<PARATHYROID HORMONES (The Calcium Regulating Gland)> first recognized in 1850 by Richard Owen. <INTRODUCTION>Parathyroid glands are small glands of the endocrine system which are located in the neck behind the thyroid.><Called parathyroid due to proximity to the thyroid gland.><Yellowish brown, small ovoid bodies about 6 mm long, 3mm wide and 2mm thick.><Human being have 4 tiny parathyroid glands.><Each weighting around 30-50mg, but may weight as much as 70 mg, and in diameter is 3-4 or till 8 millimeters> <Each parathyroid gland is made up of chief cells and oxyphil cells.><Chief cells more numerous, smaller, with a slightly eosinophilic cytoplasm.><secrete Parathyroid hormone (PTH). Also known as parathormone or parathyrin.> <PARATHORMONE>Protein in nature (84 amino acids)><Molecular weight= 9,500.>< Half- life = 10 minutes><Normal plasma level of PTH = 1.5 to 5.5 ng/dL> <SYNTHESIS OF AND SECRETION OF PARATHORMONE>PTH is encoded by a gene in chromosome 11><After translation, it become pre-pro-parathyroid hormone (pre-pro-PTH) contains 115 amino acids><In endoplasmic reticulum 29 amino acids removed, so it called pro-parathyroid hormone (pro-PTH) contains 89 amino acids><In the Golgi, removed more amino acids by peptidase to become mature hormone (PTH).><It is stored in secretory vesicles within the cells, and released when required> <METABOLISM OF PTH>Half-life= 4 minute><60- 70 % of PTH is degraded by kupffer cells of liver, by means of proteolysis><Degradation of about 20-30% PTH occurs in kidneys and to a lesser extent in other organs> <Half life – 4 min. How does PTH produce its effect on biological system?> <REGULATION OF PARATHORMONE SECRETION>Regulators of secretion of PTH include calcium, vit D and phosphorus.> <MECHANISM OF SECRETION OF PARATHORMONE> <CALCIUM-SENSING RECEPTORS (CaSR)><CaSR is a plasma membrane or a cell surface receptor, structured as G protein-coupled that is expressed in the parathyroid hormone-producing chief cells of the parathyroid gland and the cells lining the kidney tubule. (Hendy & et al., 2000)><PTH RECEPTORS>PTHR1 is physiologically more important than others two.><PTHR = 60-80 kDa membrane glycoprotein.> <ACTION OF PTH>Important role in maintaining blood calcium level.>< Also controls blood phosphate level> <DISORDERS OF PARATHORMONE.><increased pth secretion leads to an increase in serum levels by increasing bone resorption and enhancing renal calcium reabsorption. > <3 TYPES>Primary hyperparathyroidism, Secondary hyperparathyroidism, Tertiary hyperparathyroidism.><The most common cause of hypercalcaemia is primary hyperparathyroidism>

1. PARATHYROID HORMONES
(The Calcium Regulating
Gland)
Submitted to:- Dr. K.S. Khera
Priyanka Rana
L-2016-BS-89-D

3. CONTENTS:
 INTRODUCTION.
 PARATHORMONE.
 MECHNISM OF SYNTHESIS OF
PARATHORMONE.
 METABOLISM OF PTH.
 ACTION OF PARATHORMONE.
 REGULATION OF SECRETION OF
PARATHORMONE.
 MODE OF ACTION OF
PARATHORMONE.
 DISORDERS OF PARATHORMONE.

4.  The parathyroid gland was first
recognized in 1850 by Richard Owen
during a dissection of an Indian
rhinoceros at the London Zoo.
 The credit for the discovery of the
parathyroid has, however, been given
to the Uppsala anatomist Ivar
Sandström, who was the first to
demonstrate the gland in man.

