Parathyroi

d hormone
Prof Dr Zafar H Tanveer
 LEARNING OBJECTIVES
• Describe the regulation of Calcium and Phosphate in ECF and
Plasma

• Discuss the non-bone physiological effects of altered calcium

and phosphate concentration with in body

• Describe the role of PTH in regulation of calcium and phosphate

metabolism
It is an essential intracellular- CALCIUM
signaling molecule and also
plays a variety of extracellular
functions, thus the control of
bodily calcium concentrations
is vitally important.
 IMPORTANCE OF
CALCIUM
• Regulates neuromuscular excitability

• Blood coagulation

• Secretory processes

• Membrane integrity

• Plasma membrane transport

• Enzyme reactions

• Release of hormones and

neurotransmitters

• Bone mineralization

• Muscle activity
DISTRIBUTION OF CALCIUM

• About 99% of the calcium in the body

is in crystalline form within the
skeleton and teeth.

• Remaining 1%, about 0.9% is found in

intracellular fluid within the soft
tissues is less than 0.1% is present in
the ECF.
• The free Ca in the plasma and interstitial fluid is
considered a single pool.
• Only this free ECF-Ca is biologically active and subjected
to regulation
• Free fraction of ECF-Ca plays a vital role in a number of
essential activities in the body such as effect of calcium
on the heart, the nervous system, and bone formation.
 CALCIUM-REGULATING
HORMONES
• 1,25-Dihydroxycholecalciferol (Vit D)

• Parathyroid hormone (PTH)

• Calcitonin
PHOSPHATE REGULATION IN
THE ECF AND PLASMA
85% in
bones
Total
phosphate in 14-15% in
body cells

< 1% in ECF
INORGANIC PHOSPHATE IN
THE EXTRACELLULAR
FLUIDS
• Present in two forms: • The average total
HPO4- 1.05 mmol/L quantity of is about 4
H2PO4- 0.26 mmol/L mg/dl,
• 3 to 4 mg/dl in adults

• 4 to 5 mg/dl in children
ABSORPTION AND EXCRETION
OF Ca+ & PO4-
Ca+ intake CELLS Bone
1000mg/day 13,000mg 100,000mg/day
Absorption Deposition
350mg/day 500mg/day
ECF
1300mg
Secretion Reabsorption
250mg/day 500mg/day

Filtration 9980 mg/day

Faecal loss Urine Reabsorption 9880 mg/day
900mg/day 100mg/day
BONE AND ITS RELATION TO EXTRACELLULAR
CALCIUM AND PHOSPHATE

Organic Matrix of Bone.

• 90 to 95 percent collagen fiber (tensile strength)
• Gelatinous ground substance. (ECF, chondroitin sulphate
and hyaluronic acid.
Bone Salts.
• The crystalline salts composed principally of calcium and
phosphate.
PRECIPITATION AND ABSORPTION IN NON OSSEOUS TISSUE

Inhibitors (e.g. pyrophosphate) in tissues and plasma prevent

precipitation in ECF and plasma despite supersaturation
• Under Abnormal Conditions precipitate in
arterial walls in arteriosclerosis and cause
the arteries to become bonelike tubes.
• Likewise, calcium salts frequently deposit
in degenerating tissues or in old blood
clots.
MECHANISM OF BONE CALCIFICATION.

1. Secretion of collagen monomers and ground substance

……osteoblasts.
2. Polymerization of collagen monomers to form collagen
fibers……osteoid,
3. Osteoblasts become entrapped in osteoid …..osteocytes.
4. Within a few days Ca+ salts begin to precipitate on the
surfaces of the collagen fibers…..as hydroxyapatite
crystals
CALCIUM EXCHANGE BETWEEN
BONE AND EXTRACELLULAR
FLUID
• Exchangeable calcium provides a rapid buffering
mechanism to keep calcium ion concentration in the
extracellular fluids from rising to excessive levels or
falling to low levels under transient conditions of
excess or decreased availability of calcium
DEPOSITION AND RESORPTION
OF BONE—REMODELING OF BONE
• Bone is continually being
deposited by osteoblasts,
• Continually being resorbed
where osteoclasts are active
• Osteoblasts are found on the
outer surfaces of the bones and
in the bone cavities.
• A small amount of osteoblastic
activity occurs continually in all
living bones
Resorption of Bone
• Bone is also being continually
resorbed in the presence of
osteoclasts.
• PTH controls the bone resorptive
activity of osteoclasts.
• The osteoclasts send out villus ­like
projections …proteolytic enzymes and
several acids, including citric acid
and lactic acid
• The enzymes digest or dissolve the
organic matrix of the bone, and the
acids cause dissolution of the bone
salts.
VITAMIN D
(1,25DIHYDROXY
CHOLECALCIFEROL)
Vitamin D has a potent effect to
increase calcium absorption from
the intestinal tract.

