“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.

“ Whether you think you can or you can't, you are right…!”

– Henry Ford

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

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. Pathogenesis of symptoms ?

2. Further questions ?

3. Differential diagnosis ?

4. Learning issues? PFT

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.

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,

COPD: Questions Bronchiectasis ? Atelectasis ? Lung abscess ? Honeycomb lung ? Pneumothorax ? Tension pneumothorax? Pleural effusion Emphysema types.

• Panacinar - α1AT def.• Paraseptal• Irregular• Bullous• compensatory Text Book:

Robbins Basic Pathology, 8th or 9th edition

• 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.

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 ?

The cigarette does the smoking,..!

Normal Lung

Dia

ph

r.

CP a

ngle

Tr.Air Sh

Br. Mar.

CP angle

Gastr

ic a

ir

Colon air

Normal Lung Tissue

LungHistology

Type 1-Pneumocyte

Type 2 Alv. Macro.

RBC-Cap

Type 2

Bronchiole

Alveoli

There is only one secret to staying young, being happy, and

achieving success - You've got to

“enjoy what you do”…!

Including studying pathology…..

Pathology of

COPD, Chronic lung diseases & Pneumonia*

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

00

0.50.5

1.01.0

1.51.5

2.02.0

2.52.5

3.03.0

Proportion of 1965 Rate Proportion of 1965 Rate

0.0

0.5

1.0

1.5

2.0

2.5

3.0

1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998

–59%–59% –64%–64% –35%–35% +163%+163% –7%–7%

CoronaryHeart

Disease

CoronaryHeart

Disease

StrokeStroke Other CVDOther CVD COPDCOPD All OtherCauses

All OtherCauses

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998

4th leading cause of death, women more, smoking >80%

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.

Smoking effects: FEV 1 & Age

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.

Ask, Aspire, Achieve..! …..Ask questions

J. Robin Warren Australian 2005 Nobel price in Medicine - at RCPA conference 2006 Sydney.

Pathogenesis of

COPD

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

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

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

Pathogenesis – Chronic Bronchitis

3pK-RasC-myc

p53

Irritation COPD Initiation Promotion Ca.

Pathogenesis:1. Smoking – carcinogens2. 3p – tumor suppressor gene loss3. Mutations (p53, KRAS, EGFR..)4. Dysplasia5. Infiltration6. Spread7. Metastases.

Chronic Bronchitis

COPD Pathogenesis: Emphysema

COPD: Overlap of Clinical syndromes

COPD

Both affected COPD (common)

Chronic Bronchitis - Emphysema:

Predominant Bronchitis

Predominant Emphysema

Age (yr) 40-45 50-75Dyspnea Mild; late Severe; earlyCough Early; copious sputum Late; scanty sputumInfections Common OccasionalRespiratory insufficiency

Repeated Terminal

Cor pulmonale Common Rare; terminalAirway resistance

Increased Normal or slightly increased

Elastic recoil Normal LowChest radiograph

Prominent vessels; large heart

Hyperinflation; small heart

Appearance Blue bloater Pink puffer

Both affected COPD (common)

“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

Lung Normal & in Smokers:

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.

C

Normal - Emphysema

Normal Emphysema

Normal - COPD

CB

Emphysema

Centrilobular Emphysema:

Pink Puffer:Lean/weight lossNo cyanosisForward stoopingBarrel chestFlat diaphragmHyperlucent Lung

Whether you think that you can or that you can't,

you are right…!

– Henry Ford

Chronic Bronchitis:

• Squamous Metaplasia.

• mucous gland. Hyperplasia

Normal Chronic Bronchitis

Emphysema: Other types Panacinar

• Congenital, α1AT def. Paraseptal, Bullous

• Old scar. Irregular

• Past diffuse scaring.

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

RV LV

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

significance)

Bronchiectasis:

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

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.

Self Study

- Restrictive Lung Disorders.- IPF, Diffuse fibrosis, - Honeycomb lung.- Pneumoconiosis - Silicosis, Asbestosis, Coal.

- Tuberculosis.- Asthma- Good pasteur’s syndrome.- DAD: ARDS/HMD

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…..?

