Regulation of Calcium and Phosphate Metabolism

Question 1

As you age, what happens to the amount of calcium absorbed and the amount of calcium consumed?

Answer 1

Decreases

Question 2

What happens to bone cells as you age?

Answer 2

Existing bone cells are absorbed by the body faster than new bone is made

Aging also contributes to osteopenia and osteoporosis

Question 3

What is hypocalcemia? What are the symptoms and indicators?

Answer 3

Decreased plasma Ca2+ concentration; symptoms include hyperreflexia, spontaneous twitching, muscle cramp, tingling, numbness; indicators are Chvostek sign or Trousseau sign

Question 4

What is a Chvostek sign?

Answer 4

Twitching of the facial muscles elicited by tapping on the facial nerve

Question 5

What is a Trousseau sign?

Answer 5

Carpopedal spasm upon inflation of a blood pressure cuff

Question 6

What is hypercalcemia? What are the symptoms?

Answer 6

Increased plasma Ca2+ concentration; symptoms are decreased QT interval, constipation, lack of appetite, polyuria, polydipsia, muscle weakness, hyporeflexia, lethargy, coma

Question 7

What do changes in plasma protein concentrations do to calcium?

Answer 7

Alters total calcium concentration in the same direction (both either increase or decrease); no change in Ca2+ ionized

Question 8

What do changes in anion concentrations do to calcium?

Answer 8

Change the fraction of Ca2+ complexed with anions (if phosphate concentration increases, ionized Ca2+ concentration decreases

Question 9

What do acid-base abnormalities do to calcium?

Answer 9

Alter the ionized Ca2+ concentration by changing the fraction of Ca2+ bound to albumin

Question 10

What is acidemia?

Answer 10

Free ionized Ca2+ concentration increases because less Ca2+ is bound to albumin

Question 11

What is alkalemia?

Answer 11

Free ionized Ca2+ concentration decreases, often accompanied by hypocalcemia

Question 12

What is the relationship between Ca2+ and phosphate?

Answer 12

Extracellular concentration of Pi is inversely related to that of Ca2+; extracellular concentration of Pi is regulated by the same hormones that regulates Ca2+ concentration

Question 13

What is the normal range of extracellular Pi concentration?

Answer 13

2.5-4.5 mg/dL

Question 14

Where is most of the Pi found in the body?

Answer 14

Bone (85%)

Question 15

What does chronic hypercalcemia cause?

Answer 15

Causes decreased synthesis and storage of PTH, increased breakdown of stored PTH and release of inactive PTH fragment into the circulation

Question 16

What does chronic hypocalcemia cause?

Answer 16

Causes increased synthesis and storage of PTH and hyperplasia of parathyroid glands (secondary hyperparathyroidism)

Question 17

What effect does magnesium have on PTH secretion?

Answer 17

Parallel but less significant effects on PTH secretion; however, with severe hypomagnesemia (as in alcoholism), causes inhibition of PTH synthesis, storage, and secretion

Question 18

What is the function of vitamin D?

Answer 18

Promotes mineralization of new bone through its coordinated actions in the regulation of both Ca2+ and Pi plasma concentrations; acts synergistically with PTH to stimulate osteoclast activity and bone resorption

Question 19

What are the short-term actions of PTH?

Answer 19

Bone formation (via direct action on osteoblast); basis for the use of intermittent synthetic PTH administration in osteoporosis treatment

Question 20

What role does M-CSF (macrophage colony stimulating factor) have in bone formation and resorption?

Answer 20

Induce stem cells to differentiate into osteoclast precursors, mononuclear osteoclasts, and finally mature, multinucleated osteoclasts

Question 21

What role does RANKL have in bone formation and resorption?

Answer 21

Cell surface protein produced by osteoblasts, bone lining cells, and apoptotic osteocytes; primary mediator of osteoclast formation

Question 22

What role does RANK have in bone formation and resoprtion?

Answer 22

Cell surface protein receptor on osteoclasts and osteoclast precursors

Question 23

What role does OPG (osteoprotegerin) have in bone formation and resorption?

Answer 23

Soluble protein produced by osteoblasts; decoy receptor for RANKL; inhibits RANKL/RANK interaction

Question 24

What does PTH cause in terms of bone formation and resportion?

Answer 24

Increased RANKL and decreased OPG

Question 25

What does vitamin D cause in terms of bone formation and resorption?

Answer 25

Increased RANKL

Question 26

What action does PTH have in the bone on Ca2+ and Pi?

Answer 26

Promotes osteoblastic growth and survival; regulates M-CSF, RANKL, and OPG production by osteoblast; sustained elevated levels of PTH shift the balance to a relative increase in osteoclast activity, thereby increasing bone turnover and reducing bone density

Question 27

What action does PTH have in the kidney on Ca2+ and Pi?

Answer 27

Stimulates 1-alpha-hydroxylase activity; stimulates Ca2+ reabsorption by the thick ascendinglimb of Henle's loop and the distal tubule; inhibits Pi reabsorption by proximal nephrons

Question 28

What action does PTH have in the small intestine and parathyroid gland on Ca2+ and Pi?

Answer 28

No direct actions

Question 29

What action does vitamin D have in the small intestine on Ca2+ and Pi?

Answer 29

Increases Ca2+ and Pi absorption

Question 30

What action does vitamin D have in bone on Ca2+ and Pi?

Answer 30

Sensitizes osteoblasts to PTH; regulates osteoid production and calcification

Question 31

What action does vitamin D have in the kidneys on Ca2+ and Pi?

Answer 31

Promotes Pi reabsorption by proximal nephrons; minimal actions on Ca2+

Question 32

What action does vitamin D have in the parathyroid glands on Ca2+ and Pi?

Answer 32

Directly inhibits PTH gene expression; directly stimulates CaSR gene expression

Question 33

What are the actions of calcitonin on Ca2+ and Pi?

Answer 33

Decreased blood Ca2+ and Pi concentrations by inhibiting bone resorption (only at high circulating levels of hormone); decreased activity and number of osteoclasts; major stimulus is increased plasma Ca2+ concentration

Question 34

What does a thyroidectomy cause?

Answer 34

Decreased calcitonin but no effect in Ca2+ metabolism

Question 35

What does a thyroid tumor cause?

Answer 35

Increased calcitonin but no effect in Ca2+ metabolism

Question 36

What is vitamin D dependent rickets type 1?

Answer 36

Decreased 1-alpha-hydroxylase

Question 37

What is vitamin D dependent rickets type 2?

Answer 37

Decreased vitamin D receptor

Question 38

What is osteomalacia?

Answer 38

Nutritional osteomalacia that could originate from either a GI disorder or suboptimal nutrition and inadequate sun exposure; could be suspected in cases of bone pain associated with malabsorption

Question 39

What are some clinical manifestations of osteomalacia?

Answer 39

Bone pain, muscle weakness, bone tenderness, fracture, muscle spasms, cramps, positive Chvostek's sign, tingling/numbness

Question 40

How can you treat osteoporosis?

Answer 40

Anabolic therapy (PTH) or antiresorptive therapy with bisphosphonates, estrogen, selective estrogen receptor modulators, calcitonin, RANKL inhibitors