Skip to main content
SpringerLink
Log in
Book cover

Metabolic Support of the Critically Ill Patient pp 294–305Cite as

The Importance of the Gut as a Central Organ in the Pathogenesis of MOF

  • Chapter

  • 58 Accesses

Part of the book series: Update in Intensive Care and Emergency Medicine ((UICM,volume 17))

Abstract

In 1988, Wilmore et al. [1] proposed that the intestinal tract plays a central role in the pathophysiologic responses to severe injury or infection. Others, including Deitch and colleagues [2], Border et al. [3], and Meakins and Marshall [4], also have championed this concept. The barest outlines for the gut hypothesis for multiple organ dysfunction (MOF) can be summarized as follows: “derangements in the barrier function of the gut permit the dissemination of intraluminal microbes and/or microbial products to mesenteric lymph nodes (MLN) or other organs (particularly the liver), which are downstream from the intestinal tract”. The pathological dissemination of microbes or microbial products beyond the confines of the intestinal lumen leads to pathological modulation of immune cells. This results in excessive release of a wide variety of pro-inflammatory mediators, including cytokines, such as IL- 1 and TNFα, and lipids, like PAF, which can promote organ injury via numerous mechanisms.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Wilmore DW, Smith RJ, O’Dwyer ST, Jacobs DO, Ziegler TR, Wang XD (1988) The gut: A central organ after surgical stress. Surgery 104:917–923

    PubMed  CAS  Google Scholar 

  2. Mainous MR, Deitch EA (1992) Bacterial translocation and its potential role in the pathogenesis of multiple organ failure. J Intensive Care Med 7:101–108

    Google Scholar 

  3. Border JR, Hasset JM, LaDuca J, et al. (1987) Gut origin septic states in blunt multiple trauma (ISS=40) in the ICU. Ann Surg 206:427–448

    Article  PubMed  CAS  Google Scholar 

  4. Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV (1985) Multiple-organ-failure syndrome. Arch Surg 121:196–208

    Google Scholar 

  5. Goris RJ, Beokhorst PA, Nuytinck KS (1985) Multiple organ failure: Generalized autodestructive inflammation. Arch Surg 120:1109–1115

    Article  PubMed  CAS  Google Scholar 

  6. Marshall JC, Christou NV, Horn R, Meakins JL (1988) The microbiology of multiple organ failure: The proximal gastrointestinal tract as an occult reservoir of pathogens. Arch Surg 123:309–315

    Article  PubMed  CAS  Google Scholar 

  7. Alexander JW, Boyce ST, Babcock GF, et al (1990) The process of microbial translocation. Ann Surg 212:496–512

    Article  PubMed  CAS  Google Scholar 

  8. Mora EM, Cardona MA, Simmons RL (1991) Enteric bacteria and ingested inert particles translocate to intraperitoneal prosthetic materials. Arch Surg 126:157–163

    Article  PubMed  CAS  Google Scholar 

  9. Alexander JW, Gianotti L, Pyles T, Carey MA, Babcock GF (1991) Distribution and survival of Escherichia coli translocating from the intestine after thermal injury. Ann Surg 213:558–567

    Article  PubMed  CAS  Google Scholar 

  10. Redan JA, Rush BF, McCullough JN, et al (1990) Organ distribution of radiolabelled enteric Escherichia coli during and after hemorrhagic shock. Ann Surg 211:663–668

    Article  PubMed  CAS  Google Scholar 

  11. O’Brien R, Murdoch J, Kuehn R, Marshall JC (1992) The effect of albumin or crystalloid resuscitation on bacterial translocation and endotoxin absorption following experimental bum injury. J Surg Res 52:161–166

    Article  PubMed  Google Scholar 

  12. Deitch EA, Bridges W, Baker J, et al (1988) Hemorrhagic shock-induced bacterial translocation is reduced by xanthine oxidase inhibition or inactivation. Surgery 104:191–198

    PubMed  CAS  Google Scholar 

  13. Deitch EA, Ma L, Ma JW, et al (1989) Inhibition of endotoxin-induced bacterial trans- . location in mice. J Clin Invest 184:36–42

    Article  Google Scholar 

  14. Deitch EA, Morrison J, Berg R, Specian RD (1990) Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats. Crit Care Med 18:529–536

