C25+L53+Pathophysiologies2025.pdf

Pathophysiologies 1 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis  Defence against infection Inna...

Pathophysiologies 1 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis  Defence against infection Innate Adaptive Epithelia Specific response Cilia, sputum, cough to specific antigen Alveolar macrophage Antigen presentation synergy Neutrophils T lymphocytes Natural killer cells B lymphocytes Complement Memory cells ©J P Jamison Pathophysiology for medical students Cells and humoral adaptive immune competency Bone marrow Lymphoid progenitor cells Thymus B- lymphocytes T-lymphocytes Plasma cells Antibody Cytotoxic Effective cell mediated humoral responses responses ©J P Jamison Pathophysiology for medical students  Immune regulation Immune tolerance Immune response is suppressed - against self → autoimmune diseases - terminates acute response to infection - prevents damaging excessive inflammatory response to foreign antigen - oncogenesis progression Mechanisms - apoptosis - anergy - T reg cells ©J P Jamison Pathophysiology for medical students  Hypersensitivity Gell & Coombs classification I II III IV IgE IgG & IgM Immune Cell mast cells autoimmune complexes mediated ©J P Jamison Pathophysiology for medical students  Type I Immediate very fast - minutes IgE pre-formed, attached to mast cells, eosinophils and basophils Th2 helper cells, cytokines IL5 Antigen presents - mediators released Examples; Parasite defence, atopic eczema, asthma, anaphylaxis ©J P Jamison Pathophysiology for medical students  Type II IgG & IgM humoral autoimmunity Failure to tolerate self Neutrophils, macrophages, complement Examples: Goodpasture disease – basement membranes in alveoli and glomeruli ©J P Jamison Pathophysiology for medical students  Type III IgG/antigen complex cause inflammation and self damage Antigen presents – antibody formed, complexes deposited in tissues, neutrophils macrophages, complement Hypersensitivity pneumonitis (allergic alveolitis) eg pigeon fancier, farmer’s lung ©J P Jamison Pathophysiology for medical students  Type IV Delayed - > 3 days Cell mediated - T-lymphocytes migrate to form granular deposits in tissues Th1 helper cells, cytokines and chemokines Tuberculosis Mantoux test, transplant rejection, contact dermatitis, coeliac disease, tumour immunity ©J P Jamison Pathophysiology for medical students  Type V Subset of type II Autoimmune stimulation of hormone secretion Graves disease: antibody simulates TSH receptors and stimulates thyroxine secretion from the thyroid ©J P Jamison Pathophysiology for medical students Pathophysiologies 2 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis Asthma obstructive ventilatory defect which varies with time allergic immune response reversible to 2 agonist bronchial hyper-responsiveness bronchial wall thickening eosinophilic inflammation (can be neutrophilic) smooth muscle constriction ©J P Jamison Pathophysiology for medical students Asthma pathology ©J P Jamison Pathophysiology for medical students Spirometry - normal FVC Normal Peak expiratory flow Vol expired FEV1 Flow Volume 1 Time 6s % predicted = 100 × actual value/predicted value standard deviate (z) = (actual-predicted)/residual standard deviation ©J P Jamison Pathophysiology for medical students Spirometry - obstruction FVC Normal Vol expired FEV1 Flow Volume 1 Time 6s Obstruction Vol expired FVC Flow Flow FEV1 Volume Volume Volume 1 Time 6s Asthma Emphysema Extrathoracic ©J P Jamison Pathophysiology for medical students Pathophysiologies 3 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis  Hypersensitivity pneumonitis (Extrinsic allergic alveolitis) Very fine allergen inhaled – penetrates to alveoli Pigeon droppings Farmer’s lung (mouldy hay, thermophilic actinomyces) Other chemicals Immune complex IgM and IgG with allergen (type III) Inflammation in alveoli, increased vascular permeability Restriction, decreased compliance and gas transfer Also cell mediated (type IV) Responds to avoidance, otherwise progresses to fibrosis Hypersensitivity Pneumonitis - alveoli Normal Alveoli thickened, inflammation ©J P Jamison Pathophysiology for medical students  Acute →Chronic Prolonged or repeated exposure to the allergen induces other cytokines, some Type IV hypersensitivity and eventually collagenous fibrosis in alveolar walls – pulmonary fibrosis ©J P Jamison Pathophysiology for medical students Pathophysiologies 4 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis Pulmonary fibrosis pathophysiology increased interstitial collagen – alveolar wall inflammation – decreased lung compliance – decreased gas transfer – ventilation:perfusion mismatch – pulmonary hypertension causes – idiopathic – allergic – infective – toxic, irritant – connective tissue disease ©J P Jamison Pathophysiology for medical students Pulmonary fibrosis presentation dyspnoea, exercise intolerance dry cough causes – occupational – recreational – environmental – systemic features fine inspiratory crepitations restrictive ventilatory defect decreased transfer factor chest X-ray, high resolution CT scan ©J P Jamison Pathophysiology for medical students Spirometry - restriction FVC Normal Vol expired FEV1 Flow Volume 1 Time 6s Restriction Vol expired FVC FEV1 Flow Volume 1 Time 6s ©J P Jamison Pathophysiology for medical students Idiopathic pulmonary fibrosis increased interstitial markings, most marked at bases shaggy heart border ©J P Jamison Pathophysiology for medical students Pathophysiologies 5 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis Chronic obstructive pulmonary disease Chronic bronchitis – cough & sputum 3 months, 2 years COPD – obstructive ventilatory defect Usually cigarette smoking Progressive symptoms – dyspnoea, cough, sputum, infective exacerbations Coarse crepitations & wheeze ©J P Jamison Pathophysiology for medical students Pathophysiologies 6 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis Emphysema Destruction of elastin fibres cigarette smoking 1 anti trypsin deficiency increased lung compliance increased TLC increased airway resistance increased work of breathing loss of alveoli decreased transfer factor ©J P Jamison Pathophysiology for medical students Alveolar destruction in emphsyema ©J P Jamison Pathophysiology for medical students Spirometry – emphysema obstruction FVC Normal Vol expired FEV1 Flow Volume 1 Time 6s Obstruction Vol expired FVC Flow Flow FEV1 Volume Volume Volume 1 Time 6s Asthma Emphysema Extrathoracic ©J P Jamison Pathophysiology for medical students Pathophysiologies 7 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis Pulmonary hypertension pathophysiology increased pulmonary vascular resistance – idiopathic – hypoxia – thrombo-embolism – schistosomiasis back pressure - left side heart dysfunction or pulmonary veno-occlusion increased flow - left to right shunt ventilation:perfusion mismatch ©J P Jamison Pathophysiology for medical students Pulmonary hypertension presentation often under- or late-diagnosed non-specific - dyspnoea, fatigue, exercise intolerance, syncope, pain, cough, haemoptysis – symptoms often overwhelmed by underlying causative disease lung heart connective tissue disease increased pulmonary second heart sound right ventricular heave chest X-ray, echocardiogram right heart catheter (normal 25/10 mmHg) ©J P Jamison Pathophysiology for medical students Pulmonary hypertension due to left to right atrial shunt distended central pulmonary arteries ©J P Jamison Pathophysiology for medical students Pathophysiologies 8 Immune regulation, tolerance and hypersensitivity Asthma Hypersensitivity pneumonitis Pulmonary fibrosis Chronic obstructive pulmonary disease Emphysema Pulmonary hypertension Bronchiectasis Bronchiectasis pathophysiology focal distension of bronchi > 2mm – transmural bronchial wall inflammation – outward traction by pulmonary parenchyma – collapse in expiration – poor clearance of secretions – obstructive ventilatory defect – recurrent infection causes – infection – cystic fibrosis - increased viscosity of secretions – ciliary dyskinesia – gamma globulin deficiency ©J P Jamison Pathophysiology for medical students Bronchiectasis presentation cough with profuse mucopurulent sputum occasional haemoptysis rhonchi, course crepitations, squawks obstructive ventilatory defect chest X-ray, high resolution CT scan – cylindrical – cystic – varicose ©J P Jamison Pathophysiology for medical students Bronchiectasis CT scan of right lung varicose ©J P Jamison Pathophysiology for medical students ##/## Join at: vevox.app ID: 151-048-964 Question slide A 20-year-old man presents with several years history of wheeze, breathlessness and chest tightness. His symptoms vary with seasons and are worst in the early morning. His FEV1 is 60% predicted and FVC 100% predicted. 15 minutes after inhaling a beta 2 agonist his FEV1 was 80 % predicted. What blood cell count is most likely to help diagnosis? basophils 0% eosinophil 0% erythrocyte 0% lymphocyte 0% neutrophil 0%  ##/## Join at: vevox.app ID: 151-048-964 Question slide A 54 year old woman presents with a one year history of progressive dyspnoea on exertion. Loud 2nd heart sound. SpO2 is 98 %. Echocardiogram ejection fraction 70 %; pulmonary artery pressure 44/25 mmHg What is the most likely diagnosis? left ventricular disease 0% lung disease 0% pulmonary embolism 0% pulmonary hypertension 0% ventilation;perfusion mismatch 0% ##/## Join at: vevox.app ID: 151-048-964 Question slide A 35-year-old woman presents with a several year history of cough productive of 100 mL sputum daily, sometimes gray often greenish and foul smelling. On auscultation there are widespread rhonchi and course crepitations. FEV1 is 40% predicted, FVC 60% predicted. What is the most likely diagnosis? asthma 0% bronchiectasis 0% chronic obstructive pulmonary disease 0% hypersensitivity pneumonitis 0% pulmonary vascular disease 0%