I am often asked to explain what celiac disease is and why it matters. I decided to write this post to provide an overview of what happens to the small intestine of a person with untreated celiac disease. This discussion focuses on intestinal damage and how that impacts digestion and absorption of nutrients.
People with celiac disease have an impaired ability to digest and absorb the protein gluten from wheat, rye, barley, and other closely related grains.
People with celiac disease have an impaired ability to digest and absorb the protein gluten from wheat, rye, barley, and other closely related grains.
- Digestion is the chemical breakdown and release of nutrients from larger compounds to smaller ones. In the small intestine, proteins called enzymes facilitate this. Enzymes come from the pancreas and from cells lining the small intestine.
- Absorption is the process of bringing nutrients from the gastrointestinal tract into body.
- Gluten is a protein from wheat, rye, barley and other closely related grains (such as triticale) that forms when two proteins, gliadin and glutelin, interact with water (Medeiros & Wildman, 2014).
By BruceBlaus (Own work) [CC-BY-3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons
- The majority of digestion and absorption occurs in the small intestine.
- There are three regions of the small intestine - the duodenum, jejunum, and ileum (see figure above).
- A healthy small intestine regenerates itself and does this on an ongoing basis.
- When unfolded, the human small intestine is longer than a billiard table, is longer and wider than the kitchen in the studio apartment I rented in Milwaukee, Wisconsin. Yes, it is a fact that when unfolded the human small intestine is 10 feet long.
- The small intestine fits into the abdominal cavity because it is highly folded. These folds and projections exist throughout the length of the small intestine and increase its surface area and absorptive capacity.
- With regard to celiac disease, we are particularly interested in structures called villi, cells called absorptive cells, and intestinal crypts.
Villi, Absorptive Cells, Intestinal Crypts
- Fingerlike projections called villi (villus is singular form) exist throughout the small intestine. An example is illustrated in the cartoon below. The fingerlike structure maximizes the potential for nutrients to interact with enzymes and be absorbed into the body.
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By Boumphreyfr (Own work) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0) via Wikimedia Commons
- Absorptive cells line the villi and are very important for getting nutrients out of the tube that is the small intestine and into the body. Illustrations of absorptive cells are shown in the above cartoon.
- On the outer membrane portion of the absorptive cells are extremely small brushlike projections called microvilli. Microvilli are in constant motion. This facilitates their ability to capture nutrients. Microvilli play a role in digesting nutrients and bringing them into the absorptive cells.
- Microvilli are depicted in the "absorptive cell" illustration above. They are the top portion of the cell and are represented by the comb or burshlike features on top of the cell.
- Absorptive cells at or near the top of each villus slough off (fall off) every 3-5 days. Sloughed-off cells get eliminated from the body with other un-absorbed matter.
- Between each villus there are indentations and within these are the intestinal crypts (see illustration above). These crypts contain stem cells that go on to become new absorptive cells. Some stem cells become some specialized immune cells. New absorptive cells migrate up from the crypt and slowly make their way up to the top of each villus.
- Our bodies are designed to elicit rapid and efficient inflammatory responses.
- An inflammatory process begins with an inciting incident like tissue injury. Cells and chemicals respond rapidly, travel to the site of injury, and get to work. These cells and chemicals protect the area of injury, clean up the dead and damaged tissue, and begin to repair and renew the site. As the area is cleaned up and repaired, the inflammatory response ends. Resolution is important. It's important for relationships (so I hear) and for inflammatory responses.
- Gluten is the trigger of chronic inflammation in celiac disease.
- There is no tissue injury triggering the inflammatory response. Instead, there has been what is called a break in "oral tolerance." Gluten is perceived as harmful rather than a normal and tolerable dietary component that it really is (Murphy, et al., 2008, Taylor & Baumert, 2014).
- Once the body recognizes gluten as harmful, immune cells elicit a localized inflammatory response in the small intestine.
- The problem with this is that gluten is a regular, non-harmful, non-pathogenic food protein that is widely present in food, medications, and other types of products.
Is chronic inflammation in the small intestine really such a big deal?
- Consider that structure = function and chronic inflammation damages the structure of the small intestine which damages its integrity.
- Chronic inflammation in the small intestine damages the villi, microvilli, absorptive cells and intestinal crypts (Taylor & Baumert, 2014).
- Malabsorption, nutrient deficiencies (such as iron deficiency anemia, folate deficiency, vitamin B12 deficiency, protein deficiency), failure-to-thrive in infants and children are all common occurrences in people before celiac disease is diagnosed and treated (Taylor & Baumert, 2014).
