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Celiac disease – causes, symptoms, diagnosis, treatment & pathology

Celiac disease – causes, symptoms, diagnosis, treatment & pathology

It’s becoming more and more common to see
things like “gluten-free pizza” or “gluten-free buns” at restaurants, grocery stores, or
other food-based businesses. This is partly because there’s this increasing recognition,
awareness and diagnosis of a disease called celiac disease, sometimes called celiac sprue,
and as many as 1 in 100 north americans are diagnosed with it. Celiac disease is currently understood as
an immune system-mediated disorder where the gluten in food triggers the body’s immune
cells to attack the cells in the small intestine. Gluten’s found in all sorts of wheats and
grains, including rye and barley. If we take a look at wheat, you’ve got your individual
wheat kernels, and then inside each kernel’s there’s the endosperm, which has a bunch
of nutrients for the seed’s embryo, mostly protein and starch, and some vitamins. The
type of protein here is gluten, the main culprit in Celiac disease. Well, really the main culprit
behind celiac disease is a 33 amino acid peptide component of gluten called gliadin. Okay,
so the gliadin in gluten is what triggers immune attack in Celiac disease, hence the
need for gluten-free pizza or buns in hamburgers, right? Well, that’s not the whole story…since
we’ve known about Celiac disease for quite some time, like 70 years. So why the recent
push? Well, within the last few years there’ve been proposals of non-celiac gluten-related
disorders, like gluten sensitivity, where gluten is thought to cause GI symptoms that
seemingly improve when gluten’s taken out of the equation. Unfortunately, as of this
moment in February 2016, there’s very little solid scientific evidence to back a removal
of gluten from the diet unless you have celiac disease, although some people do seem to have
improved GI symptoms on a gluten-free diet, whether that’s from removing gluten specifically,
or a more broadly, an adherence to a diet that’s typically much lower in processed
foods and carbohydrates, remains to be seen! Alright, back to celiac disease, so, if somebody
with celiac disease eats a wheat-based pizza, it’s broken down in the stomach into gliadin…and
a whole lot of other stuff, gliadin’s a tough little bugger though and resists being
broken down by all sorts of enzymes. When gliadin gets to the small intestine, it’s
bound to secretory IgA in the mucosal membrane, which is an antibody that helps protect gut
epithelial cells called enterocytes from toxins and pathogens. Usually, things bound to secretory
IgA are marked for immune cell destruction, but in Celiac diseasve, this gliadin-IgA complex,
for some reason, binds to a transferrin receptor, TfR, which is usually used to help absorb
iron and seems to be over-expressed in patients with Celiac disease. Once bound to the receptor,
it’s trancytosed across the cell from the apical to the basolateral membrane, or across
the enterocyte and into the lamina propria which is a thin layer that lines the gut wall.
Once there, an enzyme called tissue transglutaminase, or tTG, cuts off of an amide group from the
protein. Deamidated gliadin’s then eaten up by macrophages and served up on its MHC
class II molecules. Remember, macrophages are in the gut and are always doing a bit
of “gut sampling” where they grab proteins (which a lot of times are from foods that
we’ve eaten) and show them to the immune cells. MHC stands for Major Histocompatibility
Complex and is that name of the “serving platter” for the stuff that is served up.
It’s a normal way to make sure that there are no pathogenic bacteria lurking in the
gut. Now there are a ton of different types of
MHC class II “serving platters” and these serving platters are encoded by genes called
human leukocyte antigen genes, or HLA genes. These genes determine what things the MHC
class II molecules “serve up”, so, for example, HLA-DR encodes
for an MHC that “serves up” something different than the one HLA-DQ encodes for.
. Researchers have noticed that patients with celiac disease typically have specific deamidated
gliadin “serving platters” such as one called HLA-DQ2 or HLA-DQ8, which is an interesting
clue that helps us better understand celiac disease. It’s at this point—where the HLA protein
