Parathyroids

PARATHYROID PARATHYROID GLANDSGLANDS

Total Body CalciumTotal Body Calcium

99% of calcium of body calcium is in 99% 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 by Ionized calcium is tightly regulated by hormonal mechanismshormonal mechanisms

Got Calcium?Got Calcium? Ca2+

Importance of Ionic Calcium in Importance 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

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

CARPOPEDAL SPASM

HYPERCALCEMIAHYPERCALCEMIA

Depressed nervous system, sluggish Depressed nervous system, sluggish reflexesreflexes

s/s: constipation, polyuria, polydipsia, s/s: constipation, polyuria, polydipsia, hyporeflexia, lethargy, coma hyporeflexia, 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

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

Excreted infeces

(Salivary, pancreatic,Intestinal fluids)

NET: 200mg

VITAMINVITAMIN D D

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

7-DEHYDROCHOLESTEROL

CHOLECALCIFEROL (vitamin D3) DIET

LIVER

25-OH-CHOLECALCIFEROL

1,25 dihydroxyCholecalciferol (active)

24,25 (OH2)-Cholecalcalciferol(inactive)

1α hydroxylase

↓ Ca2+

↑ PTH↓ PO4

(+)

UV light (skin)

Kidneys (proximal tubules)

VITAMIN DVITAMIN D

Effect: Effect: 1. increase calcium absorption from 1. increase calcium absorption from

the GITthe GIT2. decreases renal calcium and 2. decreases renal calcium and

phosphate excretion (weak effect)phosphate excretion (weak effect)3. extreme quantities 3. extreme quantities → → causes bone causes bone

absorptionabsorption smaller quantities smaller quantities → promotes bone → promotes bone

calcificationcalcification

Biosynthesis, Storage & Secretion of PTH

synthesized as the preprohormone synthesized as the preprohormone (Preproparathyroid Hormone) by chief (Preproparathyroid Hormone) by chief cellscells

PTH is PTH is synthesized continuouslysynthesized continuously

PTH is released by exocytosis in PTH is released by exocytosis in response to reduced plasma calciumresponse to reduced plasma calcium

PARATHYROID HORMONEPARATHYROID HORMONE

ROLE: regulate the concentration of CaROLE: regulate the concentration of Ca 2+2+ in the ECFin the ECF

Stimulus: hypocalcemiaStimulus: hypocalcemia Target organs: bone, kidneys, intestineTarget organs: bone, kidneys, intestine

REGULATION OF PTH SECRETIONREGULATION OF PTH SECRETION

PTHSECRETION

MECHANISM OF PTH SECRETIONMECHANISM OF PTH SECRETION

CaCa2+2+ sensing receptors (parathyroid cell sensing receptors (parathyroid cell membrane) linked via a G-protein to membrane) linked via a G-protein to phospholipase Cphospholipase C

When CaWhen Ca2+ 2+ is is ↑, Ca↑, Ca2+2+ binds to the receptor binds to the receptor and activates phospholipase C → and activates phospholipase C → increased levels of IPincreased levels of IP33/Ca/Ca2+2+ which inhibits which inhibits

PTH secretionPTH secretion

ACTIONS OF PTHACTIONS OF PTH

Overall effect: to increase plasma CaOverall effect: to increase plasma Ca 2+2+

Direct action on bone and kidneysDirect action on bone and kidneys

- mediated by cAMP- mediated by cAMP

Indirect action on intestines: via activation Indirect action on intestines: via activation of vitamin D of vitamin D

BONEBONE PTH receptors are located on osteoblasts but not PTH receptors are located on osteoblasts but not

on osteoclastson osteoclasts

Effects:Effects: direct action on osteoblasts (brief): Increase direct action on osteoblasts (brief): Increase

bone formation bone formation long lasting action on osteoclasts (indirect); long lasting action on osteoclasts (indirect);

Increase in bone resorption Increase in bone resorption (mediated by cytokines released (mediated by cytokines released

from osteoblasts)from osteoblasts)

Overall effect of PTH: promote bone Overall effect of PTH: promote bone resorption resorption ( delivering both Ca( delivering both Ca2+2+ and PO and PO44 to to

ECF)ECF)

the phosphate released from the bone will the phosphate released from the bone will complex with calcium in ECF and limit the complex with calcium in ECF and limit the rise in ionized calciumrise in ionized calcium

Hence, in order to effect increase ionized Hence, in order to effect increase ionized calcium …. Coordinated effect on kidneys calcium …. Coordinated effect on kidneys – phosphaturic action of PTH– phosphaturic action of PTH

BONEBONE

2 actions of PTH:2 actions of PTH:

1. inhibits phosphate reabsorption1. inhibits phosphate reabsorption

- by inhibiting Na- by inhibiting Na++ PO PO44 cotransport in PCT cotransport in PCT

- effect: phosphaturia- effect: phosphaturia

2. stimulates Ca2. stimulates Ca2+2+ reabsorption reabsorption

- on DCT- on DCT

KIDNEYSKIDNEYS

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)

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

Hormonal Control of Blood CaHormonal Control of Blood Ca2+2+

Figure 6.11

Calcitoninstimulatescalcium saltdepositin bone

Parathyroidglands releaseparathyroidhormone (PTH)

