This document discusses the metabolic response to trauma and injury. It describes how injury disrupts homeostasis and causes physiological, metabolic and clinical changes as the body attempts to restore homeostasis. The stress response is mediated by hormones like cortisol and cytokines which cause hypermetabolism, increased protein breakdown, and insulin resistance. These changes are initially beneficial for survival but can become harmful if prolonged. Modern trauma and critical care aims to minimize this response through techniques like early feeding and pain control to promote recovery.

1. METABOLIC RESPONSE TO
TRAUMA
Dr. Neeraj Kumar Jain
Department of Surgery

3.  This chapter aims to review the
mediators of the stress response, the
physiochemical and biochemical
pathway changes associated
with surgical injury and the changes in
body composition that occur following
surgical injury.
 Emphasis is laid on why knowledge of
these events is important to understand
the rationale for modern ‘stress-free’
perioperative and critical care.

4. Basic Concepts in
Homeostasis
1. Homeostasis is the foundation of
normal physiology.
2. Stress-free peri-operative care helps to
restore homeostasis following elective
surgery.
3. Resuscitation, surgical intervention & critical
care can return the severely injured patient
to a situation in which homeostasis
becomes possible once again.

5. • As a consequence of modern
understanding to metabolic response to
injury, elective surgery practice seeks to
reduce the need for a homeostatic
response by minimizing the primary insult
(as for e.g – Minimal access surgery )

6. Response Components
• Physiological Consequences
• Metabolic Manifestations
• Clinical Manifestations
• Laboratory Changes

7. Response Components
• Increased Cardiac
Output
• Increased Ventilation
• Increased
Membrane
Transport
• Weight loss
• Wound Healing
PHYSIOLOGICAL
METABOLIC • Hypermetabolism
• Acclerated
Gluconeogene
sis
• Enhanced
Protein
breakdown
• Increased Fat
oxidation

8. Response Components
CLINICAL
• Fever
• Tachycardia
• Tachypnea
• Presence of wound or
Inflammation
• Anorexia
LABORATORY
• Leucocytosis/Leucopenia
• Hyperglycemia
• Elevated CRP/Altered
acute phase reactants
• Hepatic/Renal dysfunction

9. Graded Nature of the injury
response
• Metabolic response to injury is Graded
and evolves with time

11. Mediators of injury
response
• Neuro endocrine ( Hormonal )
• Metabolic and Cytokine axes

12. Hormona
l

13. Neuro-endocrine response to
injury/critical illness
The Neuro-endocrine response to
severe injury/critical illness is
biphasic
1. Acute phase characterized by an actively
secreting pituitary & elevated counter regulatory
hormones (cortisol, glucagon,
adrenaline).Changes are thought to be
beneficial for short-term survival.
2. Chronic phase associated with hypothalamic
suppression & low serum levels of the respective
target organ hormones. This Changes contribute
chronic wasting.

14. Purpose of Neuro- endocrine changes
following injury
The constellation of Neuro-endocrine
changes following injury acts to
1. Provide essential substrates for survival
2. Postpone anabolism
3.Optimise host defense
These changes may be helpful in the
short term, but may be harmful in the
long-term, especially to the severely
injured patient who would otherwise not
have survived without medical
intervention

15. Proinflammatory cytokines
1. Il 1, Il 6, TNF alfa
2. NO (Nitric Oxide)
3. Endothelin 1
Cytokine antagonist
• Interleukin receptor antagonist, TNF
soluble receptors are released within
hours of injury

16. Physiological response to
injury
The natural response to injury
includes
1. Immobility
2. Anorexia
3. Catabolism

17. • In 1930, Sir David Cuthherstson derived
the metabolic response to injury in
humans into “ebb “ and “flow” phases

18. Metabolic changes after major trauma
(Cuthbertson, Lancet, 1942)
 EBB (Untreated shock)
• Dec body temp
• Dec O2 consumption
• Lactic acidosis
• Inc stress hormones
• Dec Insulin
• Hyperglycemia
• Gluconeogenesis
• Inc substrate
consumption
• Hepatic Acute phase
response
• Immune activation
 FLOW PHASE
• Inc body temp
• Inc O2 consumption
• Negative Nitrogen bal
• Inc stress hormone
• Normal to Inc Insulin
• Hyperglycemia
• Gluconeogenesis
• Proteinolysis
(autocannabalism)
• Lipolysis
• Immunosuppression

19. Ebb and Flow

20. Eb
b
• Starts at the time of injury and lasts for
approximately 24-48 hours
• Main hormones in ebb phase are catecholamines,
cortisol, and aldosterone
• It may be attenuated by proper resuscitation but not
completely abolished
• The main physiological role of this phase is to conserve
both circulating volume and energy stores for recovery and
repair

