METABOLIC RESPONSE TO TRAUMA

PRESENTED BY

ALAGBE F.A
OUTLINE
• INTRODUCTION
• TRIGGERS OF METABOLIC RESPONSE
• MEDIATORS OF METABOLIC RESPONSE
• FACTORS INFLUENCING MAGNITUDE OF METABOLIC RESPONSE
• PHASES OF METABOLIC RESPONSE
• EFFECT OF METABOLIC RRESPONSE
• AVOIDABLE FACTORS
• CONCLUSION
INTRODUCTION
• Trauma is the response to a deeply distressing or disturbing event that
overwhelms an individual's ability to cope.

• To increase the chances of surviving trauma, there is a complex set of

mechanisms that act locally and systemically to restore the body to its
preinjury condition

• By minimizing and manipulating the metabolic response to trauma, surgical

mortality, morbidity and recovery times can be greatly improved.

• It is important to recognize that the response to injury is graded; the more

severe the injury, the greater the response
Triggers of metabolic response
Pain
• Pain from the damaged tissues activate the neuro-endocrine
response through the afferent sensory and sympathetic nerves to the
central nervous system.

• Impulses from the pain receptors in the injured tissues pass through
the afferent nerves (mainly the C fibres) and the spinothalamic
pathway to the thalamus, hypothalamus and finally the sympathetic
center and pituitary.
Triggers of metabolic response
Hypovolaemia
• Reduction in the effective circulating blood volume, e.g. from
bleeding or hypotension, evokes sympatho-adrenal response.

• increased release of catecholamines, ADH and aldosterone to correct

the haemodynamic derangement and protect the functional
extracellular fluid volume.
Triggers of metabolic response
Inflammatory reaction
• The damaged tissues provoke an inflammatory reaction and their
products activate macrophages, monocytes and lymphocytes to
produce cytokines-

• These cytokines act locally as part of the inflammatory and immune

reactions; but in the general circulation lead to consequent adverse
systemic
Mediators of Metabolic response

• Neuro endocrine system

• Afferent nerve stimulation and sympathetic nervous system activation
• Increased secretion of stress hormones
• Decreased secretion of anabolic hormones

• Immune system
• Inflammatory cells (macrophages, monocytes, neutrophils)
• Proinflammatory cytokines and other inflammatory mediators
• Endothelium
Neuro endocrine system

• Neuro-endocrine response to injury/critical illness is Biphasic :

• Acute phase - An actively secreting pituitary & elevated counter regulatory
hormones (cortisol, glucagon, adrenaline).Changes are thought to be
beneficial for short-term survival.

• Chronic phase - Hypothalamic suppression & low serum levels of the

respective target organ hormones. Changes contribute chronic wasting.
Immune system
• Proinflammatory phase
• IL-1, IL-6, TNF-alpha
• Hypothalamus– pyrexia
• Hepatic acute phase proteins

• Counter regulatory phase

• IL-1 receptor antagonist and TNF soluble receptors
• Prevent excessive pro inflammatory activities
• Restore homeostasis
 Cytokines involved in the acute inflammatory
response
Cytokine Relevant actions
• TNF-α Proinflammatory; release of leucocytes by bone marrow;
activation of leucocytes and endothelial cells

• IL-1 Fever; T-cell and macrophage activation

• IL-6 Growth and differentiation of lymphocytes; activation of

the acute-phase protein response

• IL-8 Chemotactic for neutrophils and T cells

• IL-10 Inhibits immune function

Factors that Influence magnitude of
metabolic response
Patient-related factors

Factor Comment
• Genetic predisposition Genotype determines changes in gene expression in
response to injury and/or infection
• Coexisting disease Cancer and/or pre-existing inflammatory disease may
influence the metabolic response
• Drug treatments Antiinflammatory 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
Acute surgical/trauma-related factors

