9. Gastroenterology

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

Part of esophagus

Type of muscle


Additional points

Upper one-third

Skeletal muscles only,which are innervated by somatic (voluntary) nervous system.

Diseases that primarily affect

  • Skeletal muscles (e.g., myasthenia gravis, myositis syndromes)

  • Somatic nerves (e.g., motor nerve palsy)

Squamous cell carcinoma usually occurs in upper or middle part of esophagus. Its major risk factors are alcohol, smoking, achalasia, lye ingestion, etc.

Middle third

Upper part of middle esophagus is mostly skeletal muscles and lower part is mostly smooth muscle cells.

Lower third

Smooth muscle cells only, which are innervated by autonomic nervous system.

Diseases that primarily affect

  • Smooth muscles (e.g., scleroderma)

  • Autonomic nerves (e.g., achalasia cardia)

Adenocarcinoma usually occurs in the lower third. Its major risk factor is chronic gastroesophageal reflux disease.

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.

a All causes of chronic dysphagia can result in weight loss, so weight loss does not necessarily point toward malignancy.

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.

Achalasia cardia (idiopathic achalasia)

Pseudoachalasia (a.k.a. secondary achalasia)

Primary pathology

Idiopathic destruction of myenteric (Auerbach’s) plexus

Denervation/destruction of myenteric plexus by:

  • Tumor (esophageal or gastric adenocarcinoma, lymphoma, etc.): presence of hx of long-standing GERD features may point toward adenocarcinoma of lower esophagus

  • Vagal nerve denervation (e.g., surgical vagotomy)

  • Infection (e.g., Chagas disease which can cause megaesophagus)

Barium swallow appearance

Smooth distal esophageal narrowing or tapering (called “bird beak’s appearance”). Proximal esophageal dilation signals advanced disease.

Source: In: Michael J, Sircar S, eds. Fundamentals of Medical Physiology. 1st ed. Thieme; 2010.

In malignancy, the tapering is usually NOT smooth; proximal esophagus may or may not be dilated.

Note the irregular proximal contour (arrow) and the distal margin of the stenosis.

EGD and biopsy

Primary destruction of the neural plexus in absence of other pathologic featuresa

Usually reveals the underlying disorder, e.g., lymphoma cells in myenteric plexuses


  • In low-surgical-risk patients, do pneumatic dilationb or surgeryc (pyloromyotomy)

  • In patients with high risk of complication with invasive procedures (e.g., advanced age), give botulinum toxin injection into lower esophageal sphincter via EGD. It usually requires retreatment. If it fails, use nitrates and calcium channel blockers

Treat underlying disorder

aNever miss the chance of detecting malignancy in its earliest stage. Endoscopy and biopsy are mandatory even in apparent achalasia cardia.

bPotential complication includes esophageal perforation.

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.

  • Intermittent heart burn or food regurgitation.


  • 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.

      1 Corkscrew esophagus pattern in barium swallow.

    • 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

Both can present as neuromuscular dysphagia.

9.2.6 Upper Neuromuscular Dysphagia

Definition: It refers to difficulty initiating swallowing, nasal regurgitation, and choking or coughing while eating.

Etiology: Dementia

3 This form of neuromuscular dysphagia is common in elderly patients with advanced dementia. They forget how to swallow.

and bulbar/pseudobulbar palsy.

Pseudobulbar palsy

Bulbar palsy

9, 10, 11, 12 cranial nerve involvement

Upper motor neuron palsy

Lower motor neuron palsy


Stroke (MCC), multiple sclerosis

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.

In a nutshell

Type of dysphagia


Clinical history

Steps in diagnosis

Mechanical dysphagia

Peptic stricture, malignancy, etc.

Dysphagia for solids, progressing on to dysphagia of liquids

EGD (+/- pre-EGD barium swallowa)

Lower neuromuscular dysphagia

Achalasia and pseudoachalasia

Dysphagia with difficulty swallowing both liquids and solids simultaneously

EGD (+/- pre-EGD barium swallowa), followed by manometry

Upper neuromuscular dysphagia (aka oropharyngeal dysphagia)

Dementia and bulbar/ pseudobulbar palsy

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





Esophageal rings

Development of soft mucosal concentric rings in esophagus, therefore, only food with a certain diameter gets stuck

  • Schatzki’s ring is one subtype and associated with hiatal hernia

  • Rings due to eosinophilic esophagitis are associated with other findings suggestive of this disorder

Nonprogressive episodic dysphagia, particularly with larger-size food chunks

Dx is made by barium swallow, or EGD and biopsy.
Rx: EGD with pneumatic dilatation, followed by PPI therapy

Esophageal webs

Formation of thin mucosal eccentric fold that protrudes into esophageal lumen, which typically occurs in upper cervical area of esophagus

  • When it occurs with iron deficiency anemia, it is called Plummer-Vinson syndrome. It has higher risk of squamous esophageal carcinoma

  • Other associated conditions include pemphigus disorders, chronic graft versus host disease, etc.

