The adrenal gland Flashcards
Where are the adrenal glands located?
Located on the superior pole of the kidney in the retroperitoneal space, each weighing ~4g in adults.
Identify the labels
What is the structure of the adrenal glands?
Similar to the pituitary, the adrenal gland is composed of two quite separate endocrine glands rolled into one structure
Adrenal medulla - 25%
Adrenal cortex - 75%
What is the adrenal medulla?
Neuroendocrine gland - it a modified sympathetic ganglion
It releases catecholamines from postganglionic cells:
mainly Epinephrine (adrenaline)
Norepinephrine
Dopamine
What is the adrenal cortex?
A true endocrine gland - which secretes 3 classes of steroid hormones:
Mineralocorticoids - eg Aldosterone
Glucocorticoids - eg Cortisol
Sex steroids - eg Testosterone
What do the hormones produced by the Adrenal cortex regulate?
Mineralocorticoids - eg Aldosterone:
- Involved in regulation of Na+, K+
Glucocorticoids - eg Cortisol:
- Involved in maintaining plasma glucose
Sex steroids - eg testosterone:
- do sex stuff
The adrenal gland produces hormones that play a role in the body’s response to _______
The body’s response to stress
Aldosterone and cortisol are essential for survival.
What are the histological regions of the adrenal glands (from out to in)
Capsule
Adrenal cortex:
- Zona Glomerulosa
- Zona Fasciculata
- Zona Reticularis
Adrenal Medulla
Identify the histological regions and what they secrete
Fill in the blanks about the adrenal cortex
“All steroid hormones are derived from ________, but different _______ are found in different adrenal zones, resulting in different end products e.g. enzymes needed to make aldosterone are found only in the zona _________”
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
Congenital defects in which enzyme are a common cause of adrenal hyperplasia?
What would be the effect of this?
21-hydroxylase
Results in the deficiency of cortisol and aldosterone - leading to disruption of salt and glucose balance.
Androgen biosynthesis is only viable pathway - leading to excessive adrenal androgen production
Describe how deficit of 21-hydroxylase causes 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.
- Babies become very ill within a few days of birth
What is cortisol?
A steroid hormone produced by the Zona Fasciculata of the adrenal cortex
It is a Glucocorticoid hormone than influences glucose metabolism
How does cortisol exist in the blood?
95% of plasma cortisol exists bound to carrier proteins called Cortisol binding globulin
Only free cortisol can cross into target cells
What cells does cortisol target?
Every fkn one of em
Every nucleated cell has cytoplasmic glucocorticoid receptors which bind to cortisol
What is the effect of cortisol binding to cytoplasmic receptors?
The cortisol/receptor complex moves to the nucleus
Binds to DNA via Hormone response element
Alters gene expression
Describe the daily release of cortisol
Cortisol release initiated by release of ACTH which follows a Circadian rhythm
Cortisol “burst” persists longer than ACTH burst because half-life is much longer
Peak is ~ 6-9am, nadir (lowest level) is ~ midnight
What is the effect of a lack of cortisol (ie if the adrenal glands were removed) on the body?
Loss of cortisol means animals cannot deal with stress, particularly in terms of maintaining blood glucose levels.
Cortisol as a glucocorticoid is crucial in helping to protect the brain from hypoglycaemia.
It has a permissive action on glucagon, which is vital as glucagon alone is inadequate in responding to a hypoglycaemic challenge
What is the effect of a lack of aldosterone on the body?
Lack of aldosterone would render an individual unable to regulate their extracellular fluid volume
What are the actions of cortisol (glucocorticoid action) on glucose metabolism?
Gluconeogenesis:
- Cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogensis and glucose formation
- This is aided by cortisols action on the muscle…
Proteolysis:
- Cortisol stimulates the breakdown of muscle protein to provide gluconeogenic substrates for the liver
Lipolysis:
- 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
Insulin:
- Decreases insulin sensitivity of muscles and adipose tissue
Why is too much cortisol diabetogenic?
Cortisol acts to oppose insulin
What are the additional (non-glucocorticoid) actions of cortisol?
Negative effect on Ca2+ balance
Impairment of mood and cognition
Permissive effects on norepinephrine
Suppression of the Immune System
How does cortisol have a negative effect on Calcium balance?
Decreases absorption from gut
Increases excretion from kidney
Increases bone resorption (which is then excreted)
How does cortisol affect mood and cognition?
depression and impaired cognitive function are strongly associated with hypercortisolaemia.
What are the permissive effects of 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.
How does cortisol suppress the immune system?
Cortisol reduces circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response
Latter effect can be useful clinically e.g. asthma/ulcerative colitis/organ transplant
Complete the diagram hehe
What are the side effects of glucocorticoid therapy?
Muscle wastage
Loss of percutaneous fat (thinning of skin)
Increased frequency of infection - such as thrush etc
Why must withdrawal from long-term glucocorticoid treatment be done gradually?
Enhanced negative feedback loop from exogenous cortisol may cause ATROPHY of the adrenal gland
This would thus cause adrenal insufficiency
What is aldosterone?
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.
It thus plays a role in governing fluid balance in tissues
What controls the release of aldosterone?
The secretion of aldosterone by the adrenal cortex is primarily controlled by a complex reflex pathway originating in the kidney, the renin-angiotensin-aldosterone system (RAAS)
What are the effects of increased aldosterone release?
Increased aldosterone release stimulates Na+ (and H2O) retention and K+ depletion
This results in increased blood volume and increased blood pressure
What are the disorders of cortisol secretion?
Hypersecretion of cortisol:
- Cushing’s syndrome/disease
- Iatrogenic - too much cortisol given
Hyposecretion of cortisol:
- Addison’s disease
- much less common
What causes Cushing’s disease and Cushing’s syndrome?
Hypersecretion of cortisol - caused by a tumour in either:
- Adrenal cortex - 1o hypercortisolism = Cushing’s syndrome
-
Pituitary gland - 2o hypercortisolism = Cushing’s disease
- Much more common
- Excess ACTH
What causes Addison’s disease?
Autoimmune destruction of the Adrenal cortex
Causes Hyposecretion of all adrenal steroid hormones - Cortisol, aldosterone, sex steroids etc
What are the effects of Cushing’s disease on body appearance?
Moon face and fatty belly
Wasting in extremities and limbs
How does stress increase the vulnerability to infection via the HPA?
CRH & ACTH release promoted by stress
Alcohol, caffeine and lack of sleep all “disinhibit” the Hypothalamo-Pituitary-Adrenal Axis (HPA).
Alcohol, in particular, depresses the neurons involved in negative feedback further enhancing stress effect and increasing levels of CRH and ACTH.
This increases cortisol levels - which turns down the immune system
What is the adrenal medulla and how does it secrete into the blood?
Modified sympathetic ganglion that serves a neuroendocrine role (similar to posterior pituitary)
In it - pre-ganglionic sympathetic fibres terminate on specialised post-ganglionic cells in the adrenal medulla
These cells have no axons - but instead release their neurohormone (adrenaline) directly into the blood
What is Pheochromocytoma?
Pheochromocytoma is a rare neuroendocrine tumour of the adrenal medulla
It causes excess release of catecholamines which increases HR, CO and thus causes hypertension (constant symp stimulation)
It also causes Diabetes due to adrenergic action impacting on glucose metabolism
How is pheochromocytoma treated?
Surgery - responds very well
In each pathway - state the impact on the levels of:
CRH
ACTH
Cortisol
