alteration in metabolism in surgical patients. energy metabolism l in order to mount a metabolic...

Alteration in Alteration in MetabolismMetabolism

ininSurgical PatientsSurgical Patients

Energy MetabolismEnergy Metabolism

In order to mount a metabolic In order to mount a metabolic response to injury the body uses response to injury the body uses as a fuel glucose, fat and proteinas a fuel glucose, fat and protein

How much fuel does the body How much fuel does the body have?have?

Body CompositionBody Composition

SourceSource kgkg kcal kcal

FatFat 1414 125,000125,000

ProteinProteinskeletal muscleskeletal muscle 66 24,00024,000otherother 66 24,00024,000

GlycogenGlycogenmusclemuscle 0.150.15 600600liverliver 0.0750.075 300300free glucosefree glucose 0.020.02 8080


Even though protein is used as a fuel Even though protein is used as a fuel

in stress, its depletion is detrimental in stress, its depletion is detrimental


GlycogenGlycogen -- FuelFuel

FatFat - - FuelFuel

ProteinProtein - - Structure Structure (use as a fuel should be (use as a fuel should be minimised)minimised)

Protein & Amino AcidProtein & Amino AcidMetabolismMetabolism

ProteinProtein 15% body weight - 15% body weight - ½½ intracellular intracellular Enzymes, transport, hormones, immune Enzymes, transport, hormones, immune

Fx, muscleFx, muscle It is not usually a foodIt is not usually a food when needed it is converted to glucosewhen needed it is converted to glucose

Total protein turnoverTotal protein turnover 300g300g /day/day

Obligatory N loss in urineObligatory N loss in urine 12g12g /day/day

or 80g protein /dayor 80g protein /day


Nitrogen BalanceNitrogen Balance

NN balancebalance = N = N intakeintake - N - N outout

Negative in starvation, injury, Negative in starvation, injury, severe infectionsevere infection


Response toResponse toStarvation vs InjuryStarvation vs Injury

ParameterParameter StarvationStarvation TraumaTrauma

BMRBMR -- ++++

MediatorsMediators -- ++++++

Major fuelMajor fuel FatFat MixedMixed

Ketone productionKetone production ++++++ +/-+/-

Hepatic ureagenesisHepatic ureagenesis ++ ++++++

Neg N balanceNeg N balance ++ ++++++

GluconeogenesisGluconeogenesis ++ ++++++

Muscle proteolysisMuscle proteolysis ++ ++++++

Hepatic protein synthesisHepatic protein synthesis ++ ++++++

If protein is depleted via proteolysis –If protein is depleted via proteolysis –ability to adapt in stress is compromisedability to adapt in stress is compromised

protein depletion results in protein depletion results in decreased wound healingdecreased wound healing decreased immune responsedecreased immune response defective gut-mucosal barrierdefective gut-mucosal barrier decreased mobility/ respiratory effortdecreased mobility/ respiratory effort


Homeostatic ResponsesHomeostatic Responsesto Stressto Stress

Designed to maintain homeostasisDesigned to maintain homeostasis

Same response in controlled or Same response in controlled or uncontrolled stressuncontrolled stress

Trigger mechanisms:Trigger mechanisms: Volume lossVolume loss Tissue damageTissue damage PainPain FearFear

Volume Loss & Tissue UnderperfusionVolume Loss & Tissue Underperfusion

Pressure & Stretch receptors activated Pressure & Stretch receptors activated

HR / SV increasedHR / SV increased

ADH / Aldosterone secreted - ADH / Aldosterone secreted - renal and hypothalamic mechanismrenal and hypothalamic mechanism

Need for adequate resuscitationNeed for adequate resuscitation


Tissue DamageTissue Damage

Most important triggerMost important trigger

Neural pathways from wound Neural pathways from wound reach hypothalamusreach hypothalamus efferents go to pancreas efferents go to pancreas glucagon glucagon insulininsulin efferents to adrenal efferents to adrenal cortisol, catecolamines cortisol, catecolamines

Release of cytokinesRelease of cytokines


Pain & FearPain & Fear

Increased levels of Increased levels of catecholaminescatecholamines

Fight or flight responseFight or flight response


Homeostatic ResponseHomeostatic Response

Elective operationElective operation min tissue damagemin tissue damage pain/fear managedpain/fear managed less hypotensionless hypotension infection rareinfection rare stress response in controlledstress response in controlled

Homeostatic ResponseHomeostatic Response

TraumaTrauma major tissue damagemajor tissue damage pain/fear excessive managedpain/fear excessive managed hypotension commonhypotension common infection commoninfection common Stress response uncontrolledStress response uncontrolled

TriggersTriggers ResponseResponse

Volume loss Volume loss Neurohormonal andNeurohormonal and

Tissue damageTissue damage Inflammatory armsInflammatory arms

Pain & Fear Pain & Fear


Mediators ofMediators ofStress ResponseStress Response

Neurohormonal armNeurohormonal arm Catecolamines, glucocorticoids, Catecolamines, glucocorticoids,

glucagon, ADH, aldosteroneglucagon, ADH, aldosterone

Inflammatory armInflammatory arm Cytokines, complement, eicisanoids, Cytokines, complement, eicisanoids,

