Endocrine Day 5- Adrenal and Ca Flashcards
1
Q
What is the master stress hormone of the body?
Where is it released from?
What does it stimulate?
A
- CRH= master sex hormone
- Released from PARAventricular nucleus
- Stimulates corticotrophs to release ACTH
2
Q
What is effect of ACTH?
A
- 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
3
Q
What is ACTH?
A
- 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
4
Q
What are the cellular zones of the adrenal cortex?
A
- 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)
5
Q
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?
A
- 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
6
Q
What can stimulate ACTH secretion (also increase CRH)
A
-
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
7
Q
What inhibits ACTH secretion?
A
Cortisol increase <– main one
enkphalins
opiates
acth
8
Q
What time of day is largest release in ACTH/cortisol?
A
8 am
- Helps when glycogen stores decreased after sleep
- BP may be a bit lower, surge of cortisol helps compensate
9
Q
Low cortisol level is ____
High cortisol level is____
A
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
10
Q
What is RAAS system role in aldosterone production?
A
RAAS system produces angiotensin II which increases aldosterone which increases Na/H2O reabsorbtion and K secretion
11
Q
What is cushing disease?
A
- 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
12
Q
What is cushing’s syndrome?
A
- 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
13
Q
What is congenital adrenal hyperplasia?
A
- 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
14
Q
What is treatment for congenital adrenal hyperplasia?
A
- Give cortisol
- Not having cortisol is life-threatening
- by reinstating negative feedback, ACTH levels drop and reduce andronergic pathway
15
Q
What is addion’s disease?
A
- 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
16
Q
What does calcium regulation look like in body?
A
- 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
17
Q
What are the 3 main types of bone cells
A
- Osteoblasts
- Osteoclasts
- Osteocytes (which are absorbed osteoblasts)
18
Q
What are osteoblasts?
A
- 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
19
Q
What are osteoclasts?
A
- liberate ca/phosphate from bone aka breakdown bone
20
Q
What are osteocytes?
A
- Absorbed osteoblasts
21
Q
What are the osteocystic/osteoblastic membranes role in Ca regulation?
A
- 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
22
Q
What exists outside of calcified bone?
A
- Bone fluid exists between blasts and bone
23
Q
What is parathyroid hormone?
A
- peptide hormone synthesized by parathyroid glands
- 4 parathyroid glands embedded posteirorly in 4 lobes thyroid gland
24
Q
What cell scretes PTH?
A
Chief cells in parathyroid gland
25
Q
What is the main target of PTH?
A
- 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
26
Q
What happens with removal of parathyroid glands?
A
- Loss of ability to regulate Ca which untreated, will result in rapid death
- (just need to supplement with external Ca)
27
Q
What cells monitor Ca concentrations?
A
Chief cells
- When Ca levels decline in blood, chief cells increase output of PTH to restore Ca concentration
- Ca and PTH have inverse relationship
28
Q
What is the summary of sites of action of PTH?
A
- 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
29
Q
What is PTH’s effect on plasma calcium and phosphate?
A
Increase Ca, decrease phosphate
30
Q
What is pathway for formation of VIt D3?
A
- 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
31
Q
Summary of Vit D3?
Active form?
Principal sites of action?
Cellular mechanism of action?
A
- 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
32
Q
What is calcitonin? Where is it produced?
A
- 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
33
Q
SUmmary of calcitonin action?
A
- 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
34
Q
What is hypoparathyroidism
A
- 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
35
Q
What is hyperparathyroidism?
A
- 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
36
Q
What is rickets?
A
- Vita D3 deficiency (not eating enough/making enough)
- Decreased Ca, decreased Phosphate (can’t absorb)
- Bone:
- decrease mineralization
- deformities: wide epiphyses
- Muscle:
- tetany
