Parathyroid glands

General characteristics and tissue organization

Normally, a human has four parathyroid glands — two superior and two inferior. These are very compact structures with an average size of only $6 \times 4 \times 2$ mm. The glands are located on the posterior surface of the lateral lobes of the thyroid gland. They are often completely embedded directly within its capsule. Such anatomical proximity creates a high risk of accidental gland removal during surgery (thyroidectomy).

Embryologically, they develop from the epithelium of the III and IV pharyngeal pouches. The cells divide intensively, form dense clusters, then detach and migrate to their permanent location.

Externally, the organ is covered by a thin connective tissue capsule. Layers of loose fibrous connective tissue extend inward from it, carrying a rich network of blood vessels. A distinct histological feature of the stroma is the presence of adipocytes (fat cells).

The parenchyma of the gland is represented by epithelial cords and clusters that can form compact groups or rosette-like structures. In older age, follicle-like structures filled with a fluid resembling colloid may appear in the tissue. However, it is important to remember that this fluid has no hormonal activity.

Cellular composition: parathyroid cells

All secretory tissue consists of two main cell types (transitional forms are sometimes also distinguished).

1. Chief parathyroid cells These are small polygonal cells whose nuclei are located very close to each other (tight packing effect). Depending on functional activity, they are divided into light (resting, inactive) and dark (actively working) cells. The cytoplasm of dark chief cells is characterized by pronounced basophilia. The reason is a powerfully developed rough endoplasmic reticulum (rER). An abundance of ribosomes and a developed protein-synthesizing apparatus are necessary for the continuous assembly of the polypeptide hormone.

2. Oxyphil parathyroid cells These cells are noticeably larger than the chief cells. Their cytoplasm exhibits oxyphilia (affinity for acidic dyes), and a huge number of densely packed large mitochondria are found inside. With age, the number of oxyphil cells increases. Their function is not fully understood (the situation is analogous to Askanazy cells in the thyroid gland). There is a hypothesis that these are aging or degenerating forms of chief cells. However, the high enzymatic activity of their mitochondria contradicts the theory of simple degeneration.

Biosynthesis and sites of action of parathyroid hormone

Dark chief parathyroid cells synthesize the hormone as a long precursor that undergoes stepwise proteolysis (chain shortening) with a gradual increase in biological activity:

1. Synthesis on the rER. Preproparathyroid hormone (115 amino acid residues) is formed. It has no hormonal activity.
2. Processing in ER cisternae. A part of the molecule is cleaved, forming proparathyroid hormone (90 residues). Primary biological activity appears.
3. Maturation in the Golgi complex. Additional proteolysis yields the final mature parathyroid hormone (84 residues) — the most active polypeptide.

The final physiological effect of parathyroid hormone is increasing the concentration of $Ca^{2+}$ ions in the blood. This is achieved in three ways:

• Bone tissue: the hormone stimulates osteoclasts. They break down the bone matrix, releasing calcium into the blood.
• Kidneys: reabsorption of $Ca^{2+}$ ions from primary urine back into the bloodstream is enhanced.
• Gastrointestinal tract: calcium absorption from food is intensified. This effect is indirect. Parathyroid hormone causes the kidneys to convert vitamin $D_3$ into its active form — calcitriol, and it is this form that causes the intestine to absorb calcium.

Regulation and pathology (tetany)

The parathyroid glands are independent of pituitary control. The chief parathyroid cells themselves act as ion-receptor cells: they monitor the concentration of $Ca^{2+}$ directly in the extracellular fluid. A significant decrease in calcium levels serves as an immediate signal to increase parathyroid hormone release (feedback principle).

If the parathyroid glands are removed, tetany develops. Due to the lack of parathyroid hormone, the level of $Ca^{2+}$ in the blood drops sharply. Normally, extracellular calcium ions stabilize cell membranes, limiting their permeability to sodium. In hypocalcemia, the $Na^+$ channels of the muscle sarcolemma easily open. The excitation threshold drops, and muscle excitability increases sharply. Interestingly, inside the muscle fibers themselves (in terminal cisternae) enough calcium remains stored to trigger contraction. The problem lies precisely in uncontrolled membrane excitability leading to severe tetanic spasms.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Morphological and functional similarity of oxyphil parathyroid cells and Askanazy cells of the thyroid gland.
• Biochemistry of proteolysis: why preproparathyroid hormone lacks activity.
• Molecular mechanism of osteoclast stimulation in bone tissue by parathyroid hormone.
• The role of the kidneys in the synthesis of the active form of vitamin D3 (calcitriol).
• Ionic mechanisms of tetany: the effect of hypocalcemia on sarcolemmal sodium channels.

Other topics in the "Endocrine System" section

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