Respiratory System Pathology PDF

Respiratory System: Pathology Ariette Acevedo, O.D. BMS 2 Diagnostic Testing • Radiographic Imaging • Chest X-Ray (CXR) • PA/lateral • CT • MRI/MRA • Spirometry • Arterial Blood Gases • Sputum analysis Normal CXR COVID-19 Pneumonia CXR Spirometry • Simplest, most commonly performed pulmona...

Respiratory System: Pathology Ariette Acevedo, O.D. BMS 2 Diagnostic Testing • Radiographic Imaging • Chest X-Ray (CXR) • PA/lateral • CT • MRI/MRA • Spirometry • Arterial Blood Gases • Sputum analysis Normal CXR COVID-19 Pneumonia CXR Spirometry • Simplest, most commonly performed pulmonary function test. • Measures Forced Vital Capacity (FVC), the amount of air that can be forcefully exhaled from the lungs. • Begins with maximal inhalation and ends with lung emptying to residual volume. • Forced Expiratory Volume (FEV) can also be measured • Ratios can be performed, which if below the normal limit can be indicative of obstructive lung disease. Arterial Blood Gas • Diagnostic tool used to evaluate the partial pressure of gas in blood and acid-base content. • Measures the PaO2 and PaCO2 in arterial blood • Measures pH • Blood gas analysis: can use blood from anywhere • Arterial blood gas (ABG): need arterial blood • Expected Values: • pH: 7.35-7.45 • PaO2: 75-100mmHg • PaCO2: 35-45mmHg Pleural Biopsy • Performed when: • suspected lung neoplasia • Determine the cause of exudative pleural effusion Respiratory Symptoms • Cough • Hemoptysis • Dyspnea: Shortness of Breath (SOB) • Abnormal Lung Sound on Auscultation • https://youtu.be/U8byn2NT_lo?si=9QszWip-pLAYPjtL Obstructive Disease • • • • Asthma Chronic Bronchitis Emphysema Cystic Fibrosis Epidemiology: S/S: M>F, pre-puberty F>M, post-puberty 8% USA population 340 million worldwide & 420,000 deaths/year Pathophysiology: • Commonly S/S present before 25 y/o, but can develop at any given time. • SOB • Cough • Wheezing • Increased respiratory rate (tachypnea) • Tachycardia • • • • • Abnormal pulmonary function tests • In moderate to severe cases, altered ABGs • CXR tends to be normal, except in severe cases. • Clinical syndrome of unknown etiology characterized by recurrent episodes of airway obstruction that resolve spontaneously or with treatment. • Physiological hallmark: increased resistance to airflow due to airway obstruction resulting from smooth muscle constriction, thickening of the airway epithelium and secretions. Asthma • • • • • DX: • Treatment is aimed at • Controlling symptoms & preventing exacerbations. • Rescue treatments & Controller treatments Inhaled glucocorticoids combined with Beta-agonist Short or long-acting β-2 adrenergic agonist. Inhaled Antimuscarinic agents (ex: Ipratropium) Oral Antileukotrienes (ex. Montelukast) Systemic Glucocorticoids TX: Inhaled Common Glucocorticoids Agent Brand Name Budesonide Pulmicort Fluticasone propionate Flovent Fluticasone furoate Arnuity Ellipta Inhaled Common Short-Acting β-Adrenergic Agonist Agent Brand Name Albuterol Proventil HFA, Ventolin HFA Levalbuterol Xopenex HFA Common Combination Inhalers Agent Brand Name IGC: budesonide LABA: formoterol Symbicort ICG: fluticasone propionate LABA: salmetrol Advair Diskus, Advair HFA, Wixela Inhub ICG: fluticasone furoate LABA: vilanterol Breo Ellipta Chronic Obstructive Pulmonary Disease (COPD) • Chronic Bronchitis • Emphysema • Cystic Fibrosis Epidemiology: • • • Adult presentation, typically 60 y/o or older. 