Respiratory Tract Diseases: Structure and Defense

• The material covers respiratory tract diseases, including their structure, defense mechanisms, pulmonary infections, lung diseases and lung cancer.

Structure of the Respiratory System

• Airways are divided into cartilaginous (trachea and bronchi) and non-cartilaginous (bronchioles) types.
• Lung parenchyma consists of pulmonary lobules derived from small bronchioles and pulmonary acini from a single terminal bronchiole.
• The lungs have a dual blood supply from pulmonary and bronchial arteries.

Pulmonary Defense Mechanisms

• Airways use mucus, containing IgA and antibacterial substances, to create a physical barrier against organisms.
• Cilia push secretions out of the lungs.
• Alveoli contain alveolar macrophages for phagocytosis and chemotaxis, antibodies (mainly IgG), and complement.

Pulmonary Infections - Introduction

• Pneumonia is inflammation of the lungs, especially the respiratory portion and is termed pneumonitis.
• Pneumonia is a major health issue, causing 8.5% of all hospitalizations in the U.S.
• Nosocomial pneumonia affects 0.7% of hospital patients, with a higher rate (up to 13%) in intensive care units.
• Immunosuppressed patients have a higher risk, with pneumonia affecting up to one-third of them.

Routes and Classification of Pulmonary Infection

• Pulmonary infections can occur via airways (inhalation or aspiration), bloodstream, traumatic implantation, or direct spread through lymphatics.
• Pneumonias are classified as acute vs. chronic, alveolar vs. interstitial, primary vs. secondary, or by etiology.

Etiologic Types of Pulmonary Infections: Bacterial Pneumonia

• Bacterial pneumonia involves intra-alveolar exudate and lung parenchyma consolidation.
• Lobar pneumonia affects a large portion or the entire lobe.
• Streptococcus pneumoniae causes 90% of lobar pneumonia cases.
• Other bacteria include Klebsiella pneumoniae, Staphylococcus aureus, Hemophilis influenzae, Pseudomonas aeruginosa, and Proteus species.

Morphology and Clinical Manifestations of Pneumonia

• Untreated lobar pneumonia progresses through stages: congestion, red hepatization, gray hepatization, and resolution.
• Clinical signs include sudden shaking chills, fever, prostration, chest pain, cough, dyspnea, rusty sputum, and leukocytosis.
• Bronchopneumonia is patchy consolidation around bronchi and bronchioles, commonly caused by staphylococci, streptococci, Hemophilis influenzae, Pseudomonas aeruginosa, and Proteus species; often secondary to other conditions.
• Clinical signs of bronchopneumonia: variable fever, cough and sputum production.

Complications of Pneumonia

• Pneumonia can lead to abscess formation, pleuritis, pleural effusion, empyema, organization, or bacteremic dissemination leading to sepsis.

Tuberculosis (TB)

• Tuberculosis is a communicable disease causing necrotizing granulomatous inflammatory reactions and remains a leading cause of death worldwide.
• TB is the leading cause of death of AIDS patients in the world.
• TB incidence is increasing, with drug-resistant Mycobacterium tuberculosis hominus strains identified.
• TB is caused by Mycobacterium tuberculosis hominus, an obligate aerobe with acid-fast properties.

Etiology and Pathogenesis of TB

• "Atypical" TB infections can be caused by other mycobacteria.
• Infection usually occurs through direct inhalation.
• Primary TB develops in previously unexposed individuals, with inhaled bacilli implanting in the lower part of the upper lobe or upper part of the lower lobe.
• The primary infection leads to a Ghon focus, and with nodal involvement, it is known as the Ghon complex.
• Lesions consist of granulomatous inflammatory reactions including caseating and noncaseating tubercles which become fibrocalcific scars but may harbor viable organisms.
• Clinically, primary TB is often asymptomatic, recognized by a positive TB skin test or calcification on X-ray.

Secondary TB

• Secondary TB arises in a previously sensitized host, typically from reactivation but may occur after reinfection.
• Localized to the apices of the upper lobes.
• Secondary lesions may occur spontaneously or w/ treatment and may resolve through fibrous encapsulation and calcification.
• Clinical manifestations include gradual onset of malaise, anorexia, fever, night sweats; later symptoms include cough, sputum production, or pleuritic pain.
• Miliary TB may present as a fever of unknown origin.

