The adrenal gland Flashcards by Seojung Park

Where are the adrenal glands?

On the top of the kidneys

see diagram 4/58

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What does the left adrenal vein drain into?

the renal vein

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What does the right adrenal vein drain into?

IVC

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How many veins do both adrenal glands have?

only one vein

but have many arteries

(see diagram 10/58)

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Describe the microanatomy of the adrenal glands

Split into adrenal cortex + adrenal medulla

adrenal cortex:

Zona glomerulosa
Zona fasciculata
Zona reticularis (seems to be disappearing in humans)

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What does the adrenal cortex secrete?

corticosteroids (e.g. cortisol)

mineralocorticoids (aldosterone) --> controls minerals [Na+ & K+]
glucocorticoids (cortisol)
sex steroids (androgens, oestrogens)

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What does the adrenal medulla secrete?

catecholamines (e.g. adrenaline)

adrenaline/epinephrine (80%)
noradrenaline/norepinephrine (20%) [dopamine]

secreted by neuroendocrine/chromaffin cells

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Which part of the adrenal cortex secretes aldosterone?

Zona glomerulosa

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Which part of the adrenal cortex secretes cortisol (androgens, oestrogens)?

Zona fasciculata

Zona reticularis

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Describe the microanatomy of the adrenal cortex.

Capsule
Zona glomerulosa
Zona fasciculata
Zona reticularis
--
medulla

(see diagram 17-18/58)

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What is a steroid?

biologically active organic compound with four rinds arranged in a specific molecular configrations.

have 2 principal biological functions:

membrane fluidity
signalling molecules

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What is the precursor for adrenal gland secretions?

cholesterol

27 carbons

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What is an enzyme?

protein that catalyses a specific reaction

there are various enzymes present in cells

specific enzymes catalyse the synthesis of particular alterations to the molecule

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How is aldosterone formed from Cholesterol?

cholesterol -> pregnenolone -> progesterone -> [21 Hydroxylase] 11 deoxycorticosterone -> [11 hydroxylase] corticosterone -> [18 hydroxylase] aldosterone

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How is cortisol formed from Cholesterol?

cholesterol -> pregnenolone -> progesterone -> [17 hydroxylase] 17 hydroxy-progesterone -> [21 hydroxylase] 11 deoxy-cortisol -> [11 hydroxylase] cortisol

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How is oestrogen formed from cholesterol?

cholesterol -> pregnenolone -> progesterone -> [17 hydroxylase] 17 hydroxy-progesterone -> sex steroids -> (androgens) -> (oestrogen)

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What is the role of aldosterone?

Controls blood pressure, sodium and lowers potassium.

Stimulates Na+ reabsorption in distal convoluted tubule and cortical collecting duct in kidney (and in sweat glands, gastric glands, colon)
Stimulates K+ and H+ secretion, also in distal convoluted tubule and cortical collecting duct

increased sodium reabsorption + water reabsorption -> raising blood volume
major net effect: conserve body sodium by stimulating its reabsorption

(See diagrams 27-28/58)

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How is aldosterone regulated?

ANGIOTENSIN II REGULATES ALDOSTERONE RELEASE

When b.p. falls - release renin

when b.p. high - suppress renin

At low b.p.:

Decreased renal perfusion pressure (normally associated with decreased arterial BP)
Increased renal sympathetic activity (direct to JGA cells)
Decreased Na+ load to top of loop of Henle (macula densa cells)

— RENIN–
(see diagram 31/58)

What is the role of renin?

acts on a protein known as angiotensinogen, resulting in the release of angiotensin I

How is renin work?

released by liver, acts on angiotensinogen which is secreted by the liver

produces angiotensin I -> Angiotensin II -> angiotensin II regulates aldosterone release (therefore goes to the adrenal gland to switch on the 3 enzymes)

zona glomerulosa secretes aldosterone

What are the effects of angiotensin II on the adrenals?

Activation of the following enzymes:
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase 
21 hydroxylase
11 hydroxylase 
18 hydroxylase

(see diagram 33+39/58)

What is cortisol secretion regulated by?

ACTH (which comes from the pituitary gland)

What are the physiological effects of cortisol?

