Pathology of COPD

1. “Within the mind are all the resources required for successful living. Ideas are present in the consciousness, which when released and given scope to grow and take shape, lead to successful events” - Wings of Fire: An Autobiography of Dr. APJ Abdul Kalam.

2. “ Whether you think you can or you can't, you are right…!” – Henry Ford

3. CPC14: Mrs. PT. 64y Fem. SOB  Mrs. P.T. 64 y female, to ED at TTH.  Worsening SOB, years, worst today - At rest • Previously SOB after exertion- COPD. • Gradually worsening over the years, now O2 at night. • Sputum chronic clear white, but light brown today. • Cough - on and off for years, No wheeze, no hemoptysis, • Chest pain worse with breathing today, fever, sweaty. • Smoked 3 packs/day for 35 years; quit 7y ago.  Foreign travel: Norfolk Island 3wks. No health problem.  RX: Pneumonia, COPD, Emphysema, CCF

4. CPC: 2011 – 58M Chronic cough. Trevor is 58 year old Caucasian man, years of coughing. pneumonia 3 years ago; bronchitis several times a year, Dyspnoea, Hoover’s & Campbell sign positive, leans forward for breathing. heavy smoker (30+/day); quit 3 years ago. Previous PFT: FEV1 = 1.3 FVC = 2.6 FEV1/FVC = 50%. (too sick to perform PFT today.)   • What is the significance of… 1. Leaning forward – “arms on knees” 2. Intercostal in-drawing 3. Hoover's sign ? Tracheal tug ? 4. Campbell's sign ? 1. 2. 3. 4. Pathogenesis of symptoms ? Further questions ? Differential diagnosis ? Learning issues? PFT

5. Clinical Feature - ? Pathogenesis  SOB, Dyspnoea  Cough  Wheezing, Stridor.  Rhonchi, Crackles/ Rales.  Dullness  Hyper-resonance  Hyperventilation  Tachypnoea  Pleural rub  Pleurisy (pleuritis)  Sleep apnoea central/obstructive. • White sputum (frothy) • Rusty, Yellow, green sputum • Haemoptysis • Night sweats • Sleep apnoea • Kussmaul’s breathing. • Ataxic breathing • Apneustic breathing. • Cheyne-Stokes breathing. • Paradoxical breathing • Resp acidosis / alkalosis.

6. COPD: Questions  What is Chronic Bronchitis & Emphysema ?  Pathogenesis of COPD/CB/Emphysema ?  Smoking – Disease, Pathogenesis ?  Difference.. Obstructive / Restrictive disease ?  What findings on PFT expected ?  How is he maintaining normal pO2 & pCo2 ?  why is he pink & puffing ?  What Gross & Microscopic features in his lung ?  What complications are expected ?  Pneumoconiosis, TB, DPF,

7. COPD: Questions  Bronchiectasis ?  Atelectasis ?  Lung abscess ?  Honeycomb lung ?  Pneumothorax ?  Tension pneumothorax?  Pleural effusion  Emphysema types. • Panacinar - α1AT def. • Paraseptal • Irregular • Bullous • compensatory Tuberculosis Primary, secondary, anergic, milliary, caseous, fibrocaseous, fibrosing. Asthma – types. Atopic, non-atopic, drugs, occupational etc. Pathogenesis, gross, micro Curschmann spirals, Charcot- Leyden crystals. Pneumoconioses Silicosis, Anthracosis, Asbestosis IPF – Ideopathic pulm. fibrosis. • • • • • • • • • • Text Book: Robbins Basic Pathology, 8th or 9th edition

8. Core Learning Issues:  Major: • COPD Pathology – Restrictive / Obstructive. • Emphysema & Bronchitis – types, pathology & clinical. • Pathology of Tobacco related disorders. • PFT - FEV1/FVC & its use and interpretation. • Pneumonia – types & Pathology (Lobar, Broncho & Int.) • Allergic bronchitis, Asthma, Tuberculosis * self study.  Minor: • Pneumoconiosis – Asbestosis, silicosis etc. • Cor pulmonale, Pulmonary hypertension. • Diffuse Pulmonary Fibrosis & honeycomb lung. • Acute lung injury - ARDS, DAD, HMD of infants. • Sarcoidosis ?

