Calcium and Phosphorus Homeostasis

Question 1

What do calcium phosphate salts in bone provide?

Answer 1

Structural integrity

Question 2

What are calcium ions in ICF and ECF responsible for?

Answer 2

Neuromuscular excitability
Blood coagulation
Hormonal secretion
Enzymatic regulation
Cell signalling

Question 3

What is the role of PO4^3- ions in cellular processes?

Answer 3

Signal transduction

Question 4

What is the role of PO4^3- ions in structure?

Answer 4

DNA/RNA
Membrane phospholipids
ATP/Creatine phosphate
Complex carbohydrates

Question 5

What are 3 things does hypocalcemia cause?

Answer 5

Increased membrane Na+ permeability
Nerves and muscles become overexcitable
Involuntary muscle spasms

Question 6

What 6 things does hypercalcemia cause?

Answer 6

Decreased neuromuscular sensitivity
Constipation
Fatigue
Bone pain
Kidney stones
Cardiac arrhythmias

Question 7

What % of Ca2+ is found outside of the skeleton?

Answer 7

0.9% intracellular
0.1% extracellular

Question 8

How is the extracellular concentration for calcium split up?

Answer 8

50% bound
50% free (ionised) Ca2+ bioligically active

Question 9

What % of phosphorus is found and where?

Answer 9

80% - skeleton
15% - soft tissues
5% - plasma

Question 10

How is the conc. of phosphorus in plasma split up?

Answer 10

85% diffusible - 35% complexed to different ions and 50% ionized
13% - non diffusible protein bound state
Remainder occurs as ATP, cAMP

Question 11

How are Ca2+ and PO4^3- levels related?

Answer 11

Inversely related so Ca2+ X PO4^3- is constant

Question 12

What are 3 processes that calcium phosphate play a role in?

Answer 12

Absorption
Osteocytic osteolysis
Osteoclastic resorption

Question 13

What is precipitated on the organic collagen matrix?

Answer 13

Inorganic crystalline form of Ca2+

Question 14

What serves as a reservoir for Ca2+ storgae?

Answer 14

Mineralized CaPO4 in bone

Question 15

What serves as a rapidly accessible pool of Ca2+?

Answer 15

Non-mineralized CaPO4 in bone

Question 16

What are osteoblasts?

Answer 16

Differentiated bone forming cells which secret bone matrix on which CaPO4 precipitates

Question 17

What are osteoclasts?

Answer 17

Large multinucleated cells derived from monocytes whose function is to resorb bone

Question 18

What are osteocytes?

Answer 18

Mature bone cells enclosed in bone matrix for bone maintenance

Question 19

What 3 hormones regulate Ca2+ and PO4^3-?

Answer 19

Parathyroid hormone
1,25-digydroxy Vitamin D3
Calcitonin

Question 20

What do the 3 hormones regulate?

Answer 20

Ca2+ and PO4^3- resorption, reabsorption, absorption and excretion in bone, kidney and intestine

Question 21

What is osteocytic osteolysis?

Answer 21

Rapid exchange of calcium from pool to plasma

Question 22

What are 3 features of osteocytic osteolysis?

Answer 22

Does not require bone resorption or decrease bone mass
Activation of PTH dependent Ca2+ pumps in osteocytic-osteoblastic membrane
Release predominatly Ca2+

Question 23

What us osteoclastic resorption?

Answer 23

Slow exchange of Ca2+ from calcium pool to plasma

Question 24

What are 3 features of osteoclastic resorption?

Answer 24

Loss of bone mass and destruction of organic collagen matrix
Releases ca2+ and PO4^3-
Stimulated by PTH

Question 25

What is PTH?

Answer 25

Peptide hormone with high degree of evolutionary conservation

Question 26

Where is PTH secreted?

Answer 26

Parathyroid gland by chief/principal cells

Question 27

What are actions mediated by PTH receptor?

Answer 27

Type 1 - kidney and bone Type 2 - CNS/pancreas/testis/placenta

Question 28

What us PTH related peptide protein (PTHrP)?

