Metabolic Response to trauma

E. E. Okon MD
 Contents

Introduction

Features of metabolic response

Phases

Mediators

Neurohormonal

Inflammatory

Activators of metabolic response

Influencers of metabolic response

Factors affecting metabolic response

Methods to limit response

References
 Introduction

Trauma – leading cause of mortality & morbidity for
individuals under age 45.
 Accidental or operative

Metabolism – complex system of interrelated
biochemical reactions & physiological responses
necessary to sustain life.

Traumatic injury triggers certain responses – CVS,
metabolic, neurohormonal and inflammatory.
 Adaptive or stress responses
 Introduction

Why these changes?
 Return the body to pre-trauma/pre-injury state



Magnitude of metabolic response is directly proportional to the
severity of injury



Goal of metabolic response is to maintain homeostasis and
return the individual to health, however, major response may
progress to SIRS & MODS



Modern surgical principles are to minimize metabolic response
and shorten recovery times
 Features of metabolic response


Sir David P. Cuthbertson in 1930 divided the
metabolic response to trauma in humans into

Ebb phase – 24-48hrs

Flow phase – Days to weeks
 Phases

Ebb Phase – occurs within 24 – 48hours

Characterized by
 Hypovolemia
 Decreased basal metabolic rate
 Reduced cardiac output
 Hypothermia
 Lactic acidosis



Trigger and upregulate the neuro-endocrine system leading to
the release of hormones and catecholamines
 CRH-ACTH-Cortisol, GH, Ghrelin, ADH, Aldosterone
 Sympathetic Nervous system -Catecholamines


Following resuscitation during the ebb phase, leads to a
hypermetabolic phase similar to SIRS.
 Increased basal metabolic rate
 Increased cardiac output
 Raised body temperature
 Leukocytosis
 Increased oxygen consumption
 Increased gluconeogenesis



Main physiological role of the ebb phase is to conserve both
circulating volume and energy stores for recovery and repair.
 Endocrine response

CRH-ACTH-Cortisol (HPA Axis)
 Rises rapidly after trauma
 Maintains energy supply
 Depresses the action of insulin
 Impairs cellular immunity
 Stimulates Hepatic acute phase protein synthesis
with IL-6
 Growth Hormone-IGF-1

Raised for days

Gh acts directly with GH receptors and via
Hepatic IGF-1

Suppression of IGF-1-IGFBP
 Ghrelin

A natural ligand for GH-secretagogue receptor 1a(GHS-R1a)

Appetite stimulant

Role in promoting GH release

Studies –
 Inhibits proinflammatory cytokine release
 Reduces neutrophil infiltration
 Ameliorates intestinal barrier dysfunction
 Attenuates organ injury
 Improves survival
 Positive predictor of ICU-survival in septic patients
 ADH

Mediates anti-diuresis

Stimuli
 Osmotic factors
 Non-osmotic factors
 Aldosterone

Released by zona glomerulosa

Stimuli
 Renin-angiotensin mechanism
 Decreased extracellular Na+
 Increased blood K+
 ACTH
 Catecholamines

Released from adrenal medulla

Increased with seconds of trauma

Functions
 Vasoconstriction
 Maintains energy supply by stimulating
glycogenolysis, gluconeogenesis and lipolysis
 Impairs T-cell proliferation, IL-2 receptor expression
and immunoglobulin production by B-cells
 Flow Phase

Initial Catabolic phase – lasts 3 -10 days

Anabolic phase – lasting weeks
 Flow phase
Initial catabolic phase


Hypermetabolism & Energy Metabolism

Increase in BMR

Alterations in skeletal muscle protein

Increased gluconeogenesis

Alterations in liver protein

Acute phase reactants

Cytokines, lipid mediators

Insulin resistance
 Anabolic phase

Restoration of lean body mass, body weight

Full recovery

 Flow phase - Hypermetabolism

Increase in Resting Energy Expenditure (R.E.E)
after trauma.

Severity of injury, state of nutrition determine
the degree & duration of hypermetabolism

Average REE in a normal adult – 6300-7500J
(1500 – 1800 kcal) in 24hr
 Major operation – 10%
 Major fracture – 10-25%
 Sepsis – 50-80%
 Sever burns - >40-100%
 Hypermetabolism

Normal resting energy expenditure calculation

Harris-Benedict formula

Male: 66+(13.7*wt)+(5*ht)-(6.8*age)

Females: 65.5+(9.6*wt)+(1.7*ht)-(4.7*age)

Increased activity of CVS, respiratory &
endocrine.

