2. INTRODUCTION
ClASSIFICATION
FEATURES OF METABOLIC RESPONSE
FACTORS MEDIATING METABOLIC RESPONSE
CONSEQUENCES OF METABOLIC RESPONSE
FACTORS MODIFYING METABOLIC RESPONSE
APPLIED ASPECTS
3. • Following accidental or deliberate injury, a characteristic
series of changes occurs, both locally at the site of injury and
within the body generally; these changes are intended to
restore the body to its pre-injury condition.
• The magnitude of the metabolic response is generally
proportional to the severity of tissue injury and the presence
of ongoing stimulation but can be modified by additional
factors such as infection
• The response to injury has probably evolved to aid
recovery,by mobilizing substrates and mechanisms of
preventing infection, and by activating repair processes
• Although the metabolic response aims to return an
individual to health, a major response can damage organs
distant to the injured site itself.
• In modern surgery, a major goal is to minimize the metabolic
response to surgery in order to shorten recovery times.
4. • Classically, these responses have been described as stress
response, a term coined by the scottish chemist CUTHBERTSON
in 1932.
• Intial response is directed at maintaining adequate substrate
suppy to the vital organs, in particular oxygen and energy
• When the inflammatory response impairs function of organs or
organ systems, the term multiple organ dysfunction syndrome
is applied (MODS)
• SIRS, systemic infalmatory response syndrome is a the term
used to describe the body’s response to infections and
noninfectious causes and consists of two or more of the
following
• Hyper/hypo thermia
• Leukopenia/ leukocytosis
• Tachycardia
• Tachyapnea
5. Classification
• Aller and colleagues propose a modern perspective on the
metabolic events associated with the inflammatory response to
major trauma
• the "ischemia/reperfusion phenotype” –phenotype represents the
immediate, nervous system-related alteration in response to injury, in
which neuronal and humoral responses and edema formation
predominate. This phase is characterized by regulating the metabolic
supply to cells via the least elaborate mechanism:diffusion.
• the "leukocytic phenotype“ – is characterized as the intermediate (or
"immune") phase of the metabolic response to trauma. This phase is
characterized by leukocytic and bacterial infiltration of previously
damaged tissues, which occurs in an edematous, oxygen-poor
environment. The resulting post-shock hypercatabolism and
hypermetabolism is related to a hyperdynamic response with increased
body temperature, increased oxygen consumption,
glycogenolysis,lipolysis, proteolysis and futile substrate cycling
• The “ Angeogenic phase “- third ("angiogenic") phenotype is defined as
the late (or"endocrine") phase of systemic response to injury. This phase
is characterized by a return of oxidative metabolism,favoring
angiogenesis in damaged tissues and organs. This process creates a
capillary bed that facilitates tissue repair and regeneration
6. Ebb and Flow phases
• 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.
7. • Unmodified metabolic response
• Ebb phase -phase of metabolic response to acute stress
• Flow phase - phase of metabolic response after operation
• Anbolic phase - recovery from operation
Time
EnergyExpenditure
Ebb
Phase
Ebb
Phase
Flow
Phase
Flow
Phase
8. Metabolic Response to
Trauma:
Ebb Phase (upto 24 hours)• Characterized
• Hypovolemic shock
• reversible
• Irreversible
• Release of Catacholamines/ vasoactive hormones
• ↑ Cardiac Output
• Peripheral Vasoconstriction
• ↑ Respiratory Rate
• Delivery of Maximum oxygen Levels
• ↑ Blood Glucose
• Mobilization of free Fatty acids
Fonseca : Oral and Maxillofacial Trauma Vol.1
9. Metabolic Response to
Trauma:
Flow Phase (may last for
weeks)∀↑ Catecholamines
∀↑ basal metabolic Rates
∀↑ Glucocorticoids
∀↑ Glucagon
• Release of cytokines, lipid mediators
• Acute phase protein production
Fonseca : Oral and Maxillofacial Trauma Vol.1
12. • 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.
