Alteration in Metabolism in Surgical Patients

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Alteration in MetabolisminSurgical Patients
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Energy Metabolism

• In order to mount a metabolic response to injury
  the body uses as a fuel glucose, fat and protein
• How much fuel does the body have?

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Body Composition
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Body Composition

• Even though protein is used as a fuel in stress,
  its depletion is detrimental

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Body Composition

• Glycogen - Fuel
• Fat - Fuel
• Protein - Structure (use as a fuel should be
  minimised)

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Protein Amino AcidMetabolism

• Protein
• 15 body weight - ½ intracellular
• Enzymes, transport, hormones, immune Fx, muscle
• It is not usually a food
• when needed it is converted to glucose

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Protein Amino AcidMetabolism

• Total protein turnover 300g /day
• Obligatory N loss in urine 12g /day
• or 80g protein /day

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Protein Amino AcidMetabolism

• Nitrogen Balance
• N balance N intake - N out
• Negative in starvation, injury, severe infection

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Response toStarvation vs Injury
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Protein Amino AcidMetabolism

• If protein is depleted via proteolysis
• ability to adapt in stress is compromised
• protein depletion results in
• decreased wound healing
• decreased immune response
• defective gut-mucosal barrier
• decreased mobility/ respiratory effort

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Homeostatic Responsesto Stress

• Designed to maintain homeostasis
• Same response in controlled or uncontrolled
  stress
• Trigger mechanisms
• Volume loss
• Tissue damage
• Pain
• Fear

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Homeostatic Responsesto Stress

• Volume Loss Tissue Underperfusion
• Pressure Stretch receptors activated
• HR / SV increased
• ADH / Aldosterone secreted -
• renal and hypothalamic mechanism
• Need for adequate resuscitation

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Homeostatic Responsesto Stress

• Tissue Damage
• Most important trigger
• Neural pathways from wound
• reach hypothalamus
• efferents go to pancreas ? ?glucagon ?insulin
• efferents to adrenal ? ? cortisol, catecolamines
• Release of cytokines

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Homeostatic Responsesto Stress

• Pain Fear
• Increased levels of catecholamines
• Fight or flight response

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Homeostatic Response

• Elective operation
• min tissue damage
• pain/fear managed
• less hypotension
• infection rare
• stress response in controlled

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Homeostatic Response

• Trauma
• major tissue damage
• pain/fear excessive managed
• hypotension common
• infection common
• Stress response uncontrolled

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Homeostatic Responsesto Stress

• Triggers ? Response
• Volume loss ? Neurohormonal and
• Tissue damage ? Inflammatory arms
• Pain Fear ?

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Mediators ofStress Response

• Neurohormonal arm
• Catecolamines, glucocorticoids, glucagon, ADH,
  aldosterone
• Inflammatory arm
• Cytokines, complement, eicisanoids, PAF

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Mediators of Stress Response

• Neurohormonal Arm
• - Counterregulatory Hormones
• catecholamines
• maintain circulation,
• hepatic glycolysis, lipolysis, gluconeogenesis, ?
  BMR
• glucagon
• glycogenolytic, gluconeogenic
• glucocorticoids?/ACTH
• mobilise muscle protein, gluconeogenesis
• ADH. Aldosterone
• Retain water and Na

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Mediators ofStress Response

• Inflammatory Arm - Cytokines
• TNF-alpha, IL-1, IL-2, IL-6, IFN-gamma
• Local effects - para or autocrine
• Response to tissue injury

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Mediators ofStress Response

• Cytokines
• In elective surgery
• confined to wound
• Trauma/sepsis
• spill over/ endocrine effect

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Mediators ofStress Response

• Cytokines - local effect
• Promote wound healing
• Stimulate angiogenesis
• White cell migration
• Ingrowth of fibroblasts
• Localise the wound

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Mediators ofStress Response

• Cytokines - spill over
• Mobilisation of AA, stimulation of acute phase
  protein synthesis
• Increase WBC counts/Hypoferremia
• Fever, subjective discomfort, sleep

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Mediators ofStress Response

• Cytokines - severe trauma /sepsis
• Increased organ vascular permeability
• Multiple organ dysfunction
• Hypotension

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Stress Response

• The stress just described response may be
  characterised as a adrenergic corticoid phase
• When the patient recovers the adrenergic
  corticoid phase changes to an anabolic phase

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Stress ResponseAdrenergic-Corticoid Phase

• ? ACTH and cortisol
• mobilises protein?gluconeogenesis
• Catecolamines
• circulatory adjustment
• metabolic response if prolonged
• Aldosterone and ADH
• Salt and water retention
• ? Insulin and ? glucagon (via epinephrine)
• gluconeogenesis
• Cytokines confined to wound

