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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, bodytemperature and oxygen consumption
Often associated with hemorrhage, resulted in
hypoperfusion and lactic acidosis With restoration of blood volumemore
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 > 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 phaseprotein synthesis)
Initiation of process of local control and elimination ofoffending agent
(fever response, neutrophil and macrophagerecruitment)
Signals to specific immune system to elimination ofoffending 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 (chief:cytokines 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 +PG+IL-1: acute phase response
fever, acute phase protein synthesis, insulinresistance
Peak early and disappear from plasma
Stimulate IL-6 release: reduce level of insulin-like growth factor (IGF-1) proteolysis andamino acid release from muscle, acute phaseproteins
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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 frominflammation
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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
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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