The Lymphatic System

The main perception of the lymphatic system so far has been one of little significance and almost negligence by mainstream medicine. This conclusion can be drawn from a number of sources: limited information during medical education, small number of medical scientific studies regarding exclusively the lymphatic system, very few diagnostic procedures regarding the lymphatic system, therapeutic procedures almost totally avoiding the lymph and the lymphatic vessels. While it is widely recognized and accepted that the lymphatic system poses a major factor in the physiology on the human body, little is been done in terms of exploring or harnessing that importance for therapeutic purposes. If we analyze the number of studies where “lymph” turns out as a keyword, almost all of them refer to the lymphatic system merely as a pathway for dispersion of malignant cells throughout the body.

But does indeed all the medical importance of the lymphatic system boil down to “route of malignant cells”? Could this be a serious under appreciation of an extremely important vital system? What are the true possibilities behind this picture of a secondary circulatory system?

In the following, we will make the case that attention to the lymphatic system is not only needed, but essential, if we are in the pursuit of establishing balance back in the body. There are several important arguments that support this notion:

• Drainage and detoxication functions of lymphatic system at regional level are of outmost importance. Lymph-detoxification is regarded as a unity of biophysical, biochemical and immune actions upon the lymph in lymphoid structures of an anatomical region. Regional lymphatic drainage is considered as a three-component mechanism that includes interstitial pathways of nonvascular microcirculation, regional lymphatic vessels and lymph nodes. As a whole, this construction represents a lymphatic region that includes, besides the pathways of vascular and non-vascular lymph circulation, other lymphoid structures, which are present in this region (individual cells, constant and temporary aggregations of lymphoid tissue).

• Defense mechanisms are crucial for all organisms, and most of the immune potent cells are located in the lymph. The cells also produce proteins and waste products and the lymph absorbs these products and carries them away. Any random bacteria that enter the body also find their way into this inter-cell fluid. One job of the lymph system is to drain and filter these fluids to detect and remove the bacteria. Small lymph vessels collect the liquid and move it toward larger vessels so that the fluid finally arrives at the lymph nodes for processing.

• Prevention of edema – lymphatic contractility plays crucial roles in the regulation and generation of lymph transport. A number of studies both in situ and in vitro have clearly demonstrated that lymphatic vessels possess both tonic and phasic changes in contractility. It also has been shown that human lymphatic contractility can be influenced by a number of neural and humoral factors such as noradrenaline, histamine, and prostaglandins. This review focuses chiefly on the function of the system and emphasizes recent advances in understanding the lymphatic pump and the factors on the contractions of the lymph vessels.

• Link between lymphatic vessels and adipose tissue has only recently been recognized. There is growing number of documented evidence that supports a close relationship between lymphatic vessels and adipose tissue biology. Lymphatic vessels mediate lipid absorption and transport, share an intimate spatial association with adipose tissue, and regulate the traffic of immune cells that rely on specialized adipose tissue depots as a reservoir of energy deployed to fight infection. There has also been recent evidence connecting lymphatic vascular dysfunction with the onset of obesity.

• Disturbances in blood capillary exchange of fluid, macromolecules, and cells across intact and abnormal micro-vessels and deranged lymphatic transport are integral, interacting components in disorders of tissue swelling. Lymphedema or low-output failure of the lymph circulation is often not observable for many years before lymphatic insufficiency (failure) and tissue swelling emerge and persist. Superimposed occult or overt infection

