Ca-Phosphate Homeostatsis Pt 2

Question 1

What is the second renal action of PTH?

Answer 1

Complements the increase in plasma Ca that resulted from the combination of bone resorption and phosphaturia
Occurs in the distal convoluted tubule
The cAMP generated in the cells of the proximal tubule is exerted in urine (urinary cAMP)
Inhibition of NPT by PTH causes phosphaturia (increased excretion of Pi in urine)

Question 2

What is the action of PTH on the small intestine?

Answer 2

No direct actions

Indirectly via vitamin D

Question 3

What are the actions of PTH on bone?

Answer 3

Promotes osteoblastic growth and survival
Regulates MCSF, RANKL and OPG production by osteoblasts
Sustained elevated levels of PTH shift the balance to a relative increase in osteoclast activity thereby increasing bone turnover and reducing bone density

Question 4

What are the actions of PTH on the kidney?

Answer 4

Stimulates 1a-hydroxylase activity
Stimulates Ca reabsorption by the thick ascending limb of Henle’s loop and distal tubule
Inhibits Pi reabsorption by proximal nephrons (represses NPT2a expression)

Question 5

What are the actions of vitamin D on the small intestine?

Answer 5

Increase Ca and Pi absorption

Question 6

What are the actions of vitamin D on bone?

Answer 6

Sensitizes osteoblasts to PTH

Regulates osteoid production and calcification

Question 7

What are the actions of vitamin D on the kidneys?

Answer 7

Promotes Pi reabsorption by proximal nephrons (stimulates NPT2a expression)
Minimal actions on Ca

Question 8

What are the actions of vitamin D on the parathyroid glands?

Answer 8

Directly inhibits PTH gene expression and stimulates CaSR gene expression

Question 9

What is calcitonin?

Answer 9

Has primary actions on the bone and kidneys
Decreases blood Ca and Pi concentrations by inhibiting bone resorption (effect occurs only at high circulating levels of the hormone)
Calcitonin receptors are expressed on osteoclasts
Decreased activity and decreases number of osteoclasts
Major stimulus is increased plasma Ca
Secreted by thyroid gland
No role in the chronic (min to min) regulation of plasma Ca

Question 10

What effect does a thyroidectomy have on calcitonin?

Answer 10

Decreases calcitonin but no effect on Ca metabolism

Question 11

What effect do thyroid tumors have on calcitonin?

Answer 11

Increase calcitonin but no effect on Ca metabolism

Question 12

What role does estradiol-17-beta have on Ca and Pi metabolism?

Answer 12

Stimulates intestinal Ca absorption and renal tubular Ca reabsorption
One of the most potent regulators of osteoblasts and osteoclast function
Estrogen promotes survival of osteoblasts and apoptosis of osteoclasts; favoring bone formation over resorption

Question 13

What effect do the adrenal glucocorticoids have on Ca and Pi metabolism?

Answer 13

Promote bone resorption and renal Ca wasting and inhibit intestinal Ca absorption
Pts treated with high levels of a glucocorticoid can develop glucocorticoid induced osteoporosis

Question 14

What is primary hyperparathyroidism?

Answer 14

Caused by an adenoma on the parathyroid gland
Increases PTH secretion resulting in increase bone resorption (release of Ca and Pi), activation of vitamin D to cause Ca absorption in intestines, Pi excretion and increase Ca reabsorption in the kidneys
Results in hypercalcemia/hypophostatemia
Hypercalciuria (stones), increased bone resorption (bones) and constipation (groans)
Tx usually requires parathyroidectomy

Question 15

What are the concentrations of PTH, Ca, Pi and vitamin D during primary hyperparathyroidism?

Answer 15

Increase PTH, Ca and vitamin D

Decreased Pi

Question 16

What is secondary hyperparathyroidism?

Answer 16

Increase in PTH levels is secondary to low Ca in the blood
Low Ca in the blood may be caused by renal failure or vitamin D deficiency
Parathyroid glands are normal but stimulated to secrete PTH due to low Ca leading to chronic kidney disease and bone disease

Question 17

What are the concentrations of PTH, Ca, Pi and vitamin D in secondary hyperparathyroidism caused by renal failure?