5. INTRODUCTION
 Parathyroid glands are small glands
of the endocrine system which are
located in the neck behind the
thyroid.
 Called parathyroid due to proximity
to the thyroid gland.
 Yellowish brown, small ovoid bodies
about 6 mm long, 3mm wide and
2mm thick.
 Human being have 4 tiny
parathyroid glands.
 Each weighting around 30-50mg,
but may weight as much as 70 mg,
and in diameter is 3-4 or till 8
millimeters.
 Women usually have larger

6.  Each parathyroid gland is made up of chief cells
and oxyphil cells.
 Chief cells more numerous, smaller, with a
slightly eosinophilic cytoplasm
 secrete Parathyroid hormone (PTH). Also
known as parathormone or parathyrin.
 Oxyphil cells are degenerative chief cells.Less
numerous, larger, and have a very eosinophilic
cytoplasm due to numerous mitochondria.
 These may secrete parathormone during
pathological conditions called parathyroid
adenoma.
The number of oxyphil cells increase after
puberty.
Oxyphil cells increase in number in parathyroid
glands of patients with chronic kidney disease
(CKD) and are even more abundant in patients
receiving treatment for hyperparathyroidism
with calcitriol. (Ritter & et al., 2012).
 Major function: Maintain the blood calcium

7. PARATHORMONE
 Protein in nature (84 amino acids)
 Molecular weight= 9,500.
 Half- life = 10 minutes
 Normal plasma level of PTH = 1.5 to 5.5
ng/dL

8. SYNTHESIS OF AND SECRETION
OF PARATHORMONE.
 PTH is encoded by a gene in
chromosome 11
 After translation, it become pre-pro-
parathyroid hormone (pre-pro-PTH)
contains 115 amino acids
 In endoplasmic reticulum 29 amino
acids removed, so it called pro-
parathyroid hormone (pro-PTH)
contains 89 amino acids
 In the Golgi, removed more amino
acids by peptidase to become mature
hormone (PTH).
 It is stored in secretory vesicles within
the cells, and released when required.

10. METABOLISM OF PTH
 Half-life= 4 minute.
 60- 70 % of PTH is degraded by kupffer cells of
liver, by means of proteolysis.
 Degradation of about 20-30% PTH occurs in
kidneys and to a lesser extent in other organs.

11. Half life – 4 min. How does PTH
produce its effect on biological
system?

12. REGULATION OF PARATHORMONE
SECRETION.
 Regulators of secretion of PTH include
calcium, vit D and phosphorus.
 PTH secretion is inversely proportional to
blood calcium level.
 The major stimulus for its secretion is
decrease in the blood and extracellular fluid
concentration of calcium.

13. MECHANISM OF SECRETION OF
PARATHORMONE
CALCIUM-SENSING RECEPTORS (CaSR)
Intracellular calcium-sensing proteins
 Extracellular calcium-sensing proteins
 Parathyroid cells respond to decreases in
extracellular calcium concentration by
means of the calcium-sensing receptor, a
cell surface receptor that alters
phosphatidylinositol turnover and
intracellular calcium, ultimately effecting an
increase in parathyroid hormone secretion.
(Hendy & et al., 2000 )
 CaSR is a plasma membrane or a cell
surface receptor, structured as G protein-
coupled that is expressed in the parathyroid
hormone-producing chief cells of the
parathyroid gland and the cells lining the
kidney tubule. (Hendy & et al., 2000 )
 Studies have demonstrated that the CaSR is
expressed in the kidney, the parathyroid
glands (Riccardi & Brown,2010 ;Hendy & et
al., 2000) brain and gastrointestinal tract
(Hebert, & et al., 1997).

15. PTH RECEPTORS
 PTH receptors are of 3 types which are G protein
coupled receptors (GPCR).
(1) PTHR1
(2) PTHR2
(3) PTHR3
 PTHR1 is physiologically more important than others
two.
 PTHR = 60-80 kDa membrane glycoprotein.
 PTH’s regulation activity of calcium is mainly through
PTH1R however the role in regulating calcium is
unknown.
 PTH1R has the highest abundance in kidneys ( PCT
& CT) and bones (osteoblasts).
 PTH1R is a GPCR that is coupled to 2 G proteins

16.  On the target cells, PTH binds with PTHR1
which is coupled to G proteins and forms
hormone-receptor complex cause formation
of cAMP (act as 2nd messenger of the
hormone).
 it binds the N- terminal fragments, the
active 84 aa PTH and PTH related peptides
(PTHrP).

18. ACTION OF PTH
 Important role in maintaining blood calcium
level.
 Also controls blood phosphate level.

19. ACTION OF PTH IN BLLOD
CALCIUM LEVEL
 Maintain the blood calcium level within the critical range of
9- 11 mg/dl.
 Maintained critically because it is very important for many
of the activities in the body.
 PTH maintains blood calcium level by acting on:
1.Breaking down the BONE (where most of the body's
calcium is stored) and causing calcium release.
2.Increasing the KIDNEY's ability to retain calcium that would
otherwise be lost in the urine.
3.Increase the GIT ability to absorb calcium from food.

