Gastroenterology

NEJM 1994 330:17 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 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 ★ SCAR ★ S epsis C alcium (hypocalcemia) A bdominal (necrotizing pancreatitis ± hemorrhage, pancreatic pseudocyst ± hemorrhage [10–20%], pancreatic abscess, splenic vein thrombosis, fistula, cholangitis R espiratory failure (ARDS) and aspiration pneumonia R enal failure ★ SCAR ★ S epsis C alcium (hypocalcemia) A bdominal (necrotizing pancreatitis ± hemorrhage, pancreatic pseudocyst ± hemorrhage [10–20%], pancreatic abscess, splenic vein thrombosis, fistula, cholangitis R espiratory failure (ARDS) and aspiration pneumonia R enal failure S epsis C alcium (hypocalcemia) A bdominal (necrotizing pancreatitis ± hemorrhage, pancreatic pseudocyst ± hemorrhage [10–20%], pancreatic abscess, splenic vein thrombosis, fistula, cholangitis R espiratory failure (ARDS) and aspiration pneumonia R enal failure —abdominal pain, nausea and vomiting, fever, anorexia, past medical history (previous pancreatitis, recent ERCP, biliary stones, alcohol use, HIV), medication history (diuretics, antibiotics) —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) 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 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 —acute pancreatitis, pancreatic cancer, pancreatic duct obstruction, perforated peptic ulcer, bowel infarction, intestinal obstruction, renal failure on admission —age >55, WBC >16 × 10 9 /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 [6 L prognosis —0–2 = 2% mortality, 3–4 = 15%, 5–6 = 50%, 7–8 = 100% on admission —age >55, WBC >16 × 10 9 /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 [6 L prognosis —0–2 = 2% mortality, 3–4 = 15%, 5–6 = 50%, 7–8 = 100% —ABC, O 2 , 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 —enteral or parenteral. Early aggressive nutrition may not be warranted — gallstone pancreatitis (ERCP and biliary sphincterotomy within 72 h, cholecystectomy). Necrotizing pancreatitis (ICU admission, surgical debridement) 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) 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)

(10%) — Salmonella , Shigella , Campylobacter , Yersinia , E. coli (EHEC, EIEC), C. difficile , Amoeba —colorectal cancer, small bowel cancer, polyp —inflammatory bowel disease (IBD) —ischemic colitis —angiodysplasia, diverticulosis, radiation colitis, hemorrhoids, anal fissure, intussusception, Meckel’s diverticulum —volume of bleed, melena, abdominal pain, past medical history (IBD, cancer, diverticulosis), medication history (anticoagulants, antiplatelet drugs, NSAIDs) —acute bleeding, sinus tachycardia, supine hypotension (SBP 30/min or dizziness, anemia (conjunctival, facial or palmar pallor), abdominal tenderness. Perform a rectal examination and test for fecal occult blood 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 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 imaging —for obscure bleed, consider 99 Tc 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 imaging —for obscure bleed, consider 99 Tc 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 —no obvious melena or bright red blood per rectum (BRBPR), but possible bleed as fecal occult blood or fecal immunochemical test positive —obvious bleeding but source cannot be found —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 — ABC , O 2 , IV hydration (two large-bore IVs). Transfusion (especially if hemoglobin <70 g/L [<7 g/dL], platelets <50 × 10 9 /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

NEJM 2008 359:9 —gastric, duodenum — esophagitis (CMV, medications), gastritis (acute, chronic), inflammatory bowel disease (Crohn’s) —esophagus, stomach —esophagus, stomach, duodenum —Mallory–Weiss tear, Boerhaave’s syndrome, Dieulafoy’s lesion, arteriovenous malformation, aortoduodenal fistula, hemobilia —epistaxis, hemoptysis —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) —acute bleeding, sinus tachycardia, supine hypotension (SBP 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 —bismuth subsalicylate, iron, spinach, charcoal 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 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” 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 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) 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 Shock (p. 108) 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” 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 labs —CBCD, lytes, urea, Cr, type/cross-match, PTT, INR, AST, ALT, ALP, bilirubin, albumin, fecal occult blood imaging —CXR, AXR gastroscopy labs —CBCD, lytes, urea, Cr, type/cross-match, PTT, INR, AST, ALT, ALP, bilirubin, albumin, fecal occult blood imaging —CXR, AXR gastroscopy 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 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 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) 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) — ABC , O 2 , IV hydration (two large-bore IVs). Transfusion (especially if hemoglobin <70 g/L [<7 g/dL], platelets <50 × 10 9 ). 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 — 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) —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 —perforations, bleeding, sedation-related respiratory failure —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