    Article  PubMed  CAS  Google Scholar 

  15. Bienenstock J, Befus AD (1980) Mucosal immunology. Immunology 41:249–270

    PubMed  CAS  Google Scholar 

  16. Casanova JE (1992) Transepithelial transport of macromolecules. Chest 101:55S-58S

    Article  PubMed  CAS  Google Scholar 

  17. Sterns M, Walker WA (1984) Food proteins and gut mucosal barrier. I. Bunding and uptake of cow’s milk proteins by adult rat jejunum in vitro. Am J Physiol 246:556–562

    Google Scholar 

  18. Walker WA, Cornell R, Davenport LM, Isselbacher KJ (1972) Macromolecular absorption: Mechanism of horseradish peroxidase uptake and transport in adult and neonatal rat intestine. J Cell Biol 54:195–205

    Article  PubMed  CAS  Google Scholar 

  19. Warshaw AL, Walker WA, Cornell R, Isselbacher KJ (1971) Small intestinal permeability to macromolecules. Transmission of horseradish peroxidase into mesenteric lymph and portal blood. Lab Invest 25:675–684

    PubMed  CAS  Google Scholar 

  20. Carter EA, Gonnell A, Tompkins RG (1992) Increased transcellular permeability of rat small intestine after thermal injury. Burns 18:117–120

    Article  PubMed  CAS  Google Scholar 

  21. Wells CL, Jechorek RP, Erlandsen SL (1990) Evidence for the translocation of Ente- rococcus faecalis across the mouse intestinal tract. J Infect Dis 162:82–90

    Article  PubMed  CAS  Google Scholar 

  22. Alexander JW, Boyce ST, Babcock GF, et al (1990) The process of microbial translocation. Ann Surg 212:496–512

    Article  PubMed  CAS  Google Scholar 

  23. Alverdy J, Aoys E, Moss GS (1988) Total parenteral nutrition promotes bacterial translocation from the gut. Surgery 104:185–190

    PubMed  CAS  Google Scholar 

  24. Mainous MR, Tso P, Berg RD, Deitch EA (1991) Studies of the route, magnitude, and time course of bacterial translocation in a model of systemic inflammation. Arch Surg 126:33–37

    Article  PubMed  CAS  Google Scholar 

  25. Navaratnam NRL, Morris SE, Traber DL, et al (1990) Endotoxin increases mesenteric vascular resistance and bacterial translocation. J Trauma 30:1104–1115

    Article  PubMed  CAS  Google Scholar 

  26. Tokyay R, Loick HM, Traber DL, et al (1992) Effects of thromboxane synthetase on postburn mesenteric vascular resistance and the role of bacterial translocation in a chronic porcine model. Surg Gynecol Obstet 174:125–132

    PubMed  CAS  Google Scholar 

  27. Morris SE, Navaratnam N, Townsend CM, Herndon DN (1988) Bacterial translocation and mesenteric blood flow in a large animal model after cutaneous thermal and smoke inhalation injury. Surg Forum 39:189–190

    Google Scholar 

  28. Saydjari R, Beerthuizen GIJM, Townsend CM, et al (1991) Bacterial translocation and its relationship to visceral blood flow, gut mucosal ornithine decarboxylase activity, and DNA in pigs. J Trauma 31:639–644

    Article  PubMed  CAS  Google Scholar 

  29. Sheng ZY, Dong YL, Wang XH (1992) Bacterial translocation and multiple system organ failure in bowel ischemia and reperfusion. J Trauma 32:148–153

    Article  CAS  Google Scholar 

  30. Jones WG II, Barber AE, Minei JP, Fahey TJ III, Shires GT III, Shires GT (1991) Differential pathophysiologicy of bacterial translocation after thermal injury and sepsis. Ann Surg 214:24–30

    Article  PubMed  Google Scholar 

  31. Alverdy JC, Aoys E (1992) The effect of dexamethasone and endotoxin administration on biliary IgA and bacterial adherence. J Surg Res 53:450–454

    Article  PubMed  CAS  Google Scholar 

  32. Alverdy J, Aoys E (1991) The effect of glucocorticoid administration on bacterial translocation: Evidence for an acquired mucosal immunodeficient state. Ann Surg 214:719–723

