Calcium

Question 1

Why is it important for serum calcium levels to be maintained?

Answer 1

Calcium plays a critical role in many cellular processes:

• Hormone secretion
• Nerve conduction
• In/activation of enzymes
• Muscle contraction
• Exocytosis

Question 2

What is serum level of calcium maintained at?

Answer 2

Ca2+ (physiologically active form) maintained at 1.0 to 1.3mM, or 4.0 to 5.2mg/dl)

Question 3

How can calcium exist in plasma

Answer 3

• free ionised species that is bound to/associated with anionic sites on serum proteins (especially albumin)
• complexed with low-molecular-weight organic anions (e.g. citrate and oxalate)

Question 4

How is calcium and phosphate metabolism linked?

Answer 4

• Calcium and phosphate are the major components of hydroxyapatite crystals [Ca10(PO4)6(OH)2], which constitute the major portion of the mineral in bone.
• They’re regulated by the same hormones, primarily parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol) and, to a lesser extent, the hormone calcitonin.

Question 5

Which hormones control serum calcium levels?

Answer 5

• Parathyroid Hormone
• Calcitriol
• Calcitonin

Question 6

Where is parathyroid hormone secreted from?

Answer 6

-Parathyroid glands

Question 7

How is vitamin D converted into calcitriol?

Answer 7

• Hydroxylation

- C1-hydroxylase needed

Question 8

Where is calcitonin secreted from?

Answer 8

Parafollicular cells of the thyroid gland

Question 9

Describe how parathyroid hormone is regulated

Answer 9

-Changes in Ca2+ concentration alter PTH by negative feedback.
-Chief cells have unique G-protein calcium receptors on the cell surface. Increased Ca2+ binds to the G-protein receptors and stimulates Phospholipase C (PLC)
-adenylate cyclase inhibited
-reduced cAMP and reduced PTH release.

The reverse occurs when Ca2+ is low.

Question 10

How does parathyroid hormone affect renal function?

Answer 10

-PTH affects tubular cells within the kidney, increasing Ca2+ reabsorption in the distal convoluted tubule (DST).

-Pi is removed from circulation by inhibition of Kidney proximal tubule (PT) reabsorption, this prevents calcium stone formation.

Question 11

Where is vitamin D absorbed from?

Answer 11

-formed in the skin or absorbed from the gut

Question 12

What are the 4 forms of vitamin D and where are they found?

Answer 12

Vitamin D2- absorbed by gut (prohormone)

Vitamin D3- formed in skin by UV light (prohormone)

Calciferol- formed in liver by first hydroxylation of vitamin D (prohormone)

Calcitriol- formed in kidney after second hydroxylation

Question 13

Describe the condition of hypocalcaemia

Answer 13

Results in hyper-excitability in the nervous system, including the neuromuscular junction, leading to:

• paraesthesia (tingling sensation)
• then tetany (involuntary muscle contraction)
• paralysis
• convulsions.

-This is due to the low amount of Ca2+ bound to the NMJ membrane, allowing Na+ to depolarise it much more readily

Question 14

Describe the condition hypercalcaemia

Answer 14

• formation of kidney stones (renal calculi)
• constipation
• dehydration
• kidney damage
• tiredness
• depression.

Question 15

What is PTHrP?

Answer 15

• Parathyroid hormone related peptide (PTHrP) is a peptide hormone produced in tumours, which may lead to Hypercalcaemia. The measurement of PTHrP can be of assistance in determining the cause of an otherwise unexplained hypercalcaemia.
• PTHrP is secreted by some cancer cells leading to humeral hypercalcaemia of malignancy (HHM).
• Commonly in patients with breast/prostrate cancer and occasionally with myeloma.

Question 16

Which tissues do PTH and calcitriol act on?

Answer 16

• the bone
• the kidneys
• the gastrointestinal tr
• the actions of these hormones on calcium and phosphate are opposed.

Question 17

How PTH act on bones?

Answer 17

PTH increases the number and activity of osteoclasts. The increase in activity of already existing osteoclasts is the initial effect of PTH, and begins in minutes and increases over a few hours. Continued elevation of PTH levels increases the abundance of osteoclasts. This leads to a greater resorption of calcium and phosphate ions

Question 18

Describe the action of calcitonin

Answer 18

in animals lowers serum calcium but suggested only to preserve the maternal skeleton during pregnancy

Question 19

Describe the action of calcitriol

Answer 19

Increased Ca2+ absorption by binding to Ca2+ in the gut

note: PTH stimulates Calcitriol production by affecting activity of C1-Hydroxylase in kidney

Question 20

Describe the action of PTHrP

Answer 20

PTHrP is similar to PTH:

• ­calcium release from bone
• renal calcium resorption and renal phosphate excretion

However PTHrP does not increase C-1 hydroxylase activity and therefore does not increase calcitriol concentration.