Weatherly's Woes - Large Intestine

INFLAMMATORY BOWEL DISEASES

IBD

There are two big autoimmune conditions that affect the bowel: Crohn’s Disease and Ulcerative Colitis. While most of your attention should go towards differentiating the two, I’ll first cover their similarities. They have similar time courses (adult onset, asymptomatic baseline, occasional flare ups), symptoms (abdominal pain and diarrhea) and treatments (powerful immunosuppressants). Patients are treated with one or more of the following drugs:

- - Steroids - blocks NFkb, B-cells and T-cells
  - Budesonide - steroid that stays inert until the Ileum (great for Crohn’s)
  - Azathioprine / 6-MP - blocks purine synthesis and lymphocytes
  - Methotrexate - blocks Thymidine synthesis (dihydrofolate reductase)
  - Infliximab / Adalimumab - antibodies that block TNF-a
  - Sulfasalazine - an inert NSAID that isn’t activated until the colonic flora. Only targets the colon (great for Ulcerative Colitis).
  - 5-ASA (Mesalamine) - same MOA as Sulfasalazine, but it’s non-Sulfa and it’s a little weaker.

ULCERATIVE COLITIS

Normal on the left. UC on the right.

Crypt Abscess

Severe case of pseudopolyps

CROHN DISEASE

The terminal ileum

Granuloma

Colonoscopy

String sign (narrowed lumen)

IRRITABLE BOWEL SYNDROME

Aka the Western diet

Irritable Bowel Syndrome (IBS) refers to vague, chronic gastrointestinal problems without an identifiable cause. Patients typically complain of abdominal pain plus diarrhea and / or constipation. Their symptoms are typically mild, persistent, frustrating and annoying.

The diagnostic criteria for IBS are laughably vague (the Rome criteria), but I bring it up because one of them frequently appears on vignettes. Their abdominal pain changes when they poop; either getting better or worse. This will usually be your clue in a question stem.

IBS is a little controversial, because science can’t explain it. Having worked at a GI clinic for a year, I’ve seen plenty of patients diagnosed with IBS. Most of them were overweight middle-aged adults with poor diets and sedentary lifestyles. The gastroenterologist would do a colonoscopy, because that's what gastroenterologists do. The colonoscopy would be normal. So the doctor would throw his hands up and say “Well shoot! I guess you have IBS.” It’s a diagnosis of exclusion. The treatment is aimed at minimizing symptoms rather than treating an underlying cause. Unfortunately, treatment rarely works (only 20% achieve symptom remission).

Let’s talk about the treatment algorithm. The first step is to lose weight, exercise and adopt the FODMAP diet (which is low in gas-producing foods). RCTs on exercise are difficult to conduct, but working out seems to be the most promising treatment. Next, patients are told to take fiber, although this is rarely effective. Now there is a fork in the pathway, and we’re either going to focus on treating the constipation or the diarrhea. For constipation, we start with polyethylene glycol (osmotic), then we try Lubiprostone (secretory) then Tegaserod (serotonin agonist). For diarrhea, treatment mainly consists of Loperamide, although a few patients benefit from bile acid sequestrants. One of the most surprising developments in IBS was the discovery that some patients improved with antidepressants like a TCA or SSRI. It’s still too early to say if probiotics are helpful.

Call me a skeptic, but I don’t believe that a disease called IBS exists. Rather, I think it’s an umbrella diagnosis that encompasses a wide variety of intestinal problems. There is no clear scientific consensus on the true cause, but instead a heterogenous mixture of explanations. Some retrospective studies have found that most patients initially diagnosed with IBS were later found to have a “real” cause, one which responded well to treatment. There are no biomarkers. There are no lesions on endoscopy. There’s no reliable testing. From my experience working at a GI clinic, I observed that encounters with IBS patients were frustrating for both the doctor and the patient.

REMINDER

IBS is very, very different from IBD.

APPENDICITIS

Appy

Appendicitis refers to inflammation of the appendix, a mysterious vestigial worm-shaped tube that dangles below the cecum. Its function is debated, but some scientists speculate that it serves as a microbiome safety depository box. When you catch a diarrheal infection, the lymphatic tissue that lines the entrance of the appendix swells shut, sealing a small bacterial colony inside. Meanwhile, the colonic flora are wiped away by diarrhea. Rates of C. difficile colitis are 4x higher in those without an appendix! This is a very common condition.