20. ON BONE
 PTH promotes both bone resorption and
bone synthesis.
 persistent increases on bone bone
resorption.
 intermittent increase in plasma in plasma
PTH predominantly bone synthetic effects.
 surface receptors of PTH are expressed
on osteoblasts not osteoclasts.

21.  PTH increases serum ca2+ concentration in
2 phases.
 Rapid phase = during this phase,
mobilization of ca2+ from the internal bone
stores.
 Slow phase= liberating both ca2+ and
phosphate through bone resorption.

22. THE OSTEOCYTIC MEMBRANE
SYSTEM
 This system is formed
by both osteoblasts and
osteocytes.
 It provides a membrane
that separates bone
from ECM.
 Osteoblasts on outer
surface & some other
osteoblasts on inner
surface close to blood
vessels.
 Osteocytes sitting in
the center of
osteoblasts.

23.  PTH activates the Ca2+ pump found on the
cells of the osteocytic membrane by
increasing the permeability of it bone fluid
side.
 Subsequently, Ca2+ diffuse from the fluid to
the membrane cells leading to the
stimulation of Ca2+ pumps on the other side
& the expulsion of Ca2+.

24.  Slow phase: in this phase, PTH acts on
osteoblasts and osteocytes to release
certain factors subsequently, these factors
indirectly activate osteoclasts.
 Osteoclasts activation occurs in 2 stages:
(1) Immediate activation of the already
existing osteoclasts.
(2) Formation of new osteoclasts.

25. Bone formation
 PTH can promote bone synthesis by 2
mechanism.
(1) Directly : PTH activate Ca2+ channels in
osteocytes.
 Ca2+ transfer from bone fluid
osteocytes and then through gap junction
osteoblasts EC space contributing to
mitochondria.
(2) Indirectly – in the osteoclastic bone
resorption leads to the release of growth
factors (IGF-1, 2 AND TGF-B)

26. ON KIDNEY
 PTH promotes the reabsorption of calcium
ions
 inhibits the reabsorption phosphate.
 stimulate the last step of synthesis of 1,25
dihydroxy vit D ( active vit D)

27. CALCIUM REABSORPTION
PROMOTION
 Most filtered calcium ~65% is passively
reabsorbed in PCT and thick ascending limb
~25%
 PTH acts on :
 Cortical thick ascending limb of loop of
Hanle (cTAL ~25%)
 Distal convoluted tubule (DCT).

28. PHOSPHATE REABSORPTION
INHIBITION
 PTH inhibits phosphate reabsorption:
 Proximal convoluted tubule (PCT)
 Distal convoluted tubule (DCT)
 PTH decreases the activity internalize and
degrade Na/Pi- co transporter in the luminal
membrane of the proximal tubules.

29. Indirect action of PTH on
intestine
 Synthesis of calcitrol (1,25 dihydroxy vit D).
 2 mechanism:
 Increase the synthesis of 1 alpha
hydroxylase in the proximal tubules which
converts calcidiol to calcitriol.
 PTH decreases the activity of 24
hydroxylase that inactivates calcitriol.
 Increased calcitriol enhances both Ca2+
and phosphate absorption in the intestine.

31. Vit D
 Inactive form and converted to active form
 Exist in 2 forms
 Vit D 3 (Cholecalciferol): mainly formed from
7- dehydro cholesterol; but conc. also be
obtained from different sources.
 Vit D 2 (ergosterol): can only be obtain from
dietary sources; mainly vegetables.

32. Different forms of vit D

33. Effects of vit D
 On bones
 Kidney
 Intestines

34. ON BONES
 resorption – through high amounts of vit D
 deposition- through small amounts of vit D.
 Mechanism is unknown although some
believe that it is because of increased
calcium transport across the membrane.
 absence of vit D- action of PTH on bones
causing their reabsorption is greatly
reduces or even prevented.

35. ON KIDNEY AND INTESTINE
 Increases absorption of both calcium and
phosphate. However this effect is weak and
hardly play role in the regulation of ECF
conc. of these hormones.
 in intestine – increase the absorption of
calcium and phosphate.

