The adrenal gland Flashcards
just know
Describe the anatomy of the adrenal glands
- Adrenal glands are situated on the superior pole of the kidney in the retroperitoneal space, each weighing ~4g in adults
- Anatomy differs slightly between L and R
Left adrenal vein drains into left renal vein, while R adrenal drains directly into the inferior vena cava (Implications for surgery) - Similar to the pituitary, the adrenal gland is composed of two quite separate endocrine glands rolled into one structure:
- Adrenal medulla
- Adrenal cortex
Describe the structure and function of the adrenal medulla
- It is a modified sympathetic ganglion derived from neural crest tissue
- Secretes catecholamines, mainly epinephrine (adrenaline), also norepinephrine and dopamine
Describe the structure and function of the adrenal cortex
- It is a true endocrine gland derived from mesoderm and secretes 3 classes of steroid hormones, the first 2 of which are of particular importance:
- Mineralocorticoids e.g. aldosterone: involved in the regulation of Na+ and K+
- Glucocorticoids e.g. cortisol: involved in maintaining plasma glucose
- Sex steroids e.g. testosterone
What are the zones of the adrenal cortex and what do they produce (from the outside to the centre of the adrenal gland)
- Zona glomerulosa: Aldosterone
- Zona fasciculata: Glucocorticoids
- Zona reticulata: sex steroids
What are the vague synthetic pathways in the adrenal cortex
Cholesterol -> progesterone (21-hydroxylase)-> Corticosterone-> Aldosterone
Cholesterol-> Progesterone or DHEA-> Androstenedione-> Testosterone-> Dihydrotestosterone (DHT)
Cholesterol-> Progesterone or DHEA-> Androstenedione-> Esterone or testosterone-> Estradiol
Describe the hypothalamic- pituitary- adrenal pathway
Hypothalamus-> CRH-> Anterior pituitary-> ACTH- Adrenal cortex-> cortisol-> target tissue-> response
Why does a deficit 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
Describe cortisol release
- Plasma levels of cortisol show a very characteristic pattern
- There is a marked circadian rhythm, preceded by a similar pattern of release of ACTH
- Cortisol “burst” persists longer than ACTH burst because half-life is much longer
- Peak is ~ 6-9am, nadir (lowest level) is ~ midnight.
- Other fluctuations during the day are due to effects of other stimuli which are related to stress
What happens if you lose cortisol?
- 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 hypoglycemia
- It has a permissive action on glucagon, which is vitals as glucagon alone is inadequate in responding to a hypoglycaemic challenge
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
What are the additional actions of cortisol (non-glucocorticoid)?
- Negative effect on Ca2+ balance: decrease absorption from gut, increases excretion at kidney resulting in net Ca2+ loss
- Also increase bone resorption -> osteoporosis
- Impairment of mood and cognition: depression and impaired cognitive function are strongly associated with hypercortisolemia
- Permissive effects on norepinephrine: particularly in vascular smooth muscle (alpha-receptor effect = vasoconstrictive)
- Cushing’s Disease (hypercortisolemia) is strongly associated with hypertension
- Likewise, low levels of cortisol are associated with hypotension
- 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 end effects of aldosterone?
- 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 increased [K+]plasma, resulting in diminished blood volume and decreased blood pressure
How do you get hypersecretion of cortisol?
Cushing’s syndrome/disease
- Hypersecretion is most commonly due to a tumour in :
* adrenal cortex (1o hypercortisolism = Cushing’s syndrome)
or
* pituitary gland (2o hypercortisolism = Cushing’s disease). Most common. Excess ACTH.
Iatrogenic
- Too much cortisol administered therapeutically
How do you get hyposecretion of cortisol?
- is much less common than hypersecretion
- Addison’s disease
- Hyposecretion of all adrenal steroid hormones
- Due to autoimmune destruction of adrenal cortex
What is pheochromocytoma?
- It is a rare neuroendocrine tumour, found in adrenal medulla which results in XS catecholamines:
- Increased HR-> increased CO-> very increased BP
- Diabetogenic due to adrenergic effect on glucose metabolism.
- Responds well to surgery
