1. Systemic Response to Injury and Metabolic Support
Aaron Lesher
9/1/09
Injury includes trauma, surgery, infection

2. Definitions Infection SIRS Sepsis Severe Sepsis Septic shock
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)
Mediated by TNF alpha and IL1

3. The Systemic Inflammatory Response Syndrome (SIRS)
2 phases: proinflammatory then antiinflammatory
CARS=counterregulatory antiinflammatory response syndrome

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
Ach=impt anti inflammatory cascade
Decrease HR, inc gut motility, dilates arterioles, pupil constriction
Epidural and spinal anesthesia may decrease this response

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
Synthesized by ant pituitary
Circadian pattern altered greatly in injury

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
Maintain intravascular volume by reabsorption of Na
Early distal convoluted tubules of nephrons

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 IL-1 IL-6
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
TNF big deal in MOSF

16. Impt Eicosanoids Prostacyclin (PGI2) Thromboxane (TXA2)
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
Low affinity initially
Activated neutrophil releases proteases, oxidants and phospholipids, resulting in endothelial cell injury and increased microvascular permeability

21. Nitric Oxide A. Is primarily made in hepatocytes
B. Has a half-life of minutes
C. Is formed from oxidation of L-arginine
D. Can increase thrombosis in small vessels
Derived from endothelial surfaces
Half life of a few seconds

22. Basic metabolic needs = 25 kcal/kg/day
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
Every year

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: Cori cycle
Amino acids
(alanine)
Lactate
Pyruvate
Glycerol
Cori cycle
In late starvation gluconeogenesis occurs in kidney
Recycling of lactate and pyruvate for cori cycle

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. C. Ask her to increase the carbohydrate intake.
The nutritionist in the ICU informs you that one of your intubated patients “Greuner”’s metabolic cart study has revealed a respiratory quotient of 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
Want to increase branched cahin AAs b/c can potentially reverse encephalopathy
Answer A true for renal failure

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

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

43. Thanks!
Questions?