La inflamación, la desnutrición y la infección por SARS-CoV-2: una combinación nefasta / Inflammation, malnutrition, and SARS-CoV-2 infection: a disastrous combination

La infección por SARS-CoV-2 se relaciona con un riesgo alto de malnutrición, principalmente por el aumento de los requerimientos nutricionales y la presencia de un estado inflamatorio severo y universal. Los síntomas asociados contribuyen a la hiporexia, que perpetúa el balance nutricional negativo. Además, la disfagia, especialmente posintubación, empeora y hace poco segura la ingesta. Este riesgo es mayor en pacientes ancianos y multimórbidos. La inflamación en distinto grado es el nexo común entre la COVID-19 y la aparición de desnutrición, siendo más correcto hablar de desnutrición relacionada con la enfermedad (DRE). La DRE empeora el mal pronóstico de la infección por SARS-CoV-2, sobre todo en los casos más severos. Por ello es necesario identificar y tratar precozmente a las personas en riesgo, evitando la sobreexposición y el contacto directo con el paciente. No podemos olvidarnos del papel que juega la dieta saludable tanto en la prevención como en la recuperación tras el alta

SARS-CoV-2 infection is associated with a high risk of malnutrition, mainly due to increased nutritional requirements and the presence of a severe and universal inflammatory state. Associated symptoms contribute to hyporexia, which perpetuates the negative nutritional balance. Furthermore, dysphagia, especially post-intubation, worsens and makes intake unsafe. This risk is greater in elderly and multimorbid patients. Inflammation to varying degrees is the common link between COVID-19 and the onset of malnutrition, and it is more correct to refer to disease-related malnutrition (DRM). DRM worsens the poor prognosis of SARS-CoV-2 infection, especially in the most severe cases. Therefore, it is necessary to identify and treat people at risk early, avoiding overexposure and direct contact with the patient. We cannot forget the role that a healthy diet plays in both prevention and recovery after discharge

[Inflammation, malnutrition, and SARS-CoV-2 infection: a disastrous combination]. / La inflamación, la desnutrición y la infección por SARS-CoV-2: una combinación nefasta.

SARS-CoV-2 infection is associated with a high risk of malnutrition, mainly due to increased nutritional requirements and the presence of a severe and universal inflammatory state. Associated symptoms contribute to hyporexia, which perpetuates the negative nutritional balance. Furthermore, dysphagia, especially post-intubation, worsens and makes intake unsafe. This risk is greater in elderly and multimorbid patients. Inflammation to varying degrees is the common link between COVID-19 and the onset of malnutrition, and it is more correct to refer to disease-related malnutrition (DRM). DRM worsens the poor prognosis of SARS-CoV-2 infection, especially in the most severe cases. Therefore, it is necessary to identify and treat people at risk early, avoiding overexposure and direct contact with the patient. We cannot forget the role that a healthy diet plays in both prevention and recovery after discharge.

[Inflammation, malnutrition, and SARS-CoV-2 infection: a disastrous combination]. / La inflamación, la desnutrición y la infección por SARS-CoV-2: una combinación nefasta.

SARS-CoV-2 infection is associated with a high risk of malnutrition, mainly due to increased nutritional requirements and the presence of a severe and universal inflammatory state. Associated symptoms contribute to hyporexia, which perpetuates the negative nutritional balance. Furthermore, dysphagia, especially post-intubation, worsens and makes intake unsafe. This risk is greater in elderly and multimorbid patients. Inflammation to varying degrees is the common link between COVID-19 and the onset of malnutrition, and it is more correct to refer to disease-related malnutrition (DRM). DRM worsens the poor prognosis of SARS-CoV-2 infection, especially in the most severe cases. Therefore, it is necessary to identify and treat people at risk early, avoiding overexposure and direct contact with the patient. We cannot forget the role that a healthy diet plays in both prevention and recovery after discharge.

[Changes in the fat composition and histomorphology of the liver in TPN, with and without ultra-short bowel]. / Cambios en la composición de la grasa y en la histomorfología hepáticas tras NPT, con y sin intestino ultra-corto.

