Calcium and Phosphorus Homeostasis Flashcards
What do calcium phosphate salts in bone provide?
Structural integrity
What are calcium ions in ICF and ECF responsible for?
Neuromuscular excitability
Blood coagulation
Hormonal secretion
Enzymatic regulation
Cell signalling
What is the role of PO4^3- ions in cellular processes?
Signal transduction
What is the role of PO4^3- ions in structure?
DNA/RNA
Membrane phospholipids
ATP/Creatine phosphate
Complex carbohydrates
What are 3 things does hypocalcemia cause?
Increased membrane Na+ permeability
Nerves and muscles become overexcitable
Involuntary muscle spasms
What 6 things does hypercalcemia cause?
Decreased neuromuscular sensitivity
Constipation
Fatigue
Bone pain
Kidney stones
Cardiac arrhythmias
What % of Ca2+ is found outside of the skeleton?
0.9% intracellular
0.1% extracellular
How is the extracellular concentration for calcium split up?
50% bound
50% free (ionised) Ca2+ bioligically active
What % of phosphorus is found and where?
80% - skeleton
15% - soft tissues
5% - plasma
How is the conc. of phosphorus in plasma split up?
85% diffusible - 35% complexed to different ions and 50% ionized
13% - non diffusible protein bound state
Remainder occurs as ATP, cAMP
How are Ca2+ and PO4^3- levels related?
Inversely related so Ca2+ X PO4^3- is constant
What are 3 processes that calcium phosphate play a role in?
Absorption
Osteocytic osteolysis
Osteoclastic resorption
What is precipitated on the organic collagen matrix?
Inorganic crystalline form of Ca2+
What serves as a reservoir for Ca2+ storgae?
Mineralized CaPO4 in bone
What serves as a rapidly accessible pool of Ca2+?
Non-mineralized CaPO4 in bone
What are osteoblasts?
Differentiated bone forming cells which secret bone matrix on which CaPO4 precipitates
What are osteoclasts?
Large multinucleated cells derived from monocytes whose function is to resorb bone
What are osteocytes?
Mature bone cells enclosed in bone matrix for bone maintenance
What 3 hormones regulate Ca2+ and PO4^3-?
Parathyroid hormone
1,25-digydroxy Vitamin D3
Calcitonin
What do the 3 hormones regulate?
Ca2+ and PO4^3- resorption, reabsorption, absorption and excretion in bone, kidney and intestine
What is osteocytic osteolysis?
Rapid exchange of calcium from pool to plasma
What are 3 features of osteocytic osteolysis?
Does not require bone resorption or decrease bone mass
Activation of PTH dependent Ca2+ pumps in osteocytic-osteoblastic membrane
Release predominatly Ca2+
What us osteoclastic resorption?
Slow exchange of Ca2+ from calcium pool to plasma
What are 3 features of osteoclastic resorption?
Loss of bone mass and destruction of organic collagen matrix
Releases ca2+ and PO4^3-
Stimulated by PTH
What is PTH?
Peptide hormone with high degree of evolutionary conservation
Where is PTH secreted?
Parathyroid gland by chief/principal cells
What are actions mediated by PTH receptor?
Type 1 - kidney and bone
Type 2 - CNS/pancreas/testis/placenta
What us PTH related peptide protein (PTHrP)?
PTH like actions that has a minor role in calcium homeostasis
Secreted by many tumours
What 3 cells are found in the parathyroid?
Chief cells
Oxyphil cells
Adipocytes
What is PTH the dominant regulator of?
Plasma/free ionised Ca2+
Inversely related to Ca2+
What is a trigger for PTH secretion?
Hypocalcaemia
What is the Calcium Sensing Receptor?
G-protein coupled receptor found on chief cells and other calcium sensitive cells
What are 2 mutations of CaSR and what do they cause?
activating = familial hypoparathyroidism and hypercalciuria
inactivating - familial benign hypocalciuric hypercalcemia and neonatal severe primary hyperparathyroidism
What is the overall action of PTH?
Prevent/reverse hypocalcemia by increasing free plasma ca2+ levels
How does PTH act on the bone and kidneys?
Bone - increase Ca2+ release
Kidneys - increase Ca2+ reabsorption and decrease PO4^3- reabsorption
How does PTH act on the intestine?
Indirectly by stimulating 1.25-(OH)2-D synthesis in kidney
What are 2 sources that Vit D is derived from?
Photo-dependent production in keatinocytes
Ingested in diet
What receptors does Vit D bind to?
Steroid hormone family receptors
How does Vit D circulate?
Complexed to Vit D binding protein
How does Vit D play a role in calcium homeostasis?
Promoting intestinal Ca2+ absorption - enhances renal absorption
How is Vit D synthesused?
7-dehydrocholesterol converted to Vit D3 in keratinocytes
Hydorxylated in liver to yield 25(OH)D3
2nd hydroxylation producing 1,25(OH)2D3
What and where is the second hydroxylation of 25(OH)D3?
In kidney by 1 alpha hydroxylase
What 4 ways is 1 alpha hydroxylase activity regulated?
Decreased Feedback inhibition of 1,25(OH)2D3
Increased PTH
Increased hypophosphatemia
Increased prolactin
How does Vit D promote intestinal Ca2+ absorption?
Ca2+ bound by Vit D inducible high affinity Ca2+ binding protein called calbindin 9k
How does calbindin work?
Binds 2 Ca2+ ions
Maintains favourable gradient of Ca2+ across apical membrane -> promotes reabsorption
How does Ca2+ enter enterocytes?
Facilitated/active transport via specific Ca2+ transporter that is Vit D dependent
How is PO43- absorbed in the intestine?
Transcellular route by a NaPO4^3- cotransporter
Downregulated by PTH
How does Vit D promote phosphate absorption in intestine?
Increasing NPT2 receptors
Where is calcitonin produced?
thyroid C cells (parafollicular cells)
What are 3 physiological actions of calcitonin?
Inhibits osteoclastic activity in bone
Inhibits Ca2+ reabsorption by kidney
Inhibits Ca2+ by intestine
What are 2 major stimulus’ for calcitonin secretion?
Increases plasma Ca2+ levels
Functional antagonist of PTH
What are 2 causes of hyperparathyroidism?
85% single parathyroid adenoma
15% hyperplasia
What are 3 symptoms of hyperparathyroidism?
Asymptomatic
History of kidney stones and unexpected fractures
Elevated calcium and PTH
What are 3 causes of primary hypoparathyroidism?
Trauma
Idiopathic
Congenital deficiency
What are 6 symptoms of hypoparathyroidism?
Fatigue
Psychological disturbances
Wheezing and dyspnea
Tetany
low or absent PTH
hypocalcemia