Answer 28

PTH like actions that has a minor role in calcium homeostasis Secreted by many tumours

Question 29

What 3 cells are found in the parathyroid?

Answer 29

Chief cells Oxyphil cells Adipocytes

Question 30

What is PTH the dominant regulator of?

Answer 30

Plasma/free ionised Ca2+ Inversely related to Ca2+

Question 31

What is a trigger for PTH secretion?

Answer 31

Hypocalcaemia

Question 32

What is the Calcium Sensing Receptor?

Answer 32

G-protein coupled receptor found on chief cells and other calcium sensitive cells

Question 33

What are 2 mutations of CaSR and what do they cause?

Answer 33

activating = familial hypoparathyroidism and hypercalciuria inactivating - familial benign hypocalciuric hypercalcemia and neonatal severe primary hyperparathyroidism

Question 34

What is the overall action of PTH?

Answer 34

Prevent/reverse hypocalcemia by increasing free plasma ca2+ levels

Question 35

How does PTH act on the bone and kidneys?

Answer 35

Bone - increase Ca2+ release Kidneys - increase Ca2+ reabsorption and decrease PO4^3- reabsorption

Question 36

How does PTH act on the intestine?

Answer 36

Indirectly by stimulating 1.25-(OH)2-D synthesis in kidney

Question 37

What are 2 sources that Vit D is derived from?

Answer 37

Photo-dependent production in keatinocytes Ingested in diet

Question 38

What receptors does Vit D bind to?

Answer 38

Steroid hormone family receptors

Question 39

How does Vit D circulate?

Answer 39

Complexed to Vit D binding protein

Question 40

How does Vit D play a role in calcium homeostasis?

Answer 40

Promoting intestinal Ca2+ absorption - enhances renal absorption

Question 41

How is Vit D synthesused?

Answer 41

7-dehydrocholesterol converted to Vit D3 in keratinocytes Hydorxylated in liver to yield 25(OH)D3 2nd hydroxylation producing 1,25(OH)2D3

Question 42

What and where is the second hydroxylation of 25(OH)D3?

Answer 42

In kidney by 1 alpha hydroxylase

Question 43

What 4 ways is 1 alpha hydroxylase activity regulated?

Answer 43

Decreased Feedback inhibition of 1,25(OH)2D3 Increased PTH Increased hypophosphatemia Increased prolactin

Question 44

How does Vit D promote intestinal Ca2+ absorption?

Answer 44

Ca2+ bound by Vit D inducible high affinity Ca2+ binding protein called calbindin 9k

Question 45

How does calbindin work?

Answer 45

Binds 2 Ca2+ ions Maintains favourable gradient of Ca2+ across apical membrane -> promotes reabsorption

Question 46

How does Ca2+ enter enterocytes?

Answer 46

Facilitated/active transport via specific Ca2+ transporter that is Vit D dependent

Question 47

How is PO43- absorbed in the intestine?

Answer 47

Transcellular route by a NaPO4^3- cotransporter Downregulated by PTH

Question 48

How does Vit D promote phosphate absorption in intestine?

Answer 48

Increasing NPT2 receptors

Question 49

Where is calcitonin produced?

Answer 49

thyroid C cells (parafollicular cells)

Question 50

What are 3 physiological actions of calcitonin?

Answer 50

Inhibits osteoclastic activity in bone Inhibits Ca2+ reabsorption by kidney Inhibits Ca2+ by intestine

Question 51

What are 2 major stimulus' for calcitonin secretion?

Answer 51

Increases plasma Ca2+ levels Functional antagonist of PTH

Question 52

What are 2 causes of hyperparathyroidism?

Answer 52

85% single parathyroid adenoma 15% hyperplasia

Question 53

What are 3 symptoms of hyperparathyroidism?

Answer 53

Asymptomatic History of kidney stones and unexpected fractures Elevated calcium and PTH

Question 54

What are 3 causes of primary hypoparathyroidism?

Answer 54

Trauma Idiopathic Congenital deficiency

Question 55

What are 6 symptoms of hypoparathyroidism?

Answer 55

Fatigue Psychological disturbances Wheezing and dyspnea Tetany low or absent PTH hypocalcemia