The Body's metabolic response to injury.

1. METABOLIC RESPONSE TO
INJURY
BY;
BIRABWA MARTHA
ZZIMBE ALRED WILLIAM
PASCAL MAIBE DONALD.

2. CONTENTS
• 1. Introduction
• 2. Graded nature of Injury Response
• 3. Response Components 1. Physiological Components 2. Metabolic Manifestations 3. Clinical
Manifestations 4. Laboratory Changes
• 4. Mediators of Metabolic Response 1. Neuroendocrine response 2. Immune System Response
• 5. The metabolic stress response to surgery and trauma 1. The EBB phase 2. The flow phase
• 6. Key catabolic elements of the flow phase 1. Hypermetabolism 2. Alteration in skeletal muscle
protein metabolism 3. Alterations in hepatic protein metabolism 4. Insulin resistance
• 7. Changes in body composition after injury
• 8. Avoidable factors that compound the response to injury

3. INTRODUCTION
• Following accident or deliberate injury, a characteristic series of changes occur, both locally at the site of
injury and within the body generally. These changes are leveled as metabolic response to injury in the body.
• These changes are intended to restore the body to its pre-injury condition.
• The magnitude of the metabolic response is generally proportional to the severity of the tissue injury and
the presence of ongoing stimulation but can be modified by various other factors. Eg -: infection. • The
response to injury has probably evolved to help recovery, by mobilizing substrates and mechanisms of
preventing infection and by activating the tissue repair process in the body
• Although the metabolic response aims to return an individual to normal health, but sometimes a major
response to the trauma can damage organs distant to the injured site itself • So in modern surgery practices,
a major goal is to minimize the metabolic response to surgery in order to shorten the recovery time.
• Classically these responses have been described as stress response, this term has been coined by a Scottish
chemist CUTHERBERTON in 1932 • Initial response is directed at maintaining adequate substrate (oxygen
and energy) supply to vital organs • Stress hormones and cytokines play an important role in these reactions
• When inflammatory response impairs the function of an organ or organ system, then the term multiple
organ dysfunction syndrome is applied (MODS)

4. GRADED NATURE OF INJURY RESPONSE
• It is important to recognize that
the response to injury is graded.
The more severe the injury, the
greater the response. This
concept not only applies to
physiological / metabolic
changes but also to
immunological changes

5. RESPONSE COMPONENTS.
PHYSIOLOGICAL
Increased Cardiac output
Increased Ventilation
Increased Membrane transport
Weight loss
Wound healing
METABOLIC
Hyper metabolism
Accelerated gluconeogenesis
Enhanced protein breakdown
Increased fat oxidation
CLINICAL
Fever
Tachycardia
Tachypnoea
Presence of wound or inflammation
Anorexia
LABORATORY
Leukocytosis/Leukopenia
Hyperglycemia
Elevated CRP/Altered acute phase reactants
Hepatic/Renal dysfunction
Response
Components

6. MEDIATORS OF METABOLIC RESPONSE
• Neuro-endocrine response (Hormonal)
• Immune system response (cytokines)

7. NEUROENDOCRINE RESPONSE

8. Cont:
• Corticotrophin-releasing factor
(CRF) released from hypothalamus
increases adrenocorticotrophic
hormone (ACTH) release from
anterior pituitary ACTH then acts
on adrenal glands to increase the
secretion of cortisol Hypothalamic
activation of sympathetic nervous
system causes release of
adrenaline and release of glucagon
• NEUROENDOCRINE RESPONSE IS
BIPHASIC ;
• ACUTE PHASE : It is characterized by an
actively secreting pituitary gland and
elevated counter-regulatory hormones
(cortisol, glucagon, adrenaline) These
hormonal changes are thought to be
beneficial for short term survival
• CHRONIC PHASE : It is associated with
hypothalamic suppression and low serum
levels of the respective target organ
hormones. These changes contribute to
chronic wasting

