Parathyroid Anatomy

HISTOLOGY OF THE NORMAL PARATHYROID GLANDS

• Embryology and Number
  • Derived from branchial pouches III and IV.
  • Typically four parathyroid glands, though can range from two to six.
  • Lower glands are generally larger than the upper glands.
• Gross Anatomy
  • Ovoid (bean-shaped) glands measuring about 4–6 mm × 2–4 mm × 0.5–2 mm.
  • Weigh approximately 30 mg each.
  • Color varies from yellow to tan, depending on vascularity and proportion of oxyphil cells and stromal fat.
• Childhood Gland Composition
  • Sheets of closely packed chief cells, with little stroma.
  • Oxyphil (oncocytic) cells appear at puberty.
  • Fat cells appear in the stroma in late childhood and increase with age.
• Adult Gland Composition
  • Composed of cords, sheets, and acini of chief cells in a loose areolar stroma containing many mature fat cells.
  • Chief cells may be in:
    • Active (dark) phase: prominent endoplasmic reticulum (ER) and Golgi
    • Resting (light) phase: less developed ER
  • Oxyphil cells are scattered individually or in groups among the chief cells.
• Chief Cells
  • ~8 μm in diameter.
  • Well-defined cell membrane, centrally located nucleus (~4–5 μm).
  • Nuclei: either densely packed chromatin (almost pyknotic) or finely fibrillar with peripheral margination; nucleoli are rare.
  • Cytoplasm is clear and amphophilic with H&E stain.
  • Periodic acid–Schiff (PAS): abundant glycogen.
  • Also contain abundant neutral lipid droplets (demonstrable by azure B, Erie garnet A, oil red O, or Sudan IV).
  • Immunohistochemistry: stronger parathyroid hormone (PTH) staining than oxyphil cells.
• Oxyphil (Oncocytic) Cells
  • Larger than chief cells (12–20 μm diameter), polygonal shape.
  • Cell membranes usually clear.
  • Nucleus similar to chief cell nucleus.
  • Cytoplasm: highly eosinophilic, fine granules (stain carmine with Bensley acid aniline fuchsin [BAAF], dark blue with phosphotungstic acid hematoxylin).
  • Packed with mitochondria (hence “oncocytic”).
  • Little intracytoplasmic lipid or glycogen.
  • Transitional oxyphilic cells: smaller, less eosinophilic.
• Ultrastructure of Chief Cells
  • Chief cells arranged in cords and nests, separated by a basal lamina from the interstitium.
  • Plasma membranes: straight, with desmosomes linking adjacent cells.
  • Active phase:
    • Enlarged Golgi apparatus, numerous vacuoles and vesicles in Golgi region.
    • Many mature secretory granules (50–300 nm).
    • Granules are oval/dumbbell-shaped, with a single membrane, a thin clear space inside, and a dense area of short rodlike profiles.
  • Secretion pathway:
    • Granules move from cell → basement membrane → pericapillary space → capillary basement membrane → fenestrated endothelium → bloodstream (liberating PTH).

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PHYSIOLOGY OF THE PARATHYROID GLANDS

• Primary Function: Regulate and maintain normal serum ionized calcium levels (8.9–10.1 mg/dL).
• Hormone: Parathyroid hormone (PTH).
• Regulation:
  • Ionized calcium in blood modulates PTH secretion.
  • Low Ca²⁺ → ↑PTH release; high Ca²⁺ → ↓PTH.
  • Calcium-sensing receptors (CaSRs) on parathyroid glands sense serum Ca²⁺.
  • CaSRs in kidneys also adjust tubular Ca²⁺ reabsorption.
• Importance of Calcium
  • Critical for neuromuscular function, bone structure, signal transduction (e.g., cytosolic free calcium as second messenger).
  • Hypercalcemia can cause muscle weakness, anorexia, constipation, confusion, coma.
  • Hypocalcemia can cause anxiety, muscle twitching, carpopedal spasm, seizures, stridor, bronchospasm.
• Calcium Balance
  • Daily dietary Ca²⁺: 300–1500 mg; net GI absorption ~200 mg/day.
  • Urinary Ca²⁺ excretion ~200 mg/day (about 2% of filtered load).
  • Stool Ca²⁺ excretion varies greatly with body needs/diet (normally 500–700 mg/day).
• Phosphate Metabolism
  • Dietary phosphate: ~800–900 mg/day.
  • GI absorption enhanced by 1,25-dihydroxyvitamin D.
  • Fecal excretion ~30% dietary intake; renal excretion varies inversely with PTH.
• Homeostatic Mechanisms
  • Low serum Ca²⁺ → parathyroid releases PTH → increased renal 1α-hydroxylation of 25(OH)D → forms 1,25(OH)₂D (calcitriol) → ↑intestinal Ca²⁺ absorption.
  • PTH enhances renal tubule Ca²⁺ reabsorption & bone resorption → net rise in serum Ca²⁺.
  • High serum Ca²⁺ → suppressed PTH secretion → less 1α-hydroxylation → less Ca²⁺ absorption; also more renal Ca²⁺ excretion & reduced bone resorption.
• Hypoparathyroidism
  • If parathyroids are absent or nonfunctional:
    • Serum Ca²⁺ can fall to ~7 mg/dL, but seldom below 5 mg/dL (body’s skeletal reservoir stabilizes).
• Effects of Excess PTH
  • Osteoclast activation → bone matrix resorption → mobilization of Ca²⁺ and phosphate.
  • Bone turnover response: osteoclasts & subsequent osteoblastic repair → raised serum alkaline phosphatase.
  • PTH-induced bone resorption is also linked to GI absorption of calcium & phosphate (via upregulated 1,25(OH)₂D).

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BONE REMODELING UNIT

• Overview
  • Bone = collagen matrix + hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂).
  • Modeling (childhood): changes in bone size/shape.
  • Remodeling (lifelong): maintenance/repair via coordinated osteoclast & osteoblast cycles.
• Bone Cells
  • Osteoblasts: form bone, derived from mesenchymal stem cells.
    • Respond to PTH, 1,25(OH)₂D, estrogen, etc.
    • Secrete collagen & osteoid; become osteocytes or line bone surface or undergo apoptosis.
  • Osteoclasts: multinucleated, large cells from monocyte/macrophage lineage; resorb bone via acid & enzymes.
• Remodeling Cycle
  1. Resorption (∼2 weeks)
     • Osteoblasts release cytokines (RANK ligand, M-CSF) → osteoclast differentiation → degrade bone mineral & collagen.
     • Self-limited by local factors (high Ca²⁺, TGF-β, etc.).
  2. Reversal (∼4 weeks)
     • Mononuclear cells deposit a cement line & recruit osteoblast precursors.
  3. Formation (∼16 weeks)
     • Osteoblasts lay osteoid until resorbed cavity is refilled.
     • Osteoid → mineralized.
     • Cycle returns to quiescent state.
• Defective Remodeling
  • Excessive osteoclastic resorption or incomplete osteoblastic refilling → net bone loss.
    • Found in osteoporosis, hyperparathyroidism, etc.
  • Impaired osteoclast function → overly dense bones (osteopetrosis).