Dra. Cabarles Tuesday April 30

1. PARATHYROIDPARATHYROID
GLANDSGLANDS

2. Total Body CalciumTotal Body Calcium
 99% of calcium of body calcium is in99% of calcium of body calcium is in
bonebone
- 99% of that calcium is in the mineral- 99% of that calcium is in the mineral
phasephase
- remaining calcium (1%) is- remaining calcium (1%) is
exchangeableexchangeable
41% protein bound41% protein bound
9% complexed with anions (phosphate)9% complexed with anions (phosphate)
50% ionized in the biologically active form50% ionized in the biologically active form
 Ionized calcium is tightly regulated byIonized calcium is tightly regulated by
hormonal mechanismshormonal mechanisms

3. Got Calcium?Got Calcium? Ca2+

4. Importance of Ionic Calcium inImportance of Ionic Calcium in
the Bodythe Body
 Calcium is necessary for:Calcium is necessary for:

Transmission of nerve impulsesTransmission of nerve impulses

Muscle contractionMuscle contraction

Blood coagulationBlood coagulation

Secretion by glands and nerve cellsSecretion by glands and nerve cells

Cell divisionCell division

5. HYPOCALCEMIAHYPOCALCEMIA
 Plasma calcium below 50%
 Lowers the threshold potential
 increased excitability of excitable cells,
including sensory and motor nerves and
muscle
 s/s: hyper-reflexia, spontaneous twitching,
muscle cramps, tingling and numbness
 Specific indicators: Chvostek sign
Trousseau sign

6. CARPOPEDAL SPASM

7. HYPERCALCEMIAHYPERCALCEMIA
 Depressed nervous system, sluggishDepressed nervous system, sluggish
reflexesreflexes
 s/s: constipation, polyuria, polydipsia,s/s: constipation, polyuria, polydipsia,
hyporeflexia, lethargy, comahyporeflexia, lethargy, coma
and deathand death
 Begin to appear when blood CaBegin to appear when blood Ca2+2+
>12mg/dl>12mg/dl
 >17mg/dl>17mg/dl → calcium phosphate crystals→ calcium phosphate crystals

8. OVERALL CALCIUM HOMEOSTASISOVERALL CALCIUM HOMEOSTASIS
 Interaction between:Interaction between:
Organs : bone, kidney, intestineOrgans : bone, kidney, intestine
Hormones: PTH, calcitonin, vitamin DHormones: PTH, calcitonin, vitamin D

9. Excreted in
feces
(Salivary, pancreatic,
Intestinal fluids)
NET: 200mg

10. VITAMINVITAMIN DD
 Released from skin by sunlightReleased from skin by sunlight
 Two step activation: liver & kidneysTwo step activation: liver & kidneys
 Increases calcium absorption in intestineIncreases calcium absorption in intestine

11. 7-DEHYDROCHOLESTEROL
CHOLECALCIFEROL (vitamin D3) DIET
LIVER
25-OH-CHOLECALCIFEROL
1,25 dihydroxy
Cholecalciferol
(active)
24,25 (OH2)-
Cholecalcalciferol
(inactive)
1α
hydroxylase
↓ Ca2+
↑ PTH
↓ PO4
(+)
UV light (skin)
Kidneys (proximal tubules)

12. VITAMIN DVITAMIN D
 Effect:Effect:
1. increase calcium absorption from1. increase calcium absorption from
the GITthe GIT
2. decreases renal calcium and2. decreases renal calcium and
phosphate excretion (weak effect)phosphate excretion (weak effect)
3. extreme quantities3. extreme quantities →→ causes bonecauses bone
absorptionabsorption
smaller quantitiessmaller quantities → promotes bone→ promotes bone
calcificationcalcification

14. PTH

15. Biosynthesis, Storage &
Secretion of PTH
 synthesized as the preprohormonesynthesized as the preprohormone
(Preproparathyroid Hormone) by chief(Preproparathyroid Hormone) by chief
cellscells
 PTH isPTH is synthesized continuouslysynthesized continuously
 PTH is released by exocytosis inPTH is released by exocytosis in
response to reduced plasma calciumresponse to reduced plasma calcium

