Endocrinology 6- Calcium and Phosphate Flashcards
Symptoms of hypocalceumia
muscle failure, tetany, convulsions, death
Symptoms of hypercalcemia
renal dysfunction, calcification of soft tissues, muscle weakness, coma
hyperphosphatemia and reason it often happens
usually result of severe crush injury, 10x more pi than Ca in soft tissue
What affects free calcium (ionized) in blood
changes in albumin and changes in pH
The 3 regulators of calcium, and which are the two main ones?
parathyroid hormone (PTH), vitamin D are the main two, calcitonin which is a thyroid hormone is potentially not important for humans
What cells in parathyroid gland synthesize PTH
chief cells
What kind of hormone is parathyroid hormone
peptide hormone
What is parathyroid hormone related peptide
You typically do not find in circulation but has paracrine effects in cells that make it - mimics action of PTH in bone and kidney if it gets into blood, but it usually isn’t a maor regulator of calcium because it isn’t in the blood. It can be made by tumors, however, and can lead to effect that seems like hyperparathyroidism. Sequences of PTH and PTHrP are very similar.
Both PTH and PTHrP bind to what receptor
PTH1
Does PTHrP bind to PTH2 receptor
Nno
Where is PTH1R
Osteoblasts, kidney, GPCR (Gs and Gq)
Net effects of PTH on bone and kidney
Increase plasma calcium, decrease plasma phosphate
Where is 99% of body calcium
bone
Osteoblasts
bone formation and mineralization, high expression of PTH recetpors, derived from mesenchymal stem cells
Osteoclasts
bone resorption, derived from hematopoietic stem cells, no PTH recetpors
Osteocytes
Make up bone matrix, terminally differentiated osteoblasts
Is PTH’s affect on bone resorption direct or indirect
indirect
How does PTH stimulate breakdown of bone?
- stimulates macrophate colony stimulating factor - stimulates hematopoietic stem cells to make more osteoclast precursors
- Stimulates RANK ligand - released from osteoblasts and important for maturation of osteoclasts
- Osteoblasts export calcium and phosphate into Extracellular space for bone mineralization
- RANK ligand binds to receptor, causes bone resorption.
How can we protect bones from too much resorption
Osteoprotegrin is also released and binds up RANK ligand and prevents it from being stimulated, which prevents bones from being broken down. After menopause this protective effects no longer exists. Cortisol also inhibits osteoprotegrin which can lead tobones breaking down in stress
How does PTH target kidney
Stimulates calcium channel insertion into apical membrane of distal tubule into kidney, leads to calcium reabsorption
* happens in TAL
Stimulates CYP1a - which encodes 1-a-hydroxylase which converts active form of Vitamin D
What is the enzyme that converts vit D to be active
1-a hydroxylase
How is PTH regulated
Regulated by calcium
Low calcium - lots of PTH released
High calcium - not a lot of PTH released
Sensing of calcium is done by chief cells in parathyroid gland
What is the receptor on PTH chief cells, kidney tubules, and C cells that sense calcium
calcium sensing receptor (CaSR)
What does vitamin D bind
Vitamin D receptor (nuclear receptor)
how does vitamin D regulate PTH
inhibits PTS synthesis at promoter level, stimulates CaSR gene transcription (indirect regulation of PTH)
What is the other name for vitamin D
cholecalciferol
What does vitamin D require to be active
light
hat organs does vitamin D target
intestines, kidneys, bone
how does vitamin D affect bone
mobilize calcium from bone because osteoblasts and osteoclasts have vitamin D receptors - vitamin D stimulates osteoclast proliferation and differentation, and vitamin D increases plasma calcium which promotes bone minearlization
How does vitamin D target intestine
increses transcellular Ca absorption in duodenum and stimulates Pi reabsorption from small intestine - opposite of PTH
Osteoporosis
reduced bone density, trabecular bone and osteocytes are not going to be maintained properly so bone density goes down. There is a genetic component but something like menopause would also play a role (loss of osteoprotegrin), as well as glucocorticoids. Txt is estrogens, calcitonin, bisphosphates. If you hve vitamin D and bisphosphates you might get increased risk in fractures
PTH overproduction
primary - tumors of parathyroid gland, leads to hypercalcemia and kidney stones. Can have a secondary problem due to chronic renal failure – kidney cannot respond to PTH, cannot have 1-a hydroxylase enzyme so no active vitamin D –> lose negative feedback signal, get excess PTh
Hypoparathyroidism
Hypocalcemic tetany, facial muscles will twitch in response to tapping of facial nerve (sign of this tetany)
Chvostek sign
twitching of facial muscles in response to tapping of facial nerve
Rickets and osteomalacia
Vitamin D deficiency, bowing of long bones, decreased bone strength
Pseudohypoparathyroidism
Congenital defect in G protein that associates with PTHR1, so hormones that also use this g protein but aren’t PTH will also be affected (ex. PTH, TSH, LH, and FSH)
Clinical signs are low calcium, high phosphate, elevated PTH, and short stature
Calcitonin
Inhibits calciumr resorption from bone? Maybe but physiological importance is unclear, because if taking thyroid glands out but parathyroids remain, the nrmal physiological range of calcium is unaltered. With very high C cell from tumors, which would produce a lot of calcitonin, calcium levels are also not affected
how is calcitonin used therapeutically
to inhibit osteoclast resoprtion and slow burn turnover as a treatment for paget disease - however the rapid downregulation of calcitonin causes the antiosteoclastic ctions of calcitonin to diminish in a few hours, so this is not a very effective txt
