Systemic Response to Injury and Metabolic Support

1. Systemic Response to Injury and Metabolic Support Aaron Lesher 9/1/09

2. Definitions • Infection • Identifiable source of microbial insult • SIRS • 2 or more of the following: • Temp >38 or <36 • HR > 90 • RR >20 or PaCO2 <32 or mechanical ventilation • WBC >12,000 or <4000 or >10% bands • Sepsis • Identifiable source of infection + SIRS • Severe Sepsis • Sepsis + organ dysfunction • Septic shock • Sepsis + cardiovacular collapse (requiring vasopressor support)

3. The Systemic Inflammatory Response Syndrome (SIRS)

4. CNS regulation of inflammation • Integral role in inflammatory response that is mostly involuntary • Autonomic system regulates HR, BP, RR, GI motility and temp

5. CNS Regulation of Inflammation

6. Hormonal Response to Injury • Includes: • Cytokines • Glucagon • Insulin • Epinephrine • Serotonin • Histamine • Glucocorticoids • Prostaglandins • leukotrienes

7. ACTH • A. Is synthesized in the hypothalamus • B. Is superceeded by pain, anxiety and injury • C. Continues to be released in a circadian pattern in injured patients • D. Causes the release of mineralocorticoids from the adrenal in a circadian pattern

8. ACTH

9. Cortisol • Essential for survival during physiologic stress • Potentiates the effects of glucagon and epinephrine manifesting as hyperglycemia • In liver, stimulate gluconeogenesis • Induces insulin resistance in skeletal muscle and adipose tissue • In skeletal muscle induces protein breakdown and release of lactate • Immunosuppressive agent

10. A primary action of aldosterone is to: • A. Convert angiotensinogen to angiotensin • B. Decrease Cl reabsorption in the renal tubule • C. Decrease K secretion in the renal tubule • D. Increase Na reabsorption in the renal tubule • E. Increase renin release by the juxtaglomerular apparatus

11. Catecholamine elevation after injury • A. Is limited to epinephrine only • B. Is limited to norepinephrine only • C. Increases by 10- to 20-fold after injury • D. Is sustained 24-48 hours before decreasing

12. C-reactive protein • A. Is secreted in a circadian rhythm with higher levels in the morning • B. Increases after eating a large meal • C. Does not increase in response to stress in patients with liver failure • D. Is less sensitive than ESR as a marker of inflammation

13. Mediators of Inflammation • Cytokines • Heat shock proteins • Reactive oxygen metabolites • Reperfusion injury • Eicosanoids • Includes prostaglandins, leukotrienes, thromboxane • Fatty Acid metabolites • Kallikrien-Kinen system • Serotonin • histamine

14. Cytokine Response to Injury • Lots of cytokines • Most potent mediators of inflammatory response • Pro- and anti-inflammatory

15. Cytokines…. • TNF-Α • one of the earliest and most potent mediators of host response • Primary source: monocytes/macrophages and T cells • Half life of 20 min but potent • Many functions • IL-1 • Primarily released by macrophages and endothelial cells • Half life less than 6 mins, “sneaky” • Classic febrile response to injury • IL-6 • Linked to hepatic acute phase proteins production

16. Impt Eicosanoids • Prostacyclin (PGI2) • From endothelium • Decreases platelet aggregation • Promotes vasodilation • Thromboxane (TXA2) • From platelets • Increases platelet aggregation • Promotes vasoconstriction

19. Cellular Response to Injury • Transcription factors impt in inflammatory response as they dictate the manner and magnitude with which a cell can respond to injury

20. Endothelium-mediated Injury L-selectins Beta 2 integrins Activated Neutrophil E- or P-selectins ICAM-1,2

21. Nitric Oxide • A. Is primarily made in hepatocytes • B. Has a half-life of 20-30 minutes • C. Is formed from oxidation of L-arginine • D. Can increase thrombosis in small vessels

22. Surgical Metabolism Basic metabolic needs = 25 kcal/kg/day

23. Where do we get our caloric needs? • Fat 9 kcal/g • Protein 4 kcal/g • Oral carbs 4 kcal/g • Dextrose (in IV fluids) 3.4 kcal/g

