Parathyroid

Question 1

Parathyroid anatomy

Answer 1

Tiny round structures usually embedded in the thyroid gland
Location vary between species
Usually at the poles of the 2 thyroid glands
Most species have 2 but pigs only one

Question 2

Calcium and phosphate metabolism

Answer 2

Parathyroid gland is the main organ involved in the calcium and phosphate metabolism- these ions play a major role in physiological homeostasis

Question 3

Phosphate metabolism

Answer 3

Phosphate ions play a major role in physiological homeostasis
Participate as chemical buffers
Make up the composition of cell membrane and intracellular components
-nucleic acid
-ATP
-ADP

85% in bones, 14% intracellular 1% ECF

Question 4

Calcium metabolism

Answer 4

Calcium ions are key ions for:

• muscle contraction
• nerve cell activity
• release of hormones by exocytosis
• activation of several enymes
• coagulation
• maintenance of membrane stability
• structural integrity of bones and teeth

99% in bones, <1% intracellular 0.1% ECFs

3 forms of calcium in blood
40% bound to proteins- mainly albumin
10% is combines with other anions - sulphate, phosphate etc
50% is ionized (iCa)- biologically active form. Precisely regulated

Regulation of calcium levels involves control of the movement of calcium between the ECF and bones, GI tract nd kidneys
3 hormones involves: PTH, VIT D, Calcitonin

Question 5

Parathyroid hormone

Answer 5

PTH is produced by one of the 2 types of cells present in the parathyroid glandular tissue
Active cells=chielf cells- produced PTH or parathormone
Inactive or degeneratied= oxyphil cells- unknown function

Question 6

PTH syntehsis

Answer 6

Chief cells are very sensitive to decline in iCa
They have calcium sensing receptors on membrane surface (GPCR)
A decrease in iCa activates the receptor- during normal Ca levels the receptor is inactive

After stimulation PTH is produced as other protein hormones
Prepro-PTH is synthesized in ER and then cleaves to pro-PTH
The pro portion is removed by the golgi and the resultingg PTH is secreted by exocytosis
-metabolized by kidney and liver
-half life of 5-10 minutes

Question 7

PTH Action

Answer 7

Overall effect of PTH is to increase calcium and decrease phosphate concentrations in ECFs
Direct effect on bone and kidney metabolism of calcium
Indirect effect on GI metabolism of Ca (kidney to VIT D in SI)

Question 8

PTH: bone

Answer 8

Direct effect on bone
Binds to its receptors on osteocytes and stimulates osteocytic-osteolysis
-osterocytes pump Ca from the fluids within bone canaliculi into the interstitial fluid and bloood
Binds to receptors on bone osteoblast cells and stimulates the production of osteoclast-activating factor
-causes activation of nearby osteroclasts
-moves toward the bone and begin to digest the organic matrix
-release Ca and P into blood

Question 9

PTH: kidney

Answer 9

Direct effect on kidney
Increase absorption of calcium in the distal convoluted tubules of the kidneys
Decreases reabsorption of phosphate in the proximal tubules of the kidneys
Activation of VIT D by the kidneys
Binds to its receptors on proximal renal tubule cells and stimulates the enzyme that covers 25-hydroxyvitamin D to a hormone called 1,25-dihydroxyvitamin D
1-alpha hydroxyls enzyme-only active when PTH has acted on the cell

Question 10

Vitamin D metabolism

Answer 10

VIT D only becomes an active hormone under PTH action on renal cells
D3 and D2 to liver
Liver converts them to 25-hydroxyvitamin D
+ calcidiol and 25(OH)D
Kidney converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D

Question 11

PTH: GI

Answer 11

Indirect effect on GI
Calcitriol stimulates the active transport of dietary calcium across the intestinal epithelium
-without calcitriol most animals are unable to acquire enough calcium from the diet to support normal bone structure
-by regulating calcitriol concentration the animal can regulate Ca entering the blood from diet

Except horse and rabbit- handout fermenters

• intestinal mechanisms to absorb calcium all the time
• regualte blood Ca by increasing/decreasing urinary loss
• -chalky white urine

Question 12

PTH regulation

Answer 12

PTH secretion is mainly controlled by iCa
Depends upon the free (ionized) calcium concentration in the blood
Decrease in iCa stimulates pTH secretion and vice-versa

Question 13

PTH synthesis, secretion, control

Answer 13

Synthesized and secreted by parathyroid glands
Production is stimulated by low extracellular or blood Ca levels and controlled through negative feedback mechanism
Primary action is response to hypocalcemia is to increase calcium

PTH target tissues:

• bone- stimulate osteoclast activity (breakdown of bone) and inhibits deposition of calcium
• Kidney- stimulate tubular reabsorption-inhibits excretion of calcium
• Digestive tract-stimulate intestinal uptake of Ca; indirectly inhibits excretion of Ca; PTH stimulates production of VIT D by kidneys, which stimulates production of a Ca binding protein that facilitates absorption of Ca from GI tract

