D Deficiency

Vitamin D deficiency produces changes in bone growth which result in the condition known as rickets, the principal morphological characters of which, in the human, were first described by Pommer in 1885. A full review of the literature of human rickets is given by Hess.  

Mellanby in 1918 first described experimental rickets, using the puppy as his experimental animal, and shortly afterwards McCollum et aZ. described the same disease in the rat. It is of interest that Mellanby later found that confinement of his dogs predisposed them toward development of rickets. Also, it is of interest that the rat is normally resistant to vitamin D deficiency and for such a condition to express itself in this animal there must be concomitant unbalance of the calcium-phosphorus ratio or else a deficiency of these elements (Shohl and Wolbach ). McCollum and his co-workers showed that cod-liver oil added to the diet of vitamin D-deficient rats induced calcification to take place. 

Pommer, Untersuchungen uber Osteomalacie und Rachitis, F. C. W. Vogel, Leipzig, 1885. 

Rickets, Osteomalacea and Tetany, Lea Febiger, Philadelphia, 1929. 

Most animals appear to require vitamin D. Rickets has been induced in a large number of different species of animals. Most work on this subject, however, apart from Mellanby s, appears to have been carried out on rats. The characteristic epiphyseal changes which take place in vitamin D deficiency have been described by a variety of authors. 

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In this period, the empirical healing of certain diseases by foods was estabUshed. Examples (3) were the treatment of night blindness (vitamin A deficiency) with hver ia many cultures over centuries, of beriberi (vitamin deficiency) by use of unpoHshed rice by the Japanese navy, of scurvy (vitamin C deficiency) by citms fmits ia the British navy or piae needle extracts by North American natives, and pellagra (niacia deficiency) by a dietary shift away from corn-based foods ia many countries. Other, nondietary empirical treatments iavolved, eg, exposure of children ia northern latitudes to sunlight to cute tickets (vitamin D deficiency) (4). 

Calcium-binding protein is not found in the intestinal mucosa of vitamin D-deficient animals. It is synthesized only in response to the presence of a material with vitamin D activity. Thus, using antisemm specific to intestinal calcium-binding protein, a radioimmunodiffusion assay (98) conducted on ... 

Clinical stresses which interfere with vitamin metabohsm, can result in calcium deficiency leading to osteomalacia and osteoporosis (secondary vitamin D deficiency). These stresses include intestinal malabsorption (lack of bile salts) stomach bypass surgery obstmctive jaundice alcoholism Hver or kidney failure decreasing hydroxylation of vitamin to active forms inborn error of metabohsm and use of anticonverdiants that may lead to increased requirement. 

Vitamin D deficiency in animals may be caused by the fact that the vitamin is not available to the hvestock. Modem animal husbandry subjects animals to total confinement with htde or no exposure to sunlight. This mandates that they be given vitamin D-fortified diets. The vitamin is sensitive to oxidation, heat, light, and minerals, and significant losses may occur in the fortified feed unless the product is adequately protected. Mycotoxins in feeds also interfere with utilization of vitamin D in feeds (207—209). 

Disease States. Rickets is the most common disease associated with vitamin D deficiency. Many other disease states have been shown to be related to vitamin D. These can iavolve a lack of the vitamin, deficient synthesis of the metaboUtes from the vitamin, deficient control mechanisms, or defective organ receptors. The control of calcium and phosphoms is essential ia the maintenance of normal cellular biochemistry, eg, muscle contraction, nerve conduction, and enzyme function. The vitamin D metaboUtes also have a function ia cell proliferation. They iateract with other factors and receptors to regulate gene transcription. 

One of the triumphs of the science of nutrition is the careful investigation that linked childhood rickets with vitamin D deficiency. This work, which led to methods for treating the disease, is too familiar to need repetition. A direct consequence of these efforts was the elucidation of the pivotal role played by vitamin D in calcium metabolism, as well as the structural studies that revealed that this compound (102) is in fact a steroid derivative. The past... 

