Obstructive airway

diseases
DR .G .S.S . HEG ODA
DE PA RTMENT OF PAT HOLOGY
FACULT Y OF ME DI CI NE
Normal lung structure and function
Lung histology
Lung spirometry
What is meant by an obstructive lung
diseases?
It is a pattern of lung behavior where,

1. Exhalation is difficult
2. FEV1/FVC <0.7
3. Air gets trapped within alveoli
4. Total lung capacity is increased
 FVC(Obs)

FEV1 (Obs)

FEV1/ FVC <0.7 (70%)

 Obstructive vs restrictive lung diseases
Obstructive lung diseases Restrictive lung diseases
Harder to get air out (Difficult exhalation) Harder to get air in(Difficult inhalation)
Due to high resistance to air flow caused by complete Due to reduced expansion of the lung parenchyma
or partial obstruction at any level
FEV1 is reduced, FVC is slightly reduced or normal FEV1 is slightly reduced or normal, FVC is reduced

FEV1/FVC <0.7 FEV1/FVC >0.7

 Obstructive vs restrictive lung diseases
Obstructive lung diseases Restrictive lung diseases
Air gets trapped, Residual volume is increased and No air trapping, Residual volume and total lung
total lung capacity is increased volume is reduced.

Residual volume Residual volume

Total lung capacity

Total lung capacity
 Obstructive vs restrictive lung diseases
Obstructive lung diseases Restrictive lung diseases

Reduced lung expansion due to

Obstruction stiffness of the lung in parenchymal
maybe due to lung diseases or chest wall disorders
anatomic airway
narrowing or due
to loss of elastic
recoil.

Examples include COPD, asthma, bronchiectasis, Examples include Interstitial lung diseases/pulmonary
brochiolitis etc fibrosis, pneumoconiosis, neuromuscular diseases,
scoliosis
 Obstructive
airway diseases

Chronic
obstructive Asthma Bronchiectasis
airway disease

Emphysema

Chronic
bronchitis
Chronic obstructive pulmonary
disease(COPD)
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines define COPD as,

“Adisease state characterized by airflow limitation that is not fully

reversible, is usually progressive, and is associated with an
abnormal inflammatory response of the lungs to inhaled noxious
particles or gases”
Chronic obstructive pulmonary
disease(COPD)
• A common progressive chronic respiratory disorder showing an irreversible obstructive pattern.
•Has high morbidity and mortality. 3rd leading cause of death worldwide.
•Prevalence is high in Sri Lanka and it is among the top ten causes of deaths in the country.
•It also consumes a significant amount of our health budget due to need of chronic life long
therapy(Supplemental oxygen therapy, medications), clinic visits and frequent hospitalizations
due to acute exacerbations.
•Strongly associated with smoking
•It is an umbrella term which describes two disease subtypes namely,
1. Chronic bronchitis
2. Emphysema
 COPD
Emphysema vs Chronic bronchitis

Emphysema Chronic bronchitis

 Emphysema Vs. Chronic bronchitis
Emphysema Chronic bronchitis

Acinus(Lobule) is involved Airways are involved.

Gas exchange parts are involved. Gas conducting pathways are involved.

Has a specific morphological appearance/pattern Is clinically defined

Due loss of elastic tissue in the surrounding alveolar Chronic irritation leading to chronic inflammation,
septa, radial traction on the small airways is reduced, ciliary dysfunction, excessive mucus production,
so they tend to collapse during expiration mucus gland hyperplasia, smooth muscle spasms
leading to narrowed airways
Main causative factor- Smoking Main causative factor- Smoking

Other etiologies- Alpha-1-antitrypsin deficiency, Air Other etiologies- Air pollutants

pollutants

“Pink puffers” “Blue bloaters”

Dilated overinflated lungs/ Barrel chested
Emphysema
“Permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by
destruction of their walls without significant fibrosis”
Has four types
1. Centriacinar emphysema
2. Panacinar emphysema
3. Distal acinar emphysema
4. Irregular emphysema
 Types of emphysema
Centriacinar (centrilobular) Panacinar (panlobular) Distal acinar (paraseptal) Irregular emphysema
emphysema emphysema emphysema

