Interstitial Fluid Accumulation Research Articles

Tolvaptan for Heart Failure Patients with Volume Overload

Edema is defined as a state of extracellular fluid accumulation, mostly of intercellular fluid, and clinically as a state where the subcutaneous tissues become enlarged because of the accumulation of interstitial fluid. Edema is often observed in daily clinical practice and the most serious causes include heart failure (HF), hepatic cirrhosis, and nephrotic syndrome. Patients with HF are often in a volume overload state because of the increases in extracellular volume, plasma volume, and blood volume; collectively, these disorders result in lower limb edema, jugular venous distension, hepatomegaly, and pulmonary congestion. In patients with HF, volume overload usually accounts for an increase in body weight of as much as 2–5 kg [1]. Volume overload in patients with heart diseases is generally called “cardiac edema”.

The lung at high altitude

The lung at high altitude

A prospective analysis of the incidence of postoperative lymphedema 1 to 2 years after surgery and axillary dissection in early breast cancer (BC) patients treated with concomitant irradiation and anthracyclines followed by paclitaxel.

e11059 Background: Lymphedema (LE), a debilitating complication after axillary dissection and irradiation, is caused by the accumulation of interstitial fluid of the affected arm due to a blockage ...

Myocardial microvascular permeability, interstitial oedema, and compromised cardiac function

The heart, perhaps more than any other organ, is exquisitely sensitive to increases in microvascular permeability and the accumulation of myocardial interstitial oedema fluid. Whereas some organs can cope with profound increases in the interstitial fluid volume or oedema formation without a compromise in function, heart function is significantly compromised with only a few percent increase in the interstitial fluid volume. This would be of little consequence if myocardial oedema were an uncommon pathology. On the contrary, myocardial oedema forms in response to many disease states as well as clinical interventions such as cardiopulmonary bypass and cardioplegic arrest common to many cardiothoracic surgical procedures. The heart's inability to function effectively in the presence of myocardial oedema is further confounded by the perplexing fact that the resolution of myocardial oedema does not restore normal cardiac function. We will attempt to provide some insight as to how microvascular permeability and myocardial oedema formation compromise cardiac function and discuss the acute changes that might take place in the myocardium to perpetuate compromised cardiac function following oedema resolution. We will also discuss compensatory changes in the interstitial matrix of the heart in response to chronic myocardial oedema and the role they play to optimize myocardial function during chronic oedemagenic disease.

Fluid Administration in Critically Ill Patients with Acute Kidney Injury

Physiologic end points for fluid resuscitation in septic shock patients with acute kidney injury (AKI) have been undertaken in randomized studies using the Early Goal-Directed Therapy (EGDT) approach. These studies have demonstrated a beneficial effect on in-hospital mortality with EGDT. The Saline versus Albumin Fluid Evaluation (SAFE) randomized study in critically ill patients demonstrated no difference in survival when saline versus albumin solutions were used for resuscitation. However, a benefit of albumin has been demonstrated in a randomized study on renal function and survival in cirrhotic patients with spontaneous bacterial periotonitis. On the other hand, recent observational studies have shown a correlation between fluid overload and mortality in AKI patients whether or not they necessitated dialysis. Moreover, the Adult Respiratory Distress Syndrome (ARDS) network performed a randomized study in critically ill patients to compare liberal versus conservative fluid administration. The liberal fluid administration group exhibited worse pulmonary function and no protection of renal function. Constancy of central venous pressure (CVP) measurements in the 12-mmHg range were observed in the liberal fluid group despite a mean increase in positive fluid balance of 7 L, thus suggesting increased interstitial fluid accumulation leading to pulmonary congestion. The review presented here discusses these various aspects of fluid administration in critically ill patients, particularly those with AKI, and indicates the potential deleterious effects of fluid overload on lung, heart, and kidney function that could contribute to increased mortality.