9. Purpose –Neuro endocrine response
Provide essential substrates for survival
Postpone anabolism
Optimise host defence

10. IMMUNE SYSTEM RESPONSE

11. Immunological response
PROINFLAMATORY ANT-INFLAMATORY
IL-1,IL-6,IL-8 ,TNF alpha act on hypothalamus to cause
pyrexia
IL-1Ra , TNF soluble receptors (55 and 75) prevent
excessive proinflammatory activities
These also act on the liver to release acute phase
reactants eg. CRP (C-reactive protein), fibrinogen .
Th2 counter inflammatory response (1L4,IL5,13,9 and
TGF beta lead to CARS
They play a complex role in developing insulin
resistance
Other mediators like NO and endothelin 1 may also be
involved. All these lead to SIRS (a serious condition in
which there’s inflammation throughout the body) and
MODS (multiple organ dysfunction syndrome).

13. •THE METABOLIC STRESS RESPONSE TO SURGERY AND TRAUMA
In the natural world, if a human is injured, it displays a characteristic response, which includes ; immobility,
anorexia and catabolism.
THE EBB AND FLOW MODEL
In 1930, Sir David Cuthbertson from
Glasgow in U.K. divided the metabolic
response to injury in humans into ‘EBB’
phase and a ‘FLOW’ phase.
The ebb phase starts at the time of injury
and lasts approximately 24-48 hours.
It maybe attenuated by proper resuscitation ,
but not completely abolished.

14. Cont;
• The ebb phase is characterized by hypovolemia, decreased basal metabolic rate,
reduced cardiac output, hypothermia and lactic acidosis.
• The predominant hormones regulating the ebb phase are catecholamines ,cortisol
and aldosterone (following activation of renin –angiotensin system)
• The magnitude of this neuroendocrine response depends on the degree of blood
loss and the stimulation of somatic afferent nerves at the site of injury
• The main physiological role of ebb phase is to conserve both circulating volume and
energy stores for recovery and repair. Following resuscitation, the ebb phase
evolves into a hypermetabolic flow phase , which corresponds to SIRS. This phase
involves the mobilization of body energy stores for recovery and repair and the
subsequent replacement of lost or damaged tissue.

15. Metabolic response to trauma in ebb phase
• its characterized by hypovolemic shock. Its priority is to maintain life/
homeostasis. It involves. Decreased cardiac output
Decreased oxygen consumption
Decreased blood pressure.
Decreased tissue perfusion
Decreased body temperature
Decreased metabolic rate

16. Flow phase;
• This phase is concerned with recovery and repair following the initial injury. Its subdivided into catabolic and anabolic
phase in the order of evolution.
• The catabolic phase lasts approximately 3-10 days, followed by anabolic phase which may last for weeks if extensive
recovery and repair are required following serious injury
• Its characterized by;
 By tissue edema (from vasodilation and increased capillary leakage)
 Increased BMR (hyper metabolism)
 Increased cardiac output
 Raised body temperature
 Leukocytosis
 Increased oxygen consumption
 Increased gluconeogenesis

17. Cont;
• During the catabolic phase, the increased production of counter –regulatory hormones including
catecholamines , cortisol, insulin and glucagon) and inflammatory cytokines e.g. (IL-1,IL-6 and TNF) results in
significant fat and protein mobilization, leading to significant weight loss and increased urinary nitrogen
excretion.
Phase duration role physiological hormones
CATABOLIC 3-10 days Mobilization of
energy stores-
recovery and repair
Increased BMR,
temperature, oxygen
consumption and
carbondioxide
Cytokines,
insulin, glucagon
cortisol,
catechol, but
insulin resistant.
anabolic 10-60 days Replacement of lost
tissue
Positive nitrogen
balance
Growth
hormones, IGF.

18. Metabolic response to trauma: flow phase
• Increased catecholamines
• Increased glucocorticoids
• Increased glucagon.
• Release of cytokines, lipid mediators
• Acute phase protein production.

