Pathology of Respiratory System Disorders

1. Pathology of Respiratory System Disorders MX1002-PAS-Wk7-RSThe only place wheresuccess comes beforework is in a dictionary…!Vidal Sassoon

2. MX1002-PAS-Wk7-RSPathophysiologyRespiratory SystemDr. Venkatesh M. Shashidhar.Associate Professor & Head of Pathology MX1002-PAS-Wk7-RSPathophysiologyRespiratory SystemDr. Venkatesh M. Shashidhar.Associate Professor & Head of Pathology

3. PAS-Respiratory PathophysiologyIntroduction to Resp. Sys:• 10,000L/day of air – filtered, moistened,warmed, O2/Co2. exchanged.!• Full capacity 6L. (500ml at rest)• Sinusitis, pharyngitis, laryngitis…* URI• Pneumonia: Inflammation of lung * LRI• Chronic: COPD, Fibrosis – Smoking.• Commonest internal Cancer.• Respiratory tract inflammations -commonest in medical practice.• Enormous morbidity & mortality.• Important medical learning. Doctors daily bread….! PAS-Respiratory PathophysiologyIntroduction to Resp. Sys:• 10,000L/day of air – filtered, moistened,warmed, O2/Co2. exchanged.!• Full capacity 6L. (500ml at rest)• Sinusitis, pharyngitis, laryngitis…* URI• Pneumonia: Inflammation of lung * LRI• Chronic: COPD, Fibrosis – Smoking.• Commonest internal Cancer.• Respiratory tract inflammations -commonest in medical practice.• Enormous morbidity & mortality.• Important medical learning. Doctors daily bread….!

4. PAS-Respiratory PathophysiologyNormal Lung

5. PAS-Respiratory PathophysiologyRespiration – Respiratory system:5 PAS-Respiratory PathophysiologyRespiration – Respiratory system:5

6. PAS-Respiratory PathophysiologyRespiration – Respiratory system:6 PAS-Respiratory PathophysiologyRespiration – Respiratory system:6

7. Normal Lung

8. PAS-Respiratory PathophysiologyAlveolar Gas Exchange:8Co2O2 PAS-Respiratory PathophysiologyAlveolar Gas Exchange:8Co2O2

9. PAS-Respiratory PathophysiologyLung Function testing:9Expiration0 ------- Volume ---------------6LInspiration PAS-Respiratory PathophysiologyLung Function testing:9Expiration0 ------- Volume ---------------6LInspiration

10. . PAS-Respiratory PathophysiologyLung Function Testing:• Total Lung Capacity (TLC) 6L male/4.7L fem.• Tidal Volume (TV) – 500 / 390ml• Forced Vital Capacity (FVC) 4.8L / 3.7L• Forced Expiratory Volume in 1 Sec - FEV1• FEV1/FVC (FEV1%) - 75–80% normal.1. In Obstructive diseases (COPD) FEV1 low& FVC high. So FEV1/FVC is low (<80%).2. In Restrictive diseases (fibrosis) the FEV1and FVC are both low proportionally and theFEV1/FVC value normal or high. Volume (%FYC)

11. . MX1002-PAS-Wk7-RSFirst step to make yourdreams come trueis to wake up!— Paul Valery

12. . PAS-Respiratory PathophysiologyPneumonia: Infection of lung (LRT)• Inflammation of alveoli• Etiology: pathogens vs defence.• Types: Bacterial, viral, fungal, other.• Clinical: Lobar / Broncho pneumonia.• Symptoms: Fever, cough, dyspnoea.• Complications: Spread  septicemia,abscess, scarring.

13. . PAS-Respiratory PathophysiologyPneumonia Types:Etiologic Types:• Infective– Viral– Bacterial– Fungal– Tuberculosis• Non Infective– Toxins– chemical– AspirationMorphologic types:• Lobar• Broncho• InterstitialDuration:• Acute• ChronicClinical:• Primary / secondary.

14. . 1. Congestion 2.Red HepatisationNormal 4. Resolution 3. Grey HepatizationPathogenesis of Pneumonia

15. . PAS-Respiratory PathophysiologyPneumonia:

16. . PAS-Respiratory PathophysiologyLobar Pneumonia - Primaryin healthy people in community. Gram Positive Cocci, wholelobe unilateral. heals without scar. Rare complications.

