Adrenal Cortex And Function

Question 1

What are the regions of the adrenal glands?

Answer 1

Separated into the cortex and the medulla.

Question 2

What is the medulla of the adrenal gland?

Answer 2

Innermost region formed of neural tissue, and produces water-soluble hormones of catecholamines from the precursor tyrosine in response to stimulation from pregnaglionic sympathetic fibres.

Question 3

What is the Cortex of the adrenal glands?

Answer 3

Formed of glandular tissue which produce lipid soluble steroid hormones in response to stimulation from the RAAS system or ACTH from precursors of cholesterol. It contains 3 zones:
Zona reticulata, zona glomerulosa and the zona fasiculata.

Question 4

What is the outermost layer of the cortex?

Answer 4

Zona glomerulosa- this receives stimulation from angiotensin II, formed in the lungs by the action of ACE. It causes activation of the B-hydroxylase enzyme to form mineralcorticoids from the cholesterol precursor.

Question 5

What are the effects of mineralcorticoids?

Answer 5

It acts on principal cells in the DCT and pumps in the colon to increase Na+ and H20 reabsorption and promote the loss of H+ and K+ excretion in the urine, causing an increase in blood volume and pressure.

It acts on alpha-intercalated cells in the DCT to increase H+ loss and uptake of HCO3-.

Question 6

What is the middle layer of the adrenal cortex?

Answer 6

Zona fasiculata.
Stress results in corticotropin releasing hormone (CRH) release from the paraventricular ncleus of hypothalamus to release ACTH hormone from the anterior pituitary gland. This causes production of the corticosteroid/glucocorticoid cortisol which is important for glucose metabolism, especially in times of high stress.

Cortisol will act in negative feedback to inhibit the hypothalamus and anterior pituitary gland

Question 7

What are the systemic effects of cortisol?

Answer 7

Cortisol increases blood pressure by promoting vasooconstriction of blood vessels and inhibits glucose uptake by the tissues in the body. It promotes the proteolysis of muscle and lipolysis of fat stores, and acts on the kidneys to cause glycogenolysis and increase gluconeogenesis.

Cortisol inhibits Ca2+ reabsorption and promotes osteoclasts activity, resulting in low bone mass. It inhibits the action of fibroblasts so wound healing is slow.

Question 8

What is the innermost layer of the adrenal cortex?

Answer 8

Zona reticularis, which responds to ACTH hormone to produce dihydroepiandosterone which is a precursor for androgens like testosterone and oestrogen, by the action of the B-hydroxylase enzyme.

Question 9

What is the stimulation to the adrenal medulla?

Answer 9

Pre-ganglionic neurons of the sympathetic chain produce acetylcholine which acts on the nicotine cholinergic receptors of the neural tissue in the adrenal medulla. This stimulates chromaffin cells to produce the catecholeamines adrenaline and noradrenaline to be released in the bloodstream and act on target tissues.

Question 10

What is the pattern of cortisol release?

Answer 10

Follows diurnal secretion, where cortisol release is greatest in the morninon first waking up around 8am and steadily drops during the day to the lowest at nighttime. There is a small spike at 12pm which is related to meal consumption.

Question 11

What causes activation of the RAAS system?

Answer 11

Hypovolemia
Dehydration
Haemorrhage
-> This stimulates renin release from the juxtaglomerular cells of the kidneys

Question 12

What is the function of angiotensin II?

Answer 12

Causes vasoconstriction of arterioles and acts on the zona glomerulosa in the adrenal glands to stimulate mineralcorticoid production by activating beta-hydroxylase.

Question 13

What causes the inactivation of bradykinin?

Answer 13

Angiotensin Converting enzyme (ACE)

Question 14

What is an important feature of the mineralcorticoid receptor?

Answer 14

It has equal affinity for both aldosterone and cortisol, therefore at high concentrations of cortisol such as Cushing’s syndrome, cortisol will induce Na+ and H20 reabsorption and worsen hypertension.

However, the mineralcorticoid receptor is co-expressed with the enzyme 11- beta hydroxylase, therefore this enzyme metabolises cortisol into the inactive cortisone.

Question 15

What are the systemic effects of catecholeamines?

Answer 15

Involved in the flight or fight reflex and causes:
Bronchodilaton to increase airflow
Vasoconstriciton to divert blood to vital organs
Increased HR and RR
Increases metabolism for nutrient availability.

Question 16

What is Addison’s disease?

Answer 16

Insufficiency of the adrenal cortex which is commonly caused by an autoimmune disease that results auto-antibody against adrenal cortical cells and the enzyme 21-betahydroxylase. This causes reduced production of glucocorticoids, mineralcorticoids and androgens that causes high circulating ACTH which binds to melanocortin receptors and causes over activation of the pituitary gland, stimulating production of prolactin and propiomelanocortin hormone.

Question 17

What is the presentation of Addison’s disease?

