Inflammatory bowel disease: Pathology review

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Case Study0:00–0:45

Alex is a 21 year old college student who has a 2 month history of frequent episodes of abdominal pain and bloody diarrhea.
Chris is also a 21 year old college student with painful ulcers in the mouth, intermittent abdominal pain, and non-bloody diarrhea that’s been going on for years.
In addition, Chris has a history of recurrent kidney stones. After careful examination, colonoscopy is ordered in both cases.
In Alex’s case, there’s circumferential inflammation that’s continuous throughout an entire section of the rectum and colon.
On the other hand, in Chris’ case, there are linear patches of damaged colon with normal mucosa in between, and the rectum is not involved.Alex and Chris both have inflammatory bowel disease or IBD, which is characterized by chronic gastrointestinal tract inflammation due to autoimmune reactions, as well as systemic symptoms like fatigue, fever and unintentional weight loss.

Pathology0:45–1:15

IBD typically has its onset before the age of 30. The exact cause is unknown, but there’s definitely a genetic component because it runs in families.
Now, there are two types of IBD - Crohn’s disease and ulcerative colitis. Okay, now let’s look at each specific disease, starting with Crohn’s disease, which is mostly caused by an abnormal Th1 cellular response, and a known risk factor is smoking.

Crohn's Disease1:15–3:33

In Crohn’s disease, the inflammation can pop up anywhere in the GI tract, from the mouth to the anus, but the rectum is often spared.
It tends to be most severe at the terminal ileum.Gastrointestinal symptoms include crampy abdominal pain, watery diarrhea that may or may not be bloody, and sometimes malabsorption symptoms like malnutrition, steatorrhea, or B12 deficiency.
A very frequent finding to keep in mind are aphthous ulcers in the mouth. Some individuals may also present esophageal involvement, with odynophagia and dysphagia.
Extraintestinal symptoms include arthritis, uveitis and episcleritis, and skin lesions like pyoderma gangrenosum and erythema nodosum.
In addition, a high yield fact is that Crohn’s disease leads to a higher risk of kidney stones and gallstones. That’s because damage to the terminal ileum decreases absorption of fats and bile salts in the intestine.
The fats bind to calcium, which prevents the calcium from binding to oxalates. Free oxalates are absorbed in the intestine and eventually lead to calcium oxalate stones in the kidneys.
On the other hand, the bile salts normally bind to cholesterol to make it water soluble. If there’s a decreased absorption of bile salts, cholesterol can collect and form stones in the gallbladder.Over time, Crohn’s disease may lead to complications like strictures, which can cause bowel obstruction.
Another complication are fistulas, which are communications between two epithelial organs, like from one part of the intestines to another, or from the intestines to another organ like the bladder or the skin surface.
Sometimes, a phlegmon can form, which is where there’s a localized area of inflammation in the intestinal wall that can get infected and become an abscess.
Sometimes individuals get perianal abscesses, fissures, and fistulas. Finally, individuals with Crohn's disease may be at increased risk for colorectal cancer.

Ulcerative Colitis3:33–5:01

Okay, let’s switch gears to ulcerative colitis, which is mostly caused by an abnormal Th2 cellular response. Now, strangely enough, smoking has a protective effect in ulcerative colitis.
The inflammation usually starts in the rectum and goes retrograde through the colon, but doesn’t extend to the rest of the GI tract.
Gastrointestinal symptoms include colicky abdominal pain, bloody diarrhea due to the inflammation that makes the GI mucosa frail, and tenesmus due to rectal involvement.
Extraintestinal symptoms can include iron deficiency anemia due to blood loss, as well as arthritis, uveitis and episcleritis, primary sclerosing cholangitis, and skin lesions like pyoderma gangrenosum and erythema nodosum.
Finally, complications of ulcerative colitis include severe gastrointestinal bleeding and fulminant colitis, which is continuous bleeding and over 10 stools per day.
Another dangerous complication is toxic megacolon, which is where the nerves and muscles are damaged and the colon becomes atonic and dilated.
In severe cases, it can lead to perforation with peritonitis, which causes fevers and severe abdominal pain. Finally, it’s important to know that ulcerative colitis increases the risk for colorectal cancer even more than Crohn’s disease.All right, so for diagnosis of IBDs, an endoscopy or colonoscopy with biopsy is needed, and you need to know the findings for your exams!