BACKGROUND & AIMS: Short Bowel syndrome is a serious intestinal insufficiency. The most common etiology in adults nowadays is intestinal ischemia and inflammatory disease, while in children the most common are congenital anomalies, volvolus and necrotizing enterocolaitis, which makes the TPN obligatory. However the intestine is intimately related to the liver through the entero-hepatic circulation and different endocrinological entero-hepatic systems. Massive intestinal resections and TPN would alter this relationship, and could change the hepatic tissue composition and its histomorphology. The aim of this work is to know these changes in more detail. MATERIALS AND METHODS: We used 3 experimental groups: Group A (10 guinea pigs), which was given anesthetic and a simple laparotomy and fed for 10 days with NPT. Group B (10 guinea pigs), underwent total thin intestine resection and were fed for 10 days with NTP. The control group (6 guinea pigs) underwent anesthetic and a simple sham laparotomy and were fed orally. After this period blood and hepatic tissue samples were taken in order to study the liver fat (total fat, proportion of neutral and polar lipids, proportion of phospholipids and fatty acids). Liver biopsies were taken and studied under an optical microscope. RESULTS: The animals from group A and B, underwent NPT, showed a significant increase in glycemie and serum triglycerides, decreasing the cholesterol in GB. There was a significant decrease in weight and in the proportion of fat per g of the liver tissue, at a maximum level in GB, and an even higher decrease in the LP/LN ratio in GA and GB. There was also a change in the proportion of phospholipids, decreasing the Phosphatidilinositol and increasing the Phosphatidiletanolamine. There was also a decrease in the AG w6/w3 ratio. Histologically appear a steatohepatitys, with a striking decrease in the mitochondrial density, being more intensive in GB. CONCLUSIONS: NPT alters the composition of the hepatic fat and the hystomorphology of the liver. The short bowel syndrome have more lesional mechanisms, favouring the hepatic damage caused by NPT.

Cambios en la composición de la grasa y en la histomorfología hepáticas tras NPT, con y sin intestino ultracorto / Changes in the fat composition and histomorphology of the liver in TPN, with and without ultra-short bowel

Introducción: El síndrome de intestino corto es una insuficiencia grave intestinal cuya etiología más frecuente en adultos son la isquemia intestinal y la enfermedad inflamatoria y en niños las malformaciones congénitas, el vólvulo y la enterocolitis necrotizante, obligando al uso de la NPT. Pero el intestino está íntimamente relacionado con el hígado a través de la circulación entero-hepática y de diferentes sistemas endocrinos entero-hepáticos. La resección intestinal y la Nutrición Parenteral alterarán esta relación, pudiendo variar la composición del tejido hepático y su histomorfología. El objetivo de este trabajo es conocer más concretamente estos posibles cambios. Materiales y métodos: Utilizamos 3 grupos experimentales: Grupo A (10cobayos), sometidos a una anestesia y laparotomía simple y nutridos durante 10 días con NPT. Grupo B (10cobayos), con resección intestinal yeyunoileal total y nutridos durante 10 días con NPT. Grupo Ctr (6 cobayos), sometidos a anestesia y laparotomía simple y nutridos oralmente. Tras este período se estudiaron muestras de sangre y de tejido hepático, tanto para el estudio de la grasa hepática (grasa total, proporciones de lípidos neutros y polares, proporciones de fosfolípidos y de ácidos grasos) como para estudio histológico. Resultados: Los animales de los grupos A y B, sometidos a NPT, presentan incrementos significativos en la glucemia y en los triglicéridos séricos, y descensos en el colesterol. Disminuyen el peso y la proporción de grasa por g de hígado, máxime en el GB, así como el cociente LP/LN en los GA y GB. Se modifican las proporciones de fosfolípidos, disminuyendo el fosfatidilinositol y aumentando la fosfatidiletanolamina; disminuyendo también el cociente de los AG w6/w3. Histológicamente, aparece una esteatohepatitis, con disminución marcada de la densidad mitocondrial, siendo mas intensos en el GB. Conclusión: la NPT altera la composición de la grasa hepática y la histomorfológica del hígado. El SIUC tiene más mecanismos lesionales, potenciándose el daño hepático causado por la NPT (AU)