“serving platter” serves up gliadin—that the immune system kicks in. The macrophage
throws it up top and is like “hey, uh, guys? What do you think about this molecule…?”
and T helper cells, also known as CD4+ T-cells, from the immune system that recognize the
gliadin zoom over and are like “Yep, I’ll take it from here”, and they release inflammatory
cytokines, molecules that initiate inflammation, like interferon gamma and tumor necrosis factor,
which can directly damage and destroy epithelial cells in the villi of the small intestine.
Not only that though, the helper T cell stimulates B cells to start pumpin’ out IgA antibodies
against the gliadin, the transglutaminase enzyme, and endomysial antibodies, or EMAs,
which are actually another type of antibody for transglutaminase, but for the transglutaminase
found in the endomysium, a layer of connective tissue around muscle fibers. It’s not totally
understood why these are produced since they don’t seem to cause any muscle related damage
or symptoms; it’s possible they’re produced simply because of their structural similarity
to the transglutaminase in the lamina propria. They are, however, helpful in making a diagnosis.
Finally, the helper T cells also recruit killer CD8+ T cells, which is when things get nasty.
Killer T cells are drawn to and destroy cells undergoing inflammation. So, in short, as
patients eat gluten, the immune system is stimulated and epithelial cells are destroyed.
It’s possible that the destruction of these cells lets more gliadin across the epithelium,
since they’re not bunched together as tightly as they were before. Tests for the antibodies in the blood can
be used clinically to help screen for celiac disease, IgA blood tests for both tTG and
endomysial tTG can be effective ways to determine whether someone has Celiac disease, especially
in more severe cases, although for more common, mild forms of Celiac, these tests are less
effective. Tests for IgA or even IgG antibodies against gliadin may also be used. For reasons
that aren’t well understood, a small amount of the patients are IgA deficient, meaning
they aren’t able to produce any IgA antibodies in general, so in this case they’d need
to have an IgG screening test done. Now this whole fiasco mainly happens in the
duodenum, probably because it’s the first part of the small intestine and so the first
to be exposed to gluten, the jejunum and ileum are also involved, but the duodenum is where
most of the damage goes down. So a biopsy of the duodenum shows pretty clearly the extent
of the damage. Healthy duodenum should look like this, where you have these really tall
villi and these crypts that don’t go down too far. With celiac disease, these villi
can be destroyed and flattened out, called villous atrophy, and the crypts can get longer;
these changes are called crypt hyperplasia, possibly from infiltration of immune cells
or from the remodeling process that begins to take place during chronic inflammation.
You’ll also be able to see this infiltration of immune cells, or lymphocytes, in the epithelium.
An endoscopic biopsy of this tissue can be an effective, yet more invasive way to diagnose
celiac disease. Children with celiac disease often present
with symptoms like abdominal distension or bloating, as well as failure to thrive and
diarrhea. Adults typically have chronic diarrhea and bloating as well, but the symptoms vary
wildly. Also, patients can frequently have dermatitis herpetiformis as a complication,
which actually has nothing to do with the herpes virus. It’s actually a bumpy skin
rash that pops up from circulating IgA antibodies in the blood, where they mistakenly bind to
the transglutaminase in the dermal papillae of the epidermis. Once they’ve bound, neutrophils
swing by and start up an inflammatory reaction that’s noticed on the skin as this rash. Now, the main bad guy in this whole story
that provokes the immune system and causes this whole mess, is gluten. So symptoms and
issues typically resolve when patients adapt a gluten-free diet. For some patients that
start to adhere to a gluten-free diet, even for many years, there’s still an increased
risk of refractory disease, like small bowel cancer and T-cell lymphoma, presumably due
to inflammation and immune system activation over time.

