Metabolic Response to Injury

Metabolic response to injury. Source - Bailey & Love.

1. Metabolic Response to Injury Part - I

2. Nature of the injury response The response to injury is graded and evolves with time.

3. Elective surgery Transient and modest rise in Temp, HR, RR, energy expenditure and TLC Major trauma/sepsis Systemic inflammatory response syndrome (SIRS), Hypermetabolism Marked catabolism Shock Multiple organ dysfunction (MODS)

4. Mediators of the metabolic response to injury 1. Neuroendocrine response Injury ---> afferent nociceptive neurons ---> the spinal cord ---> thalamus ---> hypothalamus - --> pituitary Acute phase actively secreting pituitary elevated cortisol, glucagon, adrenaline Chronic phase hypothalamic suppression and low serum levels of the respective target organ hormones chronic wasting

5. Other neuroendocrine mediators: ↓ insulin release and sensitivity ↓ IGF-1 ↑ prolactin and GH ↓ thyroid hormones and gonadal function GH: Lipolysis insulin-antagonist proinflammatory

6. Mediators of the metabolic response to injury 2. Immune response Proinflammatory cytokines produced within first 24 hours interleukin-1 (IL-1) tumour necrosis factor alpha (TNFα) IL-6 IL-8 nitric oxide (NO) and prostanoids

7. Proinflammatory cytokines ---> peripheral insulin resistance

8. Endogenous cytokine antagonists act to control the proinflammatory response e.g. interleukin-1 receptor antagonist (IL-1Ra) and TNF soluble receptors (TNF-sR-55 and 75))

9. Th2-type counterinflammatory response Regulated by IL-4, -5, -9 and -13 and TGFβ If prolonged, it may evolve into counterinflammatory response syndrome (CARS) and result in immunosuppression

10. Specialised pro-resolving mediators (SPM): local mediators in inflamed tissue E.g. essential fatty acid-derived lipoxins, resolvins , protectins and maresins reduce proinflammatory cytokines and lipid mediators

11. The Ebb and Flow model In 1930, Sir David Cuthbertson divided the metabolic response to injury in humans into ‘ebb’ and ‘flow’ phases.

12. The Ebb phase Approximately 24–48 hours from time of injury It may be shortened by proper resuscitation Characterised by Hypovolaemia Decreased basal metabolic rate ↓ cardiac output Hypothermia Lactic acidosis

13. The Ebb phase The predominant hormones regulating the ebb phase are catecholamines, cortisol and aldosterone (following activation of the renin–angiotensin system) Conserve both circulating volume and energy stores for recovery and repair Following resuscitation, the ebb phase evolves into a hypermetabolic flow phase, which corresponds to SIRS.

14. The Flow phase This phase involves the mobilisation of body energy stores for recovery and repair, and the subsequent replacement of lost or damaged tissue. It is characterised by tissue oedema (from vasodilatation and increased capillary leakage), increased basal metabolic rate (hypermetabolism), increased cardiac output, raised body temperature, leukocytosis, increased oxygen consumption and increased gluconeogenesis

15. The Flow phase

16. Key catabolic elements of the flow phase of metabolic response to injury The body reprioritises limited resources away from peripheral tissues towards key viscera (liver, immune system) and the wound.

17. 1. Hypermetabolism Energy expenditures approx 15–25 % above predicted healthy resting values Patient energy expenditure may be increased by central thermodysregulation increased sympathetic activity abnormalities in wound circulation increased protein turnover nutritional support Standard intensive care counteract the hypermetabolism in stress response

18. 2. Alterations in skeletal muscle protein metabolism Muscle wasting occurs as a result of increase in muscle protein degradation (via enzymatic pathways) decrease in muscle protein synthesis It provides amino acids for the metabolic support of central organs/tissues

19. Major sites of protein loss: peripheral skeletal muscle respiratory muscles and gut (reducing gut motility) Cardiac muscle mostly spared The predominant mechanism involved in the wasting of skeletal muscle is the ATP-dependent ubiquitin–proteasome pathway.

20. Under extreme conditions of catabolism (e.g. major sepsis), urinary nitrogen losses can reach 14–20 g/day The muscle catabolism cannot be inhibited fully by providing artificial nutritional support as long as the stress response continues. The nutritional support should be at a modest level.

21. Clinically, a patient with skeletal muscle wasting will experience asthenia, increased fatigue, reduced functional ability, decreased quality of life and an increased risk of morbidity and mortality Can result in immobility and contribute to hypostatic pneumonia and death if prolonged and excessive.

22. 3. Alterations in hepatic protein metabolism (Acute phase protein response) Hepatic protein synthesis : structural proteins and export proteins Albumin is the major export protein The transcapillary escape rate (TER) of albumin is about ten times the rate of synthesis Albumin TER may be increased three-fold following major injury/sepsis The acute phase protein response (APPR) is a ‘double-edged sword’ for surgical patients It provides proteins important for recovery and repair, at the expense of valuable lean tissue and energy reserves

23. 4. Insulin resistance Following surgery or trauma, hyperglycaemia develops due to ↑ glucose production and ↓ glucose uptake in peripheral tissues. Decreased glucose uptake is a result of insulin resistance. The mainstay of management of insulin resistance is intravenous insulin infusion.

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