Proximal acinus. The whole acinus is involved Distal acinus is involved. Irregular involvement of the
(Distal alveoli are spared) (Dilated) acinus

Upper lobes are usually Lower lung zones are usually Usually seen adjacent to Associated with scarring/
affected. affected. areas of fibrosis, scarring or healed inflammatory lesions.
Associated with smoking Associated with α1- anti atelectasis.
trypsin deficiency Usually seen in upper lung
zones.
Cause is usually unknown.
Etiology- emphysema
1. Inhalants
Cigarette smoking is the main culprit
other environmental pollutants also contribute
2. Genetic factors
Alpha-1-antitrypsin deficiency
Smoking and emphysema
•Smokers have a greater number of neutrophils and macrophages in their alveoli. Smoking
irritates alveolar macrophages, which in turn release neutrophil chemotactic factors, such as
interleukin 8, thus recruiting neutrophils.
• Nicotine is chemotactic for neutrophils, and smoke can activate the alternative complement
pathway (an inflammatory cascade).
•Proteases, particularly elastase, are secreted by these neutrophils and macrophages.
•Proteases are enzymes that are capable of digesting lung tissue and these chemicals are
responsible for the damage seen in emphysema.
•Oxidants and free radicals in smoke also inhibit the alpha-1-antitrypsin circulating in the lung
that protects alveoli from proteases.
Alpha-1-antitrypsin deficiency
•Alpha1-antitrypsin is a major protease inhibitor (especially elastase).
•Secreted by neutrophils during inflammation.
•It is encoded by a by a gene in the proteinase inhibitor (pi) locus on chromosome 14. Pi locus is
usually polymorphic.
•Homozygosity for the Z allele(PiZZ), is associated with markedly decreased serum levels of α1-
anti-trypsin.
•More than 80% of these individuals develop symptomatic panacinar emphysema, at an earlier
age and is of greater severity if the individual smokes.
To sum up pathogenesis- Emphysema
•There is destruction of lung parenchymal tissue surrounding lung lobules with loss of elastic
recoil.
•This destruction is caused by,
1. Chronic inflammation (Mediated by smoking and other noxious particles in air)
2. Protease mediated destruction of elastin
3. Oxidative stress –Reactive oxygen species generated by cigarrate smoke and inflammatory
cells cause additional tissue damage and progress the inflammation.
4. Infections – Although infections does not play a role in initiation of emphysema it causes
acute exacerbations of the disease.
Emphysema morphology
• Grossly appear as pale, voluminous lungs especially in panacinar type. Centriacinar type is
usually less affected macroscopically.
•X ray- Overinflated hyperlucent lungs, Flattened hemidiaphrams and a narrow mediastinum.
•Enlarged airspaces with destroyed and fragmented alveolar walls. Usually no fibrosis.
Panacinar emphysema Centriacinar emphysema

Voluminous pale lungs with dilated air spaces More subtle changes, has “hole”
like dilated airspaces.
Anthrocosis is also present.
Emphysema chest Xray

• Hyperlucent and hyperinflated

lung fields
• Flattened hemidiapragms
• Narrow mediastinum
Loss of alveolar walls with
remaining dilated airspaces.
Chronic bronchitis
“Defined clinically as presence of a chronic productive cough for at least 3 months duration in
at least 2 consecutive years (other causes of cough being excluded)”
•Common among smokers and urban dwellers.
•Airflow limitation in chronic bronchitis is due to narrowing of airway caliber and increase in
airway resistance.
•The defining feature of chronic bronchitis is hypersecretion of mucus.
 Chronic bronchitis pathophysiology
Chronic irritation by cigarette smoke and other air pollutants (Sulfur dioxide, nitrogen dioxide)

Induce mucous gland hyperplasia in

trachea and bronchi and hyperplasia of chronic inflammation
the goblet cells in the respiratory
epithelium

Mucus hypersecretion Inflammatory cell infiltrate and Induce smooth Bronchiolar wall
oedema of the bronchiolar wall muscle hyperplasia fibrosis
Associated ciliary dysfunction
makes it hard to get rid of
mucus in the airways

