Anatomy and Physiology

Anatomy

Discovery of the human parathyroid

glands was said to be accidental. It was
years ago when surgeons were puzzled by
their patients who have undergone partial
or even total thyroid gland removal

that

some of them recovered but some suffered

muscle

spasms,

severe

pain,

and

eventually died. It was only then that a

distinction was made between the separate
hormonal functions of the thyroid and
parathyroid gland. [1]
Source: Guyton: Textbook of Medical
Physiology 11th Edition

The parathyroid glands are tiny, grayish tan to yellow-gray in colour each
weighing 30-40 mg [1]. They are nearly hidden in the posterior view of the thyroid
gland. [2] A normal adult normally has four glands which averages a total
parathyroid tissue mass of 120-160 mg.

Although, the precise number of

parathyroid glands vary in different individuals from six, eight or more. [1] It is said
that 10% of people have extra number of parathyroid gland.[3] The inconsistency of
the location and number of parathyroid gland in every individual sometimes causes

problems in searching the neck to locate diseases in the gland during surgical
operations. [4]
There are two parathyroid glands located on each side one positioned on a
higher area called the superior parathyroid glands, while the ones on the lower two
are called the inferior parathyroid glands. On opposite sides of the neck is a branch
of superior thyroidal artery that supplies the upper parathyroid gland, while the
lower parathyroid gland is supplied by the inferior thyroidal artery. [1]
The superior parathyroid glands are located at the fourth branchial pouches
of the embryo. And because they are closely related to the thyroid gland, they are
positioned along the dorsal portion of the upper thyroid. [4] Anatomically, the upper
parathyroid glands are located in the posterior to the middle one third of the thyroid
gland. They are near the point of junction between the middle thyroid artery and
the regular laryngeal nerve. Different locations of the parathyroid gland may be in
the tracheoesophageal groove and the retroesophageal space. The inferior thyroid
artery generally supplies the upper parathyroid gland its sufficient needed blood. [3]
The lower or inferior parathyroid glands are situated from the lateral to the
lower pole of the thyroid gland. It is third in the branchial pouch, and in contrast to
the upper parathyroid gland, it descends in a distance with the thymic anlage. As a
result, its position is more variable than that of the superior parathyroid glands.
Inferior thyroid arteries supplies blood to the inferior parathyroid glands. Common
ectopic glands can be found in the thymic remnants, anterior the mediastinum. [4]
The PTG consist mostly of chief cells and oxyphil cells embedded with a
fibrous capsule intermixed with adipose tissue which increases with age and may
reach 60-70% of the gland volume. [1] The chief cells are 12-20m in diameter,

central, round, and uniform in nuclei. They vary in colour depending on the stain
that is used

and

its glycogen

content, from light to dark pink

with hematoxylin and eosin stains.
These

cells

water-clear
Source: Marieb,Hoehn: Human Anatomy and
Physiology 7th Edition

sometimes
due

to

appear
lack

of

glycogen. They secrete granules

that contain parathyroid hormone

(PTH). On the other hand, Oxyphil cells can be found in single or small clusters
throughout the parathyroid. What differs them from chief cells is that they are
slightly larger in size, acidophilic cytoplasm, and mitochondria are tightly packed.
Glycogen is present but unlike Chief cells, secretory granules are sparse or absent.
[5]
The Parathyroid hormone or parathormone, is the most important protein
hormone that is produced by the parathyroid gland. Base on structure, it is an 84amino-acid single-chain peptide. [2] Its release is triggered by decreased Ca2+
levels in the bloodstream. [5] Further functions of the PTH will be described on the
physiology of the parathyroid gland.

Physiology
The parathyroid gland possesses
specialized

calcium-sensing

receptors

that respond to rising or falling ambient

calcium by increasing or decreasing PTH
secretion, respectively. The parathyroid
glands

are

hormones

not

controlled

secreted

by

by

the
the

hypothalamus and the pituitary rather it is controlled by the amount of free calcium
that is contained in the bloodstream. [5] The gland secrets a polypeptide hormone
called the parathyroid hormone (PTH) that is needed to regulate Ca2+ homeostasis.
[6] It stimulates three main organs: the skeleton, the kidneys, and the intestine. [1]
Normally, when a decrease in the levels of free calcium in the body is
detected, stimulation of the parathyroid source: Marieb,Hoehn: Human Anatomy and
Physiology 7th Edition

gland is made to secrete and synthesize PTH. PTH has its metabolic functions to
regulate calcium as well: (these action increases calcium level in the body therefore
inhibiting further PTH secretion) [1]

To increase calcium reabsorption in the renal tubules to conserve calcium

To increase vitamin D conversion to dihydroxy (active form) in the kidneys

To increase phosphate excretion through urine excretion to lower serum

phosphate levels
To enhance gastrointestinal calcium absorption [5]
PTH increases renal Ca2+ reabsorption in the distal tubule,