Background & Aims: Short Bowel syndrome is a serious intestinal insufficiency. The most common etiology in adults nowadays is intestinal ischemia and inflammatory disease, while in children the most common are congenital anomalies, volvolus and necrotizing enterocolaitis, which makes the TPN obligatory. However the intestine is intimately related to the liver through the enterohepatic circulation and different endocrinological entero-hepatic systems. Massive intestinal resections and TPN would alter this relationship, and could change the hepatic tissue composition and its histomorphology. The aim of this work is to know these changes in more detail. Materials and methods: We used 3 experimental groups: Group A (10 guinea pigs), which was given anesthetic and a simple laparotomy and fed for 10 days with NPT. Group B (10 guinea pigs), underwent total thin intestine resection and were fed for 10 days with NTP. The control group (6 guinea pigs) underwent anesthetic and a simple sham laparotomy and were fed orally. After this period blood and hepatic tissue samples were taken in order to study the liver fat (total fat, proportion of neutral and polar lipids, proportion of phospholipids and fatty acids). Liver biopsies were taken and studied under an optical microscope. Results: The animals from group A and B, underwent NPT, showed a significant increase in glycemie and serum triglycerides, decreasing the cholesterol in GB. There was a significant decrease in weight and in the proportion of fat per g of the liver tissue, at a maximum level in GB, and an even higher decrease in the LP/LN ratio in GA and GB. There was also a change in the proportion of phospholipids, decreasing the Phosphatidili-nositol and increasing the Phosphatidiletanolamine. There was also a decrease in the AG w6/w3 ratio. Histologically appear a steatohepatitys, with a striking decrease in the mitochondrial density, being more intensive in GB. Conclusions: NPT alters the composition of the hepatic fat and the hystomorphology of the liver. The short bowel syndrome have more lesional mechanisms, favouring the hepatic damage caused by NPT (AU)

Cambios en la composición de la grasa y en la histomorfología del hígado tras resecciones intestinales parciales / Changes in the fat composition and histomorphology of the liver after partial intestinal resections

Introducción y objetivos: Teóricamente, las resecciones intestinales parciales podrían afectar al hígado a través de la absorción de nutrientes y de la circulación enterohepática de los ácidos biliares, por las posibles alteraciones sobre el complejo hormonal duodeno-bilo-hepato-pancreático y por los efectos secundarios de la translocación bacteriana intestinal. Estos mecanismos fisiopatológicos pueden sumarse modificando la composición y la histomorfología hepática, específicamente la composición de la grasa hepática. El objetivo de este trabajo experimental es conocer mas profunda y concretamente las alteraciones secundarias a las resecciones intestinales parciales. M & M: Utilizamos 26 cobayos divididos en 3 grupos: Grupo A (n=10), con resección yeyunal; Grupo B (n=10) con resección ileal y Grupo control (GCtr, n=6). Los animales fueron nutridos oralmente durante 21 días. Al final se obtuvieron muestras para analizar la bioquímica sérica y se homogeneizó el tejido hepático para estudio de la grasa hepática (grasa total, proporciones de lípidos neutros y polares y proporciones de fosfolípidos y de ácidos grasos). Se tomaron muestras para estudio histomorfológico. Resultados: Los animales con resección yeyunal e ileal presentaron disminución del colesterol sérico, del peso de la gota grasa/g tejido y del cociente w6/w3 y del C18-2/C18-3, sin alteraciones en la distribución de fosfolípidos. Se halló macroesteatosis y disminución de la densidad mitocondrial en los animales del G-B. Conclusiones: las resecciones intestinales parciales, especialmente las ileales sí parecen influir a corto plazo en la composición de la grasa estructural del hígado. Estos cambios en los lípidos estructurales y en la histomorfología pudieran ser compensados a medio plazo. Estos hallazgos pueden ayudarnos a entender mejor la relación hepato-intestinal (AU)