it also has important effects on

bone deposition and bone
resorption.
SYNTHS
IS OF
VITAMI
N D
 1. HORMONAL EFFECT OF VITAMIN D TO
PROMOTE INTESTINAL CALCIUM
ABSORPTION
• It promotes formation of calbindin, a calcium-
binding protein, in the intestinal epithelial cells.
VITAMIN D
• This protein functions in the brush border of
these cells to transport calcium into the cell
cytoplasm.

• The rate of calcium absorption is directly

proportional to the quantity of this calcium-
binding protein.
OTHER MECHANISMS INVOLVED IN
FORMATION OF CALBINDIN ARE

(1) a calcium-stimulated adenosine triphosphatase in

the brush border of the epithelial cells

(2) an alkaline phosphatase in the epithelial cells.

 Effects of Vitamin D

Intestines Bones Kidney

Promotes Decreases renal

Effects in
Ca+/PO4absorpti Ca+ &
relation to PTH
on PO4excretion
 PARATHYROID HORMONE
• Four parathyroid glands, which are
situated on the posterior surface of
upper and lower poles of thyroid gland.
• Parathormone secreted by parathyroid
gland is essential for the maintenance
of blood calcium level
Source of Secretion
Chief cells of the parathyroid glands.
Chemistry
Protein in nature, having 84 amino acids.
Half life
Parathormone has a half-life of 10 minutes
Metabolism

60-70%degraded by Kupffer cells of liver, 20% to 30% in

kidneys and to a lesser extent in other organs
 PHYSIOLOGICAL ACTIONS OF
PTH
• Primary action of PTH is to maintain the blood calcium level
within the critical range of 9 to 11 mg/dl.

• PTH maintains blood calcium level by acting on

1. Bones

2. Kidney

3. Gastrointestinal tract.
 ON BONES
• Parathormone enhances the resorption of calcium from the
bones (osteoclastic activity) by acting on osteoblasts and
osteoclasts of the bone in

two phases:

i. Rapid phase

ii. Slow phase.

PTH HORMONAL EFFECTS ON
BONE
Action Rapid phase Slow phase
Onset of action Within minutes Days to weeks
Action on Increased activity of Formation of new
Osteoclasts osteoclasts and osteoclasts
osteocytic pump
Resorptive Of amorphous Resorption of bone
action calcium salts and PO4 itself osteoporosis
(Osteolysis)
 ON KIDNEY
Increased 1
reabsorption  Decreases loss of
Of Mg & H+ Ca in urine by
stimulating Ca+
reabsorption
 Inhibits PO4 2
Decreased reabsorption
reabsorption INCREASED
Of Na,K+ & CALCIUM Stimulates
aminoacids DECREASED production
PHOSPHATE of Vit D
 ON GIT
• PTH increases the absorption of Ca+

ions from the GI tract by increasing

the formation of vit D in kidneys

• Thus, the activated vitamin D is very

essential for the absorption of calcium from the GI tract. And PTH is
essential for the formation of activated vitamin D.
SEQUENCE
OF EVENTS
REGULATION OF PTH
Plasma Plasma
Calcium Calcium • Not influenced by
hypothalamus or pituitary
- - • Controlled by plasma Ca and
Thyroid C
PTG cells to lesser extent by Mg by –ve
feed back mechanism
• Increase plasma Ca+, Vit D
PTH Calcitonin and bone diseases leading to
bone resorption
Plasma Plasma
decreased PTH secretion
Calcium Calcium
 DECREASED CALCIUM INCREASED CALCIUM

PARATHYROID KIDNEY THYROID

GLAND
SUMMARY
PTH VITAMIN D CALCITONIN

BONE INTESTINE BONE

INCREASED INCREASED INHIBITION OF
RESORPTION ABSORPTION RESORPTION &
AND RELEASE OF OF Ca+ DEPOSITION OF Ca+
Ca+

NORMAL CALCIUM
BLOOD LEVEL OF PHOSPHATE

PTH secretion is directly proportional to

blood phosphate level.

