CHRONIC OBSTRUCTIVE

PULMONARY DISEASE- COPD/COAD

PROF. DR. HARI K. DARNAL, MBBS, M.D,FAM, FICA, FIAPM, GCHE, MGSTF, IAP, FRSPH(UK)
UNIVERSITY MAHSA
DATED 21 MAY 2017
Modified 9th April 2018
0175765118
drharikumar@mahsa.edu.my
 DLO
• At the end of this session the students should acquire the ability to

1. define and list COPDs and Restrictive lung diseases

2. differentiate obstructive and restrictive types of lung disease and able to

co-relate with lung function tests

3. describe the normal lung morphology and air-blood barrier.

4. Explain the pathogenetic mechanism of alveolar destruction in COPD.

5. differentiate the patients of different types of COPD.

 Recap of normal anatomy
• Embryology:
• Anterior out-pouch of primitive gut (5th IU life) 2 lateral outgrowth (rt and
lt lungs)
• Lobes: Rt lung 3 lobes (upper, middle and lower) and Lt lung 2 lobes
(upper and lower)- pleural linning
• 10 Bronchopulmonary segments in each lungs have separate artery and
bronchus
• Endodermal origin ( cyst may have respiratory or GIT epithelium)
• Lower respiratory tract:
– trachea, bronchi, bronchiole, alveolar duct and alveoli
 Identification of lung structures

• Trachea - C- cartilage, muscle, mucus glands

• Bronchi - discontinuous cartilage plate + all above
• Bronchiole - no cartilage or gland, ciliated epithelium with clara
cells,
• Alveolar duct - no cilia or gland, flat epithelium
• Alveoli- type I, II pneumocytes on BM
• 3-5 terminal bronchioles and its acini form LOBULE
• Terminal respiratory unit distal to terminal bronchiole - ACINUS
– Respiratory bronchiole, alveolar duct and alveolus.
Terminal respiratory Unit vs emphysema
 Microanatomy of Alveolar-blood barrier

DIFFUSION

VENTILATION HYPOXEMIA

HYPERVENTILATION

PERFUSION
HYPO-
CAPNIA

Interstitial tissue once damaged it is irreversible

INTERFERENCE IN V/P/D LEADS TO RESPIRATORY FAILURE AS DIAGNOSED BY ABG
ANALYSIS
 RESPIRATORY FAILURE
• ACUTE/ CHRONIC
– Ventilation failure
– Perfusion failure
– Diffusion failure
 Ventilation failure
• Restrictive lung diseases
– Ventilator muscle, chest wall defects, Myasthenia gravis,
GB syndrome, polio, pneumothorax, obesity, muscular
dystrophy, kyphoscoliosis, acute or chronic interstitial
fibrosis, pneumonitis, granulomatous inflammation and
pneumoconiosis.
• Obstructive lung diseases
– FB, angioedema, pulmonary edema, bronchiolitis
obliterans, bronchial asthma, epiglottis, diphtheria,
malignancy, emphysema, bronchitis, bronchiectasis, cystic
fibrosis etc.
 Perfusion failure
• Perfusion failure increase dead space- areas of
ventilated lung but not perfused or perfused but not
ventilated leading areas of right to left shunt
situation. ( Pco2 > and Po2 <)
• Pulmonary embolism
• Fat embolism
• Hypercoagulabities
• Anti phospholipid antibodies
• Thromboembolism
• vasculitides
 Diffusion failure
• Diffusion membrane disorders
– DAD, ARDS, hyaline membrane disease, shock,
Interstitial pneumonitis, sarcoidosis, IPF,

– Pulmonary oedema, acute left ventricular failure,

toxic gases, chronic congestive heart diseases.
 ABG analysis in respiratory failure
Ventilation Po2 < PCo2 > pH < Unventilated
lung – R-L shunt
failure >PCo2, < Po2

Perfusion Po2 < N N  Dead space

failure  Hyperventila
tion correct
PCo2 level
but not O2.
Diffusion Po2 < < > Affect O2, not
CO2 (readily
failure diffusible)
Hyperventilatio
n washes out
CO2-
hypocapnia and
reduced
acidosis.
 Diffuse pulmonary diseases
• Obstructive disease (COPD/ COAD)
– Partial or complete airway obstruction

• Restrictive disease (CRPD)

– Reduced lung expansion capacity
Major Restrictive lung diseases
– Chest wall abnormality, normal lungs
- Obesity, Guillian-Barre syndrome, polio
– Acute interstitial lung disease
• Acute : ARDS- DAD- sepsis, trauma, diffuse infections
– Imbalance of pro and anti-inflammatory mediators.
– Neutrophils products- epithelial necrosis, membrane +
– Chronic : pneumoconiosis, sarcoidosis
• interstitial lung fibrosis (ILF) of unknown etiology
 Obstructive vs Restrictive lung diseases and
lung functions
• Obstructive (airway)
– Obstruction from trachea to respiratory bronchiole
– Decreased expiratory flow rate (FEV1:FVC <75% PEFR)
– FVC and TLCO – N or increased (AC barrier normal)
– COPDs, FB, Tumours

