Hypoalbuminemia: Pathogenesis and Clinical Significance Soeters, Peter B.; Wolfe, Robert R.; Shenkin, Alan
JPEN, Journal of parenteral and enteral nutrition/JPEN. Journal of parenteral and enteral nutrition,
February 2019, Letnik:
43, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical significance. Inflammation ...increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half‐life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma. Hypoalbuminemia, therefore, results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity. Increasing or decreasing serum albumin levels are adequate indicators, respectively, of improvement or deterioration of the clinical state. In the interstitium, albumin acts as the main extracellular scavenger, antioxidative agent, and as supplier of amino acids for cell and matrix synthesis. Albumin infusion has not been shown to diminish fluid requirements, infection rates, and mortality in the intensive care unit, which may imply that there is no body deficit or that the quality of albumin “from the shelf” is unsuitable to play scavenging and antioxidative roles. Management of hypoalbuminaemia should be based on correcting the causes of ongoing inflammation rather than infusion of albumin. After the age of 30 years, muscle mass and function slowly decrease, but this loss is accelerated by comorbidity and associated with decreasing serum albumin levels. Nutrition support cannot fully prevent, but slows down, this chain of events, especially when combined with physical exercise.
Summary Background The worldwide debate over the use of artificial nutrition and hydration remains controversial although the scientific and medical facts are unequivocal. Artificial nutrition and ...hydration are a medical intervention, requiring an indication, a therapeutic goal and the will (consent) of the competent patient. Methods The guideline was developed by an international multidisciplinary working group based on the main aspects of the Guideline on “Ethical and Legal Aspects of Artificial Nutrition” published 2013 by the German Society for Nutritional Medicine (DGEM) after conducting a review of specific current literature. The text was extended and introduced a broader view in particular on the impact of culture and religion. The results were discussed at the ESPEN Congress in Lisbon 2015 and accepted in an online survey among ESPEN members. Results The ESPEN Guideline on Ethical Aspects of Artificial Nutrition and Hydration is focused on the adult patient and provides a critical summary for physicians and caregivers. Special consideration is given to end of life issues and palliative medicine; to dementia and to specific situations like nursing care or the intensive care unit. The respect for autonomy is an important focus of the guideline as well as the careful wording to be used in the communication with patients and families. The other principles of Bioethics like beneficence, non-maleficence and justice are presented in the context of artificial nutrition and hydration. In this respect the withholding and withdrawing of artificial nutrition and/or hydration is discussed. Due to increasingly multicultural societies and the need for awareness of different values and beliefs an elaborated chapter is dedicated to cultural and religious issues and nutrition. Last but not least topics like voluntary refusal of nutrition and fluids, and forced feeding of competent persons (persons on hunger strike) is included in the guideline.
Selenium in Intravenous Nutrition Shenkin, Alan
Gastroenterology (New York, N.Y. 1943),
11/2009, Letnik:
137, Številka:
5
Journal Article
Recenzirano
Selenium (Se) is an essential nutrient for human beings, with serious consequences resulting from clinical deficiency. It therefore should be provided intravenously to all patients who require ...parenteral nutrition (PN). Moreover, because the effects of suboptimal status are variable and unclear, this supplementation should be provided from the beginning of the course of PN. In most patients receiving PN at home or after surgery, 60–100 mcg/day will meet their requirements. Patients who commence PN already depleted in selenium may require more. Critically ill patients or those with severe burns may have higher requirements. There is good evidence that up to 400 mcg/day is beneficial in burn patients, but the evidence is inconclusive regarding the benefit of high-dose selenium in severe sepsis. Where increased Se provision is used, or in long-term PN, selenium status should be monitored by measurement of plasma Se together with a measure of systemic inflammatory response syndrome, such as C-reactive protein. There are many research issues, including which biochemical measurements best reflect tissue function, especially immune function in seriously ill patients, the clinical consequences of suboptimal biochemical Se status, whether high-dose Se improves outcome in critically ill patients, and whether extra Se always should be given with extra intakes of other antioxidants.
Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical ...illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress.
We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 microg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo.
Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 +/- 3.2 versus -4.2 +/- 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045).
The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation.
Clinical Trials.gov RCT Register: NCT00515736.
Summary Background & Aims This study aimed to assess the effect of high dose selenium (Se) supplementation on Se status in blood, oxidative stress, thyroid function and possible effects on ...requirement for renal replacement therapy (RRT) in severely septic patients admitted to the intensive care unit (ICU). Methods This prospective single-centre study was carried out in 40 septic ICU patients who were randomized to high dose Se (Se+ group, N =18 (474, 316,158 μg/day), each for 3 consecutive days followed by a standard dose of 31.6 μg/day of Se given as sodium selenite whereas the control group (Se−, N =22) received only the standard dose of Se. Plasma Se, glutathione peroxidase (GSH-Px), F2 isoprostanes, thyroid function tests (total T4 and total T3), C-reactive protein (CRP) and red blood cell (RBC) GSH-Px were estimated on day 0, 3, 7, 14. Results In the Se+ group, plasma Se increased by day 3 and 7 ( P <0.0001) and day 14 ( P =0.02), plasma GSH-Px increased by day 3 and 7 ( P =0.01) as compared to Se− group. There was a significant negative correlation between plasma Se and SOFA (sepsis related organ failure assessment) ( r =−0.36, P =0.03) along with low plasma Se and high CRP at the time of admission. Requirement for renal replacement therapy was not significantly different between the groups. Conclusion Although high dose Se supplementation increased plasma Se and GSH-Px activity, it did not reduce oxidative damage or the requirement for RRT. Se levels in blood are influenced by redistribution and severity of illness and therefore should be interpreted with caution.
This study was carried out to investigate whether zinc can potentiate renal toxicity using monolayer cultures of kidney proximal tubular cells and if so to establish the chemical species and the ...mechanism involved.
Zinc was prepared as the citrate complex at pH 7.4 in phosphate buffered saline. Monolayers of kidney proximal tubular cells under standard cell culture conditions were exposed to zinc concentrations of 0, 5 10, 20, 50 and 100μmol/L. To assess cellular damage, thiazol blue (MTT) uptake, NAG and LDH release, DAPI staining and Tunel assay were used. Cytoprotective agents: trolox, cysteine, glutathione, ascorbic acid and sodium selenite were used to investigate if the damage was reversible.
Incubation of kidney cells with zinc citrate showed a dose related reduction in cell viability (p<0.005) associated with cellular uptake of zinc ions. After 24h incubation with 100μmol/L Zn citrate, NAG release was not significantly different compared to the control whereas LDH increased 3 fold. DAPI staining showed apoptotic bodies within the cells confirmed by Tunel assay using flow cytometry. Electron microscopy showed significant morphological changes including loss of brush border, vacuolated cytoplasm and condensed nuclei. Trolox almost completely (>85±5%) and sodium selenite partially recovered (40±4%) the viability of cells exposed to Zn but no protection was observed with other cytoprotectants, e.g. glutathione, cysteine or ascorbic acid.
In conclusion zinc can induce damage to kidney cells by a mechanism dependent on zinc ions entering the cell, binding to the cell organelles and disrupting cellular processes rather than damage initiated by free radical and ROS production.
The key role of micronutrients Shenkin, Alan
Clinical nutrition (Edinburgh, Scotland),
02/2006, Letnik:
25, Številka:
1
Journal Article
Recenzirano
Micronutrients play a central role in metabolism and in the maintenance of tissue function, but effects in preventing or treating disease which is not due to micronutrient deficiency cannot be ...expected from increasing the intake. There is a highly integrated system to control the flux of micronutrients in illness, and this demonstrates just how important the body perceives the micronutrients to be. An adequate intake therefore is necessary to sustain metabolism and tissue function, but provision of excess supplements to individuals who do not need them may be harmful. Clinical benefit is most likely in those individuals who are severely depleted and at risk of complications, and is unlikely if this is not the case. Much more research is needed to characterise better markers of micronutrient status both in terms of metabolic effects and antioxidant effects, so that at-risk patients can be identified and supplementation modified accordingly. Large-scale trials of different doses of micronutrients are required with precise outcome markers to optimise intakes in different groups of patients as well as in the general population.
