Prof. Ulysses Fagundes Neto

Esta é a transcrição completa da palestra, por mim proferida a convite do professor Fima Lifshitz, chefe do Serviço de Pediatric Research do North Shore University Hospital afiliado da Cornell University Medical College, como saudação da minha chegada para a realização do Pos-Doutorado em 1977. It is well known that 2/3 of the children living in the world are hungry and suffer some degree of malnutrition. Diarrhea is the major cause of death in infancy in the underdeveloped countries and almost of the children that died due to diarrheal disease had been malnourished. Malnutrition and diarrhea are a binomial factor the main component of a vicious cycle that is extremely hard to be broken, being by this own reason the responsible cause of the high rates of mortality observed in these children. While for you (Americans) and for all the physicians who work in the so-called developed countries malnutrition is almost always secondary to diseases, such us malabsorption syndromes (Cystic fibrosis, Celiac disease etc.), for me and for all the physicians who work in the underdeveloped countries malnutrition is almost always a consequence of a socioeconomic problem. Overcrowding and wretched conditions where promiscuity, contaminated environment, lack of water and sanitary supply, associated to poor personal hygiene, with deficient formula intake, these are the basic determinants of an unsteady state that can be tipped over, at any moment, to a state of overt malnutrition.

Vista aérea de uma fração da Favela Cidade Leonor.

Registros fotográficos do Córrego da Água Espraiada evidenciando barracos construídos em suas margens.

However, at the time that we are involved with a considerable number of malnourished children due to socioeconomic problems, we must be alerted to correctly diagnose those children who are undernourished due to secondary causes, like this seventeen-month-old child that came to us with a history of diarrhea, weight loss and failure to grow for the last 5 months. A daily fecal fat excretion of 12 grams and a D-xylose absorption with values of 12 mg% in the first hour and 9 mg% in the second hour, associated with total villous atrophy in the small bowel biopsy practically made the diagnosis of Celiac Disease. After receiving a gluten free diet for 6 months the clinical appearance showed a complete nutritional recovery, with normal values of the intestinal function tests, although there were still some mild alterations in the intestinal morphology. This child, like several other children, could easily been labeled as suffering from primary malnutrition in a more simplistic approach and at this moment could be carrying all the undesirable stigmas of malnutrition. Este foi o primeiro relato de caso publicado de Doença Celíaca (DC) com investigação completa e recuperação clínica e nutricional em 1974 (Disciplina de Gastroenterologia Pediátrica da Escola Paulista de Medicina). 

Paciente portador de desnutrição proteico-calórica devido a Doença Celíaca (DC) no momento da internação, após alguns dias em dieta isenta de glúten, e 6 meses ainda recebendo dieta isenta de glúten. Primeira biópsia intestinal revela atrofia vilositária subtotal e hipertrofia das glândulas crípticas e a recuperação morfológica durante o tratamento.   The reason for secondary causes of malnutrition associated to diarrhea within this large population of primary undernourished children is one of the most important challenges in our daily medical practice. Another striking difference between you and me, that is, in the children that you must follow up and those that I must follow up is related to the dietary scheme used in the first year of life. While for you it may make no real difference at all whether the child is being breastfed or not, to me this is a very important matter. It has been well demonstrated that children while exclusively breastfed, despite living in poor conditions, have a growth chart very similar to those ones of the healthiest British children, but when human’s milk is replaced by cow’s milk formula, or other new foods are incorporated to the infant’s diet repeated infectious diarrheic episodes appear and malnutrition supervenes. This is the classical picture known by the name of “weanling diarrhea”. To confirm this hypothesis which has been proven by the classical studies in Punjab and in Guatemala, I invite you to follow me on a long trip to a Brazilian Indian Reservation, called Xingu National Park. The Reservation is in the heart of the country just on the beginning of the Amazon region. The only means of transportation to reach this area is by plane.

  Archeological studies indicate that the Indians settled this area at least for the II century of our Era, and due to some geographic peculiarities, the Indians remained in complete isolation until the last years of the 19^TH century. Nowadays these people are allowed to live in their most natural way of living, and all their traditions, customs and culture have been respected. They live in their little villages in houses built by themselves.

Diversas aldeias do Alto Xingu

Registro fotográfico da minha primeira viagem ao Parque Indígena do Xingu, em dezembro de 1970, semanas antes das solenidades da minha graduação em Medicina pela Escola Paulista de Medicina.

Their basic food supply are fish and starch obtained from a special kind of root, called manioc, and wild fruits, mainly “piqui”, that is rich in vitamin A.

Os rios e os lagos são abundantes fontes de peixes

Registro das principais etapas do laborioso processo de elaboração do Biju

Breastfeeding is universal and the most important kind of food during the first year of life, being practically the only nutritional supply in this period of life, except for a special kind of juice made of manioc and native fruits, that is offered near the end of the first year of life. There is no other way to get animal milk since they have no pastoral tradition, and so, human milk is the only option. Breastfeeding lasts approximately until the third or fourth year of life and after weaning milk is never again consumed by these population. In general, soon after the fifth year of life the Indians become lactose intolerants due to a genetically lactase deficiency acquisition.

