Biology of Lymphedema Brix, Bianca; Sery, Omar; Onorato, Alberto ...
Biology,
03/2021, Letnik:
10, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This narrative review portrays the lymphatic system, a poorly understood but important physiological system. While several reviews have been published that are related to the biology of the lymphatic ...system and lymphedema, the physiological alternations, which arise due to disturbances of this system, and during lymphedema therapy, are poorly understood and, consequently, not widely reported. We present an inclusive collection of evidence from the scientific literature reflecting important developments in lymphedema research over the last few decades. This review aims at advancing the knowledge on the area of lymphatic system function as well as how system dysfunction, as seen in lymphedema, affects physiological systems and how lymphedema therapy modulates these mechanisms. We propose that future studies should aim at investigating, in-detail, aspects that are related to fluid regulation, hemodynamic responses, and endothelial and/or vascular changes due to lymphedema and lymphedema therapy.
Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus ...erythematosus, systemic sclerosis, and Sjögren’s syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main underlying cause of cardiovascular diseases. Currently, because of finding macrophages and lymphocytes at the atheroma, atherosclerosis is considered a chronic immune-inflammatory disease. In active inflammation, the liberation of inflammatory mediators such as tumor necrotic factor alpha (TNFa), interleukine-6 (IL-6), IL-1 and other factors like T and B cells, play a major role in the atheroma formation. In addition, antioxidized, low-density lipoprotein (LDL) antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF) are higher in the atherosclerotic patients. Traditional risk factors like gender, age, hypercholesterolemia, smoking, diabetes mellitus, and hypertension, however, do not alone explain the risk of atherosclerosis present in autoimmune diseases. This review examines the role of chronic inflammation in the etiology—and progression—of atherosclerosis in autoimmune rheumatic diseases. In addition, discussed here in detail are the possible effects of autoimmune rheumatic diseases that can affect vascular function. We present here the current findings from studies that assessed vascular function changes using state-of-the-art techniques and innovative endothelial function biomarkers.
We investigated changes in volume regulating hormones and renal function at high altitudes and across gender.
Included in this study were 28 subjects (n = 20 males; n = 8 females. ages: 19 - 65 yrs), ...who ascended to a height of 3440m (HA1), on the 3rd day and to 5050m (HA2), on the 14th day. Plasma and urinary creatinine and urinary osmolality as well as plasma levels of plasma renin activity (PRA), Aldosterone, antidiuretic hormone (ADH), and atrial natriuretic peptide (ANP) were measured. The plasma volume loss (PVL) was estimated from plasma density and hematocrit. Glomerular filtration rate (GFR) was measured based on nocturnal (9 hour) creatinine clearance; this was compared with various methods for estimation of GFR.
The mean 24-hour urine production increased significantly in both sexes across the expedition. But PVL reached significance only in males. No changes in Na+ in plasma, urine or its fractional excretion were seen at both altitudes. Urinary osmolality decreased upon ascent to the higher altitudes. ADH and PRA decreased significantly at both altitudes in males but only at HA2 in females. However, no changes in aldosterone were seen across the sexes and at different altitudes. ANP increased significantly only in males during the expedition. GFR, derived from 9-h creatinine clearance (CreaCl), decreased in both sexes at HA1 but remained stable at HA2. Conventional Creap-based GFR estimates (eGFR) showed only poor correlation to CreaCl.
We report details of changes in hormonal patterns across high altitude sojourn. To our knowledge we are not aware of any study that has examined these hormones in same subjects and across gender during high altitude sojourn. Our results also suggest that depending on the estimation formula used, eGFR underestimated the observed decrease in renal function measured by CreaCl, thus opening the debate regarding the use of estimated glomerular filtration rates at high altitudes.
To determine whether there are differences in autonomic nervous system function in early- versus late-onset preeclampsia.
Matched case-control study. Cases were defined as singleton pregnancies with ...preeclampsia at < 34+0 weeks of gestation (early-onset preeclampsia) and ≥ 34+0 weeks of gestation (late-onset preeclampsia). For each case in each of the preeclampsia subgroups, three "control"uncomplicated singleton pregnancies were matched by maternal age, height, and week of gestation. Blood pressure and heart rate were measured continuously for 30 minutes in each participant. Baroreceptor reflex sensitivity (assessed using sequence technique), time and frequency domain heart rate variability measures, as SDNN, RMSSD, LFRRI, HFRRI and LF/HFRRI of R-R intervals, were compared between groups (p<0.05 significant).
24 women with preeclampsia (10 with early-onset and 14 with late-onset preeclampsia) and 72 controls were included in the study. SDNN, RMSSD and HFRRI were significantly higher in the late-onset preeclampsia group compared to gestational age matched controls (p = 0.033, p = 0.002 and p = 0.018, respectively). No significant differences in SDNN RMSSD and HFRRI between early-onset preeclampsia group and gestational age matched controls were observed (p = 0.304, p = 0.325 and p = 0.824, respectively). Similarly, baroreceptor reflex sensitivity was higher in late-onset preeclampsia compared to controls at ≥ 34 weeks (p = 0.037), but not different between early-onset preeclampsia compared to controls at < 34 weeks (p = 0.50).
