Alpha-1 Antitrypsin Deficiency (AAD) was first described in 1963, and of the five patients identified, three were found to have severe emphysema at an early age. Subsequent studies that the deficiency was inherited, and in most of the early studies, emphysema and chronic bronchitis were common features.
The deficiency was shown to be associated with a marked reduction in the ability of the plasma to inhibit the serine proteinase trypsin, and later studies showed that this also reflected an inability of the serum to inhibit the enzyme neutrophil elastase (Pauwels, Postma, and Weiss, 2004 p.
446). Human neutrophil elastase was shown to produce both emphysema and chronic bronchial disease in animal models. Emphysema can be directly inherited via a single gene defect. The genetic disorder, known as alpha-1-antitrypsin deficiency, results from a defective gene transmitted by each parent equally to the affected offspring. This gene codes for the enzyme antitrypsin, which, when deficient, results in the loss of normal lung elasticity and in progressive overinflation and destruction of lung tissue.
Antitrypsin deficiency is also the most common genetic cause of childhood liver disease (cirrhosis) and the most common reason for liver transplantation in children. A family history of early onset emphysema or childhood liver disease points toward this diagnosis, which can be confirmed by DNA analysis. DNA testing can be used to detect carriers of alpha-1-antitrypsin deficiency as well as to facilitate prenatal diagnosis for a couple found to be carriers, who face a 25 percent risk of having an affected child (Millunsky, 2001 p. 128-129). Scope and Limitations
AAD is one of the rarest diagnosed conditions in our current time; hence, focused study of such condition is essential. The case study involves the subject of pathological conditions linked with the condition of progression of defective genetic manifestations. Utilizing physiological and genetical approach, we shall center into the discussion of the disease causation, processes and manifestations involved. It is indeed essential to employ the principles of wellness and its components. The following shall be utilized in the overall study. A.
To be able to determine and elaborate the actual disease processes involved, as well as the disease conditions manifested B. To be able to relate genetic causalities and factors in the aspects of disease progression utilizing the domains, components, and principles of wellness C. To be able to provide necessary health interventions, suggest enhancing lifestyle modifications and preventive behaviors related to the condition imposed Purpose of the Study The value significance of this study provides awareness to the public especially in terms of what can these contributing factors impregnate to the condition occurrence.
Most likely, the degenerative character of AAD is very much rehabilitated if this awareness is enhanced through education. The study mainly expands health awareness on both AAD patients and non-patients who are greatly may or otherwise exposed in factors that contribute to its genetic occurrence. Moreover, the knowledge on this topic may further aid the patients and those involved in the reduction of anxiety and ignorance of the condition imposed. Discussion The Functions of ? 1-Antitrypsin and Involved Mediators
Blood and other body fluids contain a serum protein classified as an alpha-a globulin that is capable of neutralizing trypsin and many other proteolytic (protein digesting) enzymes such as fibrinolysis and thrombin (Bross and Gregersen, 2003 p. 39; Crowley, 2004 p. 399). This specialized protein is called alpha-1 antitrypsin, and its concentration in the blood is generally determined. Most individuals produce normal amounts of antitrypsin, others are severely deficient, and a third group have subnormal levels of this protein (Crowley, 2004 p. 399).
?1-Antitrypsin (AA) is an inhibitor of serine protease in general but its most important targets are neutrophil elastase, cathepsin G, and proteinase 3, proteases released by activated neutrophils. Several line of evidence suggest that inhibition of these neutrophil proteases is the major physiologic function of AA (Bross and Gregersen, 2003 p. 39). • First, individuals with AAD are susceptible to premature development of emphysema, a lesion that can be induced in experimental animals by instillation of excessive amounts of neutrophil elastase.
These observations have led to the concept that destructive lung disease may result from the perturbation of the net balance of elastase and AA within the local environment of the lung. • Second, the kinetics of association for AA and neutrophil elastase are more favorable, by several orders of magnitude, than those for AA and any other serine protease. • Third, AA constitutes more than 90% of the neutrophil elastase inhibitory activity in one body fluid that has been examined, pulmonary alveolar lavage fluid (Suchy, Sokol, and Balistreri, p. 549).
AA is the archetype of serine protease inhibitor (SERPIN) supergene family. Its primary function is inhibition during the host response to inflammation/tissue injury, for which it has been termed a hepatic acute-phase reactant (Suchy, Sokol, and Balistreri, p. 549; Bross and Gregersen, 2003 p. 39). AA acts competitively by allowing its target enzymes to bind directly to a subrate-like region within its reactive center loop. The reaction between enzyme and inhibitor is essentially second order, and the resulting complex contains one molecule of each of the reactants (Bross and Gregersen, 2003 p.
39; Fessler, reiley and Sugarbaker, 2004 p. 155). A reactive-site peptide bond within the inhibitor is hydrolyzed during the formation of the enzyme-inhibitor complex. Hydrolysis of this bond; however, does not proceed to completion (Suchy, Sokol, and Balistreri, p. 549). The predominant site of synthesis of plasma AA is in located biologically in the liver wherein in most clearly shown by conversion of plasma AA to the donor phenotype after orthoptopic liver transplantation (Bross and Gregersen, 2003 p.
39; Suchy, Sokol, and Balistreri, 2007 p. 551). It is synthesized in human hepatoma cells as a 52-kDa precursor; undergoes post translational, dolichol phosphate-linked glycosylation at three asparagines residues, and undergoes tyrosine sulfation. It is secreted as a 55-kDa native single-chain glycoprotein with a half time for secretion of 35 to 40 minutes (Suchy, Sokol, and Balistreri, 2007 p. 551). The absence or insufficiency of AA initiates genetic anomaly in terms of failure to suppress immunity response (Porth, 2007 p. 501).
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