midterm physio deck 2 Flashcards
thyroid
thyroid develops from oral endoderm and travels down from foramen cecum
parathyroid development
inferior glands form from 3rd pharyngeal pouchsuperior glands form in 4th pharyngeal pouch, then detach and migrate inferiorly and medially
thyroid gland has no ________ but has many __________
glands; blood vessels
thyroid functional unit
follicle = filled w colloid (thyroglobulin) and lined by thyrocytes (follicular epithelium)
thyroid is the only endocrine gland to…
store hormone extracellularly in inactive form (thyroglobulin)
thyroglobulin iodination
2 tyrosines are iodinated and coupled to form thyroxine (t4)
thyroxine (thyroid hormone) synthesis
-thyroglobulin exocytosed into follicle-iodide transported into cell, oidized to iodine and released into follicle-1 or 2 iodine molecules are added to tyrosineson thyroglobulin (organification), catalyzed by thyroid peroxidase in the presence of hydrogen peroxidet3 = MIT + DIT (mono and di ioidothyronine)t4 = DIT +DITts/t4 are formed by oxidative coupling of 2 iodinated tyrosyls near each other — one donates and the other accpts iodotyrosyl; the acceptor remains attached to thyroglobulint3 is active
thyroid parafollicular cells (c cells)
next to follicles; neural crest originsecrete calcitonin
can you live without parathyroid glands?
absence is fatalyou need parathyroid
parathyroid gland cell types and their jobs
chief cells make PTHoxyphils are eosinophilic due to lots of mitochondria (job unknown)
PTH
stimulates bone resorption to increase serum caalso retains ca in the kidney and gutstored by chief cells and released when ca is low–works through its receptor on osteoblasts to make RANKL –> this stimulates osteoclasts formation and increased absorption in intestines and kidney
normal range of serum calcium
8.5-10.250% is free and 50% is bound to protein
vitD and PTH roles in ca regulation
vit D increases intestinal absorptionPTH causes bone resorption, increases vit D activation, and increases renal Ca absorption
how are changed in levels of blood Ca sensed?
detected by the calcium sensing receptor (CaSR) on the chief cells
Parathyroid Hormone Paradox
injectable PTH stimulates bone formationcontinuous levels of PTH leads to bone loss while intermittent short bursts can be anabolic for boneintermittent PTH favors osteoblasts; continuous favors osteoclasts
how osteoblasts influence osteoclasts
PTH causes osteoblasts to produce RANKLRANKL binds to RANK on osteoclasts and activates them
OPG
osteoprotegerinOPG binds RANKL and inhibits osteoclast activation (in absence of PTH)opg increases in response to estrogen (inhibits osteoclasts)opg decreases in response to PTH
RANKL
binds rank on osteoclastsmade by osteoblasts in response to PTHdecreased by estrogen
denosumab
antiresorptive drug that is sn antibody against RANKLused to treat post-menopausal osteoporosis; increases BMD
estrogen and testosterone have what effect on bones?
stimulate bone formation! (decrease in osteoclasts)
hyperparathyroidism causes
excess PTH –> osteoporosis
how does lack of Ca cause convulsions
NMJ is more permeable to ions and readily depolarizes –> convulsions/tetany
1-hydroxylase
forms bioactive vitamin DPTH increases 1-hydroxylase levels
ca absorption in the intestine is directly dependent on_______ and indirectly on ________
directly on bioactive vit Dindirectly on PTH which forms the vit D
ca and phosphate: bone/intestine vs kidneys
in bone/intestine phosphate and go same directionbut in kidney, ca and phosphate go opposite directtions(PTH retains Ca and excretes phosphate)
where is ca [ ] higher :1) bone or plasma?2) extra cellular or intracellular
1 - plasma; hydroxyapatite has los solubility2 - extracellular; gradient allows it to act as a diffusible messenger to bind regulatory proteins
CaM
calmodulinsca binding proteins that transduce ca signalslocated in cytoplasm, membranes and organelles; also aids in mitotic spindleundergo transformational change when bound to ca ; can bind up to 4 cahigh affinity and specificity
calcitriol
active vit D3 (1,25 - OH2D3)
vit D biosynthesis
cholesterol –> 7-dehydrocholesterolphotochemically converted to pre-vitamin D3isomerizes to cholecalciferol (D3)opens B ring to form a sterolhydroxylation at 25 (liver) by 25 hydroxylase–> 25-OHD3hydroxylation at 1 (kidney) by 1-hydroxylase–> 1,25-OH2D3
1-hydroxylase
only in the kidney (inner mito membrane)so the kidney is the only site 1,25 vit D can be madephosphate depletion activates 1-hydroxylationhyperphosphatemia inhibits itinduced by hypocalcemia/PTH
can you make 1,25-OH2D3 after renal failure or bilateral nephrectomy?
no; kindeys are the only place where 1-hydroxylase is
how does decline in estrogen affect vit D?
–> lowers 1 hydroxylaseless 1,25 OH2D3–> post menopausal osteoporosis
24-hydroxylase
24 hydroxylase is in the kidney24 hydroxylation results in 24,25 OH2D3 which is inactiveinduced in hypercalcemia; suppressed by hypocalcemia
PTH has no direct effect on
intestine
blood ca and calcitonin are ____ related
directly
osteoporosis vs osteopenia
osteoporosis = BMD more than 2.5 std dev below meanosteopenia = between -1 and -2.5
osteoporosis vs osteomalacia
OP = bone volume is reduced but mineralization is normalOM = abnormal mineralization
ca and vit D supplements can cause
constipation
risk of estrogen therapy for osteoporosis
breast cancer, thromboembolism, stroke. MI
drug of choice for bad osteoporosis?
bisphosphonatesalendronate or risedronatenot absorbed well - so take w water and remain upright for 30 min
risk of alendronate
esophagitis, esophageal ulcer
SERMs
selective estrogen receptor modulatorsRALOXIFENE - used for osteoporosis
less BMD improvement than bisphosphonates**reduces MI and cancer risk though!!
who should not use SERMs?
pregnant womenit is teratogenic!!!
salmon calcitonin
analgesic effect for osteoprosis fractures
pattern of ca and phos in PTH mediated disease
ca increases and phos decreases or vv
pattern of ca and phos in vitD mediated disease
ca and phos go in same direction
stones bones abd groans and psych moans
hypercalcemia
