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

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

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

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

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

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

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

ACTH

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

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

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

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

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

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

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

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

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

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

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 Derived from endothelial surfaces Half life of a few seconds

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

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

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

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

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

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

Metabolism following Injury

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

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

Protein metabolism

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

Nutrition facts Albumin half life = 18 days Prealbumin = 3 days

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

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 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.

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

Enteral Nutrition

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

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

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

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%)

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

Thanks! Questions?