Background & Aims: The partial resection of the intestine could affect the liver through alteration in nutrient absorption, loss of the bile acids via the enterohepatic circulation, alterations in the hepato-duodenobilio-pancreatic hormonal complex as well as a bacterial translocation. All these factors could sum up and induce changes in the tissue composition and in hepatic histomorphology. The aim of this experimental study is to acquire a profound knowledge of these hepatic alterations after the partial intestinal resection. M & M: 26 Dunkin Hartley guinea pigs were used: Group A with only jejunum resection, Group B with only ileum resection, and Group CtrG, the control group. They were monitored for 21 days. At the end, blood samples were taken for serum biochemical analysis. Samples of hepatic tissue were taken for histomorphological optical study. All the rest liver was homogenize and the fat liver composition was analysed (total fat, lipid fractions, phospholipids fractions and fatty acids of the liver). Results: There was a significant decrease in serum cholesterol in both GA & GB. There was also a decrease of the total fat/g liver tissue, without changes in the phospholipids fraction and decreases in the C18-2/C18-3 and w6/w3 ratios. There was a minimal macrosteatosis and reduction of the number of mitochondries in GB. Conclusions: the partial intestinal resection, specially ileum resections, looks like influence the structural fat liver composition. However, these changes could be compensated for by the liver and oral nutrition. These findings help us to improve the liver-intestinal relationships (AU)

[Changes in the fat composition and histomorphology of the liver after partial intestinal resections]. / Cambios en la composición de la grasa y en la histomorfología del hígado tras resecciones intestinales parciales.

BACKGROUND & AIMS: The partial resection of the intestine could affect the liver through alteration in nutrient absorption, loss of the bile acids via the enterohepatic circulation, alterations in the hepato-duodenobilio-pancreatic hormonal complex as well as a bacterial translocation. All these factors could sum up and induce changes in the tissue composition and in hepatic histomorphology. The aim of this experimental study is to acquire a profound knowledge of these hepatic alterations after the partial intestinal resection. M & M: 26 Dunkin Hartley guinea pigs were used: Group A with only jejunum resection, Group B with only ileum resection, and Group CtrG, the control group. They were monitored for 21 days. At the end, blood samples were taken for serum biochemical analysis. Samples of hepatic tissue were taken for histomorphological optical study. All the rest liver was homogenize and the fat liver composition was analysed (total fat, lipid fractions, phospholipids fractions and fatty acids of the liver). RESULTS: There was a significant decrease in serum cholesterol in both GA & GB. There was also a decrease of the total fat/g liver tissue, without changes in the phospholipids fraction and decreases in the C18-2/C18-3 and w6/w3 ratios. There was a minimal macrosteatosis and reduction of the number of mitochondries in GB. CONCLUSIONS: the partial intestinal resection, specially ileum resections, looks like influence the structural fat liver composition. However, these changes could be compensated for by the liver and oral nutrition. These findings help us to improve the liver-intestinal relationships.

[What happens in the liver during artificial feeding?]. / Qué sucede en el hígado durante la alimentación artificial?

The livers of healthy individuals, where different products are synthesized and metabolized, carries out a series of complex metabolic functions. Furthermore, there is an important relationship with the digestive apparatus, such as for the secretion, excretion and re-circulation of bile, and also with the various hormonal systems or the bacterial microflora of the intestine. When artificial feeding (AF) is used, this may lead to changes in the functionality and structure of the liver, which may or may not be reversible depending on the base situation of the patient and the type of AF administered. This would be enough to bring about a series of changes followed by adaptive phenomena in the liver itself. The degree of hepatic damage triggered by artificial feeding will depend on the interaction of all these elements and the specific characteristics of each case.

¿Qué sucede en el hígado durante la alimentación artificial? / What happens in the liver during artificial feeding?

