Chronic bronchitis and emphysema.
Chronic bronchitis is diagnosed from a clinical perspective. Patients present with expectoration of mucus for, at least, three months a year for two successive years. In chronic bronchitis the mucous secreting glands (goblet cells and submucosal glands) experience hypertrophy and hyperplasia. What causes the goblet cells and submucosal glands to undergo these changes is the repeated exposure of the tracheobronchial tree to the irritants and insults of cigarette smoke.
Frequent contact with the contents of cigarette smoke often leads to the process of squamous cell metaplasia, or squamous cell dysplasia. Squamous cell metaplasia is essentially remodeling of the epithelial lining of the airways. Initially, cilia are "stunned," or paralyzed, by assaults from the contents of cigarette smoke. After decades of smoking, cilia gradually disappear and the ciliated stratified columnar epithelium of the tracheobronchial tree becomes bald. This transformation of the mucociliary escalator, along with hypertrophy and hyperplasia of the mucous secreting structures, leads to retained secretions. Chronic hypersection and retention of mucus also cause an accumulation of inflammatory mucous exudates in the lumens of the airways and thickening of the airway walls. This accumulation of inflammatory exudates and other inflammatory mediators further damages the airway epithelial lining and contributes to air flow obstruction.
As the onslaught of cigarette smoke to the respiratory mucosa continues, the denuded columnar cells differentiate and become cuboidal. The cell type that eventually evolves from non-ciliated cuboidal cells is the simple squamous cell. Interestingly, squamous cell carcinoma accounts for 25% to 30% of all lung cancers.
Aside from airway remodeling and the associated risk of developing bronchogenic carcinoma, chronic bronchitis patients experience airway inflammation and retention of mucus both of which cause partial and complete airway obstructions. Retained secretions produce the familiar cascade of events, i.e., increased airway resistance, uneven distributions of ventilation, ventilation-perfusion inequities, alveolar collapse, intrapulmonary shunting, impaired oxygenation, infection, and increased work of breathing. Maldistribution of ventilation translates into ventilation-perfusion disturbances, which alter arterial blood gas values and create acid-base abnormalities.
The obstructive pattern caused by chronic bronchitis can eventually lead to air trapping and hyperinflation. The subsequent result is chronic hypoxemia and chronic CO2 retention. An important point to make is that the CO2 retention that develops in COPD patients has nothing to do with an inability of CO2 to diffuse across the alveolar-capillary membrane. Quite the contrary, no lung pathology exists that impairs the diffusion of CO2 from pulmonary capillary blood into the alveoli. In other words, no lung disease causes a CO2 diffusion impairment problem, similar that seen with O2, for example, cardiogenic pulmonary edema and pulmonary fibrosis. What accounts for CO2 retention in chronic bronchitis is the derangement of pulmonary mechanics. Expiratory airflow can become severely compromised and produce air trapping, hyperinflation, and CO2 retention. The alveoli simple do not empty sufficiently and fail to eliminate CO2 from the lungs. This situation elevates the alveolar CO2 gas tension and adversely affects the P("v" -A)CO2 gradient, leading to more CO2 remaining in arterial blood.
As ventilation-perfusion inequalities become widespread and severe, chronic bronchitis patients become chronically hypoxemic, chronically hypercapnic, and chronically acidemic. These arterial blood gas and acid-base abnormalities cause pulmonary hypertension, forcing the right ventricle to work harder and experience an increased afterload, i.e., pulmonary hypertension. Consequently, the right ventricle will hypertrophy from the increase workload and will eventually fail, causing cor pulmonale.
Emphysema is defined in terms of anatomical changes to the distal, or peripheral, structures of the lungs, i.e., the terminal bronchioles, alveolar ducts, and alveolar sacs. Emphysema represents a pathological diagnosis involving permanent enlargement of alveoli. As in chronic bronchitis, cigarette smoking is the primary etiological factor. Research has demonstrated that cigarette smoking induces cellular senescence. Cellular senescence is the irreversible termination of cellular replication. In other words, when alveolar epithelial cells (Types I and II) experience programmed cell death (apoptosis), cellular replication and proliferation cease and the cells are not replaced. Again, cigarette smoking can result in the destruction of alveolar septae, causing lung tissue to experience decreased elastic recoil. Consequently, the compliance of the lungs increases and the lung elastance decreases. What follows in the wake of this lung tissue damage is air trapping, which leads to lung overinflation in emphysema. Emphysema patients characteristically present with overdistention, which produces the "barrel-chest" deformity.
While alveolar epithelial cells are being destroyed, pulmonary capillaries suffer the same fate. The ultimate result of this destructive process is a loss of surface area to the alveolar-capillary membrane. Gas exchange becomes compromised, as emphysema patients typically demonstrate decreased DLCO results. Decreased DLCO findings reflect an inability of these patients to oxygenate their arterial blood adequately. Subsequently, hypoxemia develops, which causes polycythemia, which in turn results from the renal release of erythropoietin. The kidneys release erythropoietin to induce the red bone marrow to increase its production of red blood cells (erythrocytes). Hypoxemia causes pulmonary vasoconstriction and polycythemia increases the viscosity of the blood. The combination of these two responses increases the work load of the right ventricle. Right ventricular hypertrophy and right heart failure (cor pulmonale) are developments with emphysema.
The alveolar-capillary bed destruction associated with emphysema is predominantly mediated by the release of proteolytic enzymes by alveolar macrophages and neutrophils. This pathogenic mechanism is especially true in cases of alpha-1 antiprotease deficiency. This inherited condition is characterized by a low serum level of alpha-1 antiprotease, which causes low alveolar concentrations. Normally, the body has sufficient amounts of antiprotease to counteract the devastating effects of protease when it is released by neutrophils and alveolar macrophages as they defend the lungs against infection and irritants. Antiprotease neutralizes protease and prevents it from damaging lung tissue. At the same time, protease destroys various microbes invading the lungs.
When a person smokes a cigarette, contents of cigarette smoke temporarily stun and disable alveolar macrophages. Then, some time afterward, macrophages revive and additional macrophages are summoned to the lungs by chemoattractants to clean up the debris. As this multitude of macrophages unleashes proteolytic enzymes, the concentration of released protease overwhelms the normal concentration of antiprotease in the alveoli. Chemotactic factors recruit more of these cells to the site, and the destructive process perpetuates. Decades of these insults produce destruction of alveolar septa and pulmonary capillaries, leading to loss of gas exchange surface area. This protease-antiprofease imbalance is believed to be pathogenesis of emphysema.
William Wojciechowski, MS, RRT, is chair and associate professor in the department of cardiorespiratory care at the Univ of S. Alabama, Mobile.
by Bill Wojciechowski, MS, RRT
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|Title Annotation:||RESPIRATORY CLINICAL KEEPER|
|Publication:||FOCUS: Journal for Respiratory Care & Sleep Medicine|
|Date:||Nov 1, 2010|
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