Flashcards in The parathyroid glands and vitamin D Deck (37)
where is the majority of calcium found?
in bone , largely as precipaited calcium phosphate
what are the roles of calcium?
-Membrane stability (promotes electrical stability of nerves & muscles – later slide)
-Neurotransmitter release (e.g. ACh release at n.m.j.)
-Secretory processes (e.g. ADH release from post.pit.)
-Intracellular 2nd messenger
what is the role of calcium in membrane stability?
-Decrease in free ECF Ca2+ increases Na+ permeability
-Depolarizes Em, moving Em closer to threshold
-Consequence: during hypocalcemia, excitable cells reach threshold in response to normally ineffective stimuli.
-Results in muscle spasm (spontaneous contraction of respiratory muscles can lead to death by asphyxiation)
what is the role of calcium in excitation-contraction coupling of cardiac and smooth muscle cells?
-Action Potential increases Ca2+ permeability. Entry of ECF Ca2+ into cardiac and smooth muscle cells triggers contractile mechanism.
-(In sk. muscle Ca2+ is released from i/c stores in response to an AP)
what are the effect of increase in cytosolic calcium and free ECF calcium?
↑ cytosolic Ca2+ causes contraction, whereas an ↑ in free ECF Ca2+ decreases neuromuscular excitability (& ↓ likelihood of contraction).
what is the narrow range of plasma calcium?
2.2 to 2.6 mmol/l
what is the intracellular calcium level?
Describe the roles of phosphate balance.
-Component of ATP so plays an important part in cellular energy metabolism
-Crucial in activation and deactivation of enzymes (kinases and phosphatases)
-Unlike calcium the plasma phosphate concentration is not strictly regulated (levels fluctuate throughout the day, especially after meals)
how are calcium and phosphate balance linked?
1. Both are the principal components of hydroxyapatite crystals in bone
2. Both are regulated by the same hormones: primarily parathyroid hormone (PTH) and calcitriol (and, to a much lesser extent, calcitonin)
what 3 systems do PTH, calcitriol and calcitonin act on?
where are the 4 parathyroid glands located?
2 located on the posterior surface of the left lobe of the thyroid gland and 2 more on the right
what is the parathyroid gland composed of and what does it synthesise?
-composed of Chief cells, which synthesise and secrete PTH
what is the main regulatory of parathyroid hormone?
plasma calcium concentration
what does a decrease in plasma calcium conc (hypocalcemia stimulate?
PTH secretion (as does an increase in plasma [phosphorus])
Describe the PTH.
-a peptide hormones stored in secretory granules
-circulates freely in plasma and is rapidly metabolised
what do chief cells express?
a plasma membrane Ca2+ sensing receptor
what does activation of PLC result in?
-results in the release of Ca2+ from intracellular stores and activation of PKC
-Unlike other endocrine cells, the rise in [Ca2+]i and activation of PKC inhibit hormone secretion
what are the net effects of PTH on kidney and bone?
to increase plasma [Ca2+] and to lower plasma [phosphate]
what do PTH modify transepithelial transport to do?
1. Stimulate renal Ca2+ reabsorption (TAL & DCT), and
2. Inhibit renal phosphate reabsorption (PCT) – PTH-induced phosphaturia prevents precipitation when Ca2+ mobilisation is needed
what are the actions of 1,25-dihydroxyvitamin (calcitriol)?
1. Enhance renal Ca2+ reabsorption
2. Enhance Ca2+ absorption by the small intestine
3. Modulate movement of Ca2+ and phosphate in and out of bone
In bone, what can PTH promote?
net resorption or net deposition
what does persistent increases of PTH on bone favour?
indirectly increases both the number and activity of bone-resorbing osteoclasts
what do intermittent increases in plasma (PTH) favour?
bone deposition (synthesis):
--Net transfer of Ca2+ from bone fluid to osteoblasts via activation of Ca2+ channels on osteocytes
-Promotes osteoblast differentiation and inhibition of osteoblast apoptosis
what are the two forms of vitamin D and how are they synthesised?
D3- can be synthesised by the skin if sufficient UV light is absorbed, also found in eggs
D2-only obtained from the diet, largely from vegetables
what is the action of vitamin D and how does it do this?
-to raise the plasma concentrations of both Ca2+ and phosphate by:
-Enhancing absorption of Ca2+ and phosphate from the intestine, and
-Enhancing reabsorption of Ca2+ and phosphate from the renal tubules
what are the biological actions of 1,25-dihydroxyvitamin (calcitriol)?
Acts on the small intestine and kidney to raise plasma [Ca2+] (effects on bone are complex)
what effect does calcitriol have on the small intestine (duodenum)?
-Up-regulates transcellular reabsorption of Ca2+ by increasing expression of epithelial Ca2+ channels, pumps and binding proteins
-Also stimulates the synthesis of a NaPi cotransporter to increase phosphate absorption
what effect does calcitriol have on the kidney?
-Acts synergistically with PTH to enhance Ca2+ reabsorption in the DCT and promotes phosphate reabsorption
-Effects are less dramatic than PTH
what effect does calcitriol have on bone?
Actions are complex (as a result of direct and indirect actions) and depends on levels of vitamin D