Heart rate variability and baroreceptor reflex sensitivity are increased in late- but not early-onset preeclampsia compared to healthy pregnancies. This indicates a better autonomic nervous system mediated adaptation to preeclampsia related cardiovascular changes in late-onset disease.
Background: The etiology of autoimmune rheumatic diseases is unknown. Endothelial dysfunction and premature atherosclerosis are commonly seen in these patients. Atherosclerosis is considered one of ...the main causes of cardiovascular diseases. Hypertension is considered the most important traditional cardiovascular risk. This case-control study aimed to investigate the relationship between autoimmune diseases and cardiovascular risk. Methods: This study was carried out in patients with rheumatoid arthritis, RA (n = 10), primary Sjögren syndrome, PSS (n = 10), and healthy controls (n = 10). Mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse wave velocity (PWV, an indicator of arterial stiffness) were assessed via a Vicorder device. Asymmetric dimethylarginine (ADMA) was measured via ELISA. Retinal photos were taken via a CR-2 retinal camera, and retinal microvasculature analysis was carried out. T-tests were conducted to compare the disease and control groups. ANOVA and ANOVA—ANCOVA were also used for the correction of covariates. Results: A high prevalence of hypertension was seen in RA (80% of cases) and PSS (40% of cases) compared to controls (only 20% of cases). Significant changes were seen in MBP (RA 101 ± 11 mmHg; PSS 93 ± 10 mm Hg vs. controls 88 ± 7 mmHg, p = 0.010), SBP (148 ± 16 mmHg in RA vs. 135 ± 16 mmHg in PSS vs. 128 ± 11 mmHg in control group; p = 0.007), DBP (77 ± 8 mmHg in RA, 72 ± 8 mmHg in PSS vs. 67 ± 6 mmHg in control; p = 0.010 in RA compared to the controls). Patients with PSS showed no significant difference as compared to controls (MBP: p = 0.240, SBP: p = 0.340, DBP: p = 0.190). Increased plasma ADMA was seen in RA (0.45 ± 0.069 ng/mL) and PSS (0.43 ± 0.060 ng/mL) patients as compared to controls (0.38 ± 0.059 ng/mL). ADMA in RA vs. control was statistically significant (p = 0.022). However, no differences were seen in ADMA in PSS vs. controls. PWV and retinal microvasculature did not differ across the three groups. Conclusions: The prevalence of hypertension in our cohort was very high. Similarly, signs of endothelial dysfunction were seen in autoimmune rheumatic diseases. As hypertension and endothelial dysfunction are important contributing risk factors for cardiovascular diseases, the association of hypertension and endothelial dysfunction should be monitored closely in autoimmune diseases.
Background: Lymphedema arises due to a malfunction of the lymphatic system, leading to extensive tissue swelling. Complete decongestive therapy (CDT), which is a physical therapy lasting for 3 weeks ...and includes manual lymphatic drainages (MLD), leads to fluid mobilization and increases in plasma volume. Here, we investigated hemodynamic responses induced by these fluid shifts due to CDT and MLD. Methods: Hemodynamic parameters were assessed continuously during a sit-to-stand test (5 min baseline, 5 min of standing, and 5 min of recovery). This intervention was repeated on days 1, 2, 7, 14, and 21 of CDT, before and after MLD. Volume regulatory hormones were assessed in plasma samples. Results: A total number of 13 patients took part in this investigation. Resting diastolic blood pressure significantly decreased over three weeks of CDT (p = 0.048). No changes in baseline values were shown due to MLD. However, MLD led to a significant decrease in heart rate during orthostatic loading over all epochs on therapy day 14, as well as day 21. Volume regulatory hormones did not show changes over lymphedema therapy. Conclusion: We did not observe any signs of orthostatic hypotension at rest, as well as during to CDT, indicating that lymphedema patients do not display an elevated risk of orthostatic intolerance. Although baseline hemodynamics were not affected, MLD has shown to have potential beneficial effects on hemodynamic responses to a sit-to-stand test in patients undergoing lymphedema therapy.