    Article  PubMed  CAS  Google Scholar 

  33. Cappeller WA, Bloch KJ, Hatz RA, et al (1992) Reduction in biliary IgA after burn injury: Role of diminished delivery via the thoracic duct and of enhanced loss from the systemic circulation. Ann Surg 215:338–343

    Article  PubMed  CAS  Google Scholar 

  34. Alverdy JA, Aoys E, Weiss-Carrington P, Burke DA (1992) The effect of glutamine- enriched TPN on gut immune cellularity. J Surg Res 52:34–38

    Article  PubMed  CAS  Google Scholar 

  35. Deitch EA, Sittig K, Li M, Berg R, Specian RD (1990) Obstructive jaundice promotes bacterial translocation. Am J Surg 159:79–84

    Article  PubMed  CAS  Google Scholar 

  36. Rush BF Jr, Redan JA, Flanagan JJ, et al (1989) Does the bacteremia observed in hemorrhagic shock have clinical significance? A study in germ-free animals. Ann Surg 210:342–347

    Article  PubMed  Google Scholar 

  37. Bruce CJ, Rush BF Jr, Ferraro FJ, Murphy TF, Hsieh JT, Machiedo GW (1992) The effect of the germ-free state on survival following hemorrhagic shock. A study in germfree and germ-bearing rats. Surg Form 53:47–49

    Google Scholar 

  38. Zweifach BW, Gordon HA, Wagner M, Reyniers JA (1958) Irreversible hemorrhagic shock in germ-free rats. J Exp Med 107:437–450

    Article  PubMed  CAS  Google Scholar 

  39. McNulty WP Jr, Linares R (1960) Hemorrhagic shock of germ-free rats. Am J Physiol 198:141–144

    Google Scholar 

  40. Gathiram P, Wells MT, Brock-Utne JG, Gaffin SL (1988) Oral administered nonabsorbable antibiotics prevent endotoxemia in primates following intestinal ischemia. J Surg Res 45:187–193

    Article  PubMed  CAS  Google Scholar 

  41. Gathiram P, Gaffin SL, Brock-Utne JG, Wells MT (1987) Time course of endotoxemia and cardiovascular changes in heat-stressed primates. Aviation Space Environ Med 58:1071–1075

    CAS  Google Scholar 

  42. Gaffin SL, Brock-Utne JG, Zanotti A, Wells MT (1986) Hypoxia-induced endotoxemia in primates: Role of reticuloendothelial system function and anti-lipopolysaccharide plasma. Aviation Space Environ Med 57:1044–1049

    CAS  Google Scholar 

  43. Zanotti AM, Gaffin SL (1985) Prophylaxis of superior mesenteric artery occlusion shock in rabbits by antilipopolysaccharide (anti-LPS) antibodies. J Surg Res 38:113–115

    Article  PubMed  CAS  Google Scholar 

  44. Gaffin SL, Grinberg Z, Abraham C, Birkhan J, Shechter Y (1981) Protection against hemorrhagic shock in the cat by human plasma containing endotoxin-specific antibodies. J Surg Res 31:18–21

    Article  PubMed  CAS  Google Scholar 

  45. Gathiram P, Wells MT, Brock-Utne JG, Gaffin SL (1987) Antilipopolysaccharide improves survival in primates subjected to heat stroke. Circ Shock 23:157–164

    PubMed  CAS  Google Scholar 

  46. Goris RJA, Boekholtz WKF, van Bebber IPT, Nuytinck JKS, Schillings PHM (1986) Multiple-organ failure and sepsis without bacteria. Arch Surg 121:897–901

    Article  PubMed  CAS  Google Scholar 

  47. Deitch EA, Kemper AC, Specian RD, Berg RD (1992) A study of the relationships among survival, gut-origin sepsis, and bacterial translocation in a model of systemic inflammation. J Trauma 32:141–147

    Article  PubMed  CAS  Google Scholar 

  48. Goris RJA, van Bebber IPT, Mollen RHM, Koopman JP (1991) Does selective decontamination of the gastrointestinal tract prevent multiple organ failure? An experimental study. Arch Surg 126:561–565

    Article  PubMed  CAS  Google Scholar 

  49. Fukushima R, Gianotti L, Alexander JW, Pyles T (1992) The degree of bacterial translocation is a determinant factor for mortality after burn injury and is improved by prostaglandin analogs. Ann Surg 216:438–445