• Restrictive (parenchyma)
– Reduced expansion - < lung volume,<FVC< TLCO, N-EFR
– FEV1:FVC normal; PEFR- normal
– Increased lung density on CXR
– Chest wall disorders (GB syndrome, Polio)
– Interstitial disease
• Acute: ARDS, pneumonia
• chronic (pneumoconiosis and infiltrative condition)
 Characteristic of COPD
• Group of condition with chronic or recurrent
obstruction to airflow resulting in dyspnea
• Major cause of morbidity
– Cigarette smoking
– Environmental pollutants
 COPD
• 1. Emphysema
• 2. Chronic bronchitis
• 3. Bronchiectasis
• 4. Bronchiolitis
• 5. Bronchial asthma
 Characteristic of COPDS
• 1. Emphysema
– Acinus - Beyond terminal bronchiole
– Permanent (irreversible) Airspace enlargement
– Wall destruction
– Dyspnea
• TOBACCO AND A1AT DEFICIENCY (ZZ GENOTYPE)
 Emphysema
• Permanent enlargement of airways
• Distal to terminal bronchiole
• Destruction of wall
• Without fibrosis
 Pathogenesis of emphysema
• Protease- antiprotease imbalance
• Oxidant – antioxidant imbalance

– The inflammatory cells- source of proteases and

free radicles (oxidants)- together they cause tissue
injury and inactivates antiproteases.
– Cigarette smoking contributes by free radical
generation.
 Subtypes of Emphysema
• Centriacinar / centrilobular
– Smoking related
– Apical segments upper lobes
• Panacinar / panlobular
– A1-antitrypsin deficiency
– Lower lung segments
• Distal / paraseptal
– Upper half adjacent to
– pleura, fibrosis
– Atelectatic foci- bullae-
– pneumothorax
• Irregular acinar involement
– Scarring of healed inflammation
 Added features in Emphysema
• Chronic bronchitis concurrently may be
associated in emphysema- smoking common
denominator for both.

• “Pink puffers” are characteristically seen in

pure emphysema. Cf to “blue blotters” in CB.
 Clinical course in Emphysema
• Dyspnea insidious but progressive
• Weight loss
• FEV1:FVC reduced- expiration difficulty.
• Barrel chest, long expiration, sitting
• Hyperventilation- adequate Arterial blood
gas (ABG) values
• Dyspnea + hemoglobin-N (pink puffer)
 Gross and micro: emphysema

Upper lobe emphysema - centriacinar

Emphysema with anthracotic pigments
type

Narrowed PULMONARY ARTERY BRANCH with

muscular wall due to hypoxia.
 Complications on emphysema
• Secondary pulmonary hypertension
– Hypoxia induced vascular spasm
– Loss of pulmonary capillary due to alveolar damage
• Death from Pulmonary failure with
– respiratory acidosis
– Hypoxia
– Coma or
– Right sided heart failure (corpulmonale)
Sponge lung in emphysema- pulmonary edema
 Major characteristic of COPDs
• 2. Chronic bronchitis
– Bronchus
– Mucus gland hyperplasia
– Hypersecretion + inflammation
• Cough, sputum -3 months, 2 years

» TOBACCO
» AIR POLLUTION
 Types of chronic bronchitis
• Chronic cough, sputum for 3months/yr for 2 yrs

• Simple chronic bronchitis

– Productive cough, no obstruction to airflow
• Chronic asthmatic bronchitis
– Severe dyspnea, wheezing due to viral infection or irritants
• Obstructive chronic bronchitis
– Heavy smoker, chronic airway obstruction with emphysema
 Pathogenesis of CB
• Chronic irritation - initiator ( Cigarette smoke)
• Infections (promoter)

• Initiator- promoter- initiator are proven

experimental basis of multistep carcinogenesis
in animal by Knudson and Molgowkar et al
1970
• Explains inflammation induced malignancy.
 Morphology of CB
• Mucosal hyperemia, swelling and bogginess
• Excessive mucous secretion, cast or pus in the bronchioles
• HP:
– Reid Index >0.4 (submucosal gland hyperplasia)
– Goblet cell hyperplasia- mucous plugging
– Inflammation and fibrosis
– Bronchiolitis obliterans in severe cases
 Clinical consequences of CB
• Persistent cough - copious sputum
• Dyspnea on exertion
• Hypercapnia, hypoxemia, mild cyanosis
• Cor pulmonale and CCF.
 CHARARCTERISTIC OF COPDS
• 3. Bronchiectasis
– Bronchus
– Airway dilatation, scarring
– Persistent severe infections
• Cough
• Purulent sputum
• fever
 Bronchiectasis ( ectasis= dilatation)

