Calcium and phosphate metabolism

Question 1

What and where are the body stores of calcium?

Answer 1

1.3kg, 99% skeleton, 1% intracellular, 0.1% ECF.

Question 2

What is the standard dietary intake and absorption of calcium?

Answer 2

Approx 25 mmol, with net absorption 3mmol

Question 3

Describe the turnover of calcium stores.

Answer 3

Bone turnover of 500mmol, with cell mediated bone turnover of 7mmol. GF (what is this????) 250mmol, reabsorbed 247mmol, 3mmol excreted.

Question 4

Where is calcium absorbed? What is active absorption dependant on?

Answer 4

There is active absorption in the duodenum and upper jejunum. This is dependant on calcitriol. A small amount of passive absorption occurs downstream.

Question 5

What inhibits calcium absorption?

Answer 5

Phosphates, oxalates, FA -> (??) form insoluble Ca2+ compounds.

Question 6

How is calcium found in the plasma?

Answer 6

45% is protein bound to albumin, 45% is ionised (active fraction and regulated (??), 10% is in various complexes.

Question 7

What is calcium binding to albumin dependant on?

Answer 7

pH. Acidosis causes decreased binding and therefore more free calcium. Alkalosis increases binding, makes less free calcium and increases risk of tetany.

Question 8

What is the effect of PTH on the kidney?

Answer 8

PTH stimulates reabsorption in the distal tubule.

Question 9

What occurs to calcium in the kidney?

Answer 9

Ionised and complexed calcium is filtered, with 99% reabsorbed. 60% in the proximal tubule, and 40% in the ascending limb of the loop of hence and the distal tubule.

Question 10

Describe the body stores of phosphate.

Answer 10

Total body stores of phosphate are 700g, with 85% in the skeleton and a significant amount in cellular molecules.

Question 11

What is the plasma concentration of phosphate?

Answer 11

1.2mmol/L but this varies.

Question 12

What is phosphate absorption dependant on?

Answer 12

Dietary intake, but calcitriol stimulates absorption.

Question 13

Describe urinary excretion of phosphate. What inhibits this?

Answer 13

85-90% of filtered phosphate is reabsorbed in the proximal tubule. This is inhibited by PTH.

Question 14

Describe the parathyroid glands.

Answer 14

Each parathyroid gland is a richly vascularised disk 3x6x2mm containing two types of cells; chief cells (majority) and oxyphil cells(minority).

Question 15

What is the role of chief cells?

Answer 15

Chief cells contain a prominent golgi apparatus, endoplasmic reticulum and secretory granules, and secrete PTH

Question 16

What is the role of oxyphil cells?

Answer 16

Oxyphil cells are larger than chief cells and have an unknown function.

Question 17

Where is PTH synthesised?

Answer 17

In the chief cells.

Question 18

Describe the synthesis and molecular makeup of PTH

Answer 18

Liner polypeptide with a molecular weight of 9500; 84AA. PreproPTH->EF->proPTH->PTH secretory granules.

Question 19

What is the normal plasma level and half life of PTH?

Answer 19

10-55pg/mL, t1/2 10mins, cleared by the kidneys.

Question 20

What stimulates increased secretion of PTH?

Answer 20

Low calcium low magnesium, high phosphate.

Question 21

What inhibits secretion of PTH?

Answer 21

High calcium, high magnesium, calcitriol.

Question 22

What are the actions of PTH?

Answer 22

PTH increases plasma Ca2+
Decreases plasma phosphate
??can cause a mild acidosis
Long term, PTH stimulates osteoblasts and osteoclasts

Question 23

How does PTH increase plasma calcium levels?

Answer 23

PTH acts directly on bone to increase bone resorption and mobilise calcium.
PTH also increases the reabsorption of calcium in the renal tubules, although if ??Ca2+ concentration is too high this system may be overwhelmed and renal secretion may increase.
PTH also increases the formation of 1,25 DHCC which increases GI Ca2+ reabsorption

Question 24

How does PTH decrease plasma phosphate?

Answer 24

PTH increases urinary phosphate excretion due to a decreased reabsorption of phosphate in the proximal tubules.

Question 25

What is the mechanism of action of PTH?

Answer 25

Probably via 3 different receptors: G2 coupled -> adenlylxxx? cyclase -> this increases intracellular cAMP

Question 26

What regulates secretion of PTH?

Answer 26

Circulating ionised calcium acts directly on the PTH glands in a negative feedback fashion. The key is a cell membrane Ca2+ receptor which when bound inhibits PTH secretion.

Question 27

If Ca2+ is high, ...... secretion is ...... and calcium is deposited in ....... . If Ca2+ is low, ....... is secreted, and ...... is mobilised.

Answer 27

PTH, inhibited, bones. PTH, calcium

Question 28

What is the effect of 1,25 DHCC on PTH secretion?