21. Flow
• It lasts for several weeks
• This phase involves mobilization of body
energy stores for repair and recovery
• Following resuscitation , Ebb phase evolves
into hypermetabolic flow phase, which
corresponds to SIRS

22. Key catabolic elements of flow
phase
• Hypermetabolism
• Alterations in skeletal muscle
protein
• Alterations in Liver protein
• Insulin resistance

23. Hypermetabolism
Majority of trauma patients demonstrate
energy expenditure approximately 15-25%
above predicted healthy resting values
Factors which increases this metabolism are
centreal thermodysregulation, increased
sympathetic activity, increased protein
turnover, wound circulation abnormalities etc..

24. Hypermetabolism
Hyper metabolism following injury:
1.Is mainly caused by an acceleration of
futile metabolic cycles
2.Is limited in modern practice on account of
elements of routine critical care.

25. Skeletal muscle wasting
1.Provides amino acids for protein
synthesis in central organ/tissues
2.Is mediated at a molecular level mainly
by activation of the ubiquitin-protease
pathway
3.Can result in immobility & contribute to
hypostatic pneumonia & death if prolonged
and excessive

26. Hepatic acute phase response
• The Hepatic acute phase response represents
a reprioritization of body protein metabolism
towards the liver & is characterized by:
• 1. Positive reactants (CRP) : plasma
concentration increases
• 2. Negative reactants (albumin) : :
plasma concentration decreases

27. Insulin resistance
• The degree of insulin resistance is
directly proportional to magnitude of the
injurious process.
• Following routine upper abdominal
surgery, insulin resistance may persist for
approx 2 wks
• Postop patients with insulin resistance behave
in a similar manner to individuals with type 2
diabetes
• The mainstay of treatment is i.v insulin.
• Intensive insulin infusions are better
over conservative approach.

29. • Main labile energy reserve in the body is fat.
• Main labile protein reserve in the body is
skeletal muscle.
• While fat mass can be reduced without major
detriment to function, loss of protein mass
results not only in skeletal muscle wasting,
but also depletion of visceral protein mass.

30. • With lean issue, each 1 g of nitrogen is
contained within 6.25 g of protein, which is
contained in approximately 36 g of wet weight
tissue.
• Thus the loss of 1 g of nitrogen in urine is
equivalent to the breakdown of 36 g of wet
weight lean tissue.
• Protein turnover in the whole body is of the
order of 150-200 g per day.

31. • A normal human ingests 70-100 g of protein
per day, which is metabolized and excreted
in urine as ammonia and urea(14 g N/day)
• During total starvation, urinary loss of
nitrogen is rapidly attenuated by a series
of adaptive changes
• Loss of body weight follows a similar
course,thus accounting for the survival of
hunger strikers for a period of 50-60 days

32. • Following major injury, and particularly in the
presence of ongoing septic complications ,
this adaptive change fails to occur, and
there is a state of auto cannibalism ,
resulting in continuing urinary nitrogen
losses of 10-20 g/day(500 g lean
tissue/day)
• As with total starvation, once loss of
body protein mass has reached 30-40
% of the total, survival is unlikely

33. In critically ill patients with
resuscitation,
• <24 hrs – Body weight increases due to extracellular
water expansion by 6-10 litres.
– This can be overcome by careful intra operative
management of fluid balance
• 1-10 days – Total body protein will diminish by 15% and
body weight will reach negative balance as the expansion
of extra cellular space resolves
– This can be overcome by blocking Neuro endocrine
responsewith epidural analgesia and early enteral feeds

35. Avoidable factors that compound
the response to injury
1. Continuing hemorrhage
2. Hypothermia
3. Tissue edema
4. Tissue under perfusion
5. Starvation
6. Immobility

36. • Volume loss: Careful limitation of intra
operative administration of colloids and
crystalloids so that there is no net weight
gain
• Hypothermia : RCT(Randomized Clinical
Trial) have shown that normothermia by
an upper body forced air heating cover
reduces wound
infection, cardiac complications and
bleeding and transfusion requirements

37. • Tissue edema : During systemic
inflammation, fluid,plasma,
proteins, leucocytes,
macrophages and electrolytes
leave the vascular space and
accumulate in the tissues.
• This can diminish the alveolar diffusion of
oxygen and may lead to reduced renal
function

