Precipitating Factors

Precipitating factors include factors that begin to alter mucosal integrity throughout the body, referred to as hyperpermeability. This occurs primarily in the GALT (Gut-Associated Lymphatic Tissue), but may often occur in other body tissues such as urogenital tissue through MALT (Mucosa-Associated Lymphatic Tissue). Other tissues that often become involved are sinus, ears, eyes, lungs, and throat. Precipitating factors also may cause microbiological imbalancing such as the increase of indigenous flora including Enteroccocus, E. coli, and Candida Albicans. If these factors create changes in mucosal integrity of the intestines, it is referred to as hyperpermeability, and if it causes microbial changes in the intestines, it is referred to as SIBO (Small Intestinal Bacterial Overgrowth). Either condition may lead to the other. Furthermore, these conditions then in turn lead to LGS (Leaky Gut Syndrome), Bacterial Translocation (BT) or Microbial Translocation (MT). The dynamics of these syndromes are very similar and involve the abnormal transference of antigens into systemic circulation from the imbalance in the small intestine. In the case of BT or MT the transference is thought to be occurring through the normal physiological pathway of transcytosis entering from the M cells on Peyer’s Patches that are groupings of lymphatic tissues that line the small intestine, (Berg et. al, 1993) This is the pathway through which the mucosal system (MALT) communicates. And, LGS is said to leak antigens through paracellular migration, (Rona, 2006; Galland, 2006).

Many may agree that once the system becomes imbalanced all of these factors are generally involved but in different proportions. Other tissues then are often consequently affected from the imbalance in the small intestine such as, the mesenteric lymph nodes, urogenital tissue, reproductive tissues, eyes, ears, nose and throat, lungs and organs such as the spleen, liver, and kidneys (that ultimately affect the urinary bladder). The connections between the small intestine imbalance and the system tissues occur through the MALT.

In IC, the urogenital tissue may be primarily affected and not be stemming from a primary imbalance in the small intestine in some cases. However, it is more common for the small intestine to be the primary source of the imbalance.

These changes occur over time due to numerous and various factors. This author is of the opinion that these factors are numerous because primarily these factors have arisen due to the negative aspects of modern advances in health, medicine, and diet and are pervasive elements of our society.

Precipitating Factors are:

Poor diet that includes the over-consumption of sugar or sugar substitutes, and/or alcohol (and other substance abuse); or dietary practices such as anorexia, bulimia, vegetarianism.

Over-use of or inappropriate use of supplements such as laxatives, weight loss products, and others.

Overuse or inappropriate use of antibiotics, antifungals, steroids, NSAIDS, hormone prescriptions, and many other medications such as anti-depressants and anti-anxiety medications.

Chronic stress that may go as far as childhood and involve issues of bonding.

Certain repetitive exposures to chemicals such as those found in hair dyes, tooth whitening products, and, chlorine through water supply.

Changes to urogenital environment:

Transmission of sexual fluids containing certain pathogenic organisms.

Hormonal changes such as menopause creating mucosal and microbiological imbalances.

Changes in gastrointestinal balance affecting urogenital tissue through MALT.

There are numerous researchers focusing on the various kinds of imbalances referred to above occurring relative to chronic illness. In an effort to clarify these theories, while drawing conclusions regarding IC and other chronic disease from them, this author cites from the following researchers at the forefront of their fields, the first compilation of which is general followed by more specifically organized statements below it:

“Each organism lives in a continuous interaction with its environment: this interaction is of vital importance but at the same time it could be life-threatening. The largest and most important interface between the organism and its environment is represented by surfaces covered by epithelial cells. Of these surfaces mucosae represent in humans about 300 m2 while skin covers approximately 2 m2 surface of the human body. Starting from first hours after the delivery from the sterile uterine environment (mammalian foetuses are born germ-free) the interaction of the macro-organism with micro-organisms begins: the main portal of entry of microbes is skin and mucosal surfaces of the gastrointestinal, respiratory and urogenital tracts. Physiologically occurring interaction with bacteria leads to colonization of epithelial surfaces and this co-existence is usually harmonious, and beneficial for the host (commensalisms). A complex, open ecosystem, formed by resident bacteria and transiently present microbes interacting with macro-organism is founded. However, under some conditions the interaction with “endogenous” microbes can be harmful for the host (parasitism) and opportunistic infections can occur. The microflora interacts with its host both locally and systemically. (Tlaskalová-Hogenová, p. 97, 2006).