24. Surgical MetabolismMetabolism during fasting • Starvation: fat is the main source of energy in trauma and starvation • Carbohydrates are stored in the form of glycogen (2/3 skeletal muscle, 1/3 liver) • Due to deficiency in glucose-6-phosphatase, skeletal muscle not available for systemic use and therefore, liver stores are used quickly

25. Gluconeogenesis • Occurs in the liver • Precursors include: • Amino acids (alanine) • Lactate • Pyruvate • Glycerol • Cori cycle • In late starvation gluconeogenesis occurs in kidney

26. Nitrogen wasting during (simple) starvation • Sig amounts of protein must be degraded to be used for gluconeogenesis • Urine nitrogen excretion increases from 7-10g/day to up to 30g/day • Protein degradation occurs mostly in skeletal muscles, but also some in solid organs

27. Nitrogen wasting during (prolonged) starvation • Systemic proteolysis decreases • Urinary nitrogen approx 2-5g/day • Reflects change to using ketone bodies as energy source • Brain begins to use ketones as energy source after 2 days, and this becomes the principal energy source by 24 days

28. Metabolism following Injury

29. Fat digestion • Broken down into micelles and FFAs • Micelles enter enterocytes • Chylomicrons are formed which enter thoracic duct • Medium and short chain amino acids enter portal system with amino acids and carbs

30. Protein Metabolism • 6 g protein = 1 g N • Provides substrates for gluconeogenesis and acute phase proteins • 1g protein=4kcal

31. Protein metabolism

32. Healthy patients undergoing uncomplicated surgery can remain NPO (with IVF) for how many days before significant protein catabolism occurs? 2 days 4 days 7 days 10 days Healthy patients without malnutrition undergoing uncomplicated surgery can tolerate 10 days of partial starvation before any significant protein catabolism occurs

33. Nutrition facts • Albumin half life = 18 days • Prealbumin = 3 days

34. Nutrition in the Surgical Patient • Harris-Benedict equation calculates basal energy expenditure (nutrition needs) based on weight, height, age and gender • Usually estimate 30kcal/kg/day • Goals: • Provide adequate nonprotein calories to prevent lean muscle breakdown • Meet substrate requirements for protein synthesis • Estimate 1.5-2 g protein/kg/day • Want 100-150 calories of non protein calories for each 1 g of nitrogen

35. The nutritionist in the ICU informs you that one of your intubated patients “Greuner”’s metabolic cart study has revealed a respiratory quotient of 1.2. What do you do? • A. Smile. Thank her politely for the information and run to google.com to figure out what she is talking about. • B. Ask her to decrease the daily carbohydrates that the patient is receiving. • C. Ask her to increase the carbohydrate intake. • D. Do nothing, you are tired and the respiratory quotient is not important in this patient.

36. Respiratory Quotient (RQ) • Ratio of CO2 produced to O2 consumed – measurement of energy expenditure • RQ>1 = lipogenesis (overfeeding) • RQ<1 = ketosis and fat oxidation (starving) • Fat RQ = 0.7 • Protein RQ = 0.8 • Carbohydrate RQ = 1.0

37. Enteral Nutrition

38. Enteral Nutrition • Intact GI tract can tolerate complex solutions • If GI tract has not been fed for a long period of time, less likely to tolerate complex carbohydrates • Results in a reduction of infectious complications in critically ill patients

39. Which of the following would be typical of an enteral hepatic-failure formula? • A. Lower fluid volume, K, PO4, Mag • B. 50% reduction of carbs • C. 50% of proteins are in the form of branched chain amino acids (leucine, isoleucine, and valine) • D. Increased arginine, omega 3 fatty acids, and B carotene

40. Parenteral Nutrition • Preoperative PN has been shown to be beneficial to some surgical patients, especially in those with severe malnutrition • Postoperatively it is associated with higher risk of infectious complications when used inappropriately • Still fewer infectious risks when compared with no feeding at all

41. Parenteral Nutrition • TPN • Dextrose concentration is high (15-25%) • macro- and micronutrients avail via this route • PPN • Reduced dextrose (5-10%) • Reduced protein (3%)

42. Deficiencies • Chromium  • hyperglycemia, neuropathy • Zinc  • Most frequent in pt on PN • Perioral rash • Copper  • Microcytic anemia

43. Thanks! Questions?