A common problem associated with the administration of the bile acid sequestrants is constipation. Constipation may be severe and may occasionally result in fecal impaction. Hemorrhoids may be aggravated. Additional adverse reactions include vitamin A and D deficiencies, bleeding tendencies (including gastrointestinal bleeding) caused by a depletion of vitamin K, nausea, abdominal pain, and distention. 

D Deficient Fluid Volume related to uncontrolled vomiting or diarrhea... 

D Deficient Fluid Volume related to inadequate fluid intake, need to inotease dose of drug, failure to recognize symptoms of dehydration (diabetes insipidus)... 

In the vitamin D deficiency disease rickets, the bones of children are undermineralized as a result of poor absorption of calcium. Similar problems occur in adolescents who are deficient during their growth spurt. Osteomalacia in adults results from demineralization of bone in women who have little exposure to sunlight, often after several pregnancies. Although vitamin D is essential for prevention and treatment of osteomalacia in the elderly, there is little evidence that it is beneficial in treating osteoporosis. 

Vitamin A (retinol), present in carnivorous diets, and the provitamin (P-carotene), found in plants, form retinaldehyde, utilized in vision, and retinoic acid, which acts in the control of gene expression. Vitamin D is a steroid prohormone yielding the active hormone derivative calcitriol, which regulates calcium and phosphate metaboUsm. Vitamin D deficiency leads to rickets and osteomalacia. 

The methods now used to measure 25-OH-D are competitive protein-ligand binding assays that use either serum globulin (diluted rat serum) (27)28) or a vitamin D-deficient rat kidney... 

The basic clinical tool used at the present time Is the competitive ligand binding assay for 25-OH-D. Although concentrations are low In the serum of patients with osteomalacia and v . tamln D deficiency rickets, we have recently noted the Interesting paradox that levels can be only 1/2 normal In the face of oyert bone disease (32). This had led us to propose that substrate levels of 25-OH-D3 available to the hydroxylase In kidney which Is responsible for the conversion of 25-OH-D3 to the tissue active metabolite, l,25(OH)2D3, may be rate limiting for this enzyme. 

Causes of hypocalcemia include hypoparathyroidism, hypomagnesemia, alcoholism, hyperphosphatemia, blood product infusion (due to chelation by the citrate buffers), chronic renal failure, vitamin D deficiency, acute pancreatitis, alkalosis, and hypoalbuminemia. Medications that cause hypocalcemia include phosphate replacement products, loop diuretics, phenytoin (Dilantin, available as generic), pheno-barbital (available as generic), corticosteroids, aminoglycoside antibiotics, and acetazolamide (available as generic).34,39,42... 

For acute symptomatic hypocalcemia, 200 to 300 mg of elemental calcium is administered IV and repeated until symptoms are fully controlled. This is achieved by infusing 1 g of calcium chloride or 2 to 3 grams of calcium at a rate no faster than 30 to 60 mg of elemental calcium per minute. More rapid administration is associated with hypotension, bradycardia, or cardiac asystole. Total calcium concentration is commonly monitored in critically ill patients. Under normal circumstances, about half of calcium is loosely bound to serum proteins while the other half is free. Total calcium concentration measures bound and free calcium. Ionized calcium measures free calcium only. Under usual circumstances, a normal calcium level implies a normal free ionized calcium level. Ionized calcium should be obtained in patients with comorbid conditions that would lead to inconsistency between total calcium and free serum calcium (abnormal albumin, protein, or immunoglobulin concentrations). For chronic asymptomatic hypocalcemia, oral calcium supplements are given at doses of 2 to 4 g/day of elemental calcium. Many patients with calcium deficiency have concurrent vitamin D deficiency that must also be corrected in order to restore calcium homeostasis.2,37,38... 

Some osteoporosis risk factors (see Table 53-1) are non-modifiable, including family history, age, ethnicity, sex, and concomitant disease states. However, certain risk factors for bone loss may be minimized or prevented by early intervention, including smoking, low calcium intake, poor nutrition, inactivity, heavy alcohol use, and vitamin D deficiency. 

