Emphysema
Classification and external resources
Micrograph demonstrating emphysema (left of image - large empty spaces) and lung tissue with relative preservation of the alveoli (right of image). H&E stain.
ICD-10	J43.
ICD-9	492
DiseasesDB	4190
MedlinePlus	000136
eMedicine	med/654
MeSH	D011656

Emphysema is a long-term, progressive disease of the lung that primarily causes shortness of breath. In people with emphysema, the lung tissues necessary to support the physical shape and function of the lung are destroyed. It is included in a group of diseases called chronic obstructive pulmonary disease or COPD (pulmonary refers to the lungs). Emphysema is called an obstructive lung disease because the destruction of lung tissue around smaller airways, called bronchioles, makes these airways unable to hold their functional shape upon exhalation.

[edit] Presentation

Emphysema is characterized by loss of elasticity (increased pulmonary compliance) of the lung tissue caused by destruction of structures feeding the alveoli, in some cases owing to the action of alpha 1-antitrypsin deficiency. This causes the small airways to collapse during forced exhalation, as alveolar collapsibility has decreased. As a result, airflow is impeded and air becomes trapped in the lungs, in the same way as other obstructive lung diseases. Symptoms include shortness of breath on exertion, and an expanded chest. However, the constriction of air passages isn't always immediately deadly, and treatment is available.

Signs of emphysema include pursed-lipped breathing and central cyanosis. The chest has hyperresonant percussion notes, particularly just above the liver, and a difficult to palpate apex beat, both due to hyperinflation. There may be decreased breath sounds and audible expiratory wheeze. In advanced disease, there are signs of fluid overload such as pitting peripheral edema. The face has a ruddy complexion if there is a secondary polycythemia. Sufferers who retain carbon dioxide have asterixis (metabolic flap) at the wrist.

[edit] Classification

Emphysema can be classified into primary and secondary color. However, it is more commonly classified by location.

Emphysema can be subdivided into panacinary and centroacinary (or panacinar and centriacinar,^[1] or centrilobular and panlobular).^[2]

• Panacinar (or panlobular) emphysema is related to the destruction of alveoli, because of an inflammation or deficiency of alpha 1-antitrypsin. It is found more in young adults who do not have chronic bronchitis.
• Centroacinar (or centrilobular) emphysema is due to destruction of terminal bronchioli muchosis, due to chronic bronchitis. This is found mostly in elderly people with a long history of smoking or extreme cases of passive smoking.

Other types include distal acinar and irregular.^[1]

A special type is congenital lobar emphysema (CLE).

[edit] Congenital lobar emphysema

CLE is results in overexpansion of a pulmonary lobe and resultant compression of the remaining lobes of the ipsilateral lung, and possibly also the contralateral lung. There is bronchial narrowing because of weakened or absent bronchial cartilage.^[3]

There may be congenital extrinsic compression, commonly by an abnormally large pulmonary artery. This causes malformation of bronchial cartilage, making them soft and collapsible.^[3]

CLE is potentially reversible, yet possibly life-threatening, causing respiratory distress in the neonate.^[3]

[edit] Pathophysiology

Pathology of lung showing centrilobular emphysema characteristic of smoking. Closeup of fixed, cut surface shows multiple cavities lined by heavy black carbon deposits. (CDC/Dr. Edwin P. Ewing, Jr., 1973)

In normal breathing, air is drawn in through the bronchi and into the alveoli, which are tiny sacs surrounded by capillaries. Alveoli absorb oxygen and then transfer it into the blood. When toxicants, such as cigarette smoke, are breathed into the lungs, the harmful particles become trapped in the alveoli, causing a localized inflammatory response. Chemicals released during the inflammatory response (e.g., elastase) can eventually cause the alveolar septum to disintegrate. This condition, known as septal rupture, leads to significant deformation of the lung architecture.^[4] These deformations result in a large decrease of alveoli surface area used for gas exchange. This results in a decreased Transfer Factor of the Lung for Carbon Monoxide (TLCO). To accommodate the decreased surface area, thoracic cage expansion (barrel chest) and diaphragm contraction (flattening) take place. Expiration increasingly depends on the thoracic cage and abdominal muscle action, particularly in the end expiratory phase. Due to decreased ventilation, the ability to exude carbon dioxide is significantly impaired. In the more serious cases, oxygen uptake is also impaired.

As the alveoli continue to break down, hyperventilation is unable to compensate for the progressively shrinking surface area, and the body is not able to maintain high enough oxygen levels in the blood. The body's last resort is vasoconstricting appropriate vessels. This leads to pulmonary hypertension, which places increased strain on the right side of the heart, the side responsible for pumping deoxygenated blood to the lungs. The heart muscle thickens in order to pump more blood. This condition is often accompanied by the appearance of jugular venous distension. Eventually, as the heart continues to fail, it becomes larger and blood backs up in the liver.

Patients with alpha 1-antitrypsin deficiency (A1AD) are more likely to suffer from emphysema. A1AD allows inflammatory enzymes (such as elastase) to destroy the alveolar tissue. Most A1AD patients do not develop clinically significant emphysema, but smoking and severely decreased A1AT levels (10-15%) can cause emphysema at a young age. The type of emphysema caused by A1AD is known as panacinar emphysema (involving the entire acinus) as opposed to centrilobular emphysema, which is caused by smoking. Panacinar emphysema typically affects the lower lungs, while centrilobular emphysema affects the upper lungs. A1AD causes about 2% of all emphysema. Smokers with A1AD are at the greatest risk for emphysema. Mild emphysema can often develop into a severe case over a short period of time (1–2 weeks).

