1. Alteration in Metabolism in Surgical Patients

2. Energy Metabolism l In order to mount a metabolic response to injury the body uses as a fuel glucose, fat and protein l How much fuel does the body have?

3. Body Composition Sourcekgkcal Fat14125,000 Protein skeletal muscle624,000 other624,000 Glycogen muscle0.15600 liver0.075300 free glucose0.0280

4. Body Composition Even though protein is used as a fuel in stress, its depletion is detrimental

5. Body Composition Glycogen-Fuel Fat- Fuel Protein- Structure (use as a fuel should be minimised)

6. Protein & Amino Acid Metabolism Protein l 15% body weight - ½ intracellular l Enzymes, transport, hormones, immune Fx, muscle l It is not usually a food l when needed it is converted to glucose

7. Total protein turnover300g/day Obligatory N loss in urine12g/day or 80g protein /day Protein & Amino Acid Metabolism

8. Nitrogen Balance N balance = N intake - N out J Negative in starvation, injury, severe infection Protein & Amino Acid Metabolism

10. Response to Starvation vs Injury ParameterStarvationTrauma BMR-++ Mediators-+++ Major fuelFatMixed Ketone production++++/- Hepatic ureagenesis++++ Neg N balance++++ Gluconeogenesis++++ Muscle proteolysis++++ Hepatic protein synthesis++++

11. If protein is depleted via proteolysis – ability to adapt in stress is compromised l protein depletion results in u decreased wound healing u decreased immune response u defective gut-mucosal barrier u decreased mobility/ respiratory effort Protein & Amino Acid Metabolism

13. Homeostatic Responses to Stress l Designed to maintain homeostasis l Same response in controlled or uncontrolled stress l Trigger mechanisms: n Volume loss n Tissue damage n Pain n Fear

14. Volume Loss & Tissue Underperfusion l Pressure & Stretch receptors activated l HR / SV increased l ADH / Aldosterone secreted - n renal and hypothalamic mechanism Need for adequate resuscitation Homeostatic Responses to Stress

15. Tissue Damage l Most important trigger l Neural pathways from wound n reach hypothalamus n efferents go to pancreas   glucagon  insulin n efferents to adrenal   cortisol, catecolamines l Release of cytokines Homeostatic Responses to Stress

16. Pain & Fear l Increased levels of catecholamines l Fight or flight response Homeostatic Responses to Stress

17. Homeostatic Response l Elective operation u min tissue damage u pain/fear managed u less hypotension u infection rare u stress response in controlled

18. Homeostatic Response l Trauma u major tissue damage u pain/fear excessive managed u hypotension common u infection common u Stress response uncontrolled

19. Triggers  Response Volume loss  Neurohormonal and Tissue damage  Inflammatory arms Pain & Fear  Homeostatic Responses to Stress

20. Mediators of Stress Response l Neurohormonal arm n Catecolamines, glucocorticoids, glucagon, ADH, aldosterone l Inflammatory arm n Cytokines, complement, eicisanoids, PAF

21. Mediators of Stress Response Neurohormonal Arm - Counterregulatory Hormones l catecholamines u maintain circulation, u hepatic glycolysis, lipolysis, gluconeogenesis,  BMR l glucagon u glycogenolytic, gluconeogenic l glucocorticoids?/ACTH u mobilise muscle protein, gluconeogenesis l ADH. Aldosterone u Retain water and Na

22. l Inflammatory Arm - Cytokines l TNF-alpha, IL-1, IL-2, IL-6, IFN-gamma l Local effects - para or autocrine l Response to tissue injury Mediators of Stress Response

23. Cytokines l In elective surgery n confined to wound l Trauma/sepsis n spill over/ endocrine effect Mediators of Stress Response

24. l Cytokines - local effect l Promote wound healing l Stimulate angiogenesis l White cell migration l Ingrowth of fibroblasts l Localise the wound Mediators of Stress Response

