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Metabolic Response To Trauma
Metabolic Response To Trauma
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T.S. WALSH
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INTRODUCTION
Following accidental or deliberate injury, a characteristic
series of changes occurs, both locally at the site of injury
and within the body generally; these changes are intended
to restore the body to its pre-injury condition. They are
mediated via many different systems, which interact in
a complex manner and may be modified by external factors,
such as drugs and other treatments administered to the
patient. The magnitude of the metabolic response is
generally proportional to the severity of tissue injury, but
can be modified by additional factors such as infection.
The response to injury has probably evolved to aid recovery,
by mobilizing substrates and mechanisms of preventing
infection, and by activating repair processes. However,
many of these physiological changes can now be modified
or corrected by treatments. Although the metabolic response
aims to return an individual to health, it can sometimes
have harmful effects. For example, a major response can
damage organs distant to the injured site itself. In modern
surgery, a major goal is to minimize the metabolic response
to surgery in order to shorten recovery times. This has
been achieved through surgical techniques that minimize
tissue damage. When a major metabolic response does
occur, the emphasis is on managing the patient in a way
that minimizes further tissue damage either at the original
site of injury or in other organs. This chapter describes the
principal physiological systems involved in the metabolic
response to injury, how they function and are controlled,
and at what stage they are important.
Relevant actions
TNF-a
IL-1
IL-6
IL-8
IL-10
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Bacterial invasion
Macrophage activation
Phagocytosis
Cytokine release
Prostanoid release
Protease release
Stimulation of afferent
nerve impulses
Haemorrhage into
injured tissue
Neutrophil accumulation
Phagocytosis
Cytokine release
Protease release
Neutrophilendothelial
cell adherence and
neutrophil migration
Endothelial activation
Vasodilatation
Increased capillary
permeability
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Bacterial infection
Pituitary
Adrenal
Pancreatic
Others
Increased secretion
Adrenaline
Cortisol
Aldosterone
Glucagon
Renin
Angiotensin
Unchanged secretion
Thyroid-stimulating
hormone (TSH)
Luteinizing hormone (LH)
Follicle-stimulating
hormone (FSH)
Decreased secretion
Insulin
Testosterone
Oestrogen
Thyroid
hormones
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Mechanism
Contributing factors
Blood
Haemorrhage
Electrolyte-containing fluids
Vomiting
Nasogastric drainage
Diarrhoea
Water
Plasma-like fluid (third-space losses)
Sweating
Evaporation
Capillary leak/sequestration in tissues
Fluid-conserving measures
Oliguria, together with sodium and water retention, is very
common after major surgery or injury. It may occur because
of decreased renal perfusion as a result of hypovolaemia,
but frequently arises even after normal circulating volume
is restored. Characteristic changes affect urine after major
surgery, which result from neuroendocrine responses.
Aldosterone
Aldosterone secretion from the adrenal cortex is increased
by the following mechanisms (Fig. 1.2):
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Anterior pituitary:
Secretes ACTH
ACTH actions:
Stimulation of aldosterone
secretion by adrenal cortex
Kidney juxtaglomerular
apparatus (JGA):
Secretes renin
Adrenal gland cortex:
Secretes aldosterone
Reninangiotensin system
Aldosterone actions:
Na+ and water retention
from distal renal tubules
Negative feedback on
anterior pituitary
Renin (JGA)
Angiotensin I
Angiotensinogen
(plasma) Angiotensinconverting enzyme
(lung and other tissues)
Angiotensin II
Angiotensin II actions:
Stimulates aldosterone
secretion
Stimulates thirst centres
in brain
Potent vasoconstrictor
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Thalamus
Pyrexia
Heart and
cardiovascular system
Sympathetic activation
Tachycardia
Liver
Glycogenolysis
Gluconeogenesis
Lipolysis
Ketone body production
Acute-phase protein release
Site of injury/surgery
Inflammation
Oedema
Endothelial activation
Blood flow
Afferent nerve stimulation
Pituitary
ACTH
Antidiuretic hormone
Suprarenal gland
Aldosterone
Cortisol
Adrenaline (ephinephrine)
Kidney
Reninangiotensin system
activation
Na+ reabsorption
K+ reabsorption
Urine volumes
Poor erythropoietin response
to anaemia
Pancreas
Insulin release
Glucagon release
Skeletal muscle
Muscle breakdown
Release of amino acids into
circulation
Bone marrow
Impaired red cell production
Carbohydrate metabolism
Glycogenolysis in the liver results in rapid depletion
of glycogen stores, which last for only 812 hours.
Gluconeogenesis is increased, particularly in the liver,
which converts substrates released from other tissues, such
as amino acids, into glucose. Insulin secretion is decreased
as a result of inhibition of pancreatic b-cells by cate-
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free fatty acids into glucose, but the liver converts them
into ketone bodies that are water-soluble and can support
cerebral energy metabolism. Following severe trauma,
200500 g of fat may be broken down daily.