175 million worldwide 3.2 million deaths/year, 3rd leading cause in world. • • • • S/S: Breathlessness with exertion Chronic SOB Cough w or w/o sputum production Some present wheezing. Pathophysiology: • Risk factors: smoking (80-90%), occupational exposure to chemicals or dust, rarely AR alpha-1 antitrypsin deficiency. • Progressive lung disease • Damage to airways distal to terminal bronchioles (acinus) causing abnormal and permanent dilatation of the airspaces and destruction of the walls. • Resulting in a decreasing surface area, thus decreasing gas exchange. Emphysema • Abnormal pulmonary function tests • If severe, abnormal CXR • If young, it is recommended they are tested for alpha-1 antitrypsin deficiency. DX: • No intervention, except lung transplant can reverse or cure • Tx is aimed at risk factor modification and managing symptoms. • Smoking cessation • Bronchodilators, either as monotherapy or in combination with anti-inflammatory • SABA/LABA & SAMA/LAMA • Inhaled corticosteroids • Supportive therapy includes oxygen therapy and ventilatory support to maintain oxygen saturation above 90%. TX: Epidemiology: • • • 3-7% of healthy adults But as high as 74% of those Dx w/COPD. Elder patients/smokers higher risk. S/S: Pathophysiology: • Characterized by a productive cough lasting 3 mos or more and occurring within a span of 2 years. • Causative factor: smoking, inhaled pollutants • Acute bronchitis: bacterial or viral infections. • Caused by the overproduction and hypersecretion of mucus from goblet cells. • Airways become clogged, impeding airflow • Color of sputum may vary (clear, yellow, green, at times blood tinged) • Fever is uncommon, if present it suggest infection • Wheezing • • • • CXR if suspected pneumonia CBC w/diff to rule out infectious origin If infection is suspected, sputum culture Altered pulmonary function tests DX: Chronic Bronchitis • Bronchodilators: • SABA/LABA & anticholinergics • Glucocorticoids • Antibiotic therapy is not indicated in cases of chronic bronchitis, unless there is an infection. • Smoking cessation TX: Epidemiology: • Prevalence in US 1: 10,000 • 1/2000 live birth in white population • AR S/S: • • • • Pathophysiology: Median age of dx: 6/months old Chronic productive cough Crackles on auscultation Chronic wheezing • Caused by a deficient or absent cystic fibrosis transmembrane conductance regulator (CFTR) protein. • This causes a dehydration of mucosal surfaces and visceral secretions that obstruct luminal compartments and ducts. • Can affect the lungs, pancreas, sweat glands, liver and other organs. • Major abnormality in calcium ion channels • Lung disease results from mucus plugging the bronchioles leading to poor ventilation. • Prone to infections (Staph and Pseudomonas) • Altered pulmonary function tests • Some may have radiographic evidence of sinusitis • In the USA at birth newborns are tested for CF by measuring immunoreactive trypsinogen, if test is positive further confirmatory testing is needed. • CXR or chest CT are typically abnormal with evidence of cystic bronchiectasis. DX: Cystic Fibrosis • Airway clearance • Mucolytics • Osmotic drugs (7% hypertonic saline solution inhaled) • Bronchodilators • Beta-adrenergic • Anticholinergics • Anti-inflammatory agents • Macrolide antibiotics, glucocorticoids, Ibuprofen • Lung transplantation TX: Epidemiology: • • • 1 billion people globally US 25-30% of men and 9-17% of women Higher prevalence in Hispanic, Black and Asian. S/S: Pathophysiology: • Loud, chronic snoring • Excessive daytime somnolence (50% of pts) • Witness sleep-related choking or gasping. • Ocular manifestations: • Floppy eyelid syndrome • Nighttime in-laboratory polysomnography DX: • Characterized by episodes of absent (apnea) or attenuated (hypopnea) upper airway flow for at least 10 seconds followed by arousal and resumption of ventilation. • Hallmark repetitive cycle of asphyxia and sleep fragmentation. • Risk factors include obesity, chest wall movement restrictions, upper airway narrowing. Obstructive Sleep Apnea (OSA) • Lifestyle changes and managing of underlying medical conditions • Positive Airway Pressure (PAP) Therapy • C-PAP: continuous • BPAP: bilevel TX: Infectious Disease of the Lungs • Viral/Bacterial/Fungal Pneumonias • URI Epidemiology: • • CAP: most common infectious cause of hospitalization/death in US. More common in elders S/S: • • • • • Cough Dyspnea (SOB) Tachypnea Chest pain Can present w or w/o fever • Depending on infecting pathogen, patients may present severely ill or not. • Crackles over the affected area • Abnormal opacities in the lungs on CXR or imaging • Lab work: demonstrating an elevated WBC count • Neutropenia: Bacterial • Leukopenia: Viral • Sputum Culture • PCR Viral testing DX: Pathophysiology: • Acute infection of the lung parenchyma associate with at least one respiratory symptom and abnormal chest imaging. • Pneumonia can be viewed as an alteration of homeostasis, leading to a dominant pathogen. • Categorized by the etiology of the infecting organism. • Hospital Acquired or Community Acquired • CAP: Typical or Atypical Pneumonia • According to infectious etiology TX: Community Acquired Bacterial Organisms Typical Atypical • Strep. pneumoniae (15-30%) • Staph. aureus • H. influenzae • P. aeruginosa • E. coli • K. pneumoniae • M. catarrhalis • Mycoplasma pneumoniae • Chlamydia pneumonia • Chlamydia pstiacci • Chlamydia trachomatis • Legionella spp. Hospital Acquired Bacterial Organisms • Gram negative bacteria • Klebsiella pneumoniae • Serratia marcescens • Pseudomonas spp. • Methicillin resistant Staph. Aureus (MRSA) Community Acquired Viral Organisms • Human rhinoviruses • Influenza A and B viruses • Human metapneumovirus • Respiratory syncytial virus (RSV) • Parainfluenza viruses 1-3 • Coronaviruses Fungi/Parasites Fungi • • • • • • • • Pneumocystis jiroveci Aspergillus spp. Mucorales spp. Histoplasma spp. Cryptoccocus spp. Blastomyces spp. Cocidioides spp. Talaromycosis spp. Parasites • Toxoplasma gondii • Strongyloides stercoralis Epidemiology: • • • • Top 3 dx in outpatient setting Adults 3-4/per year Children up to 8/per year Fall season higher incidence S/S: • • • • • • • • Cough Sore throat Runny nose/congestion Headache Low-grade fever Sneezing Malaise Myalgias Pathophysiology: • Involve the nose, sinuses, pharynx, larynx and large airways. • ”Common cold” • Most common etiology: rhinoviruses but can also be caused by: • Influenza, adenovirus, enterovirus and RSV • S. pyogenes, Group A streptococcus • Organism is usually acquired by inhalation of infected droplets • Can present with concurrent viral conjunctivitis. • Clinical diagnosis • Nasopharynx swab for PCR testing for viral if deemed necessary • Strep swabs can be used to r/o bacterial pharyngitis DX: URTI • Symptom relief • Decongestants/cough relief TX: Epidemiology: S/S: Present worldwide, but developing countries have a higher incidence. WHO: 1.7 million latent infections • Chronic cough • Hemoptysis • Weight-loss • • Low-grade fever • Night sweats • Ocular manifestations include: • Anterior uveitis • Posterior uveitis • Vitritis • • Tuberculin skin testing: Mantoux test • PPD: Purified protein derivative • Interferon release assays (IGRA) (more specific) • Abnormal CXR DX: Pathophysiology: • Granulomatous disease cause by Mycobacterium tuberculosis. • Infection from inhaling aerosol from an infected person. • Multisystemic disease, with primarily affection of the lungs. • For most people, initial contact with M. tuberculosis leads to a latent stage, which can last a long period. • Granulomas are the hallmark of TB • Caseating granulomas Tuberculosis (TB) • First Line Treatment • Isoniazid • Rifampicin** • Rifabutin • Rifapentine • Pyrazinamide • Ethambutol** • Other antimicrobials TX: Interstitial Disease of the Lungs Epidemiology: • • 80/100,000 men 70/100,000 women • • • • S/S: Most frequent reported symptoms is dyspnea of gradual