Hypothalamic pituitary relationships and feedback part 2 Flashcards
what is found in the Zona glomerulosa and what is its function
Mineralcorticoid which produce aldosterone which regulates the salt and volume homeostasis
What is found in the zona fasciculata and what is its function
Glucocorticoid which produce cortisol and androgens (DHEAS)
cortisol is a longeracting stress response steroid hormone that regulates glucose utilization, immune and inflammatory homeostasis
WHat is found in the zona reticularis and what is its function
glucocortocoid cortisol and androgens DHEAS
androgens are important for secondary sex characteristics
what is the axes of cortisol
Hypothalamus releases CRH which acts on the anterior pituitary that releases ACTH which acts on MC2R receptors in the adrenal cortex that releases cortisol
cortisol then serves as negative feedback
What are causes for the release of CRH
Emotional stress
Physical stress
Metabolic stress
Infection and inflammation
does the circadian rhythm play a factor in cortisol
yes, the secretory rates of cortisol are high in the mornings but are low in the late evenings
ACTH is fairly constant through out the day
what is the pathway and regulation of aldosterone secretion
if their is a decrease in BP or decrease in Na+
hypothalamus releases CRH onto the anterior pituitary which releases ACTH which releases Aldosterone from the adrenal cortex
this targets the kidneys to reabsorb Na+ and water that leads to an increase n BP
What is Cushings syndrome and what are some symptoms
high cortisol
buffalo hump truncal obesity immunosuppression hypertension edema weakness osteoporosis acne purple striae
How does a low dose Dexamethasone suppression test work
dexamethasone is a synthetic glucocorticol
at low doses it differentiates patients with Cushings syndrome vs patients who dont have it
if their is no ACTH suppression then it indicates Cushings syndrome
however it doesn’t specify source of ACTH over production
How does a high dose dexamethasone suppression test work
Distinguishes patients with cushings disease has a pituitary tumor or a ectopic tumor
if their is a decrease in ACTH levels due to negative feedback then it is a pituitary tumor
if their is no change in ACTH then it is an ectopic tumor
if Cushings syndrome is caused by a adrenal tumor what is the levels of CRH, ACTH, and cortisol
decrease in CRH
Decrease in ACTH
and increase in Cortisol
thats because the adrenal cortex is overactive and still get the negative feedback
if cushings syndrome is caused by pituitary disease what is the levels of CRH, ACTH, and cortisol
decrease in CRH
increase in ACTH
increase in Cortisol
this is because it is in the anterior pituitary therefore the only thing getting a negative feedback is the hypothalamus
if cushings syndrome is caused by ectopic secreting ACTH tumor what is the levels of CRH, ACTH, and cortisol
low CRH
High ACTH
High cortisol
however the pituitary and hypothalamus is inhiibited therefore the release of ACTH is coming not from the pituitary
if cushings syndrome is caused by exogenous glucocorticoids what is the levels of CRH, ACTH, and cortisol
low CRH
Low ACTH
Low cortisol
but the exogenous corticoids mimic cortisol actions showing cushings disease symptoms
iatorgenic cushings disease
what is significant about the exogenous glucocorticoids especially on the zona fasciculata and that are some examples of drugs
they have the same negative feedback as cortisol
but can cause atrophy to zona fasciculata
Prednisone
methylprednisone
dexamethasone
What is the primary action of aldosterone
renal sodium reabsorption and potassium secretion in the distal nephron
does this by altering trnscription of creating new channels in the distal nephraon
what is ACTH derived from
made in anterior pituitary and derived from Post translational processing of POMC
is a peptide hormone
what happens when their is a supraphysiological level of ACTH
leads to hyperpigmentation
ACTH has a low binding affinity for MC1R which is melanocytes in the skin and increase production of Melanin
causes darkening of the skin and production of MSH
what does the cosyntropin stimulation test detect
Adrenal gland insufficiency
-high increase of cortisol after 30 min
low levels/normal means secondary or tertiary Adrenal insufficency
elevated levels of ACTH means Primary adrenal insufficency
cosyntropin is a synthetic ACTH
