Calcium and Phosphate Regulation Flashcards Preview

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Flashcards in Calcium and Phosphate Regulation Deck (58)
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1

What is the normal range of Ca?

Tightly regulated range in plasma (2.2 - 2.6 mM)

2

What is the most abundant cation?

Calcium

3

What is the function of phosphate?

Cellular energy metabolism (ATP)
Intracellular signaling pathways
Nucleic acid backbone
Bone structure
Enzyme activation/deactivation

4

What is the function of calcium?

Membrane stability and cell function
Neuronal transmission
Bone structure/formation
Blood coagulation
Muscle function Hormone secretion

5

What is Ca found as in the plasma?

Half Ca is bound to albumin
Half is ionized

6

What is Pi found as in the plasma?

Most of Pi is ionized

7

What does hypocalcemia result in?

Muscle failure, tetany, convulsions, death

8

What does hypercalcemia result in?

Renal dysfunction, calcification of soft tissues, muscle weakness, coma

9

What often causes hyperphosphatemia?

Result of severe tissue injury “crush”

10

What are the main 2 regulators of calcium?

PTH
Vitamin D

11

What is the function of the chief/principal cells in the parathyroid gland?

Make PTH

12

What is the function of the oxyphil cells in the parathyroid gland?

No known function, increase with age and chronic kidney disease

13

What is the function of the 1-34 PTH fragment (N terminal)?

N-terminal fragment 1-34 biologically active – binds to PTH receptor

14

What is the function of the 35-84 PTH fragment?

C-terminal fragment 35-84 has longer half-life than other fragments – inactive

15

What is the clinical importance of the 1-84 PTH fragment?

Intact 1-84 fragment: half-life of 4 min and is clinically measured.

16

How is PTH synthesized?

The signal peptide directs it to the ER for processing after translation

17

What is the function of PTHrP (related peptide)?

Parathyroid hormone-related peptide (PTHrP) is highly homologous to PTH 1-34 AA.

It mimics the action of PTH in the bone and kidney.

18

What is the relationship of PTHrP to disease?

Many tumors produce PTHrP (renal, bladder, lymphoma, head/neck) resulting in hypercalcemia

19

What are the PTH receptors?

PTH 1R
PTH 2R

20

Describe PTH 1R.

Primary receptor and is found in the osteoblasts and kidney and it is a GPCR.

Binds 1-34 fragment, 1-84, PTHrP

21

Describe PTH 2R.

Physiological importance in humans unclear

Binds 1-34
Does not bind PTHrP

22

What are the targets of PTH?

Bone and Kidney

23

What are the effects of PTH?

Increase plasma Ca2+, decrease plasma Pi

24

What is the function of osteoclasts?

Bone reabsorption
Do not express PTH receptors

25

What is the function of osteoblasts?

Bone formation and mineralization
High expression of PTH receptors

26

What is the mechanism of PTH action?

-PTH stimulates macrophage colony-stimulating factor (M-CSF) in osteoblasts by binding the PTH receptor.

-M-CSF stimulates differentiation of osteoclast precursors

27

What is the the type of action PTH has on osteoclasts?

Indirect via M-CSF from the osteoblasts

28

What is the effect of PTH on RANK ligand?

PTH stimulates RANK ligand – leads to maturation of osteoclast and bone reabsorption. Bone degradation releases Ca2+ and Pi to systemic circulation.

29

What is Osteoprotegerin (OPG)?

It is an antagonist of RANK ligand which leads to the down regulation of osteoclasts

30

How does increased cortisol lead to osteoporosis?

Cortisol inhibits OPG -> more bone breakdown and can lead to osteoporosis

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