It is estimated that the population of human gut microbiome is around 100 trillion bacterial cells. That would mean there are more bacterial cells inside us than our own human cells.
This gut microbiome is considered not only a passive synergistic system but also an active system with its own signaling chemicals that has a positive and protective effect on the human body. To this gut microbiome, broad-spectrum antibiotics, sadly,are nuclear bomb equivalent. So, even though antibiotics can be life-saving, be aware of its effect on our friendly and beneficial gut microbiome. Dictum is to give as narrowest spectrum antibiotics as possible, for the shortest period of time as permitted.
9.1 Esophageal Pathology Based on Location
9.2 Dysphagia (Difficulty in Swallowing)—Mechanical and Neuromuscular
9.2.1 Mechanical Dysphagia
Definition: Dysphagia for solids, progressing on to dysphagia of liquids can be defined as mechanical dysphagia. Patients presenting with such history usually have a structural lesion that is progressively obstructing the lumen of the esophagus. MCC is esophageal stricture.
Workup: In patients with prior hx of conditions that are associated with complex esophageal anatomy (e.g., hx of radiation, caustic injury, surgery for esophageal or laryngeal cancer), do barium swallow prior to endoscopy (It provides a road map for endoscopy and makes it safer.). Otherwise, go directly for upper gastrointestinal (GI) endoscopy, a.k.a. esophagogastroduodenoscopy (EGD). If structural lesion is found, do biopsy.
9.2.2 Lower Neuromuscular Dysphagia
Definition: It can be defined as difficulty in swallowing both liquids and solids that starts simultaneously. This kind of dysphagia is most likely due to esophageal motility problems.
Etiology: Achalasia-pseudoachalasia (problem with esophageal smooth muscle innervation), scleroderma (esophageal smooth muscle itself is replaced by fibrous tissue), and other esophageal motility disorders (e.g., diffuse esophageal spasm).
Workup: EGD followed by manometry. Manometry is the most accurate test.
9.2.3 Achalasia and Pseudoachalasia
Background: After food ingestion, the autonomic nervous system signals esophageal peristalsis to propel food downward and when food reaches the lower part of esophagus, it signals the lower esophageal sphincter (LES) to relax. This relaxation is very important for food to pass into the stomach. Loss of autonomic innervation results in inadequate peristalsis and inability of LES to relax, resulting in dysphagia for both solids and liquids.
Denervation/destruction of myenteric plexus by:
Smooth distal esophageal narrowing or tapering (called “bird beak’s appearance”). Proximal esophageal dilation signals advanced disease.
In malignancy, the tapering is usually NOT smooth; proximal esophagus may or may not be dilated.
Primary destruction of the neural plexus in absence of other pathologic featuresa
Usually reveals the underlying disorder, e.g., lymphoma cells in myenteric plexuses
aNever miss the chance of detecting malignancy in its earliest stage. Endoscopy and biopsy are mandatory even in apparent achalasia cardia.
cIn patients younger than 40 years of age who are low risk for surgery, surgical approach may be preferred over pneumatic dilatation, as risk of recurrence in pneumatic dilatation is higher.
9.2.4 Other Esophageal Motility Disorders (Esophageal Spasm)
Intermittent crushing substernal chest pain unrelated to exertion, which is sometimes aggravated by hot or cold liquids.
Intermittent feeling of food (solids or liquids) getting stuck in esophagus.
In patients presenting with chest pain, always do electrocardiogram (EKG) first. In patients with dysphagia, do endoscopy first. In patients with prominent heart burn symptoms, if patient fails high-dose proton pump inhibitor (PPI) therapy, do esophageal pH and impedance testing to rule out gastroesophageal reflux disease (GERD).
If above test is inconclusive, NSIDx is manometry, which can show typical high-pressure episodic contractions.
If contractions are diffuse, diagnosis is diffuse esophageal spasm.
If contractions are localized to a specific area of esophagus, diagnosis is “nutcracker” esophagus (aka hypertensive peristalsis). (They say the pressure is so high, it can even crack a nut.)
If patient has high LES (lower-esophageal sphincter) resting tone, dx is hypertensive LES.
Rx: Calcium channel blockers (diltiazem, nifedipine) or tricyclic antidepressants such as imipramine (M-antagonist effect). Sublingual nitroglycerin can relieve the pain/spasm.
9.2.5 Esophageal Manometry
Test description: A thin flexible plastic tube is inserted (e.g., a nasogastric feeding tube) and pressures are monitored by this tube while swallowing.
aLES resting pressure is high in achalasia cardia and low in scleroderma.
