Vzájemný vztah přirozených bariér: GIT a plíce. Novák I. JIP I. interní klinika FN Plzeň

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1 Vzájemný vztah přirozených bariér: GIT a plíce. Novák I. JIP I. interní klinika FN Plzeň

2 3 bariéry v přímém kontaktu s okolním prostředím: kůže, plíce, GIT GIT přirozená bariéra s kontaminovaným obsahem (~ 400 bakteriálních a mykotických kmenů) Splanchnikus SBF při jakémkoli inzultu stresová odpověď na inzult

3 Colonization of GI tract CFU/ml Stomach Duodenum Jejunum Colon

4 Lyell s sy (34 let) - toxic epidermal necrolysis

5 Ale jak vypadá sliznice GIT u kriticky nemocného po inzultu??? Lyell s sy (34 let) - toxic epidermal necrolysis

6 Terapeutický management Priority 1. Hemodynamická stabilizace (EGDT a kapilární recruitment) 2. Kontrola infekce a antimikrobiální léčba 3. Kontrola homeostázy a hemostázy 4. Nutriční intervence 5. Ochrana bariér (UPV, SBF, nutrice) 6. Minimalizovat iatrogenní poškození v rámci neadekvátní léčby opožděné, zbytečné intervence, tekutinový overload, VILI, TRIM...)

7 Patofyziologický základ dysfunkce GIT 1.Perfůze splanchniku porucha mikrocirkulace 2. dodávka substrátů (GLU, GLN) - starvace 3. oxidační stres SIRS mitochondriální dysfunkce

8 Resuscitace splanchniku SBF O2 barrier GLN GLU 1.MAP, CVP 2.Realimentace 3.GIT perfůze, peristaltika

9 Perfůzní komponenta a bariérová funkce GIT

10 Hormonální reakce na inzult sekrece - KA, kortisol, glukagon, GH glykémie srdeční výdej FFA H e m o d y n a m i k a syntéza proteinů akutní fáze SBF Riziko okultní hypoperfůze splanchniku!?

11 Early gut wall glucose concentrations further suggest that substrate supply may be as crucial for oxidative metabolism as oxygen itself

12 Střevní slizniční mikrocirkulace SBF

13 PLoS ONE children - gut mucosal barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and urinary presence of tight junction protein claudin-3. Intestinal mucosal perfusion was measured by gastric tonometry (PrCO2, Pr-aCO2-gap). The development of gut barrier loss in children undergoing major nonabdominal surgery, which is related to preceding hypotension and mesenterial hypoperfusion

14 Prospective observational cohort study in 96 adult trauma patients. Upon arrival at the emergency room (ER) plasma levels of i-fabp

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16 Nutriční komponenta a bariérová funkce GIT

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18 providing < 40% of the total nutrient intake enterally does not have significant intestinal trophic effects piglet model D.G. Burrin, Am J Clin Nutr 2000;71:

19 Moderate caloric intake 33 to 65% of ACCP targets (from 9 to 18 kcal/kg/24h) was associated with better outcomes than higher levels of caloric intake.

20 siga production through the mucosal immune system 1. Luminal Ag taken up by M cells, sensitized T and B ly attracted into the Peyer's patches by mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) 2. The lymphocytes migrate through mesenteric lymph nodes, the thoracic duct and into the blood stream 3. IgA produced by plasma cell is transported to the mucosal surfaces by polymeric immunoglobulin receptor (pigr) and secreted as a secretory IgA, which binds to bacteria to prevent invasive nfection

21 GIT lung

22 IgA IgA

23 It is estimated that 50% of the body s immunity resides within the human lamina propria, accounting for 70% of total antibody production. Sensitization of most B cells and T cells for mucosal immunity occurs within the Peyer s patches for distribution throughout the body Catheterized mice were given 0.9% NaCl solution of 4 ml/d for 48 hours and underwent intranasal inoculation of the H1N1 influenza virus.

24 2003

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26 TPN depletes lymphocyte populations within the intestinal lamina propria effector site and levels of intestinal polymeric Ig receptor (pigr), the protein responsible for active transport of IgA across the epithelium to the mucosal surface. The most important and clinically relevant mucosal immune change induced by TPN: 1. in luminal IgA levels at the intestinal and respiratory mucosal surfaces 2. TPN without enteral stimulation inhibits the ability to generate new pulmonary mucosal immune responses 3. TPN significantly survival in animals challenged with respiratory pathogens

27 TPN 50% TPN 75% TPN 100% EN TPN GLN Mice TPN for 7 days TPN (50% of Eneeds) TPN -75% of ENeeds TPN - 100% of ENeeds E-Nutrition apoptosis

28 Dietary glutamine and oral antibiotics each improve indices of gut barrier function in rat short bowel syndrome GLN is a major fuel substrate for both intestinal epithelial and circulating and fixed immune cells This amino acid is an important substrate for synthesis of purines and pyrimidines, ammonia, glucose and amino acids GLN inhibits apoptosis and stimulates cell proliferation in both intestinal and immune cells = crucial for GALT activation in response to bacterial invasion. Dietary or iv GLN supplementation inhibits bacterial translocation in a number of catabolic animal models with intact intestine Rats with SBsy T. Ziegler et al Am J Physiol Gastrointest Liver Physiol (December 18, 2008)

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31 Systémová inflamace a bariérová funkce GIT

32 Intestinal histology Septic shock Septic shock + L-NIL

33 EFFECTS OF COMBINING inos INHIBITOR AND RADICAL SCAVENGER DURING PORCINE BACTEREMIA Matejovic M et al Shock 2007 Ileal mucosal perfusion Ileal mucosal-arterial PCO 2 gap [Perfusion units] # # # Control L-NIL+Tempol # # # [kpa] Control L-NIL+Tempol # # # # # # Time after start of PSAE [hrs] Time after start of PSAE [hrs] Treatment substantially attenuated mesenteric and hepatic venous acidosis, preserved sepsis-induced impairment of hepatosplanchnic redox state

34 Intestinal histology Adekvátní a včas podaná antimikrobiální léčba!!! Septic shock Septic shock + L-NIL

35 Závěr GIT dysfunkce je frekventně přítomná součást sy MODS Bariérové funkce se velmi rychle alterují s tíží a délkou inzultu (SBF, substráty, O2, oxidační stres) GIT dysfunkce signalizuje souběžnou dysfunkci sliznice respiračního traktu a vysoké riziko infekční komplikací - VAP

36 Děkuji za pozornost!