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

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

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

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

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

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

Starvation & Injury

Metabolic Response to Fasting

Starvation – Early Stage Intestine Muscle Liver Brain Kidney Gluconeogenesis Ketogenesis Ureagenesis Glutamine Alanine / Pyruvate Glucose Ketones Urea NH 3 Ketones Glycerol AGL Fat

Starvation – Late Stage Intestine Muscle Liver Brain Kidney Gluconeogenesis Ketogenesis Ureagenesis Glutamine Alanine / Pyruvate Glucose Ketones Urea NH 3 Ketones Glycerol AGL Fat

Metabolic Response to Starvation Hormone Norepinephrine Epinephrine Thyroid Hormone T4 Source Sympathetic Nervous System Adrenal Gland Thyroid Gland (changes to T3 peripherally) Change in Secretion        Landberg L, et al. N Engl J Med 1978;298:1295.

Energy Expenditure in Starvation Long CL et al. JPEN 1979;3: Partial Starvation Days Nitrogen Excretion (g/day) Total Starvation Normal Range

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

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;12:1-55 Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3 rd ed. 1997

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;12:1-55 Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3 rd ed. 1997

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

Metabolic Changes after Trauma Intestine Muscle Liver Brain Kidney Gluconeogenesis Ketogenesis Ureagenesis Glutamine Alanine / Pyruvate Glucose Ketones Urea NH 3 Ketones Glycerol AGL Fat

Metabolic Response to Trauma Nitrogen Excretion (g/day) Days Long CL, et al. JPEN 1979;3:

Severity of Trauma: Effects on Nitrogen Losses and Metabolic Rate Adapted from Long CL, et al. JPEN 1979;3:

Comparing Starvation and Trauma Metabolic rate Body fuels Body protein Urinary nitrogen Weight loss Starvation conserved slow Trauma or Disease wasted rapid 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

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

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

Metabolic Response to Injury Questions

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

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. 5 th ed. Chicago: American Dietetic Association; 1996 Long CL, et al. JPEN 1979;3: Injury Minor surgery Long bone fracture Cancer Peritonitis/sepsis Severe infection/multiple trauma Multi-organ failure syndrome Burns Stress Factor 1.00 – – – – – 2.00 Activity Confined to bed Out of bed Activity Factor

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

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 exceed 5 mg/kg/min Barton RG. Nutr Clin Pract 1994;9: ASPEN Board of Directors. JPEN 2002; 26 Suppl 1:22SA

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

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

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

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: Calder PC. Clin Nutr 1994;13:2-8; Furst P. Eur J Clin Nutr 1994;48: Standen J, Bihari D. Curr Opin Clin Nutr Metab Care 2000;3:

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. Barbul A. JPEN 1986;10: ; Barbul A, et al. J Surg Res 1980;29: “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

Key Vitamins and Minerals Vitamin A Vitamin C B Vitamins Pyridoxine Zinc Vitamin E Folic Acid, Iron, B 12 Wound healing and tissue repair Collagen synthesis, wound healing Metabolism, carbohydrate utilization Essential for protein synthesis Wound healing, immune function, protein synthesis Antioxidant Required for synthesis and replacement of red blood cells