Scurvy, ascorbic acid deficiency

Deficiency may occur in infants if no fruits or vegetables are added to their milk formulas. In alcoholics, and in elderly subjects who consume inadequate diets vitamin C deficiencies are frequent. Severe ascorbic acid deficiency is characterized by the syndrome known as scurvy. Its manifestations are generally based on a loss of collagen. Symptoms include hemorrhages, loosening of teeth. In children cellular changes in the long bones occur. 

Hydroxyproline and hydroxylysine result from the hydroxylation by specific hydroxylases of proline and lysine residues after their incorporation into a-chains. The enzymes require ascorbic acid as a cofactor. [Note An ascorbic acid deficiency results in scurvy.] The hydroxyl group of the hydroxylysine residues of collagen may be enzymatically glycosy lated (most commonly, glucose and galactose are added sequentially to the triple helix). 

The vitamin is indicated fur the treatment and prevention of ascorbic acid deficiency. Although scurvy occurs infrequently. it is. seen in the elderly, infants, alcoholic.s. and drug users. Ascorbic acid (but not the sodium. salt) frequently is administered with methcnaminc to improve the effectiveness of this antibacterial agent. Because a.scorbic acid increases imn chelation by deferoxamine, it is u.scd in the treatment of chronic iron toxicity. It is also a useful adjunct in the ireatment of methemoglobinemia. 

Ascorbic Acid Deficiency. Scurvy is the classical disease associated with ascorbate deficiency. It is a disease of the connective tissue and probably is caused by inadequate crosslinking attributed to a lack of hydroxy-lated proline and lysine. Many consider scurvy to be an advanced stage of ascorbate deficiency. Chronic deficiencies may also (l)in-crease risk for malignancies, as evidenced by oxidized DNA markers and increased concentrations of reactive oxygen species (2) decreased immune function, as evidenced by less vitamin in neutrophils and lymphocytes (3) cardiovascular disease caused by the inflammatory response on the blood vessel walls and (4) cataract formation caused by decreased concentrations of ascorbate in the ocular tissues. 

Ascorbic acid, a water-soluble vitamin (1(X) to 250 mg p.o. daily), is indicated in the treatment of frank and subclinical scurvy in extensive bums, delayed fracture or wound healing, postoperative wound healing severe febrile or chronic disease states and in prevention of ascorbic acid deficiency in those with poor nutritional habits or increased requirements. In addition, ascorbic acid has been used for potentiation of meth-enamine in urine acidification and as an adjunctive therapy in the treatment of idiopathic methemoglobinemia. 

Even the most ardent supporters of the belief that ascorbic acid is concerned in the synthesis of cortical hormones would probably hesitate today to suggest that this is the most important function of ascorbic acid in the body, still less its only function there are too many obvious reasons for thinking otherwise. The first is that human patients whose adrenals have been destroyed suffer from Addison s disease but do not develop scurvy. They continue to show normal levels of ascorbic acid in the blood (Jenovese el al., 1940), and there is no evidence that their collagen is affected. Though there were some initial reports (e.g., Wilkinson and Ashford, 1936) that patients with Addison s disease suffered from ascorbic acid deficiency, this idea has faded from the recent literature. Secondly, the amount of ascorbic acid in the adrenal cortices is less than 1 per cent of the total amount in the human body (Section III, 2) it would be against what we know of the economy of the body to think that all the rest of this active metabolite was simply hanging around in the other tissues, waiting for the adrenals to find a use for it. 

Because wounds fail to heal in scurvy, ascorbic acid has been administered routinely to surgical cases, usually in the absence of any evidence that the tissues of the patients were depleted of the vitamin. Yet the observations of Crandon et al. (1940) make it clear that it requires a really severe dietary deficiency of the vitamin to produce any impmrment in the healing of wounds. If any measurable amount of ascorbic acid is present in the plasma, it is most unlikely that doses of ascorbic acid wUl make any difference to the rate of healing or the strength of the scar. The present writer disagrees, in this matter only, with the views of Hunt (1941). 

The most prominent symptom of ascorbic acid deficiency is scurvy, which is a complex of disorders that result mainly from the decreased ability to synthesize collagen. This lack of collagen synthesis leads to an elevated fragility of the capillar blood system and consequently to bleeding of skin, mucous membranes, organs,... 

