Lungs Structure and Diseases PDF

LM 202 Dr. Hassan Kofahi Lungs: Structure Each lung is divided into lobes The right lung is divided into three lobes The left lung is divided into two lobes. The trachea branches into two main bronchi. Each bronchus branches into smaller bronchi which branches further to give...

LM 202 Dr. Hassan Kofahi Lungs: Structure Each lung is divided into lobes The right lung is divided into three lobes The left lung is divided into two lobes. The trachea branches into two main bronchi. Each bronchus branches into smaller bronchi which branches further to give rise to progressively smaller airways, termed bronchioles. Lungs: Structure Bronchioles are distinguished from bronchi by the lack of cartilage and submucosal glands in their walls. Additional branching of bronchioles gives terminal bronchioles. Structures distal to the terminal bronchiole form the acinus. The acinus is composed of: Respiratory bronchioles which branches from the terminal bronchioles. Alveolar ducts Alveolar sacs Alveoli The wall of normal airways The wall of a normal airway contains the following layers: Mucosa: Mucus: forms a sticky blanket that traps microorganisms. Epithelium: contains Ciliated pseudostratified columnar epithelial cells. The cilia is important for pushing the mucus and microorganisms out of the lungs. Goblet cells: produce mucus Basement membrane. Lamina propria: connective tissue layer Submucosa: contains the following layers Smooth muscles Connective tissue layer: in bronchi, this layer contains mucus glands that secrets most of the mucus Cartilage: only in bronchi not in bronchioles Lung structure: alveoli Alveoli are the sites of gas exchange between the blood and the air. The alveolar walls consist of the following components: The capillary endothelium and basement membrane. The pulmonary interstitium: composed of fibers and few cells. Alveolar epithelium: composed of a continuous layer of two types of cells: Type I pneumocytes: cover 95% of the alveolar walls Type II pneumocytes: synthesize pulmonary surfactant and important for the repair of damaged type I cells. Pulmonary surfactant is a complex (phospholipid + protein) that reduces the surface tension in the alveoli. Reducing the surface tension increases the pulmonary compliance and prevents the collapse of alveoli. Lung diseases Atelectasis (collapse) Atelectasis is a loss of the lung volume. Develops when the alveoli within the lung become deflated. Atelectasis may affect part of the lung or the entire lung. Results in an inadequate oxygenation of the blood thus giving rise to hypoxemia. Atelectasis is potentially reversible (except contraction atelectasis). Atelectasis: Forms Based on the underlying mechanism and the distribution of collapse, atelectasis is classified into three forms: Resorption atelectasis (also known as obstruction atelectasis): Occurs as a result of airways obstruction. The trapped air, distal to the site of obstruction, gradually becomes absorbed leading to alveolar collapse. Causes: postoperative intrabronchial mucus, foreign body aspiration (particularly in children), bronchial asthma, chronic bronchitis, or intrabronchial tumor. Compression atelectasis: Results from the accumulation of fluids, blood or air in the pleural cavity. Causes: pleural effusion (edema) due to heart failure and leakage of air into the pleural cavity (pneumothorax). Contraction atelectasis: Occurs when local or diffuse fibrosis of the lungs prevents full expansion of the lung. Acute Respiratory Distress Syndrome (ARDS) ARDS is a respiratory failure occurs within one week of a known clinical insult. Caused by severe inflammation in the lungs. lead to extensive bilateral injury to alveoli. Can be triggered by: Direct lung injury: e.g., aspiration, pneumonia, COVID-19 Severe systemic inflammation, such as: Sepsis Pancreatitis Transfusion reactions Severe ARDS is characterized by rapid onset of life-threatening respiratory insufficiency, cyanosis and severe arterial hypoxemia. ARDS: Pathogenesis ARDS is caused by an acute inflammatory reaction in the alveoli. Pathogenesis: The insult triggers the alveolar macrophages to produce inflammatory cytokines (such as IL-1 and TNF). The cytokines stimulate the endothelial cells and recruit neutrophils to the interstitium and the alveoli. The neutrophils is stimulated to produce harmful products, such as proteases and reactive oxygen