General Characteristics and Tissue Organization
Normally, humans have 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. Frequently, they are completely embedded directly within its capsule. This anatomical proximity creates a high risk of accidental gland removal during surgical procedures (thyroidectomy).
Embryologically, they develop from the epithelium of the 3rd and 4th pharyngeal pouches. The cells divide intensively, form dense clusters, then detach and migrate to their final anatomical location.
Externally, the organ is covered by a thin connective tissue capsule. Septa of loose fibrous connective tissue extend inward from the capsule, carrying a rich vascular network. A distinctive 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 colloid-like fluid may appear in the tissue. However, it is important to note that this fluid has no hormonal activity.
Cellular Composition: Parathyroid Cells
All secretory tissue consists of two main cell types (transitional forms are also sometimes described).
1. Chief (Principal) Parathyroid Cells These are small polygonal cells whose nuclei are located very close to each other (dense packing effect). Depending on their functional activity, they are divided into light (resting, inactive) and dark (actively functioning) cells.
The cytoplasm of dark chief cells exhibits prominent basophilia. This is due to a well-developed rough endoplasmic reticulum (rER). An abundance of ribosomes and a developed protein-synthesizing apparatus are essential for the continuous assembly of the polypeptide hormone.
2. Oxyphil Parathyroid Cells These cells are noticeably larger than chief cells. Their cytoplasm shows oxyphilia (affinity for acidic stains), and a massive number of densely packed, large mitochondria are found inside. The number of oxyphil cells increases with age. The function of these cells is not yet fully understood (similar to Askanazy cells of the thyroid gland). One hypothesis suggests they are senescent or degenerating forms of chief cells. However, the high enzymatic activity of their mitochondria contradicts the theory of simple degeneration.
Biosynthesis and Target Sites of Parathyroid Hormone
Dark chief cells synthesize the hormone as a long precursor that undergoes step-by-step proteolysis (chain shortening) with a progressive increase in biological activity:
- Synthesis on the rER. Preproparathyroid hormone (115 amino acid residues) is formed. It lacks hormonal activity.
- Processing in ER cisternae. Part of the molecule is cleaved off, forming proparathyroid hormone (90 residues). Primary biological activity appears.
- Maturation in the Golgi apparatus. Additional proteolysis yields the final mature parathyroid hormone (84 residues), which is the most active polypeptide.
The ultimate physiological effect of parathyroid hormone is an increase in blood $Ca^{2+}$ ion concentration. This is achieved through three pathways:
- Bone tissue: The hormone stimulates osteoclasts. They resorb the bone matrix, releasing calcium into the blood.
- Kidneys: Reabsorption of $Ca^{2+}$ ions from the primary urine back into the bloodstream is enhanced.
- Gastrointestinal tract: Calcium absorption from food is intensified. This effect is indirect. Parathyroid hormone prompts the kidneys to convert vitamin $D_3$ into its active form—calcitriol—which in turn stimulates intestinal calcium absorption.
Regulation and Pathology (Tetany)
The parathyroid glands do not depend on pituitary control. Chief parathyroid cells act directly as ion-sensing cells: they monitor the $Ca^{2+}$ concentration directly in the extracellular fluid. A significant drop 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 absence of parathyroid hormone, blood $Ca^{2+}$ levels drop sharply. Normally, extracellular calcium ions stabilize cell membranes by limiting their permeability to sodium. In hypocalcemia, the $Na^+$ channels of the muscle sarcolemma open easily. The threshold of excitation drops, and muscle excitability increases dramatically.
Interestingly, inside the muscle fibers themselves (in the terminal cisternae), there remains enough stored calcium to trigger contraction. The problem lies specifically in uncontrolled membrane excitability, leading to severe tetanic spasms.