Excess Extracellular Fluid Research Articles

Furosemide Use in Chronic Kidney Disease Patients

Chronic kidney disease is defined as kidney disease occurring for more than three months and is characterized by a decreasing glomerular filtration rate, reaching below 60 mL/min/1.73 m2 . Decreased kidney function can reduce the kidney’s capacity to excrete sodium. Excess extracellular fluid will cause hypertension, and lower and upper extremity edema. Loop diuretics, such as furosemide, are known to increase sodium excretion by 20%, thereby reducing the amount of extracellular fluid. This study aimed to determine the patterns of furosemide use in chronic kidney disease patients at University of Muhammadiyah Malang General Hospital. Observational, descriptive, and retrospective data collection methods were used. The use of a single furosemide pattern was given to 25 patients (40%); a two-combination to 12 patients (20%); a three-combination to 9 patients (15%); a four-combination to 12 patients (20%); and a five-combination to 4 patients (5%). The most commonly used single furosemide was furosemide (3 x 40 mg, intravenous [iv]), which was administered to 16 patients (73%); the most common two-combination was furosemide (3 x 40 mg, iv) + amlodipine (1 x 10 mg, oral), which was given to 2 patients (20%); the most common three-combination was furosemide (3 x 40 mg, iv) + candesartan (1 x 16 mg, oral) + amlodipine (1 x 5 mg) and furosemide (3 x 40 mg, iv) + candesartan (1 x 16 mg, oral) + amlodipine (1 x 10 mg, oral), which was given to 2 patients (23%); the most common four-combination was furosemide (3 x 40 mg, iv) + nifedipine (3 x 10 mg, oral) + clonidine (3 x 0.15 mg, oral) + captopril (2 x 25 mg, oral), which was given to 3 patients (28%); and the most common five-combination was given to 1 patient (25%) with 4 patterns. In short, there were 22 patterns of furosemide switch therapy.
 Keywords: furosemide, edema, chronic kidney disease

The influence on behavior and physiology of white-feathered end-of-cycle hens during simulated transport

Transportation is a stressful procedure that can alter end-of-cycle hen (EOCH) behavior and physiology. This study (5 × 3 × 2 factorial arrangement) aimed to assess the effects of temperature (T)/relative humidity (RH) (−10°C uncontrolled RH (−10), +21°C 30%RH (21/30), +21°C 80%RH (21/80), +30°C 30%RH (30/30), +30°C 80%RH (30/80)), duration (4, 8, 12 h), and feather cover [well (WF) and poorly-feathered (PF)] on white-feathered EOCH (65–70 wk) behavior and physiology. EOCH (n = 630) from 3 commercial farms were housed for adaptation (3–5 d), fasted (6 h), crated (53 kg/m2), and placed in a climate-controlled chamber. Data collected included chamber and crate conditions, feather condition score, mortality, core body temperature (CBT), behavior, and delta (∆) blood physiology. Analyses were conducted via ANOVA in a randomized complete block design (farm of origin) with significance declared at P ≤ 0.05. PF EOCH had higher mortality than WF hens during cold exposure (−10). EOCH ∆CBT demonstrated a greater (positive) change at 12 h for all T/RH compared to 4 h at 21/30, 21/80, and −10 (negative). Cold exposure (−10) resulted in a higher percentage of time spent shivering and motionless, while heat exposure resulted in a higher percentage of time spent panting for WF EOCH exposed to 30/30 and WF and PF hens exposed to 30/80. Hen ∆glucose had a greater (negative) change at 4 and 12 h for −10 compared to 4 h at 21/30, and all durations for 21/80, 30/30, and 30/80. PF hens exposed to −10 had a greater (positive) change in ∆sodium, ∆hemoglobin, and ∆hematocrit compared to WF birds (negative). The development of metabolic alkalosis was supported by the increase in ∆blood pH over time and the increase in ∆partial pressure of carbon dioxide, ∆bicarbonate, and ∆base excess extracellular fluid during cold exposure (−10). These results indicated that EOCH exposed to heat endured thermal stress while PF hens exposed to cold were unable to cope with cold stress.

Detecting fluid imbalance

Bioengineering Patients with end-stage kidney disease often experience swelling in the lower limbs caused by excess extracellular fluid. Fluid status must also be closely monitored during hemodialysis. Colucci et al. devised a portable nuclear magnetic resonance (NMR) sensor to assess tissue fluid status. The portable sensor detected changes in the extracellular fluid space in the leg muscles of dialysis patients that were similar to those detected by NMR relaxometry measured by magnetic resonance imaging. Thus, nonimaging NMR sensors can provide objective, rapid bedside evaluation of fluid status in patients. Sci. Transl. Med. 11 , eaau1749 (2019).