PAFPAF

Mediators of Stress ResponseMediators of Stress Response

Neurohormonal ArmNeurohormonal Arm- Counterregulatory Hormones- Counterregulatory Hormones

catecholaminescatecholamines maintain circulation, maintain circulation, hepatic glycolysis, lipolysis, hepatic glycolysis, lipolysis,

gluconeogenesis, gluconeogenesis, BMR BMR glucagonglucagon

glycogenolytic, gluconeogenicglycogenolytic, gluconeogenic glucocorticoids?/ACTHglucocorticoids?/ACTH

mobilise muscle protein, gluconeogenesismobilise muscle protein, gluconeogenesis ADH. AldosteroneADH. Aldosterone

Retain water and NaRetain water and Na

Inflammatory Arm - CytokinesInflammatory Arm - Cytokines

TNF-alpha, IL-1, IL-2, IL-6, TNF-alpha, IL-1, IL-2, IL-6, IFN-gammaIFN-gamma

Local effects - para or autocrineLocal effects - para or autocrine

Response to tissue injuryResponse to tissue injury


CytokinesCytokines

In elective surgeryIn elective surgery confined to woundconfined to wound

Trauma/sepsisTrauma/sepsis spill over/ endocrine effectspill over/ endocrine effect


Cytokines - local effectCytokines - local effect

Promote wound healing Promote wound healing

Stimulate angiogenesisStimulate angiogenesis

White cell migrationWhite cell migration

Ingrowth of fibroblastsIngrowth of fibroblasts

Localise the woundLocalise the wound


Cytokines - spill over Cytokines - spill over

Mobilisation of AA, stimulation of Mobilisation of AA, stimulation of acute phase protein synthesisacute phase protein synthesis

Increase WBC counts/HypoferremiaIncrease WBC counts/Hypoferremia

Fever, subjective discomfort, sleepFever, subjective discomfort, sleep


Cytokines - severe trauma /sepsisCytokines - severe trauma /sepsis

Increased organ vascular permeabilityIncreased organ vascular permeability

Multiple organ dysfunctionMultiple organ dysfunction

HypotensionHypotension


Stress Stress Response Response

The stress just described response The stress just described response may be characterised as a may be characterised as a adrenergic adrenergic corticoid phasecorticoid phase

When the patient recovers the When the patient recovers the adrenergic corticoid phase changes adrenergic corticoid phase changes to an to an anabolic phaseanabolic phase

Stress ResponseStress ResponseAdrenergicAdrenergic--Corticoid PhaseCorticoid Phase

ACTH and cortisolACTH and cortisol mobilises proteinmobilises proteingluconeogenesisgluconeogenesis

CatecolaminesCatecolamines circulatory adjustmentcirculatory adjustment metabolic response if prolongedmetabolic response if prolonged

Aldosterone and ADHAldosterone and ADH Salt and water retentionSalt and water retention

Insulin and Insulin and glucagon (via epinephrine) glucagon (via epinephrine) gluconeogenesisgluconeogenesis

Cytokines confined to woundCytokines confined to wound

Stress ResponseStress Response

Adrenergic - corticoid phaseAdrenergic - corticoid phase

Remains until insult correctedRemains until insult corrected

Hypermetabolism-BMR Hypermetabolism-BMR increasesincreases

10-15%10-15% in elective operationin elective operation

25% 25% in long bone fracturein long bone fracture

200% 200% in 50% burnin 50% burn

Stress Stress ResponseResponse

Adrenergic - corticoid phaseAdrenergic - corticoid phase

Altered Glucose MetabAltered Glucose Metab

Normal/low insulin and insulin resistanceNormal/low insulin and insulin resistance

persisting hyperglycaemiapersisting hyperglycaemia

injured tissue uses glucoseinjured tissue uses glucose


ADRENERGIC - CORTICOID PHASEADRENERGIC - CORTICOID PHASE

Altered protein metabolismAltered protein metabolism Extensive muscle protein releaseExtensive muscle protein release extensive urine N loss extensive urine N loss reduced by feedingreduced by feeding

Altered fat metabolismAltered fat metabolism Accelerated lipolysis via hormone Accelerated lipolysis via hormone

sensitivesensitive lipaselipase Ketosis bluntedKetosis blunted

ANABOLIC PHASEANABOLIC PHASE gluconeogenesisgluconeogenesis catecolaminescatecolamines

aldosterone and ADHaldosterone and ADH Salt and water lossSalt and water loss

insulin and insulin and glucagon glucagon protein anabolismprotein anabolism

cytokines reductioncytokines reduction


Elective Elective OperationsOperations

Adrenergic corticoid Adrenergic corticoid phasephase period of catabolism period of catabolism lasts 1-3 dayslasts 1-3 days

Anabolic phaseAnabolic phase starts D3-D6starts D3-D6 positive N balancepositive N balance protein synthesisprotein synthesis recovery of lean massrecovery of lean mass

Nutritional SupportNutritional Supportfor Elective Operationsfor Elective Operations

