural pressure gradients of 20-30 mm Hg (normally 4-6 mm Hg) to overcome the tendency of the lungs to collapse 40 NEWBORN RDS • The problem is compounded as the newborn’s muscles are still very weak • Deficiency in surfactant leads to alveolar instability and severe respiratory failure • Life threatening condition • Newborn RDS can be treated by: a) Artificially increasing atmospheric pressure b) Treating with exogenous surfactant 41 Useful Textbooks Rhoades & Bell, 3rd ed. Medical Physiology: Principles of Clinical Medicine. LWW Boron & Boulpeap, 2nd ed. Medical Physiology: Saunders 42