Emphysema

Emphysema

PKGhatak,MD

Emphysema is a Greek word, it means inflation or blown with puffed cheeks. In medicine, emphysema is classified under chronic obstructive lung disease. The underlying structural problem in emphysema is the fragmentation of elastic tissues. In the normal lung, elastic tissues are abundant in the walls of small air sacs called alveoli.

To demonstrate the fragmentation of elastic tissue: Take two identical balloons. Blow one to its full capacity and hold it for a minute then release the air. The balloon will collapse but will not return to its original size. The balloon will appear larger and flabbier compared with the other. In the process of inflation, some of the elastic fibers of the balloon were stretched beyond their limits and fractured. When the air was released, the elastic recoil could not bring the balloon back to the original size and appeared flabby. Emphysematous lungs are like that flabby balloon.

An alveolus (air sac) is the structural and functional unit of the lung. Each lung has about 300 million alveoli. Each alveolus is about 250 microns across and lined with one layer of cells and is connected with a tiny airway through which air enters and leaves as one breathes in and out. These airways are the terminal branches of the main airway called bronchus. Alveoli are supported and kept separated by walls made up of connective tissue. Blood enters the lungs by the pulmonary artery, it branches repeatedly and the arterial branches follow the bronchial branches very closely. At the very end, the pulmonary artery becomes a capillary- just one cell in thickness and lies in apposition with the liner- cells of the alveolus. Blood picks up oxygen and releases carbon dioxide easily across this thin membrane. As a consequence of loss of elasticity, alveoli lose support and one alveolus joins with its adjacent alveoli and becomes a larger alveolus. Mathematics tells us the sum of the surface area of two equal sized spheres is much larger than the surface area of a larger sphere made of two such spheres. The final effect of these changes results in a reduction of the total surface area of the lungs and is a major cause of oxygen deprivation. The carbon dioxide, however, diffuses 40 times faster than oxygen and no retention of carbon dioxide takes place in this stage of the disease.

As we inhale (inspiration) the diaphragm descends and the chest wall moves outwards, creating more room in the chest cavity and the intrathoracic pressure falls. This pressure difference drives outside air into the lungs via the nose and air reaches the alveoli. Exhalation (expiration) is a passive process: muscle contraction, which was holding the chest wall in an expanded condition, is terminated and the lungs return to the original state by the recoil of the elastic tissues. The pressure inside the chest cavity rises just above the outside pressure and the air from the lungs is forced out. Elastic tissues and their distribution around the terminal branches of the airways are essential in holding these tiny airways open during expiration.  In fact, airways not only become shorter but also wider because of radial pull generated by elastic recoil during expiration. In emphysema loss of elastic recoil leads to obstruction of air movement during expiration. Thus, emphysema is also an obstructive airway disease. And because the process takes a long time to develop it is called chronic. Nowadays the term chronic obstructive airway diseases of the lung (COLD) is replaced by COPD- the word “lung” is replaced by pulmonary.

What are the causes of Emphysema.

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1. The elastic tissue is made of a protein called elastin. Throughout our lives, elastin is laid down and removed continuously in the lungs. For removal, elastin is digested by an enzyme called Elastase produced locally by white blood cells- neutrophils and tissue macrophages.  When the digestion is complete, the action of elastase is stopped by another enzyme called alpha-1Anti Trypsin (a-1AT). The a-1AT belongs to a family of enzymes called Serpina-1. The long arm of chromosome 14 at the 32.1 locus contains the genetic code for the production of serpina-1. The mode of inheritance of this gene is by autosomal codominance, meaning that both genes are active in an individual, and determine the genetic trait. The normal allele (a pair - one from each parent) of this gene is designated as MM based on the appearance of the band in the middle of the gel used in electrophoresis.  More than 120 mutations in this gene are known. The normal phenotype is MM and an individual with MM allele has a normal blood level of a-1AT, whereas the ZZ phenotype has a profound deficiency.  SS phenotype has a moderate deficiency. Antitrypsin is produced in the liver and transported to the lungs via blood.  The normal blood levels of antitrypsin are 150 to 350 mg /dL. The blood levels of antitrypsin vary depending on the inheritance of the various combinations of these alleles.  In ZZ phenotype people the digestive action of elastase on the elastic tissues proceeds uninhibited and they become candidates for an early onset of emphysema.

