Parathyroid Hormone Metabolism Flashcards
Parathyroid Gland embryology?
derived from the 3rd an 4th branchial pouches that migrate
Parathyroid Hormone (PTH) is the main player in controlling what? 2
CA2+ and phosphate homeostasis in the body
What cells comprise the parathyroid glands? 2
chief cells- PTH
Oxyphil cells
PTH is packaged in cytoplasmic granules that contain what?
What is the half life once it is released?
proteases
Very short half-life (minutes)—once released
PTH feeds back to stimulate conversion of 25-hydroxycholecalciferol in the kidney to 1,25-dihydroxycholecaleciferol. Or in basic terms?
Calcitriol
Once PTH released—quickly degraded by what?
Normal calcemic state what is the percentage of circluating PTH?
Hypocalcemia PTH increases to?
Hypercalcemia PTH decreases to?
liver and kidney (within 2-4 minutes)
20%
33%
4%
The net effect of PTH on calcium and phophate is what?
an increase in the plasma calcium concentraation with no chang or decrease in the plasma phophate concentration
What controls the secretion of PTH?
Parathyroid cells have what kind of receptor?
CaR is also expressed in the kidney and Regulates what?
Hence hypercalcemia directly promotes what?
Ca2+
calcium-sensing receptor (CaR)
Ca2+ is the ligand
Regulates Ca2+ handling by the renal tubules
Hence hypercalcemia directly promotes excretion of Ca2+
Adequate/elevated Ca2+ levels block what?
Adequate intake blocks what?
Adequate levels maintain what? 2
Adequate/elevated Ca2+ levels block PTH from activating Calcitriol
Adequate intake blocks leaching Ca2+ from bones
Adequate levels maintain balanced renal absorption of Ca2+ and phosphate
PTH-Related Protein (PTHrP)
secreted by what? 2
What does this cause? 2
Less likely to stimulate what?
Does it increase Ca2 absorption from the intestnie?
Secreted by nonmetastatic solid tumors and some patients w/ non-Hodgkin lymphoma
Increases bone resorption and distal tubule Ca2+ reabsorption
Less likely to stimulate 1, 25-dihdroxy vitamin D production
Does not increase Ca2+ absorption from the intestines!
Calcitonin is secreted by what?
What is it stimulated by?
How does it decrease plasma Ca2 levels? 2
Peptide hormone secreted by the thyroid gland—parafollicular cells
High Ca2 levels
- Decreases absorptive activities osteoclasts
- Decreases formation of new osteoclasts
Calcium is partially absorbed where?
Filtration where?
Where is 99% of our calcium found?
Where is the rest of it found (active calcium)?
Involves partial absorption from the intestines
Filtration in the kidneys with 100-200mg excreted
99% remains in bone as: hydroxyapatite—Ca10(PO4)6(OH)2 (Serves as a reservoir)
1% in extracellular fluid/flows in and out of cells
of which 50% bound to albumin/50% ionized state (nonactve calcium
Where is most of the phosphate in the body found?
85% of the body’s phosphate is stored in bone
14-15% in the cells
What helps absorb calcium in intesine?
PTH stimulates calc absoprtion from where and release from where?
If Ca2 is too low what is secreted?
Vitamin D
absorption from kidneys and release frrom bones
PTH
more calcium in blood stream
Calcium’s Role in the Body
5
- Normal bone density
- Clotting cascade
- Muscle function: smooth, cardiac and skeletal
- Transmission of nerve signals
- Intracellular signaling of many cellular hormones
Ca2 and PO4 levels tend to be correlated how?
Important to note that Ca2+ and PO4- tend to be opposite
When one rises the other falls
Both necessary for normal bone density
- How is Vitamin D made in the skin?
- How is Vitamin D further metabolized?
- Where do we get intestinal absorption from?
- Where is Vit D stored and where is excess stored?
2
- Photoisomeriztion of provitamin D in the skin to vitamin D3(cholecalciferol)
- Binds to vitamin D binding proteins (DBP) and is further metabolized
- Intestinal absorption from the diet:
Fortified milk**
Fatty fish and cod-liver oil
Lesser extent eggs
Liver stores Vitamin D, excess stored in adipose tissue
Calcitriol causes Ca and phosphate levels do do what in the:
GI?
