Gastroenterology

Chopra, Angeli

doi:10.1007/978-3-319-11821-5_5

Angeli Chopra MD, FRCPC, ABIM⁴

5185 Accesses

Abstract

organic—infections, tumors, multiple sclerosis, vestibular nerve or brain stem lesions

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Gastroenteritis: Gastrointestinal Infections

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Nausea and Vomiting

Differential Diagnosis

NEUROLOGIC

organic—infections, tumors, multiple sclerosis, vestibular nerve or brain stem lesions
drugs—chemotherapy, SSRI, opioids, antibiotics, hormonal therapy, chronic marijuana use
psychiatric—anorexia nervosa, bulimia nervosa, rumination

GASTROINTESTINAL

infections—acute gastroenteritis, food poisoning, UTI, pyelonephritis, pneumonia
neoplastic—gastric, ovarian, paraneoplastic, renal
obstruction—stomach, small bowel, colon, functional, gastric volvulus
postop—vagotomy, gastrectomy, fundoplication
inflammation—esophagus, stomach, duodenum
gastroparesis—ischemic, diabetic, amyloidosis, scleroderma, drugs
others—eosinophilic gastroenteritis, hepatobiliary disease, pancreatic disease, peritoneal irritation, functional gastrointestinal disorders, retroperitoneal fibrosis

METABOLIC

endocrine—diabetes, adrenal insufficiency, hypercalcemia, hyperthyroidism, hyperparathyroidism, hyperemesis gravidarum, porphyria
others—uremia, pregnancy, migraine

IDIOPATHIC

Pathophysiology

REFLEX PATHWAY

afferent—(1) humoral factors (drugs, toxins, neurotransmitter, peptides) → area postrema in floor of 4th ventricle (chemoreceptor trigger zone) → nucleus tractus solitarius (NTS) in medulla serves as central pattern generator for vomiting; (2) neuronal GI tract stimuli → vagus nerve → NTS; (3) nociceptive stimuli → sympathetic nervous system → brain stem nuclei and the hypothalamus
efferent—NTS → paraventricular nuclei of the hypothalamus and the limbic and cortical regions → gastric electromechanical events are perceived as normal sensations or nausea or discomfort → vagus nerve → gastric and lower esophageal sphincter relaxation, retrograde contraction in proximal small bowel and antrum, abdominal muscle contraction and initial cricopharyngeus contraction followed by relaxation seconds before vomiting

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, Ca, Mg, PO₄, AM cortisol, urinalysis
microbiology—urine C&S
imaging—CXR, AXR

SPECIAL

gastroscopy, gastric emptying study
CT head

Management

SYMPTOM CONTROL

H1 antagonists—dimenhydrinate 25–50 mg PO/PR q4h, diphenhydramine 25–50 mg PO/IV/IM q4h, cyclizine 50 mg PO/IM q4h or 100 mg PR q4h, meclizine 25–50 mg PO daily, promethazine 12.5–25 mg PO/IM q4h or 12.5–25 mg PR daily
D2 antagonists—benzamides (metoclopramide 5–10 mg PO/IV/IM q4h), phenothiazine (prochlorperazine 5–10 mg PO q6–8 h, chlorpromazine 10–25 mg PO q4–6 h), butyrophenones (droperidol 1.25–5 mg IM q4h, haloperidol 0.5–1 mg IV/PO q4h)
5HT3 antagonists—ondansetron 4–8 mg PO/IV q8h, granisetron 2 mg PO or 1 mg IV, dolasetron 100 mg PO/IV daily
M1 antagonists—scopolamine 1.5 mg TD q72h
steroid—dexamethasone 4 mg PO/SC/IV BID–TID
tube feed—NJ tube, G tube

TREAT UNDERLYING CAUSE

Dysphagia

Differential Diagnosis

OROPHARYNGEAL

(upper esophagus and pharynx, or upper esophageal sphincter dysfunction)

neurological—stroke, multiple sclerosis, Parkinson’s, dementia, amyotrophic lateral sclerosis, Guillain–Barre, myasthenia gravis, cerebral palsy, Huntington’s, tardive dyskinesia, brain stem tumors, trauma
myopathic—myotonic dystrophy, dermatomyositis, connective tissue disease, sarcoidosis, paraneoplastic
structural—cricopharyngeal bar, Zenker’s diverticulum, cervical webs, oropharyngeal tumors, osteophytes and skeletal abnormality, congenital abnormality, ill-fitting dentures
infectious—syphilis, Lyme disease, botulism, mucositis
metabolic—Cushing’s, thyrotoxicosis, Wilson’s, amyloidosis, Sjögren’s syndrome
iatrogenic—chemotherapy, neuroleptics, postsurgical, radiation
functional (globus sensation)

ESOPHAGEAL

(body of esophagus, lower esophageal sphincter, cardia)

structural—tumors (benign, malignant), esophagitis/stricture (reflux, caustic/erosive, infectious, eosinophilic, pill, radiation), tylosis, diverticula, iatrogenic (post-surgery, radiation), esophageal ring/web, extrinsic compression (enlarged aorta, left atrium, mediastinal mass, lung cancer, lymphoma, osteophytes, subclavian artery)
motility—achalasia, scleroderma, Chagas disease, diffuse esophageal spasm, hypertensive lower esophageal sphincter, nutcracker esophagus, non-specific esophageal motility disorders

Clinical Features

DIAGNOSTIC CLUES

—history of heartburn may suggest GERD leading to erosive esophagitis, peptic stricture, or esophageal adenocarcinoma. History of atopic diseases especially in a young adult with recurrent dysphagia may suggest eosinophilic esophagitis. Also check for odynophagia, regurgitation, hematemesis, coffee ground emesis, respiratory symptoms, weight loss, and medication history (tetracycline, bisphosphonates, potassium supplements)

PRACTICAL APPROACH TO DYSPHAGIA

1.
Features of oropharyngeal dysphagia (problems initiating swallowing, extending neck/arms when swallowing, changes in speech, coughing, choking, or nasal regurgitation)? Consider workup for oropharyngeal dysphagia. Otherwise, proceed to step 2
2.
Difficulty swallowing both solids and liquids? If yes, consider motility disorders and proceed to step 3. If progressing from solids to liquids, consider structural disorders and proceed to step 4
3.
For motility disorders, is the dysphagia progressive? If yes, consider achalasia or scleroderma. If intermittent, consider diffuse esophageal spasm or non-specific esophageal motility disorder
4.
For structural disorders, is the dysphagia progressive? If yes, consider tumors and peptic stricture. If intermittent, consider esophageal ring
5.
Any caustic ingestion history?

Investigations

BASIC

imaging—barium swallow (esophageal), videofluoroscopy (oropharyngeal)
swallowing assessment—occupational therapy or speech pathology

SPECIAL

gastroscopy—for esophageal lesions and biopsy for eosinophilic esophagitis
esophageal manometry—definitive for achalasia, useful for diffuse esophageal spasm
p H monitoring—for refractory GERD, especially if gastroscopy normal
fiberoptic nasopharyngeal laryngoscopy—for oropharyngeal dysphagia

Management

SYMPTOM CONTROL

—postural/nutritional/behavioral modifications, swallowing rehabilitation, esophageal dilation

TREAT UNDERLYING CAUSE

Specific Entities

ACHALASIA

pathophysiology—a motor disorder with lack of peristalsis in the body of the esophagus and incomplete relaxation of the lower esophageal sphincter on manometry
diagnosis—endoscopy is essential for ruling out malignancy (“pseudoachalasia”). Barium swallow (beak-like narrowing), esophageal manometry (definitive)
treatments—endoscopic intrasphincteric injection of botulinum toxin, pneumatic dilation, and surgical myotomy

INFECTIOUS ESOPHAGITIS

pathophysiology—common organisms include Candida albicans, CMV, and HSV. Happens more commonly in immunocompromised host
diagnosis—gastroscopy and biopsy/viral cultures

EOSINOPHILIC ESOPHAGITIS

pathophysiology—food allergens and genetic factors leading to eosinophilic infiltration and stricture (frequently presents in young males with esophageal foreign body)
diagnosis—gastroscopy (esophageal trachealization) and biopsy
treatments—control reflux, dilatation, dietary modification, fluticasone (administered as MDI and swallowed), and oral steroids (viscous budesonide slurry)

Dyspepsia

Differential Diagnosis

NON-GASTRIC CAUSES

—cardiac (myocardial infarction), pulmonary (pneumonia), hepatobiliary (biliary colic), pancreatic (pancreatitis), colonic (irritable bowel syndrome), musculoskeletal, dietary indiscretion

PEPTIC ULCER DISEASE

(PUD, 10–20%)—H. pylori, ASA, NSAIDs (COX-2 inhibitors slightly decreased risk), cancer, Zollinger–Ellison, smoking

MEDICATION SIDE EFFECTS

—NSAIDs, ASA, theophylline, calcium channel blockers, erythromycin, metronidazole, bisphosphonates, orlistat, acarbose, iron, potassium supplements

GASTROESOPHAGEAL REFLUX DISEASE

(GERD, 20%)

★ACIDS★
- Acid hypersecretion—Zollinger–Ellison disease
- Alcohol abuse
- Connective tissue disease—scleroderma
- Infections of esophagus—CMV, HSV, candidiasis
- Diabetic gastroparesis
- Drug therapy
- Smoking

NON-ULCER DYSPEPSIA

(50%)—cause unclear. Diagnosis of exclusion (rule out organic cause)

Pathophysiology

COMPLICATIONS OF PUD

—perforation, hemorrhage, gastric outlet obstruction, pancreatitis

COMPLICATIONS OF GERD

—esophageal complications include esophagitis, esophageal ulcer, esophageal stricture, and Barrett’s esophagus. Extra-esophageal complications include asthma, aspiration, chronic cough, hoarseness, chronic laryngitis, and dental erosions

Clinical Features

SYMPTOM DEFINITIONS

dyspepsia—chronic or recurrent epigastric pain, often with regurgitation, heartburn, bloating, nausea, and post-prandial fullness (indigestion)
heartburn—retrosternal burning sensation secondary to lower esophageal sphincter relaxation = more specific for GERD

RATIONAL CLINICAL EXAMINATION SERIES: CAN THE CLINICAL HISTORY DISTINGUISH BETWEEN ORGANIC AND FUNCTIONAL DYSPEPSIA?

	LR+	LR–
Organic dyspepsia
Diagnosis reached by the clinician or computer model	1.6	0.46
Peptic ulcer disease
Diagnosis reached by the clinician or computer model	2.2	0.45
Esophagitis
Diagnosis reached by the clinician or computer model	2.4	0.5

APPROACH—“functional dyspepsia is defined as pain or discomfort centered in the epigastrium with a normal endoscopy. Neither clinical impression nor computer models that incorporated patient demographics, risk factors, history items and symptoms adequately distinguished between organic and functional disease in patients referred for endoscopic evaluation of dyspepsia”

JAMA 2006 295:13

PRACTICAL APPROACH TO DYSPEPSIA

1.
Consider non-gastric causes of dyspepsia (cardiac, pulmonary, hepatobiliary, colonic, musculoskeletal, medications, and dietary indiscretion) and investigate those causes if likely. Otherwise proceed to step 2
2.
If age >50 or alarm symptoms ★Very BAD★ (Vomiting, Bleed/anemia, Abdominal mass/weight loss, Dysphagia), refer for gastroscopy to check for gastric cancer. Otherwise proceed to step 3
3.
If ASA or NSAIDs use, stop medications if possible. If not, consider empiric proton pump inhibitor/H₂ blocker trial and proceed to step 4
4.
If GERD predominant symptoms (heartburn, regurgitation), treat as GERD. Otherwise, proceed to step 5
5.
If H. pylori urea breath test positive, treat with triple therapy. Otherwise, proceed to step 6
6.
If none of the above, diagnosis of non-ulcer dyspepsia

Canadian Dyspepsia Working Group. Can J Gastroenterol 2005 19:5

Investigations

BASIC

labs—CBCD, lytes, glucose, AST, ALT, ALP, bilirubin, lipase, Ca, albumin
imaging—upper GI series, US abd, CT abd

SPECIAL

urea breath test
H. pylori serology
24- h esophageal p H monitoring
endoscopy with biopsy—urease test, C&S for H. pylori
proton pump inhibitor test—sens 78% for GERD

Management

PEPTIC ULCER DISEASE

—avoid NSAID use. Antisecretory treatment (ranitidine 150–300 mg PO BID, omeprazole 20–40 mg PO daily, lansoprazole 15–30 mg PO daily, pantoprazole 40 mg PO daily; all 30–60 min before meals; 8 week course). H. pylori eradication (★CAO★: clarithromycin 500 mg PO BID, amoxicillin 1 g PO BID, omeprazole 40 mg PO daily × 10 days; ★CMO★ (if penicillin allergy): clarithromycin 500 mg PO BID, metronidazole 250 mg PO QID, omeprazole 40 mg PO daily × 10 days; ★BMT★ (if macrolide allergy or failed first line): bismuth 30 mL PO QID, metronidazole 250 mg PO QID, tetracycline 500 mg PO QID × 2 weeks)

GERD

—lifestyle changes (avoid coffee, alcohol, chocolate, high-fat meals, acidic or spicy foods. More frequent, smaller portions, exercise/weight loss, smoking cessation, elevate head of bed, loose garments). Antisecretory treatment (proton pump inhibitors more effective than H2 blockers for esophagitis. Use antacids as breakthrough). Nissen fundoplication

NON-ULCER DYSPEPSIA

—lifestyle changes (avoid alcohol, caffeine, tobacco). Antisecretory treatment (see above). H. pylori eradication (may or may not relieve symptoms). Promotility agent (domperidone)

Specific Entities

GERD

causes—obesity, lower esophageal sphincter pressure (transient relaxation of lower esophageal sphincter), decreased esophageal peristalsis, gastric acid hypersecretion, delayed gastric emptying, anatomic disruption lower esophageal sphincter (hiatal hernia)
pathophysiology—reflux of stomach contents, leading to a multitude of symptoms including heartburn, regurgitation, dysphagia, chest pain, complicated by esophagitis, esophageal stricture, Barrett’s esophagus, and esophageal adenocarcinoma
clinical features—esophageal (heartburn, regurgitation), extra-esophageal (wheeze, cough, pneumonia, waterbrash, hoarseness, sore throat, globus, dental erosions)
diagnosis—clinical based on symptoms (≥2/week). Endoscopy to look for complications and rule out other potential diagnoses

NEJM 2008 359:16

NSAIDS-INDUCED GASTROPATHY

pathophysiology—NSAIDs inhibit COX-1 (normally protective effect through mucus secretion, bicarbonate secretion, mucosal circulation) and COX-2 (inducible inflammatory activity, also in kidneys). It also has direct toxic mucosal effect → dose related but even low dose baby ASA may contribute to ulcer formation. Overall ~20% patients on NSAIDs develop ulcers. Risk factors include age >60, pre-existing peptic ulcer, multiple NSAIDs, high-dose NSAIDs, concomitant glucocorticoid or anticoagulant therapy
treatments—primary prophylaxis includes proton pump inhibitor and misoprostol. If ulcer developed while on NSAIDs but must continue, should give proton pump inhibitor