Answer 17

Symptoms typically appear when majority of the adrenal cortex has been damaged and unable to renew, causing:

Dehydration
Pigmentation of the skin and buccal areas of the mouth and gums
Weight loss
Hyperkalemia, metabolic acidosis and hyponatremia, so there is a craving for salty foods
Hair loss
Vomiting and diarrhoea

->Autoimmunity will increase the risk of autoimmune skin condition like vitiligo.

Question 18

How does Addison’s disease affect sex hormones?

Answer 18

Men are relatively unaffected because the majority of androgen production occurs in the testes. Women will experience a lower sex drive and less pubic and armpit hair.

Question 19

What are the common causes of Addison’s disease in developing countries?

Answer 19

Carcinoma of the adrenal gland
Metastatic carcinoma of adrenal gland
Post-infection, typically with tuberculosis.

Question 20

What is Addison’s crisis?

Answer 20

Typically occurs after infection, surgery or trauma where there is increased demand for mineralcorticoids, however the insufficiency of the adrenal cortex due to Addison’s disease results in hypovolemic shock and can lead to death within 3 days to 2 weeks.

Can occur when patient with Addison’s disease stops taking their medication.

Question 21

How is Addison’s crisis treated in the short-term?

Answer 21

Saline solution in the first 12-24 hours
Hypoglycaemia is prevented by intravenous dextrose sugar solution
Glucocorticoids are administered

Question 22

What is the long-term treatment of Addison’s crisis?

Answer 22

Provision of hydrocortisone with greater dose in the early mornings, and lower doses for lunch and the evening.
Fludrocortisone will replace low mineralcorticoids.
Women will receive testosterone supplements.

Question 23

How is Addison’s disease diagnosed?

Answer 23

Synacthen test with injection of ACTH to monitor the production of cortisol from the adrenal glands, which should be over 540mmol.
Serum cortisol is tested, ideally early in the morning to measure peak production.
Prescence of serum auto-antibodies against the adrenal glands.

Question 24

How are hormones affected in primary adrenal insufficiency?

Answer 24

Insufficiency of the adrenal gland causes compensatory increase in:
ACTH from anterior hypothalamus and CRH from paraventricular nuclei of hypothalamus.

Question 25

How are hormones affected in secondary adrenal insufficiency?

Answer 25

Damage to the pituitary gland results in:
High levels of CRH from hypothalamus
Low ACTH and adrenal cortex hormone production

Question 26

How are hormones affected in tertiary adrenal insufficiency?

Answer 26

Damage to the hypothalamus results in:
Low CRH
Low ACTH
Low adrenal steroid production

Question 27

What is the causes of secondary adrenal insufficiency?

Answer 27

There is low production of adrenal steroids as a result of low ACTH release due to
->Pituitary insult
->Long term use of steroids, which causes negative feedback.

Question 28

How can secondary adrenal insufficiency be differentiated from primary adrenal insufficiency ?

Answer 28

There is no hyperpigmentation because the pituitary gland is under active and no hyperkalemia occurs because aldosterone production is dependent on angiotensin II. Hypoglycaemia is more common and depending on the cause, pituitary tumour symptoms may also be present.

Question 29

What is Cushing’s syndrome?

Answer 29

Excessive production of glucocorticoids that leads to suppression of the HPA axis, which is commonly caused by iatrogenic cause of exogenous corticosteroid use.

Question 30

What are the symptoms of Cushing’s syndrome?

Answer 30

Thinning of the skin and poor wound healing
Moon face due to oedema
Buffalo hump due to fat deposition in the neck
Muscle hypertrophy of proximal muscles

Question 31

What is Cushing’s disease?

Answer 31

Pituitary adenoma which produces excess ACTH despite negative feedback leads to hypercortisolemia. This is a subtype of Cushing’s syndrome and the second most common cause.

Question 32

What is pseudo-Cushing’s state?

Answer 32

Medical condition where patient presents with the typical symptoms of Cushing’s syndrome, however there is no disorder of the HPA axis. It occurs due to stress or surgery that causes high cortisol, or depression, alcoholism and bulimia.

Question 33

How is Cushing’s syndrome screened?

Answer 33

24 hour urine test for levels of free cortisol
Midnight serum cortisol or late night serum cortisol
Dexamethasone suppression test

Question 34

What is the dexamethasone suppression test?

Answer 34

Injection of dexamethasone, a potent form of cortisol to assess suppression of the HPA axis.

Question 35

What are the serum abnormalities in Cushing’s syndrome?

Answer 35

Raised WBC count
Hyperglycaemia due to cortisol
Hypokalemia metabolic acidosis

Question 36

What is the blood supply to the adrenal glands?

Answer 36

Suprarenal arteries.

Question 37

What gives off the superior suprarenal artery?

Answer 37

Comes off the inferior phrenic artery.

Question 38

What gives off the middle suprarenal artery?

Answer 38

Directly comes off aorta.

Question 39

What gives off the inferior suprarenal artery?

Answer 39

Branch of the renal artery.

Question 40

What gives off the inferior suprarenal artery?

Answer 40

Renal artery.