EXAM #1: CALCIUM METABOLISM

Question 1

Which cells of the parathyroid gland secrete PTH?

Answer 1

Chief cells of the parathyroid

Question 2

Describe the synthesis of PTH.

Answer 2

1) Prepro-PTH in ribosomes
2) pro-PTH in ER
3) PTH in secretory granules of Golgi complex

Question 3

What regulates the synthesis of PTH?

Answer 3

Ca++ and Vitamin D

Question 4

How does Ca++ physiologically regulate PTH synthesis?

Answer 4

• CaR (Ca++ sensing GPCR) is present on chief cells of the parathyroid
• PLC pathway is activated by Ca++ binding leading to the synthesis of leukotrienes
• Leukotrienes cause PTH degradation

Question 5

How does Vitamin D regulate PTH?

Answer 5

Vitamin D decreases the stability of PTH mRNA

Question 6

What is the receptor for PTH signaling?

Answer 6

PTHR1 (GPRC) present on the surface of target cells

Question 7

What are the two pathways for PTH signaling?

Answer 7

1) Adenylate Cyclase pathway using:
- cAMP
- PKA

2) PLC
- DAG
- IP3
- PKC

Question 8

What determines the signaling pathway a cell utilizes?

Answer 8

NHERF1- Na+/H+ exchange regulatory factor

• Neg= AC
• Pos= PLC

Question 9

What are the functions of PTH?

Answer 9

Net effect is to INCREASE serum Ca++ by:

1) Ca++ reabsoprtion in the kidney
2) Ca++ mobilization from bones
3) Intestinal absorption

Question 10

How does PTH stimulate the reabsorption of Ca++ in the kidney?

Answer 10

Insertion and opening of a Ca++ channel

Question 11

How does PTH effect Vitamin D in the kidney?

Answer 11

Increases the enzyme that makes active Vitamin D

Question 12

Describe the effect of PTH binding to PTHR1 on osteoblasts.

Answer 12

1) PTH binds PTHR1 receptor on OSTEOBLASTS
2) RANKL (ligand) is synthesized by the osteoBLAST
3) RANKL binds RANK on the osteoCLAST
4) OsteoCLAST is activated to resorb bone

*Note that PTH also decreases the production of osteoprotegerin, a molecule that prevents RANKL and RANK binding

Question 13

What are the major electrolyte changes that occur in response to hyperparathyroidism?

Answer 13

1) Hypercalcemia
2) Hypercalciuria
3) Decreased plasma phosphate

Question 14

Why does chronic renal failure lead to hyperparathyroidism?

Answer 14

1) Decreased Vitamin D
2) NO negative feedback on parathyroid
3) PTH increases

Question 15

What is the most common cause of hypoparathyroidism?

Answer 15

Surgical removal of the parathyroid glands

Question 16

What is the major effect on Ca++ in hypothyroidism?

Answer 16

Hypocalcemia

Question 17

What is the difference between Vitamin D2 and Vitamin D3?

Answer 17

1) Ergocalciferol (D2)= plant

2) Cholecalciferol (D3)= human

Question 18

How is Vitamin D3 synthesized?

Answer 18

1) UV light causes formation of provitamin D3 from a cholesterol precursor
2) Provitamin D3 is isomerized to Vitamin D3 (cholecalciferol) and is transported to the liver
3) Cholecalciferol in the liver is hydroxylated to 25-OH Vitamin D3
4) A second hydroxylation occurs in the kidney, forming the active form of Vitamin D–1,25 OH Vitamin D3 (Calcitriol)

*1a-hydroxylase is key in kidney

Question 19

How is Vitamin D3 transported in the circulation to the liver?

Answer 19

Bound to Vitamin D Binding Protein (DBP)

Question 20

What is the effect of high serum Ca++ on Vitamin D?

Answer 20

Ca++ inhibits hydroxylation 25-OH Vitamin D3

Question 21

What is the effect of PTH on Vitamin D?

Answer 21

• PTH increases 1-a hydroxylase activity in the kidney

- Thus, 1,25-OH Vitamin D3 is increased (Calcitriol)

Question 22

How does Calcitriol (Vitamin D) effect Ca++ absorption in the gut?

Answer 22

Increases Ca++ absorption

Question 23

What transported mediates the uptake of Ca++ from the gut?

Answer 23

TRPV6

Question 24

What mediates Ca++ exit from the gut on the basolateral side of the epithelium?

Answer 24

1) PMCA

2) Na+/Ca++ exchanged (NCX)

Question 25

What is the effect of Calcitriol on the kidneys?

Answer 25

Increased renal Ca++ reabsorption

Question 26

How does Calcitriol stimulate renal Ca++ reabsorption?

Answer 26

1) Activation of Ca++ ATPase

2) Calbindin-D28K

Question 27

What is the effect of Calcitriol on bone?

Answer 27

Stimulation of bone resorption, mobilizing Ca++

Question 28

What can excess Vitamin D result in?

Answer 28

• Calcinosis (i.e. calcification of soft tissues)
• Deposition of Ca++ in kidney (stones)
• Hypercalcemia

Question 29

What major bone disorders are caused by Vitamin D deficiency?

Answer 29

Rickets and osteomalacia

Question 30

Where is Calcitonin synthesized?

Answer 30

Parafollicular C cells of the thyroid

Question 31

What does increased Ca++ do to Calcitonin?

Answer 31

Increased synthesis of Calcitonin

Question 32

What is the effect of Calcitonin in bone?

Answer 32

Inhibition of bone resorption

*****Opposite of PTH and Calcitriol

Question 33

What is the effect of Calcitonin in the kidney?

Answer 33

Increases urinary Ca++ excretion

*****Opposite of PTH and Calcitriol

Question 34

What is the effect of Calcitonin on serum Ca++?

Answer 34

Decreased serum Ca++

Question 35

Clinically, how can Calcitonin be utilized?

Answer 35

Treatment of osteoporosis/ prevention of hypercalcemia in malignancy

*Note that high or low Calcitonin is not directly implicated in any disease state/disorder

Question 36

What does Calcistat refer to?

Answer 36

Multiorgan calcium homestasis