Obstructive Lung Diseases Pathology

Diseases of the Pulmonary Parenchyma, Pleura, Mediastinum & Pulmonary Circulation

• This is a general pathology topic.
• The lecture covers obstructive lung diseases.

Obstructive Lung Diseases

• These are a group of pulmonary disorders that result in dyspnea (shortness of breath), characterized by an obstructive pattern of expiratory airflow limitation on spirometry.
• Disorders include Chronic Obstructive Pulmonary Disease (COPD), asthma, cystic fibrosis (CF), bronchiectasis, and bronchiolar disorders.
• These disorders sometimes overlap clinically.
• Symptoms include wheezing, sputum production, chronic airway-centered inflammation, and episodic worsening of clinical status (exacerbations).

Classification of Obstructive Lung Diseases

• Obstructive lung diseases can be classified based on reversible or irreversible airflow obstruction.
• Emphysema and chronic bronchitis are irreversible/partially reversible airflow obstructions.
• Chronic obstructive pulmonary disease (COPD) is an umbrella term encompassing both emphysema and chronic bronchitis.
• Asthma is a reversible airflow obstruction.

Features of Obstructive Lung Disease

• Key clinical and laboratory findings are summarized for common disorders. -Chronic obstructive pulmonary disease: Chronic progressive dyspnea, cough, sputum production, and exacerbations -Asthma: Chronic cough, purulent sputum, wheezing, and exacerbations -Bronchiectasis: Chronic cough and purulent sputum production -Cystic fibrosis: Sinusitis, bronchiectasis, meconium ileus, malabsorption, infertility -Bronchiolar disorders: Progressive dyspnea, history of connective tissue disease or inflammatory bowel disease

• Laboratory findings for each disorder vary and may include spirometry results (reduced FEV₁/FVC), and various blood tests (e.g., elevated sweat chloride for cystic fibrosis).

Asthma

• Asthma is a chronic inflammatory disorder of the airways.
• Characterized by airway hyper-responsiveness leading to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, especially at night or early morning.
• Episodes are usually associated with widespread but variable airflow obstruction.
• The prevalence of asthma has increased significantly.
• Affects all age groups and is one of the most common and long-term respiratory conditions in terms of global years lived with disability.

Asthma Pathology

• Chronic airway inflammation is a major feature of asthma.
• Patients with asthma have increased numbers of activated inflammatory cells (like eosinophils, mast cells, macrophages, and T lymphocytes) in the airway wall and epithelium.
• These cells produce cytokines, leukotrienes, and bradykinins.
• Airway inflammation is driven by a type 2 helper T-cell response. Some severe asthma cases have a neutrophilic response.
• Airway hyperresponsiveness is a hallmark of asthma.
• Inhaled allergens cause mast cell degranulation.

Clinical Presentation of Asthma

• Major symptoms include episodic dyspnea, wheezing, chest tightness, and cough.
• Symptoms can vary from mild to catastrophic attacks.
• Wheezing is commonly associated but not specific to asthma.
• Symptoms often worsen at night or in the morning.
• Other associated symptoms include sputum production and chest pain/tightness.
• Some patients may present with only cough (cough-variant asthma).
• Exercise-induced bronchoconstriction can cause wheezing.
• Diagnosis can be made by a compatible clinical history and additional diagnostics (FEV-1, PEF).

How to Make a Diagnosis of Asthma

• A clinical history that is compatible with asthma combined with respiratory tests.
• FEV1 ≥ 12% (and 200 mL) increase following administration of a bronchodilator or a trial of glucocorticoids is a positive indicator.
• A PEF diary also gives information regarding asthma exacerbation and appropriate management
• Increase in FEV is greater if it is > 15% and >400 mL.
• A 20% diurnal variation in PEF over 2 weeks is helpful.
• A 15% decrease in FEV1 following exercise is a positive indicator

Management Approach in Adults Based on Asthma Control

• The management strategy for asthma varies based on the severity of symptoms.
• The strategy is centered around maintaining the lowest possible therapy.
• Using inhalers accordingly, and other therapeutic interventions

How to Use a Metered-Dose Inhaler

• Follow specific steps to use an inhaler correctly to ensure medication reaches the respiratory system properly and safely.

