The document summarizes the anatomy, histology, physiology, and pathologies related to the parathyroid glands. It discusses that the parathyroid glands are four small oval bodies located on the posterior surface of the thyroid gland, each side having a superior and inferior gland. The chief cells of the parathyroid glands secrete parathyroid hormone (PTH) which regulates calcium levels in the body by acting on the kidneys and bones. Conditions such as hypoparathyroidism can cause low calcium levels and tetany while hyperparathyroidism results in high calcium levels.

2. Anatomy of Parathyroid Glands
 They are four small, oval, yellowish- brown bodies which are
embedded in the posterior surface of pituitary gland; there are two
glands on each side, superior and inferior one.
 They are supplied by inferior thyroid artery.
 Nerve supply: Superior and middle cervical ganglia of the
sympathetic trunk.
 N.B: These fibers are not secretory to the gland because the
parathyroid activity is controlled by the level of the blood calcium.
Histology of Parathyroid gland :
Stroma composed of Ct capsule sending septa with reticular fibres ,
and many fenestrated capillaries and lipid cells also may be found (
Increase with aging to be 50 % of parathyroid cells )
Parenchyma is composed of
Chief cells Oxyphil
Size Small Large
Number Numerous Few
Nucleus Large Vesicular Small dense
Cytoplasm Pale Acidophilic
EM Ultrastructure of protein
secreting cells ( rER , Golgi A. ,
Secretory granules ,
Mitochondria )
Glycogen granules are numerous
causing pale staining of cytoplasm
Large number of
mitochondria with
cristae causes the
acidophilic colour of
cytoplasm
Function Secretion of Parathormone Non specific

3. Physiology of parathyroid
Parathyroid hormone:
 It’s the main hormone responsible for calcium metabolism in the
body. It acts on 2 main organs; kidney and bones.
 It increases calcium and phosphate mobilization from bones leading
to increased calcium levels in blood, while phosphate is excreted by
the kidney leading to decreased blood level.
 This function is essential to keep the solubility product constant to
prevent deposition of excessive calcium phosphate in undesirable
body parts or calcium deficiency that may lead to many functional
disturbances.
 It acts directly on bones and kidney while it acts indirectly on the
intestine leading to increased calcium absorption by increasing
synthesis of calbindin (this effect is caused by Vit D3 activated in
the kidneys)
Regulation:
1) Calcium levels: hypercalcemia leads to decreased secretion and
vice versa.
2) Phosphate levels.

4. Calcium regulating hormones
3 hormones:
a. Increasing Ca++ level
 Parathyroid H
 Calciterol (active vitamin D )
b. Decreasing Ca++ level
c. Calcitonin H
Notes:
 PTH precursor …. 115 amino acids
 Active PTH …. 84 amino acids
 Calcitonin ….. 32 amino acids
1st
Ca++ raising hormones:
Synthesis of active vitamin D ( calciterol ):
 7-dehydrocholesterol in the skin >> ultra violet rays >>
cholecalciferol
 Cholecalciferol ( from the skin or dietary ) >> carried by D-binding
protein >> liver >> hydroxylation >> 25 hydroxycholecalciferol
 25 hydroxycholecalciferol >> kidneys by D-binding protein >> 1
alpha hydroxylase in the mitochondria of proximal convoluted
tubules >> 1,25 dihydroxycholecalciferol ( the most potent form )
N.B.
High level of calciterol or Ca++ ions >> feedback inhibition of 1 alpha
hydroxylase >> inhibition of 1 hydroxylation & stimulate 24
hydroxylation >> 24,25 dihydroxycholecalciferol ( less active form )

