Chronic Obstructive Pulmonary Disease

This term is commonly used to consider two common conditions

1. Chronic bronchitis 2. Emphysema

When a patient with these conditions comes with SOB, there will be considerable airway obstruction which is irreversible

These two conditions usually coexist because of same pathogenesis - smoking however, can occur alone.

Common in men

Emphysema:- Defined pathologicallyPermanent enlargement of airspaces distal

to the terminal bronchioles accompanied by destruction of their walls

Here pathological process confined to Acinus and structure dislat to the terminal bronchioles

What is Acinus- part of lung distal to Terminalbronchiole

Terminal bronchiole Respiratory bronchiole

Alveoli Alveolar duct

Lobule-: 3-5 Acinus together forms lobule

Alveoli

Terminal.bronchioe Alveolar duct Respiratory bronchiole Alveoli originates from terminal bronchiole to alveolar

duct

Types of Emphysema1. Centriacinar2. Pan aciner3. Distal Acinar

Centriacinar EmphysemaThe proximal parts of the acini formed by

respiratory bronchioles are affected with spairing of distal Alveoli.

In severe cases can involve distal acinai also.

Commonly involve apical segment of upper lobe

Commonly seen in smokers without 1

Antitrypsin deficiency

Pan Acinar EnphysemaAll parts of Acini is affectedCommon in lower zonesCommon in patients with 1 Antitrypsin

deficiecy

Distal Acinar typeDistal part of acini is affectedCommon in upper half of lung juxta

pleural parts of lung and margins of lobules

Also occur adjacent to fibrosis, scaring and atelectasis

Characteristically multiple enlarged air spaces forms cystlike structure

Prograssively enlarge and forms bullae

PathogenesisIt occurs due to two critical imbalances1. Protease – antiprotease imbalance2. Oxidant – antioxidant imbalance

Usually both coexist and cause additive pathogenesis

Protease – Antiprotease imbalance1 antitrypsin is protease inhibitor present

in serum, tissue fluid and macrophages It is codes on (Pi) locus of chromosome 14Protease are secreted by neutrophils during

inflammation which leads to tissue damageSo whenever there is inflammation in the

lung with neutrophil infiltration the lung is liable to damage when 1 Antitrypsin is deficient. So emphysema is common in patient with 1 Antitrypsin deficiency

In smokers without alpha 1 antitypsin

deficiency How it causes emphysema?– Nocotine & O2 free radicles in smok

act as chemoaltractant for Neutrophil& macrophage Activate transcription of Nuclear factor kB(NFkB)

Gene for Tumor necrosis factor & IL 8

Activate neutrophil

Activated Neutrophils

Release Granules

Protease Proteinase 3 Cathepsin G Metaloproteins Tissue

damage

*Smoking also elastase activity in macrophages*This elastase cannot be inhibited by 1

Antitrypsin *This elastase can digest the 1 antitrypsin

So relative deficiency of antitrypsin. So proteolytic tissue damage is increased

Metaloprotenases derieved from macrophages and neutrophils also causes tissue destruction

Oxidant – antioxidant imbalanceUsually the lung has antioxidants = superoxide Dismutase & GlutathioneThese prevent oxidative damageCigarette smoke contain large amount of

reactive O2 specis – free redicalsThis deplete the antioxidants tissue

damage

Activated neutrophils also produce O2 free radicles Oxidative injury also inactivate antiprotease

functional 1 Antitrypsin

Macroscopic appearance – Pan acinar typeWhen chest wall is opened upLung is pale, hyper inflated, obliterate the

heart

Centri acinar EmphysemaLungs appear deep pink, over inflatedUpper part of the lung is severly over

inflatedEmphysematous bullac may be visibleHistologyThinning and destruction of alveolar

wallsLoss of elastic tissue in the alveola

septaAdjacent alveoli becomes confluent and

leads to large air spaces.

Terminal and respiratory bronchioles deformed

Fibrosis of respiratory bronchiole.

Because of loss of elastic tissue in the alvolar septa

reduced radial traction on small airway

Small airways collapse on expiration

Air trapingAlveolar capillary surface also deminished

Clinical presentationProgressive SOB (hyperventilation)Pink puffer pink but puffing

Secondary pulmonary HT R heart failure

Due to - hypoxia with vascular spasm - pulmonary vascular reduction

So feattures of R heart failure pedal oedema

Chronic Bronchitis – clinical definitionInflammation of all part of bronchial system

Defnition -: consecutive productive cough for at lease 3 consecutive months in last 2 consecutive years

It will affect both small and large airwaysLarge airway – trachea & BronchiMucus hyper secretion coughInflamationSmall airways – bronchiolesPeribronchiolar fibrosis air way

obstruction

4 different types1. Simple chronic bronchits cough & mucoid sputum No obstruction2. Mucopurulent bronchitis cough with purulent sputum3. Chronic asthmatic bronchites Demonstrate hyper-responsiveness

4. Chronic obstructive bronchitis Shows significant airflow obstruction Obstruction mainly occurs at bronchiolar

level

It result from inflammation, fibrosis and narrowing of

bronchioles usually there will be emphysema alsoPathogenesis Epidermal growth factor receptor

Cigarette smoke irritate upper airway Air pollution Nicotin recurint SO2, N2O neutrophils

Inflamation sets in

Inflammation with cellular infiltrate Neutrophil,CD8 Lymphocyte,

Macrophages

Mucus secretion with hypertrophy of mucus gland and increased number of goblet cells, Epithelial damage

Metaplasia Dysplasia and fibrosis

MorphoogyMacroscopy – Hyperinflated lung Cut surface – secretions in the large bronchoi Mucosa thick and oedematous hyperaemic mucosa

Microscopy1. Section of large bronchia. Mucosa is inflamed, increased Goblet cellb. Loss of cilliated epithilium squamous

metaplasia Dysplastic changes in the lining epithelial cellsc. Infiltrated with neutrophils, macrophage &

lymphocytes

d. Enlargement of mucus secreting gland-: (Reid index) Ratio of submucosal gland is to bronchial wall thicknes is

increased2. Small airway a. shows secretions which has

neutrophils, and lymphocytes b. mucoas inflamed c. Globet cell number increased& metaplasia d. smooth muscle hyperplasia e. fibrosis of peribronchial wall f. Narrow airways

Conditions that mimic emphysema1. Compensatory emphysema – when one

bronchus is blocked and collapsed other lung expands with air

2. Senile emphysema3. Obstructive over inflation when a bronchus is obstructed partially with

each respiratory cycle the is traped in

4. Mediastinal emphysema leakage of air in the mediastinal tissue

in – rib #5. subcutaneous emphysema