Metabolic Response to Injury Metabolism of substrates and micronutrients is altered by starvation and trauma. During periods of starvation, metabolic processes slow down to conserve energy and adapt to calorie deprivation. After trauma, the body’s hormonal situation changes, increasing the demand for energy, proteins, and micronutrients. If nutritional requirements are not recognized and met during starvation or trauma, there may be a loss of body mass, body protein, and impairment or loss of body functions.

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 Lesson objectives are: Explain the differences between metabolic responses to starvation and trauma. Explain the effect of trauma on metabolic rate and substrate utilization. Determine calorie and protein requirements during metabolic stress. This session will also review macronutrients during metabolic stress, highlighting the role of conditionally-essential nutrients in specific situations.

Metabolism of substrates and micronutrients is altered by starvation and trauma. During periods of starvation, metabolic processes slow down to conserve energy and adapt to calorie deprivation. After trauma, the body’s hormonal situation changes, increasing the demand for energy, proteins, and micronutrients. If nutritional requirements are not recognized and met during starvation or trauma, there may be a loss of body mass, body protein, and impairment or loss of body functions.

Mediating the Response The Acute Inflammatory Response Cellular activation Inflammatory mediators (TNF, IL1, etc) Paracrine Vs endocrine effects Lesson objectives are: Explain the differences between metabolic responses to starvation and trauma. Explain the effect of trauma on metabolic rate and substrate utilization. Determine calorie and protein requirements during metabolic stress. This session will also review macronutrients during metabolic stress, highlighting the role of conditionally-essential nutrients in specific situations.

Mediating the Response The Endothelium Selectins, Integrins, and ICAMs Nitric Oxide Tissue Factor Lesson objectives are: Explain the differences between metabolic responses to starvation and trauma. Explain the effect of trauma on metabolic rate and substrate utilization. Determine calorie and protein requirements during metabolic stress. This session will also review macronutrients during metabolic stress, highlighting the role of conditionally-essential nutrients in specific situations.

Mediating the Response Afferent Nerve Stimulation Sympathetic Nervous System Adrenal Gland Medulla Lesson objectives are: Explain the differences between metabolic responses to starvation and trauma. Explain the effect of trauma on metabolic rate and substrate utilization. Determine calorie and protein requirements during metabolic stress. This session will also review macronutrients during metabolic stress, highlighting the role of conditionally-essential nutrients in specific situations.

Mediating the Response The Endocrine System Pituitary Gland (GH, ACTH, ADP) Adrenal Gland (Cortisol, Aldosterone) Pancreatic (Glucagon,  Insulin) Others (Renin, Angiotensin,  Sex hormones,  T4) Lesson objectives are: Explain the differences between metabolic responses to starvation and trauma. Explain the effect of trauma on metabolic rate and substrate utilization. Determine calorie and protein requirements during metabolic stress. This session will also review macronutrients during metabolic stress, highlighting the role of conditionally-essential nutrients in specific situations.

Consequences of the Response Limiting injury Initiation of repair processes Mobilization of substrates Prevention of infection Distant organ damage Lesson objectives are: Explain the differences between metabolic responses to starvation and trauma. Explain the effect of trauma on metabolic rate and substrate utilization. Determine calorie and protein requirements during metabolic stress. This session will also review macronutrients during metabolic stress, highlighting the role of conditionally-essential nutrients in specific situations.

Starvation & Injury The metabolic response to fasting is an adaptation by the body to preserve protein by using alternative sources of energy. The carbohydrate deposits of the body last about 18 to 20 hours and new glucose is produced through gluconeogenesis of amino acids from the lean body mass. Lesson objectives are: Explain the differences between metabolic responses to starvation and trauma. Explain the effect of trauma on metabolic rate and substrate utilization. Determine calorie and protein requirements during metabolic stress. This session will also review macronutrients during metabolic stress, highlighting the role of conditionally-essential nutrients in specific situations.

Metabolic Response to Fasting The metabolic response to fasting is an adaptation by the body to preserve protein by using alternative sources of energy. The carbohydrate deposits of the body last about 18 to 20 hours and new glucose is produced through gluconeogenesis of amino acids from the lean body mass. Ruderman NB. Muscle amino acid metabolism and gluconeogenesis. Annu Rev Med 1975;26:248.