Background
Alkaptonuria (AKU) is a disorder of tyrosine/protein metabolism leading to accumulation of homogentisic acid. Clinical management historically recommended reducing dietary protein intake, ...especially in childhood, which has since been discredited in the literature. For the first time, analysis of baseline cross‐sectional nutritional surveillance data from a large cohort of AKU patients is presented, which has clinical implications in all aspects of treatment planning.
Method
Seventy‐four patients (mean 55 years) admitted to the National Alkaptonuria Centre (NAC), underwent a global nutritional assessment, which included objective anthropometry, bioimpedance measures, habitual nutritional intake using a 7‐day food diary and key nutritional biomarkers, including 24 hours urinary nitrogen, serum albumin, total protein and total 25‐hydroxy vitamin D. All data was compared with cohort norms or recommended nutrient intakes for health (RNI). The potential beneficial impact of protein and anti‐inflammatory nutrients such as vitamin C, selenium, and zinc were statistically interrogated against the AKU severity score index (AKUSSI)—a validated measure of disease progression stratified by age.
Results
Fifty percent of AKU patients reported some level of protein restriction at some point in their lives. In comparison with national data sets, AKU patients present with significantly lower than predicted mid‐upper arm circumference, grip strength, BMI, total energy and protein intake, and higher than predicted percentage body fat. They therefore meet the ESPEN criteria as “clinically undernourished.” Severity fluctuates over the life course. No statistical association is identified between protein intake, expressed as %RNI or g/kg, or anti‐inflammatory nutrients, including vitamin C as a high dose supplement on the severity of the disease, when correlated against the validated AKUSSI score.
Conclusion
AKU patients are at risk of protein depletion associated with a “perfect storm” of risk factors: historical, poorly evidenced recommendations to reduce total protein intake; limited mobility as the condition progresses, compromising muscle integrity; frequent hospital admissions for major surgery associated with multiple joint replacements, creating pinch points of high metabolic demand and the potential impact of the disease itself. As this is the first time this risk has been identified, the authors consider the dietetic implications of nitisinone treatment, which requires dietary protein control to manage the acquired tyrosinaemia. The lack of statistically significant evidence to support dietary manipulation of any kind to impede disease progression in AKU is demonstrated.
Assessment of micronutrient (MN) status is of particular importance in patients who require medical nutrition therapy, especially those requiring parenteral nutrition. Blood testing is generally the ...only tool available in clinical settings to assess MN status. However, using plasma or serum concentration faces pitfalls mainly because of the impact of inflammation that diverts the MNs from the circulating compartment. This review aims to review the blood tests that are useful and provide information about how to integrate functional markers of status to reach a clinically relevant diagnosis. Most impacted, with a significant and proportional decrease in plasma concentrations, are iron, selenium, zinc, thiamin, folic acid, cobalamin, and vitamins A, C, and D; copper is the only MN for which the plasma concentration increases. Therefore, a surrogate marker of inflammation, C‐reactive protein, must always be determined simultaneously. Validated intracellular and functional tests are proposed to improve status assessment. A protocol is suggested for tests required both on commencing and during nutrition support. A timely turnaround of analysis is essential for results to be clinically useful. In some cases, the appropriate provision of MNs should be commenced before results have been obtained to confirm the clinical assessment. Laboratory tests of MN status are an area prone to misuse and misinterpretation. The appropriate use and interpretation of such tests are essential to ensure the correct management of nutrition problems.
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