BARRETT’S ESOPHAGUS

pathophysiology—prolonged heartburn → intestinal squamous metaplasia (abnormal salmon-colored mucosa extending proximally from the gastroesophageal junction to the normal pale esophageal mucosa) → dysplasia → adenocarcinoma of esophagus and gastric cardia. Barrett’s develops in 5–8% of patients with GERD. Transformation to low-grade dysplasia 4%/year, high-grade dysplasia 1%/year and cancer 0.5%/year
diagnosis—screen with surveillance endoscopy every 2–3 years if age ≥50, white race, male, obese, chronic GERD, or presence of hiatal hernia. Mucosal biopsy after the initial diagnosis of Barrett’s esophagus to look for dysplasia. Once diagnosed with Barrett’s, endoscopy with biopsy every 3–5 years, 6–12 months if low-grade dysplasia
treatments—high-grade dysplasia should be evaluated for esophagectomy, endoscopic mucosal resection, or ablative therapy

GASTROPARESIS

causes—systemic diseases (diabetes, scleroderma), drugs (anticholinergic agents, narcotics), idiopathic
pathophysiology—impairment of gastric emptying due to dysfunction of the neuromuscular unit → dyspepsia, bloating, nausea, vomiting, and weight loss
diagnosis—gastric emptying study, barium swallow, gastroscopy
treatments—frequent, small, low-fat, low-fiber feedings, prokinetic agents (metoclopramide 10 mg PO TID ac meals, erythromycin 250 mg PO TID ac meals, domperidone 10 mg PO QID), nutritional support

NEJM 2007 356:8

HELICOBACTER PYLORI

pathophysiology—chronic inflammation → causative role in 50–80% of duodenal ulcers, 40–60% of gastric ulcers, 80% of gastric cancers, and 90% of gastric lymphomas
diagnosis—urea breath test (sens 90%, spc 95%. Particularly good in post-treatment setting; testing for eradication should be performed off antibiotic and proton pump inhibitor therapy), serology (sens 90%, spc 80%) is of limited value as it tests for IgG which only indicates previous exposure, endoscopy (culture, histologic assessment, urease testing)
treatments—see H. PYLORI ERADICATION above

Acute Abdominal Pain

Differential Diagnosis

GI

—peptic ulcer disease, pancreatitis, cholangitis, hepatitis, cholecystitis, inflammatory bowel disease, gastroenteritis, appendicitis, diverticulitis, bowel obstruction (small, large), volvulus

GU

—pyelonephritis, renal colic, cystitis, prostatitis, testicular torsion, inguinal hernia

GYNECOLOGIC

—ectopic pregnancy, ruptured ovarian cyst, pelvic inflammatory disease, fibroid torsion, endometriosis, endometritis

VASCULAR

—acute mesenteric ischemia, ischemic colitis, chronic mesenteric ischemia, abdominal aortic aneurysm rupture

SYSTEMIC

—Addison’s disease, diabetic ketoacidosis, uremia, hypercalcemia, porphyria, familial Mediterranean fever

OTHERS

—myocardial infarction, pneumonia, splenic injury, shingles, musculoskeletal, peritonitis

Pathophysiology

CAUSES OF ABDOMINAL PAIN

—any intra-abdominal organs (e.g. GI, GU, gynecological, spleen) × (ischemia, infection, obstruction, tumors) + systemic causes + referred pain

Clinical Features

HISTORY

—characterize abdominal pain (onset, location, duration, severity, radiation, aggravating and relieving factors), N&V, bleeding, fever, inquire about last menstrual period and pregnancy if female, past medical history (CAD, diabetes, hypertension, renal stones), past surgical history (abdominal adhesions), medication history (analgesics)

PHYSICAL

—vitals, respiratory and cardiac examination, abdominal examination, CVA tenderness, pelvic and rectal examination

APPENDICITIS SEQUENCE

—vague pain initially located in the epigastric or periumbilical region; anorexia, nausea, or non-sustained vomiting; migration of the initial pain to the RLQ; low-grade fever

RATIONAL CLINICAL EXAMINATION SERIES: DOES THIS PATIENT HAVE APPENDICITIS?

	Sens	Spc	LR+	LR–
History
Migration of pain to RLQ	64%	82%	3.18	0.5
RLQ pain	81%	53%	8.0	0.15
Pain before vomiting	100%	64%	2.76	–
No similar pain previously	81%	41%	1.5	0.32
Physical
Rigidity	27%	83%	3.76	0.82
Fever	67%	79%	1.94	0.58
Rebound tenderness	63%	69%	3.7	0.4
Psoas sign	16%	95%	2.38	0.90
Obturator sign	–	–	–	–
Rectal exam	–	–	–	–
Combination of Findings
Alvarado score ≥7	81%	74%	3.1	0.26

APPROACH—“migration of pain, RLQ pain and pain before vomit suggest appendicitis. Rigidity, positive psoas sign, fever and rebound tenderness increase likelihood of appendicitis. Absence of above and similar pain previously suggest appendicitis is less likely”

JAMA 1996 276:19

UPDATE—The Alvarado score (MANTRELS–Migration, Anorexia-acetone, Nausea-Vomiting, Tenderness RLQ [2 points], Rebound pain, Elevation of temperature, Leukocytosis [2 points], Left shift) is a user-friendly and powerful tool for assessing likelihood of acute appendicitis

The Rational Clinical Examination. McGraw-Hill, 2009

DISTINGUISHING FEATURES BETWEEN PERITONITIS, SMALL BOWEL OBSTRUCTION, AND ABDOMINAL WALL PAIN

peritonitis—rigidity (LR+ 5.1), guarding (LR+ 2.0), rebound tenderness (LR+ 2.0), positive cough test (LR+ 2.0). Other special tests include Rovsing’s sign, psoas sign (flexion of hip against resistance increases abdominal pain), obturator sign (internal rotation of hip increases abdominal pain), and rectal/pelvic examination
small bowel obstruction—visible peristalsis (LR+ 18.8), absent/tinkling/high-pitched bowel sounds (LR+ 5.0), abdominal bloating
abdominal wall pain—Carnett’s test (palpate area of most intense tenderness while patient supine, then palpate again with patient half sitting up. If pain is intra-abdominal, the pain will not increase as tensed rectus muscles protect the underlying viscus)

EXAMINATION OF ABDOMINAL MASSES

right upper quadrant mass—liver (downward with inspiration, left lobe, bruit/venous hum), right kidney (downward with inspiration, ballotable, palpable upper border), gallbladder (downward with inspiration, smooth and regular), colon or gastroduodenal (does not move with inspiration, ill-defined mass, high-pitch bowel sounds), lymphoma (does not move with inspiration, usually more central)
left upper quadrant mass—spleen (downward and medially with inspiration, notch, bruit), left kidney (downward with inspiration, ballotable, palpable upper border), colon (splenic flexure), gastric or pancreatic (ill-defined mass, difficult to clearly differentiate these masses on examination), lymphoma (does not move with inspiration, usually more central)
right lower quadrant mass—colon, distal small bowel, or appendix (lower GI masses are ill-defined and difficult to clearly differentiate on examination), ovary, uterus, fallopian tube (pelvic structures require bimanual examination), lymphoma (does not move with inspiration, usually more central)
left lower quadrant mass—colon, distal small bowel (lower GI masses are ill-defined and difficult to clearly differentiate on examination), ovary, uterus, fallopian tube (pelvic structures require bimanual examination), lymphoma (does not move with inspiration, usually more central)

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, lipase, amylase, lactate, INR, PTT, Ca, albumin, urinalysis, urine βhCG (if ♀ of reproductive age)
microbiology—urine C&S, stool C&S
imaging—CXR, AXR, US abd/pelvic

SPECIAL

imaging—IVP, barium contrast, CT abd
ECG—if suspect cardiac involvement
endoscopy

Diagnostic Issues

APPROACH TO ABDOMINAL X-RAYS

free air—pneumoperitoneum suggests perforation. Look for free air under right diaphragm on CXR view or R lateral decubitus view. On supine abd view, look for outline of bowel wall (normally can only see inside of lumen. If outside of bowel wall also seen, free air present)
small bowel—more central location, valvulae closer together, thin and cross completely. Dilated if >3 cm [1.2 in.], multiple air fluid levels suggest small bowel obstruction
large bowel—more peripheral location, colonic haustra wider apart, thick, and cross part way. Normally some air–fluid levels in ascending colon. Dilated if >5 cm [2 in.]. Thumb printing (mural edema) and dilated bowel suggest toxic megacolon. Check for air in bowel wall (pneumatosis intestinalis)
stool in bowel—cannot distinguish from abscess
kidneys—ureter runs along transverse processes. May see calculi along tract. If see kidney outline, suggests pneumoretroperitoneum
psoas—air around psoas suggests perforated retroperitoneal structures (rectum, duodenum). Lack of psoas outline suggests retroperitoneal inflammation (decreased fat)
biliary structures—common bile duct up to 6 mm in size. Check for air in portal vein or common bile duct (bowel infarction)
other structures—liver, spleen, bones

Management

ACUTE

—ABC, O₂, IV hydration. NPO, NG if severe N&V/obstruction. Morphine 2.5–5 mg SC q3–4 h PRN and 1–2.5 mg IV q1h PRN. Dimenhydrinate 50 mg IM/IV q4h PRN

TREAT UNDERLYING CAUSE

—early surgical consult if peritonitis. Empiric antibiotics if fever or suspect peritonitis (ceftriaxone 1 g IV q24h plus metronidazole 500 mg IV q8h, or piperacillin-tazobactam 3.375 g IV q6h, or ciprofloxacin 400 mg IV q12h plus metronidazole 500 mg IV q8h, or meropenem 1 g IV q8h)

Specific Entities

GALLSTONE DISEASE SPECTRUM

—asymptomatic (70%), biliary colic (20%, intermittent obstruction), acute cholecystitis (cystic duct obstruction), choledocholithiasis (common bile duct obstruction), ascending cholangitis (stasis and infection of biliary tract; may be secondary to choledocholithiasis; see p. 156 for more details), gallstone pancreatitis (pancreatic duct obstruction), gallstone ileus, gallbladder cancer

ACUTE CHOLECYSTITIS

pathophysiology—abnormalities of bile acid secretion, mucus generation, and gallbladder motility → gallstone formation → migrate to obstruct the cystic duct and even common bile duct/pancreatic duct → gallbladder inflammation and sometimes secondary infection → gallbladder necrosis and gangrene with perforation in severe cases. Risk factors include older age, obesity, fertility, women (i.e. forty, fat, fertile, female), ethnicity (Aboriginal, Hispanic), TPN, and rapid weight loss

RATIONAL CLINICAL EXAMINATION SERIES: DOES THIS PATIENT HAVE ACUTE CHOLECYSTITIS?

HISTORY—RUQ pain, N&V, anorexia, fever

PHYSICAL—Murphy sign (arrest of inspiration while palpating the gallbladder during a deep breath), guarding, rigidity, RUQ mass, rebound, rectal tenderness

	Sens	Spc	LR+	LR–
Murphy sign	65%	87%	2.8	0.5
RUQ tenderness	77%	54%	1.6	0.4
Bedside US with gallstones and positive sonographic Murphy sign	–	–	2.7	0.13

INVESTIGATIONS—leukocytosis, ALP >120 U/L, elevated ALT or AST, elevated bilirubin

APPROACH—“no single clinical finding or laboratory test carries sufficient weight to establish or exclude cholecystitis without further testing (i.e. ultrasound). Clinical gestalt (without ultrasound) is estimated to have LR+ 25–30, bringing the probability of cholecystitis from 5% pretest to 60% post test. The evaluation of patients with abdominal pain suggestive of cholecystitis will continue to rely heavily on clinical gestalt and diagnostic imaging”

JAMA 2003 289:1

UPDATE—clinicians with training and experience in bedside ultrasound can visualize the gallbladder in most patients. For patients with low pretest probability of cholecystitis and definitively negative bedside ultrasound, formal ultrasound may not be required.

The Rational Clinical Examination. McGraw-Hill, 2009

diagnosis—US abd, endoscopic US, ERCP, percutaneous transhepatic cholangiography, MRCP, HIDA/DISIDA cholescintigraphy (acalculous cholecystitis), CT abd
treatments—supportive measures include NPO, IV fluids, pain control (NSAIDs, opioids), antiemetics and antibiotics (ceftriaxone 1 g IV q24h plus metronidazole 500 mg IV q8h, or piperacillin-tazobactam 3.375 g IV q6h, or ciprofloxacin 400 mg IV q12h plus metronidazole 500 mg IV q8h, or meropenem 1 g IV q8h). Cholecystectomy (laparoscopic, open) or percutaneous cholecystostomy to facilitate drainage (if non-operative because of high risk). If biliary pain despite cholecystectomy, consider possibility of a retained common bile duct stone, sphincter of Oddi dysfunction, or functional pain

NEJM 2008 358:26

ACUTE MESENTERIC ISCHEMIA

pathophysiology—embolism in the celiac or superior mesenteric artery from valvular heart disease or atrial fibrillation, thrombosis, or shock (low flow state) → sudden and severe periumbilical pain out of proportion with physical findings, N&V, leukocytosis, ↑ lactate, ileus
diagnosis—high clinical suspicion, CT abd (+ contrast). Angiography gold standard
treatments—IV fluids, immediate surgery, anticoagulation if mesenteric arterial embolism or mesenteric venous thrombosis

ISCHEMIC COLITIS

pathophysiology—low-flow state in the mesentery affecting mainly the “watershed” area of the middle colic and inferior mesenteric arteries → hematochezia, diarrhea, abdominal pain
diagnosis—AXR (“thumbprinting” or edematous haustral folds), CT (focal or segmental bowel wall thickening or intestinal pneumatosis with portal vein gas), colonoscopy, laparoscopy
treatments—supportive (hydration), antibiotics

CHRONIC MESENTERIC ISCHEMIA

pathophysiology—↓ blood flow from atherosclerosis of the proximal mesenteric vessels → intestinal angina with post-prandial abdominal pain → fear of eating, extensive weight loss
diagnosis—CT abdomen/pelvis (initial), mesenteric duplex US (sens 90% for stenosis of >50%), CT angiography
treatments—angioplasty, surgical revascularization, management of vascular risk factors

Upper GI Bleed

NEJM 2008 359:9

Differential Diagnosis

PEPTIC ULCER DISEASE (PUD)

—gastric, duodenum

INFLAMMATION

—esophagitis (CMV, medications), gastritis (acute, chronic), inflammatory bowel disease (Crohn’s)

VARICES

—esophagus, stomach

TUMORS

—esophagus, stomach, duodenum

STRUCTURAL

—Mallory–Weiss tear, Boerhaave’s syndrome, Dieulafoy’s lesion, arteriovenous malformation, aortoduodenal fistula, hemobilia

OTHERS

—epistaxis, hemoptysis

Clinical Features

HISTORY

—volume of hematemesis, melena, and hematochezia, vomiting, past medical history (PUD, H. pylori infection, alcohol-related disorders, liver cirrhosis with varices, renal failure, metastatic cancer, heart disease/HF), medication history (anticoagulants, NSAIDs)

PHYSICAL

—acute bleeding, sinus tachycardia, supine hypotension (SBP <95 mmHg), postural pulse increase >30/min or dizziness, anemia (conjunctival, facial or palmar pallor), cirrhosis (facial telangiectasia, palmar erythema, spider angiomas, gynecomastia, abdominal wall veins, Terry’s nails/leukonychia, peripheral edema). Perform a rectal examination and test for fecal occult blood. Examine vomitus or nasogastric aspirate and test for occult blood

BLACK STOOL THAT MAY MIMIC MELENA

—bismuth subsalicylate, iron, spinach, charcoal

RATIONAL CLINICAL EXAMINATION SERIES: DOES THIS PATIENT HAVE A SEVERE UPPER GASTROINTESTINAL BLEED?

