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Актуальность. Острая хирургическая патология характеризуется высоким риском возникновения послеоперационных осложнений и смертности. Цель исследования — определить исходныe патофизиологические изменения у больных с неотложной патологией органов брюшной полости и их зависимость от степени хирургического риска пациентов. Материалы и методы. Обследовано 200 больных, оперированных ургентно в объеме лапаротомии. В зависимости от степени операционного риска, определяемого по шкале Р-POSSUM, больные были разделены на 2 группы — среднего (n = 100) и высокого (n = 100) хирургического риска. Изучали рутинные клинико-лабораторные показатели, состояние центральной гемодинамики и водных секторов организма методом неинвазивной биоэлектрической интегральной оценки состава тела с помощью аппаратного комплекса «Диамант». Результаты. У всех пациентов среднего хирургического риска наблюдалось уменьшение внеклеточного объема за счет снижения объема плазмы (83 % от нормы в 1-й группе (p < 0,05), 86 % от нормы (p < 0,05) во 2-й группе). Статистически достоверных изменений внутриклеточного объема не отмечалось у пациентов обеих групп. Гемодинамический ответ у всех больных имел приспособительный характер. Так, увеличение ударного объема на 105 % от нормы (p < 0,05) при снижении ударного индекса на 122 % от нормы (p 0,05). У пациентов 2-й группы отмечался относительно гиподинамический тип кровообращения (показатели сердечного индекса соответствовали 84,6 % от нормы; p < 0,05) при высоком напряжении сердечно-сосудистой системы (показатели ЧСС превышали норму на 45 %; p

Understanding fluid physiology in homeostasis and disease is a key part of anaesthesia and intensive care. Decision making in perioperative fluid therapy is guided by knowledge of fluid compartments, shifts in illness and surgery and the composition of commonly used intravenous fluids. The implication of poor fluid management has significant outcomes for the patient, with both under-resuscitation and over administration of fluids leading to organ dysfunction and postoperative morbidity and mortality. Increasing use of haemodynamic monitoring within a guideline framework is advised. The evidence base for type of fluid, timing, and volume remain areas of investigation and ongoing clinical debate and it is vital as clinicians involved in perioperative care to continually update our knowledge of this area. Research is currently ongoing to determine whether restrictive, liberal or goal-directed fluid therapy is optimal to guide our practice. In the meantime, advice is to both individualize management to the patient condition and develop local protocols where possible.

Objective Although fluid resuscitation is the cornerstone of treatment for sepsis, the role of body water status in sepsis is poorly understood. This study aimed to understand how body water and its distribution are modified in patients with sepsis and those with non-septic infection compared to healthy individuals.Methods Two groups of adults presumed to have non-septic infection (n=87) and sepsis (n=54) were enrolled in this prospective study in a single emergency department, and they were compared to sex-, age-, and height-matched (1:3 ratio) healthy controls (n=11,190) from retrospective data in a health promotion center. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW), determined using direct segmental multi-frequent bioelectrical impedance analysis (InBody S10) were expressed as indices for normalization by body weight (BW). The ratio of ECW to TBW (ECW/TBW) was evaluated to determine body water distribution.Results TBW/BW, ICW/BW, and ECW/BW were significantly higher in the non-septic infection group than in the healthy group (P

Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity and reduce treatment burden in neovascular age-related macular degeneration. This systematic review aimed to determine the impact of persistent/new subretinal fluid, intraretinal fluid, and subretinal pigment epithelial fluid on visual acuity over 1 year of treatment.Publication eligibility and data extraction were conducted according to Cochrane methods: 27 of the 1,797 screened records were eligible.Intraretinal fluid negatively affected visual acuity at baseline and throughout treatment, with foveal intraretinal fluid associated with lower visual acuity than extrafoveal intraretinal fluid. Some studies found that subretinal fluid (particularly subfoveal) was associated with higher visual acuity at Year 1 and longer term, and others suggested subretinal fluid did not affect visual acuity at Years 1 and 2. Data on the effects of subretinal pigment epithelial fluid were scarce, and consensus was not reached. Few studies reported numbers of injections associated with fluid status.To optimally manage neovascular age-related macular degeneration, clinicians should understand the impact of fluid compartments on visual acuity. After initial treatment, antivascular endothelial growth factor regimens that tolerate stable subretinal fluid (if visual acuity is stable/improved) but not intraretinal fluid may enable patients to achieve their best possible visual acuity. Confirmatory studies are required to validate these findings.

Disorders of fluid balance and electrolyte homeostasis are commonly observed in critically ill patients and in those who require emergency anaesthesia. Consequently, anaesthetists and intensive care physicians must understand the physiological principles that govern fluid balance. This article discusses the compartmentalization of total body water and describes methods by which the volume of the fluid compartments may be measured. The novel concept of the endothelial glycocalyx is discussed in addition to the conventional and contemporary models of capillary filtration dynamics. The core elements of fluid balance and cardiovascular homeostasis are also explored.

Purpose: In vivo MR elastography (MRE) holds promise as a neuroimaging marker. In cerebral MRE, shear waves are introduced into the brain, which also stimulate vibrations in adjacent CSF, resulting in blurring and biased stiffness values near brain surfaces. We here propose inversion-recovery MRE (IR-MRE) to suppress CSF signal and improve stiffness quantification in brain surface areas. Methods: Inversion-recovery MRE was demonstrated in agar-based phantoms with solid-fluid interfaces and 11 healthy volunteers using 31.25-Hz harmonic vibrations. It was performed by standard single-shot, spin-echo EPI MRE following 2800-ms IR preparation. Wave fields were acquired in 10 axial slices and analyzed for shear wave speed (SWS) as a surrogate marker of tissue stiffness by wavenumber-based multicomponent inversion. Results: Phantom SWS values near fluid interfaces were 7.5 ± 3.0% higher in IR-MRE than MRE (P = .01). In the brain, IR-MRE SNR was 17% lower than in MRE, without influencing parenchymal SWS (MRE: 1.38 ± 0.02 m/s; IR-MRE: 1.39 ± 0.03 m/s; P = .18). The IR-MRE tissue-CSF interfaces appeared sharper, showing 10% higher SWS near brain surfaces (MRE: 1.01 ± 0.03 m/s; IR-MRE: 1.11 ± 0.01 m/s; P < .001) and 39% smaller ventricle sizes than MRE (P < .001). Conclusions: Our results show that brain MRE is affected by fluid oscillations that can be suppressed by IR-MRE, which improves the depiction of anatomy in stiffness maps and the quantification of stiffness values in brain surface areas. Moreover, we measured similar stiffness values in brain parenchyma with and without fluid suppression, which indicates that shear wavelengths in solid and fluid compartments are identical, consistent with the theory of biphasic poroelastic media.

Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration. This review describes how these anatomical features relate to the visual acuity and the efficacy of dosing regimens that make use of these features for determining dosing interval durations., Purpose: Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration, as evidenced by clinical trials that have used these features for inclusion criteria, retreatment criteria, and outcome measures of the efficacy of intravitreal injections of anti–vascular endothelial growth factor agents. Methods: A literature review of anatomical measures of disease activity was conducted. Results: Treatment goals for neovascular age-related macular degeneration include improving/maintaining vision by drying the retina, and several analyses have evaluated the relationship between visual function and anatomy. The change in retinal thickness has been found to correlate with the change in the visual acuity, and variation in retinal thickness may predict visual acuity outcomes. In addition, specific fluid compartments may have different prognostic values. For example, the presence of intraretinal fluid has been associated with poorer visual acuity, whereas the presence of subretinal fluid has been associated with better visual acuity. Retinal fluid and thickness are important for selecting dosing interval durations in clinical trials and clinical practice. Conclusion: Retinal thickness and retinal fluid are common anatomical measures of disease activity in neovascular age-related macular degeneration. Further research is required to fully elucidate the relationship between anatomical features and visual outcomes in neovascular age-related macular degeneration.

Background The kidney is central for maintaining water balance. As a corollary, patients with impaired kidney function are prone to pathological fluid volumes. Total body water (TBW) is distributed between the extracellular (ECW) and intracellular fluid compartments (ICW). In clinical practice, the judgment of hydration status does not allow to distinguish between ECW and ICW. Here, we evaluate the hydration status in children with chronic kidney disease by analyzing TBW, ECW, and ICW. Methods Hydration was quantified using whole-body bioimpedance spectroscopy (BCM) in 128 outpatients (1–25 years, 52 girls). Forty-two were transplanted (TPL), 43 suffered from chronic kidney disease without kidney replacement therapy (CKD), 21 were on peritoneal dialysis (PD), and 22 on hemodialysis (HD). HD patients were investigated before, after, and sequentially during dialysis. Results The ECW and ICW values obtained by BCM were of the same magnitude as those from the literature using isotope dilution. When compared with a healthy control group, TBW was increased in 9 TPL, 9 CKD, 1 PD, and 11 HD patients before but in none after dialysis. The decline of overhydration during dialysis (p n = 22) correlated with the change in body weight (R2 = 0.62). The kinetics of fluid compartment changes assessed twice in six HD patients revealed a reproducible linear decay of the ECW/ICW ratio due to an increase of ICW and a decrease of ECW. Conclusion BCM quantifies TBW and acute changes of ECW and ICW in children with chronic kidney failure. The clinical utility of measuring TBW, ECW, and ICW should be defined in the future.

Lymphedema can lead to a series of complicated and irreversible chronic pathological changes, including lymphatic fluid retention, infiltration of inflammatory cells, lipid deposition, and fibrosis of the surrounding tissues. Typically, compression physiotherapy is recommended for early lymphedema. However, the chronic fluid compartments will lead to fat deposition, skin fibrosis, and hyperkeratosis. Few treatment methods are available for patients with lymphedema. Previous studies have attempted to apply diuretics, diosmin, and sodium β-aescinate to treatment for venous edema, but the curative effect was unsatisfactory. There is currently no established effective treatment for lymphedema. In this paper, we investigated the effects of the traditional Chinese medical prescription Linba Fang as a treatment for lymphedema using a mouse model. A lymphedema model was established in C57BL/6 mice through lymphatic ablation at the base of tails. Negative controls were administered with 0.5% sodium carboxymethyl cellulose solution by gavage twice daily, positive controls with aescuvenforte, and test mice with Linba Fang. Aescuvenforte and Linba Fang were dissolved in 0.5% sodium carboxymethyl cellulose solution to produce a homogeneous mixture. After treatment for 2–4 weeks, tail diameter and weight, inflammatory cytokine levels (IL-1, IL-6, and TNF-α), lipid deposition, and fibrosis were evaluated. The results showed that none of the mice died during the treatment with Linba Fang. The levels of tail swelling, inflammation, lipid deposition, and fibrosis in mice treated with Linba Fang were significantly decreased compared with negative and positive controls. Among mice treated with the same dose of Linba Fang, the levels of tail swelling, inflammation, lipid deposition, and fibrosis in mice treated for 4 weeks were significantly lower than those treated for 2 weeks. Among mice treated for the same duration of time, the levels of tail swelling, inflammation, lipid deposition, and fibrosis showed a decreasing tendency following increasing doses. Notably, the inflammation in tail tissues decreased to the similar level of normal group after treatment for 4 weeks using the high dose of Linba Fang. In conclusion, the traditional Chinese medical prescription Linba Fang could inhibit the pathological changes caused by lymphedema, including swelling, inflammation, lipid deposition, and fibrosis.

