Substrate Metabolism – Rest versus Stress

OVERVIEW

• rest = basal metabolic rate + minimal exercise
• major stress = 50% burn
• the body’s goal is to preserve plasma glucose levels for brain metabolism.

REST

• least expensive form of energy production utilized:
  carbohydrate -> fat -> protein in decreasing ratios.

Carbohydrate

Sources

• glucose, fructose and galactose from GI tract
• glycogen
• gluconeogenesis
• gluconeogenic amino acids (alanine + others)
• glycerol from triglycerides

(1) glucose enters the cell by insulin promoted facilitated diffusion with a Na+ cotransporter
(2) phosphorylated to glucose-6-phosphate (e.g. glucokinase in the liver)
(3) forms 2 pyruvates -> transported into matrix of mitochondria
(4) converted into ACoA -> enters the Citric acid cycle -> oxidative phosphorylation

Protein

• proteins broken down to amino acids (liver)
• leucine, isoleucine, phenylalanine & tryrosine = ketogenic -> produce acetoacetate
• alanine + others are  gluconeogenic

Fat

(1) triglycerides -> hydrolysed to FFAs & glycerol
(2) transported to tissues
(3) glycerol -> glycerol-3-phosphate & enters glycolytic pathway
(4) FF’s transported to mitochondria by carnitine carrier -> degraded to ACoA (beta-oxidation) -> enters the citric acid cycle.

• essential fatty acids = linolenic, linoleic & arachidonic acid
• used in the production of leukotrienes, prostaglandins, prostacyclin

STRESS

• increase in basal metabolism proportional to the degree of sepsis/trauma/burn
• if metabolic needs aren’t met -> the patient will mobilize protein, fat and carbohydrate to meet metabolic demand

Energy requirements

• most hospitalized patients require 25-30 kcal/kg/day (remember 4.18 kJ/kcal!)
• mechanically ventilated are on the lower end of range
• burns and trauma patient may require 45kcal/kg/day

Effects

• loss of whole body water and protein
• reduction in protein synthesis and increased degradation
• rapid catabolic muscle wasting -> reduction in cross-sectional area of muscle fibers
• 50% decline in respiratory and skeletal muscle function (in first 2 weeks)

Sepsis

• resting energy expenditure increases by 40%
• increased plasma glucose
• cytokines increase glucose membrane transporter (non-insulin mediated) -> saturate Citric acid cycle -> increase lactate production.
• catabolic state

Burns

• 60% burns doubles the resting energy expenditure
• catabolic state mediated by cortisol
• decreased protein synthesis in muscles

Trauma

• protein catabolism
• increased resting energy expenditure
• increased in catabolic hormones (adrenaline & norad) -> glucose turnover increases.
• feed enterally soon if possible

MANAGEMENT

• provision of high quality amino acids along with insulin
• ‘feed appropriately’

Burns

• early enteral feeding
• in absence of indirect calorimetry, use of the Toronto equation (Schofield in children) for energy requirement determination (risk of overfeeding)
• elevated protein requirements (1.5-2 g/kg in adults, 3 g/kg in children)
• maintain fat administration ≤ 30% of total energy delivery
• glucose delivery to a maximum of 55% of energy and 5 mg/kg/h associated with moderate blood glucose (target ≤ 8 mmol/l) control by means of continuous infusion
• trace element and vitamin substitution early on
• consider non-nutritional strategies to attenuate hypermetabolism by pharmacological (propranolol, oxandrolone) and physical tools (early surgery and thermo-neutral room) during the first weeks after injury

References and Links

• Rousseau AF, Losser MR, Ichai C, Berger MM. ESPEN endorsed recommendations: Nutritional therapy in major burns. Clin Nutr. 2013 Mar 14. MID: 23582468.