Lec 5 calcium and Phosphorus

• Hormones involved in regulating plasma calcium and phosphate concentrations are PTH, CT(calcatonin),and Vit D3

  
• Organs involved in the regulation of plasma calcium and phosphate concentrations are bones, kidneys, and intestines

  
• Normal serum calcium level

  Dogs: 8.6-11.8 mg/dl; Cats: 8-10.5 mg/dl

  
• PTH


  Increases calcium level

  
• CT(calcatonin)


  Decreases calcium level

  
• Vit D3


  Increases calcium level

  
• Free ionized calcium (Ca2+)


  Physiologically important, can diffuse, involved in cellular processes e.g. muscle contraction

  
• Complexed Ca2+


  Bound to negatively charged molecules e.g. phosphate, can diffuse, not involved in cellular processes
• Complexed Ca2+


  Bound to large negatively charged proteins, non-diffusible, not involved in cellular processes e.g. albumin
• Normal serum phosphate level

  Dogs: 2.5-5.5 mg/dl; Cats: 2.5-6.0 mg/dl
• Phosphorus exists in both organic and inorganic forms, including phospholipids, ester phosphates and inorganic phosphates; inorganic phosphates are completely ionized, circulating primarily as HPO4^2- or H2PO4-
• There is an inverse relationship between calcium and phosphorus
• PTH (parathyroid hormone)


  The most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid

  
• PTH is not under the control of the hypothalamus or anterior pituitary, it is controlled by plasma calcium levels (negative feedback mechanism)

  
• PTH synthesis and secretion

  1. Synthesized as a preprohormone

  2. After intracellular processing, the mature hormone is packaged within the Golgi into secretory vesicles

  3. Secreted into blood by exocytosis

  
• PTH


  Secreted as a linear protein of 84 amino acids
• Parathyroid cell


  Monitors extracellular free calcium concentration via an integral membrane protein that functions as a calcium-sensing receptor

  
• Low extracellular concentrations of free calcium

  Stimulates PTH secretion

  
• Decreased serum calcium concentration and increased serum phosphate (calcium phosphate complex formation)

  Stimulates PTH secretion

  
• Increased serum calcium concentration

  Inhibits PTH secretion

  
• Effects of PTH


  • Mobilization of calcium from bone
  • Enhancing absorption of calcium from the small intestine
  • Suppression of calcium loss in urine

  
• Calcitonin (CT)


  Produced by parafollicular or C-cells of the thyroid glands
• Calcitonin


  Polypeptide hormone; 32 amino acid peptide cleaved from a larger prohormone
• Extracellular concentration of ionized calcium


  The most prominent factor controlling CT secretion

  
• Elevated blood calcium levels

  Stimulate CT secretion

  
• Calcium concentration falls below normal


  Suppresses CT secretion

  
• Calcitonin


  Counteracts PTH by reducing calcium levels in the blood (inhibits osteoclast activity in bones; inhibits renal tubular cells [principal cells of DCT] re-absorption of calcium and phosphorus allowing them to be excreted in the urine)

  
• The actions of PTH and calcitonin are antagonistic on bone resorption but synergistic on decreasing the renal tubular re-absorption of phosphorus

  
• There are species differences in the importance of CT as a factor affecting calcium homeostasis; in fish, rodents and some domestic animals, CT appears to play a significant role in calcium homeostasis; in humans, CT has a minor role in regulating blood concentrations of calcium

  
• Vitamin D3 (Cholecalciferol)


  Steroid hormone, bound to carrier proteins, increases concentrations of serum calcium and phosphorus, promotes mineralization of bone

  
• Vitamin D3


  Synthesized in the skin of animals when light energy is absorbed by a precursor molecule 7-dehydrocholesterol

  
• Vitamin D3 metabolism


  1. Within the liver: Hydroxylated to 25-hydroxycholecalciferol by the enzyme 25-hydroxylase

  2. Within the kidney: 25-hydroxycholecalciferol serves as a substrate for 1-alpha-hydroxylase, yielding 1,25-dihydroxycholecalciferol, the biologically active form

  
• Hepatic synthesis of 25-hydroxycholecalciferol is only loosely regulated and blood levels reflect the amount of vitamin D produced in the skin or ingested

  
• The activity of 1-alpha-hydroxylase in the kidney is tightly regulated and serves as the major control point in production of the active hormone

  
• The major inducer of 1-alpha-hydroxylase is PTH; it is also induced by low blood levels of phosphate
• The skin of dogs and cats contains significantly lower quantities of 7-dehydrocholesterol than other species, and its photochemical conversion to cholecalciferol is quite inefficient - rely on dietary intake of vitamin D more than do other animals
• Actions of Vitamin D3

  • Bone: Acts synergistically with PTH to stimulate osteoclast activity, bone resorption, increase calcium and phosphate concentration (for new bone mineralization)
  • Kidneys: Stimulates calcium and phosphate reabsorption
  • Intestine (small): Stimulates calcium and phosphate absorption

  
• Primary hyperparathyroidism


  Result of parathyroid gland disease, most commonly due to a parathyroid tumour (adenoma) which secretes the hormone without proper regulation
• Secondary hyperparathyroidism


  Disease outside of the parathyroid gland leads to excessive secretion of parathyroid hormone, common causes include kidney disease and inadequate nutrition
• Hypoparathyroidism


  Inadequate production of PTH, resulting in decreased concentrations of calcium and increased concentrations of phosphorus in blood, common causes include surgical removal of the parathyroid glands and disease processes that lead to destruction of parathyroid glands