Background Tolvaptan has been shown to improve congestion in heart failure patients. The purpose of this study was to evaluate the pharmacology and clinical efficacy of combined tolvaptan and furosemide therapy. Methods This study included 40 patients with systemic volume overload who were hospitalized for heart failure. Patients who showed no improvement in the condition after receiving 20 mg intravenous furosemide were included and were randomly selected to receive tolvaptan as an add-on to furosemide or to receive an increased dose of furosemide. We evaluated the bioelectrical impedance analyzer parameters, the parameters of the inferior vena cava using echocardiography, vital signs, body weight, urine output, and laboratory data for 5 days. Results In the changes from baseline between intracellular water volume (ICW) and extracellular water volume (ECW) after additional use of tolvaptan or furosemide from Day 1 to Day 5, there were no significant differences observed between ICW and ECW over 5 days in the tolvaptan + furosemide group, although differences were found in the furosemide group from Day 2 onward. Changes in the respiratory collapse of inferior vena cava increased significantly, and systolic blood pressure decreased significantly only in the furosemide group. Conclusions The present study clearly demonstrates that combined therapy with tolvaptan and furosemide removed excess ICW and ECW to an equal extent, while furosemide alone primarily removed ECW, including intravascular water.

Purpose: Biological soft tissues often have a porous architecture comprising fluid and solid compartments. Upon displacement through physiological or externally induced motion, the relative motion of these compartments depends on poroelastic parameters, such as coupling density (rho 12) and tissue porosity. This study introduces inversion recovery MR elastography (IR-MRE) (1) to quantify porosity defined as fluid volume over total volume, (2) to separate externally induced shear strain fields of fluid and solid compartments, and (3) to quantify coupling density assuming a biphasic behavior of in vivo brain tissue. Theory and Methods: Porosity was measured in eight tofu phantoms and gray matter (GM) and white matter (WM) of 21 healthy volunteers. Porosity of tofu was compared to values obtained by fluid draining and microscopy. Solid and fluid shear-strain amplitudes and rho 12were estimated both in phantoms and in in vivo brain. Results T-1-based measurement of tofu porosity agreed well with reference values (R = 0.99,P < .01). Brain tissue porosity was 0.14 �� 0.02 in GM and 0.05 �� 0.01 in WM (P < .001). Fluid shear strain was found to be phase-locked with solid shear strain but had lower amplitudes in both tofu phantoms and brain tissue (P < .05). In accordance with theory, tofu and brain rho 12were negative. Conclusion: IR-MRE allowed for the first time separation of shear strain fields of solid and fluid compartments for measuring coupling density according to the biphasic theory of poroelasticity. Thus, IR-MRE opens horizons for poroelastography-derived imaging markers that can be used in basic research and diagnostic applications.

Purpose Anti–vascular endothelial growth factor (VEGF) treatment of neovascular age-related macular degeneration (AMD) is a highly effective advance in the retinal armentarium. OCT offering 3-dimensional imaging of the retina is widely used to guide treatment. Although poor outcomes reported from clinical practice are multifactorial, availability of reliable, reproducible, and quantitative evaluation tools to accurately measure the fluid response, that is, a “VEGF meter,” may be a better means of monitoring and treating than the current purely qualitative evaluation used in clinical practice. Design Post hoc analysis of a phase III, randomized, multicenter study. Participants Study eyes of 1095 treatment-naive subjects receiving pro re nata (PRN) or monthly ranibizumab therapy according to protocol-specified criteria in the HARBOR study. Methods A deep learning method for localization and quantification of fluid in all retinal compartments was applied for automated segmentation of fluid with every voxel classified by a convolutional neural network (CNN). Three-dimensional volumes (nanoliters) for intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were determined in 24 362 volume scans obtained from 1095 patients treated over 24 months in a phase III clinical trial with randomization to 2 drug dosages (0.5 mg and 2.0 mg ranibizumab) and 2 regimens (monthly and PRN). A multivariable mixed-effects regression model was used to test for differences in fluid between the arms and for fluid/function correlation. Main Outcome Measures Fluid volume in nanoliters, structure-function as Pearson’s correlation coefficient, and as a coefficient of determination (R2). Results Fluid volumes were quantified in all visits of all patients. Automated segmentation demonstrated characteristic response patterns for each fluid compartment individually: Intraretinal fluid showed the greatest and most rapid resolution, followed by SRF and PED the least. The loading dose treatment achieved resolution of all fluid types close to the lowest levels attainable. Dosage and regimen parameters correlated directly with resulting fluid volumes. Fluid/function correlation showed a volume-dependent negative impact of IRF on vision and weak positive prognostic effect of SRF. Conclusions Automated quantification of the fluid response may improve therapeutic management of neovascular AMD, avoid discrepancies between clinicians/investigators, and establish structure/function correlations.

The canine adenohypophysis starts to be identifiable from 25 day of pregnancy. ACTH-immunoreactive cells migrate until day 38 after which the number of ACTH-producing cells increases but their distribution does not change. The STH- and LH-producing cells first appear on day 38 of pregnancy. The primordium of the adrenal glands appears as a slender structure on day 27 and forms the definitive cortical structure on day 35. The histological pattern of the foetal adrenal cortex differs from the post-natal structure in so far as the three cortical zones (definitive zone, transitional zone and foetal zone) extend from the outside towards the inside of gland. The mass of foetal and neonatal adrenals is more than 10 times larger than the adult adrenals relative to body weight. The cortisol concentration in the amnion is slightly lower than in the allantois but the foetal serum cortisol concentration is significantly higher than in the maternal and foetal fluid compartments. The thyroxine concentrations in the allantois and amnion fluids exceed the foetal serum concentrations except in the ninth week of pregnancy, but thyroxine levels in foetal fluids and serum are below the physiological levels of adult animals. The exocrine and endocrine functions of the pancreas develop and act in parallel. Pancreatic cells are first detected at 30 days when the branched structure is clearly detectable immunohistochemically, and at that time, insulin-positive β-cells and α-cells are visible as well. The foetal serum glucose concentration exceeds the healthy adult range, but the glucose concentration in the allantois and amnion fluid remains below the physiological blood glucose concentration of mature dogs. The insulin concentration in the allantois fluid greatly exceeds the foetal serum and amnion insulin concentrations.

