Emphysema Classification and external resources
H&E (haematoxylin and eosin) stained lung tissue sample from an end-stage emphysema patient. Haematoxylin, hematoxylin, Natural Black 1, or CI 75290 is extracted from the wood of the Logwood tree Eosin is a Fluorescent red Dye resulting from the action of Bromine on Fluorescein. RBCs are red, nuclei are blue-purple, other cellular and extracellular material is pink, and air spaces are white. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed
ICD-10	J43.
ICD-9	492
DiseasesDB	4190
MedlinePlus	000136
eMedicine	med/654
MeSH	D004646

Emphysema is a chronic obstructive pulmonary disease (COPD), formerly termed a chronic obstructive lung disease (COLD). The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings J00-J99 - Diseases of the respiratory system (J00-J06 Acute upper respiratory infections ( Acute Nasopharyngitis ( Common cold) The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books In Medicine, pulmonology (aka pneumology) is the specialty that deals with Diseases of the Lungs and the Respiratory tract. Chronic obstructive pulmonary disease ( COPD) is a Disease of the lungs in which the Airways become narrowed lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive It is often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke. A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low A chemical substance is a Material with a definite chemical composition. Tobacco Smoking is the inhalation of smoke from burned dried or cured leaves of the Tobacco plant most often in the form of a Cigarette.

Emphysema is caused by loss of elasticity (increased compliance) of the lung tissue, from destruction of structures supporting the alveoli, and destruction of capillaries feeding the alveoli, due to the action of alpha 1 antitrypsin deficiency. An alveolus (plural alveoli, from Latin alveolus, "little cavity" is an anatomical structure that has the form of a hollow cavity Capillaries are the smallest of a body's Blood vessels measuring 5-10 μm in diameter which connect Arterioles and Venules and enable the interchange Thus the small airways collapse during exhalation, as alveolar collapsibility has increased. This impedes airflow and traps air in the lungs, as with other obstructive lung diseases. Symptoms include shortness of breath on exertion and later at rest, hyperventilation, and an expanded chest. In Medicine, hyperventilation (or overbreathing) is the state of Breathing faster and/or deeper than necessary bringing about lightheadedness and other

Mild emphysema sufferers often maintain perfect blood oxygen levels by hyperventilating, and so are sometimes called "pink puffers". By contrast, sufferers of chronic bronchitis (another COPD disorder) are called "blue bloaters" because they have cyanosis (inadequate oxygen) due to an almost normal ventilatory drive caused by decreased sensitivity to carbon dioxide secondary to chronic hypercapnia. Bronchitis is an Inflammation of the bronchi (medium-size airways in the Lungs Acute bronchitis is usually caused by Viruses Cyanosis is a blue coloration of the Skin and mucous membranes due to the presence of deoxygenated Hemoglobin in Blood vessels near the skin surface Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single Hypercapnia or hypercapnea (from the Greek hyper = "above" and kapnos = " Smoke " also known as hypercarbia is But any COPD disease results in hypoxaemia (decreased blood partial pressure of oxygen) and hypercapnia (increased blood partial pressure of carbon dioxide). Hypoxaemia (or hypoxemia is a deficiency in the concentration of dissolved oxygen in Arterial blood Hypercapnia or hypercapnea (from the Greek hyper = "above" and kapnos = " Smoke " also known as hypercarbia is Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single