(lymphangitis) are probably major contributors to progressive limb deformity. Long-standing lymphedema is characterized by trapping in the skin and subcutaneous tissue of fluid, extravasated plasma proteins, and other macromolecules: impaired immune cell trafficking; abnormal processing of autologous and foreign antigens; heightened susceptibility to superimposed infection; local immuno-dysregulation; defective lymphatic (lymphangion) propulsion from an imbalance of mediators regulating vaso-motion; soft tissue overgrowth; scarring and hypertrophy; and exuberant angiogenesis occasionally culminating in vascular tumors. In contrast to the blood circulation, where flow depends primarily on the propulsive force of the heart, lymph propulsion depends predominately on intrinsic truncal contraction. Whereas venous “plasma” flows rapidly (2-3 l/min) against low vascular resistance, lymph flows slowly (1-2 ml/min) against high vascular resistance. On occasion, impaired transport of intestinal lymph may be associated with reflux and accumulation and leakage of intestinal chyle in a swollen leg. Although the term “lymphedema” is usually reserved for extremity swelling, the pathogenesis of a wide variety of visceral disorders also may be traceable to defective tissue fluid and macromolecular circulation and impaired cell trafficking of lymphocytes and macrophages. Thus, lymph stasis, with impaired tissue fluid flow, underlies or complicates an indolent subclinical course with a long latent period and sporadic episodes of lymphangitis, which culminates in intense scarring. Examples are pulmonary fibrosis (e.g., pneumoconiosis), regional enteritis, retroperitoneal fibrosis, and perhaps chronic pancreatitis and cirrhosis of the liver. Transdifferentiation and ultimately transformation of endothelial and other vascular accessory cells during lymph stasis also may be pivotal to a wide range of dysplastic and neoplastic vascular disorders, including Stewart Treves Angiosarcoma, AIDS-associated Kaposi’s sarcoma, and lymphangitic metastatic carcinomatosis.

Based on these important arguments, the POH method strives for harnessing the full potential of a balanced lymph system and all the benefits it brings for the wellbeing of the human body.

Mainstream medicine often ignores this important system, but it is essential to the health of the immune system. The lymphatic system can be compared to a freeway and when congested, nothing moves. The lymphatic system affects every organ and cell in our body. When our lymphatic system’s drainage becomes blocked, the body cannot eliminate toxic material. When the lymph fails to function properly, it becomes sluggish or even stagnant. The clear lymph fluid becomes cloudy and thick, changing from a condition like water to milk to yogurt-like substance. Thickened, gel-like stagnant lymph overloaded with toxic waste is the ideal environment for the onset of numerous illnesses, including cancer. 

The lymphatic system includes a vast network of capillaries that transport the lymph – a series of nodes throughout the body that collect the lymph and 3 organs; the tonsils, spleen, and thymus gland, which produce white blood cells. The space between cells occupies about 18% of the body. Fluid containing plasma proteins, foreign particles, and bacteria that accumulate in these spaces between cells, is called lymph. The primary purpose of the lymph system is to collect the lymph and to return its contents to the bloodstream. More specifically, the lymph system collects waste products and cellular debris from the tissues to eliminate toxins from the body. The lymph flows upward through the body to the chest (at the rate of 3 quarts per 24 hours) where it drains into the bloodstream through two large ducts. Lymph also flows down from the head and neck into these drainage sites. Unlike the blood supply, the lymphatic system does not have a pump (the heart} to move it along. Rather, its movement depends on such factors as muscle contraction or manual manipulation (why inactivity can lead to increased illness). The lymph circulation is also a one-way circulation – it only returns fluid to the bloodstream. The lymph system becomes particularly active during times of illness (such as the flu), when the nodes (particularly at the neck) visibly swell with collected waste products. When the collecting terminals become blocked, it’s like a bottleneck; lymph starts backing up in the system creating a toxic oxygen deprived environment conducive to degeneration and disorder. Toxic lymph can be stored for a long time in the system. This is not a healthy condition. Moving stagnant lymph is a key to wellness. Once we clear up the lymph flow, which is an essential component of the immune system, we can enhance the body’s natural healing ability to clear up illness. The lymph system is actually a vital circulatory system with an extensive network of vessels throughout the body. Your body contains about 50% more lymphatic fluid than blood. The system contains over 600 collection sites called lymph nodes. These nodes are formed at the junction sites of the lymph vessel network. The system is responsible for supplying plasmarich protein to your blood as well as carrying away toxins and other debris. It is your primary defense against bacteria, viruses and fungus. Most chronic (disease) problems occur at the junction of lymph vessels called lymph nodes.

