Endocrine Day 5- Adrenal and Ca Flashcards
What is the master stress hormone of the body?
Where is it released from?
What does it stimulate?
- CRH= master sex hormone
- Released from PARAventricular nucleus
- Stimulates corticotrophs to release ACTH
What is effect of ACTH?
- ACTH causes adrenal cortex to release hormones
- cortisol (type of glucosteroid)
- aldosterone (mineralocorticoid)
- allows us to increase Na/h2o reabsorption from tubule
- cortisol can also act like aldosterone at kidney, causing increase H2O/Na reabsorption
- androgen precursor
- angiotensin
What is ACTH?
- Adrenocorticotropic Hormone derived from precursor pro-opiomelanocortin (POMC) from pit corticotroph cells by enzymatic clevage of precursor products
- POMC–> ACTH intermediate–> ACTH
- ACTH can be further cleaved into MSH and CLIP (only mention MSH)
- MSH can cause increase melanin release by bindign to melanin receptors
- ACTH is very similar to MSH so it can also bind to receptors in very high concentrations
What are the cellular zones of the adrenal cortex?
- C=connective tissue capsule
- ZG=zona glomerulosa produces aldosterone (mineralocorticoids)
- ZF=zona fasciculata produces cortisol (glucocorticoids)
- ZR=zona reticularis produces adrenal androgens
- M=adrenal medulla produces norepi and epi (most central area)
What are 2 major enzymes involved in synthesis of cortisol, aldosterones, and androgens by the cortex? What can happen if you’re deficient in either enzyme?
- Two major enzymes
- 21 alpha hydroxylase
- 11 beta hydroxylase
- If deficient in either enzyme, won’t be able to make mineralocorticoids (aldosterone) or glucocorticoids (cortisol)
- This will force the pathway into andonergic pathway, causing increase in systemic androgens
What can stimulate ACTH secretion (also increase CRH)
-
Cortisol decrease
- adrenalectomy
- sleep-wake transition- need cortisol to get out of bed
-
stress
- hypoglycemia
- anesthesia
- sx- contributing factor to puffiness post op is excess cortisol
- trauma
- infection
- pyrogens
-
Psych disturbance- both anxiety/depression can increase cortisol and incrase cortisol can cause anxiety/depression
- anxiety
- depression
- alpha agonists- NE/E incrase cortisol
- beta adrenergic antagonist
- serotnin
-
ADH- stress hormone
- causes constriction of vessels, raising BP
- corticotorphs also have ADH receptors
- gaba
What inhibits ACTH secretion?
Cortisol increase <– main one
enkphalins
opiates
acth
What time of day is largest release in ACTH/cortisol?
8 am
- Helps when glycogen stores decreased after sleep
- BP may be a bit lower, surge of cortisol helps compensate
Low cortisol level is ____
High cortisol level is____
anabolic; catabolic
- Low levels cortisol are anabolic and promote gluconeogenesis and storage of glucose as glycogen
- Higher livels of cortisol are catabolic and promote breakdown of muscle/fat (proteolysis and lipolysis)
- glycogenolysis also occurs in liver in order to increase substrates glucose, aa, ffa, aa for use in stress response
What is RAAS system role in aldosterone production?
RAAS system produces angiotensin II which increases aldosterone which increases Na/H2O reabsorbtion and K secretion
What is cushing disease?
- Cushing disease is due to pituitary tumor over-secreting ACTH and causing excess cortisol secreiton
- Causes
- swelling on face
- body fat redistrubted to back of neck and trunk
- proteolysis of connective tissue collagen elements, leading to appearance of purple striae
- hyperglycemia
- impaired immune response
What is cushing’s syndrome?
- Another version cushing disorder but called cushing syndrome
- due to adrenal cortical tumor over-producing cortisol
- excess cortisol drives same s/s as seen in previous cuhsing’s disease
What is congenital adrenal hyperplasia?
- Cuased by 21-alpha hydroxylase deficiency
- blocks biosynthetic pathway to produce cortisola nd aldosterone
- forced substrates into androgen pathway
- lack of cortiosl negative feedback causes excess ACTH release that stimulates excess androgen production
- has virilizing effect
What is treatment for congenital adrenal hyperplasia?
- Give cortisol
- Not having cortisol is life-threatening
- by reinstating negative feedback, ACTH levels drop and reduce andronergic pathway
What is addion’s disease?
- Autoimmune attack on adrenal cortex destorys cells making cortisol
- develops cortisol deficiency
- increased output ACTH from pituitary from loss negative feedback
- can’t survive without cortisol
- increased output ACTH from pituitary from loss negative feedback
- Highly pigmented skin due to melatonin from stimulation of MSH/increased ACTH levels
- not hazardous but diagnostic tool
What does calcium regulation look like in body?
