The document summarizes information about the parathyroid gland and parathyroid hormone (PTH). It discusses: - The location and function of the parathyroid glands in regulating calcium levels. - How PTH acts on bones and kidneys to increase blood calcium levels by promoting bone resorption and renal reabsorption. - Other hormones involved like calcitonin which decreases blood calcium levels. - Disorders that can result from too little or too much PTH such as hypocalcemia, hyperparathyroidism, and renal complications.

1. Parathyroid Gland
- Dr. Chintan

2. Parathyroid Gland
4 parathyroid glands in humans; they are located immediately
behind the thyroid gland
difficult to locate during thyroid operations because they often
look like just another lobule of the thyroid gland - total or
subtotal thyroidectomy frequently resulted in removal of the
parathyroid glands
Removal of half the parathyroid glands usually causes no
major physiologic abnormalities - removal of three of the four
normal glands causes transient hypoparathyroidism
remaining parathyroid tissue - hypertrophy

4. Parathyroid Hormone
Ribosomes – preprohormone - 110 amino acids
Prohormone - 90 amino acids
Hormone - 84 amino acids by ER and Golgi apparatus, and finally is
packaged in secretory granules in the cytoplasm of the cells -
molecular weight of about 9500

5. PTH - Bone
1st rapid phase (Osteolysis) that begins in minutes and increases
progressively for several hours - activation of osteocytes to promote
calcium and phosphate absorption
PTH causes removal of bone salts from two areas in the bone:
(1) from the bone matrix in the surrounding area of the osteocytes
lying within the bone
(2) in the vicinity of the osteoblasts along the bone surface
the osteoblasts and osteocytes form a system of interconnected
cells that spreads all through the bone and over all the bone
surfaces
long, transparent processes extend from osteocyte to osteocyte
throughout the bone structure, and these processes also connect
with the surface osteocytes and osteoblasts - osteocytic membrane
system - separates the bone from ECF

6. PTH - Bone
Between the osteocytic membrane and the bone is a small amount
of bone fluid
the osteocytic membrane pumps Ca ions from the bone fluid into
the ECF, creating a Ca ion concentration in the bone fluid only 1/3rd
that in the ECF
When the osteocytic pump becomes excessively activated, the bone
fluid Ca concentration falls even lower - calcium phosphate salts are
then absorbed from the bone – Osteolysis - occurs without
absorption of the bone’s fibrous and gel matrix
When the pump is inactivated, the bone fluid Ca concentration rises
to a higher level, and calcium phosphate salts are redeposited in the
matrix

7. PTH - Bone
cell membranes of both the osteoblasts and the osteocytes
have receptor proteins for binding PTH - activate the calcium
pump strongly, thereby causing rapid removal of calcium
phosphate salts
Increases the Ca permeability of the bone fluid side of the
osteocytic membrane, thus allowing calcium ions to diffuse
into the membrane cells from the bone fluid
The Ca pump on the other side of the cell membrane transfers
the calcium ions into the ECF
Actual bone – bone fluid – osteocytic membrane - ECF

8. PTH - Bone
2nd slower phase, requiring several days or even weeks to
become fully developed - proliferation of the osteoclasts,
followed by greatly increased osteoclastic reabsorption
osteoclasts do not themselves have membrane receptor
proteins for PTH
the activated osteoblasts and osteocytes send a secondary but
unknown “signal” to the osteoclasts, causing them to set about
their usual task of gulping up the bone over a period of weeks
or months
(1) immediate activation of the preformed osteoclasts
(2) formation of new osteoclasts

9. PTH - Bone
After a few months of excess PTH, osteoclastic resorption of bone
can lead to weakened bones and secondary stimulation of the
osteoblasts that attempt to correct the weakened state.
the late effect is actually to enhance both osteoblastic and
osteoclastic activity
Bone contains such great amounts of Ca in comparison with the
total amount in all the ECF (1000 times) that even when PTH causes
a great rise in Ca concentration in the fluids, it is impossible to
determine any immediate effect on the bones
Prolonged administration or secretion of PTH—over a period of
many months or years—finally results in very evident absorption in
all the bones and even development of large cavities filled with
large, multinucleated osteoclasts

10. PTH - Kidneys
Administration of PTH causes rapid loss of phosphate in the
urine owing to the effect of the hormone to diminish proximal
tubular reabsorption of phosphate ions
PTH increases renal tubular reabsorption of Ca - in the late
distal tubules, the collecting tubules, the early collecting ducts,
and possibly the ascending loop of Henle to a lesser extent
It increases the rate of reabsorption of Mg ions and H ions
it decreases the reabsorption of Na, K and amino acid
No PTH - continual loss of Ca into the urine would eventually
deplete both the ECF and the bones

