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B&B Week 7 Flashcards > Lecture 38: The HPA Axis > Flashcards

Lecture 38: The HPA Axis Flashcards

1
Q

Why do we care about the HPA axis?

A

Because it functions to regulate stress

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2
Q

What is the HPA axis?

A

The hypothalamic pituitary adrenal axis

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3
Q

In the HPA, what are the key hormones?

A
  1. Corticoid releasing factor (CRF) from hypothalamus
  2. Adrenocroticotrophic hormone (ACTH) from anterior pituitary
  3. Glucocorticoids and catecholamines from adrenal gland
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4
Q

What are the function of glucocorticoids and catecholamines?

A
  • metabolic mobilization
    • increased HR, blood pressure and respiration
    • redistribution of blood flow
    • suppression of immune/digestive systems
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5
Q

What happens to immune and digestive system during stress?

A

Suppression

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6
Q

What is the primary glucocorticoid in humans?

A

Cortisol

-can bind to both minearalocorticoid and glucocorticoid receptors

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7
Q

What is the primary mineralocorticoid in humans?

A

Aldosterone

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8
Q

What are examples of synthetic agonists?

A
  1. Dexamathasone (GR)
  2. Prednisone (GR)
  3. Spironolactone (MR)
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9
Q

How does cortisol mediate stress response?

A

By binding to BOTH Mineralocoriticoid receptor and GR

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10
Q

What happens when cortisol binds to GR?

A

Increased gene expression to mediate long term effects of stress (slow-acting)
Fast acting mechanisms still being researched

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11
Q

What is the marker for HPA dysfunction in mental disorders?

A

Cortisol concentration in blood

  • In patients with depression, high cortisol
  • however, cortisol level is NOT diagnostic…because it is all about comparison to baseline
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12
Q

What is the significance of diurnal rhythm in the body? Significance?

A

From 4-10am, Glucocorticoid RELEASE is at its greatest
When treated with prednisone, there is SUPPRESSIVE effect on cortisol because there is a negative feedback mechanism that prevents the GC spike in the morning

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13
Q

When is glucocorticoid (cortisol) release the greatest?

A

4-10am

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14
Q

What are the consequences of treating patients with prednisone?

A

Mental disorders such as

  1. Depression
  2. panic
  3. hypomania/mania
  4. Delirium
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15
Q

What are the acute effects of glucocorticoid?

A
  1. promoting survival
    • alter metabolism
    • maintain fluid balance
    • affects multiple brain regions (increase emotional/habitual memory while diminishing declarative/episodic memory/cognition)
  2. Inhibit nonessential systems
    • immune cells, inflammatory reactions, pituitary gonadotropins, inhibits osteoblastic activity
  3. Decrease bone mass
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16
Q

What is the CNS response to chronic corticosteroids (stress)?

A 
-promotes emotional (amygdala) and habitual (striatum memory
Diminishes declarative (hippocampal) memory
17
Q

What are the pathological results of cortisol release?

A
  1. Sleep disturbance
  2. Attentional disruption
  3. Hippocampal memory IMPAIRMENT (episodic memory)
  4. Amygdala memory enhancement (PTSD
  5. CV disease
    • HTN, clotting, fat deposition
  6. Sexual disorders
  7. Susceptibility to infection
18
Q

What is the takehome point of HPA stress regulation?

A

Acute stress is adaptive

Chronic stress leads to pathology

19
Q

What is the relationship between addictive behaviors and HPA activity?

A

Addictive behavior DECREASES HPA activity and thus stress

  1. consumption of high fat foods/drugs = termination of HPA response to stress
  2. decreased amygdala
  3. cannabinoid, opioid and GABA inhibit acitivyt of brain regions that drive HPA activity
  4. Withdrawal of drugs of abuse or high fat foods are HPA activating and perceived as stressful
20
Q

What is the effect that cortisol has on the brain?

A
  1. Hippocampal neurons DECREASE in arborization

2. Amygdala neurons INCREASE in arborization

21
Q

What is the difference between cortisol levels in depressed patients and PTSD patients?

A

Depression = HIGHER cortisol (as expected)

PTSD patients = LOWER cortisol (unexpected)

22
Q

When you give someone with PTSD glucocorticoid, what happens?

A

Brain HYPERSUPPRESSES cortisol release

Unknown if it is the TRAUMA or the DISORDER that leads to lower cortisol levels

23
Q

What is the significance of Corticotrophin Releasing Factor (CRF)?

A

Implicated in the negative effects of stress on psychological health
-secretes ACTH
-initiates SNS
-released ACROSS the brain
CRF receptors EVERYWHERE, like pancreas, skeletal muscle, etc.

24
Q

Where is CRF produced/released?

A

Paraventricular nucleus of the hypothalamus

25
Q

What are the effects produced by stress and central CRF administration?

A
  1. Increased sympathetic activity
  2. Alterations in GI function (decreases activity)
  3. Cognitive effects (increase arousal, memory, seizures)
  4. Alterations in behavior
    • change in locomotor activity, decrease feeding
  5. Immunological effects (decrease)
  6. suppression of groth hormone
26
Q

What is the significance of CRF-R1?

A

Bound by CRF and urocortin I

Activates stress

27
Q

What is significance of CRF-R2?

A

Bound by urocortin I

Relieves symptoms of stress

28
Q

What is the significance of Urocortin?

A

A hormone that binds to both CRF-R1 and CRF-R2

29
Q

Why can’t HPA activity be used diagnostically?

A

Because that shit changes by day and we don’t understand

30
Q

What is HPA predictivity for?

A

HPA activity is predictive for recovery

-more cortisol = more risk for relapse

31
Q

How do adverse early life events affect a person in relation to HPA axis?

A

Can increase the risk of depression/anxiety via EPIGENETIC alterations in glucocorticoid receptor availability in the adult organism
Less? glucocorticoid receptor availability = greater response to cortisol
Example: offspring of PTSD patients also have suppression of cortisol
-how someone is raised has a big effect on HPA axis

B&B Week 7 Flashcards (16 decks)

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