Metabolic Response to Trauma 2007

7/29/2019 Metabolic Response to Trauma 2007

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Stress response toTrauma

Dr. Jagathi Perera


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Systemic responses to injury

Sympathetic nervous systemactivation

Endocrine response

Immunological Haematologicalchanges

Cytokine production

Acute phase reaction Neutrophil leucocytosis

Lymphocyte proliferation


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Stress response

Hormonal and metabolic changes thatfollow injury / trauma

Part of systemic responses to injury

Sympathetic nervous sys activation

Endocrine response

Immunological Haematological changes

Cytokine production

Acute phase reaction

Neutrophil leucocytosis

Lymphocyte proliferation


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Any stress, will initiate stress response injury, surgery, anaesthesia, burns, vascular occlusion,

dehydration, starvation, sepsis, acute medical illness, oreven severe psychological stress

Response local and general

Local response - inflammation

General response characterize by an acute catabolic reaction leading to

recovery and repair. protective, conserves fluid and provides energy for repair. Proper resuscitation may attenuate the response, but will

not abolish it.


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Phases

Ebb phase = period of shock depressed enzymatic activity Low oxygen consumption. below normal Cardiac output subnormal core temperature

lactic acidosis Flow phase

body is hypermetabolic, Increase cardiac output and oxygen consumption Increase glucose production. catabolic flow phase

Mobilize fat and protein Increase urinary nitrogen excretion and weight loss

anabolic flow phase restores fat and protein stores Gain weight


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Phases

Phase Duration

Role Physiological Hormones

Ebb 24hrs

Or less

maintenance ofblood volume

decr. BMR,decr. Temp,decr. O2 consump;vasoconstriction; incr.

CO, incr. HR; acutephase proteins

Catecholamines

Cortisol,Aldosterone

Flow

Catabolic

3-10

days

maintenance ofenergy

incr. BMR,incr. Temp.,incr. O2 consumptionnegative nitrogen

balance

Incr. glucagon,cortisol,catecholaminesinsulin, but

insulinresistance

Anabolic 10-60days

replacement

of lost tissue

positive nitrogenbalance

Growth hormone,

IGF


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Metabolic responses to trauma

Adaptive reactions to promoterecovery

Similar responses seen to trauma,

burns, sepsis and surgery Extent of response proportional to

severity of insult

An appropriate response maintainshomeostasis and allows woundhealing


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But,

An excessive response can producea systemic response

can cause systemic inflammatoryresponse syndrome (SIRS)

Multiple organs dysfunction syndrome

(MODS) can result from SIRS


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Understanding these

Improve supportive therapies

Adapt strategies for altering theresponses

Enhance beneficial features and promoterecovery

suppress or limit debilitating features thatlead to organ dysfunction.


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Activation of the response

afferent neuronal impulses fromsite of injury (Endocrine response)

Sensory nerve spinal cord

medulla hypothalamus

Cytokines released from cells

Activated leucocytes, fibroblasts,

endothelial cells


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Endocrine response

Hypothalamus

Sympathoadrenalresponse

Hypothalamic-pitutary- adrenalaxis

Adrenalmedulla

PresynapticN. terminals

Adrenalin Noradrenalin

Antpitutary

Postpitutary

ACTH Prolactin

ADHGH


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Endocrine response

Characterized by

Inc secretion of pituitary hormones Act on target organs hormones

Activation of sym nervous system Overall effects

Inc catabolism to mobilize substrates toprovide energy

Retain salt and water Maintain fluid volume

Cardiovascular homeostasis


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Endocrinegland

Hormones Change in secretion

Anteriorpituitary

ACTHGrowth hormoneTSH

FSH and LH

IncreasesIncreasesMay increase or decrease

May increase or decrease

Posteriorpituitary

ADH Increases

Adrenal cortexCortisolAldosterone

IncreasesIncreases

PancreasInsulinGlucagon

Often decreasesUsually small increases

ThyroidThyroxine,tri-iodothyronine

Decrease

Hormonal changes


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Metabolic sequelae of endocrine response

Net effect is inc catabolic hormones

Provide food substrates fromcatabolism of

Carbohydrate

fat

Protein


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Cytokines 1

Low molecular wt proteins IL, Interferone

Produced early in the response from activated leucocytes

Fibroblasts Endothelial cells

Mediate immunity and inflammation

Effects produce by influencing protein synthesis Influence cell proliferation, development, and function

Regulate local inflammation and wound healing.

activate multiple cellular responses


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Acute phase response

=Changes stimulated by cytokines

Produce acute phase proteins inliver

Eg; C-reactive proteins, fibrinogen,macroglobulins

Act as inflammatory mediators,

Anti-proteinases, scavenges

Help in tissue repair


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Why all these arenecessary ?

Healing wound need moreenergy


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Integrated Metabolic Response

wound / inflammatory focus

involve liver, skeletal muscle,kidneys

heart plays a major role

By providing the force for the highrate of blood flow

to support increased exchange ofnutrients and other substances betweenorgans.


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Regulation

Central nervous system

Autonomic nervous system Endocrine tissues

Mediators


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Regional Metabolic response

All processes occur simultaneously.

Evident Clinically as

Increased energy expenditure

Heat production and fever

Accelerated nitrogen excretion andmuscle wasting

Glucose intolerance.


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Healing wound has intense metabolic activity. requires energy and a variety of substrates.

Glucose is the principal fuel

Inflammatory cells utilize glucose for energy

production Cells have a marked capacity for glycolysis.

ATP is generated without consuming oxygen.

Ability persists even when oxygen delivery issufficient.

Lactate released into the circulation fortransport to the liver.