Clinical signs

Signs of emphysema include pursed-lipped breathing, central cyanosis and finger clubbing. Cyanosis is a blue coloration of the Skin and mucous membranes due to the presence of deoxygenated Hemoglobin in Blood vessels near the skin surface In Medicine, clubbing, finger clubbing, or digital clubbing is a deformity of the Fingers and fingernails that is associated with a The chest has increased percussion notes, particularly just above the liver, and a difficult to palpate apex beat, both due to hyperinflation. Percussion is a method of tapping on a surface to determine the underlying structure and is used in Clinical examinations to assess the condition of the Thorax or The liver is a vital organ in the human body and is present in Vertebrates and some other animals Palpation used as part of a Physical examination in which an object is felt (usually with the hands of a Healthcare practitioner to determine its size shape firmness There may be decreased breath sounds and audible expiratory wheeze. In advanced disease, there are signs of fluid overload such as pitting peripheral edema. Peripheral Edema is the Swelling of tissues, usually in the lower limbs, due the accumulation of fluids The face has a ruddy complexion if there is a secondary polycythemia. Polycythemia (or polycythaemia or erythrocytosis) is a condition in which there is a net increase in the total number of Blood cells, primarily Red Sufferers who retain carbon dioxide have asterixis (metabolic flap) at the wrist. Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single Asterixis (also called the flapping tremor) is a Tremor of the wrist when the wrist is extended (dorsiflexion sometimes said to resemble a bird flapping its wings In Human anatomy, the wrist is the flexible and narrower connection between the Forearm and the palm. Many sufferers whose emphysema was caused by cigarette smoke have cigarette stains on the fingers. A finger is a type of digit, an organ of manipulation and sensation found in the Hands of Humans and other Primates Normally humans have five digits

Classically, clinical examination reveals no overt crackles, but in some patients the fine opening of airway 'popping' can be heard. It is unlike the fine crackles of pulmonary fibrosis or coarse crackles of mucus or oedematous fluid. Idiopathic pulmonary fibrosis (IPF, also known as cryptogenic fibrosing alveolitis, is a Chronic, progressive interstitial lung disease with an unknown In vertebrates mucus is a slippery secretion produced by and covering Mucous membranes It is a viscous Colloid containing Antiseptic enzymes (such as Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling hi

Diagnosis

CT scan of a patient with end-stage emphysema

Diagnosis is by spirometry (lung function testing), including diffusion testing. Computed tomography (CT is a Medical imaging method employing Tomography. Spirometry (meaning the measuring of breath) is the most common of the Pulmonary Function Tests (PFTs measuring Lung function specifically the measurement Findings will often demonstrate a decrease in FEV1 but an increase in Total Lung Capacity (TLC). Spirometry (meaning the measuring of breath) is the most common of the Pulmonary Function Tests (PFTs measuring Lung function specifically the measurement Lung volumes refers to physical differences in lung volume while lung capacities represent different combinations of lung volumes usually in relation to inhalation and exhalation Diffusion tests such as DLCO will show a decreased diffusion capacity. DLCO stands for the Diffusing capacity of the Lung for Carbon monoxide, the test used to determine this parameter Other investigations might include X-rays, high resolution spiral chest CT-scan, bronchoscopy (when other lung disease is suspected, including malignancy), blood tests, pulse. It might also be under the category of Alpha-1 Antitrypsin Deficiency, AAT. A way to help AAT is to put more into the blood flow and eat more protein.

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 bronchial passages and down into the increasingly fine network of tubing in the lungs called the alveoli, which are many millions of tiny sacs surrounded by capillaries. An alveolus (plural alveoli, from Latin alveolus, "little cavity" is an anatomical structure that has the form of a hollow cavity These absorb the oxygen and transfer it into the blood. Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products When toxins such as smoke are breathed into the lungs, the particles are trapped and cause a localized inflammatory response. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Chemicals released during the inflammatory response (e. g. , elastase) can break down the walls of alveoli (alveolar septum). In Molecular biology, elastase is an Enzyme from the class of Proteases (peptidases, that break down Proteins Forms and This crucial pathogenic event (septal rupture) leads to significant, purely mechanical modifications of lung architecture[1], driven by lung elastic recoil which causes parenchyma collapse of the septal rupture confining area and intrapulmonary air collections that exceed the sum of alveoli area made in communication by the septal rupture;^[1][2][2]. As far as the process proceeds thoracic cage expansion (barrel chest) and diaphragm contraction (flattening) occur to enhance inspiratory reexpansion/ventilation of the residual partially collapsed healthy parenchyma. Moreover, expiration increasingly depends on the thoracic cage and abdominal muscle action, particularly in the end expiratory phase, instead that on the physiological elastic lung recoil, thus triggering the bronchial obstruction. Mainly decreased is the ability to exude carbon dioxide due to ventilation deficit and, in the more serious cases, oxygen uptake is also impaired. The activity of another molecule called alpha 1-antitrypsin normally neutralizes the destructive action of one of these damaging molecules.