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 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 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 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 endocrine —diabetes, adrenal insufficiency, hypercalcemia, hyperthyroidism, hyperparathyroidism, hyperemesis gravidarum, porphyria others —uremia, pregnancy, migraine endocrine —diabetes, adrenal insufficiency, hypercalcemia, hyperthyroidism, hyperparathyroidism, hyperemesis gravidarum, porphyria others —uremia, pregnancy, migraine IDIOPATHIC 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 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 labs —CBCD, lytes, urea, Cr, glucose, Ca, Mg, PO 4 , AM cortisol, urinalysis microbiology —urine C&S imaging —CXR, AXR labs —CBCD, lytes, urea, Cr, glucose, Ca, Mg, PO 4 , AM cortisol, urinalysis microbiology —urine C&S imaging —CXR, AXR gastroscopy, gastric emptying study CT head gastroscopy, gastric emptying study CT head 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 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 Chemotherapy-Induced Nausea and Vomiting (p. 254) Nausea and Vomiting in the Palliative Setting (p. 448)

NEJM 2004 350:16 cardiac —right heart failure, tricuspid regurgitation, constrictive pericarditis hepatic — presinusoidal (portal vein thrombosis, schistosomiasis), sinusoidal (cirrhosis), postsinusoidal (Budd–Chiari, veno-occlusive) cardiac —right heart failure, tricuspid regurgitation, constrictive pericarditis hepatic — presinusoidal (portal vein thrombosis, schistosomiasis), sinusoidal (cirrhosis), postsinusoidal (Budd–Chiari, veno-occlusive) —malnutrition, liver disease, nephrotic syndrome, protein-losing enteropathy infections —spontaneous bacterial peritonitis malignancy —ovarian, peritoneal metastasis pancreatitis infections —spontaneous bacterial peritonitis malignancy —ovarian, peritoneal metastasis pancreatitis —hypothyroidism 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 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 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 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 laparoscopy with peritoneal biopsy laparoscopy with peritoneal biopsy 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 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])” 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 FEATURES SUGGESTIVE OF PORTAL HYPERTENSION 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 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] 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] — 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 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 —stop alcohol consumption —renal (nephrotic syndrome), cardiac (HF, tricuspid regurgitation, constrictive pericarditis), liver (cirrhosis), thyroid (hypothyroidism), malignancy (venous/lymphatic obstruction) 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 [10 g/L [>1.0 g/dL], glucose <2.8 mmol/L [ 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 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 [10 g/L [>1.0 g/dL], glucose <2.8 mmol/L [ 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