Because the adrenergic-corticoid phase is Because the adrenergic-corticoid phase is short in elective, uncomplicated surgery short in elective, uncomplicated surgery

– Fluid therapy with 5% dextrose is Fluid therapy with 5% dextrose is enough for up to 5-7 daysenough for up to 5-7 days

Nutritional SupportNutritional Supportfor Severe Stressfor Severe Stress

The adrenergic-corticoid phase is The adrenergic-corticoid phase is prolonged inprolonged in

severe injury severe injury Malnourished patientsMalnourished patients Infected patientsInfected patients

Nutritional therapy is neededNutritional therapy is needed

Stress ResponsesStress Responses

The response is The response is affectedaffected

MalnutritionMalnutrition

Age Age

GenderGender

InfectionInfection

ConsequencesConsequencesof Malnutritionof Malnutrition

Metabolic response needs increased energy Metabolic response needs increased energy expenditureexpenditure

If intake < expenditure - protein/fat mass lostIf intake < expenditure - protein/fat mass lost Loss of 15% BW interacts with disease Loss of 15% BW interacts with disease

process toprocess to compromise immune response - sepsis, MOFcompromise immune response - sepsis, MOF poor wound healingpoor wound healing edema due to edema due to albumin albumin reduced mobility, reduced mobility, respiratory muscle strength & respiratory muscle strength &

vital capacity vital capacity pneumonia pneumonia altered GI function/breached mucosal barrieraltered GI function/breached mucosal barrier

Normal Post Op Normal Post Op DripDrip

Energy provided as dextroseEnergy provided as dextrose

1 L of D5W - 50g or 170 kcal1 L of D5W - 50g or 170 kcal

Typical post op patient gets 500 kcal/dTypical post op patient gets 500 kcal/d enough to stimulate pancreatic insulinenough to stimulate pancreatic insulin not enough to support a severe stress not enough to support a severe stress

reactionreaction

Need for nutritional support to match Need for nutritional support to match energy expenditure if stress is prolongedenergy expenditure if stress is prolonged

Metabolic ResponseMetabolic Responseto Trauma / to Trauma /

Severe Surgical StressSevere Surgical Stress

Unfed trauma patients rapidly use their Unfed trauma patients rapidly use their protein and fat stores resulting in protein and fat stores resulting in increased susceptibility to effects of increased susceptibility to effects of haemorrhage, operations and infection haemorrhage, operations and infection resulting in organ system failure, sepsis resulting in organ system failure, sepsis and deathand death

Malnourished patients are at greater riskMalnourished patients are at greater risk

Determinants of HostDeterminants of HostResponses to Surgical StressResponses to Surgical Stress

AgeAge Fat mass increase with ageFat mass increase with age Loss of muscle massLoss of muscle mass Loss of strength with immobilityLoss of strength with immobility Decreased sensitivity to perturbationsDecreased sensitivity to perturbations Decreased effectiveness to maintain Decreased effectiveness to maintain

homeostasishomeostasis

GenderGender Lean body mass less in Lean body mass less in

femalesfemales

N loss more pronounced in N loss more pronounced in muscular malesmuscular males


Invasive InfectionInvasive Infection

May complicate any operation / injuryMay complicate any operation / injury

Results in increases metabolic rate - Results in increases metabolic rate - fever, hyperventilation, etcfever, hyperventilation, etc

Nutritional depletion synergysticNutritional depletion synergystic


Cuthbertson described in 1930 theCuthbertson described in 1930 the Ebb or shock phaseEbb or shock phase Flow phaseFlow phase

CuthbertsonCuthbertson ModernModernEbbEbb unresuscitatedunresuscitatedFlow Flow adrenergic-adrenergic-

corticoidcorticoidnot describednot described anabolic anabolic



Cuthbertson Cuthbertson Ebb or shock phaseEbb or shock phase

12-24 hours12-24 hours BP, BP, CO, CO, Temp, Temp, O O22 consumption consumption due to haemorrhage, hypoperfusion, due to haemorrhage, hypoperfusion,

lactic acidosislactic acidosis Flow phase (adrenergic - corticoid)Flow phase (adrenergic - corticoid)

hypermetabolism, hypermetabolism, CO, CO, Urine N loss, Urine N loss, altered glucose, tissue catabolismaltered glucose, tissue catabolism

similar to elective surgery but greatersimilar to elective surgery but greater



Questions ?Questions ?

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

Describe the metabolic responses this patient has.Describe the metabolic responses this patient has.

What are the confounding factors that may What are the confounding factors that may complicate his recovery?complicate his recovery?

In a severely injured patient the priorities In a severely injured patient the priorities are:are: - resuscitation- resuscitation

- wound care- wound care

Nutritional support usually after 48 hrsNutritional support usually after 48 hrs

The next lecture will cover all aspects The next lecture will cover all aspects of nutritionof nutrition

Coming soon to aComing soon to aLecture Theatre near youLecture Theatre near you

– Nutritional Support– Nutritional Support

QuestionsQuestions

alteration in metabolism in surgical patients. energy metabolism l in order to mount a metabolic...

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