	LR+	LR–
Clinical Factors Distinguishing UGIB vs. LGIB
Prior history of UGIB	6.2	0.81
Age <50 years	3.5	0.80
Cirrhosis	3.1	0.97
History of melena	5.1–5.9	0.06–0.27
Melenic stool on examination	25	0.52
Nasogastric lavage with blood or coffee grounds	9.6	0.58
Clots in stool	0.05	1.2
Serum urea nitrogen:creatinine ratio >30	7.5	0.53
Clinical Factors Determining Need for Urgent Evaluation of UGIB
History of malignancy or cirrhosis	3.7	0.83
Cirrhosis	3.2	0.89
Syncope	3.0	0.95
Pulse rate >100/min	4.9	0.34
Nasogastric lavage with red blood	3.1	0.32
Hemoglobin level <8 g/dL	4.5–6.2	0.36–0.41
Serum urea nitrogen >90 mg/dL	3.6	0.45
Blatchford score = 0	1.2	0.02

Blatchford score: determined by blood urea, hemoglobin, systolic blood pressure, pulse > 99 beats/min, presentation with melena, presentation with syncope, hepatic disease, cardiac failure

APPROACH—“tachycardia (pulse rate of >100/min; LR, 4.9), a history of cirrhosis or malignancy (LR+ 3.7), hemoglobin level of less than 8 g/dL (LR+ range, 4.5-6.2), or a nasogastric lavage with red blood (LR+ 3.1) increase the likelihood of severe bleeding. All patients with a UGIB should have a Blatchford score, which does not require a nasogastric lavage, to help assess the severity (Blatchford score = 0; LR- 0.02 for identifying patients requiring urgent evaluation). When negative, prediction rules combining symptoms, signs, and routine laboratory test results almost definitively rule out severe UGIB, thereby identifying at least some patients who can be safely evaluated as an outpatient”

JAMA 2012 307:10

RATIONAL CLINICAL EXAMINATION SERIES: IS THIS PATIENT HYPOVOLEMIC? HYPOVOLEMIA DUE TO ACUTE BLOOD LOSS

	Sens	Spc
For moderate blood loss
Postural pulse increment ≥30/min or severe postural dizzines	22%	–
Postural hypotension ≥20 mmHg SBP drop	9%	94%
Supine tachycardia	0%	96%
Supine hypotension	13%	97%
For large blood loss
Postural pulse increment ≥30/min or severe postural dizziness	97%	98%
Supine tachycardia	12%	96%
Supine hypotension	33%	97%

NOTE: postural change is measured first with supine vitals counting pulse for 30 s (after waiting 2 min), then standing vitals (after waiting 1 min)

JAMA 1999 281:11

HYPOVOLEMIA DUE TO VOMITING, DIARRHEA, DECREASED INTAKE, DIURETICS

	Sens	Spc	LR+	LR–
Symptoms
Postural pulse increment ≥30/min	43%	75%	1.71	0.8
Postural hypotension ≥20 mmHg	29%	81%	1.5	0.9
Dry axilla	50%	82%	2.8	0.6
Dry oral/nasal mucous membrane	85%	58%	2.0	0.3
Dry tongue	59%	73%	2.1	0.6
Tongue with furrows	85%	58%	2.0	0.3
Sunken eyes	62%	82%	3.4	0.5
Confusion	57%	73%	2.1	0.6
Upper/lower extremity weakness	43%	82%	2.3	0.7
Speech not clear or expressive	56%	82%	3.1	0.5
Capillary refill time > normal	34%	95%	6.9	0.7

APPROACH—“for patients with suspected acute blood loss, severe postural dizziness (preventing upright vitals measurements) or postural pulse increment are predictive. Postural hypotension has no incremental value. For patients with suspected hypovolemia not due to blood loss, severe postural dizziness, postural pulse increment, or dry axilla can be helpful. Moist mucous membranes and tongue without furrows argue against it. Capillary refill time and poor skin turgor have no proven diagnostic value”

JAMA 1999 281:11

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, type/cross-match, PTT, INR, AST, ALT, ALP, bilirubin, albumin, fecal occult blood
imaging—CXR, AXR
gastroscopy

Prognostic Issues

RISK STRATIFICATION FOR PEPTIC ULCER DISEASE

clinical R ockall scoring—age 60–79 = 1; age ≥80 = 2; heart rate >100 beats/min = 1; systolic BP <100 mmHg = 2; co-existing illnesses (ischemic heart disease, HF, other major illness) = 2; co-existing illnesses (renal failure, hepatic failure, metastatic cancer) = 3
complete Rockall scoring—in addition to clinical Rockall score, add the following based on endoscopic findings: no lesion observed, Mallory–Weiss tear = 0; peptic ulcer, erosive disease, esophagitis = 1; cancer of upper GI tract = 2; clean base ulcer, flat pigmented spot = 0; blood in upper GI tract, active bleeding, visible vessel, clot = 2
interpretation—low risk for bleeding or death = clinical Rockall score 0 or complete Rockall score ≤2

RISK OF ULCER RE-BLEED

high - risk features—active spurting/oozing during endoscopy (90% chance), non-bleeding visible vessel (50% chance), adherent clot (25–30% chance). If none of above factors and clinically not severe bleed, very low chance of rebleed and may consider discharging shortly after. Other factors include size and location of ulcer
low - risk features—flat spot (10% chance), clean ulcer base (3–5% chance)

Management

ACUTE

—ABC, O₂, IV hydration (two large-bore IVs). Transfusion (especially if hemoglobin <70 g/L [<7 g/dL], platelets <50 × 10⁹). NPO, consider NG tube. Hold antihypertensive and diuretic therapy. If prolonged PT/PTT, vitamin K 10 mg IV (small risk of anaphylaxis) and FFP 2–4 U IV or unactivated prothrombin complex concentrates (PCC) 1000–3000 U IV (dosing based on INR and severity of bleeding), if rapid reversal required. If on heparin, consider protamine infusion (1 mg antagonizes 100 U of heparin—beware of excessive protamine which can cause paradoxical coagulopathy). If suspect varices, octreotide 50 μg IV bolus, then 25–50 μg/h. Pantoprazole 80 mg IV bolus, then 8 mg/h until endoscopy. If cirrhosis and acute variceal hemorrhage, transfuse platelet and FFP PRN, antibiotics for 7 days (ceftriaxone 1 g IV q24h, cefotaxime 1 g IV q8h, ciprofloxacin 400 mg IV q12h, ciprofloxacin 500 mg PO BID, or norfloxacin 400 mg PO BID). Consult GI for gastroscopy and consider erythromycin 250 mg IV 30–90 min before endoscopy for clot lavage

TREAT UNDERLYING CAUSE

—avoid ASA, NSAIDs. Peptic ulcer (endoscopic hemostasis with thermal coagulation/fibrin sealant/endoclips plus 1:10,000 ratio epinephrine injection. After endoscopy, start pantoprazole 80 mg IV bolus if not given already, then 8 mg/h × 72 h [if high-risk lesion], switch to 40 mg PO BID × 1 month then daily). Varices (endoscopy within 12 h with ligation/band/glue/sclerotherapy → balloon tamponade → transjugular intrahepatic portosystemic shunt (TIPS) → portacaval/distal splenorenal shunt, or liver transplant. Continue octreotide for 3 days. Repeat endoscopy every 2–4 weeks until varices obliterated, then at 1–3 months and again every 6–12 months afterward. Consider non-selective β-blocker such as nadolol 40–80 mg PO daily or propranolol 20 mg PO BID. Mallory–Weiss tear (omeprazole 20 mg PO daily). H. pylori eradication (see DYSPEPSIA p. 125 for treatment). Intractable or recurrent bleed (consult surgery. See TREATMENT ISSUES below)

Treatment Issues

CRITERIA FOR SURGICAL CONSULT FOR ULCER BLEED

—hemodynamic instability despite resuscitation (>3 U PRBC), shock, recurrent hemorrhage after two endoscopic attempts, continued slow bleed requiring >3 U PRBC/day), high-risk endoscopic lesion

COMPLICATIONS OF ENDOSCOPY

—perforations, bleeding, sedation-related respiratory failure

DISCHARGE DECISIONS FOR PATIENTS’ PEPTIC ULCER DISEASE

—patients with low-risk of re-bleed (complete Rockall score ≤2, low risk endoscopic features), with Hb >80–100 g/L [>8–10 g/dL] without further need of transfusions, normal INR/PTT, and have adequate social support may be safely discharged home shortly after endoscopy with follow-up, while patients with high-risk features should be admitted and monitored closely

Lower GI Bleed

Differential Diagnosis

UPPER GI SOURCE WITH BRISK BLEEDING

(10%)

INFECTIOUS

—Salmonella, Shigella, Campylobacter, Yersinia, E. coli (EHEC, EIEC), C. difficile, Amoeba

TUMORS

—colorectal cancer, small bowel cancer, polyp

INFLAMMATORY

—inflammatory bowel disease (IBD)

ISCHEMIC

—ischemic colitis

STRUCTURAL

—angiodysplasia, diverticulosis, radiation colitis, hemorrhoids, anal fissure, intussusception, Meckel’s diverticulum

Clinical Features

HISTORY

—volume of bleed, melena, abdominal pain, past medical history (IBD, cancer, diverticulosis), medication history (anticoagulants, antiplatelet drugs, NSAIDs)

PHYSICAL

—acute bleeding, sinus tachycardia, supine hypotension (SBP <95 mmHg), postural pulse increase >30/min or dizziness, anemia (conjunctival, facial or palmar pallor), abdominal tenderness. Perform a rectal examination and test for fecal occult blood

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, type/X-match, PTT, INR, AST, ALT, ALP, bilirubin, albumin
microbiology—stool C&S, fecal occult blood
endoscopy—colonoscopy, gastroscopy

SPECIAL

imaging—for obscure bleed, consider ⁹⁹Tc RBC scan (detects 0.1 mL/min), angiography (detects 0.5 mL/min), capsule endoscopy, push enteroscopy, double balloon enteroscopy, MR enterography and/or Meckel’s scan

Diagnostic Issues

OCCULT BLEED

—no obvious melena or bright red blood per rectum (BRBPR), but possible bleed as fecal occult blood or fecal immunochemical test positive

OBSCURE BLEED

—obvious bleeding but source cannot be found

OVERALL APPROACH

—gastroscopy and/or colonoscopy (start with the end with the most likely source of bleed, then scope the other end if no yield) → if negative, repeat panendoscopy → if negative, small bowel follow-through → if negative, consider angiography, RBC scan, capsule, push or double balloon endoscopy, or laparotomy

Management

ACUTE

—ABC, O₂, IV hydration (two large-bore IVs). Transfusion (especially if hemoglobin <70 g/L [<7 g/dL], platelets <50 × 10⁹/L). NPO. Hold antihypertensive and diuretic therapy. If prolonged PT/PTT, vitamin K 10 mg IV (small risk of anaphylaxis) [see above comment for UGIB] and FFP 2–4 U IV or unactivated prothrombin complex concentrates (PCC) 1000–3000 U IV (dosing based on INR and severity of bleeding), if rapid reversal required. If on unfractionated heparin, protamine infusion (1 mg antagonizes 100 U of heparin). Consult GI for endoscopy

TREAT UNDERLYING CAUSE

Inflammatory Bowel Disease Exacerbation

Differential Diagnosis

See differential diagnosis for
ACUTE ABDOMINAL PAIN (p. 128)
LOWER GI BLEED (p. 134) and
CHRONIC DIARRHEA (p. 138)

Pathophysiology

TYPES

Crohn’s—mild to moderate (relatively asymptomatic, tolerating oral diet), moderate to severe (failed treatment for mild disease, symptomatic), severe to fulminant (failed steroid treatment, very symptomatic)
ulcerative colitis—ulcerative proctitis (limited to rectum), distal colitis/protosigmoiditis (extending up to mid-sigmoid colon), left-sided colitis (extending up to splenic flexure), extensive colitis (extending up to but not including cecum), pancolitis (extending up to cecum)

Clinical Features

DISTINGUISHING FEATURES BETWEEN CROHN’S DISEASE AND ULCERATIVE COLITIS

	Crohn’s disease	Ulcerative colitis
Degree of involvement	Segmental (“skip lesions”)	Continuous
	Rectal sparing
Symptoms	Abd pain	Bloody diarrhea
	Diarrhea	Tenesmus
	Anorexia	Fever
	Perianal disease
Serology	Anti-Saccharomyces cerevisiae IgG antibody (sens 77%, spec 92%, PPV 82%)	p-ANCA (sens 70%, spc 88%, PPV 75%)
Pathology	Transmural granuloma	Mucosal inflammation
		No granulomas
Complications	Obstruction	Toxic megacolon (1–2%)
	Strictures Fistulas Fissures Abscesses Colorectal cancer	Colorectal cancer (1%/year after 10 years)

EXTRAINTESTINAL MANIFESTATIONS

—fever, clubbing, uveitis, iritis, anemia, jaundice (primary sclerosing cholangitis), aphthous ulcers (Crohn’s only), arthritis (spondylitis; type I arthropathy: pauciarticular and related to IBD activity; type II arthropathy: polyarticular and unrelated to IBD activity), erythema nodosum, pyoderma gangrenosum, DVT, amyloidosis

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, ESR, CRP, Fe, TIBC, ferritin, % sat, AST, ALT, ALP, bilirubin, albumin, Ca, Mg, PO₄, vitamin B12, folate, fecal calprotectin, fecal lactoferrin
microbiology—stool C&S, fecal occult blood, stool for C. difficile toxin assay
Serology—antineutrophil cytoplasmic antibodies (pANCA), anti-Saccharomyces cerevisiae antibodies (ASCA)
imaging—AXR, CT/MR enterography, contrast-enhanced US
endoscopy—flexible sigmoidoscopy, colonoscopy, double-balloon enteroscopy

Management

SUPPORTIVE THERAPY

diet and nutrition—if mild, low-fiber diet, elemental diet; if severe, TPN and bowel rest
antidiarrheal agents—contraindicated in severe exacerbation and toxic megacolon

ANTIINFLAMMATORY AGENTS

5ASA suppositories—if localized (i.e. rectal/left-sided) disease. Mesalamine 1 g PR qhs, glucocorticoid enema/suppositories daily-BID
systemic 5ASA—for induction and maintenance (sulfasalazine induction 0.5 g PO BID, then titrate to 0.5–1.5 g PO QID, maintenance 1 g PO BID–QID; mesalamine 800–1600 mg PO TID maintenance 400–800 mg PO TID; olsalazine)
glucocorticoids—for flares (methylprednisolone 30 mg IV BID, prednisone 50 mg PO daily, reduce by 5 mg/week)
immunosuppressive agents—azathioprine 50 mg PO daily, increase by 25 mg daily every 2 weeks to a max of 2–2.5 mg/kg/day as tolerated (monitor CBC, liver enzymes), methotrexate 25 mg IM weekly
antibiotics—metronidazole 500 mg PO TID, ciprofloxacin 500 mg PO BID
biological agents—infliximab IV infusions of 5 mg/kg at 0, 2, 6 weeks, followed by 5–10 mg/kg every 8 weeks for maintenance; or adalimumab 160 mg SC initially then 80 mg SC at 2 weeks, 40 mg SC at 4 weeks, followed by 40 mg SC every other week for maintenance. Drug coverage for anti-TNF therapy differs between Canadian provinces

SURGERY

Treatment Issues

CROHN’S COLITIS

stepwise treatment—oral 5ASA or sulfasalazine for 3–4 weeks. If failed, add metronidazole and ciprofloxacin. If failed, add oral steroids for 4 weeks. If failed, consider immunosuppressive therapy. Consider metronidazole and ciprofloxacin, biologic therapy for treatment of perianal fistula