This review article discusses normal and abnormal sodium balance in small animals. The terms and concepts central to understanding normal sodium and water balance are presented as well as of the physiology of body fluid compartments and the movement of fluid between those compartments. As dysnatremia is a very common disorder across the spectrum of critically ill patients, the main focus of the article is to present several clinical examples of both acute and chronic hypernatremia and hyponatremia and their practical, clinical management.

This comprehensive review comparatively evaluates the safety and benefits of parenteral fluids used in resuscitation with a focus on sepsis. It also provides a random-effects meta-analysis of studies comparing restrictive resuscitation and usual care in sepsis with the primary outcome of mortality. In the septic patient, fluid therapy remains a complex interplay between fluid compartments in the body, the integrity of the endothelial barrier, and the inflammatory tone of the patient. Recent data have emerged describing the pharmacokinetics of fluid resuscitation that can be affected by the factors just listed, as well as mean arterial pressure, rate of infusion, volume of fluid infusate, nature of the fluid, and drug interactions. Fluid overload in sepsis has been associated with vasodilation, kidney injury, and increased mortality. Restrictive resuscitation after the initial septic insult is an emerging practice. Our search strategy of Medline databases revealed six randomized studies with 706 patients that examined restrictive resuscitation in sepsis. Results of this meta-analysis demonstrated no differences in mortality with restrictive resuscitation compared with usual care (30.6% vs 37.8%; risk ratio 0.83, 95% confidence interval 0.66-1.05, respectively) but was limited by the small number of studies and larger quantities of pre-randomization fluids. Another approach to address fluid overload is active (diuresis) de-resuscitation strategies that may shorten the need for mechanical ventilation and intensive care unit length of stay. Data suggest that colloids may confer mortality benefit over saline in the most severely ill septic patients. Compared with isotonic saline, balanced resuscitation fluids are associated with a lower incidence of acute kidney injury and mortality. The benefits of balanced resuscitation fluids are most evident when higher volumes of fluids are used for sepsis. Clinicians should consider these pharmacotherapeutic factors when selecting a fluid, its quantity, and rate of infusion.

There is growing awareness that brain mechanical properties are important for neural development and health. However, published values of brain stiffness differ by orders of magnitude between static measurements and in vivo magnetic resonance elastography (MRE), which covers a dynamic range over several frequency decades. We here show that there is no fundamental disparity between static mechanical tests and in vivo MRE when considering large-scale properties, which encompass the entire brain including fluid filled compartments. Using gradient echo real-time MRE, we investigated the viscoelastic dispersion of the human brain in, so far, unexplored dynamic ranges from intrinsic brain pulsations at 1 Hz to ultralow-frequency vibrations at 5, 6.25, 7.8 and 10 Hz to the normal frequency range of MRE of 40 Hz. Surprisingly, we observed variations in brain stiffness over more than two orders of magnitude, suggesting that the in vivo human brain is superviscous on large scales with very low shear modulus of 42��13 Pa and relatively high viscosity of 6.6��0.3 Pa���s according to the two-parameter solid model. Our data shed light on the crucial role of fluid compartments including blood vessels and cerebrospinal fluid (CSF) for whole brain properties and provide, for the first time, an explanation for the variability of the mechanical brain responses to manual palpation, local indentation, and high-dynamic tissue stimulation as used in elastography.

Background: Fluid therapy is a life-saving measure, which is fundamental in managing horses with colic. It is essential for the clinician to be familiar with the available options when devising a fluid plan, so that it is both beneficial to the patient and financially viable for the owner. Underpinning this is an understanding of basic physiology associated with body fluid compartments and an awareness of the potential adverse effects of fluid therapy. Aim of the article: This article, the first in a two-part series, discusses basic physiological concepts of body fluids, available fluid types and the practicalities of administration in the adult horse. The second part, covering clinical aspects of fluid therapy in adult horses with colic and some of the controversies surrounding fluid rates, fluid types and the management of metabolic acidosis, will be published in a subsequent issue of In Practice

During development, embryos perform a mesmerizing choreography, which is crucial for the correct shaping, positioning and function of all organs. The cellular properties powering animal morphogenesis have been the focus of much attention. On the other hand, much less consideration has been given to the invisible engine constituted by the intercellular fluid. Cells are immersed in fluid, of which the composition and physical properties have a considerable impact on development. In this review, we revisit recent studies from the perspective of the fluid, focusing on basolateral fluid compartments and taking the early mouse and zebrafish embryos as models. These examples illustrate how the hydration levels of tissues are spatio-temporally controlled and influence embryonic development.

INTRODUCTION: Little is known about the use of bioelectrical impedance analysis (BIA) in critically ill patients. The objective of this study was to evaluate the reproducibility of BIA measurements by comparing non-dominant versus dominant body-side measurements at 2 separate time points in healthy volunteers in order to extrapolate key elements that may be of relevance in critically ill patients. MATERIAL AND METHODS: A prospective observational validation experiment was carried out in healthy volunteers. Full-body and segmental multiple frequency BIA measurements were carried out at the non-dominant and the dominant body side, consecutively, and on 2 separate occasions within 1 week. Parameters of interest were both raw data (impedance and phase angle) at the individual frequencies (5-50-100-200 kHz) and body fluid compartment volume estimations (total body water, extracellular water volume, intracellular water volume, volume excess). RESULTS: A total of 42 measurements were performed in 22 volunteers. Median (interquartile range) age and time between measurements was 26 years (24; 35) and 2.07 days (1.00; 2.99), respectively. The intraclass-correlation coefficients (ICCs) for body fluid compartment volumes estimated by full-body BIA, were greatly above 90%, showing excellent agreement, except for volume excess which showed moderate agreement. Full-body raw impedance and phase angle measurements showed highly variable and much lower ICCs. For both estimated body fluid compartment volumes and raw measurements, segmental BIA showed also highly variable and low ICCs. CONCLUSIONS: Overall this study showed that in healthy volunteers, BIA-derived fluid parameters are reproducible, and differences can be attributed to the changes in clinical status. ispartof: ANAESTHESIOLOGY INTENSIVE THERAPY vol:53 issue:3 pages:193-199 ispartof: location:Poland status: published