“While the skin surface is protected mechanically by several epithelial layers, surfaces of the gastrointestinal, respiratory and urogenital tracts, conjunctivae and outlets of endocrine glands are mostly covered with a single-layered epithelium and require, therefore, a more extensive protection: this is represented by a complex of mechanical and chemical agents responsible for effective degradation and removal of heterogeneous substances. In addition, both mucosa and internal environment of the organism are protected by a most effective innate and highly specific immune systems. Basic functions of the mucosal immune system are protection against pathogenic micro-organisms and prevention of penetration of immunogenic components from mucosal surfaces into the internal environment of the organism (barrier and anti-infectious functions). Another important function is induction of unresponsiveness of the systemic immunity to antigens present on mucosal surfaces (“oral, mucosal tolerance”) and maintenance of the homeostasis on mucosal surfaces (immunoregulatory function). Among the basic features of mucosal immunity differentiating it from systemic immunity, are strongly developed mechanisms of innate immunity and existence of characteristic populations of lymphocytes that differ from, e.g. blood lymphocytes in origin, phenotype and secreted products. Other features characteristic of mucosal immunity are: colonisation of mucosal surfaces and exocrine glands by cells originating from lymphatic follicles of intestine or bronchi (migration and homing of mucosal lymphocytes establishing the so-called “common mucosal system”) and the well-known epithelial transport of polymeric immunoglobulins produced by mucosal plasma cells through the epithelium (secretory immunoglobulins, mainly IgA isotype). A balance in intestinal mucosa may be disturbed by pathogenic micro-organisms and their toxins, or by inadequately functioning components of the mucosal immune system. On the other hand, an expression of pathologically increased immunological activity may induce various inflammatory processes. Thus, numerous chronic diseases may occur as a result of disturbances of mucosal barrier function or of changes in mechanisms regulating mucosal immunity. This may involve infectious diseases, inflammatory diseases (allergies), multiorgan failure but also autoimmune diseases developing either in their initial phase or throughout on mucosal surfaces” (Tlaskalová-Hogenová, p. 98, 2006). “The main mechanical barrier of mucosal surfaces is formed by a layer of epithelial cells covered with glycocalyx composed of complex glycoproteins. The epithelium of most mucosal surfaces consists of a layer of interconnected, polarised epithelial cells separated by a basal membrane from the connective and supporting tissue surrounding various types of cells present in the lamina propria. Intestinal epithelial layer is reinforced by tight junctions present in paracellular spaces of epithelial cells and forming an interconnected network. Tight junctions were found to act as a dynamic and strictly regulated port of entry that opens and closes in response to various signals (e.g. cytokines) originating in the lumen, lamina propria and epithelium. Tight junctions participate in preserving cellular polarity and are regarded as key elements in intestinal diffusion mechanisms.” (Tlaskalová-Hogenová, p. 99, 2006).

“It has been recently found that intestinal epithelial cells as an important part of the innate immune system are directly involved in various immune processes, in addition to their absorptive, digestive and secretory functions. (Tlaskalová-Hogenová, p. 99, 2006).

SIBO: (Lin, 2004) “Bacterial translocation, a known complication of SIBO, isthe

movement of gut bacteria from the lumen across the mucosalbarrier. In rats, experimentally induced SIBO leads to theappearance of gut bacteria in the mesenteric lymph nodes andvisceral organs. A potentially important consequence of bacterialtranslocation is immune activation. In a report of 11 patients,an increase in the number of intraepithelial lymphocytes wasobserved as mucosal evidence of this immune response to confirmedbacterial translocation. This adverse outcome could explainwhy the normal gut has defensive mechanisms in place to keepthe bacterial flora away from the small intestine, particularlythe bowel proximal to the ileum. It is well recognized that there is a high degree of overlapbetween IBS, fibromyalgia, interstitial cystitis, and chronicfatigue syndrome. While interstitial cystitis andIBS are diagnoses associated with hypersensitivity at thelevel of the bladder and gut, respectively, fibromyalgia maybe considered a kind of hypersensitivity at the musculoskeletallevel. Although the cause of the hypersensitivity in thesedisorders is not well understood, the striking overlap of hypersensitivityin these functional disorders suggests the possibility of aunifying explanation.