2 Also, scleroderma can present with mechanical and/or neuromuscular dysphagia
• Poor LES tone → GERD → peptic stricture → mechanical dysphagia
• Smooth muscles of lower half of esophagus gets replaced by fibrous tissue → diminishing peristalsis → neuromuscular dysphagia
9.2.6 Upper Neuromuscular Dysphagia
Definition: It refers to difficulty initiating swallowing, nasal regurgitation, and choking or coughing while eating.
3 This form of neuromuscular dysphagia is common in elderly patients with advanced dementia. They forget how to swallow.
Guillain–Barre syndrome, syringobulbia, myasthenia gravis, lower motor neuron disease, etc.
Workup: Videofluoroscopy (modified barium swallow under fluoroscopic surveillance).
Rx: Usually supportive. Address underlying cause.
Dysphagia for solids, progressing on to dysphagia of liquids
EGD (+/- pre-EGD barium swallowa)
Dysphagia with difficulty swallowing both liquids and solids simultaneously
EGD (+/- pre-EGD barium swallowa), followed by manometry
Difficulty initiating swallowing, nasal regurgitation, and/or choking or coughing while eating
aIn patients with prior hx of conditions that are associated with complex esophageal anatomy (e.g., hx of radiation, caustic injury, surgery for esophageal or laryngeal cancer), do barium swallow prior to endoscopy.
9.3 Other Esophageal Disorders Related to Dysphagia Disorders
9.4 Gastroesophageal Reflux Disease
Reflux of gastric contents and acid into esophagus can occur either due to
Obesity, pregnancy, delayed stomach emptying (gastroparesis), etc.
Clinical pathophysiology: Patients can present with various symptoms such as chest pain, “heartburn,” hoarse voice, cough, etc. Physical exam may reveal inflamed pharynx and larynx.
• Avoid smooth muscle relaxants (which can relax the lower esophageal sphincter) such as calcium channel blockers, nitrates, chocolate, peppermint (commonly found in chewing gums).
• Weight loss is recommended in obese patients.
• Elevate head of the bed at night; use more pillows.
cIndications for EGD in GERD include presence of any of the following alarm features:
• New-onset dyspepsia at age ≥ 60 years.
• Recurrent or persistent nausea and vomiting.
• Any evidence of GI bleeding: positive fecal occult blood test, melena (hx of black tarry stool), or microcytic iron deficiency anemia.
• Family hx of gastrointestinal cancer in a first-degree relative.
dEGD findings suggestive of GERD include peptic stricture, reflux esophagitis, and Barrett’s esophagus.
eEsophageal pH and impedance monitoring is a highly sensitive and specific test for GERD, but is a cumbersome study that takes 24 hours to perform. Impedance detects movement of intraluminal contents. Combined with pH monitoring, it can differentiate between acid and nonacid reflux.
Surgical treatment for GERD: Patients who require high doses of PPI to control symptoms can be offered surgery (e.g., Nissen fundoplication), particularly in young patients. Before doing surgery for intractable GERD, multiple tests as given below need to be done to confirm the diagnosis and make sure that the surgery will benefit the patient:
Esophageal pH and impedance monitoring.
Upper gastrointestinal (UGI) endoscopy (EGD).
Gastric emptying study to make sure that the stomach is emptying properly, and gastroparesis is not contributing to refractory GERD.
9.4.2 Management of GERD Complications Depend on EGD Findings
aEndoscopic eradication treatment involves using radiofrequency or cryotherapy to remove dysplastic tissue.
bWhen 1st EGD reveals gross findings suggestive of Barrett’s esophagus, NSIM is to take 4-quadrant biopsies. Once biopsy confirms Barrett’s, do EGD surveillance every 3–5 year. If biopsy reveals low-grade dysplasia or indeterminate for dysplasia manage as shown in the right.
9.5 Dyspepsia (Indigestion)
Definition: Presentation of vague epigastric pain, discomfort, or bloating is known as dyspepsia. Patient may have other symptoms of indigestion such as nausea, excessive flatulence, occasional exacerbation of pain or, in severe cases, diarrhea.
