Corticosteroids and stress response Flashcards
stressor
a stimulus that disrupts homeostasis and causes the stress response:
- a predator running towards you
- a difficult and important exam
what is the stress response:
a suite of physiological and behavioural responses to a stressor that help to restore homeostasis
what is the two step physiological stress response
- sympathetic nervous system
- quick response system, within seconds
- release of epinephrine - HPA Axis (hypothalamic-pituitary-adrenal axis)
- slower response system, minutes to hours
- release of cortisol
what does the hypothalamus release that acts on the pituitary gland to produce ACTH
CRH (corticotrophin-releasing hormone)
Consequences of the stress response
- increased heart rate
- increased oxygen intake
- increased blood glucose levels
- increased blood flow to muscles
- increased alertness
- inhibition of digestion and the immune system
- release of endorphins
- dilation of the pupils
Chronic stress related to several health problems:
– Heart disease – Diabetes – Ulcers – Growth problems – Compromised immune system
what percentage of depressed patients have elevated cortisol
50%
tell me about rhythmic cortisol release
high in the morning 7-9am and low 11-4am
this may be the reason for sleep disturbances in depression
Dexamethasone Suppression Test
- People usually have high cortisol in the morning
- If given Dex HPA negative feedback turns this off, so no cortisol surge
- Not true of depressed patients
what disease is often associated with depression
cushings disease
- increased ACTH
- high cortisol
Addisons disease
- low cortisol
- adrenal insufficiency
Stress response and the immune system timeline
- 1st few minutes – immune system is enhanced
- After about an hour of stress – immune system returns to normal
- Chronic stress suppresses immune system functioning
what is the role of cortisol as an anti-stress hormone
- helps reduce inflammation during stress, but it also acts as an immunosuppressant
exam stress study what was the conclusion
Lowered levels of Interferon gamma (IFN-g), which is normally released by T lymphocytes and natural killer (NK) cells.
There was a significant decrease in the number of macrophages, interferons, lymphocytes and natural killer (NK) cells.
what are the physical stressors of space flight
- G-force acceleration
* Cosmic radiation •Pressure variations
what are the emotional stresses of space flight
- flight tasks
- Public events
- Being strapped to a rocket!!
conclusion of astronauts and EBV virus study
• There was a decrease in the virus specific antibodies in all the astronauts.
most commonly prescribed steroid
prednisolone
- low potency and a short half life
dexamethasone
- high potency
- long half life
glucocorticoids suppress cell-mediated immunity… give my a couple examples of what they inhibit the production of
IL-1,IL-2,IL-3,IL-4,IL-5,
IL-6, IL-8, TNF-a
• Suppress 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
Side-effects of steroids
- Immunosuppression
- Hyperglycemia due to gluconeogenesis, insulin resistance, impaired glucose tolerance
- Skin fragility, bruising
- Osteoporosis
- Weight gain
- Adrenal insufficiency
- Muscle breakdown
- Irregular menstruation
- CNS
- Cushing syndrome
why’d o you have to be careful when withdrawing steroids
- excess use suppress CRH and ACTH and prolonged use leads to adrenal atrophy
- less than one week = abruptly is ok
- 6-10 days = taper for 4 days
- 11-30 days = twice replacement, then by 25% every 4 days then there will be a three month recovery
- > 30 days = reduce to twice replacement, then by 25% per week, then 0800h check with cortisone. Recovery may take 1 year.
what are the two stages of autoimmunity in diabetes
- 1st stage: insulitis - lymphocyte invasion of pancreatic islets.
- 2nd stage: overt diabetes, massive death of islet B cells - loss of glucose homeostasis
link between pancreas and the GI system
PLN sample self-antigens from pancreas and also gut. Non-specific gut pertubations influence b-reactive
T cells. Potential explanation for relationship between diseases Like coeliac and type 1 diabetes. Link between neonatal immune system development and gut development.