ULCERATIVE COLITIS

ulcerative proctitis—5ASA suppositories or enemas for 2–4 weeks for active treatment. If failed, add steroid foams. Consider oral 5ASA if patient cannot tolerate suppositories. Maintenance therapy may be required
distal colitis / protosigmoiditis and left - sided colitis—similar treatment to ulcerative proctitis, push to maximal dose if necessary. If failed, add budesonide enemas. If failed, add oral prednisone. Maintenance therapy is recommended
extensive and pancolitis (mild-moderate)—oral 5ASA or sulfasalazine, plus topical 5ASA or steroid enemas. Add oral prednisone if failed or severe symptoms. Maintenance therapy is required
extensive and pancolitis (severe)—hospitalize with bowel rest, hydration, nutrition, parenteral steroids, and adjunctive rectal and oral therapy. Consider adding metronidazole, ciprofloxacin, and infliximab or cyclosporine. May need surgical consult

TOXIC MEGACOLON

pathophysiology—a potential complication of inflammatory bowel disease, infectious colitis (C. difficile, other inflammatory organisms), ischemic colitis, and obstructive colon cancer
clinical features—the combination of abdominal distension and diarrhea (may be bloody) should prompt investigations for toxic megacolon. Patient usually toxic with fever, hypotension, delirium, and abdominal pain
diagnosis—dilated colon on X-ray (usually transverse or right colon, >6 cm), plus three of the following (fever >38 °C [100.4 °F], tachycardia >120/min, leukocytosis >10.5 × 10⁹/L, anemia), plus one of the following (dehydration, delirium, electrolyte disturbances, hypotension)
treatments—supportive therapy (NPO, IV fluids, hold all opioids, antidiarrheal and anticholinergic agents). For IBD-related toxic megacolon, give hydrocortisone 100 mg IV q6h and antibiotics (ceftriaxone plus metronidazole). For C. difficile-related toxic megacolon, treat aggressively with IV metronidazole and PO/NG vancomycin. Patients with toxic megacolon who do not respond to therapy within 72 h should be considered for colectomy. ICU admission for monitoring. Serial blood tests and AXR daily to assess progress

Acute Diarrhea

NEJM 2004 350:1

Differential Diagnosis

INFLAMMATORY/INVASIVE

(fever, bloody diarrhea, tenesmus)

invasive infections—Salmonella, Shigella, Campylobacter, Yersinia, EHEC, EIEC, Vibrio parahaemolyticus, Clostridium difficile, Entamoeba
inflammatory—ulcerative colitis, Crohn’s
ischemic colitis
radiation colitis

NON-INFLAMMATORY

non - invasive infections—bacterial (Vibrio cholera, Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, C. difficile, ETEC, EPEC), viral (Rotavirus, norovirus, CMV), parasites (Giardia, Cryptosporidium, Amoeba)
medications—antibiotics, laxatives, chemotherapy

Pathophysiology

DEFINITION OF DIARRHEA

—3 bowel movements/day or at least 200 g of stool/day. Acute diarrhea is defined as <2 weeks, whereas chronic diarrhea is defined as ≥2 weeks duration

DIARRHEA AND ASSOCIATED SYNDROMES

salmonella—may cause septicemia in patients with sickle cell anemia or AIDS
shigella—precedes reactive arthritis
campylobacter—precedes 10–30% of Guillain–Barre syndrome
yersinia—mesenteric adenitis, erythema nodosum, polyarthritis, reactive arthritis, bacteremia, may mimic appendicitis

DIARRHEA AT VARIOUS SETTINGS

community acquired—Salmonella (prevalence 16/100,000), Campylobacter (13/100,000), Shigella (10/100,000), E. coli O157:H7 (1.7/100,000), Cryptosporidium (1.4/100,000)
traveler ’ s—ETEC
nosocomial—C. difficile
persistent diarrhea (>7 days)—Giardia, Isospora belli, Cyclospora, Cryptosporidium
immunocompromised—Microsporidia, MAC, CMV

NATURAL HISTORY

—most diarrheal illnesses are self-limited or viral-induced and nearly 50% last <1 day

Clinical Features

HISTORY

—characterize diarrhea (duration, frequency, volume, blood, floating), infectious contacts, recent food intake, abdominal pain, past medical history (IBD, lactose intolerance), medication history (laxatives, antibiotics), travel history

PHYSICAL

—vitals and check for dehydration. Abdominal tenderness. Perform a rectal examination. Inspect stool sample if available

SALMONELLA AND CAMPYLOBACTER

—although they are classified as inflammatory, patients usually only develop fever and severe diarrhea and not bloody diarrhea

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, lactate
microbiology—stool C&S (sens 1.5–5.6%), O&P, C. diff toxin A + B, viral culture

SPECIAL

fecal testing—fecal leukocytes (inflammatory, sens 73%, spc 84%), fecal lactoferrin (inflammatory, sens 92%, spc 79%), Giardia toxin, fecal occult blood
endoscopy—flexible sigmoidoscopy, colonoscopy

Management

SYMPTOM CONTROL

—IV hydration. Antidiarrheal agents if not inflammatory (bismuth subsalicylate 2 tab PO q1h PRN or loperamide 4 mg × 1 dose, then 2 mg PO PRN, maximum 16 mg/day)

TREAT UNDERLYING CAUSE

—Shigella , Salmonella , Campylobacter , E. coli other than EHEC (ciprofloxacin 500 mg PO BID × 3 days, levofloxacin 500 mg PO daily × 3 days). Vibrio cholera (tetracycline 500 mg PO QID × 3 days, doxycycline 300 mg PO × 1 dose, or azithryomycin 1 g PO × 1 dose). Isospora and Cyclospora (trimethoprim–sulfamethoxazole 160/800 PO BID × 7–10 days). C. difficile , Giardia, and Entamoeba (metronidazole 500 mg PO TID × 10 days)

Specific Entities

ANTIBIOTICS-ASSOCIATED DIARRHEA AND PSEUDOMEMBRANOUS COLITIS

pathophysiology—organisms include C. difficile (particularly with clindamycin, cephalosporins, penicillins) and non-C. difficile organisms (Salmonella, C. perfringens, S. aureus, Candida). Relapse occurs in 20–25% of patients and typically between 3 and 21 days after discontinuation of treatment: 3–5% of patients have more than 6 relapses. Note emergence of virulent C. difficile strain NAP-1/027 characterized by increased secretion of toxins A/B, binary toxin production and fluoroquinolone resistance, and associated with increased outbreaks and mortality
risk factors—onset of diarrhea ≥6 days after the initiation of antibiotic therapy, hospital stay ≥2 weeks, fecal leukocytes, semi-formed stools, cephalosporin use
clinical features—usually watery diarrhea (may be bloody if severe colitis), abdominal pain. In patients with severe C. difficile infection, significant leukocytosis, pseudomembranous colitis, toxic megacolon (see p. 135), acute renal failure, and hypotension may develop
diagnosis—C. difficile toxin A/B from stool sample, flexible sigmoidoscopy (pseudomembranous colitis). C. difficile toxin levels are usually unnecessary immediately after treatment completion as up to one-third of patients have positive assays despite successful treatment
treatments—IV hydration. Discontinue implicated antibiotics. Avoid use of antiperistaltic agents (opiates, loperamide). C. difficile treatment (metronidazole 250 mg PO QID × 10–14 days, metronidazole 500 mg PO TID × 10–14 days, or vancomycin 125–500 mg PO QID × 10–14 days). For severe cases, consider oral vancomycin as first-line agent. If significant ileus or toxic megacolon, give vancomycin via NG or enema and add metronidazole 500 mg IV QID. Avoid repeating stool assays after treatment unless patient has moderate or severe diarrhea. A positive C. difficile toxin without significant symptoms should not prompt treatment. For C. difficile recurrence, consider retreatment with 14-day course and minimize use of other antibiotics. For further recurrences, consider tapering doses of vancomycin 125 mg PO QID × 1 week, then BID × 1 week, then daily × 1 week, then every other day × 1 week, then every 3 days × 2 weeks. Alternatives include vancomycin 125 mg PO QID in combination with rifampin 600 mg BID × 7 days, or Saccharomyces boulardii 250 mg PO QID in combination with metronidazole or vancomycin, or fidaxomicin 200 mg PO BID × 10 days

NEJM 2002 346:5; NEJM 2008 359:18

Chronic Diarrhea

NEJM 1995 332:11

Differential Diagnosis

★MISO★

MOTILITY—hyperthyroidism, diabetic neuropathy, bacterial overgrowth, irritable bowel syndrome (IBS), scleroderma
INFLAMMATORY
- infections—Salmonella, Shigella, Yersinia, Campylobacter, E. coli (EHEC, EIEC), C. difficile, Amoeba
- inflammatory—ulcerative colitis, Crohn’s, ischemic, radiation, toxic
SECRETORY
- infections—Cholera, Staphylococcus, B. cereus, C. perfringens, E. coli (ETEC, EPEC), Rotavirus, norovirus, CMV, Giardia, Cryptococcus, Amoeba
- neuroendocrine tumors—carcinoid, VIPoma, calcitonin excess, gastrinoma, somatostatinoma
- medications—laxatives
- others—bile salt enteropathy, fatty acid induced, collagenous colitis, lymphocytic colitis
OSMOTIC
- maldigestion / malabsorption—pancreatic insufficiency, celiac disease, lactose intolerance, short bowel syndrome, enteric fistula
- medications—antacids, antibiotics, Mg citrate, Mg hydroxide, lactulose, sorbitol (i.e. “chewing gum diarrhea”), colchicine, metformin

Clinical Features

HISTORY

—characterize diarrhea (duration, frequency, volume, blood, floating), infectious contact, abdominal pain, weight loss, past medical history (diabetes, hyperthyroidism, IBS, lactose intolerance, bowel surgery, scleroderma), medication history (laxatives)

PHYSICAL

—obtain body weight and inspect stool sample. Abdominal tenderness. Perform a rectal examination and test for fecal occult blood

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, albumin, TSH, antitransglutaminase antibody, endomysial antibody
microbiology—stool C&S, O&P, C. diff toxin A + B, Giardia toxin

SPECIAL

fecal testing—fecal leukocytes, fecal fat, fecal lytes, fecal occult blood, stool for phenothalin (laxative abuse), α-1 antitrypsin
imaging—SBFT, CT abd
endoscopy—upper and lower, for biopsy

Investigation Issues

DISTINGUISHING FEATURES

inflammatory—bloody stool, fecal leukocytes
secretory—fecal osmotic gap <50 mOsm/kg, >500 g of stool with fasting
osmotic—fecal osmotic gap >50 mOsm/kg; <500 g of stool with fasting

FECAL OSMOTIC GAP

—280 − 2 × (stool Na + K)

Management

SYMPTOM CONTROL

—hydration and nutritional support. Empiric treatment with antidiarrheal agents if not inflammatory (bismuth subsalicylate 2 tab PO q1h PRN or loperamide 4 mg × 1 dose, then 2 mg PO PRN, maximum 16 mg/day)

TREAT UNDERLYING CAUSE

—cholestyramine for bile acid-induced diarrhea

Specific Entities

CELIAC DISEASE

pathophysiology—sensitivity to gluten in Barley, Rye, Oat, Wheat ★BROW★ → T-cell-mediated immune reaction to gliadin → intestinal epithelial cell death → villous atrophy, crypt hyperplasia → malabsorption in small bowel. More common in females (2–3:1). Associated with type 1 diabetes, dermatitis herpetiformis (p. 409), IgA deficiency, liver dysfunction, and small bowel lymphoma (especially if no response to celiac diet)
clinical features—abdominal bloating (especially after inadvertent ingestion of gluten), isolated weight loss, iron-deficiency anemia in the absence of gastrointestinal blood loss, nutritional deficiency, osteoporosis (sometimes osteomalacia), diarrhea (sometimes), liver dysfunction
diagnosis—antitransglutaminase IgA (sens 94%, spc 99%), antiendomysial IgA, antigliadin IgG (celiac patients with IgA deficiency may not be antitransglutaminase positive). Small bowel biopsy recommended for confirmation of diagnosis (intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and good response to gluten-free diet). HLA DQ2 (~95%) and HLA DQ8 (~5%) may be present (absence of both DQ2/DQ8 makes celiac disease highly unlikely). Once diagnosed, a bone mineral density scan is recommended
treatments—gluten-free diet lifelong. Steroids, if symptoms persist despite gluten-free diet, and consider workup for enteropathy-associated lymphoma

NEJM 2007 357:17

Malabsorption Syndromes

Differential Diagnosis

SALIVARY

(lipase, amylase; rare cause)—radiation, sicca

STOMACH

(intrinsic factor, R factor; rare cause)—pernicious anemia, gastrectomy, vagotomy

HEPATOBILIARY

(bile acids; 10% of extra-colonic cases)—hepatic failure, cholestasis, biliary obstruction, terminal ileal resection

PANCREAS

(lipase, amylase, HCO₃; 90% of extra-colonic causes)—cancer, chronic pancreatitis, cystic fibrosis

SMALL INTESTINE

(brush border/enterocytes)—celiac disease, lymphoma, infectious colitis, inflammatory colitis, ischemic colitis, radiation colitis

OTHERS

—β-lipoprotein (abetalipoproteinemia), lymphatics (lymphoma)

Pathophysiology

COMPLICATIONS OF MALNOURISHMENT

—infections (sepsis, abscess, pneumonia), poor wound healing, respiratory failure, death

Clinical Features

HISTORY

—diarrhea (watery, steatorrhea), flatus, abdominal distension, abdominal pain (suggests chronic pancreatitis, Crohn’s disease, or pseudoobstruction as otherwise uncommon in malabsorption), N&V, symptoms in relation to meals (may occur within 90 min of carbohydrate ingestion), anorexia, weight loss, diet, past medical history (type 1 diabetes, celiac disease, IBD, recurrent peptic ulcer disease, previous surgery, psychiatric disorders, alcohol), medications (laxatives, diuretics, illicit drugs)

RATIONAL CLINICAL EXAMINATION SERIES: IS THIS PATIENT MALNOURISHED?

history—weight change (overall loss in past 6 months, change in past 2 weeks), dietary intake change relative to normal (duration, types include suboptimal solid diet, hypocaloric liquids, full liquid diet, starvation), gastrointestinal symptoms >2 weeks (nausea, vomiting, diarrhea, anorexia), functional capacity (duration, working suboptimally, ambulatory, bedridden)

physical—loss of subcutaneous fat (triceps, chest), muscle wasting (quadriceps, deltoids), swelling (ankle edema, sacral edema, ascites)

risk of major postoperative complications based on subjective global assessment (SGA)

	LR+
Well nourished
Defined as <5% weight loss or >5% total weight loss but recent gain and improvement in appetite	0.66
Moderately malnourished
Defined as 5–10% weight loss without recent stabilization or gain, poor dietary intake, and mild (1+) loss of subcutaneous tissue	0.96
Severely malnourished
Defined as ongoing weight loss of >10% with severe subcutaneous tissue loss and muscle wasting often with edema	4.44

APPROACH—“SGA is an accurate predictor of patients who are at higher risk of developing complications such as infection or poor wound healing”

JAMA 1994 271:1

UPDATE—several markers have been compared to the SGA for predicting malnutrition. Serum albumin <3.0 g/dL increases likelihood of moderate/severe malnutrition (LR + 3.3), but is not specific. A positive simplified Malnutrition Screening Tool (have you lost weight without trying, how much weight have you lost [kg], and have you been eating poorly because of decreased appetite) increases likelihood of malnutrition (LR+ 13)

