Lung I 2025 PDF

Lung I RICHARD GALBRAITH, MD Learning Objectives - 1 List and briefly describe the more common congenital lung abnormalities. Define atelectasis, and describe the principal types. Distinguish hemodynamic pulmonary edema from pulmonary edema arising from microvascular injury. Understand and recogniz...

Lung I RICHARD GALBRAITH, MD Learning Objectives - 1 List and briefly describe the more common congenital lung abnormalities. Define atelectasis, and describe the principal types. Distinguish hemodynamic pulmonary edema from pulmonary edema arising from microvascular injury. Understand and recognize the morphologic changes seen with hemodynamic pulmonary edema. Describe ALI/ARDS, and understand the associated pathogenesis, morphologic changes, and clinical course. Describe pulmonary vascular diseases, their pathogenesis and courses; including pulmonary embolism, pulmonary hypertension, and pulmonary hemorrhage syndromes. Learning Objectives - 2 Relate factors predisposing patients to pulmonary infections. List and briefly describe common causative organisms in community- associated bacterial pneumonia. Describe the morphologic changes and clinical course of community-acquired bacterial pneumonia. List the common viruses implicated in community-acquired viral pneumonia. Explain the concept of antigenic drift and antigenic shift as observed in Influenza virus, type A. Relate the pathogenesis of Influenza virus pneumonia, and the morphologic features of viral pneumonia generally. Learning Objectives - 3 Describe health care-associated pneumonia, hospital-associated pneumonia, aspiration pneumonia, the type of patients typically affected and the organisms commonly implicated. Describe lung abscess, its pathogenesis, morphologic features and clinical course. Discuss the fungal causes of chronic pneumonia, the epidemiologic features, and the clinical and pathologic findings. Describe pneumonia in an immunocompromised patient, and list common causative organisms. Briefly discuss pulmonary disease in HIV-infected patients. Learning Objectives - 4 Define obstructive lung disease, and explain the common pulmonary function test findings. Describe the clinically important subtypes of emphysema, and their anatomic patterns of involvement, and their clinical associations. Relate the pathogenesis and morphologic changes seen in emphysema. Explain why emphysema is an obstructive lung disease. Relate its clinical course. Describe the effect of a deficiency of α1-1 antitrypsin on lung tissue. Define chronic bronchitis and relate its pathogenesis, morphologic features, and clinical features. Describe asthma, and relate the pathogenesis of atopic asthma. Give several examples of stimuli known to precipitate asthma. Describe the changes seen in “airway remodeling.” Learning Objectives - 5 Relate genetic and environmental factors known to predispose and precipitate asthma. Describe the morphologic changes and clinical course of asthma. Describe bronchiectasis, and list several examples of precipitating causes. Relate the pathogenesis, morphologic features and clinical course. Describe the general features of chronic diffuse (restrictive) lung diseases. Describe the clinical features, pathogenesis and morphologic findings of the fibrosing restrictive lung diseases, including idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, autoimmune disease-associated lung disease, pneumoconiosis, and therapy- related lung diseases. Learning Objectives - 6 Describe the morphologic features of usual interstitial pneumonia. Describe the pathogenesis, morphologic findings and clinical features of granulomatous lung diseases, including sarcoidosis and hypersensitivity pneumonitis. Relate the clinical and morphologic findings in smoking-related interstitial lung diseases, including desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease. Describe the clinical and morphologic features of pulmonary Langerhans cell histiocytosis. Discuss the clinicopathologic features of pulmonary alveolar proteinosis and surfactant function disorders. Learning Objectives - 7 Discuss the epidemiology, etiology and pathogenesis of lung carcinoma. Describe the clinical and pathological characteristics of the major histologic subtypes of lung carcinoma. Know common mutational abnormalities associated with these subtypes. Understand precursor lesions to lung carcinoma. Describe typical and atypical carcinoid tumor of the lung, and the clinical features of a functioning carcinoid tumor. Describe the common patterns of metastases to