Physiology of Parathyroid glands Outline : - Location of Parathyroid glands. - Who discovered the glands. - Some info. about it. - Parathyroid hormone. - Histology of the gland. - PTH biosynthesis. - The calcium-sensing receptors (CaSR) - Why Calcium is so Important? - Calcitonin - vitamin D -Metabolic bone diseases (Hypercalcaemia and hypocalcaemia)

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By: Taha A. Sindi
Lecturer: Asst. Prof. Dr. Roslina Abdul Rahim
2015-2016
Sem II
Physiology of Parathyroid
Gland
International Islamic University Malaysia
Kulliyah of Medical Science
Dep. Of Basic Medical Sciences
s

2. Outline :
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• Location of Parathyroid glands.
• Who discovered the glands.
• Some info. about it.
• Parathyroid hormone.
• Histology of the gland.
• PTH biosynthesis.
• The calcium-sensing receptors (CaSR)
• Why Calcium is so Important?
• Calcitonin
• 1,25-Dihyroxyvitamin D
• Metabolic bone diseases
(Hypercalcaemia and hypocalcaemia)

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Location of thyroid Glands
*Source: parathyroidglands.com
= around
Para

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Richard Owen, (1804 – 1892) who
discovered the parathyroid glands in 1850
a rhinoceros.
*Source: the Natural History Museum
Interesting Fact:

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• 4 tiny parathyroid glands, in the neck , on the posterior surface
of thyroid gland . Have two superiorly and 2 inferiorly
• Small in size(a grain of rice), each weighting around 30-50mg,
but may weight as much as 70 mg, and in diameter is 3-4 or till 8
millimeters.
• Woman usually have larger parathyroid gland than men
(Hinson, et al., 2010)
• It’s produce only one hormone (abbreviate: PTH)
• control the body's calcium levels
(why?)
Parathyroid Glands
*source: thyroid.com.au

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Parathyroid hormone (PTH)
 Also known as parathormone or parathyrin
*source: wiki English
Produced by chief cells as a polypeptide
hormone containing 84 amino acids.
PTH half-life is approximately 4 minutes
PTH acts to increase the concentration of
ionic calcium (Ca2+) in the blood.
The major target end organs for parathyroid
hormone (PTH) action are the kidneys, skeletal
system, and intestine

7. *source:thyroid.com
7
Target organs: bones, GIT and the kidneys

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An image of the parathyroid gland reveals
two cell types:
*source: School of Anatomy and Human
Biology - The University of Western Australia
Histology
(Principal Cells): These cells release PTH.
are more numerous, smaller, with a slightly
eosinophilic cytoplasm
1- Chief cells

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2- Oxyphil cells
are less numerous, larger, and have a very
eosinophilic cytoplasm due to numerous
mitochondria. They are found individually, or
clustered in groups. The function of these cells
is unknown, yet their presence assists in
identifying this organ. Large numbers of
glycogen granules. Lack secretory vesicles.
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)
*source: School of Anatomy and Human
Biology - The University of Western Australia

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PTH biosynthesis
 PTH is encoded by a gene in chromosome 11 (Hinson, et al., 2010).
 after translation, it become preproparathyroid hormone (preproPTH)
contains 115 amino acids
 in endoplasmic reticulum 29 amino acids removed, so it called
proparathyroid hormone (proPTH) contains 89 amino acids
 In the Golgi, removed more amino acids by peptidase to become
mature hormone.
 It is stored in secretory vesicles within the cells, and released when
required.
©The McGraw-Hill Companies, Inc. science.psu.edu

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Kumar, R., & Thompson, J. R. (2011). The
regulation of parathyroid hormone
secretion and synthesis. Journal of the
American Society of Nephrology,22(2),
216-224.
©2011 by American Society of Nephrology
For more on biosynthesis:

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The Role of the Parathyroid Glands
PTH raises the blood calcium level by:
1. breaking down the BONE (where most of the body's
calcium is stored) and causing calcium release.
2. increase the GIT ability to absorb calcium from food.
3. increasing the KIDNEY's ability to retain calcium that
would otherwise be lost in the urine.

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*The calcium-sensing receptors (CaSR) are
receptor which senses levels of calcium ion.

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The 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).
 CaSR: are receptors which senses levels of calcium ion

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A specific gland just to maintain Ca level !
Why Calcium is so Important?
 Stimulate hormone secretion.
 Muscle contraction.
 Blood clotting.
 Nerve function- transmit nerve impulse.
 Necessary for the activation of some enzyme.
 Transport ion across membrane.
 Maintain regular heart beat (conduct electricity).
most of Calcium stored in the skeleton complexed
with phosphate, Ca++ has a wide range of functions:

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Calcium Homeostasis
in Calcium homeostasis process many key components are involving:
 parathyroid hormone (PTH) : action on GIT, Kidneys and bones
 1,25-dihydroxyvitamin D-3 (active form of vitamin D )
 Calcitonin
Normal level of Ca in the blood is :
Around 10 mg/dL (Ganong’s review of med. Phy.)

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• hormone produced by the
parafollicular cells (also known as C-cells) of
the thyroid, that regulates calcium levels.
Calcitonin
• also known as thyrocalcitonin is a
32-amino acid linear polypeptide
• Action:
receptors for Calcitonin are found in
the bones and the kidneys.
• It inhibits the activity of osteoclasts
and also increase Ca++ in the urine.

