Gut failure in critical care: old school versus new school

Abstract

The concept of bacterial translocation and gut-origin sepsis as causes of systemic infectious complications and multiple organ deficiency syndrome in surgical and critically ill patients has been a recurring issue over the last decades attracting the scientific interest. Although gastrointestinal dysfunction seemingly arises frequently in intensive care unit patients, it is usually underdiagnosed or underestimated, because the pathophysiology involved is incompletely understood and its exact clinical relevance still remains controversial with an unknown yet probably adverse impact on the patients' outcome. The purpose of this review is to define gut-origin sepsis and related terms, to describe the mechanisms leading to gut-derived complications, and to illustrate the therapeutic options to prevent or limit these untoward processes.

Keywords: Gut failure; bacterial translocation; immunonutrition; selective gut decontamination.

Figure 1

Events occurring as the normal intestinal barrier becomes impaired in sepsis, ischemia and other harmful conditions: enterocytes go on to apoptosis, tight junctions are breached and microbes penetrate the intestinal wall. The latter are further taken up by phagocytes, innate immune receptors are activated, chemokines and proinflammatory cytokines are released, innate and adaptive immune cells are attracted to the site and the immune response is further propagated TLR, toll-like receptor; IL, interleukin; TNFR, tumor necrosis factor receptor; TNF, tumor necrosis factor

Figure 2

Overview of the “old school” approach of the pathophysiology of the gut-derived sepsis. Gut hypoperfusion and ischemia-reperfusion injury are key events for the breach of the mucosal integrity, allowing the entry of bacteria and their products in the circulation and the initiation of the sepsis cascade SIRS, systemic inflammatory response syndrome; ARDS, acute respiratory distress syndrome; MODS, multiple organ deficiency syndrome

Figure 3

The three-hit hypothesis. In this model a major role is attributed to the gut immune system and its response to circulatory insults SIRS, systemic inflammatory response syndrome; MODS, multiple organ deficiency syndrome

Figure 4

Overview of the “gut-lymph” theory, according to which the principal gateway of intestinal bacteria and their products is the gut lymph vessels and their downstream lymphatics up to the left subclavian vein and the pulmonary circulation, where the processes of ALI and ARDS are initiated ALI, acute lung injury; ARDS, acute respiratory distress syndrome

Figure 5

The cholinergic anti-inflamatory pathway. Dietary fat and other factors stimulate the vagal nerve for Ach release. The latter binds to receptors on cells of the monocyte/macrophage lineage within the liver and other organs inhibiting the release of pro-inflammatory mediators and thus minimizing the systemic inflammatory response Ach, acetylcholine; TNF, tumor necrosis factor; IL, interleukin