    Article  PubMed  CAS  Google Scholar 

  50. Miller TA (1983) Protective effects of prostaglandins against gastric mucosal damage: Current knowledge and proposed mechanisms. Am J Physiol 243:601–623

    Google Scholar 

  51. Deitch EA (1989) Simple intestinal obstruction causes bacterial translocation in man. Arch Surg 124:699–701

    Article  PubMed  CAS  Google Scholar 

  52. Ambrose NS, Johnson M, Burdon DW, Keighley MRB (1984) Incidence of pathogenic bacteria from mesenteric lymph nodes and ileal serosa during Crohn’s disease surgery. BrJ Surg 71:623–625

    Article  CAS  Google Scholar 

  53. Rush BF, Sori AJ, Murphy TF, et al (1988) Endotoxemia and bacteremia during hemorrhagic shock. Ann Surg 207:549–554

    Article  PubMed  Google Scholar 

  54. Moore FA, Moore EE, Poggetti R, et al (1991) Gut bacterial translocation via the portal vein: A clinical perspective with major torso trauma. J Trauma 31:629–638

    Article  PubMed  CAS  Google Scholar 

  55. Peitzman AB, Udekwu AO, Ochoa J, Smith S (1991) Bacterial translocation in trauma patients. J Trauma 31:1083–1087

    PubMed  CAS  Google Scholar 

  56. Madara JL (1989) Loosening of tight junctions: Lessons from the intestine. J Clin Invest 83:1089–1094

    Article  PubMed  CAS  Google Scholar 

  57. Ma TY, Hollander D, Erickson RA, Truong H, Krugliak P (1991) Is the small intestinal epithelium truly “tight” to inulin permeation? Am J Physiol 260 : G669–G676

    PubMed  CAS  Google Scholar 

  58. Pappenheimer JR, Volpp K (1992) Transmucosal impedance of small intestine: Correlation with transport of sugars and amino acids. Am J Physiol 263 : C480–C493

    PubMed  CAS  Google Scholar 

  59. Madara JL, Carlson S (1991) Supraphysiologic L-tryptophan elicits cytoskeletal and macromolecular permeability alterations in hamster small intestinal epithelium in vitro. J Clin Invest 87:454–462

    Article  PubMed  CAS  Google Scholar 

  60. Bjaranson I, Wilhams P, Smethurst P, Peters TJ, Levi AJ (1986) Effect of nonsteroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut 27:1292–1297

    Article  Google Scholar 

  61. Madara JL, Stafford J (1989) Interferon-7 directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest 83:724–727

    Article  PubMed  CAS  Google Scholar 

  62. Kubes P (1992) Nitric oxide modulates epithelial permeability in the feline small intestine. Am J Physiol 262:G1138–G1142

    PubMed  CAS  Google Scholar 

  63. Petros A, Bennett D, Vallance P (1991) Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 338:1557–1558

    Article  PubMed  CAS  Google Scholar 

  64. Lubbe AS, Garrison RN, Cryer HM, Alsip NL, Harris PD (1992) EDRF as a possible mediator of sepsis-induced arteriolar dilation of skeletal muscle. Am J Physiol 262 : H880–H887

    PubMed  CAS  Google Scholar 

  65. Meyer J, Traber LD, Nelson S, et al (1992) Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. J Appl Physiol 73:324–328

    PubMed  CAS  Google Scholar 

  66. Bulkley GB, Kvietys PR, Parks DA, Perry MA, Granger DN (1985) Relationship of blood flow and oxygen consumption to ischemic injury in the canine small intestine. Gastroenterol 89:852–857

    CAS  Google Scholar 

  67. Langer JC, Sohal SS (1992) Increased mucosal permeability after intestinal ischemia- reperfusion injury is mediated by local tissue factors. J Ped Surg 27:329–332

    Article  CAS  Google Scholar 

  68. Horton JW (1992) Alterations in intestinal permeability and blood flow in a new model of mesenteric ischemia. Circ Shock 36:134–139

    PubMed  CAS  Google Scholar 

  69. Salzman A, Wollert PS, Wang H, et al (1993) Intraluminal oxygenation ameliorates ischemia/reperfusion-induced hyperpermeability in pigs. Circ Shock (in press)

    Google Scholar 

  70. Fink MP, Antonsson JB, Wang H, Rothschild HR (1991) Increased intestinal permeability in endotoxic pigs. Limited role for mesenteric hypoperfusion. Arch Surg 126:211–218