The appendix is easily clogged by poop (fecalith) in adults or inflammation (lymphoid hyperplasia) in kids. It usually affects kids between ages 8 to 18. The classic tetrad of findings are RLQ pain, vomiting, fever and leukocytosis. Initially the inflamed appendix will only irritate its lining (visceral peritoneum), which only has visceral innervation and results in vague periumbilical pain at first. But after a few days the inflamed appendix will grow so large that it irritates the next lining layer (parietal peritoneum), which has somatic innervation and results in the perception of pain migrating to the RLQ. Abdominal tenderness should be most pronounced at McBurney’s point, located two-third of the distance between the umbilicus and ASIS. Inflamed appendixes are prone to rupture, which would result in peritonitis and sepsis (peritoneal signs include rigidity, rebound, guarding). You diagnose appendicitis with a CT scan (ultrasound in kids and pregnancy). Usually treated surgically, although some simple cases are treated with observation and antibiotics. The appendix is usually sent to the pathology lab after surgery, because there’s a small chance of appendiceal cancer.

Appendix possible positions

CT scan (this is hard, you aren’t expected to read this)

A retrocecal appy lies over the psoas muscle. Worsen the pain by extending the right leg.

A pelvic appy lies against the obturator internus muscle. Worsen the pain by internally rotating the right leg

DIVERTICULAR DISEASE

Ouch my pouch

Diverticulum - pouch

Diverticula - pouches

Diverticulosis - having pouches

Diverticulitis - inflamed pouch

Diverticulosis refers to having lots of little outpouchings in the colon. They’re common and mostly harmless. Diverticulosis is caused by constipation. When people are constipated, they have to strain hard to poop. Bearing down generates high intraluminal pressure, which can result in outpouching. Specifically, the pressure forces the mucosa and submucosa out past the muscular layer. The muscular layer is especially weak wherever the vasa recta arteries penetrate through it. This is a false diverticulum, since all three layers aren’t bulging out. The pouches are fragile and stretched out, which can cause painless rectal bleeding. Diverticulosis is one of the most common causes of hematochezia. There are misconceptions about diverticulosis -- seeds and nuts do NOT cause or worsen diverticular disease. But a lack of fiber does!

Diverticulitis is inflammation of diverticula. It causes LLQ pain, fever and leukocytosis, like left-sided appendicitis. You treat it with antibiotics* and surgery (if severe). The bacteria is likely enteric, so a gram negative rod like E. coli. This isn’t an emergency, but it’s taken fairly seriously as it mostly affects elderly people and can have some major consequences. The infection can wall itself off (abscess), narrow the colon (bowel obstruction), tunnel to the bladder (rectovesical fistula → poopy urine) or pop the pouch (perforation → peritonitis). Diagnose with a CT.

*Recent studies have called the use of routine antibiotics into question.

CONSTIPATION

Poop pile up

Causes include a low fiber diet (Western diet), opioids, anticholinergics (Atropine), nondihydropyridine calcium channel blockers (Verapamil and Diltiazem), amiodarone, aluminum hydroxide antacid (prevented by combining with diarrhea-prone Magnesium Hydroxide), hypothyroidism, hypercalcemia (“groans”) and IBS.

Consequences include anal fissures, hemorrhoids, diverticular disease and bowel obstruction.

*Docusate (Colase) doesn’t actually work.

Opioids are one of the most important causes of constipation. Most opioid side effects diminish with time, but the constipation persists no longer how long you take them. It’s the most commonly cited reason when people stop taking their opioids (they’d rather be in pain!). Use Methylnaltrexone to immediately relieve their constipation (they will shit their brains out 30 minutes after taking it).

DIARRHEA

Chocolate rain

You can treat diarrhea with a peripheral opioid (Loperamide), but don’t use it during a GI infection. Here’s how to classify Diarrhea

GI BLEEDING

Bloody hell

GASTROENTERITIS

Stomach bug

Acute infectious gastroenteritis is characterized by the rapid onset of nausea, vomiting and diarrhea. Very few of these infections require treatment. Most of them aren’t even routinely diagnosed, but test writers absolutely love to give a “classic story” and ask you to pick the organism.

