mineral metabolism

Question 1

Roles of Calcium

Answer 1

The first is a structural role, since it is a major constituent of the mineral matrix of bone. The second is a biochemical role. Calcium is an essential regulator of excitation-contraction coupling, stimulus-secretion coupling, blood clotting, membrane excitability, cellular permeability and other metabolic functions

Question 2

Ca compartmentalization in body

Answer 2

1. Bone- 99% of body calcium in the form of hydroxyapatite. 2. Intracellular - 10g total. 50-100nM free cytosolic Ca. 3. Extracellular- 2.5mM total. 50% is free and filtered by kidneys, 10% as salts which are filtered by kidney, the rest is bound to albumin.

Question 3

What maintains the level of cytosolic Ca

Answer 3

Intracellular mobile calcium buffers, compartmentalization into ER calcium stores, by an ATP linked calcium pump and a Na/Ca antiporter.

Question 4

How much Ca does the kidney filter per day

Answer 4

10g- 98% of this is reabsorbed

Question 5

Overall Ca balance

Answer 5

amount consumed = amount removed via feces (83%) and urine (17%). Ther is also a fast exchange of up to 20g/day btw the ECF and labile bone mediated by osteocytes

Question 6

Roles of phosphate

Answer 6

Phosphate plays a structural role, since it is part of the mineral matrix of bone. In addition, it is a common intracellular buffer. It is required for phosphorylation reactions, which transfer energy from one compound to another as well as regulate cellular functions

Question 7

What proportion of serum phosphate exists in free ionized active form

Answer 7

85%

Question 8

Overall Phosphate balance

Answer 8

amount consumed= amount lost in feces (36%) and urine (64%). There is a balance btw bone formation and resorption

Question 9

Overall function of parathyroid hormone

Answer 9

increases plasma calcium and decreases plasma phosphate by acting on bone, kidney and GI tract

Question 10

PTH actions on bone

Answer 10

Rapid effect: increased efflux of labile bone calcium, not accompanied by phosphate. Slow effect: increased bone remodeling, releases both calcium and phosphate (seen mainly in pathological conditions)

Question 11

PTH actions on kidney

Answer 11

Increased calcium reabsorption in distal tubule, Decreased phosphate reabsorption, Increased synthesis of 1,25 (OH)2 Vitamin D

Question 12

PTH actions on GI tract

Answer 12

Indirect via Vitamin D, which enhances calcium absorption-requires 1 day

Question 13

Regulation of PTH release

Answer 13

PTH secretion is stimulated by a fall in the free ionized calcium in the plasma and inhibited by a rise in free ionized Ca in plasma

Question 14

Calcitonin regulation

Answer 14

It is secreted in response to elevated calcium as well as certain GI hormones such as gastrin, cholecystokinin, secretin and glucagon.

Question 15

Calcitonin actions

Answer 15

It acts on bone to decrease efflux oflabile bone calcium. Requires high levels to see an effect

Question 16

Synthesis of Vitamin D

Answer 16

7-Dehydrocholesterol in skin + sun > Vitamin D (inert) > 25-OH Vitamin D in liver > 1,25 (OH)2 Vitamin D in kidney catalyzed by 1-hydroxylase > 1,25 (OH)2 Vitamin D is the active form

Question 17

24,25 (OH)2 Vitamin D

Answer 17

formed in the kidney by 24-hydroxylase. It is inactive

Question 18

Transport of Vitamin D

Answer 18

Vitamin D is mostly transported in the blood bound to transcalciferin.

Question 19

Actions of Vitamin D

Answer 19

GI tract: Increases synthesis of Ca binding protein which increases Ca and Phosphate absorption. Bone: Mobilizes Ca from bone, possibly by sensitizing bone to PTH actions

Question 20

Regulation of Vitamin D synthesis

Answer 20

1. 1,25 (OH)2 Vitamin D negatively feedsback on 1-hydroxylase. 2. PTH: high PTH increases 1-hydroxylase activity and decreases 24-hydroxylase activity. Low PTH has the opposite effect. 3. phosphate: decreased phosphate increases 1-hydroxylase and decreases 24-hydroxylase activity.

Question 21

Short term regulation of serum Ca

Answer 21

Minute-to-minute regulation of Ca is carried out by PTH which mobilizes Ca into plasma. Also, calcitonin may be useful in increasing rate of storage of acute Ca load.

Question 22

Long term regulation of serum Ca

Answer 22

Vitamin D is most important - regulation of intestinal absorption of Ca and phosphate. If body stores are low, Vitamin D will increase absorption

Question 23

Primary hyperparathyroidism- causes and Sx

Answer 23

Increased PTH increases calcium levels in plasma and urine (leading to renal stones). Hypercalcemia causes muscle weakness, depression, GI disorders, bone pain/fractures

Question 24

Causes of secondary hyperparathyroidism

Answer 24

Any disorder where plasma calcium is low such as rickets and renal failure lead to elevated PTH

Question 25

Primary Hypoparathyroidism

Answer 25

Decreased PTH causes decreased plasma Ca levels leading to increased neuromuscular excitability that can cause muscle cramps, seizures and mental changes. Bone demineralization is not a problem b/c there is increased serum phosphate (increased reabsorption from kidneys)

Question 26

Test for hypoparathyroidism

Answer 26

Chvosteks sign- tap the facial nerve and it evokes facial muscle spasms

Question 27

Hypoparathyroidism treatment

Answer 27

Vitamin D and Ca supplements

Question 28

Vitamin D deficiencies

Answer 28

This condition is called rickets in children and osteomalacia in adults. Rickets can lead to severe skeletal deformities whereas symptoms of osteomalacia can include bone pain and pathological fractures. Seen in liver diseases, renal dysfunction and rarely dietary deficiencies

Question 29

Vitamin D excess

Answer 29

Ingestion of large quantities of Vit D causes hypercalcemia leading to muscle weakness, depression, GI disorders, bone pain/fractures and calcification of soft tissues