0
METABOLIC RESPONSE TO
TRAUMA
Sudarsan Agarwal
sushiagarwal@gmail.com
Pinnamaneni Medical College
Vijayawada
JOHN HUNTER
(1794)
• “Treatise on the
Blood, Inflammation and
gunshot wounds”
• “Impressions are
capable of producing or
i...
Basic Concepts in Homeostasis
1. Homeostasis is the foundation of normal
physiology.
2. Stress-free peri-operative care he...
• As a consequence of modern understanding to
metabolic response to injury, elective surgery
practice seeks to reduce the ...
Response Components
•
•
•
•

Physiological Consequences
Metabolic Manifestations
Clinical Manifestations
Laboratory Change...
Response Components
•
•
•
•
•

PHYSIOLOGICAL
Increased Cardiac Output
Increased Ventilation
Increased Membrane
Transport
W...
Response Components
•
•
•
•
•

CLINICAL
Fever
Tachycardia
Tachypnea
Presence of wound or
Inflammation
Anorexia

•
•
•
•

L...
Graded Nature of the injury response
• Metabolic response to injury is Graded and
evolves with time
Mediators of injury response
• Neuro endocrine ( Hormonal )
• Metabolic and Cytokine axes
Hormonal
Neuro-endocrine response to
injury/critical illness
The Neuro-endocrine response to severe
injury/critical illness is biph...
Purpose of Neuro- endocrine changes
following injury
The constellation of Neuro-endocrine changes
following injury acts to...
Proinflammatory cytokines
1. Il 1, Il 6, TNF alfa
2. NO
3. Endothelin 1
Cytokine antagonist
• Interleukin receptor antagon...
Physiological response to injury
The natural response to injury includes
1. Immobility
2. Anorexia
3. Catabolism
• In 1930, Sir David Cuthherstson derived the
metabolic response to injury in humans into
“ebb “ and “flow” phases
Metabolic changes after major trauma
(Cuthbertson, Lancet, 1942)
•
•
•
•
•
•
•
•
•
•

EBB (Untreated shock)
Dec body temp
...
Ebb and Flow
Phase

Duration

Role

Physiological

Hormones

Ebb

<24 hrs

Maintenance of blood Dec BMR, Dec temp,
Catecho...
Ebb
• Starts at the time of injury and lasts for
approximately 24-48 hours
• Main hormones in ebb phase are
catecholamines...
Flow
• It lasts for several wks
• This phase involves mobilization of body
energy stores for repair and recovery
• Followi...
Key catabolic elements of flow phase
•
•
•
•

Hypermetabolism
Alterations in skeletal muscle protein
Alterations in Liver ...
Hypermetabolism
Majority of trauma patients demonstrate energy
expenditure approximately 15-25% above
predicted healthy re...
Hypermetabolism
Hyper metabolism following injury:
1. Is mainly caused by an acceleration of futile
metabolic cycles
2. Is...
Skeletal muscle wasting
1. Provides amino acids for protein synthesis in
central organ/tissues
2. Is mediated at a molecul...
Hepatic acute phase response
• The Hepatic acute phase response represents a
reprioritization of body protein metabolism t...
Insulin resistance
• The degree of insulin resistance is directly
proportional to magnitude of the injurious
process.
• Fo...
• Main labile energy reserve in the body is fat
• Main labile protein reserve in the body is
skeletal muscle

• While fat ...
• With lean issue, each 1 g of nitrogen is
contained within 6.25 g of protein, which is
contained in approximately 36 g of...
• A normal human ingests 70-100 g of protein
per day, which is metabolized and excreted in
urine as ammonia and urea(14 g ...
• Following major injury, and particularly in the
presence of ongoing septic complications , this
adaptive change fails to...
In critically ill patients with
resuscitation,
• <24 hrs – Body weight increases due to extracellular water
expansion by 6...
Avoidable factors that compound the
response to injury
1. Continuing hemorrhage
2. Hypothermia
3. Tissue edema
4. Tissue u...
• Volume loss: Careful limitation of intra
operative administration of colloids and
crystalloids so that there is no net w...
• Tissue edema : During systemic
inflammation, fluid, plasma
proteins, leucocytes, macrophages and
electrolytes leave the ...
• Systemic inflammation and tissue under perfusion: the
vascular endothelium controls vasomotor tone and micro
vascular fl...
• Starvation : During starvation, the body is faced with
an obligate need to generate glucose to sustain
cerebral energy m...
• Eventually , accelerated loss of lean tissue is reduced as
a result of the liver converting free fatty acids into
ketone...
• Immobility : Has been recognized as a potent
stimulus for inducing muscle wasting. Early
mobilization is an essential me...
A prospective approach to prevent unnecessary
aspects of the surgical stress response
1. Minimal access techniques
2. Bloc...
Therapeutic implications
The catabolic response to injury is always a
major concern in postoperative care. Three
types of ...
Nutritional :
Three important aspects of nutrition have to be
considered
• Route of administration (enteral/parenteral): e...
Composition of feeding(nutritional
supplements): commonly tried are
• Glutamine (both for enteral & parenteral
nutrition)
...
• Unsaturated fatty acids: They can modulate
cytokine biology. Anti inflammatory effect of fish
oil is due to n-3 polyunsa...
• Dietary nucleotides: may improve cellmediated immunity. A combination of
arginine, n-3 polyunsaturated fatty acids &
nuc...
Hormonal treatment:
• Anabolic hormones –GH, IGF-1 & insulin promote
positive nitrogen balance.
• GH supplementation impro...
Biologic treatment:
• Various strategies have been tried, which include
antibodies to endotoxin, TNF or IL-6.
• But most p...
Metabolic response to injury
Metabolic response to injury
Metabolic response to injury
Metabolic response to injury
Metabolic response to injury
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Metabolic response to injury

