Physio 4 Flashcards
adrenal medulla
derived from neural crest. epinephrine, norepi, dopa, and dopamine made here. modified post-ganglionic sympathetic nerve cells. total loss is not life threatening
adrenal cortex
derived from mesoderm. secretes glucocorticoids, mineralocorticoids, and androgens. essential for life. loss of function is fatal in 4-14 days
hormone synthesis in the adrenal cortex
pregnenolone is made into a bunch of different hormones. pregnenolone comes from cholesterol via the side chain cleavage enzyme. the cholesterol to pregnenolone step is the rate limiting step. 17-alpha-hydroxylase converts pregnen to various things like DHEA and androstenedione
aldosterone synth in zona glomerulosa
rate limited by how fast the glomerulosa cells can synth it. major action of aldosterone is to stim the kidney to reabsorb sodium and water and enhance potassium secretion. zona glomerulosa doesnt have 17-alpha-hydroxylase so it cant convert pregenenelone to the things that the cortex can
synth of cortisol and androgens in the zona fasciculata and zona reticularis
layers lack aldosterone synthase but have 17-alpha-hydroxylase. DHEA reaches peak production in the 20s. it is important for maintenance of sex drive. converted to androstenediol. androstenedione can be converted to testosterone in the peripheral tissue.
cortisol mechanisms of action
free cortisol enters target cell by diffusion. binds to cytoplasmic receptor. migrates to the nucleus where it modifies gene transcription.
cortisol inhibits expression of CRH receptor and ACTH in the corticotrophs of the anterior pituitary. Cortisol inhibits transcription of POMC gene
aldosterone and cortisol interaction
mineralocorticoid receptor has similar affinity to cortisol and aldosterone. body has much more cortisol than aldosterone. renal tubule cells express 11-beta-hydroxysteroid dehydrogenase type II, which converts cortisol to cortisone. Cortisone has very low affinty for the mineralocorticoid receptor. If this enzyme is inhibited you get high blood pressure
metabolic effects of cortisol
stims gluconeogenesis in liver. enhances protein breakdown in muscle cells. stimulates lipolysis in adipose tissue for an alternative fuel to glucose. decreases osteoblastic activity in trabecular bone and interferes with Ca ++ absorption from gut
anti-inflammatory effects of cortisol
inhibits production of cytokines and chemo-attractant molecules. stabilize lysosomal enzymes. contributes to vasoconstriction and decreased capillary permeability
immunosuppressive effects
decreases lymphocyte proliferation, inhibits hypersensitivity reactions
ACTH action
major hormone. binds to melanocortin2 receptor. this activates PKA which phosphorylates enzymes, one of which is the side chain cleavage enzyme. PKA increases synthesis of several enzymes
CRH action
regulates ACTH secretion. This comes from the hypothalamus. It binds to the CRH receptor, also a g-protein coupled receptor. this activates PKA which increases synthesis of ACTH and opens Ca channels which leads to more ACTH secretion
feedback inhibition of CRH and ACTH
circulating cortisol exerts negative feedback control on the release of both ACTH and CRH. cortisol inhibits POMC gene expression and inhibits release of synthed ACTH in anterior pituitary. in the hypothalamus, cortisol decreases mRNA and peptide levels of CRH and inhibits release of premade CRH
POMC (pro-opiomelanocortin)
corticotrophs make ACTH by post translation processing of POMC. In the anterior pituitary, processing of POMC gives rise to ACTH and beta-lipoprotein
diurnal variation in ACTH and cortisol production
highest levels of cortisol in the early morning, lower levels in the evening. CRH release from hypotyhal is in pulses which results in pulsatile secretion of ACTH. stress can enhance CRH and therefore ACTH secretion
21 alpha hydroxylase deficiency
mutation causing decreased production of cortisol and aldosterone. Leads to increased ACTH due to lack of neg feedback, adrenal hyperplasia, increased androgen production, ambiguous genetalia in female, hypoglycemia, hypotension, loss of salt, dehydration. Test with ACTH stimulation test. can use prednisolone and dexamethasone can be subbed for cortisol.
17 alpha hydroxylase deficiency
reduced cortisol and androgen synth. increased cortisterone and aldosterone, causing hypertension and hypokalemia. reduced estrogen synth. sexual infantilism in genetic females. hermaphrodite in males. treat with glucocorticoid replacement, and some surgery or testosterone replacement
cushing’s syndrome
hyperadrenal function. happens when body is exposed to excess cortisol for long periods of time. syndrome refers to excess cortisol of any etiology. cushings disease is hypercortisolism secondary to excess production of ACTH from a pituitary gland adenoma. symptoms are moon face, red face, fat upper body, round face. osteopenia, infections, glucose intolerence, hypokalemia and hypertension
diagnosis of cushings disease
urinary or salivary cortisol measurement. dexamethasone suppression test. this is a potent synthetic cortisol mimic that provides negative feedback and prevents ACTH secretion. takes the dose of dexameth and then cortisol levels are measured in the morning. if high, test is positive and patient has cushing’s syndrome. adrenal tumor = high cortisol low ACTH. ACTH producing tumor = high cortisol and high ACTH
treatment of cushing’s disease
surgery to remove adenoma. if both adrenals are removed, replacement with hydrocortisone or prednisolone is needed. can try to inhibit cortisol synth with drugs
addison’s disease
hypoadrenal fnction. caused by failure of the adrenal glands to produce enough cortisol. if primary adrenal insufficiency, aldosterone is also deficient. hyperkalemia. production of adrenaline is also diminished or eliminated. mostly caused by autoantibodies directed against adrenal cells containing 21-hydroxylase
diagnosis of addisons disease
determine cortisol levels. ACTH stimulation test. Normal response is an increase in blood and urine cortisol, adrenal insufficiency shows poor response or none at all. CRH stim test. Patients with primary adrenal insuff have high ACTH but no cortisol, and patients with secondary insuff have deficient cortisol responses but absent or delayed ACTH responses
treatment of addison’s disease
replace missing cortisol and possible fludrocortisone as replacement for missing aldosterone
