Surgical Factors Affecting Metabolism

1
Surgical Factors Affecting Metabolism

• Trauma/Surgical Wound Pain, infection,
  inflammation
• Paracrine and Endocrine
• Iatrogenic Factors
• Inflammatory mediators LPS, IL-1, TNF-a, IL-6

2
Immuno-Metabolic Mediators IL-1

• IL-1
• Macrophages
• Hyperthermia via COX-2 in Hypothalamus
• increases PGE2 , increases BMR, increases CRH
• Hypotension via iNOS
• increasesNO

3
Immuno-Metabolic Mediators TNF

• Cachectin
• Apoptosis mediated via caspase activation
• Gene transcription via NF-kB, c-jun
• increases IL-1, IL-2, IL-2R, multiple other
  cytokines
• amplifies inflammatory response
• paracrine and endocrine

4
Immuno-Metabolic Mediators IL-6

• Liver
• Acute phase proteins
• protease inhibitors
• c-reactive protein
• compliment
• decreased albumin, transferrin, ferritin

5
Physiology of Injury

• Increased Glucocorticoids, epinephrine, glucagon
  and GH
• Carbohydrate intolerance, gluconeogenesis,
  glucogenesis, proteolysis, lipolysis
• Increased Aldosterone and ADH
• retention of salt and water, loss of potassium,
  magnesium

6
Physiology of Injury

• Increased FFA
• Increased Catecholamines
• Increased myocardial work
• Increased oxygen consumption
• Increased lactate
• Elevated Insulin levels/Increased Resistance

7
Physiology of Injury

• Muscle breakdown
• Gut breakdown
• decreased musosal barrier
• decreased immune function
• loss of tight intracellular junction
• stasis with bacterial overgrowth

8
Altered Protein Metabolism

• Muscle catabolism- provides glutamine and other
  amino acids for wounds
• Glutamine substrate for gut metabolism
• Alanine and glutamine for gluconeogenesis (liver)
• Branched Chain Amino Acids (BCAA) substrate for
  skeletal and cardiac muscle metabolism

9
Altered Glucose Metabolism

• Glycogenolysis rapidly depleted (300 kcal)
• Peripheral hydrolysis of lipids
• provides FFA for energy substrate
• Glucogenesis (Cori cycle)
• lactate to glucose
• Gluconeogenesis
• Alanine and glutamine converted to Glucose urea

10
Alterations in Metabolic Rate

• Elective surgery 10 increase
• Fistula w/o complication 10 increase
• Peritonitis 25 increase
• Long Bone fx 25 increase
• Multiple injuries 50 increase
• Sepsis 50 increase
• Burn 40 100 increase

11
Modification of the Metabolic Response

• Beta blockade significantly reduces metabolic
  rate in thermal injury. Wilmore et al., Ann Surg
  180653,1974.
• Beta blockade modifies post-traumatic protein
  catabolism. Hulton et al., J Surg Res
  39310,1985.
• Epi-dural anesthesia improves nitrogen balance.
  Tsuji et al., Br J Surg 74421, 1987 Heindorf et
  al., Surgery 111543,1992.

12
Modification of the Metabolic Response

• Increased infusion of insulin may overcome
  glucagon stimulated gluconeogenesis. Ferrannini
  et al., Am J Physiol 242E73,1982.
• Tight glucose control with insulin in critically
  ill patients reduces morbidity and mortality. Van
  Den Berghe et al., N Engl J Med 3451359, 2001.

13
Adrenal Insufficiency

• Inappropriate adrenal response to critical
  illness
• Hypotension that is refractory to vasopressors
• ACTH stimulation test
• baseline cortisol level
• synthetic ACTH iv bolus (250mcg)
• cortisol level at 60min.

14
Adrenal Insufficiency