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Metabolic response to injury and its clincal usefulness to minimize morbidity

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  1. 1. METABOLIC RESPONSE TO TRAUMA Sudarsan Agarwal sushiagarwal@gmail.com Pinnamaneni Medical College Vijayawada
  2. 2. JOHN HUNTER (1794) • “Treatise on the Blood, Inflammation and gunshot wounds” • “Impressions are capable of producing or increasing natural actions and are then called stimuli, but they are capable of producing too much action as well as depraved, unnatural or what we call diseased action.”
  3. 3. Basic Concepts in Homeostasis 1. Homeostasis is the foundation of normal physiology. 2. Stress-free peri-operative care helps to restore homeostasis following elective surgery. 3. Resuscitation, surgical intervention & critical care can return the severely injured patient to a situation in which homeostasis becomes possible once again.
  4. 4. • As a consequence of modern understanding to metabolic response to injury, elective surgery practice seeks to reduce the need for a homeostatic response by minimizing the primary insult (as for e.g – Minimal access surgery )
  5. 5. Response Components • • • • Physiological Consequences Metabolic Manifestations Clinical Manifestations Laboratory Changes
  6. 6. Response Components • • • • • PHYSIOLOGICAL Increased Cardiac Output Increased Ventilation Increased Membrane Transport Weight loss Wound Healing • • • • METABOLIC Hypermetabolism Acclerated Gluconeogenesis Enhanced Protein breakdown Increased Fat oxidation
  7. 7. Response Components • • • • • CLINICAL Fever Tachycardia Tachypnea Presence of wound or Inflammation Anorexia • • • • LABORATORY Leucocytosis/Leucopenia Hyperglycemia Elevated CRP/Altered acute phase reactants Hepatic/Renal dysfunction
  8. 8. Graded Nature of the injury response • Metabolic response to injury is Graded and evolves with time
  9. 9. Mediators of injury response • Neuro endocrine ( Hormonal ) • Metabolic and Cytokine axes
  10. 10. Hormonal
  11. 11. Neuro-endocrine response to injury/critical illness The Neuro-endocrine response to severe injury/critical illness is biphasic 1. Acute phase characterized by an actively secreting pituitary & elevated counter regulatory hormones (cortisol, glucagon, adrenaline).Changes are thought to be beneficial for short-term survival. 2. Chronic phase associated with hypothalamic s uppression & low serum levels of the respective target organ hormones. Changes contribute chronic wasting.
  12. 12. Purpose of Neuro- endocrine changes following injury The constellation of Neuro-endocrine changes following injury acts to 1. Provide essential substrates for survival 2. Postpone anabolism 3. Optimise host defense These changes may be helpful in the short term, but may be harmful in the longterm, especially to the severely injured patient who would otherwise not have survived without medical intervention
  13. 13. Proinflammatory cytokines 1. Il 1, Il 6, TNF alfa 2. NO 3. Endothelin 1 Cytokine antagonist • Interleukin receptor antagonist, TNF soluble receptors are released within hours of injury
  14. 14. Physiological response to injury The natural response to injury includes 1. Immobility 2. Anorexia 3. Catabolism
  15. 15. • In 1930, Sir David Cuthherstson derived the metabolic response to injury in humans into “ebb “ and “flow” phases
  16. 16. Metabolic changes after major trauma (Cuthbertson, Lancet, 1942) • • • • • • • • • • EBB (Untreated shock) Dec body temp Dec O2 consumption Lactic acidosis Inc stress hormones Dec Insulin Hyperglycemia Gluconeogenesis Inc substrate consumption Hepatic Acute phase response Immune activation • • • • • • • • • • FLOW PHASE Inc body temp Inc O2 consumption Negative Nitrogen bal Inc stress hormone Normal to Inc Insulin Hyperglycemia Gluconeogenesis Proteinolysis (autocannabalism) Lipolysis Immunosuppression
  17. 17. Ebb and Flow Phase Duration Role Physiological Hormones Ebb <24 hrs Maintenance of blood Dec BMR, Dec temp, Catechol, volume, Dec O2 consump, Cortisol, catecholamines vasoconst, Inc CO, Inc aldosterone heart rate, acute phase proteins 3 – 10 days Maintenance of energy Inc BMR, inc Temp, inc O2 consump, -ve N2 balance Inc. Insulin, Glucagon, Cortisol, Catechol but insulin resistance Replacement of lost tissue +ve Nitrogen balance Growth hormone, IGF Flow Catabolic Anabolic 10 – 60 (MOORE) days
  18. 18. Ebb • Starts at the time of injury and lasts for approximately 24-48 hours • Main hormones in ebb phase are catecholamines, cortisol, and aldosterone • It may be attenuated by proper resuscitation but not completely abolished • The main physiological role of this phase is to conserve both circulating volume and energy stores for recovery and repair