    Article  PubMed  CAS  Google Scholar 

  71. Epstein MD, Tchervenkow JI, Alexander JW, Johnson JR, Vester JW (1991) Increased gut permeability following bum trauma. Arch Surg 126:198–200

    Article  PubMed  CAS  Google Scholar 

  72. Illig KA, Ryan CK, Hardy DJ, Rhodes J, Locke W, Sax HC (1992) Total parenteral nutrition-induced changes in gut mucosal function: Atrophy alone is not the issue. Surgery 112:631–637

    PubMed  CAS  Google Scholar 

  73. Deitch EA, Specian RD, Berg RD (1991) Endotoxin-induced bacterial translocation and mucosal permeability: Role of xanthine oxidase, complement activation, and macrophage products. Crit Care Med 19:785–791

    Article  PubMed  CAS  Google Scholar 

  74. Fink MP, Kaups KL, Wang H, Rothschild HR (1991) Maintenance of superior mesenteric arterial perfusion prevents increased intestinal mucosal permeability in endotoxic pigs. Surgery 110:154–161

    PubMed  CAS  Google Scholar 

  75. Fink MP, Kaups KL, Wang H, Rothschild HR (1992) Ibuprofen improves survival but does not ameliorate increased gut mucosal permeability in endotoxic pigs. Arch Surg 127:49–54

    Article  PubMed  CAS  Google Scholar 

  76. Ferry DM, Butt TJ, Broom MF, Hunter J, Chadwick VS (1989) Bacterial chemotactic oligopeptides and the intestinal mucosal barrier. Gastroenterology 97:61–67

    PubMed  CAS  Google Scholar 

  77. Lichtman SN, Okoruwa EE, Keku J, Schwab JH, Sartor RB (1992) Degradation of endogenous bacterial cell wall polymers by the muralytic enzyme mutanolysin prevents hepatobiliary injury in genetically susceptible rats with experimental intestinal bacterial overgrowth. J Clin Invest 90:1313–1322

    Article  PubMed  CAS  Google Scholar 

  78. Stimpson SA, Schwab JH, Janusz MJ, Anderle SK, Brown RR, Cromartie WJ (1986) Acute and chronic inflammation induced by peptidoglycan structures and polysaccharide complexes. In: Seidle PH, Schleifer KH (eds) Biological properties of peptidoglycan. Walter de Gruyter, Berlin, pp 273–290

    Google Scholar 

  79. O’Dwyer S, Michie HR, Zeigler TR, Revhaug A, Smith RJ, Wilmore DW (1988) A single dose of endotoxin increases intestinal permeability in healthy humans. Arch Surg 123:1459–1464

    Article  PubMed  Google Scholar 

  80. Ziegler TR, Smith RJ, O’Dwyer ST, Demling RH, Wilmore DW (1988) Increased in- testinal permeability associated with infection in bum patients. Arch Surg 123:1313–1319

    Article  PubMed  CAS  Google Scholar 

  81. Deitch EA (1990) Intestinal permeability in burn patients shortly after injury. Surgery 107:411–416

    PubMed  CAS  Google Scholar 

  82. Ryan CM, Yarmush ML, Burke JF, Tompkins RG (1992) Increase permeability early after burns correlates with the extent of burn injury. Crit Care Med 20:1508–1512

    Article  PubMed  CAS  Google Scholar 

  83. Harris CE, Griffiths RD, Freestone N, Billington D, Atherton ST, Macmillan RR (1992) Intestinal permeability in the critically ill. Intensive Care Med 18:38–41

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. M. P. Fink
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Laboratory for Surgical Metabolism, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachussetts, 02115, USA

    Douglas W. Wilmore

  2. L. Deloyers Laboratory for Experimental Surgery, Free University of Brussels, Avenue J. Wybran 40, 1070, Brussels, Belgium

    Yvon A. Carpentier

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Fink, M.P. (1993). The Importance of the Gut as a Central Organ in the Pathogenesis of MOF. In: Wilmore, D.W., Carpentier, Y.A. (eds) Metabolic Support of the Critically Ill Patient. Update in Intensive Care and Emergency Medicine, vol 17. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85011-0_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-85011-0_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-85013-4

  • Online ISBN: 978-3-642-85011-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation