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MD4001 Physiology > Corticosteroids and Stress Response > Flashcards

Corticosteroids and Stress Response Flashcards

1
Q

What is the definition of a ‘stressor’?

A
  • A stimulus that disrupts homeostasis and causes the stress response
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2
Q

What is the ‘stress response?

A

A suite of physiological and behavioural responses to a stressor that help to restore homeostasis

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3
Q

What are the 2-steps of the physiological stress response?

A 
Sympathetic nervous system 
- Quick response (seconds)
- Adrenaline release
Hypothalamic-Pituitary-adrenal axis 
- Slower 
- Release of cortisol
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4
Q

Consequences of the stress response?

A
  • 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
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5
Q

What health problems can be associated with chronic stress?

A
  • Heart disease
  • Diabetes
  • Ulcers
  • Growth problems
  • Compromised immune system
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6
Q

What percentage of depressed patients have elevated cortisol?

A

50%

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7
Q

At what time of the day are cortisol levels usually higher?

A

Morning: 7-9 am
Low: 11pm-4am
- Sleep disturbance may be linked with depression

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8
Q

What can the dexamethasone test show?

A
  • 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
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9
Q

What levels of cortisol are thought to be associateed with low mood / depression?

A
  • Very high (e.g Cushing’s)

- Very low (e.g Addison’s)

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10
Q

How does stress affect the immune system in the 1st few minutes?

A

Enhances (after about an hour of stress it returns to normal)

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11
Q

What immune cells would you expect to be lowered when an individual is stressed?

A
  • IFN-gamma produced by T lymphocytes and natural killer cells
  • Lowered T-helper 1 (Th1) cellular immunity
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12
Q

How can steroids short-term ccause an increase in WBCs?

A
  • Increase in polymorphonuclear leukocytes (e.g neutrophils)
  • Innate arm of immune response relatively untouched
  • Adaptive arm e.g B cells and T cells reduced
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13
Q

Describe the pathway by which a glucocorticoid causes an anti-inflammatory response?

A
  • 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
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14
Q

What is the half-life of hydrocortisone?

A

8 hours

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15
Q

Name a potent synthetic glucocorticoid?

A

Dexamethasone (25-80 times more potent than hydrocortisone)

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16
Q

How much more potent is prednisolone than hyf=drocortisone?

A

4 times

17
Q

WHat is the half-life of prednisolone?

A

16 - 36 hours

18
Q

What is the half-life of dexamethasone?

A

36 - 54 hours

19
Q

What do glucocorticoids suppress the production of?

A
  • 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
20
Q

What are the side-effects of glucocorticoids?

A
  • 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
21
Q

What withdrawal of glucocorticoid treatment cause?

A
  • Excess use of high dose steroids suppress CRH and ACTH

- Flare up of underlying condition

22
Q

What can prolonged use of glucocorticoids lead to?

A

Adrenal atrophy

23
Q

When can a glucocorticoid be withdrawn completely?

A
  • When treatment lasts less than one week

- The longer a patient is on a glucocorticoid the slower / longer / more gradual the withdrawl of treatment

24
Q

What are the 2 stages of type 1 diabetes?

A
  • Insulitis: lymphocyte invasion of pancreatic islets

- Overt diabetes, massive death of islet B cells - loss of glucose homeostasis

25
Q

What immune cells are thought to attack the B cells in Type 1 diabetes?

A

T lymphocytes

  • Naive B-reactive T cells
  • Antigens delivered to pancreatic lymph nodes by dendritic cells
26
Q

Where is tolerance to pancrease first broken down?

A

Pancreatic lymph nodes

27
Q

When does lymphocyte access to the Pancreatic lymph node occur?

A

Infancy

- Similar timecourse to when dendritic celss capable of presenting pancreatic autoantigens also appear

28
Q

What disease is linked to insulitis?

A

Coeliac

MD4001 Physiology (22 decks)

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