What is the stress response?

The stress response is a complex neuroendocrine response to physiological stress. The most commonly encountered stressors are trauma, burns, surgery and critical illness; the magnitude of the neuroendocrine response is directly related to the magnitude of the stressor. In addition to its metabolic effects, the stress response leads to activation of the immunological and haematological systems.

The stress response, often referred to as the ‘fight or flight’ response, was once a useful survival strategy. However, in the context of modern surgery, many of the physiological changes that accompany the stress response adversely affect surgical outcomes and extend hospital stay.

How is the stress response initiated? What are its effects on the endocrine system?

The hypothalamus coordinates the stress response through the secretion of pituitary hormones and the activation of the sympathetic nervous system. It is stimulated to do so through two mechanisms:

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  Relay of autonomic and sensory afferent nervous impulses from the area of injury to the hypothalamus.

  
  
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  Local activation of inflammation in the area of injury with cytokine release, complement activation, leukocyte attraction, platelet activation and initiation of the coagulation cascade. Cytokines such as interleukin-6, interferons and tumour necrosis factor spill over into the systemic circulation, triggering the hypothalamus to activate the stress response.

Once activated, the hypothalamus:

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  Increases sympathetic nervous outflow, resulting in:

  
  
  
  
  1. 
     

     – Systemic release of adrenaline from the adrenal medulla;

     
     
  2. 
     

     – Systemic release of noradrenaline from postganglionic sympathetic nerve terminals, resulting in some spillover of noradrenaline into the systemic circulation;

     
     
  3. 
     

     – Renin release by the kidney, which increases aldosterone secretion from the adrenal cortex (through the production and action of angiotensin II);

     
     
  4. 
     

     – Glucagon release from the α-cells of the islets of Langerhans;

     
     
  5. 
     

     – Reduced insulin secretion from the β-cells of the islets of Langerhans (see Chapter 77).

  
  
  
  
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  Signals the pituitary to release:

  
  
  
  
  1. 
     

     – Adrenocorticotropic hormone, which stimulates cortisol release from the adrenal cortex. Cortisol is known as the ‘stress hormone’ owing to the multitude of effects it mediates in response to physiological stress. The mineralocorticoid effects of aldosterone and cortisol result in excess Na⁺ and water reabsorption.

     
     
  2. 
     

     – Growth hormone (GH).

     
     
  3. 
     

     – Antidiuretic hormone (ADH). Increased ADH results in reabsorption of water at the renal collecting duct.

  The secretion of the other pituitary hormones is not altered by the stress response.
  

What are the metabolic effects of the hormonal changes?

The stress response has effects on all of the major metabolic substrates:

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  Carbohydrate. Hyperglycaemia occurs in proportion to the severity of trauma due to:

  
  
  
  
  1. 
     

     – Low insulin concentration;

     
     
  2. 
     

     – High glucagon concentration;

     
     
  3. 
     

     – The anti-insulin effects of catecholamines, cortisol and, to a lesser extent, GH.

  
  
  
  
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  Protein. Protein metabolism has two phases:

  
  
  
  
  1. 
     

     – Initially, protein anabolism is inhibited.

     
     
  2. 
     

     – After 12–14 h, skeletal muscle is catabolised: amino acids are required for use as substrates for gluconeogenesis and for the synthesis of acute-phase proteins.

  
  
  
  

  The extent of protein catabolism is proportional to the severity of the trauma. This is referred to as negative nitrogen balance, where the amount of nitrogen excreted from the body is greater than that ingested. The hormones involved are:

  
  
  
  
  1. 
     

     – Cortisol, which promotes protein breakdown and gluconeogenesis;

     
     
  2. 
     

     – GH, which has greater anabolic than catabolic effects on body protein and thus may limit skeletal muscle breakdown.

  
  
  
  
• 
  

  Fat. Lipolysis and ketogenesis are promoted by:

  
  
  
  
  1. 
     

     – High glucagon concentration;

     
     
  2. 
     

     – Low insulin concentration;

     
     
  3. 
     

     – Increased catecholamine, cortisol and GH concentrations.