Management of Mild to Moderate Asthma Exacerbations & Acute Severe Asthma

• Doubling inhaled glucocorticoid doses does not prevent impending exacerbation.
• Short courses of rescue glucocorticoids (like prednisolone 30-60 mg daily) are often needed to control symptoms.
• Tapering the dose of glucocorticoids is not always necessary.
• Acute severe asthma may require higher dosages

Chronic Obstructive Pulmonary Disease (COPD)

• Definition is based on persistent, reproducible, and expiratory airflow limitation.
• Previous definitions focused on emphysema and chronic bronchitis.
• COPD has a progressive nature and has abnormal inflammation in the lungs and airways.
• Airflow limitation is a key factor, but the condition also includes potentially preventable and treatable risk factors.

Mechanisms of Cigarette Smoke-Induced Inflammation and Oxidant Injury

• Cigarette smoke induces a sequence of events leading to lung injury.
• Macrophage activation is triggered by radical oxygen species which leads to the release of cytokines, growth factors, which ultimately induce inflammation and edema.
• Subsequent inflammatory response induces immune cell recruitment and neutrophil activation, ultimately leads to lung tissue destruction.

Pulmonary Fibrosis

• Clinical presentation is characterized by:

  • Central cyanosis
  • Tachypnea
  • Fine inspiratory crackles at the bases
  • Dull percussion at lung bases

• Chest X-rays/CT scans show some of the physical features of the disease

Pneumonia

• An acute respiratory illness associated with radiological pulmonary shadows (segmental, lobar, or multilobar).
• Community-acquired pneumonia (CAP) is often caused by Streptococcus pneumoniae.
• Hospital-acquired pneumonia (HAP) occurs at least 2 days after hospital admission.
• Factors predisposing to CAP and HAP include reduced host defenses, aspiration, and presence of bacteria in the respiratory tract.

Clinical Features of Pneumonia

• Symptoms include:
  • Systemic features such as fever, rigors, and malaise.
  • Loss of appetite and headaches.
  • Short coughs that are painful and dry (initially) and become mucopurulent.
  • Rust-colored sputum.
  • Hemoptysis.
  • Diagnostic test such as blood tests and radiographic tests (chest x-ray) are important to determine the presence and nature of pneumonia,

Work-up for Pleural Effusion

• A process for diagnosing and determining the management of pleural effusions. This process involves laboratory testing (pleural fluid analysis, blood tests) and determining if the result is a transudate or exudate.
• Treatment generally addresses the underlying cause and typically involves drainage if complicated.
• In general, further treatment depends on the result of further tests.

Management of Pleural Effusion

• Thoracic tube positioning and management.
• Avoiding the removal of too much fluid at once.
• Identifying the underlying cause and treatment accordingly to resolve the underlying condition.

Empyema

• Empyema is the accumulation of pus in the pleural space.
• Characterized by symptoms like fever and chest pain, and accompanied by radiographic evidence and ultrasound imaging

Tuberculosis (TB)

• Infectious disease caused by Mycobacterium tuberculosis.
• Significant resurgence in past century.
• Notification has decreased by 1.5% per year since 2000.
• Primarily affects the pulmonary region, but also the CNS and other systems
• Diagnosis often relies on sputum analysis, tissue biopsies, radiographic tests, and possibly blood tests.

