Parathyroid, regulation of calcium

Question 1

Good indicators of calcium availability

Answer 1

Albumin levels (Ca binds to calcium)

Question 2

Net uptake of calcium in humans

Answer 2

200 mg/day

Question 3

Number of parathyroid glands in humans

Answer 3

4

Question 4

Typical calcium levels

Answer 4

2.6 - 2.6 mM
8.8 - 10.3 gm/100mL
(tightly regulated)

Question 5

Chief cells (parathyroid gland) synthesize _________

Answer 5

PTH

Question 6

Chief cells (gastric) release __________

Answer 6

Pepsinogen, gastric lipase

Question 7

Chief cells (gastric) release __________

Answer 7

Pepsinogen, gastric lipase

Question 8

Biologically active fragment in PTH

Answer 8

N-terminal fragment 1-34. Binds to PTH receptor

Question 9

Cells present in parathyroid

Answer 9

Chief cells, oxyphil cells (no known function)

Question 10

Biologically inactive fragment in PTH

Answer 10

C-terminal fragment 35-84 (cleaved quickly)

Question 11

PTHrP function

Answer 11

Mimics action of PTH in bone and kidney

NOT a regulator of plasma Ca2+

Question 12

Do tumors produce PTHrP?

Answer 12

Yes, resulting in hypercalcemia

Question 13

PTH receptors

Answer 13

PTH 1R = primary receptor. Located in osteoblasts and kidney. G-coupled. Binds N-terminal 1-34 and PTHrP
PTH 2R = secondary. Binds N-terminal 1-34, but does NOT bind PTHrP

Question 14

Effect of PTH

Answer 14

Increase serum Ca2+, decrease plasma Pi

Question 15

These express PTH receptors

Answer 15

Osteoblasts

Question 16

Do not express PTH receptors

Answer 16

Osteoclasts

Question 17

Bone formation and mineralization

Answer 17

Osteoblasts

Question 18

Bone reabsorption

Answer 18

Osteoclasts

Question 19

Osteocytes

Answer 19

Relatively inert; may exert control over osteoblasts/osteoclasts. Also able to destroy bone through rapid process

Question 20

PTH stimulates _________ in osteoblasts

Answer 20

M-CSF (macrophage - colony stimulating factor)

Question 21

Mediates the differentiation of osteoclast precursors

Answer 21

M-CSF

Question 22

_____ stimulates RANK ligand

Answer 22

PTH

Question 23

Function of RANK ligand

Answer 23

Osteoclast differentiation

Question 24

Antagonist of RANKL

Answer 24

Osteoprotegerin (OPG)

Question 25

Stimulator of OPG

Answer 25

Estrogen (promotes bone health, prevents osteoporosis)

Question 26

Inhibitor of OPG

Answer 26

Cortisol, other glucosteroids

Question 27

Inhibitor of OPG

Answer 27

Cortisol, other glucosteroids

Question 28

RANKL stands for

Answer 28

Receptor activator of nuclear factor kappa-B ligand

Question 29

PTH action in the kidney

Answer 29

``` Stimulates CYP1alpha (converts active form of Vitamin D3) Stimulates Ca2+ channel insertion in apical membrane of distal tubule ```

Question 30

PTH action in the kidney

Answer 30

1) Stimulates CYP1alpha, which encodes 1alpha-hydroxylase (converts active form of Vitamin D3) 2) Stimulates Ca2+ channel insertion in apical membrane of distal tubule 3) Reduces phosphate reabsorption in both tubules, but especially in the proximal tubule

Question 31

Site of action of PTH in kidney

Answer 31

Distal nephron, TAL of Loop of Henle. Distal and proximal tubules of the kidney

Question 32

Site of action of PTH in kidney

Answer 32

Distal nephron, TAL of Loop of Henle. Distal and proximal tubules of the kidney

Question 33

PTH regulation sites

Answer 33

Chief cells, kidney tubules, and C cells

Question 34

C cell function

Answer 34

Secretion of calcitonin

Question 35

CaSR role

Answer 35

Inhibits PTH synthesis at promoter level, and stimulates degradation of preformed PTH

Question 36

Vitamin D

Answer 36

Binds nuclear receptor - VDR Inhibits PTH synthesis at promoter level (direct) Stimulates CaSR gene transcription (indirect regulation of PTH)

Question 37

CaSR role

Answer 37

``` Binds ionized (free) Ca2+ Inhibits PTH synthesis at promoter level, and stimulates degradation of preformed PTH ```

Question 38

Vitamin D function

Answer 38

Binds nuclear receptor - VDR Inhibits PTH synthesis at promoter level (direct) Stimulates CaSR gene transcription (indirect regulation of PTH)

Question 39

Vitamin D function (calcitriol)

Answer 39

Binds nuclear receptor - VDR Inhibits PTH synthesis at promoter level (direct) Stimulates CaSR gene transcription (indirect regulation of PTH)

Question 40

Vitamin D function (calcitriol)

Answer 40

Binds nuclear receptor - VDR Inhibits PTH synthesis at promoter level (direct) Stimulates CaSR gene transcription (indirect regulation of PTH)

Question 41

Vitamin D renal function (calcitriol)

Answer 41

Binds nuclear receptor - VDR Inhibits PTH synthesis at promoter level (direct) Stimulates CaSR gene transcription (indirect regulation of PTH)

Question 42

Vitamin D bone function

Answer 42

Direct: increases Ca2+ mobilization from bone; increases osteoclast activity Indirect: increases plasma Ca2+, promoting bone mineralization

Question 43

Vitamin D intestinal function

Answer 43

Increases transcellular Ca2+ absorption in duodenum; stimulates Pi reabsorption from small intestine

Question 44

Vitamin D intestinal function

Answer 44

Increases transcellular Ca2+ absorption in duodenum; stimulates Pi reabsorption from small intestine

Question 45

Common cause of hyperphospotemia

Answer 45

Traumatic crush injury

Question 46

Binds/transports Ca2+ in intestinal epithelial cells

Answer 46

Calbindin 9k

Question 47

Binds/transports Ca2+ in intestinal epithelial cells

Answer 47

Calbindin 9k

Question 48

Reduced bone density - mainly trabecular bone

Answer 48

Osteoporosis

Question 49

Hyperplasia carcinoma of parathyroid gland

Answer 49

Hyperparathyroidism

Question 50

Hypocalcemic tetany; Chvostek sign observed

Answer 50

Hypoparathryoidism

Question 51

Unmineralized bone due to Vitamin D deficiency

Answer 51

Rickets (children) | Osteomalacia (adults)

Question 52

Unmineralized bone due to Vitamin D deficiency

Answer 52

Rickets (children) | Osteomalacia (adults)

Question 53

Uses of calcitonin

Answer 53

Treatment of Paget disease | Function: inhibits osteoclast reabsorption and slows bone turnover (net → slows bone turnover)