Hereditary surfactant synthesis and metabolism disfunctions in respiratory distress syndrome

Plućni surfaktant predstavlja jedinstvenu kombinaciju lipida i proteina koji smanjujući površinsku napetost na granici između zraka i tekućine sprječava alveolarni kolaps na kraju ekspirija. Programirani slijed u ekspresiji gena koji sudjeluju u sintezi surfaktanta važan je za uspostavu njegove funkcije nakon poroda. Mutacije tih gena uzrokuju različiti spektar bolesti od neizlječivog respiratornog distres sindroma novorođenčadi ukoliko je zahvaćen SFTPB gen do intersticijske bolesti pluća u novorođenčadi, starije djece ili odraslih u slučajevima mutacija SFTPC gena. Mutacije ABCA3 gena povezane su s oba prethodno navedena fenotipa. Unatoč navedenoj klasifikaciji, zbog nerijetkog preklapanja kliničke slike i histoloških karakteristika striktna distinkcija među njima ponekad nije moguća. Prepoznavanje i razumijevanje uzroka i složenih patofizioloških mehanizama nastanka ovih bolesti neophodno je za pronalaženje novih, uspješnijih metoda liječenja i njihovu implementaciju u kliničku praksu. U ovom preglednom radu opisuju se sličnosti i razlike kliničke prezentacije ovih poremećaja s naglaskom na histokemijske, ultrastrukturne značajke te patogenetske mehanizme osvrćući se pri tom na ulogu i metabolizam samog surfaktanta.Pulmonary surfactant is a unique combination of lipids and proteins that reduces the surface tension at the air-liquid interface, preventing the collapse of the lung at the end of expiration. Its components and their expression are regulated developmentally and this is crucial for pulmonary surfactant function at birth. Mutations in this area can lead to a variety of disorders such as fatal respiratory distress in the neonatal period if SP-B gene is affected or interstitial lung disease in older infants, children and adults if SP-C gene is mutated. Mutations in the ABCA3 gene are associated with both phenotypes. Despite this classification there is a considerable overlap in the clinical and histologic characteristics of these genetic disorders. Mechanisms involved in this pathological process are certainly complex, but nonetheless they must be well known so that future clinical implementations could be realized. In this review, similarities and differences in the presentation of these disorders with an emphasis on their histochemical and ultrastructural features will be described, along with a brief discussion of surfactant metabolism. Mechanisms involved in the pathogenesis of lung disease caused by mutations in these genes will also be discussed