what happens to levels of cortisol and aldosterone secretion in primary adrenal insufficiency
decrease secretion in both cortisol and aldosteron
what happens to levels of cortisol and aldosterone secretion in secondary and tertiary adrenal insufficiency
decrease in cortisol
aldosterone still exists due to the renin-angiotensin-aldosterone axis
what are the causes and treatments of primary adrenal insufficiency (addisons disease)
autoimmune disease
adrenal hemorrhage
waterhose-friedrichsen syndrome
tuberculosis
meningitidis
tumor to the adrenal gland
treatment: replace cortisol and aldosterone
aldosterone: fludrocortisone
cortisol: dexamethasone
What is the plasma cortisol, plasma CRH, Plasma ACTH, and pigmentation if you have a disorder of: Primary (excess)
high cortisol
low CRH
low ACTH
no hyperpigmentation
What is the plasma cortisol, plasma CRH, Plasma ACTH, and pigmentation if you have a disorder of: Secondary excess
high cortisol
low CRH
High ACTH
yes pigmentation
What is the plasma cortisol, plasma CRH, Plasma ACTH, and pigmentation if you have a disorder of: Primary deficiency
low cortisol
high CRH
High ACTH
yes hyperpigmentation
What is the plasma cortisol, plasma CRH, Plasma ACTH, and pigmentation if you have a disorder of: Secondary deficiency
low cortisol
high CRH
low ACTH
no hyperpigmentation
primary Hyperaldosteronism
excessive aldosterone from the cortex
conns syndrome: adenoma in the adrenal cortex
hypertension
hypokalemia
Secondary hyperaldosteronism
excessive renin secretion by the juxtaglomerular cells in the kidney
hypertension
hypokalemia
Hypoaldosteronism
destruction of the adrenal cortex
defects in aldosterone synthesis
inadequate stimulation of aldosterone secretion
what enzymes are used to make androgens
17, 20, 3B(to make a minor proust)
What enzymes are used to make aldosterone
3B, 21, DOC (serves as a mineralcorticoid), 18
what enzymes are used to make cortisol
3B, 17, 21, 11
How is the mineralcorticoid receptor protected from activation via cortisol
11B-HSD2 converts cortisol to cortisone
All congenital adrenal enzyme deficiencies are chacracterized by what
Enlargement of both adrenal glands due to the increase ACTH stimulation due to the decrease of cortisol
what is the Mineralcorticoids, cortisol, sex hormones, blood pressure, potassium levels, labs, and other presentations of an enzyme deficiency: 17a
high mineralcorticoids low cortisol low sex hormones high blood pressure low potassium decrease in androstenedione men, undescended testes women, lack of secondary sexual development
what is the Mineralcorticoids, cortisol, sex hormones, blood pressure, potassium levels, labs, and other presentations of an enzyme deficiency: 21B
decrease in mineralcorticoids low cortisol high sex hormones low blood pressure high potassium high renin activity high 17-hydroxy progesterone salt wasting precocious puberty virilization
what is the Mineralcorticoids, cortisol, sex hormones, blood pressure, potassium levels, labs, and other presentations of an enzyme deficiency: 11B
decrease in Aldosterone increase in DOC (increase in BP) decrease in Cortisol increase in sex hormones high BP Low potassium decrease in renin activity Virilization
Pheochromocytoma
tumor that increases the secretion of catecholamines that stimulate both alpha and beta receptors hypertension sweating palpitations headaches
synthesis of Catecholamines is under the control of what activity
Sympathetics (Acetylcholine) and the CRH-ACTH-cortisol axes
cortisol upregulates the PNMT enzyme
phenylethanolamine N methyl transferase
How is norepinephrine and epinephrine synthesized
Rate limiting step is the hydroxylation of tyrosine by tyrosine hydroxylase making DOPA
converted to DA then transported into a secretory vesicle (chromaffin granule)
in the granule the DA is converted to NE by dopamine B hydroxylase
then NE diffuses out of chromaffin granule and is methylated via PNMT to form Epinephrine
then transported back to granule via VMATs
What are chromogranins
Multimolecular complexes thought to decrease the osmotic burden of storing E
these can be used as a biomarker for sympathetic paraganglion derived tumors
How are catecholamines degrared
COMT: catecholamine O methyltransferase
MAO: monoamine oxidase
response of receptors to NE vs E
alpha and B3 receptors respond more to NE
B1 responds equally to NE and E
B2 responds more to E