36.  Vit D and its Ca2+ reabsorption in
intestine.
 Ca2+ absorbed by 2 mechanism:
1. Paracellular mechanism
II. Trancellular mechanism

38. DISORDERS OF PARATHORMONE.
 Hyperparathyroidism
 Hypoparathyroidism

39. HYPERPARATHYROIDISM
 Increased PTH secretion leads to an
increase in serum calcium levels by
increasing bone resorption and enhancing
renal calcium reabsorption.
 PTH also enhance 1-hydroxylation of 25-
Hydroxyvitamin D, which is responsible for
its indirect effect of increasing intestinal
calcium absorption.

40. 3 TYPES
 Primary hyperparathyroidism- due to
development of tumor in one or more parathyroid
gland
 Secondary hyperparathyroidism- due to the
physiological compensatory hypertrophy of
parathyroid glands, in responses to hypocalcaemia
which occurs due to other pathological conditions
such as:
Chronic failure
Vit D deficiency
Rickets
 Tertiary hyperparathyroidism- Due to hyperplasia
(abnormal increase in the number of cells) of the
parathyroid gland that develop due to chronic

41. HYPERCALCEMIA
 The most common cause of hypercalcaemia is
primary hyperparathyroidism.
 The problem is usually a tumor, or adenoma.
 The tumor is benign, which means that it doesn't
spread through the body.
 The parathyroid gland enlarges and the additional
cells produce extra parathyroid hormone, causing
an elevated calcium level in the blood.
 The bones may weaken as PTH stimulates them to
release calcium, and extra calcium may enter the
kidneys, producing kidney stones.
 The parathyroid gland tumor can be removed by
surgery.

42. OTHER CAUSES OF
HYPERCALCEMIA.
 Adrenal gland failure
 Certain medications, especially thiazide diuretics (“water
pills”) or lithium
 Taking large amounts of calcium or vitamin D
supplements for a long time may also increase the
calcium level in the blood.
 Dehydration can produce a temporary increase in the
concentration of calcium in the bloodstream.
 Kidney or adrenal gland problems can produce
hypercalcemia.

43. SYMPTOMS OF HYPERCALCEMIA
 Bone problems: pain, curvature of bones,
fractures
 Muscle problems: weakness, twitches
 Gastrointestinal tract problems: pain,
nausea, vomiting, loss of appetite,
constipation
 Kidney problems: back pain, thirst,
frequent urination
 Nervous system problems: memory loss,
confusion, depression, fatigue
 hypertension

44. HYPOPARATHYROIDISM
 Sign and symptom-complex that follows due
to low levels of PTH is referred to as
hypoparathyroidism. Almost all features
thereof are due to hypocalcaemia.
 May be – congenital or acquired;
temporary or permanent.

45. HYPOCALCEMIA
 In the blood calcium level is too low
 Causes :
- Parathyroidectomy
- Renal failure
- Low levels of albumin
- Vitamin D deficiency
- Malabsorption
- Acute Pancreatitis (Precipitation of
calcium )

46. SYMPTOMS OF
HYPOCALCEMIA
 brittle nails
 hair loss
 dry skin
 anxiety
 depression
 headaches
 memory loss
 muscle twitches
 weakness and fatigue
 muscle aches or cramps
 tingling in the lips, fingers or toes

47. OSTEOPRORSIS
 Very common bone
disease.
 Characterized by the loss
of bone matrix and
minerals.
 Means porous bones.
 Due to excessive bone
resorption and decreases
bone formation.
 Is common in women
after 60 years.
 Bone becomes fragile with

50. RICKETS
 Bone disease in children, characterized by inadequate mineralization of bone
matrix.
 occurs due to deficiency.
 Deficiency –
develops due to insufficiency in diet and due to in adequate exposure to
sunlight.
 affects the reabsorption of calcium and phosphorus from renal tubules,
resulting on calcium level.

51. OSTEOMALACIA OR ADULT
RICKETS
 Rickets in adults.
 Occurs due to deficiency of Vit D
 Also occurs due to prolonged damage of
kidney
FEATURES OF OSTEOMALACIA
 Vague pain
 Tenderness in bones and muscles.
 Hypoglycemic tetany
 Myopathy leading to waddling gait
(gait means the manner of walking)