The Hypothalamic Pituitary Adrenal Axis

Question 1

Name some experimental stressors.

Answer 1

Toxic injection, trauma, infection, cold environment, swimming to exhaustion.

Question 2

Name some experimental responses.

Answer 2

Adrenal hyperplasia, atrophy of the immune system organs (thymus, spleen, lymph node), peptic ulcers.

Question 3

What is physiological stress?

Answer 3

Any event that increases secretion of cortisol.

Question 4

What are the 3 endocrine responses to stress?

Answer 4

1) Alarm - fight or flight, increase adrenaline, pre-stored and exocytosed = increase glycogenolysis, increase lipolysis, increase CO, increase blood to skeletal muscle, increase ventilation.
2) Resistance to stress - chronic = increase [cortisol] x10. Cortisol - steroid hormone produced in SER on demand. Binds receptor in cytoplasm, translocates to nucleus, receptor binds promoter - and affects gene expression.
3) Exhaustion - immune suppression and illness and death.

Question 5

Explain the release of cortisol.

Answer 5

Stress/non stress signals to the hypothalamus to increase CRH secretion. Increase ACTH secretion from the AP - increase cortisol secretion from adrenal cortex.

Question 6

Explain the catabolic effects of cortisol and their clinical importance.

Answer 6

Opposes insulin!
Stimulate protein breakdown.
Stimulate hepatic gluconeogensis
Stimulate lipolysis (FA anf glycerol)

CI: protein catabolism is associated with illness and surgery - and as it opposes insulin, must watch the dose of insulin in ill diabetics.

Question 7

Explain the enhanced CV reactivity to caetcholamines as a response of increased cortisol and their clinical importance.

Answer 7

Allows vasoconstriction in response to NAdr - therefore can causes hypertension in chronic stress.
If low levels - hypotension.

Question 8

Explain the effect cortisol has on the immune response and their clinical importance.

Answer 8

Inhibits the inflammatory and immune response.
Inflammatory cytokines stimulate ACTH and therefore cortisol secretion in a negative loop to dampen down the immune response.
CI: good for antiinflammatory therapy but long term use - cushings, decrease ACTH and adrenal atrophy.

Also, chronic stress = immune supression = infection!

Question 9

Explain the non-essential functions that are inhibited as a result of increased cortisol and their clinical importance.

Answer 9

Decrease bone rensity, decrease skin thickness, decrease muscle mass (catabolic process to generate fuel).

Increase cortisol in;
…childhood = growth retardation
…adulthood = infertility.

Question 10

Addison’s Disease?

Answer 10

Adrenal insufficiency.
Adrenal cortex is damaged by TB/autoimmune destruction.
Hypotension, hypoglycemia, tiredness, weakness, anorexia, vomiting, depression.
Progressive (sometimes misdiagnosed as ME)
Inability to respond to stress = Addisonian crisis - can be fatal.

Hyperpigmentation…AMSH normally acts on melanocytes to increase melanin. But AMSH is in ACTH therefore increase melanin.

(No negative feedback)

STEROID REPLACEMENT.

Question 11

Cushing’s syndrome?

Answer 11

Adrenal cortex tumor = increase cortisol
Pituitary adenoma = increase ACTH = cushings disease.

Catabolic effects -
Oppose those of insulin (diabetogenic)
Protein/fat breakdown (wasting, hyperglycemia, redistribution)
Bone catabolism (osteoporosis, spinal deformity)
Skin thining (bruising)

Cv effects-
- vasoconstriction - hypertension

Immune system effects
- immunisupression, infection!