En las personas sanas el hígado, como lugar de síntesis y metabolización de diferentes productos, realiza una serie de funciones metabólicas complejas. Asimismo mantiene una importante relación con el aparato digestivo, tales como la secreción, excreción y recirculación biliar, o la relación con diferentes sistemas hormonales o con la microflora bacteriana intestinal. Cuando utilizamos alimentación artificial (AA), ésta puede originar cambios en la funcionalidad y en la estructura hepática, que podrán ser irreversibles o no según la situación de base del paciente y el tipo de AA administrada. Esta provocará por sí misma una serie de cambios, que vendrán seguidos de fenómenos adaptativos por parte del propio hígado. De la interación de todos ellos y de las características concretas de cada caso dependerá el grado de daño hepático que pueda originar la alimentación artificial (AU)

The livers of healthy individuals, where different products are synthesized and metabolized, carries out a series of complex metabolic functions. Furthermore, there is an important relationship with the digestive apparatus, such as for the secretion, excretion and re-circulation of bile, and also with the various hormonal systems or the bacterial microflora of the intestine. When artificial feeding (AF) is used, this may lead to changes in the functionality and structure of the liver, which may or may not be reversible depending on the base situation of the patient and the type of AF administered. This would be enough to bring about a series of changes followed by adaptive phenomena in the liver itself. The degree of hepatic damage triggered by artificial feeding will depend on the interaction of all these elements and the specific characteristics of each case (AU)

[Male with sudden-onset dementia associated with long lasting diarrhea as manifestations of Whipple's disease]. / Varón con demencia de aparición brusca, asociada a diarrea de larga evolución como manifestaciones de la enfermedad de Whipple.

A case of a 55-year old male with Whipple's disease who consulted for dementia (aggressivity, memory loss of recent events, sleep rhythm disturbances) is presented. Furthermore, the patient had referred changes in intestinal movement four years beforehand in addition to erratic arthralgias. Response to treatment (trimethoprim-sulfamethoxazole for one year) was favorable with resolution of both the neurologic and gastrointestinal pictures. The radiologic alterations of this entity are reviewed and suggest that this disease should be considered as a cause of dementia.

[Parenteral nutrition-associated cholestasis: the effect of diets free of taurine and its metabolic precursors on bile composition and liver structure]. / Colestasis asociada a nutrición parenteral: influencia de las dietas exentas de taurina y de sus precursores metabólicos sobre la composición biliar y la estructura hepática.

PURPOSE: To study the morphological and biliary alterations associated with taurine-free parenteral nutrition and its other precursors. EXPERIMENTAL GROUPS: One fed a standard taurine-free amino acid formula, a group fed without taurine or its metabolic precursors, and a control group. At the beginning and end of the experiment, analyses were made of nutritional parameters, hepatic enzymes, biliary composition, plasmatic aminogram and optical and electronic microscopy of the liver. RESULTS: Significant increases of threonine, glutamine, alanine, lysine, histidine and arginine, and insignificant increases of taurine, serine, isoleucine and leucine in groups with PN. Increased Non-conjugated AB, particularly lithocholic and taurolithocholic acid in groups without taurine precursors. Fat microsteatosis in area 3 of the acinus in the group without taurine, and in the three areas in the group without precursors. Standard taurine-free PN causes changes in the biliary composition and liver histology, which increase in the absence of taurine precursors.

Liver lipid composition and intravenous, intraperitoneal, and enteral administration of intralipid.

We studied the variations arising in plasma and liver lipids after intravenous (i.v.), intraperitoneal (IP), and intragastric (IG) administration of a fat overdose on the order of 4 g.kg-1 body wt.day-1 in the form of Intralipid (ITL) 20% to 33 New Zealand rabbits for 15 days. The control group was submitted for surgery but did not receive an ITL supplement. The results show weight gain in all animals and normal liver enzyme values. There was an increase in plasma lipids in groups supplemented by the parenteral route (i.v. and IP), and fatty acids showed a similar distribution, in terms of percentages, to that for ITL. In liver tissue, there was an increase in the fractions related to ethanolamine and a decrease in phospholipids of choline and serine. In the i.v. group, neutral lipids predominated compared with other groups. The livers of all supplemented animals (i.v., IP, and IG) showed a higher content of stearic and linoleic acid and a reduction in oleic acid. Study with optical microscopy showed a microvacuolization affecting the three areas of the hepatic acini in the i.v. group, seen with electron microscopy as vacuoles lacking membranes and surrounded by mitochondria. In conclusion, there is an increase in hepatic steatosis in parenteral groups and a greater deposit of neutral lipids in the i.v. group, related to the administration route, without biochemical signs of liver dysfunction.

