scholarly journals Secondary lymphedema: Pathogenesis

2021 ◽  
Vol 3 ◽  
pp. 7-15
Author(s):  
Smitha Ancy Varghese
Keyword(s):  
Interstitial Fluid ◽  
Molecular Mechanisms ◽  
Subcutaneous Tissue ◽  
Lymphatic Vessels ◽  
Therapeutic Interventions ◽  
Elastic Fibers ◽  
Therapeutic Approaches ◽  
Secondary Lymphedema ◽  
Common Causes ◽  
The Common

Secondary lymphedema follows an acquired defect in the lymphatic system. The common causes leading to a defective lymphatic function include infection, inflammation, malignancy, trauma, obesity, immobility, and therapeutic interventions. Understanding the pathogenesis of lymphedema is of prime importance in offering effective treatment. The pathogenetic mechanisms such as lymphatic valvular insufficiency, obliteration/ disruption of lymphatic vessels, and decreased lymphatic contractility aggravate lymphatic hypertension and lymphstasis. Accumulation of lymph, interstitial fluid, proteins, and glycosaminoglycans within the skin and subcutaneous tissue eventually stimulates collagen production by fibroblasts, causes disruption of elastic fibers, and activates keratinocytes, fibroblasts, and adipocytes. These result in thickening of skin and cause fibrosis of subcutaneous tissue. However, the sequence of these pathomechanisms, their inter-relationship and progression vary depending on the specific etiology of the lymphedema. In this article, we discuss the possible cellular and molecular mechanisms involved in the pathogenesis. Further studies to delineate the exact sequence of pathogenic processes surrounding the primary triggering event can help to formulate tailored therapeutic approaches.

scholarly journals Secondary lymphedema: Pathogenesis

2021 ◽  
Vol 3 ◽  
pp. 7-15
Author(s):  
Smitha Ancy Varghese
Keyword(s):  
Interstitial Fluid ◽  
Molecular Mechanisms ◽  
Subcutaneous Tissue ◽  
Lymphatic Vessels ◽  
Therapeutic Interventions ◽  
Elastic Fibers ◽  
Therapeutic Approaches ◽  
Secondary Lymphedema ◽  
Common Causes ◽  
The Common

Secondary lymphedema follows an acquired defect in the lymphatic system. The common causes leading to a defective lymphatic function include infection, inflammation, malignancy, trauma, obesity, immobility, and therapeutic interventions. Understanding the pathogenesis of lymphedema is of prime importance in offering effective treatment. The pathogenetic mechanisms such as lymphatic valvular insufficiency, obliteration/ disruption of lymphatic vessels, and decreased lymphatic contractility aggravate lymphatic hypertension and lymphstasis. Accumulation of lymph, interstitial fluid, proteins, and glycosaminoglycans within the skin and subcutaneous tissue eventually stimulates collagen production by fibroblasts, causes disruption of elastic fibers, and activates keratinocytes, fibroblasts, and adipocytes. These result in thickening of skin and cause fibrosis of subcutaneous tissue. However, the sequence of these pathomechanisms, their inter-relationship and progression vary depending on the specific etiology of the lymphedema. In this article, we discuss the possible cellular and molecular mechanisms involved in the pathogenesis. Further studies to delineate the exact sequence of pathogenic processes surrounding the primary triggering event can help to formulate tailored therapeutic approaches.

scholarly journals Lymphedema: Anatomy, Physiology and Pathogenesis

1997 ◽  
Vol 2 (4) ◽  
pp. 321-326 ◽  
Author(s):  
Andrzej Szuba ◽  
Stanley G Rockson
Keyword(s):  
Lymph Nodes ◽  
Interstitial Fluid ◽  
Subcutaneous Tissue ◽  
Lymphatic Vessels ◽  
Lymphatic Transport ◽  
Elastic Fibers ◽  
Regional Lymph Nodes ◽  
External Compression ◽  
Suction Force ◽  
Anatomy And Physiology

