Calcium Metabolism

Question 1

What are the 5 homeostatic effects of calcium?

Answer 1

1. Neurotransmitter release
2. Excitation-contraction coupling
3. Signal transduction
4. Enzyme cofactor
5. Bone

Question 2

What are the four homeostatic effects of phosphorus?

Answer 2

1. Acid buffer
2. Necessary for DNA/RNA
3. Regulatory phosphorylations
4. Bone

Question 3

How does most of calcium travel in blood?

Answer 3

Albumin (which is made in the liver)

Question 4

If you have hepatitis, what happens to your levels of free calcium?

Answer 4

Drops because with hepatitis, more albumin is made

Question 5

How is phosphorus measured in labs?

Answer 5

Not as free phosphorus, but as different levels of phosphates

Question 6

Where are calcium and phosphate absorbed? Where does resorption occur? Reabsorption?

Answer 6

Intestine
Bone
Kidney

Question 7

What is the effect of PTH and PTHrp on calcium and PO4 serum levels?

Answer 7

calcium - increase

PO4 - decrease

Question 8

What is the effect of 1,25(OH)2-D3 on calcium and PO4 serum levels?

Answer 8

calcium - increase

PO4 - increase

Question 9

What is the effect of calcitonin on calcium and PO4 serum levels?

Answer 9

calcium - decrease

PO4 - decrease

Question 10

Where is PTHrp made?

Answer 10

Ducts of lactating breasts, skin, NOT parafollicular cells like PTH

Question 11

What increases levels of FGF-23?

Answer 11

High levels of phosphorus in the blood

Question 12

What cell makes FGF-23

Answer 12

Osteoblasts

Question 13

What does FGF-23 do? What is the mechanism for this?

Answer 13

Decreases PO4 reabsorption. Goes to kidney and inhibits 1-a-hydroxylase so that less active vitamin D3 is made.

Question 14

What is more potent, PTH or calcitonin?

Answer 14

PTH - ability to increase Ca levels is stronger than calcitonin’s ability to lower Ca levels

Question 15

What is the effect of PTH on bone?

Answer 15

• Activates osteoblasts to make RANKL
• RANKL activates osteoclasts
• Bone is broken down, calcium released into blood

Question 16

What is the effect of PTH on kidneys?

Answer 16

• Activates 1-a-hydroxylase which makes activated Vitamin D3
• Increases calcium reabsorption so less is excreted in urine
• Diminishes expression of phosphate reabsorbers so more is excreted in urine

Question 17

What is the effect of PTH on intestine?

Answer 17

• Active Vitamin D increases calcium absorption in the gut

Question 18

What types of cells release calcitonin?

Answer 18

Parafollicular cells in the parathyroid gland

Question 19

What is is effect of calcitonin on bone?

Answer 19

Slightly diminishes bone resorption

Question 20

What is effect of calcitonin on kidney?

Answer 20

• Slightly diminishes Ca reabsorption, so more is excreted in urine
• Slightly diminishes PO4 reabsorption, so more is excreted in urine

Question 21

How is vitamin D synthesized?

Answer 21

1. Skin - UV turns cholesterol into pre-D3 and then cholecalciferol
2. Liver - 25 hydroxylase increases potency of vitamin D and 25-OH-D3 is made
3. Kidney - 1-alpha-hydroxylase increases potency of molecule (1,25-OH2-D3) is made

Question 22

What activates 1-a-hydroxylase?

Answer 22

PTH, low levels of phosphorus, low calcium levels

Question 23

What deactivates 1-a-hydroxylase?

Answer 23

FGF-23

Question 24

What is effect of Vitamin D on enterocytes?

Answer 24

• Increases transcription and synthesis of calcium binding proteins
• Regulates Ca-ATPase so that it is more active (more absorption from gut)
• Increases phosphate and calcium absorption

Question 25

What is effect of Vitamin D on bone?

Answer 25

Promotes PTH action, so it increases calcium resorption, higher levels of Ca in blood

Question 26

What is effect of Vitamin D on kidneys?

Answer 26

Increases calcium reabsorption | Increases phosphate reabsorption

Question 27

What are the inorganic constituents of bone?

Answer 27

Ca and PO4 in hydroxyapatite crystals

Question 28

What is the organic constituent of bone?

Answer 28

Osteoid - type I collagen and proteoglycans, cells

Question 29

What is function of osteoblasts? What molecule do they produce that converts pre-osteoclasts into mature osteoclasts?

Answer 29

Osteoid synthesis OPGL/RANKL

Question 30

What hormones enhance osteoblast production of OPGL/RANKL? What inhibits it?

Answer 30

Enhances: PTH, PTHrp, Vit D Inhibits: Calcitonin, estrogens

Question 31

What is function of osteoclasts?

Answer 31

Resorption

Question 32

What is function of osteocytes?

Answer 32

Inhibit bone degradation - prevents excess osteoclast activity through paracrine signaling: Osteoprotegerin (OPG) and sclerostin

Question 33

What does osteoprotegerin do?

Answer 33

Dummy soluble receptor that blocks RANKL on osteoblasts from binding to osteoclasts

Question 34

What does sclerostin do?

Answer 34

Downregulates synthesis of OPGL in osteoblast

Question 35

What is the process of epiphyseal plate activity?

Answer 35

Chondroctye --> Cartilage synthesis --> Calcification --> Erosion --> Osteoblast invasion --> Osteoid --> Mineralization

Question 36

What factors increase growth of epiphyseal plate activity? Decrease it?

Answer 36

Increase: IGF-1, insulin Decrease: T3, sex steroid

Question 37

What does hyperparathyroidism result in for Ca and PO4 levels? What clinical problems can it cause?

Answer 37

High calcium and low phosphorus serum levels | Kidney stones due to excessive calcium, psychosis, fractured bones

Question 38

What does hypoparathyroidism do to Ca and PO4 levels?

Answer 38

Low calcium, high phosphorus

Question 39

What is pseudohypoparathyroidism?

Answer 39

Have sufficient PTH hormone, but receptors don't work

Question 40

What bone disease does low vitamin D cause?

Answer 40

Osteomalacia and rickets

Question 41

What disease results from bone mineral loss?

Answer 41

Osteoperosis

Question 42

Why are females more likely to get osteoperosis?

Answer 42

Have decreased bone density after menopause and faster decline in bone density than males Loss of sex steroids after menopause allow for excessive osteoclast activity as well