Tuberculosis Pathology

• Features of primary tuberculosis, including primary complexes such as obstructive emphysema, cavitation, pleural effusion, and miliary dissemination, pericarditis.
• Hypersensitivity features such as erythema nodosum, and phlyctenular conjunctivitis.
• A wide range of presentations and clinical features

Systemic Presentation of Extrapulmonary Tuberculosis

• Presents with a range of symptoms, including:
  • Headache, vomiting, seizures, delirium
  • Lymphocytic meningitis, hydrocephalus, space occupying lesions.
  • Chronic back pain, kyphosis, cord compression
  • Abdominal mass, psoas abscess
  • Pericardial effusion, constrictive pericarditis, exudative ascites, mesenteric adenitis, intestinal obstruction, haematuria/dysuria, infertility in women, and epididymitis.
  • General symptoms like weightloss, fever, and night sweats

Tuberculosis Diagnosis & Treatment

• Diagnosis involves patient samples (sputum samples, bronchoscope, washings or BAL, gastric washings)
• Diagnostic testing include tuberculin skin test, stain (Ziehl-Neelsen), fluorescence microscopy, nucleic acid amplification, culture (solid or liquid media), and response to treatment.
• Treatment usually involves multiple anti-TB drugs for an extended period (Standard & Continuation phase).
• Isoniazid (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E) are common drugs.

Pulmonary Vascular Diseases

• A broad term for any disease affecting the blood vessels within the lungs
• Most conditions are associated with diseases of: pulmonary embolism; and pulmonary hypertension.

Pulmonary Vascular Disease Pathology

• The normal pulmonary vasculature is characterized by high flow, low resistance, and high capacitance.
• The right ventricle (RV) is well adapted in this way. However, large increases in afterload, associated with acute pulmonary embolism or chronic pulmonary hypertension, causes the RV to become overburdened.
• Pulmonary hypertension is defined as a mean pulmonary arterial pressure (mPAP) >= 25mmHg. This can be classified into five types, mainly based on the pathophysiological mechanisms that lead to the increase in pressure.

Pulmonary Hypertension Clinical Presentation

• Early symptoms of pulmonary hypertension include:
  • Dyspnea
  • Fatigue
• As the disease progresses, signs of right-side heart failure appear (peripheral edema, decreased appetite, ascites).
• Severity is assessed by the degree of exercise limitation (using NYHA functional class I-IV).
• Chest X-rays can reveal signs of prominent pulmonary arteries or RV enlargement.

Pulmonary Thromboembolism (PE)

• Occurs when a clot (thrombus) travels to the pulmonary artery
• Usually arises from lower limb deep vein thrombosis.
• Additional rare causes include septic emboli, tumors (e.g., choriocarcinoma), fat (after long bone fractures), air, and amniotic fluid emboli.
• Diagnosis includes asking three key questions:
  • Is the clinical presentation consistent with PE?
  • Does the patient have risk factors for PE?
  • Are there any alternative diagnoses that can explain the patient's presentation?

PE Clinical Presentation and Management

• Acute massive PE can cause major hemodynamic effects, resulting in acute right-heart failure.
• Symptoms may include crushing central chest pain, faintness, or collapse.
• Signs/Symptoms include tachycardia, hypotension, and peripheral edema.
• Short-term treatment involves sufficient oxygen, treatment of circulatory shock with intravenous fluids or vasodilators, and use of opiates when needed.
• Long-term treatment includes anticoagulation, thrombolytic therapy, and/or surgical interventions (e.g., caval filters).

Pleural Effusion

• Accumulation of serous fluid in pleural space.
• Can be exudate or transudate based on the pleural fluid analysis.
• Management involves treating the underlying cause, and/or therapeutic aspiration to reduce distresses.

Pleural Effusion and Work-up

• Work-up for pleural effusion is crucial to understand diagnosis and management.
• Fluid analysis (protein, LDH, pH, cells) is key in determining transudate or exudate, which may provide clues about the underlying disease.
• Additional diagnostic procedures and treatment may be needed based on the test results.

This quiz covers the key aspects of obstructive lung diseases, including COPD, asthma, cystic fibrosis, and bronchiectasis. Students will learn about the pathophysiology, symptoms, and classifications of these disorders, focusing on their impact on pulmonary function and associated clinical features.