Metabolic response to injury 14 03-16

Metabolic Response to Injury - D

r.R.Durai

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METABOLIC RESPONSE TO INJURY

DR.R.DURAI MSASSISSTANT PROFESSOR

DEPT.OF GENRERAL SURGERYMGMCRI

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Metabolic Response to Injury - Dr.R.Durai

2JOHN HUNTER (1794)

“Treatise on the Blood, Inflammation and gunshot wounds”

“Impressions are capable of producing or increasing natural actions and are then called stimuli, but they are capable of producing too much action as well as depraved, unnatural or what we call diseased action.”

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3Objectives

Homeostasis - Concept Components of Responses Mediators of Responses Phases of Responses & Key elements Factors – Exacerbate & Avoidable

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4Homeostasis

Maintenance of nearly constant conditions in the internal environment.

Essentially all organs and tissues of the body perform functions that help maintain these constant conditions.

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5Basic Concepts in Homeostasis

Homeostasis is the foundation of normal physiology.

Stress-free peri-operative care helps to restore homeostasis following elective surgery.

Resuscitation, surgical intervention & critical care can return the severely injured patient to a situation in which homeostasis becomes possible once again.

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6Nature of the injury response

Metabolic response to injury is Graded and evolves with time

the more severe the injury, the greater the response Immunologica

l

HormonalCellular response

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9Response Components

Physiological Consequences

Metabolic Manifestations

Clinical Manifestations

Laboratory Changes14-03-2016


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PHYSIOLOGICAL METABOLIC

Response Components

↑ Cardiac Output ↑ Ventilation ↑ Membrane

Transport Weight loss Wound Healing

Hypermetabolism Acclerated

Gluconeogenesis Enhanced Protein

breakdown Increased Fat

oxidation14-03-2016


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CLINICAL LABORATORY

Response Components

Fever Tachycardia Tachypnoea Presence of wound

or Inflammation Anorexia

Leucocytosis/Leucopenia Hyperglycemia Elevated CRP/Altered

acute phase reactants Hepatic/Renal

dysfunction

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12Mediators of Injury Response

Neuro – Endocrine [ Hormonal ]

Immune System [ Cytokines ]

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13Neuro-endocrine response to injury/critical

illness

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.

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CRF ACTH CORTISOL

ADRENALIN &

GLUCAGON

METABOLIC

RESPONSE

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16Purpose - Neuro-endocrine response

Provide essential substrates for survival

Postpone anabolism

Optimize host defense

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Proinflammatory phase

Counter regulatory phase

Immunological response

IL-1, IL-6, TNF-alpha Hypothalamus → pyrexia Hepatic acute phase protein

IL-1 receptor antagonist (IL-1Ra) and TNFsoluble receptors (TNF-sR-55 and 75)

Prevent excessive proinflammatory activities

Restore homeostasisSIRS

MODSCOMP. ANTI-INFLAMMATORY RESPONSE SYNDROME { CARS } 14-03-2016


18Phases – Physiological response

[ David Cuthbertson – 1930 ] Injury

EBB24-48 HRS

FLOW3-10 DAYS

RECOVERY

SHOCK CATABOLISM

ANABO LISM

Hours

Days Weeks

BREAKING DOWN ENERGY STORES

BUILDING UP USED ENERGY14-03-2016


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Ebb and Flow Phases

Phase Duration Role Physiological Hormones

Ebb 24 - 48 hrs

Conserve - blood volume & energy reserves - Repair

↓ BMR, ↓ temp, ↓ CO, hypovolaemia, lactic acidosis

Catecholamines, Cortisol, aldosterone

FlowCatabolic 3 – 10

daysMobilisation of energy stores – Recovery & Repair

↑ BMR, ↑ Temp, ↑ O2 consump, ↑ CO

Cytokines + ↑ Insulin, Glucagon, Cortisol, Catechol but insulin resistance

Anabolic 10 – 60 days

Replacement of lost tissue

+ve Nitrogen balance Growth hormone, IGF

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20Key catabolic elements of flow

phase

Hypermetabolism Alterations in skeletal muscle protein Alterations in Liver protein Insulin resistance

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211. Hypermetabolism

Majority of trauma patients - energy expenditure appr. 15-25% > predicted healthy resting values.