5. Mechanism of action of Ca++ raising hormones:
PTH Calciterol
1. One of group II hormones (
hydrophilic )
2. Binds to membrane receptor >>
activation of adenyl cyclase
enzyme >> increased cAMP >>
activation of cAMP dependant
protein kinase >> phosphorylation
of enzymes >> metabolic effect
3. Its receptors in bones & kidneys
4. Acts indirectly on small intestine
1. One of group I hormones (
lipophilic)
2. Binds to nuclear receptors >>
activation of certain genes >>
mRNA >> Ca++ binding proteins
>> increase Ca++ and PO4—
absorption
3. Its receptors in the intestinal
cells
4. Acts directly on small intestine
Functions of Ca++ raising hormones:
Similarities Differences
1. They increase Ca++ & PO4--
absorption from small
intestine
2. They increase Ca++
reabsorption from distal
convoluted tubules &
collecting ducts
3. PTH & large doses of vitamin
D increase bone resorption by
increasing the function & no.
of osteoclasts
1. Regulating PO4—ions conc:
a. PTH lower PO4—level by increasing
its excretion in the urine by
proximal convoluted tubules
b. Calciterol elevate PO4—level by
increasing its absorption from
intestine
2. Normal dose of vitamin D enhance
bone mineralization ( Ca++ & PO4—
deposition )

6. Control of Ca++ raising hormones ( 2 factors ):
Ca++ ions conc. PO4—ions conc.
1. Decreased Ca++ level :
 Increasing PTH release ( hypertrophy
of parathyroid in persistant low Ca++
level ) >> activation of 1 alpha
hydroxylase >> synthesis of calciterol
>> increased Ca++ level back to normal
2. Increased Ca++ level :
 Decreased PTH secretion
(parathyroid size is reduced ) >>
decreased synthesis of calciterol >>
decreasing Ca++ level back to normal
1. Decreased PO4-- level:
 Decreased PTH secretion
 Increased calciterol
formation
2. Increased PO4-- level:
 Increased PTH secretion
 Decreased Calciterol
formation
2nd
Ca++ lowering hormone (calcitonin):
1. Mechcanism of action:
The same as group II hormones as it’s a peptide
2. Functions( lowering Ca++ & PO4-- level by 3 ways):
On the bone:
a. Inhibits bone resorption by inhibiting the function of
osteoclasts
b. Prolonged effect: inhibit proliferation of osteoclasts
On the kidneys:
a. It increase excretion of Ca++ , PO4-- , Na, K & Mg in the
urine
b. Inhibit synthesis of Calciferol

7. 3. Control:
Its secretion is increased by:
a. Increased Ca++ level
b. Dopamine, estrogens, gastrin, CCK & glucagon
Calcium metabolism
 Calcium in our body:
It’s used in many body functions such as muscular contraction,
nerve conduction and blood coagulation. The biggest portion
enters in bone and teeth formation.
 Calcium content:
 1100 gm
 99%: Bones and Teeth
 1% ECF
 Calcium in blood:
 9-11 Mg/dl
 Some of which (45%) is Non diffusible through the capillary
membrane as it’s combined to plasma proteins.
 The rest (55%) is diffusible and is found in 2 forms:
o Non-ionized (5%): inactive
o Ionized (50%): active

8.  Calcium in bones:
1-Stable hydroxyappatite (slowly exchangeable with plasma
calcium-99%)
2-Exchangeable Mobilizable amorphous calcium phosphate (1%) (this
form of exchangeable calcium is also present in the mitochondria
of many cells such as hepatocytes.
 Control of calcium homeostasis
1. The first line of defense is the buffer function of the
exchangeable calcium.
2. The second line of defense is the hormonal control mechanism:
1ry: (Calcitonin-PTH-Vit D)
2ry: Glucocorticoids, growth hormone, thyroid hormones,
estrogen and testosterone.
Parathyroid abnormalities (Physiology & Pathology)
Hypoparathyroidism
 Less common
 It's due to
o surgical removal
o agenesis
o radiation injury
o autoimmune destruction
 Manifestations

