Parathyroid Gland

• Function of the parathyroid gland

• Calcium metabolism & its regulation
• Secretion & function of calcitonin
 Parathyroid Hormone
• Controls extracellular calcium and phosphate
concentrations by regulating intestinal
reabsorption, renal excretion, and exchange
between the extracellular fluid and bone of these
ions.
• Hypercalcemia→ Excess activity of the
parathyroid gland causes rapid absorption of
calcium salts from the bones
• Hypocalcemia→ hypofunction of the parathyroid
glands
 Physiologic Anatomy of the Parathyroid Glands
• There are four parathyroid glands in humans;
located immediately behind the thyroid gland
—one behind each of the upper and each of
the lower poles of the thyroid.
• Each parathyroid gland is about 6 millimeters
long, 3 millimeters wide, and 2 millimeters
thick
• contains mainly chief cells secrete PTH mainly
and a small to moderate number of oxyphil
cells,
 Chemistry of Parathyroid Hormone
• Ribosomes→ preprohormone, a polypeptide
chain of 110 amino acids
• ER & GA → cleaved first to a prohormone with 90
amino acids, then to the hormone itself with 84
amino acids
• Finally packaged in secretory granules in the
cytoplasm of the cells.
• The final hormone has a molecular weight of
about 9500.
• Smaller compounds with as few as 34 amino
acids adjacent to the N terminus of the molecule
have also been isolated from the parathyroid
glands that exhibit full PTH activity.
 Effect of Parathyroid Hormone on Calcium and
Phosphate Concentrations in the Extracellular Fluid
• PTH to increase calcium and
phosphate absorption from
the bone and decreases the
excretion of calcium by the
kidneys.
• The decline in phosphate
concentration is caused by a
strong effect of PTH to
increase renal phosphate
excretion, to override
increased phosphate
absorption from the bone.
 Parathyroid Hormone Increases Calcium and Phosphate
Absorption from the Bone

PTH has two effects on bone in

causing absorption of calcium and
phosphate
1) Rapid phase results from
activation of the already existing
bone cells (mainly the osteocytes) to
promote calcium and phosphate
absorption
2) results from proliferation of the
osteoclasts, followed by greatly
increased osteoclastic reabsorption
of the bone itself
 Parathyroid Hormone Decreases Calcium
Excretion and Increases Phosphate Excretion by
the Kidneys
• PTH also increases renal tubular reabsorption of calcium at
the same time that it diminishes phosphate reabsorption.
• It increases the rate of reabsorption of magnesium ions and
hydrogen ions while it decreases the reabsorption of sodium,
potassium, and amino acid ions in much the same way that it
affects phosphate.
Parathyroid Hormone Increases Intestinal Absorption
of Calcium and Phosphate
• PTH greatly enhances both calcium and phosphate absorption from the
intestines by increasing the formation in the kidneys of 1,25-
dihydroxycholecalciferol from vitamin D
• Within a few minutes after PTH administration, concentration of cAMP
increases in the osteocytes, osteoclasts, and other target cells. This cAMP
causes osteoclastic secretion of enzymes and acids to cause bone
reabsorption and formation of 1,25-dihydroxycholecalciferol in the
kidneys.
 Control of Parathyroid Secretion by
Calcium Ion Concentration
• Decrease in calcium ion concentration in the
ECF causes the PG to increase their rate of
secretion within minutes.
• If decrease in concentration persists, glands
will hypertrophy, sometimes fivefold or more
• Conditions causing enlarged parathyroid gland:
• Rickets
• Pregnancy
• Lactation
• Conditions causing reduced sized parathyroid
gland
• Excessive calcium in diet
• Increased vit D in diet
• Bone absorption caused by factors other than
PTH
• Changes in extracellular fluid calcium ion
concentration are detected by a calcium-sensing
receptor (CaSR) in parathyroid cell membranes.
• The CaSR is a G protein–coupled receptor that, when
stimulated by calcium ions, activates phospholipase C
and increases intracellular inositol 1,4,5-triphosphate
and diacylglycerol formation.
• This stimulates release of calcium from intracellular
stores, which, in turn, decreases PTH secretion.
Conversely, decreased extracellular fluid calcium ion
concentration inhibits these pathways and stimulates
PTH secretion.
• long-term, chronic
changes in calcium
concentration of only a
few percentage points
can cause as much as 100
percent change in
parathyroid hormone
concentration.
• Increase in plasma
calcium concentration of
about 10% causes an
immediate twofold or
more increase in the rate
of calcitonin (blue line)
Summary of Effects of Parathyroid
Hormone
 Calcitonin
• A peptide hormone secreted by the thyroid
gland, tends to decrease plasma calcium
concentration and, in general, has effects
opposite to those of PTH.
• Synthesis and secretion of calcitonin occur in
the parafollicular cells, or C cells, lying in the
interstitial fluid between the follicles of the
thyroid gland.
• The primary stimulus for calcitonin secretion is
increased plasma calcium ion concentration.
• calcitonin ↓ Ca⁺ plasma concentration
• The immediate effect is to decrease the absorptive
activities of the osteoclasts
• Prolonged effect of calcitonin is to decrease the
formation of new osteoclasts.
• Minor effects on calcium handling in the kidney
tubules and the intestines
• Effects are opposite to PTH , but of little important
• Calcitonin Has a Weak Effect on Plasma
Calcium Concentration in the Adult Human.
• The effect of calcitonin in children is much
greater because bone remodeling occurs
rapidly in children
• In Paget’s disease , in which osteoclastic
activity is greatly accelerated, calcitonin has a
much more potent effect of reducing the
calcium absorption.
 Disorders of PTH
• Hypoparathyroidism

