Exact Morphological and Anatomical Changes in the Respective Type of Emphysema - Research Paper Example

Introduction Emphysema is a progressive and chronic lung disease in which patients complain of dyspnea or shortness of breath because of enlargement of air sacs. In emphysema there is destruction of the tissue responsible for maintaining the physical structure and function of lungs and this destruction of lung parenchyma are responsible for the symptoms that patients present with. Emphysema is generally grouped together with chronic bronchitis and bronchiectasis under the topic of chronic obstructive pulmonary disease or COPD. The former is considered as an obstructive disease of the lung because the tissue damage causes irreversible airflow obstruction as air is trapped in the alveoli and patients find it very difficult to exhale this trapped air. The entrapment of the air also leads to decreased exchange of gases between pulmonary capillaries and alveoli. Since a range of similar diseases come under the heading of chronic obstructive pulmonary disease it is important to precisely define emphysema to avoid confusion. Emphysema is defined according to two standard changes noticed in the lungs; i.e. changes identified in the lung morphology as well as the anatomical distribution of involved area. Morphological changes consist of the alterations seen in the specific lung structures e.g. formation of bullae from alveoli etc. Emphysema generally affects the area of the respiratory tree which is distal to the terminal bronchioles. This area is called the acinus and consists of respiratory bronchioles which lead to the alveolar duct from which tiny air sacs called alveoli out pouch. Alveoli mark the end of the respiratory tree and are very elastic. Alveoli increase in size when a person inspires to collect the inhaled air and are lined with very thin endothelium to allow easy movement of gases between themselves and the blood in surrounding capillaries. The exact morphological and anatomical changes are discussed in more detail with their respective type of emphysema. (Schiffman 2011,emedicine) Types There are four types of emphysema seen and these types are differentiated according to the part of the acinus affected and the gross changes seen in the lungs. The four types are; panacinar emphysema, centriacinar emphysema, distal acinar emphysema and irregular emphysema. In panacinar emphysema as the name suggests the whole acinus is inflated from the distal end of terminal bronchioles till the alveoli. This type normally seen in lower lobes of the lungs and grossly the lungs appear to be large and voluminous. Panacinar emphysema is a very severe form and the patient is continuously out of breath and hyper ventilating. This type of emphysema is associated with alpha 1 anti-trypsin deficiency. In centriacinar emphysema the proximal and mid acinus are generally affected and thus both normal and damaged portions of an acinus exist together. Centriacinar emphysema is more common in upper lung zones e.g. the apices. Grossly the lungs appear less voluminous as compared to panacinar emphysema and there is weakening and destruction of alveolar walls. The weakening and destruction of alveolar walls lead to bullae formation (bullae are large air spaces with little elasticity) as ruptured alveoli coalesce with adjacent alveolus to form larger air spaces. As there is significant loss of elastic tissue with bullae formation, the reduced recoil capacity of these larger air spaces becomes an important cause of obstruction as air gets trapped in them. With destruction of alveolar wall the capillaries surrounding these walls are also damaged leading to decrease in the latter’s number and thus reduced gaseous exchange. In severe forms of centriacinar emphysema the distal acinus also gets affected and it becomes difficult to distinguish it from panacimar emphysema. Centriacinar emphysema is the type of emphysema commonly seen in smokers. In Distal acinar emphysema the distal part of an acinus is affected and bullae are seen in this type too. When Distal acinar emphysema occurs in the upper lungs especially bear fibrosed or scarred tissue it is much more severe. This pattern is also seen in margins of lungs and the septae of connective tissues between these lobules. Irregular emphysema refers to an irregular pattern of acinus destruction and is pretty rare. This form of emphysema is seen after scarring of lung tissue.(Goljan 2007) Causes and Pathogenesis One of the primary risk factors in the etiology of emphysema is smoking cigarettes. Cigarette smoking is a habit strongly associated with development of emphysema although about twenty percent of patients of emphysema in the United States are non-smokers. Tobacco smoke harms the lungs in two ways which contribute to the pathogenesis of emphysema. Firstly smoke from cigarettes has harmful toxins which cause direct tissue damage in the lungs. At the same time cigarette smoke also contains substances which cause irritation of the airway lining and inflammation. The tissue damage and inflammation along cause disruption of the normal physiological balance and causes airway obstruction. Direct damage to lung tissue from tobacco smoke occurs in many ways. First of all cigarettes smoke irritate the airway lining and disrupt the movement of cilia (tiny hairs on the airway) responsible for clearing out mucus and other secretions. With continued smoking the airway lining starts to undergo cell changes as a protective method to the