  To evaluate the nutritional status of the children population below 5 years of age we have done a prospective study during 3 consecutive years. This study showed that the prevalence of malnutrition in these children was 5.8% and despite malaria which is endemic in this region of the country we did not find severe cases of malnutrition and the mortality rate was very low. So, these people, some of the most primitive human beings still alive, live in close relationship with nature showing a perfect state of adaptation and integration. We can state by now that they do not demand any special medical care, except of course for the routinary immunization schedule, to maintain their nutritional status.

Foto registrada pela premiada fotografa Maureen Bisilliat, em 1974, quando do meu trabalho de tese de Doutorado intitulado “Avaliação do estado nutricional das crianças índias do Alto Xingu”, defendida em abril de 1977.

Este poster foi exposto, no mural do Carnegie Hall em Nova York, durante a temporada de concertos do cantor Sting em março de 1993, escrito em inglês e por mim vertido para o português. Vale ressaltar que Sting é um grande amigo do cacique Raoni desde longa data, e financiou parte da demarcação do Parque Indígena do Xingu.

On the other hand, when the descendants of these people move up to our traditional western type of civilization, this happy and healthy appearance gradually starts to disappear and becomes more difficult to be seen in a considerable proportion of our general population. A clinical picture of overt malnutrition can now be seen more frequently, and kwashiorkor is one of the most common types of severe protein-energy malnutrition seen in the rural zones of the country. However, when you reach the large cities, the problems are multiplied, and the iceberg of malnutrition becomes more visible in an earlier age.

  These people original inhabitants of the rural zones are attracted by the illusion of the great cities, and they constitute a considerable migratory mass moving to the big urban centers. Most of these families have numerous children and a very low income that compel them to live in promiscuous environment with no potable water and lack of sewage system in the periphery of the cities. Theses deleterious factors together with precocious weaning predispose the children to suffer repeated episodes of diarrheal diseases. Moreover, the high prices of formulas result on the consumption of diluted preparation of the feeding bottles, thus contributing to the aggravation of the nutritional status. Repeated infectious diseases, frequent hospital admissions and deficient protein-energy intake are the main factors of a vicious cycle that leads to severe protein-energy malnutrition in the first five years of life and consequently to high rates of death. Marasmus is the most common clinical picture of protein-energy malnutrition observed among us.

Registro fotográfico do Projeto de Avaliação do Estado Nutricional das Crianças moradoras na favela e o nosso voluntário Tuta, morador da favela que se incorporou ao projeto.

Nutritional deficiencies of minerals, vitamins, protein, and calories, associated to a contaminated environment, create a vicious cycle that induce several alterations in the digestive system, mainly a malabsorption syndrome. Currently, it is admitted that the alterations reported in the digestive-absorptive function represent a summation of effects, among possible others, between malnutrition itself and the changes observed in the intestinal microbiota. Careful studies on pancreatic structure and function indicate that the zymogen granules are decreased in the severe protein-energy malnutrition and that after the stimulation with secretin and pancreozymin, pancreatic output is also markedly reduced. The enzyme activity of the pancreatic output is lower than normal, lipase, trypsin, chymotrypsin, and amylase being reduced in that order.

In severe protein-energy malnutrition the intestinal wall becomes thin and hypotonic, and the enteric mucosa can show histological abnormalities in variable degrees of severity. In general, it can be said that in kwashiorkor the villi aberrations although significant are non-specific. However, some authors have shown severe alterations like those observed in untreated celiac disease, in as many as 10-60% of the patients. The enterocyte may show a cuboidal transformation and the mitotic index of the crypt cells remains practically normal, while the crypt glands may be found to be elongated. In marasmus patients, on the other hand, the morphological studies of the intestinal mucosa have shown controversial results. Brunser et al. did not find significant changes in the small intestinal morphology but have shown a low mitotic index in the crypt cells, suggesting a low rate of cellular proliferation in the crypt glands. In our experience, on the other hand, we have found alterations in varying degrees in the intestinal morphology in 63% of the studied patients. In half of the studied material the abnormalities were found to be non-specific, and we never found total villous atrophy like that described in celiac disease. In 54% of the patients, however, the small intestinal mucosa showed a very peculiar morphological pattern of alteration that we called Diminished Villi Population.

Alterações morfológicas da mucosa do intestino delgado com atrofia parcial das vilosidades e aumento da distância entre elas, caracterizando população vilositária diminuída (Tese de Mestrado por mim apresentada e aprovada com nota máxima ao IBEPEGE em abril de 1977).