9.5.1 Management Steps of Dyspepsia
aIn patients with history of significant alcohol, aspirin, or NSAIDs use, H. pylori testing may be deferred. Empiric antacid therapy and avoidance of precipitating factor can be tried first.
bStop PPI therapy 1 to 2 weeks before H. pylori testing. PPI, antibiotics, and bismuth can lead to false negative result.
cTriple therapy for H. pylori: PPI + Amoxicillin + Clarithromycin. If patient is penicillin-allergic, use Metronidazole instead of amoxicillin;
dQuadruple therapy = Bismuth subsalicylate + Metronidazole + Tetracycline (or doxycycline) + PPI. Alternative quadruple therapy is PPI + Amoxicillin + Clarithromycin + Metronidazole;
eDuring EGD, rapid urease testing can be done to detect H. pylori, which has urease activity.
fWhen no underlying pathology can be found for dyspeptic symptoms, dx of nonulcer (functional) dyspepsia can be made. As majority of dyspepsia are ultimately classified as nonulcer or functional; it is the most common cause of dyspeptic symptoms. NSIM is trial of PPI.
Serology (i.e., checking serum antibody against H. pylori) has low predictive value and is not recommended.
9.6 Peptic Ulcer Disease (PUD)
Definition: Peptic ulcer disease (PUD) refers to gastric and/or duodenal ulcer.
Etiology: Major causes are Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) use. Other causes of PUD include the following:
Presentation: PUD presents with dyspepsia +/- alarm features (as given before in algorithm).
9.7 Gastrinoma (Zollinger–Ellison Syndrome)
Background: Gastrinoma is a tumor that autonomously secretes a lot of gastrin. Common location of the tumor is in pancreatic or duodenal area. It can be associated with multiple endocrine neoplasia (MEN) I syndrome.
Hypergastrinemia stimulates gastric acid production, increases gastric pH and risk for subsequent ulcer formation (usually multiple).
Hypergastrinemia stimulates gastric mucosal cells leading to mucosal hypertrophy and prominent gastric folds. There is an increased risk of gastric carcinoma.
aPPIs decrease gastric acid production that leads to increase in compensatory gastrin secretion. So, PPI use can cause false positive hypergastrinemia.
bAchlorhydria is absence of gastric acid, that is, alkaline (elevated) pH. It leads to compensatory secondary hypergastrinemia. Causes of achlorhydria include atrophic gastritis (pernicious anemia), chronic renal failure, chronic H. pylori infection, surgical vagotomy, etc.
c Mechanism: Normal gastric acid production is inhibited by secretin. In contrast, gastrinoma cells secrete more gastrin in response to secretin hormone.
d1st step is to do an EGD (if not yet done), CT or MRI scan and somatostatin receptor scintigraphy (octreotide scan). If these tests are negative for primary tumor, NSIDx is endoscopic ultrasound. (This has greater sensitivity for diagnosing small tumors.)
If gastrinoma is localized and/or with limited or isolated metastasis, NSIM is surgical resection. Do endoscopic ultrasound (US) prior to surgery to ensure proper staging.
If widespread, do medical treatment with large doses of PPIs to block acid secretion.
Hereditary genetic syndrome associated with triad of pancreatic, parathyroid, and pituitary tumors (the board favorite): look for hypercalcemia (parathyroid adenoma), galactorrhoea-amenorrhea syndrome (pituitary adenoma), and features of gastrinoma or other pancreatic or parapancreatic
9.8 Stomach Cancer
Smoking and alcohol (they are synergistic).
Diet rich in nitrosamines which are found in smoked, salted, or barbequed meat.
Conditions that increase gastrin level: gastrinoma and chronic achlorhydria (due to pernicious anemia, chronic H. pylori infection, etc.).
Presentation: early satiety, weight loss, dyspepsia, upper GI bleeding.
Workup: NSIM is EGD and biopsy. If positive for malignancy, NSIM is CT scan. Depending on CT study results, positron emission tomography (PET)/CT, endoscopic US, or laparoscopy might be indicated for staging.
Rx: Localized disease is treated surgically. In advanced stages, chemotherapy +/- palliative surgery are indicated (e.g., patient has a bulky mass which is causing obstruction or inability to eat any solid food).
9.9 Gastric Mucosa-Associated Lymphoid Tissue Tumor
Background: It is the MC type of extranodal marginal zone lymphoma and the only type associated with H. Pylori infection. Most MALTomas are of low grade and commonly remain localized.
Presentation: Symptoms or complication of PUD (e.g., upper GI bleeding or dyspepsia).
EGD will reveal ulcer or ulcerated mass. Biopsy will reveal non-Hodgkin’s lymphoma. Testing for H. pylori should be done.
NSIDx: CT scan of chest/abdomen/pelvis to look for metastasis.