Spontaneous intracerebral hemorrhage (ICH) is the most devastating form of stroke. To refine treatments, improved understanding of the secondary injury processes is needed. We compared energy metabolic, amyloid and neuroaxonal injury biomarkers in extracellular fluid (ECF) from the perihemorrhagic zone (PHZ) and non-injured (NCX) brain tissue, cerebrospinal fluid (CSF) and plasma. Patients (n = 11; age 61 +/- 10 years) undergoing ICH surgery received two microdialysis (MD) catheters, one in PHZ, and one in NCX. ECF was analysed at three time intervals within the first 60 h post- surgery, as were CSF and plasma samples. Amyloid-beta (A beta) 40 and 42, microtubule associated protein tau (tau), and neurofilament-light (NF-L) were analysed using Single molecule array (Simoa) technology. Median biomarker concentrations were lowest in plasma, higher in ECF and highest in CSF. Biomarker levels varied over time, with different dynamics in the three fluid compartments. In the PHZ, ECF levels of A beta 40 were lower, and tau higher when compared to the NCX. Altered levels of A beta peptides, NF-L and tau may reflect brain tissue injury following ICH surgery. However, the dynamics of biomarker levels in the different fluid compartments should be considered in the study of pathophysiology or biomarkers in ICH patients. Funding Agencies|Linkoping University; County Council Ostergotland; Swedish State Support for Clinical Research (ALF) [Lio-925101]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2017-00915, 2018-02532]; European Research CouncilEuropean Research Council (ERC)European Commission [681712]; Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862]; AD Strategic Fund [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]; Alzheimers AssociationAlzheimers Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]; Olav Thon Foundation; Erling-Persson Family Foundation; Stiftelsen for Gamla Tjanarinnor; Hjarnfonden, Sweden [FO2017-0243, FO2019-0228]; European UnionEuropean Commission [860197]; UK Dementia Research Institute at UCL; Swedish Alzheimer Foundation [AF-742881]; Swedish government [ALFGBG-715986]; Swedish County Councils, the ALF-agreement [ALFGBG-715986]; European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]; National Institute of Health (NIH), USAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01AG068398-01]; Swedish State Support for Clinical Research [ALFGBG-720931]

Bikram yoga is practiced in a room heated to 105°F with 40% humidity for 90 min. During the class a large volume of water and electrolytes are lost in the sweat, specifically, sodium is lost, the main cation of the extracellular fluid. There is little known about the volume of sweat and the amount of sodium lost in sweat during Bikram yoga or the optimum quantity of fluid required to replace these losses. The participants who took part in this small feasibility study were five females with a mean age of 47.4 ± 4.7 years and 2.6 ± 1.6 years of experience at Bikram yoga. The total body weight, water consumed, serum sodium concentration, serum osmolality, and serum aldosterone levels were all measured before and after a Bikram yoga practice. Sweat sodium chloride concentration and osmolality were measured at the end of the practice. The mean estimated sweat loss was 1.54 ± 0.65 L, while the amount of water consumed during Bikram yoga was 0.38 ± 0.22 L. Even though only 25% of the sweat loss was replenished with water intake during the Bikram yoga class, we did not observe a change in serum sodium levels or serum osmolality. The sweat contained 82 ± 16 mmol/L of sodium chloride for an estimated total of 6.8 ± 2.1 g of sodium chloride lost in the sweat. The serum aldosterone increased 3.5‐fold from before to after Bikram yoga. There was a decrease in the extracellular body fluid compartment of 9.7%. Sweat loss in Bikram yoga predominately produced a volume depletion rather than the dehydration of body fluids. The sweating‐stimulated rise in serum aldosterone levels will lead to increased sodium reabsorption from the kidney tubules and restore the extracellular fluid volume over the next 24 hr., A large amount of water and salt is lost in sweat during 90 min of Bikram yoga. This fluid loss produced a volume depletion of the extracellular fluid compartment rather than dehydration or disturbance in the body electrolyte levels. The lost fluid will be restored with salt in the diet over the next 24 hr.

Blood dynamically and richly supplies the cerebral tissue via microvessels invested in pia matter perforating the cerebral substance. Arteries penetrating the cerebral substance derive an investment from one or two successive layers of pia mater, luminally apposed to the pial-glial basal lamina of the microvasculature and abluminally apposed to a series of aquaporin IV-studded astrocytic end feet constituting the soi-disant glia limitans. The full investment of successive layers forms the variably continuous walls of the periarteriolar, pericapillary, and perivenular divisions of the perivascular fluid compartment. The pia matter disappears at the distal periarteriolar division of the perivascular fluid compartment. Plasma from arteriolar blood sequentially transudates into the periarteriolar division of the perivascular fluid compartment and subarachnoid cisterns in precession to trickling into the neural interstitium. Fluid from the neural interstitium successively propagates into the venules through the subarachnoid cisterns and perivenular division of the perivascular fluid compartment. Fluid fluent within the perivascular fluid compartment flows gegen the net direction of arteriovenular flow. Microvessel oscillations at the central tendency of the cerebral vasomotion generate corresponding oscillations of within the surrounding perivascular fluid compartment, interposed betwixt the abluminal surface of the vessels and internal surface of the pia mater. The precise microanatomy of this most fascinating among designable spaces has eluded the efforts of various investigators to interrogate its structure, though most authors non-consensusly concur the investing layers effectively and functionally segregate the perivascular and subarachnoid fluid compartments. Enlargement of the perivascular fluid compartment in a variety of neurological disorders, including senile dementia of the Alzheimer's type and cerebral small vessel disease, may alternately or coordinately constitute a correlative marker of disease severity and a possible cause implicated in the mechanistic pathogenesis of these conditions. Venular pressures modulating oscillatory dynamic flow within the perivascular fluid compartment may similarly contribute to the development of a variety among neurological disorders. An intimate understanding of subtle features typifying microanatomy and microphysiology of the investing structures and spaces of the cerebral microvasculature may powerfully inform mechanistic pathophysiology mediating a variety of neurovascular ischemic, neuroinfectious, neuroautoimmune, and neurodegenerative diseases.

