Endocrinology 6- Calcium and Phosphate

Question 1

Symptoms of hypocalceumia

Answer 1

muscle failure, tetany, convulsions, death

Question 2

Symptoms of hypercalcemia

Answer 2

renal dysfunction, calcification of soft tissues, muscle weakness, coma

Question 3

hyperphosphatemia and reason it often happens

Answer 3

usually result of severe crush injury, 10x more pi than Ca in soft tissue

Question 4

What affects free calcium (ionized) in blood

Answer 4

changes in albumin and changes in pH

Question 5

The 3 regulators of calcium, and which are the two main ones?

Answer 5

parathyroid hormone (PTH), vitamin D are the main two, calcitonin which is a thyroid hormone is potentially not important for humans

Question 6

What cells in parathyroid gland synthesize PTH

Answer 6

chief cells

Question 7

What kind of hormone is parathyroid hormone

Answer 7

peptide hormone

Question 8

What is parathyroid hormone related peptide

Answer 8

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.

Question 9

Both PTH and PTHrP bind to what receptor

Answer 9

PTH1

Question 10

Does PTHrP bind to PTH2 receptor

Answer 10

Nno

Question 11

Where is PTH1R

Answer 11

Osteoblasts, kidney, GPCR (Gs and Gq)

Question 12

Net effects of PTH on bone and kidney

Answer 12

Increase plasma calcium, decrease plasma phosphate

Question 13

Where is 99% of body calcium

Answer 13

bone

Question 14

Osteoblasts

Answer 14

bone formation and mineralization, high expression of PTH recetpors, derived from mesenchymal stem cells

Question 15

Osteoclasts

Answer 15

bone resorption, derived from hematopoietic stem cells, no PTH recetpors

Question 16

Osteocytes

Answer 16

Make up bone matrix, terminally differentiated osteoblasts

Question 17

Is PTH’s affect on bone resorption direct or indirect

Answer 17

indirect

Question 18

How does PTH stimulate breakdown of bone?

Answer 18

1. stimulates macrophate colony stimulating factor - stimulates hematopoietic stem cells to make more osteoclast precursors
2. Stimulates RANK ligand - released from osteoblasts and important for maturation of osteoclasts
3. Osteoblasts export calcium and phosphate into Extracellular space for bone mineralization
4. RANK ligand binds to receptor, causes bone resorption.

Question 19

How can we protect bones from too much resorption

Answer 19

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

Question 20

How does PTH target kidney

Answer 20

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

Question 21

What is the enzyme that converts vit D to be active

Answer 21

1-a hydroxylase

Question 22

How is PTH regulated

Answer 22

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

Question 23

What is the receptor on PTH chief cells, kidney tubules, and C cells that sense calcium

Answer 23

calcium sensing receptor (CaSR)

Question 24

What does vitamin D bind

Answer 24

Vitamin D receptor (nuclear receptor)

Question 25

how does vitamin D regulate PTH

Answer 25

inhibits PTS synthesis at promoter level, stimulates CaSR gene transcription (indirect regulation of PTH)

Question 26

What is the other name for vitamin D

Answer 26

cholecalciferol

Question 27

What does vitamin D require to be active

Answer 27

light

Question 28

hat organs does vitamin D target

Answer 28

intestines, kidneys, bone

Question 29

how does vitamin D affect bone

Answer 29

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

Question 30

How does vitamin D target intestine

Answer 30

increses transcellular Ca absorption in duodenum and stimulates Pi reabsorption from small intestine - opposite of PTH

Question 31

Osteoporosis

Answer 31

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

Question 32

PTH overproduction

Answer 32

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

Question 33

Hypoparathyroidism

Answer 33

Hypocalcemic tetany, facial muscles will twitch in response to tapping of facial nerve (sign of this tetany)

Question 34

Chvostek sign

Answer 34

twitching of facial muscles in response to tapping of facial nerve

Question 35

Rickets and osteomalacia

Answer 35

Vitamin D deficiency, bowing of long bones, decreased bone strength

Question 36

Pseudohypoparathyroidism

Answer 36

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

Question 37

Calcitonin

Answer 37

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

Question 38

how is calcitonin used therapeutically

Answer 38

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