Vitamin C

Volume III

Alan B. Clemetson

• Publisher: CRC Press
• Year: 2018
• Print ISBN: 9781315898483
• eBook ISBN: 9781351094481
• Edition: 1
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

The factors affecting blood vitamin C levels are described in detail in this series. Many factors such as aging, smoking, infection, trauma, surgery, hemolysis, hormone administration, heavy metals, pregnancy, alcohol, ionizing radiation and several medicines have been found to cause a disturbance of ascorbic acid metabolism and to reduce blood vitamin C levels. Indeed, abnormalities of ascorbic acid metabolism, due to factors such as smoking, occur much more frequently than does dietary vitamin C deficiency today.It is now known that low blood vitamin C levels are associated with histaminemia (high blood histamine levels), and also that ascorbate-responsive histaminemia is common in apparently healthy people. High blood histamine levels are believed to cause small hemorrhages within the inner walls of the blood vessels and these may lead to the deposition of cholesterol, as an aberrant form of wound healing. Ascorbic acid not only reduces blood histamine levels, but also aids the conversion of cholesterol to bile acids in the liver. The clinical pathological and chemical changes observed in ascorbic acid deficiency are discussed in detail. Several diseases and disorders associated with low blood vitamin C levels are also described. Possible toxic effects resulting from the oxidation of ascorbic acid are noted, and reasons for the use of D-catechin or other chelating fiber to prevent or minimize the release of ascorbate-free radical are detailed. An excellent reference for physicians, nutritionists and other scientists

Clinical Conditions Associated with Disorders of Ascorbic Acid Metabolism

Chapter 10

RHEUMATIC FEVER

I. EXPERIMENTAL PRODUCTION IN THE GUINEA PIG

The role of ascorbic acid in rheumatic fever has been the subject of much dispute since Rinehart and Mettier (1933), working at the University of California Medical Center in San Francisco, discovered that they could produce degenerative and proliferative lesions of the heart valves, the endocardium, and the myocardium in guinea pigs, which resemble those of human rheumatic carditis, by infecting vitamin C-deficient guinea pigs with beta hemolytic streptococci. This led them to conduct a series of experiments to determine the effects upon the heart valves and muscle of acute and chronic scurvy, of scurvy combined with infection, and of infection alone (Rinehart and Mettier, 1934).

A. Controls

Eight control guinea pigs were maintained on a basal vitamin C-deficient diet, supplemented with adequate amounts of orange juice. None of these animals showed any gross pathology. Macroscopically the heart valves of these control animals had a smooth, glistening surface and microscopically they had a compact, rich, fibrous stroma consisting of abundant tightly packed, wavy, uninterrupted collagen fibrils. All but one had a normal endocardium. In one animal a very mild proliferation of the endocardial layer was seen overlying the insertion of one of the chordae tendineae.

B. Infection

A total of 20 animals receiving the basal ration supplemented with orange juice were infected with beta hemolytic streptococci or with B. aertrycke by intracutaneous injection of a pure culture of the organisms into the skin of the thigh below the groin. One animal showed a necrotizing mitral valvulitis, a second showed an accumulation of a few polymorphonuclear leukocytes near the base of the tricuspid valve. Another developed uremia due to obstruction of the urinary tract and was found to have mild atypical mitral valvulitis. No lesions were seen in the myocardium.

C. Scurvy

Eight out of nine adequately examined hearts from guinea pigs with uncomplicated scurvy revealed thinning, fragmentation, and disorganization of the regular axial arrangement of the collagen fibers of the heart valves. A loss of the normal wavy contours and, at times, a hyaline degenerative change of the fiber substance was observed. In two animals there was also noted a mild but definitely proliferative reaction of the endothelial and subendothelial cells.

D. Combined Scurvy and Infection

Of 31 animals subjected to one or another combination of scurvy and infection with beta hemolytic streptococci or B. aertrycke, reasonably adequate examination of the heart was secured in 24 instances. All of these showed recognizable degenerative and/or proliferative changes in one or more of the heart valves. The mitral and aortic valves were most commonly and most severely involved, showing a mucoid degenerative appearance of the stroma and a distinct nodular proliferative reaction at the lines of closure. Multinucleate cells were seen in some of the proliferative verrucous lesions. Elsewhere homogeneous eosinophilic hyaline material, paler mucoid material, and proliferating cells made up the lesion. Mostly the proliferation was subendothelial, but in places the surface layer was eroded. The valvular pathology produced in the guinea pig by this combination of scurvy and infection is virtually identical to that classically described in rheumatic fever, where the verrucous lesions are formed by an edematous, mucoid, hyaline, fibrinoid swelling of the subendothelial layer, which pushes the endothelium before it into a warty nodule.

Judging their own work in a critical manner, Rinehart and Mettier stated that they could not fairly claim to have reproduced Aschoff nodes in the heart muscle. However, they pointed out that proliferative lesions were seen in the myocardium and beneath the mural endocardium in animals subjected to a combination of scurvy and infection, which bear a strong resemblance to and are believed to be fundamentally similar to reactions seen in rheumatic fever.

Although rheumatic fever develops in susceptible individuals following an upper respiratory infection due to group A beta hemolytic streptococci, Rinehart and Mettier found that beta hemolytic streptococci of group C and other natural guinea pig pathogens were capable of causing these myocardial and valvular lesions when combined with vitamin C deficiency in the guinea pig.

