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

GLUCOSE UTILIZED (g/hora)

II

III

40

IV

Exogenous
Glycogen
Gluconeogenesis

30

20

10

LEGEND

II

III

FUEL FOR
BRAIN

GLUCOSE

GLUCOSE

GLUCOSE

IV
GLUCOSE,
KETONES

V
GLUCOSE,
KETONES

Ruderman NB. Annu Rev Med 1975;26:248

Starvation Early Stage

Muscle

Alanine / Pyruvate

Brain

Glucose

Glutamine
Glycerol

Gluconeogenesis
Ketogenesis

Fat

AGL

Ureagenesis
Ketones

Liver

Urea
NH3

Intestine

Ketones

Kidney

Starvation Late Stage

Muscle

Alanine / Pyruvate

Brain

Glucose

Glutamine
Glycerol

Gluconeogenesis
Ketogenesis

Fat
AGL

Ureagenesis
Ketones

Liver

Urea
NH3

Intestine

Ketones

Kidney

Metabolic Response to
Starvation
Hormone

Source

Norepinephrine
Norepinephrine
Epinephrine
Thyroid Hormone T4

Sympathetic Nervous System

Adrenal Gland
Adrenal Gland
Thyroid Gland (changes to T3
peripherally)

Landberg L, et al. N Engl J Med 1978;298:1295.

Change in Secretion

Energy Expenditure in Starvation

Nitrogen Excretion (g/day)

12

Normal Range

Partial Starvation

Total Starvation
0

10

20

Days
Long CL et al. JPEN 1979;3:452-456

30

40

Energy Expenditure

Metabolic Response to Trauma

Ebb
Ebb
Phase
Phase

Flow
Flow
Phase
Phase

Time

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. 3rd 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. 3rd ed. 1997

Metabolic Response to Trauma

Fatty Deposits
Endocrine
Response

Fatty Acids

Liver & Muscle

(glycogen)

Glucose

Muscle
(amino acids)

Amino Acids

Metabolic Changes after Trauma

Muscle

Alanine / Pyruvate

Brain

Glucose

Glutamine
Glycerol

Gluconeogenesis
Ketogenesis

Fat
AGL

Ureagenesis
Ketones

Liver

Urea
NH3

Intestine

Ketones

Kidney

Metabolic Response to Trauma

Nitrogen Excretion (g/day)

28
24
20
16
12
8
4
0

10

Long CL, et al. JPEN 1979;3:452-456

20

Days

30

40

Severity of Trauma: Effects on

Nitrogen Losses and Metabolic
Rate

Nitrogen Loss in Urine

Major
Ciruga
mayor
Surgery
Moderate
Quemadura
to Severe
moderadaBurn
a grave

Infeccin
Infection

Severe
Sepsis
grave
Sepsis

Elective
Ciruga
electiva
Surgery

Basal Metabolic Rate

Adapted from Long CL, et al. JPEN 1979;3:452-456

Comparing Starvation and

Trauma
Metabolic rate
Body fuels
Body protein
Urinary nitrogen
Weight loss

Starvation

Trauma or Disease

conserved
conserved

wasted
wasted

slow

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.

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

We can modify the metabolic response before and

sometimes after injury

Metabolic response to injury is an adaptive response

Metabolic response could overwhelm the body and lead
to increased morbidity and mortality

Metabolic Response to Injury

Questions

Determining Calorie
Requirements

Indirect calorimetry
Harris-Benedict x stress factor x activity factor
25-30 kcal/kg body weight/day

Metabolic Response to Starvation

and Trauma: Nutritional
Requirements
Example:
Injury
Stress Factor
Minor surgery
Long bone fracture
Cancer
Peritonitis/sepsis
Severe infection/multiple trauma
Multi-organ failure syndrome
Burns
Activity
Confined to bed
Out of bed

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

Energy requirements for

patient with cancer in bed
= BEE x 1.10 x 1.2

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

Metabolic Response to
Overfeeding

Hyperglycemia
Hypertriglyceridemia
Hypercapnia
Fatty liver
Hypophosphatemia, hypomagnesemia, hypokalemia

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

Barton RG. Nutr Clin Pract 1994;9:127-139

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: 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

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

Determining Protein Requirements

for Hospitalized Patients

No Stress

Moderate Stress

Severe Stress

Calorie:Nitrogen Ratio

> 150:1

150-100:1

< 100:1

Percent Potein / Total

Calories

< 15%
protein

15-20%
protein

> 20%
protein

Protein / kg Body Weight

0.8
g/kg/day

1.0-1.2
g/kg/day

1.5-2.0
g/kg/day

Stress Level

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

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

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