Pathophysiology of Crohn's Disease
Inflammatory Bowel Disease (IBD): An chronic autoimmune disease involving the intestines, of which there are two types, ulcerative colitis (UC) and Crohn's disease. Historically, incidence of IBD has been highest in North America with Israel, Australia and South Africa close behind. However, trends suggest that the incidence of IBD (especially UC) are increasing in Latin America, Japan, South Korea, Singapore and northern India. Onset of the disease is typically between the ages of 15 and 30, with another peak between the ages of 60 and 80. Predilection for the disease is somewhat familial in nature.
Pathogenesis: The cause of IBD is not well understood. It appears to be the end-result of multiple factors that collide to cause malfunction of the enteric mucosal immune barrier. There are exogenous causes (gut bacterial flora) and endogenous factors (genetics and/or innate and adaptive immune function) as well as environmental influences (smoking, exposure to gut pathogens.)
Pathophyiology: An amazing property of the GI tract is its ability to differentiate between "good" bacteria of the normal flora and pathological invaders. This is due in part to the massive number of immune cells within the gut. In the presence of an infection, the full immunologic defenses of the gut are activated, but then quickly suppressed due the probability that these responses could be damaging to normal tissues and flora as well as invading pathogens. This robust immune competency appears to be poorly controlled in IBD.
Pathogenesis: The cause of IBD is not well understood. It appears to be the end-result of multiple factors that collide to cause malfunction of the enteric mucosal immune barrier. There are exogenous causes (gut bacterial flora) and endogenous factors (genetics and/or innate and adaptive immune function) as well as environmental influences (smoking, exposure to gut pathogens.)
Pathophyiology: An amazing property of the GI tract is its ability to differentiate between "good" bacteria of the normal flora and pathological invaders. This is due in part to the massive number of immune cells within the gut. In the presence of an infection, the full immunologic defenses of the gut are activated, but then quickly suppressed due the probability that these responses could be damaging to normal tissues and flora as well as invading pathogens. This robust immune competency appears to be poorly controlled in IBD.
In Crohn's disease, Th1 cells of the acquired immune system appear to become inappropriately activated in response to normal flora. These unrestrained inflammatory cells elaborate interleukins and cytokines (such as Tissue Necrosis Factor or TNF) that enhance the localized inflammatory response by recruiting more inflammatory cells resulting in injury to the bowel tissue. Early on in the disease process, very small areas of inflammation begin to form in intestinal crypts, but soon involve submucosal intestinal layers. Granulomas begin to form throughout the affected area of bowel as a result of this process. These granulomas can involve the full thickness of the intestinal wall, the mesentery and even regional lymph nodes. The continued damage to intestinal villi and crypts can result in abscess formation and eventually render the involved area of bowel unable to participate in absorption of food and fluids. As stated above, CD is a transmural process. Inflammation and edema of the full thickness of intestine will narrow the inner lumen, a process that can even cause on-again, off-again obstruction. The continuous, unremitting tissue damage that characterizes Crohn's lesions, however, may "eat" it's way through an area of intestine and into any nearby structures or tissues, producing fistula's into (for example) nearby loops of intestine, the bladder, vagina, or even the abdominal wall where it produces a tract that drains to the outside of the body. When patients with Crohn's disease experience bowel obstructions, it is often secondary to the edematous bowel wall and associated spasm. Though these are amenable to treatment (anti-inflammatory agents) the process may eventuate in scarring and strictures that cannot be managed conservatively and may require surgery.
Differentiating between Crohn's Disease and Ulcerative Colitis: There is significant overlap between UC and CD.
(1) Neither disease has an obvious diagnosable cause (bacterial or viral infections, for example.)
(2) In both diseases the GI tract tissues are inflamed.
(3) Both UC and CD are associated with systemic symptoms
(4) Both tend to run in families.
However, unlike CD, UC only affects the bowel submucosa, and occurs only in the large bowel. CD involves the full thickness of the gut wall causing it to be inflamed and thickened. Left unchecked, this process results in scarring and strictures. Additionally, CD, unlike UC, can occur anywhere in the GI tract from the mouth to the anus. A pattern of involvement typical in CD is referred to as "skip lesions", since it often occurs in multiple places within the intestine with perfectly normal tissue in-between. (40% of CD patients will have lesions in the small bowel only, 30% in the large bowel only, and 30% of patients will have the disease in both small and large intestine.) A common complication of CD is malnutrition, since the disease can impair function of the small bowel where most nutrients, much fluid and electrolytes are absorbed.
The Symptoms of Crohn's Disease: The clinical features of CD may be relapsing/remitting in nature. However, patients with active CD frequently manifest colicky abdominal pain, diarrhea, malaise and low grade fever. Particular nutritional deficiencies the patient experiences depends upon the section of bowel that is involved. Regardless, patients with CD are commonly malnourished and experience dangerous fluid and electrolyte imbalances. [Aside: In health the bowel secretes between 7-8 liters of fluid each day but reabsorbs it, along with ingested liquid (usually 2 liters/day). Because the absorptive surface of the bowel comes to 500 square meters, the amount of fluid lost through normal digestion is limited to about 200 ml included in feces per day. This is the reason cholera (which disables the bowel's ability to reabsorb liquid) can become so quickly fatal. CD, like cholera can interfere with this absorption/reabsorption process, if not as fulminantly and severely.]
Differentiating between Crohn's Disease and Ulcerative Colitis: There is significant overlap between UC and CD.
(1) Neither disease has an obvious diagnosable cause (bacterial or viral infections, for example.)
(2) In both diseases the GI tract tissues are inflamed.
(3) Both UC and CD are associated with systemic symptoms
(4) Both tend to run in families.
However, unlike CD, UC only affects the bowel submucosa, and occurs only in the large bowel. CD involves the full thickness of the gut wall causing it to be inflamed and thickened. Left unchecked, this process results in scarring and strictures. Additionally, CD, unlike UC, can occur anywhere in the GI tract from the mouth to the anus. A pattern of involvement typical in CD is referred to as "skip lesions", since it often occurs in multiple places within the intestine with perfectly normal tissue in-between. (40% of CD patients will have lesions in the small bowel only, 30% in the large bowel only, and 30% of patients will have the disease in both small and large intestine.) A common complication of CD is malnutrition, since the disease can impair function of the small bowel where most nutrients, much fluid and electrolytes are absorbed.
The Symptoms of Crohn's Disease: The clinical features of CD may be relapsing/remitting in nature. However, patients with active CD frequently manifest colicky abdominal pain, diarrhea, malaise and low grade fever. Particular nutritional deficiencies the patient experiences depends upon the section of bowel that is involved. Regardless, patients with CD are commonly malnourished and experience dangerous fluid and electrolyte imbalances. [Aside: In health the bowel secretes between 7-8 liters of fluid each day but reabsorbs it, along with ingested liquid (usually 2 liters/day). Because the absorptive surface of the bowel comes to 500 square meters, the amount of fluid lost through normal digestion is limited to about 200 ml included in feces per day. This is the reason cholera (which disables the bowel's ability to reabsorb liquid) can become so quickly fatal. CD, like cholera can interfere with this absorption/reabsorption process, if not as fulminantly and severely.]