Alteration in Metabolism in Surgical Patients

1. Alteration in MetabolisminSurgical Patients

2. 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?

3. Source kg kcal Fat 14 125,000 Protein skeletal muscle 6 24,000 other 6 24,000 Glycogen muscle 0.15 600 liver 0.075 300 free glucose 0.02 80 Body Composition

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 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

7. Protein & Amino AcidMetabolism Total protein turnover 300g /day Obligatory N loss in urine 12g /day or 80g protein /day

8. Protein & Amino AcidMetabolism Nitrogen Balance Nbalance = Nintake - Nout • Negative in starvation, injury, severe infection

10. Parameter Starvation Trauma BMR - ++ Mediators - +++ Major fuel Fat Mixed Ketone production +++ +/- Hepatic ureagenesis + +++ Neg N balance + +++ Gluconeogenesis + +++ Muscle proteolysis + +++ Hepatic protein synthesis + +++ Response toStarvation vs Injury

11. 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

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

14. 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

15. 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

16. Homeostatic Responsesto Stress Pain & Fear • Increased levels of catecholamines • Fight or flight response

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

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

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

20. Mediators ofStress Response • Neurohormonal arm • Catecolamines, glucocorticoids, glucagon, ADH, aldosterone • Inflammatory arm • Cytokines, complement, eicisanoids, PAF

21. 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

22. 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

23. Mediators ofStress Response Cytokines • In elective surgery • confined to wound • Trauma/sepsis • spill over/ endocrine effect

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

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

27. Mediators ofStress Response Cytokines - severe trauma /sepsis • Increased organ vascular permeability • Multiple organ dysfunction • Hypotension

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 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

31. 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

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

33. 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

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

35. 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

36. 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

37. Nutritional Supportfor Severe Stress • The adrenergic-corticoid phase is prolonged in • severe injury • Malnourished patients • Infected patients • Nutritional therapy is needed

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

39. Consequencesof Malnutrition • Metabolic response needs increased energy expenditure • If intake < 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

40. 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

41. 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

42. 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

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

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

45. 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

46. 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

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

48. 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

49. Questions