Starvation – Early Stage Intestine Muscle Liver Brain Kidney Gluconeogenesis Ketogenesis Ureagenesis Glutamine Alanine / Pyruvate Glucose Ketones Urea NH3 Glycerol AGL Fat The initial response to fasting is mediated by a drop in serum insulin and an increase in glucagon. During this period energy is provided mainly by glucose from gluconeogenesis. However, lipolysis generates free fatty acids which are oxidized into ketones.

The initial response to fasting is mediated by a drop in serum insulin and an increase in glucagon. During this period energy is provided mainly by glucose from gluconeogenesis. However, lipolysis generates free fatty acids which are oxidized into ketones.

Starvation – Late Stage Intestine Muscle Liver Brain Kidney Gluconeogenesis Ketogenesis Ureagenesis Glutamine Alanine / Pyruvate Glucose Ketones Urea NH3 Glycerol AGL Fat After several days, most of the body organs are using ketones (acetoacetic, propionate, and butyric acids) for energy and gluconeogenesis decreases to half of the early phase. Brain, red blood cells, and nerve tissue still rely partially on glucose for energy.

After several days, most of the body organs are using ketones (acetoacetic, propionate, and butyric acids) for energy and gluconeogenesis decreases to half of the early phase. Brain, red blood cells, and nerve tissue still rely partially on glucose for energy.

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     Conservation of energy is one of the basic adaptive responses to calorie reduction; when food is in short supply, metabolic activity decreases to spare fuel. Adjustments in the energy requirements of the body in response to changes in caloric intake occur through the action of several hormones, primarily norepinephrine and thyroid hormone. Norepinephrine is produced by the sympathetic nervous system and the adrenal glands, located near the kidneys. Thyroid hormone T4 is produced by the thyroid gland, and is modified in the periphery to the active hormone T3. Both norepinephrine and T3 participate in the decrease in metabolic activity when calorie intake decreases. Landsberg L, et al. N Engl J Med 1978;298:1295. Landberg L, et al. N Engl J Med 1978;298:1295.

Conservation of energy is one of the basic adaptive responses to calorie reduction; when food is in short supply, metabolic activity decreases to spare fuel. Adjustments in the energy requirements of the body in response to changes in caloric intake occur through the action of several hormones, primarily norepinephrine and thyroid hormone. Norepinephrine is produced by the sympathetic nervous system and the adrenal glands, located near the kidneys. Thyroid hormone T4 is produced by the thyroid gland, and is modified in the periphery to the active hormone T3. Both norepinephrine and T3 participate in the decrease in metabolic activity when calorie intake decreases.

Energy Expenditure in Starvation 10 20 30 40 Partial Starvation Days Nitrogen Excretion (g/day) 12 8 4 Total Starvation Normal Range The two lines on this graph show another adaptive response to severely reduced calorie intake. Urinary nitrogen excretion gradually decreases, indicating conservation of body protein and demonstrating adaptation to starvation. Long CL et al. JPEN 1979;3:452-456 Long CL et al. JPEN 1979;3:452-456

The two lines on this graph show another adaptive response to severely reduced calorie intake. Urinary nitrogen excretion gradually decreases, indicating conservation of body protein and demonstrating adaptation to starvation.

Metabolic Response to Trauma Time Energy Expenditure Ebb Phase Flow Phase Trauma causes major alterations in energy and protein metabolism. The response to trauma can be divided into the ebb phase and the flow phase. The ebb phase occurs immediately after trauma and lasts from 24-48 hours followed by the flow phase. After this, comes the anabolism phase and finally, the fatty-replacement phase. Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55. Cutherbertson DP, et al. Adv Clin Chem 1969;12:1-55

Trauma causes major alterations in energy and protein metabolism. The response to trauma can be divided into the ebb phase and the flow phase. The ebb phase occurs immediately after trauma and lasts from 24-48 hours followed by the flow phase. After this, comes the anabolism phase and finally, the fatty-replacement phase.

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 The ebb phase is characterized by hypovolemic shock. Cardiac output, oxygen consumption and blood pressure all decrease, thereby reducing tissue perfusion. These mechanisms are usually associated with hemorrhage. Body temperature drops. The reduction in metabolic rate may be a protective mechanism during this period of hemodynamic instability. Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55 Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. Philadelphia, PA: WB Saunders; 1997. Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55 Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. 1997

The ebb phase is characterized by hypovolemic shock The ebb phase is characterized by hypovolemic shock. Cardiac output, oxygen consumption and blood pressure all decrease, thereby reducing tissue perfusion. These mechanisms are usually associated with hemorrhage. Body temperature drops. The reduction in metabolic rate may be a protective mechanism during this period of hemodynamic instability.

