Calcium and Phosphate Homeostasis Flashcards Preview

S&F IV: Exam One > Calcium and Phosphate Homeostasis > Flashcards

Flashcards in Calcium and Phosphate Homeostasis Deck (31):
1

Organic Mineral of Bone

Hydroxyapatite

2

RANK-L/RANK System

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

3

OPG

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

4

m-CSF

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

5

Bone Resorption

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

6

CTX

Product of Type I collagen degradation

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

7

Bone Formation

Osteoblasts secrete type I collagen, osteocalcin, and AP

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

8

Period of quiescence

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

9

Calcium Intestinal Absorption

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

10

Phosphate Intestinal Absorption

Absorbed transcellularly via Na+/Pi co-transport

11

PTH effects on Kidney Tubules

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

12

C-terminal fragments of PTH

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

13

Parathyroid response to hypocalcemia

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

14

Effects of Hypercalcemia on Parathyroid

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

15

PTH/PTHrP Receptor

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

16

Hyperparathyroidism

-Bone lesions

-Duodenal ulcers

-Kidney stones

-Decreased membrane excitability leading to muscle weakness, constipation, lethargy

17

Hypoparathyroidism

Causes tetany in the hand and easily excitable cell membranes

18

PTHrP

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

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


19

Humoral Hypercalcemia of Malignancy

Numerous tumors secrete factors into the blood promoting excessive bone resorption

*Mediated by PTHrP

20

Vitamin D synthesis

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

21

Vitamin D effects on the intestine

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

2. Increases the absorption of PO43-

22

Vitamin D effects on the parathyroid

1. Inhibits PTH secretion

2. Induces expression of more CaSR

23

Vitamin D effects on bone

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

24

Vitamin D Mechanism of Action

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

25

Vitamin D Defeciencies

Growing Bone= Rickett's

Adult Bone= Osteomalacia

26

Organic Protein of Bone

Type I Collagen

27

Estradiol

Inhibits expression of RANK-L

28

cAMP

PTH stimulates increase in AC activity to produce results

29

Most apparent consequence of Vitamin D deficiency

Decreased bone mineralization

30

Para follicular cells

Found in the thyroid; secrete calcitonin

31

Calcitonin

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

*Gastrin=> Increased calcitonin secretion