The intestine is an important organ for maintaining nutrition and immunity of the body, and it is also the largest reservoir of bacteria and endotoxins in the body. The intestinal barrier can be altered by various stimuli, so that the intestinal immune function is suppressed, the intestinal bacteria are displaced, and endotoxin, bacteria, and antibody mediators continuously enter the blood and lymphatic fluid, leading to the release of a variety of inflammatory mediators, triggering and aggravating the uncontrolled inflammatory response syndrome, and the occurrence of SIRS aggravates the intestinal damage, forming a vicious circle, which eventually leads to MODS.
In recent years, nutritional support, the concept of intestinal rehabilitation and the improvement of small bowel transplantation have made new progress in the treatment of intestinal dysfunction.
1, the new understanding of intestinal dysfunction
Before 1980s, the main function of intestine was digestion and absorption, therefore, the index of clinical monitoring of intestinal function was mainly the degree of digestion and absorption. after 1980s, with the deepening of clinical research, there was a new understanding of intestinal function, especially the significant role of intestinal mucosal barrier function damage and intestinal bacterial translocation in causing pathophysiological changes in critically ill patients.
In critically ill patients, the intestinal barrier function is disrupted due to intestinal mucosa damage and intestinal immune system malfunction, and bacteria and bacterial toxins in the intestine are transferred to the outside of the intestine and spread in each organ system (i.e., mutual bacterial translocation occurs, which eventually leads to structural and functional changes in each organ system and produces intestinal dysfunction, while bacterial translocation and tissue ischemia-reperfusion injury can lead to intestinal macrophages and intestine-related The bacterial translocation and tissue ischemia-reperfusion injury can lead to excessive activation of intestinal macrophages and intestinal-associated lymphoid tissue;
The release of cytokines (such as tumor necrosis factor, interleukin-6, interleukin-8, etc.) and other mediators over-activate neutrophils, causing multi-organ damage and eventually developing multi-organ failure.
2.The pathogenesis of intestinal dysfunction
The intestinal barrier plays an important role in the process of digestion and absorption of various nutrients while inhibiting bacteria and their metabolites in the intestine through the bacterial membrane barrier. The intestinal barrier includes normal intestinal flora, mucosal layer, intestinal immune system, intestinal-liver axis, defensins, etc. Damage to the intestinal barrier causes displacement of bacteria and endotoxins, which in turn causes intestinal dysfunction.
Changes in gastrointestinal hormone levels As the largest endocrine organ in the body, the gastrointestinal tract is mainly influenced by the innervation of the enteric nervous system and humoral factors. Gastrointestinal hormones are important factors regulating gastrointestinal motility, which can be regulated by acting on the corresponding receptors of smooth muscle cells in the gastrointestinal tract via blood circulation or by releasing neurotransmitters through peptidergic nerves. In addition, gastrointestinal peptides affect gastrointestinal motility at the central nervous level or through the autonomic nervous system. Disturbed gastrointestinal hormone secretion in critically ill patients leads to slowed intestinal motility, bacterial overgrowth and translocation in the gut, increased absorption of toxins in the intestine, and consequent intestinal dysfunction.
Glutamine metabolism disorders Glutamine is a non-essential amino acid. It accounts for 61% of the total free amino acids in muscle tissue and 20% of the total plasma free amino acids in blood, making it the most abundant amino acid in the body. Glutamine has important physiological roles: it provides a source of nitrogen; it is an important precursor for protein synthesis; it is a precursor for DNA and RNA synthesis; it provides metabolic energy for the gastrointestinal mucosa and immune cells.
Glutamine provides 80% of the energy of the gastrointestinal mucosa cells. It also directly supplies energy to immune cells such as lymphocytes. Under stressful conditions such as strenuous exercise, trauma and infection, the body’s need for glutamine greatly exceeds the body’s ability to synthesize glutamine, and the body’s glutamine is decomposed and used in large quantities, so additional supplementation is needed, otherwise protein synthesis will be impaired, the small intestine mucosa atrophy, and the intestinal immune function is low.
