PATH375 Respiratory System PDF

PATHOLOGY 375 RESPIRATORY SYSTEM MIKE NIMMO, MD, FRCPC CLINICAL PROFESSOR DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE FACULTY OF MEDICINE, UNIVERSITY OF BRITISH COLUMBIA LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper,...

PATHOLOGY 375 RESPIRATORY SYSTEM MIKE NIMMO, MD, FRCPC CLINICAL PROFESSOR DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE FACULTY OF MEDICINE, UNIVERSITY OF BRITISH COLUMBIA LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 2 Nasopharynx Oropharynx Larynx Trachea Right and Left Bronchi Right Lung (upper, middle and lower lobes) Left lung (upper and lower lobes) Diaphragm 3 https://commons.wikimedia.org/wiki/File:Respiratory_system_complete_no_labels.svg https://commons.wikimedia.org/wiki/File:2313_The_Lung_Pleurea.jpg STRUCTURE AND FUNCTION Upper respiratory tract: – Structures: Nasal cavity, sinuses, nasopharynx. Larynx. – Function: Filter, warm, humidify air, speech. Lower respiratory tract: – Structures: Trachea, lungs. – Function: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/vocal-cord Air exchange. 4 STRUCTURE AND FUNCTION Branching of airways into smaller ducts: – Bronchi  bronchioles (terminal bronchiole respiratory bronchiole)  alveolar ducts  alveoli. Air exchange occurs in most distal spaces (alveoli). – Diffusion barrier: Alveolar pneumocyte, common basement membrane, endothelial cell. Respiratory defense mechanisms: – Mucus, mucociliary escalator. Sun S, et al. Nat Rev Cancer 2007;7:778-790. – Alveolar macrophages. – Cough/sneeze reflexes. Pulmonary circulation: – Dual blood supply. 5 https://upload.wikimedia.org/wikipedia/commons/b/ba/Blausen_0766_RespiratoryEpithelium.png PULMONARY MEDICINE/PATHOLOGY TERMS Dyspnea: – term used to describe subjective feeling of shortness of breath. Tachypnea: – increased rate of breathing (normal respiratory rate 12-20 per minute). Pneumothorax: – air in pleural cavity. Hemothorax: – blood in the pleural cavity. Pleural effusion: – fluid in pleural cavity. 6 PULMONARY MEDICINE/PATHOLOGY TERMS Pleuritis: inflammation of the pleura (membrane lining lungs). Atelectasis: – Term used to describe incomplete expansion of alveoli. – Causes: Compression of alveoli from outside. Resorption of air distal to obstruction. Deficiency of surfactant. 7 https://www.verywellhealth.com/understanding-atelectasis-2248927 LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 8 UPPER RESPIRATORY TRACT INFECTIONS - Involve structures of the upper respiratory tract (nose, oro/nasopharynx, larynx). - ‘Common cold’:  Most frequent illness in many countries.  Viral infection of mild upper respiratory tract with classic symptoms (nasal congestion, runny nose, sore throat, sneezing).  Handful of culprits, most common cause: Rhinovirus, coronavirus (not the three highly pathogenic species).  Self limited disease heals spontaneously.  Treatment: symptomatic relief (no antibiotics)!  May have similar upper respiratory tract symptoms to mild cases of ‘flu’ (influenza virus) and ‘COVID-19’ (SARS-CoV-2). 9 https://www.cdc.gov/coronavirus/2019-ncov/downloads/COVID19-symptoms.pdf https://www.aafa.org/media/2631/respiratory-illness-symptoms-chart-coronavirus-flu-cold-allergies.png Causes of sore throat and fever….. Strep throat: – Most common cause of bacterial pharyngitis in children and adolescents. – Caused by Streptococcus pyogenes (group A streptococcus). – Diagnosed by identifying the bacteria. – Treatment requires antibiotic therapy. – Complications: rheumatic heart disease, post- streptococcal glomerulonephritis. Diphtheria: – Greek: leather (describes tough pseudomembrane in the throat). – A bacterial infection (Corynebacterium diphtheriae) of the throat. – May be fatal, used to be leading cause of childhood death. 