9. o All manifestations are due to ''Hpocalcemia'' below 9 mg, which
leads to increased CNS and peripheral nervous system including
neuromuscular junction excitability .. why ?
 low amount of ca++ in the ECF leads to out flux of Ca++ which
needs a carrier to go outside the cell so leads to increase
membrane permeability to Na+ ions.
o So the nerves become so excitable and discharge spontaneously
and leads to spastic muscle contraction (Tetany)
 Tetany :-
o spastic muscle contraction
o it occurs due to increased neuromuscular excitability
o Main Causes are :- hypoparathyroidism, renal failure, alkalosis
o it may also be induced by low vitamin D level and low Ca++ in diet
o Types:
 Manifest tetany :-
 occurs if plasma Ca++ level is lower than 7 mg %
 occurs spontaneously during rest
 it's spastic contraction involving muscles of extremities
(carpo-pedal spasm) = flexion elbow, wrist,
metacarpopharyngeal joints with wxtension of fingers
and adduction thumb
 in hypocalcemia it may induce generalized convulsions and
it occurs so quickly
that may lead to
severe contraction of
laryngeal muscles
leading to laryngeal
stridor >> DEATH

10.  Latent Tetany :-
 occurs if plasma Ca++ level is about 7 mg %
 Needs a stimulus to be provoked (Certain tests) :
o trousseau's sign : occlusion of the circulation by tying a blood
pressure cuff around the arm and arresting blood supply to the
hand ---> carpal spasm.
o chvostek's sign : tapping angle of the jaw (↑facial nerve) --- >
quick contraction of ipsilateral facial muscles
Hyperparathyroidism :-
 Primary hyperparathyroidism
 Overproduction of parathyroid hormone leading to hypercalcemia
 More common in females than males
 May occur sporadically or in association with other endocrine
syndromes
 it occurs due to :
 adenoma (80 %)
 1ry hyperplasia (15 %)
 parathyroid carcinoma (5%)
 Manifestations :-
 Bone manifestations :-
 osteoclastic absorption is severe leading to decalcification
of bone
 X-ray :-Bone may be eaten away and filled with multiple
cysts (ostitis fibrosa cystica)
 this leads to hypercalcemia which leads to :-
 CNS and peripheral nervous system depression
 muscle weakness

11.  constipation, abdominal pain, loss of appetite >
depressed GIT motility
 increased systolic time and decreased diastolic time
 metastatic calcification (in alveoli - thyroid - kidney -
walls of arteries ) > fatal
 Secondary hyperparathyroidism :-
 Due to chronic renal insufficiency & renal failure
 Decrease in vitamin D synthesis -- > reduce intestinal
absorption of Ca++.
 This leads to hypocalcemia and hyperphosphatemia
 Parathyroid then is stimulated.
 Clinically:- there is renal osteodystrophy.

12. Ca controlling medications
 Hypocalcaemia:
For short term management:
Calcium gluconate is injected IV very slowly.
Rapid IV injection may lead to calcium rigor and cardiac arrest
during systole.
For long term control:
Calcium gluconate is given initially followed by vitamin D
supplements.
 Hypercalcaemia:
Calcitonin is used
 Calcitonin:
It is used in:
1. Osteoporosis. (as it prevents bone resorption)
2. Hypercalcaemia in case of malignancy. (ectopic calcium
production)
3. Paget's disease.
 Bisphosphonates:
- They inhibit osteoclastic activity and formation.
- They increase osteoclastic apoptosis.
- They inhibit hydroxyappatite dissolution by inhibition of
proton pump found in osteoclasts.
- Uses: same as calcitonin.
 Very Imp:
- Calcitonin (rapid onset in comparison to bisphosphonates) is
used as initial treatment for paget’s disease and
osteoporosis followed by bisphosphonates (start action
after months). Vitamin D and calcium supplements could be
added for long term control.

13. - Bisphosphonates are taken only orally although only 20% of
the dose is absorbed.
- Bisphosphonates are taken on an empty stomach with 3
glasses of water to prevent gastric irritation.

