Hello, in this video we're going to talk about celiac disease. This is an overview and introduction. Celiac disease is an inflammatory disease, a process which occurs in susceptible individuals in response to ingestion of wheat protein, gluten, specifically the protein gliadin. The clinical presentation of celiac disease include abdominal pain, abdominal discomfort, bloating, diarrhea.
Stinky stool, steatorrhea, which is essentially a fatty stool, anemia, weight loss, failure to thrive, specifically in children, the young. But celiac disease can also present asymptomatically in one third of people who have it. It's important to remember that if someone presents with diarrhea, weight loss or anemia, anemia can be iron deficiency or vitamin b12 to think of celiac disease. Some signs of celiac disease around the face include development of aphthous ulcers, atrophic glossitis from the anemia as well as anorexia from the malabsorption.
Dermatitis hepatiformis is also another sign and this is also known as Düring's disease and it's a chronic blistering skin condition that is itchy and usually are on extensive surfaces such as your elbow, ankles, below the knees. There are many differential diagnoses of celiac disease but we will not go into that. If one presents with these clinical signs and symptoms it's important to order investigations.
Investigations include a full blood count which will detect anemia or any possible infections. Electrolyte urea creatinine is important to check for any electrolyte derangement as well as malabsorption. LFTs is also important to see to rule out differential diagnoses that can affect the liver or the biliary tree.
Blood smear is also important to check for what type of anemia. Serology tests can also be you serology tests can also be ordered to test for the presence of autoantibodies seen in celiac disease. Specifically, autoantibodies to transglutaminase, endomycin, as well as gliadin. Finally, an endoscopy can be performed and it is gold standard for the diagnosis of celiac disease. And this is essentially where a camera is fed through the esophagus down to the small intestine where a tissue biopsy can be taken.
And using this tissue biopsy, a diagnosis can be made. However, for a proper diagnosis, the person suspected of having celiac disease should not eat gluten-containing foods initially. Then a biopsy will be taken.
This is followed by eating normal gluten-containing food, and then another tissue biopsy taken. And this is in order to check for the differences in small intestine tissue architecture. And the changes seen in active celiac disease include increase in lymphocytes in the area, hypertrophy of the crypts, as well as villus atrophy.
And this is the hallmark for the diagnosis of celiac disease. Management is ongoing and includes mainly a gluten-free diet. A gluten-free diet means not eating foods containing gluten.
And gluten-containing foods can be remembered with the acronym BROW. So B as in barley, R as in rye, O as in oats, and W as in wheat. So these four things contain a lot of gluten and therefore should be avoided. Further, if malabsorption is an issue, supplements such as calcium, iron, as well as other vitamin supplements can be offered.
During periods of exacerbations, from celiac disease, aka celiac crisis, quick treatment is important. Celiac crisis is a life-threatening condition and it is rare. People who present usually have unexplained diarrhea with severe malabsorption and massive electrolyte imbalance. Treatment of celiac crisis include rehydration with electrolytes and also corticosteroids to reduce the inflammation and pain that is occurring. Now let us talk about the pathophysiology, the mechanism of disease of celiac disease.
So here is the jejunum, the duodenum, and the stomach. We are looking at the lumen of the jejunum and the cells here. So here is a zoomed in view of the area.
Here is the lumen where food will pass through or parts of the food. The jejunum is made up of enterocytes and below these enterocytes is a lamina. which contains other types of cells. On top of the enterocytes here in yellow is the mucus. The small intestine forms crypts and villi.
The enterocytes of the small intestine also have microvilli which are essentially small finger-like projections that increases the surface area to increase absorption essentially. As mentioned here in yellow is the mucus which actually lines and protects. the mucosal cells, the enterocytes, and residing on top of the mucus we can find antibodies, IgA dimeric antibodies, and IgA antibodies are the antibodies of the mucosal immune system and help defend against infections. Within the lamina propria, which is the level below the enterocytes, you can find some other cells including antigen presenting cells which are important cells in the communication between the innate immune system and the adaptive immune system. Some people essentially have a predisposition to developing celiac disease, and these are risk factors, and these risk factors include having a family history of celiac disease, an autoimmune thyroid disease, having type 1 diabetes, having IgA deficiency, and inflammatory obesity.
bowel disease. The pathophys of celiac disease is a mystery, but here and now I'm just going to draw about the current, I guess, theory. So drawing it out, I'm just drawing the same picture on the left. Here we have the lumen of the small intestine, the enterocytes, and above the enterocytes is the mucus in yellow. Below the enterocytes is the lamina propria, where we can find some cells, including the antigen-presenting cells.