—HBV, HCV, HDV, schistosomiasis, toxoplasmosis —alcohol, non-alcoholic steatohepatitis (NASH) —acetaminophen/paracetamol (chronic use, controversial) —autoimmune hepatitis —hepatoma, cholangiocarcinoma —hemochromatosis, Wilson’s, α1-antitrypsin deficiency, glycogen storage disease —primary biliary cirrhosis, primary sclerosing cholangitis, secondary biliary cirrhosis (stones, strictures) —chronic right-sided heart failure Points Encephalopathy Ascites Albumin Total bili INR 1 0 None >35 g/L <34 μM 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 51 μM >2.3 [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 —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 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/ —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) 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) 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) The liver has no palpable upper border and extends more laterally and medially The liver is not usually ballotable, but the kidney is because of its retroperitoneal position The percussion note is dull over the liver but is usually tympanic over the kidney A friction rub may occasionally be heard over the liver, but never over the kidney because it is too posterior The liver has a shaper edge while kidney is usually more rounded The liver has no palpable upper border and extends more laterally and medially The liver is not usually ballotable, but the kidney is because of its retroperitoneal position The percussion note is dull over the liver but is usually tympanic over the kidney A friction rub may occasionally be heard over the liver, but never over the kidney because it is too posterior The liver has a shaper edge while kidney is usually more rounded 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 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 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 —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 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 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 labs —ANA, anti-smooth muscle antibodies (anti-actin antibodies), anti-liver-kidney-microsomal (LKM) antibody, AMA, ferritin, ceruloplasmin, α 1-antitrypsin, AFP, antitransglutaminase gastroscopy —to check for varices liver biopsy fibroscan labs —ANA, anti-smooth muscle antibodies (anti-actin antibodies), anti-liver-kidney-microsomal (LKM) antibody, AMA, ferritin, ceruloplasmin, α 1-antitrypsin, AFP, antitransglutaminase gastroscopy —to check for varices liver biopsy fibroscan —consideration for liver transplantation —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 —for all patients with cirrhosis, and those with HBV and hepatocellular carcinoma risk factors, repeat AFP and abdominal US every 6 months for surveillance 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 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 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 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 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 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 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 99 mTc-labeled serum albumin may be helpful to confirm diagnosis treatments —O 2 , salt restriction, diuretics, therapeutic paracentesis, may need thoracentesis, TIPS. Avoid chest tube if possible (high risk of SBP and hepatorenal syndrome) 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 99 mTc-labeled serum albumin may be helpful to confirm diagnosis treatments —O 2 , salt restriction, diuretics, therapeutic paracentesis, may need thoracentesis, TIPS. Avoid chest tube if possible (high risk of SBP and hepatorenal 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 —O 2 , liver transplant 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 —O 2 , liver transplant NEJM 2007 358:22 pathophysiology —portal hypertension → unknown substance reaches pulmonary vasculature causing vasoconstriction → findings similar to primary pulmonary hypertension diagnosis —echocardiogram, right heart catheterization treatments —O 2 , diuretics, sildenafil, prostaglandins, calcium channel blockers, liver transplant pathophysiology —portal hypertension → unknown substance reaches pulmonary vasculature causing vasoconstriction → findings similar to primary pulmonary hypertension diagnosis —echocardiogram, right heart catheterization treatments —O 2 , diuretics, sildenafil, prostaglandins, calcium channel blockers, liver transplant 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 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 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 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 Acute Hepatic Failure (p. 143) Ascites (p. 153) Encephalopathy (p. 152) Hemochromatosis (p. 482) Hepatitis B (p. 145) Hepatitis C (p. 147) Jaundice (p. 155)

NEJM 1997 337:7 alcohol —acute intoxication, withdrawal, Wernicke–Korsakoff psychoactive —benzodiazepines, cocaine, heroine, ecstasy others —salicylates alcohol —acute intoxication, withdrawal, Wernicke–Korsakoff psychoactive —benzodiazepines, cocaine, heroine, ecstasy others —salicylates —spontaneous bacterial peritonitis, pneumonia, UTI, meningitis, encephalitis, abscess organ failure —hepatic, azotemia, hypothyroidism, hypoxemia, CO 2 narcosis electrolytes —ketoacidosis, hyponatremia, hypomagnesemia, hypercalcemia, glucose (hypo, hyper) organ failure —hepatic, azotemia, hypothyroidism, hypoxemia, CO 2 narcosis electrolytes —ketoacidosis, hyponatremia, hypomagnesemia, hypercalcemia, glucose (hypo, hyper) hemorrhage —subarachnoid, epidural, subdural, intracerebral stroke —basilar tumor epilepsy hemorrhage —subarachnoid, epidural, subdural, intracerebral stroke —basilar tumor epilepsy NEUROPSYCHIATRIC 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 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 ↑ 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 ↑ 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 —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) —vitals, signs of chronic liver disease, rectal examination (if suspect GI bleed), neurological examination, check for asterixis labs —CBCD, lytes, urea, Cr, glucose, TSH, AST, ALT, ALP, bilirubin, INR, PTT, NH 4 (poorly correlated with degree of encephalopathy), Ca, Mg, PO 4 , 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 labs —CBCD, lytes, urea, Cr, glucose, TSH, AST, ALT, ALP, bilirubin, INR, PTT, NH 4 (poorly correlated with degree of encephalopathy), Ca, Mg, PO 4 , 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 CT head —delirium workup ABG —if critically ill gastroscopy —to check for varices liver biopsy EEG —symmetric, high voltage, slow wave pattern CT head —delirium workup ABG —if critically ill gastroscopy —to check for varices liver biopsy EEG —symmetric, high voltage, slow wave pattern 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 H 2 O 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 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 H 2 O 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 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 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 Delirium (p. 432)