14. MCQs
1. The pale cytoplasm of chief
cells in parathyroid glands is
due to
a. numerous mitochondria
b. secretory granules
c. glycogen granules
d. all of the above
2. Acidophilia in oxyphil cells is
due to :
a. glycogen granules
b. lysosomes
c. numerous mitochondria
d. all of the above
3. The chief cells are large
polygonal cells with small
vesicular cytoplasm:
a. true
b. false
4. With age , oxyphil cells
become adipocytes:
a. true
b. false
5. A patient with parathyroid
deficiency 10 days
after thyroidectomy will
show:
a. a low plasma phosphate nd
Ca++ levels and tetanus
b. a low plasma Ca++ levels,
increased muscular
excitability and Trousseaus
sign
c. high plasma phosphate and
Ca++ and bone
demineralization
d. increased muscular
excitability, high plasma
Ca++ and bone
demineralization
6. Which of the following is
not involved in regulation of
plasma Ca++ levels :
a. kidneys
b. skin
c. lungs
d. intestine

15. 7. Parathyroid hormone :
a. decreases Ca++
mobilization of bone
b. increases Ca++ mobilization
from bone
c. decreases circulating levels
of free Ca++
d. increases urinary excretion
of Ca++
8. organs affected directly by
parathormone :
a. intestine
b. kidney
c. heart
d. muscular tissue
9. function of parathyroid
hormone :
a. elevation of calcium ion
concentration and elevation
of phosphate concentration
b. elevation of calcium ion
concentration and
depression of phosphate
concentration
c. depression of calcium ion
concentration and
depression of phosphate
concentration
d. . depression of calcium ion
concentration and elevation
of phosphate concentration
10. effect of PTH on bone is
:
a. increases bone resorption
and mobilization of calcium
to the blood
b. increases bone absorption
and mobilization of calcium
and phosphate to the blood
c. decrease bone resorption
and mobilization of calcium
and phosphate to the blood
d. increases bone resorption
and mobilization of calcium
and phosphate to the blood
11. effect of PTH on kidney
by decreasing phosphate
reabsorption in:
a. distal convoluted tubules
b. proximal convoluted
tubules.
c. Collecting ducts
d. Both A & C
12. the PTH glands will
hypertrophied in such cases
except :
a. Rickets
b. Pregnancy
c. Osteoporosis
d. Lactation

16. 13. Conditions that increase
the calcium ion concentration
are all of the above except:
a. Excessive amount of
calcium in diet
b. Increased vitamin D in
diet.
c. Bone reabsorption
d. Both A & B
14. When phosphate
concentration increases :
a. elevation of calcium ion
concentration in the
extracellular fluid
b. stimulates PTH secretion
c. decreased of activity and
reduced sizes of
parathyroid glands
d. all of the above
True or false:
15. rapid phase of PTH in
bones result from activation
of osteoblast
16. effect of PTH on intestine
by increasing of 1,25
dihydroxycholecalciferol
17. Calcitriol synthesis is
completed in :
a. The liver
b. The renal distal convoluted
tubule
c. The renal proximal
convoluted tubule
d. None of the above
18. Which of the following
statements about calcitriol
is incorrect?
a. Increases synthesis of
calcium binding protein
b. At high levels ,it stimulates
the enzyme 1-α hydoxylase
c. It's the most potent
metabolite of vitamin D
d. Increases the absorbtion
of intestinal calcium and
phosphate

17. 19. The mechanisms by which
calcium is transported acoss
the intestinal cell to the
circulation,"to enter the cell
then.. leave it to the blood"
are:
a. Diffusion..osmosis
b. Active transport..diffusion
c. Facilitated
diffusion..active transport
d. None of the above
20. There's a/an
…..relationship between the
plasma calcium level and the
rate of synthesis of 1,25
DHCC
a. Direct
b. Inverse
c. No relation
21. When phosphate plasma
level is elevated ..it has a
direct stimulatory effect on
the enzyme 1-α hydoxylase
a. True
b. False
22. Which of the following
statements about calcitonin
is incorrect?
a. It inhibits osteoclasts
function
b. It inhibits synthesis of
calcitriol
c. It acts mainly as a long
term regulator to calcium
ion concentration as
compared to PTH
d. It increases the excretion
of phosphate
23. One of the following
inhibits calcitonin secretion
a. Glucagon
b. Dopamine
c. Decreased plasma calcium
concentration
d. Estrogens
24. Hypoparathyroidism is
caused by:
a. renal failure
b. alkalosis
c. Di George's syndrome
d. vitamin D deficiency
25. The main effect of
hypoparathyroidism is:
a. hypocalcemia
b. hypokalemia
c. hypercalcemia
d. hyperkalemia

