Why is calcium essential for the body?
Intracellular signaling (membrane potential, signaling cascades)
Hormone secretion (e.g., insulin release)
Blood clotting (cofactor in coagulation)
Neural excitability
Muscle contraction
Building & maintaining bone
Where is calcium found in the body?
9% in bone (hydroxyapatite crystals)
~1% in cells + extracellular fluid (ECF/plasma)
Which compartments regulate calcium balance?
Bone ↔ ECF ↔ intracellular space; intake via small intestine, excretion via kidneys.
Which cells control bone dynamics?
Osteoblasts → bone-forming cells.
Osteoclasts → bone-resorbing cells (secrete acid + proteases).
Osteocytes → maintain bone (retired osteoblasts).
In what form is calcium in the body?
Calcium in bone is mainly in crystals (hydroxyapatite = Ca10(PO4)6(OH2))
A small fraction is ionized and readily exchangeable with the plasma ECF
Making bone = creating calcium phosphate complexes (calcium crystallization)
Bone is hydroxyapatite, so what you really want to do is create this combination of calcium and phosphate complexes to crystalize it
How do osteoclasts resorb bone?
Attach to matrix → secrete HCl (acidifies environment) + proteases → dissolve bone → Ca²⁺ enters bloodstream.
These cells have what seems like a ruffled border that eats away at the bones
They attach to the bone matrix like a suction cup and they secrete acid (HCL), which eats away at the bones underneath it
They also secrete proteases (enzymes) that breakdown bone and they like to act at low pH
So the acid and the enzymes dissolve the matrix
Once release by osteocytes, what happens to the Ca+?
Now the released Ca2+ becomes part of the ionized calcium pool which can then enter the bloodstream
Where you have carbon dioxide and water, carbonic anhydrase, is going to produce free protons and bicarbonate
In this case the bicarbonate is going to trave into the bloodstream into the capillary
And the bloodstream is going to send in chloride so that the free protons and the chloride are going to form HCl, lowering the pH of this environment and aiding in the absorption of the bone
What is the RANKL/RANK/OPG system?
Osteoblasts express RANKL → binds RANK on osteoclast precursors → activates osteoclasts.
OPG (from osteoblasts) blocks RANKL, inhibiting osteoclast activation.
Longer version:
Osteoclasts have a RANK receptor
And the Osteoblast has a specific ligand, RANKL, that the RANK receptor on the osteoclast bonds to
When these two come together, this promotes the osteoclasts to be activated, to differentiate and to fuse together to form a larger, multinucleated cell (the active cell that will absorb bone.
Remodeling Cycle of Bone
In normal bone remodeling, the bone is very dynamic, meaning that it is constantly being reabsorbed and built up, again and again.
On the left, we see an osteoclast, eating away at the bone, they become activated and ruffled and are creating this pit
Then the osteoblasts come in and they start to fill in that gap and remodel that bone in that area and to repair it.
In a normal organism the two cell types work closely together to get just the right amount of remodeling needed
How is Denosumab used clinically?
Monoclonal antibody that mimics OPG by binding RANKL → prevents osteoclast activation → treats osteoporosis.
Which three hormones regulate plasma calcium?
PTH, Calcitriol (Vit D hormone), Calcitonin.
Target tissues for calcium regulation?
Bone, kidney, intestine.
Where is PTH (Parathyroid Hormone) secreted?
Chief cells of the 4 parathyroid glands (on thyroid).
Stimulus for PTH release?
Low plasma Ca²⁺ (sensed by Ca²⁺-sensing GPCRs on parathyroid cells).
They sense (Stimulus: Low plasma Ca2+) low calcium in the body, and are then able to increase the calcium concentration to fix the low Ca2+ levels.
Main actions of PTH?
↑ Bone resorption (indirectly via osteoblasts: ↑RANKL, ↓OPG).
↑ Renal Ca²⁺ reabsorption.
↓ Renal phosphate reabsorption.
↑ Calcitriol synthesis (kidney).
How do parathyroid cells sense changes in Ca2+
The parathyroid cells have on them a large G protein coupled receptor – Gq in this case
So as long as calcium is bound to this receptor the signaling that takes place in the cell, there is inhibition of cell growth and the cell does not release parathyroid hormone.
Notice that as you follow the pathway there are conditions under which the pathway can be inhibited and to reduce synthesis to begin with
Calcitriol
Vitamin D Hormone
3 organs are crucial in the development of calcitriol
1) Skin
2) Liver
3) Kidney
Organs involved in calcitriol production?
Skin (UV converts precursor (cholesterol) → Vit D3) → Liver (hydroxylated) → Kidney (PTH activates → calcitriol).
Actions of calcitriol?
↑ Intestinal Ca²⁺ absorption.
↑ Renal Ca²⁺ reabsorption.
↑ Bone resorption (with PTH) if needed.
↑ Phosphate absorption (important for hydroxyapatite).
How does calcitriol act at the molecular level?
Lipophilic → enters nucleus → binds Vitamin D Receptor (VDR) → dimerizes with RXR → binds Vitamin D Response Elements (VDREs) → regulates transcription of calcium-handling proteins.
Where is calcitonin secreted?
C cells of the thyroid gland.
Calcitonin is a peptide hormone
Release triggered by high plasma [Ca2+]
C cells also have Ca2+ sensing receptors
Calcitonin “Tones down” calcium levels
Phosphate in bone
Bone is made up of these hydroxyapatite crystals that contain phosphates, so when you break down bone to release calcium, you also get phosphate released;
PTH increases phosphate release as it increases calcium release but it also decreases phosphate reabsorption in the kidney, so that the phosphate can be filtered out.
Calcitriol increases phosphate absorption by intestine and reabsorption by kidney because you need phosphate to make bone
How do PTH & calcitriol correct a calcium deficit?
PTH → ↑ bone resorption & kidney reabsorption + stimulates calcitriol → calcitriol ↑ intestinal absorption → net ↑ plasma Ca²⁺
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Nervous System28
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Nervous System 273
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Endocrine System 197
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Endocrine System 271
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Endocrine Pancreas51
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CNS Lecture 150
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Introduction to the Senses37
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Optics of the Eye51
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Visual Processing79
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Growth54
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Cranial Nerves12
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Hearing and Equilibrium41
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Color Vision49
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Somatic Senses75
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Smell and Taste29
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Hypothalamic Control of Feeding63
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Circadian Rhythm30
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Critical Motor Control Part 139
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Muscles 1 & 285
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ANS54
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CPG35
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Motor Control and Movement - Cortical Motor Areas56