The digestive-absorptive function is impaired and patients suffering from severe protein-energy malnutrition show steatorrhea and a marked decrease in the D-xylose absorption test, the second hour being significantly higher than the first hour. This observation may be due to a delayed gastric emptying and/or intestinal hypomotility. Dean et al, in 1952, were the first authors to indicate the possibility of lactose or other carbohydrate intolerance in malnourished patients. Disaccharidase deficiency, mainly lactase in up to 82% of the patients and sucrase in up to 54% have been exhaustively reported in malnourished children. The well-known deleterious effects of carbohydrate malabsorption, therefore, can be seen not only to lactose intolerance, but also with sucrose intolerance, and even in the more severe cases glucose malabsorption have been described in the classical papers published by Lifshitz et al. In our personal experience with marasmus patients 73% showed lactose, 23% sucrose and 5% glucose malabsorption. A striking feature described in protein-energy malnutrition is small intestine bacterial overgrowth. In normal condition the stomach, duodenum and upper jejunum are practically sterile or have a sparce microflora consisting predominantly of Gram+, facultative microorganisms, that are derived from the oral cavity, colonizing the stomach and the upper bowel in a variable wave like fashion following the meals. The distal portion of the ileum shows a change of the flora composition with the appearance of Gam- microorganisms such as coliforms and anaerobic Bacteroides. In the colon an evident change in the number and types of microorganisms can be seen and of note is the increase in the anaerobic population. The acid gastric secretion, the secretory IgA production, the bile salts, and the intestinal peristaltic movements are the most important regulatory mechanisms that maintain the equilibrium of the microflora, avoiding an abnormal bacterial overgrowth. In protein-energy malnutrition most of these regulatory mechanisms are deranged. Gastric achlorhydria, intestinal hypotonia and hypomotility, and immunological deficiencies have been described in malnourished children. These factors acting together with the lack of sanitary environmental conditions will favor a chronic bacterial overgrowth in the small intestine of these children. This bacterial overgrowth is considered one of the most important causes of malabsorption reported in malnourished children. The bacteria compete with the host for food and attack proteins, folic acid, vitamin B12, nondigested carbohydrate, and for this reason may provoke nutritional depletion in the host.  Intestinal bacteria present in the upper portions of the small intestine, especially the anaerobes, cause deconjugation of the primary bile salts and 7 alpha dehydroxilation. The lowered concentration of the conjugated bile salts together with the transformation in secondary bile salts may result in fat malabsorption when they are reduced to a concentration below the critical micellar level. The presence of deconjugated and secondary bile salts in the jejunum otherwise defaulting fat absorption, will damage the intestinal mucosa and impair glucose absorption by the enterocytes. Bacterial proliferation into the jejunal lumen also competes with the host in carbohydrate absorption causing fermentation with the production of osmotically active particles increasing water loses leading to metabolic acidosis. In conclusion as you can see now it is easy to answer why malnutrition and diarrhea constitute a binomial complex that come almost always together and becomes easier to explain why the experimental conditions not always reproduce the exact model observed in the clinical practice dealing with malnourished children. The environment makes the whole difference due to lack of sewage, no potable water supply, leading to contaminated foods, precocious weaning, no hygienic education, numerous proles, low family income, all together acting as the trigger factor of the vicious cycle malnutrition-diarrhea. This binomial complex is one of the numerous challenges that Health Care Professionals must face and try to solve in the underdeveloped countries. Thank you.

Projeto de implantação de promoção do aleitamento natural na comunidade da Favela Cidade Leonor: uma profilaxia temporária retardando a ocorrência da Enteropatia Ambiental (Teses de Mestrado em 1988 e Doutorado em 1993, de Fatima Lindoso, por mim orientada apresentada ao curso de Pós-Graduação da Escola Paulista de Medicina).

Nota de Esclarecimento

• As fotos registradas nesse trabalho não coincidem necessariamente com a cronologia da palestra proferida, posto que a maioria delas foi obtida após o meu retorno ao país.
• Toda a documentação fotográfica exposta nesse documento foi por mim realizada, exceto naquelas fotos em que estou presente.
• A documentação fotográfica realizada no Parque Indígena do Xingu (PIX), foi registrada entre 1970 e 2000, intervalo de tempo em que trabalhei na referida área por meio de visitas anuais.
• O trabalho de campo realizado na Favela Cidade Leonor tratou-se de um projeto de assistência e pesquisa da Disciplina de Gastroenterologia Pediátrica da Escola Paulista de Medicina (EPM), por mim coordenado, como parte do Programa de Pós-Graduação da nossa instituição, a partir de 1981, envolvendo Mestrandos e Doutorandos, e que resultou na elaboração de inúmeras teses de Mestrado e Doutorado.
• A Favela Cidade Leonor foi erguida a partir dos anos 1950, às margens do córrego da Água Espraiada, o qual nasce na região do ABC e desagua no rio Pinheiros. Informações mais detalhadas deste trabalho de campo, estão descritas no Livro “Enteropatia Ambiental. Uma consequência do fracasso das políticas sociais e de saúde pública”, por mim escrito e  editado pelo Editora REVINTER em 1996.