Calcium metabolism

1. Calcium
Homeostasis
Dr. Hettiarachchi
Lead - Anaesthesia and
SICU
SBSCH
shaankh@icloud.com

2. Ca2+ -
Essential
intracellular
signalling
molecule

3. Variety of
extracellular
functions1. Blood coagulation
2. Muscle contraction
3. Nerve function

4. 1,25-
Dihydroxycholecalcif
erol
Three hormones

5. Three hormones
Parathyroid
hormone
(PTH)

6. Calcitonin
Three hormones

7. Plasma calcium ion concentration
1.2 mmol/L
Or
2.4 mEq/L
(Because calcium is a
divalent ion)

8. Calcium metabolism in an adult human

9. Vitamin D

11. Intestinal
absorption of
calcium

12. Terminology
Transient Receptor Potential
Vanilloid - type 6 (TRPV6)
Calbindin-D – Calbindin D9K, Calbindin
D28K
Na+ /Ca 2+ exchanger (NCX1)
Ca2+ - dependent ATPase

13. Mechanism of action of 1,25 DHCC
Transcriptional
regulator in
its ligand-
bound form
(TRPV6)
Calbinding ∞ absorbed

14. No 1,25 DHCC is produced when plasma
Ca2+ level is high

15. 1 α-hydroxylase is stimulated
by
PTH
And Low levels of plasma
Ca 2+

16. Phosphate
Inhibits 1α hydroxylase
(direct)

17. Facilitates Ca2+ reabsorption
in the proximal tubules in
kidneys
Actions of Vitamin D

18. TRPV5 receptors (Kidney)

19. Increases the synthetic
activity of
osteoblasts
Vitamin D
Necessary
for normal
calcification
of matrix

20. osteoprotege
rin ligand
OPGL

21. Vitamin D
Stimulation of
osteoblasts
brings
about a
secondary
increase in the
activity of
osteocla
sts

22. Four principal actions of vitamin
D
4. Acts directly on
the parathyroid
glands to decrease
preproPTH
mRNA
1. Increase
Bone resorption
2. Increase GI Ca2+ absorption
through Ca2+ channel and
pump upregulation
3. Ca 2+ reabsorption via
increased TRPV5 expression
in the proximal tubules

23. Hypocalcemic tetany
Extensive spasms
of skeletal muscles
A decreasein extracellular
Ca2+ exerts a net excitatory effect on nerve

24. Severe Laryngospasm
Airway obstruction
and
fatal asphyxia

25. pH and Ca2+ binding
When pH is increasing,
Ca2+ binding with protein also is
increasing

26. PHOSPHAT
E
Required for
synthesis of ATP
and
2,3-
diphosphoglycerate
(2,3-DPG)

27. Proximal,Phosphate,PTH
Phosphate
Reabsorbed in
Proximal tubule
A small percentage is
rebsorbed by the DCT

28. PTHinhibits phosphate reabsorption by
degradation of Na+-Pi Co-transporters
in the renal epithelium’s apical membrane
When ECF phosphate
levels are low
Na+-Pi Co-
transporters retain
phosphate

29. Increasedplasma phosphate
1. Lowers plasma levels of free Ca 2+ to
stimulates PTH secretion
2. Inhibit the formation of 1,25-
dihydroxycholecalciferol

30. Parathyroid gland

31. Chief cells
Oxyphil cells

32. Chief cells
Contain prominent
Golgi apparatus,
endoplasmic
reticulum,
secretary granules.
Synthesize and secrete
PTH

33. Oxyphil cells
Contain
oxyphil granules and large
numbers of mitochondria
in their cytoplasm

34. PTH

35. When plasma Ca2+ raised
1. Ca2+ is sensed by a GPCRlinked to PLC.
PLC liberates DAG and IP3
2. DAGactivates PKC
3. PKC inhibits PTH release
4. IP3 starts Ca2+ release from the ER
5. A rise in intracellular free Ca2+
also inhibits PTH secretion

37. PKC and Ca2+ effects
together cause plasma Ca2+ to fall
through PTH
Reduced reabsorption
from the renal tubule
and decreased bone
resorption

38. Mechanism of action

39. Actions of PTH

40. Increase bone resorption and
mobilize Ca2+
Osteoprotegerin ligand (OPGL)

41. Phosphaturic action
Due to a decrease in
reabsorption of
phosphate via effects
on NaPi -IIa in the
proximal tubules

42. Increase Ca2+
reabsorption
by increasing TRPV5
open probability
Increased reabsorption of Ca2+ in the
distal tubules

43. Increased reabsorption of Ca2+ in the
distal tubules

44. Increased formation of
1,25-dihydroxycholecalciferol
This increases
Ca2+
absorption from
the intestine
(indirectly)

46. Lithium
Desensitizes parathyroid cells to Ca2+
So Higher levels are required to suppress PTH release
PTH secretion increases
1. Renal Ca2+
reabsorption
2. Bone resorption