- 1000 mg calcium ingested daily
- GI tract net uptake= 175 mg
- Bone net even (500 mg in, 500 mg out)
- Kidney excretes 175 mg from kidney
- insures that amount Ca in blood remains constant around 900 mg in ECF
What are the 3 main types of bone cells
- Osteoblasts
- Osteoclasts
- Osteocytes (which are absorbed osteoblasts)
What are osteoblasts?
- osteoblasts are found on surface of bone
- deposit Ca and phosphate into bone
- involved in movment of Ca PO4 out of bone, into fluid and into circulation
What are osteoclasts?
- liberate ca/phosphate from bone aka breakdown bone
What are osteocytes?
- Absorbed osteoblasts
What are the osteocystic/osteoblastic membranes role in Ca regulation?
- membrane is target for PTH and calcitiol (active form of VIt D)
- acts on membrane to cause rapid movmeent of Ca of PO4 into blood= rapid phase Ca/Po4 mobilization
- To replace bone fluid Ca and PO4 later, PTH stimulates slow phase of Ca mobilization by activating osteoclasts that will digest (reabsorb) bone and liberate Ca PO4 into bone fluid
What exists outside of calcified bone?
- Bone fluid exists between blasts and bone
What is parathyroid hormone?
- peptide hormone synthesized by parathyroid glands
- 4 parathyroid glands embedded posteirorly in 4 lobes thyroid gland
What cell scretes PTH?
Chief cells in parathyroid gland
What is the main target of PTH?
- Osteoclasts of bone (although indirectly)
- PTH actually binds to osteoblasts, in turn osteoblasts secrete cytokines and stimulate osteoclasts to digest bone, which moves Ca/PO4 out of bone and into blood stream
- kidney tubules
- gut (via D3)
INCREASES the availability of Ca in blood
What happens with removal of parathyroid glands?
- Loss of ability to regulate Ca which untreated, will result in rapid death
- (just need to supplement with external Ca)
What cells monitor Ca concentrations?
Chief cells
- When Ca levels decline in blood, chief cells increase output of PTH to restore Ca concentration
- Ca and PTH have inverse relationship
What is the summary of sites of action of PTH?
- Bone: promote Ca and phosphate resorption (into blood)
- increases remodeling of bone
- Kidney: calcium reabsorption, phosphate excretion (need to decrease phosphate levels so crystals dont’ form in blood)
- involved in final hydroxylation of 25-hydroxy vit d3
- Intestine: indirect effects via dihydroxy vit D3
What is PTH’s effect on plasma calcium and phosphate?
Increase Ca, decrease phosphate
What is pathway for formation of VIt D3?
- 7-Dehydrocholesterol in skin changes sturcutre when exposed to UV light
- Vit D3 is delivered to liver, acted on by 25-hydroxylase
- then taken to kidney
- PTH activates enzyme 1-hydroxylase
- creates active form VIT D3 aka calcitriol
- main target is GI tract to stimulate uptake of ca/po4 from gut, into circulation
Summary of Vit D3?
Active form?
Principal sites of action?
Cellular mechanism of action?
- Active form- 1,25 dihydroxy cholecalciferol
- Princaripal site:
- intestine: promote ca /po4 absorption
- bone: calcium and phosphate resorption
- shor tterm effect: synergism with PTH
- promotes mineralization (indirectly)
- Cellular mechanism of action
- promotes nuclear transritpion
- role of ca binding proteins
What is calcitonin? Where is it produced?
- Calcitonin is synthesized by parafollicular cells or C-cells that are dispersed throughout thyroid tissue and reside next to thyroid follicles
- Calcitonin increases net disposition of Ca and phosphate into bone by inhibiting osteoclastic activity., leaving osteoblastic activity unopposed
- Calcitonin not too important in adults, but very important in kids for growing
SUmmary of calcitonin action?
- Principle sites of action
- bone
- inhibtion of osteoclsts
- net deposition of calcium and phosphtae
- decreased remodeling
- kidney
- ca, phosphate excretion
- intestine
- decreased Ca absorption
- bone
- Effect on plasma Ca, phosphate
- decreased Ca decreased phosphtae
- Control of calcitonin secretion
- directly related to plasma Ca
- role of age
What is hypoparathyroidism
- Decrease in plasma Ca and increase phosphate
- Bone: decrease remodeling. density normal
- Muscle: tetany
- not sufficient Ca in blood stream, not available to interfere with movement of Na into muscle
- Na freely flows into muscle cells, causing muscle cell contraction and causes tetany
What is hyperparathyroidism?
- Excessive PTH output d/t tumor
- Plasma: Ca increase, phosphate decrease
- Bone:
- remodeling increase (excessive to where osteoporosis occurs)
- Muscles
- hypotonia: due to blocked Na channels in membrane, get flaccid muscle activity leading to hypotonia
- Kidney:
- nephrocalcinosis (kidney stones)
- renal insufficiency
What is rickets?
- Vita D3 deficiency (not eating enough/making enough)
- Decreased Ca, decreased Phosphate (can’t absorb)
- Bone:
- decrease mineralization
- deformities: wide epiphyses
- Muscle:
- tetany