Effect of hormone PTH on extracellular fluid calcium and phosphate concentrations
PTH has two mechanisms for mobilizing calcium and phosphate from bone. One is a rapid mechanism that usually begins in minutes and gradually increases over several hours.
The figure shows an estimate of the blood calcium and phosphate concentrations caused by the sudden injection of PTH in animals and continued for many hours. Note that at the beginning of the infusion calcium ion concentrations begin to rising and plateau in about 4 hours. However, phosphate levels decreased more rapidly than increased calcium and reached their lowest level within 1 or 2 hours. The increase in calcium concentration is mainly due to 2 effects: (1) the effect of PTH to increase calcium and phosphate reabsorption from the bone, and (2) the rapid effect of PTH to reduce the renal excretion of calcium. The decrease in phosphate concentration is caused by the strong effect of PTH by increasing renal phosphate excretion, which is usually large enough to exceed the amount of phosphate reabsorbed from the bone.
Figure. Estimation of changes in calcium and phosphate concentrations during the first 5 h of a moderate parathyroid hormone infusion
The hormone PTH mobilizes calcium and phosphate from the bones
PTH has two mechanisms for mobilizing calcium and phosphate from bone. One is a rapid mechanism that usually begins in minutes and gradually increases over several hours. This mechanism results from the activation of ready-made bone cells (primarily bone cells (osteocytes)) to promote the release of calcium and phosphate. The second mechanism is much slower, requiring a few days or even weeks to peak, it results from an increase in osteoclasts, which increases bone resorption, not merely the dissolution of bone. release calcium and phosphate salts from the bone.
Mechanism of rapid release of calcium and phosphate from bone resorption
When large amounts of PTH are injected, blood calcium ion levels begin to rise within minutes, very quickly before new bone cells are formed. Histological and physiological studies have shown that PTH removes bone salts from two areas in bone: (1) from the bone matrix in the adjacent region of osteoblasts located in bone and (2) in the vicinity of osteoblasts along the bone surface.
It is not thought that either osteoblasts or osteoblasts (osteocytes) are responsible for mobilizing bone salts, because both cell types are derived from pre-osteoblasts (or stem cells). of bone tissue) and are commonly known for their bone deposition and calcification. However, studies have shown that osteoclasts and osteoblasts form an interconnected system that spans the entire bone, across all bone surfaces, except for small contiguous surfaces. with osteoclasts. Indeed, over time, this system extends from osteocyte to osteocyte throughout the bone and connects to both surface and osteoblastic osteoblasts. This extensive system is called the osteolytic membrane system, and it is thought to provide a membrane that separates bone from the extracellular fluid.
Between the bone cell membrane and the bone, there is a small amount of bone fluid. Experiments show that the osteocyte membrane pumps calcium ions from the bone fluid into the extracellular fluid, producing a concentration of calcium ions in the fluid that is only one-third that of the extracellular fluid. When these pumps are overactive, the bone fluid calcium concentration falls even lower, and calcium and phosphate salts are then released from the bone. This mechanism is called osteolysis, and it happens without the phenomenon. destruction (reabsorption) of bone matrix. When the pump is inactivated, bone fluid calcium concentrations are elevated and high phosphate salts are deposited back into the matrix.
When will PTH join here? First, the cell membranes of both osteoblasts and osteoclasts have PTH-binding receptor proteins.
PTH can strongly activate calcium pumps, thereby causing rapid removal of calcium phosphate salts from bone amorphous crystals located near the cells. PTH stimulates this pump by increasing the calcium permeability of the bone fluid adjacent to the osteocyte membrane, thereby allowing calcium ions to diffuse across this membrane from the bone fluid. Then the calcium pump on the other side of the cell membrane transports the rest of the calcium ions into the extracellular fluid.
Slow mechanism of bone resorption and calcium phosphate release, activation of osteoclasts
A known and more well-documented mechanism of PTH is the activation of osteoclasts. However, osteoclasts themselves do not have membrane receptor proteins for PTH. Instead, activated osteoclasts and osteoblasts send secondary "signals" to the osteoclasts. As discussed in the previous chapter, a primary type of secondary signalling is RANKL, which activates receptors on osteoclasts and differentiates them into mature osteoclasts that persist and destroy bone for several weeks to a month.
Activation of the osteoclast system occurs in two phases: (1) immediate activation of already formed osteoclasts and (2) formation of new osteoclasts.
After several days when PTH levels increase, osteoclast systems are proliferated, which can continue for many months under the strong influence of large amounts of PTH.
After several months of excessive PTH levels, osteoclastic bone destruction can weaken the bone and secondarily stimulate osteoclasts involved in the repair of the condition. Therefore, the ultimate effect is actually enhancing the activity of osteoblasts and osteoclasts.
However, even in the end effect, bone resorption is always more than bone deposition under the effect of PTH excess.
Bone contains a large amount of calcium relative to the total amount of calcium in the extracellular fluid (about 1000 times more) that even when PTH increases the calcium concentration in the extracellular fluid, no immediate change cannot be observed. ie on the bone. Prolonged hypersecretion of PTH- over many months and years leads to bone resorption in all bones, even large internal cavities filled with large multinucleated osteoclasts.
The hormone PTH reduces calcium excretion and increases urinary phosphate excretion
Control of PTH causes rapid loss of phosphate in the urine by reducing the reabsorption of phosphate ions in the proximal tubule. PTH also increases calcium tubular reabsorption of calcium while it decreases phosphate reabsorption. Furthermore, it increases the reabsorption of magnesium ions and hydrogen ions and decreases the reabsorption of sodium, potassium, and amino acids by the same mechanism as phosphate. Increased reabsorption occurs mainly in the distal tubules, collecting ducts and possibly in the loop of Henle to a lesser extent without the effect of PTH on the kidney to increase calcium reabsorption. Continuous loss in urine can lead to depletion of extracellular fluid and bone calcium sources.
Parathyroid hormone increases intestinal absorption of calcium and phosphate
At this point, we know that PTH enhances the absorption of calcium and phosphate from the intestine by increasing the synthesis of 1,25-dihydroxycholecalciferol from vitamin D in the kidney.
Cyclic Adenosine Monophosphate (Cyclic Adenosine Monophosphate) mediates the action of PTH
A large part of the effect of PTH on target organs is mediated by the second messenger mcyclic adenosine monophosphate (cAMP). Within minutes of PTH, cAMP levels increase in osteoblasts, osteoclasts, and other target cells. cAMP is responsible for the secretion of enzymes and acids involved in bone resorption, as well as the formation of 1,25-dihydroxycholecalciferol in the kidney. The direct mechanism of action of PTH is independent, possibly not via a second messenger.