Metabolic response in injury Metabolic response in injury

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Metabolic response in injury
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Metabolic response in injury

• 1930s, Cuthbertson
• 2 distinct periods of the post-traumatic
  responses
• Ebb phase
• Flow phase

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Ebb or shock phase

• Immediately following injury
• Usually brief in duration 12 to 24 hours
• Reduce Blood pressure, cardiac output, body
  temperature and oxygen consumption
• Often associated with hemorrhage, resulted in
  hypoperfusion and lactic acidosis
• With restoration of blood volume ? more
  accelerated responses

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Flow phase

• Hypermetabolism
• increase in basal metabolic rate
• increased oxygen consumption
• degree related to severity of inflammatory
  response
• temperature reasonable indicator

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Flow phase

• Hypermetabolism
• Increased cardiac output, increased urinary
  nitrogen losses, altered glucose metabolism,
  accelerated tissue catabolism
• Accidental injury similar to elective operation,
  but much more intensive and extend over a long
  period

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Altered glucose metabolism

• Hyperglycemia
• Ebb phase
• parallel severity of stress
• low insulin levels
• glucose production only slightly elevated
• Flow phase hyperglycemia persist
• insulin levels-normal or elevated
• increase hepatic glucose production
• profound insulin resistance

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Alteration in protein metabolism

• Extensive urinary nitrogen loss
• related to extent of trauma
• but also depend on previous nutritional status,
  age, sex (muscle mass)
• Unfed patients
• protein breakdown gt synthesis negative balance
• Exogenous calories and nitrogen ? increase
  protein synthesis, nitrogen loss not attenuated

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Alteration in fat metabolism

• Stored triglyceride mobilized
• Oxidized at accelerated rate (lipolysis)
• Ketosis is blunted

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Difference between elective and accidental injury
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Injury response

Neurohormonal
Inflammatory
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Inflammation

• Inflammatory response
• Primitive
• Complex
• Nonspecific immune system
• Inflammatory ? change in body composition ? acute
  challenge to homeostasis

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Inflammation

• Localized
• rubor(redness)
• tumor(swelling)
• calor(pain)
• dolor(heat)
• function laesa
• (loss of function)

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Inflammation

• Systemic
• hypermetabolism
• body protein catabolism
• insulin resistance
• fever
• acute phase protein response
• ? Dysregulation ? Septic multiple organ failure
  (major cause of death in ICU)

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Inflammation
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Advantages of inflammatory response

• Mobilization of fuel and substrates from muscle
  and adipose tissue to maximize visceral functions
  
• (gluconeogenesis, glutamine synthesis, acute
  phase protein synthesis)
• Initiation of process of local control and
  elimination of offending agent
• (fever response, neutrophil and macrophage
  recruitment)
• Signals to specific immune system to elimination
  of offending agent
• Reduction of fluid loss to maintain hydration
• Inflammatory response internal nutrition
  support, fluid resuscitation and antibiotic
  therapy

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Inflammation

• Mediated by host biochemicals
• hormones, growth factors, enzymes, kinins,
  complement, cytokines and eicosanoid
• Initial injury ? local mast cells? release
  numerous mediators (chiefcytokines and
  eicosanoids)
• Pro-inflammatory forms
• and anti-inflammatory forms

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Pro-inflammatory forms

• Early
• TNF, IL-1, IL-6,PGE2, LT4 (leukotriene-4)
• TNF PGIL-1 acute phase response
• fever, acute phase protein synthesis, insulin
  resistance
• Peak early and disappear from plasma
• Stimulate IL-6 release reduce level of
  insulin-like growth factor (IGF-1)? proteolysis
  and amino acid release from muscle, acute phase
  proteins

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Anti-inflammatory forms

• Inflammatory stimulus controlled and eliminated
• Anti-inflammatory cytokines
• IL-4, IL-10, IL-13, ecosanoids (PGE2,LT5)
• Bring inflammatory response to conclusion

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Neurohormonal response
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Neurohormonal response

• Afferent stimuli to vagus nerve
• Cytokine (e.g. TNF-alpha, IL-1)
• Baroreceptors
• Chemoreceptors
• Thermoreceptors
• CNS hypothalamus
• Parasympathetic acetylcholine
• Reduces tissue macrophage activation
• Release of proinflammatory mediators
  (Anti-inflammatory pathways)

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Neurohormonal response

• Glucagon, glucocorticoids and epinephrin
• Ebb phase
• Epinephrine sympthoadrenal axis help to maintain
  pressure, blood flow
• Flow phase
• Glucagon glycogenolytic and gluconeogenesis
• Cortisol mobilized amino acids from skeletal
  muscle and increases gluconeogenesis
• Catecholamines glycolysis and gluconeogenesis,
  increase lactate production form skeletal muscle,
  increase metabolic rate and stimulate lipolysis

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Acute phase proteins

• Fibrinogen
• C-reactive protein
• Inhibit generalized tissue destruction from
  inflammation

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Volume loss and tissue hypoperfusion

• Hemorrhage or plasma loss ? compensate to
  maintain adequate organ perfusion
• Pressure receptors (aortic arch, carotid artery)
• Volume receptors (wall of left atrium)
• Signal to brain
• Heart rate and stroke volume increase
• Stimulate release of ADH and aldosterone
• Prolonged shock ? oxygen delivery inadequate ?
  anaerobic metabolism ? lactic acidosis

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Tissue damage, Pain and Fear

• Injury of body tissue most important factor
  initiating stress response
• Afferent neural pathways from wound ?
  hypothalamus injury occurred
• Tissue destruction sensed in conscious patient as
  pain
• Stress response (pain and fear)? Efferent
  pathways from brain ? catecholamine ?fight or
  flight response

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THE END