In men the inguinal nodes, in the crease of the groin, are the primary channel for release of accumulated lymph from the prostrate. In women the axillary nodes, located in the arm pit, are the primary channel for releasing accumulated lymph from the breasts. There are many inter-linked conditions that can contribute to sluggish lymph circulation and may be improved by lymphatic treatment. These include but are not limited to: allergies, menstrual cramps, arthritis, prostate disorders, ulcers, breast lumps, parasites, eating disorders, cancer, respiratory infections, cellulite, emphysema, sinus headaches, intestinal blockages, muscle and tissue tension, structural misalignment in the neck and shoulders, and mental confusion and emotional disorder. Most physical difficulties can be aggravated by blockage of the lymph flow. Factors that can contribute to lymph system blockages include chronic constipation, stress, lack of movement, inflammation, poor eating habits and other factors that hamper the natural cleansing process. Artificial and restrictive clothing (such as polyester blouses and tight bras and jeans), air-conditioning, and even antiperspirant deodorants prevent excretion and natural cleansing of toxins.

The lymphatic system plays an essential role in the maintenance of tissue homeostasis, removing interstitial fluid and macromolecules from extracellular spaces and returning them back to the blood circulation, thereby preventing edema. The system is also a fundamental component of the immune response, transporting antigens and antigen-presenting cells to lymph nodes where immune cells can be activated, and providing a path for immune competent cells to return to the blood stream. An essential property of lymphatic vessels – conferring the ability to perform these functions – is their capacity to exhibit spontaneous rhythmical constrictions. The lymphatic contractile function is particularly important to the resolution of inflammation-associated edema, where vessel pumping must help offset increase in interstitial fluid resulting from increases in vascular permeability. A common condition associated with the inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), is submucosal edema; this has been a consistent observation since the first accurate description of CD, and has been described as one of the essential histological features of the disease (Robb-Smith 1971). Examination by Heatley (1980) of human patients undergoing surgery for CD was one of many investigations demonstrating mesenteric lymphatic obstruction during inflammatory processes. In fact, lymphatic obstruction and dilation are frequently observed in IBD, suggesting impaired function and poor drainage of extracellular fluid, proteins, and other macromolecules. A consequence of interstitial edema is the accumulation of dead cells and bacteria, which can cause tissue hypoxia and fibrosis. It is this dense fibrosis and muscular hypertrophy that determines the stenosis and strictures that can occur in IBD (Robb-Smith 1971). Thus, lymphatic circulation may play an imperative role in IBD, as impaired function may actively participate in the delayed immmunological response, exacerbate microbial infections, and hinder the prompt resolution of inflammation-associated edema.

Lymphatic vessels serve as a drainage system for the pool of fluid that collects in the interstitium. This interstitial fluid, along with various molecular and cellular components, enters the lymphatic system through blindended initial lymphatics, while bicuspid valves within the lymphatic vessels promote the flow of fluid into the collecting vessels by preventing backflow. Initial lymphatics empty their contents into collecting lymphatics, which have layers of smooth muscle in their wall that are responsible for spontaneous vessel constrictions (Ryan 1989). The phasic contractions of the smooth muscle layer cause a transient compression of the chambers, propelling lymph, macromolecules, antigenic substances, and/or lipids through the one-way valves into the downstream chambers in a pulsatile manner. The ability of the lymphatic vessels to exhibit spontaneous phasic constrictions is the mechanism by which the system performs its essential functions. The lymphatic system is especially important in inflammatory conditions, where vasodilation and an increase in vascular permeability occur in response to a release of inflammatory mediators due to trauma to the body. This results in an increase of plasma fluid and protein leakage into the interstitial space. These changes in vascular permeability must be offset by increases in lymphatic vessel function. However, efficient reuptake does not always occur, resulting in edema, a cardinal sign of inflammation. Although lymphatic vessels have an intrinsic ability to constrict spontaneously, smooth muscle contractility is subject to regulation by various physiological factors. Changes in the interstitial and intraluminal environment occur frequently, and so lymphatic vessels must adapt in changing their behaviour. Lymphatic vessels have the ability to modulate their contractile function in response to factors such as mechanical, endothelial, neural, hormonal, and humoral, factors.

