Flashcards in Calcium and Phosphate Regulation Deck (58)
What is the normal range of Ca?
Tightly regulated range in plasma (2.2 - 2.6 mM)
What is the most abundant cation?
What is the function of phosphate?
Cellular energy metabolism (ATP)
Intracellular signaling pathways
Nucleic acid backbone
What is the function of calcium?
Membrane stability and cell function
Muscle function Hormone secretion
What is Ca found as in the plasma?
Half Ca is bound to albumin
Half is ionized
What is Pi found as in the plasma?
Most of Pi is ionized
What does hypocalcemia result in?
Muscle failure, tetany, convulsions, death
What does hypercalcemia result in?
Renal dysfunction, calcification of soft tissues, muscle weakness, coma
What often causes hyperphosphatemia?
Result of severe tissue injury “crush”
What are the main 2 regulators of calcium?
What is the function of the chief/principal cells in the parathyroid gland?
What is the function of the oxyphil cells in the parathyroid gland?
No known function, increase with age and chronic kidney disease
What is the function of the 1-34 PTH fragment (N terminal)?
N-terminal fragment 1-34 biologically active – binds to PTH receptor
What is the function of the 35-84 PTH fragment?
C-terminal fragment 35-84 has longer half-life than other fragments – inactive
What is the clinical importance of the 1-84 PTH fragment?
Intact 1-84 fragment: half-life of 4 min and is clinically measured.
How is PTH synthesized?
The signal peptide directs it to the ER for processing after translation
What is the function of PTHrP (related peptide)?
Parathyroid hormone-related peptide (PTHrP) is highly homologous to PTH 1-34 AA.
It mimics the action of PTH in the bone and kidney.
What is the relationship of PTHrP to disease?
Many tumors produce PTHrP (renal, bladder, lymphoma, head/neck) resulting in hypercalcemia
What are the PTH receptors?
Describe PTH 1R.
Primary receptor and is found in the osteoblasts and kidney and it is a GPCR.
Binds 1-34 fragment, 1-84, PTHrP
Describe PTH 2R.
Physiological importance in humans unclear
Does not bind PTHrP
What are the targets of PTH?
Bone and Kidney
What are the effects of PTH?
Increase plasma Ca2+, decrease plasma Pi
What is the function of osteoclasts?
Do not express PTH receptors
What is the function of osteoblasts?
Bone formation and mineralization
High expression of PTH receptors
What is the mechanism of PTH action?
-PTH stimulates macrophage colony-stimulating factor (M-CSF) in osteoblasts by binding the PTH receptor.
-M-CSF stimulates differentiation of osteoclast precursors
What is the the type of action PTH has on osteoclasts?
Indirect via M-CSF from the osteoblasts
What is the effect of PTH on RANK ligand?
PTH stimulates RANK ligand – leads to maturation of osteoclast and bone reabsorption. Bone degradation releases Ca2+ and Pi to systemic circulation.
What is Osteoprotegerin (OPG)?
It is an antagonist of RANK ligand which leads to the down regulation of osteoclasts