Cancer-related secondary lymphoedema due to cutaneous lymphangitis carcinomatosa: clinical presentations and review of literature

Lymphoedema is a clinical condition caused by impairment of the lymphatic system, leading to swelling of subcutaneous soft tissues. As a result, accumulation of protein-rich interstitial fluid and lymphostasis often causes additional swelling, fibrosis and adipose tissue hypertrophy leading to progressive morbidity and loss of quality of life for the patient. Lymphoedema can be distinguished as primary or secondary. Lymphoedema is a complication frequently encountered in patients treated for cancer, especially after lymphadenoectomy and/or radiotherapy based on destruction of lymphatics. However, although lymphatic impairment is sometimes caused by obstructive solid metastasis, we present three cases of secondary lymphoedema with minor dermatological features without detectable solid metastasis. Sometimes this type of lymphoedema is mistakenly called malignant lymphoedema. All patients were previously treated for cancer without clinical signs of recurrence, presented with progressive lymphoedema and minor dermatological features of unknown origin. Clinical and histopathological examination of the skin revealed diffuse lymphangitis carcinomatosa, leading to secondary lymphoedema and adjustment of the therapeutic approach and prognosis. We reviewed literature on these rare presentations of cancer recurrence and recommend, where appropriate, consulting a dermatologist when discrete skin abnormalities are seen in patients with a history of cancer and developing lymphoedema.

No evidence for interstitial lung oedema by extensive pulmonary function testing at 4,559 m

The aim of the present study was to better understand previously reported changes in lung function at high altitude. Comprehensive pulmonary function testing utilising body plethysmography and assessment of changes in closing volume were carried out at sea level and repeatedly over 2 days at high altitude (4,559 m) in 34 mountaineers. In subjects without high-altitude pulmonary oedema (HAPE), there was no significant difference in total lung capacity, forced vital capacity, closing volume and lung compliance between low and high altitude, whereas lung diffusing capacity for carbon monoxide increased at high altitude. Bronchoconstriction at high altitude could be excluded as the cause of changes in closing volume because there was no difference in airway resistance and bronchodilator responsiveness to salbutamol. There were no significant differences in these parameters between mountaineers with and without acute mountain sickness. Mild alveolar oedema on radiographs in HAPE was associated only with minor decreases in forced vital capacity, diffusing capacity and lung compliance and minor increases in closing volume. Comprehensive lung function testing provided no evidence of interstitial pulmonary oedema in mountaineers without HAPE during the first 2 days at 4,559 m. Data obtained in mountaineers with early mild HAPE suggest that these methods may not be sensitive enough for the detection of interstitial pulmonary fluid accumulation.

The Effect of Duration of Surgery on Fluid Balance During Abdominal Surgery: A Mathematical Model

There is controversy regarding which fluid management regimen provides the best postoperative outcome. Interstitial fluid accumulation may adversely affect postoperative outcome, but the effect of surgical duration on fluid balance is unknown. In this study, we used a mathematical model to describe fluid distribution. Previously published data from bioimpedance analysis in patients undergoing abdominal surgery were used to calculate changes to interstitial volume (DeltaV(IT), percent change relative to baseline) in uninjured and injured tissues. Ratios of DeltaV(IT) in uninjured and injured tissues at the end of surgery to total fluid volume infused during surgery (V(INF), mL/kg) were compared between surgeries of duration <3 h (n = 5) and > or = 3 h (n = 25). Critical values for change in plasma volume (DeltaV(PL), percent change relative to baseline) and DeltaV(IT), which give rise to adverse outcome, were calculated from previously published data on the physiological effects of IV fluid administration in healthy volunteers. Finally, simulated abdominal surgery in a 70 kg man for 1-8 h was used to determine the effect of crystalloid infusion rate between 2 and 30 mL x kg(-1) x h(-1) on DeltaV(PL) and DeltaV(IT). Fluid infusion rates that maintained DeltaV(PL) and DeltaV(IT) in uninjured tissue within critical values were then computationally determined as a function of duration of surgery. Bioimpedance data showed that the differences in DeltaV(IT)/V(INF) ratios between uninjured and injured tissues were significant only for surgical duration > or = 3 h (0.30 +/- 0.17% x kg/mL vs 1.55 +/- 0.73% x kg/mL, P < 0.0001). Differences of DeltaV(IT)/V(INF) ratios between surgical durations <3 and > or = 3 h were found only for injured tissue (0.45 +/- 0.35% x kg/mL vs 1.55 +/- 0.73% x kg/mL, P = 0.003). The range of fluid infusion rates required to maintain DeltaV(PL) and DeltaV(IT) within the critical values (>-15% and <20%, respectively) was wide for short-duration surgery (2-18.5 mL x kg(-1) x h(-1) for a 2 h-surgery), whereas it was narrow for long-duration surgery (5-8 mL x kg(-1) x h(-1) for a 6 h-surgery). Based on our model, it should be possible to increase the fluid infusion rate without significant interstitial edema for abdominal surgery of <3 h duration. However, our model predicts that restrictive fluid management should be used in abdominal surgery of >6 h duration to avoid excessive interstitial edema.

