Parathyroid Quiz 1

Vitamin D Metabolism

• Vitamin D3 is made within the skin using UV or obtained from eggs or oily fish, while Vitamin D2 is only obtained via diet.
• Vitamin D3 or D2 is converted into calcidiol in the liver.
• Calcidiol is converted into calcitriol (active Vitamin D) in the kidneys due to PTH action.

Parathyroid Hormone (PTH)

• PTH acts on the kidneys to increase calcium reabsorption, decrease renal phosphate reabsorption, and stimulate the conversion of calcidiol to calcitriol.
• PTH acts on distal convoluted tubules to increase calcium reabsorption.
• PTH acts on proximal convoluted tubules to decrease renal phosphate reabsorption.
• PTH stimulates the activation of vitamin D in the kidneys.

Calcitriol

• Calcitriol is the active version of vitamin D.
• It is lipophilic and requires transport proteins.
• Calcitriol increases calcium absorption in the GI tract.
• Calcitriol enhances PTH with bone metabolism of calcium.

Bone Metabolism

• Osteocytes are involved in biomineralization and maintaining bone tissue.
• Osteoblasts create bone tissue/matrix.
• Osteoclasts destroy bone tissue (reabsorb bones).
• Osteogenic cells are stem cells.
• Osteoclasts differentiate from monocytes (hemopoietic stem cells).
• Osteocytes differentiate from osteoblasts (mesenchymal stem cells).

Calcitonin

• Calcitonin is produced by parafollicular cells (C-Cells) in the thyroid gland.
• Increased ionized calcium levels in the blood stimulate calcitonin release.
• Calcitonin counterbalances PTH by decreasing ionized calcium levels in the blood.
• Calcitonin decreases calcium movement from bones to the ECF, inhibiting osteoclast reabsorption.
• Calcitonin increases phosphate movement into bones from the ECF, increasing calcium storage.
• Calcitonin increases renal excretion of calcium and phosphate via urine.
• GI hormones (gastrin, secretin, CCK) stimulate calcitonin release when too much calcium is being absorbed in the intestines.

PTH and GI Tract

• Calcitriol stimulates active transport of dietary calcium across intestinal epithelium and regulates ionized calcium levels entering the blood from the diet.
• Without calcitriol, animals won't have enough calcium to support bone structure.

Primary Hyperparathyroidism

• Primary hyperparathyroidism is the excessive secretion of PTH by abnormal chief cells within the parathyroid gland (parathyroid adenomas).
• It causes persistent hypercalcemia and negative feedback control is lost.
• Hypercalcemia impacts kidneys, neuromuscular system, and GI tract.
• Symptoms include polydipsia and polyuria, calcinuria, decreased excitability of PNS/CNS, cardiac arrhythmias, and decreased cell membrane permeability of muscles.

Secondary Hyperparathyroidism

• Secondary hyperparathyroidism is referred to as Nutritional Secondary Hyperparathyroidism (NSH) or "Big Head Disease".
• It is caused by the lack of calcium in the diet, leading to hypermobilization of calcium from the skeleton under the influence of PTH.
• It can also be caused by increased levels of phosphorus, inverted calcium-phosphate ratio, or increased oxalate levels in forages.
• Oxalates prevent the digestion and absorption of calcium.

Nutritional Metabolic Bone Disease (NMBD)

• NMBD is also known as Nutritional Secondary Hyperparathyroidism (NSHP).
• Predisposing factors include low dietary calcium and vitamin D3 intake, inverted calcium-phosphate ratio, and lack of UV-B light exposure.
• Inappropriate diets cause excessive PTH production in response to hypocalcemia, leading to calcium reabsorption from bones and weakened bones.

Hypoparathyroidism

• Hypoparathyroidism is a deficiency of PTH.
• It is caused by idiopathic factors, surgical destruction of the parathyroid gland, or trauma.
• Low PTH levels cause decreased calcitriol production, hypocalcemia, and hyperphosphatemia.
• Symptoms include fever, pain, muscle weakness, cramps, seizures, neuromuscular and neurological signs, cardiac manifestations, skeletal deformities, and other bone effects.

Parathyroid Anatomy

• Most species have 2 pairs of parathyroid glands.
• Rats and pigs have 1 pair located on the poles of the thyroid gland lobes.
• Chief cells secrete PTH.
• Oxphil cells are larger than chief cells and have unknown function.

Hormone Synthesis

• Hormone synthesis involves the synthesis of pre-prohormones in the rER, which are then cleaved into prohormones in the golgi.
• The prohormones are then cleaved into hormones and packaged into secretory vesicles.
• PTH is synthesized in the parathyroid gland.

PTH Synthesis

• PTH synthesis involves the sensing of calcium levels in the blood by calcium sensing receptors on the parathyroid gland's membrane surface.
• Low levels of calcium trigger the release of PTH.
• PTH is synthesized in the rER and cleaved into proPTH in the golgi.
• PTH is then secreted via exocytosis and metabolized by the liver and kidney.

Phosphate and Calcium Metabolism

• Phosphate and calcium are both involved in the metabolism of ATP and AMP.
• Phosphate is also involved in the nucleic acid buffer system.
• 85% of phosphate is found in bones, 14% in intracellular compartments, and 1% in ECF.
• Calcium is involved in muscle contraction, nerve cell activity, blood coagulation, enzyme activation, membrane stability, and structural roles in teeth and bones.
• 99% of calcium is stored in bones, <1% in intracellular compartments, and 0.1% in ECF.

Calcium-Phosphate Ratio

• Phosphate binds to calcium, reducing available ionized calcium.
• More phosphate = more calcium = less ionized calcium.
• Less phosphate = less calcium = more ionized calcium.
• When calcium and phosphate are not balanced, the body will start taking calcium from other parts of the body (like the bones) to help maintain homeostasis.