Parathyroid Flashcards
What does the pararhyroid gland do?
Produce parathyroid hormone (PTH), which acts to maintain optimal concentrations of calcium in the blood and interstitial fluid
What are the two cell types found in the parathyroid?
Oxyphil & Chief cells
What is the make-up of the parathyroid gland?
four glands embedded in the posterior thyroid
Encased in a thin capsule which invaginates creating poorly defined lobules
Cells are formed into cords/clusters surrounded by reticular fibers, blood vessels, lymphatics and nerves
What is the cellular make-up of parathyroid chief cells and their function?
Small, pale, cells that are the major functional cells
contain dense granules containing parathyroid hormone (PTH) that is released by exocytosis, large round nucleus with a small amount of clear cytoplasm
What is the cellular make-up of parathyroid oxyphil cells and their function?
Round large cells found singly or in clusters with a acidophillic cytoplasm, small nucleus and a large amount of cytoplasm containing numerous mitochondria, Do not appear to secrete hormone
What is the distribution of chief cells in the parathyroid gland?
smaller and more numerous, distributed throughout the glands and are the principal cells in the parathyroid glands
What does PTH do?
secreted in response to low blood calcium levels. PTH indirectly promotes osteoclast proliferation and increases their activity of absorption of bone tissue to increase blood calcium levels, increase absorption of calcium from food in intestines, conservation in the kidney, conversion of 25 OH vit D3 to 1,25-OH D3
What does calcitonin do?
increased blood calcium leads to increased release of calcitonin, acts rapidly to reduce plasma calcium levels
By what mechanisms are Ca levels regulated? PO4?
absorption (intestine), reabsorption/secretion (Bone), excretion (kidney); PO4 linked to Ca homeostasis
How is intracellular Ca regulated?
active pumping of Ca to the exterior of the Cell via CaATPase and NCX, active pumping of Ca into ER and mitochondria via CaATPase (ER) and Ca pump (Mit), and sequestered by binding proteins (or binding to other molecules in cellular processes)
What are the 2 primary targets of PTH?
kidney and bone
How is PTH stored? released? half life?
as precurosor in secretory vessicles, cleaved to active form just prior to release, PTH is N-terminus portion; 4 min 1/2 life
How is PTH response to Ca changed in people with FHH
familial hypocalciuric hypercalcemia; [Ca] must raise to higher levels before it will inhibit; normal PTH but high Ca
What receptor do chief cells utilize for Ca regulation? What intracellular relay mechanism is utilized if Ca binds?
G=protein calcium receptor (CaSR); Ca binding stimulate PLC via Gq, PIP2->IP3 and DAG, Dag activates PKC, IP3 relases Ca from ER; activated receptor inhibits adenylyl cyclase (low cAMP), both prevents exocytosis of PTH vessicles
What happens intracellularly if low [Ca]?
CaSR not activated, adenylyl cyclase gets activated, increase cAMP and triggers exocytosisof PTH vessicles
How does PTH effect the intestines?
by increasing conversion of inactive 25-OHD3 to active 1,25-OHD3 which increases Ca absorption
how does the PTH affect of Ca in the kidney also affect PO4?
increased Ca reabsorption causes a decrease in Po4 reabsorption
By what mechanism does PTH affect osteoblasts and osteoclasts?
PTH binding to receptors on osteoblast precursors to increase the production of macrophage stimulating hormone (M-CSF) and RANK (receptor activator of nuclear factor kB); M-CSF and RANK stimulate osteoclast production, RANK stimulates activity of mature osteoclasts; PTH also decreases OPG production (osteoprotegrin) which blocks RANK and RANK ligand interaction
What regulates the activity of 1-a-25-hydroxylase in the kidney?
PTH, phosphate and calcium; decrease in Ca and PO4 stimulate the activity of enzyme, 1,25-OHD3 regulates synthesis by decreasing transcription of 1-a-25hydroxylase
how does 1,25-OHD3 do in the bone?
works with PTH cooperatively to stimulate bone resorption by osteoclasts
What are the two methods of absorption of Ca in the intestinal cell? Which is D3 dependent? Where do they occur?
passive paracellular absorption (throughout entire intestine) and active transcellular, only in the duodenum is D3 dependent
How does D3 effect absorption of Ca specifically?
increasing expression of luminal Ca channels, calbindins and transporters
What is the exact mechanism of the transcellular pathway of Ca?
Ca enters throu Ca channels on luminal side, binds to calbindin and diffuses to basolateral membrane, CA extruded via NCATPase and CaHX to interstitial space
How does D3 effect gene expression? why is 1,25-OHD3 the active hormone?
D3 and 1,25-OHD3bind to receptors as heterodimers with retinoid X receptor at VDRE (hormone response element); higher affinity for receptor than D3