Arachidonic acid and its metabolites are among the most important mediators of inflammatory reactions. Importantly, these substances have been shown to directly act on lymphatic vessels and are important modulators of lymphatic function (Johnston 1987). Because of the numerous metabolites that can be produced from arachidonic acid, response of lymphatics to arachidonic acid itself is variable, depending on the predominant metabolite into which it is converted; some are inhibitory, while others are excitatory. Early studies on cyclooxygenase (COX) inhibitors and inhibitors of other pathways of arachidonate metabolism showed that spontaneous lymphatic pumping was abolished when these metabolic participants were repressed (Johnston & Gordon 1981). These studies also showed that application of some leukotrienes as well as a prostaglandin H2/thromboxane A2 (PGH2/ TXA2) mimetic induced rhythmic constriction in non-contracting vessels. In a study on rat iliac lymphatics, arachidonic acid caused a significant decrease in vessel diameter via production of constrictor prostaglandins (Mizuno et al. 1998). These effects were blocked by indomethacin, suggesting that these metabolites were produced through COX. The constrictions caused by arachidonic acid were converted to dilations when PGH2/TXA2 receptors were blocked by antagonists. In the same study, PGE2 caused a dilation in lymphatic vessels that was unaffected by indomethacin (Mizuno et al. 1998). When the endothelial layer was removed from the lymphatic vessel, response to arachidonic acid was significantly reduced, suggesting that the endothelium plays a role in its production, but that other non-endothelial cells may also release prostaglandins. Substance P and ATP were shown to enhance the rate of constriction in guinea-pig mesenteric lymphatics. Attenuation of this increase by indomethacin and SQ29548 suggested that prostanoid PGH2/TXA2 released from the endothelium is activated by both substance P and ATP (Rayner & van Helden 1997, Gao et al. 1999). These studies illustrate the complicated nature by which the lymphatic system responds to its modulators.

IBD is an ensemble of complex disorders, such as CD and UC, involving chronic inflammation of the gastrointestinal tract. The inflammation is often characterized by periods of flare-ups, with symptoms such as diarrhea, abdominal pain, and cramping followed by resolution or “remission”. Current theories about the pathogenesis of IBD point to an impaired mucosal immune response in a susceptible host to the microbes within the intestinal flora. However, the exact mechanisms of immune, environmental, and genetic involvement remain poorly understood. IBD has variable expressions with a multitude of morphological appearances. CD can affect any part of the gastrointestinal tract from the mouth to the anus, and is characterized by patches of inflammation with intermittent areas of healthy tissue. The inflammation extends through all layers of the gastrointestinal wall. UC-associated inflammation typically begins in the rectum and extends proximally and abruptly stops. It is superficial, rarely penetrating beyond the mucosa. In contrast to CD, the rectum is almost always involved, and the inflammation is continuous and uniform with no skip lesions. Vascular abnormalities are common in the pathology of IBD, as microvascular compromise is a common precursor to tissue damage. It is believed that the increase in vascular permeability, resultant edema and local ischaemia may perpetuate the disease (Allison 1998). These characterizing features of IBD – submucosal edema, inflammation, and changes in microvasculature suggest the involvement of the lymphatic system in disease resolution, as lymphatics are intimately linked to each of these altered physiological functions.

Following an enormous amount of research into the role of prostagandins in mucosal defense, it has been well established that suppression of COX leads to gastrointestinal ulceration associated with the use of nonsteroidal anti-inflammatory drugs (Vane 1971). It has been shown that prostaglandins exert a cytoprotective role by maintaining mucosal blood flow, enhancing epithelial resistance to cytotoxin injury, and by enhancing secretion of mucous and bicarbonate ion in the gastrointestinal tract (Hawkey & Rampton 1985). Many studies have also shown that inhibition of COX may exacerbate mucosal injury. For example, administration of a COX-2 selective inhibitor to rats with gastric ulcers or colitis led to an intensified inflammation and inhibition of ulcer healing (Reuter et al. 1998). It has been hypothesized that prostaglandins can down-regulate inflammatory responses and limit the severity of mucosal injury by inhibiting the function of inflammatory cells within the mucosa. For example, Kunkel et al. (1988) demonstrated that prostaglandin E2 is a potent suppressor of tumor necrosis factor (TNF)-α gene expression in macrophages. However, inhibition of COX with non-steroidal anti-inflammatory drugs increased the release of TNF-α from macrophages (Santucci et al. 1994). Because COX metabolites clearly have a significant effect on intestinal inflammation, and have been shown to have direct effects on lymphatic function, it follows that COX metabolites should exert their effects on the lymphatic system during IBD. These effects are important with respect to the ability of lymphatic vessels to reduce the inflammation-associated edema and to the role that the inflammatory mediators play in IBD.