• Severity of injury Greater tissue damage is associated with a greater metabolic response
• Nature of injury Some types of tissue injury cause a disproportionate metabolic
response (e.g., major burns)
• Ischaemia–reperfusion Reperfusion of ischaemic tissues can trigger an injurious
Inflammatory cascade that further injures organs injury
• Temperature Extreme hypo- and hyperthermia modulate the metabolic response
• Infection Infection is associated with an exaggerated response to injury. It can
result in systemic inflammatory response syndrome, sepsis or
septic shock
• Anaesthetic techniques The use of certain drugs, such as opioids, can reduce the release of
stress hormones. Regional anaesthetic techniques (epidural or
spinal anaesthesia) can reduce the release of cortisol,
adrenaline and other hormones, but has little effect on cytokine
responses
Phases of metabolic response
The Ebb Phase
• First 24-48 hrs.
• It may be attenuated by proper resuscitation, but not completely
abolished.
• It is characterized
• Hypovolaemia,
• decreased metabolic rate,
• reduced cardiac output,
• hypothermia and
• lactic acidosis.
• ROLE—to conserve both circulatory volume and energy stores for
recovery.
The flow phase
• The flow phase may be subdivided
• catabolic phase, lasting approximately 3–10
• anabolic phase, which may last for weeks
• Hypermetabolic phase, Involves mobilisation of body energy stores
recovery and repair, replacement of lost tissues.
• It is characterized by
• Tissue oedema,
• Increased basal metabolic rate,
• cardiac output,temp.,
• o2 consumption,
• leucocytosis
• gluconeogenesis
Effect of metabolic response
• The retention of water and sodium
• Increase renal excretion of potassium
• Altered Protein Metabolism and Nitrogen Balance
• Hypermetabolism with increase resting energy metabolism
• Changes in plasma protein
• Immunosuppression
• Increase secretion of cortisol, catecholamine, renin-aldosterone
system, ACTH, ADH, glucagon, GH,
Retention of water and sodium
• Primarily due to the release of antidiuretic hormone (ADH) and
aldosterone

• Is common after major surgery or injury, and may persist even after
normal circulating volume has been restored
Retention of water and sodium
• Secretion of ADH from the posterior pituitary is increased in response to:

• Afferent nerve impulses from the site of injury

• Atrial stretch receptors (responding to reduced volume) and the aortic and carotid
baroreceptors (responding to reduced pressure)

• Increased plasma osmolality (principally the result of an increase in sodium ions)

detected by hypothalamic osmo receptors
•
• Input from higher centers in the brain (responding to pain, emotion and anxiety).

• ADH promotes the retention of free water (without electrolytes) by cells of the distal
renal tubules and collecting ducts
Retention of water and sodium
• Aldosterone secretion is controlled by the following factors
• Activation of the renin–angiotensin system.

• Increased adrenocorticotropic hormone (ACTH) secretion by the anterior

pituitary in response to hypovolemia and hypotension via afferent nerve
impulses from stretch receptors in the atria, aorta and carotid arteries. ACTH
secretion is also increased by ADH.

• Direct stimulation of the adrenal cortex by hyponatraemia or hyperkalaemia.

Increased renal excretion of potassium
• Maximal in the 1st day and return to normal within 3days
• Also caused by increase secretion of Aldosterone
• Other causes
• Blood shed
• Breakdown of protein and injured tissues

• During anabolic phase, when protein is replenished, potassium is

required and renal excretion is diminished
Altered Protein Metabolism and Nitrogen
Balance
• In major trauma or sepsis, protein turnover, catabolism and synthesis,
are increased

• But catabolism is greater than synthesis resulting in negative nitrogen

balance.
Altered Protein Metabolism and Nitrogen
Balance
• The muscle intracellular response consists of an increase in essential
amino acids, especially branched amino acids (leucine, isoleucineand
valine)

• reduction by 50 % of non-essential amino acids particularly glutamine

and alanine, substrates for gluconeogenesis and the immune system.
Altered Protein Metabolism and Nitrogen
Balance
• Glutamine, which constitutes about 50% of the body's amino acid
pool, is a fuel for enterocytes, colonocytes, lymphocytes and
proliferating cells.

• It also appears to have a role in the prevention of bacterial and

endotoxin translocation from the gut lumen into the portal circulation
• The amino acids so produced are used to:
• provide the liver with carbohydrate intermediates i.e pyruvic, oxaloacetic and
ketoglutaric acids,

• maintain the structural integrity, and also the functional efficiency, of the
essential organs and mononuclear cell mass,

• synthesize enzymes, protein-derived hormones and plasma proteins,

especially acute phase proteins, whose turnover is increased after trauma or
during infection.
• provide glycine, proline, lysine, tryptophane and tyrosine needed by the liver to
synthesize collagen, necessary for wound repair.