16. PARATHYROID HORMONEPARATHYROID HORMONE
 ROLE: regulate the concentration of CaROLE: regulate the concentration of Ca2+2+
in the ECFin the ECF
 Stimulus: hypocalcemiaStimulus: hypocalcemia
 Target organs: bone, kidneys, intestineTarget organs: bone, kidneys, intestine

17. REGULATION OF PTH SECRETIONREGULATION OF PTH SECRETION
PTH
SECRETION

18. MECHANISM OF PTH SECRETIONMECHANISM OF PTH SECRETION
 CaCa2+2+
sensing receptors (parathyroid cellsensing receptors (parathyroid cell
membrane) linked via a G-protein tomembrane) linked via a G-protein to
phospholipase Cphospholipase C
 When CaWhen Ca2+2+
isis ↑, Ca↑, Ca2+2+
binds to the receptorbinds to the receptor
and activates phospholipase C →and activates phospholipase C →
increased levels of IPincreased levels of IP33/Ca/Ca2+2+
which inhibitswhich inhibits
PTH secretionPTH secretion

19. ACTIONS OF PTHACTIONS OF PTH
 Overall effect: to increase plasma CaOverall effect: to increase plasma Ca2+2+
 Direct action on bone and kidneysDirect action on bone and kidneys
- mediated by cAMP- mediated by cAMP
 Indirect action on intestines: via activationIndirect action on intestines: via activation
of vitamin Dof vitamin D

20. BONEBONE
 PTH receptors are located on osteoblasts but notPTH receptors are located on osteoblasts but not
on osteoclastson osteoclasts
 Effects:Effects:

direct action on osteoblasts (brief): Increasedirect action on osteoblasts (brief): Increase
bone formationbone formation

long lasting action on osteoclasts (indirect);long lasting action on osteoclasts (indirect);
Increase in bone resorptionIncrease in bone resorption
(mediated by cytokines released(mediated by cytokines released
from osteoblasts)from osteoblasts)
 Overall effect of PTH: promote boneOverall effect of PTH: promote bone
resorptionresorption ( delivering both Ca( delivering both Ca2+2+
and POand PO44 toto
ECF)ECF)

21.  the phosphate released from the bone willthe phosphate released from the bone will
complex with calcium in ECF and limit thecomplex with calcium in ECF and limit the
rise in ionized calciumrise in ionized calcium
 Hence, in order to effect increase ionizedHence, in order to effect increase ionized
calcium …. Coordinated effect on kidneyscalcium …. Coordinated effect on kidneys
– phosphaturic action of PTH– phosphaturic action of PTH
BONEBONE

22.  2 actions of PTH:2 actions of PTH:
1. inhibits phosphate reabsorption1. inhibits phosphate reabsorption
- by inhibiting Na- by inhibiting Na++
POPO44 cotransport in PCTcotransport in PCT
- effect: phosphaturia- effect: phosphaturia
2. stimulates Ca2. stimulates Ca2+2+
reabsorptionreabsorption
- on DCT- on DCT
KIDNEYSKIDNEYS

23. SMALL INTESTINE
 INDIRECTLY, stimulates intestinal Ca2+
absorption via activation of vitamin D
 PTH stimulates renal 1α
-hydroxylase, the
enzyme that converts 25-
hydroxycholecalciferol to the active form,
(vit D3 ) 1,25 dihydroxycholecalciferol
(stimulates intestinal Ca2+
absorption)

24. BONE KIDNEYS INTESTINES
↑ PTH SECRETION
↓ PLASMA CALCIUM
↑ Bone resorption ↓ phosphate reabsorption
(phosphaturia)
↑ calcium reabsorption
↑ urinary cAMP
↑ calcium absorption
(indirect via 1,25 di-
Hydroxycholecalciferol)
↑ plasma calcium toward NORMAL

25. Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+
Figure 6.11
Calcitonin
stimulates
calcium salt
deposit
in bone
Parathyroid
glands release
parathyroid
hormone (PTH)
Thyroid
gland
Thyroid
gland
Parathyroid
glands
Osteoclasts
degrade bone
matrix and release
Ca2+
into blood
Falling blood
Ca2+
levels
Rising blood
Ca2+
levels
Calcium homeostasis of blood: 9–11 mg/100 ml
PTH
Imbalanc
e
Imbalance
calcitonin;
PTH
secreted
↑calcitonin

26. Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+
Falling blood
Ca2+
levels
Calcium homeostasis of blood: 9–11 mg/100 ml
Imbalance
Imbalance
Figure 6.11

27. Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+
Parathyroid
glands release
parathyroid
hormone (PTH)
Thyroid
gland
Parathyroid
glands
Falling blood
Ca2+
levels
Calcium homeostasis of blood: 9–11 mg/100 ml
PTH
Imbalance
Imbalance
Figure 6.11

28. Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+
Parathyroid
glands release
parathyroid
hormone (PTH)
Thyroid
gland
Parathyroid
glands
Osteoclasts
degrade bone
matrix and release
Ca2+
into blood
Falling blood
Ca2+
levels
Calcium homeostasis of blood: 9–11 mg/100 ml
PTH
Imbalance
Imbalance
Figure 6.11

29. PTH stimulates bone to release calcium (Ca+2) and the kidneys to conserve
calcium. It indirectly stimulates the intestine to absorb calcium. The resulting
increase in blood calcium concentration inhibits secretions of PTH

30. CALCITONINCALCITONIN
 polypeptide hormonepolypeptide hormone
 synthesized and secreted by the parafollicular C-synthesized and secreted by the parafollicular C-
cells of the thyroid glandcells of the thyroid gland
 NOT AS IMPORTANT AS PTH AND VITAMIN DNOT AS IMPORTANT AS PTH AND VITAMIN D
 Stimulus for secretion: hypercalcemiaStimulus for secretion: hypercalcemia
 EFFECTS:EFFECTS:
inhibit osteoclastic bone resorptioninhibit osteoclastic bone resorption
-- immediate effect
decrease formation of new osteoclasts
– more prolonged effect

31. Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+
Figure 6.11
Rising blood
Ca2+
levels
Calcium homeostasis of blood: 9–11 mg/100 ml
Imbalance
Imbalance

32. Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+
Figure 6.11
Thyroid
gland
Rising blood
Ca2+
levels
Calcium homeostasis of blood: 9–11 mg/100 ml
Imbalance
Imbalance

33. Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+
Figure 6.11
calcitonin
secreted
Thyroid
gland
Rising blood
Ca2+
levels
Calcium homeostasis of blood: 9–11 mg/100 ml
Imbalance
Imbalance
↑calcitonin

34. Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+
Figure 6.11
Calcitonin
stimulates
calcium salt
deposit
in bone
Thyroid
gland
Rising blood
Ca2+
levels
Calcium homeostasis of blood: 9–11 mg/100 ml
PTH;
calcitonin
secreted
↑calcitonin

35. Calcitonin has effects opposite of PTH effects on bones,
kidneys.

36. Other PTH RegulatorsOther PTH Regulators
 HypermagnesemiaHypermagnesemia inhibits PTH secretioninhibits PTH secretion
 HypomagnesemiaHypomagnesemia stimulates secretionstimulates secretion
 CatecholaminesCatecholamines (acting on(acting on ββ adrenergicadrenergic
receptors) stimulate PTH secretionreceptors) stimulate PTH secretion

37. HypoparathyroidismHypoparathyroidism
 Can be caused by injury or inadvertentCan be caused by injury or inadvertent
surgical removalsurgical removal
 Main problem:Main problem: Decreased PTHDecreased PTH
hypocalcemiahypocalcemia
- decreased bone resorption- decreased bone resorption
- decreased renal Ca- decreased renal Ca2+2+
reabsorptionreabsorption
- decreased intestinal Ca- decreased intestinal Ca2+2+
absorptionabsorption
hyperphosphatemiahyperphosphatemia
- increased PO- increased PO44 reabsorptionreabsorption

38. SIGNS AND SYMPTOMS OFSIGNS AND SYMPTOMS OF
HYPOPARATHYROIDISMHYPOPARATHYROIDISM
 Positive Chvostek’s (facial muscle twitch) signPositive Chvostek’s (facial muscle twitch) sign
- Positive Trousseau’s (carpal spasm) sign- Positive Trousseau’s (carpal spasm) sign
- Delayed cardiac repolarization with- Delayed cardiac repolarization with prolongationprolongation
of the QT intervalof the QT interval
- Paresthesia- Paresthesia
- Tetany- Tetany
 Treatment: oral calcium supplements; vit DTreatment: oral calcium supplements; vit D

