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

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Presentation on theme: "Systemic Response to Injury and Metabolic Support Aaron Lesher 9/1/09."— Presentation transcript:

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 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 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

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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 E- or P- selectins Beta 2 integrins ICAM-1,2 Activated Neutrophil

21 Nitric Oxide AA. Is primarily made in hepatocytes BB. Has a half-life of minutes CC. Is formed from oxidation of L- arginine D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 Metabolism Metabolism 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 g protein/kg/day  Want 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 Does the gut work? ` Yes Enteral Nutrition PO feeds? YesNo NGT feeds? No Post pyloric feeds Consider G-J tube Yes Consider G tube No Parenteral Nutrion

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?


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