2. JOHN HUNTER (1794)
“Treatise on the Blood,
Inflammation and gunshot
wounds”
“Impressions are capable of
producing or increasing natural
actions and are then called
stimuli, but they are capable of
producing too much action as
well as depraved, unnatural or
what we call diseased action.”
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3. Objectives
Homeostasis - Concept
Components of Responses
Mediators of Responses
Phases of Responses & Key elements
Factors – Exacerbate & Avoidable
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4. 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.
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5. Basic Concepts in Homeostasis
Homeostasis is the foundation of normal
physiology.
Stress-free peri-operative care helps to restore
homeostasis following elective surgery.
Resuscitation, surgical intervention & critical care
can return the severely injured patient to a
situation in which homeostasis becomes possible
once again.
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6. Nature of the injury response
Metabolic response to injury is Graded and
evolves with time
the more severe the injury,
the greater the response Immunological
Hormonal
Cellular
response
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12. Mediators of Injury Response
Neuro – Endocrine [ Hormonal ]
Immune System [ Cytokines ]
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13. Neuro-endocrine response to injury/critical
illness
Biphasic :
Acute phase - An actively secreting pituitary & elevated
counter regulatory hormones (cortisol, glucagon,
adrenaline).Changes are thought to be beneficial for short-
term survival.
Chronic phase - Hypothalamic suppression & low serum levels
of the respective target organ hormones. Changes contribute
chronic wasting.
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18. Phases – Physiological response
[ David Cuthbertson – 1930 ]
Injury
EBB
24-48 HRS
FLOW
3-10 DAYS
RECOVERY
SHOCK
CATABOL
ISM
ANABO
LISM
Hours Days Weeks
BREAKING DOWN
ENERGY STORES
BUILDING UP
USED ENERGY14-03-2016Metabolic Response to Injury - Dr.R.Durai
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19. Ebb and Flow Phases
Phase Duration Role Physiological Hormones
Ebb 24 - 48
hrs
Conserve - blood
volume & energy
reserves - Repair
↓ BMR, ↓ temp, ↓
CO, hypovolaemia,
lactic acidosis
Catecholamines
, Cortisol,
aldosterone
Flow
Catabolic 3 – 10
days
Mobilisation of
energy stores –
Recovery & Repair
↑ BMR, ↑ Temp, ↑ O2
consump, ↑ CO
Cytokines + ↑
Insulin,
Glucagon,
Cortisol,
Catechol but
insulin
resistance
Anabolic 10 – 60
days
Replacement of lost
tissue
+ve Nitrogen balance Growth
hormone, IGF14-03-2016 Metabolic Response to Injury - Dr.R.Durai
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20. Key catabolic elements of flow phase
Hypermetabolism
Alterations in skeletal muscle
protein
Alterations in Liver protein
Insulin resistance
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21. 1. Hypermetabolism
Majority of trauma patients - energy expenditure appr.
15-25% > predicted healthy resting values.
Factors which increases this metabolism :
* Central thermodysregulation
* Increased sympathetic activity
* Increased protein turnover
* Wound circulation abnormalities
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22. 2.Skeletal muscle – Metabolism
1. Muscle wasting – result of ↑ muscle protein degradation
+ ↓ muscle protein synthesis. (RS & GIT). Cardiac muscle is
spared.
2. Is mediated at a molecular level mainly by activation of
the ubiquitin-protease pathway.
3. Lead - Increased fatigue, reduced functional ability,
↓QOL & ↑ risk of morbidity & mortality.
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23. 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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24. 4.Insulin resistance
Hyperglycaemia is seen – ↑ glucose
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.
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25. Changes in Body composition
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
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27. 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.
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)
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28. 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
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
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29. 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 response
with epidural analgesia and early enteral feeds
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32. Avoidable factors that compound the
response to injury
Continuing haemorrhage
Hypothermia
Tissue oedema
Tissue underperfusion
Starvation
Immobility
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33. Avoidable Factors
Volume loss : Careful limitation of intra operative
administration of colloids and crystalloids so that
there is no net weight gain.
Hypothermia : RT – maintaining normothermia by
an upper body forced air heating cover ↓ wound
infection, cardiac complications and bleeding and
transfusion requirements.
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34. Avoidable Factors
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.
Maintaining the inormoglycemia with insulin infusion
during critical illness has been proposed to protect the
endothelium and thereby contribute to the prevention
of organ failure and death.
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35. Avoidable Factors
Starvation : During starvation, the body is faced
with an obligate need to generate glucose to
sustain cerebral energy metabolism(100g of
glucose per day).
Provision of at least 2L of IV 5% dextrose for
fasting patients provides glucose as above.
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36. Avoidable Factors
Tissue oedema : is mediated by the variety of
mediators involved in the systemic inflammation.
Careful administration of anti-mediators & reduce
fluid overload during resuscitation reduces this
condition.
Immobility : Has been recognized as a potent
stimulus for inducing muscle wasting. Early
mobilization is an essential measure to avoid muscle
wasting.
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37. App. to prevent unnecessary aspects of
stress response
Minimal access techniques
Minimal periods of Starvation
Epidural analgesia
Early mobilization
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