18. 26. In hypocalcemia, the
increased excitability occurs
in:
a. central nervous system
b. peripheral nervous system
c. neuromuscular junctions
d. all of the above
27. Hypocalcemia causes
increased membrane
permeability to:
a. sodium
b. potassium
c. calcium
d. phosphate
28. Tetany:
a. is astate of spastic
contraction
b. caused by increased
neuromuscular excitability
c. predisposed by increased
calcium levels
d. all of the above
e. a and b
29. All of the following are
causes of tetany except:
a. renal failure
b. acidosis
c. hypoparathyroidism
d. low calcium intake
30. About manifest tetany:
a. plasma calcium level is 9
mgdl
b. occurs during rest
c. produces cotracrion of the
trunk
d. all of the above
31. Tapping on the angle of
jaw is:
a. Di George's test
b. Troussaeau's test
c. Chvostek's test
d. heal-knee test
32. Carpal spasm includes the
following except:
a. abduction of the thump
b. flexion of the elbow
c. extension of the finger
d. flexion of the rest
33. The main cause of
hyperparathyroidism is:
a. primary parathyroid
hyperplasia
b. parathyroid carcinoma
c. parathyroid adenoma
d. none of the above

19. 34. The bony manifestation
of hyperparathyroidism is:
a. acromegaly
b. cretinism
c. gigantism
d. ostitis fibrosa cystica
35. Chronic decrease in
calcium serum level causes:
a. primary
hyperparathyroidism
b. secondary
hyerparathyroidism
c. primary hyperthyroidism
d. secondary hyperthyroidism
36. The most common cause
of secondary
hyperparathyroidism:
a. chronic renal insufficiency
b. diabetes incipidus
c. renal failure
d. a and c
37. Daily requirement of
calcium in normal adult
individual is :
a. 5gm
b. 1gm
c. 10gm
d. none of the above
38. Percentage of calcium
present in bone and teeth is
a. 50%
b. 70%
c. 1%
d. 99%
39. Non diffusible calcium:
a. about 45% of calcium
present in plasma
b. physiologically inert
c. about 55%of calcium
present in plasma
d. a&b
40. Concerning non diffusible
calcium, all true except :
a. combined with citrate
and bicarbonate
b. physiologically inert
c. 45%of calcium present
in the plasma
d. combined with plasma
proteins
41. Diffusable calcium :
a. 45% of plasma calcium
b. 55% of plasma calcium
c. ionized and non ionized
d. b&c

20. 42. The following forms of
calcium don’t have
physiological
functions,except:
a. non diffusible calcium
b. non ionized diffusible
calcium
c. ionized diffusible
calcium
d. none of the above
43. Hydroxyappatities :
a. exchangable form of
calcium
b. stable salts
c. more than 99% of
calcium of bones
d. b&c
44. Concerning exchangeable
calcium , all true except:
a. calcium reservoir for
equilibrium
b. more than99% of
calcium of bones
c. small portion of it
present in mitochondria
especially of the liver
and intestine
d. provides a rapid
buffering mechanism of
calcium
45. First line of defense for
controlling calcium
homeostasis:
a. parathormone
b. buffering action of
exchangeable calcium
c. calcitonin
d. all of the above
46. Parathormone:
a. increase plasma calcium
level
b. increases intestinal
absorption of calcium in
a direct way
c. decreases plasma
calcium level
d. a&b
47. The adult human body
contains about 2000 gm of
calcium:
a. true
b. false