• Primary hyperparathyroidism

• Secondary hyperparathyroidism
 hypoparathyroidism
• ↓PTH → ↓Ca+ reabsorption from bone →↓Ca+ level
on body fluids

• Bone remains strong

• If parathyroid glands are suddenly removed

• 1) Ca+ levels fall from 9.4mg/dl to 6-7ng/dl within 2-3
days
• 2) phosphate concentration may double
• 3) decrease in Ca+ → tetany (tetanic spasm of the
laryngeal muscles)
 Treatment
• Hypothyroidsim is usually not treated with
PTH administration

• Large quantities of vit D daily 100,000

units/day along with 1-2 grams of calcium

• 1,25-dihydroxycholecalciferol
 Primary Hyperparathyroidism
• An abnormality of the parathyroid glands causes
inappropriate, excess PTH secretion
• The cause of primary hyperparathyroidism
ordinarily is a tumor of one of the parathyroid
glands; such tumors occur much more frequently
in women than in men or children.
• Hyperparathyroidism causes extreme osteoclastic
activity in the bones. This elevates the calcium
ion concentration in the extracellular fluid while
usually depressing the concentration of
phosphate ions
• In severe hyperparathyroidism the bone ma be
eaten away entirely
• Indeed, the reason a hyperparathyroid person
seeks medical attention is often a broken bone
• Radiographs of the bone show extensive
decalcification and, occasionally, large punched-
out cystic areas of the bone that are filled with
osteoclasts in the form of so-called giant cell
osteoclast “tumors.”
• The cystic bone disease of hyperparathyroidism is
called osteitis fibrosa cystica
• Osteoblastic activity in the bones also increases
greatly in attempt to make up for the old bone
absorbed by the osteoclastic activity.
• When the osteoblasts become active, they
secrete large quantities of alkaline phosphatase.
• Therefore, one of the important diagnostic
findings in hyperparathyroidism is a high level of
plasma alkaline phosphatase.
• Effects of Hypercalcemia in Hyperparathyroidism.
• Hyperparathyroidism can cause the plasma calcium level to
rise to 12 to 15 mg/dl

• The effects of such elevated calcium levels are:

• depression of the central and peripheral nervous systems,
• muscle weakness
• constipation
• abdominal pain
• peptic ulcer
• lack of appetite
• depressed relaxation of the heart during diastole
Parathyroid Poisoning and Metastatic
Calcification
• extreme quantities of PTH are secreted
• ↑Ca⁺ ,↑phosphate
• CaHPO₄ crystals deposition in:
• alveoli of the lungs
• the tubules of the kidneys,
• the thyroid gland,
• the acid-producing area of the stomach mucosa,
• the walls of the arteries
• Calcium level in blood must rise above 17 mg/dl before
there is danger of parathyroid poisoning.
• but once such elevation develops along with concurrent
elevation of phosphate, death can occur in only a few days.
 Formation of Kidney Stones in
Hyperparathyroidism
• Mild hyperparathyroidism leads to formation
of kidney stones(calcium phosphate, calcium
oxalate stones)
• Kidney stones are more common in alkaline
urine(low solubility in alkaline media)
• treatment include acidotic diet & acidic drugs.
 Secondary Hyperparathyroidism
• High levels of PTH occur as a compensation
for hypocalcemia
• this contrasts with primary
hyperparathyroidism, which is associated with
hypercalcemia.
• caused by vitamin D deficiency or chronic
renal disease in which the damaged kidneys
are unable to produce sufficient amounts of
the active form of vitamin D