Can present similar to esophageal rings. Patient complains of difficulty swallowing, particularly in the cervical zone of esophagus. Lab test may reveal iron deficiency anemia

Dx is made by barium swallow, or EGD and biopsy.
For Plummer–Vinson syndrome, NSIM is iron replacement (it may lead to resolution of dysphagia).
In patients with significant symptoms, EGD +/- dilatation might be needed. Usually webs are easily ruptured by the endoscope itself

Zenker’s diverticulum

Motor dysfunction and weakness of esophageal muscles can lead to development of diverticular pouch in the upper part of posterior esophagus.

Dysphagia, foul breath, regurgitation of previously eaten food

  • High risk of aspiration pneumonia

NSIDx: barium esophagogram.
Rx: endoscopic or surgical correction

Source: Steffers G, Credner S, eds. General Pathology and Internal Medicine for Physical Therapists. 1st ed. Thieme; 2012.


Drugs: tetracycline, doxycycline, aspirin, NSAIDs, alendronate (bisphosphonates), oral potassium/ iron supplements, etc.
Other causes: infectious esophagitis (candida, CMV, HIV, HSV), eosinophilic esophagitis, etc.

Acute onset painful swallowing (odynophagia) + difficulty swallowing (dysphagia) +/- vague to sharp persistent central chest pain

If dx is not apparent or if severe, NSIDx is EGD
Rx: supportive (may use acid suppression). If medication that caused esophagitis cannot be discontinued, use its liquid formulation, which has less risk.

Abbreviations: CMV, cytomegalovirus; EGD, esophagogastroduodenoscopy; HIV, human immunodeficiency virus; HSV, Herpes simplex virus; NSAIDs, nonsteroidal anti-inflammatory drugs.

9.4 Gastroesophageal Reflux Disease


Reflux of gastric contents and acid into esophagus can occur either due to

Underlying cause

Increased intra-abdominal pressure

Obesity, pregnancy, delayed stomach emptying (gastroparesis), etc.

Decreased contraction of lower esophageal sphincter

Scleroderma, smoking, 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.


aLifestyle modifications:

• 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.


4 Most drugs ending with “prazole” are PPIs: omeprazole, lansoprazole, pantoprazole, etc.

is generally added when lifestyle modifications fail to improve symptoms or when symptoms are moderate to severe. In mild GERD, histamine-2 receptor antagonists (e.g., famotidine, ranitidine) can be used.

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.

• Weight loss or anorexia.

• Odynophagia or dysphagia.

• 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).

  • Esophageal manometry.

  • Gastric emptying study to make sure that the stomach is emptying properly, and gastroparesis is not contributing to refractory GERD.

9.4.1 Complications of Untreated or Uncontrolled 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.

Clinical Case Scenarios

1. A 28-year-old pregnant woman presents to emergency department with new-onset burning substernal chest pain. She does not have any risk factors for atherosclerotic disease. What is the NSIM?

  1. CXR

  2. EKG

  3. EGD

  4. Esophageal pH monitoring

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.


Abbreviations: GI, gastrointestinal; NSAIDs, nonsteroidal anti-inflammatory drugs.

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.


CAP H. pylori CMP (complete metabolic profile).


MRS MTBP (Master the boards points) Quadruple CAMP.

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:

High-stress situations

  • Severe burn injuries

  • Head trauma and increased intracranial pressure (traumatic brain injury)

  • Intubation and mechanical ventilation > 48 hrs

Empiric PPI or H-2 blocker for ulcer prophylaxis is recommended in these situations.

Stomach cancer

All gastric ulcers should be biopsied. By contrast, no need for routine biopsy of duodenal ulcer.

Rare causes include MALToma, Zollinger-Ellison syndrome and Crohn’s disease

Abbreviation: PPI, proton pump inhibitor.

Presentation: PUD presents with dyspepsia +/- alarm features (as given before in algorithm).

Gastric ulcer

Classic presentation is epigastric pain worsened by eating food. Food stimulates production of gastric acid which irritates the ulcer.

