Source:  Emphysema    Tag:  alpha 1 emphysema

  Emphysema in Greek means inflation or blown with puffed cheeks. In medicine emphysema is classified under chronic obstructive lung disease. The underlying structural problem in emphysema of lung is the fragmentation of elastic tissues which are abundant in the walls separating small air sacs called alveoli.
To demonstrate  the fragmentation of elstic tissue:  Take two identical balloons. Blow one to its full capacity and hold it at this state for a minute then release the air. The balloon will collapse but will not return to its original size; it will appear larger and flabbier compared with the other. In the process of inflation, the balloon has lost some of its elasticity. Emphysematous lungs are like that flabby balloon.

An alveolus (air sac) is the structural and functional unit of lung. Each lung has about 300 million alveoli. Each alveolus is about 250 micron 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 braches of the main airway called   bronchus. Alveoli are supported and kept separated by walls made up with connective tissue.   Blood enters lungs by pulmonary artery, it branches repeatedly and the arterial branches follow 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 alveolus. Blood picks up oxygen and releases carbon-dioxide easily across this thin membrane. As a consequence of loss of elasticity alveoli loose support and one alveolus joins with its adjacent alveoli and becomes a lager alveolus.   Mathematics tells us the surface area of two equal sized spheres is much lager than the surface area of a larger sphere made of two such spheres. The final effect of these changes result in reduction of total surface area of lungs and 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 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 nose and air reaches the alveoli. The exhalation (expiration) is a passive process: muscle contraction, that was holding chest wall in an expanded condition, is terminated and lungs return to the original state by recoil of the elastic tissues. The pressure inside the chest cavity rises just above the outside pressure and the air from 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. Now a days the term chronic obstructive airway diseases of lung (COLD) is replaced by COPD- the ward “lung” is replaced by pulmonary.

What are the causes Emphysema.
1. The elastic tissue is made of a protein called elastin. Throughout our lives, the elastin is laid down and removed continuously in lungs. For removal, the elastin is digested by an enzyme called elastase produced locally by white blood cell- neutrophils and tissue macrophages.  When the digestion is complete, the action of elastase is stopped by another enzyme called alpha-1Anti Tripsin (a-1AT). The a-1AT belongs to a family of enzymes called Serpina-1. The long arm of chromosome 14 at 32.1 locus contains the genetic code for production of serpina-1. The mode of inheritance of this gene is by autosomal codominence, meaning that both genes are active in an individual, and determine the genetic trait. The normal allele (a pair - one from each parents) of this gene is designated as  MM based on its appearance of the band in the middle of the gel used in electrophorasis.  More than 120 mutations of this gene are known. The normal phenotype is MM and individual with MM allele has a normal blood level of a-1AT, whereas ZZ phenotype has profound deficiency.  SS phenotype has 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 Antitrypsin is produced in the liver and transported to the lungs via blood.  The blood levels of antitrypsin vary depending on inheritance of the various combination 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 mutation of this gene but the hereditary cause of emphysema accounts only 1 to 2 % of the vast number of emphysema patients.
2. Cigaretts smoke.
Oxidants in cigarette smoke inactivate deacetylase-2 of the macrophages. Then a chain of chemical events follows resulting in 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 are 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. Others 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 lungs, even though the coal is inert. The coal dusts are picked up by macrophages when dust particles reach lungs and carried to the walls of alveoli. Here macrophages release enzyme elatase and collagenase and the destruction of lungs begins.
Silica dusts and silica crystals inhaled by mine workers in various mining related industries suffer from COPD and more severe changes are seen in cigarette samkers.
6. Air pollution.
Ozone in air is particularly harmful. Sulfurdioxide and nitogendioxide damage lung tissue directly.
Cotton dust inhalation causes lung damage. Cadmium fumes exposure a known cause of emphysema and bronchitis.
7. Allergy and hypersensitivity.
Airway hypersensitivity in 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 lungs may produce loss of lung surface area and specially 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 lung because of emphysematous changes of the top of lung or just underneath the pleura. An enzyme Lysyl oxidase responsible for cross linkage of elastin. In individual 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 lungs uniformly; in some cases upper lobes are damaged; in other cases 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.

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 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.

A history of cigarette smoking, 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 PA and lateral views of chest radiographs are all that are required to make a diagnosis. Subsequently, all emphysema patients should have complete pulmonary function tests, oximetery, and serum alpha-1antitrysin levels determined. Then they may be categorized as early, moderately-advanced   and far-advanced stages of the disease.

It is never too late in giving up smoking. All available facilities should be explored in helping patients in 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 oxygen saturation 87% or below at rest, should use oxygen on 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 progression of pulmonary hypertension and heart failure, improves quality of patients’ lives and extends abilities to stay engaged in work place.

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]steroid.
 [A] Bronchodilators are many but can be mentioned here under three headings.
1. Anticholine: Atropine like synthetic compounds are administered by inhalation either from a can or by a hand held nebulizer. It counteracts effects of acetylcholine. Acetylcholine produces bronchial smooth muscle constriction when released at the neuromuscular junction by stimulation of vagus nerve in the lung. People having prostrate 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 now a days because of   gastrointestinal and cardiac side effects. It inhibits  enzyme phosphodiasterase thereby  produces  dilatation of bronchial muscles. It increases force of muscle contractions  of the diaphragm and chestwall muscles by enhancing calcium uptake by muscles; delays onset of fatigue and improves functional capacity of muscles.
[B] Steroid.  Corticosteroid like many synthetic steroid hormones  are extensively used in medicine.    It has direct anti-inflammatory effect when delivered locally or in the entire body  when given orally or intravenously. Steroid also helps to stabilize macrophage and mast cell membranes and thereby prevents release of chemicals that initiate and prolong inflammatory and allergic reactions. Steroid has a long list of significant side effects, just too many to list here.
In emphysema it is used mostly as an inhaler. Since it encourages fungal growth in mouth and tongue known as thrush or oral candidiasis, the patient should rinse  mouth with warm water 5- 10  minutes  after its use.

Several years later, from the onset of symptoms, the patients will develop one or more major complications. At that time patients will require hospitalization and proper treatment.
At some point in the progression of emphysema certain patient  may benefit from surgical treatment.  A markedly diseased lobe or lobes, when interfere with normal functions of other relatively healthy lobes of 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 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, 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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