Analytical study of results of experimental and theoretical works on pathogenesis of psoriatic disease was conducted. Psoriasis is dermal implication of systemic psoriatic process (SPP). New SPP model explaining results of clinical and laboratory experiments was formulated. According to Y-model there are two main factors: hyperpermeability of small intestine for bacterial products and colonization of its walls by Gram+ bacteria (incl. psoriagenic bacteria PsB) and Gram(-) TLR4-active bacteria. Inside SPP there is a vicious cycle which is supported by disturbance of production and-or circulation of bile acids. SPP central subprocess is PAMP-nemia, namely chronic kPAMP-load on blood phagocytes (neutrophiles, monocytes and dendritic cells). The load results in increase of blood kPAMP level. The major key PAMP (kPAMP) are LPS and PG (incl. PG-Y - peptidoglycan of psoriagenic bacteria). Chronically increased kPAMP-load possibly provides tolerization of some neutrophils Neu, monocytes Mo and dendritic cells DC in blood flow. The chemostatus of tolerized blood Neu-T in process of their aging changes similarly to chemostatus nonactivated Neu and, hence, they carry endocytosed content from blood flow into the bone marrow. Chemostatuses of tolerized Mo-T and DC-T are similar to nonactivated ones. So they don't bring endocytosed content to lymph nodes or spleen and remain in blood. Tolerized phagocytes degrade endocytosed fragments of bacterial products containing kPAMP slowly and incompletely, Tolerized phagocytes appeared to be (PG-Y)-carriers are named by R-phagocytes and are designated as Neu-R, Mo-R and DC-R. SPP severity predetermines possibility of psoriasis initialization and maintenance because Mo-R and DC-R along with normal Mo and DC participate in homeostatic and inflammatory renewal of pool of dermal macrophages and DC of non-resident origin. Part 2 - arXiv:1201.2900
Epidermis self-renewal is regular process. New cells are born in basal layer. They mature, vary, migrate outside and form external horny layer. Then they die away and exfoliate. Standard duration of epidermis cell life (renewal period) for areas of skin with average thickness is 20-25 days. Psoriasis accelerates self-renewal. Cells live 4-10 days (Baker 2000, Iizuka 2004, Weinstein 1985). Cells migrating outside have no time to differentiate and they aren't quite functional. Psoriatic plaques have red shade. They are tender, they are covered by white flakes due to intensive lost of cells and they are much thicker.
Psoriasis isn’t contagious. There are various types of psoriasis: vulgaris or plaque (L40.0), flexural or inverse (L40.83-4), erythrodermic (L40.85), pustular (L40.1-3, L40.82), guttate (L40.4). Codes of diseases are given according to ICD-10. Chronic plaque psoriasis (CPs) is the most frequent type (more than 80% of total number of cases). Up to 15% of psoriatics also suffer from psoriatic arthritis (L40.5). Psoriasis strikes about 2-3% of population (120-180 million people). New diagnosis of psoriasis gets 4-6 million people every year. Disease appears after birth or in extreme old age. Psoriasis is a chronic disease so there are periods of aggravation and remission. Sometimes there is no cause for period change and sometimes aggravation can be decreased as a result of treatment. Serious psoriasis can result in disability. Psoriasis course is similar in men and women. Afro-Americans, Indians, Chineses and Japaneses suffer from psoriasis less frequently and Eskimos don’t suffer from psoriasis at all (Piruzian 2006, Giardina 2004).
Psoriasis is registered in “Online Mendelian Inheritance in Man” at number OMIM177900. Psoriasis is disease with hereditary predisposition: concordance of uniovular twins is 70%. If one parent suffers from psoriasis children are diagnosed the disease in 15-25% of cases; if both parents suffer from psoriasis children are diagnosed the disease in more than 40-60% of cases. The interrelation of allele HLA-Cw0602 (chromosome 6p21) and psoriasis of the first type which is characterized by early beginning is proved (Weisenseel 2002). This allele is found in more than 60% of psoriatics (not more than 15% of healthy people). Locuses of other chromosomes have weaker interrelations (Piruzian 2006, Giardina 2004). Psoriasis can’t begin only in presence of genetical deflections. External exposure is necessary for beginning and maintenance of psoriasis. Infections, skin traumas, stresses, reaction to medications, climatic changes and other causes can provoke onset of psoriasis or its aggravation (Molochkov 2007, Bos 2005, Fry 2007b, Gudjonsson 2004).
Accelerated proliferation of keratinocytes is likely to be caused by erroneous actions of mechanisms of skin antibacterial protection. Influence of beta-hemolitic streptococci (first of all causing tonsillar infections) on initialization and aggravations of psoriasis is avowed (Molochkov 2007, Khairutdinov 2007, Baker 2006a, Baker 2003, Baker 2000, Fry 2007b, Gudjonsson 2004). There is no uniform point of view on etiology and pathogenesis of psoriasis. Researches offer various models (Baltabaev 2005, Korotkii & Peslyak 2005, Khardikova 2000, Baker 2000, Baker 2006b, Bos 2005, Danilenko 2008, Gudjonsson 2004, Gyurcsovics 2003, Iizuka 2004, Lowes 2007, Majewski 2003, Nestle 2005b, Nickoloff 2000, Sabat 2007).
Note. Appendix 11 contains the list of all essential changes and additions (in comparison with the pregoing edition) and the reference to particular places. In the text the significant new or revised fragme nts are marked with a vertical line on the right. New works included into the bibliography are marked the same way.
Present work is review and analytical study of interrelation of disfunction of small intestine, hepatobiliary system, intestinal microflora and blood phagocytes (neutrophiles, monocytes and dendritic cells). The aim of the study was substantiation of new model of psoriasis pathogenesis (further Y-model). Model of pathogenesis of psoriasis was formulated in previous work (Korotkii & Peslyak 2005). It was based on colonization of intestine by beta-hemolitic streptococci (BS) associated with hyperpermeability of intestinal walls for BS-proteins. Appreciable part of new results confirms this model. However results of new studies of psoriasis (Baker 2006a, Baker 2006b, Boyman 2007, Boyman 2004, Clark 2006, De Jongh 2005, Fry 2007b, Gudjonsson 2004, Lande 2007, Majewski 2003, Nestle 2005a, Nestle 2005b, Ritchlin 2007, Sabat 2007, Gumayunova 2009a, Nesterov 2009) and mechanisms of cellular immune protection (Bachmann 2006, Blander 2006, Blander 2007, Buckley 2006, Fasano 2005, Medvedev 2006, Merad 2007, Myhre 2006, Noverr 2004, Sozzani 2005, Toivanen 2003) demanded specification, development and more detailed formulation of model.
Publications with subject of examination of GIT and hepatobiliary system, investigatio
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