Gastrointestinal Physiology. Intensive Care Training Program Radboud University Nijmegen Medical Centre

Transcription

1 Gastrointestinal Physiology Intensive Care Training Program Radboud University Nijmegen Medical Centre

2 Content Gastrointestinal blood flow Portal hypertension Motility disorders Specific metabolic disorders hepatic encephalopathy hepatorenal syndrome lactate metabolism insulin resistance

3 Gastrointestinal blood flow 20% of cardiac output (70-80% to mucosa) GI blood flow doubles after a meal Low-flow states result in early splanchnic vasoconstriction Blood flow below 50% results in lactate production Patients with sepsis have an increaser in general GI blood flow but a sever decrease in mucosal flow

4 Volunteers 25% in blood volume Hamilton-Davies C. Intensive Care Med 1997;23:

5 Vasopressin and GI flow Cardiac surgery Septic shock Nygren A.. Acta Anaesthesiol Scand 2009;53: van Haren FMP. Chest 2003,124:

6 Gastrointestinal blood flow and MV Decrease in mesenteric and hepatic oxygen consumption with PEEP > 15 despite adequate fluid resuscitation No increase in GBF with permissive hypercapnia Prone position increases IAP but only slightly decreases GBF GBF increases with spontaneous breathing Putensen C. Curr Opin Crit Care 2006;12:

7 Gastric mucosa flow Colon mucosa flow

8 Portal venous system Portal hypertension 20% blood flow 80% blood flow

9 Portal hypertension Normal portal pressure 7-12 mm Hg Portal pressure measurement usually by hepatic venous pressure gradient (HVPG): normal 5 mm Hg Portal hypertension = HVPG 6 Clinical complications usually with HVPG > mm Hg

10 HPVG measurement HPVG = Wedged HPV - Free HVP Wedged HPV = sinusoidal pressure Wedged HPV and Free HVP equally affected by IAP HPVG underestimates PH with prehepatic/presinusoidal causes

11 Portal hypertension Prehepatic Thrombosis PV / SV A-V fistula Intrahepatic Presinusoidal Sinusoidal Postsinusoidal Schistosomiasis/PBC Sclerosing cholangitis Fibrosis - Spleen Cirrhosis Acute hepatitis Drug toxicity Veno-occlusive disease Posthepatic Cardiac diseases IVC obstruction

12 Portal hypertension pp = Q (approximately 40%) R (approximately 60%)

13 Fundal relaxation Stomach - Dopamine - Motilin Motor Migrating Complex (MMC) CCK Peptide YY Motilin Glucagon like peptide-1 Gherelin

14 Motility disorders Gastroparesis - Paralysis - Constipation

15 Prokinetic agents Metoclopramide Dopamine-2 & 5-HT3 antagonist - weak 5-HT4 agonist - increases antral and small intestinal motility - extrapyramidal symptoms Neostigmine reversible acetylcholine esterase inhibitor - stimulates colonic motility - bradycardia, increase broncho-tracheal secretion, cramps Erythromycin Motilin receptor agonist in antrum and proximal duodenum Cispride: withdrawn for cardiac toxicity

16 Treatment & prophylaxis Methylnaltrexone (μ-receptor antagonist)

17 Digestion and Absorption

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19 Carbohydrate digestion 45% of total energy needs of western diet Requires hydrolysis to monosaccharides Non digestible carbohydrates are fibre 45-60% of dietary carbohydrate is in the form of starch (plants) 30-40% are oligosaccharides (lactose and sucrose) 5-10% are monosaccharides (glucose and sucrose)

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22 Lactase deficiency

23 Lactase deficiency Very common in nonwhites Diarrhea, cramps and flatus Unabsorbed lactose is metabolized in the to short-chain fatty acids, CO2 and H2 Usually no other defects in intestinal function

24 Protein digestion Proteins require hydrolysis by proteases to oligopeptides or amino acids before absorption 50% comes from endogenous sources Less than 4% of ingested nitrogen is excreted in the stool

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26 Peptide and AA absorption

27 Lipid digestion Dietary lipids are predominantly triacylglycerols 55% of energy Essential in digestion is lipid hydrolysis by luminal lipases

28 Lipid absorption

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30 Encephalopathy/ICP Brain edema cytotoxic edema vasogenic edema Altered CBF regulation with an increase in intracranial blood volume

31 Detry O. World J Gastroenterol 2006;12:

32 Ammonia-glutamine hypothesis Tofteng F. J Cereb Blood Flow Metab 2006;26:21-27

33 Ammonia-glutamine hypothesis Tofteng F. J Cereb Blood Flow Metab 2006;26:21-27

34 Hepatorenal Syndrome Turban S.World J Gastroenterol 2007;14:

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36 Lactate metabolism Muscle (25%) Skin (25%) Brain (20%) Intestine (10%) RBC (20%) Liver (60%) Kidney (30%) 1500 mmol/d Production Metabolism 2 mmol/l Pyruvate + NADH + H + Lactate + NAD +

37 Lactate metabolism Glucose Pyruvate pathway oxaloacetate alanine Pyruvate Lactate Krebs cycle Cori cycle Glycogen Glucose (Liver 60%- Kidney 30%) 36 ATP

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39 Tissue hypoxia pyruvate dehydrogenase Glucose Pyruvate NADH NAD +++ Pyruvate pathway oxaloacetate alanine Lactate pyruvate carboxylase Krebs cycle Cori cycle Glycogen Glucose (Liver 60%- Kidney 30%) 36 ATP

40 Lactate/pyruvate ratio Normal 8 ± 2 Cardiogenic / severe septic shock 40 ± 6 Stabilised patients with septic shock 14 ± 1

41 Lactate & hypoperfusion Cardiogenic shock Haemorrhagic shock Septic shock with catecholamine resistant failure, especially low cardiac output Septic shock before volume resuscitation

42 Lactate & metabolic adjustment Most cases of sepsis Normal to high VO 2 Tissue PO 2 appears to be high Tissue ATP is normal Dichloroacetate reduces lactate Lactate production is regional

43 Sepsis and lactate Increased aerobic glycolysis exceeding the oxidative capacity of the mitochondria Induced by endogenous and exogenous catecholamines and inhibition of PDH

44 Muscle tissue Lactate used for glucose production in liver (Cori)

45 Lactate oxidation in brain en cardiac muscle as preferred source of energy

46 Other causes for nonhypoxic lactate in sepsis Reduction in lactate clearance Pyruvate dehydrogenase dysfunction Protein catabolism