Fungal Infections of the Lungs

• Fungi can cause lung infections that range from acute pneumonitis to chronic granulomatous conditions similar to TB.
• Histoplasmosis (Histoplasma capsulatum) causes a TB-like disease, endemic in the Ohio and central Mississippi River Valleys, Appalachian Mountains, and southeastern U.S and contains budding intracellular yeast.
• Coccidioidomycosis (Coccidioides immitis) may cause asymptomatic infection, progressive pulmonary disease, or miliary disease, endemic to the southwestern U.S.
• North American Blastomycosis (Blastomyces dermatitidis) may cause asymptomatic pulmonary infection, progressive pulmonary disease, or miliary disease.
• Cryptococcus (Cryptococcus neoformans) is rare in normal individuals, often causing progressive pneumonia with dissemination to the meninges in immunocompromised patients and is not transmitted person to person.
• Pigeon droppings serve as its reservoir.

Fungal Infections in Immunosuppressed

• Candidiasis (Candida species), especially Candida albicans, causes superficial infections and may involve the lungs, heart, kidney, liver, GI tract, and central nervous system in immunocompromised hosts, and is invasive.
• Aspergillosis (Aspergillus species) has three types of infection, bronchial, mycetoma, and necrotizing pneumonia and appears as branched, septate, and nonseptated hyphae.

Viral Infections of the Lung

• Viruses are common causes of respiratory infections and cause morbidity/mortality in infants, the elderly, and immunocompromised patients.
• Types of viral respiratory tract infections: "common cold", "flu", "acute bronchitis", and "pneumonia" which manifests generally as diffuse interstitial infiltrates
• Common viral pathogens include influenza A, B, C; measles, parainfluenza, respiratory syncytial virus; rhinovirus, enterovirus, Coxsackie B, echovirus; coronavirus; adenovirus, herpes simplex, varicella-zoster, cytomegalovirus.

Diffuse Infiltrative Lung Disease

• Diffuse infiltrative lung disease includes a group of lung diseases with clinical and radiologic features in common.
• These disorders are characterized by dyspnea and diffuse "infiltration" on chest radiographs and lab studies show hypoxemia, impaired oxygen exchange, and decreased lung volumes and compliance in advanced stages.
• Subclassifying these diseases is difficult due to their number and the potential for identical reactions to have multiple causes.

Pathogenesis of Diffuse Infiltrative Lung Disease

• The pathogenesis involves injury leading to alveolitis and inflammation by endothelial/epithelial cells, collagen fibers, elastic tissue, proteoglycans, fibroblasts, mast cells, and inflammatory cells.
• Resident inflammatory cells increase in number and change in proportion, releasing mediators and products that perturb the lung's connective tissue framework.
• Continual injury can lead to scarring.

Acute and Chronic Diffuse Infiltrative Lung Diseases

• Acute diffuse infiltrative lung disease is also known as diffuse alveolar damage (DAD) has synonyms.
• DAD is termed respiratory distress syndrome of the newborn or hyaline membrane disease in premature infants and is characterized by heavy, firm lungs with boggy, red parenchyma.
• Microscopic pathology: early stages show edema, congestion, and fibrin deposition becoming evident after 24 hours as protein- and fibrin-containing edema fluid, cytoplasmic and lipid cellular debris.
• Healing: if the cause is removed, edema resolves and Type II pneumocytes repair the alveolar lining; organization: progression leads to organization of the fibrin exudate and interstitial fibrosis.
• Chronic diffuse infiltrative lung disease includes idiopathic pulmonary fibrosis (IPF) also called usual interstitial pneumonia (UIP) which accounts for the majority of cases and ends in respiratory failure. It has a poor response to corticosteroids.
• Connective tissue diseases may cause interstitial inflammation and fibrosis and its pathology is often indistinguishable from UIP.
• Pneumoconiosis: Infiltrative lung diseases can be caused by inorganic dusts.

End-Stage Diffuse Infiltrative Lung Disease and Clinical Manifestations

• End-stage diffuse infiltrative lung disease is known as "honeycomb lung".
• In the late stages of the disease, a diagnosis from pathological grounds alone can be difficult.
• Gross pathology shows multiple small cysts resembling honeycombs, microscopically shows extensive interstitial fibrosis.
• Clinical manifestations are dyspnea, cough, sputum production, and weight loss; medical and occupational history are important in determining the cause.

Pulmonary Embolism

• Pulmonary embolism is a major cause of death, with an annual incidence of 650,000 in the U.S. and a 40% mortality rate.
• Pulmonary emboli mostly comes from thrombi that form in the deep veins of the legs.
• Venous thrombosis and pulmonary emboli commonly occur secondary to immobilization, congestive heart failure, trauma, or postpartum.
• Consequences depend on the size of the emboli, the state of the occluded arteries, and the general pulmonary circulation.

