Respiratory Disease Diagnosis

• Pathophysiologies covered include immune regulation, tolerance and hypersensitivity, asthma, hypersensitivity pneumonitis, pulmonary fibrosis, chronic obstructive pulmonary disease, emphysema, pulmonary hypertension, and bronchiectasis

Defence Against Infection

• Innate defenses include epithelia, cilia, sputum, cough, alveolar macrophages, neutrophils, natural killer cells and complement
• Adaptive defenses involve a specific response to a specific antigen, antigen presentation, T lymphocytes, B lymphocytes and memory cells
• Synergy between innate and adaptive immunity enhances defense

Cells and Humoral Adaptive Immune Competency

• Bone marrow produces lymphoid progenitor cells
• Lymphoid progenitor cells differentiate into T-lymphocytes in the thymus, and B-lymphocytes in other locations
• T-lymphocytes mediate cytotoxic cell responses
• B-lymphocytes become plasma cells
• Plasma cells produce antibodies for effective humoral responses
• Signalling occurs between T-lymphocytes and B-lymphocytes

Immune Regulation

• Immune tolerance is when the immune response is suppressed to prevent autoimmune diseases, terminate acute responses to infection, prevent damaging excessive inflammatory responses to foreign antigens and inhibit oncogenesis progression
• Mechanisms of immune tolerance include apoptosis, anergy, and T regulatory cells

Hypersensitivity - Gell & Coombs classification

• Type I involves IgE and mast cells
• Type 2 involves IgG & IgM autoimmune
• Type 3 involves immune complexes
• Type 4 is cell mediated

Type I Hypersensitivity

• This is immediate and very fast, occurring within minutes
• IgE is pre-formed and attached to mast cells, eosinophils, and basophils
• Th2 helper cells and cytokines like IL5 are involved
• Antigen presentation leads to mediator release
• Examples include parasite defense, atopic eczema, asthma, and anaphylaxis

Type II Hypersensitivity

• Involves IgG & IgM humoral autoimmunity
• Due to a failure to tolerate self
• Mediated by neutrophils, macrophages, and complement
• An example is Goodpasture disease, which affects basement membranes in alveoli and glomeruli

Type III Hypersensitivity

• IgG/antigen complexes cause inflammation and self-damage
• Antigen presentation leads to antibody formation and deposition of complexes in tissues
• Neutrophils, macrophages and complement are involved
• Hypersensitivity pneumonitis, such as allergic alveolitis in pigeon fanciers and farmer's lung are examples

Type IV Hypersensitivity

• Delayed reaction, occurring > 3 days
• Cell mediated with T-lymphocytes migrating to form granular deposits in tissues
• Th1 helper cells, cytokines, and chemokines are involved
• Examples include the Tuberculosis Mantoux test, transplant rejection, contact dermatitis, coeliac disease, and tumor immunity

Type V Hypersensitivity

• It is a subset of type 2
• Autoimmune stimulation of hormone secretion
• Grave's disease, where antibodies stimulate TSH receptors and thyroxine secretion from the thyroid, is an example

Asthma

• Characterized by obstructive ventilatory defects that vary
• Allergic immune response
• Reversible to β2 agonists
• Bronchial hyper-responsiveness, and wall thickening
• Eosinophilic or neutrophilic inflammation
• Smooth muscle constriction

Asthma Pathology

• Mucus plugs with inflammatory cells
• Eosinophilic inflammation
• Adventitial and subintimal
• Smooth muscle hypertrophy
• Basement membrane hypertrophy
• Secretory cell hypertrophy

Spirometry - Normal

• Spirometry is the measurement of airflow over time
• FVC is the Forced Vital Capacity the total volume of air that can be forcibly exhaled after a full inspiration
• FEV1, Forced Expiratory Volume in 1 second, is the volume of air exhaled during the first second of the FVC test
• Percentage predicted is calculated as 100 x (actual value/predicted value)
• The standard deviate (z) = (actual-predicted)/residual standard deviation

Spirometry - Obstruction

• Obstruction leads to reduced airflow, especially during expiration, affecting the shape of the flow-volume loops
• Asthma demonstrates a characteristic obstructive pattern, with reduced FEV1/FVC ratio and response to bronchodilators
• Emphysema, and extrathoracic obstructions also show distinct flow-volume loop patterns

Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)

• Very fine allergens are inhaled and penetrate to alveoli
• Causes include pigeon droppings, farmer's lung (mouldy hay, thermophilic actinomyces), and other chemicals
• Involves immune complexes of IgM and IgG with the allergen (type III hypersensitivity)
• Inflammation in alveoli, increasing vascular permeability
• Restriction, decreased compliance, and impaired gas transfer
• It is also cell mediated (type IV hypersensitivity)
• Responds to allergen avoidance, otherwise progresses to fibrosis
• Alveoli show thickening and inflammation

Acute to Chronic Hypersensitivity Pneumonitis

• Prolonged or repeated exposure to the allergen induces cytokines and sometimes Type IV hypersensitivity that leads to collagenous fibrosis in alveolar walls that causes pulmonary fibrosis

Pulmonary Fibrosis Pathophysiology

• Characterized by increased interstitial collagen
• Alveolar wall inflammation, decreased lung compliance, decreased gas transfer, ventilation-perfusion mismatch, and pulmonary hypertension
• Caused by idiopathic factors, allergies, infections, toxins, irritants and connective tissue diseases

Pulmonary Fibrosis Presentation

• Dyspnoea, exercise intolerance, and dry cough
• Occupational, recreational, environmental, and systemic factors
• Fine inspiratory crepitations
• Restrictive ventilatory defects and transfer factor
• Requires chest X-rays and high-resolution CT scans for diagnosis

Spirometry in Restriction

• Reduction in lung volumes and airflow, resulting in reduced FVC and a normal or elevated FEV1/FVC ratio

Idiopathic Pulmonary Fibrosis

• Shows increased interstitial markings, most marked at the bases of the lungs, along with a shaggy heart border on X-ray

Chronic Obstructive Pulmonary Disease

• Chronic bronchitis, defined as a cough with sputum for three months over two years, characterizes it
• COPD results in obstructive ventilatory defects
• Typically associated with cigarette smoking
• Progressive symptoms of dyspnea, cough, sputum, and infective exacerbations
• Characterized by coarse crepitations and wheezing

Emphysema

• Entails the destruction of elastin fibres due to cigarette smoking or α1-antitrypsin deficiency
• Increases lung compliance and TLC (total lung capacity)
• This leads to increased airway resistance, increased work of breathing, loss of alveoli, and decreased transfer factor
• Results in alveolar destruction

Pulmonary Hypertension Pathophysiology

• Defined by increased pulmonary vascular resistance
• Idiopathic causes, hypoxia, thromboembolism and schistosomiasis
• Back pressure from left-sided heart dysfunction or pulmonary veno-occlusion
• Increased flow from left-to-right shunts
• Ventilation-perfusion mismatch

Pulmonary Hypertension Presentation

• Often under- or late-diagnosed
• Non-specific symptoms include dyspnoea, fatigue, exercise intolerance, syncope, pain, cough, and haemoptysis
• Symptoms overwhelmed by underlying disease: lung, heart, or connective tissue disease
• Increased pulmonary second heart sound and possible right ventricular heave
• Diagnose via chest X-ray, echocardiogram, and right heart catheter (normal is 25/10 mmHg)

Pulmonary Hypertension due to Left to Right Atrial Shunt

• Distended central pulmonary arteries can be seen on chest X-ray

Bronchiectasis Pathophysiology

• Focal distension of bronchi greater than 2mm
• Transmural bronchial wall inflammation
• Outward traction by pulmonary parenchyma
• Collapse in expiration, poor clearance of secretions, and obstructive ventilatory defect, and recurrent infection
• Caused by infection, cystic fibrosis, ciliary dyskinesia, and gamma globulin deficiency

Bronchiectasis Presentation

• Cough with profuse mucopurulent sputum and occasional haemoptysis
• Rhonchi, coarse crepitations, and squawks on auscultation
• Obstructive ventilatory defect
• Diagnosed with chest X-ray and high-resolution CT scans, which show cylindrical, cystic or varicose bronchi

Bronchiectasis imaging

• CT scan of right lung shows varicose bronchi

Questions focus on diagnosing respiratory diseases based on patient symptoms, pulmonary function tests (FEV1, FVC), and other clinical findings, using blood cell counts. Conditions include asthma, pulmonary hypertension, and bronchiectasis.