Wound plays a principal role


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Liver

Produces glucose for wound healing From glycogenolysis From gluconeogenesis

amino acids from gut and skeletal muscles

From lactate from inflammatory cells in wound

Synthesizes proteins acute phase proteins Amino acids obtained from skeletal muscles

Energy required are obtained by fatoxidation


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Skeletal muscles 1

Provide amino acids

To liver

To kidney

Stop storing glucose

So available for wound


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Skeletal muscles 2

Muscles in healthy persons

sensitive to insulin

serves as a site of glucose storage But muscle is resistant to insulin

after injury or critical illness

storage capacity is reduced

contributes to glucose intolerance

direct glucose to the healing wound.


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Skeletal muscles 3

muscle protein breaks down rapidly Release creatine and creatinine,

3-methylhistidine, potassium, magnesium, andamino acids.

Amino acids Precursors for protein synthesis in wound and in liver

Alanine and glutamine are disproportionately released

Alanine - readily converted to glucose in the liver

Glutamine serves

As a fuelfor the gut and rapidly proliferating cells(including inflammatory cells and fibroblasts)

As a precursor for renal ammonia production important mechanism for neutralizing excreted acid loads


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Contribution of Kidney

Kidneys must excrete an increasedsolute load

Urea, potassium, magnesium, weak acids,

and other intracellular constituents Increased Production of ammonia from

glutamine

to neutralize acid loads

Many of these processes require energy.


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Hypermetabolism

= increase total body metabolism Seen as increase

VO2, cardiac output, Metabolic rate

Degree is proportional to severity oftrauma. But there is a limit to this rise

Is affected by patient's age State of health before the illness


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Carbohydrate Metabolism

Liver normally produces sufficient glucose

During stress response,

endogenous glucose production is increased

Cortisol, catecholamines

Reduction in peripheral use

Hyperglycaemia persists

Glucose is directed to the wound

taken up and metabolised via glycolysis, evenwith adequate or increased oxygen delivery.


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Glucose production in liver

Hydrolysis of hepatic glycogen

Mobilizes glucose rapidly

Most important immediately after injury and

during acute stress states, such as shock, fever, pain, and anxiety (ebb-phase

responses).

Glycogen - not the major source of hepaticglucose production during recovery

As reserves are limited

From lactate and from Alanine


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Glucose Intolerance and InsulinResistance

During ebb-phase, blunt insulinresponse to hyperglycemia

During flow phase, normal or

exaggerated response Insulin resistance is caused by a

post-receptor defect.

Peripheral tissueprincipally skeletalmuscleis a major site of insulinresistance


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Protein metabolism

Stimulate by cortisol (inhibit by insulin )

Skeletal Muscle wasting - most strikingfeature

Both Injured and uninjured skeletal muscle Peak shortly after the onset of trauma

Return to normal with recovery. similar pattern to that of increased oxygen

consumption. Measured indirectly by nitrogen loss in

urine

Di l ti f k l t l l


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Dissolution of skeletal muscleprotein

Serve many purposes.

Provides amino acids for protein synthesis In wound, other inflammatory foci, and the liver.

Provides amino acids for glucose production by the liver ammonia production in the kidneys

Provides glutamine A specific fuel for the gut mucosa

Other tissues with rapid cell turnover wound, bone marrow, and macrophages of GIT


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Water & electrolyte metabolism

No of hormones influence

ADH

promote water retention

may lasts 3-5 days

Renin result of sym stimulation

Stimulate angiotensin II aldosterone Na & water retention

Support preservation of adequatebody fluid volumes


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Can we manipulate stressresponse ?


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Excellent surgical care.

Aggressive and prompt resuscitation

Restoration of tissue oxygenation

Debridement of necrotic tissue

Drainage of pus

Wound repair

Manipulating the metabolic Response1


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Regional anesthesia( adequatesomatic and sympathetic block)

Prevent endocrine and metabolic

responses Improve postoperative nitrogen balance

Decrease muscle protein breakdown



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Nutritional support Promote protein synthesis & other

anabolic processes

Reduce the net protein loss Enteral nutrition is preferred

Exercise and mobility

have clear anti-catabolic effects should be initiated as early as possible



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Provision of glutamine Enteral preparations enriched with glutamine

are now commercially available

Antibodies to endotoxin, IL-1, and TNF None of these demonstrated clinical benefit in

controlled trials.

Growth hormone

markedly reduced cumulative nitrogen loss. also preserved muscle strength.

? Routine clinical use*



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Manipulating metabolic Response 4

Insulin Attenuates Cortisol-induced breakdown of skeletal

muscle protein Hyperglycemia facilitate glucose uptake by the

inflammatory cells in the wound,

But excessive elevationsin excess of 10 mol/L (180mg/dl) will Impair phagocytosis and immune function increase CO2 production and ventilatory requirements increase vascular tone and reduce regional blood flow alter collagen formation.

Tight control of blood sugar with insulin prevent above effects Reduce net protein loss.


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Influence of anaesthetic agents

Opioids high doses suppress pit adr axis cortisol

IV induction agents Etomidate

Decrease Cortisol & aldosterone synthesis (6-12hrs)

High dose benzodiazepine Decrease cortisol secretion

Clonidine Inhibit stress responses mediated by SNS

So reduce sympathoadrenal and Cardiovascular effects

Inhalation agents Dec catecholamine prior to surgery

No effect after the operative stimulus


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Stress response -summary

Hormonal changes initiated by neuronalactivation of hypothalamic pituitary-adrenal axis

Overall metabolic effect is catabolism ofstored body fuels

Magnitude and duration is proportionalto surgical injury and complications

Other changes inc cytokine production,triggered locally as a tissue response toinjury

Metabolic Response to Trauma 2007

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