PA – RTS K12

PATHOLOGY OF
CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
( COPD )

dr. Lidya Imelda Laksmi, M.Ked (PA), Sp.PA

dr. Causa Trisna Mariedina, M.Ked (PA), Sp.PA
 Obstructive vs. Restrictive
•OBSTRUCTIVE:
Airflow obstruction with normal or hyper-expansion of lungs
COPD

RESTRICTIVE:
Reduced expansion of the lung (e.g. due to fibrosis or oedema)
Chest wall disorders
Acute or chronic interstitial & infiltrative diseases

Different pulmonary function tests

 Obstructive Airways Disease
Spectrum of disorders associated with airflow
obstruction:

 Chronic bronchitis
Chronic bronchiolitis (small airways disease)
 Emphysema
 Asthma
 Bronchiectasis
All characterized by airflow limitation, but involve different
mechanisms and parts of the respiratory tract.

BRONCHIAL LEVEL: Chronic bronchitis  hypersecretory &

obstructive
ACINAR LEVEL: Emphysema  destructive

Frequently co-exist and overlap:

‘CHRONIC OBSTRUCTIVE PULMONARY DISEASE’

(COPD)
 Chronic Obstructive Pulmonary
Disease (COPD)
COPD = Chronic Bronchitis &/or emphysema +/- asthma

• Cigarette smoking in majority (10% non-smokers)

• 4th leading cause of morbidity & mortality (USA)

• Classically 2 clinical syndromes based on mechanism - but

frequent overlap:

“BLUE BLOATER vs. PINK PUFFER”

Emphysema predominates* Chronic bronchitis
predominates*
 Chronic Bronchitis
 Definition
• Persistent cough with sputum production for:
• at least 3 months,
• in at least 2 consecutive years.

 Middle-aged & elderly, M > F

 Mucoid sputum (initally - progressive)

 Cigarette smoke, air pollution, dust exposure – cadmium,

smog
Chronic Bronchitis
Pathology
• Irritants
• Release of proteases from neutrophils
• Hypersecretion of mucus in large airways
- Hyperplasia & hypertrophy of mucus producing cells

Small airways initially affected (Chronic Bronchiolitis):

• Goblet cell metaplasia - mucus plugging
• Chronic inflammation & fibrosis - focal stenosis
• Squamous metaplasia
• Hypoxic pulmonary vasoconstriction – hypertension – cor
pulmonale
 Obstructive Airways Disease

Normal
Bronchial
mucus
gland
hyperplasia
Chronic
bronchitis
Acute on Chronic Bronchitis
Loss of airway ‘tapering’ in chronic bronchitis
 Chronic Bronchitis
 Clinical Features

• Early Stages: Chronic cough with sputum

• Later Stages: Progressively more severe

• Right heart failure (cor pulmonale) or respiratory failure

 Complications

• Recurrent infections / acute exacerbations

• Malignancy (SCC)
 Emphysema
 Definition:
Destructive, permanent enlargement of the airspaces
distal to the terminal bronchioles, without obvious
fibrosis

 Airflow limitation is due to premature closure of

airways because of diminished elastic recoil

 Reduced surface area for gas exchange

 Emphysema
 Pathogenesis: Proteases vs Antiproteases

• Neutrophils & macrophages - sources of elastase –

increased in smokers / infection / inflammation

• Smoking stimulates release and enhances activity of

elastase

• Oxidants in cig smoke inhibit native 1-AT activity

• 1-AT deficiency - unopposed elastase activity

3 main types of Emphysema
Normal acinar
unit
CENTRIACINAR
• Destruction of central portion with
sparing of distal airways Centriacinar
• Upper lobes > lower emphysema
• Cause: smoking

PANACINAR
• Uniform injury Panacinar
• Lower lobes > upper emphysema
• Cause: 1-antitrypsin deficiency

PARASEPTAL
• Destruction of distal portion;
normal proximal portion of acinus
(septal / subpleural)
• Upper lobes > lower
• Incidental / Spontaneous
pneumothorax Alpha-1-AT
Neutrophils
Centriacinar Emphysema Paraseptal Emphysema
Paraseptal Emphysema

• Large solitary bullae

• May grow large enough to

cause respiratory failure by
compressing adjacent ‘normal’
lung.

• Corrective bullectomy or ‘lung

reduction’ may return
pulmonary function to normal
Panacinar Emphysema
 Bronchial Asthma
 Commonly co-exists with COPD
 Hyper-reactive airways
Increased responsiveness of the tracheobronchial tree
to various stimuli
Episodic, reversible bronchconstriction

 Extrinsic / Atopic / Allergic

Allergy to exogenous substances

 Intrinsic / Non-atopic
No exogenous factors identified
 Extrinsic Asthma
 Atopic (allergic) asthma is the most common form,
begins in childhood
 Other allergic manifestation: allergic rhinitis,
urticaria, eczema.
 Skin test with antigen result in an immediate
wheel and flare reaction
 Other family member is also affected
 Serum IgE and eosinophil are increased
immune related, TH2 subset of CD4+ T cells
 Pathogenesis of Bronchial Asthma

EXAGGERATED BROCHOCONTRICTION
 Two components:
1. Chronic airway inflammation.
2. Bronchial hyperresponsiveness.
 The mechanisms have been best studied in
atopic asthma.
 Pathogenesis of Atopic Asthma
 A classic example of type 1 IgE-mediated
hypersensitivity reaction.
 In the airway – initial sensitization to antigen (allergen) with
stimulation of TH2 type T cells and production of cytokines
(IL-4, IL- 5, and IL-13).