Normal stress response

Metabolic effects
• peripheral protein catabolism
• hepatic gluconeogenesis
• increased blood glucose concentration
• fat metabolism (lipolysis in adipose tissue)
• enhanced effects of glucagon and catecholamines

Weak mineralocorticoid effects

Renal and cardiovascular effects
• excretion of water load
• increased vascular permeability

Describe the hypothalamo-pituitary-adrenal (HPA) axis.

pituitary gland secretes ACTH to boost production of cortisol -> cortisol feeds back negatively to the pituitary and the hypothalamus via circulation

pituitary gland makes the hormone corticotrophin-releasing hormone that switches on the release of ACTH and release of cortisol

(see diagram 36-37/58)

Does cortisol have diurnal rhythm?

yes has a circadian rhythm - peak at 8:30am - lowest at midnight (if asleep at midnight) (see diagram 40-42/58)

Define circadian rhythm.

natural, internal process that regulates the sleep-wake cycle and repeats on each rotation of the Earth roughly every 24hrs.

Define diurnal rhythms.

circadian rhythm synced with day and night

What is Addison's disease?

Thomas Addison (18th century) Primary adrenal failure Autoimmune disease where the immune system decides to destroy the adrenal cortex (UK) Tuberculosis of the adrenal glands (commonest cause worldwide) Pituitary starts secreting lots of ACTH and hence MSH (melanocyte stimulating hormone) -> this is why you become tan Adrenal glands do not produce sufficient steroid hormones --- * Cortisol deficiency * Aldosterone deficiency * Salt loss * Low blood pressure * Eventual death

What are the signs and symptoms of Addison's disease?

- Increased pigmentation - Autoimmune vitiligo may coexist - No cortisol or aldosterone, so low blood pressure - hyperpigmentation - low blood pressure, weakness, weight loss - (gastrointestinal) nausea, diarrhoea, vomiting, constipation, abdominal pain - vitiligo (see diagram 44/48)

What does an adrenal crisis consist of?

``` fever syncope convulsions hypoglycaemia hyponatremia severe vomiting and diarrhoea ```

Why do patients with Addison's disease have a tan?

POMC (Pro-opio-melanocortin) is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins Thus people who have pathologically high levels of ACTH may become tanned If you have high ACTH, then you will have high MSH

What is the urgent treatment for Addisonian crisis?

- Rehydrate with normal saline - Give dextrose to prevent hypoglycaemia which could be due to the glucocorticoid deficiency - Give hydrocortisone or another glucocorticoid

What is Cushing's syndrome?

too much cortisol caused by tumour of the adrenal gland (excess cortisol) or tumour of the pituitary gland (excess ACTH) Occurs due to an excess of cortisol or other glucocorticoid

List 4 possible causes of Cushing's syndrome.

``` • Taking steroids by mouth (common) • pituitary dependent Cushing’s disease (pituitary adenoma) • Ectopic ACTH (lung cancer) • adrenal adenoma or carcinoma ```

What are the clinical signs of Cushing's syndrome?

* Thin skin * Proximal myopathy * Centripetal obesity (lemon on sticks) * Diabetes, hypertension and osteoporosis * Immunosuppression (reactivation of TB) * Moon face * Striae - inter-scapular fat pad - red and round face - CNS irritability, emotional disturbances - cardiac hypertrophy - hyperplasia, tumor - purple striae - osteoporosis - muscle wasting - skin ulcers - obesity (fat deposition on abdomen and back of neck) "Lemon on sticks" (rude) In females: - amenorrhea, hirsutism In males: - erectile dysfunction (See diagram 51/58)

What is the precursor for Adr + NA synthesis?

tyrosine

Where are catecholamines stored?

cytoplasmic granules

When are catecholamines released in response to?

in response to ACh from preganglionic sympathetic neurones

What is the medulla derived from?

ectodermal neural crest

How do you form dopamine from tyrosine?

Tyrosine is oxidised to form Dopa Dopa is decarboxylated to form Dopamine (See diagram 55/58)

How do you form Epinephrine from Dopamine?

Dopamine gets a hydroxyl group to form Norepinephrine Norepinephrine combines with a methyl group to form epinephrine (see diagram 56/58)

What is the role of catecholamines?

'Fight or flight response’ e.g. tachycardia, sweating, increased blood glucose, alertness, vasoconstriction

What are NA + Adr bound to when in circulation?

albumin

Which two hepatic enzymes are catecholamines degraded by?

monoamine oxidase catechol-O-methyl transferase