GASTRITIS
Tummy trouble
Gastritis is inflammation of the stomach mucosa. It's really common. Left untreated it leads to ulcers (and if you’re unlucky, to cancer). At the end of the day, Gastritis is damage induced by stomach acid. The stomach has to constantly excrete protective mucus to avoid being damaged by its own acid, and that requires a lot of energy to maintain. There are a lot of ways this system can fall out of whack!
There’s a lot of symptom overlap among these stomach / esophagus conditions, so don’t get too bogged down by the clinical presentations. Know that the constellation of symptoms caused by gastritis is called dyspepsia. Dyspepsia is a pretty vague term (you really only use it if you already know the diagnosis), but it generally refers to gnawing epigastric pain, nausea, vomiting and poor appetite. Treat with PPIs or H2 blockers.
Inflammation attracts WBCs, which are normally not found in the stomach’s epithelium. WBCs trick the stomach into thinking that it’s adjacent to a Peyer’s patch (found in the intestines), and so the stomach’s epithelium changes (metaplasia) into intestinal epithelium (characterized by plump Goblet cells). Intestinal metaplasia is a precursor to Adenocarcinoma, which comprises 95% of all stomach cancers (MALT Lymphoma is the other 5%).
PARIETAL CELLS
Parietal cells secrete acid. They live at the top of the stomach (body and fundus). They are influenced in many different ways. Our most effective gastritis medications, PPIs and H2 Blockers, work by modulating receptors on this cell.
Proton Pump Inhibitors work by breaking the proton pump on parietal cells. They are the most effective and safe gastritis medication. These drugs are overall well tolerated, but since they are so commonly consumed, we should pay close attention to the side effects. It turns out that stomach acid is acidic for good reason. It effectively kills bacteria and spores. That’s why PPIs increase the rate of C. diff colitis. For reasons that are still being debated, PPIs slightly increase the rate of pneumonia. Stomach acid also helps us to absorb magnesium and calcium, so PPIs can predispose to osteoporosis in the elderly. And lastly, Omeprazole (Pepcid) inhibits CYP450.
H2 Blockers were a miracle drug when they were introduced. Before then, peptic ulcer disease was a massive worldwide health crisis. In recent years they’ve become less popular thanks to PPIs. Cimetidine was the first drug in this class, and it’s an especially nasty drug. It causes potent CYP450 inhibition, blocks androgens (low libido), can cross the blood brain barrier (confusion) and is somewhat nephrotoxic. Modern H2 Blockers do not have these side effects, although Ranitidine was taken off the market in 2020 because it seemed to slowly decompose into a carcinogenic compound during storage.
PERNICIOUS ANEMIA
Autoimmune Gastritis
Pernicious Anemia is the autoimmune destruction of Parietal Cells. This is a Type 4 hypersensitivity reaction. If you understand Parietal Cells, this disease is easy.
Parietal cells are found in the Fundus and Body of the stomach → inflammation leads to atrophy of the Fundus and Body.
Parietal cells make stomach acid → Less stomach acid (achlorhydria) → Reflexive rise in Gastrin → G Cell hyperplasia.
Parietal cells make Intrinsic Factor → Less B12 absorption in ileum → B12 deficiency (megaloblastic anemia, neuro symptoms).
HELICOBACTER PYLORI
H. pylori
H. pylori is a bacteria that can live inside stomach acid. It survives by secreting urease, which turns stomach acid more basic. They swim above the stomach epithelium, secreting cytotoxic compounds. Over time, the epithelial cells can totally die off, leaving behind a painful ulcer. H. pylori likes to live in the antrum of the stomach. Perhaps that’s due to gravity -- these bacteria are free floating after all. You can test for H. pylori by looking at the breath (urea breath test) or the poop (stool antigen test). H. pylori raises the risk for Adenocarcinoma (like all forms of gastritis), but it can uniquely lead to a rare cancer called MALT Lymphoma. This is a cancer of the B-cells of the Mantle zone. You can often cure this cancer by treating the H. pylori with antibiotics.
H. pylori is clearly a hardy bug. So it requires aggressive treatment. Specifically, you need at least 3 different drugs (triple therapy): Amoxicillin, Clarithromycin and a PPI. For resistant infections, add Bismuth (quadruple therapy). For penicillin allergies, replace Amoxicillin with Metronidazole. Keep in mind that these formulations are hotly debated, and will probably look different by the time we’re attendings.
