Stress response to Trauma

Dr. Jagathi Perera

Systemic responses to injury

Sympathetic nervous system activation Endocrine response Immunological Haematological changes

Cytokine production Acute phase reaction Neutrophil leucocytosis Lymphocyte proliferation

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Stress response
Hormonal and metabolic changes that follow 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, or even severe psychological stress

Response local and general

Local response General response

inflammation

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

Flow phase

depressed enzymatic activity Low oxygen consumption. below normal Cardiac output subnormal core temperature lactic acidosis

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

anabolic flow phase

Mobilize fat and protein Increase urinary nitrogen excretion and weight loss restores fat and protein stores Gain weight

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Phases
Phase Ebb Durati on 24hrs Or less Role maintenance of blood volume Physiological decr. BMR, decr. Temp, decr. O2 consump; vasoconstriction; incr. CO, incr. HR; acute phase proteins
incr. BMR, incr. Temp., incr. O2 consumption negative nitrogen balance positive nitrogen balance

Hormones Catecholamines Cortisol, Aldosterone

Flow Catabolic

3-10 days

maintenance of energy

Incr. glucagon, cortisol, catecholamines insulin, but insulin resistance Growth hormone, IGF

Anabolic 10-60
days

replacement of lost tissue

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Metabolic responses to trauma

Adaptive reactions to promote recovery Similar responses seen to trauma, burns, sepsis and surgery Extent of response proportional to severity of insult An appropriate response maintains homeostasis and allows wound healing

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But,
An excessive response can produce a systemic response
can cause systemic inflammatory response syndrome (SIRS) Multiple organs dysfunction syndrome (MODS) can result from SIRS

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Understanding these
Improve supportive therapies Adapt strategies for altering the responses

Enhance beneficial features and promote recovery suppress or limit debilitating features that lead to organ dysfunction.

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Activation of the response

afferent neuronal impulses from site of injury (Endocrine response)

Sensory nerve spinal cord medulla hypothalamus Activated leucocytes, fibroblasts, endothelial cells

Cytokines released from cells

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Endocrine response
Hypothalamus
Sympathoadrenal response
Adrenal medulla Presynaptic N. terminals

Hypothalamic-pitutary- adrenal axis

Ant pitutary
Prolactin GH ADH Post pitutary

Adrenalin

Noradrenalin

ACTH

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Endocrine response

Characterized by

Inc secretion of pituitary hormones

Act on target organs hormones

Activation of sym nervous system Inc catabolism to mobilize substrates to provide energy Retain salt and water

Overall effects

Maintain fluid volume Cardiovascular homeostasis

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Hormonal changes
Endocrine gland Hormones ACTH Growth hormone TSH FSH and LH ADH Cortisol Aldosterone Insulin Glucagon Thyroxine, tri-iodothyronine Change in secretion Increases Increases May increase or decrease May increase or decrease Increases Increases Increases Often decreases Usually small increases Decrease
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Anterior pituitary
Posterior pituitary Adrenal cortex

Pancreas
Thyroid
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Metabolic sequelae of endocrine response

Net effect is inc catabolic hormones Provide food substrates from catabolism of

Carbohydrate fat Protein

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Cytokines

Low molecular wt proteins

IL, Interferone leucocytes Fibroblasts Endothelial cells

Produced early in the response from activated

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 in liver

Eg; C-reactive proteins, fibrinogen, macroglobulins

Act as inflammatory mediators, Anti-proteinases, scavenges Help in tissue repair

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Why all these are necessary ?

Healing wound need more energy

Integrated Metabolic Response

wound / inflammatory focus involve liver, skeletal muscle, kidneys heart plays a major role

By providing the force for the high rate of blood flow

to support increased exchange of nutrients and other substances between organs.

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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 and muscle wasting Glucose intolerance.

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Wound plays a principal role

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 is sufficient. Lactate released into the circulation for transport to the liver.

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Liver

Produces glucose for wound healing

From glycogenolysis From gluconeogenesis

From lactate

amino acids from gut and skeletal muscles from inflammatory cells in wound

Synthesizes proteins

Energy required are obtained by fat oxidation

acute phase proteins Amino acids obtained from skeletal muscles

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Skeletal muscles

Provide amino acids

To liver To kidney

Stop storing glucose

So available for wound

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Skeletal muscles

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

muscle protein breaks down rapidly Release creatine and creatinine, 3-methylhistidine, potassium, magnesium, and amino 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 increased solute 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

Degree is proportional to severity of trauma.

VO2, cardiac output, Metabolic rate

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

Glucose is directed to the wound

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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 hepatic glucose production during recovery

As reserves are limited

From lactate and from Alanine

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Glucose Intolerance and Insulin Resistance

During ebb-phase, blunt insulin response to hyperglycemia During flow phase, normal or exaggerated response Insulin resistance is caused by a post-receptor defect.

Peripheral tissueprincipally skeletal muscleis a major site of insulin resistance

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Protein metabolism
Stimulate by cortisol (inhibit by insulin ) Skeletal Muscle wasting - most striking feature

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

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Dissolution of skeletal muscle protein

Serve many purposes. Provides amino acids for protein synthesis

In wound, other inflammatory foci, and the liver. glucose production by the liver ammonia production in the kidneys A specific fuel for the gut mucosa Other tissues with rapid cell turnover

Provides amino acids for

Provides glutamine

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 adequate body fluid volumes

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Can we manipulate stress response ?

Manipulating the metabolic Response1

Excellent surgical care.

Aggressive and prompt resuscitation Restoration of tissue oxygenation Debridement of necrotic tissue Drainage of pus Wound repair

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Manipulating the metabolic Response2

Regional anesthesia ( adequate

somatic and sympathetic block) Prevent endocrine and metabolic responses

Improve postoperative nitrogen balance Decrease muscle protein breakdown

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Manipulating the metabolic Response2

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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Manipulating the metabolic Response3

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.

markedly reduced cumulative nitrogen loss. also preserved muscle strength. ? Routine clinical use*
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Growth hormone

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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 (180 mg/dl) will

Tight control of blood sugar with insulin

Impair phagocytosis and immune function increase CO2 production and ventilatory requirements increase vascular tone and reduce regional blood flow alter collagen formation.

prevent above effects Reduce net protein loss.

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Influence of anaesthetic agents

Opioids

high doses suppress pit adr axis cortisol Etomidate

IV induction agents

Decrease Cortisol & aldosterone synthesis (6-12hrs)

High dose benzodiazepine

Decrease cortisol secretion

Inhibit stress responses mediated by SNS So reduce sympathoadrenal and Cardiovascular effects

Clonidine

Inhalation agents

Dec catecholamine prior to surgery No effect after the operative stimulus

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Stress response -summary

Hormonal changes initiated by neuronal activation of hypothalamic pituitaryadrenal axis Overall metabolic effect is catabolism of stored body fuels Magnitude and duration is proportional to surgical injury and complications Other changes inc cytokine production, triggered locally as a tissue response to injury

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