9.10 Malabsorption Syndromes
There are various causes of malabsorption, but all usually share the following common features:
9.10.1 Diagnostic Workup of Malabsorption
To diagnose malabsorption, do fecal fat quantification test. Spot test can be done for screening, but if negative and when suspicion is high, 72-hour fecal fat testing is recommended which has high sensitivity and specificity to diagnose steatorrhea (malabsorption). Generally, malabsorption should be confirmed before doing invasive procedures such as EGD with biopsy.
9.10.2 Different Etiologies of Malabsorption
In malabsorption, patient’s history generally provides clues to etiology:
Giardia stool antigen or nucleic acid testing.a Also, do stool microscopy for cysts, ova, parasites, and leukocytes. If these tests are negative consider serology to look for other infections such as Strongyloides, Entamoeba histolytica, etc.
If stool antigen or nucleic acid testing is positive for giardia, start treatment.
If small bowel biopsy reveals blunting of villi/chronic inflammation, celiac sprue testing is negative, and there is positive travel history, preliminary dx is made.
Carbohydrate breath test: after oral carbohydrate load, bacteria metabolize it to hydrogen and methane, which gets absorbed into circulation, excreted in breath and can be measured.
Migratory arthralgia, lymphadenopathy +/- skin hyperpigmentationb +/- central nervous system involvement (e.g., memory impairment)
Whipple’s disease (caused by infection with Tropheryma whipplei)
EGD with small bowel biopsy with PAS (periodic acid-Schiff) staining
Rx: IV ceftriaxone or penicillin G, followed by oral trimethoprim-sulfamethoxazole (or doxycycline)
a Alternatively, patients with recent hx of travel and acute onset of symptoms suggestive of malabsorption can be empirically treated with metronidazole. If symptoms resolve, it is most likely giardiasis.
bCaution: Looks somewhat similar to hemochromatosis. Hemochromatosis can also present with malabsorption (due to pancreatic insufficiency), joint pain, and skin pigmentation. Presence of lymphadenopathy points toward Whipple’s disease.
Recurrent epigastric pain +/- diabetes mellitus (due to endocrine pancreas deficiency)
Document presence of the following:
Epigastric pain: Endoscopy shows multiple ulcers in the stomach +/- duodenum or ulcers in unusual places like second or third part of duodenum or jejunum
Surgical resection if localized disease or with surgically resectable metastasis. If widespread, do medical treatment with large doses of PPIs to block acid secretion
Colonoscopy can reveal dark brown discoloration of colon (melanosis coli)
Rx: cognitive behavioral therapy + nutritional rehabilitation +/- SSRI or olanzapine
Intensely pruritic papulovesicular lesions on the extremities (dermatitis herpetiformis)
Remove BReWed beer from diet (i.e., Barley, Rye, Wheat, and beer, which is made from barley). These grains contain gluten protein, which when ingested, elicits an immune reaction in susceptible individuals
aPatients with celiac sprue may have increased risk of lymphoma and GI malignancy. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CFU, colony forming unit; EGD, esophagogastroduodenoscopy; GGT, gamma-glutamyl transferase; MRCP, magnetic resonance cholangiopancreatography; PPI, proton pump inhibitor; SSRI, selective serotonin reuptake inhibitor.
9.10.3 Diagnostic algorithm of celiac disease
aIgA anti-tissue transglutaminase (TTG) antibody. Another antibody that can be checked is IgA antiendomysial antibodies.
bSelective IgA deficiency is common in celiac sprue and can lead to false negative IgA anti-TTG.
cBest test is small bowel biopsy (biopsy of duodenal bulb + other duodenal areas +/- jejunum), which typically shows blunting or loss of villous architecture with increased inflammatory cells. Note: tropical sprue has the same picture. Absence of travel history to tropical countries points toward celiac. Note that in some patients with high probability of celiac (e.g., positive dermatitis herpetiformis or coexistent autoimmune disease such as type I DM, autoimmune hepatitis), we can go directly for EGD along with serology.
dIf patient is already on gluten-free diet, antibody serology testing can be negative. In this instance, we can check HLA DQ2 and DQ8 genotypes. If positive, gluten challenge and repeat serology need to be done.
Even if D-xylose test for malabsorption is not used anymore, the basic science behind it is interesting, hence questions on it are still asked on exam.
D-xylose is a simple sugar that does not need to be digested for absorption.
If D-xylose is not absorbed into the circulation, then there is a problem with the absorptive surface (e.g., celiac sprue, tropical sprue).
