Pathophysiology of parathyroid hormone and vitamin D
Calcium and phosphate are not released from the bones, the bones remain mostly strong. When the parathyroid glands are suddenly removed, the blood calcium threshold falls and blood phosphate levels can double.
When the parathyroid glands do not secrete enough PTH, bone resorption is reduced and the osteoclasts are almost completely inactive. As a result, calcium release from the bones is reduced, causing calcium concentrations in body fluids to decrease.
However, because calcium and phosphate are not released from the bones, the bones remain mostly strong. When the parathyroid glands are suddenly removed, the blood calcium threshold falls from a normal value of about 9.4 mg/dl to 6-7 mg/dl within 2-3 days and blood phosphate levels may increase. double. When the calcium threshold is low, the usual symptoms of tetany appear. The muscle group that is sensitive to tetany is the larynx. This muscle spasm interferes with breathing, which is a common cause of death from tetany if not treated promptly.
Treat hypoparathyroidism with PTH and Vitamin D. PTH is rarely used to treat hypoparathyroidism.
However, hypoparathyroidism is not usually treated with PTH because the hormone is expensive, its effects most often last for a few hours, and because the body tends to develop antibodies against it. In all patients with hypoparathyroidism, maintenance of very large amounts of vitamin D, approximately 100,000 units per day, together with an intake of 1-2 grams of calcium, helps to keep calcium ion concentrations at an average level. Sometimes it is necessary to maintain 1,25-dihydroxycholecalciferol in place of inactive vitamin D because of its stronger and faster action. However, maintenance of 1,25-dihydroxycholecalciferol can also cause undesirable effects because it is sometimes difficult to prevent the overactivity of this form of vitamin D.
In primary hyperparathyroidism, the abnormality of the parathyroid glands produces disordered, over-secreted PTH. The cause of primary hyperparathyroidism is usually a tumour of one of the parathyroid glands; It occurs more often in women than in men or in children, mainly because pregnancy and lactation make the parathyroid glands stimulated, leading to tumour growth. Hyperparathyroidism enhances bone resorption activity, increasing the concentration of calcium ions in the extracellular fluid while usually decreasing the concentration of phosphate ions due to increased renal excretion.
Bone disease in hyperparathyroidism. Although new bone may be deposited rapidly enough to compensate for the increased bone resorption in individuals with mild hyperparathyroidism, in severe hyperparathyroidism the rapid bone resorption far exceeds the deposition, and can be completely destroyed. Indeed, fractures are often the cause of hospitalization for hyperparathyroidism. Bone radiographs show extensive calcium loss, sometimes, a large cystic area of bone densely packed with osteoclasts in the form of giant cell osteoclasts “tumours. Many pathological fractures can result from minor trauma, particularly where the tumour develops. The cystic bone disease of hyperparathyroidism is called osteitis fibrosa cystica.
The osteoblastic activity in the bone also greatly increases the futile efforts to create enough new bone to compensate for the old bone reabsorbed by bone resorption. When the osteoblasts are activated, they secrete large amounts of alkaline phosphatase. Therefore, one of the signs in the diagnosis of hyperparathyroidism is an elevated plasma alkaline phosphatase level.
Effect of hypercalcemia in hyperparathyroidism. Hyperparathyroidism can cause plasma calcium levels to rise to 12 to 15 mg/dl and even higher. The effects of such high calcium concentrations, as discussed previously, are decreased central and peripheral nervous system activity, decreased muscle activity, constipation, abdominal pain, peptic ulcer disease. colon, loss of appetite, and decreased cardiac rest during diastole.
Parathyroid toxicity and diffuse calcium deposition (Metastatic Calcification). In rare cases, when too much PTH is secreted, the body's fluid calcium threshold rapidly rises further. Even extracellular phosphate concentrations are often markedly increased rather than lowered, possibly because the kidneys are not able to excrete all of the rapidly reabsorbed phosphates from bone. Causes saturation of calcium and phosphate in body fluids, and thus calcium phosphate (CaHPO4) crystals begin to be deposited in the lungs, renal tubules, thyroid gland, and the acid-producing area of the gastric mucosa. and into arteries throughout the body. This diffuse deposition of calcium phosphate develops after only a few days.
Normally, the blood calcium level must be above the threshold of 17 mg/dl before the dangerous effects of thyrotoxicosis occur, but once it is accompanied by a concomitant elevation of phosphate, the patient may die later some days
Kidney stones and hyperparathyroidism. Most patients with mild hyperparathyroidism have few signs of bone disease and some disturbances due to the effects of calcium levels, but they are at increased risk of kidney stone formation. The reason for this risk is that calcium and phosphate absorbed from the intestines or mobilized from the bone in patients with hyperparathyroidism are excreted by the kidneys, causing an increased proportion of these substances in the urine. As a result, calcium phosphate crystals tend to be deposited in the kidneys, forming calcium phosphate stones. In addition, calcium oxalate stones also develop because of elevated calcium levels even though oxalate is not affected.
Since the solubility of most kidney stones is small in alkaline media, the propensity to form nephrolithiasis in alkaline urine is much greater than in acidic urine. For this reason, the acidotic diet and acidogenic drugs are often used to treat urolithiasis.