Metabolic Response to Trauma: Flow Phase  Catecholamines  Glucocorticoids  Glucagon Release of cytokines, lipid mediators Acute phase protein production The ebb phase is characterized by hypovolemic shock. Cardiac output, oxygen consumption and blood pressure all decrease, thereby reducing tissue perfusion. These mechanisms are usually associated with hemorrhage. Body temperature drops. The reduction in metabolic rate may be a protective mechanism during this period of hemodynamic instability. Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55 Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. Philadelphia, PA: WB Saunders; 1997. Cuthbertson DP, et al. Adv Clin Chem 1969;12:1-55 Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. 1997

Metabolic Response to Trauma Fatty Acids Glucose Amino Acids Fatty Deposits Liver & Muscle (glycogen) Muscle (amino acids) Endocrine Response Endocrine response in the form of increased catecholamines, glucocorticoids and glycogen, leads to mobilization of tissue energy reserves. These calorie sources include fatty acids and glycerol from lipid reserves, glucose from hepatic glycogen (muscle glycogen can only provide glucose for the involved muscle) and gluconeogenic precursors (eg, amino acids) from muscle.

Endocrine response in the form of increased catecholamines, glucocorticoids and glycogen, leads to mobilization of tissue energy reserves. These calorie sources include fatty acids and glycerol from lipid reserves, glucose from hepatic glycogen (muscle glycogen can only provide glucose for the involved muscle) and gluconeogenic precursors (eg, amino acids) from muscle.

Metabolic Changes after Trauma Intestine Muscle Liver Brain Kidney Gluconeogenesis Ketogenesis Ureagenesis Glutamine Alanine / Pyruvate Glucose Ketones Urea NH3 Glycerol AGL Fat The response to trauma includes a breakdown of muscle tissue. This mechanism provides amino acids for gluconeogenesis and for synthesis of proteins involved in immunologic response and tissue repair. However, this process can lead to a loss of body mass, most notably body protein. Prolonged metabolic stress without provision of adequate calories and protein leads to impaired body functions and ultimately malnutrition. The remainder of this session deals with nutritional requirements during metabolic stress. Moore EE, et al. J Am Coll Nutr 1991;10:633-648.

The response to trauma includes a breakdown of muscle tissue The response to trauma includes a breakdown of muscle tissue. This mechanism provides amino acids for gluconeogenesis and for synthesis of proteins involved in immunologic response and tissue repair. However, this process can lead to a loss of body mass, most notably body protein. Prolonged metabolic stress without provision of adequate calories and protein leads to impaired body functions and ultimately malnutrition. The remainder of this session deals with nutritional requirements during metabolic stress.

Metabolic Response to Trauma 28 24 20 16 12 8 4 Nitrogen Excretion (g/day) This slide illustrates nitrogen losses in relation to trauma. With respect to protein, the greater the trauma, the greater the effect on the nitrogen balance. Similar to metabolic rate, patients experience nitrogen losses according to the severity and duration of the trauma. The normal range is indicated by the shaded area. The amount of protein requirement relative to calories increases in patients with metabolic stress. Long CL, et al. JPEN 1979;3:452-456. 10 20 30 40 Days Long CL, et al. JPEN 1979;3:452-456

This slide illustrates nitrogen losses in relation to trauma This slide illustrates nitrogen losses in relation to trauma. With respect to protein, the greater the trauma, the greater the effect on the nitrogen balance. Similar to metabolic rate, patients experience nitrogen losses according to the severity and duration of the trauma. The normal range is indicated by the shaded area. The amount of protein requirement relative to calories increases in patients with metabolic stress.

Severity of Trauma: Effects on Nitrogen Losses and Metabolic Rate Basal Metabolic Rate Cirugía mayor Cirug í a electiva Infecci ó n Sepsis grave Quemadura moderada a grave Nitrogen Loss in Urine Major Surgery Elective Infection Severe Moderate to Severe Burn This graph illustrates that severity of injury correlates to increasing urinary nitrogen loss and increasing energy needs. Elective surgery being least traumatic and the lowest nitrogen loss in urine, whereas burn results in an increase in basal metabolic rate and urinary loss of nitrogen. Adapted from Long CL, et al. JPEN 1979;3:452-456. Adapted from Long CL, et al. JPEN 1979;3:452-456

This graph illustrates that severity of injury correlates to increasing urinary nitrogen loss and increasing energy needs. Elective surgery being least traumatic and the lowest nitrogen loss in urine, whereas burn results in an increase in basal metabolic rate and urinary loss of nitrogen.