26. l Cytokines - spill over l Mobilisation of AA, stimulation of acute phase protein synthesis l Increase WBC counts/Hypoferremia l Fever, subjective discomfort, sleep Mediators of Stress Response

27. Cytokines - severe trauma /sepsis l Increased organ vascular permeability l Multiple organ dysfunction l Hypotension Mediators of Stress Response

28. 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

29. Stress Response Adrenergic - Corticoid Phase l  ACTH and cortisol n mobilises protein  gluconeogenesis l Catecolamines n circulatory adjustment n metabolic response if prolonged l Aldosterone and ADH n Salt and water retention l  Insulin and  glucagon (via epinephrine) n gluconeogenesis l Cytokines confined to wound

31. Stress Response Adrenergic - corticoid phase l Remains until insult corrected l Hypermetabolism-BMR increases 10-15%in elective operation 25% in long bone fracture 200% in 50% burn

32. Stress Response Adrenergic - corticoid phase l Altered Glucose Metab n Normal/low insulin and insulin resistance n persisting hyperglycaemia n injured tissue uses glucose

33. Stress Response ADRENERGIC - CORTICOID PHASE l Altered protein metabolism n Extensive muscle protein release n extensive urine N loss n reduced by feeding l Altered fat metabolism n Accelerated lipolysis via hormone sensitive n lipase n Ketosis blunted

34. ANABOLIC PHASE l  gluconeogenesis l  catecolamines l  aldosterone and ADH n Salt and water loss l  insulin and  glucagon n protein anabolism l cytokines reduction Stress Response

35. Elective Operations l Adrenergic corticoid phase n period of catabolism n lasts 1-3 days l Anabolic phase n starts D3-D6 n positive N balance n protein synthesis n recovery of lean mass

36. Nutritional Support for 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

37. Nutritional Support for Severe Stress l The adrenergic-corticoid phase is prolonged in n severe injury n Malnourished patients n Infected patients l Nutritional therapy is needed

38. Stress Responses The response is affected l Malnutrition l Age l Gender l Infection

39. Consequences of Malnutrition l Metabolic response needs increased energy expenditure l If intake < expenditure - protein/fat mass lost l Loss of 15% BW interacts with disease process to n compromise immune response - sepsis, MOF n poor wound healing n edema due to  albumin n reduced mobility,  respiratory muscle strength & vital capacity  pneumonia n altered GI function/breached mucosal barrier

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

41. Metabolic Response to Trauma / Severe Surgical Stress l 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 l Malnourished patients are at greater risk

42. Determinants of Host Responses to Surgical Stress Age l Fat mass increase with age l Loss of muscle mass l Loss of strength with immobility l Decreased sensitivity to perturbations l Decreased effectiveness to maintain homeostasis

43. Gender l Lean body mass less in females l N loss more pronounced in muscular males Determinants of Host Responses to Surgical Stress

44. l Invasive Infection l May complicate any operation / injury l Results in increases metabolic rate - fever, hyperventilation, etc l Nutritional depletion synergystic Determinants of Host Responses to Surgical Stress

45. Cuthbertson described in 1930 the n Ebb or shock phase n Flow phase CuthbertsonModern Ebbunresuscitated Flow adrenergic-corticoid not describedanabolic Metabolic Response to Trauma / Severe Surgical Stress

46. Cuthbertson l Ebb or shock phase n 12-24 hours n  BP,  CO,  Temp,  O 2 consumption n due to haemorrhage, hypoperfusion, lactic acidosis l Flow phase (adrenergic - corticoid) n hypermetabolism,  CO,  Urine N loss, altered glucose, tissue catabolism n similar to elective surgery but greater Metabolic Response to Trauma / Severe Surgical Stress

47. 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. Describe the metabolic responses this patient has. What are the confounding factors that may complicate his recovery?

48. In a severely injured patient the priorities are:- resuscitation - wound care l Nutritional support usually after 48 hrs l The next lecture will cover all aspects of nutrition Coming soon to a Lecture Theatre near you – Nutritional Support

49. Questions