17. . PAS-Respiratory PathophysiologyBronchopneumonia - Secondaryin Sick patients, Gram Negative bacilli, bilateral,basal. More complications, heals by scarring.

18. . PAS-Respiratory PathophysiologyBroncho-pneumonia – Lobar-pneumonia• Extremes of age.• Secondary, in sick.• Both genders.• Klebsiella, E.coli• Patchy, basal, bilateral.• Around Small Bronchi• Not limited by anatomicboundaries.• Usually bilateral.• Middle age – 20-50• Primary in a healthy adult.• males common.• 95% pneumococcus• Entire lobe consolidation• Diffuse• Limited by anatomicboundaries.• Usually unilateral

19. . PAS-Respiratory PathophysiologyTuberculosis:• Mycobacterium tuberculosis (typical)• Primary & Secondary,• Chronic, Hypersensitivity to bacteria,• Caseating Granuloma + Fibrosis.• debilitating, weight loss.• Upperlobe, cavity + fibrosing.• Systemic spread, miliary spread.• Tuberculin Test – hypersensitivity.

20. . MX1002-PAS-Wk7-RS“Whether you think that youcan or that you cant,you are right…!”– Henry Ford

21. . MX1002-PAS-Wk7-RSChronic Lung disorders:Obstructive & Restrictive

22. . PAS-Respiratory PathophysiologyRestrictive vs Obstructive• Interstitial fibrosis• Stiff hard lung• Increased tissue• Normal FEV1:FVC ratio• Normal PEFR.• Types:– Fibrosis,– Pneumoconiosis• Obstruction to air flow.• Soft lung• Loss of tissue.• Low FEV1:VC ratio• Low PEFR.• Types:–COPD–Asthma

23. . PAS-Respiratory PathophysiologyRestrictive - Obstructive

24. . PAS-Respiratory Pathophysiology• Irreversible, fibrotic pulmonarydisease due to the inhalationof large amounts of silica dustover time.• Road, civil & mining workers.• Toxic  Inflam  fibrosis.• dyspnea, fatigue, weight loss,fever, and pleuritic pain.• Multiple small, fibrotic Nodulesbilateral + emphysema.• Restrictive pattern of PFT.• TB association common.Silicosis: Restrictive COPDFine nodular shadows

25. . PAS-Respiratory Pathophysiology• Beaded protein coveredneedle like microscopic .Asbestos bodies• Within alveoli & sputum.• Dyspnoea, dry cough• Diffuse fibrosis: Honey comblung  Pulmonary failure.• Mesothelioma – pleuralcancer.Asbestosis: Restrictive

26. . MX1002-PAS-Wk7-RSPathology ofChronic ObstructivePulmonary Diseases (COPD)Dr. Venkatesh M. ShashidharAssociate Professor of Pathology

27. . PAS-Respiratory PathophysiologyObstructive Airway Disease:• Localized: Foreign body, aspiration, tumor..• Diffuse – Distal airway diseases– Transient reversible spasm - Asthma– Chronic irreversible permanent – COPD.

28. . PAS-Respiratory PathophysiologyAsthma Clinical Pathology:Chronic hypersensitivity inflammatorydisease of bronchi  excess mucousand spasmodic occlusion.Causes• Allergic: allergens, infection• non-allergic:neurogenic,psychogenicSigns and symptoms• dyspnea, wheezing, catching for air.• cough – viscous thick sputum• Tachycardia & chest pain

29. . BronchialInflammationTRIGGERSAllergens, Exercise,Cold Air, SO2 ParticulatesAirwayHyperresponsivenessGenetic*INDUCERSAllergens,Chemical sensitisers,Air pollutants, Virus infectionsAirflow Limitation

30. . PAS-Respiratory PathophysiologyChronic Obstr. Pulm Disease: COPD• Chronic, irreversible airway obstruction withdestruction of bronchi & alveoli.• Clinical: Chronic bronchitis, Emphysema orCOPD (combined).• Smoking / pollution – commonest cause• 15% smokers develop COPD.• Finally leads to lung failure or Cancer.