[edit] Pathogenesis

Severe emphysema

While A1AD provides some insight into the pathogenesis of the disease, hereditary A1AT deficiency only accounts for a small proportion of the disease. Studies for the better part of the past century have focused mainly upon the putative role of leukocyte elastase (also neutrophil elastase), a serine protease found in neutrophils, as a primary contributor to the connective tissue damage seen in the disease. This hypothesis, a result of the observation that neutrophil elastase is the primary substrate for A1AT, and A1AT is the primary inhibitor of neutrophil elastase, together have been known as the "protease-antiprotease" theory, implicating neutrophils as an important mediator of the disease. However, more recent studies have brought into light the possibility that one of the many other numerous proteases, especially matrix metalloproteases might be equally or more relevant than neutrophil elastase in the development of non-hereditary emphysema.

The better part of the past few decades of research into the pathogenesis of emphysema involved animal experiments where various proteases were instilled into the trachea of various species of animals. These animals developed connective tissue damage, which was taken as support for the protease-antiprotease theory. However, just because these substances can destroy connective tissue in the lung, as anyone would be able to predict, doesn't establish causality. More recent experiments have focused on more technologically advanced approaches, such as ones involving genetic manipulation. One particular development with respect to our understanding of the disease involves the production of protease "knock-out" animals, which are genetically deficient in one or more proteases, and the assessment of whether they would be less susceptible to the development of the disease. Often individuals who are unfortunate enough to contract this disease have a very short life expectancy, often 0–3 years at most.

[edit] Associations

Emphysema is commonly associated with bronchitis and chronic bronchitis. Since it is difficult to delineate "pure" cases of emphysema or chronic bronchitis, they are generally grouped together as chronic obstructive pulmonary disease (COPD).

See above for alpha 1-antitrypsin deficiency. Severe cases of A1AD may also develop cirrhosis of the liver, where the accumulated A1AT leads to a fibrotic reaction.

[edit] Prognosis and treatment

Emphysema is an irreversible degenerative condition. The most important measure to slow its progression is for the patient to stop smoking and avoid all exposure to cigarette smoke and lung irritants. Pulmonary rehabilitation can be very helpful to optimize the patient's quality of life and teach the patient how to actively manage his or her care. Patients with emphysema and chronic bronchitis can do more for themselves than patients with any other disabling disease.

Emphysema is also treated by supporting the breathing with anticholinergics, bronchodilators, steroid medication (inhaled or oral), and supplemental oxygen as required. Treating the patient's other conditions including gastric reflux and allergies may improve lung function. Supplemental oxygen used as prescribed (usually more than 20 hours per day) is the only non-surgical treatment which has been shown to prolong life in emphysema patients. There are lightweight portable oxygen systems which allow patients increased mobility. Patients can fly, cruise, and work while using supplemental oxygen. Other medications are being researched, and herbal organic remedies are being offered by companies.

Lung volume reduction surgery (LVRS) can improve the quality of life for certain carefully selected patients. It can be done by different methods, some of which are minimally invasive. In July 2006 a new treatment, placing tiny valves in passages leading to diseased lung areas, was announced to have good results, but 7% of patients suffered partial lung collapse. The only known "cure" for emphysema is lung transplant, but few patients are strong enough physically to survive the surgery. The combination of a patient's age, oxygen deprivation and the side-effects of the medications used to treat emphysema cause damage to the kidneys, heart and other organs. Transplants also require the patient to take an anti-rejection drug regimen which suppresses the immune system, and so can lead to microbial infection of the patient. Patients who think they may have contracted the disease are recommended to seek medical attention as soon as possible.

A study published by the European Respiratory Journal suggests that tretinoin (an anti-acne drug commercially available as Retin-A) derived from vitamin A can reverse the effects of emphysema in mice by returning elasticity (and regenerating lung tissue through gene mediation) to the alveoli.^[5][6]

While vitamin A consumption is not known to be an effective treatment or prevention for the disease, this research could in the future lead to a cure. A follow-up study done in 2006 found inconclusive results ("no definitive clinical benefits") using Vitamin A (retinoic acid) in treatment of emphysema in humans and stated that further research is needed to reach conclusions on this treatment.^[7]

[edit] Notable cases

Notable cases of emphysema have included Ava Gardner, Don Cornell, Spencer Tracy,^[8] Leonard Bernstein, Eddie Dean,^[9] Dean Martin, Norman Rockwell, Samuel Beckett, Johnny Carson, Al Capp, T. S. Eliot, Tallulah Bankhead, Dick York, James Franciscus, R. J. Reynolds, R. J. Reynolds Jr., R. J. Reynolds, III,^[10] Don Imus,^[11] Ike Turner, Charlie Simpson, Elizabeth Dawn, Jerry Reed, Boris Karloff and Amy Winehouse.^[12]

[edit] Additional images

H&E (haematoxylin and eosin) stained lung tissue sample from an end-stage emphysema patient. RBCs are red, nuclei are blue-purple, other cellular and extracellular material is pink, and air spaces are white.

[edit] See also

• Paraseptal emphysema
• Subcutaneous emphysema

[edit] Footnotes

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