(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 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 ↓ 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 ↓ 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 gallstones cancer —pancreas, bile ducts, ampulla biliary structures —post-cholecystectomy, PSC, biliary atresia gallstones cancer —pancreas, bile ducts, ampulla biliary structures —post-cholecystectomy, PSC, biliary atresia —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) —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 —signs of chronic liver disease, liver and spleen examination —becomes clinically evident at levels of bilirubin >70 μmol/L [>41 mg/dL] —suggests conjugated hyperbilirubinemia —suggests cholestasis (bile cannot be secreted into the biliary system) —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 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, α 1-antitrypsin, AFP, LDH, haptoglobin, peripheral smear, reticulocyte counts imaging —US, CT abd 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, α 1-antitrypsin, AFP, LDH, haptoglobin, peripheral smear, reticulocyte counts imaging —US, CT abd endoscopic US MRCP ERCP liver biopsy endoscopic US MRCP ERCP liver biopsy TREAT UNDERLYING CAUSE 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 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 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 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

—cardiac (myocardial infarction), pulmonary (pneumonia), hepatobiliary (biliary colic), pancreatic (pancreatitis), colonic (irritable bowel syndrome), musculoskeletal, dietary indiscretion (PUD, 10–20%)— H. pylori , ASA, NSAIDs (COX-2 inhibitors slightly decreased risk), cancer, Zollinger–Ellison, smoking —NSAIDs, ASA, theophylline, calcium channel blockers, erythromycin, metronidazole, bisphosphonates, orlistat, acarbose, iron, potassium supplements (GERD, 20%) ★ ACIDS ★ A cid hypersecretion—Zollinger–Ellison disease A lcohol abuse C onnective tissue disease—scleroderma I nfections of esophagus—CMV, HSV, candidiasis D iabetic gastroparesis D rug therapy S moking ★ ACIDS ★ A cid hypersecretion—Zollinger–Ellison disease A lcohol abuse C onnective tissue disease—scleroderma I nfections of esophagus—CMV, HSV, candidiasis D iabetic gastroparesis D rug therapy S moking A cid hypersecretion—Zollinger–Ellison disease A lcohol abuse C onnective tissue disease—scleroderma I nfections of esophagus—CMV, HSV, candidiasis D iabetic gastroparesis D rug therapy S moking (50%)—cause unclear. Diagnosis of exclusion (rule out organic cause) —perforation, hemorrhage, gastric outlet obstruction, pancreatitis —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 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 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 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” 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 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 If age > 50 or alarm symptoms ★ Very BAD ★ ( V omiting, B leed/anemia, A bdominal mass/weight loss, D ysphagia), refer for gastroscopy to check for gastric cancer. Otherwise proceed to step 3 If ASA or NSAIDs use, stop medications if possible. If not, consider empiric proton pump inhibitor/H 2 blocker trial and proceed to step 4 If GERD predominant symptoms (heartburn, regurgitation), treat as GERD. Otherwise, proceed to step 5 If H. pylori urea breath test positive , treat with triple therapy. Otherwise, proceed to step 6 If none of the above, diagnosis of non-ulcer dyspepsia 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 If age > 50 or alarm symptoms ★ Very BAD ★ ( V omiting, B leed/anemia, A bdominal mass/weight loss, D ysphagia), refer for gastroscopy to check for gastric cancer. Otherwise proceed to step 3 If ASA or NSAIDs use, stop medications if possible. If not, consider empiric proton pump inhibitor/H 2 blocker trial and proceed to step 4 If GERD predominant symptoms (heartburn, regurgitation), treat as GERD. Otherwise, proceed to step 5 If H. pylori urea breath test positive , treat with triple therapy. Otherwise, proceed to step 6 If none of the above, diagnosis of non-ulcer dyspepsia Canadian Dyspepsia Working Group. Can J Gastroenterol 2005 19:5 labs —CBCD, lytes, glucose, AST, ALT, ALP, bilirubin, lipase, Ca, albumin imaging —upper GI series, US abd, CT abd labs —CBCD, lytes, glucose, AST, ALT, ALP, bilirubin, lipase, Ca, albumin imaging —upper GI series, US abd, CT abd 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 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 — 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) — 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 — lifestyle changes (avoid alcohol, caffeine, tobacco). Antisecretory treatment (see above). H. pylori eradication (may or may not relieve symptoms). Promotility agent (domperidone) Esophageal Cancer (p. 215) Gastric Cancer (p. 217) Gastric Lymphoma (p. 193) 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 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 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 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 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 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 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 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 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 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

