Pathophysiology

In COPD, the airflow limitation is both progressive and associated with an abnormal
inflammatory response of the lungs to noxious particles or gases. The inflammatory
response occurs throughout the airways, parenchyma, and pulmonary vasculature.
Because of the chronic inflammation and the body’s attempts to repair it, narrowing
occurs in the small peripheral airways.
Inhalational exposures can trigger an inflammatory response in airways and alveoli that
leads to disease in genetically susceptible people. The process is thought to be
mediated by an increase in protease activity and a decrease in antiprotease activity.
Lung proteases, such as neutrophil elastase, matrix metalloproteinases, and
cathepsins, break down elastin and connective tissue in the normal process of tissue
repair. Their activity is normally balanced by antiproteases, such as α1-antitrypsin,
airway epithelium-derived secretory leukoproteinase inhibitor, elafin, and matrix
metalloproteinase tissue inhibitor. In patients with COPD, activated neutrophils and
other inflammatory cells release proteases as part of the inflammatory process;
protease activity exceeds antiprotease activity, and tissue destruction and mucus
hypersecretion result. Neutrophil and macrophage activation also leads to accumulation
of free radicals, superoxide anions, and hydrogen peroxide, which inhibit
antiproteases and cause bronchoconstriction, mucosal edema, and mucous
hypersecretion.
Neutrophilinduced oxidative damage, release of profibrotic neuropeptides (eg,
bombesin), and reduced levels of vascular endothelial growth factor may contribute to
apoptotic destruction of lung parenchyma.
The inflammation in COPD increases with increasing disease severity, and, in severe
(advanced) disease, inflammation does not resolve completely with smoking cessation.
This inflammation does not seem to respond to corticosteroids.
The parenchymal changes may also be consequences of inflammation, environmental,
or genetic factors (eg, alpha1 antitrypsin deficiency).
Early in the course of COPD, the inflammatory response causes pulmonary vasculature
changes that are characterized by thickening of the vessel wall. These changes may
occur as a result of exposure to cigarette smoke or use of tobacco products or as a
result of the release of inflammatory mediators.
Respiratory infection (which COPD patients are prone to), in conjunction with cigarette
smoking, may amplify progression of lung destruction.
Bacteria, especially Haemophilus influenzae, colonize the normally sterile lower airways
of about 30% of patients with COPD. In more severely affected patients (eg, those with
previous hospitalizations),
Pseudomonas aeruginosa colonization is common. Smoking and airflow obstruction
may lead to impaired mucus clearance in lower airways, which predisposes to infection.
Repeated bouts of infection increase the inflammatory burden that hastens disease
progression. There is no evidence, however, that long-term use of antibiotics slows the
progression of COPD.

Venous blood entering the pulmonary circulation passes through the underventilated area and exits to the left side of the heart poorly oxygenated. Bronchospasm may also occur in patients with reactive airway disease. or it results from aspiration of flora present in the oropharynx. although hypoxia is also caused by ventilation/perfusion (V/Q) mismatch. These changes lead to loss of elastic recoil and lung hyperinflation. patients with pneumonia caused by infectious agents often have an acute or chronic underlying disease that impairs host defenses. Increased work of breathing may lead to alveolar hypoventilation with hypoxia and hypercapnia. Pneumonia often affects both ventilation and diffusion. Areas of the lung are not adequately ventilated because of secretions and mucosal edema that cause partial occlusion of the bronchi or alveoli. Bronchiectasis results from conditions associated with repeated damage to bronchial walls and with abnormal mucociliary clearance. Pneumonia arises from normally present flora in a patient whose resistance has been altered. as does lung hyperinflation.The cardinal pathophysiologic feature of COPD is airflow limitation caused by airway obstruction. or both. It may also result from bloodborne organisms that enter the pulmonary circulation and are trapped in the pulmonary capillary bed. bronchospasm. mucosal edema. mostly neutrophils. with a resultant decrease in alveolar oxygen tension. Inflammation and destruction of the structural components of the bronchial wall lead to chronic abnormal dilatation Upper airway characteristics normally prevent potentially infectious particles from reaching the normally sterile lower respiratory tract. a ventilation–perfusion mismatch occurs in the affected area of the lung. White blood cells. also migrate into the alveoli and fill the normally air-containing spaces. or a combination of these mechanisms. contributing to loss of airway support and airway closure during expiration. . Enlarged alveolar spaces sometimes consolidate into bullae. Thus. Increased airway resistance increases the work of breathing. they occasionally occupy the entire hemithorax. leading to a breakdown in the supporting tissue adjacent to the airways. Bullae may be entirely empty or have strands of lung tissue traversing them in areas of locally severe emphysema. Alveolar attachments and alveolar septa are destroyed. producing an exudate that interferes with the diffusion of oxygen and carbon dioxide. loss of elastic recoil. Because of hypoventilation. The mixing of oxygenated and unoxygenated or poorly oxygenated blood eventually results in arterial hypoxemia. peribronchial fibrosis. becoming a potential source of pneumonia. Airway obstruction is caused by inflammation-mediated mucus hypersecretion. defined as airspaces ≥ 1 cm in diameter. An inflammatory reaction can occur in the alveoli. mucus plugging.

having originated in one or more localized areas within the bronchi and extending to the adjacent surrounding lung parenchyma.” The term “bronchopneumonia” is used to describe pneumonia that is distributed in a patchy fashion. Bronchopneumonia is more common than lobar pneumonia . the disease is referred to as “lobar pneumonia.If a substantial portion of one or more lobes is involved.