species. Neutrophils’ products and cytokines cause the following: Damage to alveolar epithelium and endothelium Increasing the vascular permeability, leading to edema. Inactivation of the surfactant which render the alveolar unit unable to expand. Stimulation of fibroblast growth and collagen deposition. ARDS microscopic morphology: alveolar edema, epithelial necrosis, accumulation of neutrophils, and presence of hyaline membranes lining the alveolar wall. ARDS: Clinical features The mortality rate of ARDS is high (40%). Some ARDS survivors recover normal respiratory function within 6 to 12 months. The rest develop diffuse interstitial fibrosis leading to chronic respiratory insufficiency. Note: ARDS should not be confused with the respiratory distress syndrome of the newborn, which is caused by the reduced production of surfactant due to the prematurity. Chronic Obstructive Pulmonary Disease (COPD) COPD is an umbrella term used to describe progressive lung diseases including emphysema and chronic bronchitis. In most of the cases, emphysema and chronic bronchitis co-exist, because cigarette smoking is the main cause of both. COPD is a progressive, irreversible disease (there is no cure for COPD). The main causes of COPD are: Cigarette smoking (the leading cause of COPD). Long term exposure to air pollution. Genetic disorders: α1- antitrypsin deficiency. Respiratory infections may worsen COPD. COPD affects 10% of the population and is the third leading cause of death in the USA. Emphysema Emphysema is caused by pathological changes in the acini. Characterized by: 1. Destruction of the alveolar walls (septa) leading to permanent enlargement of the air spaces in the acini. The destruction of the walls results in merging normal alveoli into larger dysfunctional airspaces. This reduces the surface area for gas exchange, thus reduces the oxygenation of blood. 2. Loss of external support for respiratory bronchioles. This results in a premature collapse of the respiratory bronchioles during expiration leading to airflow obstruction. Types of emphysema Centriaciner emphysema: Affects respiratory bronchioles in the central or proximal parts of the acini. Distal alveoli are not affected except in severe centriacinar emphysema. More common in the upper lobes of the lungs. Caused by cigarette smoking. Panacinar emphysema: The acini are uniformly enlarged. Occurs more commonly in the lower lung zones. Associated with α1 antitrypsin deficiency. Emphysema: Pathogenesis Inhaled cigarette smoke and other noxious particles cause emphysema by inducing inflammation which, particularly in patients with a genetic predisposition, result in the pathological changes in the acini. Alveolar wall destruction in emphysema is caused by the following: Inflammatory cells activation and the production of inflammatory mediators. Imbalance between proteases and anti-proteases: Inflammatory cells release proteases, which break down the connective tissue. Anti-proteases, such as α1-antitrypsin, inhibit the proteases and protect against tissue damage. Patients with emphysema may have a relative deficiency in the protective anti-proteases. Oxidative stress: Reactive oxygen species (ROS) cause tissue damage in the lungs: ROS is generated by cigarette smoke ROS is released from activated inflammatory cells. Emphysema: Clinical features The classic presentation of emphysema (without chronic bronchitis) is: Dyspnea: difficulty in breathing Prolonged expiration with pursed lips Hyperinflation of the lungs and Barrel chest Weight loss Until very late in the disease, gas exchange is adequate and blood gas values are relatively normal. Emphysema patients are often called “pink puffers.” Progression of the disease results in pulmonary hypertension, cor pulmonale and right sided heart failure. Expiration with pursed-lips Chronic bronchitis Chronic  lasts for long time Bronchitis inflammation of the bronchi Chronic bronchitis Is defined clinically as: the presence of a persistent productive cough (i.e., a cough that produces mucus) for at least 3 consecutive months in at least 2 consecutive years. Often, coexist with emphysema. Caused by cigarette smoking or air pollution. Characterized by the excessive production of mucus in the airways. Chronic bronchitis: Pathogenesis Cigarette smoking and air pollution induces Inflammation Hypertrophy of the mucous glands An increase in the number of the goblet cells Destruction of