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Flashcards in mineral metabolism Deck (29):
1

Roles of Calcium

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

2

Ca compartmentalization in body

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.

3

What maintains the level of cytosolic Ca

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

4

How much Ca does the kidney filter per day

10g- 98% of this is reabsorbed

5

Overall Ca balance

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

6

Roles of phosphate

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

7

What proportion of serum phosphate exists in free ionized active form

85%

8

Overall Phosphate balance

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

9

Overall function of parathyroid hormone

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

10

PTH actions on bone

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)

11

PTH actions on kidney

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

12

PTH actions on GI tract

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

13

Regulation of PTH release

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

14

Calcitonin regulation

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

15

Calcitonin actions

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

16

Synthesis of Vitamin D

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

17

24,25 (OH)2 Vitamin D

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

18

Transport of Vitamin D

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

19

Actions of Vitamin D

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

20

Regulation of Vitamin D synthesis

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.

21

Short term regulation of serum Ca

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.

22

Long term regulation of serum Ca

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

23

Primary hyperparathyroidism- causes and Sx

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

24

Causes of secondary hyperparathyroidism

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

25

Primary Hypoparathyroidism

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)

26

Test for hypoparathyroidism

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

27

Hypoparathyroidism treatment

Vitamin D and Ca supplements

28

Vitamin D deficiencies

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

29

Vitamin D excess

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