Healthy sedentary
70 kg man
Total energy expenditure
about 1800 kcal/day
Basal metabolic rate
comprises enzymes and
ion pumps (85%) and the
mechanical work of the
heart and respiratory
system (15%)
Fat metabolism
Adipose tissue is a large triglyceride store that constitutes
the principal source of energy following trauma. The stress
hormones released as part of the metabolic response to
injury (catecholamines, glucagon, cortisol and growth
hormone) are all capable of activating the enzyme,
triglyceride lipase, within fat cells. This process is
exacerbated by the state of insulin resistance. Cortisol
is a potent stimulus for lipolysis, and circulating cortisol
concentrations increase from normal baseline levels of
400 nmol/l to levels of > 1500 nmol/l within hours of
major surgery. Triglycerides are broken down into glycerol
and free fatty acids. Glycerol is a substrate for gluconeogenesis, and free fatty acids can be directly metabolized
by most tissues to generate energy. The brain is unable to
use free fatty acids for energy production, and in health
relies on glucose supply. Animals are unable to convert
Protein metabolism
Skeletal muscle is the major labile protein store in the
body. Following major injury, skeletal muscle is broken
down, releasing amino acids into the circulation. These
are metabolized principally in the liver, which converts a
major proportion into glucose for re-export to tissues for
energy metabolism. Amino acids are also used in the liver
as substrate for the acute-phase protein response. This
response involves the liver increasing the production of
one group of proteins (positive acute-phase proteins) and
decreasing the production of others (negative acute-phase
proteins) (Table 1.4). The acute-phase response is mediated
in the liver by cytokines, especially IL-1, IL-6 and TNF.
Its function is not fully understood, but is probably concerned with fighting infection and promoting healing.
The mechanism by which muscle catabolism occurs
is also incompletely understood. It is mediated by inflammatory mediators and hormones, such as cortisol, released
as part of the metabolic response to injury. Trauma or
surgery associated with a minimal metabolic response
is usually accompanied by minimal muscle catabolism.
In patients with major tissue injury, marked catabolism
and loss of skeletal muscle can occur, especially when
factors that enhance the metabolic response, such as
sepsis, are present.
In health, 80120 g/day dietary protein (1220 g
nitrogen) is ingested (1 g nitrogen = 6 g protein). Normally,
approximately 2 g/day nitrogen is lost in faeces and 1018
g/day in urine (mainly in the form of urea). During
catabolism, nitrogen intake is often reduced but urinary
losses can increase markedly, reaching 2030 g/day in
patients with severe trauma, sepsis or burns. Following
uncomplicated surgery, this negative nitrogen balance
usually lasts only 58 days, but in patients with prolonged
sepsis, burns or conditions associated with prolonged
inflammation (for example, acute pancreatitis) it may
persist for many weeks. Severe catabolism and negative
nitrogen balance cannot be reversed by feeding, but the
provision of protein and calories can attenuate the processes.
Even patients undergoing uncomplicated abdominal surgery
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Table 1.5 A COMPARISON OF NITROGEN AND ENERGY LOSSES IN A MODERATE TO SEVERE CATABOLIC STATE AND DURING THE
DIFFERENT PHASES OF STARVATION*
Catabolic state
Acute starvation
Compensated starvation
2025
14
22002500
1800
1500
Acute starvation
This is accompanied by metabolic changes that preserve
the glucose supply to the brain. Glycogenolysis and gluconeogenesis occur in the liver, releasing glucose for cerebral
energy metabolism. Lipolysis in fat stores releases free
fatty acids for use by other tissues, and glycerol which
is converted to glucose in the liver. These processes can
sustain the normal energy requirements of the body
(about 1800 kcal/day for a 70 kg adult) for approximately
10 hours.
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Chronic starvation
This is initially accompanied by muscle breakdown to
release amino acids, which are converted to glucose by
hepatic gluconeogenesis. In addition, fatty acids released
from adipose tissue are converted by the liver to ketones.
Tissue energy supply is in the form of glucose, fatty acids
and ketones. The brain is unable to utilize free fatty acids
and uses about 70% of the glucose generated by hepatic
gluconeogenesis. With prolonged starvation, the brain
adapts to utilize ketones as the primary energy substrate,
rather than glucose. This adaptation reduces muscle protein
loss and switches metabolism to increase fat consumption,
so that net body nitrogen loss is reduced. Hepatic gluconeogenesis from amino acids decreases to about 25% of
its previous rate, and overall metabolic rate and energy
requirements fall, the latter from 1800 kcal/day to about
1500 kcal/ day (Table 1.5). This state is termed compensated
starvation, which continues until body fat stores are
depleted. At this stage, when an individual is often close
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Table 1.6 FACTORS ASSOCIATED WITH THE MAGNITUDE OF THE METABOLIC RESPONSE TO INJURY
Factor
Comment
PATIENT-RELATED FACTORS
Genetic predisposition
Coexisting disease
Recent evidence shows that gene subtype for inflammatory mediators is associated with
how an individual responds to injury and infection
The presence of disease, such as cancer and chronic inflammatory disease, may influence
the metabolic response
Pre-existing anti-inflammatory or immunosuppressive therapy, such as steroids, may alter
responses
Malnourished patients may have decreased immune function or deficiency in important
substrates. Malnutrition prior to surgery or trauma is associated with poor outcomes
Drug treatments
Nutritional status
ACUTE SURGICAL/TRAUMA-RELATED FACTORS
Severity of injury
Nature of injury
Ischaemiareperfusion injury
Temperature
Infection
Anaesthetic techniques
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ANABOLISM
Anabolism is the process of regaining weight, restoring
skeletal muscle mass and strength, and replenishing fat
stores. It is unlikely to occur until the processes
associated with catabolism, such as the release of inflammatory mediators, have subsided. This point is often
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