Regulation of calcium and phosphate metabolism

Question 1

What is the active form of Ca2+ in the body? Where is most calcium stored?

Answer 1

Free ionized Ca2+. Most is stored in bones and teeth

Question 2

Why is extracellular calcium concentration important?

Answer 2

It affects the excitability of neurons

Question 3

What is the effect of aging on Ca2+?

Answer 3

Decrease in dietary intake of calcium and how much calcium is absorbed from diet (osteopenia or osteoporosis)

Question 4

What symptoms does hypocalcemia usually present as?

Answer 4

Low Ca2+ > lower threshold of neurons for AP > lots of random AP so hyperreflexia, twitching, cramping, tingling and numbness, aka excite the nervous system

Question 5

What are Chovstek sign and trousseau signs? What do these indicate?

Answer 5

Chovstek: facial twitching triggered by tapping on CN VII
Trousseau: carpopedal spasm upon inflation of blood pressure cuff
-Indicative of hypocalcemia

Question 6

What symptoms does hypercalcemia usually present with?

Answer 6

High Ca2+ > higher threshold of neurons for AP > less Aps > muscle weakness, hyporefelxia, lethargy, no appetite aka depress the nervous system

Question 7

How can you alter Ca2+ concentration in blood?

Answer 7

• plasma protein concentration (directly proportional)
• Anion concentration (inversely proportional)
• change the fraction of Ca2+ bound to albumin (acid/base)

Question 8

Acidemia does what to Ca2+ concentration? How?

Answer 8

If there’s lots of H+, they occupy most of the binding sites in albumin, leaving Ca2+ in the blood

Question 9

Alkalemia does what to Ca2+ concentration? How?

Answer 9

If there’s less H+, Ca2+ can bind to albumin > less Ca2+ floating around in the blood

Question 10

What are the roles of these molecules in Ca2+ homeostasis?
Vitamin D
PTH
Calcitonin

Answer 10

• absorb the Ca2+ from the intestines, bone resorption
• increase Ca2+ in the blood (resorption of bone)
• decrease Ca2+ in the blood (reabsorption by bone and excretion by kidney)

Question 11

What is the relationship of extracellular phosphate concentration to Ca2+ concentration? What regulates phosphate and where is it found?

Answer 11

Inversely proportional, regulated by the same hormones that regulate Ca2+ and found mostly in bone

Question 12

What produces PTH?

Answer 12

Chief cells of the parathyroid gland

Question 13

Describe the synthesis of PTH

Answer 13

preproPTH > pro PTH > cleaved by Golgi to PTH > packaged to granules

Question 14

Draw the pathway of regulation of PTH synthesis and secretion

Answer 14

Ok

Question 15

What happens to PTH synthesis if you have chronic hypercalcemia? How about chronic hypocalcemia?

Answer 15

• decreases (since lots of Ca2+ feedback)

- increases (since no Ca2+ feedbacks)

Question 16

How does magnesium affect PTH secretion?

Answer 16

Same as Ca2+. But severe hypomangesemia (alcoholics) can inhibit PTH altogether

Question 17

Draw the mechanism of action of PTH

Answer 17

Ok

Question 18

What is active Vitamin D? What is its main function in relation to Ca2+ and Pi?

Answer 18

1-25, dihydroxycholecalciferol. Increase Ca2+ and Pi blood concentration

Question 19

What is the mechanism of action of Vitamin D?

Answer 19

It’s a steroid so it travels in the blood via binding protein > attaches to RXR nucleus receptor and ups/downs gene expression with end goal to increase ca

Question 20

Draw the synthesis of Vitamin D

Answer 20

Ok

Question 21

How is 1a hydroxylase regulated?

Answer 21

Comes from CYP1a gene. Activated by PTH binding to receptor in proximal tubule cell and deactivated by Ca binding to receptor in proximal tubule cell.

Question 22

How exactly does PTH increase Ca2+ in blood?