100 thoughts on “Celiac disease – causes, symptoms, diagnosis, treatment & pathology

  1. Can u help me with section when u say " usually this complex ……" It's around 2.20-2.30…plz rply I m not Abel to understand

  2. I don't know if I have celiac disease but all I know is I can hardly eat any regular foods because I feel like someone punched me in the gut and I feel faint from the pain from being so dizzy. So I decided to slowly cut out foods that contain gluten. I did an experiment on myself where I think I ate peanuts that contained gluten and felt like shit and an hour later, I made myself some chicken breast with a small amount of basil and salt, with a side of white rice and a little bit of ketchup. I looked up all these ingredients to find out if they had gluten and they didn't, which made sense because my horrible pain went away and I actually cried out of happiness from not feeling so much pain in my stomach. I do have to switch from Hunt's ketchup to Heinz and I will have to make many adjustments but the way my body feels when I'm gluten-free is like worth all the trouble that I have to go to find the right foods, ingredients to cook with and restaurants to go to. I'm already doing the research and I will talk to my doctor to actually get tested soon as well but I know my body and I know this works for me and I don't feel like someone punched me in the gut anymore.

  3. I thought this was a bullshit pseudoscience until I got lab results back confirming that I have Celiac disease and carry the
    Celiac gene

  4. thank you guys, it was really helpfull, but I didn't understand the difference between Celiac disease and Gluten Sensitivity!!?

  5. hi .thank you for this well done work ; but can i ask you the software that you are using to make this fabulous video ; i hope i can have the answer . and thank you again =)

  6. also when eating gluten with ceoliac desiese you get a lot of stomach pain and throwing up. A LOT.

  7. So, once the damage has been done to the walls of the small intestine, can that damage be undone once gluten is stopped? I’m currently waiting on the results of a celiac test because I was diagnosed with malabsorption and I’m so worried that my body will never absorb nutrients properly again 🙁

  8. For the first time i understood what the hell HlA is what endomysial is and the shit transglut are ..thanks osmosis helps alot ur channel.keep up

  9. I have stage 6 celiac and I’m 12 years old and was diagnosed when I was 1 and a half and almost died there is only one other diagnosed person in the world with stage 6 and has a lot more side affects then the ones named in this video because 99 percent of celiac patients are a level 3 or under which means they really only have the gluten intolerance and not the hundreds of other side affects. I am a fighter and will continue being a fighter

  10. EMA attack seems to be logical, if you think about a next layer of tissues over lamina, the muscles in a third layer of mucous membranes (tunica mucosa), that covers your guts. All of a tunica mucosa gets inflamed, and a muscle layer too. Only thing that is missing – symptoms of inflammation in a muscle layer of mucous membrane.
    It could be a problems with intestinal tone or so.

  11. Btw, gluten "sensitivity" does not exist. You either have celiac disease or you don't. Also, a gluten free diet does not help with weight loss. Please do your research people (American's).

  12. came to post that my symptons got cured. took about a year and 3 months after it started happening. basically no sugar, exercise and try to relax. also sleep is important. but yeah, took a lot of effort. some meditation.

  13. Cause: Vaccines, they train the body to think that foreign proteins which shouldn't be in the blood, enter the blood through an inflammatory basis in combination (TH2),and not through mucus membranes and thus, send the antibodies to attack the invader resulting in auto-immune, or allergies (asthma)

  14. Oddly enough if you eat bread from non processed sources, or countries where bread is baked fresh you have no GI issues. Clearly it's the hundreds of additives that they put in bread that are the culprits, not to mention the added sugar. In a study they found that serving processed food which all contains sugar added and non added sugar foods people's allergies and health greatly improved. Even when compared to removing other unnecessary ingredients , it was the lack of sugar that yielded the best results. So in all fairness to food, eat less sugar. There is even evidence that sugar might be the culprit behind higher blood pressure( more so than sodium) and Alzheimer's.

  15. The wheat is one of the oldest food in earth so I want to ask why all of these thousand and thousand years nobody had any problem to eating bread. Bread it was the king of the table. For many centuries the main foods was Bread, cheese and vegetables and the life wasn't easy. However now many people can't eat bread and I suppose after few years much more people will can not eat wheat bread. Is it not strange? What is the deference before and now? Explain me please. Thanks

  16. Great video and ultra informative. But i want to know why. Why do people have this reaction/disease.. mutation? Lack of exposure, gm crops? It would be interesting to know the cause.

