2B SURGERY 1

METABOLIC RESPONSE OF TISSUE TO INJURY

S-04 Dr. DO MINGO | SEPTEMBER 26, 2018

Topic Outline
NATURE OF THE INJURY RESPONSE
I. Homeostasis  Metabolic response to injury is Graded
II. Nature of the injury response and evolves with time
III. Mediators of responses
IV. Phases of response and key elements
V. Factors- exacerbate and avoidable

HOMEOSTASIS

REFERENCE:
METABOLIC RESPONSE OF TISSUE TO
INJURY
Prof. Utham Murali. M.S; M.B.A.

Why??
 Restore tissue function
 Eradicate invading Microorganisms.

Objectives
 Homeostasis - Concept
 Components of Responses
 Mediators of Responses
 Phases of Responses & Key elements
 Factors – Exacerbate & Avoidable

Homeostasis
 Maintenance of nearly constant
conditions in the internal environment.
 Essentially all organs and tissues of the
body perform functions that help
maintain these constant conditions.

Basic Concepts in Homeostasis

 Homeostasis is the foundation of normal Response Components
physiology.
 Stress-free peri-operative care helps to  Physiological Consequences
restore homeostasis following elective
surgery.  Metabolic Manifestations
 Resuscitation, surgical intervention &  Clinical Manifestations
critical care can return the severely
injured patient to a situation in which  Laboratory Changes
homeostasis becomes possible once
again.

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RESPONSE COMPONENTS respective target organ hormones.
Changes contribute chronic wasting.
Physiological
 ↑ Cardiac Output
 ↑ Ventilation
 ↑ Membrane Transport
 Weight loss
 Wound Healing

Metabolic
 Hypermetabolism
 Acclerated Gluconeogenesis
 Enhanced Protein breakdown
 Increased Fat Oxidation

Clinical
 Fever
 Tachycardia
 Tachypnoea
 Presence of wound or Inflammation Corticotrophin-releasing factor (CRF)
 Anorexia released from the hypothalamus increases
adrenocorticotrophic hormone (ACTH)
Laboratory release from the anterior pituitary.
 Leucocytosis/Leucopenia
 Hyperglycemia  ACTH then acts on the adrenal to
 Elevated CRP/Altered acute phase increase the secretion of cortisol.
reactants  Hypothalamic activation of the
 Hepatic/Renal Dysfunction sympathetic nervous system causes
release of adrenalin and also stimulates
MEDIATORS OF INJURY RESPONSE release of glucagon.
 Intravenous infusion of a cocktail of
 Neuro – Endocrine [ Hormonal ] these ‘counter-regulatory’
 Immune System [ Cytokines ] hormones(glucagon, glucocorticoids
and catecholamines) reproduces many
aspects of the metabolic response to
Neuro-endocrine response to injury/critical injury.
illness  Innate immune system (principally
macrophages) interacts in a complex
Biphasic : manner with the adaptive immune
system (T cells, B cells) in co-generating
 Acute phase - An actively secreting the metabolic response to injury.
pituitary & elevated counter regulatory
hormones (cortisol, glucagon, Purpose - Neuro-endocrine response
adrenaline).Changes are thought to be
beneficial for short-term survival.  Provide essential substrates for
survival
 Chronic phase - Hypothalamic  Postpone anabolism
suppression & low serum levels of the  Optimise host defence

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Key catabolic elements of flow phase

 Hypermetabolism
 Alterations in skeletal muscle protein
 Alterations in Liver protein
 Insulin resistance

1. Hypermetabolism

 Majority of trauma pts - energy

expenditure appr. 15-25% > predicted
healthy resting values.

PHASES
PHYSIOLOGICAL RESPONSE
[ DAVID CUTHBERTSON – 1930 ]
Factors which increases this metabolism :
 Central thermodysregulation
 Increased sympathetic activity
 Increased protein turnover
 Wound circulation abnormalities

2. Skeletal muscle – Metabolism

 Muscle wasting – result of ↑ muscle

protein degradation + ↓ muscle protein
synthesis. (RS & GIT). Cardiac muscle
is spared.
EBB AND FLOW PHASES
 Is mediated at a molecular level mainly
by activation of the ubiquitin-protease
pathway.
 Lead - Increased fatigue reduced
functional ability, ↓QOL & ↑ risk of
morbidity & mortality.