Comparing Starvation and Trauma Metabolic rate Body fuels Body protein Urinary nitrogen Weight loss Starvation conserved slow Trauma or Disease wasted rapid The metabolic response to starvation can be contrasted to trauma or disease: Metabolic rate drops during starvation, while in trauma patients it rises in proportion to the trauma severity. Body fuels and body proteins are conserved during starvation, but are wasted during trauma. Urinary nitrogen values fall with inadequate protein and calorie intake, but increase in response to metabolic stress. Weight loss is slow in underfed patients but rapid in trauma patients. Changes in body composition with trauma usually occur two to three times faster than during starvation. Popp MB, et al. In: Fischer JF, ed. Surgical Nutrition. Boston: Little, Brown and Company; 1983. 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.

The metabolic response to starvation can be contrasted to trauma or disease: Metabolic rate drops during starvation, while in trauma patients it rises in proportion to the trauma severity. Body fuels and body proteins are conserved during starvation, but are wasted during trauma. Urinary nitrogen values fall with inadequate protein and calorie intake, but increase in response to metabolic stress. Weight loss is slow in underfed patients but rapid in trauma patients. Changes in body composition with trauma usually occur two to three times faster than during starvation.

Modifying the Response Medication (before or after injury) Nutritional status Severity of injury Temperature Anesthetic technique Lesson objectives are: Explain the differences between metabolic responses to starvation and trauma. Explain the effect of trauma on metabolic rate and substrate utilization. Determine calorie and protein requirements during metabolic stress. This session will also review macronutrients during metabolic stress, highlighting the role of conditionally-essential nutrients in specific situations.

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 In summary, the body responds differently to starvation and trauma. Starvation is associated with a decreased metabolic rate, which allows the body to adapt to reduced intake. After trauma, metabolic changes are associated with increased nutritional requirements. If nutritional requirements are not met during trauma, loss of protein and body mass can produce significant impairment.

In summary, the body responds differently to starvation and trauma In summary, the body responds differently to starvation and trauma. Starvation is associated with a decreased metabolic rate, which allows the body to adapt to reduced intake. After trauma, metabolic changes are associated with increased nutritional requirements. If nutritional requirements are not met during trauma, loss of protein and body mass can produce significant impairment.

Metabolic Response to Injury Questions Metabolism of substrates and micronutrients is altered by starvation and trauma. During periods of starvation, metabolic processes slow down to conserve energy and adapt to calorie deprivation. After trauma, the body’s hormonal situation changes, increasing the demand for energy, proteins, and micronutrients. If nutritional requirements are not recognized and met during starvation or trauma, there may be a loss of body mass, body protein, and impairment or loss of body functions.

Determining Calorie Requirements Indirect calorimetry Harris-Benedict x stress factor x activity factor 25-30 kcal/kg body weight/day There are a wide variety of methods for estimating energy requirements. Common methods include indirect calorimetry and the Harris-Benedict Equation. Indirect calorimetry is based on calculating heat production by measuring oxygen consumed and carbon dioxide produced, through analysis of exhaled gas or use of pulmonary catheters. The Harris-Benedict Equation calculates basal energy requirements for healthy people, but has also been applied to sick patients through the use of correction factors for stress and activity. The simplest estimate of adequate energy intake for patients in metabolic stress is the “rule of thumb” of 25-30 kcal/kg body weight per day.

Metabolism of substrates and micronutrients is altered by starvation and trauma. During periods of starvation, metabolic processes slow down to conserve energy and adapt to calorie deprivation. After trauma, the body’s hormonal situation changes, increasing the demand for energy, proteins, and micronutrients. If nutritional requirements are not recognized and met during starvation or trauma, there may be a loss of body mass, body protein, and impairment or loss of body functions.