47. CALCITONIN
Ca 2+ - lowering
hormone
Produced by the
parafollicular cells
(clear or C cells)
of the thyroid gland

48. Calcitonin SECRETION
When Ca2+ level
is
9.5 mg/dL
Calcitonin ∞ Ca2+

49. Stimuli for calcitonin secretion
β-Adrenergic agonists
Dopamine
Oestrogens Gastrin
cholecystokinin
(CCK)
glucagon
secretin

50. Zollinger–Ellison syndrome
(Supraphysiological value of
gastrin concentration is found)
Calcitonin

51. Receptors for
calcitonin are
found in
and
Calcitonin

52. ACTIONS of Calcitonin
1. lowers Ca2+ and PO4
-3 levels
2. Inhibit bone resorption
3. inhibits the activity of osteoclasts
4. Increases Ca2+ excretion in the urine

53. EFFECTS OF
OTHER
HORMONES
& HUMORAL
AGENTS ON
CALCIUM
METABOLISM

54. Glucocorticoids
Lower plasma Ca2+ levels
by inhibiting osteoclast
formation and activity
but long term they
cause osteoporosis by
decreasing bone
formation and
increasing bone
resorption

55. Decrease bone formation by
inhibiting protein synthesis in osteoblasts
Glucocorticoids
Decrease the absorption of Ca2+ and PO4
3–
from the intestine
Increase the renal excretion
of Ca2+ and PO4
3–

56. Growth hormone
Increases Ca2+ excretion in the urine, but it
Increases intestinal absorption of Ca2+ (Greater)
Net positive calcium balance
Insulin-like growth factor I (IGF-I) generated by
the action of growth hormone stimulates
protein synthesis in bone

57. Thyroid hormones
Hypercalcemia
Hypercalciuria
(in some instances, osteoporosis)

58. Insulin
Increases bone formation
(significant bone loss in untreated diabetes)

59. Estrogens
Prevent osteoporosis
by inhibitingthe stimulatory effects of
certain cytokineson osteoclasts

60. 1. With regards to calcium metabolism
a. It is the ionised calcium concentration which
influences the physiological effects
b. The normal value of ionised calcium is 2.12
2.65mmol/l
c. Calcitonin plays a major role in calcium
homeostasis in humans
d. Absorption of Ca2+ from the GI tract is regulated
by parathyroid hormone
e. 98-99% of filtered calcium is reabsorbed in the
kidney

61. 2. TFFFT

62. 2. Total plasma calcium:
a) increases with phosphate
b) increases with a rise in albumin,
c) changes its degree of ionisation with pH
changes
d) is decreased in osteoporosis
e) is affected by vitamin D

63. 3. A patient with parathyroid deficiency 10 days after inadvertent
damage to the parathyroid glands during thyroid surgery would
probably have
A. low plasma phosphate and Ca2+ levels and tetany.
B. low plasma phosphate and Ca2+ levels and tetanus.
C. a low plasma Ca2+ level, increased muscular excitability, and spasm of
the muscles of the upper extremity (Trousseau sign).
D. high plasma phosphate and Ca2+ levels and bone demineralization.
E. increased muscular excitability, a high plasma Ca2+ level, and bone
demineralization.

64. 6. Which of the following is not involved in
regulating plasma Ca 2+ levels?
A. Kidneys
B. Skin
C. Liver
D. Lungs
E. Intestine

65. 5. In an experiment, a rat is infused with a small volume of a
calcium chloride solution, or sodium chloride as a control.
Compared to the control condition, which of the following
would result from the calcium load?
A. Bone demineralization
B. Increased formation of 1,25-dihydroxycholecalciferol
C. Decreased secretion of calcitonin
D. Decreased blood coagulability
E. Increased formation of 24,25-dihydroxycholecalciferol

66. 7. 1,25-Dihydroxycholecalciferol affects
intestinal Ca2+ absorption through a
mechanism that
A. includes alterations in the activity of genes
B. activates adenylyl cyclase
C. decreases cell turnover
D. changes gastric acid secretion
E. involves degradation of apical calcium
channels

67. 8. Which of the following would you expect to
find in a patient whose diet has been low in
calcium for 2 months?
A. Increased formation of 24,25
dihydroxycholecalciferol
B. Decreased amounts of calcium-binding
protein in intestinal epithelial cells
C. Increased parathyroid hormone secretion
D. A high plasma calcitonin concentration
E. Increased plasma phosphate