  19. 19. Flow • It lasts for several wks • This phase involves mobilization of body energy stores for repair and recovery • Following resuscitation , Ebb phase evolves into hypermetabolic flow phase, which corresponds to SIRS
  20. 20. Key catabolic elements of flow phase • • • • Hypermetabolism Alterations in skeletal muscle protein Alterations in Liver protein Insulin resistance
  21. 21. Hypermetabolism Majority of trauma patients demonstrate energy expenditure approximately 15-25% above predicted healthy resting values Factors which increases this metabolism are centreal thermodysregulation, increased sympathetic activity, increased protein turnover, wound circulation abnormalities etc..
  22. 22. Hypermetabolism Hyper metabolism following injury: 1. Is mainly caused by an acceleration of futile metabolic cycles 2. Is limited in modern practice on account of elements of routine critical care.
  23. 23. Skeletal muscle wasting 1. Provides amino acids for protein synthesis in central organ/tissues 2. Is mediated at a molecular level mainly by activation of the ubiquitin-protease pathway 3. Can result in immobility & contribute to hypostatic pneumonia & death if prolonged and excessive
  24. 24. Hepatic acute phase response • The Hepatic acute phase response represents a reprioritization of body protein metabolism towards the liver & is characterized by: • 1. Positive reactants (CRP) : plasma concentration increases • 2. Negative reactants (albumin) : : plasma concentration decreases
  25. 25. Insulin resistance • The degree of insulin resistance is directly proportional to magnitude of the injurious process. • Following routine upper abdominal surgery, insulin resistance may persist foe appr 2 wks • Postop patients with insulin resistance behave in a similar manner to individuals with type 2 diabetes • The mainstay of treatment is i.v insulin • Intensive insulin infusions are better over conservative approach.
  26. 26. • Main labile energy reserve in the body is fat • Main labile protein reserve in the body is skeletal muscle • While fat mass can be reduced without major detriment to function, loss of protein mass results not only in skeletal muscle wasting, but also depletion of visceral protein mass
  27. 27. • With lean issue, each 1 g of nitrogen is contained within 6.25 g of protein, which is contained in approximately 36 g of wet weight tissue. • Thus the loss of 1 g of nitrogen in urine is equivalent to the breakdown of 36 g of wet weight lean tissue. • Protein turnover in the whole body is of the order of 150-200 g per day.
  28. 28. • A normal human ingests 70-100 g of protein per day, which is metabolized and excreted in urine as ammonia and urea(14 g N/day) • During total starvation, urinary loss of nitrogen is rapidly attenuated by a series of adaptive changes • Loss of body weight follows a similar course , thus accounting for the survival of hunger strikers for a period of 50-60 days
  29. 29. • Following major injury, and particularly in the presence of ongoing septic complications , this adaptive change fails to occur, and there is a state of auto cannibalism , resulting in continuing urinary nitrogen losses of 10-20 g/day(500 g lean tissue/day) • As with total starvation, once loss of body protein mass has reached 30-40 % of the total, survival is unlikely
  30. 30. In critically ill patients with resuscitation, • <24 hrs – Body weight increases due to extracellular water expansion by 6-10 litres. – This can be overcome by careful intra operative management of fluid balance • 1-10 days – Total body protein will diminish by 15% and body weight will reach negative balance as the expansion of extra cellular space resolves – This can be overcome by blocking Neuro endocrine response with epidural analgesia and early enteral feeds
  31. 31. Avoidable factors that compound the response to injury 1. Continuing hemorrhage 2. Hypothermia 3. Tissue edema 4. Tissue under perfusion 5. Starvation 6. Immobility
  32. 32. • Volume loss: Careful limitation of intra operative administration of colloids and crystalloids so that there is no net weight gain • Hypothermia : RCT have shown that normothermia by an upper body forced air heating cover reduces wound infection, cardiac complications and bleeding and transfusion requirements
  33. 33. • Tissue edema : During systemic inflammation, fluid, plasma proteins, leucocytes, macrophages and electrolytes leave the vascular space and accumulate in the tissues. • This can diminish the alveolar diffusion of oxygen and may lead to reduced renal function