Much Ado about N…atrium: modelling tissue sodium as a highly sensitive marker of subclinical and localized oedema.

Hypertonic Na+ accumulation in peripheral tissues is a recently described phenomenon: it has been associated with ageing, hypertension, diabetes, chronic kidney disease and heart failure, but its clinical meaning has yet to be determined. This concept conflicts with the classic physiological paradigm of constant balance between salt intake and excretion, and its water-independent nature is still a matter of debate.We developed a theoretical model explaining changes in the chemical composition of tissues as a function of extracellular volume fraction and excess extracellular fluid, i.e. oedema. The model suggests that the proportional increase in absolute Na+ content and concentration due to different degrees of oedema is higher than the parallel increase in water content, thus making Na+ a more sensitive index to detect this oedema.Our model would explain some of the recent findings of high tissue Na+ content in pathological conditions. More importantly, it prompts the reappraisal of tissue Na+ analysis from being a topic of niche interest to a potential diagnostic tool with broad applicability in the investigation of subclinical systemic and localized oedema.

Effects of acute lipopolysaccharide-induced toxemia model on some neglected blood parameters.

The presence of lipopolysaccharide (LPS) in blood induces an inflammatory response which leads to multiple organ dysfunction and numerous metabolic disorders. Uncontrolled, improper or late intervention may lead to tissue hypoxia, anaerobic glycolysis and a disturbance in the acid -base balance. The effects of LPS-induced toxemia on biological and immunological markers were well studied. However, parameters such as base excess, ions, and acid-base balance were not fully investigated. Therefore, the objective of this study was to examine these blood parameters collectively in LPS-induced inflammatory toxemia in rat's model. After induction of toxemia by injecting LPS at a rate of 5 mg/kg body weight intravenously, blood was collected from the tail vein of twenty rats and immediately analyzed. After 24 hours, the animals were sacrificed and the blood was collected from the caudal vena cava. The results revealed that the levels of pH, bicar- bonate, partial pressure of oxygen, oxygen saturation, Alveolar oxygen, hemoglobin, hematocrit, magnesium (Mg2+), and calcium (Ca2+) were significantly decreased. On the other side, the levels of Base excess blood, Base excess extracellular fluid, partial pressure of carbon dioxide, lactate, Ca2+/Mg2+, potassium, and chloride were significantly increased compared to those found pre toxemia induction. However, sodium level showed no significant change. In conclusion, Acute LPS-toxemia model disturbs acid-base balance, blood gases, and ions. These parameters can be used to monitor human and animal toxemic inflammatory response induced by bacterial LPS conditions to assist in the management of the diagnosed cases.

Effects of Supplemental Dietary Glutamine and Arginine on Broiler Live Performance, Blood Chemistry, and Incidence of White Striping and Wooden Breast

ObjectivesThe broiler industry has been recently plagued with muscle myopathies, namely wooden breast (WB) and white striping (WS). These myopathies negatively affect the most valuable cut of a broiler, the pectoralis major muscle, whereby there is reduced protein content and increased fat and collagen content, resulting in reduced meat quality and consumer preference. The current cause of WB and WS in broilers is yet to be fully elucidated. One theory is that increased corn prices, availability of distiller’s dry grains with solubles, and other food industry co-products have led to less soybean meal and more synthetic amino acids in broiler diets can result in marginal dietary levels of glutamine (Gln) and amino acids such as arginine (Arg). It was hypothesized that increasing intracellular Gln and Arg may relate to an increased rate of protein synthesis, decreased inflammatory immune responses, a reduction of muscle proteolysis, and consequently a reduced incidence of WB and WS.Materials and MethodsA total of 288 male broiler chicks were allocated to 1 of 4 diets that had 0 or 1% supplemental Gln or 0 or 0.25% supplemental Arg to complete a 2x2 factorial design. Chicks were housed in Alternative Design cages with 8 chicks/cage and 9 replicates/treatment. Individual body weights (BW) were recorded weekly, blood chemistry was analyzed at 28 and 41 d using iStat, and 2 birds/pen were scored for WB and WS after being harvested at 42 d of age. Shear force, drip loss, cook loss, and meat pH were then evaluated. Data were analyzed using PROC GLM and PROC MIXED on SAS (SAS Inst. Inc., Cary, NC).ResultsThere were no differences among feed conversion ratio, BW, or WS. Total carbon dioxide, partial pressure of oxygen, and pH of the blood at 28 d were reduced by supplementing Gln at 1% (P < 0.05). Similarly, the base excess extracellular fluid and potassium of the blood at 28 d were reduced by supplementing Gln at 1% (P < 0.01). Broilers fed diets with Arg or Gln alone exhibited significantly greater WB incidence when compared to those fed the control (0% Gln and 0% Arg) or combined interaction levels of 1% Gln and 0.25% Arg (P < 0.05).ConclusionThese data demonstrated that Gln and Arg were able to reduce the incidence of WB when supplemented simultaneously as opposed to individually in broiler diets.