Mucus plugging of airways

Airflow obstruction
Recurrent infections
 Chronic bronchitis- Gross morphology
• Mucosal aspect of airways appear
hyperemic and swollen.
•It is covered by a thick layer of
mucus.
•The wall of bronchi appear
thickened.
 Chronic bronchitis- Microscopy
•Submucosal mucus secreting gland
hyperplasia.
•Increased number of goblet cells in the
repiratory epithelium.
•Variable inflammatory cell infiltrate
(Neutrophils, lymphocytes,
macrophages) in the wall with oedema.
•Fibrosis of the bronchiolar wall.
•Reid index: ratio of thickness of mucus
gland layer to thickness of wall between
epithelium and cartilage; normal is 0.4,
increased in chronic bronchitis
Clinical features of COPD
A. Clinical features due to local pulmonary effects - Patients typically present with a
combination of signs and symptoms of chronic bronchitis and emphysema.
Most common symptoms are,
1. Chronic cough –Productive cough, white sputum, worse in early mornings
2. Progressive breathlessness
3. Wheezing
B. Clinical features due to complications
C. Systemic features
 Characteristic features of
emphysema
• Patients may be very thin with a barrel
chest
•Patients typically have little or no cough or
expectoration
•Breathing may be assisted by pursed lips
and use of accessory respiratory muscles;
patients may adopt the tripod sitting
position
•The chest may be hyperresonant, and
wheezing may be heard
•Heart sounds are very distant
 Characteristic features of chronic
bronchitis
•Patients may be obese
•Cyanosis
•Frequent cough and expectoration
are typical
•Use of accessory muscles of
respiration is common
•Coarse rhonchi and wheezing may
be heard on auscultation
 Complications of COPD
1. Recurrent infections and acute exacerbations. – Ciliary dysfunction together with excess mucus
secretion and mucus plugging increase the risk of infections
2. Secondary pulmonary hypertension and right heart failure/Cor-pulmonale
Hypoxia induced vascular spasms, loss of pulmonary capillary surface area from alveolar
destruction and narrowing of pulmonary vascular lumina due to medial wall thickening and
muscularization of non muscular arteriolar walls caused by hypoxia
secondary pulmonary hypertension
Increased right ventricular afterload
Right ventricular hypertrophy
Right ventricular failure (Cor-pulmonale)
3. Respiratory failure
4. COPD is an independent risk factor for lung carcinoma, particularly for squamous cell carcinoma
Systemic manifestations of COPD
•Osteoporosis
•Anemia
•Depression
•Pulmonary hypertension
•Cor pulmonale
•Cognitive impairment
Diagnosis of COPD

Formal diagnosis is based on

spirometry,
when, FEV1/FVC <70%
 Asthma
•A common chronic disease worldwide and the most common chronic disease in childhood.
• The hallmarks of asthma are,
 Intermittent reversible airway obstruction
 chronic bronchial inflammation with eosinophils
 bronchial smooth muscle cell hypertrophy and hyperreactivity
 Increased mucus secretion
•Patients characteristically present with wheezing, cough, breathlessness and chest tightness.
•It is an obstructive lung disease but differs from COPD by its reversible nature. There, either by
removing the triggering agent or by medications the airway can be brought to its near normal state.
 Asthma subtypes
Depending on the trigger, asthma can be classified in to,
1. Atopic asthma
2. Non-atopic asthma
Atopic asthma –Predisposition towards hyper-reaction to normal allergens( Pollen, animal dander, dust
etc.) Type 1 hypersensitivity reaction.
Non-atopic – Not allergenic, could be related to stress, drugs (asprin), occupational toxins, cold weather)
Pathogenesis of atopic asthma
•It’s a type 1 hypersensitivity reaction.
First exposure to the allergen
Dendritic cells in the airways phagocytose the allergen, process present the antigen to the T
helper cells
T helper cells get activated and start producing cytokines (IL4)
IL4 act on the B cells and activate and transforming them in to plasma cells and causes class
switching to produce IgE antibodies
These IgE antibodies bind to FC receptors on mast cells
With subsequent exposure to the same allergen
Allergen binds to mast cells that are already primed with specific IgE antibodies
Activation of mast cells
 Pathogenesis of atopic asthma-
Immediate reaction
Activated mast cells start producing chemical mediators