11 – Vaccine exists, uncommon in developed countries. https://commons.wikimedia.org/wiki/File:Strep_throat2010.JPG https://commons.wikimedia.org/wiki/File:Dirty_white_pseudomembrane_classically_seen_in_diphtheria_2013-07-06_11-07.jpg  12 https://immunizebc.ca/sites/default/files/graphics/vaccine-schedule-infants-children-2019-screen.pdf Causes of sore throat and fever…. Mononucleosis: – Aka. Infectious mononucleosis, mono, ‘kissing disease’. – A viral infection caused by EBV (Epstein-Barr virus). – 90-95% of adults are EBV seropositive (evidence of previous infection). – Spread via saliva (kissing, sharing eating utensils, drinking from same glass). – Triad of fever, tonsillar pharyngitis, and lymphadenopathy. – Treatment: supportive, symptomatic. – Splenomegaly common: Avoid athletic activities for 3 weeks after onset of symptoms, 4 weeks for contact sports (risk of 13 splenic rupture). https://jetem.org/infectious_mononucleosis/ https://www.mayoclinic.org/diseases-conditions/enlarged-spleen/symptoms-causes/syc-20354326 MIDDLE RESPIRATORY TRACT INFECTIONS Croup (3mo -3yo): – Typically due to parainfluenza virus (no specific treatment). – Acute viral infection of larynx in children. – “Barking seal” cough. – Causes a non-productive cough. Acute epiglottitis (3yo-7yo): – Infection of the epiglottis due to bacteria H. influenzae B. – May be life threatening (swelling and closure of airway). – Immunization. – No cough. Bronchiolitis (< 2yo): – Usually due to Respiratory Syncytial Virus. – Inflammation of bronchi and bronchioles (but not alveoli). – Non-productive cough. 14 LOWER RESPIRATORY TRACT INFECTIONS Inflammation/ infection of the lungs occurring in x two forms: – Alveolar (typical) pneumonia (intra-alveolar x x inflammation). Focal: bronchopneumonia. Diffuse: lobar pneumonia. Usually caused by bacteria. – Interstitial (atypical) pneumonia (inflammation of alveolar septa). Usually diffuse and bilateral. Usually caused by viruses or Mycoplasma pneumoniae. 15 https://scx2.b-cdn.net/gfx/news/2020/usingalveola.jpg https://i.pinimg.com/originals/05/97/13/05971322485a51eb88cfae4640bb8b4f.jpg TYPICAL PNEUMONIAS Infection affecting the air spaces characterized by a cough that produces sputum (productive cough), high fever, chills, dyspnea, tachypnea, prostration. Causative agents depend on where infection acquired. – Community acquired: Streptococcus pneumoniae, Hemophilus influenzae, Staphylococcus aureus. – Hospital acquired: Gram negatives (Escherichia coli, Pseudomonas aeruginosa). – Fungi, parasites and viruses may also cause pneumonia. Travel history is important (re: possible exposure), immunocompromised patients susceptible to unusual organisms. Routes of infection: – Inhalational (air droplets, most commonest cause), hematogenous (bacteremia), aspiration (infected secretions https://www.pathologyoutlines.com/topic/lungnontumorinfectionsgeneral.htm l 16 from upper respiratory tract or stomach contents). ATYPICAL PNEUMONIAS Infection affecting the interstitial lung tissue characterized by a non-productive cough. ‘Atypical’, historical term since several differences from typical pneumonia: – Symptoms: milder, ‘walking pneumonia’. – Chest x-ray findings. – Different response to antibiotics used for ‘typical’ cases. Bacteria: – Mycoplasma pneumoniae (most commonest cause of atypical pneumonia). – Legionella pneumophila. Viruses: – Influenza, parainfluenza, coronavirus (SARS, MERS, COVID-19). – May progress to secondary bacterial pneumonia. 17 https://commons.wikimedia.org/wiki/File:Respiratory_syncytial_virus_(RSV)_infection_x401.jpg PNEUMONIA COMPLICATIONS  If inflammation extends to pleural surface:  Pleuritis: inflammation of the pleura (membrane lining lungs).  Pyothorax: pus in the pleural cavity.  Empyema: pockets of pus in the pleural cavity.  Abscess.  Chronic lung disease.  Bronchiectasis: pus inside bronchi  destruction of walls and dilatation.  Destruction of lung parenchyma, fibrosis  honeycomb appearance. 18 Fig 8-9. Pathology for the Health Professions, 2012 LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 19 TUBERCULOSIS Infection due bacteria called Mycobacteria tuberculosis (Mtb). Mtb causes granulomatous reaction with caseous necrosis (type IV hypersensitivity reaction). Initial primary infection: – Characterized by Ghon complex = consists of a Ghon focus (localized granuloma in lung) along with pulmonary lymphadenopathy (enlarged hilar nodes). Mtb isolated within the granulomas preventing spread. – >90% cases Ghon complex heals spontaneously. 20 TUBERCULOSIS Secondary TB ( reinfection. – Tissue destruction facilitates intrapulmonary and extrapulmonary spread. Diagnosis: – Chest x-ray. – Mantoux tuberculin test. – Identifying acid fast bacilli in sputum or biopsy samples. – Culture, PCR. Management: – Not easily treated. – Several months of antibiotics. 