Pulmonary Complications After Acute Kidney Injury

The development of respiratory failure in patients with AKI is a particularly devastating consequence that greatly increases patient mortality. When respiratory failure and AKI occur together, the mortality is greater than 80%. A clear understanding of the mechanisms leading to respiratory failure is of great clinical relevance to patients with AKI in order to prevent and treat this life-threatening complication. Pulmonary edema leading to respiratory failure has been a recognized complication of kidney failure since 1901. Remarkably, the pathogenesis of this complication remains elusive, despite over 100 years of clinical and experimental debate in the literature. A review of this literature suggests that there are 4 causes of pulmonary edema leading to respiratory failure in patients with AKI: (1) volume overload (cardiogenic edema), (2) left ventricular dysfunction (cardiogenic edema), (3) increased lung capillary permeability (noncardiogenic edema), and (4) acute lung injury (noncardiogenic edema with inflammation). In this review, these mechanisms are presented in historical context including the original descriptions of pathology and pathophysiology, recent epidemiologic data, and experimental studies in animals. Although volume overload is a well-accepted mechanism of pulmonary edema in patients with AKI, the purpose of this review was to highlight the evidence showing that noncardiogenic edema and acute lung injury also occur. By recognizing that the pulmonary complications of AKI are not simply from volume overload, specific treatment strategies may be discovered and used to improve outcomes in patients with the ominous and life threatening combination of AKI and respiratory failure.

Acute edema blisters in a hereditary angioedema cutaneous attack

Hereditary angioedema is a rare autosomal dominant disease characterized by recurrent episodes of acute edema affecting the skin and the respiratory and digestive tracts. Acute edema blisters or hydro-static bullae develop after rapid accumulation of interstitial fluid usually associated to cardiac insufficiency. Lesions contain sterile fluid and break up easily resolving without scars. Blisters disappear when fluid accumulation resolves. We describe a patient developing recurrent acute edema blisters as a consequence of cutaneous hereditary angioedema attacks.