(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) 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) (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 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 —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) 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 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 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 For structural disorders, is the dysphagia progressive? If yes, consider tumors and peptic stricture. If intermittent, consider esophageal ring Any caustic ingestion history? 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 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 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 For structural disorders, is the dysphagia progressive? If yes, consider tumors and peptic stricture. If intermittent, consider esophageal ring Any caustic ingestion history? imaging —barium swallow (esophageal), videofluoroscopy (oropharyngeal) swallowing assessment —occupational therapy or speech pathology imaging —barium swallow (esophageal), videofluoroscopy (oropharyngeal) swallowing assessment —occupational therapy or speech pathology 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 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 —postural/nutritional/behavioral modifications, swallowing rehabilitation, esophageal dilation TREAT UNDERLYING CAUSE 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 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 pathophysiology —common organisms include Candida albicans , CMV, and HSV. Happens more commonly in immunocompromised host diagnosis —gastroscopy and biopsy/viral cultures pathophysiology —common organisms include Candida albicans , CMV, and HSV. Happens more commonly in immunocompromised host diagnosis —gastroscopy and biopsy/viral cultures 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) 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) Esophageal Cancer (p. 215) Stroke (p. 337)

NEJM 2001 345:1 —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) 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 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 —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 —liver examination, stigmata of chronic liver disease, weight. Also examine for extrahepatic manifestations of HCV Acute Liver Failure (p. 143) Chronic Liver Failure (p. 149) HCV/HIV Co-infection (p. 291) Hepatitis B (p. 145) Hepatoma (p. 227) 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 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 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 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 liver biopsy —not mandatory before starting treatments FibroScan —non-invasive assessment of liver fibrosis using ultrasound liver biopsy —not mandatory before starting treatments FibroScan —non-invasive assessment of liver fibrosis using ultrasound —age <40, female, weight <75 kg [165 lbs], low titer, genotype 2/3, mild fibrosis —age of infection ≥40, male, high BMI, alcoholism, HIV co-infection —genotype, viral load, route of transmission (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 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 —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 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 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 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 —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

NEJM 2003 349:14 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 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 labs —CBCD, lytes, urea, Cr, glucose, TSH, Ca, Mg imaging —AXR labs —CBCD, lytes, urea, Cr, glucose, TSH, Ca, Mg imaging —AXR —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 —wheat bran , high-bran cereals, psyllium/Metamucil 2–3 teaspoon/day, exercise , hydration (8–10 glasses/day) — 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 —stop potentially constipation-causing medications if possible 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 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 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 × 10 9 /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 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 × 10 9 /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 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” 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 Abdominal Pain (p. 128) Constipation in the Palliative Setting (p. 448) Nausea and Vomiting (p. 123) Opioid Use (p. 443) associations —patients with IBS are more likely to have functional dyspepsia, urinary symptoms, dysmenorrhea, dyspareunia, sexual dysfunction, proctalgia fugax, a history of physical or sexual abuse, and fibromyalgia diagnosis —IBS is a diagnosis of exclusion. Consider flexible sigmoidoscopy/colonoscopy, evaluation for celiac sprue (p. 139), and stool cultures to rule out other diseases treatments —reassurance, stress reduction, fiber supplementation. For constipation-prone IBS, consider osmotic laxatives (first-line), and linaclotide 290 μg PO daily (for persistent constipation). For diarrhea-prone IBS, consider loperamide 2–4 mg PO daily (first-line), and alosetron 0.5–1 mg PO BID × 12 weeks (for ♀ with severe diarrhea; 5HT3 antagonist). For abdominal pain, consider antispasmodics ( hyoscyamine 0.125–0.25 mg PO q4–6 h PRN), TCAs ( amitriptyline 10–75 mg qhs), desipramine 25–150 mg PO daily, and SSRIs for abdominal pain. Cognitive behavioral therapy may also be useful associations —patients with IBS are more likely to have functional dyspepsia, urinary symptoms, dysmenorrhea, dyspareunia, sexual dysfunction, proctalgia fugax, a history of physical or sexual abuse, and fibromyalgia diagnosis —IBS is a diagnosis of exclusion. Consider flexible sigmoidoscopy/colonoscopy, evaluation for celiac sprue (p. 139), and stool cultures to rule out other diseases treatments —reassurance, stress reduction, fiber supplementation. For constipation-prone IBS, consider osmotic laxatives (first-line), and linaclotide 290 μg PO daily (for persistent constipation). For diarrhea-prone IBS, consider loperamide 2–4 mg PO daily (first-line), and alosetron 0.5–1 mg PO BID × 12 weeks (for ♀ with severe diarrhea; 5HT3 antagonist). For abdominal pain, consider antispasmodics ( hyoscyamine 0.125–0.25 mg PO q4–6 h PRN), TCAs ( amitriptyline 10–75 mg qhs), desipramine 25–150 mg PO daily, and SSRIs for abdominal pain. Cognitive behavioral therapy may also be useful NEJM 2008 358:16