Mid-regional pro-atrial natriuretic peptide and the assessment of volaemic status and differential diagnosis of profound hyponatraemia.

Hyponatraemia is common and its differential diagnosis and consequent therapy management is challenging. The differential diagnosis is mainly based on the routine clinical assessment of volume status, which is often misleading. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is associated with extracellular and cardiac fluid volume. A total of 227 consecutive patients admitted to the emergency department with profound hypo-osmolar hyponatraemia (Na < 125 mmol L(-1) ) were included in this prospective multicentre observational study conducted in two tertiary centres in Switzerland. A standardized diagnostic evaluation of the underlying cause of hyponatraemia was performed, and an expert panel carefully evaluated volaemic status using clinical criteria. MR-proANP levels were compared between patients with hyponatraemia of different aetiologies and for assessment of volume status. MR-proANP levels were higher in patients with hypervolaemic hyponatraemia compared to patients with hypovolaemic or euvolaemic hyponatraemia (P = 0.0002). The area under the curve (AUC) to predict an excess of extracellular fluid volume, compared to euvolaemia, was 0.73 [95% confidence interval (CI) 0.62-0.84]. Additionally, in multivariate analysis, MR-proANP remained an independent predictor of excess extracellular fluid volume after adjustment for congestive heart failure (P = 0.012). MR-proANP predicted the syndrome of inappropriate antidiuresis (SIAD) versus hypovolaemic and hypervolaemic hyponatraemia with an AUC of 0.77 (95% CI 0.69-0.84). MR-proANP is associated with extracellular fluid volume in patients with hyponatraemia and remains an independent predictor of hypervolaemia after adjustment for congestive heart failure. MR-proANP may be a marker for discrimination between the SIAD and hypovolaemic or hypervolaemic hyponatraemia.

Extracellular hydration, cardiovascular risk, and the interstitium: a three-dimensional view

Volume expansion is a major contributor to poor cardiovascular outcomes in kidney disease. The relationship of extracellular volume (ECV) overload to cardiovascular changes in chronic kidney disease (CKD) remains speculative. Recent studies are challenging traditional concepts and providing new insight into mechanisms and the relationship of ECV to cardiovascular health. A dynamic role of the extracellular interstitium in inducing cardiovascular risk is emerging in CKD.

Heatstroke model for desert dry-heat environment and observed organ damage

BackgroundHeatstroke is one of the most common clinical emergencies. Heatstroke that occurred in a dry-heat environment such as desert is usually more seriously effective and often leads to death. However, the report of the pathophysiologic mechanisms about heatstroke in dry-heat environment of desert has not been seen. ObjectivesOur objectives are to establish a rat model of heatstroke of dry-heat environment of desert, to assess the different degrees of damage of organ, and to preliminarily discuss the mechanism of heatstroke in dry-heat environment of desert. MethodsThe first step, we have established a rat heatstroke model of dry heat environment of desert. The second step, we have accessed changes in morphology and blood indicators of heatstroke rats in dry-heat environment of desert. ResultsThe heatstroke rats have expressed the changing characteristics of mean arterial pressure, core temperature, and heart rate. The organ damage changed from mild to serious level, specifically in the morphology and blood enzymology parameters such as alanine aminotransferase, aspartate aminotransferase, creatinine, urea, uric acid, creatine kinase-MB, creatine kinase, and blood gas parameters such as base excess extracellular fluid and bicarbonate ions (HCO3−). ConclusionsWe have successfully established the rat heatstroke model of dry-heat environment of desert. We have identified heatstroke rats that presented changing characteristics on physiological indicators and varying degrees of organ damage, which are aggravated by the evolution of heatstroke in dry-heat environment of desert. We have preliminarily discussed the mechanism of heatstroke in dry-heat environment of desert.

