Corticosteroids and Stress

Question 1

Summarise the stress response

Answer 1

Fight or flight response - 2 step physiological process

1. SNS (quick response, release of adrenaline)
2. HPA axis (slower system response, release of cortisol)

Question 2

What are the physiological effects of the stress response?

Answer 2

• increased HR and O2 intake
• increased blood glucose and flow of blood to muscles
• increased alertness
• inhibition of digestion and immune system
• release of endorphins
• dilation of pupils

Question 3

What types of health problems are associated with chronic stress?

Answer 3

• heart disease
• diabetes
• ulcers
• growth problems
• compromised immune system
• psychological problems (eg. depression)

Question 4

What test can be carried out to measure cortisol levels and the association with depression?

Answer 4

Dexamethasone suppression test

• normal will show high cortisol that peaks in the morning then starts to decrease throughout the day pre-DEX
• post-DEX, HPA will stimulate negative feedback which turns off cortisol release
• depressed patients show deranged cortisol production throughout the day
• shows no response to DEX

Question 5

Describe how the stress response affects the immune system

Answer 5

• in first few minutes, immune system is enhanced (slight increase in white cells as part of innate immune response - polymorphonuclear leucocytes (neutrophils))
• returns to normal after an hour
• chronic stress will suppress immune system

Question 6

Describe the mode of glucocorticoid action (immunosuppressant and anti-inflammatory)

Answer 6

• affecting adaptive immune response (B and T cells)
• goal of steroid treatment is to stop new gene synthesis (for things like antibodies and cytokines)

Achieves this through numerous mechanisms:

• transactivation (production of anti-inflammatory protein eg. IL-10): glucocorticoid enters cytosol through plasma membrane and interacts with a response element which drives upwards the production of an anti-inflammatory gene which dampens immune response
• transrepression: cytokine interacts with protein on membrane then binds to its own response element to drive the production of an inflammatory gene (eg. TNF-alpha). Then glucocorticoid causes block in production of inflammatory protein.

Question 7

Give an example of a short, intermediate and long acting synthetic glucocorticoid

Answer 7

• short: hydrocortisone (8hrs)
• intermediate: prednisolone (16-36hrs)
• long: dexamethasone (36-54hrs)

Question 8

What are the immunosuppressive actions of glucocorticoids

Answer 8

• suppress cell-mediated immunity
• inhibit production of interleukins and TNF-alpha
• suppress humoral immunity: beta cells express less IL-2R and secrete less IL-2
• downregulation of Fc receptors on macrophages (reduced phagocytosis of opsonised cells and bacteria)

Question 9

What are the side effects of glucocorticoids?

Answer 9

• immunosuppression (global)
• hyperglycaemia (due to gluconeogenesis, insulin resistance and decreased tolerance to glucose)
• skin fragility and bruising
• osteoporosis
• weight gain
• adrenal insufficiency (risk of atrophy in withdrawal)
• muscle breakdown
• irregular menstruation
• CNS effects
• Cushing’s Syndrome

Question 10

What are the 2 stages of type 1 diabetes?

Answer 10

• 1: insulitis: lymphocyte invasion of pancreatic islets

- 2: overt diabetes, massive death of islet B cells and loss of glucose homeostasis