the lung. Describe malignant mesothelioma, its epidemiologic, clinical and pathologic features. Learning Objectives - 8 Describe the morphologic and clinical characteristics of sinonasal and nasopharyngeal tumors, including nasopharyngeal angiofibroma, sinonasal papilloma, olfactory neuroblastoma, and nasopharyngeal carcinoma. Describe benign mass-forming lesions of the larynx, including reactive nodules and squamous papillomas. Describe the clinical characteristics and morphologic features of squamous cell carcinoma of the larynx. Understand the hyperplasia – dysplasia – carcinoma sequence. Congenital anomalies Pulmonary hypoplasia ◦ Decreased weight, volume and acini for age/body weight ◦ Compression of the lung(s) in utero (eg, diaphragmatic hernia) ◦ If severe, then fatal shortly after birth Foregut cyst ◦ Bronchogenic, esophageal, or enteric Pulmonary sequestration ◦ A segment of lung tissue without connection to the airway, and with systemic circulatory supply (not pulmonary) Atelectasis Refers to an area (or areas) of airless pulmonary parenchyma, due to collapse or incomplete expansion. Resorption atelectasis: ◦ Complete obstruction of an airway ◦ Air within the dependent lung is resorbed → collapse ◦ Mediastinum shifts toward the affected lung Atelectasis Compression atelectasis: ◦ Fluid, tumor or air accumulate within the pleural space, preventing normal expansion ◦ Mediastinum shifts away from the affected lung Atelectasis Contraction atelectasis: ◦ Pulmonary or pleural fibrosis preventing normal expansion ◦ Not reversible Pulmonary edema 1. Hemodynamic pulmonary edema ◦ Intra-alveolar fluid accumulation due to increased hydrostatic pressure in the pulmonary circulation ◦ Fluid accumulates basally at first ◦ Alveolar capillaries are congested, and an intra-alveolar transudate is seen, pink and granular ◦ Hemosiderin-laden macrophages may be seen within alveoli (“heart failure cells”) with chronic pulmonary edema, and the lungs may become brown and indurated ◦ ↓oxygenation, ↑ chance of infection Pulmonary edema 2. Edema secondary to microvascular (alveolar) injury ◦ Injury to and inflammation of alveolar vascular endothelium and/or respiratory epithelium ◦ Infectious or toxic insults ◦ May be localized or diffuse Acute lung injury & acute respiratory distress syndrome Acute lung injury Inflammation-induced vascular permeability, leading to diffuse pulmonary edema and rapid onset of hypoxemia Severe ALI is termed acute respiratory distress syndrome (ARDS) Many predisposing conditions have been identified, including infectious agents, physical injury, toxic substances, and hemodynamic disturbances, among others Sepsis, diffuse pulmonary infection, gastric aspiration, trauma account for >50% of cases Acute lung injury - pathogenesis 1. endothelial activation 2. neutrophil accumulation and activation 3. accumulation of intraalveolar fluid and hyaline membranes 4. resolution of injury Acute lung injury Morphology (diffuse alveolar damage - DAD): ◦ Grossly: heavy, firm and wet lungs ◦ Micro: congested, interstitial and intraalveolar edema, necrosis of type I and type II pneumocytes, presence of hyaline membranes, collapse of some alveoli ◦ With resolution, granulation tissue may form and resolve, reestablishing functional tissue. Occasionally interstitial scarring may occur. Clinical course: largely depends upon the underlying cause, and the severity of the lung injury ◦ Mortality is approximately 40% Diseases of pulmonary vessels 1. PULMONARY EMBOLISM Pulmonary embolism Important cause of morbidity and mortality ◦ 10% of acute deaths among hospitalized adults ◦ 95% originate in deep veins of the legs ◦ Incidence at autopsy is 1% in the general population of hospital patients to 30% in patients with severe burns, trauma or fractures. Risk factors: ◦ Post-surgical (esp. hip/knee) ◦ Severe trauma/burn ◦ Disseminated cancer ◦ Congestive heart failure ◦ OCPs/pregnancy ◦ Primary hypercoagulable state ◦ Immobility Pulmonary embolism Clinical significance is dependent on: ◦ Extent to which pulmonary artery blood flow is obstructed ◦ The size of the occluded vessel ◦ The cardiovascular health of the patient ◦ The number of emboli Consequences of PE: ◦ Increase in pulmonary artery pressure from blockage of flow and vasospasm ◦ Ischemia of the downstream pulmonary parenchyma ◦ Sudden death often occurs due to blockage of blood flow through the lungs, or due to acute right sided heart failure ◦ Usually >60% of the pulmonary vasculature obstructed Pulmonary embolism Saddle embolus when large emboli