  34. 34. • Systemic inflammation and tissue under perfusion: the vascular endothelium controls vasomotor tone and micro vascular flow and regulates trafficking of nutrients and biologically active molecules. • Administration of activated protein C to critically ill patients has been shown to reduce organ failure and death and is thought to act, in part, via preservation of the micro circulation in vital organs • Maintaining the normoglycemia with insulin infusion during critical illness has been proposed to protect the endothelium, probably in part, via inhibition of excessive iNOS- induced NO release , and thereby contribute to the prevention of organ failure and death
  35. 35. • Starvation : During starvation, the body is faced with an obligate need to generate glucose to sustain cerebral energy metabolism(100g of glucose per day) • This is achieved in the first 24 hours by mobilizing glycogen stores and thereafter by hepatic gluconeogenesis from amino acids, glycerol and lactate. • The energy metabolism of other tissues is sustained by mobilizing fat from adipose tissue • Such fat metabolisation is mainly dependent on a fall in circulating insulin levels.
  36. 36. • Eventually , accelerated loss of lean tissue is reduced as a result of the liver converting free fatty acids into ketone bodies, which can serve as a substitute for glucose for cerebral energy metabolism. • Provision of 2 litres of iv 5% D as iv fluids for surgical patients who are fasted provides 100g of glucose per day and has a significant protein sparing effect. • Modern guidelines on fasting prior to anesthesia allow intake of clear fluids upto 2 hours before surgery. • Administration of carbohydrate drink at this time reduces perioperative anxiety and thirst and decreases post operative insulin resistance
  37. 37. • Immobility : Has been recognized as a potent stimulus for inducing muscle wasting. Early mobilization is an essential measure to avoid muscle wasting
  38. 38. A prospective approach to prevent unnecessary aspects of the surgical stress response 1. Minimal access techniques 2. Blockade of afferent painful stimuli (epidural anesthesia) 3. Minimal periods of starvation 4. Early mobilization
  39. 39. Therapeutic implications The catabolic response to injury is always a major concern in postoperative care. Three types of interventions were tried to reduce this. These are: –Nutritional –Hormonal –Biologic
  40. 40. Nutritional : Three important aspects of nutrition have to be considered • Route of administration (enteral/parenteral): enteral nutrition is preferred. It improves the protein balance & clinical outcome • Timing (early versus late feeding): – enteral nutrition is started as early as possible. Early is superior in its effects on catabolic & hyper metabolic response to injury. – A slower rate of fluid resuscitation after trauma hemorrhage leads to a faster restoration of the depressed cell-mediated immunity. Whereas rapid fluid resuscitation produces a prolonged depression of immune responses.
  41. 41. Composition of feeding(nutritional supplements): commonly tried are • Glutamine (both for enteral & parenteral nutrition) • Branched chain amino acids – leucine, isoleucine & valine • Arginine can stimulate GH & IGF-1 release and is a substrate for NO production. At high doses it promotes wound healing
  42. 42. • Unsaturated fatty acids: They can modulate cytokine biology. Anti inflammatory effect of fish oil is due to n-3 polyunsaturated fatty acids. • Fats rich in n-6 polyunsaturated fatty acids enhance IL-1 production & tissue response to cytokines. • Fats rich in n-3 polyunsaturated fatty acids have the opposite effect. • Monounsaturated fatty acids decrease tissue responsiveness to cytokine. IL-6 production is enhanced by total unsaturated fatty acid intake.
  43. 43. • Dietary nucleotides: may improve cellmediated immunity. A combination of arginine, n-3 polyunsaturated fatty acids & nucleotides has been used as “immune enhancing “diet.
  44. 44. Hormonal treatment: • Anabolic hormones –GH, IGF-1 & insulin promote positive nitrogen balance. • GH supplementation improves wound healing & decreases postoperative wound infection rate. • IGF-1 mediates most of the metabolic effects of GH. Exogenous IGF-1 reduces gut mucosal atrophy in trauma. • Both GH & IGF-1 are powerful modulators of the effector function of phagocytic cells.
  45. 45. Biologic treatment: • Various strategies have been tried, which include antibodies to endotoxin, TNF or IL-6. • But most patients with sepsis have elevated levels of cytokines & other mediators. • So this can be given as “prophylaxis” for patients with high risk, for example, those undergoing major surgical procedures. • Genetic alterations can occur during injury & infection. Hence in the future, gene therapy will have a role in the management of trauma patients who are critically ill.
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