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 ?

Goodpasture Synrome:? Etiology? Clinical? Pathogenesi

s? Diagnosis.

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.

Saddle Thomboemobulus:? Etiology? Clinical? Pathogenesi

s? Diagnosis.

The cigarette does the smoking,..!

Clinical Problem Solving - Course

Free online course from UCSFhttps://class.coursera.org/clinprobsolv-001/class/index

Future of Education…?

Restrictive lung disorders:Definition: Reduced expansion of lung.A. Intrinsic Lung Disorders:

• Sarcoidosis, diffuse fibrosis, pneumoconiosis.• Tuberculosis, Interstitial Pneumonia

B. Extrinsic Disorders (chest wall):• Scoliosis, Kyphosis, Gross Obesity,• Pleurisy, rib fracture etc.

C. Neuromuscular Disorders:• Paralysis of the diaphragm, Myasthenia Gravis,

Poliomyelitis, • Generalized Weakness – malnutrition.

Restrictive Disorders: Pathogenesis Interstitial inflammation

& fibrosis. Lymph+Macrophages.

Idio. Pulm. Fibr.(IPF)>50y, ?viral, ?Imm ?Env "dry Velcro like inspiratory

crackles.UIP (usual Int. Pneum) /

Cryptogenic fibrosing alveolitis.Bilateral, lower and peripheral

coarse reticulonodular shadowing and small lungs.

CT – Peripheral honeycomb & scarring.

Poor prognosis. (~3years)

Idiopathic Pulmonary Fibrosis: UIP/IFA

Type 2 Pneum

Pneumoconioses: Disease due to inhaled dusts inorganic (mineral) or organic Reaction may be inert, fibrous,

allergic or neoplastic. Morphologic Types: Inert - coal-worker's pneum. Fibrous - asbestosis, silicosis Allergic - extrinsic allergic

alveolitis (Bird Neoplastic - mesothelioma, lung

carcinoma.

Silicosis: Inorganic – sand &

stone dust. Toxic to macrophages –

destruction fibrosis. Scattered multiple

small,fibrotic Nodules Surrounding Irregular

emphysema. Restrictive pattern of

PFT.

Asbestosis: Asbestos bodies in sputum.

• (Protein & Hemosiderin)

“Inconsumable”, Beaded 5-100mm x 0.25mm.

Within alveoli at lung bases. Dyspnoea, dry cough Clubbing is common. Diffuse fibrosis: Honey comb

lung: Massive fibrosis: Coal-miners.

Coal Miner’s Lung: Athraco-Silicosis: Dense cardon

pigmentation – Anthracosis and nodules of silicosis.

Commonly seen in coal miners.

Sarcoidosis: Granulomatous, immune,

multisystem, ??? Etiology. Multiple fine nodules. Like TB (no caseation). Smokers – Uncommon SOB, Erythema nodosum,

lymphadenopathy, hypercalcemia, nephrocalcinosis, occular, skin & nerve damage.. Etc.

Stage I asymptomatic to Stage IV – Pulm fibrosis.

Honeycomb lung: click for online link

Tuberculosis: Mycobacterium tuberculosis (typical) Atypical mycobacteria – HIV Primary & Secondary, Pulm/non-pulm Chronic, Hypersensitivity, debilitating,

weight loss. Upperlobe, nodular/cavity/fibrosing. Pleural effusion Caseating Granuloma

• lymph, marcrophages fibrosis Macrophages - LH giant cells.

Systemic spread, miliary spread. Tuberculin Test – hypersensitivity.

Restrictive vs Obstructive

Interstitial - (stiff lung)Increased tissue Relatively normal FEV1:FVC ratio

Normal PEFR. Types:Acute – ARDS,Viral.Chronic - pneumoconioses & sarcoidosis, Int. fibrosis.