The Rational Clinical Examination. McGraw-Hill, 2009

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, INR, PTT, fasting lipid profile, Ca, Mg, PO₄, albumin, pre-albumin, carotene, Fe, ferritin, antitransglutaminase antibody, vitamin B12, RBC folate
imaging—US abd

SPECIAL

colonoscopy—for Crohn’s
gastroscopy—for Celiac disease
mrcp/endoscopic us—if suspect chronic pancreatitis
stool fat— > 6 g/day suggests steatorrhea
d - xylose test—if suspect malabsorption
breath test—for carbohydrate malabsorption, small bowel bacterial overgrowth and lactose intolerance, including H₂, ¹⁴CO₂, or ¹³CO₂
antiintrinsic factor antibody—for vitamin B12 deficiency (has replaced historical Schilling test)

Management

SYMPTOM CONTROL

—dietician consult. Consider supplemental nutrition

TREAT UNDERLYING CAUSE

Specific Entities

MARASMUS SYNDROME

—deficiency of calories resulting in stunted growth in children, loss of body fat, and generalized wasting of lean body mass without significant edema

KWASHIORKOR SYNDROME

—deficiency of protein with preserved adipose tissue but significant edema, muscle atrophy, and amenorrhea

FAT-SOLUBLE VITAMIN DEFICIENCY ★KADE★

vitamin K deficiency—increased bleeding tendencies
vitamin A deficiency—follicular hyperkeratosis, night blindness
vitamin D deficiency—paresthesia, tetany, weakness, fractures due to osteomalacia
vitamin E deficiency—skeletal myopathy, spinocerebellar ataxia, pigmented retinopathy, and hemolysis

WATER-SOLUBLE VITAMIN DEFICIENCY

vitamin B1 ( thiamine ) deficiency—Wernicke syndrome, Korsakoff syndrome, Leigh’s syndrome (subacute necrotizing encephalomyopathy)
vitamin B3 ( niacin , nicotinic acid ) deficiency ★DDDD★—Dermatitis (photosensitive, pigmented, pellagra), Diarrhea, Dementia, Death
vitamin B6 ( pyridoxine ) deficiency—cheilosis, painless glossitis, acrodermatitis, angular stomatitis
vitamin C deficiency—scurvy with impaired collagen synthesis leading to ecchymoses, gum bleeding, petechiae, hyperkeratosis, impaired wound healing, arthralgia, weakness, neuropathy, and depression

Constipation

NEJM 2003 349:14

Differential Diagnosis

★DUODENUM★

DIET—low fiber, dehydration
ΨSYCHIATRY —depression, somatization, obsessive compulsive disorder
OBSTRUCTION—cancer, strictures, adhesions
DRUGS—opioids, TCAs, neuroleptics, antihistamines, calcium channel blockers, iron, antacids
ENDOCRINE—diabetes, hypothyroidism, hypercalcemia, hypokalemia, hypomagnesemia, uremia
NEUROLOGIC—spinal cord compression/injury, Parkinson’s, multiple sclerosis, stroke, autonomic neuropathy (cachexia–anorexia syndrome)
UNKNOWN
MISCELLANEOUS—irritable bowel syndrome (IBS), amyloidosis, scleroderma, immobility

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, TSH, Ca, Mg
imaging—AXR

Diagnostic Issues

CONSTIPATION SCORE

—based on flat abdominal X-ray. Divide into four quadrants (ascending, transverse, descending, and rectosigmoid colon). Rate amount of stool in each quadrant from 0–3. A total score >6/12 suggests constipation

Management

LIFESTYLE CHANGES

—wheat bran, high-bran cereals, psyllium/Metamucil 2–3 teaspoon/day, exercise, hydration (8–10 glasses/day)

SYMPTOM CONTROL

—laxatives (in order of increasing potency: docusate 100–240 mg PO daily-QID, senna 1–4 tabs PO daily-QID, milk of magnesia 15–30 mL PO BID, sorbitol 15–30 mL PO daily-BID, lactulose 15–60 mL PO daily, magnesium citrate 150–300 mL PO daily, bisacodyl/dulcolax suppositories 1 PR PRN, tap water enema 500 mL PR PRN, mineral oil enema 100–250 mL PR PRN, polyethylene glycol electrolyte solution [PEG] 250–4000 mL PO PRN). Manual disimpaction. For patients with spinal cord injury, it is important to use rectal measures (enemas, suppositories) as significant diarrhea/leakage could occur with oral medications alone

TREAT UNDERLYING CAUSE

—stop potentially constipation-causing medications if possible

Specific Entities

IRRITABLE BOWEL SYNDROME (IBS)

pathophysiology—heightened response to noxious visceral stimuli, such as balloon distention of the rectum and sigmoid colon
clinical features—Rome criteria define IBS as >3 months of abdominal pain relieved with defecation, associated with a change in the frequency or consistency of stool, plus two of the following for >25% of days: disturbed defecation (>3 bowel movements/day or <3 bowel movements/week), altered stool formation, altered stool passage (straining, urgency, or feeling of incomplete evacuation), passage of mucus, bloating, or feeling of abdominal distention

RATIONAL CLINICAL EXAMINATION SERIES: WILL THE HISTORY AND PHYSICAL EXAMINATION HELP ESTABLISH THAT IRRITABLE BOWEL SYNDROME IS CAUSING THIS PATIENT’S LOWER GASTROINTESTINAL TRACT SYMPTOMS?

MANNING CRITERIA—abdominal pain relieved by defecation, more frequent stools with onset of pain, looser stools with onset of pain, passage of mucus per rectum, feeling of incomplete emptying, patientreported visible abdominal distension

ROME I CRITERIA—abdominal pain or discomfort relieved with defecation or associated with a change in stool frequency or consistency for ≥3 months, plus ≥2 of the following on at least 25% of occasions or days: (1) altered stool frequency, (2) altered stool form, (3) altered stool passage, (4) passage of mucus per rectum, (5) bloating or distension

KRUIS MODEL—a computer model based on a number of symptoms and signs. Symptoms include (1) abdominal pain, flatulence, or bowel irregularity for >2 years; (2) description of abdominal pain as “burning, cutting, very strong, terrible, feeling of pressure, dull, boring, or not so bad”; and (3) alternating constipation and diarrhea. Signs include (1) abnormal physical findings and/or history pathognomonic for any diagnosis other than IBS, (2) ESR >10 mm/h, (3) leukocytosis >10 × 10⁹/L, (4) hemoglobin <120 g/L [<12 g/dL] for females or <140 g/L [<14 g/dL] for males, (5) impression by the physician that the patient’s history suggests blood in the stool

	Sens	Spc	LR+	LR–
Symptoms
Lower abd pain	90%	32%	1.3	0.29
Passage of mucus	45%	65%	1.2	0.88
Feeling of incomplete evacuation	74%	45%	1.3	0.62
Looser stools at onset of pain	59%	73%	2.1	0.59
More frequent stools at onset of pain	53%	72%	1.9	0.67
Pain relieved by defecation	60%	66%	1.8	0.62
Patient reported visible abdominal distension	39%	77%	1.7	0.79
Diagnostic criteria
Manning criteria	78%	72%	2.9	0.29
Rome I criteria	71%	85%	4.8	0.34
Kruis system	77%	89%	8.6	0.26

APPROACH—“absence of abdominal pain reduced the likelihood of IBS. Overall, individual symptoms have limited accuracy for diagnosing IBS in patients referred with lower GI symptoms. The accuracy of the Manning criteria, Rome I criteria and Kruis scoring system were only modest”

JAMA 2008 300:15

Acute Liver Failure

Differential Diagnosis

HEPATOCELLULAR INJURY PATTERN

(↑↑ AST/ALT ± ↑ ALP/bili)

infectious—HAV, HBV, HCV (rare), HDV, HEV, EBV, CMV, HSV, VZV, schistosomiasis, toxoplasmosis, bacterial cholangitis
fatty liver—alcoholic, non-alcoholic steatohepatitis (NASH)
toxic—acetaminophen, NSAIDs, amiodarone, labetalol, statins, phenytoin, valproic acid, fluoroquinolones, amoxicillin/clavulanate, sulfonamides, tetracyclines, isoniazid, azoles, halothane, glyburide, propylthiouracil, Amanita phalloides mushroom, heavy metals, anabolic steroids, cocaine, ecstasy, phencyclidine
vascular—ischemic (“shock liver”), Budd–Chiari, congestive, venoocclusive disease (BMT, chemotherapy, OCP)
neoplastic—hepatoma
autoimmune—autoimmune hepatitis
hereditary—Wilson’s, hemochromatosis, α1-antitrypsin deficiency, glycogen storage disease
pregnancy—acute fatty liver of pregnancy, HELLP
others—liver surgery, Reye’s syndrome with viral illness, and ASA use
non - hepatic—celiac sprue, adrenal insufficiency, myopathy, strenuous exercise

CHOLESTATIC PATTERN

(↑↑ ALP/bilirubin ± ↑ AST/ALT)

bacterial cholangitis
biliary epithelial damage—hepatitis, cirrhosis, biliary colic
intrahepatic cholestasis—sepsis, drugs (amoxicillin–clavulanate, erythromycin, trimethoprim–sulfamethoxazole, indinavir, nevirapine, allopurinol, carbamazepine, captopril, chlorpromazine, diltiazem, estrogens, fluphenazine, gold, imipramine), TPN, primary biliary cirrhosis
biliary ductal obstruction—choledocholithiasis, pancreatic cancer, cholangiocarcinoma, pancreatitis, primary sclerosing cholangitis

INFILTRATIVE PATTERN

(↑↑ ALP with ↑ GGT ± ↑ bili/AST/ALT)

infectious—TB, histoplasmosis, abscess (bacterial, amoebic)
neoplasm—hepatoma, lymphoma
granulomatous disease—sarcoidosis, TB, fungal
others—amyloidosis

ISOLATED HYPERBILIRUBINEMIA

(↑↑ bilirubin only)—see JAUNDICE (p. 155)

Pathophysiology

Definitions

abnormal liver enzymes—defined as ±2 standard deviations, so 5% of the population would have abnormal liver enzymes by definition
acute ( fulminant ) liver failure—development of jaundice, coagulopathy, and encephalopathy within 8 weeks of onset of hepatocellular injury; subclassified into hyperacute (day 0–7), acute (day 8–28) and subacute (day >28)
chronic hepatitis—↑ ALT >6 months

LIVER ENZYMES BY CATEGORY

synthetic function—INR (dependent on factors I, II, V, VII, IX, X), bilirubin (heme breakdown product), albumin (synthesis), fibrinogen
hepatic injury—AST (intracellular; liver, heart, skeletal, kidneys, brain, pancreas, lungs, RBC, WBC), ALT (intracellular; specific for Liver), ALP (liver, gut, bone, placenta), GGT, 5’NT, LDH (bone, muscle, liver, lungs)

COMPLICATIONS OF HEPATIC FAILURE

★SCREAM★
- Sepsis
- Coagulopathy
- Renal failure
- Encephalopathy
- Ascites
- Metabolic changes (hypoglycemia, electrolyte abnormalities, acidosis)

Investigations

BASIC

labs—CBCD, peripheral smear, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, INR, albumin, HAV IgM, HAV IgG, HBsAg, HBsAb, HBcIgM, HBcIgG, lactate
imaging—US abd (with Doppler), CT abd

SPECIAL

labs—EBV, CMV, HSV, ANA, anti-smooth muscle antibody (ASMA), anti-mitochondrial antibody (AMA), quantitative immunoglobulin, ferritin, Fe, TIBC, % sat, ceruloplasmin, α1-antitrypsin, AFP, antitransglutaminase antibody, lipase, amylase, LDH, haptoglobin, acetaminophen, CK, TSH
ERCP/MRCP
gastroscopy
liver biopsy

Diagnostic and Prognostic Issues

↑ AST/SGOT

—do panel of liver function tests. If isolated rise, consider non-hepatic causes. Otherwise, same as ALT workup. AST > ALT suggests alcoholic liver disease, fatty liver, or cirrhosis

↑ ALT/SGPT

—if symptomatic and presence of risk factors for liver disease, liver dysfunction (↓ albumin, ↑ INR, ↑ bili), ↑ ALT or AST >3× upper limit of normal, or ↑ ALT >6 months, consider basic workup including abdominal US with Doppler, viral serologies, ANA, ASMA, quantitative Ig, ceruloplasmin, iron studies, antitransglutaminase antibody, and possibly liver biopsy

↑ ALP/BILI

—ask about pain, symptoms of infiltrative disease, or IBD. To confirm liver involvement, perform bilirubin fractionation, GGT, 5’NT, abdominal US, AMA, and quantitative Ig. Consider MRCP/ERCP/EUS and liver biopsy

MONITORING

—INR and bilirubin are much more useful to monitor liver function compared to transaminases

SURVIVAL IN ACUTE HEPATIC FAILURE

—35% in hyperacute, 7% in acute, and 14% subacute

Management

SYMPTOM CONTROL

acute—ABC, O₂, IV hydration
elevated intracranial pressure—for cerebral edema, consider prophylactic phenytoin, raise head of bed, hyperventilate, dexamethasone, mannitol, avoid excessive fluids
sepsis—antibiotics
coagulopathy—vitamin K 10 mg IV/PO, FFP 2–4 U IV (only if active bleeding or invasive procedures, or difficult to follow INR afterward)
acute renal failure—supportive renal replacement. Consider midodrine, octreotide, and albumin
encephalopathy—limit protein intake up to 1 g/kg/day. Lactulose 30 g PO QID PRN titrate to 2–4 bowel movements/day; if patient obtunded and NPO, consider lactulose 300 mL (mixed with 700 mL of H₂O or NS) PR via rectal balloon catheter QID until awake
acidosis—3 amp NaHCO₃ diluted in 1000 mL D5W (i.e. 150 mmol/L of HCO₃ ⁻) as continuous IV infusion at 150–250 mL/h. Give with caution as risk of cerebral edema with increased fluid
hypoglycemia—D10W, tube feed, TPN
detoxification—N-acetylcysteine 150 mg/kg IV (~60 mL) in 200 mL D5W over 1 h, then 50 mg/kg (~20 mL) in 500 mL D5W over 4 h, then 100 mg/kg (~40 mL) in 1 L D5W over 16 h. Alternatively, N-acetylcysteine 140 mg/kg PO/NG, followed by 70 mg/kg q4h for 17 doses. May continue N-acetylcysteine until INR normalized

PREVENTION

—hepatitis B vaccine (0, 1, 6 months), HBIG (post-exposure), hepatitis A vaccine (see p. 305)

TREAT UNDERLYING CAUSE

—hepatitis B (if acute liver failure from HBV, provide supportive care only without active HBV treatment). Hepatitis C (pegylated interferon ± ribavirin). Alcoholic hepatitis (abstinence, nutrition, prednisolone 40 mg PO × 28 days but avoid if pancreatitis, GI bleed, renal failure, or active infection; pentoxifylline 400 mg PO TID × 28 days [expect ↓ bilirubin on day 7 vs. day 1. A lack of response suggests limited survival benefit]). Autoimmune hepatitis (steroids). Wilson’s disease (D-penicillamine, trientine)

LIVER TRANSPLANT

—patients with fulminant liver failure should be transferred to acute care centers with liver transplant expertise

