Calcium and Phosphate Homeostasis

Question 1

Organic Mineral of Bone

Answer 1

Hydroxyapatite

Question 2

RANK-L/RANK System

Answer 2

RANK-L is expressed by osteoblast cells and they directly bind to RANK on preosteoclasts activating their differentiation and fusion into multi-nucleated cells

*Also prolong osteoclast life by inhibiting apoptosis

Question 3

OPG

Answer 3

Secreted by osteoblasts to bind to RANK-L and inhibit the differentiation of pre-osteoclasts

Question 4

m-CSF

Answer 4

Promotes the differentiation of monocytes that work together w/ RANK-L to promote osteoclastogenesis

Question 5

Bone Resorption

Answer 5

Osteoclasts bind to bone via B-integrins and form the ruffled border

=>Secretion of H+ via H-ATPases and proteases leading to the degradation of hydroxapatite and Type I collagen

Question 6

CTX

Answer 6

Product of Type I collagen degradation

*Can be measured in the urine to determine activity of osteoclasts

Question 7

Bone Formation

Answer 7

Osteoblasts secrete type I collagen, osteocalcin, and AP

*Increased AP levels are assoc. w/ childhood growth and bone repair

Question 8

Period of quiescence

Answer 8

Entered by oseteocytes after bone formation; some communicate w/ osteoblasts via canalliculi and others control the influx/efflux of mineral ions (lining cells)

Question 9

Calcium Intestinal Absorption

Answer 9

Transcellular: Ca2+ moves across TRPV5 & 6, gets bound to calbindin-d9k and transported to the basolateral surface to a Ca2-ATPase
*More common

Paracellular: Occurs when dietary Ca2+ is increased

Question 10

Phosphate Intestinal Absorption

Answer 10

Absorbed transcellularly via Na+/Pi co-transport

Question 11

PTH effects on Kidney Tubules

Answer 11

1. Increases Ca2+ transporters in the DCT (only accounts for ~9% of reabsorption)
2. Removes Na+/Pi transporters in the PROXIMAL tubules
3. Activates renal 1-a hydroxylase

Question 12

C-terminal fragments of PTH

Answer 12

Formed by proteolytic enzymes that degrade the biologically active N-terminal in secretory granules in response to hypercalcemia

Question 13

Parathyroid response to hypocalcemia

Answer 13

1. Gs activates AC leading to increased PTH secretion
2. PTH mRNA stability increases
3. Proliferation of chief cells
4. Decreased degradation of n-terminals

Question 14

Effects of Hypercalcemia on Parathyroid

Answer 14

1. Gi inhibits AC and Gq inhibits PLC leading to an increase in intracellular Ca2+ and a DECREASE in secretion of PTH
   - *Uniquely different

-Vitamin D acts at genomic level to inhibit PTH secretion

Question 15

PTH/PTHrP Receptor

Answer 15

Increases intracellular AC and IP3 promoting RANK-L expression in the bone and PO43- excretion/Ca2+ reabsorption/1a-hydroxlyase activation in the kidneys

Question 16

Hyperparathyroidism

Answer 16

• Bone lesions
• Duodenal ulcers
• Kidney stones
• Decreased membrane excitability leading to muscle weakness, constipation, lethargy

Question 17

Hypoparathyroidism

Answer 17

Causes tetany in the hand and easily excitable cell membranes

Question 18

PTHrP

Answer 18

Secreted locally (paracine) and is capable of eliciting the same effects as PTH

*Regulates the proliferation of embyonic tissues; controls Ca2+ thru the placenta

Question 19

Humoral Hypercalcemia of Malignancy

Answer 19

Numerous tumors secrete factors into the blood promoting excessive bone resorption

*Mediated by PTHrP

Question 20

Vitamin D synthesis

Answer 20

1. 7-dehydrocholesterol in the skin is activated by UV light to Vitamin D3
2. D3 undergoes conversion to 25(OH)D in the blood and further to 1,25 (OH)2D in the PT of the kidneys (highly regulated step)
   * 25 (OH)D is high in concentration and is clinically measured in the serum
   * !,25(OH)2D is the most active form of Vitamin D

Question 21

Vitamin D effects on the intestine

Answer 21

1. Increases the # of Ca2+ channels and calbindin-d9k

2. Increases the absorption of PO43-

Question 22

Vitamin D effects on the parathyroid

Answer 22

1. Inhibits PTH secretion

2. Induces expression of more CaSR

Question 23

Vitamin D effects on bone

Answer 23

Promotes bone mineralization and osteoclastogenesis (increased RANK-L/decreased OPG)

Question 24

Vitamin D Mechanism of Action

Answer 24

Binds to VDR, forms a complex w/ RXR, binds to regulatory component on genes

Question 25

Vitamin D Defeciencies

Answer 25

Growing Bone= Rickett’s

Adult Bone= Osteomalacia

Question 26

Organic Protein of Bone

Answer 26

Type I Collagen

Question 27

Estradiol

Answer 27

Inhibits expression of RANK-L

Question 28

cAMP

Answer 28

PTH stimulates increase in AC activity to produce results

Question 29

Most apparent consequence of Vitamin D deficiency

Answer 29

Decreased bone mineralization

Question 30

Para follicular cells

Answer 30

Found in the thyroid; secrete calcitonin

Question 31

Calcitonin

Answer 31

Acts via a cAMP dependent pathway to decrease Ca2+ levels in the blood

*Gastrin=> Increased calcitonin secretion