4-Calcium homeostasis Flashcards
Features of calcium
Comes out of solution at very low concentrations
Feature of the skeleton
Living tissue that is constantly dying and regenerating
how much calcium do we absorbed a day
200mg net intake
What i the total plasma Ca levels
2.5mM
40% bound to macromolecular proteins
5% complexed as salts
1.2mM of free ionised calcium
You regulate the 1.2mM not the 2.5mM
How many parathyroid glands do you have
4,
5% of people have more than 4
Found in a butterfly spot like shape on the thyroid gland
What is the origin of the PT gland
derived from the pharyngeal pouch endoderm driven by Gcm-2
Gcm-2 also expressed in the pharyngeal pouch of the internal gill
PT glands in neck as derived from the gill
Parathyroid hormone
Produced in cheif cells of the PT gland
84 alpha helix
Relationship between extracellular Ca and PTH
PTH secretion is inversely proportional to serum Ca
EC50=1.2mM
Steep sigmoidal relationship
Occurs over a fifth of an order
One of the most tightly regulated relationships in the body
Ca sensing receptor (GPCR)
Doesn’t desensitise like other GPCRs so continuously sensing calcium
responsive to both Ca and Mg but less sensitive to Mg
Present in parathyroid cells and the kidneys
limits Ca reabsorption in kidneys
2 GPCRs, one Gi one Gq
Bone reabsorption
Daily pulsatile release of PTH secretion leads to bone formation
Chronically elevated PTH breaks bone down
Renal Ca absorption
Distal convoluted tubule is the last control point
Most reabsorption happens in proximal tubule (70%)
PTH acts upon the thick ascending limb and the DCT to increase absorption
Vitamin D
Does what PTH does and more
Pro-vitamin D3 converted to preVitamin D3 by UVB (sun)
Increases net intestinal Ca uptake (no PTH receptors in gut but there are VD3 ones)
Increases bone resorption (demineralisation)
Increases renal reabsorption
Intestinal Ca absorption
Active absorption through TRPV5&6 but mainly 5
Passive absorption occurs too
Binds to CalD inside
Moved to blood through PMCA and NCX
VD3 increases expression of CalD and TRPV6
Ca and cell death
Ca drives apoptosis
Make less ATP with age so can’t pump Ca out
Cells die with age
Calbindins
CaB -D28k mainly expressed in the kidneys
D9K in the gut
Provide (re)absorptive epithelia with protection from Ca mM
Expression dependent on VD3