Corticosteroids and Stress Response Flashcards
What is the definition of a ‘stressor’?
- A stimulus that disrupts homeostasis and causes the stress response
What is the ‘stress response?
A suite of physiological and behavioural responses to a stressor that help to restore homeostasis
What are the 2-steps of the physiological stress response?
Sympathetic nervous system - Quick response (seconds) - Adrenaline release Hypothalamic-Pituitary-adrenal axis - Slower - Release of cortisol
Consequences of the stress response?
- Increased HR
- Increased oxygen intake
- Increased blood glucose levels
- Increased blood flow to muscles
- Increased alertness
- Inhibition of digestion, immune system
- Release of endorphins
- Dilation of pupils
What health problems can be associated with chronic stress?
- Heart disease
- Diabetes
- Ulcers
- Growth problems
- Compromised immune system
What percentage of depressed patients have elevated cortisol?
50%
At what time of the day are cortisol levels usually higher?
Morning: 7-9 am
Low: 11pm-4am
- Sleep disturbance may be linked with depression
What can the dexamethasone test show?
- HPA negative feedback can turn off, so not cortisol surge
- In depressed patients cortisol levels are still elevated
- Gives information on whether an individual has abnormal production of cortisol
What levels of cortisol are thought to be associateed with low mood / depression?
- Very high (e.g Cushing’s)
- Very low (e.g Addison’s)
How does stress affect the immune system in the 1st few minutes?
Enhances (after about an hour of stress it returns to normal)
What immune cells would you expect to be lowered when an individual is stressed?
- IFN-gamma produced by T lymphocytes and natural killer cells
- Lowered T-helper 1 (Th1) cellular immunity
How can steroids short-term ccause an increase in WBCs?
- Increase in polymorphonuclear leukocytes (e.g neutrophils)
- Innate arm of immune response relatively untouched
- Adaptive arm e.g B cells and T cells reduced
Describe the pathway by which a glucocorticoid causes an anti-inflammatory response?
- Crosses into cytosol where it binds to a glucocorticoid receptor
- This then interacts with a glucocorticoid resopnse element which drives upwards the production of an anti-inflammatory gene
What is the half-life of hydrocortisone?
8 hours
Name a potent synthetic glucocorticoid?
Dexamethasone (25-80 times more potent than hydrocortisone)
How much more potent is prednisolone than hyf=drocortisone?
4 times
WHat is the half-life of prednisolone?
16 - 36 hours
What is the half-life of dexamethasone?
36 - 54 hours
What do glucocorticoids suppress the production of?
- Cell-mediated immunity
- Production of new cytokines
- Production of: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, TNF-alpha
- Humoral immunity - B cells express less IL-2R and secrete less IL-2
- Downregulation of Fc receptors on macrophages - reduced phagocytosis of opsonised cells and bacteria
What are the side-effects of glucocorticoids?
- Immunosuppression
- Hyperglycemia due to gluconeogenesis, insulin resistance, impaired glucose tolerance
- Skin fragility, bruising
- Osteoperosis
- Weight gain
- Adrenal insufficiency
- Muscle breakdown
- Irregular menstrauation
- CNS
- Cushing’s syndrome
What withdrawal of glucocorticoid treatment cause?
- Excess use of high dose steroids suppress CRH and ACTH
- Flare up of underlying condition
What can prolonged use of glucocorticoids lead to?
Adrenal atrophy
When can a glucocorticoid be withdrawn completely?
- When treatment lasts less than one week
- The longer a patient is on a glucocorticoid the slower / longer / more gradual the withdrawl of treatment
What are the 2 stages of type 1 diabetes?
- Insulitis: lymphocyte invasion of pancreatic islets
- Overt diabetes, massive death of islet B cells - loss of glucose homeostasis