39. HyperparathyroidismHyperparathyroidism
 Can be caused by a tumorCan be caused by a tumor
 Problem: Increased PTH secretionProblem: Increased PTH secretion
 Bones are resorbed and soften, deformBones are resorbed and soften, deform
more easily. Fracture spontaneouslymore easily. Fracture spontaneously
 Excess calcium and phosphate releasedExcess calcium and phosphate released
into body fluids may be deposited ininto body fluids may be deposited in
abnormal places. (kidney stones)abnormal places. (kidney stones)

41. HyperparathyroidismHyperparathyroidism

42. SECONDARYSECONDARY
HYPERPARATHYROIDISMHYPERPARATHYROIDISM
 Can be caused by vitamin D deficiency orCan be caused by vitamin D deficiency or
chronic renal disease in which the kidneyschronic renal disease in which the kidneys
are unable to produce sufficient amountsare unable to produce sufficient amounts
of the active form of vitamin D, 1,25of the active form of vitamin D, 1,25
dihydroxycholecalciferoldihydroxycholecalciferol
 Occurs as a compensation forOccurs as a compensation for
hypocalcemiahypocalcemia

43. VITAMIN D DEFICIENCYVITAMIN D DEFICIENCY
 IMPAIRED ABSORPTION OF CALCIUMIMPAIRED ABSORPTION OF CALCIUM
 PTH MAINTAINS PLASMA LEVEL ATPTH MAINTAINS PLASMA LEVEL AT
EXPENSE OF BONESEXPENSE OF BONES
 RICKETS IN CHILDRENRICKETS IN CHILDREN
 OSTEOMALACIA IN ADULTSOSTEOMALACIA IN ADULTS

44. Homeostatic ImbalancesHomeostatic Imbalances
 RicketsRickets

Occurs in childrenOccurs in children

inadequate bone mineralizationinadequate bone mineralization

Bowed legs and deformities of theBowed legs and deformities of the
pelvis, skull, and rib cage are commonpelvis, skull, and rib cage are common

Caused by insufficient calcium in theCaused by insufficient calcium in the
diet, or by vitamin D deficiencydiet, or by vitamin D deficiency

45. Homeostatic ImbalancesHomeostatic Imbalances
 OsteomalaciaOsteomalacia

Occurs in adultsOccurs in adults

Main symptom is pain when weight isMain symptom is pain when weight is
put on the affected boneput on the affected bone

Causes: insufficient calcium in the dietCauses: insufficient calcium in the diet
vitamin D deficiencyvitamin D deficiency
- usually occurs as a result of- usually occurs as a result of
steatorrheasteatorrhea

46. Homeostatic ImbalancesHomeostatic Imbalances
 OsteoporosisOsteoporosis

Most common of all bone diseases inMost common of all bone diseases in
adults especially in old ageadults especially in old age

Main problem: diminished organic boneMain problem: diminished organic bone
matrixmatrix

bone reabsorption > bone depositionbone reabsorption > bone deposition

47. OSTEOPOROSISOSTEOPOROSIS

Spongy boneSpongy bone of the spine is most vulnerableof the spine is most vulnerable

Bones become so fragile that sneezing orBones become so fragile that sneezing or
stepping off a curb can cause fracturesstepping off a curb can cause fractures

CAUSES:CAUSES:
1. lack of physical stress on the bones1. lack of physical stress on the bones
2. malnutrition2. malnutrition
3. lack of vitamin C3. lack of vitamin C
- formation of osteoid by osteoblasts- formation of osteoid by osteoblasts

48. OSTEOPOROSISOSTEOPOROSIS
4. postmenopausal lack of estrogen secretion4. postmenopausal lack of estrogen secretion
- estrogens decrease the number and activity- estrogens decrease the number and activity
of osteoclastsof osteoclasts
5. old age5. old age
6. Cushing’s syndrome6. Cushing’s syndrome
- decreased deposition of protein and- decreased deposition of protein and
increased catabolism of proteinincreased catabolism of protein
- depresses osteoblastic activity- depresses osteoblastic activity

49. Thank