21 – Patients need to be isolated. LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 22  OBSTRUCTIVE VS RESTRICTIVE AIRWAY DISEASE Chronic, non-infectious, diffuse lung disease physiologically classified as either: – Obstructive disease: Increased resistance to airflow, any level from trachea to alveoli. ↓ flow rate  air trapping. – Restrictive disease: Reduced expansion of lung with decreased total lung capacity. ↓ lung volume, ↓ compliance. Diagnosis made by pulmonary function tests. 23 https://www.physio-pedia.com/Pulmonary_Function_Test https://www.aastweb.org/blog/obstructive-lung-disease-vs-restrictive-lung-disease-causes-diagnosis-and-treatment-options OBSTRUCTIVE AIRWAY DISEASES 1. Chronic obstructive pulmonary disease (COPD). Chronic bronchitis. Emphysema. 2. Bronchiectasis. 3. Asthma. 4. Cystic fibrosis. 24 COPD Chronic bronchitis (‘blue bloaters’): – Clinical Dx: persistent cough with sputum for at least 3 months during 2 consecutive years. – Obstruction is due to narrowing of airways caused by thickened mucosal lining and increased mucus. 25 https://meetings.ami.org/2018/wp-content/uploads/2018/07/tseng_a_18I-1_1.jpg  COPD Emphysema (‘pink puffers’): – Enlargement of airspaces distal to terminal bronchioles with destruction of distal air spaces. – Classified based on anatomic distribution: Centrilobular emphysema: most common form of emphysema, usually secondary to smoking. Panlobular emphysema: deficiency of α-1 anti-trypsin (inactivates proteases). 26 https://meetings.ami.org/2018/wp-content/uploads/2018/07/tseng_a_18I-1_1.jpg COPD CLINICAL FEATURES Many patients have overlapping features of damage (cigarette smoking – common denominator). Blue bloater (chronic bronchitis): – Patients are hypoxic. – Hypoxemia results in cyanosis (blue). – Frequently obese (“bloater”). Pink puffer (emphysema): – Destruction of lung tissue: Reduced respiratory surface  compensatory tachypnea. – Chest is over-inflated (barrel chest), lean forward. – Use of accessory muscles of respiration. – Hyperventilate to keep blood oxygenated (“puffer”). 27 Emphysema (‘pink puffers’): Enlargement of airspaces distal to terminal bronchiole. Centrilobular (centriacinar) emphysema: – Widening of air spaces in center of a lobule (primarily involves respiratory bronchioles). – Most common form of emphysema, usually secondary to smoking. – Involves upper lobes. Panlobular emphysema: – Widening of all air spaces distal to terminal bronchiole. – Secondary to deficiency of α-1 anti-trypsin (inactivates proteases). – Preferentially involves lower lobes. Fig 8-13. Pathology for the Health Professions, 2012 LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 29 BRONCHIECTASIS Irreversible, abnormal permanent dilatation of a bronchus secondary to destructive infection. Similar to COPD presents with persistent cough and sputum production. – COPD: physiological diagnosis (air flow obstruction) – Bronchiectasis: structural diagnosis (usually diagnosed by CT). Larger bronchi usually show cystic/sacular dilatation. Smaller bronchi usually show cylindrical/tubular diltation. 30 https://upload.wikimedia.org/wikipedia/commons/6/65/Bronchiectasis_NHLBI.jpg https://radiopaedia.org/articles/bronchiectasis BRONCHIECTASIS Common etiologies: – Bronchial obstruction: Foreign body (food aspiration). Tumor (intraluminal obstruction). – Congenital or hereditary conditions: Cystic fibrosis (genetics lecture). Primary ciliary dyskinesia (Kartagener’s syndrome). – Infections: TB, measles, pneumonia. 31 LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 32 ASTHMA Respiratory disease characterized by increased reactivity of bronchial tree to variety of stimuli (reactive airway disease). Two major forms recognized (extrinsic and intrinsic). Extrinsic asthma: – Attacks precipitated by exposure to triggering allergens (type I Hypersensitivity reaction). – Associated with other atopic diseases (eczema, hay fever, allergies). – Begins before age 10, last several years, many improve spontaneously. Intrinsic asthma: – Attacks precipitated by non-immune mechanisms. Exercise, stress, temperature, chemical irritants and air pollution, aspirin. – Begins in adulthood (usually before age 40). 