Parathyroid

Question 0

Where is most of the calcium stored in the body?

Answer 0

-Skeleton

Question 1

What is the normal range of serum calcium and what propotion of this is biologically active?

Answer 1

• 2.2-2.5mM total

- 1-1.3mM biologically active

Question 2

What are the functions of calcium?

long list

Answer 2

• Builds and maintains teeth and bones
• Regulates heart rhythm
• Helps regulate nutrient uptake
• Assists in normal blood clotting
• Helps maintain nerve and muscle function
• Lowers blood pressure
• Important in normal kidney function
• Needed for activity of some enzymes and some hormone receptor binding
• Reduces blood cholesterol
• Important in intracellular signalling
• Appropriate levels required for nerve transmission at NMJ

Question 3

In what form is calcium stored in bone?

Answer 3

-Hydroxyapatite crystals

Question 4

How much calcium is exchanged between bone and ECF per day?

Answer 4

-300-600mg

Question 5

What is the major rapid short-term regulator of calcium?

Answer 5

-Parathyroid hormone

Question 6

How does PTH increase calcium levels?

Answer 6

• Stimulate Ca2+ release from bone; in part by stimulating bone resorption
• Decreases urinary loss of Ca2+ by stimulating reabsorption from the kidney
• Indirectly stimulates Ca2+ absorption in the small intestine by stimulating the synthesis of active vitamin D in the kidney
• Decreases Ca2+ excretion causing increased P excretion

Question 7

How is PTH controlled?

Answer 7

-Negative feedback of calcium and phosphate
Calcium
-High calcium levels in ECF binds to the Ca receptor on parathyroid cells
-Receptor activation leads to inhibition of PTH release
-Fall in Ca levels means that there is less Ca to bind to ca receptors on parathyroid cells
-PTH released
Phosphate
-High phosphate levels leads to increased PTH secretion in order to excrete phosphate

Question 8

Describe the actions of PTH on bone

Answer 8

• PTH induces osteoblastic cells to synthesis and secrete cytokines
• Cytokines stimulate differentiation and activity of osteoclasts and also protect them from apoptosis
• PTH also decreases osteoblast bone-synthesising activity exposing the bony surface to osteoclasts
• Resorption of mineralised bone and release of Ca2+ into ECF

Question 9

What is an indicator of high bone turnover?

Answer 9

-Alkaline phosphatase

Question 10

Describe the actions of PTH on the kidney

Answer 10

• Affects tubular cells within the kidney (predominantly DCT) causing an increase in reabsorption of Ca2+ from the ascending limb and DCT
• Thus calcium excretion is reduced

Question 11

Why does Phosphate need to be excreted if the levels of calcium are increased?

Answer 11

-To prevent kidney stone formation

Question 12

What effect does PTH have on vitamin D

Answer 12

-Stimulates the synthesis of active vitamin D

Question 13

Why is vitamin D important in calcium regulation?

Answer 13

-Active vitamin D increase Ca2+ uptake in the gut by activating transcellular uptake of vitamin D by active transport (Usually only 30% of the ca in the gut is absorbed by paracellular uptake)

Question 14

What type of regulator is vitamin D on calcium?

Answer 14

-Long-term

Question 15

What is the chemical name for the vitamin D group?

Answer 15

-Hydroxycholecalciferols

Question 16

What is the chemical name for active vitamin D?

Answer 16

-Dihydroxycholecalciferol or calcitriol

Question 17

How is active vitamin D synthesised?

Answer 17

• Vitamin D undergoes two hydroxylation reactions to form calcitriol
• The first hydroxylation is in the liver on C25 and forms 25-hydroxycholecalciferol
• The second hydroxylation is at C1 and occurs in the kidney forming 1,25-dihydroxycholecalciferol

Question 18

Do both hydroxylation reactions of vitamin D occur at the same time?

Answer 18

-No the first hydroxylation occurs in the liver and then 25-hydroxycholecalciferol circulates in the blood for 15-20 days

Question 19

What causes the second hydroxylation of 25-hydroxycholecalciferol?

Answer 19

-Upon being filtered through the kidney, if there are high PTH levels then the 25-hydroxycholecalciferol will undergo the second hydroxylation to form active vitamin D (calcitriol)

Question 20

What type of control is the second hydroxylation of vitamin D? Explain this

Answer 20

• Negative feedback
• If there is low calcium, PTH is stimulated which is detected in the kidney resulting in the second hydroxylation. When calcium levels rise, PTH levels fall. This is detected by the kidney and the second hydroxylation of Vitamin D stops

Question 21

What are the effects of calcitriol?

Answer 21

• Stimulates transcellular uptake in the gut via active transport at the apical membrane and endocytosis at the basolateral membrane
• Stimulates bone resorption same as PTH
• Effects the kidney by decreasing Ca2+ excretion

Question 22

Where is calcitonin secreted from and what is its function?

Answer 22

• Parafollicular cells of the thyroid
• Involved in Ca2+ regulation however has minimal effect in humans (extensive effect in animals)
• May become important during pregnancy

Question 23

What is the normal response of the body to hypercalacaemia?

Answer 23

• Increase in plasma calcium
• Decreased PTH secretion (suppresses basal secretion)
• Kidney-> Decreased hydroxylation of 25-VitD causing decreased uptake from the gut; decreased calcium reabsorption
• Bone-> decreased resorption of bone and increased building of bone
• Plasma calcium levels fall

Question 24

What is the normal response of the body to hypocalacaemia?

Answer 24

- Decrease in plasma calcium - Increase in PTH secretion - Kidney-> increased hydroxylation of 25-VitD causing increased calciuim uptake from the gut; increased calcium reabsorption from kidney tubules - Bone-> increased bone resorption - Plasma calcium levels rise

Question 25

What are the signs and symptoms of hypocalcaemia?

Answer 25

``` -Hyper-excitability of NMJ leading to: Pins and needls Tetany (muscle spasms) Paralysis Convulsions -Death ```

Question 26

Why does hypocalcaemia effect bone?

Answer 26

-Serum calcium is the priority so if calcium is deficient in the diet, serum calcium is maintained at the expense of bone

Question 27

Name a metabolic bone disease associated with hypocalcaemia

Answer 27

- Rickets in children | - Osteomalacia in adults

Question 28

What is hypoparathyroidism?

Answer 28

-Decreased PTH levels meaning that serum calcium cannot be maintained so life-threatening hypocalcaemia develops VERY RARE

Question 29

What is the main cause of hypoparathyroidism?

Answer 29

-Surgical removal of parathyroid glands during thyroidectomy

Question 30

What are the signs and symptoms of hypercalcaemia?

Answer 30

- Renal calculi (stones) - Kidney damage due to high reabsorption - Constipation due to high levels in the gut - Dehydration - Tiredness - Depression

Question 31

What is the main cause of hypercalcaemia?

Answer 31

-Hyperparathyroidism usually caused by a parathyroid adenoma

Question 32

Why can tumours not associated with the parathyroid gland cause hypercalcaemia?

Answer 32

-Tumours can secrete PTHrp which behaves like PTH

Question 33

What is the usual cause of PTHrp?

Answer 33

-Metastases

Question 34

Why does PTHrp not cause increased activation of vitamin D?

Answer 34

-Unlike PTH, PTHrp does not increase the activity of C1-hydroxylase, the enzyme responsible for the second hydroxylation of 25-VitD in the kidney

Question 35

Name a tumour which can secrete PTHrp?

Answer 35

-Squamous cell carcinoma in the lung