Regualtion Of Calcium And Phosphate

Question 1

What are the signs of hypercalcemia?

Answer 1

Decreased QT interval, hyporeflexia, polyuria, poludipsia

Question 2

What does hypocalcemia do to the membrane potential?

Answer 2

Reduces activation threshold of Na+ channels. These are Ca+ dependent Na+ channels. Ca2+ normally inhibits them.

Question 3

What does hypercalcemia due to the membrane potential?

Answer 3

Increase activation threshold (more negative), makes it harder to elicit an action potential

Question 4

What does academia do to free ionized calcium levels?

Answer 4

Increases free ionized calcium concentration due to less Ca2+ bound to albumin

Question 5

What does alkalemia due to free ionized Ca2+ levels?

Answer 5

Decrease free ionized Ca2+.

Question 6

What three hormones regulate Ca2+?

Answer 6

PTH, Calcitonin, Vit. D,

Question 7

What is the relationship between Phosphate and Calcium concentrations?

Answer 7

Inverse.

Question 8

Increase in extracellular Ca2+ concentration inhibits PTH release via what molecular sensor?

Answer 8

CaSR. Inhibits PTH gene expression and PTH exocytosis.

Question 9

What are the actions of PTH?

Answer 9

Increase serum calcium and decrease serum phosphate.

Question 10

What are the actions of PTH on bone, kidney, and intestine?

Answer 10

Bone-> incrase resorption
Kidney-> decrease phosphate reabsorption, increase Ca2+ reabsorption, increase urinary cAMP
Intestine-> increase Ca2+ absorption via Vit D.

Question 11

What is the second messenger for PTH?

Answer 11

CAMP

Question 12

PTH stimulates what gene expression in response to low calcium concentration?

Answer 12

CYP1-alpha. This increases the activity of 1 alpha-hydroxylase.

Question 13

what cell type of bone are PTH receptors located on?

Answer 13

Osteoblasts

Question 14

What are the short term and long term actions of PTH on bone?

Answer 14

Short term-> bone formation via direct action on osteoblast.

Long term-> increase bone resorption via indirect action of osteoclasts mediated by cytokines released from osteoblasts.

Question 15

Vit D and PTH both have what effect on bone?

Answer 15

Bone resorption.

• but Vit D increases phosphate reabsorption and PTH decreases it*

Question 16

What is the primary mediator of osteoclast formation?

Answer 16

RANKL ( receptor activator for NF-kappaB ligand)

Question 17

What is Osteoprotegrin?

Answer 17

Soluble protein produced by osteoblasts, decoy receptor for RANKL. Inhibits RANKL/RANK interaction.

Question 18

What is the mechanism of action of PTH on the proximal tubule in relation to phosphate?

Answer 18

Decrease uptake by inhibiting the Na+/phosphate cotransporter on the basolateral membrane. This will also cause the increase in cAMP in the urine.

Question 19

What are the actions of Vit D on the kidney?

Answer 19

Ca2+ and phosphate reabsorption

Question 20

What is the mechanism of action of Vit D on the intestine for Calcium reabsorption?

Answer 20

• Increase phosphate reabsorption via the Na/ phosphate cotransporter (luminal side).
• Increase Na/ Ca antiporter on the basolateral side.
• Also incrase active transport of Ca on basolateral side.

-Actions are is Calbindin protein

Question 21

Where does PTH stimulate Ca2+ reabsoprtion in the kidney?

Answer 21

Distal Tubule.

Question 22

What are the actions of calcitonin on bone and kidney?

Answer 22

• inhibits bone resorption thus decreasing Ca2+ and phosphate levels.
• major stimulus for release in increased serum Ca2+.

Question 23

What is the effect of estradiol -17beta on Ca2+ and phosphate in the blood?

Answer 23

-stimulates intestinal Ca2+ absorption and renal tubular Ca2+ reabsorption.

Question 24

What is estrogens effect on osteoblasts and osteoclasts?

Answer 24

-Stimulates osteoblasts survival and osteoclast apoptosis

Question 25

What are the effects of adrenal glucocorticoids on Ca2+ regulation?

Answer 25

-Promote bone resorption and renal Ca2+ wasting. Also inhibit intestinal Ca2+ absorption.

Question 26

What are the findings for PTH, Ca2+, Pi, and Vit D levels for Primary hyperparathyroidism?

Answer 26

``` PTH- high Ca2+- high Pi- low Vit D- high -also increased bone resorption. ```

Question 27

What are the levels of PTH, Ca2+, Pi, and Vit D for Secondary hyperparathyroidism (Renal cause and Vit D deficiency)?

Answer 27

``` Renal: PTH- high Ca2+- low ( due to Ca2+ completing with phospahte) Pi- high Vit D- low Vit D deficiency: PTH-high Ca2+- low Pi- low Vit D- low ```

Question 28

What are the levels of PTH, Ca2+, Pi, Vit D in Hypoparathyroidism?

Answer 28

PTH- low Ca2+- low Pi- high Vit D- low

Question 29

What is the etiology of Albright hereditary osteodystropy?

Answer 29

-Inherited autosomal dominant disorder, Gs for PTH in bone and kidney is defective.

Question 30

What are the levels of PTH, Ca2+, Pi, Vit D in Albright hereditary osteodystropy?

Answer 30

PTH- high Ca2+- low Pi- high Vit D- low

Question 31

What is the etiology of Humoral hypercalcemia of malignancy?

Answer 31

PTH-related peptide,produced by a tumor, can bind to the same receptor as PTH and stimulate it.

Question 32

What are the levels of PTH, Ca2+, Pi, and Vit D in humoral hypercalcemia of malignancy?

Answer 32

PTH- low Ca2+- high Pi- low Vit D- low

Question 33

What is the etiology of familial hypocalcuiric hypercalcemia?

Answer 33

Autosomal dominant disorder. Mutation that inactivates CaSR and leads to increased release of PTH

Question 34

What are the levels of serum Ca2+, urine Ca2+, in familial hypocalcuiric hypercalcemia?

Answer 34

Serum calcium- increased | Urine calcium- decreased

Question 35

What is the cause of Rickets?

Answer 35

- Insufficient amount of Ca2+ and Pi are available to mineralize growing bone. - Characterized by growth failure and skeletal deformities

Question 36

What is osteomalacia?

Answer 36

New bone fails to mineralize. Characterized by bending and softening of weight-bearing bones.

Question 37

What is the deficiency in vitamin D-dependent rickets type 1?

Answer 37

1 alpha- hydroxylase

Question 38

What is the deficiency in vitamin D-dependent rickets type 2?

Answer 38

Vitamin D receptor.

Question 39

What are the symptoms of hypocalcemia?

Answer 39

- Hyperflexia, spontaneous twitching, tingling, numbness. | - positive Chvostek sign and trousseau sign