Q1 LONG ANSWER 10M ★ High-yield

Define chronic obstructive pulmonary disease. Describe chronic bronchitis and emphysema with their types, pathogenesis and morphology.

Pathology · 2nd Professional — Para-Clinical

Definition

Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow limitation that is not fully reversible and is usually progressive. It comprises chronic bronchitis and emphysema, which usually coexist.

Disease	How it is defined	Definition
Chronic bronchitis	Clinically	A persistent productive cough for at least 3 months in each of 2 consecutive years, with other causes excluded
Emphysema	Morphologically	Permanent enlargement of the airspaces distal to the terminal bronchiole, with destruction of their walls and without obvious fibrosis

The two are defined on completely different grounds — one by history, the other by anatomy — which is why one can be diagnosed at the bedside and the other cannot
Smoking is responsible for the great majority; in India, biomass fuel smoke from indoor cooking is a major additional cause, particularly in women who have never smoked

Chronic Bronchitis

Chronic irritation by tobacco smoke, biomass smoke, dust or pollution → hypersecretion of mucus — hypertrophy and hyperplasia of the submucosal glands in large airways and increase in goblet cells in small airways → Impaired ciliary function and squamous metaplasia → Small airway disease — inflammation, fibrosis and mucus plugging of bronchioles → Airflow obstruction, recurrent infection and eventually cor pulmonale

REID index — the ratio of the thickness of the mucous gland layer to the thickness of the bronchial wall between epithelium and cartilage. Normal is under 0.4; it is raised in chronic bronchitis
The obstruction is chiefly in the small airways, not in the large ones where the mucus is most obvious — the sputum is a marker of the disease rather than its mechanism

Emphysema — Types

Type	Part of acinus affected	Distribution	Association
Centriacinar (centrilobular)	Central and proximal parts — respiratory bronchioles; distal alveoli spared	Upper lobes and apical segments	Smoking — by far the commonest type, about 95%
Panacinar (panlobular)	The whole acinus uniformly, from respiratory bronchiole to alveoli	Lower zones and anterior margins	Alpha-1 antitrypsin deficiency
Paraseptal (distal acinar)	Distal acinus; proximal part normal	Adjacent to the pleura and septa, upper lobes	Spontaneous pneumothorax in young adults, from ruptured subpleural bullae
Irregular	Acinus irregularly involved	Around scars	The commonest form at autopsy but usually asymptomatic

Conditions wrongly called emphysema

Compensatory hyperinflation — dilatation without destruction, after lobectomy
Obstructive overinflation — air trapped behind a partial obstruction
Interstitial ("surgical") emphysema — air in the connective tissue, not in the airspaces at all
Senile hyperinflation — age-related alveolar duct enlargement without wall destruction

Pathogenesis of Emphysema

Protease–antiprotease imbalance → Smoking attracts neutrophils and macrophages to the alveoli → They release elastase, proteinases and matrix metalloproteinases → Smoking also causes oxidant stress, which inactivates alpha-1 antitrypsin — a "functional antitrypsin deficiency" even in people with normal genes → Unopposed proteolysis destroys elastin in alveolar walls → Loss of elastic recoil and of the radial traction that holds small airways open → Airways collapse on expiration → air trapping and airflow obstruction

Alpha-1 antitrypsin deficiency — the PiZZ genotype; a protease inhibitor made in the liver. Causes panacinar emphysema in the lower lobes in a young non-smoker, together with liver cirrhosis from accumulation of misfolded protein in hepatocytes (PAS-positive, diastase-resistant globules). Smoking accelerates it enormously

CLINICAL PEARL

The obstruction in emphysema is caused by loss of tethering, not by anything inside the airway. Alveolar walls normally exert radial traction that holds the small airways open. Destroy them and the airways collapse during expiration, trapping air. This is why emphysema causes obstruction despite having no mucus, no bronchospasm and no wall thickening — and why patients instinctively purse their lips to raise airway pressure and splint the airways open.

Clinical Correlation

Feature	Predominant chronic bronchitis	Predominant emphysema
Nickname	"blue bloater"	"pink puffer"
Age at presentation	40–45	50–75
Dyspnoea	Mild, late	Severe, early
Cough and sputum	Early and copious	Late and scanty
Chest	Not hyperinflated	Barrel-shaped, hyperinflated
Cyanosis	Marked	Absent or slight
Arterial gases	Hypoxaemia and hypercapnia	Near normal until late
Cor pulmonale	Early and common	Late and uncommon
Chest radiograph	Prominent vessels, large heart	Hyperinflation, flat diaphragm, small heart, bullae

Complications and Course of COPD

Complication	Mechanism
Recurrent infective exacerbations	Impaired mucociliary clearance; Haemophilus influenzae, pneumococcus, Moraxella, viruses
Respiratory failure	Type II (hypoxaemia with hypercapnia) in chronic bronchitis; type I in emphysema until late
Pulmonary hypertension and cor pulmonale	Hypoxic vasoconstriction plus loss of the capillary bed → right ventricular hypertrophy and failure
Secondary polycythaemia	Chronic hypoxaemia drives erythropoietin
Pneumothorax	Rupture of a bulla
Weight loss and muscle wasting	Increased work of breathing and systemic inflammation
Increased risk of lung carcinoma	Shared causation with smoking, and independent of it

Cor pulmonale is right heart failure caused by lung disease, and is the usual terminal event in chronic bronchitis

Applied Aspects

Spirometry is essential for diagnosis — a post-bronchodilator FEV1/FVC below 0.7 confirms irreversible obstruction and separates COPD from asthma
Stopping smoking is the only intervention that alters the rate of decline in FEV1; drugs relieve symptoms but do not change the trajectory
Long-term oxygen therapy improves survival in chronic hypoxaemia, and is one of the few treatments that does
Give oxygen carefully in severe COPD — in the minority who rely on hypoxic drive, uncontrolled oxygen worsens carbon dioxide retention; controlled oxygen with monitoring is the answer, and hypoxia must never be left untreated
COPD in India is often not smoking-related — biomass exposure, occupational dust and post-tuberculous lung damage are major contributors, and improved cooking stoves are a genuine public health measure
Suspect alpha-1 antitrypsin deficiency in emphysema under 45, in a non-smoker, with basal changes, or with unexplained liver disease
Pulmonary rehabilitation improves exercise capacity and quality of life more than any drug, and is under-used everywhere
Vaccination against influenza and pneumococcus reduces exacerbations and hospital admission

All questions in Respiratory Pathology

Every Pathology chapter →