11. Calcium Regulation Flashcards
Where is calcium found in the body?
Calcium found in functionally distinct pools in body;
- Bony skeleton: 99%
- Intracellular pool: ~1%
- Extracellular pool: ~0.1%
Describe calcium uptake
Only in = dietary calcium;
- dietary habits
- supplements
Intestinal absorption;
- absorbed across int epith cell’s brush border membrane
- TRPV6 channel proposed: k/o didn’t change uptake
- TRPM7 linked: k/o = strongly reduced Ca in serum/bones (prob for bulk intest uptake)
After cell uptake Ca bound to calbindin (vit D dependent Ca binding protein);
- transfers to cells ER
- transports to basal membrane on opposite side of cell (doesn’t enter cytosol/ICF)
Ca pumps (PMCA1) actively TP Ca into body;
- occurs primarily in duodenum when Ca intake low
- passive paracellular TP in jejunum + ileum when Ca intake high (independent of vit D level)
Active absorption from gut regulated by calcitriol in blood;
- increases rate of absorption
Why does Ca need to be regulated?
Excitable cells, e.g. neurons, v sensitive to changes in Ca+ conc;
Hypercalcemia = progressive depression of nervous system
Hypocalcemia = progressive excitation of nervous system
Where is phosphate found in the body?
- Bones: 85%
- ICF: 15%
- ECF: <1%
What role do the bones play in calcium homeostasis?
Bones serve as large reservoirs;
- release Ca when ECF conc decreases
- store excess Ca
Describe serum Ca
Ref range: 2.2-2.6mmol/L
Required for normal neuromuscular function
Only ~50% exists as free ions - rest mostly bound to albumin (bio-inactive)
- physiological functions depend on ionised Ca not the total Ca (inc bound)
List the circulating calcium fractions in the serum
50% ionised (free) - biologically active
40% protein-bound, non-diffusable - biologically inactive + not excreted
10% complexed with phosphate, bicarbonate + citrate
Describe Dr Sydney Ringers experiments on calcium
Experiments on calcium + frog heart contraction 1883
Recorded frog heart contractions when perfused with blood mixture;
- substituted blood for saline: amplitude of contractions declined
- when calcium chloride was added to the solution the contractions recovered to almost normal amplitude
Describe the findings in early publications on calcium ion concentration by McClean + Hastings 1934
“frog’s heart sensitive to changes in conc of Ca2+ but not to changes in conc of Ca2+ in non-ionised form”
Showed ionised/free Ca2+ correlated with heart contraction;
- protein/citrate-bound Ca2+ had no effect
Developed first assay for ionised/free Ca2+
Showed in blood this was closely regulated (humans: 1.18mmol/L)
What are the components of separated whole blood?
Plasma;
- if anticoagulant present: contains fibrinogen
Serum;
- no anticoagulant present
Clot;
- formed encapsulating cells
How is blood correctly collected + stored for calcium testing?
Preferred specimen for total Ca2+ = free flowing venous sample;
- serum
- lithium heparin-plasma
Avoid anti-coagulants, e.g. EDTA/oxalate, as bind Ca2+ tightly + interfere with measurement
Loss of CO2 increases pH = samples need to be collected anaerobically
Serum from sealed evacuated tubes can be used if clotting + centrifugation are done quickly (<30min) at room temperature
Describe the lab methods for Ca2+ measurement
Colorimetric;
- Ca2+ released from protein carrier by acidification if sample before dye-binding reaction
- ortho-cresophthaleine complexone (CPC) or arseno III dye forms complex with Ca2+
- CPC method uses 8-hydroxyquinoline to prevent Mg2+ interference
AAS (atomic absorption spectroscopy) is reference method for total Ca2+ but rarely used clinically
Commercial analysers use ISEs to measure free Ca2+;
- use membranes with molecules that selectively + reversibly bind Ca2+ ions
- as Ca2+ binds membranes, electric potential develops proportional to ionised Ca2+ conc
When measuring Ca2+ why and how do we adjust for albumin?
Ca2+ = metabolically active
40-50% of measured total Ca bound to albumin (inactive);
- serum albumin must be considered when assesing Ca2+
Labs use formula to adjust measured Ca2+ relative to albumin levels;
- “adjusted Ca” = approximation of metabolically active Ca2+
Adjusted calcium = measured calcium + 0.02 (40 - albumin conc)
Errors are greatest at extremes of albumin concentration + when there is a suspicion/evidence of acidosis/alkalosis
How does the reference range for calcium vary?
Total Ca2+ varies with age;
- higher in adolescence when bone growth most active
Ionised Ca2+ changes from day 1-3 of life then stabilises at relatively high levels with gradual decline through adolescence
Describe calcium balance + its consequences
Calcium balance: intake = output
Negative balance: output>intake = osteoporosis
Positive balance: intake>output = occurs during growth
Why is calcium considered essential?
We can’t synthesis it, must acquire through diet
Which organ systems are involved in calcium metabolism?
Skeleton
GI tract
Kidneys
