Parathyroid and regulation of calcium (L8)

Question 1

Important physiologic processes involving calcium (6)

Answer 1

Membrane stability and cell function
Hormone secretion
Bone structure/formation
Blood coagulation
Muscle function
Neuronal transmission

Question 2

Important physiologic processes involving phosphate (5)

Answer 2

Cellular energy (ATP)
Intracellular signalling pathways
Nucleic acid backbone
Bone structure
Enzyme activation/deactivation

Question 3

Indicator of free calcium availability

Answer 3

Calcium bound to albumin minus the concentration of albumin

Question 4

Two primary regulators of calcium concentration

Answer 4

Parathyroid hormone and vitamin D/calcitriol

Question 5

Daily calcium turnover in humans

Answer 5

1000 mg intake
Half absorbed in the intestines
Some also excreted
Net ~200 mg absorption
~200 mg excreted in urine

Question 6

Chief cells of parathyroid gland

Answer 6

Synthesize PTH

Question 7

Oxyphil cells

Answer 7

Unknown function, increase with age

Question 8

1-84 fragment

Answer 8

Half life of 4 minutes, clinically important for measurement

Question 9

N-terminal fragment

Answer 9

1-34: biologically active

Question 10

C-terminal fragment

Answer 10

35-84: has longer half life than others, but is inactive

Question 11

Parathyroid hormone related peptide

Answer 11

Mimics action of PTH in bone and kidney

Question 12

Physiologic concentration of PTHrP

Answer 12

Normally very low, doesn’t affect Ca2+ concentrations; however, some tumors secrete it and cause hypercalcemia

Question 13

Primary parathyroid hormone receptor

Answer 13

PTH1R, present in the osteoblasts and kidneys

Question 14

Second messengers of PTH1R

Answer 14

Adenylyl cyclase/cAMP pathway

IP3/DAG pathway

Question 15

To what does the PTH1R bind?

Answer 15

1-34 fragment, 1-84 fragment, PTHrP

Question 16

PTH2R

Answer 16

Only binds to 1-34 fragment, function is unclear

Question 17

Net effects of PTH on the bones and kidney

Answer 17

Increases plasma Ca2+ concentration, decreases plasma Pi concentration

Question 18

How much of the body’s calcium is in the bone?

Answer 18

99%

Question 19

PTHR expression on bone cells

Answer 19

Present on osteoblasts, but not on osteoclasts

Question 20

Difference in derivation between osteoclasts and osteoblasts

Answer 20

Osteoblasts: from mesenchymal stem cells
Osteoclasts: from hematopoietic stem cells

Question 21

Osteocytes

Answer 21

Terminally differentiated from osteoblasts; make up most of the bone matrix

Question 22

M-CSF

Answer 22

Macrophage colony stimulating factor; stimulates differentiation of osteoclasts

Question 23

PTH stimulation of osteoclasts

Answer 23

INDIRECT through M-CSF

Question 24

RANK ligand

Answer 24

Leads to maturation of osteoclasts and bone resorption, stimulated by PTH

Question 25

Osteoprotegerin

Answer 25

Antagonist of RANKL

Question 26

Hormonal regulation of OPG

Answer 26

Estrogens stimulate; glucocorticoids inhibit

Question 27

How does the osteoclast resorb bone?

Answer 27

Releases H+ and acid proteases into the lacuna, dissolving bone mineral and hydrolyzing bone matrix proteins

Question 28

PTH stimulates what gene in the kidney?

Answer 28

CYP1alpha, which encodes for 1alpha-hydroxylase

Question 29

1-alpha-hydroxylase

Answer 29

Converts Vitamin D3 into its active form

Question 30

What does PTH do to the infrastructure in the kidney?

Answer 30

Stimulates insertion of calcium protein channels into the apical membrane of distal tubule

Question 31

PTH effect on phosphate in the kidney

Answer 31

Reduces phosphate absorption in both proximal and distal tubules; greater in the proximal

Question 32

Calcium sensing receptor - location

Answer 32

Located in chief cells, kidney tubules, and C cells

Question 33

What does CaSR do?

Answer 33

Binds ionized calcium, inhibits PTH synthesis at the promoter level, and degrades existing PTH

Question 34

What does Vitamin D3 do?