Lin (2004) has been correlating IBS, previously a symptom based diagnosis with a bacterial overgrowth in the small intestine. If we take this research which supports the argument for gastrointestinal disruption due to bacterial imbalance and combine it with the above information regarding the leaking of bacteria into the circulatory and lymphatic systems, it is very easy to see how bacteria may invade the body systemically and translocate into other organ systems, including the bladder. IBS commonly presents with a host of other problems, such as chronic fatigue syndrome, fibromyalgia visceral hypersensitivity, autonomic dysfunction, immune activation, and others, which, in the past have been regarded as separate issues. This practice is making increasingly less sense, challenging researchers to find the common thread that binds these conditions and may be the reason that such separation may be becoming “an artifact of medical specialization”. Small Intestine bacterial overgrowth (SIBO) may be that common finding. These researchers have verified that translocation of bacteria from the small intestine is possible and may travel to mesenteric lymph nodes as well as visceral organs as well as the presence of intraepithelial lymphocytes, substantiating the idea that the small intestine may become hyperpermeable, a controversial condition referred to as “leaky gut syndrome”. Lastly, sleep disturbance, flu-like symptoms of fatigue, anxiety, depression, and impaired cognition were among the immune responses linked with this abnormal condition of the small intestine disrupting the immune and autonomic nervous systems, (Lin, 2004).

(Rodriguez, 2005) has found in his practice that a disruption in gastrointestinal flora is the starting point for most chronic illnesses. He finds that this disruption weakens immunity and triggers the otherwise normally occurring trillions of non pathogenic bacteria and fungi into pathogenesis mode that create numerous chronic illness such as IBS, CFS, chronic anemia, skin disorders, and many others including chronic cystitis.

LGS: This is understood as a condition that provides passage between enlarged spaces, (also known as paracellular translocation) in the lining of the small intestine of “bacteria, fungi, parasites and their toxins, undigested protein, fat and waste normally not absorbed into the bloodstream in the healthy state” “Due to the enlarged spaces between the cells of the gut wall, larger than usual protein molecules are absorbed before they have a chance to be completely broken down as occurs when the intestinal lining is intact. The immune system starts making antibodies against these larger molecules because it recognizes them as foreign, invading substances. The immune system starts treating them as if they had to be destroyed. Antibodies are made against these proteins derived from previously harmless foods. (Rona, 2006). “Leaky Gut Syndromes are usually provoked by exposure to substances which damage the integrity of the intestinal mucosa, disrupting the desmosomes which bind epithelial cells and increasing passive, para-cellular absorption, (Galland, 2006).

Hyperpermeability: Numerous researchers are exploring issues of gastrointestinal hyper-permeability. This hypothesis is based upon the small intestine housing “the gut-associated lymphatic tissue (GALT), the largest lymphatic organ of the body” (Tlaskalová-Hogenová et al., 2004) and its central role in chronic disease. Due to the fundamental role of the small intestine in health, it’s imbalance becomes pivotal to the disease process affecting the body systemically including immune, nervous, endocrine and exocrine systems. Referring to imbalances of the small intestine, (Tlaskalová-Hogenová et. Al, 2004), states that, “A balance in intestinal mucosa may be disturbed by pathogenic micro-organisms and their toxins, or by inadequately functioning components of the mucosal immune system. On the other hand, an expression of pathologically increased immunological activity may induce various inflammatory processes. Thus, numerous chronic diseases may occur as a result of disturbances of mucosal barrier function or of changes in mechanisms regulating mucosal immunity. This may involve infectious diseases, inflammatory diseases (allergies), multiorgan failure but also autoimmune diseases developing either in their initial phase or throughout on mucosal surfaces.” “The intestinal epithelium represents the primary site for active transport of fluid and electrolytes from the gut lumen through the transcellular pathway; however the predominant route for passive transpithelial solute flow is the paracellular pathway. Gut mucosa serves as the main barrier to the passage of macromolecules, that is, foreign antigens entering the host via the oral route, components of commensal flora such as toxins. The majority of luminal proteins cross the intestinal barrier through the transcellular pathway, followed by lysosomal degradation. Lysosomal degradation changes proteins into nonimmunogenic peptides. Small but immunologically significant amounts of antigens cross the barrier intact form through the paracellular pathway. The paracellular pathway involves a subtle regulation of intercellular tight junctions that leads to antigen (mucosal) tolerance. When the integrity of the tight junctions is compromised for example, as a consequence of prematurity, exposure to toxins, drugs, or radiation, aberrant immune reactions to environmental antigens occur and could lead to inflammatory and autoimmune diseases.”(Tlaskalova-Hogenova et. Al, 2005, p.4). “The balance in intestinal mucosa may be disturbed by pathogenic microorganisms and toxins attacking the mucosa by qualitative or quantitative changes in the composition of mucosal microbiota, or by inadequately functioning components of the innate or adaptive immune system occurring in cases of dysregulated mechanisms of mucosal immunity or in immunodeficiencies. An expression of pathologically increased immunological activity may induce inflammatory processes of a different character, depending on the type and mediators of inflammation. Thus, numerous chronic diseases may occur as a result of disturbances of mucosal barrier function or of changes in mechanisms regulating mucosal immunity. The main characteristics of chronic ‘idiopathic’, inflammatory, and autoimmune diseases are tissue destruction and functional impairment as a consequence of immunologically mediated mechanisms that are principally the same as those functioning against dangerous (pathogenic) infections).”(Tlaskalova-Hogenova et. Al, 2005, p.4).