Cytokines promote:
1. IgE production by B cell.
2. Growth of mast cells.
3. Growth and activation of
eosinophils.
Pathogenesis of Atopic Asthma
• IgE-mediated reaction to inhaled allergens
elicits:
1. acute response (within minutes)
2. a late phase reaction (after 4-8 hours)
 Pathogenesis of Atopic Asthma
Acute-phase response
 Begin 30 to 60 minutes after inhalation of antigen.
 Mast cells on the mucosal surface are activated.
 Mediator produced are :
 Leukotrienes C4, D4 & E4 (induce bronchospasm, vascular permeability &
mucous production)
 Prostaglandins D2, E2, F2 (induce bronchospasm and vasodilatation)
 Histamine ( induce bronchospasm and increased vascular permeability)
 Platelet-activating factor (cause agggregation of platlets and release of
histamine)
 Mast cell tryptase (inactvate normal bronchodilator).
 Mediators induce bronchospasm, vascular permeability
& mucous production.
 Pathogenesis of Atopic Asthma
Late phase reaction:
 recruitment of leukocytes mediated by product of
mast cells including:
1. Eosinophil and neutophil chemotactic factors
2 . IL-4 & IL-5 and induceTH2 subset ofCD4+ T cells
3. Platelet-activating factor
4. Tumor necrosis factor.

 Other cell types are involved: activated epithelial cells,

macrophages and smooth muscle.
 Pathogenesis of Atopic Asthma
Late phase reaction:
 The arrival of leukocytes at the site of mast cell
degranulation lead to:
1. Release of more mediators to activate more mast cells
2. Cause epithelial cell damage .

 Eosinophils produce major basic protein, eosinophilic

cationic protein and eosinophil peroxidase ( toxic to
epithelial cells).

 These amplify and sustains injury without additional

antigen.
 Non-Atopic Asthma
 Triggered by respiratory tract infection
including viruses and inhaled air pollutants
e.g. sulfur dioxide, ozone.
 Positive family history is uncommon.
 Serum IgE – normal.
 No other associated allergies.
 Skin test – negative.
 Hyperirritability of bronchial tree.
 Subtypes:
1. Drug-induced asthma.
2. Occupational asthma.
 Morphology of Asthma
 Grossly:
lung over distended (over inflation),
occlusion of bronchi and bronchioles
by thick mucous.

 Histologic finding:
 mucous contain Curschmann spirals,
eosinophil and Charcot-Leyden
crystals.
 Thick BM.
 Edema and inflammatory infiltrate in
bronchial wall.
 Submucosal glands increased.
 Hypertrophy of the bronchial wall
muscle.
 Curschmann spirals

Coiled, basophilic plugs of mucus formed in the lower airways

and found in sputum and tracheal washings
 Charcot-Leyden crystals
Eosinophilic needle-shaped crystalline structures
 Clinical Coarse
 Classic asthmatic attack – dyspnea, cough, difficult
expiration, progressive hyperinflation of lung and mucous
plug in bronchi. This may resolve spontaneously or with Rx.
 Status asthmaticus – severe cyanosis and persistent
dyspnea, may be fatal.
 May progress to emphysema.
 Superimposed bacterial infection may occur.
 Bronchiectasis
 Permanent dilatation of
bronchi & bronchioles

 Caused by destruction
of muscle & elastic
tissue secondary to
recurrent inflammation

• Fibrosis in the surrounding

parenchyma
• Obliteration of smaller bronchioles
 Bronchiectasis
 Congenital/Hereditary:
• Cystic fibrosis
• Primary ciliary dyskinesia
• Kartagener’s syndrome

 Acquired (post-infective, post-obstructive):

• Children - Whooping cough, pneumonia & measles

• Adults - Necrotizing pneumonias (e.g. TB), bronchial obstruction

(e.g. tumour, foreign body)
 Bronchiectasis
 Usually lower lobes, bilateral

 May be sharply localised with tumour or foreign body

obstruction

 Gross examination:
Dilated bronchi exending to pleural surface (characteristic),
surrounding scarring

 Microscopy:
Mucosal ulceration, submucosal CI & granulation tissue, adjacent
organising pneumonia
 Bronchiectasis
 Clinical:
• Fever
• Severe, persistent cough (foul sputum)
• Haemoptysis
• Recurrent infections
• Paroxysmal cough
Worse in morning due to drainage into bronchi of
collected pus
 Bronchiectasis
 Complications:
Depend on severity & co-existent disease

 Recurrent infections (common)

H. influenzae & Pseudomonas

 Rare: Cor pulmonale, metastatic brain

abscesses & amyloid
 TERIMA KASIH
&
SELAMAT BELAJAR