Download Calcium homeostasis

Calcium homeostasis
Organs in calcium homeostasis
• Small intestain
• Uptake from dietary
• Normal adult diet contains 25mmol, which
absorped only 5 mmol /day
• Blood/plasma
• Coagulation
• Transporting with albumin
• Main carrier of proteinbound calcium
• The plasma total calcium
concentration is in the range of
2.2-2.6 mmol/L
• The normal ionized calcium is 1.31.5 mmol/L (50-60%)
• Protein-bound in albumin (35-50%)
• Complexes in organic acids and
phosphates (5-10%)
Organs in calcium homeostasis
• Hormone system
• Intracellular secondary messenger
• Thyroid gland
• Calcitonin
• Parathyroid gland
• Parathyroid hormone (PTH)
• Skeletal system
• Storage
• 99% of body's total calcium
• Calcium makes bones strength
• Liver
• Cell signaling
• Extra cellular fluid
• Storage
• Transporting to the cells
• Cell signaling
• Muscle
• Contraction
• Kidneys
• Calcitriol
• Remove to urine
• In ions 5 mmol/day
Calcium homeostasis
• Calcium concentration in blood is
regulated by calcitonin and PTH activated
calcitriol
• Calcitriol is released from kidneys. It
stimulate cells releasing calcium from
bone, increase uptake to gastrointestinal
tract and increase reabsorption in renal
tubule
• Calcitonin is released from thyroid gland
and it stimulate calcium deposition in
bones and reduce uptake in kidneys
when calcium remove to urine
Vitamin-D as the regulatory factor of calcium
homeostasis
• Vitamin-D increases calcium intake from intestine, bones and kidneys
• Calcitriol is a vitamin d metabolite that upregulates calcium binding
protein expression causing uptake of calcium
• Kidneys observe calcium level in blood and produce calcitriol
• With the help of renin, calcitriol reabsorbs calcium in the kidneys
• Calcium binding proteins can be intracellular and extracellular and
they have many functions such as free calcium regulation, calcium
transport and signalling (for example calmodulin).
Intracellular calcium homeostasis
ER
Cytosol
• High concentration of Ca2+ in
rest
• IP3 activates calcium release to
cytosol through ion-channels
• In muscle the sarcoplasmic
reticulum releases Ca2+ after
synaptic signal
• Active pumping of calcium into
the ER
• Low concentration of Ca2+
• Calcium works as secondary
messenger
• Calcium can activate some
proteins that regulate exocytosis
• Intake from ER and extracellular
space
Calcium pumps and calcium transport
• Calcium is actively pumped out of
cytosol with Plasma membrane Ca2+
ATPase (PMCA) and Sodium-calcium
exchanger (NCX)
• PMCA has high affinity but low
capacity where as NCX has low affinity
but high capacity
• This makes PMCA slow and steady when
NCX works fast in high Ca2+ concentrations
(during signalling where Ca2+ is a
secondary messenger)
Calcium regulated homeostasis and transport
• Calcium has a major role in biomembrane fusion thus regulating
many other homeostatic events in the organism
• Most of membrane fusions require calcium, such as exocytosis, so the
calcium can be released from the vehicle itself or from the ER
• Calcium isn't required always and can also inhibit some membrane
fusions like pre-golgi-fusion
Disorders in calcium metabolism
High
Deficiency
• Hypercalcemia
• Milk-alkali syndrome (Burnett's
syndrome)
• Calcinosis (Calciphylaxix,
Calclinosis cutis)
• Calcificaltion (Metastatic calcification,
Dystrophic calcification)
• Familial hypocalciuric hypercalcemia
• Excitotoxicity
• Hypocalcemia
• Osteomalacia
• Pseudohypoparathyroidism
(Albright's hereditary,
osteodystrophy)
• Pseudopseudohypoparathyroidism
Hypocalcemia
Hypercalcemia
[𝐶𝑎2+ ]𝐸𝐶𝐹
too high
[𝐶𝑎2+ ]𝐸𝐶𝐹 too low
Voltage-gated ionchannels opening
spontaneously
Calcium react
with phosphate
ions
Nerve and muscle
cells come
hyperactive
Involuntary muscle
spasms
(hypocalcemic
tetany)
Forming
calciumphosphate
stones to the blood
vessels and to the
kidneys
Voltage-gated
ion channels
don´t open so
easily
Nervous system is
depressed