onset Cough Hemoptysis Can also be asymptomatic Pathophysiology: • Collection of distinctive lung disorder characterized by acute and chronic lower respiratory tract disorder with many potential causes. • May affect gas exchange units (alveolar walls, capillaries, alveolar space, and acini), bronchiolar lime, terminal bronchioles and pulmonary parenchyma • Etiology can include: • Environmental/occupational exposure • Auto-immune disease • Idiopathic disease Interstitial • Drug-induced • Abnormal pulmonary function tests • Abnormal imaging • Important to inquire about exposure risk factors DX: Lung Disease • Depending on the etiology TX: Epidemiology: 11/100,000 in whites 34/100,000 in AA Typically, before age 50 y/o • • • • • • • S/S: Persistent dry cough Fatigue SOB Can present skin lesions, cardiac problems, ect.. Pathophysiology: • Multisystem disorder of unknown etiology • Presents with noncaseating granulomas in various organs • Can affect the lungs, skin, eyes and joints. • • Ocular manifestations: • Anterior/Intermediate/Poste rior or Pan-uveitis • Most common: bilateral anterior uveitis Sarcoidosis • • • • • CBC w/differential ESR and C-Reactive protein are typically elevated Lambda sign and Panda sign on gallium scans Elevated serum lysozymes Elevated Angiotensin-Converting Enzyme (ACE) DX: • In some cases it can be asymptomatic and require no treatment • In cases where treatment is required: • Glucocorticoids TX: ƛ Lung Neoplasm Lung Neoplasms • Lung cancers grow from a single abnormal cell or small group of abnormal cells to develop into large macroscopic masses that may be several centimeters in diameter. • Most lung cancers originate in the bronchial epithelium • These are known as bronchogenic carcinomas • Non-carcinoma lung cancers are less common and may include: • Carcinoid, pulmonary blastomas (common in younger patients) and sarcomas. Lung Neoplasm • Smoking is the most common cause of lung cancer • Attributed 90% of lung cancer • One of the leading causes of death in the USA and the most commonly diagnoses cancer worldwide • Estimated 225,000 new cases of lung cancer in the US annually • 160,000 deaths/year • Relatively rare disease until the beginning of the 20th century, attributed to an increase in smoking. Epidemiology: • Most common cancer worldwide • • • • • • • • S/S: No specific symptoms Cough (50-75%) Hemoptysis (15-30%) Chest pain (20-40%) Dyspnea (25-40%) Weight loss Fatigue 15% can be asymptomatic at diagnosis time • Pulmonary nodule or mass seen in CXR or CT • Bronchoscopic endobronchial ultrasoundtransbronchial needle aspiration DX: Pathophysiology: • Risk factors: smoking (80-90%), occupational exposure to carcinogens (asbestos) & radon. • Complex pathophysiology but hypothesized that repeated exposure to carcinogens leads to lung epithelium dysplasia, eventually leading to genetic mutations and affected protein synthesis. Lung Neoplasm • According to lung cancer type & staging • Surgical intervention • Radiation Therapy • Systemic (Chemotherapy) Therapy TX: Primary Lung Malignancies-Histologic Classifications • Non-small cell lung carcinoma (NSCLC) (70-75%) • Adenocarcinoma (30-35%) • Squamous Cell Carcinoma (25-30%) • Large Cell Carcinoma (10-15%) • Small Cell Carcinoma (SCLC) (20-25%) • Combined pattern (2-10%) • Mixed squamous and adenocarcinoma • Mixed squamous and small cell lung carcinoma Ocular Manifestations • Lung Pancoast Tumor: wide range of tumors invading the apical chest wall • Producing: Pancoast-Tobias Syndrome • Pancoast-Tobias Syndrome • Severe shoulder/arm pain along the C8, T1, T2 nerve trunk • Horner’s Syndrome (miosis, anhidrosis and ptosis) • Atrophy of the intrinsic hand muscles • These tumors account for 3-5% of lung cancers • Out of these 95% are Non-small cell lung cancer