21. 48. Plasma contains less than
1 % of total calcium
amount:
e. true
f. false
49. Non ionized calcium is
combined to plasma proteins:
g. true
h. false
50. Non diffusible calcium is
physiologically inert:
i. true
j. false
51. Hydroxyappatities form
reservoir for calcium :
k. true
l. false
52. Which of the following
hormones could be
administered as nasal spray
a. Desmopressin
b. Oxytocin
c. Salmon calcitonin
d. None of the above
e. All of the above
53. Parathyroid hormones
could be given to treat:
a. Chronic hypocalcemia
b. Acute hypocalcemia
c. none of the above
54. In cases of hypocalcemic
tetany..which drug of the
following should be urgently
given
a. PTH
b. Ca+2
gluconate (IV infusion)
c. Ca+2
gluconate (IM)
d. Ca+2
+vit D
e. All of the above
55. All of the following
statements about
bisphosphonates are correct
except:
a. Decrease osteoclastic
formation
b. Nearly only 5% of its dose
is deposited in bones
c. It has short duration of
action
d. Responsible for the
inhibition of the
osteoblastic proton pump
activity
e. Help in keeping bone
integrity and prevent its
fracture

22. 56. Bisphosphonates are
contraindicated in cases of
a. Renal diseases
b. Peptic ulcer
c. Liver disease
d. Lactation
e. A and b
f. A and c
Answers:
1. c
2. c
3. b
4. b
5. b
6. c
7. b
8. b
9. b
10. d
11.b
12. c
13. c
14. d
15. false
16. true
17. c
18. b
19. c
20. a
21. b
22. c
23. c
24. c
25. a
26. d
27. a
28. e
29. b
30. b
31. c
32. a
33. c
34. d
35. b
36. d
37. b
38. d
39. d
40. a
41. d
42. c
43. d
44. b
45. b
46. a
47. b
48. a
49. b
50. a
51. b
52. e
53. c
54. b
55. d
56. e

23. Essay Questions:
1. Compare between the chief cell (principle) and oxyphil in the
parenchyma of parathyroid gland.
2. What is the general effect of Parathormone?
3. What is effect of parathormone on bones?
4. What is effect of parathormone on intestine?
5. What is effect of parathormone on kidneys?
6. What is role of Calcium and Phosphate in regulation of
parathormone secretion?
7. Define PTH
8. Discuss its mechanism of action
9. Give an account on the hormone receptor interaction
10. Explain the action of the hormone on :
 Solubility product
 Bone
 Intestine
 Kidney
11.Mention th mechanism by which ca 2+ ions in blood can regulate
PTH secretion
12. Enumerate the mechanisms that regulate the PTH secretion
13. Define calcitonin
14. Mention calcitonin functions
15. Give an account on the control of calcitonin secretion
16. Mention the steps by which the calcitriol is biosynthesized
17. Explain the mechanism of action of calcitriol

24. 18. Enumerate the actions of 1,25DHCC
19. Explain the actions of calcitriol
20. Mention the affect of plasma ca 2+ level on 1,25DHCC
21. Give an acoount on the control of calcitriol secretion
22. Mention the Ca++
functions in the body?
23. Give a short account on body requirement of the Ca++?
24. Mention Ca++resources
25. Give a short account on plasma Ca++content
26. Give a short account on bones Ca++ content
27. Discuss the exchangeable Ca++in the bones
28. Talk about control of Ca++ homeostasis
29. Compare between Actions of Parathormone, Vitamin D and
Calcitonin
30. What are the causes of the hypothyrodism?
31. Discuss the effects of hypothyrodism ?
32. What are the acuses of the tetany?
33. Discuss the types and manifestaions of tetany?
34. Discuss the incidence and acuses of primary
hyperparathyroidism
35. What are the manifestaions of primary
hyperparathyroidism?
36. Discuss the secondary hyperparathyroidism
37. How Hypocalcaemic tetany is treated?
38. What do we use in long term management of
hypoparathyroidism?
39. What are therapeutic uses of Calcitonin ?
40. Mention the preparations of Calcitonin ?
41. Mention examples of non hormonal agents affecting bone
mineral homeostasis?
42. Mention mechanism of action of Bisphosphonates?
43. Discuss pharmacokinetics of Bisphosphonates?

25. 44. Mention its therapeutic uses?
45. Mention adverse effects of Bisphosphonates?
46. Mention its contraindications?