31. . PAS-Respiratory PathophysiologySmoking – Pathogenesis• Increase in– Alveolar marcrophages– CD8 Lymphocytes– Neutrophils– Proteases.• Tissue irritation / destruction• Airway damage- Bronchitis• Alveoli damage- Emphysema.Emphysema Bronchitis

32. . PAS-Respiratory PathophysiologySmoking effects: FEV 1 & Age

33. . PAS-Respiratory PathophysiologyPathogenesis – Smoke - Lung Dis.CancerInflam COPDIrritation  Inflammation  Mucous  Infections  destr. COPD  Cancer

34. . PAS-Respiratory PathophysiologyNormal - COPD

35. . PAS-Respiratory PathophysiologyCombined  COPD (common)

36. . PAS-Respiratory PathophysiologyLung Normal & in Smokers:

37. . PAS-Respiratory PathophysiologySmokers lung – COPD Bronchitis

38. . PAS-Respiratory PathophysiologyEmphysema

39. . PAS-Respiratory PathophysiologyEmphysema:Pink Puffer:• Lean/weight loss• Forward stooping• Barrel chest• Flat diaphragm• Hyperlucent Lung

40. . PAS-Respiratory PathophysiologyComplications of COPD:1. Cor Pulmonale – Heart failure.2. Acute Exacerbations.3. Recurrent pneumonia.4. End-stage lung disease.5. Polycythemia – hypoxia.6. Bronchiectasis.7. Lung Cancer.

41. . PAS-Respiratory PathophysiologyBronchiectasis:• Permanent dilatation ofbronchi with pus.• Cough, copious purulentsputum (pus).• Lower lobes common• Complications -Pneumonia, septicemia,meningitis.• Management – surgicalresection.

42. . MX1002-PAS-Wk7-RS“Get me well so I can get ontelevision and tell people tostop smoking…!”-- Nat King Cole

43. . “Troubles are often the tools by whichnature fashions us for better things”- Henry Ward Beecher

44. . Life’s battles don’t go always to the stronger orfaster man, sooner or later, The man who wins isthe man who thinks he can….!

45. . MX1002-PAS-Wk7-RSPathology ofLung tumors(Lung Cancer)Dr. Venkatesh M. ShashidharA/Prof. & Head of PathologySchool of Medicine45

46. . PAS-Respiratory PathophysiologyLung Cancer Intro:• Most common & fatal cancer (internalmalignancy)• Kills more people than colorectal,breast, and prostate cancers combined.• Significant increase in incidence..(developing countries*)• Now Increasing in females > breastcancer.• 90% of lung cancers are related tosmoking..! (passive smoking in 5%)• Mutagen sensitive genotype : P-450enzyme• Poor prognosis ~ 5% 5y survival *46

47. . PAS-Respiratory PathophysiologyLung Cancer Incidence:47

48. . PAS-Respiratory PathophysiologyLung Cancer & Smoking:• Proportional to duration, amount & quality of smoking &deep inhaling.• 90% are smokers and 10% are non smokers• 20 fold risk if >40cigarettes per day• >100 fold combined with Asbestos, coal, radon, etc.• Atypical cells in sputum in 96.7% of smokers - 0.9% in nonsmokers.• Smoke has several irritants & carcinogens.– Initiators – Benzo[o]pyrenes– Promoters – Phenol derivatives– Radioactive substances – Polonium, C14, K4048

49. . PAS-Respiratory PathophysiologyLung tumors Classification:• Benign tumours – rare (Adenoma, Hamartoma)• Malignant (common):– Bronchogenic Carcinoma: (95%)– Bronchial Carcinoid Tumor (5%)– Other Tumors (<1%)– Metastasis (common)• Tumors of Pleura– Mesothelioma – asbestosis *49

50. . PAS-Respiratory PathophysiologyTypes of Bronchogenic Ca.:• Bronchogenic Carcinoma (95%)– Small cell ca. SCC – 15-20% (oat cell carcinoma)– Non Small cell NSCC– 80%• Squamous cell carcinoma – 20-30%• Adeno carcinoma – 30-40%• Large cell anaplastic carcinoma• Clinical / prognostic classification:SCC - small cell CaEarly spreadSurgery not possible.Responds to chemo50Non-SCCLate spread – localizedStaging & SurgeryDoes not respond to chemo.