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Metabolic Response to Injury

Metabolic Response to Injury. Objectives. Factors mediating the metabolic response Consequences of the metabolic response The differences between metabolic responses to starvation and trauma The effect of trauma on metabolic rate and substrate utilization Modifying the metabolic response.

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Metabolic Response to Injury

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  1. Metabolic Response to Injury

  2. Objectives • Factors mediating the metabolic response • Consequences of the metabolic response • The differences between metabolic responses to starvation and trauma • The effect of trauma on metabolic rate and substrate utilization • Modifying the metabolic response

  3. Mediating the Response • The Acute Inflammatory Response • Cellular activation • Inflammatory mediators (TNF, IL1, etc) • Paracrine Vs endocrine effects

  4. Mediating the Response • The Endothelium • Selectins, Integrins, and ICAMs • Nitric Oxide • Tissue Factor

  5. Mediating the Response • Afferent Nerve Stimulation • Sympathetic Nervous System • Adrenal Gland Medulla

  6. Mediating the Response • The Endocrine System • Pituitary Gland (GH, ACTH, ADP) • Adrenal Gland (Cortisol, Aldosterone) • Pancreatic (Glucagon,  Insulin) • Others (Renin, Angiotensin,  Sex hormones,  T4)

  7. Consequences of the Response • Limiting injury • Initiation of repair processes • Mobilization of substrates • Prevention of infection • Distant organ damage

  8. Starvation & Injury

  9. Metabolic Response to Fasting

  10. Muscle Alanine / Pyruvate Brain Glucose Glutamine Glycerol Gluconeogenesis Ketogenesis Ketones AGL Liver Ureagenesis Ketones Urea NH3 Kidney Intestine Starvation – Early Stage Fat

  11. Muscle Alanine / Pyruvate Brain Glucose Glutamine Glycerol Gluconeogenesis Ketogenesis Fat Ketones AGL Liver Ureagenesis Ketones Urea NH3 Kidney Intestine Starvation – Late Stage

  12. Metabolic Response to Starvation Landberg L, et al. N Engl J Med 1978;298:1295.

  13. 12 Normal Range 8 Nitrogen Excretion (g/day) Partial Starvation 4 Total Starvation 10 20 30 40 0 Days Energy Expenditure in Starvation Long CL et al. JPEN 1979;3:452-456

  14. Ebb Phase Flow Phase Energy Expenditure Time Metabolic Response to Trauma Cutherbertson DP, et al. Adv Clin Chem 1969;12:1-55

  15. Metabolic Response to Trauma:Ebb Phase • Characterized by hypovolemic shock • Priority is to maintain life/homeostasis  Cardiac output  Oxygen consumption  Blood pressure  Tissue perfusion  Body temperature  Metabolic rate Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. 1997

  16. Metabolic Response to Trauma:Flow Phase •  Catecholamines •  Glucocorticoids •  Glucagon • Release of cytokines, lipid mediators • Acute phase protein production Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. 1997

  17. Metabolic Response to Trauma Fatty Acids Glucose Amino Acids Fatty Deposits Liver & Muscle (glycogen) Muscle (amino acids) Endocrine Response

  18. Muscle Alanine / Pyruvate Brain Glucose Glutamine Glycerol Gluconeogenesis Ketogenesis Fat Ketones AGL Liver Ureagenesis Ketones Urea NH3 Kidney Intestine Metabolic Changes after Trauma

  19. Metabolic Response to Trauma 28 24 20 16 12 8 4 0 Nitrogen Excretion (g/day) 10 20 30 40 Days Long CL, et al. JPEN 1979;3:452-456

  20. Major Surgery Cirugía mayor Moderate to Severe Burn Quemadura moderada a grave Nitrogen Loss in Urine Severe Sepsis Sepsis grave Infecci Infection ó n Cirug Elective Surgery í a electiva Basal Metabolic Rate Severity of Trauma: Effects on Nitrogen Losses and Metabolic Rate Adapted from Long CL, et al. JPEN 1979;3:452-456

  21. Comparing Starvation and Trauma The body adapts to starvation, but not in the presence of critical injury or disease. Popp MB, et al. In: Fischer JF, ed. Surgical Nutrition. 1983.