the cilia Excessive mucus production results in a persistent productive cough and it leads to airflow obstruction. The airflow obstruction in chronic bronchitis results from: Small airway disease, induced by mucous plugging of the bronchiolar lumen, inflammation, and bronchiolar wall fibrosis. Coexistent emphysema. Chronic bronchitis: clinical features Course of chronic bronchitis disease varies between individuals. Patients experience the following symptoms: High body weight Persistent productive cough. Wheezing Recurrent infections. Hypercapnia (elevated CO2 levels in the blood), hypoxemia, and cyanosis. Pulmonary hypertension leading to cor pulmonale and right-sided heart failure. Chronic bronchitis patients are often referred to as “ blue bloaters”. COPD patients die due to right-sided heart failure or respiratory failure. Blue bloaters Pink puffers Asthma Asthma is a chronic inflammatory disorder of the airways. It causes recurrent episodes of severe and reversible bronchoconstriction that develops in response to various stimuli including cold, exogenous allergens, and some chemicals such as aspirin. Caused by a combination of genetic and environmental factors. Affect people at all ages, but usually starts during childhood. The incidence of asthma is increasing in the western world. Why? The hygiene hypothesis is a possible explanation. The hygiene hypothesis states that a lack of exposure to microorganisms in early childhood results in defects in immune tolerance and subsequent hyperreactivity to stimuli later in life. Hallmarks of asthma: Accumulation of mucus in the bronchial lumen. Increase in the number of mucus-secreting goblet cells in the mucosa Thickened basement membrane. Recruitment of eosinophils, macrophages, and other inflammatory cells in the lamina propria. Hypertrophy and hyperplasia of smooth muscle cells. Hypertrophy of the submucosal glands. Types of Asthma Atopic asthma: (Allergic) The most common type. Caused by an allergic reaction. Attacks may be triggered by allergens in dust, pollen, animal dander, food, or by infections. Non-atopic asthma: No evidence of allergic reaction Triggered by viral infections and inhaled air pollutants. Drug-induced asthma No evidence of allergic reaction. Triggered by drugs (such as aspirin). The pathogenesis is unknown Occupational asthma Triggered after an extended period of exposure to chemicals in the work environment. Asthma: Clinical features Bronchoconstriction and mucus plugging during asthma attacks result in the following symptoms: Severe dyspnea Wheezing Cough Hyperinflation of the lungs. The episodes lasts for 1 hour or several hours and subside spontaneously or in response to therapy. Occasionally, some patients may develop a severe attack that lasts for days or weeks (a condition known as status asthmaticus) and can be fatal. In most of the cases asthma is not fatal. Treatment: anti-inflammatory drugs such as glucocorticoids and bronchodilators such as beta-adrenergic drugs. Bronchiectasis Bronchiectasis refers to the presence of a permanent dilation of bronchi or bronchioles. Caused by the destruction of the smooth muscles and the supporting elastic tissue in the walls of the bronchi. As a result, mucus accumulate in the enlarged area causing a chronic productive cough. Occurs secondary to persistent infection or obstruction. Bronchiectasis: causes Bronchiectasis can be caused by the following conditions: Bronchial obstruction: By tumors, foreign bodies or mucus. Causes localized bronchiectasis. Congenital or hereditary conditions: Cystic fibrosis: causes a widespread severe bronchiectasis that results from the obstruction of airways with an abnormally thick mucus. Congenital Immunodeficiency: localized or widespread bronchiectasis develop as a result of recurrent bacterial infections. Necrotizing, or suppurative, pneumonia e.g., infections with Staphylococcus aureus or Klebsiella pneumonia. Bronchiectasis: Pathogenesis 1. Accumulation of mucus or foreign body aspiration results in the obstruction of airways. 2. This blocks the clearance of secretions. 3. Results in a favorable environment for superimposed bacterial infection and induces inflammation. 