PTH may have direct and some indirect actions in bones than is evident
within minutes. [2] This is considered to be a slow process than can go on for days.
PTH increases Ca2+ released by the bones to the bloodstream through the increase
of osteoclasts in bones leading to bone breakdown. The red bone marrow is
stimulated by stem cells to differentiate into osteoclasts to increase osteoclast
number. Continuous elevated PTH leads to osteoclast bone resorption. [6]
Secretion of PTH
Controlled by the serum [Ca2+] by negative feedback. Decreased serum
[Ca2+]
increases PTH secretion.
Mild decreases in serum [Mg2+] also stimulate PTH secretion.
Severe decreases in serum [Mg2+] inhibit PTH secretion and produce
symptoms of hypoparathyroidism.
The second messenger for PTH secretion by the parathyroid gland is cyclic
AMP.
Secretion of parathyroid hormone is controlled chiefly by serum [Ca2+]
through negative feedback. Calcium-sensing receptors located on parathyroid cells
are activated when [Ca2+] is low.[12] The G-protein coupled calcium receptors (CaR)
sense extracellular calcium and may be found on the surface on a wide variety cells
distributed in the brain, heart, skin, stomach, C cells, and other tissues. In the
parathyroid gland, sensation of high concentrations of extracellular calcium result in

activation of the Gq G-protein coupled cascade through the action of phospholipase

C.

This

hydrolyzes

phosphatidylinositol

4,5-bisphosphate

(PIP2)

to

liberate

intracellular messengers IP3 and diacylglycerol (DAG). Ultimately, these two

messengers result in a release of calcium from intracellular stores and a subsequent
flux of extracellular calcium into the cytoplasmic space. The effect of this signaling
of high extracellular calcium results in an intracellular calcium concentration that
inhibits the secretion of preformed PTH from storage granules in the parathyroid
gland.

In

contrast

to

the

mechanism

that

most

secretory

cells

use,

calcium inhibits vesicle fusion and release of PTH. [7]

The kidneys initial response from increased PTH is to increase renal calcium
resorption and phosphate excretion. As the secretion of PTH is increased Ca2+ is
reabsorbed from the urine, goes back to the bloodstream therefore decreasing
calcium level urine excretion. [2] Blocking of phosphate resorption happens in the
proximal tubule of the kidney while calcium reabsorption happens in the ascending
loop of Henle, distal tubule, and collecting tubule. [4]
The final and most important function of the PTH is to convert 25hydroxyvitamin D to its active form , 1,25-dihydroxyvitamin D-3 [1,25-(OH) 2 D3]
through activation in the proximal tubules of the kidney by an enzyme called
enzyme 1-hydroxylase. The vitamin D in the kidneys is transported by the blood to
the epithelial cells of small intestine promoting Ca2+ transport protein synthesis.
Vitamin D formation results from the increase of blood Ca2+ levels by the PTH
which in return increases Ca2+ absorption in urine. [6] Vitamin D also promotes
intestinal absorption of phosphate ion although its mechanism is not yet clearly
defined. But as compared with PTH, vitamin D exerts slower regulatory effect on
calcium levels.

Calcium levels in the body is critical mainly because it controls calcium ion
homeostasis essential for body functions such as nerve impulse transmission,
muscle contraction, muscle contraction, and blood clotting. [1] Same with the other
endocrine glands of the body, abnormalities related with the parathyroid glands
may include both hyperfunction and hypofunction. [5]
Ca2+ metabolism/homeostasis

Serum [Ca2+] is determined by the interplay of intestinal absorption, renal

excretion and bone remodeling (bone resorption and formation). Each
component is hormonally regulated.
To maintain Ca2+ balance, net intestinal absorption must be exactly
balanced by urinary excretion:
1. Positive Ca2+ balance is seen in growing children, where intestinal
Ca2+ absorption exceeds urinary excretion and the difference is
deposited in the growing bones.
2. Negative Ca2+ balance is seen in women during pregnancy or
lactation, where intestinal Ca2+ absorption is less than urinary
excretion and the difference comes from the maternal bones. [9]

Phosphate metabolism
Phosphates are absorbed from foodstuff. Specialized channel proteins called
sodium-phosphate transporters 2b (or NaPi2b) located at the surface of the
epithelial cells of the small intestine are performing the task. About 1.5 g of
phosphate are captured daily by this process by a normal adult.

Once in the bloodstream, phosphates can be absorbed by organs and tissues.

A part of it is stored in bones. Then, phosphates reach the kidneys where most of it
is filtered out of the blood. But before being eliminated in the urine, another channel
protein (NaPi2a) similar to the one that capture phosphate from foodstuff bring it
back to bloodstream in a process called 'reabsorption'. This steps of filtration and
reabsorption taking place in the kidney are crucial for the maintenance of
phosphate levels. [8]

By: Genesis Adrianne V. Ege & Rouselle John

[7] http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch6/s5ch6_9.htm
[8] http://www.xlhresearch.net/Phosphatemetabolism.htm
[9] www.the-ainet.com/rom-med/files/.../Calcium_metabolism.pdf