19. Key catabolic changes/ elements of flow phase
There are several key elements of the flow phase that largely determine the extent of catabolism and thus
govern the metabolic and nutritional care of the surgical patient. Note that, during the response not all tissues
are catabolic thus its importance is to allow to prioritize limited resources away from peripheral tissues i.e.
skin to vital organs i.e. heart and the wound. They include:
 Hypermetabolism
 Alterations in skeletal muscles protein
 Alterations in liver proteins
 Insulin resistance.
Hypermetabolism.
Majority of the trauma patients – energy expenditure approximately 15-25% greater than predicted healthy
resting values. Factors which increase this metabolism include; central thermodysregulation, increased
sympathetic activity, increased protein turnover and wound circulation abnormalities.

20. Skeletal muscle - metabolism
 Muscle wasting as a result of increased muscle protein degradation and decreased muscle protein synthesis.(RS
AND GIT). cardiac muscle is spared.
 Is mediated at a molecular level mainly by activation of the ubiquin-protease pathway.
 Lead- increased fatigue, reduced functional ability, decreased QOL and increased risk of morbidity and mortality.
Hepatic acute phase response
 Cytokines-IL-6 results in increased synthesis of positive acute phase proteins : fibrinogen and CRP.
 Negative acute reactants: albumin decreases.
 Not compensated.
Insulin resistance
hyperglycemia is seen due to increased glucose production and decreased glucose uptake in the
peripheral tissues ( transient induction of insulin resistance seen. due to cytokines and decreased
responsiveness of insulin – regulated glucose transporter proteins.

23. Summary
Changes in body composition following major
surgery/critical illness
• Catabolism leads to a decrease in fat mass and skeletal muscle mass
• Body weight may paradoxically increase because of expansion of extracellular
fluid space

24. Changes in body composition
• 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.
• With lean issue, each one gram of nitrogen is contained within 6.2g of protein, which is contained in
approximately 36g of wet wait tissue.
• Thus the loss of 1g of N2 in urine is equivalent to the break down of 36g of wet wait lean tissue.
• Protein turn over in the whole body is of the order of 150-200g per day.
• A normal human ingests 70-100g of protein per day, which is metabolized and excreted in urine as ammonia
and urea(14gN/day).
• During total starvation, urinary loss of nitrogen is rapidly attenuated by a series of adaptive changes.

25. Cont;
• Loss of body weight follows a similar course thus accounting for the
survival of hunger strikers for a period of 50-60 days
• Following major injury, and particularly in the presence of on going
septic conditions, this adaptive change fails to occur, and there’s a
state of auto cannibalism resulting in continuing urinary nitrogen
losses of 10-20g per day (500g lean tissue /day).
• As with total starvation, once loss of body protein mass has reached
30-40% of the total, survival is unlikely

26. AVOIDABLE FACTORS THAT COMPOUND THE RESPONSE TO INJURY
As noted previously, the main features of the metabolic response are
initiated by the immune system, cardiovascular system, sympathetic
nervous system, ascending reticular formation and limbic system.
However, the metabolic stress response may be further exacerbated
by anesthesia, dehydration, starvation (including preoperative fasting),
sepsis, acute medical illness or even severe psychological stress.
Attempts to limit or control these factors can be beneficial to the
patient.

27. • Continuing haemorrhage
• Hypothermia
• Tissue oedema
• Tissue underperfusion
• Starvation
• Immobility
Avoidable factors that compound the response
to injury

28. A proactive approach to prevent unnecessary aspects
of the surgical stress response
• Minimal access techniques
•Blockade of afferent painful stimuli (e.g. epidural
analgesia)
•Minimal periods of starvation
•Early mobilization

29. Factors associated with the magnitude of the
metabolic response to injury
Patient-related factors
Genetic predisposition: Gene subtype for inflammatory mediators
determines individual response to injury and/or infection
Coexisting disease Cancer and/or pre-existing inflammatory disease may
influence the metabolic response
Drug treatments Anti-inflammatory or immunosuppressive therapy (e.g.
steroids) may alter response
Nutritional status Malnourished patients have impaired immune function
and/or important substrate deficiencies.
Malnutrition prior to surgery is associated with poor outcomes

30. Thank you for listening.