11. PTH - Intestine
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
MOA – AC – cAMP - Within a few minutes after PTH administration,
the concentration of cAMP increases in the osteocytes, osteoclasts,
and other target cells
cAMP in turn is probably responsible for such functions as
osteoclastic secretion of enzymes and acids to cause bone
reabsorption and formation of 1,25- dihydroxycholecalciferol in the
kidneys
A local hormone, parathyroid hormone-related protein (PTHrP),
acts on one of the PTH receptors and is important in skeletal
development in utero

12. Control of PTH Secretion by Ca
Even the slightest decrease in Ca ion concentration in the ECF
causes the parathyroid glands to increase their rate of
secretion within minutes
parathyroid glands become greatly enlarged in rickets,
pregnancy, lactation
Reduced size of the parathyroid glands
(1) excess quantities of calcium in the diet,
(2) increased vitamin D in the diet,
(3) Bone absorption caused by disuse of the bones

13. Calcitonin
Calcitonin, a peptide hormone secreted by the thyroid gland,
tends to decrease plasma Ca concentration and, in general, has
effects opposite to those of PTH
Parafollicular cells, or C cells, lying in the interstitial fluid
between the follicles of the thyroid gland
32-amino acid peptide with a molecular weight of about 3400
The primary stimulus for calcitonin secretion is increased
plasma Ca ion concentration - Gastrin
calcitonin decreases blood Ca ion concentration rapidly,
beginning within minutes after injection of the calcitonin

14. Calcitonin
1. The immediate effect is to decrease the absorptive activities of
the osteoclasts and possibly the osteolytic effect of the osteocytic
membrane throughout the bone
Shifting the balance in favor of deposition of calcium in the
exchangeable bone calcium salts - especially significant in young
because of the rapid interchange of absorbed and deposited Ca
2. The second and more prolonged effect of calcitonin is to decrease
the formation of new osteoclasts. Also, because osteoclastic
resorption of bone leads secondarily to osteoblastic activity -
decreased numbers of osteoblasts
the effect on plasma calcium is mainly a transient one, lasting for a
few hours to a few days at most – Kidney, intestine ???

15. Calcitonin
Calcitonin Has a Weak Effect on Plasma Calcium
Concentration
in the Adult Human
Calcitonin - ↓ Ca - ↑ PTH
Thyroid removed – no calcitonin – no effect
The effect of calcitonin in children is much greater because
bone remodeling occurs rapidly in children, with
absorption and deposition of calcium as great as 5 grams
or more per day

16. Control of Ca ion
Buffer Function of the Exchangeable Calcium in Bones — the 1st Line
of Defense – rapid reaction
amorphous calcium phosphate compounds, probably mainly
CaHPO4 or some similar compound loosely bound in the bone and
in reversible equilibrium with the Ca and phosphate ions in the ECF
Because of the ease of deposition of these exchangeable salts and
their ease of resolubility, an increase in the concentrations of ECF
Ca and phosphate ions above normal causes immediate deposition
of exchangeable salt – vice versa – more blood flow
The mitochondria of many of the tissues of the body, especially of
the liver and intestine, contain a reasonable amount of
exchangeable Ca that provides an additional buffer system

17. Control of Ca ion
Hormonal Control of Calcium Ion Concentration — the 2nd
Line of Defense
Within 3 to 5 minutes after an acute increase in the calcium ion
concentration, the rate of PTH secretion Decreases – calcitonin
increases
In young animals and possibly in young children – the
calcitonin causes rapid deposition of calcium in the bones
Young children – hormonal control – 1st line
In prolonged calcium excess or prolonged calcium Deficiency
– only PTH important

18. Control of Ca ion
When a person has a continuing deficiency of calcium in the
diet, PTH often can stimulate enough calcium absorption from
the bones to maintain a normal plasma calcium ion
concentration for 1 year or more
eventually, the bones will run out of calcium
when the bone reservoir either runs out of calcium or,
oppositely, becomes saturated with calcium, the long-term
control of extracellular calcium ion concentration resides
almost entirely in the roles of PTH and vitamin D in controlling
calcium absorption from the gut and calcium excretion in the
urine