9. The cigarette does the smoking,..!

10. Normal Lung Tr.Air Sh Br. Mar. Colon air

12. Normal Lung Tissue

13. Lung Histology Bronchiole Alveoli Type 2 Type 1-Pneumocyte

14. There is only one secret to staying young, being happy, and achieving success - You've got to “enjoy what you do”…! Including studying pathology…..

15. Pathology of COPD, Chronic lung diseases & Pneumonia* Dr. Shashidhar Venkatesh Murthy. A/Prof. & Head of Pathology

16. Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 4thleading cause of death, women more, smoking >80% Proportion of 1965 Rate 3.0 Coronary Heart Disease 3.0 All Other Causes Stroke Other CVD COPD 2.5 2.5 2.0 2.0 1.5 1.5 1.0 1.0 0.5 0.5 –59% –64% –35% +163% –7% 0.0 0 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998

17. Pathology of Smoking  Research evidence: smoking  disease  >4000 chemicals, 43 carcinogens.  >90% of COPD is due to smoking.  15% of smokers develop COPD.  Injury & inflammation central to damage.  Smoking a single cigarette results in an acute increase in neutrophils at 1 hour.  Increased neutrophils in smokers, which decrease following reduction/quitting.  Patients with COPD have sputum neutrophilia that persists even after cessation of smoking.

18. Smoking effects: FEV 1 & Age

19. Smoking related diseases:  Non-neoplastic: • Bronchitis, pneumonia, bronchiectasis. • Chronic bronchitis, emphysema (COPD) • Atherosclerosis  IHD, Stroke, MI. • Gastritis, Peptic Ulcer, Oesophagitis. • Arteriosclerosis – Berger’s disease.  Neoplastic: • Lung Cancer (many types) • Oral, laryngeal & oesophageal cancer. • Carcinoma of bladder, Pancreas, cervix, larynx.

20. Ask, Aspire, Achieve..! …..Ask questions J. Robin Warren Australian 2005 Nobel price in Medicine - at RCPA conference 2006 Sydney.

21. Pathogenesis of COPD Dr. Shashidhar Venkatesh Murthy. A/Prof. & Head of Pathology

22. Pathogenesis of COPD 1. Smoke, irritants, carcinogens. 2. Tissue irritation & destruction 3. Inflam  Mucous production. 4. Airway damage  Narrowing. 5. Alveolar damage  widening.  Increase in • Alveolar marcrophages • CD8 Lymphocytes • Neutrophils • Proteases.  Airway inflam  Bronchitis  Alveoli damage  Emphysema.  Both  COPD. α1AT def.. Emphysema Bronchitis Emphysema

23. The mind is everything. What you think you become! -- Buddha

24. Pathogenesis – Chronic Bronchitis Irritation   COPD   Initiation   Promotion   Ca. Chronic Bronchitis K-Ras C-myc 3p p53 Pathogenesis: 1. Smoking – carcinogens 2. 3p – tumor suppressor gene loss 3. Mutations (p53, KRAS, EGFR..) 4. Dysplasia 5. Infiltration 6. Spread 7. Metastases.

25. COPD Pathogenesis: Emphysema

26. COPD: Overlap of Clinical syndromes COPD

27. Both affected  COPD (common)

28. Chronic Bronchitis - Emphysema: Predominant Bronchitis 40-45 Mild; late Early; copious sputum Common Repeated Predominant Emphysema 50-75 Severe; early Late; scanty sputum Occasional Terminal Age (yr) Dyspnea Cough Infections Respiratory insufficiency Cor pulmonale Airway resistance Elastic recoil Chest radiograph Appearance Common Increased Rare; terminal Normal or slightly increased Low Hyperinflation; small heart Normal Prominent vessels; large heart Blue bloater Pink puffer

29. “Know more today about the world than yesterday and lessen the suffering of others. You'd be surprised how far that gets you.” ― Neil deGrasse Tyson

30. Lung Normal & in Smokers:

31. Smokers Lung: COPD - Emphysema  Upper lobe – black spots of anthracotic (Co2) pigmentation (centre of each lobule).  Centrilobular alveolar destruction with carbon pigmentation.  Other types: * • Panacinar • Paraseptal • Bullous • Interstitial • Irregular.