Diagnosis5:01–7:01

So Crohn’s disease lesions on endoscopy or colonoscopy look like linear patches of damaged tissue with normal GI mucosa in between, and these are called skip lesions.
These damaged areas give the bowel a “cobblestone” appearance. In some individuals, the mesenteric fat may wrap around the bowel, causing it to thicken, and this is called the “creeping fat” sign.
On the other hand, in ulcerative colitis, there’s circumferential inflammation that’s continuous throughout an entire section of the rectum or colon.
In addition, there can be areas with superficial or deep ulceration. Another important thing to note with ulcerative colitis is that the mucosa may be so friable to the touch that it can bleed during colonoscopy.Now if we look at a biopsy, in Crohn’s disease the damage of the GI wall is transmural, meaning that it involves the full thickness, and this may lead to fissures.
There can be transmural lymphoid aggregates, where the white blood cells invade down into the deep mucosa, and can organize themselves into non-caseating granulomas.
The inflamed areas can also swell or scar, forming narrow areas called strictures which can lead to obstructions. On a barium enema, strictures only allow a tiny stream of contrast material to pass through, and on a radiograph, that’s called a “string” sign.
On the other hand, in ulcerative colitis the damage is limited to the mucosa and submucosa, and there might be crypt abscesses.
Crypt abscesses are formed by white blood cells that dwell in the crypts of lieberkuhn; an invagination of the intestinal epithelium into the lamina propria.
In ulcerative colitis, the circumferential inflammation can destroy the haustras leading to a smooth section of colon, which is called the “lead pipe” sign.
An important difference with Crohn’s disease is that ulcerative colitis doesn’t present granulomas. Once the diagnosis has been made, the choice of treatment depends on the IBD type and severity.

Treatment7:01–8:32

Treatment often involves a step-up approach, where less potent anti-inflammatory medications are initiated, and if they fail, they’re changed to more potent medications.
So usually for Crohn’s disease, treatment is started with corticosteroids. If these fail, an alternative is giving 5-aminosalicylic acid or 5-ASA.
Another alternative are antibiotics like ciprofloxacin and metronidazole. Antibiotics are thought to help control symptoms by reducing bacteria levels in the intestine, as well as by curbing the immune response, since some antibiotics have anti inflammatory effects as well.
Finally, more severe cases might get a biologic agent like infliximab to suppress the immune system and it can be combined with an immunomodulator like azathioprine.
Now, for ulcerative colitis, usually the initial approach is with 5-ASA. More severe cases might be prescribed immunosuppressant medications like corticosteroids.
If those fail, biologic treatments such as infliximab can be used.Beyond that, another treatment option involves surgery and removal of the affected tissue, but one really important distinction is that in Crohn’s disease, surgery doesn’t cure the disease, since inflammation can occur anywhere along the GI tract.
On the other hand, ulcerative colitis only affects the large intestine, so surgery can actually cure the disease, but you have to weigh the benefits of curing the disease against the loss of the section or the entire large intestine!All right, as a quick recap… Crohn’s disease can involve any part of the GI tract and causes fistulas as well as kidney stones.

Review8:32–9:18

On the other hand, ulcerative colitis involves only the rectum and the colon, and acute complications include bleeding, fulminant colitis, and toxic megacolon, while chronic complications include strictures and colorectal cancer.
Diagnosis relies on a colonoscopy with biopsy. In ulcerative colitis, the colonoscopy shows continuous inflammation only in the mucosa and submucosa of the rectum and colon.
In Crohn’s disease, the colonoscopy shows transmural skip lesions that alternate with normal mucosa, giving a cobblestone appearance.
Treatment involves anti-inflammatory medications and depends on the IBD type and severity. Going back over to our cases… In Alex’s case, the fact that his diarrhea is bloody suggests that he has ulcerative colitis.

Summary9:18–9:42

And in Chris’s case, his non-bloody diarrhea and recurrent kidney stones suggest he has Crohn's disease. Colonoscopy results support this, as Alex has continuous involvement of the rectum and colon, while Chris shows skip lesions that spare the rectum.
A biopsy can be done to confirm the diagnosis.
Inflammatory bowel disease: Pathology Review Video | Osmosis