Parathyroid Glands and Calcium Hormones
Parathyroid Hormone (PTH)
-A polypeptide containing 84 Amino acids -Half life of 2-4 min
Parathyroid Hormones Key Concepts
-Calcium homeostasis is mainly regulated by PTH, Vit. D, and calcitonin. • PTH and calcitonin release is controlled by circulating Ca2+ levels and is under feedback regulation by Ca2+ and Vit. D. • In the kidney, PTH increases renal Ca2+ reabsorption and increases the activity of 1a‐hydroxylase (leading to the synthesis of active Vit. D) • In bone, PTH increases osteoclast‐mediated bone resorption. • Vit. D increases intestinal Ca2+ absorption • Calcitonin decreases bone resorption and lowers plasma Ca2+ levels
Primary Hyperparathyroidism
-Calcium homeostatic loss due to excessive PTH secretion -Due to excess PTH secreted from adenomatous or hyper plastic parathyroid tissue
Physiological Importance of Calcium
-Calcium salts in bone provide structural integrity of the skeleton
Intracellular Calcium concentration
-Control of cellular calcium homeostasis is as carefully maintained as in extracellular fluids -Stored in mitochondria and ER -"pump-leak" transport systems control Ca
Hypoparathyroidism
-HPTH‐deficient hypoparathyroidism - Reduced or absent synthesis of PTH - Often due to inadvertent removal of excessive parathyroid tissue during thyroid or parathyroid surgery • PTH‐ineffective hypoparathyroidism -Synthesis of biologically inactive PTH
Hypocalcemia
-Hypocalcemia occurs when there is inadequate response of the Vitamin D‐PTH axis to hypocalcemic stimuli -Often multifactorial -Hypocalcemia is invariably associated with hypoparathyroidism
Calcitonin
-Produced in thyroid gland -Acts to decrease plasma Ca levels -Antagonist of PTH -Target cell: osteoclast -Acts via increased cAMP levels to inhibit osteoclast motility and cell shape and inactivate them -The major effect of calcitonin administration is a rapid fall in Ca2+ caused by inhibition of bone resorption -in Kidney: increase Ca excretion by inhibiting renal tubular Ca absorption
PTH Receptor defect
-Rare disease: Jansen's metaphyseal chondrodysplasia -Characterized by hypercalcemia, hypophosphotemia, short‐limbed dwarfism • Due to activating mutation of PTH receptor • Rescue of PTH receptor knock‐out with targeted expression of "Jansen's transgene"
Actions of PTH: Intestine (via Kidney)
-in the proximal tubule of the kidney: PTH up‐regulates 25‐hydroxyvitamin D3 1‐alpha‐hydroxylase -The enzyme catalyzes the hydroxylation of Calcifediol to calcitriol (the bioactive form of Vitamin D) -Calcitriol increases the absorption of calcium -NET RESULT: ↑ plasma Ca2+
Hypercalcemia
-results from combined effects of PTH‐induced bone resorption, intestinal calcium absorption and renal tubular reabsorption -Underlying cause is generally excessive bone resorption by one of three mechanisms -Local osteolytic hypercalcemia - 20% of all hypercalcemia of malignancy • Humoral hypercalcemia of malignancy - Over‐expression of PTH‐related protein
Blood supply
1. Arterial supply (mainly inferior thyroid artery) 2. Venous drainage (inferior, middle, superior thy. veins)
Hormonal Regulation of Calcium Homeostasis
1. PTH 2. Vitamin D 3. Cacitonin
Anatomy of Parathyroid Glands
2 PAIRS of glands located on all "4 corners" of Thyroid -Superior Parathyroid glands -Inferior Parathyroid glands
Extracellular Calcium
3 Definable fractions of calcium in serum: 1. Ionized calcium (50%) 2. Protein-bound calcium (40%) -90% bound to albumin -Remainder bound to globulins 3. Calcium complexed to serum constituents (10%) -citrate and phosphate -Only free, ionized Ca is biologically active
Which of the following steps is not stimulated by PTH? A. Osteogenesis in bones B. Ca2+ reabsorption from the kidney C. Production of calcitriol in the kidney D. Ca2+ absorption from the small intestine E. Neither step
A. Osteogenesis in bones
Calcium Absorption
Absorption occurs in the small intestine and requires Vitamin D
Histology
Composed of Chief and Oxyphil cells
Which of the following statements regarding calcium homeostasis is not true? A. Extracellular calcium concentration is monitored in the parathyroid. B. Inhibition of osteoclast activity helps restore high extracellular calcium concentration to normal levels. C. Calcitonin and parathyroid hormone have opposing effects on extracellular calcium concentration. D. Calcitriol and parathyroid hormone have opposing effects on extracellular calcium concentration.
D. Calcitriol and parathyroid hormone have opposing effects on extracellular calcium concentration.
Which of the following hormones is not important in calcium homeostasis? A. Calcitonin B. Parathyroid hormone C. Calcitriol D. Thyroid hormones
D. Thyroid hormones
Which of the following stimulates PTH secretion? A. ↑ blood Ca2+ B. ↑ blood Vit D C. ↓ blood Ca2+ D. ↓ blood Vit D E. BothCandD
E. Both C and D
PTH Receptors (2)
G protein coupled receptors (GPCR) located on membrane: 1. PTH1R- expressed in high levels in bone and kidney- regulated calcium ion homeostasis thru activation of adenylate cyclase and phospholipase C 2. PHT2R
Oxyphil Cells
Larger w/ pink cytoplasm -function unknown
Actions of PTH: Kidney
PTH acts on kidney to Increase reabsorption of calcium (decreased excretion) -Also get increased excretion of phosphate -Increased production of active vitamin D3 -NET RESULT: ↑ plasma Ca2+ ↓ plasma P -Need to get rid of waste, but selectively take back the good stuff
Actions of PTH: Bone
PTH acts to increase degradation of bone (RELEASE OF CALCIUM) -causes osteoblasts to release cytokines, which stimulate osteoclast activity - stimulates bone stem cells to develop into osteoclasts - net result: increased release of calcium from bone *Osteoblasts: MAKE bone *Osteoclasts: RELEASE bone
Regulation of PTH Secretion
PTH is released in response to change in plasma Calcium levels -Low calcium results in High PTH release -High calcium results in low PTH release -Vitamin D inhibits PTH release (neg feedback)
Chief cells
Small with scant, lightly stained cytoplasm -Synthesize and release Parathyroid Hormone (PTH)
Calcitonin Secretion stimulus
The major stimulus of calcitonin secretion is a rise in plasma Ca2+ levels
Overall function of PTH
The overall action of PTH is to increase plasma Ca2+ levels and decrease plasma phosphate levels.
