Download Blood Ca 2+

Calcium & Phosphate Metabolism
• Calcium homeostasis
• Calcium in blood & cells
•  or  Ca2+ — consequences: short term
long term
• Roles of gut, bone, kidney
• Roles of:
parathyroid hormone,
vitamin D hormone,
calcitonin
• Integrated responses
• Phosphate metabolism
Calcium
1.1 kg Ca2+ — most (99%) in bone & teeth
Blood Ca2+
(mmol/L)
Cell Ca2+
cytoplasm
(mol/L)
ECF Ca2+
(mmol/L)
Blood Ca2+
Total 2.3 – 2.5 mmol/L
ionised
 50% [ Ca2+ ]
diffusible & also complexed
protein bound
 46%
 &  Ca2+
Consequences depend on:
a) severity
b) whether a sudden or long term change
 Ca2+
short term
 Na+ permeability of cells
partial depolarisation
muscle spasm
tetany
seizures
pins & needles
 Ca2+
short term
 Na+ permeability of cells
hyperpolarisation
neurologic
dysfunction
cardiac
arrythmias
constipation
anorexia
nausea
+ Ca2+ induced
diuresis
( urine flow)
dehydration
• Long term: kidney calcification & stones
Serum Inorganic Phosphate PO43• 0.8 – 1.4 mmol/L
• higher in kids
• exact regulation: less important than Ca2+
• high PO43- : long term:
soft tissue mineral deposition
• low PO43- :
long term:
inadequate bone mineralisation
diet
cells
a) structural
requirement
for Ca/PO4
Blood
Bone
source
Gut
reabsorption
filtered
b) alternative
store
Kidney
Modulates losses
Parathyroid hormone
Vitamin D hormone
= calcitriol
= 1,25 dihydroxy vitamin D
Calcitonin
urine
Parathyroid Hormone
• PTH
• Peptide
• Parathyroid glands
• Release 1.  by low Ca2+ via
calcium sensing receptor
2.  by calcitriol
3.  by high Ca2+
Calcitriol = 1,25(OH)2D
7 dehydrocholesterol
skin
uv
Vitamin D
liver
25(OH) vitamin D
regulated
kidney
1, 25(OH)2D = calcitriol
 by PTH (low Ca2+)
low PO43growth
pregnancy
Calcitonin
• peptide
• parafollicular cells
C cells of thyroid gland
• released by gastric hormones
pentagastrin
 Ca2+
Gut
• ingested Ca2+ & PO43- (dairy foods)
• absorption: Ca2+
small fraction passive
active absorption:  by calcitriol, also PO43• main function of calcitriol is to acquire Ca2+ &
PO43- from food for bone mineral (PO43- is
relatively abundant)
Bone
• Calcium & Phosphate required
for bone mineral (hydroxyapatite)
compressive strength
• Acts as store of calcium (& phosphate)
bone turnover
Cont...
releasing
calcium and
phosphate
coupling
Protein matrix +
mineral (calcium
and phosphate)
deposited
• Short term release:
Ca2+ & PO43- from bone  by: PTH
Calcitriol*
• Inhibition of release by calcitonin
* but main function is  Ca2+ & PO43- from diet
bone
Kidney
• modulates Ca2+ & PO43- losses
Ca2+
• filtration — depends on blood Ca2+ conc.
If [Ca2+] is high  high filtered load
(high loss Ca2+ loss in urine)
• reabsorption (> 98%)
 Ca2+ reabsorption by PTH
Kidney
PO43• filtered
• reabsorbed to transport maximum
PTH
reduces PO43- reabsorption
causes PO43- dumping in urine
 PO43-
 PO43- reabsorption
PTH
 calcitriol production
 blood Ca2+
 PTH
Gut
d)  Ca2+ absorption
e)  PO43- absorption
a)  calcitriol
b) conserve Ca2+
c) dump PO43-
Bone
 resorption
g) release Ca2+
h) release PO43-
blood
So because of different PTH effects in kidney (b & c)
• extra Ca2+ being pumped into blood will be
conserved, i.e. blood Ca will rise to normal
• extra PO43- being pumped into blood will be dumped
in urine, i.e. blood PO43- remains unchanged
 PO43direct
Gut
 Ca2+ & PO43absorption
major effect
kidney
 calcitriol
 PO43- losses
tends to conserve PO43-
Bone
 resorption
release of
Ca2+ & PO43minor effect
blood
no PTH, so no conservation of Ca2+
extra Ca2+ filtered
urine
blood calcium unchanged
extra PO43- into blood tends to be conserved
Mineral metabolism
cells
gut
blood
bone
kidney
PTH maintenance of blood Ca2+
calcitriol Ca2+ & PO43- from diet
bone