• provide the gut specific nutrient glutamine, for the

• immunity of the gut and inflammatory cells

Changes in Plasma proteins
• Positive acute-phase proteins (increase after injury)
• C-reactive protein
• Haptoglobins
• Ferritin
• Fibrinogen
• α1-antitrypsin
• α2-macroglobulin
• Plasminogen
• Negative acute-phase proteins (decrease after injury)
• Albumin
• ransferrin
Hypermetabolism and Energy Metabolism
• The average healthy adult has a Rest energy expenditure(R.E.E) of
6300-7500J in24hr and this maybe increased by

• up to 10% or higher after a major operation.

• After a major fracture, the increase is 10-25 % ,

• in sepsis 50-80 % and

• in severe burns 40- l 00 % or higher.

Hypermetabolism and Energy Metabolism
• The increased R. E. E is caused by

• increased functional activity of the cardiovascular, respirator and endocrine

organs and the liver to cope with the injury and its sequelae

• the metabolic activity in the healing of the wound.

• Thermogenesis/heat energy increased by mild pyrexia

Utilization of glucose
• Glycogen, under the influence of adrenaline and glucagon, is
converted into glucose with increase in blood glucose level
• Glucose resistance occurs caused by changes to be insulin
receptor/intracellular signal pathway.

• Cellular uptake of infused glucose is also impaired by the insulin-

antagonistic activity of cortisol and growth hormone.

• All this may result in hyperglycaemia and glycosuria

Mobilization of fat
• Combustion of triglycerides provides most of the energy and as much as
500g may be metabolized daily unless exogenous carbohydrate is provided

• Lipolysis of stored triglycerides in adipose tissues produces free fatty acids

and glycerol.

• Lipolysis of triglycerides is stimulated by catecholamine, glucagon, cortisol

and growth hormone and inhibited by insulin and prostaglandin E.
Mobilization of fat
• The plasma free fatty acid level is raised markedly within 12h and
remains elevated for2-3 days

• Conversion of free fatty acids to ketone bodies by the liver is also

enhanced and within 12h the level of blood ketone bodies is very high
Weight changes
• There is weight loss , which can result from:

• increased catabolism of proteins over synthesis and energy

• lipolysis and combustion of triglycerides to provide

• diminished food intake.

Immunosuppression and Increased
susceptibility to Infection
• The traumatized patient is susceptible to sepsis

• Macrophages/monocytes, dendritic cells, lymphocytes and

polymorphonuclears, mainly responsible for the immune responses,
function abnormally after trauma.
• Abnormalities in macrophage/monocyte dendritic cell function
include:

• diminished capacity to phagocytosis,

• increased lysosome stability and reduced oxidative burst activity,
• reduced levels of expression of Major Histocompatibility Complex-Class II
Antigen (MH-II, Human Leucocyte Antigen, HLA- DR) and MHC-1 (HLA-A) on
the cell surface
• impaired antigen presentation to lymphocytes
• reduced production of cytokines- lL-1, IL-6, TNF-a,
• IL-12 after an initial rise in the first 24h,
• markedly increased production of prostaglandin E2•
• Abnormalities in lymphocyte function include:

• decreased T-lymphocyte proliferation and reduction in T4:T8 ratio from the

normal of 2: l.
• decreased natural killer (NK) and lymphokine-activated killer cell activity
• impaired T4, T8 activity
• appearance of immature T cells shift of T helper lymphocytes from type 1(
secreting TNF-b, IL-2, IL-12, IFN-g) to type2 (secreting TNF-a, IL-4, IL-6, IL-10,
IL-13) resulting in type2 dominance.
Avoidable factors

• Continuing haemorrhage
• Hypothermia
• Tissue oedema
• Tissue underperfusion
• Starvation
• Immobility
Preventing unnecessary aspects of stress response

• Minimal access techniques

• Minimal periods of Starvation
• Epidural analgesia
• Early mobilization
conclusion
• it is very clear that trauma causes multiple pathophysiological
reactions to the body.

• knowledge of these events is important to understand the rationale

for modern ‘stress free’ perioperative and critical care
References

• Badoe , et.al, Principles and Practice of Surgery, 5th edition Volume 1,

Ghana Publishing corporation, 2015.

• Garden James and Rowan Parker, Principle and practice of surgery,

Elsevier, 2018

• Norman et.al, Bailey and Love short practice of surgery, CRC press,
2018