Lecture 33

Question 1

What function is calcium involved in?

Answer 1

• Enzyme activation/inactivation
• Intracellular second messenger
• Exocytosis
• Nerve conduction
• Muscle contraction
• Structural integrity of bone

Question 2

How much calcium is taken up by each system that stores/takes up calcium?

Answer 2

• GI: +175mg/day (due to diet)
• Kidneys: -175mg/day (lost in urine)
• Bone: 0mg/day

Question 3

How much calcium does bone hold?

Answer 3

Holds about 99% or 1 kg of calcium

Question 4

What is the chemical name for calcitrol?

Answer 4

1,25-(OH)2-D

Question 5

How does parathyroid hormone affect calcium?

Answer 5

• Acts directly on bone and kidney to increase calcium
• Through stimulation of calcitrol synthesis
• Inhibits renal tubular reabsorption of phosphate which increases urinary phosphate secretion and decreases plasma levels.

Question 6

Where are parathyroid glands found?

Answer 6

On the posterior surface of the thyroid gland between capsule and surrounding connective tissue.

Question 7

How many parathyroid glands are there?

Answer 7

4 major ones, may be a few accessory glands found in mediastinum or neck.

Question 8

What do the 4 parathyroid glands derive from?

Answer 8

The third and fourth branchial pouches.

Question 9

What does the third branchial pouch differentiate into?

Answer 9

• Inferior parathyroid glands
• Thymus

Question 10

What does the fourth branchial pouch differentiate into?

Answer 10

• Superior parathyroid glands
• Ultimobranchial body

Question 11

What are the two cell types within parathyroid glands?

Answer 11

Chief cells and oxyphil cells

Question 12

What is the function of a chief cell?

Answer 12

Synthesize and secrete PTH

Question 13

What is the function of an oxyphil cell?

Answer 13

Unclear, appears to be a transitional form of chief cells.

Question 14

What are the unique characteristics of oxyphil cells?

Answer 14

• High amounts of mitochondria
• Acidophilic staining in hematoxylin-eosin preparations
• DOES NOT SECRETE PTH

Question 15

What signals chief cells to secrete PTH secretion?

Answer 15

A calcium sensing receptor (CaSR) senses a reduction in serum calcium levels.

Question 16

How does increased parathyroid hormone affect serum calcium concentrations.

Answer 16

Serum calcium is increased.

Question 17

What is DiGeorge Syndrome (velo-cardio-facial syndrome)?

Answer 17

Absence of parathyroid glands and thymus which is caused by the deletion of a piece of chromosome 22 - “Catch-22”

Question 18

How does DiGeorge Syndrome present?

Answer 18

Features vary but is associated with hypocalcemia and may include birth defects

Question 19

How is the immune system affected by velo-cardio-facial syndrome?

Answer 19

Infections are common in children due to an absent/hypoplastic thymus, which leads to problems with T-cell-mediated response

Question 20

What happens when calcium binds to CaSR?

Answer 20

The G-protein starts a signaling cascade that inhibits the PTH gene.

Question 21

How does calcitrol affect chief cells?

Answer 21

• Directly inhibits PTH gene
• Activates CaSR gene (follows central dogma, with preCaSR being the term for the pre-post translational modified protein)

Question 22

What happens when PTH gene is not inhibited?

Answer 22

PreproPTH is created from the gene, which then travels to the rough ER to be transformed into proPTH and then to PTH which is excreted via exocytosis.

Question 23

Other than repressing the gene, how does calcium sensing affect PTH secretion?

Answer 23

The downstream signaling pathway that is activated by the G protein inhibits the secretion of PTH.

Question 24

What is the signaling cascade that is caused by CaSR?

Answer 24

The G proteins inhibit adenylyl cyclase and stimulate phospholipase C (PLC) activity which results in suppression of PTH gene, accelration of intracellular degradation of PTH and inhibition of PTH release.

Question 25

How does the activation of PLC affect the intracellular workings of the chief cells?

Answer 25

Production of the second messengers inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) from phosphoinostides (PIP2)

Question 26

How does second messengers in chief cells inhibit release of PTH?

Answer 26

- IP3 increases levels of cytosolic calcium via the release of intracellular stores - DAG stimulates protein kinase C (PKC) activity - Elevated calcium and stimulated PKC inhibit release of granules containing PTH

Question 27

Why does high cytoplasmic calcium contrast in its mechanism vs. other secretory cells?

Answer 27

It inhibits the fusion of vesiles with the membrane of the parathyroid cell, which inhibits PTH.

Question 28

How do inactivating mutations of one allele of CaSR affect chief cells?

Answer 28

- Prevents increased serum calcium, leading to increased PTH - Familial benign hypercalcemia (familial hypocalciuric hypercalcemia)

Question 29

What are the effects of familial benign hypercalcemia?

Answer 29

- Severe if both alleles are inactivated - Skeletal changes of unremitting hyperparathyroidsim - Requires immediate parathyroidectomy in newborns

Question 30

How do activating mutations of CaSR affect chief cells?

Answer 30

- Chief cells assume serum calcium is elevated when it is not, leading to decreased PTH - Hypocalcemia

Question 31

What are the effects of hypocalcemia?

Answer 31

Seizures can occur

Question 32

How to treat hypocalcemia?

Answer 32

Treat with supplemental PTH

Question 33

How can CaSR be affected by autoimmunity?

Answer 33

- Inactivated - syndrome similar to familial benign hypercalcemia - Activated - hypoparathyroidism

Question 34

How does PTH affect bone?

Answer 34

Promotes calcium and phosphate resorption from bone by acting on stromal osteoblasts in the bone marrow to demineralize and release calcium

Question 35

How does PTH affect kidneys?

Answer 35

- Promotes calcium reabsorption in proximal tubules of the renal cortex and in the distal nephron - Promotes phosphate excretion from the renal tubule. - Stimulates biosynthesis of active calcitrol which increases calcium absorption in the intestinal mucosa

Question 36

How does PTH affect the GI tract?

Answer 36

Promotes calcium absorption from the GI tract

Question 37

What reaction in the skin account for the first step of vitamin D activation?

Answer 37

7-dehydrocholesterol reacts with sunlight to form vitamin D3.

Question 38

What is plasma vitamin D made of?

Answer 38

Dietary vitamin D2/D3 and vitamin D3 from skin.

Question 39

What does the liver do with plasma vitamin D?

Answer 39

It combines with 25-hydroxylase to create 25-OH D.

Question 40

What do the kidneys do with 25-OH D?

Answer 40

It combines with 1-hydroxylase to create 1,25-(OH)2D (calcitrol)

Question 41

What are the three proteins that directly account for intestinal absorption of calcium?

Answer 41

- Calcium-binding protein - Calcium-stimulated ATPase - Alkaline phosphatase

Question 42

25-Hydroxycholecalciferol has what effect secondary effect on the process of vitamin D activation?

Answer 42

Inhibits the further production of 25-hydroxycholecalciferol (25-OH D) in the liver to prevent excessive action of vitamin D3.

Question 43

Some calcium is secreted back into the small intestine

Answer 43

TRUE

Question 44

Where does calcitonin come from and where does it end up?

Answer 44

It comes from the kidney and ends up in the bones.

Question 45

What is released from bones to the extracellular fluid along with PTH?

Answer 45

- Calctriol - Cortisol

Question 46

Components of total serum calcium under normal condition:

Answer 46

- Albumin (4 Ca2+) - Phosphorus citrate (1 Ca2+) - Free Ca2+ - Normal levels of PTH