harmful effects of cigarette smoke. This is known as metaplasia and the cilia start to fall off and the cell type changes to squamous cells. There is also a lot of mucus production because of the hazardous substances in cigarette smoke. Since there are decreased numbers of cilia the excessive mucus traps in the respiratory tree and lead to obstruction. Bacteria can also colonize in the mucus which is not being cleared and cause infections and pneumonia. At the same time cigarette smoke also affects the smoker’s immune response which is in place to fight bacteria and other harmful agents. Tar and other harmful substances in cigarettes are not cleared by the immune cells and their presence contributes to recurrent episodes of infection. Recurrent infections and the inflammation caused by noxious elements in cigarette smoke lead to the release of destructive enzymes by immune cells that cause further destruction of pulmonary tissue. The subsequent obstruction leads to violent coughing commonly known as smokers cough and this puts a lot of strain on the alveoli. In addition to this the enzymes released by immune cells cause degradation of important proteins and decrease the elasticity of lung tissue. The strain caused by obstruction and the effects of the enzyme combined lead to destruction of the alveoli which lose their elasticity. Along with smoking the development of emphysema is also strongly associated with the presence of two important kinds of imbalances in the lungs which cause emphysema. These two imbalances are protease and anti-protease imbalance and oxidant anti-oxidant imbalance. The presence of smoking along with any of the two imbalances greatly speed up the pathogenesis of emphysema, indeed cigarette smoke even contributes to the development of the imbalance. Proteases are enzymes responsible for the degradation of proteins and anti-protease stop the action of proteases. It is important for this balance to be controlled otherwise there would be uncontrolled degradation of proteins including structurally and functional important proteins e.g. collagen and elastin. Protease anti-protease imbalance is found in patients with alpha 1 anti-trypsin deficiency. Alpha 1 anti-trypsin is normally found in serum, macrophages and tissue fluid. People deficient in alpha 1 anti-trypsin (AAT) are at high risk of developing emphysema. The gene encoding for the protein AAT are co dominant and are located on the proteinase inhibitor locus of chromosome fourteen. This locus is highly pleomorphic and there are a variety of alleles which can be present in this locus resulting in the respective phenotype. The M allele is the most common and results in normal production of AAT. The Z allele present in a very minor percentage of American population is associated with significantly decreased levels of AAT. AAT is responsible for destroying important enzymes including elastase (elastase breaks down the protein elastin) released by immune cells. What happens is that a person’s immune cells e.g. neutrophils and macrophages are normally sequestered in the pulmonary circulation and slowly they get to the alveoli form pulmonary capillaries. Once in the alveoli these cells are activated by a harmful stimulus e.g. an infection or cigarette smoke (ALA 1981).After activation neutrophils secrete a variety of enzymes like Cathepsin G and elastase. In normal person anti-proteases keep the activity of these enzymes in check but in a person with AAT deficiency enzymes have uncontrolled actions and degrade structurally and functionally important proteins. One of this is elastin which maintains lung elasticity and allows it to expand and relax. Elastin fibers attach radially to the outside wall of small airways and apply force of traction to keep the airway lumen open. With destruction of these fibers there is loss of radial traction and the airways collapse especially with expiration and cause obstruction. Imbalance between oxidants and anti-oxidants also supplements the development of emphysema. Anti-oxidants are physiologically found in the lungs, these anti-oxidants are glutathione, super oxide dismutase and are responsible for inhibiting the hazardous effects of free radicals and other oxidants. The shift in balance occurs much like the same way as that between proteases and anti-proteases. Initially there is a stimulus which starts an immune response and neutrophils and macrophages release oxidants to fight the inciting agent. With buildup of the oxidant concentration there is depletion of the anti-oxidants and thus tissue damage. Smoking plays a important role too in perpetuating the imbalance between oxidants and anti-oxidants. Cigarette smoke has chemo attractant substances like nicotine and reactive oxygen species which attract immune cells. The smoke from cigarettes activates transcription factor NF-kB which enhances the production of tumor necrosis factor (TNF) and other chemokines like leukotriene B4 (LTB4) and interleukin 8 (IL 8). These factors attract neutrophils and macrophages which collect in alveoli and release proteinases which in turn devitalize ling tissue leading to loss of the architecture which maintains elasticity. Smoking is especially harmful in this process as it stimulates macrophages to release matrix metalloproteinase and elastase which is not inhibited by AAT. Also cigarette smoke contains reactive oxygen species which are in addition to the oxidants released by neutrophils and macrophages and further increase the oxidative stress and subsequent