Viral gastroenteritis typically begins after about a day-long incubation period. They usually cause N/V/D.

GI PARASITES

These are neglected tropical diseases (with the exception of pinworms, giardia and cryptosporidium), meaning that they are cheap to treat and could be universally prevented with simple sanitation measures. But they persist because they only affect poor countries.

Treatment is complicated and low yield. I’m not going to focus a ton of energy on it. But here goes nothing. Albendazole treats roundworms. Metronidazole treats protozoans. Ivermectin (a chloride blocking neurotoxin) treats Strongyloides and Onchocerca. Praziquantel treats tapeworms, chinese liver fluke and schistosomiasis.

MESENTERIC ISCHEMIA

Bowel clot

Mesenteric Ischemia refers to a cessation of blood flow to the intestines.

Acute Mesenteric Ischemia is usually due to a thromboembolic blood clot, often of the SMA. Clots usually originate from the heart in the setting of atrial fibrillation, but other causes include valvular vegetations, cancer and a hypercoagulable state. It begins with ischemia, but quickly degenerates into bowel wall necrosis. Necrosis leads to currant jelly stools. It causes sudden and severe mid-abdominal pain. Importantly, the pain is usually much more impressive than the tenderness (pain out of proportion, or POOP). The diagnosis is made with a CT angiography, or even clinically. Give antibiotics and a blood thinner, then do surgery or an embolectomy.

Chronic Mesenteric Ischemia refers to atherosclerosis of the major intestinal vessels that leads to episodic cramping whenever the patient eats. That’s because when you eat, food flows down to the intestines, which requires a lot of extra blood to power digestion. But if those vessels are partially occluded, then not enough blood will reach the working gut! That causes crampy abdominal pain. This disease is also called intestinal angina, due to the pathophysiological similarities it has to cardiac angina. Over time, patients develop an understandable aversion to food, which leads to weight loss. This disease occurs in patients with cardiovascular disease, and they usually have concurrent hypertension, diabetes and heart disease.

Colonic Hypoperfusion is acute gut ischemia that manifests at the splenic flexure and rectosigmoid junction which is caused by shock. That’s because these are the watershed areas of the colon. When global blood pressure drops, these places are the first to feel the effects in the gut. Patients typically are undergoing an evaluation for shock, when they suddenly experience abdominal pain and hematochezia.

CLOSTRIDIOIDES DIFFICILE COLITIS

The artist formerly known as Clostridium difficile

C. difficile colitis refers to acute colon inflammation in the setting of microbiome dysregulation that often occurs after using antibiotics. C. difficile is a small piece of most people’s gut flora. It’s usually harmless, until it grows too numerous.

Antibiotics kill good bacteria (gut microbiome) just as much as they kill the bad ones. Taking a strong antibiotic (like clindamycin) will eradicate most bacteria in your colon. But C. difficile will rebound back faster than most other bacteria because it generates hardy spores. Spores can survive the antibiotic explosion, like little bomb shelters. That enables C. difficile to quickly reinhabit the colon, becoming the dominant bacteria!

When C. difficile overgrows the gut, it damages the colon in a characteristic fashion. It produces the A and B toxins, which are cytotoxic to the enterocytes that line the intestinal lumen. This leads to the formation of a pale pseudomembrane. This causes abdominal pain, watery diarrhea and a fever. Left untreated, it can cause toxic megacolon, shock and death. The diagnosis is made by a stool analysis, specifically using a PCR or looking for one of the toxin antigens.

The treatment of C. diff is with oral vancomycin. Since oral vancomycin isn’t actually absorbed, it localizes its antimicrobial activity to the lumen of the GI tract, killing off the rampant C. difficile. Oral Fidaxomycin is an alternative antibiotic, but it’s expensive. Once a patient has had a third episode of C. diff in a row, you should give the patient a poop transplant. A fecal transplant brings over healthy gut flora to compete with the dominant C difficile.

While antibiotic use is the strongest risk factor for C. diff, it’s not the only one. It can also occur in hospitalized patients with IBD.

The rectum has two parts.

The upper half is similar to the colon.

The lower half is similar to the anus and skin.