Treatment Issues

LIVER TRANSPLANT

allocation—based on ABO blood type, body size, wait designation, and degree of urgency
K ing ’ s College criteria for tylenol overdose acute hepatic failure (rule of 3’s)—either arterial pH <7.3 or grade III or IV encephalopathy, plus Cr >300 μmol/L [>3.3 mg/dL], plus INR >6.5 (or PT >100 s)
K ing ’ s C ollege criteria for non - tylenol acute hepatic failure—INR >3 or any 3 of following: age <10 or >40, non-A non-B hepatitis, halothane hepatitis, idiosyncratic drug reactions, duration of jaundice before onset of encephalopathy >7 days, INR >1.5, bilirubin >308 μmol/L [179 mg/dL]
contraindications—malignancy (except hepatocellular carcinoma), irreversible cardiopulmonary comorbidities, neuropsychiatric comorbidities, sepsis, substance abuse, non-compliance, HIV

Specific Entities

AST/ALT THOUSAND CLUB

—viral hepatitis, ischemic liver (hypotension, hypoxia, sepsis), drugs/toxins (acetaminophen/paracetamol), autoimmune hepatitis, gallstone disease (acute bile duct obstruction), acute Budd–Chiari syndrome, hepatic artery ligation

ALCOHOLIC LIVER DISEASE

subtypes—fatty liver, alcoholic hepatitis, micronodular cirrhosis
diagnosis—AST:ALT = 2:1 (low ALT activity due to alcohol-related pyridoxal 5-phosphate deficiency), rare for AST to be >8× normal and for ALT to be >5× normal. GGT ↑, ALP ↑, bilirubin ↑
treatments—abstinence, nutrition, prednisolone 40 mg PO × 28 days, pentoxifylline 400 mg PO TID × 4 weeks

NON-ALCOHOLIC STEATOHEPATITIS (NASH)

associations—obesity, hyperlipidemia, diabetes, Cushing’s, TPN, high-protein diets for weight loss, amiodarone, tamoxifen
diagnosis—liver biopsy
treatments—weight loss (diet, exercise), omega 3-6-9 fatty acids, metformin for diabetes, statins for dyslipidemia

Hepatitis B

NEJM 2004 350:11; NEJM 2008 359:14

Pathophysiology

NATURAL HISTORY

—acute hepatitis → chronic disease develops in >90% of neonates, in 10% if 12 years old, and in <1% if >12 years old → 12–20% with chronic hepatitis progress to cirrhosis in 5 years → 20% with compensated cirrhosis progress to decompensation in 5 years and 6–15% with compensated cirrhosis progress to hepatocellular carcinoma. Lifetime risk of hepatocellular carcinoma/death in patients with chronic hepatitis is 40% for ♂ and 15% for ♀

ACUTE HEPATITIS B

—may range from subclinical/anicteric hepatitis (70%) to icteric hepatitis (30%) and even fulminant hepatic failure (0.5–1%). Symptoms may include fever, anorexia, rash, nausea, jaundice, RUQ tenderness, arthralgia, and arthritis. ↑↑ ALT and AST

CHRONIC HEPATITIS B

replicative phase with immune tolerance (only if vertical transmission)—HBeAg positive, asymptomatic as lack of immune response in children. May last 10–30 years
replicative phase with immune clearance—HBeAg positive with seroconversion to HBeAb, may be symptomatic with increased liver enzymes due to immune response against HBV
non - replicative phase—HBeAb positive, low level of viral replication. Usually normal liver enzymes
suspect progression to cirrhosis—if hypersplenism or impaired synthetic function (↑ INR, ↑ bilirubin, hypoalbuminemia)

GENOTYPES

—there are currently eight different genotypes (A to H)

RISK FACTORS

—vertical transmission, endemic areas, transfusions, dialysis, healthcare workers, IDU, high-risk sex/homosexuals, body piercing, tattoos, organ transplantation

Clinical Features

HISTORY

—symptoms of liver failure (jaundice, bleeding, infections, ascites, confusion), weight change, risk factors of hepatitis (family history, sexual activity, IDU, tattoos, piercing, healthcare worker, transfusions, dialysis), past medical history (alcohol, HCV, HIV), medication history

PHYSICAL

—liver examination, stigmata of chronic liver disease (see p. 149), weight

EXTRAHEPATIC MANIFESTATIONS OF HBV

—polyarteritis nodosa, membranous nephropathy, membranoproliferative glomerulonephritis

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, INR, albumin, HBV serology (HBsAb, HBsAg, HBcIgM, HBcIgG to determine infection/immune status, HBeAg, HBeAb, HBV DNA to see if active replication), HAV serology, HCV serology, HDV serology, iron, TIBC, HIV serology
imaging—US abd

SPECIAL

liver biopsy
FibroScan—non-invasive assessment of liver fibrosis using ultrasound

Diagnostic Issues

HEPATITIS B SEROLOGY

HB s A g—hepatitis B surface antigen. Positive if active infection
HB c I g M—IgM antibody against hepatitis B core antigen. Suggestive of early infection (indicates the window period) or reactivation
HB s A b—antibody against hepatitis B surface antigen. Positive if immunized (through past infection or vaccination)
HB c I g G—IgG antibody against hepatitis B core antigen. Suggestive of hepatitis B exposure
HB e A g—hepatitis B envelope protein. HBeAg positivity suggests high viral replication with high infectivity. However, HBeAg negativity without HBeAb positivity suggests chronic HBV infection with pre-core mutants/promoter mutations, with a more aggressive phenotype than HBeAg + HBV, more treatment failures, and progressive hepatic injury. HBeAg negative infection is associated with fluctuating ALT and lower levels of HBV DNA. By definition, HBeAg seroconversion cannot occur
HB e A b—antibody against hepatitis B envelope protein. Suggests low/no viral replication, usually with low infectivity
HBV DNA—direct determination of hepatitis B virus DNA. HBV DNA level reflects viral replication activity and is associated with the risk of cirrhosis and hepatoma. HBV DNA determination is important in both HBeAg+ and HBeAg– individuals to determine need for antiviral therapy

	HBsAg	HBclgM	HBsAb	HBclgG	HBeAg	HBeAb
Acute infection
Early	+	–	–	–	+	–
Window	–	+	–	–	+	–
Late	–	+/−	+	–	+	–
Immunity
Vaccinated	–	–	+	–	–	–
Cured	–	–	+/−	+	–	+
Chronic infection
Infectious/active	+	–	–	+	+	–
Pre-core mutant	+	–	–	+	–	–
Low replicative	+	–	–	+	–	+

Management

LIFESTYLE CHANGES

—avoid alcohol use, sexual education, HBV vaccination

TREAT UNDERLYING CAUSE

—interferon, pegylated interferon, lamivudine, adefovir, entecavir, telbivudine, tenofovir

VACCINATION

—household and sexual contacts

Treatment Issues

TREATMENT DECISION FOR CHRONIC HEPATITIS B INFECTIONS

HB e A g positive patients—consider treatment if HBV DNA level >20,000 IU/mL and elevated ALT >1× upper limit of normal for 3–6 months; or significant inflammation and fibrosis on biopsy, FibroScan, Fibrotest, or US abd regardless of HBV DNA or ALT levels
HB e A g negative patients ( pre - core or core promoter mutations )—consider treatment if HBV DNA >2000 IU/mL and elevated ALT >1× upper limit of normal for 3–6 months; or significant inflammation and fibrosis on biopsy, FibroScan, Fibrotest, or US abd regardless of HBV DNA or ALT levels

Please see Can J Gastroenterol 2012 21:12 at www.hepatology.ca for consensus statement on management of hepatitis B

Hepatitis C

NEJM 2001 345:1

Pathophysiology

NATURAL HISTORY

—acute infection → 55–85% of total will develop chronic infection → 50% of total will develop chronic hepatitis → 5–20% of total will develop cirrhosis → 3–5%/year of acute decompensation, also 1–5%/year of developing hepatocellular carcinoma (after 10–30 years)

RISK FACTORS FOR TRANSMISSION

high—IDU, transfusions, immigration from endemic regions
low—perinatal transmission, transfusion before 1992, body piercing, long-term dialysis, occupational exposure, intranasal drug use, multiple sexual partners

Clinical Features

HISTORY

—symptoms of liver failure (jaundice, bleeding, infections, ascites, confusion), weight change, risk factors of hepatitis (sexual activity, IDU, tattoos, piercing, healthcare worker, transfusions, dialysis), past medical history (alcohol, HBV, HIV), medication history

PHYSICAL

—liver examination, stigmata of chronic liver disease, weight. Also examine for extrahepatic manifestations of HCV

EXTRAHEPATIC MANIFESTATIONS OF HCV

heent—uveitis, corneal ulcer, sialadenitis
renal—nephritic syndrome (MPGN II), nephrotic syndrome (membranous)
hematologic—aplastic anemia, lymphoma, cryoglobulinemia, ITP
vascular—necrotizing vasculitis, polyarteritis nodosa
rheumatologic—arthralgias, arthritis, myalgia, sicca
neurologic—weakness, peripheral neuropathy
endocrine—diabetes, antithyroid antibodies
dermatologic—psoriasis (20%), pruritus, Raynaud’s, porphyria cutaneous tarda, lichen planus, cutaneous necrotizing vasculitis

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, INR, albumin, anti-HCV IgM and total (sens 92–97%), HCV RNA PCR (qualitative, quantitative), genotyping, βhCG (before treatment), HAV serology, HBV serology, HDV serology, iron, TIBC, HIV serology
imaging—US abd

SPECIAL

liver biopsy—not mandatory before starting treatments
FibroScan—non-invasive assessment of liver fibrosis using ultrasound

Prognostic Issues

GOOD PROGNOSTIC FACTORS

—age <40, female, weight <75 kg [165 lbs], low titer, genotype 2/3, mild fibrosis

POOR PROGNOSTIC FACTORS

—age of infection ≥40, male, high BMI, alcoholism, HIV co-infection

UNCERTAIN PROGNOSTIC FACTORS

—genotype, viral load, route of transmission

Management

TREAT UNDERLYING CAUSE

(Note: the treatment paradigm is rapidly evolving. The regimens below are based on AASLD guidelines, and have a response rate of over 90%)

genotype 1 or 4—daily fixed-dose combination of ledipasvir/sofosbuvir for 12 weeks; OR paritaprevir/ritonavir/ombitasvir plus dasabuvir and weight-based ribavirin for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis); OR sofosbuvir plus simeprevir with or without ribavirin for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
genotypes 2—sofosbuvir plus ribavirin for 12 weeks; treatment to 16 weeks is recommended in patients with cirrhosis
genotypes 3—sofosbuvir plus ribavirin for 24 weeks
genotype 4 (alternative regimens)—daily sofosbuvir and ribavirin plus weekly pegylated interferon for 12 weeks; OR daily sofosbuvir plus simeprevir with or without weight-based ribavirin for 12 weeks

ORTHOTOPIC LIVER TRANSPLANT

Treatment Issues

TREATMENT DECISION

—complex decision depending on patient’s wishes, risk of progression, chance of response (genotypes 2 and 3 better), and any contraindications to treatment

good candidates—chronic hepatitis with significant fibrosis, compensated cirrhosis, stable CBC and Cr, good adherence. Elevated ALT is no longer considered a decision factor
special circumstances (regimen modification required and should be done under expert guidance)—acute HCV, HIV/HCV, HBV/HCV previous treatment failures, liver transplant, renal failure, current drug or alcohol use
absolute contraindication—decompensated cirrhosis

Please see Can J Gastroenterol 2012 26:6 at www.hepatology.ca for consensus statement on management of hepatitis C

NOVEL THERAPEUTICS

NS3/4A protease inhibitors—boceprevir (Victrelis), telaprevir (Incivek), and simeprevir (Olysio). The NS3/4A protease is essential for cleaving and processing the HCV-encoded polyprotein
NS5B polymerase inhibitor—sofosbuvir (Sovaldi). NS5B is necessary for HCV RNA replication
NS5A phosphoprotein inhibitor—ledipasvir (Harvoni in combination with sofosbuvir). NS5A is important for HCV RNA replication, assembly and secretion

MONITORING DURING HCV THERAPY

—CBC weekly for 4 weeks, then CBC, AST, ALT, uric acid monthly, TSH and ANA every 3 months, and HCV RNA at 4, 12, and 24 weeks during treatment and 6 months after therapy. For significant anemia and neutropenia, give EPO and GCSF, respectively. Also monitor for depression

Chronic Liver Disease: Cirrhosis

Differential Diagnosis

INFECTIONS

—HBV, HCV, HDV, schistosomiasis, toxoplasmosis

STEATOHEPATITIS

—alcohol, non-alcoholic steatohepatitis (NASH)

MEDICATIONS

—acetaminophen/paracetamol (chronic use, controversial)

AUTOIMMUNE

—autoimmune hepatitis

NEOPLASM

—hepatoma, cholangiocarcinoma

METABOLIC

—hemochromatosis, Wilson’s, α1-antitrypsin deficiency, glycogen storage disease

BILIARY CIRRHOSIS

—primary biliary cirrhosis, primary sclerosing cholangitis, secondary biliary cirrhosis (stones, strictures)

CARDIAC CIRRHOSIS

—chronic right-sided heart failure

Pathophysiology

CHILD–PUGH CLASSIFICATION OF LIVER CIRRHOSIS

Points	Encephalopathy	Ascites	Albumin	Total bili	INR
1	0	None	>35 g/L	<34 μM	<1.7
			[>3.5 g/dL]	[<2 mg/dL]
2	1–2	Slight	28–35 g/L	34–51 μM	1.7–2.3
			[2.8–3.5 g/dL]	[2–3 mg/dL]
3	3–4	Mod	<28 g/L	>51 μM	>2.3
			[<2.8 g/dL]	[>3 mg/dL]

The Child–Pugh score is calculated as either encephalopathy plus ascites plus INR, or albumin plus bilirubin plus INR. Patients with score >7 or any clinical signs of decompensation (variceal bleeding, ascites, encephalopathy) should be considered for liver transplantation. Alternative calculation is a total score of all five parameters, grade A = 5–6, grade B = 7–9, grade C = 10–15

MODEL FOR END-STAGE LIVER DISEASE (MELD) SCORE

—originally designed to predict survival in patients with portal hypertension undergoing elective TIPS procedure, now used as a tool for organ allocation in patients with chronic liver disease. The MELD score ranges from 6 to 40, with higher values indicating a worse prognosis

original MELD = 9.57 × log_e(Cr in mg/dL) + 3.78 × log_e(total bilirubin in mg/dL) + 11.2 × log_e(INR) + 6.43
united network of organ sharing MELD (UNOS-MELD) = same formula but fixed lower limit of 1 for all variables and fixed upper limit of 4 mg/dL for Cr. Furthermore, Cr set at 4 for patients on renal replacement therapy
MELD-N a = UNOS-MELD – Na – [0.025 × MELD ×(140 – Na)] + 140

For web-based calculator, please see www.mayoclinic.org/meld/

Clinical Features

HISTORY

—symptoms of liver failure (jaundice, bleeding, infections, ascites, confusion), weight change, risk factors of hepatitis (sexual activity, IDU, tattoos, piercing, healthcare worker, transfusions, dialysis), past medical history (alcohol, hereditary disorders), medication history (acetaminophen/paracetamol, other hepatotoxins)

PHYSICAL

stigmata of chronic liver disease—leukonychia, Terry’s nails, clubbing, Dupuytren’s contractures, palmar erythema, asterixis, scleral icterus, altered mental status, parotid enlargement, fetor hepaticus, spider angiomas, gynecomastia, ascites, splenomegaly, caput medusa, hemorrhoids, testicular atrophy, proximal muscle weakness, peripheral edema, petechiae
clues to etiology—obesity (fatty liver), excoriations (PBC), tattoos/needle tracks (hepatitis), bronze skin (hemochromatosis), Kayser–Fleischer rings (Wilson’s disease)

