Trauma triggers a complex metabolic response aimed at returning the body to homeostasis. This response involves two phases - an initial "ebb phase" characterized by hypometabolism followed by a "flow phase" of hypermetabolism. The hypermetabolic response is mediated by neuroendocrine and inflammatory factors like cortisol, catecholamines, cytokines and growth hormones which increase glucose and lipid metabolism while breaking down skeletal muscle. Understanding and limiting factors like hypothermia, edema and immobilization can reduce complications from this metabolic response.

1. Metabolic Response to trauma
E. E. Okon MD

2. 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

3. 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

4. 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

5. 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

7. 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


8.  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.

9. 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

10. Growth Hormone-IGF-1
 Raised for days
 Gh acts directly with GH receptors and via
Hepatic IGF-1
 Suppression of IGF-1-IGFBP

11. 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

12. ADH
 Mediates anti-diuresis
 Stimuli
 Osmotic factors
 Non-osmotic factors

13. Aldosterone
 Released by zona glomerulosa
 Stimuli
 Renin-angiotensin mechanism
 Decreased extracellular Na+
 Increased blood K+
 ACTH

14. 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

16. Flow Phase
 Initial Catabolic phase – lasts 3 -10 days
 Anabolic phase – lasting weeks

17. 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

18. Anabolic phase
 Restoration of lean body mass, body weight
 Full recovery


19. 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%

20. 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

21. 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

22. 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

23.  Endpoint
 Weight changes
 Major trauma – 400-600g/day
 Severe sepsis – 1.5kg/day

24. 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



25.  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


26. Alterations in Skeletal muscle
Protein
 Clinical Features
 Increased Fatigue
 Reduced functional ability
 Decreased quality of life
 Increased risk of morbidity & mortality

27. 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

29. 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.

30. 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

31. 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

32. 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

33. Avoidable factors that compound the
injury process
 Continuing hemorrhage
 Hypothermia
 Tissue edema
 Tissue underperfusion
 Starvation
 Immobility

34. 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


35.  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


36.  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.

38. Conclusion
 Thorough understanding of the metabolic
responses ensures proper management of the
injured patient
 Timely interventions in management reduces
morbidity and mortality.

39. References
 Principle and practice of Surgery, E.A Badoe 4
th
Edition
 Bailey's & Love Short Practice of Surgery 25
th
Edition
 Schwartz's Principles of Surgery 10
th
Edition

 Essential surgical practice 4th Edition Sir Alfred
Cuschieri