The Adrenal Gland Flashcards
Where are the adrenal glands located?
Superior pole of kidneys in retroperitoneal space

What does each adrenal gland weigh in an adult?
About 4g
What are the two seperate endocrine glands that makes up the adrenal gland?
Adrenal medulla
Adrenal cortex
What percentage of the adrenal gland is the adrenal medulla?
About 25%
What is the adrenal medulla?
Modified sympathetic ganglion derived from neural cresh tissue
What does the adrenal medulla secrete?
Catecholamines, mainly epinephrine, also norepinephrine and dopamine
What percentage of the adrenal gland is the adrenal cortex?
About 75%
What is the adrenal cortex?
True endocrine gland derived from mesoderm and secretes 3 classes of steroir hormones
What class of hormones does the adrenal cortex secrete?
Steroid
What are the 3 classes of steroid hormones that the adrenal cortex secretes?
Mineralocorticoids
Glucocorticoids
Sex steroids
What is an example of a mineralocorticoid?
Aldosterone (involved in regulation of Na and K)
What is an example of a glucocorticoid?
Cortisol (involved in maintaining plasma glucose)
What is an example of a sex steroid?
Testosterone
Is the adrenal cortex or medulla more superficial?
Adrenal cortex

What is each layer of the adrenal cortex?
Zona glomerulosa (secretes aldosterone)
Zona fasciculate (secretes glucocorticoids)
Zona reticularis (secretes sex hormones)

What does the zona glomerulosa secrete?
Aldosterone
What does the zona fasciculate secrete?
Glucocorticoids
What does the zona reticularis secrete?
Sex hormones
How is it possible for different hormones to be secreted in different layers of the adrenal cortex?
All steroid hormones are derived from cholesterol
But different enzymes found in different adrenal zones results in different end products

What is a synthetic pathway?
Route taken to build up a specific product
What enzyme is responsible for both the formations of aldosterone and cortisol?
21-hydroxylase

What does HPA stand for?
What do defects in 21-hydroxylase cause?
Congenital adrenal hyperplasia resulting in:
- deficiency of aldosterone and cortisol (so disruption of salt and glucose balance)
- androgen biosynthesis is unaffected so accumulating steroid percursors are channels into excess adrenal androgen production

What does cortisol provide long loop feedback on?
CRH

Cortisol provides long loop feedback on CRH as part of the hypothalamic-pituitary-adrenal pathway, what provides short-loop feedback?
ACTH

Explain the process of a deficit in 21-hydroxylase causing adrenal hyperplasia?
1) Lack of enzyme inhibits synthesis of cortisol
2) Removal of negative feedback on ACTH and CRH release
3) Increased ACTH secretion is responsible for enlargement of adrenal glands
4) Negative feedback of ACTH on CRH synthesis remains balanced
5) Babies become very ill within a few days of birth

What type of hormone is cortisol?
Glucocorticoid hormone (influences glucose metabolism)
What percentage of plasma cortisol is bound to carrier protein?
About 95%
What plasma protien does most cortisol bind to?
Cortisol binding globulin (CBG)
What kind of cells have cytoplasmic glucocorticoid receptors?
All nucleated cells
What happens when cortisol binds to its cytoplasmic glucocorticoid receptor?
Hormone receptor complex migrates to nucleas
Binding to DNA via a hormone-receptor element to alter gene expression, transcription and translation

What kind of rhythm do cortisol plasma levels show, and what are they preceded by?
Circadian rhythm, preceded by a similar pattern of release of ACTH
Does cortisol or ACTH have a longer half life?
Cortisol, so bursts of release persist around longer than ACTH
What time of day can the peak and lowest levels of plasma cortisol be obersed?
Peak - between 6am and 9am
Lowest - midnight
What are fluctations of cortisol levels during the day due to?
Effects of stimuli which are related to stress
What would a loss of cortisol mean?
Animals cannot deal with stress, particularly in terms of maintaining blood glucose levels
How does cortisol cause gluconeogenesis?
Stimulates formation of gluconeogenic enzymes in liver, enhancing gluconeogenesis and glucose production
Does cortisol have permissive action on insulin or glucagon?
Glucagon, which is vital as glucagon alone is inadequate in responding to a hypoglycaemia challenge
What are the consequences of removing the adrenal glands in animals?
Cannot deal with stress, particularly in terms of maintaining blood glucose levels
Incapable of maintaining their ECF volume, an effect mediated by aldosterone
What are some actions of cortisol on glucose metabolism?
Gluconeogenesis
Proteolysis
Lipolysis
Decreased insulin sensitivity
Is excess cortisol diabetogenic or the opposite?
It is diabetogenic due to its gluocse-counter regulatory effects that oppose insulin
Does cortisol have a positive or negative effect on calcium balance, and why?
Negative
Decreases absorption from gut, increases excretion at kidney resulting in net calcium loss
Also increase bone resorption, leading to osteoporosis
Other than glucose metabolism, what are some additional actions of cortisol?
How does cortisol cause an impairment on mood and cognition?
Depression and impaired cognitive function are strongly associated with hypercortisoaemia
Does cortisol have permissive or antagonistic action to norepinephrine?
Permissive
Particular in smooth muscle (a-receptor effect is vasoconstrictive)
Cushing’s disease (hypercortisolaemia) is strongly associated with hypertension, and low cortisol levels are associated with hypotension)
Does cortisol enhance or suppress the immune system, and why?
Suppression
Reduces the circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response
What are some side-effects of glucocorticoid therapy?
Increases severity and frequency of infection (due to immune suppresion)
Muscle wastage (due to proteolysis)
Loss of percutaneous fat stores gives appearance of thinning skin

