Hypothalamic-Pituitary-Adrenal Axis Function

What does the hypothalamus control?

the pituitary gland

What is the role of the pituitary gland?

secrets may different hormones, some of which affect other glands

What are the 2 lobes of the pituitary gland?

posterior pituitary - neural, connected to hypothalamus via the stalk

anterior pituitary - not neural, part that secretes hormones to rest of body- e.g PRL, LH FSH TSH GH ACTH

What do the supraoptic nucleus and paraventricular nucleus do and where are they found ?

found in the hypothalamus and produce oxytocin and vasopressin (Anti Diuretic Hormone - ADH ) which is then released from the posterior pituitary

What is the role of anriginine vasopressing AVP/ADH ? (same thing)

• increases reabsorption of water through the kidney tubules,

• secondary role increasing arteriole vessel resistance and also raising blood pressure

What does deficiency of AVP/ADH result in and what are the oral manifestations and what causes it

• failure to properly regulate water balance - excessive thirst and urination

• can lead to xerostomia (dry mouth)

• caused by: damage to hypothalamus/ pituitary gland through tumours, surgery, injury, radiotherapy

explain pituitary neuroendocrine tumours ( PitNETs) / adenomas

• tumors in anterior pituitary

• mostly benign

• usually hereditary

• can lead to acromegaly ( adult ) /gigantism ( in childhood) because of excessive growth hormone (GH) secretion

• symptoms are general patient history e/g headache, visual problems

Oral and maxillofacial manifestations of acromegaly/gigantism

what is hypopituitarism

• insufficient production of pituitary hormones

• mainly from the anterior pituitary

• happens because of damage to pituiatry or it not developing properly

Oral and maxillofacial manifestations of hypopituitarism

what is Cushings disease and its oral manifestations

• disorder caused by excess adrenocorticotrophic hormone ( ACTH) and so high cortisol levels

What is the general definition of stress?

non-specific response of the body to any factor that overwhelms or threatens to overwhelm the body's compensatory abilities to maintain homeostasis

what are the different types of stressors

What are the major physiological responses to experimental stressors?

• adrenal hyperplasia ( bigger adrenal gland)

• atrophy of immune system organs (thymus, spleen, lymph) ( getting smaller)

• peptic ulcers
  
  All stressors increase adrenal glucocorticoid secretion

What is the general adaptation syndrome (GAS) and what are the 3 phases

1. Alarm - fight or flight; short term response using adrenaline

2. Resistance to stress - chronic: glucocorticoid (cortisol) levels elevated (x10)

3. Exhaustion - immune suppression, illness, death

What is the role of hypothalamus during fight or flight in stage 1

activates the sympathetic division of the ANS and inhibits parasympathetic control of dually innervated organs

the adrenal glands respond to the hypothalamus

where are suprarenal glands ( adrenal ) situated

above the kidneys

How do adrenal glands develop?

- develop from 2 tissues
- develops from mesoderm and the neural crest

What are the distinct parts of an adrenal gland?

medulla

cortex

What does each part of the adrenal gland produce?

zona glomerulosa ⇒ aldosterone is made here

zona fasciculata ⇒ cortisol is made here in SER

zona reticularis ⇒ produces androgens

medulla ⇒ adrenaline and noradrenaline (catecholamines) are made here

- is an extension of SNS

What are the effects are adrenaline and noradrenaline?

• Increase heart rate and force of contractions à increased cardiac output
• Increase vasoconstriction leading to increased blood pressure
• Divert blood flow from viscera to skeletal muscles
• Increase glycogenolysis leading to elevated blood glucose

• Increase lipolysis to free fatty acids and glycerol, that can be used for energy
• Inhibit insulin secretion, further increasing blood glucose
• Stimulate thermogenesis
• Increase ventilation (bronchodilation, respiration rate)

stage 2 of GAS what does resistance to chronic stress do and the hypothalamus roles

chronically elevated levels of cortisol

- hypothalamus neurones secrete CRH at the median eminence which enters the portal vessels to control the release of ACTH from the anterior pituitary

- ACTH enters the venous drainage to be transported to the adrenal glands whereby ACTH receptors are stimulated to synthesise and secrete cortisol

How does negative feedback of cortisol secretion work?

