The Adrenal Gland Flashcards by Graeme Miller

How are the suprarenal glands peritonised?

Retroperitoneal

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What drains the left adrenal vein and the right adrenal vein?

Left adrenal vein: Left renal vein

Right adrenal vein: Inferior vena cava

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What are the two seperate endocrine glands of the kidney?

Adrenal Medulla

Adrenal cortex

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What does the medulla secrete?

Secretes catecholamines

(Epinephrine, norepinephrine and dopamine)

The medulla makes up around 25% of the adrenal gland

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What does the adrenal cortex secrete?

Secretes three classes of hormones

Mineralcorticoids (aldosterone - regulates sodium and potassium)
Glucocorticoids (cortisol - involved in maintaining plasma glucose)

Sex steroids (testosterone)

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Where is the adrenal medulla and the adrenal cortex derived from?

Adrenal medulla - modified sympathetic ganglion derived from neural crest tissue

Adrenal cortex - true endocrine gland derived from mesoderm

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How is the medulla and cortex arranged?

Cortex surrounds the medulla and is arranged in 3 concentric zones, producing different hormones

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What are the three zones of the cortex?

Zona glomerulosa - aldosterone

Zona fasciculata - glucocorticoids

Zona reticularis - sex hormones

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What results in different hormones being produced by different adrenal zones?

All steroid hormones are derived from cholesterol, but different enzymes are found in different adrenal zones, resulting in different end products e.g. enzymes needed to make aldosterone are found only in the zona glomerulosa.

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What are the main products of the adrenal cortex?

Cortisol

Aldosterone

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What sex hormone has a marked decline with age?

DHEA - dehydroepiandrosterone

It is a pre-hormone of testosterone and oestrogen - marked decline with age

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What is a common cause of adrenal hyperplasia?

Defects in 21-hydroxylase

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What are the consequences of adrenal hyperplasia?

Deficiency of aldosterone and cortisol - associated disruption of salt and glucose balance

Excessive adrenal androgen production as a result of accumulating steroid precursors

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What is the hormone pathway?

Hypothalamus produces Corticotrophin releasing hormone (CRH)

This then stimulates production of adrenocorticotrophic hormone from the anterior pituitary (ACTH)

The adrenal cortex then produces cortisol

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What are the negative feedback mechanisms associated with cortisol?

Cortisol reduces excretion of ACTH and CRH

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Why does a defecit in 21-hydroxylase cause adrenal hyperplasia?

Lack of 21-hydroxylase inhibits synthesis of cortisol.
This removes the negative feedback on ACTH and CRH release.
Increased ACTH secretion is responsible for enlargement of adrenal glands.
Negative feedback of ACTH on CRH synthesis remains

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What is the carrier protein for cortisol?

~95% of plasma cortisol is bound to a carrier protein, cortisol binding globulin (CBG).

What are the receptros for cortisol? Which cells express them?

All nucleated cells have cytoplasmic glucocorticoid receptors.

What happens after the cortisol combines with the cytoplasmic glucocorticoid receptors?

The hormone receptor complex migrates to the nucleus

Binds to DNA via a hormone-response element to alter gene expression, transcription and translation

What is the variation of ACTH and Cortisol throughout the day?

Follows circadian rhythm

Peak is at 6-9am

Nadir (lowest level) is midnight

Cortisol bursts persist longer than ACTH because Cortisol has a longer half life then ACTH

Why is cortisol essential for life?

Needed to maintain blood glucose levels - helps protect the brain against hypoglycaemia

Cortisol is permissive to glucagon (which alone is inadequate in responding to a hypoglycaemic challenge)

As well as maintaining glucose levels, why else is cortisol essential for life?

WIthout cortisol animals are unable to maintain their extracellular fluid volume, an effect mediated by aldosterone

What are the actions of cortisol on glucose metabolism?

Gluconeogenesis: Cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogenesis and glucose production. This is aided by cortisol’s action on muscle:
Proteolysis: cortisol stimulates the breakdown of muscle protein to provide gluconeogenic substrates for the liver.
Lipolysis: similarly, cortisol stimulates lipolysis in adipose tissue which increases [FFA] plasma creating an alternative fuel supply that allows [BG] to be protected while also creating a substrate (glycerol) for gluconeogenesis.
Decreases insulin sensitivity of muscles and adipose tissue.