Bones?
Renal?
increased intestinal absorption of calcium
Bone reabsorption
Decreased renal Ca absorption
Increased phosphate absorption
Where is Cholecalciferol (vitamin D3) formed?
Where is it converted to 25-hydroxy vit D?
Whats the most active form of Vitamin D?
Formed in the skin
Converted to 25-hydroxy Vitamin D in liver, but prevented from over accumulating (vitamin stored in liver-months)
1,25-dihydroxycholecalciferol (calcitriol)
1,25-dihydroxycholecalciferol (calcitriol) is formed where?
This step of Vit D is stimulated by what?
Formed in the proximal tubules (kidney)
Most active form of vitamin D**
This step stimulated by parathyroid hormone (PTH)
Vitamin D Metabolism is closely coupled with what?
4
- w/ Ca2+ homeostasis,
- serum Ca2+ and
- phosphate levels and
- parathyroid hormone (PTH)
In hypocalcemia increased PTH increases the activity of what?
What does this result in?
(which would result in what?)
3
of alpha-1-hydroxylase in the kidney resulting in increased levels of calcitriol
- Increased ca bone reabsorption
- decreases phohate and calcium excretion in urine
- increase intestinal absotption
Vitamin D functions? 2
What must it be converted to and where?
What does calcitriol do to Ca2 and the kidneys?
1, Increases Ca2+ absorption from GI tract
2. Important in bone deposition & absorption
Must be converted in liver & kidneys to active metabolite (Calcitriol)
Calcitriol increases absorption of Ca2+ in kidneys
Calcitriol Concentration depends on what?
2
- Availability of calcidiol
2. Activity of renal enzyme alpha-1-hydroxylase
Activity of renal enzyme alpha-1-hydroxylase: regulated by?
3
- PTH
- Low serum level of phosphate
- Plasma calcitriol concentration:
Activity of the 24-hydroxylase gene is increased by calcitriol which inactivates it.
PTH reduces the gene activity—Which would do what?
increase calcitriol
Calcitriol binds to a vitamin D receptor where?
- In intestine
2. On parathyroid glands
Most important action of calcitriol?
Other effects:
3
Most important action:
- Promote enterocyte differentiation
- Promote intestinal absorption of Ca2+**
Other effects:
- Stimulate phosphate absorption
- Direct suppression of PTH at the level of the parathyroid glands
- Allows PTH-induced osteoclast activation
Calcitriol Activity on Parathyroids:
Parathyroids contain what kind of receptors?
Calcitriol binds to the receptors inhibiting what?
Parathyroids contain vitamin D receptors
Calcitriol binds to the receptors:
- Inhibits PTH synthesis
- Inhibits parathyroid-cell proliferation
Osteoblasts do what?
- Continually deposit bone even in adults
On the outer surfaces of bone and in bone cavities
Osteoclasts do what?
Continually absorb bone
Found in the bone matrix
In adults deposition and absorption are?
equal
Describe Bone remodeling.
What is the new matrix like compared to the old?
Bone adjusts its strength to stress applied on it
New matrix is tougher and less brittle then old matrix
Bone that is “stressed” has greater deposition of bone matrix. Why?
Osteoblastic activity is stimulated
The bone is stronger and more dense
Describe bone resorption?
What regulates this process?
How long does it take?
Osteoclasts remove mineral and matrix on trabecular and cortical bone
High local concentrations of Ca2+ may regulate this process
2 weeks
Describe bone reversal. 2 steps
How long does this take?
- Mononuclear cells appear on the bone surface
- They lay down a glycoprotein-rich matrix so the new osteoblasts can adhere
4-5 weeks
Describe bone formation
2
How long does this take?
- Waves of osteoblasts lay down bone until the resorbed bone is completely replaced
- When this phase is completed the surface is covered w/ flattened lining cells and there is a prolonged resting period
Up to 4 months
PTH effects on kidney?
2
- ↑ Ca resorption in the renal tubules
2. Kidneys convert Vit D to it’s active form
PTH effects on bone?
2
- ↑ osteoclast activity
2. Release Ca2+ and PO4-
PTH effects on GI tract?
1
- GI tract ↑ absorption of Ca2+, PO4-