3. Hepatic acute phase response

 Cytokines – IL- 6 ↑ Synthesis of Positive

acute phase proteins : Fibrinogen &
CRP
 Negative acute reactants : Albumin
decreases
 Not Compensated

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4. Insulin resistance AVOIDABLE FACTORS

 Hyperglycaemia is seen – ↑ glucose a) Volume loss: Careful limitation of intra

production + ↓ glucose uptake –
peripheral tissues. (transient induction of
insulin resistance seen )
 Due – Cytokines & decreased
responsiveness of insulin- regulated
glucose transporter proteins.
 The degree of insulin resistance is ∞ to
magnitude of the injurious process.
CHANGES IN BODY COMPOSITION -
FOLLOWING SURGERY / CRITICAL ILL
PTS.
 Catabolism – Decrease in Fat mass &
Skeletal muscle mass.
 Body weight – paradoxically Increase
because of expansion of extracellular
fluid space.
operative administration of colloids and
crystalloids so that there is no net weight gain.
b) Hypothermia: RT – maintaining
normothermia by an upper body forced air
heating cover ↓ wound infection, cardiac
complications and bleeding and transfusion
requirements.
c) Administration of activated protein C - to
critically ill patients has been shown to ↓ organ
failure and death. It is thought to act, in part,
via preservation of the micro circulation in vital
organs.

FACTORS - ↑ RESPONSE TO INJURY d) Maintaining the normoglycemia with

insulin infusion during critical illness has been
1) Hypothermia proposed to protect the endothelium and
thereby contribute to the prevention of organ
2) Pain failure and death.
3) Starvation
4) Immobilisation
e) Starvation: During starvation, the body
5) Sepsis is faced with an obligate need to generate
glucose to sustain cerebral energy metabolism
6) Hypotension (100g of glucose per day).

AVOIDABLE FACTORS THAT COMPOUND f) Provision of at least 2L of IV 5%

THE RESPONSE TO INJURY dextrose for fasting patients provides glucose
as above.
1) Continuing haemorrhage
2) Hypothermia
g) Tissue edema: is mediated by the
3) Tissue oedema variety of mediators involved in the systemic
inflammation. Careful administration of anti-
4) Tissue underperfusion
mediators & reduce fluid overload during
5) Starvation resuscitation reduces this condition.

6) Immobility

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h) Immobility: Has been recognized as a
potent stimulus for inducing muscle wasting.
Early mobilization is an essential measure to
avoid muscle wasting.
App. to prevent unnecessary aspects of stress
response
 Minimal access techniques
 Minimal periods of Starvation
 Epidural analgesia
 Early mobilization
MCQ TIME
1.In stress response which one of the following
statements is false?
o A Metabolism and nitrogen excretion
are related to the degree of stress.
o B In such a situation there are
physiological, metabolic &
immunological changes.
o C The changes cannot be modified.
o D The mediators to the integrated
response are initiated by pituitary.
4.Which one of the following statements are
false regarding Optimal peri-operative care ?
o A Volume loss should be promptly
treated by large intravenous (IV)
infusions of fluid.
o B Hypothermia and pain are to be
avoided.
o C Starvation needs to be combated.
o D Avoid immobility.
5. Which one of the following interleukin
promotes the hepatic acute phase response in
injury ?
o A IL - 4
o B IL - 5
o C IL - 6
o D IL – 8

2. All of the following hormones regulate the

ebb phase except –
o A Glucagon
o B Cortisol
o C Aldosterone
o D Catecholamines

3.Which one of the following will not

exacerbate the metabolic response to surgical
injury ?
o A Hypothermia
o B Hypertension
o C Starvation
o D Immobilisation

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