It is estimated that 1 in 3,000 people in the USA may be a carrier of the mutation of this gene but the hereditary cause of emphysema accounts for only 1 to 2 % of the vast number of emphysema patients.

2. Cigarette smoke.

Oxidants in cigarette smoke inactivate deacetylase-2 of the macrophages. Then a chain of chemical events follows resulting in the release of elastase and activation of other serine proteinases in the lung   Cigarette smokers and secondhand smokers are at high risk of developing emphysema. Damage to the elastic matrix is greatest in a-1AT deficient individuals. Early and rapidly progressive emphysema is seen in these individuals.

3. Kitchen smoke.

Widespread use of wood, coal, and coke burning stoves in kitchens of poor countries is a major cause of emphysema and chronic bronchitis in women.

4. Chronic bronchitis and Asthma.

Many experts believe chronic bronchitis and emphysema in advanced stages become indistinguishable from each other. Other experts consider asthma also in this group. There is no doubt that considerable overlap exists in the pathophysiology of these three entities.

5. Coal dust.
People exposed to coal dust develop marked emphysema in the lower lobes of the lungs, even though the coal is inert. The coal dust is picked up by macrophages when dust particles reach the lungs and are carried to the walls of the alveoli. Here macrophages release enzyme elastase and collagenase and the destruction of the lungs begin.

Silica dust and silica crystals inhaled by mine workers in various mining related industries suffer from COPD and more severe changes are seen in people who also smoke cigarettes.

6. Air pollution.

Ozone in the air is particularly harmful. Sulfurdioxide and nitogendioxide damage lung tissue directly.

Cotton dust inhalation causes lung damage. Cadmium fumes exposure is a known cause of emphysema and bronchitis.

7. Allergy and hypersensitivity.

Airway hypersensitivity is an important factor in the genesis of asthma.  Poorly controlled asthma over time may progress to produce alveolar damage and loss of alveolar surface area.

8. Repeated infection.

In adults repeated inflammation or infections of the lungs may produce loss of lung surface area and especially in growing children.

9. Congenital abnormalities of collagen tissue formation due to gene abnormalities are associated with emphysema as seen in Cutes Laxa and Ehlers-Danlos syndrome. Some tall and thin young men for some unknown reason develop sudden rupture lungs because of emphysematous changes of the top of the lung or just underneath the pleura. An enzyme Lysyl oxidase is responsible for cross linkage of elastin. In individuals deficient, this enzyme develops emphysema.
These are rare examples of pulmonary emphysema. Cigarette smoking is the most harmful agent in the development of emphysema. Emphysema does not damage all the segments of the lungs uniformly; in some cases, the upper lobes are damaged; in other cases, the lower lobes are preferentially damaged. Even in a given lobe, the changes may dominate in the middle or in the periphery leaving other parts relatively normal.

Symptoms

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There may not be any symptoms at the beginning; some years later patients may complain of shortness of breath on heavy work, gradually in later years with light work and finally, patients will be short of breath even at rest. Those who have associated bronchitis will notice a chronic cough and increased sputum production. They may experience more than their usual share of seasonal cold and chest infections. At an advanced stage of the disease, they will develop heart failure and respiratory failure and many will die prematurely.

 Diagnosis.

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A history of cigarette smoking, the family history of chronic lung disease, and physical signs of inflated lungs with decreased breath sounds will be enough to suspect pulmonary emphysema. A simple breathing test and chest radiographs are all that are required to make a diagnosis. Subsequently, all emphysema patients should have complete pulmonary function tests, oximetry, and serum alpha-1antitrypsin levels determined. A CT scan of the chest delineates structural changes in the lungs in addition to the heart, blood vessels, ribs and vertebra and the diaphragm and stomach.  Then they may be categorized as early, moderately-advanced and far-advanced stages of the disease along with long term health outlooks due to the presence of associated diseases.

Treatment.

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It is never too late to give up smoking. All available facilities should be explored in helping patients with smoking cessation.

Yearly influenza vaccination is mandatory, so also pneumonia vaccination initially and repeated once 5 years later. Vaccination for shingles should be offered to elderly patients.

Those who have an oxygen saturation of 87% or below at rest, should use oxygen on a 24-hour basis; those who develop hypoxemia with physical activities should use oxygen when they undertake those activities and also during sleep. Patients having obstructive sleep apnea in addition to emphysema should use appropriate breathing devices during sleep. Oxygen is the only agent that delays or even prevents the progression of pulmonary hypertension and heart failure, improves the quality of patients’ lives and extends abilities to stay engaged in the workplace.

Patients deficient in alpha-1 antitrypsin should be considered for antitrypsin therapy; given by injection weekly. The cost of antitrypsin is about $100,000. / Year

Medications-
Two groups of medications are generally helpful- [A] bronchodilators, [B] steroids.

[A] Bronchodilators are many but can be mentioned here under three headings.

1. Anticholine: Atropine like synthetic compounds is administered by inhalation either from a can or by a handheld nebulizer. It counteracts the effects of acetylcholine. Acetylcholine produces bronchial smooth muscle constriction when released at the neuromuscular junction by stimulation of the vagus nerve in the lung. People having prostate hypertrophy or glaucoma should not use this medication without specific instructions from their physicians.

2. Beta agonists: Adrenaline like chemical compounds stimulate beta receptors of the bronchial smooth muscles and produce dilation of the airways. These agents can be taken orally or by inhalation like the anticholine. This medication may increase blood pressure and heart rate and may cause cardiac arrhythmias. To minimize the side effects inhalation is a preferred method of administration.

3. Xanthine compounds: Caffeine like chemicals i.e. Theophylline was used extensively in the past, administered orally, intramuscularly, or intravenously. It is hardly used nowadays because of gastrointestinal and cardiac side effects. It inhibits enzyme phosphodiesterase and thereby produces dilatation of bronchial muscles. It increases the force of muscle contractions of the diaphragm and chest wall muscles by enhancing calcium uptake by muscles; delays the onset of fatigue and improves the functional capacity of muscles.

[B] Steroid.  Corticosteroid, like many synthetic steroid hormones, is extensively used in medicine. The corticosteroid has a direct anti-inflammatory effect when delivered locally or in the entire body when given orally or intravenously. The steroid also helps to stabilize macrophage and mast cell membranes and thereby prevents the release of chemicals that initiate and prolong inflammatory and allergic reactions. The steroid has a long list of significant side effects.

In emphysema, it is used mostly as an inhaler. Since it encourages fungal growth in the mouth and tongue known as thrush or oral candidiasis, the patient should rinse the mouth with warm water 5- 10  minutes after its use.

Emphysema patients will develop one or more major complications several years later. At that time patients will require hospitalization and proper treatment.

At some point in the progression of emphysema, certain patients may benefit from surgical treatment.  A markedly diseased lobe or lobes, when interfere with normal functions of other relatively healthy lobes of the lung, may be removed surgically. Also, lung transplantation is an option available for a select group of patients. But it is worth mentioning here that the transplantation of a lung requires a technically superior surgical team and the risk of infection is greater. The survival rate following lung transplantation is 65%in 1 year, and 40%in 5 years.

Pulmonary emphysema is a long drawn debilitating disease. It is the right time, just now, to quit smoking.
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  Edited 2020.     

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