At the same time, the body’s catabolism exceeds anabolism, the body’s utilization of glutamine far exceeds the amount of synthesis, the glutamine content in blood and tissues decreases, and a large amount of glutamine stored in tissue cells is mobilized and released to maintain the metabolic cycle of the glutamine pool. Without the timely replenishment of exogenous glutamine, the disorder of glutamine metabolism continues and the damaged intestinal wall is not repaired, the situation will further deteriorate and the intestinal bacteria and bacterial toxins will enter the circulatory system through the damaged intestinal wall and spread to the whole body, which will eventually lead to intestinal failure.
Apoptosis is a genetically regulated, active and energy-consuming form of cell death, which is an important physiological process in epithelial cell biology. Normal gastrointestinal mucosal epithelial cell renewal is accomplished through the coordination of apoptosis and mitosis. Gastrointestinal dysfunction is the result of gastrointestinal mucosal damage caused by various reasons, and the relationship between uncontrolled apoptosis and gastrointestinal dysfunction is close. Various etiological factors can increase or decrease apoptosis of gastrointestinal cells by regulating changes in apoptotic genes and different signal transduction pathways, which can damage the integrity of the gastrointestinal mucosal barrier and then cause gastrointestinal dysfunction.
3.Treatment of intestinal dysfunction
In critically ill patients, gastrointestinal dysfunction is considered to be one of the initiating factors of MODS. Early treatment of gastrointestinal dysfunction is the key to prevent the development of the disease.
Treatment principles are:
(1) Active treatment of the primary disease, adjust the stability of the internal environment, improve the blood and oxygen supply;
(2) Optimal nutritional support;
(3) intestinal rehabilitation;
(4) Reconstruction of intestinal continuity and, if necessary, small bowel transplantation.
Nutritional support Traditionally, in addition to drug therapy, parenteral nutrition or elemental diet has been used to maintain the nutritional needs of patients with intestinal diseases. The reason is that at this time there is no food in the gastrointestinal tract to be digested and absorbed or the food can be absorbed directly without digestion, which can reduce the metabolic burden of the small intestine and reduce the activity, so that the gastrointestinal tract can get rest, and also reduce the secretion of bile and pancreatic juice, so as to reduce the damage to the intestinal mucosa by digestive juices.
Studies have shown that this view is wrong, and the disadvantages of long-term parenteral nutrition (PN) are:
(1) Infection, bleeding, tissue damage and other complications brought about by central or subclavian vein placement infusion. Infection causes mucosal and submucosal edema, increased oxygen consumption, and decreased immune function, which further aggravates intestinal failure.
(2) Hepatotoxic reaction of high nutrient metabolism: Parenteral nutrition related liver injury (PNALD) in intestinal failure. The mechanism of PNALD occurs by both physiological and PN-related factors:
(i) loss of enterohepatic circulation of bile acids due to SBS occurring after intestinal resection (generally defined as small bowel resection >200 cm), reduced gallbladder contraction and ileal reabsorption of bile acids;
(ii) Repeated sepsis events are closely associated with PNALD;
(3) Inflammation, cytokines resist bile production and increase hepatocyte fibrosis;
(4) Decreased lymphoid-like tissue associated with bowel resection and decreased immune reserve function;
(5) Bacterial overgrowth and retention, transport of large amounts of unconjugated bile acids and substances toxic to the liver, causing hepatocellular damage; PN nutrient overload, high levels of sugar, fat, and methionine that supply calories, is also a cause of PNALD;
(6) long-term intestinal starvation in the state of epithelial cell degeneration, mucosal atrophy, reduced enzyme activity, reduced blood flow to reduce the barrier function, bacterial translocation occurs. Therefore, for critically ill patients, when the intestinal function is completely lost, parenteral nutrition support should be implemented as early as possible; when the intestine is functional, enteral nutrition via nasoduodenal tube, or partial parenteral and enteral nutrition should be implemented as early as possible; when oral nutrition can be tolerated, oral or transgastric nutrition should be implemented as early as possible.
Enteral nutrition in critically ill patients is mostly administered after 24-48h of medical treatment, when respiratory and circulatory disturbances have been corrected, endostasis has entered a stable state, and autocannibalism has subsided, and if conditions permit (abdominal distension is reduced, bowel sounds are improved or restored), enteral nutrition is resumed as soon as possible, and the mucosal barrier is actively improved and maintained.