The Adrenal Gland Flashcards
Where are the adrenal cortexes located? How large are they?
- On the superior poles of the kidneys in the retroperitoneal spaces
- Weigh about 4g each
Name the 2 parts of the adrenal gland and give a brief description of each
- Adrenal medulla (25%): modified sympathetic ganglion (neuroendocrine gland) secreting catecholamines from the post-ganglionic cell
- Adrenal Cortex (75%): true endocrine gland secreting 3 classes of steroid hormone (Mineralocorticoids, glucocorticoids and sex steroids)
How are the adrenal medulla and cortex arranged anatomically? What are the 3 parts of the adrenal cortex and what does each secrete?
- Cortex surrounds the medulla
Parts of cortex: (Inner to Outer)
- Zona reticularis: sex hormones
- Zona fasciculata: glucocorticoids
- Zona glomerulosa: aldosterone
What differentiates the zones of the adrenal cortex that results in the secretion of different hormones?
- the enzymes in each layer of the cortex are different
- All steroid hormones derived from cholesterol, each layer has the same starting substrate but result in different compounds due to enzymatic composition of different cells in each layer
Which adrenal cortex pathways is 21-hydroxylase important in? What does a defect in 21-Hydroxylase often lead to?
- Important in the pathways leading to the synthesis of aldosterone and cortisol
- 21 Hydroxylase deficiency often leads to congenital adrenal hyperplasia resulting in cortisol and aldosterone deficiency
- Synthesis of androgens is unaffected so excess steroid precursors are channeled towards this
Describe the cortisol synthesis pathway and the negative feedback mechanisms involved
- Hypothalamus makes CRH, stimulates anterior pituitary to make ACTH, ACTH acts on adrenal cortex to synthesize cortisol
- Cortisol negative feedbacks on ACTH and CRH production, ACTH also negative feedbacks on CRH production
Why does a deficit in 21 Hydroxylase cause adrenal hyperplasia?
How does this present clinically?
- No 21 Hydroxylase = no cortisol synthesized, but ACTH still synthesized
- ACTH responsible for enlargement of adrenal glands
- Presentation: babies born with the defect become very ill within a few days of birth
How does cortisol alter gene expression?
- 95% of plasma cortisol bound to cortisol binding globulin (CBG), only free cortisol can move into cells
- ALL cells have intracellular cortisol receptors, free cortisol passes through cell membrane and binds receptors
- Receptors migrate to nucleus binding to DNA via a hormone-response element & alter gene expression
When is cortisol concentration high in plasma? When is it low? What other hormone follows similar release patterns?
- Follows circadian rhythm, highest from about 6-9am, lowest around midnight
- Cortisol is high when ACTH is high, cortisol burst lasts longer though bc half life is significantly longer
Why does removal of the adrenal glands lead to death within a few weeks?
- No cortisol means glucose concentrations cannot be maintained during times of stress. It is crucial in preventing hypoglycaemia
- Aldosterone is crucial for maintaining extracellular fluid volume
Describe the actions of cortisol on glucose metabolism
- Increases gluconeogenesis by formation of gluconeogenic enzymes in the liver
- Increases gluconeogenesis via stimulation of muscle protein breakdown to provide gluconeogenic substrates
- Stimulates lipolysis in adipose tissue which increases plasma [FFA] which creates both an alternative fuel supply (protecting [BG]) and glycerol as a gluconeo. substrate
- Decreases insulin sensitivity of muscle and adipose tissue
Which hormone does cortisol work in opposition to? What can cortisol excess lead to clinically?
- Insulin
- Excess cortisol can be diabetogenic
What are the non-glucose metabolism related effects of cortisol?
- Negative effect on Ca balance, decreases gut absorption and increases kidney excretion, while also increases bone resorption
- Impairment of mood and cognition: depression and impaired cognitive function
- Permissive effect on norepinephrine (particularly in smooth muscle, alpha receptor effect = vasoconstrictive)
- Suppression of the immune system (reduces the circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response)
What effect does cortisol have on blood pressure?
Cortisol has a permissive effect on norepinephrine
- alpha receptor effect = vasoconstrictive
Hypercortisolaemia (eg. Cushing’s) often associated with hypertension
Low levels of cortisol also associated with hypotension
What are the common side effects of glucocorticoid therapy?
- Increased severity and frequency of infection
- Muscle wastage due to protein catabolism
- Loss of percutaneous fat and appearance of “thinning skin” due to lipolysis in adipose tissue
Slide on withdrawing chronic glucocorticoid treatment is confusing me rn. Look at it again. Slide 19.
Dominance.
What type of hormone is aldosterone? Where does aldosterone act?
- Mineralocorticoid
- Acts on the distal tubule of the kidney to determine which minerals (Na / K) are reabsorbed / excreted
Describe the effect of increased aldosterone concentration and decreased [aldosterone]
- Increased aldosterone: Stimulates Na and H2O reabsorption and K excretion. Increases blood pressure & volume
- Decreased aldosterone: Na & H2O excretion, K retention. Diminished blood volume and pressure
What are the two most common causes of hypersecretion of cortisol? Which is more common?
- Adrenal cortex tumour: Cushing’s SYNDROME. Primary hypercortisolism
- Pituitary gland tumour: Cushing’s DISEASE. Excess ACTH leads to excess cortisol, secondary hypercortisolism
- Cushing’s disease more common
What condition leads to hyposecretion of cortisol? Pathophysiology?
- Addison’s Disease: autoimmune destruction of adrenal cortex leading to hyposecretion of all adrenal cortex hormones
- Hyposecretion much less common than hypersecretion
Signs of Cushing’s disease?
- Weight gain
- Muscle wasting around the extremities
- Depression
- Hirsutism (male like hair growth on women)
- Redistribution of fat to the face and trunk
- Osteoporosis
How does stress Increase vulnerability to infection? Other than stress, what has the same effect via similar pathway?
- Stress causes increased CRH and ACTH production, elevates cortisol which depresses immune system
Alcohol, caffeine and lack of sleep:
- Depress neurones that are responsible for negative feedback pathways that repress CRH and ACTH. Leads to elevated CRH and ACTH, increasing cortisol and therefore enhancing stress effect
How does sympathetic stimulation cause adrenal release of epinephrine / norepinephrine?
- Adrenal medulla is a neuroendocrine gland
- sympathetic fibres terminate on specialized cells in the adrenal medulla that do not have axons, but instead release neurohormones into the blood
What is a Pheochromocytoma? What is are the consequences of it?
- A rare neuroendocrine tumour, found in adrenal medulla
- Results in excess catecholamines, increases HR, CO and largely increases BP
- Diabetogenic due to adrenergic effect on glucose metabolism
- Responds well to surgery