According to Crandall (2002), Candida grows on the contents of the intestine, and also penetrates the intestinal mucosa, disrupting the wall structure. This makes the gut wall more permeable, allowing the passage of microbial cells, partially digested food particles, and other molecules from the intestine into the blood stream. When higher than normal amounts of Candida antigens cross the ‘leaky’ intestinal wall and enter the bloodstream, they induce the synthesis of higher than normal levels of anti-Candida antibodies. Then these antibodies combine with the Candida antigens circulating in the bloodstream, forming immune complexes (Crandell, 2002, p. II-3).

Woodcock et al correlates a decrease in IgA with an increase in bacterial translocation outlining the barrier that IgA creates in reinforcing the intestinal mucosal barrier. Peyer’s Patches also are involved in the formation of IgA, an immunoglobin responsible for assisting in gastrointestinal barrier integrity. This author contends that as small intestinal health is altered, the Peyer’s Patches being a fundamental part of this dynamic can no longer produce adequate amounts of IgA, (Baugmart, 2002). IgA is used as one major marker in the diagnosis of gastrointestinal hyperpermeability (Galland, 2006; Miller, 2006).

4) MT or BT: Berg: Bacterial translocation may stem from 1) small intestine bacterial overgrowth, 2) immune deficiency, or 3) mucosal injury of the gastrointestinal barrier (Berg, 1995). “Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal tract to extraintestinal sites, such as the mesenteric lymph nodes complex, liver, spleen, and blood stream.” (Berg, 1995, p. 149). The same dynamic applies to Candida Albicans and other fungal microbes and is referred to as microbial translocation.“MLN is the first organ encountered in the translocation route from the GI lumen, is readily promoted by intestinal bacterial overgrowth. In fact, the degree of translocation of certain species of enterobacteriaceae to the MLN is directly related to their levels in the small intestine and cecum. The bacteria that translocate at the greatest efficiency from the GI tract to the MLN of monoassociated ex-germ free mice are Pseudomonas Aeruginosa and gram negative, facultative, aerobic enterobacteriaceae such as Klebsiella Pneumoniae, E.coli, and Proteus Mirabilis. Gram-positive, oxygen tolerant bacteria, such as Staphylococcus Epidermis and Lactobacillus Brevis, translocate at an intermediate level.” (Berg, 1995, p.149). “…it has also been suggested that macrophages and polymorpho- nuclear leukocytes engulf particles, including bacteria, at mucosal surfaces and transport them to abscesses, lymph nodes and other sites. Much more investigation is required to delineate the roles of cell-mediated immunity in the pathogenesis of bacterial translocation.” (Berg, 1995, p.151). “In the intestinal bacterial overgrowth model…indigenous bacteria translocate through the epithelial cells (intracellularly), rather than by interrupting tight junction to pass between enterocytes (extracellularly). Even overtly pathogenic organisms such as salmonella typhimurium and Candida Albicans are seen by microscopy to cross the mucosa intracellularly through intestinal epithelial cells.”(Berg, 1995, p.150). Berg goes on to correlate the affects of antibiotics and steroids with small intestinal bacterial overgrowth.