Duodenal ulcer

Epigastric pain usually occurs within few hours after eating food, when gastric contents are being emptied into the duodenum. Eating food relieves pain, as this causes the pyloric sphincter to close, keeping the food and gastric acid in the stomach.

9.6.1 Diagnosis Is Based on Endoscopy Findings

aBiopsy of the ulcer itself is not routinely recommended in patients with benign-appearing duodenal ulcer. For gastric ulcers, do biopsy.

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.


Dyspeptic symptoms

Suspect gastrinoma if any of the following is present:

  • Multiple peptic ulcers

  • Ulcer in odd places like second or third part of duodenum or jejunum

  • Intractable ulcers or recurrent ulcers, particularly in patients with negative H. pylori testing and no hx of NSAIDs use

Malabsorption symptoms

Occur due to excessive gastric acid entering the duodenum, damaging small intestine mucosae, and inactivating pancreatic enzymes. Diarrhea is also present (mostly osmotic with some secretory component)

Abbreviation: NSAIDs, nonsteroidal anti-inflammatory drugs.


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.

MEN I syndrome

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

5 Para-pancreatic because these neuro-endocrine tumors can also be found in duodenum or jejunum.

neuroendocrine tumors, as listed below:


VIPoma (hypersecretion of vasoactive intestinal peptide)

Hypokalemia, Achlorhydria, Diarrhea (secretory type)


Migratory necrolytic erythema, Anemia, Diabetes or glucose intolerance


Hypoglycemia, elevated blood C-peptide and insulin level


I HAD VIP guests today.


MAD glucagonoma

9.8 Stomach Cancer

Risk factors:

  • 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.

6 These are the alarm features for which EGD is recommended in patients with dyspepsia.

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.


Localized disease

  • If positive for H. pylori, start H. pylori eradication therapy; the tumor generally subsides after treatment. This is a unique treatment of this form of non-Hodgkin’s lymphoma.

  • If negative for H. pylori, do radiotherapy for localized disease. Alternative regimen is rituximab.

Advanced disease

  • If positive for H. pylori, start H. pylori eradication therapy.

  • When symptoms develop, treat with rituximab +/- chemotherapy.

Follow-up: Regular surveillance EGD.

9.10 Malabsorption Syndromes

There are various causes of malabsorption, but all usually share the following common features:

GI symptoms

Chronic diarrhea, bloating, flatulence
(Note: acute diarrhea/bloating and flatulence is considered infectious until proven otherwise) Fatty greasy stools that float easily in the toilet (steatorrhea)

Features of malnutrition

  • Weight loss and fatigue

  • Children can present with failure to thrive

Vitamin A deficiency

Follicular hyperkeratosis, squamous metaplasia of cornea (called Bitot’s spot), night blindness, etc.

Vitamin K deficiency

Easy bruising and bleeding with elevated INR

Vitamin D deficiency

  • Features of hypocalcemia

  • Bone loss/thinning in adults

  • Rickets in children

Other deficiencies

Vitamin B12, folate, and/or iron deficiency can present with anemia


Normally free calcium in gut lumen binds with dietary oxalate; calcium oxalate, as a compound, cannot get absorbed through intestinal epithelial cells and gets excreted with stool. In malabsorption, increased fatty acids in stool bind with enteral luminal calcium, which in turn frees up oxalates to be absorbed into the circulation. This leads to hyperoxaluria and increased risk of calcium oxalate stones formation

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:

Malabsorption + history of the following

Think of



Travel to developing countries


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 all the above tests are negative, do fecal fat quantification to document malabsorption and celiac sprue testing (which is the major differential dx), prior to doing EGD with small bowel biopsy

If stool antigen or nucleic acid testing is positive for giardia, start treatment.
Rx: depends on age

  • > 3 yrs of age- tinidazole (single dose)

  • 1-2 yrs of age-nitazoxanide

  • < 1 year of age -metronidazole

  • For pregnant patients in their 1st trimester,if treatment is deemed necessary, paromomycin is preferred. In 2nd or 3rd trimester, any of the medication mentioned here can be given.

Tropical sprue (unknown microbiological cause)

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.
Rx: oral tetracycline for few months

  • Bowel anatomical issues (e.g., strictures, fistula, anastomosis)

  • Risk factors for reduced peristalsis (e.g., diabetes, scleroderma, Crohn’s disease)

  • Immunosuppression

Small bowel intestinal bacterial overgrowth

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.
Diagnostic test is EGD with jejunal aspirate culture growing > 1,000 CFU of bacteria, but this may not be needed.