injury to the lungs. Pollutants in air also have a similar affect in damaging alveoli in k=lungs and cause emphysema. At the same time there might be a role of genetics in the etiology of emphysema. First degree relatives of emphysema patients are more likely to develop this disease which might be due to genetic sensitivity and susceptibility to injury from smoke and other pollutants. Old age is also a risk factor for emphysema as with age there are already degenerative processes going on in the body and these changes also damage lung tissue. Other processes which destroy airways also contribute to reduced elasticity and can cause emphysema. These processes are related with abnormal reactivity of airways with leads to recurrent inflammation and infection and include conditions like asthma. There might also be a role of differences of hormonal levels in the pathogenesis of emphysema as men are more likely to develop the disease as compared to women.(Kumar 1997) Clinical features The most important symptom in an emphysema patient usually is breathlessness. It starts very late in the course of the disease, usually in the fifth decade of life. The patient tries to change his/her lifestyle in order to minimize the extent of discomfort. But a detailed history can reveal a start of the symptoms much earlier than the presentation of the patient. Usually dyspnea starts to become a problem for the patient when the FEV1 falls below 50%.Another important symptom in emphysema is productive cough. It is usually more severe in the morning and the resultant sputum produced is usually colorless. Sputum production is because of the concomitant bronchitis associated with emphysema in a wide range of patients. Patients may also present with an acute respiratory infection. Emphysematous patients are more prone to respiratory infections. These patients will present with a high fever, severe dyspnea, and greenish sputum production and in severe cases even cyanosis. In such cases it is important to evaluate the patient for a prolonged history of breathlessness and enquire about the number of pack years of smoking. On general physical examination the signs and symptoms are not very obvious in cases of mild to moderate disease but in severe disease they tend to be very specific.(Kumar 1997) Respiratory rate roughly correlates with the severity of the disease. The more severe the disease the higher the respiratory rate will be. Use of accessory muscles and chest in drawing will be obvious in severe disease. In sever disease cyanosis, elevated jugular venous pressure and peripheral edema can also be observed. Forced expiratory volume measurement is simple bedside maneuver that can help the diagnosis in these patients. It will be low depending on the severity of the disease. Physical examination of the thorax reveals a barrel chest, hyper resonant percussion, barely audible breath sounds and wheezing. The classical presentation of patients of emphysema without any concurrent obstructive disease of the lungs e.g. chronic bronchitis is that they hyperventilate without obvious signs of cyanosis. These patients would generally be seen to be barrel chested, leaning forward in clinics and putting in extra effort to force air out of their lungs on expiration. This is the reason these patients are given the term pink puffers as they are breathing heavily without any cyanotic component indicating adequate oxygenation of red blood cells. (Jenkins 1999) Diagnosis Differential diagnosis for emphysema includes the following: Bronchiectasis Bronchitis Chronic bronchitis Lymphangioleiomyomatosis. However the list of differentials is not limited to these diseases and can include a number of other differentials based on the symptoms and severity of the disease.The following lab investigations will help establish a diagnosis. Arterial blood gases will show a low PO2 value even in cases where cyanosis or hypercapnia is not evident. The sequence of change in the disease is such that there is hypoxemia which gradually gets worse and in time leads to hypercapnia. Hematocrit values will be higher than usual in emphysematous patients. Because of the hypoxemia there is a resultant increase in the hemoglobin content of the blood in order to compensate for the lack of oxygenation. Hence in these patients the hematocrit will be higher than 53 in case of a male patient while it will be higher than 47% in females. Bicarbonate value will be higher than normal in these patients. Due to CO2 retention these patients go into a respiratory acidosis and as a compensatory mechanism there is resultant metabolic alkalosis evident by a higher than normal bicarbonate value. Alpha 1 Antitrypsin Levels: will be lower than normal in patients developing emphysema because of alpha1 anti trypsin deficiency. Chest radiographs will be evident for signs of hyperinflation with flattened diaphragms, increased retrosternal space and a narrow long heart shadow. Hilar vascular shadows may be prominent in case of complicating pulmonary hypertension. High resolution CT is more specific than plain chest radiographs in diagnosing patients with emphysema. A high resolution CT clearly shows the bullae in an emphysemic patient which otherwise may not be clearly seen in a chest radiograph. It is recommended in patients who are undergoing a surgical procedure for emphysema like Bullectomy or lung volume expansion surgery. Pulmonary function tests are essential for diagnosis of patients with emphysema. Forced expiratory volume in 1 second is