[Interferences between nutrients in their absorption from the peritoneal cavity in rats]. / Interferencias entre nutrientes en su absorción desde la cavidad peritoneal de ratas.

With the aim of detecting possible interferences in the absorption of glucose, amino acids and fats we infused several combination of them into the peritoneal cavity of the Wistar rats. After intraperitoneal infusion of 2 mu Ci-L-glucose-C14 with 5 ml of D-glucose 5 per 100 and L-glucose-C14 with 5 ml of "16N" 3.5 per 100 in different groups of animals, we detected slight differences in plasma radioactivity one hour after infusion. We also found moderated differences in plasma radioactivity among the groups of animals infused with 1 mu Ci of fat radioactive amino acids plus 5 ml of D-glucose 5 per 100 and in the group infused with 1 mu Ci of 5-L-amino acid-C14 plus 5 ml of "16N" 3.5 per 100, after four hours of the infusion. We found no differences among those groups of animals infused with fat plus glucose and with fat plus amino acid with respect to those infused with fat alone. In summary, as glucose and amino acid absorption pathway are the same (capillary flow) seem reasonable that they interfere with each other when they are infused intraperitoneally. Fat infusion that not seem to interfere with other substrates possible due to the different absorption pathway (lymphatic channels) but further studies are needed to determine this.

[Nutrient absorption rate from the peritoneal cavity in rats]. / Velocidad de absorción de nutrientes desde la cavidad peritoneal de ratas.

A study has been done of the absorption/elimination kinetics of nutritive substances such as glucose, amino acids and fats from the peritoneal cavity. For this purpose, 48 male Wistar rats were administered an intravenous or intraperitoneal "bolus" of 2 microCi of L-glucose-C14/250 g of body weight, 3 microCi of D-alanine-L-C14/250 g and 0.4 g of Intralipid/250 g body weight. A two-compartment pharmacokinetic model was applied to determine the absorption, elimination and distribution constants among the different body compartments of each of these substrates, as well as the absorption and elimination halflife. When the areas under the curves were compared following intravenous and intraperitoneal infusion, the total physiological availability or fraction of dose absorbed over a given period of time were calculated. A higher absorption and elimination constant for glucose and amino acids as compared to fats was found. Higher than 90% absorption for all substrates was found, but since in the case of fats the elimination constant is lower and longer the elimination halflife, we must be cautious regarding its infusion rate.

[Intrahepatic cholestasis associated with parenteral nutrition: an experimental study in rats]. / Colestasis intrahepática asociada a nutrición parenteral: estudio experimental en ratas.

Intrahepatic cholestasis is a condition often observed in patients receiving parenteral nutrition, especially in new born babies who are underweight (< 1,000 g.) Some authors find an alteration in the amino acids transulphuration passage, which gives rise to a deficit of taurina. This makes it impossible to achieve a correct conjugation of toxic biliary acids. The access of nutrients to the liver may have an effect on this. An experimental study on rats was performed, administering an oral diet at the expense of lipids (20% Intralipid, 60% of caloric needs) and glucose (40% of caloric needs) in one group, another group received amino acid supplements to this diet (16N) at a proteic rate of 2 gr/kg of weight and day orally, with an identical diet to the above, except that the proteic intake was intraperitoneal. Two control groups were established. We found a microvacuolization in hepatic fat with the help of an electronic microscope in the groups lacking proteins and those with oral or intraperitoneal supplements of amino acids, as well as an increase in plasmatic AST.