For example, elderly patients living in musing homes will not be able to meet vitamin D requirements and will need supplementation. Vitamin D deficiency is common in elderly patients owing to decreased exposure to sunlight and subsequent decreased vitamin D synthesis in the skin, decreased gastrointestinal absorption of vitamin D, and reduction in vitamin D3 synthesis. Individuals living in northern climates also have decreased exposure to sunlight and are less likely to achieve vitamin D requirements. 

Vitamin D toxicity has been suggested as a cause of metabolic bone disease. However, vitamin D deficiency results in bone loss, and data on vitamin D excess and metabolic bone disease remain controversial. 

Renal osteodystrophy Altered bone turnover that results from sustained metabolic conditions that occur in chronic kidney disease, including secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, and vitamin D deficiency. 

Secondary hyperparathyroidism Increased secretion of parathyroid hormone from the parathyroid glands caused by hyperphosphatemia, hypocalcemia, and vitamin D deficiency that result from decreased kidney function. It can lead to bone disease (renal osteodystrophy). 

L The answer is e. (Kalzang, pp 744, 748J Vitamin is hydroxylated to 2.5-0ITDj (calcifediol). Calcifediol is then hydroxylated in the kidney to the most active form of vitamin D, which is 1,25-dihydroxyvitamin D (cal-citriol). Calcitriol has a rapid onset of action and a short half-life. The administration of calcitriol causes the elevation of serum Ca levels by enhancing the intestinal absorption of Ca. Calcitriol is indicated in vitamin D deficiency,... 

Age-related osteoporosis occurs mainly because of hormone, calcium, and vitamin D deficiencies leading to accelerated bone turnover and reduced osteoblast formation. 

Vitamin D deficiency results from insufficient intake, decreased sun exposure, decreased skin production, decreased fiver and renal metabolism, and winter residence in northern climates. 

D2 (ergocalciferol) Forvitamin D deficiency, 50,000 units once weekly or l,25(OH)2 vitamin D, other... 

Common but usually transient side effects are lethargy, incoordination, blurred vision, higher cortical dysfunction, and drowsiness. At concentrations greater than 50 mcg/mL, phenytoin can exacerbate seizures. Chronic side effects include gingival hyperplasia, impaired cognition, hirsutism, vitamin D deficiency, osteomalacia, folic acid deficiency, carbohydrate intolerance, hypothyroidism, and peripheral neuropathy. 

Hypocalcemia results from altered effects of parathyroid hormone and vitamin D on the bone, gut, and kidney. The primary causes are postoperative hypoparathyroidism and vitamin D deficiency. 

Oral calcium supplementation (e.g., 1 to 3 g/day of elemental calcium) is indicated for chronic hypocalcemia due to hypoparathyroidism and vitamin D deficiency. If serum calcium does not normalize, a vitamin D preparation should be added. 

The nutritional experiments with carotene and fish oils led to the conclusion that a second fat-soluble compound was essential for normal rat growth. Rickets, the condition caused by vitamin D deficiency, is a disease afflicting children where, because of impaired calcification, bone formation is disturbed and the bones become bowed and otherwise deformed. In adults, especially multiparous women, vitamin D deficiency produced osteomalacia—demineralization of bone, leading to tenderness over the bones, pain, and muscle weakness. Rickets was particularly prevalent in slum areas. Glasgow, Vienna, and Lahore were notorious for the high incidence of the disease. 

The two hydroxylase enzymes can also utilize the plant-derived steroid, ergocalci-ferol, (vitamin D2) as a substrate. The final product is biologically active and so food manufacturers often fortify their products with ergocalciferol to prevent the occurrence of vitamin D deficiency and consequent rickets in childhood or osteomalacia in adults. 

Vitamin D deficiency may also occur through inadequate dietary intake, gut (poor absorption), renal disease (1-hydroxylase deficiency or failure to reclaim calcium from the glomerular filtrate), or liver disease (25-hydroxylase deficiency). The slightly low haemoglobin concentration and pale stained (hypochromic) red cells suggested a coincident mild iron deficiency. 

Vitamin D deficiency after epiphyseal fusion causes osteomalacia, which produces less deformity than rickets. Osteomalacia may present as bone pain and muscle weakness. 

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