LONG-TERM EFFECTS OF A SHORT PERIOD OF MODERATELY HIGH TESTICULAR TEMPERATURES ON RAT SPERMATOGENESIS

Rats were exposed either to artificial hemicryptorchidism lasting 48 hr, or to heat treatment of both testicles to 43 °C for 30 min and the effects were followed for 175 days after treatment. Already, 3 weeks after treatment there was a 40 % decrease in the weight of the previously cryptorchid testes, and 65 % in the heat treated testes. Remarkably, between 3 weeks and 175 days there was no recovery. In sections of testes at 175 days, in the previously cryptorchid testes there was a mixture of tubules with normal full spermatogenesis and tubules with only very few germ cells. On the average 73 % of the tubules showed full spermatogenesis but in the rest, spermatogenesis was severely compromised. The short time period of heating of the testis appeared to have even more severe longterm effects than two days of cryptorchidism. In these rats, some seminiferous tubules with full spermatogenesis were found in the testes of only one of 3 rats. Interestingly, the morphological picture of spermatogenesis in the affected tubules in previously cryptorchid rat testes and heat treated rat testes was comparable. In the affected tubules in both situations on the average about 30% of the tubule cross sections contained no germ cells, while the most advanced cells were A spermatogonia in another 30%, B spermatogonia or preleptotene spermatocytes in 20% and in 20% of the tubules more advanced cells than preleptotenes were seen, including some occasional spermatids. These data indicate that there was not an arrest in the differentiation of the germ cells. Apparently, the effects of a shortterm cryptorchidism or heat treatment do not evoke a recovery reaction, for example by way of enhanced self-renewal and proliferation of stem cells as occurs shortly after irradiation. To establish whether spermatogenesis in the tubules with full spermatogenesis in the previously cryptorchid testes was completely normal, cell counts were carried. There was a highly significant 30% decrease in the number of A spermatogonia in epithelial stage VIII compared to the contralateral untreated testis. However, probably through less apoptosis of A2–A4 spermatogonia because of the low spermatogonial density, the numbers of preleptotenes were similar to those in the controls. Testosterone levels in testis vein blood plasma were higher in heated testes, but lower than control in testes which had been cryptorchid, while peripheral levels were lower in the previously cryptorchid rats but similar to controls after heating. After radiation, longterm disruption of spermatogenesis appears to be different, and has been attributed to spermatogonial arrest due to high testosterone levels and/or accumulation of interstitial extracellular fluid, but high testosterone levels do not appear to be involved in the changes following previous cryptorchidism. The morphological effects of shortterm high testicular temperatures are reminiscent of what can regularly be seen in testis biopsies of infertile human patients. Tubules showing only Sertoli cells or poor spermatogenesis together with an island of tubules with normal spermatogenesis are not uncommon. The possibility of heat-induced damage in these cases should be studied. Furthermore, shortterm cryptorchid rats and rats which received a shortterm testicular heat treatment may be a good model to find ways to stimulate spermatogenesis when the epithelium itself does not initiate recovery mechanisms. (poster)

Visual Loss after Spinal Surgery

Visual Loss after Spinal Surgery

No Correlation between Pulmonary Artery Pressure and Markers of Pulmonary Interstitial Fluid Accumulation at Altitude

PURPOSE: A previous study yielded indirect evidence by changes in closing volume that “subclinical” high altitude pulmonary edema (HAPE) occurs in a large number of mountaineers after ascent to 4559 m. Since an abnormal increase of pulmonary artery pressure (PAP) in hypoxic environment is the key mechanism of pulmonary fluid accumulation, we hypothesized that markers of interstitial pulmonary fluid accumulation correlate with the increase in PAP at high altitude. METHODS: We therefore performed pulmonary function testing by body plethysmography and measured lung compliance by oesophageal pressure measurements and systolic PAP by echocardiography in 34 healthy subjects at baseline at low altitude (LA) and after rapid ascent to 4559 m. Measurements at high altitude (HA) were performed 2–4 h (HA1), 20 h (HA2) and 44 h (HA3) after arrival at 4559 m. RESULTS: HAPE was diagnosed by clinical examination and chest x-ray in 4 subjects, which were excluded from the further analysis presented here. Pulmonary function testing showed normal values for all subjects at LA and there were no differences for the whole group in measurements at high altitude for total lung capacity, vital capacity, diffusion capacity, closing volume and dynamic or static compliance. PAP also was normal in all subjects at LA (22 ± 4 mmHg) and significantly increased by 16 ± 8 (HA1), 14 ± 6 (HA2) and 12 ± 6 (HA3), respectively (p<0.001). Maximum values of systolic PAP at high altitude varied from 30 to 60 mmHg between subjects. There was no correlation in any parameter of pulmonary function testing with the increase in systolic PAP. CONCLUSIONS: In contrast to previous studies we found that lung volumes, diffusion capacity, closing volume, and pulmonary compliance are unchanged at high altitude, which indicates that no relevant interstitial fluid accumulation occurred in our subjects despite a wide range in elevation of PAP. The lack of correlation of systolic PAP and decrements in pulmonary function parameters is evidence against the claim that the majority of climbers ascending to altitudes in the range of 4000 to 5000 meters develop subclinical HAPE.