lodge in the main pulmonary artery or at the bifurcation Small emboli travel peripherally, where they can cause infarction, and ischemic hemorrhage Pulmonary embolism Most infarcts involve the lower lobes, and most are multiple They typically extend to the periphery of the lungs as a wedge Pulmonary infarcts are initially hemorrhagic (red-blue), and will eventually form a scar Pulmonary embolism Signs and symptoms may include: ◦ Severe chest pain, dyspnea, and shock ◦ Smaller emboli are silent and cause transient chest pain and cough Patients with PE have a 30% chance of developing another one Prevention includes early mobilization, elastic stockings, graduated compression stockings, anticoagulants Treatment with anticoagulation and supportive measures Pulmonary embolism Non-thrombotic pulmonary emboli are uncommon but potentially lethal ◦ Air ◦ Fat ◦ Amniotic fluid ◦ Talc Diseases of pulmonary vessels 2. PULMONARY HYPERTENSION Pulmonary hypertension Defined as mean pulmonary arterial pressure >20 mmHg May be caused by ◦ a decrease of the cross-sectional area of the pulmonary vascular bed, or ◦ by increased pulmonary vascular blood flow Clinically: ◦ dyspnea, fatigue, syncope ◦ chest pain ◦ Right ventricular hypertrophy ◦ death due to cor pulmonale Pulmonary hypertension WHO classification 1. Pulmonary arterial hypertension ◦ fibromuscular remodeling of distal pulmonary arterioles is caused by genetic and molecular events, induced by certain toxic drugs (eg, methamphetamines, dasatinib, or anorexigens), or observed in association with systemic sclerosis, liver disease, HIV, or other predisposing conditions. 2. Pulmonary hypertension associated with left heart disease ◦ pulmonary venous hypertension, manifest by postcapillary PH on RHC 3. Chronic obstructive or interstitial lung diseases and/or hypoxia ◦ severity in patients with underlying lung disease is variable 4. Pulmonary arterial obstructions ◦ thrombotic mechanical obstruction to normal pulmonary blood flow is most common 5. Undifferentiated or multifactorial causes ◦ E.g., Schistosomiasis Pulmonary hypertension Cpc indicates combined precapillary + postcapillary PH; and Ipc, isolated postcapillary PH Humbert et al without permission. Copyright ©2023 European Society of Cardiology and European Respiratory Society Pulmonary hypertension Morphology ◦ Medial hypertrophy of pulmonary muscular and elastic arteries (B) ◦ Pulmonary arterial sclerosis (A) ◦ Right ventricular hypertrophy ◦ Plexiform lesion (tuft of capillaries spanning lumens of dilated thin walled small arteries) (C) A B C Pulmonary hypertension/RVH 1500 × 719Images may be subject to copyright. Learn Image result for pulmonary hypertension More Pulmonary hypertension Idiopathic (or “primary”) pulmonary hypertension ◦ Traditionally diagnosed when known causes are excluded Approximately 80% of “idiopathic” cases have a genetic basis (familial PH) ◦ Inactivating mutation of bone morphogenetic protein receptor type 2 (BMPR2), found in 75% of familial cases and 25% of sporadic cases ◦ BPMR mutations thought to lead to pulmonary vascular smooth muscle proliferation ◦ Most common in women who are 20-40 years of age ◦ Over time severe respiratory distress, cyanosis, right ventricular hypertrophy and death due to cor pulmonale within 2-5 years in 80% of patients Diseases of pulmonary vessels 3. DIFFUSE PULMONARY HEMORRHAGE SYNDROMES Pulmonary hemorrhage syndromes 1. Goodpasture syndrome 2. Granulomatosis and polyangiitis (formerly known as Wegener’s granulomatosis) Goodpasture syndrome Autoimmune disease Kidney and lung injury due to anti-basement membrane antibodies (against type IV collagen, a component of alveolar and glomerular basement membranes) M > F, in their teens and 20s, active smokers Usual sequence: ◦ Necrotizing hemorrhagic interstitial pneumonitis → hemoptysis, dyspnea, followed by ◦ Rapidly progressive glomerulonephritis Treatment: plasmapheresis and immunosuppressants Goodpasture syndrome morphology Lungs are heavy with areas of red brown consolidation Focal necrosis of the alveolar wall, intra-alveolar hemorrhage The alveoli contain hemosiderin laden macrophages Immunofluorescence reveals diagnostic linear immunoglobulin deposits along the basement membranes of the septal walls (also seen in renal biopsies) Granulomatosis and polyangiitis Most patients (>80%) develop upper respiratory and/or lung involvement ◦ May also develop glomerulonephritis Lung signs/symptoms: ◦ Cough, hemoptysis, chest pain URT signs/symptoms: ◦ Chronic sinusitis, epistaxis, nasal septal perforation Characterized by ◦ Necrotizing vasculitis (angiitis) ◦ Parenchymal necrotizing granulomatous inflammation Anti-neutrophil cytoplasmic antibodies (PR3-ANCAs) are found in 90% of cases Pulmonary infections Pulmonary infections – general considerations Very common: currently the 8th leading cause of death in the US Systemic conditions which may predispose to pulmonary infection include ◦ Immunodeficiency (including leukopenia) ◦ Chronic disease Pulmonary infections – general considerations Defense mechanisms specific to the lungs may also be compromised: ◦ Cough reflex ◦ Impaired or diminished ciliary function ◦ Mucus stasis ◦ Decreased pulmonary macrophage activity ◦ Pulmonary edema Pulmonary infections 1. COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA Community-acquired bacterial pneumonia Infections of bacterial pathogens may be indistinguishable from viral, clinically and radiologically ◦ CRP and procalcitonin levels may be higher in bacterial pneumonia Bacterial pneumonia may follow a viral URI Predisposing conditions: ◦ Age: young or old ◦ Chronic disease (COPD, diabetes, CHF) ◦ Absent splenic function (predisposes toward encapsulated bacterial infections) Causative organisms Streptococcus pneumoniae ◦ Most common cause of community-acquired pneumonia ◦ Gram positive, slightly elongated diplococci may be seen in sputum; beware of false positives Haemophilus influenzae ◦ Gram negative bacteria, encapsulated type b is most virulent ◦ Important cause of pediatric bacterial pneumonia, otitis media ◦ Most common cause of bacterial acute exacerbation of COPD Causative organisms Moraxella catarrhalis ◦ Elderly: bacterial pneumonia, exacerbation of COPD ◦ Pediatric: otitis media Staphylococcus aureus ◦ Important cause of 2° bacterial pneumonia, following viral infection ◦ Higher incidence of complications (abscess, empyema) Klebsiella pneumoniae ◦ Most common Gram negative bacterial pneumonia ◦ Chronic alcoholics, malnourished Causative organisms Pseudomonas aeruginosa ◦ Important cause of pneumonia in cystic fibrosis, neutropenic ◦ Hematogenous spread Legionella pneumophila ◦ Water tanks, pipes ◦ Immunosuppressed, chronic disease ◦ Urine Legionella antigen Mycoplasma pneumonia ◦ Children, young adults Morphologic changes Invasion of bacteria leads to alveolar filling with inflammatory cells and exudate, resulting in consolidation (solidification) of the lung tissue Consolidation occurs in two patterns: ◦ Bronchopneumonia ◦ Lobar pneumonia Morphologic changes Bronchopneumonia ◦ Patchy involvement of lung parenchyma ◦ Consolidated areas may coalesce ◦ Formed of acute suppuration ◦ Basal, often multilobar and frequently bilateral Morphologic changes Lobar pneumonia ◦ Consolidation occupies an entire lobe ◦ Four stages: ◦ Congestion: vascular engorgement, cell-poor intra-alveolar fluid with bacteria ◦ Red hepatization: robust exudate with neutrophils, erythrocytes, fibrin ◦ Grey hepatization: fibrinosuppurative material, erythrocyte disintegration, early organization ◦ Resolution: organizing fibrosis admixed with macrophages Bronchopneumonia Lobar pneumonia, grey hepatization Acute pneumonia Early organization Later organization Community-acquired bacterial pneumonia – clinical course Presents with abrupt fever, shaking chills, productive cough (rust colored sputum) Lobar pneumonia x-ray: opaque lobe Bronchpneumonia x-ray: focal opacities Antibiotics: culture and sensitivity Complications include: ◦ Abscess ◦ Empyema (pleural involvement) ◦ Bacteremia Pulmonary infections 2. COMMUNITY-ACQUIRED VIRAL PNEUMONIA Community-acquired viral pneumonia Common organisms: ◦ Influenza viruses (A, B and C), RSV, human metapneumovirus, adenovirus, rhinoviruses, coronaviruses Predisposing factors: ◦ Very young and elderly ◦ Malnutrition/alcoholism ◦ Chronic disease Inflammation and damage to defense systems (ciliary mechanism) may lead to bacterial superinfection  Influenza virus The major cause of influenza epidemics and pandemics Type A influenza viruses infect humans, swine, birds, and horses Two important viral proteins: ◦ Hemagglutinin (H1-H3) ◦ Binds to respiratory epithelial cells, allowing cellular infection ◦ Neuraminidase (N1-N2) ◦ Allows release of newly-created virions ◦ These proteins are important to viral virulence, and are important targets of a host antibody response Influenza virus Genome is composed of 8 RNA segments Viral RNA polymerase lacks error detection capability, so constant antigenic drift occurs Recombination of segments of the genome may occur when an individual is