DISTINGUISHING LIVER FROM RIGHT KIDNEY

1.
The liver has no palpable upper border and extends more laterally and medially
2.
The liver is not usually ballotable, but the kidney is because of its retroperitoneal position
3.
The percussion note is dull over the liver but is usually tympanic over the kidney
4.
A friction rub may occasionally be heard over the liver, but never over the kidney because it is too posterior
5.
The liver has a shaper edge while kidney is usually more rounded

DISTINGUISHING FEATURES BETWEEN PORTAL HYPERTENSION AND VENA CAVA OBSTRUCTION

portal hypertension—caput medusa veins drain away from umbilicus. Stigmata of liver disease
IVC obstruction—veins prominent in the abdomen and drain up toward the superior vena cava system. No evidence of liver disease
SVC obstruction—veins prominent in the chest and drain down toward the inferior vena cava system. No evidence of liver disease

RATIONAL CLINICAL EXAMINATION SERIES: PHYSICAL EXAMINATION OF THE LIVER

INSPECTION—bulging mass over right costal margin (low sens)
PALPATION—move fingers 2 cm [0.79 in.] up at each exhalation. Palpable liver suggests hepatomegaly (LR+ 2.0, LR 0.41)
PERCUSSION—locate upper border along midclavicular line. Locate lower border with palpation, scratch test, or percussion. Liver span >12 cm (>4.7 in.) suggests hepatomegaly. Scratch test not recommended to assess liver span
AUSCULTATION—friction rubs (tumors, infection), venous hums (portal hypertension), arterial bruit (tumors, alcohol hepatitis)
APPROACH—“if clinical suspicion low, start with palpation. If positive, percuss liver span. If negative, hepatomegaly is unlikely. If clinical suspicion is high, palpate and percuss. Overall, negative findings cannot rule out abnormal liver, and positive findings cannot rule in liver disease”

JAMA 1994 271:23

The Rational Clinical Examination. McGraw-Hill, 2009

RIEDEL’S LOBE

—an extension of the right lobe of the liver down below the costal margin along the anterior axillary line. It is often mistaken for a pathological enlargement of the liver or gallbladder. It is a normal anatomical variant

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, INR, albumin, HAV serology, HBsAg, HBsAb, HBcIgM, HBcIgG, HCV serology, quantitiative immunoglobulins
imaging—US abd (with Doppler), CT abd

SPECIAL

labs—ANA, anti-smooth muscle antibodies (anti-actin antibodies), anti-liver-kidney-microsomal (LKM) antibody, AMA, ferritin, ceruloplasmin, α1-antitrypsin, AFP, antitransglutaminase
gastroscopy—to check for varices
liver biopsy
fibroscan

Management

TREAT UNDERLYING CAUSE

—consideration for liver transplantation

SYMPTOM CONTROL

—for variceal bleed prophylaxis, consider band ligation and non-selective β-blocker if moderate/large varices or Child–Pugh B/C (nadolol 40–80 mg PO daily, propranolol 20 mg PO BID, or carvedilol 6.25 mg PO daily-BID) and titrate to target heart rate of 55–60/min. Perform initial screen for esophageal varices with endoscopy → repeat endoscopy in 3 years if no varices; repeat in 1–2 years if small varices; endoscopic treatment (banding/glue) if moderate/large varices. For active variceal bleed after failed endoscopic therapy, consider TIPS. See UPPER GI BLEED (p. 131), HEPATIC ENCEPHALOPATHY (p. 152), and ASCITES (p. 153) for details

HEPATOMA SCREENING

—for all patients with cirrhosis, and those with HBV and hepatocellular carcinoma risk factors, repeat AFP and abdominal US every 6 months for surveillance

Specific Entities

CAUSES OF HEPATOMEGALY

pseudohepatomegaly—obstructive lung disease (emphysema), subdiaphragmatic collection
congestive—right heart failure, constrictive pericarditis, tricuspid regurgitation, IVC obstruction, hepatic vein obstruction
infiltration—malignancy, amyloidosis, hemochromatosis, fatty liver
reactive—hepatitis

WILSON’S DISEASE

etiology—copper excretion defect
diagnosis—Kayser–Fleischer ring, low serum ceruloplasmin, 24-h urine for copper
treatments—dietary restriction (avoid shellfish, organs, chocolate, nuts, and mushrooms), chelating agent (d-penicillamine or trientine), and zinc. For severe liver failure, consider orthotopic liver transplantation

AUTOIMMUNE HEPATITIS

subtypes—I (classic, female predominance, extrahepatic disease, ANA >1/160, anti-smooth muscle antibody >1/40, ↑ IgG, steroid responsive), II (anti-liver-kidney-microsomal [LKM] antibody, less steroid responsive), III (anti-SLA)
diagnosis—quantitative immunoglobulins (↑ IgG), ANA, anti-smooth muscle antibody, anti-LKM antibody, liver biopsy
treatments—steroids, azathioprine, or mycophenolate mofetil. For fulminant hepatitis or cirrhosis, consider liver transplantation

HEPATIC HYDROTHORAX

pathophysiology—low oncotic pressure, congenital diaphragmatic defect, ascitic fluid moves to pleural space due to pressure gradient → transudative pleural effusion → decreased lung volumes → V/Q mismatch → hypoxemia
diagnosis—diagnostic paracentesis/thoracentesis. US abd to assess liver and ascites. CT chest and abd to rule out other lesions. Intraperitoneal injection of ⁹⁹mTc-labeled serum albumin may be helpful to confirm diagnosis
treatments—O₂, salt restriction, diuretics, therapeutic paracentesis, may need thoracentesis, TIPS. Avoid chest tube if possible (high risk of SBP and hepatorenal syndrome)

HEPATOPULMONARY SYNDROME

pathophysiology—portal hypertension → ↓ metabolism of vasodilating substance, or ↓ production of vasoconstricting substance → pulmonary capillary dilatation → diffusion–perfusion imbalance → hypoxemia, dyspnea on exertion and/or at rest, orthodeoxia and platypnea, cyanosis, clubbing and spider nevi
diagnosis—contrast echocardiogram/bubble study (presence of microbubbles in the left atrium 3–6 cardiac cycles after intravenous injection of normal saline suggests dilated pulmonary capillaries), lung perfusion scan, pulmonary angiogram (if severe hypoxemia)
treatments—O₂, liver transplant

NEJM 2007 358:22

PORTOPULMONARY HYPERTENSION

pathophysiology—portal hypertension → unknown substance reaches pulmonary vasculature causing vasoconstriction → findings similar to primary pulmonary hypertension
diagnosis—echocardiogram, right heart catheterization
treatments—O₂, diuretics, sildenafil, prostaglandins, calcium channel blockers, liver transplant

HEPATORENAL SYNDROME

pathophysiology—liver failure → dilated systemic circulation → ↑ renin–aldosterone system with ↑ cardiac output but not enough to counter splanchnic vasodilatation → pre-renal failure. Type I is more serious, defined as >50% reduction of CrCl to ≤20 mL/min in ≤2 weeks or >2× increase in creatinine to >220 μmol/L [>2.2 mg/dL]. Patients are usually oligouric or anuric. Type II includes patients not meeting criteria for type I and is characterized by ascites resistant to diuretics
diagnosis—a clinical diagnosis of exclusion; rule-out other etiologies of acute kidney injury (including pre-renal causes, ATN, infection, and GI bleed). Typically, urine Na <10 mM (<10 mEq/L), bland U/A, oliguria, and minimal improvement in renal function after volume expansion with IV albumin (1 g/kg/d and up to 100 g/d × 2 days)
treatments—stop diuretics, fluid (usually no response), albumin, vasoconstrictors (midodrine, octreotide, norepinephrine), TIPS, renal replacement therapy, liver transplant

FLOOD SYNDROME (SPONTANEOUS UMBILICAL HERNIA RUPTURE)

pathophysiology—liver failure → portal hypertension → ascites → umbilical hernia (up to 20%) → spontaneous rupture (rare)
prognosis—50% mortality with supportive care, 10–20% mortality with urgent surgical repair

Hepatic Encephalopathy

NEJM 1997 337:7

Differential Diagnosis

DRUGS

alcohol—acute intoxication, withdrawal, Wernicke–Korsakoff
psychoactive—benzodiazepines, cocaine, heroine, ecstasy
others—salicylates

INFECTIOUS

—spontaneous bacterial peritonitis, pneumonia, UTI, meningitis, encephalitis, abscess

METABOLIC

organ failure—hepatic, azotemia, hypothyroidism, hypoxemia, CO₂ narcosis
electrolytes—ketoacidosis, hyponatremia, hypomagnesemia, hypercalcemia, glucose (hypo, hyper)

STRUCTURAL

hemorrhage—subarachnoid, epidural, subdural, intracerebral
stroke—basilar
tumor
epilepsy

NEUROPSYCHIATRIC

Pathophysiology

GRADING OF HEPATIC ENCEPHALOPATHY

1—reversed sleep cycle, mild confusion, tremor, incoordination
2—lethargy or irritability, disoriented to time, asterixis, ataxia
3—somnolence or agitation, disoriented to place, asterixis, hyperreflexia, positive Babinski
4—coma, decerebrate

PRECIPITANTS OF HEPATIC ENCEPHALOPATHY

↑ NH ₄—↑ protein intake, constipation, GI bleed, transfusion, infection (spontaneous bacterial peritonitis), azotemia, hypokalemia
↑ diffusion across blood – brain barrier—alkalosis
↓ metabolism—dehydration, hypotension, hypoxemia, anemia, portosystemic shunt, hepatoma, progressive liver damage

Clinical Features

HISTORY

—characterize confusion (onset, duration, fluctuation), infectious symptoms, neurological symptoms, precipitants (diet, hydration, constipation, GI bleed, infection), past medical history (liver disease, alcohol and illicit drug use), medication history (sedatives, narcotics, missed lactulose)

PHYSICAL

—vitals, signs of chronic liver disease, rectal examination (if suspect GI bleed), neurological examination, check for asterixis

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, TSH, AST, ALT, ALP, bilirubin, INR, PTT, NH₄ (poorly correlated with degree of encephalopathy), Ca, Mg, PO₄, osmolality, CK, troponin (as part of delirium workup), urinalysis
microbiology—blood C&S, urine C&S, sputum Gram stain/C&S
imaging—US abd, CT abd
ascitic fluid analysis—cell count and diff, C&S to rule out SBP

SPECIAL

CT head—delirium workup
ABG—if critically ill
gastroscopy—to check for varices
liver biopsy
EEG—symmetric, high voltage, slow wave pattern

Management

ACUTE HEPATIC ENCEPHALOPATHY

workup for sepsis
symptom control—correct hypokalemia, if present. Lactulose 30 g PO BID–QID PRN titrate to 2–4 bowel movements/day; if patient obtunded and NPO, consider lactulose 300 mL (mixed with 700 mL of H₂O or NS) PR via rectal balloon catheter QID until awake. Consider sedation (haloperidol 1–2 mg PO/IV/SC q6h and q1h PRN) and ventilation, mannitol 1 g/kg 20% solution, acetylcysteine, epoprostenol
treat underlying cause—liver transplant

CHRONIC HEPATIC ENCEPHALOPATHY

symptom control—protein restriction no longer routinely recommended. Lactulose 30 g PO BID–QID PRN titrate to 2–4 bowel movements/day. Prophylaxis with metronidazole 800 mg PO daily (associated peripheral neuropathy), neomycin 500–2000 mg PO TID (associated ototoxicity and nephrotoxicity), or rifaximin 550 mg PO BID (in high-risk patients with ≥2 episodes of hepatic encephalopathy in last 6 months). Others (H. pylori treatment, ornithine aspartate, branched amino acids)
treat underlying cause—liver transplant

Ascites

NEJM 2004 350:16

Differential Diagnosis

↑ HYDROSTATIC PRESSURE

cardiac—right heart failure, tricuspid regurgitation, constrictive pericarditis
hepatic—presinusoidal (portal vein thrombosis, schistosomiasis), sinusoidal (cirrhosis), postsinusoidal (Budd–Chiari, veno-occlusive)

↓ ONCOTIC PRESSURE

—malnutrition, liver disease, nephrotic syndrome, protein-losing enteropathy

↑ CAPILLARY PERMEABILITY/LYMPHATIC OBSTRUCTION

infections—spontaneous bacterial peritonitis
malignancy—ovarian, peritoneal metastasis
pancreatitis

OTHERS

—hypothyroidism

Clinical Features

RATIONAL CLINICAL EXAMINATION SERIES: DOES THIS PATIENT HAVE ASCITES?

	Sens	Spc	LR+	LR–
History
↑ abdominal girth	87%	77%	4.1	0.17
Recent weight gain	67%	79%	3.2	0.42
Ankle swelling	93%	68%	2.8	0.10
Hepatitis	67%	79%	3.2	0.42
Heart failure	47%	73%	2.0	0.73
Alcoholism	60%	58%	1.4	0.69
Hx of carcinoma	13%	85%	0.91	1.01
Physical
Fluid wave	62%	90%	5.3	0.6
Shifting dullness	77%	72%	2.1	0.4
Flank dullness	84%	59%	1.7	0.4
Bulging flanks	81%	59%	1.8	0.5

APPROACH—the most useful finding for making a diagnosis of ascites is a positive fluid wave. The most useful findings to rule out ascites are a negative history of ankle swelling or increased abdominal girth. Puddle sign and auscultatory percussion not recommended

JAMA 1992 267:19

The Rational Clinical Examination. McGraw-Hill, 2009

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, AST, ALT, ALP, bilirubin, INR, PTT, albumin, amylase, lipase, TSH, urinalysis
imaging—US abd, CT abd
paracentesis—cell count + diff, Gram stain, C&S, AFB, albumin, LDH, glucose, amylase, triglyceride, cytology

SPECIAL

laparoscopy with peritoneal biopsy

Diagnostic Issues

RATIONAL CLINICAL EXAMINATION SERIES: DOES THIS PATIENT HAVE BACTERIAL PERITONITIS OR PORTAL HYPERTENSION? HOW DO I PERFORM A PARACENTESIS AND ANALYZE THE RESULTS?

