Alpha1-antitrypsin, A1AT is liver protein the main role of which consists in inactivation of proteolytic enzymes that breaks down connective tissue in the body.
The role of A1AT in human body:
To understand the function of A1AT we need to describe pathophysiological process: inflammatory response in one of the organs causes formation of connective tissue in the area of inflammation. Then this connective tissue must be destroyed with the help of proteases for recovery of the organ’s function.
However, connective tissue is present in the whole body and it needs to be protected from side effect of proteases. First of all it’s related to the lungs which contains surface-active agent. Surface-active agent coats inner surface of the lungs in the form of specific ointment and protects them from agglutination during breathing out. Normally A1AT in the surface-active agent prevents from destructive effect of proteases, but if the number of A1AT is insufficient then proteases destroy the lungs and cause development of emphysema.
Fraction of alpha1-antitrypsin is related to the acute-phase protein, their concentration in blood is increased during inflammation period.
Emphysema (“puff up, swell” from Greek) is the pulmonary disease characterized by pathological enlargement of cavities. Lungs get bigger because of the rupture of alveolar walls (small vesicles that make up pulmonary tissue) and bigger cavities with air that can’t fulfill the function of gas exchange are formed. Main symptoms are shortness of breath, respiratory difficulty, rales.
The role of A1AT is preconditioned by inherited genetic diseases which lead to either production of insufficient quantity of A1AT or to its wrong structure in the result of which it can’t fulfill its physiological function. Occurence of innate deficiency varies from 1:625 to 1:2000. Representatives of Europoid race have higher risks. Deficiency of A1AT is the cause of emphysema, chronic obstructive lung disease, chronic bronchitis, hepatic disorders and ANCA-positive vasculitis.
Lungs: It is noteworthy that emphysema and chronic obstructive lung disease emerge among patients who regularly expose their lungs to harmful factors: cigarette smoke or inhalation of industrial waste particles which subside in the lungs and damage them. But if emphysema or chronic obstructive lung disease emerge among patients who don’t smoke and live in good ecological conditions then it’s a sign of A1AT deficiency. Chemical tests showed that cigarette smoke acidifies methionine amino acid which is present in A1AT and deforms its structure that causes emphysema. The lower is the level of alpha1-antitrypsin the higher is the risk of emphysema development.
Liver: Genetic defect encoding the structure of A1AT contributes to the production of defective enzyme of A1AT that can’t be utilized by liver cells to its full extent. As a consequence, this enzyme is accumulated in the liver and damages it: fibrosis and then hepatic cirrhosis develop. The given pathology is widespread more among children than adults.
Application in laboratorial diagnosis: ABearing in mind the characteristics of alpha1-antitrypsin there are definite indications for its prescription: revealing of the alpha1-antitrypsin and jaundice, especially if patient is not subjected to the risk factors of developing the given diseases. If patient suffering from chronic obstructive lung disease has concomitant liver pathology then it can worsen the course of lung disease. Recovery of liver function is required for the effective treatment of chronic obstructive lung disease if deficiency of A1AT is detected in the blood.