The authors review the current understanding of lymphatic anatomy and physiology, and the pathophysiology of lymphedema. The skin lymphatic system consists of the initial lymphatics, which converge into lymphatic precollectors, collectors and lymphatic ducts; these in turn convey the lymph to the regional lymph nodes. Interstitial fluid and particles enter the initial lymphatics through interendothelial openings and by vesicular transport. Lymphatic uptake is enhanced by external compression. Lymphatic transport depends greatly on contraction of lymphangions, which generate the suction force that promotes absorption of interstitial fluid and expels lymph to collecting ducts. In lymphedema, various types of congenital and acquired abnormalities of lymphatic vessels and lymph nodes have been observed. These often lead to lymphatic hypertension, valvular insufficiency and lymphostasis. Accumulation of interstitial and lymphatic fluid within the skin and subcutaneous tissue stimulates fibroblasts, keratinocytes and adipocytes eventuating in the deposition of collagen and glycosaminoglycans within the skin and subcutaneous tissue together with skin hypertrophy and destruction of elastic fibers.

scholarly journals Lymphatic system and adipose tissue: Crosstalk in health and disease

2021 ◽  
Vol 18 (3) ◽  
pp. 336-344
Author(s):  
V. V. Klimontov ◽  
D. M. Bulumbaeva
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Inflammatory Cells ◽  
The Body ◽  
Push Button ◽  
Secondary Lymphedema

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

scholarly journals Crosstalk Between microRNAs and the Pathological Features of Secondary Lymphedema

2021 ◽  
Vol 9 ◽  
Author(s):  
Khairunnisa’ Md Yusof ◽  
Kira Groen ◽  
Rozita Rosli ◽  
Kelly A. Avery-Kiejda
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lymphatic Vessels ◽  
Pathological Features ◽  
Secondary Lymphedema ◽  
Immune System Dysfunction ◽  
Lymphatic Fluid

Secondary lymphedema is characterized by lymphatic fluid retention and subsequent tissue swelling in one or both limbs that can lead to decreased quality of life. It often arises after loss, obstruction, or blockage of lymphatic vessels due to multifactorial modalities, such as lymphatic insults after surgery, immune system dysfunction, deposition of fat that compresses the lymphatic capillaries, fibrosis, and inflammation. Although secondary lymphedema is often associated with breast cancer, the condition can occur in patients with any type of cancer that requires lymphadenectomy such as gynecological, genitourinary, or head and neck cancers. MicroRNAs demonstrate pivotal roles in regulating gene expression in biological processes such as lymphangiogenesis, angiogenesis, modulation of the immune system, and oxidative stress. MicroRNA profiling has led to the discovery of the molecular mechanisms involved in the pathophysiology of auto-immune, inflammation-related, and metabolic diseases. Although the role of microRNAs in regulating secondary lymphedema is yet to be elucidated, the crosstalk between microRNAs and molecular factors involved in the pathological features of lymphedema, such as skin fibrosis, inflammation, immune dysregulation, and aberrant lipid metabolism have been demonstrated in several studies. MicroRNAs have the potential to serve as biomarkers for diseases and elucidation of their roles in lymphedema can provide a better understanding or new insights of the mechanisms underlying this debilitating condition.

scholarly journals Cerebrovascular Injuries Induce Lymphatic Invasion into Brain Parenchyma to Guide Vascular Regeneration in Zebrafish

2018 ◽  
Author(s):  
Jingying Chen ◽  
Jianbo He ◽  
Qifen Yang ◽  
Yaoguang Zhang ◽  
Lingfei Luo
Keyword(s):  
Blood Vessels ◽  
Brain Edema ◽  
Interstitial Fluid ◽  
Molecular Mechanisms ◽  
Lymphatic Vessels ◽  
Lymphatic Invasion ◽  
Brain Parenchyma ◽  
Genetic Ablation ◽  
Vascular Regeneration ◽  
Promising Therapeutic Approach