Old age is associated with lower physical activity levels, suboptimal protein intake, and desensitization to anabolic stimuli, predisposing for age-related muscle loss (sarcopenia). Although resistance exercise (RE) and protein supplementation partially protect against sarcopenia under controlled conditions, the efficacy of home-based, unsupervised RE (HBRE) and multi-ingredient supplementation (MIS) is largely unknown. In this randomized, placebo-controlled and double-blind trial, we examined the effects of HBRE/MIS on muscle mass, strength, and function in free-living, older men. Thirty-two sedentary men underwent twelve weeks of home-based resistance band training (3 d/week), in combination with daily intake of a novel five-nutrient supplement (&lsquo, Muscle5&rsquo, M5, n = 16, 77.4 &plusmn, 2.8 y) containing whey, micellar casein, creatine, vitamin D, and omega-3 fatty acids, or an isocaloric/isonitrogenous placebo (PLA, n = 16, 74.4 &plusmn, 1.3 y), containing collagen and sunflower oil. Appendicular and total lean mass (ASM, +3%, TLM, +2%), lean mass to fat ratios (ASM/% body fat, +6%, TLM/% body fat, +5%), maximal strength (grip, +8%, leg press, +17%), and function (5-Times Sit-to-Stand time, &minus, 9%) were significantly improved in the M5 group following HBRE/MIS therapy (pre vs. post tests, p &lt, 0.05). Fast-twitch muscle fiber cross-sectional areas of the quadriceps muscle were also significantly increased in the M5 group post intervention (Type IIa, +30.9%, Type IIx, +28.5%, p &lt, 0.05). Sub-group analysis indicated even greater gains in total lean mass in sarcopenic individuals following HBRE/MIS therapy (TLM, +1.65 kg/+3.4%, p &lt, 0.05). We conclude that the Muscle5 supplement is a safe, well-tolerated, and effective complement to low-intensity, home-based resistance exercise and improves lean mass, strength, and overall muscle quality in old age.

Background and Aims Sleep disorders are common among end stage renal disease (ESRD)patients undergoing hemodialysis (HD). The etiology of sleep disorders in these patients is known to be multifactorial. However, the role of hydration status in sleep disorders in HD patients is not well studied. Therefore, our aim was to study the effect of predialysis fluid overload on sleep quality in HD patients. Methods This cross-sectional study included 100 prevalent HD patients from HD unit of El Sahel teaching hospital. fluid status and fluid compartments [total body water (TBW)], extracellular water (ECW)] and overhydration index (OH) were analyzed by a portable whole-body bio-impedance spectroscopy (Body Composition Monitor ‘BCM’) before mid-week dialysis session. Overhydration was defined as OH/ECW ≥15%. HD patients were then classified into 2 groups: Group 1 (non- overhydrated) and Group 2 (Overhydrated) according to OH/ECW. Sleep quality were assessed in all patients by Pittsburgh Sleep Quality Index (PSQI) questionnaire. Patients with Concurrent diagnosis of either obstructive sleep Apnea or psychiatric disorder and patients on any medications which affect the sleep pattern were excluded. Results our study included 100 HD patients (49 male, 51 female - mean age 49.3 ±11). 42 patients (42%) had overhydration (i.e. Group 2). Poor sleep quality (defined as PSQI score ≥5) was reported in 57% (n=57) of HD patients included in our study. Poor sleep quality was significantly higher in the HD patients with overhydrated (Group 2). Total PSQI scores were significantly higher in overhydrated patients (Group2) compared to non-overhydrated patients (Group1) (7.92±3.32 vs 4.83±2.27, P= Conclusion We may conclude from our study that sleep disorders are prevalent in HD patients. Predialysis fluid overload in HD patients may be associated significantly with poor sleep quality.

The normal pH of human extracellular fluid is maintained within the range of 7.35 to 7.45. The four main types of acid–base disorders can be defined by the relationship between the three variables, pH, Pco2, and HCO3–. Respiratory disturbances begin with an increase or decrease in pulmonary carbon dioxide clearance which—through a shift in the equilibrium between CO2, H2O, and HCO3–—favours a decreased hydrogen ion concentration (respiratory alkalosis) or an increased hydrogen ion concentration (respiratory acidosis) respectively. Metabolic acidosis may result when hydrogen ions are added with a nonbicarbonate anion, A−, in the form of HA, in which case bicarbonate is consumed, or when bicarbonate is removed as the sodium or potassium salt, increasing hydrogen ion concentration. Metabolic alkalosis is caused by removal of hydrogen ions or addition of bicarbonate. Laboratory tests usually performed in pursuit of diagnosis, aside from arterial blood gas analysis, include a basic metabolic profile with electrolytes (sodium, potassium, chloride, bicarbonate), blood urea nitrogen, and creatinine. Calculation of the serum anion gap, which is determined by subtracting the sum of chloride and bicarbonate from the serum sodium concentration, is useful. The normal value is 10 to 12 mEq/litre. An elevated value is diagnostic of metabolic acidosis, helpful in the differential diagnosis of the specific metabolic acidosis, and useful in determining the presence of a mixed metabolic disturbance. Acid–base disorders can be associated with (1) transport processes across epithelial cells lining transcellular spaces in the kidney, gastrointestinal tract, and skin; (2) transport of acid anions from intracellular to extracellular spaces—anion gap acidosis; and (3) intake.