There are a wide variety of methods for estimating energy requirements There are a wide variety of methods for estimating energy requirements. Common methods include indirect calorimetry and the Harris-Benedict Equation. Indirect calorimetry is based on calculating heat production by measuring oxygen consumed and carbon dioxide produced, through analysis of exhaled gas or use of pulmonary catheters. The Harris-Benedict Equation calculates basal energy requirements for healthy people, but has also been applied to sick patients through the use of correction factors for stress and activity. The simplest estimate of adequate energy intake for patients in metabolic stress is the “rule of thumb” of 25-30 kcal/kg body weight per 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 Injury Minor surgery Long bone fracture Cancer Peritonitis/sepsis Severe infection/multiple trauma Multi-organ failure syndrome Burns Stress Factor 1.00 – 1.10 1.15 – 1.30 1.10 – 1.30 1.20 – 1.40 1.20 – 2.00 When the Harris-Benedict Equation is used to calculate energy requirements, estimated basal energy expenditure is multiplied by a stress factor. As shown in this slide, the stress factor for a long bone fracture is 1.15-1.30, resulting in a metabolic rate increase of 15%-30%. Burns have a greater impact on energy requirements, increasing basal energy expenditure by 20%-100%. In addition, activity factor of 1.2 or 1.3 must be multiplied to determine the energy requirement. ADA: Manual of Clinical Dietetics. 5th ed. Chicago: American Dietetic Association; 1996. Long CL, et al. JPEN 1979;3:452-456. Activity Confined to bed Out of bed Activity Factor 1.2 1.3 ADA: Manual Of Clinical Dietetics. 5th ed. Chicago: American Dietetic Association; 1996 Long CL, et al. JPEN 1979;3:452-456

When the Harris-Benedict Equation is used to calculate energy requirements, estimated basal energy expenditure is multiplied by a stress factor. As shown in this slide, the stress factor for a long bone fracture is 1.15-1.30, resulting in a metabolic rate increase of 15%-30%. Burns have a greater impact on energy requirements, increasing basal energy expenditure by 20%-100%. In addition, activity factor of 1.2 or 1.3 must be multiplied to determine the energy requirement.

Metabolic Response to Overfeeding Hyperglycemia Hypertriglyceridemia Hypercapnia Fatty liver Hypophosphatemia, hypomagnesemia, hypokalemia Trauma or critically ill patients should not be overfed. Alterations in serum glucose and lipid levels, development of fatty liver, and electrolyte shifts have been associated with overfeeding. Trauma or critically ill patients should not be overfed. Alterations in serum glucose and lipid levels, development of fatty liver, and electrolyte shifts have been associated with overfeeding. Barton RG. Nutr Clin Pract 1994;9:127-139. Barton RG. Nutr Clin Pract 1994;9:127-139

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 Delivery of appropriate substrates or macronutients is essential. Patients require at least 100g of glucose per day during metabolic stress to prevent ketosis. During hypermetabolic stress, a carbohydrate level of 30%-40% of total calories is recommended. Glucose intake should not exceed 5 mg/kg/min. Barton RG. Nutr Clin Pract 1994;9:127-139. ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA. Barton RG. Nutr Clin Pract 1994;9:127-139 ASPEN Board of Directors. JPEN 2002; 26 Suppl 1:22SA

Delivery of appropriate substrates or macronutients is essential Delivery of appropriate substrates or macronutients is essential. Patients require at least 100g of glucose per day during metabolic stress to prevent ketosis. During hypermetabolic stress, a carbohydrate level of 30%-40% of total calories is recommended. Glucose intake should not exceed 5 mg/kg/min.

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 Dietary fat should provide between 20-35% of total calories. Maximum recommended infusion rate when administering intravenous lipids is 1.0-1.5 g/kg/day. Serum triglyceride levels in stressed patients should be monitored to ensure adequate lipid clearance. Barton RG. Nutr Clin Pract 1994;9:127-139. ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA Barton RG. Nutr Clin Pract 1994;9:127-139 ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA

Dietary fat should provide between 20-35% of total calories Dietary fat should provide between 20-35% of total calories. Maximum recommended infusion rate when administering intravenous lipids is 1.0-1.5 g/kg/day. Serum triglyceride levels in stressed patients should be monitored to ensure adequate lipid clearance.

Macronutrients during Stress Protein Requirements range from 1.2-2.0 g/kg/day during stress Comprise 20%-30% of total calories during stress Protein requirements increase during metabolic stress and are estimated at between 1.2-2.0 g/kg/day, or approximately 20% to 30% of the total calorie intake during stress. Barton RG. Nutr Clin Pract 1994;9:127-139. ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA Barton RG. Nutr Clin Pract 1994;9:127-139 ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA

Protein requirements increase during metabolic stress and are estimated at between 1.2-2.0 g/kg/day, or approximately 20% to 30% of the total calorie intake during stress.

Determining Protein Requirements for Hospitalized Patients Stress Level Calorie:Nitrogen Ratio Percent Potein / Total Calories Protein / kg Body Weight No Stress Moderate Stress Severe Stress > 150:1 150-100:1 < 100:1 < 15% protein 15-20% protein > 20% protein Calorie-to-nitrogen ratios can be used to prevent lean body mass from being utilized as a source of energy. Therefore, in the non-stressed patient, less protein is necessary to maintain muscle as compared to the severely stressed patient. Nitrogen balance can be affected by the biological value of the protein as well as by growth, caloric balance, sepsis, surgery, activity (bed rest and lack of muscle use can promote nitrogen excretion), and by renal function. 0.8 g/kg/day 1.0-1.2 g/kg/day 1.5-2.0 g/kg/day

Calorie-to-nitrogen ratios can be used to prevent lean body mass from being utilized as a source of energy. Therefore, in the non-stressed patient, less protein is necessary to maintain muscle as compared to the severely stressed patient. Nitrogen balance can be affected by the biological value of the protein as well as by growth, caloric balance, sepsis, surgery, activity (bed rest and lack of muscle use can promote nitrogen excretion), and by renal function.

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 Glutamine is one of the few nutrients included in the category of conditionally-essential amino acids. Glutamine is the body’s most abundant amino acid and is involved in many physiological functions. Plasma glutamine levels decrease drastically following trauma. It has been hypothesized that this drop occurs because glutamine is a preferred substrate for cells of the gastrointestinal cells and white blood cells. Glutamine helps maintain or restore intestinal mucosal integrity. Smith RJ, et al. JPEN 1990;14(4 Suppl):94S-99S. Pastores SM, et al. Nutrition 1994;10:385-390. Calder 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. Smith RJ, et al. JPEN 1990;14(4 Suppl):94S-99S; Pastores SM, et al. Nutrition 1994;10:385-391 Calder 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

Glutamine is one of the few nutrients included in the category of conditionally-essential amino acids. Glutamine is the body’s most abundant amino acid and is involved in many physiological functions. Plasma glutamine levels decrease drastically following trauma. It has been hypothesized that this drop occurs because glutamine is a preferred substrate for cells of the gastrointestinal cells and white blood cells. Glutamine helps maintain or restore intestinal mucosal integrity.

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. Arginine is also considered a conditionally essential amino acid. Barbul and colleagues showed that arginine supplements increased thymus weight in uninjured rats and decreased thymus involution from trauma. (Barbul A, et al. J Surg Res 1980;29:228-235) In studies on humans and animals, arginine supplements increased nitrogen retention and immune function and improved wound healing. Arginine plays other roles that are not well understood; for instance as a scretagogue (growth hormone), precursor for polyamines and nitric oxide. Therefore, one should avoid providing more than 2% of total calories as arginine. Because arginine is considered an immune-enhancing nutrient, it may not be appropriate to feed supplemental arginine to septic or inflammatory patients whose immune system is already stimulated and where addition of arginine supplementation may be detrimental. Barbul A. JPEN 1986; 10: 227-238 It is worth noting that the studies on the use of arginine supplementation were done with patients in the early phase of stress. “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

Arginine is also considered a conditionally essential amino acid Arginine is also considered a conditionally essential amino acid. Barbul and colleagues showed that arginine supplements increased thymus weight in uninjured rats and decreased thymus involution from trauma

Key Vitamins and Minerals Vitamin A Vitamin C B Vitamins Pyridoxine Zinc Vitamin E Folic Acid, Iron, B12 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 Micronutrient, trace element, vitamin, and mineral requirements of metabolically stressed patients seem to be elevated above the levels for normal healthy people. There are no specific dosage guidelines for micronutrients and trace elements, but there are plausible theories supporting their increased intake. This slide lists some of these nutrients along with the rationale for their inclusion.

Micronutrient, trace element, vitamin, and mineral requirements of metabolically stressed patients seem to be elevated above the levels for normal healthy people. There are no specific dosage guidelines for micronutrients and trace elements, but there are plausible theories supporting their increased intake. This slide lists some of these nutrients along with the rationale for their inclusion.