Rinehart et al. (1934), studying the knee joints of guinea pigs, demonstrated that chronic scurvy with infection or, to a lesser extent, chronic scurvy alone produces an arthropathy which has striking pathological similarities to rheumatic fever and also to rheumatoid arthritis. They found a subcutaneous nodule in one guinea pig, similar to those seen in rheumatic fever and drew attention to the widespread evidence of fibrinoid degeneration, which has been considered the fundamental lesion of rheumatic fever. They observed degenerative changes in the skeletal muscle, focal necrosis in the liver, fibrosis of the Malpighian bodies of the spleen, erythrophagocytosis in the lymph nodes, and focal lymphocytic accumulation in the kidneys, all of which are frequently seen in rheumatic fever.

E. Scurvy and Exotoxin

Stimson et al. (1934), who had been unable to reproduce rheumatic fever in other animals, soon confirmed the experimental work of Rinehart and Mettier by infecting vitamin C-deficient guinea pigs. Moreover, they reported that it was possible to produce degenerative and proliferative myocardial lesions resembling Aschoff nodes by injecting streptococcal exotoxin into scorbutic guinea pigs without the introduction of living organisms. Schultz (1936a) repeated the experiments of Rinehart and Mettier, with only partial confirmation. He found that chronic scurvy and chronic infection, acting synergistically, may induce nonpurulent carditis in guinea pigs. Valvulitis with fibrinoid degeneration and an intense proliferative reaction constituted the most prominent lesion. However, he concluded that the changes only slightly resembled those seen in rheumatic fever.

Taylor (1937) also observed valvulitis, myocarditis, and occasionally pericarditis, but no gross valvular vegetations, in scorbutic guinea pigs and observed Gram-positive organisms where none had been injected. The lesions were most common in the mitral valve, the atrioventricular junction, the perivascular areas in the myocardium, and the papillary muscles. Once the heart lesions have developed, he found that curing the scurvy would not cure the lesions, though it did prevent the development of congestive heart failure. He stated that this scorbutic carditis is not specific for hemolytic streptococci and concluded, “If scorbutic carditis is related to rheumatic fever, then ascorbic acid will be of greatest use in prevention and not treatment.” This seems to be true.

McBroom et al. (1937) found myocardial and valvular lesions, both degenerative and proliferative, to be equally evident in scorbutic guinea pig hearts, with or without infection. They therefore concluded that these lesions represented scorbutic carditis and had nothing to do with rheumatic carditis. If only they had known that hemolysis causes destruction of ascorbic acid (see Chapter 15, Volume I) they might have suspected (as does the present writer) that the beta hemolytic streptococcus can cause local hemolysis and thus local scurvy whenever it is active in a tissue with borderline ascorbic acid deficiency. That is what is so special about the beta hemolytic streptococcus in causing the human disease, and that explains why these special bacteria are not necessary when studying guinea pigs on an ascorbic aciddeficient diet. All are agreed that infection alone does not cause this carditis.

II. RHEUMATIC PURPURA

Rinehart (1937) suggested that a scorbutic state may be the basis of the hemorrhagic features commonly seen in the acute phases of rheumatic fever. As evidence that hemorrhagic manifestations are of frequent occurrence in rheumatic fever, he cited Poynton and Paine (1914) who described blood-stained synovial fluid in rheumatic fever, Coburn (1933) who stated that hemorrhagic lesions were widespread in all patients dying during marked activity of the rheumatic process, Chester and Schwartz (1934) who recorded the rather frequent occurrence of purpuric skin lesions on the legs and arms in rheumatic fever and considered this to be evidence of recurrent activity of the disease, Holtz and Friedman (1934) who noted a hemorrhagic eruption in the mucosa of the mouth and throat in rheumatic patients, and Van der Sande (1935) who also recorded the occurrence of hemorrhagic manifestations.

Chester and Schwartz observed that no common medication had been administered to the 10 children with purpura among 21 with rheumatic fever under his care at the Montefiore Hospital in New York in 1931. He therefore concluded that the purpuric lesions were the result of the rheumatic state.

Coburn (1933) reported on 320 patients who died with rheumatic fever, who were observed by him during life, and who, in most instances, were examined post mortem. He stated that, “when it had been possible to study the tissues of patients during the first two weeks of a rheumatic attack, hemorrhagic lesions have been conspicuous.” Indeed, “in all the patients dying during marked activity of the rheumatic process, hemorrhagic lesions were found to be widespread …” Hemorrhagic lesions in the skin, brain, kidneys, and thoracic and abdominal viscera suggested to Coburn an alteration in the vascular permeability with diapedesis and damage to the mesodermal tissues. He concluded that, “the anatomic observations on these patients with acute rheumatism indicate that, in addition to the well recognized swelling of endothelium and fragmentation of collagen, diffuse hemorrhagic changes are characteristic of activity of the rheumatic process.” Coburn observed that a marked alteration of the permeability of the walls of the blood vessels is suggested by the occurrence of epistaxis, purpuric erythemas, and hemorrhages from the urinary tract, the respiratory tract, and the intestinal tract in acute rheumatism. He stated, “The relative frequency of these hemorrhages is illustrated by the incidence of 96 nose-bleeds among 15 of 30 convalescent rheumatic children.”...

Table of contents

• Cover
• Title Page
• Copyright Page
• Table of Contents
• CHEMICAL CHANGES ASSOCIATED WITH VITAMIN C DEFICIENCY
• CLINICAL CONDITIONS ASSOCIATED WITH DISORDERS OF ASCORBIC ACID METABOLISM
• INDEX