• Permanent dilatation of bronchi and bronchioles associated

with chronic infection- 3 features
• Cough, fever, expectoration of copious foul smelling
purulent sputum
• May be associated with
– Tumour, FBs, mucous, asthma, CB
– Cystic fibrosis, Kartagener syndrome, immune defy
– TB, staphylococci, mixed infections pneumonias
Pathogenetic factors of bronchiectasis

• Infection
• Obstruction- atelectasis (collapse)

• Both are necessary for development of

bronchiectasis
 Morphology of Bronchiectasis

• Lower lobes - bilaterally

• Distal bronchi and bronchioles
– Cylindroid type
– Fusiform
– Saccular

– Can be dissected upto pleural surface

Gross and microscopy: bronchiectasis
 Triad of Kartagener syndrome
• Bronchiectasis
• Sinusitis
• Situs inversus (dextrocardia)
– Defect in ciliary motility
– Ciliopathy
– AR trait with structural ciliary defect
– Sperm tail immobility- infertility
 Characteristic of COPDs
• 4. Chronic Bronchiolitis
– Bronchioles
– Inflammatory scarring
– Obliteration of bronchioles
• Tobacco smoke
• Air pollutants.
– COUGH
– DYSPNEA
 5. BRONCHIAL ASTHMA
• Episodic Reversible bronchoconstriction
• Airway hyper-responsiveness to stimuli
• Atopic/ allergic/ extrinsic(T1HS) : TH2- IL-4,
IL-5, IL-13 important mediators
• Eosinophils major basic protein airway damage
– Non-atopic/ intrinsic : viruses, air pollutants,
• Airway remodeling
– BM thickening
– Smooth muscle hypertrophy
– Obstructive disease
 Extrinsic type of Asthma: 3 subtypes

• 1. Atopic due to allergens- most common

• 2. Occupational asthma- fumes, organic,

chemical dusts, gases etc

• 3. Alleric Bronchopulmonary aspergillosis.

 Intrinsic / Idiopathic asthma
• Stimulated by diverse nonimmune
mechanisms
– Drug induced asthma- aspirin
– Viral lung infection- most common cause
– Cold induced
– Inhaled irritants
– Stress
– Exercise
 Pathogenesis of Bronchial asthma
• Chronic airway inflammation

• Bronchial hyperresponsiveness.
 Pathogenesis of Atopic asthma?
• Childhood onset- triggered by
– Environmental triggers- dusts, dandar, foods
– Positive Family history of atopy.
– Asthma preceded by Urticaria, eczema, allergic
rhinitis
– Classical Type I IgE mediated HSR by mast cells
and eosinophils.
 Phases of Asthma
• Acute/ immediate phase response
– Presensitized IgE coated mast cells exposed to same antigen
– Occur within minutes after stimulation.
– Directly or via neuronal reflexes- the mediators- bronchoconstriction,
vaso-permeability, mucus secretion, hypotension, eosinophils influx.

• Late phase response- 4-8 hours after exposure

– Mediators released by
• Neutrophils- leukotrines C4,D4,E4-
• Monocytes
• Lymphocytes
• Basophils
• Eosinophils, endothelial, epithelial cells
 Mediators of acute and late Asthma

• Acute Phase/ early phase

– Histamine - > vasopermeability , bronchoconstriction
– PAF- activate PL, release histamine, serotonin
– Vagal stimulation- smooth muscle constriction.
• Late/ chronic phase (4-8 hrs; last 24 hours>)
– Lipoxygenase pathway- leukotrienes(c4,d4,e4) and
– Cyclooxygenase pathway- PGD2- bronchoconstriction
– Acetylcholine- bronchoconstriction.
Bronchial asthma
 Main Pathologic characteristic
• Gross:
– Lungs over-distended.
– Bronchial and bronchioles filled with thick mucous plugs
• Micro:
– Mucous plug- whorls of Curschmann spirals.
– Charcot- Leyden crystals
– Eosinophils
– Thickened BM, inflammation+, Submucosa glands
hypertrophy
– Muscular hypertrophy.
Toll like receptor in asthma and COPD
 Prognosis of Bronchial Asthma
• Asthma attack last several hours.
• Appropriate therapy relieves the attack
• Other conditions may supervens
• Emphysema, bacterial infection, chronic bronchitis or
bronchiecetasis or pneumonia may occur
• Cor pulmonale and heart failure in some cases.
 Summary
• COPD are common cause of morbidity and
mortality
• Environmental agents and cigarette smoking
are major risk factors
• Respiratory failure and alteration in pH may
be fatal
• Proper diagnosis and prompt treatment is
key to survival.