Lower body negative pressure (LBNP) application simulates hemorrhage. We investigated how seasons affect coagulation values at rest and during LBNP. Healthy participants were tested in cold ...(November–April) and warm (May–October) months. Following a 30-min supine period, LBNP was started at −10 mmHg and increased by −10 mmHg every five minutes until a maximum of −40 mmHg. Recovery was for 10 min. Blood was collected at baseline, end of LBNP, and end of recovery. Hemostatic profiling included standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and thrombin formation markers. Seven men (25.0 ± 3.6 years, 79.7 ± 7.8 kg weight, 182.4 ± 3.3 cm height, and 23.8 ± 2.3 kg/m2 BMI) and six women (25.0 ± 2.4 years, 61.0 ± 8.4 kg weight, 167 ± 4.7 cm height, and 21.8 ± 2.4 kg/m2 BMI) participated. Baseline levels of prothrombin (FII), tissue factor (TF) and markers for thrombin generation F1+2 and the thrombin/antithrombin complex (TAT) were higher during summer. Factor VIII, prothrombin fragment 1+2 (F1+2), TAT and the coagulation time showed significant increases during LBNP in both seasons. Some calibrated automated thrombography variables (Calibrated automated thrombography (CAT): lag, time to peak (ttPeak), peak) shifted in a procoagulant direction during LBNP in summer. Red blood cell counts (RBC), hemoglobin and white blood cell counts (WBC) decreased during LBNP. LBNP application reduced prothrombin time in winter and activated partial thromboplastin time in summer. Greater levels of FII, TF, F1+2, and TAT—a more pronounced LBNP-induced procoagulative effect, especially in CAT parameters (lag time (LT), Peak, ttPeak, Velindex)—were seen in summer. These results could have substantial medical implications.
Galanin and adrenomedullin plasma responses to head-up tilt and lower body negative pressure have been studied previously. However, to what extent short-arm human centrifugation (SAHC) affects these ...responses is not known. In this study, we assessed how the application of variable gradients of accelerations (
) via shifting of the rotation axis during centrifugation affects selected hormonal responses. Specifically, we tested the hypothesis, that
(participants in whom at least one of the pre-defined criteria for presyncope was fulfilled)
(participants who completed the entire protocol in both sessions)
Twenty healthy subjects (10 women and 10 men) were exposed to two g-levels 1 G
and 2.4 G
at the feet (G
) in two positions (axis of rotation placed above the head and axis of rotation placed at the heart level). Elevated baseline levels of galanin appeared to predict orthostatic tolerance (
= 0.054) and seemed to support good orthostatic tolerance during 1 G
SAHC (
= 0.034). In finishers, 2.4 G
SAHC was associated with increased galanin levels after centrifugation (
= 0.007). For adrenomedullin, the hypothesized increases were observed after centrifugation at 1 G
(
= 0.031), but not at 2.4 G
, suggesting that other central mechanisms than local distribution of adrenomedullin predominate when coping with central hypovolemia induced by SAHC (
> 0.14). In conclusion, baseline galanin levels could potentially be used to predict development of presyncope in subjects. Furthermore, galanin levels increase during elevated levels of central hypovolemia and galanin responses appear to be important for coping with such challenges. Adrenomedullin release depends on degree of central hypovolemia induced fluid shifts and a subject's ability to cope with such challenges. Our results suggest that the gradient of acceleration (
) is an innovative approach to quantify the grade of central hypovolemia and to assess neurohormonal responses in those that can tolerate (
) or not tolerate (
) artificial gravity (AG). As AG is being considered as a preventing tool for spaceflight induced deconditioning in future missions, understanding effects of AG on hormonal responses in subjects who develop presyncope is important.
Complete decongestive therapy (CDT), a physical therapy including manual lymphatic drainage (MLD) and compression bandaging, is aimed at mobilizing fluid and reducing limb volume in lymphedema ...patients. Details of fluid shifts occurring in response to CDT are currently not well studied. Therefore, we investigated fluid shifts before, during and after CDT. Thirteen patients (3 males and 10 females, aged 57 ± 8.0 years, 167.2 ± 8.3 cm height, 91.0 ± 23.4 kg weight) diagnosed with stage II leg lymphedema participated. Leg volume, limb and whole-body fluid composition (total body water (limbTBW/%TBW), extracellular (limbECF/%ECF) and intracellular (limbICF/%ICF fluid), as well as ECF/ICF and limbECF/limbICF ratios were determined using perometry and bioelectrical impedance spectroscopy. Plasma volume, proteins, osmolality, oncotic pressure and electrolytes were assessed. Leg volume (p < 0.001), limbECF (p = 0.041), limbICF (p = 0.005) and limbECF/limbICF decreased over CDT. Total leg volume and limbTBW were correlated (r = 0.635). %TBW (p = 0.001) and %ECF (p = 0.007) decreased over time. The maximum effects were seen within one week of CDT. LimbICF (p = 0.017), %TBW (p = 0.009) and %ICF (p = 0.003) increased post-MLD, whereas ECF/ICF decreased due to MLD. Plasma volume increased by 1.5% post-MLD, as well as albumin and the albumin-to-globulin ratio (p = 0.005 and p = 0.049, respectively). Our results indicate that physical therapy leads to fluid shifts in lymphedema patients, with the greatest effects occurring within one week of therapy. Fluid shifts due to physical therapy were also reflected in increased plasma volume and plasma protein concentrations. Perometry, in contrast to bioelectrical impedance analysis, does not seem to be sensitive enough to detect small fluid changes caused by manual lymphatic drainage.
PDF