Evaporative water loss via damaged skin in
burns

Hypothalamic thermodysregulation by Il-1, IL-6

Increased rate of recycling of TG & Glucose
substrates
 Changes in Glucose Metabolism

Hyperglycemia & Glucosuria occur
 Increased glycogenolysis: mediated by glucagon and EPI
 Increased gluconeogenesis: cortisol, GH, EPI
 Insulin resistance: reduced uptake of glucose into cells
due to counter-regulatory hormones
 Reduced tissue oxidation of glucose

↑Glucose turnover – essential for wound healing &
inflammatory cells
 Changes in Lipid metabolism

Lipolysis

TG breakdown – FFA & Glycerol

Lipolysis becomes principal source of energy
(75-90%) if glucose not provided after 21 days
of starvation

Endpoint
 Weight changes

Major trauma – 400-600g/day

Severe sepsis – 1.5kg/day
 Alterations in Skeletal muscle
Protein

Muscle proteolysis and breakdown due to Il-1 &
TNF- alpha
 IL-1 stimulates PGE2 activity on muscle
 Only spared muscle is the cardiac muscle

Mediated at the molecular level by activation of
ubiquitin-proteasome pathway




Sequela – Increased essential amino acids;
 Decrease in non-essential amino acids
(glutamine & alanine)

Protein catabolism exceeds synthesis resulting
in negative nitrogen balance
 Magnitude of trauma, age, sex, nutritional state

 Alterations in Skeletal muscle
Protein

Clinical Features
 Increased Fatigue
 Reduced functional ability
 Decreased quality of life
 Increased risk of morbidity & mortality
 Alterations in liver protein

Peripheral blood mononuclear cells secrete cytokines – IL-1, IL-
6, TNF-α which stimulate heaptic synthesis of Acute phase
reactants.

Positive Reactants: Increase in levels
 CRP – activates complement & opsonizes dead cells; rises
within 4-6hrs of trauma and peaks at 48hrs.
 Serum amyloid A protein – 100-1000x increase
 Fibrinogen
 Ceruloplasmin
 Factor VIII
 vWF

Negative Reactants: Decrease in levels
 Albumin – Transcapillary Escape rate (increases 3fold)
 Transferrin
 Insulin resistance

Increased insulin release mediated by alpha-2
adrenergic receptors on the pancreas

Hyperglycemia – due to increased glucose
synthesis

Decreased glucose uptake by peripheral
tissues

Insulin resistance mediated by cytokines and
decreased responsiveness of insulin-dependent
glucose transporter.

The more severe the insult, the greater the
insulin resistance.
 Immunological changes

Trauma patient is susceptible to sepsis.
 Abnormalities in APCs – macrophage/monocytes/dendritic
cells

Diminshed capacity to phagocytose

Increased lysosome stability & reduced oxidative burst.

Reduced expression of MHC Class I & II

Impaired antigen presentation to lymphocytes

Reduced production of cytokines like IL-1, IL-6, TNF-
alpha, IL-12

Increased production of PGE2
 Decreased Lymphocyte function
 Decreased PMN function
 Perioperative blood transfusion
 Gut integrity
 Activators of metabolic response

Pain
 Stimulate the release of ACTH, catecholamines, GH
and glucagon

Hypovolemia

Cytokines: IL-1,2,4,6, 8, 10 and TNF-a
 Influencers of the metabolic
response

Nature & Severity of injury and associated pain

Burns > Sepsis(peritonitis)>multiple injuries
(fractures)>elective surgery

Nutritional status of the patient

Malnourished vs Well-nourished

Age and Sex

Old/Neonates vs young

Men vs women

Hypothermia
 Avoidable factors that compound
the injury process

Continuing hemorrhage

Hypothermia

Tissue edema

Tissue underperfusion

Starvation

Immobility
 Methods to limit avoidable factors

Tissue edema: Administration of anti-mediators
and reduce fluid overload
 Careful limitation administration of colloids and
crystalloids to avoid weight gain

Volume loss: Early control of hemorrhage.

Hypothermia
 Maintaining normothermia via air heating
 Preventing hypothermia decreases the risk of
wound infections, cardiac complications, bleeding
and transfusion requirements


Maintain normoglycemia via insulin infusion

Limit prolonged fasting & starvation – 2L of IV
5% dextrose sufficient to provide energy supply

Administration of activated protein C –
decreases organ failure and death.
 Acts by preserving the microcirculation in vital
organs

Early ambulation as immobility increases risk of
muscle wasting and proteolysis
Minimal access techniques


Treatment
 IV amino acids & Glucose
 Epidural analgesia and anesthesia
 Use of appropraite antibiotics
 Wound debridement and drainage of septic foci
 Early enteral feeding, supplementation with
arginine, glutamine, RNA, fish oil.
 Conclusion

Thorough understanding of the metabolic
responses ensures proper management of the
injured patient

Timely interventions in management reduces
morbidity and mortality.
 References
th

Principle and practice of Surgery, E.A Badoe 4
Edition
th

Bailey's & Love Short Practice of Surgery 25
Edition
th

Schwartz's Principles of Surgery 10 Edition



Essential surgical practice 4th Edition Sir Alfred
Cuschieri