Factors which increases this metabolism : * Central thermodysregulation * Increased sympathetic activity * Increased protein turnover * Wound circulation abnormalities

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222.Skeletal muscle – Metabolism

1. Muscle wasting – result of ↑ muscle protein degradation + ↓ muscle protein synthesis. (RS & GIT). Cardiac muscle is spared.

2. Is mediated at a molecular level mainly by activation of the ubiquitin-protease pathway.

3. Lead - Increased fatigue, reduced functional ability, ↓QOL & ↑ risk of morbidity & mortality.

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233.Hepatic acute phase response

Cytokines – IL- 6 ↑ Synthesis of Positive acute phase proteins : Fibrinogen & CRP

Negative acute reactants : Albumin decreases

Not Compensated

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244.Insulin resistance

Hyperglycaemia is seen – ↑ glucose production + ↓ glucose uptake – peripheral tissues. ( transient induction of insulin resistance seen )

Due – Cytokines & decreased responsiveness of insulin- regulated glucose transporter proteins.

The degree of insulin resistance is ∞ to magnitude of the injurious process. 14-03-2016


25Changes 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

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With lean issue, each 1 g of nitrogen is contained within 6.25 g of protein, which is contained in approximately 36 g of wet weight tissue.

Thus the loss of 1 g of nitrogen in urine is equivalent to the breakdown of 36 g of wet weight lean tissue.

Protein turnover in the whole body is of the order of 150-200 g per day.

A normal human ingests 70-100 g of protein per day, which is metabolized and excreted in urine as ammonia and urea(14 g N/day)

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During total starvation, urinary loss of nitrogen is rapidly attenuated by a series of adaptive changes

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 ongoing septic complications , this adaptive change fails to occur, and there is a state of auto cannibalism , resulting in continuing urinary nitrogen losses of 10-20 g/day(500 g lean tissue/day)

As with total starvation, once loss of body protein mass has reached 30-40 % of the total, survival is unlikely

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29In critically ill patients with resuscitation,

<24 hrs – Body weight increases due to extracellular water expansion by 6-10 litres. This can be overcome by careful intra operative

management of fluid balance 1-10 days – Total body protein will diminish by 15% and

body weight will reach negative balance as the expansion of extra cellular space resolves This can be overcome by blocking Neuro endocrine

response with epidural analgesia and early enteral feeds

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30Factors - ↑ response to injury

Hypothermia Pain Starvation Immobilisation Sepsis Hypotension

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32Avoidable factors that compound

the response to injury

Continuing haemorrhage Hypothermia Tissue oedema Tissue underperfusion Starvation Immobility

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33 Avoidable Factors

Volume loss : Careful limitation of intra operative administration of colloids and crystalloids so that there is no net weight gain.

Hypothermia : RT – maintaining normothermia

by an upper body forced air heating cover ↓ wound infection, cardiac complications and bleeding and transfusion requirements.

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Administration of activated protein C - to critically ill patients has been shown to ↓ organ failure and death. It is thought to act, in part, via preservation of the micro circulation in vital organs.

Maintaining the inormoglycemia with insulin infusion during critical illness has been proposed to protect the endothelium and thereby contribute to the prevention of organ failure and death.

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Starvation : During starvation, the body is faced with an obligate need to generate glucose to sustain cerebral energy metabolism(100g of glucose per day).

Provision of at least 2L of IV 5% dextrose for fasting patients provides glucose as above.

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Tissue oedema : is mediated by the variety of mediators involved in the systemic inflammation. Careful administration of anti-mediators & reduce fluid overload during resuscitation reduces this condition.

Immobility : Has been recognized as a potent stimulus

for inducing muscle wasting. Early mobilization is an essential measure to avoid muscle wasting.

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App. to prevent unnecessary aspects of stress response

Minimal access techniques

Minimal periods of Starvation Epidural analgesia

Early mobilization 14-03-2016

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Metabolic response to injury 14 03-16

Health & Medicine

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