  17. Seriously, amazing videos. I am a 6th year Medical Student and this videos still help me!
    You even inspired me to make a channel on my own! I make YT videos on medical topics.
    And today I posted a video about celiac disease as well.

    Thanks for all the knowledge bombs, and thanks for the inspiration.
    My dream is to make a video together once!

    Keep it up,
    So will I!

  18. I post about gluten free and celiac on my channel!! Just starting this up since i just got dignosed! go give my first video some love!! Thanks so much!!

  19. Pls help me bro my baby cant tolerate cows milk and other powder milk how can i diagnose my baby affect caeliac disease

  20. Exellent video. Packed with information in really understandable way without taking the science out of it. Really amazing presentation. By the way my son was recently diagnosed with celiac disease he is 7 and i am trying to get informed in order to inform him about his condition.

  21. whenever i stuck in any type of concept i would not find any helpful material in order to fully understand that respective topic. But this channel absolutely really helpful for me, thank you for being serving us.

  22. Perhaps worth mentioning without getting too deep is that often symptoms in adults wildly vary due chronic “malabsorption” of important vitamins and nutrients which take celiac sufferers down a whole other path of symptoms related to these deficiencies and not just related to the immune response to gluten. These symptoms can take much longer to resolve because the gut must heal first before it does it’s job of absorption again.

  23. Yo yo, I had coeliac disease for 47 years, but I got cured just 2 years ago when I changed the way I lived my life. You won’t believe the small change I made, it is so simple even I could do it. I want other people to get cured from this disgraceful disease and that is why I am offering seminars at the low low price of $479.99 per session for a 12 week course that will completely heal you of your disease.

    This is a small price to pay for the chance to completely take back your life. I had the worst symptoms ever but now I am completely freed. Now I lift weights, drink whatever I want and slay pussy every single day. You can be like that too when you take my course. You won’t regret it.

  24. Sad when most people are here because they are studying this but I’m here because I’m extremely sick from eating gluten 😪😫

  25. This is why I decided not to go into medicine. This is just TMI for me. For example I could NOT be a GI doctor because the less detail I know about poop, the better. I couldn't get through this video since I'm undergoing tests for celiac now and found the detail too disturbing. That said, I'm sure med students find this really helpful and I like the video's style.

  26. Im confident i have Celiac Disease and i wanna die there is no good tasting glutton free diet. Your options are fruits vegitables and terrible glutton free alternatives anyone who says they are happy with the glutton free diet are lying to themselves to avoid depression if you get diagnosed with this problem might as well blow your brains out

  27. Thank you. Just found out my daughter has Celiac disease. She kept telling me "Mom I am dying right in front of you."



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  31. Years ago in summer when I did sunbathing, I experienced severe abdominal pain with vomiting. As an objective thinker I was looking for cause and I did a great observation which I experimented. I solve that situation and never have I experienced that abdominal pain and vomiting. As a clue I tell you that in Washington State the temperature in summer is max 80. After that I bought a land in Nevada where the temperature is 98 and I do sunbathing there. Now I am doing observations about urinary urgency. Just few days ago I did an observation which now I experiment. I am 75

  32. for the solid evidence, see Dr Roger Mussi, a French doctor who followed hundreds of patients over 10 years with the IgG response to the non-coeliac sensitivity. 53% of his patients suffered this non-coeliac sensitivity adding to this the 1% of coeliac disease (IgA mediated) and the Crohn disease patients. 53% of his patients had the non-coeliac sensitivity and he is quite fed up with that talk 'no solid evidence…"

  33. I've never understood the macrophage and dendritic cells presenting to the T-cells part of celiac disease. Those two cells also scavenge the tissues for cell debris and usually present them on MHC to T-cells too. When they are in disease fighting mode, they present the MHC with the protein fragment with a costimulatory signal to get the T-cells active. But in their scavenging mode, they don't give co-stimulation and turn the T-cells anergic (unresponsive). So why in Celiac disease do they provide costimulation? Most of the stuff they pick up are going to be food, not foes, unless the gut is infected with a non benign organism.

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