What kind of hormone is aldosterone?
Mineralocorticoid
What does aldosterone act on?
Distal tubule of kidney to determine to determine levels of minerals reabsorbed/excreted
How does aldosterone impact sodium and potassium?
Increases reabsorption of sodium and promotes excretion of potassium
What is secretion of aldosterone by adrenal cortex primarily controlled by?
Renin-angiotensin-aldosterone system (RAAS)
What does RAAS stand for?
Renin-angiotensin-aldosterone system
What system are the effects of aldosterone mainly on?
CNS system
What does increased aldosterone cause?
Stimulates sodium (and water) retention and potassium depletion, resulting in increased blood volume and blood pressure
What does decreased aldosterone cause?
Sodium (and water) loss and increased potassium in plasma, resulting in decreased blood volume and blood pressure
What are some examples of disorders of the HPA?
Hypersecretion of cortisol
Hyposecretion of cortisol
What are some causes of hypersecretion of cortisol?
Cushing’s syndrome/disease
What is hypersecretion of cortisol most commonly due to?
Tumour in:
- adrenal cortex (1o hypercortisolism), which is Cushing’s syndrome
- pituitary gland (2o hypercortisolism), which is Cushing’s disease
Does a tumour in the adrenal cortex cause Cushing’s disease or Cushing’s syndrome?
Cushing’s syndrome (1o hypercortisolism)
Does a tumour in the pituitary cause Cushing’s disease or Cushing’s syndrome?
Cushing’s disease (2o hypercortisolism)
Is hypersecretion or hyposecretion of cortisol more common?
Hypersecretion is much more common
What causes hyposecretion of cortisol?
Addison’s disease
- causes hyposecretion of all adrenal steroid hormones
- due to autoimmune destruction of adrenal cortex
What is Cushing’s disease characterised by?
Wasting of the extremities (due to catabolic action of cortisol)
Fat redistribution to the face (“moon face”) and trunk
What are examples of things that disinhibit the hypothalamic-pituitary-axis (HPA)?
Alcohol, caffeine and lack of sleep
- alcohol particularly depresses neurons involved in negative feedback, further enhancing stress effect and increasing levels of CRH and ACTH
- turns down immune system and increases vulnerability to infection
What is the adrenal medulla?
Modified sympathetic ganglion, not true endocrine tissue
What happens to preganglionic fibres to the adrenal medulla?
Terminate on specialised postganglionic cells in adrenal medulla, these postganglionic cells do not have axons, instead releasing their neurohormones (adrenaline) into the blood
What is an example of adrenal medulla pathology?
Pheochromocytoma

What is pheochromocytoma?
Rare neuroendocrine tumour, found in adrenal medullar which results in XS catecholamines
Causing increased heart rare, increased cardiac output so massively increased blood pressure
Diabetogenic due to adrenergic effects on glucose metabolism

What are some different sites of enodcrine pathology in HPA?
Secondary hypersecretion due to pathology in hypothalamus
Secondary hypersecretion due to pathology in anterior pituitary
Primary hypersecretion due to pathology in adrenal cortex

In secondary hypersecretion due to pathology in hypothalamus, what are:
- CRH levels
- ACTH levels
- cortisol levels
(high/low)
CRH levels - high
ACTH levels - high
Cortisol levels - high

In secondary hypersecretion due to pathology in pituitary, what are:
- CRH levels
- ACTH levels
- cortisol levels
(high/low)
CRH levels - low
ACTH levels - high
Cortisol levels - high

In primary hypersecretion due to pathology in adrenal cortex, what are:
- CRH levels
- ACTH levels
- cortisol levels
(high/low)
CRH levels - low
ACTH levels - low
Cortisol levels - high

Why is care required when withdrawing chronic glucocorticoid treatment?
Due to enhanced negative feedback effects of exogenous control
Therapeutic cortisol also enhances negative feedback on hypothalamus and pituitary, reducing release of CRH and ACTH:
- loss of trophic action of ACTH on adrenal gland causes atrophy of gland
- risk of adrenal insufficiency if withdrawal is too fast