Respiratory Pathology Part 1: Normal Function PDF

Respiratory Pathology: Part I Normal Function Dr Sarah Knight Marvar Department of Pharmacology & Physiology Office: Med-Dent NE412 Email: [email protected] 1 Source text: Robbins & Cotran Pathologic Basis of Disease Learning Outcomes Describe the anatomy of the healthy lung, including the struc...

Respiratory Pathology: Part I Normal Function Dr Sarah Knight Marvar Department of Pharmacology & Physiology Office: Med-Dent NE412 Email: [email protected] 1 Source text: Robbins & Cotran Pathologic Basis of Disease Learning Outcomes Describe the anatomy of the healthy lung, including the structure of the conducting airways and alveoli. Understand normal lung function such as normal lung volumes, gas concentrations and the mechanism of gas exchange. Discuss Obstructive lung disease and characteristic changes in lung volume tests. Describe the pathology of short term airways responses in asthma as well as long-term changes, triggers, symptoms and treatments Discuss the etiology of COPD and characteristic symptoms and causes Describe the pathology of Bronchitis, symptoms, triggers and long-term changes to the lungs. Discuss the causes of Emphysema and the structural and functional changes that occur as a result of the disease. 4 Airways Cartilage Conducting Airways No gaseous exchange: Anatomical deadspace Location of obstructive airway disease Respiratory Airways Gaseous exchange Smooth Muscle https://basicmedicalkey.com/pulmonary-disease/ Alveoli 6 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Respiratory System Function: Ventilation Inspiration Primary muscles: diaphragm (and intercostals) Chest volume increases, air moves in In order for air to get into the lungs, the pressure inside the lungs must be lower than atmospheric pressure Expiration Primary muscles: none Diaphragm relaxes and lung elastic recoil decreases volume and increases intrathoracic pressure and pushes air out Lung elasticity/recoil is important for removing air out of the lungs Air moves through airways (bronchi) Large diameter dividing into small diameter Have muscle in wall that controls their size Bronchoconstriction – smaller (narrower) Bronchodilation – bigger (wider) Dependent on elastic elements in lungs and surface tension Control of ventilation Voluntary, CO2, O2, pH, lung stretch, pain Gas Exchange Surface – Alveolar Epithelium Oxygen into pulmonary circulation Carbon dioxide into alveolus Blood-air barrier Thin, high surface area Lined by water Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Surfactant important to reduce surface tension Robbins and Cotran Pathological Basis of Disease Lung Compliance vs Elasticity Compliance depends on the elasticity and surface tension of the lungs. Compliance is inversely related to the elastic recoil of the lungs, so thickening of lung tissue will decrease lung compliance Surfactant secreted by type II pneumocytes increases lung compliance by reducing the force of surface tension Airway resistance refers to resistance in the respiratory tract to airflow. Symptoms & History Symptoms Symptom description or observation: breathing rate, cough, cyanosis, pain? Lung function testing, blood gas analysis, chest X-ray History Chronic, acute or episodic Environmental, exposure, lifestyle factors https://medlineplus.gov/emphysema.html Diagnostic Tests: Pulmonary Function Tests (PFT) FVC - forced vital capacity FEV1- forced expiratory volume in 1 second 11 Spirometry - Pulmonary Volume test 5.0 3.0 2.5 VT – Tidal Volume IRV – Inspiratory reserve volume ERV – Expiratory reserve volume VLC – Vital lung capacity RV – Residual volume TLC – Total lung capacity RFV – Functional residual volume https://doctorlib.info/physiology/medical/143.html 0 Diagnostic Tests: Pulmonary Function Tests (PFT) FVC - forced vital capacity FEV1- forced expiratory volume in 1 second Total lung capacity (TLC) Tidal volume Diffusion capacity Arterial Blood Gas Measurements Hypoxemia: low O2 levels in blood (Hypoxia = low O2 in tissues) Hypercapnia: high CO2 levels in blood (hypocapnia = low CO2) O2 saturation: below 90% indicates hemoglobin carrying issue or hypoventilation Acidosis: low pH Respiratory acidosis – as a result of reduced lung function Metabolic acidosis – eg. as a result of kidney failure Alkalosis: high pH Respiratory alkalosis – eg. hyperventilation Metabolic alkalosis – eg. Increased bicarbonate production Obstructive Lung Disease 15 Diseases of the Respiratory System Obstructive lung diseases Asthma: increased