Medical brain notes 44

  Overview of Calcium and Phosphate Regulation in the Extracellular Fluid and Plasma Extracellular fluid calcium concentration normally is regulated very precisely, seldom rising or falling more than a few per cent from the normal value of about 9.4 mg/dl, which is equivalent to 2.4 mmol calcium per liter. This precise control is essential, because calcium plays a key role in many physiologic processes, including contraction of skeletal, cardiac, and smooth muscles; blood clotting; and transmission of nerve impulses, to name just a few. Excitable cells, such as neurons, are very sensitive to changes in calcium ion concentrations, and increases in calcium ion concentration above normal  (hypercalcemia)  cause pro-gressive depression of the nervous system; conversely, decreases in calcium con-centration  (hypocalcemia)  cause the nervous system to become more excited.         An important feature of extracellular calcium regulati...

  Bone and Its Relation to Extracellular Calcium and Phosphate Bone is composed of a tough  organic matrix  that is greatly strengthened by deposits of  calcium salts . Average  compact bone  contains by weight about 30 per cent matrix and 70 per cent salts.  Newly formedbone  may have a considerably higher percentage ofmatrix in relation to salts. Organic Matrix of Bone.  The organic matrix of bone is 90to 95 per cent  collagen fibers , and the remainder is a homogeneous gelatinous medium called  ground sub-stance . The collagen fibers extend primarily along thelines of tensional force and give bone its powerful tensile strength. The ground substance is composed of extracellular fluid plus  proteoglycans , especially  chondroitin sulfate  and  hyaluronic acid . The precise function of each of these is not known, although they do help to control the deposition of calcium salts. Bone Salts.  The crystalline s...

  Precipitation and Absorption of Calcium and Phosphate in Bone-Equilibrium with the Extracellular Fluids Hydroxyapatite Does Not Precipitate in Extracellular Fluid Despite Supersaturation of Calcium and Phosphate Ions.  The concentrations of calcium and phosphate ions in extra-cellular fluid are considerably greater than those required to cause precipitation of hydroxyapatite. However, inhibitors are present in almost all tissues of the body as well as in plasma to prevent such precipi-tation; one such inhibitor is  pyrophosphate . Therefore, hydroxyapatite crystals fail to precipitate in normal tissues except in bone despite the state of supersatu-ration of the ions. Mechanism of Bone Calcification.  The initial stage in boneproduction is the secretion of  collagen molecules  (called collagen monomers) and  ground substance  (mainly proteoglycans) by  osteoblasts . The collagen monomers polymerize rapidly to form collagen fibers; the result...

  Calcium Exchange Between Bone and Extracellular Fluid If soluble calcium salts are injected intravenously, the calcium ion concentration may increase immediately to high levels. However, within 30 minutes to 1 hour or more, the calcium ion concentration returns to normal. Likewise, if large quantities of calcium ions are removed from the circulating body fluids, the calcium ion concentration again returns to normal within 30 minutes to about 1 hour. These effects result in great part from the fact that the bone contains a type of  exchangeable  calcium that is always in equilibriumwith the calcium ions in the extracellular fluids. A small portion of this exchangeable calcium is also the calcium found in all tissue cells, especially in highly permeable types of cells such as those of the liver and the gastrointestinal tract. However, most of the exchangeable calcium is in the bone. It normally amounts to about 0.4 to 1 per cent of the total bone calcium. This calcium is ...

  Deposition and Absorption of Bone-Remodeling of Bone Deposition of Bone by the Osteoblasts.  Bone is continually being deposited by  osteoblasts , and it is continually being absorbed where  osteoclasts  are active (Figure 79–4). Osteoblasts are found on the outer surfaces of the bones and in the bone cavities. A small amount of osteoblastic activity occurs continually in all living bones (on about 4 per cent of all surfaces at any given time in an adult), so that at least some new bone is being formed constantly. Absorption of Bone—Function of the Osteoclasts.  Bone is alsobeing continually absorbed in the presence of osteo-clasts, which are large phagocytic, multinucleated cells (as many as 50 nuclei), derivatives of monocytes or  monocyte-like cells formed in the bone marrow. The osteoclasts are normally active on less than 1 per cent of the bone surfaces of an adult. Later we see that PTH controls the bone absorptive activity of osteoclasts. Hist...

  Vitamin D Vitamin D has a potent effect to increase calcium absorption from the intestinal tract; it also has impor-tant effects on both bone deposition and bone absorption, as discussed later. However, vitamin D itself is not the active substance that actually causes these effects. Instead, vitamin D must first be converted through a succession of reactions in the liver and the kidneys to the final active product,  1 , 25-dihydroxycholecalciferol , also called 1,25(OH) 2 D 3 . Figure 79–6 shows the suc-cession of steps that lead to the formation of this sub-stance from vitamin D. Let us discuss these steps. Cholecalciferol (Vitamin D 3 ) Is Formed in the Skin.  Severalcompounds derived from sterols belong to the vitamin D family, and they all perform more or less the same functions. Vitamin D 3  (also called  cholecalciferol ) is the most important of these and is formed in the skin as a result of irradiation of  7-dehydrocholesterol , a sub-stance norma...

  Parathyroid Hormone Parathyroid hormone provides a powerful mechanism for controlling extracellular calcium and phosphate concentrations by regulating intestinal reabsorption, renal excretion, and exchange between the extracellular fluid and bone of these ions. Excess activity of the parathyroid gland causes rapid absorption of calcium salts from the bones, with resultant  hypercalcemia  in the extracellular fluid; conversely, hypofunction of the parathyroid glands causes  hypocalcemia , often with resultant tetany. Physiologic Anatomy of the Parathyroid Glands.  Normallythere are four parathyroid glands in humans; they are located immediately behind the thyroid gland—one behind each of the upper and each of the lower poles of the thyroid. Each parathyroid gland is about 6 mil-limeters long, 3 millimeters wide, and 2 millimeters thick and has a macroscopic appearance of dark brown fat. The parathyroid glands are difficult to locate during thyroid operations be...