Obstructive (soft lung)Destruction of tissue.Low FEV1:VC ratio

Low PEFR.Types:

•Localised & Diffuse•Reversible & progressive.•COPD •Asthma•Bronchiectasis,

Pulmonary Function Testing: FVC - Forced Vital Capacity – Liters - diagnosis of obstructive and

restrictive diseases. FEV1 - Forced Expiratory Volume in One Second –

obstructive/restrictive diseases. FEV1/FVC - FEV1 Percent (FEV1%) - it indicates what percentage

of the total FVC was expelled from the lungs during the first second of forced exhalation. critically important in differentiating obstructive from restrictive diseases.

FEV3 - Forced Expiratory Volume in Three Seconds – equal to FVC in normal.

FEV3/FVC - FEV3% - normal is 1 or 100% PEFR - Peak Expiratory Flow Rate - this is maximum flow rate

achieved by the patient. For monitoring response to treatment. FEF - Forced Expiratory Flow - is a measure of how much air can

be expired from the lungs (liters/second or liters/minute). The FVC expiratory curve is divided into quartiles and therefore there is a FEF that exists for each quartile. The quartiles are expressed as FEF25%, FEF50%, and FEF75% of FVC.

PFT: interpretation: Check FVC & FEV1 – normal normal PFT If FVC and/or FEV1 are low - Pathology. Check FEV1/FVC ratio: FEV1/FVC% (<70%) - Obstructive. FEV1 /FEVC% (>80%)- Restrictive. An improvement in FEV1 of 200ml or more after

bronchodilator suggests versibility Asthma.

“A person with belief never grovels before anyone, whining and whimpering that it’s all too much, that he lacks support, that he is being treated unfairly. Instead, such a person tackles problems head on and then affirms, I am greater than anything that can happen to me.”

- Wings of Fire: An Autobiography of Dr. APJ Abdul Kalam.

Asthma: Reversible & intermittent COPD

Increased irritability of bronchi causes bronchospasm

Paroxysmal attacks Hyper inflated lungs Mucus plugs in bronchi Enlarged bronchial mucous glands

Asthma Types: Atopic – Immune, hypersensitivity, IgE. Non-atopic – Non immune - infections Aspirin-induced – Genetic, excess cyclo-

oxygenase inhibition. Occupational – Immune, hypersensitivity. Allergic bronchopulmonary aspergillosis:

Hypersensitivity to inhalation of spores.

Asthma Pathogenetic Types:

Extrinsic (Immune)• Atopic - IgE• Occupational - IgG• A. Bronchopulomonary Aspergillosis - IgE

Intrinsic (Non immune)• Aspirin induced• Infections induced• Excercise

Asthma: Reversible & intermittent obstruction

Hyperresponsive airways• Increased irritability of bronchi causes

bronchospasm Episodic attacks Inflammation Excessive and thick mucus plugs Hyperplasia of mucous glands and smooth

muscle, minimal fibrosis

Asthma Types: Atopic – Immune, hypersensitivity. Non-atopic – Non immune - infections Aspirin-induced – Genetic hypersensitivity. Exercise induced Occupational – Immune, hypersensitivity. Allergic bronchopulmonary aspergillosis:

Hypersensitivity to inhaled aspergillus Ag

Asthma Pathogenetic Types:

Extrinsic (Immune)• Atopic - IgE• Occupational - IgG• A. Bronchopulomonary Aspergillosis - IgE

Intrinsic (Non immune)• Aspirin induced• Infections induced• Excercise

INFLAMMATIONAirflow Limitation

SYMPTOMSCough Wheeze

Dyspnoea

TRIGGERS Allergens, Exercise,

Cold Air, SO2 Particulates

Asthma Pathogenesis:

AirwayHyper-responsiveness

Genetic*

INDUCERSAllergens,Chemical sensitisers,Air pollutants, Virus infections

Hygiene hypothesis?