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Vitamin D-3 formed in the skin when a cholesterol precursor,
is exposed to ultraviolet light. Activation occurs when the substance
undergoes 25-hydroxylation in the liver and 1-hydroxylation in the
kidney.
The primary action of 1,25-(OH)2 D3 is to promote gut absorption of
calcium by stimulating formation of calcium-binding protein within the
intestinal epithelial cells. Vitamin D also promotes intestinal absorption
of phosphate ion, although the exact mechanism is unclear. Negatively
charged phosphate ion may passively flow through the intestinal cell
because of flux of the positively charged calcium ion.
In bone, vitamin D may play a synergistic role with parathyroid hormone
(PTH) in stimulating osteoclast proliferation and bone resorption.
Compared to parathyroid hormone (PTH), vitamin D exerts a much
slower regulatory effect on calcium balance.
Vitamin D

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PTH increases blood calcium concentrations when
calcium ion levels fall below normal. First, PTH
enhances reabsorption of calcium by the kidneys; it
then stimulates osteoclast activity and inhibits
osteoblast activity. Finally, PTH stimulates synthesis
and secretion of calcitriol by the kidneys, which
enhances Ca2+ absorption by the digestive system.
Summary:

20. Some
Disorders of parathyroid gland
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21. Hypercalcemia & Hypocalcemia
• Hypercalcemia is a disorder in which there is too
much calcium in the blood.
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• On the other hand, if too little PTH is made,
hypocalcemia develops.

22. • The most common cause of hypercalcemia 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.
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• 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.
Hypercalcemia

23. 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.
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24. 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
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Treatment:
Medications that prevent bone breakdown such as
calcitonin

25. Hypocalcemia
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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 )

26. 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
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Treatment :
Intravenous calcium chloride

27. References:
• Blaine, J., Chonchol, M., & Levi, M. (2014). Renal control of calcium, phosphate, and
magnesium homeostasis. Clinical Journal of the American Society of Nephrology, CJN-
09750913.
• Boundless. “Parathyroid Glands.” Accessed on 08 Jan. 2016. Retrieved 07 Apr. 2016
from boundless.com/biology/textbooks/boundless-biology-textbook/the-endocrine-system-37/endocrine-
glands-214/parathyroid-glands-806-12044
• Dr.Maizura’s lecture notes on Parathyroid glands. 2016
• Dr.Michael Barakate. How the Parathyroid Glands Work. Accessed on 17.3.2016.
thyroid.com.au/how-the-parathyroid-gland-works
• Essig, G. F.m Carron D, Carter W B, Jameson, M J , Talavera , F., Calhoun, K H Meyer,
A D ,Ramadan, H. H. (2016) Calcium Homeostasis 1.04.2016
emedicine.medscape.com/article/874690-overview
• Garmyan Yawar (2015) - Disorders of parathyroid gland
slideshare.net/GarmyanYawar/parathyroid-disorders
• Hinson, J. et al. (2010) The Endocrine System, Basic science and clinical conditions.
Elsevier Limited.
27

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• Introduction to Parathyroid Glands. Accessed on 30.03.2016
parathyroid.com/parathyroid.htm
• Histology of Thyroid and Parathyroid Glands. Accessed on 7.4.2016
quizlet.com/10459372/histology-lecture-3-thyroid-and-parathyroid-glands-flash-cards
• Hypercalcemia, Hypocalcemia and the Parathyroid Glands. Accessed on 7.4.2016 .
hubpages.com/health/Hypercalcemia-Hypocalcemia-and-the-Parathyroid-Gland
• Hypocalcemia vs. Hypercalcemia. Accessed on 7.4.2016. medbullets.com/step2-3-
renal/20703/hypocalcemia-vs-hypercalcemia .
• Kumar, R., & Thompson, J. R. (2011). The regulation of parathyroid hormone secretion
and synthesis. Journal of the American Society of Nephrology,22(2), 216-224.
• Parathyroid glands. Accessed on 17.3.2016
betterhealth.vic.gov.au/health/conditionsandtreatments/parathyroid-glands
• Hebert, S. C., Brown, E. M., & Harris, H. W. (1997). Role of the Ca (2+)-
sensing receptor in divalent mineral ion homeostasis. Journal of
Experimental Biology, 200(2), 295-302.

29. • Ritter, C. S., Haughey, B. H., Miller, B., & Brown, A. J. (2012). Differential gene expression by
oxyphil and chief cells of human parathyroid glands. The Journal of Clinical Endocrinology &
Metabolism, 97(8), E1499-E1505.
• School of Anatomy and Human Biology - The University of Western Australia.
Accessed on 7.4.2016 lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm
• The American Association of Endocrine Surgeons (AAES). Parathyroid Glands: Function.
Accessed on 17.3.2016 endocrinediseases.org/parathyroid/parathyroid_background.shtml
• The Histology Guide – university of Leeds. Accessed on 7.4.2016
histology.leeds.ac.uk/glandular/thyroid.php
• National Library of Medicine. Accessed on 9.4.2016 nlm.nih.gov
• Riccardi, D., & Brown, E. M. (2010). Physiology and pathophysiology of
the calcium-sensing receptor in the kidney. American Journal of
Physiology-Renal Physiology, 298(3), F485-F499.
• Hendy, G. N., D'Souza-Li, L., Yang, B., Canaff, L., & Cole, D. E. (2000).
Mutations of the calcium-sensing receptor (CASR) in familial
hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and
autosomal dominant hypocalcemia. Human mutation, 16(4), 281.
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