Pathogenetic role of myelitis for syringomyelia

Background CSF-flow obstruction is regarded as a mandatory factor for the development of syringomyelia. However, there are conditions in which syringomyelia is not associated with evident persistent CSF-flow obstruction, as in the case of inflammatory spinal cord lesions. In these instances we hypothesize that the accumulation of vasogenic edema may play a role in the development of the syrinx. Recently proposed theories underline, even in the event of CSF-flow obstructions, a major role for the accumulation and final coalescence of interstitial spinal fluid, rather than CSF penetration through the spinal cord. Aim To clarify the relationship between syrinx development and spinal cord inflammation, through the analysis of the role of intrinsic medullary factors versus CSF-flow block. Methods A prospective case series including patients with transient syringomyelia associated with different examples of non-infectious myelitis: sarcoidosis, post-infectious transverse myelitis, Devic's disease and multiple sclerosis. Cavitations resulting from cystic myelomalacia were excluded. CSF-flow block was assessed by structural MRI. Results Syringes associated with myelitis shared some common features: they developed during the acute phase of myelitis and disappeared after steroids, were all non-communicating cavitations involving the central canal, and occurred in the same spinal segment affected by myelitis. CSF-flow obstruction was detected in one patient (Chiari I malformation), while in the other three patients we could not detect anatomical predispositions. Conclusion Only one patient had structural abnormalities, though without evidence of a pathogenetic role in itself: however, CSF space obstruction and reduced CSF compliance could have accelerated the development of syringomyelia triggered by intramedullary inflammation. The clinical and radiological features in this patient are consistent with the label “presyringomyelia”. The absence of any anatomical predisposition in the other patients suggests a major pathophysiological role for intrinsic medullary mechanisms, including blood–spinal cord barrier breakdown, impairment of extracellular fluid drainage, and leakage of subarachnoidal CSF into the nervous tissue.

Do Changes in Lung Function Predict High-Altitude Pulmonary Edema at an Early Stage?

Ascent to high altitude is associated with alterations in lung function. The mechanisms of these changes and whether they reflect early stages of high-altitude pulmonary edema (HAPE) has been debated. Therefore, we investigated the time course of pulmonary function in relation to hemodynamics and clinical symptoms in mountaineers ascending rapidly to high altitude. In 26 unacclimatized subjects we assessed spirometry, single-breath nitrogen washout, diffusing capacity (DLCO), and Doppler echocardiography in Zurich, 490 m, after climbing within 24 h to Monte Rosa, 4559 m, and after one night at 4559 m. Mean (+/- SD) FVC fell from 103 +/- 9% predicted in Zurich to 96 +/- 10% predicted at 4559 m, FEV1/FVC increased from 0.82 +/- 0.06 to 0.84 +/- 0.08, and closing volume increased from 0.35 +/- 0.14 to 0.44 +/- 0.11 L above residual volume (P < 0.05, all changes). On the following day at 4559 m, closing volume remained elevated in 9 of 21 subjects who had a lower DLCO but similar pulmonary artery systolic pressures compared with the remaining 12 subjects (40 +/- 8 vs 43 +/- 7 mm Hg, P = NS). None of the subjects had overt HAPE. We conclude that changes in pulmonary function after rapid ascent to high altitude were consistent with interstitial fluid accumulation, but they were not related to changes in pulmonary artery pressure. Individual lung function responses to high-altitude exposure varied largely and did not predict subsequent HAPE.

In Vivo Monitoring of Cutaneous Edema using Spectral Imaging in the Visible and Near Infrared

Tissue inflammation is often accompanied by local interstitial fluid accumulation expressed as edema. Edema can be the manifestation of infection, lymphatic blockage, wound healing, or even cancer, and is typically graded visually. Here we demonstrate that the edema reaction can be objectively quantitated in vivo by the use of spectral imaging. To this end we applied the method on a histamine-induced cutaneous edema model. Apparent concentrations of oxy-hemoglobin, deoxy-hemoglobin, and water were calculated for each pixel of a spectral image stack. These values were used to construct concentration maps for each of these molecules as well as an intensity map of an optical tissue-scattering parameter. The oxy-hemoglobin and the tissue water maps are two-dimensional quantitative representations of the skin areas involved in erythema and edema, respectively. These maps demonstrated characteristics of the wheal-and-flare reaction and their gray-level intensities were dependent on the applied histamine dose. We conclude that spectral imaging can be a valuable noninvasive tool in the study of edema pathology and can be used to monitor the edema reaction in vivo or follow the efficacy of treatments in a clinical setting.