  22. Modifying the Response • Medication (before or after injury) • Nutritional status • Severity of injury • Temperature • Anesthetic technique

  23. Summary • Injury (Trauma or Surgery) leads to a metabolic response • Metabolic response to injury is an adaptive response • Metabolic response could overwhelm the body and lead to increased morbidity and mortality • We can modify the metabolic response before and sometimes after injury

  24. Metabolic Response to Injury Questions

  25. Determining Calorie Requirements • Indirect calorimetry • Harris-Benedict x stress factor x activity factor • 25-30 kcal/kg body weight/day

  26. Metabolic Response to Starvation and Trauma: Nutritional Requirements Example: Energy requirements for patient with cancer in bed = BEE x 1.10 x 1.2 ADA: Manual Of Clinical Dietetics. 5th ed. Chicago: American Dietetic Association; 1996 Long CL, et al. JPEN 1979;3:452-456

  27. Metabolic Response to Overfeeding • Hyperglycemia • Hypertriglyceridemia • Hypercapnia • Fatty liver • Hypophosphatemia, hypomagnesemia, hypokalemia Barton RG. Nutr Clin Pract 1994;9:127-139

  28. Macronutrients during Stress Carbohydrate • At least 100 g/day needed to prevent ketosis • Carbohydrate intake during stress should be between 30%-40% of total calories • Glucose intake should not exceed5 mg/kg/min Barton RG. Nutr Clin Pract 1994;9:127-139 ASPEN Board of Directors. JPEN 2002; 26 Suppl 1:22SA

  29. Macronutrientes during Stress Fat • Provide 20%-35% of total calories • Maximum recommendation for intravenous lipid infusion: 1.0 -1.5 g/kg/day • Monitor triglyceride level to ensure adequate lipid clearance Barton RG. Nutr Clin Pract 1994;9:127-139 ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA

  30. Macronutrients during Stress Protein • Requirements range from 1.2-2.0 g/kg/day during stress • Comprise 20%-30% of total calories during stress Barton RG. Nutr Clin Pract 1994;9:127-139 ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA

  31. Determining Protein Requirements for Hospitalized Patients No Stress Moderate Stress Severe Stress Stress Level Calorie:Nitrogen Ratio Percent Potein / Total Calories Protein / kg Body Weight > 150:1 150-100:1 < 100:1 < 15% protein 15-20% protein > 20% protein 0.8 g/kg/day 1.0-1.2 g/kg/day 1.5-2.0 g/kg/day

  32. Role of Glutamine in Metabolic Stress • Considered “conditionally essential” for critical patients • Depleted after trauma • Provides fuel for the cells of the immune system and GI tract • Helps maintain or restore intestinal mucosal integrity Smith RJ, et al. JPEN 1990;14(4 Suppl):94S-99S; Pastores SM, et al. Nutrition 1994;10:385-391Calder PC. Clin Nutr 1994;13:2-8; Furst P. Eur J Clin Nutr 1994;48:607-616 Standen J, Bihari D. Curr Opin Clin Nutr Metab Care 2000;3:149-157

  33. Role of Arginine in Metabolic Stress • Provides substrates to immune system • Increases nitrogen retention after metabolic stress • Improves wound healing in animal models • Stimulates secretion of growth hormone and is a precursor for polyamines and nitric oxide • Not appropriate for septic or inflammatory patients. “Giving arginine to a septic patient is like putting gasoline on an already burning fire.” - B. Mizock, Medical Intensive Care Unit, Cook County Hospital, Chicago, IL Barbul A. JPEN 1986;10:227-238; Barbul A, et al. J Surg Res 1980;29:228-235

  34. Key Vitamins and Minerals

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