Calcium and phosphate regulation

What is the active form of Vitamin D3?

1,25-(OH)2-Vitamin D

What are the steps of calcium absorption?

1. Ca enters the enterocyte passively down the electrochemical gradient through a membrane-bound calcium channel. 2. Inside the cell, calcium binds to transporting protein, calbindin. 3. Some of the intracellular calcium is loaded into vesicles 4. The calcium-calbindin complexes diffuse throughout the cell. 5. An ATP powered pump moves Ca2+ out of the enterocyte and into the blood 6. A Na-Ca countertransporter also moves Ca out of the enterocyte 7. Vesicles containing calcium undergo exocytosis, moving calcium into the vascular compartment.

How much of blood calcium is bound to anions?

10%

What type of hormone is PTH? When is it secreted?

A peptide hormone. It is secreted by parathyroid chief cells in response to decreased plasma Ca2+. Low plasma Ca2+ also increases PTH synthesis and decreases its rate of degradation

What is the generalized relationship between serum calcium concentration and PTH levels?

An inverse relationship. As serum [Ca2+] decreases, PTH goes up.

How much of blood calcium is bound to plasma proteins?

About 40%

How much of blood calcium is free ionized calcium?

About 50%

What is the most critical action of Vitamin D?

Act on intestine to increase absorption of calcium and phosphate. Other actions are real but less important.

What does calcitonin act on to lower calcium levels?

Acts on bone to oppose the actions of PTH. CT inhibits osteolysis and reduces osteoclast activity, reducing the amount of Ca released.

Why PTH cause urine hydroxyproline to increase?

Because bone is being broken down in response to PTH.

What is CT's mechanism of action?

Binds to membrane receptors and activates secondary messenger system that alter enzyme activity.

What are the 3 main effectors involved in calcium regulation?

Bone - storage for calcium and phosphate GI tract - absorb calcium and phosphate Kidney - excretion of calcium and phosphate

How do the proximal and distal tubes respodn to PTH?

By increasing cAMP production

How is PTH removed from blood?

By the liver and kidneys, with a half life of about 2-4 minutes.

What two hormones act together to regulate calcium levels?

Calcitonin and PTH

Is calcitonin essential to maintaining homeostasis and life?

Calcitonin is important in maintaining bone mass but it is NOT necessary for life or homeostasis.

How does the proximal tube react to increased cAMP?

Decreases absorption of PO4

What is the mechanism of action of PTH?

Fixed membrane receptor system.

What stimulates the release of calcitonin?

Increase in plasma Ca2+

How does PTH act on the bones?

Increases breakdown of protein matrix and bone salts, decreases osteoblast formation, and increases osteoclast activity, releasing Ca2+ into the blood

What is the biological response to PTH?

Increases plasma [Ca2+] through its action on bone and kidneys (increases resorption). It also increases the production of vitamin D which increases GI absorption of Ca2+

What is the net effect of vitamin D?

Increases plasma calcium AND phosphate.

How does the distal tube react to increased cAMP?

Increases reabsorption of Ca2+

What determines calcium concentration in the blood?

Input/output: Diet vs excretion pH of the blood (determines how much is bound and unbound to plasma proteins. The more alkaline the blood, the greater the binding of Ca2+ to proteins)

What affect does vitamin D have on the kidneys?

It acts on the kidneys to reduce calcium loss.

What does calbindin allow the enterocyte to do?

It allows saturation of calcium without damage to the enterocyte.

What contribution does Vitamin D3 have to plasma Ca2+ concentration?

It contributes long term regulation of plasma Ca2+ by increasing intestinal absorption of ingested calcium.

What is calcitonin's role in calcium regulation?

It encourages bone formation and is a factor inhibiting kidney excretion of Ca2+

What is the mechanism of action of vitamin D3?

It enters the nucleus and alters transcription; increased synthesis of calbindin facilitates absorption

How does PTH act on the kidneys?

It increases Ca2+ reabsorption and decreases PO4-2 reabsorption, and increase glomerular filtration rate (rate of flow through the kidneys)

What kind of hormone is calcitonin? Which cells secrete it?

