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Fig. 2 | Critical Care

Fig. 2

From: The digestive tract as the origin of systemic inflammation

Fig. 2

Cellular and molecular players in intestinal injury caused by systemic inflammation. A large variety of pancreatic and hepatobiliary products are involved in the complex digestive function of the small intestine, e.g., proteolytic enzymes, lipases, amylases, bicarbonate, and primary bile acids. The primary bile acids (cholic acid, chenodeoxycholic acid) are converted to secondary bile acids (e.g., lithocholic acid, DCA, UDCA) by the microbiota. The digestive enzymes derived from the host or microbiota ensure the breakdown of macromolecules to soluble nutrients, which is followed by uptake and transport to the portal circulation or intestinal lymph tract. While the intestinal microflora are crucial for these digestive functions in the lumen, their quantity and topography are tightly controlled by the thick mucus layer that contains secretory IgA and antimicrobial peptides (e.g., defensins) produced by mucosal immune cells and the epithelium. In critical illness, circulatory derangement results in gut barrier loss and the translocation of digestive enzymes, cytotoxic bile acids, free fatty acids (FFAs), and microbial substrates to the submucosa, which exacerbates local and systemic inflammatory reactions. The intestinal epithelium is also an important source of pro-inflammatory mediators that are released into the circulation, including IL-17, lipid mediators produced by phospholipase A2 (PLA 2 ), and antimicrobial peptides derived from Paneth cells. These pathogenic events also pave the way for cytotoxic components to directly leak from the intestinal lumen to mesenteric lymph vessels, which constitutes the gut–lymph–lung axis. MLN mesenteric lymph node, MMP matrix metalloproteinase, PV portal vein, VC vena cava

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