ACTH is needed to stimulate the synthesis and secrete cortisol

ACTH secretion is controlled by the hypothalamic secretion of CRH

cortisol inhibits hypothalamus and anterior pituatry

is cortisol lipophilic?

yes

cortisol is derived from cholesterol so is lipophilic

Is cortisol stored?

no

steroid hormones aren't stored and are only made when required

what are the 2 types of corticosteroids and where are they released from

mineralocorticoids, glucocorticoids

both released from the adrenal cortex

effects of mineralocorticoids (e.g aldosterone)

• Control electrolyte and fluid balance

• Act on distal tubules & collecting ducts of the kidney

• ↑ Na⁺ reabsorption, ↑ K⁺ excretion

• Na⁺ retention → water retention → ↑ ECF volume & blood pressure

• Essential for life (loss → ↓ plasma volume → shock)

• Secretion controlled by renin–angiotensin system, independent of anterior pituitary

effects of glucocorticoids ( e.g cortisol)

• Key hormone for stress adaptation (especially long-term stress)

• Catabolic effects:

  • ↑ glucose availability

  • Mobilises amino acids & fatty acids

• Acts on carbohydrate, protein, and fat metabolism

What are the catabolic effects of cortisol in response to stress?

opposite those of insulin, maintains metabolic enzyme expression

- protein breakdown in muscle, bone, liver

- associated with illness/surgery

- hepatic gluconeogenesis

- lipolysis to generate FA and glycerol

- elevated cortisol can trigger insulin resistance

-enhances cardiovascular reactivity to catecholamines by allowing vasoconstriction in response to noradrenaline and adrenaline - heart can respond better to sympathetic input important as it shows how chronic stress can cause hypertension and low cortisolcan cause hypotension

How does cortisol affect inflammatory and immune responses?

- inhibition of prostoglandin and leukotriene production (inflammatory mediators)

- inflammatory cytokines stimulate ACTH, hence cortisol secretion in a -ve loop to dampen inflammatory responses

- cortisol can be used as anti-inflamamtory therapy but prolonged use has side effectse.g. down regulation of ACTH secretion and adrenal atrophya

- chronic stress suppresses immune system = infections

How does cortisol affect reproduction and growth?

- can cause reduction in bone density, skin thickness, muscle mass

- could cause growth retardation in children

- chronic stress in adults can reduce fertility

stage 3 of GA- exhaustion

• Prolonged stress → high cortisol

• Cortisol is strongly catabolic

• Breakdown of muscle, bone, skin, immune tissues

• Substrates used for gluconeogenesis

• Leads to:

  • ↓ bone density

  • ↓ immune function

  • ↓ fertility

• Metabolic resources depleted → exhaustion

• Outcome: immune suppression, illness, possible death

Stress-related diseases (quick summary)

• Stress responses are helpful short-term for physical stress (↑ heart rate, breathing, fuel mobilisation)

• Chronic psychological stress makes these responses inappropriate

• Persistently high cortisol → ↓ immune function → ↑ infection risk (possibly cancer)

• Stress worsens diabetes by ↑ insulin resistance

• Prolonged sympathetic activation → ↑ risk of hypertension and atherosclerosis

What is Addison's disease?

Adrenal cortex damaged by TB or by autoimmune (>80%) destruction leading to cortisol deficiency

What can adrenal insufficiency cause and how is it treated ?

- hypotension, hypoglycaemia, tiredness, weakness, anorexia, vomiting, depression
- maybe misdiagnosed as chronic fatigue syndrome
- inability to respond to stress = Addisonian crisis, fatal if left untreated - treated by steroid replacement therapies