32. Normal - Emphysema

33. Normal Emphysema

34. Normal - COPD CB Emphysema

35. Centrilobular Emphysema: Pink Puffer: Lean/weight loss No cyanosis Forward stooping Barrel chest Flat diaphragm Hyperlucent Lung

36. Whether you think that you can or that you can't, you are right…! – Henry Ford

37. Chronic Bronchitis: Normal Chronic Bronchitis • Squamous Metaplasia. • mucous gland. Hyperplasia

38. Emphysema: Other types  Panacinar • Congenital, α1AT def.  Paraseptal, Bullous • Old scar.  Irregular • Past diffuse scaring.

39. Complications of COPD: 1. Pneumothorax, Infections, Bronchectasis. 2. Polycythemia – hypoxia. 3. End-stage lung disease. 4. Acute Exacerbations. 5. Cor Pulmonale – Right heart failure. • syncope, hypoxia, pedal edema, passive hepatic congestion and death.  Lung Cancer LV RV

40. Bronchiectasis:  Permanent dilatation & Infection of bronchi.  Cough, copious purulent sputum, mixed infections. Lower lobes common  Secondary to COPD, Pneumonia or localised obstructions.  Complications: • Pneumonia, empyema, septicemia, meningitis.  Types: • Cylindrical, Saccular, Fusiform (no

41. Bronchiectasis: • Permanent dilatation with secondary infection • Pus* filled, *visible bronchi till *periphery. • Abundant, greenish, sputum, mix culture +ve.

42. COPD Summary:  Definition: Progressive Irreversible Chronic airflow limitation due to inflammatory response to noxious substances. Progressive decrease in PF.  Diagnosis: FEV1<80%, FEV1/FVC <70%  Etiology • >90% smoking (15% of smokers COPD) • Pollution, 1AT def. , genetic susceptibility, Asthma, idiopathic.  Clinical Syndromes: CB, Emphysema, COPD, Asthma, & Bronchiectasis.  Complications: Pulmonary failure, RS Cardiac failure, Endstage disease, Cancer.

43.  Self Study - Restrictive Lung Disorders. - IPF, Diffuse fibrosis, - Honeycomb lung. - Pneumoconiosis - Silicosis, Asbestosis, Coal. -Tuberculosis. - Asthma - Good pasteur’s syndrome. - DAD: ARDS/HMD

44. Pneumonia: Clinical vignette  50y man, alcoholic, high fever, cough, copious foul smelling brown sputum, pleuritic rt sided chest pain.  HPC: wife reports that he was brought home in a semi- conscious state a few days ago – drunk.  Thin, distressed, pursed lip breathing, using accessory muscles of respiration, cannot speak in full sentences, leaning forwards…*  39°C, RR-22/min, peripheral cyanosis.  Chest-rib in-drawing, diminished air entry, soft expiratory wheezes, bronchial breathing L lower post chest.  PE: fever, consolidation right middle and lower lobes.  sputum microscopy - abundant PMN and mixed oral flora. Pathogenesis, Differential diagnosis…..?

45. Pneumonia: Questions  What is pneumonia? Types? pathogenesis?  Lobar, Broncho & Interstial pneumonia?  Community acquired / Nosocomial / hospital acquired pneumonia ? What is the difference ?  Acute, Chronic & recurrent pneumonia?  Typical, Atypical pneumonia?  Common organisms causing pneumonia?  Microbiology – lab diagnosis, culture, tests.  Gross and microscopy of pneumonia.  Phases of pneumonia – Congestion, Red hepatization, Grey hepatization, Resolution?  Complications of pneumonia?  Lipoid pneumonia, Carcinomatous & Aspiration pneumonia ?

46. Goodpasture Synrome: ?Etiology ?Clinical ?Pathogenesis ?Diagnosis.

47. Diffuse Alveolar Damage (DAD): ?Etiology ?Clinical ?Pathogenesis ?Diagnosis. Diffuse bilateral consolidation with honeycombing in both lower lobes, focal in upper lobes. Microscopy: Hyaline membrane in ARDS.

48. Saddle Thomboemobulus: ?Etiology ?Clinical ?Pathogenesis ?Diagnosis.

49. The cigarette does the smoking,..!

50. Clinical Problem Solving - Course Free online course from UCSF https://class.coursera.org/clinprobsolv-001/class/index