Mineral Metabolism

Question 1

What is the effect of hypocalcemia on action potentials?

Answer 1

Lowers activation threshold

Question 2

What are the forms of calcium in the plasma and their amounts? How does this differ from interstitial fluid?

Answer 2

Ionized - 50%
Protein-bound - 40%
Complexed - 10%
[Magnesium has a similar distribution]

In interstitial fluid, bound to protein is least b/c few proteins in interstitial fluid

Question 3

How does pH affect calcium levels?

Answer 3

Protons compete with calcium ions for binding to albumin

Acidemia = Increased Ionized Ca2+

Question 4

The biologic activity of PTH is due to which structure?

Answer 4

N-terminus

Question 5

What are the two mechanisms by which calcium regulates PTH formation?

Answer 5

1. Inactivation of preformed PTH (post translational)

2. Suppress gene transcription

Question 6

Which factors regulate PTH synthesis?

Answer 6

Cortisol, epinephrine stimulate

Calcium inhibits synthesis

Vit D inhibits synthesis and promotes CaSR synthesis

Magnesium can go either way

Question 7

What are the two mechanisms by which PTH-mediated Ca mobilization occurs in the bone?

Answer 7

1. Fast: ATP-dependent

2. Slow: Symport w/ HPO42-

Question 8

Calcium handling in nephron

Answer 8

1. Most Ca reabsorbed in proximal tubule
2. PTH promotes absorption in distal tubule (8%)
3. Excretion is less than 1-2%

Question 9

What are two sources of vitamin D3 and which organs convert it to the active form?

Answer 9

1) Diet
2) Cholesterol in skin, converted by UV

Modified in Liver first, Kidney second

Question 10

How are dietary and skin-based D3 transported?

Answer 10

Dietary:

• Require bile acid for absorption
• CMs deliver to liver and fat (storage)

Skin:
- Proteins carry to liver and fat (storage)

Question 11

Where does regulation of vitamin D production occur, and which enzymes are involved?

Answer 11

Kidney

1a-Hydroxylase = Active
24-Hydroxylase = Inactive

Question 12

Which factors regulate vitamin D production?

Answer 12

Stimulate: PTH, GH, Estrogen
Inhibit: CT, high Ca or PO43. Vit D itself (- feedback)

Question 13

What is the mechanism through which PTH (and Vitamin D when they are together) promotes calcium resorption from bone?

Answer 13

Bind OsteBlasts directly, but mediate effect through OsteoClasts

1. Osteoblasts produce cytokines that activate osteoclasts
2. Osteoblasts release OSTEOCALCIN, which covers bone and prevents mineralization

Binding of Vit D to Osteblasts is up-regulated by Retinoic Acid

Question 14

How does PTH affect phosphate absorption?

Answer 14

Most phosphate absorbed in the proximal tubule via SYMPORT w/ Na

PTH inhibits absorption via AC and protein kinase

Question 15

Where does most Mg reabsorption occur in the nephron and how does PTH affect it?

Answer 15

Mostly in Thick Ascending Limb

PTH stimulates reabsorption

Question 16

Vitamin D actions on Mg and Phosphate absorption

Answer 16

Stimulates transcellular absorption of Mg and Phosphate

Question 17

PTH has no direct action on _____ and _____.

Answer 17

Small Intestine and Parathyroid Gland

Question 18

In addition to calcitonin, the calcitonin gene also encodes

Answer 18

CGRP

Question 19

Calcitonin receptors are found where and are of what type?

Answer 19

1. OsteoClasts
2. Kidney (minor)
   a. Decrease vit D production
   b. Decrease Ca/P absorption
3. Intestine (indirect/minor)

GPCRs

Question 20

Mechanism of calcitonin action in kidney

Answer 20

1. Increases Ca excretion by:
   a. Opening Ca channel (apical)
   b. Stimulating Na/Ca exchanger (basal)
2. Decreases vitamin D activation
   a. Stimulates 24-a-hydroxylase

Question 21

Which is more important: PTH or Calcitonin?

Answer 21

PTH. Calcitonin is slow acting and excess/deficiency does not lead to major clinical problems. More important during growth/pregnancy

Question 22

Primary Hyperparathyroidism

Answer 22

Too much PTH

Manifestations:

• HypERcalcemia/hypercalciuria
• HypOphosphatemia/hyperphosphaturia
• Bone resorption/kidney stones

Question 23

What are 2 causes of secondary hyperparathyroidism?

Answer 23

1. Renal failure
2. Malabsorption of Ca from intestine

Low ionized Ca => Increased PTH

Question 24

Pseudo-hypoparathyroidism is caused by

Answer 24

Abnormal PTH receptors

Question 25

Effect of glucocorticoids on calcium

Answer 25

1. Decrease Ca absorption from intestine by blunting Vit D activity
2. Decrease Ca and PO43- absorption in kidney

This has the secondary effect of stimulating PTH synthesis (indirectly due to hypocalcemia)