Asthma : Pathogenesis

Early phase (immediate) and late phase reactions

Asthma Pathology:

Barnes PJ

Allergen

MucushypersecretionHyperplasia

VasodilatationNew vessels

Plasma leak Oedema

BronchoconstrictionHypertrophy/hyperplasia

Cholinergic reflex

Subepithelialfibrosis

Sensory nerve activation

Eosinophil

Mast cell

Th2 cell Neutrophil

Macrophage/dendritic cell

Mucus plugEpithelial shedding

Nerve activation

LeukotrienesC4, D4 & E4

LeukotrienesAchHistamineProstaglandin DPlatelet activating factorInterleukins

Asthma Morphology: Bronchial obstruction with overinflation

• Small areas of atelectasis (collapse) may be seen

Inflammation & thickening of mucosa. Bronchial wall smooth muscle hypertrophy Thickening of bronchial basement membrane. Mucus plugging of bronchi Curschmann spirals: whorls of shed epithelium

within mucus plugs Charcot-Leyden crystals: Within aggregates of

eosinophils – crystalloids of galectin-10

Asthma Morphology:

Asthma Microscopy1.Mucous Plugs +eosinophils2.Goblet cell hyperplasia3.Inflammation + Eosinophils4.Smooth muscle hyperplasia5.Mucous gl. Hyperplasia.

Asthma – Lung Gross features: Inflamed thick bronchi obstructed by mucous plugs.

Asthma : Microscopy

Inflammed bronchi

Obstruction by mucous plug

Alveoli (normal)

Asthma : Microscopy

Dilated BV Inflammatory cellsCartilageMucous plug over

the surface.

Asthma : Microscopy

Hyperinflation Status Asthmaticus:

Status Asthmaticus : Mucous plug

Status Asthmaticus : Mucous plug

Curschmann spirals:

Charcot-Leyden Crystals:

“ Whether you think you can or you can't, you are right…!”

– Henry Ford

Lung volumes

Total Lung Capacity (TLC) - the total volume of the lung, the volume of air contained in the lung at the end of maximal inspiration

Inspiratory Reserve Volume (IRV) - volume, which can be inspired beyond a restful inspiration

Tidal Volume (TV) – volume of a single breath, usually at rest Functional Residual Capacity (FRC) - The amount of air left in the lungs

after a tidal breath out, the amount of air that stays in the lungs during normal breathing

Vital Capacity (VC) – maximum volume which can be ventilated in a single breath

Inspiratory Capacity (IC) - the maximal volume that can be inspired following a normal expiration

Expiratory Reserve Volume (ERV) – volume, which can be expired beyond a restful expiration

Residual Volume (RV) – volume remaining in the lungs after a maximum expiration

Volumes

Forced Vital Capacity (FVC) - the volume of air that can forcibly be blown out after full inspiration, measured in litres

Forced Expiratory Volume in 1 Second (FEV1) - the maximum volume of air that can forcibly blow out in the first second during the FVC manoeuvre, measured in liters

FEV1/FVC (FEV1%) - in healthy adults this should be approximately 75–80%.

• Obstructive diseases (asthma, COPD) FEV1 is ↓ & FVC n/↑ so FEV1/FVC is decreased (<80%, often ~45%).

• In restrictive diseases (Lung fibrosis/silicosis) FEV1 and FVC are both reduced proportionally and the FEV1/FVC value may be normal or even increased as a result of decreased lung compliance

Obstructive lung diseases airway obstruction restricted expiration FEV1, FEV1/FVC compliance, elasticity

Chronic bronchitis• Bronchiolitis

Asthma Emphysema Bronchiectasia Cystic fibrosis

Normal

Asthma

COPD

Flow volume curves

Condition Major changes Causes Symptoms

Chronic Hyperplasia Tobacco smoking Productivebronchitis and hypersecretion and air pollutants cough of mucus glands

Bronchiectasis Dilation and scarring Persistent severe Cough, purulent of airways infections

sputum and fever

Asthma Smooth muscle Immunologic Episodic wheezing

hyperplasia or idiopathic cough and dyspnea

Excessive mucusInflammation

Emphysema Airspace enlargement Tobacco smoking Dyspnea Genetic and wall

destruction

Bronchogenic Carcinoma:

Asthma pathogenesis:

Pathophysiology of Cor-Pulmonale:

2013 feedback Did not go well - reorganize talk. No Asthma, restrictive disorders &

pneumonia – next week. Check quiz – remove unwanted. Next year combine pneumonia + COPD.