Nephrotic syndrome complicated by idiopathic central diabetes insipidus

There is ongoing discussion regarding the mechanisms underlying edema formation in nephrotic syndrome (NS). Many studies published in the last decade reported that primary renal sodium retention was a major factor in edema formation. However, many of the factors influencing edema formation in NS remain unclear, including the role of arginine vasopressin (AVP). We report a 12-year-old boy with steroid-dependent NS complicated by idiopathic central diabetes insipidus (CDI). He did not develop edema during his first relapse of NS after developing CDI, despite having hypoalbuminemia. He had polydipsia, polyuria, low urine osmolality, and a low serum arginine AVP level. His fractional excretion of sodium was only slightly low. Endocrinological testing and magnetic resonance imaging revealed idiopathic CDI. After starting desmopressin therapy, he developed edema when his NS relapsed. This is the first known reported case of NS in a patient with CDI. The findings suggest that appropriate AVP secretion in response to an increase in serum osmolality caused by renal sodium retention is necessary for excess extracellular fluid accumulation in NS. Further investigation is needed to more fully understand the role of AVP in edema formation in NS.

Body Mass Index-Mortality Paradox in Hemodialysis: Can It Be Explained by Blood Pressure?

To the Editor: The recent article by Agarwal,1 which described an investigation of the association of the prevalence and control of blood pressure with obesity, concluded that leaner patients on dialysis had a higher prevalence of hypertension, poorer control of hypertension, a greater left ventricular mass index, and greater evidence of excess extracellular fluid volume. …

Diuretic use in renal disease

Diuretics are agents commonly used in diseases characterized by excess extracellular fluid, including chronic kidney disease, the nephrotic syndrome, cirrhosis and heart failure. Multiple diuretic classes, including thiazide-type diuretics, loop diuretics and K(+)-sparing diuretics, are used to treat patients with these diseases, either individually or as combination therapies. An understanding of what determines a patient's response to a diuretic is a prerequisite to the correct use of these drugs. The response of patients with these diseases to diuretics, which is related to the dose, is best described by a sigmoid curve whose contour can become distorted by any of the several sodium-retaining states that are directly or indirectly associated with renal disease. Diuretic actions are of considerable importance to patients who have renal disease, as their effective use assists in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia. Diuretic-related adverse events that involve the uric acid, Na(+) and K(+) axes are not uncommon; therefore the clinician must be vigilant in looking for biochemical disturbances. As a result of diuretic-related adverse events, clinicians must be resourceful in the dose amount and frequency of dosing.

Body Mass Index-Mortality Paradox in Hemodialysis

Unlike the general population, among hemodialysis patients body mass index (BMI) is related to blood pressure (BP) and mortality inversely. To explore the reasons for this risk-factor paradox, the cross-sectional association of obesity with the following factors was examined: the prevalence of hypertension, its control, and echocardiographic left ventricular mass index (LVMI). Longitudinal follow-up explored the relationship of BMI with all-cause mortality. Furthermore, it explored whether poorer survival in leaner individuals was related to either high BP or greater LVMI. Among 368 hemodialysis patients, both the prevalence of hypertension and its poor control were inversely related to BMI. BMI was also inversely associated with evidence of excess extracellular fluid volume, but adjustment for this variable did not completely remove the inverse relationship between BP and BMI. Over 1122 patient-years of cumulative follow-up (median: 2.7 years), 119 patients (32%) died. In the first 2 years of follow-up, the mortality hazard for the lowest BMI group was increased; thereafter, the survival curves were similar. Adjusting for several risk factors including BP and LVMI did not remove the inverse relationship of BMI with mortality. In conclusion, leaner patients on dialysis have a higher prevalence of hypertension, poorer control of hypertension, more LVMI, and greater evidence of extracellular fluid volume excess. However, volume explains the greater prevalence or poorer control of hypertension only partially. Leaner patients have an accelerated mortality rate in the first 2 years; this is not completely explained by BP, LVMI, or other cardiovascular or dialysis-specific risk factors.