Cause gaps to form in Chemotaxis Chemotaxis of Leukotrienes and

between epithelial cells of neutrophils prostaglandins
eosinophils

Antigens reach lamina Smooth muscle Increased Hypersecretion

propria and stimulate Vagus constriction vascular of mucus by
afferent nerves permeability stimulating
mucus glands

Bronchospasms mediated oedema

by Vagus efferents

Airflow obstruction
 Pathogenesis of atopic asthma-Late
reaction
Continued activation of eosinophils
Activated eosinophils even without the allergen giving rise
to prolonged symptoms

Release proteins (major basic Inflammatory mediators

protein, eosinophil cationic protein) eg- leukotrienes

Epithelial damage Smooth muscle Increased Hypersecretion

constriction vascular of mucus by
permeability stimulating
mucus glands
Inflammation

Airflow obstruction
Pathogenesis asthma cont.
•Repeated bouts of inflammation lead to structural changes in the bronchial wall that are
collectively referred to as airway remodeling.
•These changes include,
1. Hypertrophy of bronchial smooth muscle and mucus glands and
2. Increased vascularity and
3. Deposition of subepithelial collagen
 Asthma- Morphology
•Lungs are distended due to air trapping (overinflation)
•Small areas of atelectasis.
•Occlusion of bronchi and bronchioles by thick, tenacious mucous plugs
 Asthma- Morphology
Mucous plugs containing whorls of shed epithelium (curschmann spirals).
Numerous eosinophils and charcot-leyden crystals (crystalloids made up of the eosinophil protein
galectin-10) .
Features of airway remodeling,
• Thickening of airway wall
• Sub-basement membrane fibrosis
• increased submucosal vascularity
• An increase in size of the submucosal glands and goblet cell metaplasia of the airway epithelium
• Hypertrophy and/or hyperplasia of the bronchial muscle
Clinical features of asthma
1. Wheezing, a musical, high-pitched, whistling sound produced by airflow turbulence
2. Cough, in children nocturnal cough is common
3. Chest tightness
4. Breathlessness
5. Recurrent infections
Basis for pharmacologic management of
asthma
1. Treatment of bronchospasms – By bronchodilators (Beta agonists, leukotriene inhibitors)
2. Treatment of inflammation – Anti-inflammatory drugs (Corticosteroids)
Bronchiectasis
“Permanent dilation of bronchi and bronchioles caused by destruction of smooth muscle and
the supporting elastic tissue”
•Usually associated with or result from chronic infections that cause tissue destruction.
•An irreversible disease.
•Obstructive pattern and infections usually co-exist.
•Relatively uncommon.
Etiology
•Worldwide commonest cause- Tuberculosis, in the US- Cystic fibrosis
•Other causes
• Necrotizing infections (Staphylococcus, klebsiella pneumonia)
• Bronchial obstruction( Tumours, foreign bodies)
• Primary ciliary dyskinesia
• Allergic bronchopulmonary aspergillosis
• Immunodeficiency states
• Congenital
Pathogenesis of bronchiectasis
Infections

Inflammation

Inflammatory Tissue destruction

exudate

Obstruction

Dilatation of bronchi
and bronchioles
 Bronchiectasis- Gross pathology
•Usually lower lobes are affected.
•Dilated airways/bronchi that
extend up to the pleural surface.
•Mucus within dilated bronchi
Bronchiectasis- Histology
•Acute and chronic inflammation
•Ulceration of bronchial wall
•Fibrosis of the bronchial and
bronchiolar walls and
peribronchiolar fibrosis.
Clinical features- Bronchiectasis
1. Chronic cough with copious amounts of foul smelling sputum.
2. Breathlessness
3. Hemoptysis
Symptoms are usually episodic and precipitated by upper respiratory tract infections.
Bronchiectasis complications
•Recurrent infections
•Severe hypoxemia, hypercapnia and respiratory failure
•Secondary pulmonary hypertension and cor-pulmonale.
•Brain abscesses
•Amyloidosis
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