L6 - Adrenal cortex Flashcards
What is the role of adrenal cortex and medulla?
Medulla - stress response
Cortex - stress, sodium and glucose homeostasis
What are the major secretions of the adrenal cortex?
Glucocorticoids - cortisol
mineralocorticoids - aldosterone
Layers of the cortex
zona glomerulosa - has 18-hydroxylase - hence aldosterone synthesis
Zona F and R have 17a-hydroxylase hence 17a-hydroxpregnenolone and 17a-hydroxprogesterone and the hormones derived from them
Cortisol is made in the ZF
Androgens are made in the ZR.
Control of glucocorticoid secretion
hypothalamus secretes CRH - causes anterior pit to secrete ACTH which causes adrenal cortex to secrete cortisol.
cortisol negatively feedbacks to hypothalamus to reduce CRH
How are glucocorticoids transported?
90% bound to plasma proteins
CBG 75%
Albumin 15%
Cortisol and metabolism
opposite action to insulin
stimulates glycogenolysis
stimulates hepatic gluconeogenesis
stimulates lipolysis
in excessive amounts, cortisol causes fat synthesis and deposition
most noticably the face, trunk
in the liver, cortisol stimulates amino acid uptake
in the periphery it inhibits amino acid and protein synthesis resulting in net loss of skeletal protein
How do glucocorticoids affect the bodys defence
They suppress the lymphoid tissue, reduce the antibody production and inhibit the cellular immune system.
• They stabilize leucocyte membranes and reduce the release of proteolytic enzymes.
• They inhibit phospholipase A2 and reduce the synthesis of the inflammatory mediators.
Mineralocorticoid control
Not influenced by ACTH.
RAAS system.
The secretion of aldosterone is directly stimulated by trauma, anxiety, hyperkalemia and hyponatremia and inhibited by ANP.
Actions of mineralocorticoids
aldosterone has particular intracellular receptors with cause expression of ion channels that transport sodium and potassium across membrane
sodium reaborption in DT of kidney.
Pharmacological uses of adrenocorticosteroids
Glucocorticoids (eg hydrocortisone = cortisol) are used in replacement therapy and for their immunosuppressive or anti-inflammatory effects in conditions such as arthritis, asthma or allergies, or for the treatment of proliferative conditions such as leukaemia.
Mineralocorticoids are used only for replacement therapy.
The short plasma half-life of aldosterone renders it unsuitable for mineralocorticoid replacement therapy thus the drug of choice is fludrocortisol.
What are the adverse effects of glucocorticoids?
Steroid usage may suppress wound healing and may exacerbate infections due to their immunosuppresant effects.
Long term use in children may cause inhibition of growth, and in adults may result in osteoporosis.
The development of diabetes mellitus and other symptoms of Cushing’s syndrome also often accompanies steroid therapy.
Probably the most adverse effect is - suppression of the HPA
chronic administration of exogenous glucocorticoids results in suppression of ACTH secretion leading to atrophy of the adrenal cortex
What happens if steroid therapy is stopped abruptly?
the adrenal cortex is unable to secrete endogenous hormones and the patient suffers an Addisonian crisis, which may be fatal. This consequence overcome by the gradual reduction of the dose of the exogenous steroid
Hydrocortisone (cortisol)
A natural glucocorticoid secreted frmo the adrenal cortex. acts by specific intracellular glucocorticoid receptors to influence gene expression.
Glucocorticoids are typically used for hormone replacement therapy, as anti-inflammatory agents and immunosuppressants. Hydrocortisone is the drug of choice for replacement therapy
Adverse effects of hydrocortisone?
hyperglycemia
osteoporosis
cushings syndrome