19. Applied - Hypoparathyroidism
When the parathyroid glands do not secrete sufficient PTH,
the osteocytic reabsorption of exchangeable calcium
decreases and the osteoclasts become inactive
As a result, calcium reabsorption from the bones is so
depressed that the level of calcium in the body fluids
decreases. Yet, because calcium and phosphates are not being
absorbed from the bone, the bone usually remains strong
the calcium level in the blood falls from the normal of 9.4
mg/dl to 6 to 7 mg/dl within 2 to 3 days, and the blood
phosphate concentration may double
Hypocalcemia – Tetany – laryngeal muscle spasm – respiratory
obstruction - death

20. Hypocalcemia
Excitation, irritability of the central and peripheral nervous systems,
Tetany
The signs of tetany in humans include Chvostek's sign - a quick
contraction of the ipsilateral facial muscles elicited by tapping over
the facial nerve at the angle of the jaw;
Trousseau's sign, a spasm of the muscles of the upper extremity
that causes flexion of the wrist and thumb with extension of the
fingers
In individuals with mild tetany in whom spasm is not evident,
Trousseau's sign can sometimes be produced by occluding the
circulation for a few minutes with a blood pressure cuff
Prolonged QT interval

21. Rx - Hypoparathyroidism
PTH is occasionally used for treating hypoparathyroidism - because of the
expense of this hormone - because its effect lasts for a few hours at most -
because the tendency of the body to develop antibodies against it
the administration of extremely large quantities of vitamin D, to as high as
100,000 units per day, along with intake of 1 to 2 grams of calcium
1,25-dihydroxycholecalciferol - much more potent and much more rapid
action
Pseudohypoparathyroidism - the signs and symptoms of
hypoparathyroidism develop but the circulating level of PTH is normal or
elevated - tissues fail to respond to the hormone - receptor disease

22. Primary Hyperparathyroidism
abnormality of the parathyroid glands causes inappropriate,
excess PTH
tumor of one of the parathyroid glands - more frequently in
women - pregnancy and lactation stimulate the parathyroid
glands
extreme osteoclastic activity in the bones – Hypercalcemia
Increase renal excretion of phosphate – hypophosphatemia
Mild - new bone can be deposited rapidly enough to
compensate
Severe – cant compensate – broken bone

23. Primary Hyperparathyroidism
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 giant
cell osteoclast tumors
Multiple fractures of the weakened bones can result from only
slight trauma, especially where cysts develop. The cystic bone
disease of hyperparathyroidism is called osteitis fibrosa cystica
Osteoblastic activity in the bones also increases – secretion of
large quantities of alkaline phosphatase - diagnostic finding

24. Hypercalcemia
depression of the central and peripheral nervous systems,
muscle weakness,
constipation,
abdominal pain,
peptic ulcer,
lack of appetite,
Shortened QT interval
Systolic arrest
Hypercalcemia of Malignancy - breast, kidney, ovary and skin

25. Parathyroid Poisoning
Metastatic Calcification
ECF phosphate concentration rises markedly instead of falling -
the kidneys cannot excrete rapidly enough all the phosphate
being absorbed from the bone.
the calcium and phosphate in the body fluids become greatly
supersaturated, so that calcium phosphate (CaHPO4) crystals
begin to deposit
alveoli of the lungs, the tubules of the kidneys, the thyroid
gland, the acid-producing area of the stomach mucosa, and the
walls of the arteries
Ca above 17 mg/dl + phosphate = Death

26. Kidney Stones
Most patients with mild hyperparathyroidism show few signs of
bone disease and few general abnormalities as a result of elevated
calcium, but they do have an extreme tendency to form kidney
stones
excess calcium and phosphate absorbed from the intestines or
mobilized from the bones in hyperparathyroidism must eventually
be excreted by the kidneys
crystals of calcium phosphate tend to precipitate in the kidney,
forming calcium phosphate stones - calcium oxalate stones develop
because even normal levels of oxalate cause calcium precipitation at
high calcium levels
solubility of most renal stones is slight in alkaline media - tendency
greater in alkaline urine - acidotic diets and acidic drugs for Rx

27. Secondary Hyperparathyroidism
high levels of PTH occur as a compensation for
hypocalcemia rather than as a primary abnormality of
the parathyroid glands
primary hyperparathyroidism associated with
Hypercalcemia
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 - 1,25
dihydroxycholecalciferol