In fact, “In healthy individuals, bacteria are continually crossing the intestinal mucosa and are then transported into lymph and extra-intestinal sites, including the mesenteric lymph nodes, liver, kidney, spleen, and bloodstream. This phenomenon is known as bacterial translocation and occurs at very low rate and involves very small numbers of microbes in healthy individuals—most of the organisms being killed by the normal host defence mechanisms. The organisms most often associated with bacterial translocation are: E.coli, K. Pneumoniae, Enterobacter spp., Pr. Mirabilis, Enterococcus, Streptococcus spp., and Candida Albicans.” (Wilson, 2005, p.312). These bacteria have commonly been found in stool and broth urine cultures ordered by this author of her patients having IC.

“The passage of indigenous bacteria colonizing the intestine through the mucosa to local lymph nodes and internal organs is termed bacterial translocation and is a critical step in the pathophysiology of various disorders, from inflammatory bowel disease and sepsis to heart failure…What is more, bacterial translocation can also be detected in healthy people, with a frequency as high as 5% of the population assayed.”(Gorski et al., p.313, 2006)

Combination of the above phrases: “Intestinal barrier function regulates transport and host defense mechanisms at the mucosal interface with the outside world. Transcellular and paracellular fluxes are tightly controlled by membranes pumps, ion channels and tight junctions adapting permeability to physiological needs. Food and microbial antigens are under constant surveillance of the mucosal immune system. Tolerance against commensals and immunity against pathogens require intact antigen uptake, recognition, processing, and response mechanisms. Disturbance at any level, but particularly bacterial translocation due to increased permeability and breakdown of oral tolerance due to compromised epithelial and T cell interaction, can result in inflammation and tissue damage.” (Baumgart et. Al, 2002, p.685). (Riordan et al. 1997) finds that small intestine hyperpermeability occurs in SIBO and that Enterobacteriaceae are amongst the most common bacteria involved with this process. This bacterium is the one that this author finds to be the most commonly occurring in broth cultures of those having IC. The following quote comes from a study on microbial translocation specifically focused on Ecolab and Candida Albia’s, “ However, in many specimen, Candida were found to be budding both within macrophages and in the extracellular spaces. Perhaps 20-30% were within extracellular spaces, many of these free within lymphatics…. in the sub mucosal lymphatics, the organisms were found both free and within macrophages, sometimes associated with leukocyte aggregates…examples were seen in which a high frequency of translocation occurred through the mucosal epithelium covering Peyer’s Patches.” (Alexander et.al 1990, p. 503). “The most important finding of our study is that both large (C. Albicans) and small (E. coli) intact microbes and endotoxin translocated directly through morphologically intact enterocytes through a similar mechanism, which is different from classical phagocytosis and exocytosis.” (Alexander et.al 1990, p. 508). “While the current studies do not address the clinical relevance of translocation, they provide evidence that translocation of viable microbes and endotoxin occurs with great frequency through morphologically intact enterocytes.” (Alexander et.al 1990, p. 510). Some hypothesize that “absorption of antigens via intestinal lymphatic may be a significant source of systemic autointoxication” (McMillin et. Al, 1999 p.3). Autointoxication, the theory of intestinal toxins entering systemic circulation is an ancient theory that recently has sprouted routes with theories such as multiple chemical sensitivities and endotoxins (McMillin et. Al, 1999). McMillin et. Al correlate lymphatic absorption of antigens with psoriasis and other autoimmune diseases. They base their opinions on the concept of bacterial translocation that ultimately leads to multiple organ failure (MOF) and death. However, McMilllin et. Al are of the position that that autoimmune inflammatory responses are activated by bacterial translocation, and that MOF is the extreme result, and chronic disease is what lies between that extreme and health. (Husebye, 2005, p.2) in his review of bacterial translocation says, “The consequences (of bacterial translocation) of the host vary from none to life-threatening complications caused by electrolyte deficiencies and septic manifestations”.