Mapping the surface astrocytes of the optic disc: a fluid‐conducting role of the astrocytic covering of the central vessels

The vitreous interface of the optic nerve has been studied to delimit the covering of Elschnig's astrocytes and interstitial pathways of flow through the prelaminar region. Perfusion of the prelaminar tissue under controlled pressure with a fluorescent marker injected into the vitreous cavity in pig eyes. The prelaminar region of the optic nerve and adjacent retina was fixed and flatmounted or frozen and cryosectioned and examined with the confocal laser microscope. Samples were also prepared for conventional transmission electron microscopy. The surface of the vitreous surface of the optic nerve is covered by a cobblestone-like pavement made of astrocytic projections. Intensely stained passages of different thickness indicate the presence of wide interconnected intercellular spaces in the covering of Elschnig's astrocytes. Those passages are absent in the intervascular areas occupied by axons and axon-linked astrocytes. Delineation of the astrocytic pavement and the preferred flow routes formed by wide extracellular spaces are conspicuous features of the prelaminar region when examined with the confocal laser microscope and the help of sticky fluorescent tracer. This suggests that excess extracellular fluid can be interchanged with the vitreous by a network of interconnected extracellular spaces or preferred flow routes. Some pathogenic mechanisms can be related to fluid interchange in the optic nerve head.

Corneal Lymphangiogenesis: Implications in Immunity

The lymphatic system is a network of vessels throughout the body that serves to return lymphatic fluid to the systemic blood circulation and serves as the immune system's highway in the afferent limb of the immune response. This paper reviews the basics of structure, function and development of the lymphatic system. The emphasis is on understanding the role of lymphatics in the cornea as related to angiogenesis and the clinical setting of corneal transplant rejection. The lymphatic system has two main functions: to drain excess extracellular fluid from capillary beds to return to the systemic blood circulation and to capture antigen for presentation to the immune system in the lymphoid compartment (e.g. nodes) connected in parallel to the lymphatic system. The normal cornea is devoid of lymphatic vessels and blood vessels, thus allowing for its unique immune privileged status. Abnormal blood vessel growth into the cornea has been studied for many years, but the study of lymphatic vessels has been hampered until the recent discovery of lymphatic-specific markers. Subsequent studies of vascularized corneas support the presence of lymphatic vessels in the cornea. The growth of new lymphatic (lymphangiogenesis) and blood (hemangiogenesis) vessels in the cornea is closely related to the abrogation of the immune privileged status of the cornea. This review summarizes our current understanding of the parallel development of hemangiogenesis and lymphangiogenesis as related to the mechanisms of immune rejection of corneal transplants.

Hepatic Circulation

Hepatic Circulation

Toward the Promise of Renal Replacement Therapy

In this issue of JASN , Tumlin et al. [1][1] report results of a revolutionary phase 2 multicenter, randomized clinical trial comparing 72 h of continuous venovenous hemofiltration (CVVH) with and without a bioartificial kidney (referred to as a renal tubule assist device [RAD]) in the management of

Vasopressin administration facilitates fluid removal during hemodialysis

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

An increase in weight worsens the respiratory state and leads to intensive care unit re-admission

We investigated the reasons for intensive care unit (ICU) readmission of patients with acute respiratory failure. Of 88 patients re-admitted to our ICU over a 15-month period, 16 were suffering from acute respiratory failure. Body weight, blood gases, time without food during the initial ICU stay and excess extracellular fluid (∆ECF) were determined. The interval until ICU readmission (D) was defined as the time between the last day of the first admission and the first day of the second admission. Significant correlations were found among the values for D, ∆ECF and P/F ratio; a patient with a P/F ratio below 200 on the day of release from ICU and a ∆ECF over 3 kg was likely to return to the ICU within four days. Hence, we conclude that fluid-management failure may be associated with ICU readmission in acute respiratory failure patients.

In vivo EIS characterization of tumour tissue properties is dominated by excess extracellular fluid

Electrical impedance spectroscopy (EIS) is a non-ionizing, non-invasive technique which can be used to detect the presence of malignant tumours based on their electrical properties. Although it has been suggested that the edema which accompanies tumours strongly influences EIS tumour characterization, such information has not, until now, been documented in the literature. Growing intramuscular rodent tumours were imaged using magnetic resonance imaging (MRI) and EIS at several time points post-tumour implantation. The amount of edema associated with the tumours was calculated from the MRI images. Electrical parameters (resistivity, permittivity, fluid index ratio and peak frequency) were extracted from the EIS spectra. Taken together, the resulting electrical parameters strongly indicate that edema is the dominating pathological feature in EIS characterization and can at times conceal the presence of the tumour. Receiver operating characteristic analysis supports these findings.