Answer 22

Binds to osteoblasts first (short term - bone formation) > osteoblast releases cytokines > binds on osteoclasts which takes the Ca2+ out of the osteoblast

Question 23

Draw the mechanism of bone resorption and formation

Answer 23

Ok

Question 24

Roles of M-CSF, RANK L, RANK and OPG in bone formation and resorption

Answer 24

M-CSF: induces maturation of osteoclasts
RANK L: binds to RANK receptor on osteoclasts > allows them to osteoclast
RANK: RANK L receptor
OPG: decoy receptor for RANK L to prevent it from enabling osteoclasts

Question 25

What are the actions of PTH and Vitamin D on RANKL and OPG?

Answer 25

PTH increases RANKL and decreases OPG | Vitamin D increases RANKL eceptor for RANK

Question 26

What is the action of the PTH on the kidney cell?

Answer 26

PTH wants to keep Ca2+ and get rid of Phosphate. Inhibits the NPT2a phosphate receptor so it can't travel to the bloodstream and stays in the urine filtrate

Question 27

Draw how Vitamin D regulates the absorption of Ca2+ from the intestine into the bloodstream

Answer 27

OK

Question 28

How does Vitamin D facilitate absorption of phosphate into bloodstream?

Answer 28

Activates NPT2a to let the phosphate in

Question 29

What does calcitonin do?

Answer 29

Bone formation and lower Ca2+ and Pi levels by binding to receptors on osteoclasts and inhibiting them

Question 30

What happens to calcitonin levels after a thyroidectomy? How about thyroid tumor?

Answer 30

Decreased calcitonin | Increased calcitonin

Question 31

How does estradiol affect Ca2+ and Pi metabolism?

Answer 31

promote GI bsorption and kidney reabsorption. of Ca2+. Osteoblast survival and osteoclast apoptosis

Question 32

How do glucocorticoids affect Ca2+ and Pi metabolism?

Answer 32

Promote resorption

Question 33

Primary hyperparathyroidism Cause Clinical Treatment

Answer 33

-Parathyroid problem (too much PTH, could be caused by adenoma) -Groans: stones and constipation, plus lots of Ca, Pi and cAMP excretion Bones: resorption -Parathyroidectomy

Question 34

Secondary hyperparathyroidism:

Answer 34

-Low blood Ca2+ (due to renal failure or vitamin D deficiency) causes increased PTH.

Question 35

What happens to phosphate in 2ndary hyperparathyroidism?

Answer 35

Kidney failure: defective kidney, phosphate isn't excreted and Ca2+ isn't reabsorbed Vitamin D deficiency: kidney is fine and getting rid of phosphate, but intestine doesn't absorb the Ca2+

Question 36

Hypoparathyroidism: Cause Clinical Treatment

Answer 36

- Insufficient PTH due to problem with parathyroid causing low Ca2+. ---- - Hypocalcemia symptoms and hyperphophatemia - Ca2+ and Vitamin D supplement

Question 37

Albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a) Cause clinical

Answer 37

- Lots of PTH but cannot activate adenylate cyclase. No response to PTH - hypocalcemia and hyperphosphatemia, lots of urinary cAMP. Short everything, obese, calcified skin

Question 38

Humoral hypercalcemia of malignancy | Cause:

Answer 38

Tumor produces PTHrP which mimics PTH and binds the type 1 PTH receptor. Low PTH but lots of PTH effects cause of the impostor

Question 39

Humoral Hypercalcemia of malignancy: | Clinical

Answer 39

Lots of PTHrP, blood Ca, urinary Ca, Pi and cAMP but low PTH

Question 40

Familial hypocalciuric hypercalcemia (FHH)

Answer 40

CaSR not working (mutated). Can't respond to Ca2+ so chief cell keeps making PTH -High blood Ca2+ and low urinary Ca2+. Normal to high PTH

Question 41

Vitamin D deficiency results in …

Answer 41

Rickets in kids and osteomalacia in adults

Question 42

Rickets:

Answer 42

Weak bones in kids. Type 1: lack of 1a hydroxylase Type 2: lack of vitamin D receptor

Question 43

Osteomalacia: Cause Clinical

Answer 43

- GI problems that it can't absorb Vitamin D, no sun exposure - bone pain, fractures, muscle cramps, positive Chvostek's sign

Question 44

Osteoporosis: Cause Treatment

Answer 44

- Loss of bone mass overtime. Lots of resorption with disproportionate formation - anything that increases osteoblast formation or inhibits osteoclasts