SUMMARYDamage to regional cerebrovascular network and neuronal tissues occurs during acute cerebrovascular diseases, such as ischemic stroke. The promotion of vascular regeneration is the most promising therapeutic approach. To understand cellular and molecular mechanisms underlying brain vascular regeneration, we developed two zebrafish cerebrovascular injury models using genetic ablation and photochemical thrombosis. Although brain parenchyma is physiologically devoid of lymphatic vasculature, we found that cerebrovascular injuries induce rapid ingrowth of meningeal lymphatics into the injured parenchyma. The ingrown lymphatics on one hand become lumenized drain interstitial fluid to resolve brain edema, on the other hand act as “growing tracks” for nascent blood vessels. The ingrown lymphatic vessels undergo apoptosis and clearance after cerebrovascular regeneration. This study reveals a pathological function of meningeal lymphatics, through previously unexpected ingrowth into brain parenchyma and a newly identified lymphatic function as vascular “growing tracks”.HIGHLIGHTSCerebrovascular injuries induce lymphatic ingrowth into the injured brain parenchyma The ingrown lymphatics drain interstitial fluid to resolve brain edema Nascent blood vessels use the ingrown lymphatic vessels as “growing tracks” The ingrown lymphatic vessels undergo apoptosis after vascular regeneration completes

scholarly journals Functional recovery of fluid drainage precedes lymphangiogenesis in acute murine foreleg lymphedema

2012 ◽  
Vol 302 (11) ◽  
pp. H2250-H2256 ◽  
Author(s):  
Uziel Mendez ◽  
Emily M. Brown ◽  
Emily L. Ongstad ◽  
Justin R. Slis ◽  
Jeremy Goldman
Keyword(s):  
Neutralizing Antibodies ◽  
Interstitial Fluid ◽  
Fluid Transport ◽  
Lymphatic Vessels ◽  
Axillary Lymph Nodes ◽  
Vegf Receptor ◽  
Axillary Lymph ◽  
Indocyanine Green Fluorescence ◽  
Secondary Lymphedema ◽  
Subcutaneous Tissues

Secondary lymphedema in humans is a common consequence of axillary lymph node dissection (ALND) to treat breast cancer. It is commonly hypothesized that lymphatic growth is required to increase fluid drainage and ameliorate lymphedema. Although there is a pronounced alteration in the balance of interstitial forces regulating fluid transport that sustains the chronic form of lymphedema, it is presently unknown whether changes occur to the balance of interstitial forces during acute lymphedema that may play a role in the recovery of fluid drainage. Here, we compared the relative importance of lymphangiogenesis of lymphatic vessels and interstitial flows for restoring fluid drainage and resolving acute lymphedema in the mouse foreleg after ALND. We found that removal of the axillary lymph nodes reduced lymph drainage in the foreleg at days 0 and 5 postsurgery, with fluid tracer spreading interstitially through subcutaneous tissues. Interstitial fluid drainage returned to normal by day 10, whereas functional regrowth of lymphatic vessels was first detected by indocyanine green fluorescence lymphography at day 15, demonstrating that the recovery of interstitial fluid drainage preceded the regrowth of lymphatic vessels. This was confirmed by the administration of VEGF receptor-3-neutralizing antibodies, which completely blocks lymphatic regrowth. It was found that the recovery of interstitial fluid drainage and the natural resolution of acute lymphedema produced by ALND were not hindered by VEGF receptor-3 neutralization, demonstrating that interstitial fluid drainage recovery and the resolution of acute lymphedema are lymphangiogenesis independent. The data highlight the central role of the interstitial environment in adapting to lymphatic injury to increase fluid drainage.

scholarly journals Iatrogenic subcutaneous emphysema – A case report

2021 ◽  
Vol 7 (4) ◽  
pp. 299-301
Author(s):  
Vaishali Gupta ◽  
Munish Singla ◽  
Harleen Kaur ◽  
Litik Mittal
Keyword(s):  
Case Report ◽  
Subcutaneous Tissue ◽  
Self Healing ◽  
Successful Management ◽  
Loose Connective Tissue ◽  
Diagnostic Features ◽  
General Terms ◽  
Common Causes ◽  
The Common ◽  
Entrapped Air

