Parathyroid Flashcards
Where is most of the calcium stored in the body?
-Skeleton
What is the normal range of serum calcium and what propotion of this is biologically active?
- 2.2-2.5mM total
- 1-1.3mM biologically active
What are the functions of calcium?
long list
- 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
In what form is calcium stored in bone?
-Hydroxyapatite crystals
How much calcium is exchanged between bone and ECF per day?
-300-600mg
What is the major rapid short-term regulator of calcium?
-Parathyroid hormone
How does PTH increase calcium levels?
- 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
How is PTH controlled?
-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
Describe the actions of PTH on bone
- 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
What is an indicator of high bone turnover?
-Alkaline phosphatase
Describe the actions of PTH on the kidney
- 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
Why does Phosphate need to be excreted if the levels of calcium are increased?
-To prevent kidney stone formation
What effect does PTH have on vitamin D
-Stimulates the synthesis of active vitamin D
Why is vitamin D important in calcium regulation?
-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)
What type of regulator is vitamin D on calcium?
-Long-term
What is the chemical name for the vitamin D group?
-Hydroxycholecalciferols
What is the chemical name for active vitamin D?
-Dihydroxycholecalciferol or calcitriol
How is active vitamin D synthesised?
- 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
Do both hydroxylation reactions of vitamin D occur at the same time?
-No the first hydroxylation occurs in the liver and then 25-hydroxycholecalciferol circulates in the blood for 15-20 days
What causes the second hydroxylation of 25-hydroxycholecalciferol?
-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)
What type of control is the second hydroxylation of vitamin D? Explain this
- 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
What are the effects of calcitriol?
- 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
Where is calcitonin secreted from and what is its function?
- Parafollicular cells of the thyroid
- Involved in Ca2+ regulation however has minimal effect in humans (extensive effect in animals)
- May become important during pregnancy
What is the normal response of the body to hypercalacaemia?
- 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