13. Flow phase
Phenomenon Effect
↑ catecholamine
↑ glucagon
↑ cortisol
↑ insulin
↑ cardiac output
↑ core body temperature
↑ aldosterone
↑ ADH
IL1, IL6, TNF
spillage from
wound
↑ consumption
of glucose, FFA,
amino acid
↑ O2 consumption
fluid retention
systemic inflammatory
response
N or ↑ glucose
N or ↑ FFA
normal lactate
↑ CO2 production
↑ heat production
multi-organ
failure
15. Comparison of metabolic response
between ebb and flow phase
Ebb phase Flow phase
Blood glucose level ↑ N or ↑
Glucose production N ↑
Free fatty acid level ↑ N or ↑
Insulin concentration ↓ N or ↑
Catecholamine ↑ ↑
16. Comparison of metabolic response
between ebb and flow phase (con’t)
Ebb phase Flow phase
Glucagon ↑ ↑
Blood lactate level ↑ N
Oxygen consumption ↓ ↑
Cardiac output ↑ ↑
Core temperature ↓ ↑
17. Strategy to attenuate metabolic response to
surgery
During ebb phase
•Prompt fluid and blood replacement to maintain blood pressure
•Adequate oxygen supply and ventilation
•Cardiovascular support by inotropes
•Antibiotics
During flow phase
•Nutritional support
•Warm room temperature
•Mobilization
•Hemodialysis
•Timely intervention for complication
24. 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.
25. 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
26. 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
27. 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
28. Determining Protein Requirements for
Hospitalized Patients
Stress Level
Calorie:Nitrogen Ratio
Percent Potein / Total
Calories
Protein / kg Body Weight
No Stress
< 15%
protein
0.8
g/kg/day
Moderate Stress
15-20%
protein
1.0-1.2
g/kg/day
1.5-2.0
g/kg/day
> 20%
protein
Severe Stress
29. • 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.
30. 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
31. • 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.
32. 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
33. 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
34. • 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.
35. Factors influencing the Extent and Duration of the
Metabolic Response
• Pain and Fear
• Surgical Factors:
• Type of surgery
• Region
• Duration
• Preoperative support
• Extent of the trauma and degree of resuscitation
• Post traumatic complications:
• Hemorrhage
• Hypoxia
• Sepsis and Fever
• Re-operation
• Pre-existing nutritional status
• Age and sex
• Anaesthetic considerations
36. Methods to Minimize the Metabolic
Response
• Replace blood and fluid losses
• Maintain Oxygenation
• Give adequate nutrition
• Provide Analgesia
• Avoid Hypothermia
37. Consequences of the Response
• Limiting injury
• Initiation of repair processes
• Mobilization of substrates
• Prevention of infection
• Distant organ damage
38. Strategy to attenuate metabolic
response to surgery
Principles
• No effective strategy to attenuate metabolic response
• Supportive measures are available
• Perfect surgery is essential
39. Strategy to attenuate metabolic response to
surgery
During ebb phase
• Prompt fluid and blood replacement to maintain blood
pressure
• Adequate oxygen supply and ventilation
• Cardiovascular support by inotropes
• Antibiotics
40. Strategy to attenuate metabolic response to
surgery
During flow phase
• Nutritional support
• Warm room temperature
• Mobilization
• Hemodialysis
• Timely surgery for complication
41. References
• Fonseca trauma Vol.1
• Metabolic response to trauma
(The journal of Bone and Joint Surgery)
• Clinical aspects of the metabolic response to trauma
(The american Journal of Clinical Nutrition: Vol.3, Number 3)
• Metabolic response to trauma
( Australian journal of physiotherapy)
• Manipulating the metabolic response to injury
(British medical bulletin 1999;55 (no.1): 181-195)
• The metabolic response to stress: an overview and update
(Anesthesiology 73:308-327, 1980)
Editor's Notes
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;12:1-55Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. Philadelphia, PA: WB Saunders; 1997.
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;12:1-55Welborn MB. In: Rombeau JL, Rolandelli RH, eds. Enteral and Tube Feeding. 3rd ed. Philadelphia, PA: WB Saunders; 1997.
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.
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.
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.
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
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
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.
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.
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.
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.
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.