Chapter 6: Calcium Flashcards
What are the major players in the Ca homeostatic control, and which controls the short-term vs long-term hemostasis?
PTH –> minute-to-minute control of serum [Ca]
Calcitriol (VitD) –> day-to-day control of serum [Ca]
How much of the Ca in the glomerular filtrate is reabsorbed by the tubular cells in a healthy animal?
almost all = 98%
How does the bone supply the body with Ca in the acute/short-term hypocalcemia?
Ca and P are mobilized from the bone ECF.
This ECF for fast Ca and P supply is separated from the rest of the bone via an osteoblast lining.
How does the bone supply the body with Ca in the chronic/long-term hypocalcemia?
osteoclastic bone resorption –> acids and proteases dissolute the mineralized bone matrix and by that mobilize Ca and P
How does decreased serum [iCa] affect PTH levels?
increased PTH secretion, causes:
- osteoclastic bone resorption
- increased renal Ca reabsorption
How does decreased serum [iCa] affect calcitriol levels?
increased calcitriol synthesis, causes:
- increased intestinal Ca absorption
- osteoclastic bone resorption
- increased renal tubular Ca reabsorption
What acts as the “calcium pool” and how much of it is readily available?
bones
< 1% is readily available in the ECF outside of the osteoblast layer –> rest as hydroxyapatite, which is poorly exchangeable
What are the 3 fractions of plasma Ca?
- ionized Ca (53%) –> biologically active form
- complexed Ca (e.g., bound to phosphorous) (10%)
- protein bound (34%)
Where is more Ca, in the ICF or ECF?
ECF –> 10,000-fold less in ICF than ECF
important because this enables rapid diffusion of ECF to ICF
What is the main function of the Calcium ion sensing receptors (CaSR)?
- regulate PTH production in the parathyroid chief cells, i.e., increased serum [iCa] –> decreased PTH production
- kidneys: increased serum [iCa] –> decreased tubular reabsorption of iCa, iMg, NaCl
- kidneys: increased serum [iCa] –> decreased water reabsorption in the collecting ducts –> further promotes Ca excretion
Where is PTH synthesized and secreted?
in the chief cells of the parathyroid gland
What is the half-life of PTH in the blood?
3-5 minutes
How is PTH secretion and synthesis regulated?
- calcitriol –> inhibits PTH mRNA synthesis + stimulates CaSR
- serum [iCa] –> high levels inhibit PTH synthesis; low levels promotes PTH synthesis (principal stimulus
Explain the mechanism behind secondary hyperparathyroidism from chronic kidney disease
- calcitriol is activated in the kidneys –> CKD –> less activation of calcitriol –> lack of negative feedback on PTH synthesis and secretion
- low serum [iCa] –> increased PTH secretion
- kidneys fail to excrete P –> high serum [P] –> inhibits calcitriol production and promotes PTH production
How does serum [Ca] affect PTH synthesis and secretion and what type of curve would illustrate their relationship in a diagram?
- within a narrow range of serum [tCa] –> small changes of [tCa] will cause large changes in [PTH], e.g., small increase in [tCa] –> steep drop in [PTH]
- out of this narrow range: effects of [tCa] on [PTH] are minimal
- relationship creates a sigmoid curve
what is FGF-23 and how does it affect PTH levels
phosphatonin fibroblast growth factor-23
- phosphaturic –> decreases serum [P] –> decreases PTH secretion
- directly inhibitory of PTH secretion
- calcitriol induces FGF-23 production –> FGF-23 in turn inhibits calcitriol synthesis
How is PTH metabolized?
Intact PTH can be taken up by fixed macrophages (e.g. Kupffer cells) and degraded into fragmented PTH. This process can also happen in bones and kidneys. Fragments of PTH are then filtered by glomeruli.
Where is the calcitriol synthesis in the kidney?
Renal epithelial cells in the proximal convoluted tubules
What are the biological effect of PTH on calcium?
- Increased the blood calcium concentration
- increase the renal tubular reabsorption of calcium -> decreased calcium loss in the urine
- increase bone resorption and the numbers of osteoclasts on bone surfaces
- induce synthesis of and activate the 1-𝜶hydroxylase in mitochondria of renal epithelial cells -> accelerate the formation of active vitamin D metabolite (1,25-dihydroxyvitamin D; calcitriol)
Describe how does the bone respond to PTH
Biphasic
Immediate effect: an increased flow of calcium from deep in bone to bone surfaces through the action of an osteocyte-osteoblast “pump”
Later effect: osteoclast causing bone resorption and remodeling
In which segments of the nephrons do PTH work on?
A direct action on the distal convoluted tubule
An indirect action on the ascending thick limb of Henle’s loop by increasing the net positive charge in the nephron lumen and creating a stimulus for diffusion out of the lumen.
There are two terminals of PTH. Which one is important for calcium regulation?
N-terminal (amino acid 1-34)
Does PTHrP participate in the normal regulation of calcium?
Yes. In fetus, PTHrP is produced by placenta and also secreted by fetal parathyroid chief cells, and is involved in the normal regulation of calcium.
PTHrP is also produced by the lactating mammary gland and is secreted into milk. It is thought to facilitates the movement of calcium from the maternal bones to the milk during lactation
What are the relationship of cholecalciferol, calcidiol and calcitriol? Which one of above is the major circulating vitamin D?
Will put pic later
25-hydroxyvitamin D (calcidiol) (produced in liver)