PTH raises Calcium

Question 14

Calcitonin

Answer 14

Produced by parafolicullar cell or C cell in thyroid gland
They are scattered through the body of the thyroid glands
Synthesized as other protein hormones
Acts as a counter balance to PTH

Question 15

Calcitonin regulation

Answer 15

Calcitonin secretion is regulated by Ca
-increased Ca stimulates calitonin secretion
GI hormones also stimulates the secretion of calcitonin
-gastrin, secretin, glucagon

Question 16

Calcitonin actions

Answer 16

Decreased the movement of Ca in the bone
-from the labile bone Ca pool (behind the osteoblast-osteocyte barrier) to the ECF
Decreased bone reabsorption through an inhibitor effect on osteoclast
Increases movement of phosphate from ECF into bone
Increases renal excretion of Ca

Question 17

Summary of Calcitonin

Answer 17

Calcitonin is a thyroid produced hormoen
Synthesized and secreted primarily by parafollicular or C cells in thyroid gland, but produced in other organs or tissues depending on species
Production is stimulated by high EC or blood Ca levels and controlled through negative feedback mechanism
Primary action in response to high blood Ca is to decrease Ca

Calcitonin target tissues:
Bone-inhibits osteroclast activity (digestion of bone)-stimulates deposition of Ca
Kidney- inhibits tubular reabsorption of Ca- stimulates excretion of Ca
Digestive tract- inhibits intestinal uptake of calcium0 stimulates excretion of Ca

Calcitonin lowers Ca

Question 18

calcitonin release when Ca is

Answer 18

too high

Question 19

Actions of Calcitonin:

Answer 19

Decrease Ca reabsorption from urine
Decrease Ca uptake in intestines
Increase Ca deposition in bones

Question 20

Parathyroid hormone release when Ca

Answer 20

too low

Question 21

PTH causes calcium levels in blood

Answer 21

to rise

Question 22

PTH actions:

Answer 22

Increase Ca uptake in intestines
Increase Ca reabsorption from urine
Increase Ca release from bones

Question 23

Thyroid related calcium disorders

Answer 23

Hyperparathyroidism
Hypoparathyroidism
Thyroid parafollicular cell dysfunction

Question 24

Hyperparathyroidism

Answer 24

An uncommon disorder where parathyroid glands produce excessive amounts of pTH that leads to extremely high blood Ca concetrations
Occurs rarely in dogs and cats, but more common in dogs
Presented as an adenoma or benign, parathyroid hormone-secreting tumor, on one or more of the parathyroid glands
Parathyroid glands may become enlarges due to hyperplasia of parathyroid or chief cells

Question 25

Hypoparathyroidism

Answer 25

A metabolic disorder characterize by low blood calcium concentrations as a result of insufficient amounts of PTH
Occurs spontaneously and is uncommon in dogs, rare in cats

Question 26

Thyroid parafollicular cell dysfunction

Answer 26

A rare disorder in dogs and cars where C cell production of calcitonin may be impaired leading to high blood calcium concentrations

Question 27

Hypercalcemia

Answer 27

A oof of diseases can case increase in Ca levels
Malignancy- PTH related protein
CKD- secondary hyperparathyroidism
Hypoadrenocorticism- cortisol reduces Ca absorption in the intestines
Primary hyperparathyroidism- increased production from hyperpalsia or neoplasia

Question 28

Hypercalcemia clinical signs

Answer 28

PU/PD or urinary incontinence

• impaired response of distal renal tubules to antidiuretic hormone
• hypercalcemia interferes with ADH binding to V2 receptors and increase in aquaporin expression and water reabsoprtion

Depression and muscle weakness
-depressed excitability of neuromuscular tissue- decrease membrane sodium permeability/inhibit depolarization

Mild Gi signs
-inapetence, weight loss and decreased GI motility- due to decrease in excitability of smooth muscle cells

Ca urolits
-more Ca excretion- urolits are more likely to form the urin is alkaline which factors precipitation of calcium phosphate

Renal failure
-not completely understood, one of the reasons is mineralization of renal tissue

Question 29

Hypocalcemia

Answer 29

A lot of diseases can cause decrease in Ca levels
Latrogenic hypoparathyroidism
-after thyroidectomy
Nutritional secondary hyperparathyroidism
-elevated PTh secondary to decreased Ca due to dietary problems
Primary hypoparathyroidism
-decreased production from immune mediate destruction of agenesia

Question 30

Hypocalcemia Clinical signs

Answer 30

Anorexia, facial rubbing, nervousness and stiff gair
-earky signs
Paresthesias, hyperventilation
Tetany and seizures
-nervous and muscular system are both absormally excitabile because hypocalcemia increase membrane Na permeability and membrane depolarization