33 ASTHMA Pathogenesis: – Reasons for increased reactivity unknown. – Likely caused by persistent inflammation of bronchial mucosa. – Mediators of inflammation cause protracted smooth muscle contraction, stimulation of excess mucus production. Pathological findings: – Similar in both forms of asthma, regardless of etiology. Smooth muscle hyperplasia. Mucus plugs, bronchial gland hyperplasia. Chronic inflammation (lots of eosinophils). Treatment: – Treat acute attacks with bronchodilators. 34 – Prevent chronic inflammation with steroids. https://onlinelibrary.wiley.com/doi/full/10.1111/resp.13251 LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 35 RESTRICTIVE LUNG DISEASE Group of respiratory diseases characterized symptoms of restrictive lung function (↓ lung volume, ↓ compliance) Two categories: – Chronic interstitial and infiltrative diseases. – Chest wall disorders. Major diseases (chronic interstitial and infiltrative diseases): 1. Hypersensitivity pneumonitis. 2. Pneumoconioses. 3. Sarcoidosis. Inflammatory process in alveolar walls with fibrosis. https://commons.wikimedia.org/wiki/File:CT_scan_in_usual_interstitial_pneumonia_(UIP).jpg Honeycomb lung is common end stage appearance. 36 HYPERSENSITIVITY PNEUMONITIS Respiratory disease due to disordered immune reaction to various inhaled antigens (exposure is usually work or hobby related). Allergens are derived from molds and fungi growing on organic material. – Farmer’s lung (moldy hay). – Pigeon fancier’s lung (pigeon droppings). Acute form (Type III reaction). – Ag-Ab immune complex activates complement Chronic form (Type IV reaction). – T cell mediated reaction. – Granulomas in alveolar septa. Treatment is avoidance of the allergen. 37 Fig 8-18. Pathogenesis of hypersensitivity pneumonitis. Pathology for the Health Professions, 2012  PNEUMOCONIOSES Respiratory disease due to inhalation of fumes, inorganic (mineral) and organic dusts. Exposure often occurs at work. Severity depends on amount, duration and type of dust. Examples: – Coal-worker’s lung: Inhalation of coal and silica particles in miners. – Silicosis: Inhalation of silica particles by sand blasters, miners, stone cutters. – Asbestosis: Inhalation of asbestos particles by shipyard workers, insulation May develop pleural plaques, lung cancer, mesothelioma. 38 Treatment is avoidance of the dust. SARCOIDOSIS Multisystem disease of unknown etiology characterized by non-caseating granulomas in various organs. Cell mediated immunity (type IV hypersensitivity reaction). Granulomas may involve any organ. – Typically lungs, lymph nodes, liver. Diagnosis: – Requires biopsy of affected tissue and presence of non-caseating granulomas. Treatment: – No specific treatment (most patients recover spontaneously). – Immunosuppression. 39 https://commons.wikimedia.org/wiki/File:Sarcoidosis_signs_and_symptoms.png LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 40 DROWNING Third leading cause of accidental deaths. Two sets of changes of drowning seen at autopsy: – Wet drowning (90%): Aspirated water enters the respiratory tract with resulting anoxia. Sea water (hypertonic) results in more pronounced pulmonary edema. Death within minutes if not resuscitated. – Dry drowning (10%): Reflex laryngospasm with closure of glottis resulting in anoxia. No water in the lungs. More easily resuscitated. Outcome depends on speed of rescue/ resuscitation. 41 LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 42 ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) Clinical condition characterized by acute respiratory failure that does not respond to oxygen. Many different causes: – Shock, pneumonia, toxic lung injury, aspiration of fluids. Pathogenesis: – Injury of alveolar lining cells (viral pneumonia or inhalation of toxic fumes) or Injury of endothelial cells in pulmonary capillaries (septic patients). – Injury causes leaky capillaries. – Fluid enters the air spaces and interstitial space from the capillaries. – Changes impair oxygenation of blood  anoxia. Histology: diffuse alveolar damage. High mortality (50%). 