Lecture 14 - Parathyroid

Question 1

PTH is responsible for minute-by-minute regulation of Ca++ and is controlled by the concentration of ____ _____ Ca++ in plasma.

Answer 1

Free Ionized Ca++ in plasma

Question 2

Calcitonin ______ (lowers or raises?) Ca++ levels in the blood?

Answer 2

Lowers!

Question 3

Ca++ in plasma is a key component of _____ and Cell-cell interactions.

Answer 3

Coagulation

Question 4

Keep in mind only about ____% of Ca++ in plasma is free ionized calcium (the rest is mostly bound to ______).

Answer 4

50%

Albumin

Question 5

What is the relationship between Ca++ binding and pH?

Answer 5

Ca++ binds deprotonated Carboxylic acid groups on proteins, so the HIGHER the pH, the more deprotonated the Carboxylic acid groups –> MORE Ca++ binding (less free Ca++).

Question 6

Only about 30% of Ingested Ca++ is absorbed into the body. It is predominantly stored and resorbed from bone, and it is very highly resorbed in the ______ (about 99% resorbed).

In contrast, Phosphate is readily absorbed in the gut and only about 80-90% is recovered by the kidneys.

Answer 6

Kidney

Question 7

Both _____ AND osteoclasts are involved in liberation of Ca++ from bone.

Answer 7

Osteocytes

Question 8

The formation of 1,25-dihydroxy D3 by the body WITHOUT sunlight requires 2 enzymes, 25-hydoxylase and 1alpha-hydroxylase. Where are these enzymes found?

Answer 8

25-hydroxylase in the liver (first)

1alpha-hydroxylase in the kidney (second)

Question 9

_________ is the primary regulatory enzyme for 1,25-dihydroxy D3 synth. It is stimulated by PTH. When 1,25-dihodroxy D3 levels are high, it is inhibited and the Kidney produces __________ (an inactive form) from 25-hydroxy D3.

Answer 9

1alpha-hydroxylase

24,25-dihydroxy D3

Question 10

________ is the protein 1,25-dihydroxy D3 binds to in plasma for transport. 1,25-dihydroxy D3 acts as a steroid hormone once inside target cells by binding the nuclear _____ acid receptor (RXR).

Answer 10

Transcalciferin

Retinoic Acid Receptor (RXR)

Question 11

The main effect of 1,25-dihydroxy D3 is to increase absorption of Ca++ from the gut. Which proteins does it increase transcription of for this process?

Answer 11

ALL of them! Ca++ channel on enterocyte apical membrane, Calbindin intracellular Ca++ transport protein, Na+/Ca++ exchanger on basolateral side of enterocytes, and Ca++-ATPase on basolateral side.

Question 12

Keep in mind 1,25-dihydroxy D3 inhibits PTH via negative feedback BUT it Enhances PTH effects on _____ _____.

Answer 12

Bone Resorption

Question 13

PTH is secreted by ____ cells in the Parathyroid gland. It is secreted as an 84AA long pro-hormone and is cleaved in the periphery into a 34AA long active hormone. Which terminal of the pro-hormone becomes the active hormone, the C- or N-terminal?

Answer 13

Chief cells

The N-terminal becomes the active.

Question 14

PTH secretion is regulated via a G-protein coupled CaR. Which G-proteins is it coupled to?

Answer 14

Gq and Gi, so at High Ca++ levels, Gi inhibits AC –> decreased PTH secretion.

Question 15

While PTH increases OsteoClast activity, it does so by binding receptors on OsteoBlasts and Osteocytes –> these cells release a paracrine factor ______ that stimulates OsteoClasts activity.

Which hormone suppresses RANKL?

Answer 15

RANKL

Estrogen suppresses it, which is why post-menopausal women are at higher risk for Osteoporosis –> RANKL more active –> more bone resorption.

Question 16

In the kidney, other than stimulating activity of 1alpha-hydroxylase, PTH _____ (increases or decreases?) reabsorption of Ca++ but ______ (increases or decreases?) reabsorption of Phosphate.

Answer 16

Increases

Decreases

Question 17

While PTHrP can act similarly to PTH, what can it not do that PTH does?

Answer 17

It CANNOT stimulate 1alpha-hydroxylase

Question 18

The major effect of Calcitonin is to directly decrease _______ activity.

Answer 18

Osteoclast

Question 19

In the kidney, Calcitonin _______ (increases or decreases?) BOTH Ca++ and Phosphate reabsorption.

Answer 19

Decreases

Question 20

Hypocalcemia allows increased _____ permeability in neurons and myocytes, which can lead to hypocalcemic tetany.

Answer 20

Na+

Question 21

What is the difference between Primary and Secondary Hyperparathyroidism, and which is worse?

Answer 21

Primary –> High serum Ca++

Secondary –> Low serum Ca++ (usually from renal disease.

Secondary is worse bc of low Ca++ –> so bone probs