Increased PO4- in blood….combines with

ionized Ca+ …..CaHPO4

This decreases ionized calcium level in

blood which stimulates PTH secretion.
 Clinical correlation

Disorders of parathyroid glands are of two types:

I. Hypoparathyroidism

II. Hyperparathyroidism
HYPOPARATHYROIDISM
• Hyposecretion of
PTH is called
hypoparathyroidism.

• It leads to
hypocalcemia
(decrease in blood
calcium level).
Hypocalcemia and Tetany
• Hypoparathyroidism …..hypocalcemia, by decreasing the
resorption of calcium from bones.

• Hypocalcemia causes neuromuscular hyperexcitability,

resulting in hypo calcemic tetany.
 TETANY Occurs when Ca+ is
<6 mg/dL

• Tetany is an abnormal condition Normal ….9-11

mg/dL.
characterized by painful muscular spasm

• It is because of hyperexcitability of nerves

and skeletal muscles due to calcium
deficiency.
Low ionized calcium levels in the ECF increase the permeability of neuronal
membranes to Na+, …….progressive depolarization, which increases the
possibility of action potentials.
SIGNS AND SYMPTOMS
• Hyperreflexia and convulsions

• Carpopedal spasm

• Laryngospasm, Arrythmias and heart failure

• Dry skin with brittle nails

• Hair loss

• Mental retardation in children

 HYPERPARATHROIDISM
AND HYPERCALCEMIA
Hypersecretion of PTH is called hyperparathyroidism.

It results in hypercalcemia. Hyperparathyroidism is of three

types:
• Primary hyperparathyroidism
• Secondary hyperparathyroidism
• Tertiary hyperparathyroidism
PRIMARY HYPERPARATHYROIDISM

DIGESTIVE SYSTEM
Due to the Loss of appetite
development Nausea / Vomiting
constipation CNS
of tumor in Fatigue
Depression
one or more Confusion MS SYSTEM
Weakness
parathyroid glands.
Aches and pains in
bones and joints RENAL SYSTEM
Sometimes, tumor may Renal stones
develop in all the four Increase thirst
Polyuria
glands.
SECONDARY
HYPERPARATHYROIDISM
Physiological compensatory
hypertrophy of parathyroid glands,

in response to hypocalcemia which

occurs due

i. Chronic renal failure

ii. Vitamin D deficiency

iii. Rickets.
 TERTIARY HYPERPARATHYROIDISM

Proliferation of all the Depression of the nervous

parathyroid glands due to system
chronic secondary Sluggishness of reflex activities
hyperparathyroidism.
Reduced ST segment and QT
Signs and symptoms
interval in ECG
Lack of appetite Constipation.
Development of bone diseases

Deposition of calcium-phosphate crystals in renal tubules,

thyroid gland, alveoli of lungs, gastric mucosa and in the wall
of the arteries, resulting in dysfunction of these organs.
Renal stones
 RICKETS
• Rickets is the bone disease in
children

• Characterized by inadequate
mineralization of bone matrix.

• It occurs due to vitamin D

deficiency.
CAUSES OF RICKETS
CLINIC
AL
FEATU
RES
OF

RICKET
S
 Features of osteomalacia
OSTEOMALACIA  Vague pain

 Tenderness in bones and muscles

ADULT
RICKETS  Myopathy leading to waddling gait
(gait means the manner of
walking). In waddling gait, the feet
are wide apart and walk resembles
that of a duck.

 Occasional hypocalcemic tetany.

1-Which of the following is not
involved in the regulation of Vitamin
D?
a. PTH
b. Prolactin
c. Alkaline phosphate
d. Serum phosphate
2. Which of the following hormones
is not important in calcium
homeostasis ?
a. Calcitonin
b. Parathyroid hormone
c. 1,25-dihydrocycholecalciferol
d. Glucagon
3.Maximum percentage of total
body Ca is present in ?
a. Bones
b. Skeletal muscle
c. plasma
d. Blood
e. Brain
4. Normal level of plasma calcium is
a. 5-6 mg/dl
b. 7-9 mg/dl
c. 9-11 mg/dl
d. 10 mg/dl
e. 12mg/dl
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