Pulmonary Notes PDF

**Pulmonary -- Module 4** - **Dyspnea** is the experience of breathing discomfort. As discussed in our conversation history, it can be caused by a wide range of pulmonary conditions, including pleural effusion, pneumothorax, asthma, pneumonia, and pulmonary embolism. - **Cough** is...

**Pulmonary -- Module 4** - **Dyspnea** is the experience of breathing discomfort. As discussed in our conversation history, it can be caused by a wide range of pulmonary conditions, including pleural effusion, pneumothorax, asthma, pneumonia, and pulmonary embolism. - **Cough** is a protective reflex that helps clear the lower airways. It can be acute (lasting 2--3 weeks) or chronic (lasting longer than 3 weeks). - **Abnormal sputum**, including **hemoptysis** (coughing up of bloody sputum). - **Abnormal breathing patterns**: - **Hyperpnea** (Kussmaul respirations) is characterized by a slightly increased ventilatory rate and very large tidal volumes. It is induced by strenuous exercise or metabolic acidosis. - **Labored breathing** occurs with increased work of breathing, especially if the airways are obstructed. - **Restricted breathing** is caused by disorders that stiffen the lungs or chest wall and decrease compliance, such as pulmonary fibrosis. - **Hyperventilation** is a state of increased ventilation in excess of metabolic demands. - **Hypoventilation** is a state of inadequate alveolar ventilation in relation to metabolic demands. It occurs when minute ventilation (respiratory rate multiplied by tidal volume) is reduced. - **Cyanosis** is a bluish discoloration of the skin and mucous membranes caused by a high concentration of deoxygenated hemoglobin in the blood. - **Hypercapnia** is an increase in PaCO2 in the blood. It is caused by hypoventilation. - **Hypoxemia** is a decrease in PaO2 in arterial blood. It is a result of problems with oxygen delivery to the alveoli, diffusion of oxygen from the alveoli to the blood, or perfusion of the pulmonary system. - **Acute Respiratory Failure** is defined as hypoxemia or hypercapnia with a pH less than or equal to 7.25. It can be caused by a direct injury to the lungs, airways, or chest wall or indirectly because of disease or injury to another body system. **Pulmonary Tuberculosis** **Risk Factors for Pulmonary Tuberculosis** - Emigration of infected individuals from high-prevalence countries - Transmission in crowded institutional settings - Homelessness - Substance abuse - Lack of access to screening and medical care - Immunocompromised status due to conditions like AIDS, cancer, renal failure, and HIV - Use of immunosuppressive medications like corticosteroids - Poor nutritional status **Pathophysiology of Tuberculosis** Tuberculosis is caused by infection with the bacillus *Mycobacterium tuberculosis*. Transmission occurs from person to person via airborne droplets. In immunocompetent individuals, *M. tuberculosis* is typically contained by the body\'s inflammatory and immune response systems. This is called **latent TB infection (LTBI)** and presents with no clinical evidence of disease. - When inhaled, the bacilli lodge in the lungs, usually in the upper lobe. - This causes localized, nonspecific inflammation of the lung tissue. - Some bacilli travel through the lymphatic system and lodge in lymph nodes, which triggers an immune response. - Alveolar macrophages and neutrophils engulf and isolate the bacilli to prevent them from spreading. - However, *M. tuberculosis* can evade the body's defenses within macrophages and resist lysosomal killing, leading to the formation of a granulomatous lesion called a **tubercle**. - Infected tissues within the tubercle die, leading to **caseous necrosis** (cheese-like material). - Collagenous scar tissue then grows around the tubercle, isolating the bacilli. After approximately 10 days, the immune response is complete, and further multiplication of bacilli is prevented. TB may remain latent for life once bacilli are isolated in tubercles. If the immune system becomes impaired, reactivation of the disease can occur, and it may spread throughout the lungs or to other organs through the blood and lymphatic system. This is called **active