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
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
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
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