Metabolic Response in Injury

7/30/2019 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, 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

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Metabolic Response in Injury