4. The inflammation causes damage to the bronchial walls and results in the accumulation of exudate which further distend the airways leading to a permanent dilation. Bronchiectasis: Clinical features Symptoms: Persistent cough associated with purulent sputum. Dyspnea Coughing up blood Chest pain Severe, widespread bronchiectasis may lead to: Hypoxemia Hypercapnia (elevated carbon dioxide (CO2) levels in the blood) Pulmonary hypertension, and cor pulmonale. Pulmonary infections: Pneumonia Pneumonia can be broadly defined as any infection of the lung. Pneumonias are classified according to the following criteria: Cause: Infectious: Viral Bacterial Non-infectious: (aspiration pneumonia) Source: Community acquired Hospital acquired Pattern: Bronchopneumonia Lobar pneumonia Pneumonia: Patterns Pneumonia has two patterns of anatomic distribution: Bronchopneumonia: characterized by a patchy consolidation of the lung. lobar pneumonia: characterized by the consolidation of a large portion of a lobe or of an entire lobe. In pneumonia, the term “consolidation,” refers to “solidification” of the lung due to replacement of the air by exudate in the alveoli. Bronchopneumonia Lobar pneumonia Community-acquired viral pneumonia The most common causes of community-acquired viral pneumonias are influenza virus, respiratory syncytial viruses, adenovirus, rhinoviruses, varicella virus and coronavirus. Viruses infect and damage respiratory epithelium causing an inflammatory response. Outpouring of exudate into alveolar spaces may occur. This replaces the air with fluids (exudate) and leads to the consolidation of the lungs. Damage and necrosis of the respiratory epithelium inhibits mucociliary clearance and predispose to secondary bacterial infections. Severe complications of viral infection are more likely to occur in infants, older adults, malnourished patients, alcoholics, and immunosuppressed individuals. Viral pneumonia: Clinical Features Symptoms: Fever Headache Malaise Later, cough with minimal sputum. Influenza virus Single stranded RNA virus (8 segments of RNA). The surface of influenza virus contains two types of antigens: hemagglutinin (H) and neuraminidase (N). H and N determines the subtype of the virus (e.g., H1N1, H5N1, H3N2). Influenza virus can infect humans, pigs, horses and birds. The virus undergo two types of genetic changes: Antigenic drift: caused by mutations in the H and N and allow the virus to escape most of the host antibodies and cause epidemics every year. Antigenic shift: occur when H or N are replaced through recombination of RNA segments with those of animal influenza viruses. Generates a new virus that can cause pandemics. In 1918, influenza pandemic (the Spanish flu, H1N1 of swine origin) killed 20-100 million people globally. In 2009, the same strain of virus (Swine H1N1) caused severe infections in young adults. H5N1 (avian flu) caused 400 deaths in humans and is a potential threat to cause the next pandemic. Coronaviruses Enveloped, single stranded RNA viruses. Spike proteins project from the surface, giving the virus a crown-like appearance under the electron microscope (hence the name “corona”. Infect mammals and birds Cause upper/lower respiratory tract infections (mild to severe) Some coronaviruses cause common cold (mild) Other coronaviruses may cause severe respiratory infections (SARS, MERS and COVID-19) COVID-19 is caused by SARS-CoV-2. SARS-CoV-2 was responsible for the first great pandemic of the 21st century that caused approximately 7 million deaths globally. COVID-19: Transmission Droplet transmission (main route of transmission): inhalation of large respiratory droplets produced from an infected person These droplets are produced with coughing, sneezing, talking or even breathing. Typically, carried by the air for a short period of time (seconds-minutes) and travel to less than 2 meters. Other possible routes of transmission Airborne transmission (aerosols): inhalation of virus-containing small droplets or virus particles. These particles travel more than 2 meters and remain suspended in the air for a longer period of time. Contact (fomite) transmission: touching contaminated surfaces or objects then touching the mouth, nose or eyes. COVID-19: Clinical features Some cases remain asymptomatic. Symptoms: range from mild (or even asymptomatic) to fatal. Risk Factors for Severe COVID-19: Age: the risk of severe COVID-19 increases with age Comorbidities: the presence of other medical conditions increase the risk of severe COVID-19 (such as diabetes, obesity, and chronic cardiac, pulmonary or renal diseases). Gender: Males are at higher risk than females Race Genetic factors SARS-CoV-2 is an RNA virus that continue to change by mutations overtime. In rare cases, these changes may generate new variants of the virus. These new variants my become more transmissible, may cause more severe illness or may evade the preexisting immunity. Community-acquired bacterial pneumonia Bacterial pneumonias often follow a viral upper-respiratory tract infection. The most common cause of community acquired bacterial pneumonia is Streptococcus pneumoniae. Spread by respiratory droplets. The inflammatory response results in acute inflammatory exudate filling the alveolar spaces. Tends to produce a bronchopneumonia. If untreated, bronchopneumonia may progress to lobar pneumonia. Bacterial pneumonia: clinical features Symptoms of typical community-acquired acute bacterial pneumonia are: Sudden onset of high fever Shaking Chills Cough, producing mucopurulent sputum Treatment: antibiotics Hospital-Acquired (Nosocomial) Pneumonias Nosocomial pneumonia is defined as pulmonary infections acquired in the course of a hospital stay. Patients on mechanical ventilators are at high risk of acquiring nosocomial pneumonia. The most common causes of hospital acquired pneumonia are the gram-negative bacteria (Enterobacteriaceae and Pseudomonas spp) and Staphylococcus aureus. Hospital-acquired bacterial pneumonia is harder to treat than community-acquired bacterial pneumonia. Why? Because the bacteria tend to be more aggressive and more resistant to antibiotic treatment in hospitals. Tuberculosis (TB) Tuberculosis is a chronic granulomatous disease. Caused by an infection with Mycobacterium tuberculosis. Affects mainly the lungs, but other organs might also be affected. Epidemiology: Tuberculosis is the most common cause of death resulting from a single infectious agent. It is estimated that 1.7 billion individuals are/were infected with M. tuberculosis worldwide (≈1/3 of the world population). In most of the cases, the infection is self-limiting, asymptomatic and does not cause disease. Transmission: direct person-to-person by inhalation of airborne droplets containing the organisms. TB: Pathogenesis Sequence of events: 1. Entry of the Mycobacterium into the macrophages by phagocytosis: Mycobacteria are recognized by macrophage surface receptors and as a result, the bacteria are phagocytosed. 2. Replication in macrophages: once internalized, Mycobacteria inhibit the fusion of lysosome with the phagosome. Thus, they persist and replicate inside the macrophages. 3. Development of cell-mediated immunity (TH1 response): 3 weeks after the infection, a subclass of T lymphocyte, called TH1, become activated. TH1 cells produce cytokines (IFN-γ) that activate the macrophages. Activated macrophages kill the internalized Mycobacteria. 4. Granulomatous inflammation and tissue damage: In addition to stimulating macrophages to kill mycobacteria, the TH1 response orchestrates the formation of granulomas and caseous necrosis (discussed in chapters 1&2). Primary tuberculosis Refers to a disease that develops in a previously unexposed patient. In the majority of the cases (95%), the only consequence of primary TB is the formation of foci of scarring and calcification (asymptomatic). Most individuals who develop primary TB have the so-called Ghon complex consisting of granulomatous lesions in lung tissue in conjunction with granulomas in draining hilar lymph nodes. The foci may harbor dormant viable organisms that might be reactivated later in life causing secondary TB. In 5% of the cases, primary infection may result in progressive primary tuberculosis. This occurs usually in immunocompromised patients, such as: HIV-positive patients Malnourished patients Secondary tuberculosis Arises in a previously infected (sensitized) patient. May appear shortly or, in most of the cases, years (or even decades) after the primary TB. Causes of secondary TB: Reactivation of a dormant primary lesion, particularly when the host immune system is weakened. Reinfection Secondary TB is often associated with more caseous necrosis and with cavitation (formation of cavities) in the lung tissues. In progressive primary and in secondary TB, the bacteria may spread via the blood vessels to other organs in the body causing a life-threatening form of disease, called Miliary TB. TB: Clinical features Symptoms: Anorexia Weight loss Fever (low grade). Night sweats Increasing amounts of sputum Coughing up blood