After a prolonged period, hyperventilation becomes inadequate to maintain high enough oxygen levels in the blood. The body compensates by vasoconstricting appropriate vessels. This leads to pulmonary hypertension, which places increased strain on the right side of the heart, the one that pumps deoxygenated blood to the lungs, and it often fails. The failure causes the heart muscle to thicken to pump more blood. Eventually, as the heart continues to fail, it becomes larger and blood backs up in the liver.

Emphysema occurs in a higher proportion in patients with decreased alpha 1-antitrypsin (A1AT) levels (alpha 1-antitrypsin deficiency, A1AD). alpha 1-Antitrypsin or α1-antitrypsin ( A1AT) is a Glycoprotein and generally known as serum trypsin inhibitor. Alpha 1-antitrypsin deficiency ( α1-antitrypsin deficiency, A1AD or Alpha-1) is a Genetic disorder caused by defective production of Alpha In A1AD, inflammatory enzymes (such as elastase) are able to destroy the alveolar tissue (the elastin fibre, for example). In Molecular biology, elastase is an Enzyme from the class of Proteases (peptidases, that break down Proteins Forms and An alveolus (plural alveoli, from Latin alveolus, "little cavity" is an anatomical structure that has the form of a hollow cavity Tissue is a cellular organizational level intermediate between cells and a complete organism Elastin is a Protein in Connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting 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 pattern of emphysema in A1AD is described as panacinar (involving the entire acinus) as opposed to the centrilobular pattern seen with smoking; the former typically affects the lower lungs, and the latter affects the upper lungs. An acinus (adjective acinar, plural acini) refers to the berry-shaped termination of an Exocrine gland, where the secretion is produced In all, A1AD causes about 2% of all emphysema. However, smokers with A1AD are in the highest risk category for emphysema.

Pathogenesis

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. In Molecular biology, elastase is an Enzyme from the class of Proteases (peptidases, that break down Proteins Forms and A protease is any Enzyme that conducts Proteolysis, that is begins protein Catabolism by Hydrolysis of the Peptide bonds that link 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. Perhaps the most interesting 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.

Associations

Emphysema is commonly associated with bronchitis and chronic bronchitis. Bronchitis is an Inflammation of the Bronchi. More specifically it may refer to Acute bronchitis, caused by viruses or bacteria and lasting Bronchitis is an Inflammation of the bronchi (medium-size airways in the Lungs Acute bronchitis is usually caused by Viruses Since it is difficult to delineate "pure" cases of emphysema or chronic bronchitis, they are generally grouped together as chronic obstructive pulmonary disease (COPD). Chronic obstructive pulmonary disease ( COPD) is a Disease of the lungs in which the Airways become narrowed

See above for alpha 1-antitrypsin deficiency. Alpha 1-antitrypsin deficiency ( α1-antitrypsin deficiency, A1AD or Alpha-1) is a Genetic disorder caused by defective production of Alpha Severe cases of A1AD may also develop cirrhosis of the liver, where the accumulated A1AT leads to a fibrotic reaction. Cirrhosis is a consequence of chronic Liver Disease characterized by replacement of liver tissue by fibrous Scar tissue as well as regenerative Fibrosis is the formation or development of excess fibrous Connective tissue in an organ or tissue as a reparative or reactive process as opposed to a formation of Fibrous

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. Quality of life is the degree of well-being felt by an individual or group of people

Emphysema is also treated by supporting the breathing with anticholinergics, bronchodilators, steroid medication (inhaled or oral), and supplemental oxygen as required. An anticholinergic agent is a substance that blocks the Neurotransmitter acetylcholine in the central and the Peripheral nervous system. Treating the patient's other conditions including gastric reflux and allergies may improve lung function. Gastroesophageal reflux disease ( American English and Canadian English) or Gastro-oesophageal reflux disease ( British English, Hiberno-English Allergy is a disorder of the Immune system often also referred to as Atopy. 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 fly, cruise, and work while using supplemental oxygen. Other medications are being researched.

