Parathyroid gland

Question 1

The parathyroid glands play an important role in calcium homeostasis and bone health, predominantly through involvement in calcium and phosphate metabolism.

What is the main hormone of the parathyroid, and what does it do? What other chemicals are important in this process?

Answer 1

The main hormone that mediates the effects of calcium regulation is parathyroid hormone, which acts on the kidneys and bone. PTH increases serum calcium while decreasing serum phosphate concentration.

Vitamin D and calcitonin also play an important role in calcium homeostasis (we’ll get to this later)

Question 2

Discuss the anatomy of the parathyroid gland as far as where they are, and what arteries and veins supply them

Answer 2

Four small pea-sized structures attached to the posterior aspect of the thyroid gland, external to the fibrous thyroid capsule. The glands are anatomically separated into two superior and two inferior parathyroids. Both sets are supplied by the inferior thyroid artery and the thyroid plexus of veins drain them.

Question 3

Discuss DiGeorge Syndrome. What causes it and how does it present?

Answer 3

DiGeorge syndrome is a consequence of abnormal development of pharyngeal pouches 3 and 4 due to chromosome 22q11.2 deletion.

Clinical manifestations include hypocalcemia secondary to absence of the parahyroid glands, immune deficiency secondary to absence of thymic tissue leading to abnormal T-Cell maturation, and congenital cardiac malformations.

Question 4

What are pharyngeal pouches and how do they relate to the parathyroid?

Answer 4

The parathyroid glands are derived from pharyngeal pouch endoderm. Four pharyngeal pouches exist during development, each contributing to the formation of important structures in the head and neck. Each pouch represents an invagination of endodermal tissue within the foregut

Question 5

Derivatives of the first branchial/pharyngeal pouch

Answer 5

Middle ear cavity, mastoid air cells

Question 6

Derivatives of the second branchial/pharyngeal pouch

Answer 6

Epithelial lining of palatine tonsil

Question 7

Derivatives of the third branchial/pharyngeal pouch, dorsal wing vs. ventral wing

Answer 7

dorsal wing - Inferior parathyroids

Ventral wing - Thymus

Question 8

Derivatives of the fourth branchial/pharyngeal pouch

Answer 8

Superior parathyroids, thyroid gland c-cells

Question 9

Branchial cysts vs. thyroglossal cysts

Answer 9

Branchial cysts are lesions found lateral to the midline of the neck. They result from failed obliteration of the temporary cervical sinuses.

Thyroglossal duct cysts, found medially, result from failed obliteration of the thyroglossal duct as the thyroid gland migrates inferiorly during development.

Question 10

When does the third pouch differentiate into two wings?

Answer 10

5 - 6 weeks gestation

Question 11

What occurs at the seventh week of gestation for the pharyngeal/branchial pouches?

Answer 11

By the 7th week of gestation, the third branchial pouch diverticulum elongates, ultimately allowing the developing thymus and inferior parathyroids to separate from the pharynx

Question 12

Discuss the derivatives of the 4 branchial clefts and the 4 branchial membranes

Answer 12

First cleft - External auditory meatus
Second, third, fourth clefts - Temporary cervical sinuses (normally obliterated)
First membrane - Tympanic membrane
Second, third, fourth membranes - Temporary structures (normally obliterated)

Question 13

What is ectopic parathyroid tissue?

Answer 13

Results from abnormal migration. Ectopic parathyroids can be found in the anterior/posterior mediastinum, retroesophageal space, or even within the thyroid or thymus.

Despite abnormal migration, the parathyroids typically remain symmetrical from side to side

Question 14

What two cell types make up the parathyroid? What are their characteristics and what do they secrete?

Answer 14

Chief cells - Most predominant. They are small, polygonal cells with secretory granules containing PTH, arranged into curvilinear cords separated by capillaries.

Oxyphil cells - Unknown function, are large cells containing abundant acidophilic mitochondria

Question 15

Where is most of our calcium? In what form is that calcium in?

Answer 15

99% stored in bone, 0.1% found in ECF (extracellular fluid)

40% serum calcium is bound to plasma protein
10% serum calcium is complexed with anions such as phosphate and citrate
50% of serum calcium is in free ionized form

Only free calcium is biologically active

Question 16

What two things affect PTH levels and how?