Strategic Leukofiltration in Cardiac Surgery

Systemic inflammatory response syndrome (SIRS) with activation of molecular cascades, cell activation, accumulation of interstitial fluid, organ dysfunction and, occasionally, organ failure is still a commonly recognized consequence of cardiac surgery. SIRS leads to costly complications and several strategies intended to ameliorate the symptoms that have been studied, including leukocyte reduction, using filtration. Although, the body of work suggests that leukoreduction attenuates SIRS, discrepancies remain within the literature. The recent literature is reviewed highlighting the areas where concordance is lacking. In our study, on the basis of indirect indicators of SIRS, platelet function by thromboelastography biomaterial evaluation by light and scanning electron microscopy, we present our conclusions regarding clinical outcomes and the role of leukofiltration.

Ultrasound: a reproducible method to measure conduit vein compliance

Classical venous occlusion plethysmography (VOP) of the leg, often used to assess venous compliance, measures properties of the whole calf, including volume changes at the arterial side and the interstitial fluid accumulation that occurs as a result of the enhanced capillary pressure during venous occlusion. We present an ultrasound technique to measure the compliance of one major conduit vein in the leg. Ultrasound measurements of the popliteal vein were compared with classical VOP measurements, which were performed simultaneously in one subject. Six healthy individuals were measured on three occasions to assess short- and long-term reproducibility of the measurements. Six motor complete spinal cord-injured (SCI) individuals were included to compare venous compliance in subjects with known pathological changes of the venous system with controls. The ultrasound and VOP measurements of venous compliance correlated significantly (r(2) = 0.39, P = 0.001). Ultrasound provides reproducible measurements with short- and long-term coefficients of variation ranging from 10 to 15% for popliteal vein compliance and from 2 to 9% for absolute diameters at the different venous pressure steps. In addition, by using ultrasound, we were able to detect an 80% reduction in the compliance of the popliteal vein in SCI individuals compared with controls (P < 0.01). In conclusion, ultrasound is a suitable and reproducible method to measure conduit vein compliance and provides the possibility to specifically assess compliance of one vein instead of the whole calf.

Characteristics of lymphatic endothelial cells in physiological and pathological conditions.

Impairment of lymphatic structure and function, e.g., inadequate endothelial permeability and intercellular openings, abnormal lymphangiogenesis and overexpression for immunoreactive agents, will result in tumor metastasis, autoimmune response alteration and accumulation of interstitial fluid and proteins. Recently, several novel molecules have been identified that allow a more precise distinction between lymphatic and blood vascular endothelium. The differences in expression of endothelial markers on the lymphatic vessel strongly suggest the possibility that there will be important divergence in the differentiating and regenerating responses in lymphatic behavior to various pathological processes. Undoubtfully, molecular techniques would also lead to the definition of unique markers found on lymphatic endothelial cells (LECs) in lymphatic-associated diseases which are mostly involved in lymphangiogenesis. This review is mainly concentrated on the characteristics of LECs in diabetes, wound healing, lymphedema and tumor, especially in the experimental models that have offered insight into the LEC role in these diseases affecting the lymphatic system. Increased knowledge of the molecular signaling pathways driving lymphatic development and lymphangiogenesis should boost the impact of therapeutics on the diseases. Although the field about the mechanisms that control the formation and lineage-specific differentiation and function of lymphatic vessels has experienced rapid progress in the past few years, an understanding of the basis of the differences and their implications in the pathological conditions will require much more investigation.

Radiologische Differentialdiagnose des Lungenödems

The most common causes of pulmonary edema are cardiac failure, renal failure and injury edema (diffuse alveolar damage). The injury edema typically shows airspace consolidation due to exsudation of fluid in the periphery of the lung with air bronchograms, no interstitial fluid accumulation can be found and only rarely pleural effusions are present. Cardiac and renal edemas often show a mixed interstitial and alveolar transudation without air bronchograms. Pleural effusions are often present. Both usually have an increased heart-size and an increased vascular pedicle width. To distinguish them better one has to look at the distribution of the pulmonary edema: The cardiac edema typically shows a gravitational and the renal edema a central distribution.