Anemia in scurvy

Anemia is frequendy associated with scurvy and may be either macrocytic, indicative of folate deficiency or hypochromic, indicadve of iron deficiency. 

Folate deficiency may be epiphenomentd, because the major dieteuy sources of folate Me the same as those of tiscorbate. However, some patients with clear megalobltistic anemia respond to the administration of vittunln C tdone, suggesting that there may be a role of ascorbate in the maintentmce of 

Iron deficiency in scurvy may well he secondtuy to reduced absorption of inorganic iron tmd impaired mobilization of tissue iron reserves (Section 3.4.5). At the same time, the hemorrhages of advtmced scurvy can cause a considerable loss of blood. 

There is also evidence that erythrocytes have a shorter htilf-life than normal in scurvy, possibly as a result of peroxidative dtimage to membrane lipids from impairment of the reduction of tocopheroxyl radictil by ascorbate (Section 13.3.7.1). 

Iron deficiency in scurvy may well be secondtuy to reduced absorption of inorganic iron and impaired mobilization of tissue iron reserves (Section 

At the same time, the hemorrhages of advtmced scurvy can cause a considerable loss of blood. 

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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. 

Most signs of scurvy can be related to inadequate or abnormal collagen synthesis. Ascorbate enhances prolyl and lysyl hydroxylase activities (Chapter 25). Collagen formed in scorbutic patents is low in hydroxyproline and poorly cross-linked, resulting in skin lesions, bone fractures, and rupture of capillaries and other blood vessels. The absolute amount of collagen made in scorbutic animals may also decrease independently of the hydroxylation defect. The anemia of scurvy may result from a defect in iron absorption or folate metabolism. 

May et al. (1950a,b, 1951) originally considered that ascorbic acid was necessary for the conversion of pteroylglutamic acid to citrovorum factor. In monkeys fed on diets deficient both in ascorbic acid and folic acid, megaloblastic anemia developed. This could be relieved by ascorbic acid, by folic acid in large doses, or by small doses of citrovorum factor. Later May et al. (1953) reported that ascorbic acid was not required for the conversion of folic acid to citrovorum factor. The severe deficiency of folic acid compounds occurring in scorbutic monkeys was probably due to nonspecific factors operating in scurvy. 

Metabolism of folic acid (folacin)—Vitamin C is required for the conversion of the inactive form of the vitamin, folic acid (folacin), to its active form, folinic acid. When there is an insufficiency of vitamin C in the diet, the metabolism of folic acid (folacin) is impaired and the megaloblastic anemia that occurs in scurvy, and sometimes in infancy, may result... 

In addition to its role in preventing scurvy (see Human Biochemistry box Ascorbic Acid and Scurvy and also Chapter 6), ascorbic acid also plays important roles in the brain and nervous system. It also mobilizes iron in the body, prevents anemia, ameliorates allergic responses, and stimulates the immune system. 

Answer E. The patient has many signs of scurvy from a vitamin C deficiency. The diet, which contains no fruits or vegetables, provides little vitamin C, Prolyl hydroxylase requires vitamin C, and in the absence of hydroxylation, the collagen a-chains do not form stable, mature collagen. The anemia may be due to poor iron absorption in the absence of ascorbate. 

Diseases of people come in many flavors. There are infectious diseases (measles, mumps, influenza, AIDS,...), nutritional deficiency diseases (scurvy, beriberi, kwashiorkor,...), degenerative diseases (Alzheimer s disease, osteoporosis,...), cancer (of the lung, breast, prostate, liver,...), and single-gene inherited diseases or molecular diseases. In the last category, an important and instructive example is provided by sickle cell anemia. Let s consider this disease and begin to develop a sense of how we can understand it on the basis of what we now know about proteins. 

The richest sources of vitamin C are citrus fruits (e.g., lemon, oranges), tomatoes, potatoes, green chilies, and human milk. Severe deficiency causes scurvy and is prevalent in malnourished infants, children, adults, alcoholics, and drug addicts. Symptoms such as bleeding gums, deformed teeth, brittle bones, impaired wound healing, anemia, and growth retardation are observed. 

It is used in the treatment of scurvy, postoperative cases, and healing bedsores and chronic leg ulcers. Vitamin C increases the absorption of iron during anemia and is frequently combined with ferrous salts. It is used in urinary tract infections to acidify urine. Large doses of vitamin C have been tried to cure everything from the common cold to cancer, with not much success. The usefulness of vitamin C in asthma, cancer, atherosclerosis, psychologic symptoms, and fertility is doubtful. Ascorbic acid is well tolerated in large doses and may cause rebound scurvy on withdrawal. There is a possibility of forming urinary stones. 

Deficiency in vitamin C leads to the disease scurvy due to the role of the vitamin in the post-translational modification of collagens. Scurvy is characterized by easily bruised skin, muscle fatigue, soft swollen gums, decreased wound healing and hemorrhaging, osteoporosis, and anemia. Vitamin C is readily absorbed and so the primary cause of vitamin C deficiency is poor diet and/or an increased requirement. The primary physiological state leading to an ihcreased requirement for vitamin C is severe stress (or trauma). This is due to a rapid depletion in the adrenal stores of the vitamin. The reason for the decrease in adrenal vitamin C levels is unclear but may be due either to redistribution of the vitamin to areas that need it or an overall increased utilization. 

Some of the dreaded nutritional diseases of the past — such as scurvy, pellagra, and pernicious anemia — are discussed in this book. Such contemporary problems as infectious diarrhea, xerophthalmia, protein/energy malnutrition, and folate deficiency are discussed, as are diabetes and cardiovascular disease, two of the most sigf cant nutrition-related diseases. The last two conditions can be controlled in part by dietary intervention. 

Anemia has frequently, but not consistently, been reported in association with scurvy in clinical cases, both in adults and infants, and in experimental scurvy in guinea pigs and monkeys. The extensive literature has been cited (M18, L19, V2). The anemias were not constant in type or severity, although all were reheved when ascorbic acid was reintroduced to tbe diet. In contrast, no anemia or abnormality of the blood picture was ever seen in experimental human scurvy. The therapeutic effect of ascorbic acid on the anemia cannot be accepted as proof of its etiology, since associated deficiencies would also be made good with the return of normal appetite. It is well recognized that the clinical cases of scurvy usually have associated deficiencies. Often, there is iron deficiency in the milk-fed infants, and folic acid or vitamin B12 deficiency in the malnourished adult. ... 

Anemia is a common but inconstant feature of human scurvy. Mettier, Minot, and Townsend (1930), in reviewing the previous literature, concluded that in a large group of adult cases one may expect to find about one third with 2 to 3 million red blood corpuscles per mm., one third with 3 to 4 million, and the remaining third showing slight anemia or none. 

The question of vitamin supplementation obviously requires an affirmative answer when one considers therapy for overt, specific deficiency syndromes such as scurvy, rickets, beriberi, pellagra, megaloblastic anemia, ariboflavinosis, and convulsions due to pyridoxine deficiency. In some syndromes, biochemical evidence of deficiency occurring before overt symptoms is accepted as indication for general preventive supplementation. For example, the hydroxyphenyluria of premature infants and decreased serum phosphate and citrate, are taken as indications for early... 

Vitamin C deficiency has been linked indirectly to psychological and physiological deteriorations in the elderly. Seven out of 254 chronic geriatric patients with low leukocyte and serum vitamin C levels were found to be confused. These patients had some signs of scurvy, primarily multiple bruises and tibial tenderness with or without anemia. The confusion, as well as the other signs, clearly responded to ascorbate in four patients the other three died (Mitra, 1971). 

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