Answer 16

PTH secretion goes up when Ca is down, and vice-versa.

Reductions in Mg also affect PTH secretion. Mild decreases in Mg stimulate PTH secretion, Severe hypomagnesemia however inhibits PTH secretion.

Question 17

How does PTH increase bone resorption?

Answer 17

PTH stimulates osteoclasts more than osteoblasts (but still hits both), leading to increased calcium and phosphate levels

PTH enhances the activity of existing osteoclasts and also promotes the differentiation of new osteoclasts from progenitor cells.

Increased resorption from bone mineral leads to the release of both calcium and phosphate into the extracellular space

Question 18

How does PTH increase renal calcium reabsorption?

Answer 18

PTH stimulates the distal renal tubule to increase eabsorption of calcium, effectively raising serum calcium levels

Question 19

How does PTH increase phosphate excretion?

Answer 19

In the proximal renal tubule, PTH inhibits phosphate reabsorption, causing more of it to be excreted . The reduction in serum phosphate reduces the quantity of complexed calcium in circulation (phosphate and calcium get all bound up together in circulation), thereby raising the amount of extracellular calcium.

Question 20

How does PTH increase intestinal Ca reabsorption?

Answer 20

PTH increases activity of 1a-Hydroxylase in the kidney. This results in increased levels of 1,25-(OH)2 Vitamin D (calcitriol). Calcitriol affects intestinal absorption of calcium and bone resorption.

Question 21

Vitamin D2 vs. D3

Answer 21

D2 (ergocalciferol) - Produced by plant and fungal sources and is not made by the human body

D3 (cholecalciferol) - Produced by animals and endogenously by the skin. Specific wavelengths of UV light react with 7-dehydrocholesterol to produce D3. So sun exposure may help prevent Vitamin D deficiency in certain individuals.

Question 22

Vitamin D deficiency leads to what in children?

Answer 22

Rickets - Inability to calcify newly formed bone matrix (osteoid) with consequent malformation (bowing) of long bones.

Question 23

Vitamin D deficiency leads to what in adults?

Answer 23

Osteomalacia - Defective mineralization of bone, like in rickets - Leads to pain, proximal muscle weakness, and bony deformities. It is treated with vitamin D replacement.

Question 24

Vitamin D3, cholecalciferol, is initially not active when made in the skin. How does it become active?

Answer 24

• Cholecalciferol goes to the liver and is hydroxylated to 25-hydroxycholecalciferol, which is the storage form of Vitamin D (this is what we are measuring when we say “Vitamin D levels”). There is a negative feedback loop in this, i.e., 25 stops further 25 from being made
• 25 goes to the kidney, where 1a-hydroxylase hydroxylates 25 to 1,25-dihydroxycholecalciferol, which is the active form of Vitamin D, and is also known as calcitriol. This enzyme is upregulated by PTH, thus, increase PTH activity leads to increase Vitamin D activity, as does low calcium and low phosphate.

Question 25

How does calcitriol increase intestinal calcium and phosphate absorption?

Answer 25

Upregulates gene transcription of the calcium binding protein calbindin D-28K in the intestinal brush border.

Question 26

How does calcitriol increase bone resorption of calcium and phosphate?

Answer 26

Increases transport across membranes, thus at the level of the bone, it promotes resorption of calcium and phosphate so they can be used for the mineralization of new bone

Question 27

How does calcitriol increase renal reabsorption of calcium and phosphate in a minor way?

Answer 27

Increases renal tubule reabsorption of both ions. Minor and contributes little.

Question 28

Where do we get calcitonin from and what does it do?

Answer 28

Polypeptide secreted by the parafollicular or c-cells of the thyroid gland. Although it promotes reduction in extracellular calcium through anti-PTH-like effects, calcitonin is not necessary for the maintenance of calcium homeostasis. Patients who have had their thyroid removed show no changes in serum Ca.

It is secreted in response to high Ca, acting primarily on bone to decrease osteoclast activity. Minorly gets help from the kidneys and intestines to limit reabsorption.