As mentioned above, ascorbic acid acts as a neuroprotective agent in in vitro models of scurvy. Therefore, it is a surprise that no symptoms of brain cell damage have been reported in conditions involving severe systemic ascorbic acid deficiency. This may be explained by the fact that the scorbutic state cannot be produced in the intact animal brain because of the brain s homeostatic mechanisms such as the highly specific ascorbic acid transport system in the choroid plexus (Spector, 1989) and the inability of ascorbic acid to cross the blood-brain barrier, which effectively isolate the ascorbic acid content of the intact brain from the rest of the body s ascorbic acid pool. The active transport of ascorbic acid from blood to cerebrospinal fluid (Spector and Eells, 1984), together with cellular uptake mechanisms, represents the base for homeostasis of brain ascorbic acid concentrations (see also Section 2). This is in agreement with the report about normal ascorbic acid concentrations in brains from patients with Parkinson s disease (Riederer et al., 1989), in which free radical damages are postulated to be involved (see below). 

Scurvy affects the structure of collagen. However, it is due to a deficiency of ascorbic acid (Chapter 45) and is not a genetic disease. Its major signs are bleeding... 

Prevention and treatment of scurvy. Parenteral administration is desirable in an acute deficiency or when absorption of oral ascorbic acid is uncertain. 

A deficiency of ascorbic acid results in scurvy, a disease character ized by sore, spongy gums, loose teeth, fragile blood vessels, swollen joints, and anemia (Figure 28.9). Many of the deficiency symptoms can be explained by a deficiency in the hydroxylation of collagen, resulting in defective connective tissue. 

Vitamin C (ascorbic acid) functions as an antioxidant and as a cofactor for hydroxyla tion reactions in procollagen. A deficiency of vitamin C results in scurvy, a disease char acterized by sore, spongy gums, loose teeth, and poor wound healing. There is no known toxicity for this vitamin. 

Ascorbic acid is synthesized by plants and many ani- mals but not by primates or guinea pigs. In scurvy, the disease associated with a severe deficiency of ascorbic acid, connective tissues throughout the body deteriorate. Weakening of the capillary walls results in hemorrhages, wounds heal poorly, and lesions occur in the bones. 

One-third of the amino acid residues in collagen are Gly, while another quarter are Pro. The hydroxylated amino acids 4-hydroxyproline (Hyp) and 5-hydroxylysine (Hyl) are formed post-translationally by the action of proline hydroxylase and lysine hydroxylase. These Fe2+-containing enzymes require ascorbic acid (vitamin C) for activity. In the vitamin C deficiency disease scurvy, collagen does not form correctly due to the inability to hydroxylate Pro and Lys. Hyl residues are often post-translationally modified with carbohydrate. 

Ascorbic acid is a vitamin in primates. In most other animals, it can be synthesized by a branch of the glucoronic acid pathway (Chapter 18). It is apparently not changed into any coenzyme in the human being and participates as a vitamin in a reducing capacity in several biochemical reactions. These include the post-translational hydroxylation of proline in collagen biosynthesis (Chapter 8) and in tyrosine metabolism (Chapter 20). Ascorbic acid is oxidized to dehydroascorbic acid, a diketo derivative of ascorbate. Scurvy is a deficiency disease caused by a shortage of dietary ascorbic acid. In children, this results in defective bone formation in adults, extensive bleeding occurs in a number of locations. Scurvy is to be suspected if serum ascorbic acid levels fall below 1 jug/mL. 

Vitamin C, or ascorbic acid, is important in the formation of collagen, a protein that holds together the connective tissues of skin, muscle, and blood vessels. Vitamin C is obtained from eating citrus fruits. A deficiency of vitamin C causes scurvy, a common disease of sailors in the 1600s who had no access to fresh fruits on long voyages. In Chapter 3, we learn why some vitamins like vitamin A can be stored in the fat cells in the body, whereas others like vitamin C are excreted in urine. 

Ascorbic acid. Vitamin C, is a water-soluble vitamin of great im-portance. A deficiency of vitamin C in the diet leads to scurvy, a disease characterized by loss of weight, general weakness, hemorrhagic condition of the gums and skin, loosening of the teeth, and other symp-toms. Sound tooth development seems to depend upon a satisfactory supply of this vitamin, and a deficiency is thought to cause a tendency to incidence of a number of diseases. 

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