constriction of smooth muscle in bronchioles, increased mucus secretion and inflammation Chronic Obstructive Pulmonary Diseases (COPD): chronic long lasting airway resistance, mainly due to smoking: encompasses bronchitis & emphysema Edema: fluid in lungs Restrictive lung diseases Pulmonary fibrosis Chest wall weakness eg ALS Medical Terminology Dyspnea – difficulty breathing, shortness of breath Tachypnea – high respiratory rate Accessory muscle use – using extra muscles to breathe Cyanosis – blue color to the skin Hypoxemia/hypoxia – low oxygen in the blood/tissues Hypercapnea – high CO2 in the blood Cyanosis 17 Dynamic Lung Volumes Obstructive diseases result from difficulties in getting air through the airways because of an increased resistance to the air flow Decreased FEV1 - forced expiratory volume in 1 second 18 Obstructive Lung Disease Increase in resistance to airflow due to diffuse airway disease, Can affect any level of the respiratory tract Reduced FEV1/FVC (below 0.7) Can have: 1. 2. 3. Acinar enlargement Bronchial component – enlarged/increased mucous glands Narrowing of small airways from inflammation Examples of Obstructive Diseases Asthma Bronchitis Emphysema Cystic Fibrosis a1-antitrypsin deficiency Asthma Acute expiratory airway obstruction caused by inflammation, airway edema & smooth muscle contraction (bronchoconstriction) partly reversible. Symptoms include: wheezing, shortness of breath, chest tightness & cough. Acute asthma attack – status asthmaticus Asthma Types Atopic Asthma: hypersensitivity reaction, usually appears in childhood with family history Non-Atopic Asthma: no allergen sensitization, respiratory infection Occupational Asthma: triggered by fumes, dusts, gases or other chemicals eg. formaldehyde Drug-Induced Asthma: aspirin and other NSAIDS Inflammation in response to triggers leads to smooth muscle constriction, increased airway edema, and thickened mucus Small airways affected preferentially Asthma Pathogenesis - Triggering Triggers for asthma exacerbation: Infections - viral respiratory: RSV, rhinovirus Allergens - dust, pets, cockroaches, molds Other - cold air, exercise, irritant exposure – smoking, occupational Exaggerated Th2 response Th2 cells secrete cytokines and stimulate B cells to make IgE, Eosinophil recruitment IgE binds to mast cells = degranulation (histamine release) Asthma Pathogenesis – Early Stages Bronchoconstriction, mucous production & vasodilation Bronchoconstriction Vagus nerve stimulation: Direct & indirect (via mast cell degranulation) Leukotrienes - Direct action of inflammatory mediators Mucus production, airway edema (increased vascular permeability) Early reaction – reversible with rescue medications Asthma Pathogenesis – Late Stage Leukocyte recruitment: eosinophils, neutrophils & other T cells Epithelial damage, increased mucus production and gland hyperplasia Airway remodeling: hypertrophy of smooth muscle, increased reactivity to triggers Airway narrowing Maintenance medication (eg. Inhaled steroids) may reduce remodeling progression Asthma: Symptoms Dyspnea, chest tightness, coughing, increased respiration rate (tachypnea), wheezing Can present as cough only (cough-variant) or induced only with exercise (exercise-variant) Acute severe asthma can last for weeks so that cyanosis or death can ensue. Exam: Increased airflow obstruction, difficulty exhaling, accessory muscle use, tachypnea Blood gas analysis: Hypoxemia and respiratory alkalosis, can progress to acidosis as obstruction worsens Obstruction can be relieved through therapy. Asthma: Causes Genetic Susceptibility Multigenic and associated with other allergic conditions eg. allergic rhinitis (hay fever), eczema & food allergies Predilection to develop IgE response to allergens Environmental Environmental Triggers Prematurity, lack of exercise City dwellers – increased exposure to airborne pollutants “Hygiene hypothesis” - early exposure to antibiotics, “cleaner” households, C-section delivery, declined infection exposure (especially parasites), declined outdoor play time Infections as Co-factors Age of onset Improvement of symptoms into adulthood Asthma: Treatment Multiple protocols for severity of symptoms, acute vs. maintenance medication Acute – quick-acting medication for exacerbations Maintenance – daily medication to prevent exacerbations Bronchodilators Dilate muscle in airway Short-acting (albuterol) and longacting Inhaled corticosteroids Reduce inflammation and mucus secretion Airway Resistance - Control Airway resistance (bronchomotor