- When the intestine becomes damaged, it can become permeable which increases the risk for infection (Murphy, et al., 2008).
- Villi:
- Over time, the villi flatten as a result of inflammatory damage. This results in a loss of absorptive capacity of the small intestine because the absorptive cells of the small intestine line the villi (Taylor & Baumert, 2014, K. Murphy, et al.)(see figure below).
- Absorptive cells & microvilli
- Nutrients must move from the tube of the small intestine, across the microvilli (brushlike border) into the absorptive cells and from there into the rest of the body.
- Some enzymes work to digest nutrients in microvilli regions of absorptive cells. When microvilli are damaged due to chronic inflammation, these enzymes cannot function properly and nutrients, like carbohydrates, may not be properly digested.
- Absorptive cells are also harmed by inflammation and this impairs the ability of these cells to absorb nutrients.
- Intestinal Crypts
- During chronic inflammation, the intestinal crypts initially try to compensate by producing more cells including more absorptive cells and more immune cells.
- However, the degree of inflammation infiltrating the region eventually exceeds the capacity of the crypts to compensate and not enough cells are produced to maintain villi structures and absorptive cell numbers (see figure below).
- The illustration below represents the impact of chronic inflammation in the jejunum region of the small intestine in someone with celiac disease. This can happen anywhere in the small intestine, this image represents one portion.
- The little dots represent the immune cells coming and causing inflammation.
- The panel labeled "0" is healthy tissue.
- The panel labled "4" is notably damaged tissue where the villi have flattened out and the crypts have been infiltrated with immune cells.
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| AdWikipedianProlific at the English language Wikipedia [GFDL (http://www.gnu.org/copyleft/fdl.html) from Wikimedia Commons |
What can a person with celiac disease do to prevent chronic inflammation?
- A person with celiac disease must remove all gluten from their diet. This includes medications and products as well as food and beverages.
- The absolute removal of gluten interrupts the cycle of chronic inflammation therefore allowing for resolution. It also provides an opportunity for the small intestine to heal.
- The majority of people with diagnosed celiac disease do experience improvement after 7-8 weeks on a completely gluten-free diet.
- Some people do have what is called "refractory" celiac disease and continue experiencing problems after being completely free of gluten. This may be due to the degree of intestinal damage already done by the time of diagnosis, but the exact reason why some people do not respond as well remains unclear.
Below are links to 3 websites I find useful regarding the definition of celiac disease:
- Mayo Clinic - Celiac Disease
- US National Library of Medicine (NCBI)
- U.S. Department of Health & Human Services - National Digestive Diseases Information Clearinghouse
Final comments
Understanding the cause(s) of celiac disease is ongoing and an active area of research; in other words, there is still a lot to learn and scientists in this field are working to figure this out. As mentioned above, I deliberately focused this post on how gluten exposure alters the integrity and function of the small intestine in celiac disease as it pertains to digestion and absorption of nutrients. I have not gone into detail about topics like specific types of immune cells that are or are suspected to be involved in celiac disease. If you would like to talk about that, please post a comment or send me an e-mail.
Update: This is an article was released November 3, 2014 at The New Yorker Magazine online. It's a good read.
What's so bad about gluten? Against the Grain. Written by Michael Specter
References:
* Medieros DM & Wildman RC. (2014). Proteins and Amino Acids. Advanced Human Nutrition, 3rd Edition. (p. 149). Burlington, MA:Jones & Bartlett Learning
* Blaus B. (October 8, 2013). Anatomy of small intestine. Retrieved August 20, 2014 from WikiMedia Commons http://commons.wikimedia.org/wiki/File:Blausen_0817_SmallIntestine_Anatomy.png.
* Boumphreyfr. (May 29 2009). Diagram of small intestine villi. Retrieved August 20, 2014 from WikiMedia Commons http://commons.wikimedia.org/wiki/File%3AVilli1.png.
* K. Murphy, P. Travers, & M. Walport (Eds.), (2008). The mucosal immune system. In Janeway's Immunobiology, 7th Edition (pp. 459-491). New York, NY: Garland Science.
* Taylor SL, Baumert JL. (2014). Food allergies and intolerances. In AC Ross, B Caballero, RJ Cousins, et al (Eds.) Modern Nutrition in Health and Disease, 11th Edition (pp. 1430-1432). Baltimore, MD: Lippincott Williams & Wilkins.
* Lange, Der. (September 12, 2006). Jejunal inflammation in coeliac disease Retrieved August 21, 2014. Retrieved from Widkimedia commons http://en.wikipedia.org/wiki/Coeliac_disease#mediaviewer/File:Coeliac_Disease.png.