Answer 28

1,25 DHCC decreases preproPTH mRNA

Question 29

What effect does plasma phosphate have on PTH secretion?

Answer 29

Increased plasma phosphate stimulates PTH secretion.

Question 30

What other electrolyte is necessary?

Answer 30

Mg2+ is required. (How???)

Question 31

How is is calcitriol known?

Answer 31

vitamin D

Question 32

Describe the formation of calcitriol

Answer 32

Cholesterols ->UV light->vitamin D3 -> liver -> 25HC (T1/2 12 days) -> 1,25HC

Question 33

What stimulates the last step of calcitriol formation?

Answer 33

PTH, decreased plasma calcium, prolactin, GH, calcitonin, and ??decreased by opposites including acidosis

Question 34

What is the mechanism of action of calcitriol?

Answer 34

Calcitriol binds to nuclear receptors and modifies DNA/RNA

Question 35

What are the effects of calcitriol?

Answer 35

??Calcitriol increases GUT uptake of calcium, increases calcium reabsorption, increases osteocyte change, and provides negative feedback to PTH.

Question 36

Where is calcitonin synthesised?

Answer 36

In the parafollicular cells of the thyroid

Question 37

What stimulates calcitonin secretion?

Answer 37

increased calcium (??et al??)

Question 38

What is the caction of calcitonin? How?

Answer 38

Calcitonin decreases calcium and decreases phosphate, by inhibiting bone reabsorption and increasing urinary excretion.

Question 39

What other hormones affect calcium homeostasis?

Answer 39

Glucocorticoids, GH, thyroid hormones.

Question 40

How do glucocorticoids affect calcium homeostasis?

Answer 40

They inhibit bone formation and gut absorption (??through bit D)

Question 41

How does growth hormone affect calcium homeostasis?

Answer 41

Growth hormone stimulates Vit D formation leading to increased Ca2+ and increased phosphate.

Question 42

How do thyroid hormones affect calcium homeostasis?

Answer 42

Thyroid hormones can increase calcium levels and cause hypercalcuria and osteoporosis.

Question 43

What are the clinical features of hypercalcaemia

Answer 43

-Weakness and and constipation due to decreased muscular excitability -Polyuria due to inhibition of ADH, and dehydration (??) -Renal calculi, hypertension, caridac arrythmias, psychological disturbance Peptic ulceration from increased gastric acid secretion secondary to increased calcium.

Question 44

Describe the symptoms of primary hyperparathyroidism

Answer 44

stones (renal), bones, (GI) groans and (psychiatric) moans

Question 45

What are the clinical features of hypocalcaemia?

Answer 45

Tetany (from increased excitability), numbness, stridor, cataracts, psychological disturbances

Question 46

What are the causes of hypocalcaemia?

Answer 46

Transient post-op, pancreatitis, prolonged hypoparathyroidism, malabsorption and CRF

Question 47

What are the causes of hypercalcaemia?

Answer 47

Hyperparathyroidism, malignancy (PTHrP, multiple myeloma, bone metastasis), sarcoidosis (increased bit D), thiazide diuretics (stimulate calcium reabsorption), thyrotoxicosis, Paget's disease

Question 48

How does chronic renal failure affect calcium homeostasis

Answer 48

Chronic renal failure results in increased plasma phosphate, decreased vitamin d production, leading to a significant decrease in calcium. This causes secondary hyperparathyroidism, leading to increased bone reabsorption with increased ALP and ectopic calcification.

Question 49

What are the effects of a parathyroidectomy? What eponymous clinical signs are associated with this?

Answer 49

PTH is essential for life. Following a parathyroidectomy there is a steady decline in plasma calcium. Low plasma calcium causes neuromuscular hyper excitability and hypocalcaemic tetany. Symptoms usually develop 2-3 days postoperatively but may be delayed. Chvostek and Trousseau's signs.

Question 50

Describe Chvostek and Trousseau's signs

Answer 50

Chvostek: nerve hyperexcitability - tap facial nerve at angle of jaw and facial muscles on that side contract momentarily Trousseau: Inflate BP cuff to occlude brachial artery for 3 minutes. Without blood flow, hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm. The wrist and metacarpophalangeal joints flex, the DIP and PIP joints extend, and the fingers adduct.

Question 51

What causes PTH excess?

Answer 51

PTH injections, parathyroid adenomas.

Question 52

What characterises parathyroid excess (is this just primary hyperparathyroidism??)

Answer 52

Hypercalcaemia and hypophosphatemia

Question 53

PTHrP is produced by .. ..... of ....... and is necessary for ......

Answer 53

a number of tissues, survival

Question 54

Why is hypercalcaemia common in malignancy?

Answer 54

20% due to bone metastasis, or 80% due to high levels of PTHrP - breast, kidney, ovary, skin.