Lymphatic drainage system

The pulmonary lymphatic system contributes to the clearance of fluid and protein from the lung tissue interstitium and helps to prevent fluid accumulation in the lungs [108], The lymphatic endothelium allows micron-sized particles (e.g. lipoproteins, plasma proteins, bacteria and immune cells) to pass freely into the lymph fluid [103], After administration of aerosolised ultrafine particles into rats, particles were found in the alveolar walls and in pulmonary lymph nodes [135], which suggests that drainage into the lymph may contribute to the air-to-blood transport of the inhaled particles. 

The interstitial fluid content of the skin is higher than in the subcutaneous fat layer and normal fluid movement is intrinsically finked to lymphatic drainage as governed by mechanical stresses of the tissue. A model of temporal profiles of pressure, stress, and convective ISF velocity has been developed based on hydraulic conductivity, overall fluid drainage (lymphatic function and capillary absorption), and elasticity of the tissue.34 Measurements on excised tissue and in vivo measurement on the one-dimensional rat tail have defined bulk average values for key parameters of the model and the hydration dependence of the hydraulic flow conductivity. Numerous in vivo characterization studies with nanoparticles and vaccines are currently underway, so a more detailed understanding of the interstitial/lymphatic system will likely be forthcoming. 

The disrupted drainage of the lymph is attributed to (1.) obliterated diaphragmatic lymph vessels, (2.) dilated visceral lymph vessels with subsequent clearly decelerated flow velocity, and (3.) limited lymph kinetics at the transition between the lymphatic system and the venous system. More and more disturbances in the fluid balance between plasma and interstitium increasingly activate the... 

What are the components of the safety factor There are in fact three key components the negative interstitial pressure, the capacity of the lymphatic system to transport more fluid than it does under normal circumstances and the fact that increased lymph drainage tends to wash protein out of the interstitial spaces, thus reducing perimicrovascular osmotic pressure. 

In some cases, selective accumulation in the target area can be achieved, and this is of major interest in cancer therapy. For example, compared to normal tissue, tumor vessels can take up conjugates with a molecular weight >40 kDa. In addition, the lymphatic system in these areas is unable to provide a full drainage function, and this may lead to an enhanced perme-abihty and retention effect (EPR) of high-molecular weight compounds. Small molecules are not accumulated as they are able to diffuse back into the blood circulation... 

Tumors generally have poor lymphatic drainage either due to underdevelopment of the lymphatic system or to lymphatic obstruction. The poor lymphatic drainage of tumors along with normally enhanced tumor vasculature permeability and hypervascularity are considered to be the main reasons for the accumulation of proteins and macromolecules in tumors. Such mechanisms could also profoundly affect the preferential localization of photosensitizers because they bind to serum proteins. 

From an engineering point of view, the authors discuss the lymphatic system as a drainage system for fluids and waste products from tissues. Basic concepts of lymphatic transport along with clinical disorders are discused, although briefly. Extensive additional sources are cited. 

The small intestine, which comprises the duodenum, the jejunum and the ileum, is the main absorption site and contains a series of finger-like projections, the vilh, which greatly increase the surface area available for absorption of nutrients. Each villus contains an arteriole and venule, together with a drainage tube of the lymphatic system, a lacteal. The venules ultimately drain into the hepatic portal system, and the lacteals into the thoracic lymphatic duct. The luminal side of each villus is covered with projections, the microvilli, which are often referred to as the brush border. 

There are two potential drainage routes for fluids in the body the venous and lymphatic systems. When one is impaired, the other somewhat compensates. There are limits and even a temporary condition can set off a cascade of impaired function, compensation, and hopefully recovery. Too often, the compensation is inadequate... 

Clinically, a limb edema is the result of swelling from excessive accumulation of serous fluid in tissue. It depends on two factors. First, excessive liquid is generated in the interstitial space due to obstructive venous diseases presenting as varicose veins or postthrombotic syndrome, heart or kidney failure, metabolic deficits with altered and low protein concentration in the blood, or many other conditions. Second, a lymphatic drainage deficit due to alteration of the lymphatic system can result in water and protein stagnation. Lymphedema frequently occurs in many upper- and lower-limb pathologies. 

Shielded polyplexes with improved blood circulating properties are interesting tools for systemic cancer therapy (see Sect. 4.2). Nanoparticles can take advantage of the enhanced permeability and retention (EPR effect) [89] for passive tumor targeting. The EPR effect is based on the leakiness of tumor vasculature, due to neovascularization in growing tumors, combined with an inadequate lymphatic drainage. Nanoparticles with an elongated plasma circulation time can extravasate and passively accumulate at the tumor site. 

The rate of absorption from an SC injection site may be retarded by immobilization of the limb, local cooling to cause vasoconstriction, or application of a tourniquet proximal to the injection site to block the superficial venous drainage and lymphatic flow. In small amounts, adrenergic stimulants, such as epinephrine, will constrict the local blood vessels and, therefore, slow systemic absorption. Conversely, cholinergic stimulants (such as methacholine) will induce very rapid systemic absorption subcutaneously. Other agents may also alter their own rate of absorption by affecting local blood supply or capillary permeability. 

There are occasional anomalies to the rule that food reduces and delays peak plasma concentration. The anti-fungal drug, griseofulvin, has enhanced absorption if taken with a meal - possibly because it becomes emulsified by bile salts and passes more readily into the lymphatic drainage of the gut which bypasses the liver, entering the venous system directly. The immuno-suppressant cyclosporin, and calcium salts in general, show a similar increase in absorption when taken with a fatty meal. 

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