PEPTIC ULCER DISEASE
PUD
Peptic Ulcer Disease means that you have an ulcer. They can occur in the stomach or duodenum. Ulcers are a natural consequence of gastritis. To get technical, an ulcer is defined by the loss of the muscularis mucosa (the tiny muscular layer sandwiched between the mucosa and submucosa). Peptic Ulcers hurt like a motherfucker (epigastric pain) and also make you queasy. One big problem with peptic ulcers is that they can cause an upper GI bleed. Smoking is a risk factor. Diagnose with an EGD.
Why does H. pylori cause so many ulcers? To start, it secrete cytotoxic chemicals. There are several different toxins, but we already know about one of them. Urease creates ammonia, which is toxic to human cells. The result is inflammation of the antrum. When the nearby G cells become inflamed, they reflexively secrete gastrin, with the intention of melting away the inciting pathogen. This leads to MORE stomach acid. This acid flows into the fragile duodenum, leading to ulcers.
You have to know how eating affects peptic ulcers. Based only on a patient’s history, you can localize the ulcer! Let’s explain why. When you eat, two things happen simultaneously. (a) The stomach floods itself with acid to help break down the meal, and (b) the duodenum fills up with basic fluids to prepare itself for the incoming waves of stomach acid. Patients with duodenal ulcers love to eat. They are tricking their duodenum into making more bicarb, which soothes their ulcers. But when they fast (like during the night) the pain worsens.
ULCER PERFORATION
Pop goes the weasel
If a peptic ulcer goes deeper than the muscular layer, we call it a perforation. This is the feared complication with all peptic ulcers. Perforations are incredibly painful and potentially lethal. Air, chyme and bacteria spill out into the sterile peritoneal cavity. Peritonitis ensues (rigid abdomen, rebound, guarding). They will have a severe upper GI bleed. They need surgery (a laparotomy) right away. The fastest test that you can perform is a chest x-ray, looking for bilateral air bubbles under the diaphragm. In healthy chest x-rays, there’s usually a bubble under the left side of the diaphragm, which represents the gastric air bubble.
Pneumoperitoneum is a very bad sign
Local complications
ZOLLINGER-ELLISON SYNDROME
Gastrin overload
ZES is when a tumor secretes gastrin. It causes an acid overload. This is the only disease that causes multiple duodenal ulcers or jejunal ulcers. ZES also causes diarrhea.
STOMACH CANCER
95% of Stomach Cancer is due to an adenocarcinoma, and the remaining 5% are MALT Lymphomas, Stromal Tumors or Carcinoid Tumors. Unfortunately the symptoms of Gastric Adenocarcinoma are vague and mild. That makes it hard to catch early on. And if you catch it late, the survival is abysmal (15% five year survival). Gastric adenocarcinoma is shockingly common in Japan (possibly related to their Nitrosamine, salted fish and fermentation-heavy diet), so they implemented a (successful) nation-wide EGD screening campaign. There are a few explosive skin conditions like acanthosis nigricans or Leser-Trelat sign (explosive Seborrheic Keratoses) that can suggest abdominal cancer. Board questions sometimes use early satiety as a tell-tale symptom (in reality this is too vague to be helpful). This is especially true in the diffuse type, since the entire stomach wall is thick and fibrosed, making it difficult to expand. The most common metastasis site is the liver (true of most abdominal cancers). There are 4 other noteworthy met / lymph spreads
Krukenberg Tumor - bilateral ovaries (often diffuse-type)
Virchow Node - left supraclavicular node
Sister Mary Joseph Nodule - belly button (Intestinal) ulceration
Blumer Shelf - pouch of Douglas (rectouterine), palpable on rectal exam
Signet Ring Cells (Diffuse)
Signet Ring
Note that most gastric mets hit the liver
MENETRIER’S DISEASE
Rugae disease
In Menetrier’s Disease the gastric epithelial cells get extra thiqq (hypertrophic gastropathy). They get very large rugae in their stomach! Gastric epithelial cells are normally responsible for making mucus and bicarb. In MD they make a ton of it. The stomach pH gets alkaline (achlorhydria) and the Parietal cells wither away. Without Pepsin, patients digest less proteins (protein losing enteropathy), leading to hypoalbuminemia and swelling. The overall MOA is not well understood. Note that Zollinger-Ellison also causes rugal thickening (mild), but involves acid HYPERsecretion
Thick stomach ruggae seen on a CT scan.
Biopsy (massive mucosa layer)
