Chronic obstructive pulmonary disease pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Philip Marcus, M.D., M.P.H. [2]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]
Overview
Chronic obstructive pulmonary disease is a group of diseases characterized by the pathological limitation of airflow in the airway that is not fully reversible.
Pathophysiology
Chronic obstructive pulmonary disease is a blanket term with two main underlying causations the influence the pathophysiologic outcome: chronic bronchitis and emphysema.
Chronic bronchitis
Chronic bronchitis is defined in clinical terms as a cough with sputum production on most days for 3 months of a year, for 2 consecutive years.[1]
Chronic bronchitis is hallmarked by hyperplasia (increased number) and hypertrophy (increased size) of the goblet cells (mucous gland) of the airway, resulting in an increase in secretion of mucus which contributes to the airway obstruction. Microscopically there is infiltration of the airway walls with inflammatory cells, particularly neutrophils. Inflammation is followed by scarring and remodeling that thickens the walls resulting in narrowing of the small airway. Further progression leads to metaplasia (abnormal change in the tissue) and fibrosis (further thickening and scarring) of the lower airway. The consequence of these changes is a limitation of airflow.[2].
Emphysema
Emphysema is defined histologically as the enlargement of the air spaces distal to the terminal bronchioles, with destruction of their walls.
The enlarged air sacs (alveoli) of the lungs reduces the surface area available for the movement of gases during respiration. This ultimately leads to dyspnea in severe cases. The exact mechanism for the development of emphysema is not understood, although it is known to be linked with smoking and age.
Pathophysiology
It is not fully understood how tobacco smoke and other inhaled particles damage the lungs to cause COPD. The most important processes causing lung damage are:
- Oxidative stress produced by the high concentrations of free radicals in tobacco smoke
- Cytokine release due to inflammation as the body responds to irritant particles such as tobacco smoke in the airway
- Tobacco smoke and free radicals impair the activity of antiprotease enzymes such as alpha 1-antitrypsin, allowing protease enzymes to damage the lung
Narrowing of the airways reduces the rate at which air can flow to and from the air sacs (alveoli) and limits the effectiveness of the lungs. In COPD, the greatest reduction in air flow occurs when breathing out (during expiration) because the pressure in the chest tends to compress rather than expand the airways. In theory, air flow could be increased by breathing more forcefully, increasing the pressure in the chest during expiration. In COPD, there is often a limit to how much this can actually increase air flow, a situation known as expiratory flow limitation.[3]
If the rate of airflow is too low, a person with COPD may not be able to completely finish breathing out (expiration) before he or she needs to take another breath. This is particularly common during exercise, when breathing has to be faster. A little of the air of the previous breath remains within the lungs when the next breath is started, resulting in an increase in the volume of air in the lungs, a process called dynamic hyperinflation.[3]
Dynamic hyperinflation is closely linked to dyspnea in COPD.[4] It is less comfortable to breathe with hyperinflation because it takes more effort to move the lungs and chest wall when they are already stretched by hyperinflation.
Another factor contributing to shortness of breath in COPD is the loss of the surface area available for the exchange of oxygen and carbon dioxide with emphysema. This reduces the rate of transfer of these gases between the body and the atmosphere and can lead to low oxygen and high carbon dioxide levels in the body. A person with emphysema may have to breathe faster or more deeply to compensate, which can be difficult to do if there is also flow limitation or hyperinflation.
Some people with advanced COPD do manage to breathe fast to compensate, but usually have dyspnea as a result. Others, who may be less short of breath, tolerate low oxygen and high carbon dioxide levels in their bodies, but this can eventually lead to headaches, drowsiness and heart failure.
Advanced COPD can lead to complications beyond the lungs, such as weight loss (cachexia), pulmonary hypertension and right-sided heart failure (cor pulmonale). Osteoporosis, heart disease, muscle wasting and depression are all more common in people with COPD.[5]
Several molecular signatures associated to lung function decline and corollaries of disease severity have been proposed, a majority of which are characterized in easily accessible surrogate tissue, including blood derivatives such as serum and plasma. A recent 2010 clinical study proposes alpha 1B-glycoprotein precursor/A1BG, alpha 2-antiplasmin, apolipoprotein A-IV precursor/APOA4, and complement component 3 precursor, among other coagulation and complement system proteins as corollaries of lung function decline, although ambiguity between cause and effect is unresolved.[6]
Acute exacerbations of COPD
An acute exacerbation of COPD is a sudden worsening of COPD symptoms (shortness of breath, quantity and color of phlegm) that typically lasts for several days. It may be triggered by an infection with bacteria or viruses or by environmental pollutants. Typically, infections cause 75% or more of the exacerbations; bacteria can be found in roughly 25% of cases, viruses in another 25%, and both viruses and bacteria in another 25%. Pulmonary emboli can also cause exacerbations of COPD. Airway inflammation is increased during the exacerbation, resulting in increased hyperinflation, reduced expiratory air flow and worsening of gas transfer. This can also lead to hypoventilation and eventually hypoxia, insufficient tissue perfusion, and then cell necrosis.[5]
References
- ↑ Longmore M, Wilkinson I, Rajagopalan S (2005). Oxford Handbook of Clinical Medicine, 6ed. Oxford University Press. pp 188-189. ISBN 0-19-852558-3.
- ↑ Kumar P, Clark M (2005). Clinical Medicine, 6ed. Elsevier Saunders. pp 900-901. ISBN 0702027634.
- ↑ 3.0 3.1 Calverley PM, Koulouris NG (2005). "Flow limitation and dynamic hyperinflation: key concepts in modern respiratory physiology". Eur Respir J. 25 (1): 186–199. doi:10.1183/09031936.04.00113204. PMID 15640341.
- ↑ O'Donnell DE (2006). "Hyperinflation, Dyspnea, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease". The Proceedings of the American Thoracic Society. 3 (2): 180–4. doi:10.1513/pats.200508-093DO. PMID 16565429.
- ↑ 5.0 5.1 Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J (2007). "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary". American Journal of Respiratory and Critical Care Medicine. 176 (6): 532–55. doi:10.1164/rccm.200703-456SO. PMID 17507545. Retrieved 2012-03-02. Unknown parameter
|month=ignored (help) - ↑ Rana GS, York TP, Edmiston JS, Zedler BK; et al. (2010). "Proteomic biomarkers in plasma that differentiate rapid and slow decline in lung function in adult cigarette smokers with chronic obstructive pulmonary disease (COPD)". Anal Bioanal Chem. 397 (5): 1809–19. doi:10.1007/s00216-010-3742-4. PMID 20442989.