These research studies illuminate the fundamental issues underlying the pathology of IC and other chronic diseases that often accompany the condition as theorized by this author. To further substantiate this connection, this author finds that the urine cultures conducted on her patients are often positive for the microbes commonly associated with MT above, i.e. E.coli, Enterococcus, K. Pneumonniae, Proteus Mirabilis, and/or Candida Albicans. And, (Keay et al, abstract, 1995) a researcher at the forefront of the field of IC found that “These data do not provide evidence that IC is associated with infection or colonization by a single microorganism. However, they do generate the hypothesis that the prevalence of microorganisms, especially bacteria at low concentrations, is greater in the urine of IC patients than of control subjects. If these results are confirmed by other controlled studies, the question of whether the presence of these organisms is a cause or a result of IC should be addressed.”

This author finds that there is often a different result between standard agar culture and broth culture urinalysis, however. Broth analysis is usually required in order to isolate the pathogens present in IC. This is a controversial issue, however, the consistency of results among patients warrants a need for a more research in this area.

Once homeostasis has been upset and this process is put into motion, pleomorphism can occur as well, complicating the process further (Appleton, 2002). (Palermo, 2003), of Washington University School of Medicine in St. Louis, is researching the issue of biofilms as a reason for ineffective antibiotic treatment in resistant and chronic infections. He describes the multicellular organism formed by thousands of bacteria working together that become a force too strong for the immune system and the antibiotics given to treat the infection. He further argues that the bacteria often reside within the tissues of the bladder rather than free flowing within the bladder organ often rendering negative results with urinalysis.

It is this author’s belief that we may only be on the cutting edge of discovering the numerous adverse affects that modernly used chemicals in medicine, diet, and other practices are having on the mucosal barrier that protects the internal environment from the external environment, and that this is the root of many chronic disorders including IC. It is this author’s opinion that if we alter many of our current practices, this disorder as well as many others may be eliminated.

Trigger Factors

The body will endeavor to protect itself against the precipitating factors through Compensation and store the pathology in its attempt to maintain Latency. Eventually, the body will be unable to continue the processes of Compensation and Latency because either too much Latency has accumulated or the body has become too depleted of the physical stores required to maintain the Latent state. In some cases, the trigger factor is so strong that precipitating factors are not required, but that is the exception, not the rule.

Basically what occurs during the precipitating phase is a change in the GALT affecting the MALT. The Western concepts of SIBO, LGS, MT and BT are the CCM processes of Compensation and Latency. Inflammation ensues from these conditions and affects other body tissue. As we said earlier in this text, Compensation and Latency present as chronic disorders involving inflammation primarily in areas such as muscles and joints (arthritis); eyes, ears nose and throat (allergies, chronic sore throats and ear infections, migraines); the pelvis (endometriosis, fibroids, cysts, PMS); skin (chronic skin conditions such as seborrhea, eczema, psoriasis); genital (chronic vaginitis, jock itch, vulvadynia); digestive system (chronic bloating and gas and IBS) to name a few examples.

The Trigger factor is the final onset of the disease process. The only exception is the acute onset of the sexually transmitted model. However, that too was created over time in the person the transmission originated from.

Trigger factors are identical to precipitating factors, the only difference being that it is the final step prior to the onset of the IC. Precipitating Factors and Trigger Factor may be the same or different. The Trigger Factor is the factor that finally brings the pathology to the urinary bladder itself, marking the time that the patient associates the onset of the disease. The only factors that are not precipitating factors but may be trigger factors are:

Childbirth: hormonal imbalance triggering an onset.

Surgical or medically invasive procedure that introduces a biofilm into the body

or triggers MT or BT.

The precipitating and trigger factors determine the course this disease takes and exactly how it will manifest itself coupled with, of course, the emotional and physical constitution and imbalances of the person.

The more suppression that has occurred, the more the pathology becomes complicated. Inappropriate treatments may also trigger Compensatory reactions as well.

The above trigger factors are non-issues for those with a healthy body. Childbirth, sexual activity, and menopause, for example will not cause problems for healthy persons. A surgical procedure, although traumatic, will not trigger IC without the precipitating factors in place first unless the way in which the procedure incited disease was the introduction of a biofilm.

There is much more to write on this subject, but, I thought this might be a good place to start: