1. Metabolic Response to Starvation and Trauma: Nutritional Requirements
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.

2. Objectives
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
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.

3. 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.

4. Fasting – Early Stage Gluconeogenesis Ketogenesis Ureagenesis Muscle
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.

5. Fasting – Late Stage Gluconeogenesis Ketogenesis Ureagenesis Muscle
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.

6. Metabolic Reaction 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.

7. Energy Expenditure in Starvation10 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:
Long CL et al. JPEN 1979;3:

8. 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 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

9. 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

10. Metabolic Response to Trauma: Flow Phase
 Catecholamines
 Glucocorticoids
 Glucagon
Release of cytokines, lipid mediators
Acute phase protein production
As blood volume is stabilized, the ebb phase is replaced by the flow phase. The flow phase consists of two successive responses: acute and adaptive.
Catabolism predominates the acute flow phase. Catabolic stress hormones (glucocorticoids, glucagon, and catecholamines) increase. This hypermetabolism is mediated by an increase in circulating levels of counter-regulatory hormones and other inflammatory mediators, such as cytokines and lipid mediators.
These hormonal conditions favor muscle tissue catabolism to provide amino acids for gluconeogenesis and synthesis of hepatic proteins, such as acute phase proteins.
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

11. 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.

12. Metabolic Response to Trauma28 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:
Days
Long CL, et al. JPEN 1979;3:

13. 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:
Adapted from Long CL, et al. JPEN 1979;3:

14. Metabolic Response to 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

15. Metabolic Response to Surgical Trauma 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:

16. 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 kcal/kg body weight per day.

17. 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 , 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; Long CL, et al. JPEN 1979;3:
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:

18. 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.
Barton RG. Nutr Clin Pract 1994;9:
Barton RG. Nutr Clin Pract 1994;9:

19. 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:
ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA.
Barton RG. Nutr Clin Pract 1994;9:
ASPEN Board of Directors. JPEN 2002; 26 Suppl 1:22SA

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

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

22. 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 :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
g/kg/day
g/kg/day

23. 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:
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:
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:

24. 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: )
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:
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: ; Barbul A, et al. J Surg Res 1980;29:

25. 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.

26. Summary Metabolic response to starvation is an adaptive mechanism
Nutritional requirements increase during 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.