Rx: (amoxicillin + clavulanate) or (rifaximin)

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.


Whipple PASSes trophy

Malabsorption + History of the following

Think of



Recurrent epigastric pain +/- diabetes mellitus (due to endocrine pancreas deficiency)
Exam CCS may give hx of alcoholism or lab/clinical features suggestive of chronic alcohol use (e.g., macrocytosis, elevated GGT, AST > ALT)

Chronic pancreatitis

Document presence of the following:
Pancreatic calcification: do either US, CT, or plain X-ray
Presence of ductal pathology: do MRCP
Abnormal pancreatic exocrine function: do either fecal elastase or 72hr fecal fat test
See chronic pancreatitis section for further details

Rx: oral pancreatic enzymes supplements

Epigastric pain: Endoscopy shows multiple ulcers in the stomach +/- duodenum or ulcers in unusual places like second or third part of duodenum or jejunum

Zollinger-Ellison Syndrome

Hold PPI and check serum fasting gastrin level after 1 week

Surgical resection if localized disease or with surgically resectable metastasis. If widespread, do medical treatment with large doses of PPIs to block acid secretion

Hx of anxiety or bulimia nervosa

Factitious diarrhea due to laxative abuse

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)
Malabsorption without any other history suggestive of abovementioned conditions

Celiac spruea

See below for diagnostic algorithm

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.

7 Do not choose anti-gliadin antibodies, which has low specificity.

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.

D-xylose test

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.

Clinical Case Scenarios

2. A 45-year-old female presents with long-standing history of symptoms of periodic diarrhea and weight loss. There is no history of travel. EGD with intestinal biopsy reveals blunting of villi. What is the best treatment? Antibiotics or dietary intervention?

9.11 Inflammatory Bowel Disease: Ulcerative Colitis and Crohn’s Disease

Ulcerative colitis

Crohn’s disease

Idiopathic inflammatory process involves

Only colon

  • Ileitis might occur, but it is almost always in presence of right-sided colitis. (This is due to inflammation of colon spilling into ileum and is known as backwash ileitis.)

Can involve the whole GI tract, including mouth

MC location

  • Rectum: inflammation can extend from there to involve the whole colon.

  • Ileum

Common presentation

  • Diarrhea, weight loss, fever, abdominal pain, etc.

  • Disease course is usually remitting-relapsing (periods of acute flare-ups followed by dormant phase).

MC presentation scenarios

Proctitis: abdominal pain, tenesmus, stool urgency, and if severe, bloody diarrhea

  • Ileitis: right lower quadrant abdominal pain and tenderness

  • Malabsorption (chronic diarrhea, weight loss, calcium oxalate stones, vitamin B12 deficiency, etc.) can result from:

    • Ileal involvement and bile salt malabsorption

    • Small intestinal bacterial overgrowth

Both can have extraintestinal manifestations a

  • Erythema nodosum, pyoderma gangrenosum, uveitis/iritis, arthritis, etc.

  • They have increased risk for venous thromboembolism

Laboratory workup

  • Look for elevated ESR, leukocytosis, and/or reactive thrombocytosis. (These are important clues to diagnosis, but these can be normal in patients with mild disease or in remission.)

  • Both UC/CD can have positive fecal occult blood and stool leukocytes

Pathology Both UC/CD are diagnosed with endoscopy and biopsy

Colonoscopy will show superficial inflammation with continuous GI mucosal involvement

  • Granulomatous transmural inflammation which may lead to

    • Perforation due to transmural involvement

    • Fibrosis → stricture formation → intestinal obstruction → perforation

    • Fistula formation → development of abscess

  • Granulomatous inflammation is a characteristic feature that differentiates CD from UC

  • Endoscopy will show skip lesions (lesions are not continuous)

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.


COlitis is COntinous Crohn’s DISease is DIScontinous


PAIR of B27 (bombers) where I = inflammatory bowel disease, the UC type


Ulcerative colitis

Crohn’s disease

First treatment of choice:
Both are treated with anti-inflammatory 5-ASA derivativesa and immunosuppressive agents such as steroids, 6-mercaptopurine, azathioprine, etc.

Mild disease

  • Proctitis: suppository Canasa

  • Proctosigmoiditis: suppository (Canasa) +enema (Rowasa)

  • Left-sided or diffuse colitis: oral 5-ASA derivatives and enema/suppository

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:

  • Oral 5-ASA derivative may be tried first

  • If not responding, do a trial of oral antibiotics +/- oral steroids (e.g., budesonide). Transmural inflammation and gut bacterial infection more likely play a role in CD

More Severe disease: For example, frequent bloody stools, frequent diarrhea, or signs of systemic toxicity such as fever, tachycardia.

