Physiology: Calcium and Phosphate Homeostasis

Question 1

Calcium and Phosphate Depend on what organs?

Answer 1

1. Intestine
2. Skeleton
3. Kidneys

Question 2

Calcium Turnover

Answer 2

• free Ca is 10-7M; plasma 8.6-10.6 mg/dL
• intracellularly: stored in the ER, mitochondria, plasma membrane
• extracellularly: skeleton
• acidosis increases and alkalosis decrease ionized Ca in plasma
• normal intake: 1000 mg, almost all excreted
• maintain balance in bone and plasma

Question 3

Phosphate Turnover

Answer 3

• plasma 2.4-4.5 mg/dl
• intestinal absorption is relatively constant
• renal excretion important for maintaining plasma levels
• stored in soft tissue and skeleton
• plasma level related to bone turnover

Question 4

Bone Modeling Unit (Osteon)

Answer 4

Osteoblast - form bone
Osteocyte - transition cell
Osteoclast - breaks down bone

Question 5

Hormone effects on: Bone Formation

Answer 5

+: GH, Estrogen, Androgen, Vitamin D, Calcitonin

-: PTH, Cortisol

Question 6

Hormone effects on: Bone Resorption

Answer 6

+: PTH, Cortisol, TH

-: Estrogen, Androgen and Calcitonin

Question 7

Bone Formation:

Answer 7

• Osteoblasts synthesize collagen - osteoid
• Ca and PO4 are deposited on osteoid (combine with hydroxide and bicarbonate) - mineralize
• Mineralized bone surrounds Osteoblasts
• Osteocytes maintain contact with osteoblasts via canliculi
• Ca and PO4 are transported to outside of bone via syncytical processes

Question 8

Bone Resorption

Answer 8

• Destroys organic mass, removes calcium and phosphate
• Accomplished by giant Osteoclasts
• Destroyed bone is a site for osteoblastic activity and bone regeneration
• Bone remodeling is a continuous process
• Inadequate plasma Ca and PO4 levels result in loss of bone mass

Question 9

Vitamin D (Hormone)

Answer 9

Stimulates intestinal Ca and PO4 absorption and bone remodeling

Question 10

Synthesis and Regulation of Vitamin D

Answer 10

Skin (UV light) - 7-dehydrocholesterol
VitaminD (inactive form) from food
in Liver converted 25-OH Vit-D which goes to Kidney
In Kidney - converted to 24,25 partially active; 1,25 most active (1,25 negative feedback on Kidney)

Question 11

Regulation on Vitamin D

Answer 11

+: low levels of Ca and PO4 on Kidney

-: high levels of Ca and PO4 on 25-OH-Vit-D

Question 12

Functions of Vitamin D

Answer 12

Stimulate synthesis of Calbindin (calcium transfer)
Induces Ca channel at brush boarder on apical surface
Induces ATP Ca pump, Na/Ca exchanger on basolateral membrane
Stimulates intestinal phosphate, Mg absorption
Osteoid formation, increase bone density
Ca uptake by sarcoplasmic reticulum

Question 13

Parathyroid Glands

Answer 13

Single chain protein, regulates calcium concentration

Question 14

Synthesis and Secretion

Answer 14

• Synthesis in Chief cells as preproPTH
• Mature PTH formed in golgi apparatus - packaged in secretory granules
• Synthesis and release regulated by plasma ionized calcium
• High calcium induces hormone degradation

Question 15

Functions of PTH

Answer 15

• PTH induces release of Ca and PO4 from bone to plasma
• Ca is reabsorbed from kidney and intestine
• 1,25 (OH) Vit D has + feedback on absorption from the intestine and kidney
• PTH has + feedback on PO4 excretion

Question 16

Calcitonin:

Answer 16

Decrease plasma calcium

Antagonizes PTH

Question 17

Calcitonin: Synthesis and Secretion

Answer 17

• Peptide synthesized in parafollicular cells
• Regulated by plasma calcium via cAMP, gastrin
• Normal levels: 10-20 pg/ml

Question 18

Calcitonin Function:

Answer 18

• acts via cell surface receptors, cAMP
• inhibits osteoclastic activity, decrease plasma calcium
• decrease plasma phosphate concentration, increase urinary phosphate excretion