Metabolic response in injury

Metabolic response in injury

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

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

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

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

Difference between elective and accidental injury

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 (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, insulin resistance Peak early and disappear from plasma

Stimulate IL-6 release: reduce level of insulinlike 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 (Antiinflammatory 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

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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

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