ESPEN Congress Prague 2007

Transcription

1 ESPEN Congress Prague 2007 Nutrition in Severe Sepsis Basic Principles of Disease B. Soeters

2 Basic Principles of Disease Peter B. Soeters

3 Basic Principles of Disease Wound Healing Effects of Wound Healing on metabolism in other tissues Appropriate Not appropriate? Inflammation and the Gut MOF Liver Disease Gut Function

4 Basic Principles of Disease Wound Healing Effects of Wound Healing on metabolism in other tissues Appropriate Not appropriate? Inflammation and the Gut MOF Liver Disease Gut Function

5 Beans et al Expert Reviews Mol Medicine 2003 Vol. 5 March

6 Singer et al, NEJM :

7 Permeability integral part of Inflammation = Healing Wound swelling = oedema, due to increased permeability, promoted by cytokines etc. Increased permeability is necessary to allow cells and proteins to get access to the places where healing is necessary Permeability therefore part of inflammation and not the cause of inflammation Inflammation is part of the healing process

8 Basic Principles of Disease Wound Healing Effects of Wound Healing on metabolism in other tissues Appropriate Not appropriate? Inflammation and the Gut MOF Liver Disease Gut Function

9 Role Neutrophil (and Macrophage)

10 Local Trauma has generalized effects on the whole organism Metabolic effects after Trauma induced by: Systemic neuro-endocrine changes Including systemic cytokine cascade (cytokines immune cells etc appear in the systemic circulation) Have influences on other tissues (muscle, liver, immune system, other organs) Neuro-endocrine and cytokine effects in principle adaptive and useful. (Leakiness?)

11 But also stimulation Immune system, generation immune cells PS PB CONTROL PS Protein kinetics Maastricht Metabolic group PB 24-h ENDOTOXEMIA PS PB PS PB Protein export

12 Distant organs react appropriately Muscle to local wounds Increases protein breakdown (also net protein breakdown = difference between synthesis and breakdown) leads to release of amino acids Increased production alanine and glutamine Increased Cori-cycling (Glucose/Lactate) Supplies liver, wound, immune system with necessary building blocks

13 Distant organs react appropriately Liver to local wounds/infection Produces protein Fibrinogen Albumin Globulins, Complement etc Increased Cori-cycling (Lactate/Glucose) Becomes Glutamine consumer These are all necessary and useful adaptations to allow wound healing/host defence

14 Distant organs react to wounds Spleen/Immunesystem Produce Immune cells and take up substrate to do this (amino acids/fatty acids) Increase Cori-cycling (Glucose/Lactate) Become Glutamine consumers Supply Immune cells for wound These are all necessary and useful adaptations to allow wound healing/host defence

15 Basic Principles of Disease Wound Healing Effects of Wound Healing on metabolism in other tissues Appropriate Not appropriate? Inflammation and the Gut MOF Liver Disease Gut Function

16 Fink et al, Clin Care Clin : Endotoxin/proinflammatory cytokines open up tight junctions in: Kidney Lung Liver Intestine Other organs? Severely: interferes with function

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18 MOF patients Generalized inflammatory response Generalized oedema due to increased permeability in all organs, also in organs that do not play major roles in host response (lung, heart, kidney). In principle adaptive but overshoot (negative side of the coin) Diminished function Generally in the presence of persisting infection (interferes with adequate wound healing; perpetuates pro-inflammatory response) Some people react stronger than others ( )

19 Basic Principles of Disease Wound Healing Effects of Wound Healing on metabolism in other tissues Appropriate Not appropriate? Inflammation and the Gut MOF Liver Disease Gut Function

20 MOF and Gut permeability Any infectious focus can cause MOF, including the gut No good correlation between mesenteric node bacteria and cause of sepsis Sepsis insidious in extra-intestinal locations (brain, kidney, gallbladder etc) Bacteria can be easily cleared Permeability the result of MOF, not the cause

21 Basic Principles of Disease Wound Healing Effects of Wound Healing on metabolism in other tissues Appropriate Not appropriate? Inflammation and the Gut MOF Liver Disease Gut Function

22 Delicate balance between gut and liver necessary for their health Bacterial overgrowth in the intestine Disturbed entero-hepatic cycling Altered bile acid composition Diminished pool size In short bowel, high output fistulae/stomata/bypass/cholestasis Intestinal inflammation/increased permeability Celiac disease, IBD, Malnutrition associated inflammation Sepsis

23 Are all significantly more often Associated with Liver Disease: Cholestasis Steatosis/Steatohepatis/Cirrhosis PBC??? PSC??? Soeters et al, Clin Opinion Clin Nutr Metabolic Care :

24 Basic Principles of Disease Wound Healing Effects of Wound Healing on metabolism in other tissues Appropriate Not appropriate? Inflammation and the Gut MOF Liver Disease Gut Function

25 Slatzle et al J GI Surg :

26 Cullen Cullen et et al al, J Surg Res J Surg Res : :90-5

27 Paralysis complete bowel Gas in all segments Abnormal gas pattern in ileocecal region

28 Medical Physiology Boron, Boulpaep Saunders

29 Medical Physiology Boron, Boulpaep Saunders

30 Slatzle et al J GI Surg :

31 Effect TNF-alpha on Na/K pump

32 Field JCI :

33 Inflammation includes Increased Permeability Decreases motility Decreases enzyme secretion (not shown/not well investigated) Decreases: Absorption Electrolytes/Water, Glucose, Amino Acids, Fat, etc Decreases uphill gradients (Glutamine/Glutathione/Amino Acids etc)

34 Conclusions I Inflammation is in principle the necessary mechanism to heal wounds/clear infection An obligatory functional part of inflammation is increased permeability Local trauma/infection has useful effects on the remainder of the organism Ongoing inflammation/infection perpetuates the proinflammatory part of the healing response and continues to induce inflammatory activity in the whole organism

35 Conclusions II Increased intestinal permeability is part of the generalized inflammatory activity induced by (unresolved) trauma/infection The site of trauma /infection does not have to be located in the gut itself. Increased intestinal permeability is therefore more often than not the sequel rather than the cause of MOF Chronic inflammatory activity in the intestine is associated with increased rates of pluriform aspecific liver diseases compared to individuals with healthy guts

36 Conclusions III It is attractive to speculate that the specific genetic built-up of the individual predisposes to develop liver disease in the presence of intestinal inflammation The inflammatory state of the intestine, at least in part mediated by TNF-α, leads to: Decreased motility Decreased Sodium linked transport = absorption of glucose, amino acids, short chain fatty acids This causes mixed osmotic/secretory diarrea Possibly decreased digestion (not very well investigated) In disease artificial nutrition should be carefully monitored