TB disease**. Active TB disease can cause pneumonia and extrapulmonary disease. **Clinical Manifestations of Tuberculosis** - **Latent TB infection** has no clinical manifestations. - **Active TB disease** presents with: - Fatigue - Weight loss - Low-grade fever - Night sweats - **Cough with purulent sputum**, which develops and increases in frequency over weeks to months - **Dyspnea**, chest pain, and hemoptysis with disease progression - **Extrapulmonary TB** can occur in immunocompromised individuals **Pneumonia and Acute Bronchitis** **Causative Microorganisms** **Pneumonia** - Viruses, including influenza and respiratory syncytial virus - *Streptococcus pneumoniae* - *Legionella pneumophila* - *Moraxella catarrhalis* - *Hemophilus influenzae* - Atypical microorganisms like *Chlamydophila pneumoniae* and *Mycoplasma pneumoniae* - Fungi, such as *Pneumocystis jirovecii*, *Aspergillus*, and *Cryptococcus*, are less common causes, primarily seen in severely immunocompromised individuals (e.g., those with HIV infection) - *Staphylococcus aureus*, including methicillin-resistant strains (MRSA) - Enterobacteriaceae - *Pseudomonas aeruginosa* - *Acinetobacter* species - *Klebsiella pneumoniae* - *Enterococcus coli* **Acute Bronchitis** - Most cases are caused by viruses. - Bacteria can also cause acute bronchitis. **Pathophysiology** **Pneumonia** - Viruses can enter the lower respiratory tract through direct inoculation, inhalation, spread from infections in the upper respiratory tract, or through the blood (hematogenously). - Viruses target airway and alveolar epithelial cells. - Viral replication leads to activation of innate and adaptive immune responses. - Severe viral pneumonia can result in a **cytokine storm** causing epithelial and endothelial damage, hypercoagulability, and increased vascular permeability, which can lead to alveolar edema and ARDS. - Viral pneumonia can also make individuals more susceptible to secondary bacterial infections. - Colonization of the upper respiratory tract, followed by aspiration of oropharyngeal secretions, is the most common route of infection. - Inhalation of certain microorganisms is another route of infection. - Bacteria can adhere to the upper airway epithelium, evade host defenses, and enter the lower airways. - In **ventilator-associated pneumonia (VAP)**, bacteria form biofilms on the endotracheal tube. - Alveolar macrophages are the primary guardian cells of the lower respiratory tract and initiate the immune response against pathogens. - Inflammatory mediators and immune complexes can damage the alveolocapillary membrane. - Some bacteria release toxins that can further damage lung tissue. **Acute Bronchitis** Acute bronchitis is an acute infection or inflammation of the bronchi. \[16\] It is usually self-limiting. The sources you provided do not go into further detail about its pathophysiology. **Clinical Manifestations** **Pneumonia** - Most cases begin with a viral upper respiratory tract infection. - Fever - Chills - Cough, which may be productive or dry - Malaise - Pleural pain - Dyspnea and hemoptysis may also be present - Signs of pulmonary consolidation: - Dullness to percussion - Inspiratory crackles - Increased tactile fremitus - Egophony - Pleural effusion **Acute Bronchitis** - Similar clinical manifestations to pneumonia, including fever, cough, chills, and malaise. - Does not present with signs of pulmonary consolidation on physical exam or infiltrates on chest radiographs (which differentiates it from pneumonia). - **Viral bronchitis**: typically presents with a nonproductive cough. - **Bacterial bronchitis**: purulent sputum may be produced. - Chest pain from coughing **Cystic Fibrosis** **Genetic and Pathophysiological Changes** - **Cystic fibrosis (CF)** is an autosomal recessive genetic disorder. - It is caused by mutations in the **cystic fibrosis transmembrane conductance regulator (*CFTR*) gene**. - The *CFTR* gene provides instructions for making the CFTR protein. The CFTR protein functions as a chloride channel and is present on the surface of epithelial cells lining the airways, bile ducts, pancreas, sweat ducts, paranasal sinuses, and vas deferens. - Mutations in the *CFTR* gene result in an abnormal CFTR protein, which disrupts the transport of chloride and water across epithelial membranes. - This leads to the production of **thick, dehydrated mucus secretions**. - The most important effects of CF are in the lungs, and respiratory failure is almost always the cause of death. **Respiratory and Non-respiratory Clinical Manifestations** **Respiratory** - Persistent cough or wheeze - Excessive sputum production - Recurrent or severe pneumonia - Barrel chest - Digital clubbing **Non-respiratory** - Chronic sinusitis - Nasal polyps - Malnutrition - Intestinal obstruction **Chronic Obstructive Pulmonary Disease** **Risk Factors for Chronic Obstructive Pulmonary Disease (COPD), Including Emphysema and Chronic Bronchitis** - **Tobacco smoke**, including cigarette, pipe, cigar, and environmental tobacco smoke - **Occupational dusts and chemicals** (vapors, irritants, and fumes) - **Indoor air pollution** from biomass fuel used for cooking and heating (in poorly vented dwellings) - **Outdoor air pollution** - Factors that affect lung growth during gestation - Certain infections such as tuberculosis - Low socioeconomic status - **Genetic abnormalities** - **E-cigarette use (vaping)** **Pathophysiology of Chronic Obstructive Pulmonary Disease (COPD)** - **COPD** is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities. - It is usually caused by significant exposure to noxious particles or gases, and host factors, including abnormal lung development, also play a role. - The two most common phenotypes of COPD are **chronic bronchitis** and **emphysema**. - Defined as hypersecretion of mucus and a chronic productive cough that continues for at least 3 months of the year for at least 2 consecutive years. - Inspired irritants lead to airway inflammation. - Continued bronchial inflammation causes: - Bronchial edema - Increase in the size and number of mucus glands and goblet cells in the airway epithelium - Smooth muscle hypertrophy with fibrosis - Narrowing of airways - The thick mucus produced cannot be cleared due to impaired ciliary function. - These changes increase susceptibility to pulmonary infections, which contributes to further injury and ineffective repair. - Airway obstruction traps air in the distal portions of the lungs (**hyperinflation**). - Characterized by destruction of alveolar walls, resulting in abnormal enlargement of gas-exchange airways (acini). - Obstruction results from inflammatory and destructive changes in lung tissues rather than mucus production (as in chronic bronchitis). - It is most often caused by inhalation of toxic gases, such as cigarette smoke. - Emphysema is characterized by inflammation, an imbalance between proteases and antiproteases, oxidative stress, and apoptosis of lung structural cells. - Destruction of alveoli leads to large air spaces within the lung parenchyma (**bullae**) and air spaces adjacent to pleurae (**blebs**). **Clinical Manifestations of Chronic Obstructive Pulmonary Disease (COPD)** - **Dyspnea** on exertion that progresses to marked dyspnea at rest is the most common symptom. - **Chronic bronchitis**: persistent productive cough - **Emphysema**: cough is usually only productive during acute exacerbations - Thin body habitus - Tachypnea with prolonged expiration - Use of accessory muscles for ventilation - Increased anteroposterior diameter of the chest (**barrel chest**) - Hyper resonant sound with percussion of the chest - Tendency to lean forward with arms extended and braced on knees when sitting - Exhalation through pursed lips - Polycythemia and cyanosis due to marked hypoxemia - Right heart failure and peripheral edema due to cor pulmonale **Comparison of Emphysema and Chronic Bronchitis** **Clinical Manifestation** **Bronchitis** **Emphysema** ---------------------------- ---------------- ---------------- Productive Cough Classic With infection Dyspnea Late Common Wheezing Intermittent Common Barrel Chest Occasionally Classic Cyanosis Common Uncommon Chronic Hypoventilation Common Late Polycythemia Common Late Cor Pulmonale Common Late **Asthma** **Pathophysiological Mechanisms of Asthma** - **Asthma** is a familial disorder. - Airway epithelial exposure to an antigen triggers both an innate and adaptive immune response in sensitized individuals. - Cells involved in the immune response include dendritic cells, T-helper 2 (Th2) lymphocytes, B lymphocytes, mast cells, neutrophils, eosinophils, and basophils. - **Early asthmatic response**: - Mast cell degranulation and release of mediators, including histamine, leukotrienes, and prostaglandins, leading to: - Bronchospasm - Vascular leak (bronchial edema) - Mucus secretion - **Late asthmatic response**: - Infiltration of inflammatory cells (eosinophils, neutrophils) into the airway, leading to: - Airway edema - Mucus hypersecretion - Epithelial damage **Clinical Manifestations of Asthma** - Individuals are typically asymptomatic between attacks, with normal pulmonary function test results. - During an asthma attack: - Chest constriction - Expiratory wheezing - Dyspnea - Nonproductive cough - Prolonged expiration - Use of accessory muscles of respiration - Tachycardia - Tachypnea - Pulsus paradoxus may be noted - Anxiety and sweating - Faint breath sounds when air movement is poor - Nasal flaring - Retractions in the substernal, subcostal, intercostal, suprasternal, or sternocleidomastoid areas - Head bobbing in infants from sternocleidomastoid muscle use **Pulmonary Embolism, Pulmonary Artery Hypertension, and Cor Pulmonale** **Pathophysiology** **Pulmonary Embolism** - **Pulmonary embolism (PE)** occurs when an embolus occludes a portion of the pulmonary vasculature. - The most common embolus is a **blood clot** that travels from a deep vein thrombosis (DVT) in the lower leg. - When a thrombus lodges in the pulmonary circulation, it causes the release of neurohumoral substances (e.g., serotonin, histamine, catecholamines, angiotensin II) and inflammatory mediators (e.g., endothelin, leukotrienes, thromboxanes, toxic oxygen-free radicals). - This leads to widespread vasoconstriction, further reducing blood flow to the lungs. **Pulmonary Artery Hypertension** - **Pulmonary hypertension (PH)** is defined as a mean pulmonary artery pressure greater than 25 mmHg at rest. - **Pulmonary artery hypertension (PAH)** is characterized by endothelial dysfunction with overproduction of vasoconstrictors and decreased production of vasodilators. - Inflammation and fibrosis lead to vascular remodeling and permanent arteriolar narrowing. **Cor Pulmonale** - **Cor pulmonale** is right ventricular enlargement due to pulmonary disorders that cause PH. - Chronic pressure overload from PH leads to right ventricular hypertrophy. - Right ventricular compliance decreases, increasing pressure in the left ventricle and systemic venous circulation. - This can eventually lead to right ventricular dilation and failure. **Clinical Manifestations** **Pulmonary Embolism** - Nonspecific clinical manifestations, often confused with other pulmonary or cardiac conditions. - DVT is often asymptomatic. - Classic presentation: - Sudden onset of pleuritic chest pain - Dyspnea - Tachypnea - Tachycardia - Unexplained anxiety - Syncope or hemoptysis may also occur - Signs with large emboli: - Pleural friction rub - Pleural effusion - Fever - Leukocytosis - Signs with recurrent small emboli: - Progressive incapacitation - Precordial pain - Anxiety - Dyspnea - Right ventricular enlargement **Pulmonary Artery Hypertension** - Symptoms may not appear until late in the disease. - Fatigue - Chest discomfort - Tachypnea - Dyspnea, particularly with exercise - Signs on physical examination: - Peripheral edema - Jugular venous distention - Precordial heave - Accentuation of the pulmonary component of the second heart sound **Cor Pulmonale** - Exertional dyspnea - Signs on physical examination: - Increased intensity of the second heart sound - Pulmonic valve murmur - Tricuspid valve murmur in the presence of right ventricular failure - Jugular venous distention - Hepatosplenomegaly - Peripheral edema **Respiratory Infections in Children** **Common Causative Microorganisms** - **Bronchiolitis**: Primarily caused by viruses, particularly respiratory syncytial virus (RSV) - **Croup**: Typically caused by the parainfluenza virus. - **Acute Epiglottitis**: *Haemophilus