Tuesday, August 19, 2008
Understanding your gut and intestinal biopsies
Many people undergoing evaluation for celiac disease are confused by the terms used to describe the GI tract and its lining as well as the microscopic findings of small bowel biopsies. This article attempts to explain the terms in a manner that is understandable and that makes sense.
The gut is the largest immune organ in the body. Besides the skin it is also the largest border of our body exposed to foreign materials or potential invaders. It consists of a long tube that begins at the entrance at the mouth and ends at the exit the anus.
The small bowel is about twenty to twenty four feet in length or long enough to wrap your waist 6-8 times. The large bowel or colon is about five feet long or a little shorter than your height. The bowel are long somewhat circular tubes and what we eat or drink travel down these tubes becoming changed into waste as nutrients are digested and then absorbed along the way. Millions of finger like projections known as villi or villous tips give the surface of the bowel a Terry cloth towel like absorptive capacity as well as house several digestive enzymes.
The normal small intestine villi are long and slender. When the small intestine becomes damaged such as in advanced celiac disease the small intestine the villi become damaged. The surface when viewed directly during scope examination may appear obviously injured with loss of the normal velvety or shag carpet surface. Sometimes obvious ulcerations or fissures can be seen.
However, often, unless the damage is severe, the signs of gluten injury are only detectable on biopsies of the surface lining that are viewed under a microscope. Such examination shows the surface lining is flattened or the finger like villi projections are blunted. In this state absorption is significantly impaired. Without the normal villi projections the bowel can be compared to a worn out or cheap towel without much Terry cloth projections on the surface. Such a towel is worthless when attempting to dry off after a shower or mopping up a spill. Similarly, damaged intestinal villi do not absorb nutrients or fluid well. The result is malnutrition, weight loss and diarrhea that are common symptoms of advanced Celiac disease.
In addition to nutrients that need to be absorbed there are billions of microbes inside the gut tube. These microbes are mostly bacteria but also include viruses, parasites and yeast that are also trying to get into our body. Chemicals, toxins, food additives and incompletely digested food particles also inside the bowel are capable of entering the body if the gut lining or border is too permeable or leaky.
Infection fighting blood cells are needed at the surface to protect the body from invasion arising form within the gut. Lymphocytes are an important type of infection fighting blood cell that are found abundantly in the gut. Small numbers are stationed in the tips of the villi or finger like projections of the small intestine. These small groups of scout lymphocytes, usually no more than 2-3 per villous tip, are on the lookout for possible attack. These scouts are stationed between intestinal absorption cells or enterocytes, a form of epithelial cell. They can signal for help and recruit additional lymphocytes or other types of infection fighting or immune cells to the surface lining depending on the type or severity of attack or invasion.
The lymphocytes are counted at the villous tip and reported as such or they can be reported per 20 enterocytes or epithelial cells. By convention the number is usually translated into number of lymphocytes per 100 intestinal lining cells variously called by their specific name enterocytes or broader name epithelial cell. Since the lymphocytes are between enterocytes or epithelial cells they are termed intraepithelial lymphocytes or IEL’s. When in excess the term is intraepithelial lymphocytosis.
Additional lymphocytes and other infection fighting cells, including mast cells, are stationed at the base of the intestinal villi. These cells are like Army or Marine troops held in reserve that are just waiting to be summoned to the fighting front at the surface of the intestinal villi, whenever the body believes it is being attacked or invaded.
The finding of increased IEL’s, or intraepithelial lymphocytosis, is the EARLIEST microscopic finding of Celiac disease and gluten injury though it is not specific for it. Cow’s milk protein allergy or sensitivity, giardia parasite and H. pylori bacteria, and viral infections can also be a cause. Usually recognizing increased numbers of lymphocytes in the tips of the intestinal villi is easy.
Most pathologist just “eye ball” the tips and subjectively judge whether there are increased numbers. Most state there either is or is not increased lymphocytes in the tips of the villi or intraepithelial lymphocytosis without specifically counting or reporting the numbers.
Special stains are available that highlight these lymphocytes allow them to be seen and counted easily. However, these stains are not done routinely and usually must be specifically requested, especially when minor changes of gluten injury are suspected, for example in someone who has already limited their diet intake of gluten.
For more than thirty years the cut off for abnormal was eight or more lymphocytes per villous tip or >40 IELs per 100 intestinal epithelial cell (enterocytes). In the past couple of years an IEL count of 7 or more villous tip or 20 enterocytes equivalent to 35 IELs/100 epithelial cells became the standard for defining abnormal intraepithelial lymphocytosis.
Such increase lymphocytes in the context of typical symptoms and abnormal blood test or tests specific for Celiac disease became accepted as diagnostic even in the absence of villous atrophy, blunting or flattening. Newer research suggests an even lower number of as few as 25/100 or about 5 lymphocytes, in the tips of the villi, is abnormal.
Unfortunately, since many pathologists still consider Celiac disease rare, this finding of subtle finding of increased lymphocytes may be missed or be unreported. As a result this earliest microscopic sign of gluten injury is either overlooked or ignored.
To further complicate the issue, it is the most specific blood tests for celiac disease, endomysial and tissue transglutaminase antibodies are negative in as many as forty percent of people with early celiac disease. Therefore, to diagnose some early cases of Celiac disease it is critical that increased IEL’s be recognized and reported on intestinal biopsies.
Combined with an elevated gliadin antibody and symptoms, increased IEL's may be adequate to make a presumptive diagnosis of celiac disease and recommend initiating a gluten free diet. This is especially true in high-risk individuals such as those who have a family member with Celiac disease or have the presence of the HLA DQ2 or DQ8 genetic patterns.
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