an easy test which is reproducible and can be used to assess the prognosis of the patient. In emphysemic patients it is markedly reduced with an increase in total lung capacity, functional residual capacity and residual volume. Vital capacity is decreased. DLCO is decreased in comparison to the severity of emphysema. After the inhalation of a bronchodilator almost one third of the patients will see an increase of 15% in the FEV1 value. In the light of all these findings it is easy to differentiate between emphysema and its other differentials. . (Schiffman 2011,emedicine) Screening and staging Screening of emphysema can be done through routine spirometry in individuals at risk. People at risk would include long-term smokers, individuals with AAT deficiency and others with symptoms of emphysema or COPD e.g. purulent cough, dyspnea etc. It is important to identify such patients as one can find a variety of cases of obstruction in a clinic with different underlying pathology and each with specific management requirements. There is no need for spirometry if none of the symptoms of COPD are present and the person is a non-smoker. At the same time about twenty percent of smokers with moderate to severe airway obstruction present asymptomatically. The ratio of FEV1 and FVC is important to note with spirometry as reduction in the ratio is indicative of obstructive diseases and in patients with a lower than normal ratio emphysema should be suspected. FEV1 is also used to stage the severity of disease although the ratio is not very precise for this purpose. Another method of staging is through the BODE index. The BODE index is calculated from the patients BMI (body mass index), airway obstruction (FEV1), degree of dyspnea and exercise capacity. Each of these criteria has scores given to them indicating their degree and the final index is measured through these scores. (Stephen 2011, uptodate) Emphysema is associated with significant morbidity and mortality and emphysema patients are at much higher risk of acute cardiac events especially right sided heart failure. Thus screening is vital to identify such patients so that management is hastened and the morbidity and mortality associated with emphysema reduced. Treatment Emphysema can be a very debilitating disease and patients with a severe form of the disease find it hard to cope with even the necessary activities of daily life. Therefore treatment once emphysema is diagnosed requires major life style modifications on part of the patient. First of all the patients are told to quit smoking. This is extremely important as cigarette smoke is harmful in numerous ways and quitting smoking slows down the progress of emphysema significantly. Lung function also gets better gradually in patients who are able to quit smoking. In patients who continue to smoke there can be upto five times decrease in lung function. In order to stop patients from smoking they can be given medications to quit or they can be recommended to join smoking cessation therapy groups. Then there is a need to ease the airway obstruction to relieve symptoms. To achieve this patients are given bronchodilating medications. There is a wide range of bronchodilators in the market some of which include alpha blockers e.g. salbutamol (Vintolin), Ipratropium (Atrovent) and Methylxanthines(theophylline). Prescription of each type of medication is based upon each patient’s individual requirement and how they respond to it. Another approach is to start the patient on steroids. Steroids reduce inflammation in the body through many mechanisms and have shown to benefit emphysema patients. Steroid also causes dilation of airways thus relieving obstruction of airways. They can be given in an inhaler form or even as inhalers. Some patients have also shown to respond to oxygen therapy. (Stephen 2011, uptodate) (Jenkins 1999) All in all emphysema is a very debilitating disease which has no long term cure. The absence of a cure and difficulty in its management are points that favor a preventive strategy to control the incidence of this disease. Smoking is heavily associated with emphysema and it is the only major risk factor in majority of the patients. We need to spread awareness regarding the devastating impact of emphysema on the quality of life of its patients in order to further reinforce the hazards of smoking. REFERENCES EMEDICINE (FIRM). (1997). Emedicine. St. Pete Beach, FL, emedicine, inc. http://www.emedicinehealth.com/emphysema/article_em.htm KUMAR, V., COTRAN, R. S., ROBBINS, S. L., & KUMAR, V. (1997). Basic pathology. Philadelphia, W.B. Saunders Co. GOLJAN, E. F. (2007). Pathology. Philadelphia, PA, Mosby Elsevier. AMERICAN LUNG ASSOCIATION. (1981). Chronic obstructive pulmonary disease. New York, American Lung Association. UPTODATE (FIRM). (2001). UpToDate. Wellesley, Mass, UpToDate. http://www.uptodate.com/contents/chronic-obstructive-pulmonary-disease-definition-clinical-manifestations-diagnosis-and-staging?source=search_result&search=emphysema&selectedTitle=1%7E150 NATIONAL HEART INSTITUTE (U.S.), & UNITED STATES. (1966). Emphysema. [Washington, D.C.], U.S. Dept. of Health, Education, and Welfare, Public Health Service. JENKINS, M. (1999). Chronic obstructive pulmonary disease practical, medical, and spiritual guidelines for daily living with emphysema, chronic bronchitis, and combination diagnosis. Center City, Minn, Hazelden Information & Educational Services. http://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=16882. Read More

 

Read More