tone) is controlled mainly by parasympathetic bronchoconstrictor supply to smooth muscle. Adrenaline causes bronchodilation. CO2 adrenaline dilation (albuterol) β2 Smooth Muscle pulmonary stretch receptors - airway irritant receptors parasympathetic nerves + mast cells, white blood cells (histamine) pollutants eg. SO2, O3 constriction COPD & Smoking Risk for developing COPD is 30 x higher if you smoke https://www.history.com/news/cigarette-ads-doctors-smoking-endorsement Chronic Obstructive Pulmonary Disease (COPD) Chronic bronchitis and emphysema Most patients have some element of both (one may predominate) Risk factor: smoking (80% of COPD patients), lung irritant exposure Presentation: progressive dyspnea, cough, wheezing, weight loss, finger clubbing, cyanosis Progressive – worsens with time Risk Factors Chronic Bronchitis Persistent cough with sputum for at least 3 months in at least 2 consecutive years. Pathogenesis Exposure to noxious or irritating inhaled substances. 90% are smokers Mucus Hypersecretion: enlargement of mucus glands in large airways & increased goblet cells in small airways Inflammation: acute & chronic inflammatory responses involving neutrophils, lymphocytes & macrophages. Smoking directly inhibits ciliary function and mucus clearance Excess mucus impedes ciliary function and increases infection risk Infections trigger episodic exacerbations Chronic Bronchitis Chronic, productive cough and cyanosis Airway obstruction, V/Q mismatch and pulmonary capillary vasoconstriction Hypoxemia leading to digital clubbing, cyanosis, and cor pulmonale Decreased respiratory drive leads to hypoventilation and increased CO2 retention Chronic hypercapnia leads to reset of respiratory centers Ventilation now more regulated by O2 status (hypoxic drive) Emphysema Irreversible enlargement of airspaces distal to terminal bronchiole due to alveolar wall destruction Healthy airspaces Enlarged airspaces Loss of elastic tissue in lungs leads to dysfunctional lung recoil and ineffective expiration Functional obstruction 2 Types – different anatomical distribution Centriacinar Panacinar A. I. D'hulst et al European Respiratory Journal 2005 26: 204-213 Types of Emphysema Centriacinar Emphysema (95% cases) - Predominant in smokers with COPD - Central or proximal acini & respiratory bronchioles - Most prevalent in upper lobes Panacinar Emphysema - Most common in a-antitrypsin deficiency Entire acinar unit involved Most prevalent in lower lung lobes Exacerbated by smoking Long-term smokers can develop both Normal lung Centriacinar Panacinar Alpha 1 Anti-Trypsin Deficiency Autosomal recessive genetic disorder leading to deficiency in a-1 anti-trypsin protein production a-1 anti-trypsin normally inhibits protease activity (elastin) secreted by neutrophils Loss of elastic tissue in walls of alveoli reduces radial traction and airway collapse in expiration Can also cause liver damage and associated with vascular, renal, GI disease Smoking increases emphysema risk and severity Common in patients with emphysema under 45 years of age or non-smokers, with family history Rare (1% of patients with emphysema) https://www.nejm.org/doi/full/10.1056/NEJMra1910234 Emphysema: Pathogenesis Most commonly found in smokers Toxic injury and inflammation: inhaled smoke damage respiratory epithelium cause inflammation and parenchymal destruction Increased oxidative stress = endothelial damage & inflammation Epithelial cells and macrophages secrete inflammatory cytokines and chemotactic factors, proinflammatory cytokines. Protease – antiprotease imbalance: Neutrophils secrete elastase granules Capillary – alveoli interface is disrupted Alveoli hyperinflation, air trapping and barrel chest Emphysema Presentation Worsening dyspnea, accessory muscle use, pursed-lip breathing Barrel chest Weight loss Diagnosis Pulmonary function tests show obstruction and decreased diffusion capacity Lung hyperinflation on imaging Blood gases may be normal at rest, patients can over ventilate to compensate http://www.pathophys.org/copd/ https://en.wikipedia.org/wiki/Emphysema#/media/File:Bullus_emphasemaCT.png Cystic Fibrosis Autosomal recessive disease, defect on CFTR gene on Chromosome 7 CFTR is important in production of sweat, digestive fluids and mucous production Obstruction of the airways by thick tenacious mucous and frequent infections Chloride permeability of bronchial cell lumen is reduced and increased sodium reabsorption from airway, increasing mucous viscosity Therapy includes removal of mucous and bronchodilators