Basically, increases gluconeogenesis by activating liver enzymes, breaks down muscle to free up more substrates, introduces glycerol into the blood stream.

It also decreases insulin sensitivity of muscles and adipose tissue

What hormone is cortisol compared with?

Insulin, cortisol acts to oppose insulin

Excess cortisol is diabetogenic

What are the additional (non-glucocorticoid) effects of cortisol?

1. Negative effect on Ca2+ balance: decrease absorption from gut, increases excretion at kidney resulting in net Ca2+ loss. Also increase bone resorption - osteoporosis 2. Impairment of mood and cognition: depression and impaired cognitive function are strongly associated with hypercortisolaemia. 3. Permissive effects on norepinephrine: particularly in vascular smooth muscle (a-receptor effect = vasoconstrictive). Cushings Disease (hypercortisolaemia) is strongly associated with hypertension. Likewise, low levels of cortisol are associated with hypotension. 4. Suppression of the Immune System: Cortisol reduces the circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response. Latter effect can be useful clinically e.g. asthma/ulcerative colitis/organ transplant.

What are the side effects of glucocorticoid therapy?

What is the effect of aldosterone on sodium and potassium?

Aldosterone is mineralocorticoid, which acts on the distal tubule of the kidney to determine the levels of minerals reabsorbed/excreted. Aldosterone increases the reabsorption of Na+ ions and promotes the excretion of K+ ions •Increased aldosterone release stimulates Na+ (and H2O) retention and K+ depletion, resulting increased blood volume and increased blood pressure. Decreased aldosterone leads to Na+ (and H2O) loss and [K+]plasma, resulting in diminished blood volume and decreased blood pressure

What is the name given to the hypersecretion of cortisol?

Cushing's syndrome

What are the causes of cushing's syndrome?

Tumour in adrenal cortex (first degree hypercortisolism) Tumour in the pituitary gland (second degree hypercortisolism = cushing's disease. This is the most common, excess ACTH Iatrogenic, too much cortisol administered therapeutically

What is hyposecretion of cortisol called?

Addison's disease - much less common than hypersecretion Due to autoimmune destruction of adrenal cortex

What are the clinical features of cushing's disease?

Wasting of the extremities (catabolic action of cortisol) Fat redistributed to the face (moon face) Striae

What promotes CRH and ACTH release?

Stress

What is the effect of alcohol, caffeine and lack of sleep on the hypothalamo-pituitary-adrenal axis? (HPA)

Disinhibits the HPA (more activity) Alcohol in particular depresses the neurons involved in negative feedback further enhancing stress effect and increasing levels of CRH and ACTH

When the HPA is turned down, what is the effect of subsequent elevated levels of cortisol?

Turns down the levels of immune system - increasing vulnerability to infection

What type of tissue is the adrenal medulla?

Not true endocrine Modified sympathetic ganglion Neuroendocrin role (ike the posterior pituitary) Contains postganglionic cells, the fibres of which do not have axons, instead they release their neurohormones (adrenaline) into the blood

What hormone acts on beta 1 and beta 2 receptors?

Beta 1 - norepinephrine Beta 2 - epinephrine

What are the autonomic effectors of the adrenal medulla action?

Smooth and cardiac muscle Some endocrine and exocrine glands Some adipose tissue

What is pheochromocytoma and what are the effects?

Pheochromocytoma is a rare neuroendocrine tumour, found in adrenal medulla which results in XS catecholamines: Increase in HR increase in CO and a large increase in BP Diabetogenic due to adrenergic effect on glucose metabolism. Responds well to surgery.

Where is the pathology in the following cases?

What is the risk of withdrawing chronic glucocorticoid treatment?

Adrenal insufficiency Trophic action of ACTH on the adrenal gland has been underused and therefore the gland will be atrophied During the cortisol treatment the negative feedback on the hypothalamus and the pituitary results in reduced release of CRH and ACTH