BackgroundEarly treatment of severe hyperglycemia involves large shifts of body fluids that entail a risk of hemodynamic instability. We studied the feasibility of applying a new electrolyte equation that estimates the degree of volume depletion and the distribution of infused 0.9% saline in this setting.MethodsThe new equation was applied to plasma and urinary concentrations of sodium and chloride measured before and 30 min after a 30-min infusion of 1 L of 0.9% saline on two consecutive days in 14 patients with severe hyperglycemia (mean age 50 years). The extracellular fluid (ECF) volume was also estimated based on the volume dilution kinetics of chloride.ResultsOn day 1, the baseline ECF volume amounted to 11.5 L. The saline infusion expanded the ECF space by 160 mL and the intracellular fluid space by 375 mL. On day 2, the ECF volume was 15.5 L, and twice as much of the infused fluid remained in the ECF space. The chloride dilution kinetics yielded baseline ECF volumes of 11.6 and 15.2 L on day 1 and day 2, respectively. No net uptake of glucose to the cells occurred during the two 1-h measurement periods despite insulin administration in the intervening time period.ConclusionsThe electrolyte equation was feasible to apply in a group of hyperglycemic patients. The ECF space was 3 L smaller than expected on admission but normal on the second day. Almost half of the infused fluid was distributed intracellularly.

Maintaining appropriate water and electrolyte content in various fluid compartments is crucial for the proper functioning of the human body. Many complex systems, including the kidneys, work together to maintain and restore this balance. Common electrolyte derangements include hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion and hyperkalemia due to acute kidney injury. Laboratory assessment of electrolyte concentrations and/or osmolality in both blood and urine plays an important role in the diagnosis of electrolyte and blood volume abnormalities. Sodium, potassium, and chloride concentrations are routinely measured by ion-selective electrode methodologies, while osmolality is most often assessed by freezing point depression. Though electrolyte measurement has become routine and straightforward, preanalytical errors still pose challenges in the interpretation of results. This chapter will focus on the analytical aspects of electrolyte and blood volume assessment as well as clinical disorders that rely on these measurements.

The disorders of the sodium concentration [Na+] are body fluid osmolality disorders called dysnatremias. They are so named because our clinical chemistry measurements are obtained from blood plasma, part of the extracellular fluid (ECF), where Na+ is the dominant osmole. Since water is highly permeable to nearly all plasma membranes, and body water osmolality is regulated, it is the amount of the major ECF cation, Na+, and its associated anions that determines the ECF volume. The amount of the major intracellular fluid (ICF) cation, K+, with associated anions determines the volume of the ICF. Thus, accounting for anions that maintain electroneutrality in each compartment, the osmolality of each fluid compartment of the total body water (TBW) is equal to that of TBW itself: $$ \mathrm{Osm}=2\left[\mathrm{ECF}\kern0.5em {\mathrm{Na}}^{+}+\mathrm{ICF}\ {\mathrm{K}}^{+}\right]/\mathrm{TBW} $$ where the units are as follows: Osm, milliosmoles/kg; Na+ and K+, Meq/kg or millimoles/kg.

This chapter reviews M2 macrophage functions in three organ systems that complement each other and have synergistic functions: the circulatory, respiratory, and excretory systems. These organ systems evolved when the complexity of the body plan made it necessary to develop fluid compartments around the cells. In the human body these fluid compartments are the interstitial fluid, the lymph, the blood, and other special fluid compartments such as the cerebrospinal fluid, the aqueous humor in the eye, and the endolymph in the inner ear. The circulatory system generates, channels, and keeps in motion these fluid components, and the respiratory system ensures oxygenation and proper carbon dioxide tension of the fluid compartments. The excretory organs maintain volume and ionic composition, and clear potentially harmful materials, such as metabolic end products. Macrophages are present in all these three organ systems: they are enriched in the vessel walls, within the heart, in the respiratory tract, and in the lung alveoli, kidney, and lower urinary tract.

A large percentage of hospitalized patients are readmitted within 90 days of discharge with heart failure. Emerging observational data suggest that positive fluid balance that occurs during the hospitalization, particularly among patients at risk for fluid retention, is associated with poor outcomes. Consequently, careful and judicious attention to both fluid administration and to overall fluid balance during the hospital stay is important. To this end, understanding the physiology of the distribution of body fluid compartments, and that both the arterial and the venous aspects of the vascular space are independently important, is critical to patient care. In this chapter, we will review the clinical data outlining the potential risk of positive fluid balance and the physiological mechanisms that might influence the physician’s decision whether to administer intravenous fluid or diuretics. Ultimately, despite a large amount of data highlighting the potential risks of excess fluid during a hospital stay, well-designed trials that use diuretics to reestablish euvolemia upon discharge are needed to further guide management.

Objective Hemodialysis (HD) patients are exposed to dysregulated fluid balance which can lead to overhydration. Poor sleep quality and excessive daytime sleepiness are particularly common in these patients, however the relationship between fluid status and sleep quality and daytime sleepiness has not yet been studied. Therefore, the aim of this study is to evaluate the correlations between fluid status and sleep quality and daytime sleepiness in HD patients. Method This cross-sectional study included 115 HD patients and 30 healthy control subjects from the HD center of Shanghai Ninth People's Hospital. Fluid compartments [total body water (TBW)], extracellular water (ECW)] and overhydration index (OH) were analyzed by multifrequency bio-impedance (BCM). Overhydration was defined as OH/ECW≥7%. HD patients were divided into an overhydration group and non overhydration group according to OH/ECW. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (PSQI), and excessive daytime sleepiness was evaluated by the Epworth Sleepiness Scale (ESS). Results The prevalence rate of fluid overload in HD patients was 65.2%. Poor sleep quality (PSQI≥5) and excessive daytime sleepiness (ESS≥11) were significantly higher in HD patients compared with the healthy controls [6 (3, 10) vs.2.11 ± 1.59, p = 0.000; 3 (0, 6) vs.1.68 ± 1.07, p = 0.045]. Furthermore, the PSQI scores were higher in HD patients with overhydration (7.8 ± 4.5 vs. 4.8 ± 3.2, p = 0.000). The component scores 1, 2, 3 and 5 of the PSQI showed significant differences between the overhydration and non overhydration groups. The ESS scores did not show differences between the two groups (3.9 ± 4.1 vs. 3.3 ± 3.5, p = 0.508). OH was correlated with Systolic BP and Diastolic BP, and additionally was an independent predictor of poor sleep quality. Conclusion Fluid overload is significantly linked with poor quality of sleep in HD patients, however there is no association with excessive daytime sleepiness. Our study provides new insight into possible treatment strategies. Future studies should examine the effects of optimizing fluid status on quality of sleep.

