Lecture 20: Parathyroid, Calcium

Question 1

Calcium regulation

Answer 1

Maintains larger EC vs smaller IC gradient
- Excitat.-contract. coupling
- Synpase transmis.
- Platelet aggreg./coag.
- IC ion for secondary message., cofactor, motility/exocytosis

Question 2

Acute hypocalcemia

Answer 2

Increased excitability -> hypocalcemic tetany
- Low plasma Ca -> lower AP threshold
- Due to PTH/Vit. D deficiency

Question 3

Hypercalcemic crisis

Answer 3

• Plasma Ca > 14 mg/dL; primary hyperparathyroidism
• Decreased excit. -> lethargy, fatigue, arrythmia; osteoporosis
• High Ca inhibs volt-gate Na channels
• Req. bone loss inhibs

Question 4

Calcium distribution

Answer 4

• 99% in bone reservoir
• Freely filtered and then reabsorbed
• Diet req. for Ca balance

Question 5

Osteoporosis

Answer 5

Low bone mass due to age, menopause (low E), lack of exercise

Question 6

Vit. D metabolism

Answer 6

• Intake from diet or synth. from cholesterol via UV
• Activation in liver/kidney to calcitriol; kidney 1-alpha-hydroxylase
• Transport by Vit. D Binding Protein

Question 7

Vit. D effects

Answer 7

Overall: provide Ca, PO4 to ECF
Gut: upreg. absorption
Kidney: upreg. reabsorption + activation
- Low Ca, PO4 stim. 1alpha-hydroxylase (Vit. D neg fb)
Bone: PTH synergy -> mobilize Ca, PO4; w/o PTH -> promote new bone mineralization
Parathyr.: downreg. pre-pro-PTH synth.

Question 8

Vit. D effects on GI

Answer 8

Increase Ca, PO4 absorption:
1. Upreg. Na/PO4 apical transporter + basal Na/K ATPase
2. Upreg. apical Ca channels + basal Ca/Na exchanger
3. Upreg. calbindin; enhance gradient

Question 9

24-hydroxylase

Answer 9

Shuttles Vit. D precursor to inactive Vit. D

Question 10

Rickets

Answer 10

Low bone density, curved limb bones due to Vit. D deficiency

Question 11

Vit. D on bone

Answer 11

Synergy w/ PTH to drive resorption by stim. Obl RANKL release -> Ocl activation

Question 12

PTHrP

Answer 12

PTH-related peptide, produced by other tissues e.g. in certain cancers
Binds PTH-Rs -> hypercalcemia -> downreg. PTH

Question 13

PTH synthesis, storage, secretion

Answer 13

Calcium Sensing Receptor (CaSR) on PT cells inhibs. PTH release
- PTH synth. as pre-pro-peptide; continuous synth. + release but can be pulsatile
- Vit. D downreg. pre-pro-PTH synth.
- PO4 -> stim. PTH secretion

Question 14

PTH effects

Answer 14

Overall: make Ca available, elim. PO4
Bone: mobilize Ca, PO4 (Vit. D synergy); time dpdt Obl, Ocl formation increase
Kidney: upreg. renal Ca reabsorption, PO4 excretion
GI: indirect Ca absorption increase

Question 15

PTH renal effects

Answer 15

Stim. only at DT; low capacity system
PTH blocks Na/PO4 cotransport in PCT -> PO4 excretion

Question 16

PTH on bone

Answer 16

W/ Vit. D -> stim Obl RANKL, M-CSF driving Ocl differentiation
- Cortisol also stims. RANKL

Question 17

Osteoprotegrin

Answer 17

Estrogen stims. OPG release from Obls for neg. reg. of Ocls

Question 18

Time dependent bone action of PTH

Answer 18

Intermittent PTH pulses -> bone formation
Short term secretion (2-3 hrs) -> resorption dominates
Long term continuous -> bone resorption (osteoporosis risk)

Question 19

Bisphosphonates

Answer 19

Cover bone surface and directly inhib. Ocls to inhib bone loss

Question 20

Calcitonin

Answer 20

Antagonist of PTH, Vit. D
- Produced by parafollicular C cells of thyroid
- Peptide hormone
- Upreg. Ca excretion, stim. 24alpha-hydroxylase for calcitriol breakdown
- Binds Ocl receptors -> inhib. resorption
Less important minute to minute vs PTH