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
9. 10
20
30
40
I II III IV V
Exogenous
Glycogen
Gluconeogenesis
GLUCOSE
UTILIZED
(g/hora)
Ruderman NB. Annu Rev Med 1975;26:248
I II III IV V
GLUCOSE
GLUCOSE GLUCOSE
GLUCOSE,
KETONES
GLUCOSE,
KETONES
FUEL FOR
BRAIN
LEGEND
Metabolic Response to Fasting
12. Metabolic Response to Starvation
Hormone
Norepinephrine
Norepinephrine
Epinephrine
Thyroid Hormone T4
Source
Sympathetic Nervous System
Adrenal Gland
Adrenal Gland
Thyroid Gland (changes to T3
peripherally)
Change in Secretion
Landberg L, et al. N Engl J Med 1978;298:1295.
13. Energy Expenditure in Starvation
Long CL et al. JPEN 1979;3:452-456
0
10 20 30 40
Partial Starvation
Days
Nitrogen
Excretion
(g/day)
12
8
4
Total Starvation
Normal Range
14. Metabolic Response to Trauma
Time
Energy
Expenditure
Ebb Phase Flow Phase
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;12:1-55
Welborn 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;12:1-55
Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. 1997
19. Metabolic Response to Trauma
10 20 30 40
28
24
20
16
12
8
4
0
Nitrogen
Excretion
(g/day)
Days
Long CL, et al. JPEN 1979;3:452-456
20. Severity of Trauma: Effects on Nitrogen
Losses and Metabolic Rate
Adapted from Long CL, et al. JPEN 1979;3:452-456
Basal Metabolic Rate
Cirugía
mayor
Cirugía
electiva
Infección
Sepsis
grave
Quemadura
moderada a grave
Nitrogen
Loss
in
Urine
Major
Surgery
Elective
Surgery
Infection
Severe
Sepsis
Moderate to Severe
Burn
21. Comparing Starvation and Trauma
Metabolic rate
Body fuels
Body protein
Urinary nitrogen
Weight loss
Starvation
conserved
conserved
slow
Trauma or Disease
wasted
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. 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
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
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
1.10 – 1.30
1.20 – 1.40
1.20 – 1.40
1.20 – 2.00
Activity
Confined to bed
Out of bed
Activity Factor
1.2
1.3
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 exceed
5 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
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
150-100:1
15-20%
protein
1.0-1.2 g/kg/day 1.5-2.0
g/kg/day
> 20% protein
< 100:1
Severe Stress
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;10:385-391
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
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.
Barbul A. JPEN 1986;10:227-238; Barbul A, et al. J Surg Res 1980;29:228-235
“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
34. 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