Answer 17

Increased PTH and Pi

Decreased Ca and vitamin D

Question 18

What are the concentrations of PTH, Ca, Pi and vitamin D in secondary hyperparathyroidism caused by vitamin D deficiency?

Answer 18

Increased PTH

Decreased Ca, Pi and vitamin D

Question 19

What is hypoparathyroidism?

Answer 19

Causes include thyroid surgery, parathyroid surgery, autoimmune or congenital (less common)
Most sx are associated with decreased Ca including muscle spasm/cramping, numbness, tingling or burning esp around the mouth and fingers, seizures, poor teeth development in kids and mental deficiency
Tx: oral Ca supplement and active form of vitamin D
Decreased PTH, Ca and vitamin D (hypocalcemia)
Increased Pi (hyperphosphatemia)

Question 20

What is Albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)?

Answer 20

Inherited autosomal dominant disorder; Gs for PTH in bone and kidney is defective
Hypocalcemia and hyperphosphatemia develop
Increased PTH levels (PTH resistance) and Pi
Administration of exogenous PTH produces no phosphaturic response and no increased urinary cAMP
Decreased Ca and vitamin D

Question 21

What is the phenotype for Albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)?

Answer 21

Short stature, short neck, obesity, subcutaneous calcification, shortened metatarsals and metacarpals

Question 22

What is humoral hypercalcemia of malignancy?

Answer 22

Hypercalcemic syndrome associated with malignancy
PTH related peptide (PTHrP) is a peptide produced by tumors with close homology in the N terminal to PTH which binds and activates same receptor as PTH (type 1 PTH receptor)
Increases PTHrP levels and produces similar profile to primary hyperparathyroidism
Increased urinary Ca, increased urinary Pi, increased cAMP, increased blood Ca (hypercalcemia), decreased blood Pi (hypophosphatemia)
Different from primary hyperparathyroidism by decreased PTH levels and vitamin D

Question 23

What is familial hypocalciuric hypercalcemia (FHH)?

Answer 23

Autosomal dominant disorder
Cause: mutations that inactivate CaSR in parathyroid glands and parallel Ca receptors in the ascending limb of the kidney
Results in decreased urinary Ca excretion (hypocalciuria) and increase serum Ca (hypercalcemia)
Increased PTH and serum Ca

Question 24

What can impaired vitamin D metabolism cause?

Answer 24

GI disorders, chronic renal failure, Pi depletion can lead to changes in vitamin D metabolism
Can cause rickets in children or osteomalacia in adults

Question 25

What is rickets?

Answer 25

Insufficient amount of Ca and Pi are available to mineralized growing bone
Characterized by growth failure and skeletal deformities
Pseudovitamin D deficient rickets or vitamin D dependent rickets type 1 (decreased alpha hydroxylase meaning they cant form active vitamin D)
Pseudovitamin D deficient rickets or vitamin D dependent rickets type II (decreased vitamin D receptor meaning it cant exert its actions)

Question 26

What is osteomalacia?

Answer 26

Nutritional osteomalacia could originate from either a GI disorder or sub optimal nutrition and inadequate sun exposure (vitamin D deficiency)
Could be suspected in cases of bone pain associated with malabsorption (e.g. gastric bypass surgery)
Some clinical manifestations include bone pain and muscle weakness, bone tenderness, fracture, muscle spasms, cramps, a positive Chvostek’s sign and tingling/numbness

Question 27

What are the concentrations of different ions and hormones in vitamin deficiency?

Answer 27

Increased PTH (secondary), urine Pi and cAMP, increased bone resorption in osteomalacia
Decreased Ca and Pi
Low vitamin D

Question 28

What is osteoporosis?

Answer 28

Time dependent changes in bone mass that occur in both females and males
Occurs due to estrogen changes and menopause in females; testosterone in males

Question 29

What are some treatments for osteoporosis?

Answer 29

Anabolic therapy (PTH)
Anti-resorptive therapy such as bisphosphonates, estrogen, selective estrogen receptor modulators (SERMs, e.g. ralozifene, tamoxifen), calcitonin, RANKL inhibitors (denosumab)