  • Systemic steroids (e.g., prednisone or IV glucocorticoids) + oral and/or rectal ASA derivatives +/- antibiotics

  • If refractory to steroids, use any of the following: anti-TNF agents (infliximab, adalimumab) or vedolizumab (anti-integrin antibody). Cyclosporine is another option for UC and certolizumab for Crohn’s disease

Long-term treatment for prevention of flare-ups

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

Other additional

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.
! Any grade of dysplasia in biopsy warrants colectomy

  • For active colonic disease or in patients with fistula, ciprofloxacin and metronidazole alone or in combination is commonly used

  • For CD with fistula, also use immunosuppressive agents. Systemic steroids and ASA derivatives have NOT been shown to induce closure of fistula

Indications for surgery

  • Toxic megacolon refractory to medical management

  • Severe flare-up refractory to medical management

  • Frequent exacerbation of disease despite medical management

  • After more than a decade of dx of UC prophylactic proctocolectomy might be offered to patients, instead of screening colonoscopy every 1–3 year

  • Symptoms refractory to medical treatment (e.g., high dose of steroids required to control symptoms) or frequent exacerbation of disease despite adequate medical therapy

  • Severe fistulating disease

  • Bowel obstruction refractory to conservative management

  • Abscess formation

  • B- perforation

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.


  • Asacol is for Colitis.

  • PENTasa—Pan ENTeric ASA: is effective for both small and large bowel inflammation, so useful in Crohn’s disease.

  • RowaSa = Rectal enema for rectum + Sigmoid colon involvement.

Topical 5-ASA derivatives

Oral 5-ASA derivatives

Rowasa is a rectal enemaa
Canasa is suppositorya

  • Pentasa is released in both small and large bowel.a

  • Asacol is efficacious mostly in ileum and colon.a

  • Sulfasalazineb is only effective in colon. (Colonic bacteria are required to cleave this drug into 5-ASA which is the active form.)

a Mesalamine-derived ASA compounds are topical Canasa, Rowasa, and oral Asacol, Pentasa.

b sulfasalazine is usually not the first line as it has higher risk of side effects. It can cause GI disturbances, skin rash, hepatitis, pancreatitis, pneumonitis, agranulocytosis, and aplastic anemia.

Clinical Case Scenarios

  1. 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.

  1. What is the best NSIDx?

  2. Abdominal X-ray reveals the following. What is the likely dx?

  3. What is the NSIM?

  4. 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?

Source: In: Gunderman R, ed. Essential Radiology. Clinical Presentation, Pathophysiology, Imaging. 2nd ed. Thieme; 2000.

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

8 It has higher incidence in people of Asian descent.

) or due to villous pathology (e.g., giardiasis, celiac sprue).

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.


• Lactose intolerance

• Osmotic laxative abuse (MgSO4, magnesium citrate, lactulose or polyethylene glycol)

• MgOH2 (antacid) ingestion

• Fat malabsorption

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

10 Some types of yogurt (e.g., Greek yogurt) or aged cheese are better tolerated.

and if symptoms resolve dx is made. If patient does not want to avoid lactose and wants to confirm the dx first, do hydrogen breath test after ingesting dairy products. In addition, lactase enzyme supplements can be used.

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.

    11 Typical hx is of bright red blood per rectum and passage of blood clots.

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).


Mild disease (low-grade fever, mild pain, and able to take PO intake)

Can be treated on an outpatient basis with clear liquid diet and oral antibiotics that cover gram negatives and anaerobes. For example, (amoxicillin-clavulanate) or (cefpodoxime + metronidazole).
CT scan is not necessarily indicated but may be indicated in patients not responding to outpatient therapy.

Severe disease (severe pain, high fever, or high leukocyte count)

NSIM is hospitalization, bowel rest, IV fluids, and IV antibiotics (e.g., ceftriaxone + metronidazole). Then NSIM is CT scan to assess severity.

If patient hasn’t had a recent colonoscopy, NSIM is to schedule colonoscopy after resolution of acute episode.

For recurrent diverticulitis, elective diverticulectomy can be done on a case-by-case basis.

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Dec 11, 2021 | Posted by in GASTROENTEROLOGY | Comments Off on 9. Gastroenterology

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