Thyroidgland

Thyroidgland

Parathyroidglands

Osteoclastsdegrade bonematrix and releaseCa2+ into blood

Falling bloodCa2+ levels

Rising bloodCa2+ levels

Calcium homeostasis of blood: 9–11 mg/100 ml

PTH

Imbalance

Imbalance

calcitonin;PTHsecreted↑calcitonin




Imbalance

Imbalance

Figure 6.11



Thyroidgland

Parathyroidglands



PTH

Imbalance

Imbalance

Figure 6.11



Thyroidgland

Parathyroidglands

Osteoclastsdegrade bonematrix and releaseCa2+ into blood



PTH

Imbalance

Imbalance

Figure 6.11

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

CALCITONINCALCITONIN

polypeptide hormone polypeptide 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 resorption inhibit osteoclastic bone resorption - - immediate effect

decrease formation of new osteoclasts – more prolonged effect


Figure 6.11



Imbalance

Imbalance


Figure 6.11

Thyroidgland



Imbalance

Imbalance


Figure 6.11

calcitoninsecreted

Thyroidgland



Imbalance

Imbalance

↑calcitonin


Figure 6.11

Calcitoninstimulatescalcium saltdepositin bone

Thyroidgland



PTH;calcitoninsecreted

↑calcitonin

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

Other PTH RegulatorsOther PTH Regulators

HypermagnesemiaHypermagnesemia inhibits PTH secretion inhibits PTH secretion

HypomagnesemiaHypomagnesemia stimulates secretion stimulates secretion

CatecholaminesCatecholamines (acting on (acting on ββ adrenergic adrenergic receptors) stimulate PTH secretionreceptors) stimulate PTH secretion

HypoparathyroidismHypoparathyroidism Can be caused by injury or inadvertent Can 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 reabsorption reabsorption

SIGNS AND SYMPTOMS OF SIGNS 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 prolongation prolongation of the QT intervalof the QT interval

- Paresthesia- Paresthesia

- Tetany- Tetany

Treatment: oral calcium supplements; vit DTreatment: oral calcium supplements; vit D

HyperparathyroidismHyperparathyroidism

Can be caused by a tumorCan be caused by a tumor Problem: Increased PTH secretionProblem: Increased PTH secretion Bones are resorbed and soften, deform Bones are resorbed and soften, deform

more easily. Fracture spontaneouslymore easily. Fracture spontaneously Excess calcium and phosphate released Excess calcium and phosphate released

into body fluids may be deposited in into body fluids may be deposited in abnormal places. (kidney stones)abnormal places. (kidney stones)

HyperparathyroidismHyperparathyroidism

SECONDARYSECONDARY HYPERPARATHYROIDISMHYPERPARATHYROIDISM

Can be caused by vitamin D deficiency or Can be caused by vitamin D deficiency or chronic renal disease in which the kidneys chronic renal disease in which the kidneys are unable to produce sufficient amounts are unable to produce sufficient amounts of the active form of vitamin D, 1,25 of the active form of vitamin D, 1,25 dihydroxycholecalciferoldihydroxycholecalciferol

Occurs as a compensation for Occurs as a compensation for hypocalcemiahypocalcemia

VITAMIN D DEFICIENCYVITAMIN D DEFICIENCY

IMPAIRED ABSORPTION OF CALCIUMIMPAIRED ABSORPTION OF CALCIUM PTH MAINTAINS PLASMA LEVEL AT PTH MAINTAINS PLASMA LEVEL AT

EXPENSE OF BONESEXPENSE OF BONES RICKETS IN CHILDRENRICKETS IN CHILDREN OSTEOMALACIA IN ADULTSOSTEOMALACIA IN ADULTS

Homeostatic ImbalancesHomeostatic Imbalances

RicketsRickets Occurs in children Occurs in children inadequate bone mineralization inadequate bone mineralization Bowed legs and deformities of the Bowed legs and deformities of the

pelvis, skull, and rib cage are commonpelvis, skull, and rib cage are common Caused by insufficient calcium in the Caused by insufficient calcium in the

diet, or by vitamin D deficiencydiet, or by vitamin D deficiency

Homeostatic ImbalancesHomeostatic Imbalances

OsteomalaciaOsteomalacia Occurs in adultsOccurs in adults Main symptom is pain when weight is Main 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

Homeostatic ImbalancesHomeostatic Imbalances OsteoporosisOsteoporosis

Most common of all bone diseases in Most common of all bone diseases in adults especially in old ageadults especially in old age

Main problem: diminished organic bone Main problem: diminished organic bone matrixmatrix

bone reabsorption > bone depositionbone reabsorption > bone deposition

OSTEOPOROSISOSTEOPOROSIS Spongy boneSpongy bone of the spine is most vulnerable of the spine is most vulnerable Bones become so fragile that sneezing or Bones 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

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 osteoclasts of osteoclasts

5. old age5. old age

6. Cushing’s syndrome 6. Cushing’s syndrome

- decreased deposition of protein and - decreased deposition of protein and increased catabolism of protein increased catabolism of protein

- depresses osteoblastic activity- depresses osteoblastic activity

Thank you

Parathyroids

Documents

Transcript of Parathyroids