In some parts of the small intestine, there are also things called Peyer's patches, and also nearby there are mesenteric lymph nodes, which are really important lymphoid tissues which help activate an immune response. In these tissues, we can find what's called naive T-cells, which are basically T-cells, an immune cell, which is not activated. Now above the mucosa, Back here again, as mentioned earlier, there are antibodies, IgA antibodies. IgA is the antibody of the mucosal immune system, and it is dimeric here.
So the pathogenesis theory goes something like this. Gluten-containing food is broken down, and a part of gluten, a specific part called gliadin, is absorbed. Gliadin, through the enzyme tissue glutaminase, or TTG, gets converted to deaminated gliadin peptides. The deaminated gliadin peptides gets picked up by these antigen-presenting cells within the area. The antigen-presenting cell will then present this peptide onto a specific class of molecule called the HLA-DQ2 or HLA-DQ8.
And so this antigen-presenting cell will bring this deaminated gliadin to nearby lymphoid tissues such as the Peyer's patches or the mesenteric lymph nodes. And here the antigen presenting cell will present this gliadin peptide to the naive T cells. This contact will actually activate the naive T cells to become either CD8 T killer cells or CD4 T helper cells. depending on the cytokines, chemical produced, and all these other stuff.
But just remember that the naive T cells become either a T killer or a T helper cell. And these cells are now primed against the deaminated gliadin peptide, or the gliadin protein, to make it easy. The CD8 T killer cell, as the name suggests, kills things.
They are aggro. and will promote inflammation when in contact with gliadin. So every time we eat gluten, which contains gliadin, inflammation will occur. The CD4 T cells, as the name suggests, they help. They actually help another cell called B cells.
What they do is they help activate B cells. And the activation of B cells means that these B cells can mature and become plasma cells. And plasma cells are the cells that produce our antibodies.
So in this scenario, this plasma cell will produce antibodies against gliadin because it was the protein that was presented in this whole scenario. Interestingly, the plasma cells activated in patients with celiac disease can actually produce other antibodies. So we mentioned anti-gliadin, but there are also anti-endomycin or endomycium or endomycin as well as anti-tissue transglutaminase.
Regardless, when these antibodies are in contact with gliadin, endomycium, or functional tissue transglutaminase, they will promote inflammation. And so every time we eat foods containing gliadin, inflammation will occur around the area. Inflammation around the small intestine will cause abdominal pain, abdominal discomfort, diarrhea, as well as bloating. Not only that, but inflammation damages the lining of the small intestine, making the crypts look all funny, and also damaging the microvilli, the small finger-like projections in the area.
So what does this mean? Well, it means that things can't be absorbed properly. So when there's damage to the mucosa, this area, things such as iron and vitamin B12 cannot be absorbed properly. Nutrients such as protein, carbohydrates cannot be absorbed properly. Iron and vitamin B12 that can't be absorbed leads to anemia.
Other nutrients not being absorbed efficiently leads to weight loss, as well as failure to thrive in children. Lipids, fats that are not being absorbed means that the lipids will still stay in the bowels and will come out in poo, and this will cause the stool to be stinky, and you get steatorrhea, which is basically fatty stool. And these things again are not absorbed properly because of the damaged mucosal lining, thanks to the inflammation.
Let's now take a closer look and focus on the pathological changes seen in the small intestine of people who have celiac disease. And there are four changes that is important here. The first is that we can see villous atrophy. We can see hyperplasia of intestinal crypts. We can see increase in lymphocytes in the lamina propria and around this area.
And finally we see cell death around the area or just destruction in general. Complications of celiac disease can be minor or life-threatening. Complications include anemia.
They have increased, I guess, risk of developing certain tumors, GIT T-cell lymphomas, they can get hyposplenism, osteoporosis, neuropathies, and dermatitis herpatiformis. Differential diagnoses of celiac disease include cow milk sensitivity, food sensitive entropathies, Crohn's disease, colitis, GIT lymphoma, Whipple's disease, Giardia lambia infection, and Irritable bowel syndrome.