Types of Pulmonary Embolism

• Sudden death can occur in massive pulmonary embolism occluding main pulmonary arteries.
• Sudden chest pain, syncope, and dyspnea can result from occlusion in large lobar or smaller vessels.
• Smaller emboli can be asymptomatic or produce a transient episode of pain, cough, and hemoptysis.

Pulmonary Hypertension

• Primary pulmonary hypertension accounts for only 1% of total cases.
• Etiology of primary pulmonary hypertension is unknown and only offers symptomatic therapy.
• Clinically shown as fatigue, syncope, dyspnea on exertion, and occasionally chest pain.
• Secondary pulmonary hypertension occurs when resistance to flow is increased or there is prolonged blood volume overload.
• Secondary pulmonary hypertension may develop at any age and present with heart failure.
• Morphology shows main pulmonary arteries, medium sized pulmonary arteries show intimal thickening and medial hypertrophy.

Obstructive Lung Disease

• Obstructive lung disease is related to a decreased ability to expire.
• Four types of obstructive lung diseases: emphysema, chronic bronchitis, asthma, and bronchiectasis.

Emphysema

• Emphysema is characterized by abnormal air space enlargement distal to the terminal bronchiole, with destruction of their walls.
• Types can be classified by anatomical distribution within the lung acinus as centriacinar, panacinar, and paraseptal; clinically, centriacinar and panacinar are the most important.

Centriacinar Emphysema

• Centriacinar emphysema affects the proximal portions of the acini, typically sparing the distal portions which can be found in the upper lobes.
• It is associated with smoking.

Panacinar Emphysema

• Panacinar emphysema uniformly affects the acini from the level of the respiratory bronchiole to the terminal alveoli and is more frequent in the lower zones of the lung.
• Panacinar Emphysema is associated with alpha-1-antitrypsin deficiency.

Pathogenesis of Emphysema

• The pathogenesis of emphysema is due to proteolytic enzymes or proteases, particularly elastase, which evolved clinical observations in patients with a deficiency in alpha-1-antitrypsin and studies of chronic bronchitis and smoking.

Chronic Bronchitis

• Chronic bronchitis is excessive mucus production, on most days for more than three months a year for two or more years.
• Development is is caused by chronic irritation of the airways of substances and infection.
• Tobacco smoke and other pollutants are the major irritants.

How Chronic Bronchitis Causes Airway Obstruction

• Excessive mucous clogs of the the bronchiolar lumen narrows the airways, and inflammation adds to the effect.
• The affected lumen can cause a secondary infection.
• Pathological indicator: Enlargement of tracheobronchial submucosal glands.

Asthma

• Asthma is characterized by reversible bronchoconstriction in response to stimuli and classified as extrinsic or intrinsic.
• Extrinsic asthma (allergic): specific allergens trigger Type I immune reactions.
• Intrinsic asthma (nonreaginic): respiratory tract infections.

Pathogenesis and Morphology of Asthma

• In asthma is due to two factors: Interaction of allergen with bound mast cells, and neurohumoral control of airway constriction.
• Morophology: Includes Mucus plugging, thickening of the basement membrane and inflammtion.

Clinical Manifestations of Asthma

• Extrinsic asthma typically develops in children.
• Intrinsic asthma typically develop in adulthood.
• S ymptoms include wheezing, dyspnea, and tachypnea.

Bronchiectasis

• Bronchiectasis is dilated airways, now less common due to antibiotics and immunizations.
• Characterized by airway obstruction, impaired clearance and peristant infection.
• Causes include infection, congenital abnormalities, and cystic fibrosis.

Morphology and Clinical Manifestations of Bronchiectasis

• Bronchiectatic airways are dialated an filled with exudate.
• Manifestions include a chronic cough. dyspnea and clubbing.

Etiology and Epidemiology of Lung Cancer

• The majority of lung tumors are malignant.
• Accounts 12-13% of all cancers in men and women.
• Generally occurs between ages 40-70.
• Tobacco smoking increases rise, there is a reduced risk in non-smokers.

Classifications

• Common types: Squamous Cell, Adenocarcinoma, Small Cell and Large Cell.
• Arise primarily in first three generations and usually in bronchogenic, mostly squamous cells.

Spread of Lung Cancer

• Spread is found to to occur in three ways: local invasion, lymphatic and blood stream

Clinical Manifestations of Lung Cancer

• Lung cancer varies and depends on site and metastasis.
• Can induce symptoms like coughing, wheezing and hemoptysis.
• Some effects outside the lungs include superior vena caval obstructions & Neuromuscular complications.

Diagnosis and Prognosis of Lung Cancer

• Diagnosed by biopsy.
• Staged Tumor size, location and node evaluation.
• Overall survivabilty is poor with current treatments.