influenzae* type b (Hib) was once the most common cause, but its incidence has significantly decreased due to widespread Hib vaccination. - **Tonsillitis**: Can be caused by viruses (e.g., adenovirus, Epstein-Barr virus, influenza virus, parainfluenza virus, enteroviruses) or bacteria (e.g., Group A *Streptococcus*, *Streptococcus pneumoniae*, *Staphylococcus aureus*, *Haemophilus influenzae*, *Moraxella catarrhalis*). - **Pneumonia**: Can be caused by viruses (e.g., RSV, influenza virus, parainfluenza virus, human metapneumovirus), bacteria (e.g., *Streptococcus pneumoniae*, *Haemophilus influenzae*, *Staphylococcus aureus*), or atypical bacteria (e.g., *Mycoplasma pneumoniae*, *Chlamydophila pneumoniae*). **Pathophysiological Mechanisms** - **Respiratory infections in children** typically involve viral or bacterial invasion of the respiratory tract, leading to inflammation and obstruction. - The immune system responds to the infection, but this can also contribute to symptoms. - **Obstructive respiratory disorders in children** are characterized by narrowing of the airways, making it difficult to breathe. - This obstruction can be caused by inflammation, mucus production, or bronchospasm. **Clinical Manifestations** - **Bronchiolitis**: rapid ventilatory rate, use of accessory muscles, low-grade fever, nonproductive cough, wheezing, hypoxemia - **Croup**: a barking cough, hoarse voice, inspiratory stridor, deep retractions, agitation, tachycardia, pallor or cyanosis in severe cases - **Acute Epiglottitis**: high fever, sore throat, difficulty swallowing, drooling, muffled voice, stridor, respiratory distress, and tripod positioning - **Tonsillitis**: sore throat, fever, difficulty swallowing, swollen tonsils with white or yellow patches, swollen lymph nodes in the neck, muffled voice - **Pneumonia**: fever, cough, rapid breathing, difficulty breathing, chest pain, fatigue, loss of appetite, wheezing **Lung Cancer** **Risk Factors** - **Non-small cell lung cancer (NSCLC)**: - **Smoking** - **Air pollution** - **Occupational hazards**, such as exposure to asbestos, arsenic, chromium, nickel, ionizing radiation - **Genetics**: polymorphisms in genes for growth factors, angiogenesis, apoptosis, DNA repair, and detoxification of smoke - **Oncogenes** and **tumor suppressor genes** - **CYP1A1 gene** in smoking populations - **Large cell carcinoma**: - Similar risk factors to NSCLC, including smoking, air pollution, and occupational hazards - Large cell carcinoma is a diagnosis of exclusion, meaning it is diagnosed after other types of NSCLC have been ruled out. - **Small cell lung cancer (SCLC)**: - **Smoking** is the strongest risk factor **Pathophysiology of Lung Cancer** - Most lung cancers, including NSCLC and SCLC, originate from cells lining the bronchi (bronchogenic carcinomas). - **Carcinogens** in tobacco smoke (and other sources like air pollution) cause mutations in the bronchial mucosa. - These mutations affect genes involved in cell growth and differentiation, leading to uncontrolled cell proliferation. - Bronchial epithelial cells undergo a series of changes, progressing from metaplasia to carcinoma in situ and finally to invasive carcinoma. - Tumors invade surrounding tissues and eventually metastasize to distant sites, including the brain, bone marrow, and liver. **Prognosis of Lung Cancers** - **Non-small cell lung cancer (NSCLC)**: - **Squamous cell carcinoma**: slow-growing and tends to metastasize late, mostly to hilar lymph nodes. Prognosis is generally better than other types of lung cancer if detected early. - **Adenocarcinoma**: has a moderate growth rate and can metastasize early to lymph nodes, pleura, bone, adrenal glands, and brain. Prognosis is variable depending on the stage at diagnosis and the presence of specific mutations. - **Large cell carcinoma**: rapid growth rate, early and widespread metastasis. It has a poor prognosis because it is often diagnosed at an advanced stage. - **Small cell lung cancer (SCLC)**: very rapid growth rate, very early metastasis (often to the mediastinum, lymph nodes, brain, and bone marrow). SCLC generally has a poor prognosis because of its aggressive nature and early metastasis.