Question 27

College Answer

a)

Starvation:

Overall an adaptive hypometabolism whereby fat is used as the primary energy fuel and protein is relatively spared. (Essential point)

Increase in lipolysis and ketosis with marginal increase in catabolism, glycogenolysis or gluconeogensis.

Mobilization of protein, glucose and lipids is passive as a result of decrease in insulin levels.

After 24-48hrs gluconeogenesis does increase from peripherally released amino acids and glycerol (from lipolysis) -supplies glucose dependant tissues e.g. brain, immune system and renal medulla.

Beyond 48hrs ketosis occurs and FFAs are used for energy, which minimizes the need for amino acids and so preserves muscle.

Decrease energy expenditure with stable albumin initially. Urine urea low if adequate protein and energy stores.

Stress:

Endogenous ‘stress’ mediators such as cortisol, catecholamines, GH, glucagon and cytokines are increased and contribute to the pattern of metabolism and mobilisation of the fuel required

Catabolism, glycogenolysis, and gluconeogenesis increased. Lipolysis with no increase in ketosis.

Mobilisation of protein is an active process. Energy expenditure is active.

Albumin levels drop precipitously.( negative acute phase reactant)

Gluconeogenesis decoupled from hormone control so can increase blood glucose levels Urine urea increases (>10g/day)

b)

• Impaired immune function
• Increased incidence of infection
• Weakness and fatigue
• Decreased ventilatory drive
• Prolonged mechanical ventilation
• Poor wound healing
• Muscle breakdown
• Depression and apathy
• Prolonged ICU and hospital stay

Discussion

The physiological responses to starvation and the stress of critical illness  are discussed elsewhere in gratuitous detail:

• The "Stress Response" to critical illness
• Physiological adaptation to prolonged starvation

In point form, the answer would resemble this:

Starvation response:

• Characterised by a switch from carbohydrate metabolism to fat metabolism, in the context of a hypometabolic state, with minimised catabolism.
• Initially, stores of carbohydrate precursors (eg. glycogen) are depleted
• Then, initially (in the first 24-48hrs) there is increased gluconeogenesis from amino acids and glycerol
• Subsequently, ketogenesis takes over, and much of the body metabolic needs are met by ketone bodies and free fatty acids. This is the consequence of decreasing insulin levels, and relatively increased influence from catecholamines and cortisol.
• Over prolonged starvation, protein catabolism begins, resulting in degradation of structurally important proteins, and organ system dysfunction

Stress response:

• Characterised by a mobilisation of available body fuels, and a hypermetabolic hypercatabolic state.
• Under the influence of cortisol, cytokines and catecholamines the rates of protein catabolism, lipolysis glycogenolysis and gluconeogenesis are increased.
• There is typically no ketosis, as there is a reasonably normal insulin response to the increase in circulating metabolic substrate. However, the insulin response is not completely coupled to the BSL, and hyperglycaemia results.
• Hyperglycaemia, uraemia and hypoalbuminaemia may result.

LITF as part of their Critical Care Compendium have excellent entries on both the starvation and stress repsonses, as a response to the stress of the 2013 CICM fellowship paper.

The consequences of malnutrition in critical illness are also discussed elsewhere.

The brief point-form list provided by the college will perhaps suffice.

In short, the consequences of malnutrition in critical illness are as follows:

• Poor wound healing
• Impaired immune function and increased risk of sepsis
• Muscle wasting due to protein catabolism:
  • Decreased ventilatory drive
  • Weakness complicating separation from the ventilator
    • Increased duration of ventilation, with associated complications (eg. increased risk of VAP)
  • Weakness complicating physiotherapy and mobilisation
    • Exposure to the complications of immobility, eg. DVT
• Cardiomyopathy as a consequence of atrophy
• Mucosal atropthy and diminished barrier function of the gut
• Apathy and depression
• Increased duration of ICU stay
• Increased in-hospital mortality

Cahill GF; Parris, Edith E.; Cahill, George F. (1970). "Starvation in man". N Engl J Med 282 (12): 668–675.

Benedict, FG: A study of prolonged fasting. Washington DC Carnegie Institute, 1915 (Publication No. 203)

Klein S, Peters EJ, Shangraw RE, Wolfe RR. Lipolytic response to metabolic stress in critically ill patients. Crit Care Med. 1991 Jun;19(6):776-9.

Epstein, Jay, and Michael J. Breslow. "The stress response of critical illness."Critical care clinics 15.1 (1999): 17-33.

Charmandari, Evangelia, Constantine Tsigos, and George Chrousos. "Endocrinology of the stress response 1." Annu. Rev. Physiol. 67 (2005): 259-284.