PARACENTESIS TECHNIQUE—two studies showed that testing for coagulation prior to paracentesis was probably unnecessary; one study showed that a 15-gauge, 3.25-in. needle-cannula was associated with less multiple peritoneal punctures and termination due to poor fluid return as compared to a 14-gauge needle in therapeutic paracentesis; one study showed immediate as compared to delayed inoculation of culture bottles improved diagnostic yield (100% vs. 77%); nine studies examined therapeutic paracentesis with or without albumin or nonalbumin plasma expanders and found no consistent effect on morbidity or mortality

FEATURES SUGGESTIVE OF SPONTANEOUS BACTERIAL PERITONITIS

	LR+	LR–
Ascitic fluid WBC/PMN
Ascitic fluid WBC >1000 cells/μL	9.1	0.25
Ascitic fluid WBC >500 cells/μL	5.9	0.21
Ascitic fluid WBC >250 cells/μL	0.9	1.1
Ascitic fluid PMN >500 cells/μL	10.6	0.16
Ascitic fluid PMN >250 cells/μL	6.4	0.20
Ascitic fluid pH and blood ascitic pH gradient
Ascitic fluid pH <7.31	4.1	0.47
Ascitic fluid pH <7.32	4.8	0.65
Ascitic fluid pH ≤7.31	5.8	0.43
Ascitic fluid pH <7.35	9.0	0.31
Ascitic fluid pH <7.40	2.5	0.23
Blood ascitic fluid pH gradient >0.11	4.6	0.47
Blood ascitic fluid pH gradient >0.10	7.1	0.30
Blood ascitic fluid pH gradient ≥0.10	11.3	0.12

FEATURES SUGGESTIVE OF PORTAL HYPERTENSION

	LR+	LR–
Serum ascites albumin gradient (SAAG)
Serum-ascites albumin gradient ≥11 g/L (≥1.1 g/dL)	4.6	0.06

APPROACH—“ascitic fluid should be inoculated into blood culture bottles at the bedside. Spontaneous bacterial peritonitis is more likely at predescribed parameters of ascitic WBC count (>1000 cells/μL), PMN count (>250 cells/μL) or blood–ascitic fluid pH (<7.35), and portal hypertension is less likely below a predescribed serum-ascites albumin gradient (<11 g/L [<1.1 g/dL])”

JAMA 2008 299:10

PARACENTESIS PROCEDURE—NEJM 2006 355:e21SERUM-ASCITES ALBUMIN GRADIENT (SAAG)

portal hypertension or congestive heart failure—(serum albumin – ascites albumin) ≥11 g/L [≥1.1 g/dL]. To distinguish between portal hypertension and HF, consider checking for ascitic fluid total protein level (generally >25 g/L [>2.5 g/dL] in cardiac ascites due to normal leaky hepatic sinusoid, while portal hypertension is associated with “capillarized” sinusoids that are less leaky)
inflammatory—(serum albumin – ascites albumin) <11 g/L [<1.1 g/dL]

Management

SYMPTOM CONTROL

—Na restriction (88 mmol/day or 2 g/day. Check urine Na for compliance, i.e. <77 mmol/day). Fluid restriction (<1.5 L/day only if Na <120 mmol/L). Diuretics (spironolactone 100–400 mg PO daily and furosemide 40–160 mg PO daily, stepwise increase). Paracentesis. Albumin (if >5 L ascitic fluid removed, then replace with albumin. In general, give 100 mL of 25% albumin for every 3 L of ascites removed over 5 L), TIPS, liver transplant

TREAT UNDERLYING CAUSE

—stop alcohol consumption

Specific Entities

DIFFERENTIAL DIAGNOSIS OF ANASARCA

—renal (nephrotic syndrome), cardiac (HF, tricuspid regurgitation, constrictive pericarditis), liver (cirrhosis), thyroid (hypothyroidism), malignancy (venous/lymphatic obstruction)

SPONTANEOUS BACTERIAL PERITONITIS (SBP)

pathophysiology—overgrowth of bacteria in bowel (usually E. coli) → bacterial translocation (migration) across bowel wall → infect ascites. Usually in patients with cirrhosis and large volume ascites with low ascites protein. Symptoms may be subtle as the visceral peritoneum is separated from the parietal peritoneum. Important to differentiate SBP from perforated bowel causing peritonitis
clinical features—may be asymptomatic if detected early. Common signs and symptoms include fever, abdominal pain and tenderness (diffuse, continuous), diarrhea, confusion, or renal deterioration. Sepsis with hypotension and paralytic ileus may develop later
diagnosis—paracentesis (ascitic fluid PMN ≥250 cells/μL, fluid protein <10 g/L [<1.0 g/dL], Gram stain, C&S), blood cultures, urine cultures. (Note that in peritonitis secondary to perforated viscous, the ascitic fluid protein is usually >10 g/L [>1.0 g/dL], glucose <2.8 mmol/L [<51 mg/dL], and LDH > upper limit of normal, and polymicrobial)
treatments—cefotaxime 2 g IV q8h (preferred) or ceftriaxone 2 g IV q24h × 5–10 days, albumin 1.5 g/kg IV within 6 h of detection, then 1 g/kg IV on day 3 (reduces mortality and incidence of hepato-renal syndrome). Secondary prophylaxis include ciprofloxacin 750 mg PO weekly, norfloxacin 400 mg PO daily, or trimethoprim–sulfamethoxazole DS 1 tab PO daily

Jaundice

Differential Diagnosis of Jaundice/Hyperbilirubinemia

PRE-HEPATIC

(hemolysis)

RBC membrane—spherocytosis, elliptocytosis
RBC enzymes—G6PD, pyruvate kinase deficiency
RBC hemoglobin—sickle cell
blood—toxins, drugs (fludarabine), infections (malaria), immune
vascular—mechanical valve, vasculitis, HUS/TTP/DIC, HELLP, severe hypertension
ineffective erythropoiesis—megaloblastic anemia

HEPATIC

↓ uptake—Gilbert’s, drugs (rifampin, contrast)
↓ conjugation—Gilbert’s, Crigler–Najjar I/II, hepatocellular diseases, drugs (chloramphenicol)
↓ excretion (cholestasis)—Dubin–Johnson, Rotor, benign recurrent cholestasis, cholestasis of pregnancy, drug-induced cholestasis, PBC, PSC, TPN
mixed—hepatocellular disease, sepsis

POST-HEPATIC

gallstones
cancer—pancreas, bile ducts, ampulla
biliary structures—post-cholecystectomy, PSC, biliary atresia

Pathophysiology

CHOLESTASIS

—any condition in which bile excretion from the liver is blocked, which can occur either in the intrahepatic bile ducts (hepatic causes) or in the extrahepatic bile ducts (post-hepatic causes)

Clinical Features

HISTORY

—characterize jaundice (duration, previous episodes), abdominal pain, abdominal mass, stool color, urine color, pruritus, weight loss, past medical history (liver disease, hepatitis risk factors, IBD/PSC, hereditary disorders), medications

PHYSICAL

—signs of chronic liver disease, liver and spleen examination

JAUNDICE

—becomes clinically evident at levels of bilirubin >70 μmol/L [>41 mg/dL]

DARK URINE

—suggests conjugated hyperbilirubinemia

PALE STOOL/PRURITUS

—suggests cholestasis (bile cannot be secreted into the biliary system)

PAIN

—painful jaundice suggests acute obstruction (by stones, masses); investigate with US abd/ERCP/MRCP/EUS. Painless jaundice suggests pancreatic cancer, infiltration, PSC, PBC, and drugs; investigate with imaging + biopsy

Investigations

BASIC

labs—CBCD, peripheral smear, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin (conjugated and unconjugated), INR, albumin, HAV IgM, HAV IgG, HBsAg, HBsAb, HBcIgM, anti-HCV, ANA, antismooth muscle antibody (ASMA), anti-mitochondrial antibody (AMA), ferritin, ceruloplasmin, α1-antitrypsin, AFP, LDH, haptoglobin, peripheral smear, reticulocyte counts
imaging—US, CT abd

SPECIAL

endoscopic US
MRCP
ERCP
liver biopsy

Management

TREAT UNDERLYING CAUSE

Specific Entities

PRIMARY BILIARY CIRRHOSIS (PBC)

pathophysiology—autoimmune destruction of intrahepatic bile ducts → cholestasis → inflammation and necrosis → cirrhosis
clinical features—pruritus, fatigue, RUQ pain, xanthelasmas, sicca syndrome, hyperlipidemia. Females >> males. With disease progression, symptoms of liver failure may be seen. Decreased bone mineral density
diagnosis—antimitochondrial antibody (sens 95%), ANA (40%), ↑ bilirubin, ↑ ALP, ↓ C4, ↑ IgM, hyperlipidemia (cholesterol, rather than TG, is what classically becomes elevated). Liver biopsy can be helpful for staging but is not essential for diagnosis. Consider DEXA scan
treatments—ursodeoxycholic acid (ursodiol) 13–15 mg/kg/day PO in 2–4 divided doses with food. Ursodeoxycholic acid has been shown to improve liver enzymes, slow disease progression (for stages I and II), delay time to transplant but does not treat pruritus. For pruritus, consider cholestyramine, rifampin, and naltrexone. Consider treating hyperlipidemia (despite hypercholesterolemia, risk of atherosclerotic death not increased). Prevent osteoporosis with calcium and vitamin D. Also provide supplement with fat-soluble vitamins (KADE), which are not well absorbed in cholestasis. Consider liver transplant if rising bilirubin, liver decompensation, refractory pruritus, or severe bone disease

NEJM 2007 357:15

PRIMARY SCLEROSING CHOLANGITIS (PSC)

pathophysiology—cholangitis → fibrosis with intra-and extrahepatic duct strictures → cirrhosis; 75% associated with ulcerative colitis, 10% with cholangiocarcinoma
diagnosis—MRCP, ERCP (beading, strictures), biopsy
treatments—liver transplant

Acute Pancreatitis

NEJM 1994 330:17

Causes

★BAD HITS★

BILIARY STONES
ALCOHOL
DRUGS—thiazides, furosemide, sulfonamide, tetracycline, calcium, estrogen, vinca alkaloids, antiretrovirals (didanosine, pentamidine)
HYPER—hypercalcemia, hyperlipidemia (V, I, IV)
INFECTIOUS—E. coli, HIV, CMV, mumps, ascariasis
IDIOPATHIC
INHERITED—familial
TRAUMA—blunt
SURGERY—ERCP (± sphincterotomy, 5% risk), sphincter of Oddi dysfunction

Pathophysiology

COMPLICATIONS OF ACUTE PANCREATITIS

★SCAR★
- Sepsis
- Calcium (hypocalcemia)
- Abdominal (necrotizing pancreatitis ± hemorrhage, pancreatic pseudocyst ± hemorrhage [10–20%], pancreatic abscess, splenic vein thrombosis, fistula, cholangitis
- Respiratory failure (ARDS) and aspiration pneumonia
- Renal failure

Clinical Features

HISTORY

—abdominal pain, nausea and vomiting, fever, anorexia, past medical history (previous pancreatitis, recent ERCP, biliary stones, alcohol use, HIV), medication history (diuretics, antibiotics)

PHYSICAL

—vitals, volume status, abdominal examination, Cullen’s sign (periumbilical ecchymoses suggestive of hemoperitoneum), Grey Turner’s sign (ecchymoses of the flanks suggestive of retroperitoneal hemorrhage), Fox’s sign (ecchymoses parallel and inferior to inguinal ligament along upper thighs suggesting retroperitoneal hemorrhage), Bryant’s sign (blue scrotum suggesting retroperitoneal hemorrhage)

Investigations

BASIC

labs—CBCD, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, INR, LDH, lipase, amylase, Ca, albumin, fasting lipid profile
imaging—US abd, CT abd (+ contrast for necrotic pancreatitis)
ercp—both diagnostic and therapeutic to relieve obstruction

Diagnostic and Prognostic Issues

DIFFERENTIAL DIAGNOSIS FOR LIPASE ELEVATION

—acute pancreatitis, pancreatic cancer, pancreatic duct obstruction, perforated peptic ulcer, bowel infarction, intestinal obstruction, renal failure

RANSON’S CRITERIA

on admission—age >55, WBC >16 × 10⁹/L, glucose >11.1 mmol/L [>200 mg/dL], AST >250 U/L, LDH >350 U/L
48 h—hematocrit ↓ >10%, urea ↑ >1.78 mmol/L [>5 mg/dL], base deficit >4 mEq/L, Ca <2 mmol/L [<8 mg/dL], sequestration of fluid >6 L
prognosis—0–2 = 2% mortality, 3–4 = 15%, 5–6 = 50%, 7–8 = 100%

Management

ACUTE

—ABC, O₂, IV hydration. NPO, NG if severe N&V or obstruction. Morphine 2.5–5 mg SC q4h PRN and 1–2 mg IV q1h PRN (for theoretical concern of morphine-causing sphincter of Oddi spasm, some consider using Demerol instead). Antiemetics (dimenhydrinate 50 mg 2IM/IV q4h, metoclopramide 10 mg IV q4h). Consider broad-spectrum antibiotics (meropenem 1 g IV q8h or imipenem 500 mg IV q6h) if infected necrosis suspected

NUTRITION SUPPORT

—enteral or parenteral. Early aggressive nutrition may not be warranted

TREAT UNDERLYING CAUSE

—gallstone pancreatitis (ERCP and biliary sphincterotomy within 72 h, cholecystectomy). Necrotizing pancreatitis (ICU admission, surgical debridement)

Specific Entities

ASCENDING CHOLANGITIS

pathophysiology—biliary calculi (choledocholithiasis), post-ERCP, tumors, primary sclerosing cholangitis, or benign stricture → biliary obstruction and stasis → bacterial colonization and infection (E. coli, Klebsiella, Enterobacter, Enterococcus, anaerobes) → liver failure, sepsis
clinical features—Charcot’s triad consists of fever, right upper quadrant pain, and jaundice. Reynold’s pentad is associated with the addition of hypotension and confusion
diagnosis—↑ bilirubin, ALP, and potentially AST and ALT. Blood cultures essential. US abd to check for common bile duct dilatation and stones, ERCP (diagnostic and therapeutic)
treatments—antibiotics (meropenem 1 g IV q8h, imipenem 500 mg IV q6h, or ampicillin plus gentamicin). Facilitate biliary drainage (urgent ERCP with sphincterotomy for infection source control, stone extraction, stent insertion, percutaneous transhepatic cholangiogram [PTC] with stent drainage, and surgical decompression as last resort)

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Authors and Affiliations

Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
Angeli Chopra MD, FRCPC, ABIM

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Angeli Chopra MD, FRCPC, ABIM
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Editors and Affiliations

The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
David Hui
Department of Medicine, University of Calgary, Calgary, Alberta, Canada
Alexander A. Leung
Division of General Internal Medicine, University of Alberta, Edmonton, Alberta, Canada
Raj Padwal

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Chopra, A. (2016). Gastroenterology. In: Hui, D., Leung, A., Padwal, R. (eds) Approach to Internal Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-11821-5_5

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REFLEX PATHWAY

Investigations

BASIC

SPECIAL

Management

SYMPTOM CONTROL

Related Topics

Dysphagia

Differential Diagnosis

OROPHARYNGEAL

ESOPHAGEAL

Clinical Features

DIAGNOSTIC CLUES

PRACTICAL APPROACH TO DYSPHAGIA

Investigations

BASIC

SPECIAL

Management

SYMPTOM CONTROL

Specific Entities

ACHALASIA

INFECTIOUS ESOPHAGITIS

EOSINOPHILIC ESOPHAGITIS

Related Topics

Dyspepsia

Differential Diagnosis

NON-GASTRIC CAUSES

PEPTIC ULCER DISEASE

MEDICATION SIDE EFFECTS

GASTROESOPHAGEAL REFLUX DISEASE

NON-ULCER DYSPEPSIA

Pathophysiology

COMPLICATIONS OF PUD

COMPLICATIONS OF GERD

Clinical Features

SYMPTOM DEFINITIONS

RATIONAL CLINICAL EXAMINATION SERIES: CAN THE CLINICAL HISTORY DISTINGUISH BETWEEN ORGANIC AND FUNCTIONAL DYSPEPSIA?

PRACTICAL APPROACH TO DYSPEPSIA

Investigations

BASIC

SPECIAL

Management

PEPTIC ULCER DISEASE

GERD

NON-ULCER DYSPEPSIA

Related Topics

Specific Entities

GERD

NSAIDS-INDUCED GASTROPATHY

BARRETT’S ESOPHAGUS

GASTROPARESIS

HELICOBACTER PYLORI

Acute Abdominal Pain

Differential Diagnosis

GI

GU

GYNECOLOGIC

VASCULAR

SYSTEMIC

OTHERS

Pathophysiology

CAUSES OF ABDOMINAL PAIN

Clinical Features

HISTORY

PHYSICAL

APPENDICITIS SEQUENCE

RATIONAL CLINICAL EXAMINATION SERIES: DOES THIS PATIENT HAVE APPENDICITIS?