The physiology of fluid balance in humans should be understood and applied in clinical practice. Fluid balance, when managed accurately and safely, can prevent significant morbidity and mortality. Anaesthesia and critical care patients are often fasted and under physiological stress. Therefore, homoeostatic regulation of fluid balance is impaired. A disturbance in normal fluid balance induces a physiological ‘stress’ response via metabolic, neuroendocrine and immune-mediated systems. Critically unwell patients may suffer morbidity secondary to high-volume fluid losses or oedema. There are three fluid compartments discussed in relation to human fluid balance. The intracellular space is surrounded by extracellular fluid, separated by the water permeable cell membrane. Extracellular fluid (ECF) compartment volume and electrolyte concentration, majorly sodium, must be tightly regulated to avoid osmosis and cell damage. The renal system maintains ECF volume by regulating sodium and osmotic concentration by retaining or excreting water.

Abnormal cerebrospinal fluid (CSF) dynamics can produce a number of significant clinical problems to include hydrocephalus, loculated areas within the ventricles or subarachnoid spaces as well as impairment of normal CSF movement between the cranial and spinal compartments that can result in a cerebellar ectopia and hydrosyringomyelia. Thus, assessing the patency of fluid flow between adjacent CSF compartments non-invasively by magnetic resonance imaging (MRI) has definite clinical value. Our objective was to demonstrate that a novel tag-based CSF imaging methodology offers improved contrast when compared with a commercially available application. In a prospective study, ten normal healthy adult subjects were examined on 3T magnets with time-spatial labeling inversion pulse (Time-SLIP) and a new tag-based flow technique—time static tagging and mono-contrast preservation (Time-STAMP). The image contrast was calculated for dark-untagged CSF and bright-flowing CSF. We tested the results with the D’Agostino and Pearson normality test and Friedman’s test with Dunn’s multiple comparison correction for significance. Separately 96 pediatric patients were evaluated using the Time-STAMP method. In healthy adults, contrasts were consistently higher with Time-STAMP than Time-SLIP (p

Background and objective Hyperactivity of the brain renin-angiotensin (Ang) system has been implicated in the development and maintenance of hypertension. AngIII, one of the main effector peptides of the brain renin-Ang system, exerts a tonic stimulatory control over blood pressure (BP) in hypertensive rats. Aminopeptidase A (APA), the enzyme generating brain AngIII, represents a new therapeutic target for the treatment of hypertension. We developed RB150, a prodrug of the specific and selective APA inhibitor, EC33. When given orally in acute treatment in hypertensive rats, RB150 crosses the gastrointestinal and blood-brain barriers, enters the brain, inhibits brain APA activity and decreases BP. We investigate, here, the antihypertensive effects of chronic oral RB150 (50 mg/kg per day) treatment over 24 days in alert hypertensive deoxycorticosterone acetate-salt rats. Methods We measured variations in Brain APA enzymatic activity, SBP, plasma arginine vasopressin levels and metabolic parameters after RB150 chronic administration. Results This resulted in a significant decrease in SBP over the 24-day treatment period showing that no tolerance to the antihypertensive RB150 effect was observed throughout the treatment period. Chronic RB150 treatment also significantly decreased plasma arginine vasopressin levels and increased diuresis, which participate to BP decrease by reducing the size of fluid compartment. Interestingly, we observed an increased natriuresis without modifying both plasma sodium and potassium levels. Conclusion Our results strengthen the interest of developing RB150 as a novel central-acting antihypertensive agent and evaluating its efficacy in salt-sensitive hypertension.

Biomolecular monitoring in the gastrointestinal tract could offer rapid, precise disease detection and management but is impeded by access to the remote and complex environment. Here, we present an ingestible micro-bio-electronic device (IMBED) for in situ biomolecular detection based on environmentally resilient biosensor bacteria and miniaturized luminescence readout electronics that wirelessly communicate with an external device. As a proof of concept, we engineer heme-sensitive probiotic biosensors and demonstrate accurate diagnosis of gastrointestinal bleeding in swine. Additionally, we integrate alternative biosensors to demonstrate modularity and extensibility of the detection platform. IMBEDs enable new opportunities for gastrointestinal biomarker discovery and could transform the management and diagnosis of gastrointestinal disease.

Summary: Background: Hereditary Multiple Exostoses (HME) is a rare autosomal disorder characterized by the presence of multiple exostoses (osteochondromas) caused by a heterozygous loss of function mutation in EXT1 or EXT2; genes involved in heparan sulfate (HS) chain elongation. Considering that HS and other glycosaminoglycans play an important role in sodium and water homeostasis, we hypothesized that HME patients have perturbed whole body volume regulation and osmolality in response to high sodium conditions. Methods: We performed a randomized cross-over study in 7 male HME patients and 12 healthy controls, matched for age, BMI, blood pressure and renal function. All subjects followed both an 8-day low sodium diet (LSD, 200 mmol/d) in randomized order. After each diet, blood and urine samples were collected. Body fluid compartment measurements were performed by using the distribution curve of iohexol and 125I-albumin. Results: In HME patients, HSD resulted in significant increase of intracellular fluid volume (ICFV) (1.2 L, p = 0.01). In this group, solute-mediated water clearance was significantly lower after HSD, and no changes in interstitial fluid volume (IFV), plasma sodium, and effective osmolality were observed. In healthy controls, HSD did not influence ICFV, but expanded IFV (1.8 L, p = 0.058) and increased plasma sodium and effective osmolality. Conclusion: HME patients show altered body fluid distribution and osmoregulation after HSD compared to controls. Our results might indicate reduced interstitial sodium accumulation capacity in HME, leading to ICFV increase. Therefore, this study provides additional support that HS is crucial for maintaining constancy of the internal environment.