What 3 hormones function in calcium regulation and where are they produced?
1. parathyroid hormone (PTH): secreted by parathyroid glands
2. vitamin D3: production involved a number of steps in skin, liver, and kidney
3. calcitonin (CT) secreted by C cells of the thyroid
What are the 3 main sites of action of PTH, vitamin D3, and calcitonin? What effects do they have on each site?
1. bone: major storage site of calcium (and phosphate). largest storage depot for calcium in the body. PTH and vitamin D3 stimulate osteoblasts directly which then stimulate osteoclasts through RANKL and M-CSF to stimulate resorption and increase blood calcium. calcitonin inhibits osteoclast activity directly
3. GI tract: site of absorption and excretion of calcium and phosphate. vitamin D3 causes increase in calcium absorption
2. kidney: site of excretion of calcium and phosphate. PTH and vitamin D inhibit excretion of calcium by kidneys. calcitonin acts on kidney to control excretion of calcium
Calcium concentration in blood is determined by what two processes (not hormones)?
1. input output balance. dietary intake of calcium vs excretion in urine and feces. is controlled by vitamin D3, PTH, calcitonin
2. binding of ionized calcium to plasma proteins. most processes that are calcium dependent are affected ONLY by FREE calcium. binding of calcium is pH dependent. the more alkaline the blood, the greater binding of calcium to proteins (mostly albumin). more alkaline blood=body thinks it needs calcium
For what proceses is calcium regulation needed?
calcium regulation is regulated to insure normal:
1. excitation/contraction coupling of muscle
2. secretion and release of neurotransmitters (triggers NT release in presynaptic neurons)
3. membrane excitability (hypocalcemia results in hyperexcitability)
4. regulation of enzyme activity. Ca2+ is an important second messengery
5. bone formation requires deposition of calcium salts in the organic bone matrix
For what processes is phosphate regulation important?
1. role in metabolism (many intermediates are phosphorylated)
3. phophate levels modulate enzyme activity
4. important constiuent of bone (predominant storage site of phosphate)
True or false: Physiological controls tend to cause [Ca2+ and [PO42-] to vary inversely to minimize salt deposition (is good in bone, bad inother tissues)
What class of hormone is PTH (peptide, steroid, etc)? What causes its release? Where is it released from? What are its results? What organs remove it from blood? What effect does it have on serium phosphate level?
1. peptide hormone
2. decreased plasma [Ca2+] causes PTH release into blood
3. is released from chief cells in the parathyroid gland
4. stimulates Ca2+ release through actions on osteoblasts which then stimulate osteoclast activity. increases renal reabsorption of calcium. increases production of vitamin D3 by stimulating proximal tubule 1-hydroxylase activity. this enzyme catalyzes active form of vit D (D3) which acts on gut to increase Ca2+ absorption. has rapid effect (on order of minutes) on kidey and slower (many hours) effects on bone and formation of vitamin D3
5. liver and kidney. has half life of 2-4 minutes
6. it decreases serum phosphate level. remember we do not want hydroxyapaite crystals forming in our blood!
note: urine exretion of Ca2+ initially increases buth then decreases because filtered load of Ca2+ rises (can only reabsorb so much Ca2+). urine hydroxyproline increases because of increaseed bone resorption-collagen type 1 breakdown!
PTH also decreases osteoblast formation
What are the effects of PTH as it pertains to cAMP production in proximal and distal convoluted tubules?
proximal and distal convoluted tubules both respond to PTH by increasing cAMP production but consequences differ. in the proximal convoluted tubule, increased cAMP decreases reasborption of phosphate. in the distal convoluted tubule, increased cAMP increases reabsorption of Ca2+
How does PTH stimulate Vitamin D3 production?
it sitmulates proximal tubule 1-hydroxylase activity which catalyzes the formation of Vitamin D3 which then acts on gut to increase Ca2+ absorption. through acting on GI tract, vitamin D3 contributes to long-term regulatino of plasma Ca2+
What is the secretory gland, secretory cells, chemical class (steroid, protein), stimulus for relase, transport in blood, removal from blood, and mechanism of action of Vitamin D3?
1. secretory gland: kidney
2. made and released by proximal cells of kidney (1-hydroxylase)
3. steroid hormone
4. stimulus for release: increase PTH and decreased plasma [Pi]
5. bound to plasma proteins in blood
6. mechanism of action: enters nucleus of cells in GI tract and alters transcription resulting in increased synthesis of calbindin-Ca2+ transporter
True or false: vitamin D is a derivative of cholesterol.
Discuss the 3 sites of Vitamin D synthesis in the body. Where are the active forms synthesized? What are names of the two forms made in the body?
1. D3 synthesized in skin in the presence of sunlight
2. 25-(OH)-vitamin D3 (calcidol) is formed in the liver
3. active form 1, 25, (OH)2 (calcitrol) is formed in proximal cells of kidney.
control of formation of calcitrol is primarly at the final hydroxylation step which is controlled by PTH and decreased plasma Pi
Discuss how Ca2+ is transported in enterocytes. Be sure to include implication of calbindin.
1. Ca2+ enters passively through enterocyte down electrochemical gradient through a membrane bond calcium channel
2. once inside the cell, Ca2+ binds to the transport protein calbindin (synthesis increased by vitamin D3)
3. some of intracelluar Ca2+ is loaded into vesicles which are exocytosed into blood
4. an ATP powered pump moves Ca2+ out of the enterocyte and into blood
6. a Na+-Ca2+ counter-transporter also moves Ca2+ out of the enterocyte
True or false: Vit D3 also acts on kidneys to limit Ca2+ excretion and upon bone to liberate Ca2+ and phophate.
True. however, these effects are much less important than its effects in the intestine
What class of hormone is calcitonin (peptide, steroid, etc.)? Where is it relased from? What stimulates its release? How is it transported in blood? Removed from blood? What is its mechanism of action? What is the result? How important is calcitonin in Ca2+ homeostasis?
1. peptide hormone
2. released from C-cells (parafollicular cells) of the thyroid gland
3. increased plasma [Ca2+] stimulates its release
4. transported in solution of blood (soluble)
5. binds to membrane receptors that activates secondary messenger systems that alter enzyme activity
6. result is decrease in plama Ca2+ concentration
7. calcitonin is not essential for Ca2+ homeostasis and is not essential for life
What are the effects of calcitonin on bone and kidney?
bone: acts in opposition of PTH. calcitonin inhibits osteocyte osteolysis and reduced osteoclast activty. thus, an important role of calcitonin is to preserve bone mass by inhibiting bone resorption
kidneys: decrease Ca2+ excretion, increase Pi excretion, increase Vitamin D production which act on intestines to increase Ca2+ and Pi absorption
***Note: effects of calcitonin on kidneys are real but of minimal significance
1. There is an a. inverse. or b. direct relationship btwn PTH level and [Ca2+]
2. There is an a. inverse or b. direct relationship btwn Calcitonin level and Ca2+
1. inverse rship btwn PTH and Ca2+ level
2. direct rship btwn Calcitonin and Ca2+ level