38. • Systemic inflammation and tissue under perfusion: the
vascular endothelium controls vasomotor tone and micro
vascular flow and regulates trafficking of nutrients and
biologically active molecules.
• Administration of activated protein C to critically ill patients
has been shown to reduce organ failure and death and is
thought to act, in part, via preservation of the micro
circulation in vital organs
• Maintaining the normoglycemia with insulin infusion during
critical illness has been proposed to protect the
endothelium, probably in part, via inhibition of excessive
iNOS(Inducible Nitric Oxide Synthatase)- induced NO
(Nitric Oxide )release , and thereby contribute to the
prevention of organ failure and death

39. • Starvation : During starvation, the body is faced
with an obligate need to generate glucose to
sustain cerebral energy metabolism(100g of
glucose per day)
• This is achieved in the first 24 hours by
mobilizing glycogen stores and thereafter by
hepatic gluconeogenesis from amino acids,
glycerol and lactate.
• The energy metabolism of other tissues is sustained
by mobilizing fat from adipose tissue
• Such fat metabolisation is mainly dependent on a fall
in circulating insulin levels.

40. • Eventually , accelerated loss of lean tissue is
reduced as a result of the liver converting free
fatty acids into ketone bodies, which can serve as
a substitute for glucose for cerebral energy
metabolism.
• Provision of 2 litres of iv 5% D as iv fluids for
surgical patients who are fasted provides 100g
of glucose per day and has a significant protein
sparing effect.
• Modern guidelines on fasting prior to anesthesia
allow intake of clear fluids upto 2 hours before
surgery.
• Administration of carbohydrate drink at this time
reduces perioperative anxiety and thirst and
decreases post operative insulin resistance

41. • Immobility : Has been recognized as a
potent stimulus for inducing muscle
wasting. Early mobilization is an
essential measure to avoid muscle
wasting

42. A prospective approach to prevent
unnecessary aspects of the surgical stress
response
1. Minimal access techniques
2.Blockade of afferent painful stimuli
(epidural anesthesia)
3. Minimal periods of starvation
4. Early mobilization

43. Therapeutic implications
The catabolic response to injury is always a
major concern in postoperative care. Three
types of interventions were tried to reduce this.
These are:
–Nutritional
–Hormonal
–Biologic

44. Nutritional :
Three important aspects of nutrition have to
be considered
• Route of administration (enteral/parenteral): enteral
nutrition is preferred. It improves the protein
balance & clinical outcome
• Timing (early versus late feeding):
– enteral nutrition is started as early as possible. Early
is superior in its effects on catabolic & hyper
metabolic response to injury.
– A slower rate of fluid resuscitation after trauma
hemorrhage leads to a faster restoration of the
depressed cell-mediated immunity. Whereas rapid fluid
resuscitation produces a prolonged depression of
immune responses.

45. Composition of feeding
(nutritional supplements):
commonly tried are
• Glutamine (both for enteral &
parenteral nutrition)
• Branched chain amino acids
– leucine, isoleucine &
valine
• Arginine can stimulate GH & IGF-1 release
and is a substrate for NO (Nitric Oxide)
production. At high doses it promotes
wound healing

46. • Unsaturated fatty acids: They can modulate
cytokine biology. Anti inflammatory effect of
fish oil is due to n-3 polyunsaturated fatty
acids.
• Fats rich in n-6 polyunsaturated fatty acids
enhance IL-1 production & tissue response
to cytokines.
• Fats rich in n-3 polyunsaturated fatty acids
have the opposite effect.
• Monounsaturated fatty acids decrease tissue
responsiveness to cytokine. IL-6 production is
enhanced by total unsaturated fatty acid
intake.

47. • Dietary nucleotides: may improve cell-
mediated immunity. A combination of
arginine, n-3 polyunsaturated fatty acids
& nucleotides hasbeen used as“immune
enhancing “diet.

48. Hormonal treatment:
• Anabolic hormones –GH, IGF-1 & insulin
promote positive nitrogen balance.
• GH supplementation improves wound healing
& decreases postoperative wound infection
rate.
• IGF-1 mediates most of the metabolic effects
of GH. Exogenous IGF-1 reduces gut
mucosal atrophy in trauma.
• Both GH & IGF-1 are powerful modulators of
the effector function of phagocytic cells.

49. Biologic treatment:
• Various strategies have been tried, which
include antibodies to endotoxin, TNF or IL-6.
• But most patients with sepsis have elevated
levels of cytokines & other mediators.
• So this canbe given as“prophylaxis” for patients
with high risk, for example, those undergoing
major surgical procedures.
• Genetic alterations can occur during injury &
infection. Hence in the future, gene therapy
will have a role in the management of trauma
patients who are critically ill.