Subcutaneous tissue emphysema in general terms is defined as an abnormal presence of air under pressure, along or between fascial planes. A sudden blast of air, during an ongoing endodontic treatment or an endodontic surgery can sometimes cause movement of this air through the loose connective tissue layers to distant areas. In case of occurrence of emphysema, the condition should be carefully examined as the entire diagnosis is based merely on clinical examination. The clinician should be aware of the common causes, characteristic diagnostic features, possible complications and the management of the condition. This entrapped air in some cases is self healing and in some cases can lead to serious complications and death. The case report described is a successful management of unintentional and unfortunate tissue emphysema. The case report also emphasis on the importance of timely and accurate diagnosis of the condition.

scholarly journals Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Micaela K. Roy ◽  
Francesca Cendali ◽  
Gabrielle Ooyama ◽  
Fabia Gamboni ◽  
Holmes Morton ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Molecular Mechanisms ◽  
Unsaturated Fatty Acids ◽  
Cell Metabolism ◽  
Oxidant Stress ◽  
Membrane Lipid ◽  
Pentose Phosphate ◽  
Therapeutic Interventions ◽  
Common Causes ◽  
Sphingosine 1 Phosphate

Background: Pyruvate kinase deficiency (PKD) is the most frequent congenital enzymatic defect of glycolysis, and one of the most common causes of hereditary non spherocytic hemolytic anemia. Therapeutic interventions are limited, in part because of the incomplete understanding of the molecular mechanisms that compensate for the metabolic defect.Methods: Mass spectrometry-based metabolomics analyses were performed on red blood cells (RBCs) from healthy controls (n=10) and PKD patients (n=5).Results: In PKD patients, decreases in late glycolysis were accompanied by accumulation of pentose phosphate pathway (PPP) metabolites, as a function of oxidant stress to purines (increased breakdown and deamination). Markers of oxidant stress included increased levels of sulfur-containing compounds (methionine and taurine), polyamines (spermidine and spermine). Markers of hypoxia such as succinate, sphingosine 1-phosphate (S1P), and hypoxanthine were all elevated in PKD subjects. Membrane lipid oxidation and remodeling was observed in RBCs from PKD patients, as determined by increases in the levels of free (poly-/highly-unsaturated) fatty acids and acyl-carnitines.Conclusion: In conclusion, in the present study, we provide the first overview of RBC metabolism in patients with PKD. Though limited in scope, the study addresses the need for basic science to investigate pathologies targeting underrepresented minorities (Amish population in this study), with the ultimate goal to target treatments to health disparities.

scholarly journals Lymphatic endothelium

2003 ◽  
Vol 163 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Michael S. Pepper ◽  
Mihaela Skobe
Keyword(s):  
Tumor Cells ◽  
Interstitial Fluid ◽  
Molecular Mechanisms ◽  
Lymphatic Vessels ◽  
Traditional View ◽  
Lymphatic Endothelium ◽  
Point Of Entry ◽  
Recent Advances ◽  
And Function

The lymphatic microvasculature is uniquely adapted for the continuous removal of interstitial fluid and proteins, and is an important point of entry for leukocytes and tumor cells. The traditional view that lymphatic capillaries are passive participants in these tasks is currently being challenged. This overview highlights recent advances in our understanding of the molecular mechanisms underlying the formation and function of lymphatic vessels.

Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

2020 ◽  
Vol 134 (17) ◽  
pp. 2243-2262
Author(s):  
Danlin Liu ◽  
Gavin Richardson ◽  
Fehmi M. Benli ◽  
Catherine Park ◽  
João V. de Souza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Cardiovascular Research ◽  
Inflammatory Processes ◽  
Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

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