coinfected with different types → antigenic shift leading to a new viral strain → pandemic Influenza virus Generally infection involves the upper respiratory tract as well, which facilitates spread Virus infect respiratory epithelium, causing ◦ Intraalveolar fluid accumulation ◦ Cell death ◦ inflammation Influenza virus Lung infection may be patchy or extensive Prominent findings include: ◦ Vascular congestion ◦ Inflammation in the alveolar wall interstitial tissue ◦ Edema ◦ Lymphocytes and macrophages Influenza virus Clinical course shows marked variability between patients Extent of the disease is affected by ◦ Host immune status ◦ Virulence of the infecting strain ◦ Presence/absence of other complicating conditions COVID-19 SARS-CoV-2 Transmission through respiratory droplets Variable clinical course ◦ Potential for abnormally increased cytokine response ◦ Potential for development of arterial and venous thrombosis Pulmonary infections 3. CHRONIC PNEUMONIA Histoplasmosis Causative organism: Histoplasma capsulatum ◦ Intracellular fungal pathogen ◦ Inhaled soil particles contaminated by bird/bat droppings In the US, endemic along the Mississippi and Ohio rivers (much of the Midwest) Targets macrophages Histoplasmosis – clinical scenarios 1. self-limited pulmonary infection 2. chronic, progressive lung infection ◦ Apical ◦ Night sweats, fever, coughing 3. extrapulmonary involvement, particularly ◦ Liver, adrenal glands, mediastinum, meninges 4. wide dissemination Histoplasmosis – morphologic findings Granulomas, often caseating May coalesce and consolidate the lung focally, or form cavities May resolve and form nodular calcified scars Demonstration of the organism (silver stain): 3-5 µm yeast In disseminated disease, the organisms are found within clusters of macrophages, and caseating granulomas are not seen Blastomycosis Causative organism: Blastomyces dermatiditis ◦ Soil-dwelling dimorphic fungus, central and southern US Pulmonary blastomycosis may result in: ◦ Productive cough, chest pain ◦ Headache ◦ Anorexia/weight loss, fever/chills, night sweats Blastomycosis - morphology In tissue, it forms a 5-15 µm yeast with a double wall and visible nucleus Blastomyces: Broad-Based Budding Forms granulomas with superimposed suppuration Most cases resolve spontaneously Coccidiomycosis Causative organism: Coccidioides immitis ◦ Southwest US Infective form is the arthroconidia, which are inhaled Taken up by macrophages, but resist intracellular killing Lung granulomas harbor giant cells containing large spherules (20-60 µm) filled with endospores Rupture of spherules may induce recruitment of neutrophils Coccidiomycosis Vast majority of infections are subclinical and self-limiting A minority present with fever, cough, detectable lung granulomas, pleuritic pain, and skin lesions (erythema nodosum, erythema multiforme): San Joaquin Valley fever Pulmonary infections 4. OTHER TYPES OF PNEUMONIA AND INFECTIONS Hospital-acquired pneumonia Pulmonary infection acquired during a hospital stay Predisposing conditions: ◦ On mechanical ventilation ◦ Severe underlying disease ◦ Immunosuppression ◦ Invasive access devices Causative organisms: ◦ Gram-positive cocci (S. aureus, S. pneumonia) ◦ Gram-negative rods (Enterobacteriaceae, Pseudomonas spp.) Aspiration pneumonia Pneumonia secondary to aspirating gastric contents Predisposing conditions: marked debilitation (unconscious, or status post stroke) ◦ May have a diminished gag and/or swallowing reflex Organisms: usually mixed flora, aerobic and anaerobic Chemical irritation from aspirated acidic gastric contents May result in necrotizing pneumonia, with a fulminant course May produce a lung abscess Pneumonia in an immunocompromised host May occur in patients who are immunosuppressed for any reason ◦ Immunosuppressive disease, chemotherapy, radiation, therapy for organ/stem cell transplant, etc. “Opportunistic” organisms: ◦ Bacteria: Pseudomonas aeruginosa, Mycobacterium spp., Legionella pneumophila, Listeria monocytogenes ◦ Viruses: cytomegalovirus (CMV), herpesvirus ◦ Fungi: Pneumocystis jirovecii, Candida spp., Aspergillus spp., Cryptococcus neoformans, Mucormycoses May cause pulmonary infiltrates on imaging, and need to be distinguished from infiltrates caused by drug reactions or tumors HIV-related lung disease Accounts for 30-40% of hospitalizations of HIV-infected patients Opportunistic infections, in addition to more usual pneumonia-inducing pathogens, often related to the patient’s CD4+ T-cell count: ◦ >200/ml: bacterial and tubercular infections more likely ◦