If D-xylose is absorbed into the circulation, then we can conclude that malabsorption is not due to problem with the absorptive surface; think of other causes such as chronic pancreatitis.
9.11 Inflammatory Bowel Disease: Ulcerative Colitis and Crohn’s Disease
Proctitis: abdominal pain, tenesmus, stool urgency, and if severe, bloody diarrhea
Both can have extraintestinal manifestations a
Pathology Both UC/CD are diagnosed with endoscopy and biopsy
Colonoscopy will show superficial inflammation with continuous GI mucosal involvement
aUC is associated with HLA-B27 related disorders, which include psoriatic arthritis, primary sclerosing cholangitis, ankylosing spondylitis, and reactive arthritis.
Abbreviations: CD, Crohn’s disease; ESR, erythrocyte sedimentation rate; GI, gastrointestinal; UC, ulcerative colitis.
First treatment of choice:
If no response, use oral glucocorticoid. (Budesonide is preferred, as it has high topical GI effect and low systemic effect due to extensive first pass metabolism by liver.)
Mild flare-up with no systemic symptoms:
More Severe disease: For example, frequent bloody stools, frequent diarrhea, or signs of systemic toxicity such as fever, tachycardia.
If steroid dependent or frequent exacerbations, start steroid sparing agents such as 6-mercaptopurine or azathioprine. Other options are biologic agents (e.g., infliximab, adalimumab). Methotrexate is an additional option for CD
After 8–10 years of dx of UC, colonoscopy with multiple blind biopsies should be done to screen for development of colon cancer, followed by serial colonoscopies at 1–3-year intervals.
a5-ASA derivatives are olsalazine (oral), balsalazide (oral), sulfasalazine (oral), and mesalamine-derived compounds (oral or topical): discussed further in the below table.
Abbreviations: ASA, aminosalicylic acid; CD, Crohn’s disease; GI, gastrointestinal; TNF, tumor necrosis factor; UC, ulcerative colitis.
A man with hx of Crohn’s disease presents with complain of fecal material in his urine. What is the likely dx?
Patient with prior long-standing history of nonspecific GI complaints presents with high fever and abdominal pain. Abdominal exam reveals diffuse tenderness and decreased bowel sounds. Lab tests reveals leukocytosis, thrombocytosis, and elevated lactate.
Abdominal X-ray reveals the following. What is the likely dx?
Patient with history of ulcerative colitis presents with few months’ hx of progressive itching and fatigue. Liver function tests (LFTs) reveal ↑ gamma-glutamyl transferase (GGT) and ↑ alkaline phosphatase (AKP). What is the likely dx?
9.12 Lactose Intolerance
Background: Virtually everyone is born with lactase, an intestinal brush border enzyme that splits lactose into glucose and galactose and helps digesting milk. Later during life, people can lose this enzyme either spontaneously (genetically determined
Pathophysiology: When lactose-containing food is ingested, the undigested lactose remains in the GI lumen, which is then fermented by bacteria producing hydrogen gas (resulting in flatulence, bloating) and osmotically active compound (osmotic diarrhea so stool osmolar gap is typically increased).
9 Stool osmolar gap is increased in osmotic diarrhea. Osmotic diarrhea occurs due to presence of osmotically active particles in gut lumen.
• Osmotic laxative abuse (MgSO4, magnesium citrate, lactulose or polyethylene glycol)
Presentation: Explosive diarrhea with flatulence and bloating any time one ingests dairy products. Exam question might not include hx of dairy ingestion. If weight loss is present, think of alternate dx.
Management: Avoid dairy products
9.13 Diverticular Disease
Background: It refers to the formation of multiple outpouchings in colon. This is common in older age population. MC location is in sigmoid colon. Risk factors include constipation, obesity, use of NSAIDs/opiates, etc.
Hx of chronic constipation alternating with diarrhea.
Sometimes patients have mild abdominal pain or bloating relieved by defecation.
Chronic lower GI bleeding can lead to iron deficiency anemia.
Acute painless lower GI bleeding.
Management: High fiber diet and stool softeners as needed. Diet low in red meat and total fat can reduce likelihood of symptomatic diverticular disease.
9.14 Acute Diverticulitis
Pathophysiology: Blockage of diverticula by colonic contents that results in peridiverticular inflammatory process.
Presentation: Acute abdominal pain and tenderness +/- signs of sepsis. MC location of abdominal tenderness is in left lower quadrant but it can occur anywhere (e.g., right lower quadrant tenderness due to pericecal diverticulitis).