The document discusses the metabolic response to injury, which aims to restore tissue function and eradicate microorganisms. It covers homeostasis, the components and mediators of the injury response, and its phases. The response involves increased cardiac output, ventilation, and membrane transport. It is graded based on injury severity. Mediators include neuroendocrine hormones and cytokines. The response has catabolic and anabolic phases to mobilize and replace lost resources. Factors like immobilization, sepsis, and hypothermia can exacerbate it, while avoiding continuing hemorrhage, hypothermia, and tissue issues can reduce its negative impacts.

1. METABOLIC
RESPONS TO
INJURY
Dr. Nabarun Biswas
(FCPS Surgery)
Registrar
Mymensingh Medical College Hospital

2. WHY ???
Restore tissue function
Eradicate invading microorganism

3. Learning Objectives
1. Homeostasis – Concept
2. Components of response
3. Mediators of response
4. Phases of response & key elements
5. Factors- exacerbate & avoidable

4. Homeostasis
Maintenance of constant condition in
internal environment
Essentially all organs & tissue of the body
perform functions that help to maintain
these constant condition

5. What is the basic concept of
Homeostasis ??
Body systems act to maintain internal
constancy
Complex homeostatic responses involving
the brain, heart, lung, kidneys and spleen
work to maintain body constancy
Response to injury, in general, beneficial to
the host and allow healing/ survival

6. Nature of injury response
Metabolic response to injury is Graded &
evolves with time; severity ∞ response
immunol
ogical
humoralcellular

7. What are the Response
component??
Physiological consequences
Metabolic manifestations
Clinical manifestation
Biochemical changes

8. Physiological
 ↑Cardiac output
 ↑Ventilation
 ↑Membrane transport
Weight loss
Wound healing

9. Metabolic
Hypermetabolism
Accelerated gluconeogenesis
Enhanced protein breakdown
Increased fat oxidation

10. Clinical
Fever
Tachycardia
Tachypnoea
Presence of wound / inflammation
Anorexia

11. Biochemical
Leucocytosis / leucopaenia
Hyperglycaemia
Elevated CRP / altered acute phase reactants
Hepatic / renal dysfunction

12. Mediators of injury response
Neuro-endocrine [Hormonal]
Immune system [Cytokines]

13. injur
y
plasma

14. Neuro-endocrine response to
injury
Biphasic:
Acute phase actively secreting pituitary
and elevated counter- regulatory hormones
(cortisol, glucagon, adrenaline). Changes
are thought to be beneficial for short-
term survival
Chronic phase  associated with hypothalamic
suppression and low serum levels of the
respective target organ hormones. Changes
contribute to chronic wasting

15. What is the purpose of this
response?
Provides essential substrates for survival
Postpone anabolism
Optimize host defense

16. Immunological response
Proinflammatory
phase
IL-1, IL-6, TNFα
Hypothalamus- pyrexia
Hepatic acute phase
protein
SIRS
MODS
Counter regulatory
phase
•IL-1 receptor antagonist &
TNF soluble receptor
•Prevent excessive
Proinflammatory activities
•Restore homeostasis
Compensated Anti-
inflammatory Response
Syndrome
(CARS)

17. How homeostasis maintained
after injury ??
@ Systemic level  cytokine antagonist
(CARS)
@ Tissue level  specialized pro-resolving
mediators (SPM)
Lipoxin
Resolvin
Protectin
Maresin

18. Phases- physiological response
(David Cuthbertson-1930)
Injury
EBB
24-48 Hrs
Hours
Shock
Flow
3-10 days
Recovery
10-60 days
Days Weeks
Anabol
ism
Catabo
lism

19. EBB & Flow phase
Phase Duration Role Physiological Hormons
EBB 24-48 Hrs Conserve –blood
volume & energy
for repair
↓BMR, ↓Temp
↓CO,
hypovolaemia,
lactic acidosis
Catecholamines,
cortisol,
aldosteron
Flow
Catabolic 3-10 days Mobilization of
energy store-
Recovery &
repair
↑BMR,
↑temp, ↑O2
consumption,
↑CO
Cytokines +
insulin,
glucagon,
cortisol,
catechole
Anabolic 10-60 days Replacement of
lost tissue
+ve Nitrogen
balance
GH, IGF

20. Key catabolic elements of
Flow phase
Hypermetabolism
Alteration in skeletal muscle protein
Alteration in liver protein
Insulin resistance

21. 1. Hypermetabolism
In trauma energy expenditure is 15-25%
above resting state
Factors that increases metabolism
– Central thermo - dysregulation
– Increased sympathetic activity
– increased protein turnover
– Wound circulation abnormality

22. 2. Skeletal muscle-metabolism
Muscle wasting = ↑Muscle protein degradation +
↓ muscle protein synthesis (RS & GIT), cardiac
muscle is spared
Provides amino acid to central organ/tissue for
metabolic support
Clinically, a patient with skeletal muscle wasting
will experience asthenia, increased fatigue, reduced
functional ability, decreased quality of life and an
increased risk of morbidity and mortality.

23. 3. Hepatic acute phase
response
Cytokines (IL-6)  ↑ synthesis of positive
acute phase protein : fibrinogen & CRP
Negative acute reactants (Albumin) : decreases
The acute phase protein response (APPR)
represents a ‘double-edged sword’

24. 4. Insulin resistance
Hyperglycaemia is seen – ↑ glucose
production + ↓ glucose uptake – peripheral
tissues. ( transient induction of insulin
resistance seen )
Due to – Cytokines & decreased
responsiveness of insulin- regulated glucose
transporter proteins.
The degree of insulin resistance is ∞ to
magnitude of the injurious process

25. Changes in Body composition
 Main labile energy reserve in the body is fat
Main labile protein reserve in the body is
skeletal muscle
Loss of protein mass results not only in
skeletal muscle wasting, but also depletion
of visceral protein mass

26. The chemical body composition of a normal 70-kg
male, fat-free mass/ lean body mass.
13 kg
12 kg
42 Li 28 Li
14 Li
3 kg
4 kg skeletal muscle
8 kg non-skeletal muscle

27. Changes in Body
composition…..cont.
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.

28. Changes in Body
composition…..cont.
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)
During total starvation, urinary loss of nitrogen
is rapidly attenuated by a series of adaptive
changes

29. Changes in Body composition…..cont.
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

30. In critically ill patients with
resuscitation
<24 hrs – Body weight increases due to
extracellular water expansion by 6-10 li
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

31. Factors - ↑ response to injury
1. Immobilization
2. Sepsis
3. Hypotension
4. Pain
5. Starvation
6. Hypothermia

33. Avoidable factors that compound
the response to injury
1. Continuing haemorrhage
2. Hypothermia
3. Tissue oedema
4. Tissue under perfusion
5. Starvation
6. Immobility

34. Avoidable Factors
Volume loss : Careful limitation of intra
operative administration of colloids and
crystalloids so that there is no net weight gain.
Hypothermia : maintaining normothermia by an
upper body forced air heating cover ↓ wound
infection, cardiac complications and bleeding and
transfusion requirements

35. 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.

36. Avoidable Factors
Maintaining the normoglycemia with insulin
infusion during critical illness has been
proposed to protect the endothelium and
thereby contribute to the prevention of organ
failure and death

37. 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

38. 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

39. Approach to prevent unnecessary
aspects of stress response
Minimal access techniques
Minimal periods of Starvation
Epidural analgesia
Early mobilization

40. To rebuild a better world for the future