L75: Parathyroid & Ca regulation

Question 1

Osteoprotegerin (OPG)

Answer 1

decoy for RANKL. It binds RANKL.

Question 2

Osteoprotegerin

Answer 2

?

Question 3

RANKL

Answer 3

?

Question 4

M-CSF

Answer 4

?

Question 5

What is the normal range of calcium (normal)?

Answer 5

2.2-2.5mM (tightly regulated)

Question 6

Albumin levels

Answer 6

good indicator of free Ca2+ availability

Question 7

2 regulators of Ca2+

Answer 7

Vitamin D PTH

Question 8

What cells secrete PTH

Answer 8

Chief cells

Question 9

These cells increase with age and chronic kidney disease. No known function.

Answer 9

Oxyphil cells

Question 10

PTHrP

Answer 10

?

Question 11

PTH1R

Answer 11

?

Question 12

PTH2R

Answer 12

?

Question 13

PTH targets

Answer 13

bone and kidney

Question 14

Net effect of PTH

Answer 14

increase plasma Ca, decrease plasma Pi

Question 15

Nucleation

Answer 15

Process of mineralizing/hardening bone…via osteoblasts

Question 16

PTH receptors are located on osteoblasts or osteoclasts?

Answer 16

Osteoblasts

Question 17

PTH stimulates osteoblasts to make

Answer 17

M-CSF. Causes stem cells to differentiate into osteoclasts

Question 18

What ligand activates mature osteoclasts?

Answer 18

RANKL

Question 19

What makes RANKL?

Answer 19

Osteoblasts

Question 20

What does cortisol do to OPG?

Answer 20

Inhibits it. This allows excess RANKL to stimulate osteoclasts, making more bone breakdown than normal.

Question 21

2 effects of PTH on kidney

Answer 21

?

Question 22

Calcium sensing receptor

Answer 22

?

Question 23

Where is CaSR located?

Answer 23

Kidney, Chief cells, C-cells

Question 24

Direct and indirect actions of CaSR

Answer 24

?

Question 25

Direct and indirect actions of 1,25 Vitamin D

Answer 25

?

Question 26

Does D3 have a high affinity for vitamin D receptor?

Answer 26

No

Question 27

3 targets of VitD

Answer 27

Bone gut kidney

Question 28

Calbindin

Answer 28

?

Question 29

Primary vs. secondary hyperparathyroidism

Answer 29

?

Question 30

Chvostek sign

Answer 30

Twitching of facial muscles in response to tapping CNVII

Question 31

Rickets/Osteomalacia

Answer 31

softening of bone (not due to density but mineralization problems)….osteoblasts are not mineralizing bone…

Question 32

Pseudohypoparathyroidism

Answer 32

Genetic defect in GPCR that associates with PTHR1…associates broadly with PTH, TSH, LH, and FSH….

Question 33

Normal phosphate range

Answer 33

0.8-1.45mM

Question 34

Urinary hydroxyproline is indicative of

Answer 34

enhanced bone resorption

Question 35

Paget disease

Answer 35

localized areas of bone resorption. Causes reactive sclerosis. Treatment: calcitonin

Question 36

Calcitonin used to treat

Answer 36

Paget’s disease. Not long-term because of escape phenomenon.

Question 37

Does PTHrP bind PTH1R or PTH2R?

Answer 37

PTH1R (found in osteoblasts and kidney)

Question 38

Does PTH bind osteoclasts?

Answer 38

No. There are 2 indirect effects of PTH:

1. PTH binds osteoblasts–>secrete RANKL–> stimulates maturation of osteoclasts
2. PTH binds osteoblatss –> secretes M-CSF –> formation of osteoclast differentiation from stem cells

Question 39

What are osteocytes?

Answer 39

Terminally differentiated osteoBLASTS resident in bone matrix

Question 40

What cells export Ca2+ and Pi into the EC for bone mineralization?

Answer 40

OsteoBLASTS

Question 41

What does estrogen do to OPG?

Answer 41

Stimulates OPG, thus decreasing bone resorption

Question 42

What does cortisol do to OPG?

Answer 42

It suppresses the synthesis of OPG, thus promoting RANKL-mediated bone resorption via osteoclast activity

Question 43

What gene encodes for 1-alpha-Hydroxylase?

Answer 43

CYP1-alpha gene

Question 44

To be continued

Answer 44

handout page 36 endo