In secondary hyperparathyroidism, a high PTH threshold occurs in response to hypocalcemia rather than parathyroid abnormalities. In contrast, primary hyperparathyroidism is often associated with hypercalcemia. Secondary hyperparathyroidism can be caused by vitamin D deficiency or chronic kidney disease that causes the kidneys to fail to produce adequate amounts of the active form of vitamin D, 1,25-dihydroxycholecalciferol. A lack of vitamin D leads to osteoporosis. imbalance in bone mineralization), and the threshold of PTH that causes increased bone resorption will be discussed below
Rickets due to vitamin D deficiency
Rickets occurs mainly in children. It is caused by a deficiency of calcium and phosphate in the extracellular fluid, usually, due to a lack of vitamin D. If the child is exposed to adequate sunlight, 7-dehydrocholesterol in the skin will be activated by ultraviolet rays and form vitamin D3, which prevents rickets by increasing absorption of calcium and phosphate from the intestine, as previously clarified. Children who stay indoors for the winter often don't get enough vitamin D if they don't get it in their diet. Rickets often occurs especially during the spring months, as vitamin D formed during the previous summer is stored in the liver and used up during the winter months. In addition, calcium and phosphate mobilization from bone can obscure clinical signs of rickets during the first few months of vitamin D deficiency.
Decreased blood calcium and phosphate levels in rickets. The plasma calcium concentration in rickets is only slightly reduced, but the phosphate concentration is greatly reduced. This is because the parathyroid gland responds to a decrease in calcium levels by promoting bone resorption every time calcium levels begin to decline. However, no strong enough mechanism exists to prevent a decrease in phosphate levels, and overactive parathyroid glands increase urinary phosphate excretion.
Rickets weakens bones. In the case of persistent rickets, a significant increase in PTH secretion causes excessive bone resorption. This causes the bone to become progressively weaker and significantly increases the physical stress on the bone, increasing the activity of the osteoblasts. Osteoblasts have to remodel many bones due to calcium and phosphate ions deficiency. As a result, new bone is formed, not calcified, weak structure replaces the old bone that has been re-destroyed.
Tetany in rickets. In the early stages of rickets, tetany is almost never seen as the parathyroid gland continuously stimulates bone resorption and, thus, maintains near-normal concentrations of calcium in the extracellular fluid. However, when the bones eventually become depleted of calcium, calcium levels can drop rapidly. When the calcium threshold falls below 7 mg/dl, the usual signs of tetany begin and the child may die of respiratory tetanic spasms if calcium is not given intravenously, which will immediately relieve the tetany.
Treatment of rickets. Treatment of rickets requires adequate dietary calcium and phosphate but equally important, vitamin D supplementation. If vitamin D is not replenished, less calcium and phosphate will be absorbed from the intestines.
Osteomalacia - "Adult rickets." Adults rarely have a diet severely deficient in vitamin D or calcium because calcium requirements in adults are less than children need for bone development. However, severe vitamin D and calcium deficiencies occasionally occur as a result of steatorrhea (fat malabsorption), as fat-soluble vitamin D and calcium tend to form fat-soluble soaps. ; therefore, in lipodystrophy, both vitamin D and calcium are usually not absorbed. Under these conditions, adults may not absorb enough calcium and phosphate to make rickets possible. Adult rickets does not have tetany but often cause severe bone destruction Rickets in adults and children can be caused by kidney disease.
"Renal rickets" is a form of osteomalacia that results from prolonged kidney damage. This condition is mainly caused by the inability of the kidneys to make 1,25-dihydroxycholecalciferol, the active form of vitamin D. In patients with lost or damaged kidneys and those being treated with dialysis. , renal rickets is a serious problem.
One type of kidney disease that can lead to rickets and osteomalacia is congenital hypophosphatemia, due to decreased reabsorption of phosphate by the renal tubules. This type of rickets must be treated with phosphate compounds instead of calcium and vitamin D, and it is called vitamin D resistant rickets.
Osteoporosis - loss of bone base
Osteoporosis is the most common bone disease in adults, especially in old age. Unlike osteomalacia and rickets, osteoporosis results from loss of organic matrix rather than poor calcification of the bone. In people with osteoporosis, osteoclast activity in the bone is often less than normal, and thus the rate of osteoid deposition in the bone decreases. Sometimes, however, as in hyperparathyroidism, the cause of bone loss may be the overactivity of osteoclasts.
Common causes of osteoporosis are (1) lack of physical stress on the bones due to inactivity; (2) malnutrition to the insufficient basis for bone formation; (3) lack of vitamin C, which is required for the secretion of intercellular substances by all cells, including the production of the osteoid by osteoblasts; (4) lack of estrogen secretion after menopause because estrogen decreases the number and activity of osteoclasts; (5) old age, with a sharp decrease in growth hormone and other growth factors, in addition to which many synthetic proteins also decrease in effect with age, so bone matrix may not be sufficiently deposited. ; and (6) Cushing's syndrome: due to a large amount of glucocorticoid secretion that reduces protein deposition throughout the body and increases protein catabolism, has a specific effect on osteoblasts and reduces their activity.