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. For other uses see Valve (disambiguation. For the electronic component see Thermionic valve. The only known "cure" for emphysema is lung transplant, but few patients are strong enough physically to survive the surgery. Lung transplantation is a surgical procedure in which a patient's diseased Lungs are partially or totally replaced by lungs which come from a donor Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental 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. The kidneys are complicated organs that have numerous biological roles The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic In Biology, an organ ( Latin: organum, "instrument tool" from Greek όργανον - organon "organ instrument Transplants also require the patient to take an anti-rejection drug regime which suppresses the immune system, and so can lead to microbial infection of the patient. Transplant rejection occurs when a transplanted organ or tissue fails to be accepted by the body of the transplant recipient An infection is the detrimental Colonization of a host Organism by a foreign Species.

Emphysema can be classified into two types: Primary and Secondary. Primary emphysema can be subdivided into panacinary and centroacinary. Panacinary emphysema is related to the destruction of alveoli, because of an inflammation or deficiency of alfa-1-antitrypsin. It is found more in young adults who do not have chronic bronchitis. Bronchitis is an Inflammation of the bronchi (medium-size airways in the Lungs Acute bronchitis is usually caused by Viruses Centroacinary 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.

A study published by the European Respiratory Journal suggests that tretinoin (an anti-acne drug commercially available as Accutane) 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. For a broader class of publications which include scientific journals see Academic journal. Tretinoin is the acid form of Vitamin A and so also known as all-trans retinoic acid or ATRA. Acne vulgaris (commonly called acne) is a Skin disease caused by changes in the Pilosebaceous units (skin structures consisting of a Hair follicle Isotretinoin ( INN) (aɪsoʊtrɨˈtɪnoʊɨn or /ˌaɪsoʊtrɨˈtɪnoʊɨn/ is a Medication used for the treatment of severe acne. Vitamin A refers to a family of similarly shaped molecules the Retinoids. A mouse (plural mice) is a small Animal that belongs to one ^[3][4] 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. ^[5]

Notable cases

Notable cases of emphysema have included Ava Gardner (67),^[6] Spencer Tracy (67),^[7] Leonard Bernstein (72), Dean Martin (78), Samuel Beckett (83), Johnny Carson (79), T. S. Eliot (76), Tallulah Bankhead (66), Dick York (63), R. J. Reynolds (67), R. Ava Lavinia Gardner ( December 24, 1922 – January 25, 1990) was an Academy Award -nominated American actress Spencer Tracy ( April 5, 1900 – June 10, 1967) was a two-time Academy Award -winning Actor of stage and WikipediaWikiProject Composers#Lead section --> WikipediaWikiProject Classical music#Biographical_infoboxes Dean Martin (born Dino Paul Crocetti; June 7 1917 &ndash December 25 1995 was an American Singer, Film Actor, television personality Samuel Barclay Beckett (13 April 1906 – 22 December 1989 was an Irish Writer, Dramatist and poet John William “Johnny” Carson ( October 23, 1925 &ndash January 23, 2005) was an American Television host and Thomas Stearns Eliot, OM (September 26 1888 – January 4 1965 was a poet Dramatist, and Literary critic. Tallulah Brockman Bankhead ( January 31, 1902 – December 12, 1968) was an American Actress, talk-show host and Dick York ( September 4, 1928 &ndash February 20, 1992) was an American Actor in Radio, Broadway stage Richard Joshua "RJ" Reynolds ( July 20, 1850 - July 29, 1918) was an American businessman and founder of the R J. Reynolds Jr. (58), R. J. Reynolds III (59),^[8] Don Imus,^[9] Ike Turner (76) and Elizabeth Dawn. John Donald Imus Jr (born July 23 1940) known simply as Don Imus, is an American radio host, Shock jock, Humorist Ike Wister Turner ( November 5 1931 &ndash December 12 2007) was an American Musician, Bandleader, Elizabeth Dawn MBE (better known as Liz Dawn, born Sylvia Butterfield on November 8, 1939 in Leeds, England is an See also Deaths from Emphysema.

See also

• Subcutaneous emphysema

Footnotes