1. Bacterial translocation and Hemodynamic change in cirrhotic patients R3 김현수

2.  Definition bacterial proliferation in the small intestine  breaching of the epithelial barrier by bacteria  proliferation in mesenteric lymph node(bacterial translocation)  entrance of bacteria into the abdominal lymphatics and transit through the thoracic duct into the systemic circulation  bacterial seeding and proliferation in ascitic fluid.  The mechanism the pathogenesis of spontaneous infections in cirrhosis the hyperdynamic circulatory state, a key factor in the pathogenesis of portal hypertension and in the development of ascites and hepatorenal syndrome. Bacterial translocation

3.  Mucosal injury to the upper gastrointestinal system chronic alcohol use  Increased gut permeability to macromolecules intestinal structural abnormalities (vascular congestion and oedema)  Intestinal bacterial overgrowth Delayed intestinal transit, Alcohol abuse, Malnutrition Deconjugation of bile acids Lower frequency of MMC (migrating motor complex)  Role of impaired liver clearance in endotoxaemia Endotoxins/cytokines via bacterial translocation Impaired RES and clearance of the liver The presence of porta-systemic shunting Impaired ability of Kupffer cells to recognize IgG-coated organisms. FACTORS CONTRIBUTING TO BACTERIAL TRANSLOCATION

4. Endotoxemia in cirrhosis Chronic peripheral vasodilatation Decreased mean arterial pressure Decreased systemic vascular resistance splanchnic and peripheral vasodilatation Endotoxemia by shunting, impaired clearance by liver NO, TNF, IL-1

6.  Selective Intestinal Decontamination Norfloxacine, ciprofloxacine, trimethoprim/sulfamethoxazole  Prokinetics Cisapride  Probiotics Bifidobacterium and Lactobacillus  Antioxidants –NAC, Lipoic acid  Others- Bile acids, Propranolol Manipulation of Gut Flora incompletely absorbed by the intestine highly active against aerobic gram-negative bacilli low activity against anaerobic bacteria rarely causes bacterial resistance low incidence of side effects when administered chronically elimination of aerobic gram-negative bacilli from the intestinal flora, but preserving the remaining aerobic and the anaerobic bacteria with oral nonabsorbable or poorly absorbable antibiotics

7. Hepatology. 1990 Oct;12(4 Pt 1):716-24 FIG. Upper graph Cumulative probability of SBP recurrence in patients from both groups. Lower graph Cumulative probability of SBP recurrence caused by aerobic gram-negative bacilli in patients from both groups. Recovered patents from an episode of SBP long-term norfloxacin administration (400 mglday; 40 patients) vs. placebo (40 patients) in the prevention of SBP recurrence. 68% 20% 60% 3%

8. nonselective effect over gram-negative bacilli and higher systemic absorption

11. Portal pressure was unchanged after norfloxacin in another group of 18 cirrhotic patients with high and 19 with normal LBP.

12.  Patients with cirrhosis low protein ascitic levels ( 9 with serum bilirubin level > 3 mg/dL) or impaired renal function (serum creatinine level > 1.2 mg/dL, blood urea nitrogen level > 25 mg/dL, or serum sodium level < 130 mEq/L)  randomized controlled trial  comparing norfloxacin (35 patients) vs placebo (33 patients

13. results

14.  The mechanism by which norfloxacin reduced the probability of developing HRS prevention of SBP improvement in circulatory function as indicated by an increase in arterial pressure and systemic vascular resistance and a suppression of plasma renin activity. related to a significant decrease in the circulating levels of lipopolysaccharide binding protein (a marker of endotoxemia), cytokines, and nitric oxide metabolites.

15.  Cisapride administration to cirrhotic rats resulted in a reduction of the IBO, which is associated with a marked decrease in BT.  On the other hand, cisapride facilitates the abolition of IBO caused by gram-negative organisms in cirrhotic patients

16. Reduce intestinal endotoxin production  Oral bile acid Cirrhotic patients diminished bile acid secretion  lowered intraluminal concentration of conjugated bile acids. Bacterial overgrowth in the intestine  deconjugate bile acids  further reduction in bile acid concentration (rapid absorbtion by nonionic diffusion)

17.  Aim changing the make-up of the indigenous microflora by administering specific strains of non-pathogenic and potentially beneficial microflora.  Stabilize intestinal epithelial barrier by reducing local proinflammatory cytokine generation  Lactobacilli can inhibit the growth of various potentially pathogenic bacteria, and have been reported to be able to stimulate host immunity Probiotics

19.  mechanisms the reduction of bacterial translocation caused by increase in intestinal motility stimulation of intestinal adrenoreceptors by β –blockers by decrease in intestinal permeability the reduction of portal pressure. through a decrease in mucosal tumor necrosis factor- α, NO

20.  Cirrhosis- hyperdynamic state High cardiac output, low systemic vascular resistance, low mean arterial pressure, increased peripheral and splanchnic vasodilation  Portal hypertension, ascites, hepatorenal syndrome  Vasodilatory effect by TNF-a, NO in endotoxemia, renin-angiotensin system  Selective intestinal decontamination, prokinetics, probiotics, propranolol, bile acids  SBP, NO mediated vasodilatory effect  hemodynamic stability Summary