Systemic Response to Injury and Metabolic Support

Systemic Response to Injury and Metabolic Support

Aaron Lesher9/1/09

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)

The Systemic Inflammatory Response Syndrome (SIRS)

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

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

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

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 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

Impt Eicosanoids

Prostacyclin (PGI2) 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

E- or P-selectins

Beta 2 integrins

ICAM-1,2

Activated Neutrophil

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

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

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

Gluconeogenesis

Occurs in the liver Precursors include:

Amino acids (alanine) Lactate Pyruvate Glycerol

Cori cycle In late starvation gluconeogenesis

occurs in kidney

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

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

Does the gut work?`

Yes No

Enteral Nutrition

PO feeds?

Yes No

NGT feeds?

No

Parenteral Nutrion

Yes

Post pyloric feeds Consider G tube

Consider G-J tube

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

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 Dextrose concentration is high (15-

25%) macro- and micronutrients avail via this

route PPN

Reduced dextrose (5-10%) Reduced protein (3%)

Deficiencies

Chromium hyperglycemia, neuropathy

Zinc Most frequent in pt on PN Perioral rash

Copper Microcytic anemia

Thanks!

Questions?