28. Rickets
Rickets occurs mainly in children. It results from calcium or
phosphate deficiency in the extracellular fluid, usually caused by
lack of vitamin D.
If the child is adequately exposed to sunlight, the 7-
dehydrocholesterol in the skin becomes activated by the ultraviolet
rays and forms vitamin D3, which prevents rickets by promoting
calcium and phosphate absorption from the intestines
Rickets tends to occur especially in the spring months because
vitamin D formed during the preceding summer is stored in the liver
and available for use during the early winter months
calcium and phosphate absorption from the bones can prevent
clinical signs of rickets for the first few months of vitamin D
deficiency

29. Rickets
The plasma calcium concentration in rickets is only slightly
depressed, but the level of phosphate is greatly
depressed.
This is because the parathyroid glands prevent the
calcium level from falling by promoting bone absorption
every time the calcium level begins to fall.
there is no good regulatory system for preventing a falling
level of phosphate, and the increased parathyroid activity
actually increases the excretion of phosphates in the
urine

30. Rickets -Weakens the Bones
During prolonged rickets, the marked compensatory increase in
PTH secretion causes extreme osteoclastic absorption of the
bone
- bone to become progressively weaker and imposes marked
physical stress on the bone,
- resulting in rapid osteoblastic activity as well
The osteoblasts lay down large quantities of osteoid, which
does not become calcified because of insufficient calcium and
phosphate ions
- the newly formed, uncalcified, and weak osteoid gradually
takes the place of the older bone
Craniotabes – rickety rosary – frontal bossing - kyphosis

32. Rickets – Tetany - Rx
when the bones finally become exhausted of calcium, the
level of calcium may fall rapidly - falls below 7 mg/dl, the
usual signs of tetany develop, and the child may die of
tetanic respiratory spasm
Rx – tetany - intravenous calcium is administered
Rx – rickets - supplying adequate calcium and phosphate
in the diet + large amounts of vitamin D.
If vitamin D is not administered, little calcium and
phosphate are absorbed from the gut

33. Osteomalacia - “Adult Rickets”
Adults rarely have a serious dietary deficiency of vitamin D
or calcium because large quantities of calcium are not
needed for bone growth as in children
serious deficiencies of both vitamin D and calcium
occasionally occur as a result of steatorrhea - vitamin D is
fat-soluble and calcium tends to form insoluble soaps with
fat - both vitamin D and calcium tend to pass into the feces
poor calcium and phosphate – adult rickets - never proceeds
to the stage of tetany,
but often is a cause of severe bone disability

35. “Renal rickets”
prolonged kidney damage - failure of the damaged kidneys to
form 1,25-dihydroxycholecalciferol, the active form of vitamin
D
In patients whose kidneys have been removed or destroyed
and who are being treated by hemodialysis, the problem of
renal rickets is often a severe one
congenital hypophosphatemia - congenitally reduced
reabsorption of phosphates by the renal tubules
Rx - phosphate compounds instead of calcium and vitamin D
Vitamin D – resistant rickets

36. Osteoporosis
Old age - it results from diminished organic bone matrix rather than
from poor bone calcification
osteoblastic activity in the bone usually is less than normal - the
rate of bone osteoid deposition is depressed
(1) Lack of physical stress on the bones because of inactivity;
(2) malnutrition to the extent that sufficient protein matrix
cannot be formed;
(3) postmenopausal lack of estrogen secretion because
estrogens decrease the number and activity of osteoclasts
– kyphosis - widow's hump

38. Osteoporosis
4. lack of vitamin C, which is necessary for the secretion of
intercellular substances by all cells, including formation of
osteoid by the osteoblasts;
5. old age, in which growth hormone and other growth
factors diminish greatly - many of the protein anabolic
functions also deteriorate with age - involutional
osteoporosis
6. disuse osteoporosis – during space flight

39. Osteoporosis
7. Cushing’s syndrome, because massive quantities of
glucocorticoids secreted in this disease cause
- decreased deposition of protein throughout the body
- increased catabolism of protein
- have the specific effect of depressing osteoblastic activity
Thus, many diseases of deficiency of protein metabolism can cause
osteoporosis
BMD – Calcium – Vitamin D – Exercise – Estrogen - Drugs

41. Osteopetrosis
a rare and often severe disease
the osteoclasts are defective and are unable to resorb
bone in their usual fashion so the osteoblasts operate
unopposed
The result is a steady increase in bone density, neurologic
defects due to narrowing and distortion of foramina
through which nerves normally pass
hematologic abnormalities due to crowding out of the
marrow cavities

42. Thank u…