Answer 34

Binds VDR, inhibits PTH synthesis at the promoter level, and stimulates CaSR transcription

Question 35

Calciferol

Answer 35

Refers to vitamin D in all its forms

Question 36

Cholecalciferol

Answer 36

Directly refers to vitamin D3

Question 37

Calcidiol

Answer 37

25-hydroxyvitamin D3; immediate precursor

Question 38

Calcitriol

Answer 38

1,25-dihydroxyvitamin D3 (active form)

Question 39

Ergocalciferol

Answer 39

Vitamin D2 from vegetables

Question 40

Synthesis of vitamin D3 in the skin

Answer 40

Precursor hormone 7-dehydrocholesterol is converted to cholecalciferol in the skin by UV light, then isomerized to form vit D3

Question 41

How is vitamin D transported to the liver?

Answer 41

Either directly through portal circulation or indirectly through chylomicron association

Question 42

Default pathway for vit D3 conversion

Answer 42

To the inactive form; 24,25-dihydroxyvitamin D3

Question 43

Factors driving conversion from inactive to active vitamin D3

Answer 43

Hypocalcemia or hypophosphatemia

Question 44

Direct effects of vitamin D3 on bone

Answer 44

Mobilize calcium from bone | Stimulation of osteoclast proliferation/differentiation

Question 45

Indirect effect of vitamin D3 on bone

Answer 45

Increases plasma calcium concentration, which promotes bone mineralization

Question 46

Effects of vitamin D3 on the intestines

Answer 46

Increases calcium absorption from duodenum | Increases phosphate absorption from small intestine

Question 47

Vitamin D3 and pathway of calcium reabsorption in the gut

Answer 47

Upregulates TRPV5/6 (apical membrane), calbindin (intracellular), and calcium ATPase pump (basolateral)

Question 48

Vitamin D3 and the pathway of phosphate reabsorption in the gut

Answer 48

Increases Pi-Na cotransporter

Question 49

Deficiency in vitamin D3 is linked to these conditions (6)

Answer 49

``` MS Asthma Major depressive disorder Colon/breast cancer CVD DMII ```

Question 50

Normal serum calcium range

Answer 50

8.8-10.3mg/dL

Question 51

Normal serum phosphate range

Answer 51

2.4-4.1mg/dL

Question 52

Urinary hydroxyproline

Answer 52

Evidence of enhanced bone resorption

Question 53

Osteoporosis definition

Answer 53

Decreased bone density, mostly in the trabeculae

Question 54

Causes of osteoporosis

Answer 54

Genetic, menopause (decreased estrogen), prolonged GC therapy/prolonged stress, low dietary calcium

Question 55

Treatment of osteoporosis

Answer 55

Estrogen replacement, bisphosphonates, calcitonin, vitamin D supplementation

Question 56

Primary hyperparathyroidism

Answer 56

Hyperplasia or carcinoma of the parathyroid, causing hypercalcemia and kidney stones

Question 57

Secondary hyperparathyroidism

Answer 57

Usually due to CRF; lack of vitamin D3 causes excess PTH from lack of inhibition

Question 58

Symptoms of hypoparathyroidism

Answer 58

Hypocalcemic tetany

Question 59

Chvostek's sign

Answer 59

Stimulation of facial nerve causes facial muscle twitching

Question 60

Rickets

Answer 60

Vitamin D deficiency in children that causes "bowing" of long bones and decreased bone strength

Question 61

Osteomalacia

Answer 61

Vitamin D deficiency in adults that causes decreased bone strength

Question 62

Calcitonin - location and length

Answer 62

Made in the C cells of the thyroid gland; 32 amino acids long

Question 63

What is the normal physiologic importance of calcitonin?

Answer 63

Unclear. Pathology/absence of C-cells does not alter calcium concentration

Question 64

Therapeutic use of calcitonin

Answer 64

Slows bone turnover and inhibits osteoclasts

Question 65

Paget disease

Answer 65

Localized regions of very high bone resorption rates and reactive sclerosis; cause unknown

Question 66

Escape phenomenon

Answer 66

Rapid downregulation of calcitonin receptors inhibits antiosteoclastic actions of calcitonin within a few hours; makes it a less effective treatment option