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Stress Response

• Adrenergic - corticoid phase
• Remains until insult corrected
• Hypermetabolism-BMR increases
• 10-15 in elective operation
• 25 in long bone fracture
• 200 in 50 burn

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Stress Response

• Adrenergic - corticoid phase
• Altered Glucose Metab
• Normal/low insulin and insulin resistance
• persisting hyperglycaemia
• injured tissue uses glucose

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Stress Response

• ADRENERGIC - CORTICOID PHASE
• Altered protein metabolism
• Extensive muscle protein release
• extensive urine N loss
• reduced by feeding
• Altered fat metabolism
• Accelerated lipolysis via hormone sensitive
• lipase
• Ketosis blunted

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Stress Response

• ANABOLIC PHASE
• ? gluconeogenesis
• ? catecolamines
• ? aldosterone and ADH
• Salt and water loss
• ? insulin and ? glucagon
• protein anabolism
• cytokines reduction

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Elective Operations

• Adrenergic corticoid phase
• period of catabolism
• lasts 1-3 days
• Anabolic phase
• starts D3-D6
• positive N balance
• protein synthesis
• recovery of lean mass

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Nutritional Supportfor Elective Operations

• Because the adrenergic-corticoid phase is short
  in elective, uncomplicated surgery
• Fluid therapy with 5 dextrose is enough for up
  to 5-7 days

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Nutritional Supportfor Severe Stress

• The adrenergic-corticoid phase is prolonged in
• severe injury
• Malnourished patients
• Infected patients
• Nutritional therapy is needed

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Stress Responses

• The response is affected
• Malnutrition
• Age
• Gender
• Infection

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Consequencesof Malnutrition

• Metabolic response needs increased energy
  expenditure
• If intake lt expenditure - protein/fat mass lost
• Loss of 15 BW interacts with disease process to
• compromise immune response - sepsis, MOF
• poor wound healing
• edema due to ? albumin
• reduced mobility, ? respiratory muscle strength
  vital capacity ? pneumonia
• altered GI function/breached mucosal barrier

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Normal Post Op Drip

• Energy provided as dextrose
• 1 L of D5W - 50g or 170 kcal
• Typical post op patient gets 500 kcal/d
• enough to stimulate pancreatic insulin
• not enough to support a severe stress reaction
• Need for nutritional support to match energy
  expenditure if stress is prolonged

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Metabolic Responseto Trauma / Severe Surgical
Stress

• Unfed trauma patients rapidly use their protein
  and fat stores resulting in increased
  susceptibility to effects of haemorrhage,
  operations and infection resulting in organ
  system failure, sepsis and death
• Malnourished patients are at greater risk

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Determinants of HostResponses to Surgical Stress

• Age
• Fat mass increase with age
• Loss of muscle mass
• Loss of strength with immobility
• Decreased sensitivity to perturbations
• Decreased effectiveness to maintain homeostasis

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Determinants of HostResponses to Surgical Stress

• Gender
• Lean body mass less in females
• N loss more pronounced in muscular males

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Determinants of HostResponses to Surgical Stress

• Invasive Infection
• May complicate any operation / injury
• Results in increases metabolic rate - fever,
  hyperventilation, etc
• Nutritional depletion synergystic

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Metabolic Responseto Trauma / Severe Surgical
Stress

• Cuthbertson described in 1930 the
• Ebb or shock phase
• Flow phase
• Cuthbertson Modern
• Ebb unresuscitated
• Flow adrenergic-corticoid
• not described anabolic

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Metabolic Responseto Trauma / Severe Surgical
Stress

• Cuthbertson
• Ebb or shock phase
• 12-24 hours
• ? BP, ? CO, ? Temp, ? O2 consumption
• due to haemorrhage, hypoperfusion, lactic
  acidosis
• Flow phase (adrenergic - corticoid)
• hypermetabolism, ? CO, ?Urine N loss, altered
  glucose, tissue catabolism
• similar to elective surgery but greater

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Questions ?

• A 64 year old 70 kg man comes for a gastrectomy.
  Prior to operation he had been eating poorly for
  4 weeks. On the 7th POD after Billroth II
  gastrectomy he was drowsy and febrile. There was
  green fluid coming from his drain.

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Coming soon to aLecture Theatre near you
Nutritional Support

• In a severely injured patient the priorities
  are - resuscitation
• - wound care
• Nutritional support usually after 48 hrs
• The next lecture will cover all aspects of
  nutrition

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Questions