43 https://commons.wikimedia.org/wiki/File:Hyaline_membranes_-_very_high_mag.jpg LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 44 LARYNGEAL CARCINOMA Majority squamous cell carcinomas. Usually occur on vocal cords. Linked to smoking and alcohol. Present as nodules or ulcerations of mucosa. Symptoms include hoarseness, loss of voice. Normal squamous mucosa Invasive squamous cell carcinoma 45 http://www.entheadandneckspecialist.com/index_html_files/63440.jpg https://link.springer.com/referenceworkentry/10.1007%2F978-1-4614-3165-7_4-2 https://medicine.uiowa.edu/iowaprotocols/sites/medicine.uiowa.edu.iowaprotocols/files/014%2520scca%2520with%2520budding%2520nests.jpg Most common malignancies in men: Most common malignancies in women: 1. Prostate 1. Breast 2. Lung 2. Lung 3. Colon 3. Colon Most common cause of death in men: Most common cause of death in women: 1. Lung 1. Lung 2. Colon 2. Breast 3. Prostate 3. Colon New Cancer cases Cancer Deaths 46 LUNG CANCER Statistics: – Number one cause of deaths due to cancer (in both men and women). – Second most common malignancy (in both men and women). Risk factors: – Cigarette smoking. – Asbestos exposure – Radiation. – Arsenic, chromium. – Genetic factors. Poor prognosis as metastasis occurs early in course of disease. Metastatic locations: brain, liver, bone, kidney, adrenals. Lung is also a common site for metastatic tumors. – Lung metastases are more common that primary lung cancers. 47 LUNG CANCER Adenocarcinoma. – Most common primary lung malignancy (40%). – Equal frequency in smokers and non-smokers. – Usually peripheral, solitary nodule. Squamous cell carcinoma (30%). – Usually smokers. – Typically more centrally located. – Precursor lesion: squamous metaplasia. Small cell carcinoma (15%) – Usually smokers. – Typically more centrally located. – Paraneoplastic syndromes common. Treatment: Sun S, et al. Nat Rev Cancer 2007;7:778-790. – Small cell carcinoma: chemotherapy. 48 – Non-small cell carcinoma: surgery (supplemented by radiation, chemo). LECTURE OBJECTIVES 1. Describe the structure and function of the respiratory system. 2. List causes and symptoms of upper, middle and lower respiratory tract infections. 3. Describe pathogenesis and lesions of tuberculosis. 4. What are the major causes of obstructive airway disease? What are 2 major causes of chronic obstructive pulmonary disease (COPD)? Define pathologic and clinical features of each. 5. What is bronchiectasis and what are common causes? 6. What is asthma? What are its causes and pathogenesis? 7. What is restrictive lung disease? List 3 major causes and their pathogenesis. 8. What is the difference between wet and dry drowning? 9. Discuss pathogenesis of Adult Respiratory Distress Syndrome (ARDS). 10. Describe typical location, pathologic and clinical findings associated with respiratory tract malignancies. 11. Describe causes of pleural effusion, pneumothorax and types of pleural malignances. 49  PLEURAL EFFUSION = Accumulation of fluid in the pleural cavity. Transudate (Less protein and fewer cells). Slide from fluids lecture: Usually results from imbalances in increased hydrostatic or low oncotic pressure. Examples: – Increased hydrostatic pressure from: Heart failure (Hydrostatic edema: left sided heart failure, ↑’d hydrostatic pressure inside pulmonary vein). – Low oncotic pressure: Cirrhosis (liver unable to make proteins). Nephrotic syndrome (proteins lost in urine). Tends to resolve without any consequences. 50  PLEURAL EFFUSION = Accumulation of fluid in the pleural cavity. Exudate (Rich in protein and cells). Slide from fluids lecture: Results from increased vascular wall permeability or impaired lymphatic drainage. Examples: – Pneumonia (increases permeability of vessel wall  inflammatory cells enter pleural space). – Malignancy (spread of cancer cells into pleural space). Pleuritis (aka pleurisy). Bacteria typically cause fibrinous or fibrinopurluent exudate  pleuritis. Pleuritis = Inflammation of the pleura typically secondary to pneumonia. 51 PNEUMOTHORAX AND PLEURAL TUMORS Pneumothorax: – Entry of air into the pleural cavity that may cause collapse of the lung. – Typically occurs after stab wound or rupture of emphysematous lung tissue. Pleural tumors: – Most common are secondary (metastases). – Primary: mesothelioma. – Mesothelioma is a malignant neoplasm of mesothelial cells. Associated with asbestos exposure. https://www.asbestos.com/wp-content/uploads/where-mesothelioma-develops-diagram.png.pagespeed.ce.i9BfGjeDka.png Very poor prognosis. 52