It is a peptide hormone that is secreted by C cells of the thyroid gland.

How is CT removed from blood?

It is removed by the kidneys, with a half life of about 10 minutes

How is vitamin D synthesized?

It is synthesized from a derivative of cholesterol. Vitamin D3 is synthesized on the skin with sunlight 25-(OH)-Vitamin D3 (calcidiol) is formed in the liver The active form, 1,25-(OH)2-Vitamin D3 (calcitriol) is formed in the liver.

What does PTH do to vitamin D?

It stimulates formation of Vitamin D, which increases intestinal absorption of Ca2+

What step of vitamin D synthesis is influenced/controlled by PTH?

PTH and low plasma [Pi] controls the final step of calcitriol, which is a hydroxylation step.

How quick is the response of PTH on the kidneys? On the bone? On formation of active vitamin D?

PTH has a fast effect on the kidneys (minutes) and a slower (hours) effect on bones and active vitamin D synthesis.

How does PTH activate osteoclast activity?

PTH stimulates osteoblasts to release signaling molecues (which function like paracrine agents) that stimulate quiescent osteoclasts and stimulate osteoclasts into increased activity. This causes increased blood calcium released from bone.

What are the three hormones that are involved in the regulation of calcium?

Parathyroid hormone (PTH) secreted by the parathyroid glands Vitamin D - Production from skin, liver, and kidney Calcitonin (CT) - Secreted by C cells of the thyroid

What kind of hormone is calcitonin?

Peptide hormone

What is the reason for phosphate regulation?

Phosphate has a role in metabolism Needed for ATP Phosphate levels modulate enzyme activity An important constituent of bone (where most phosphate is stored)

How does the body control/prevent random formation of CaPO4?

Physiological controls tend to cause [Ca2+] and [PO4-2] to vary inversely

Besides decreased resorption of PO42-, what else does PTH do to the proximal tubule?

Stimulates it to increase the activity of enzymes that creates the active form of Vitamin D3, a steroid hormone. Vitamin D3 acts on the GI tract to increase absorption of Ca2+

What gland and cell secretes calcitonin?

The C-cells of the thyroid gland (parafollicular cells)

What portion of proCT (procalcitonin) promotes bone formation and how?

The N-terminal fragment of proCT in vitro promotes bone formation by stimulating proliferation of osteoblasts. Ca is taken out of solution to build bone.

How does vitamin D increase calcium absorption?

The active form of Vitamin D, calcitriol, acts to increase the synthesis of calcium binding protein, and may also increase the synthesis of calcium transport protein. Calcitriol acts via a mobile receptor like most steroids.

How is calcium excretion controlled?

The kidney responds to CT and PTH

How is vitamin D3 removed from blood?

The kidneys remove it. The degradation products are excreted in bile, with 1/2 life of ~15 hours

What is the reason for calcium regulation?

To ensure normal: Excitation - it is used for muscle contraction Secretion and release of neurotransmitters. Ca2+ entry into presyanptic terminals triggers release of transmitter Membrane excitabilty (hypocalcemia results in hyperexcitibilty) Regulation of enzyme activity (Ca2+ is a second messenger) Bone formation

What is the primary function of calcitonin?

To preserve bone mass in the face of disturbances that would act to de-mineralize bone by decreasing plasma [Ca2+]

What affect does PTH have on phosphate control in the kidney?

Tubular reabsorption of phosphate falls due to increased reabsorption.

Why does PTH cause urine analysis to show decreased calcium, but then a quick and large increase in urine Ca levels?

Urine Ca initially decreases because of the action of PTH on the tubule (increased reabsorption), but excretion increases because the filtered load of Ca raises

What induces calbindin synthesis?

Vitamin D

What is the role of Vitamin D in calcium regulation?

Vitamin D plays a role in absorption, resorption, and inhibiting excretion (basically getting calcium).

What hormone controls the absorption of calcium in the GI tract?

Vitamin D, which is controlled by PTH

How much of the body's 1kg of calcium stored in bone is under hormonal (PTH, CT) control?

about 5%