One of the most consistent pathological features observed in patients suffering CD and UC is lymphatic obstruction and submucosal edema leading to extensive dilation of the lacteals. Pathologists have noted for decades that marked edema and engorgement of capillaries and lymphatics are one of the first morphological changes that occur in intestinal inflammation (Robb-Smith 1971). An early study, in 1936, by Reichert and Mathes demonstrated that injecting sclerosing agents into canine mesenteric lymphatics resulted in granulomatous enteritis. A similar experiment was conducted years later, demonstrating that injection of formalin into porcine mesenteric lymph nodes resulted in mucosal ulcerations and subserosal fibrosis similar to those seen in regional enteritis (Kalima 1976). In a study on normal and diseased human bowel, patients who were undergoing surgery for CD were studied to determine the efficiency of lymphatic drainage. It was found that affected, and some apparently unaffected areas of the mesentery showed a significant level of lymphatic failure. Further examination of unaffected areas with lymphatic obstruction confirmed the presence of early IBD (Heatley et al. 1980). Due to the increase in vascular permeability and resultant increase in interstitial fluid, lymph flow is generally believed to increase during inflammatory reactions. 

The lymphatic system must thus play a crucial role in edema resolution during IBD (Kirsner & Shorter 1975). It has been shown that mesenteric lymphatic pumping is increased during edemagenic stress caused by dilution of plasma in rats in vivo (Benoit et al. 1989). This was due to the increase in distension of the lymphatic wall, which may be the situation when lymphatics are overloaded in cases of edema. Although the involvement of lymphatic vessels was demonstrated in these earlier studies, relationship between lymphatics and IBD was not investigated further in the late 1980s and early 1990s. It was not until recently that investigations on lymphatic vessels in the pathogenesis of IBD began again in earnest, especially in the area of initial lymphatics. Mooney et al. demonstrated in 1995 that a significant proportion of granulomas seen in patients with CD was associated with initial lymphatic vessels and that blood vessel involvement was a secondary rather than primary phenomenon. This finding led the authors to suggest that “granulomatous lymphangitis is a primary lesion of Crohn’s disease, and the consequence of the localisation of granulomatous inflammation is the submucosal edema and fibrosis which gives rise to many of the …histological features of the disease” (Mooney et al. 1995). The authors further hypothesized that the antigens that cause CD may be taken up by macrophages, which then enter the lymphatic system. In 2003, two studies demonstrated a proliferation of initial lymphatics in all areas of the colonic mucosa of patients with UC (Kaiserling et al. 2003) and in the colonic and ileal mucosa of patients with UC and CD respectively (Geleff et al. 2003). A year later, it was shown that lymphatic capillaries in the colon, which are normally distributed beneath the muscularis mucosa, proliferate into the lamina propria and submucosa in patients with chronic UC, and that this association was proportional to the severity of the disease. In addition, this study showed that the integrity of the lamina propria, in regards to lymphatic distribution, was restored with disease resolution (Fogt et al. 2004). In a study examining the role of collecting lymphatics in IBD, Tonelli (2000) suggested that CD may be caused by a congenital lack of mesenteric lymphatic collectors, causing lymph stasis and lymphangitis, and gastrointestinal inflammation due to the inability to take up and remove toxic bacterial substances. Although this is an extreme view, this study lends support to the hypothesis that the lymphatic system plays a role in the development of IBD. The aforementioned studies suggest that intervention at the level of the lymphatic system may serve to ease some of the symptoms that IBD patients suffer. Because increased vascular permeability during inflammation is thought to be caused by release of inflammatory metabolites, they could play a pivotal role in modulating lymphatic vessel function. Although it is known that the lymphatic system is intimately involved in and highly altered during the disease, the exact role of lymphatics is not yet known. Many studies have also been conducted, illustrating the potent effect of inflammatory mediators such as COX metabolites on lymphatic function. Although a failure in the lymphatic system may not be the direct cause of the disease, the inflammation may have a significant effect on normal vessel function, and the inability of the vessels to function normally may exacerbate an already deleterious condition.