See differential diagnosis for ACUTE ABDOMINAL PAIN (p. 128) LOWER GI BLEED (p. 134) and CHRONIC DIARRHEA (p. 138) See differential diagnosis for ACUTE ABDOMINAL PAIN (p. 128) LOWER GI BLEED (p. 134) and CHRONIC DIARRHEA (p. 138) 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) 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) 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) Strictures Fistulas Fissures Abscesses Colorectal cancer —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 labs —CBCD, lytes, urea, Cr, ESR, CRP, Fe, TIBC, ferritin, % sat, AST, ALT, ALP, bilirubin, albumin, Ca, Mg, PO 4 , 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 labs —CBCD, lytes, urea, Cr, ESR, CRP, Fe, TIBC, ferritin, % sat, AST, ALT, ALP, bilirubin, albumin, Ca, Mg, PO 4 , 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 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 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 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 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 Clostridium difficile Colitis (p. 137) Inflammatory Arthritis (p. 321) 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 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 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 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 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 × 10 9 /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 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 × 10 9 /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

(lipase, amylase; rare cause)—radiation, sicca (intrinsic factor, R factor; rare cause)—pernicious anemia, gastrectomy, vagotomy (bile acids; 10% of extra-colonic cases)—hepatic failure, cholestasis, biliary obstruction, terminal ileal resection (lipase, amylase, HCO 3 ; 90% of extra-colonic causes)—cancer, chronic pancreatitis, cystic fibrosis (brush border/enterocytes)—celiac disease, lymphoma, infectious colitis, inflammatory colitis, ischemic colitis, radiation colitis —β-lipoprotein (abetalipoproteinemia), lymphatics (lymphoma) —infections (sepsis, abscess, pneumonia), poor wound healing, respiratory failure, death —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) Cachexia (p. 449) Celiac Disease (p. 139) Vitamin B12 Deficiency (p. 459) 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% 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” 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) 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) 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 labs —CBCD, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, INR, PTT, fasting lipid profile, Ca, Mg, PO 4 , albumin, pre-albumin, carotene, Fe, ferritin, antitransglutaminase antibody, vitamin B12, RBC folate imaging —US abd labs —CBCD, lytes, urea, Cr, glucose, AST, ALT, ALP, bilirubin, INR, PTT, fasting lipid profile, Ca, Mg, PO 4 , albumin, pre-albumin, carotene, Fe, ferritin, antitransglutaminase antibody, vitamin B12, RBC folate imaging —US abd 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 H 2 , 14 CO 2 , or 13 CO 2 antiintrinsic factor antibody —for vitamin B12 deficiency (has replaced historical Schilling test) 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 H 2 , 14 CO 2 , or 13 CO 2 antiintrinsic factor antibody —for vitamin B12 deficiency (has replaced historical Schilling test) —dietician consult. Consider supplemental nutrition TREAT UNDERLYING CAUSE —deficiency of calories resulting in stunted growth in children, loss of body fat, and generalized wasting of lean body mass without significant edema —deficiency of protein with preserved adipose tissue but significant edema, muscle atrophy, and amenorrhea 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 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 vitamin B1 ( thiamine ) deficiency —Wernicke syndrome, Korsakoff syndrome, Leigh’s syndrome (subacute necrotizing encephalomyopathy) vitamin B3 ( niacin , nicotinic acid ) deficiency ★ DDDD ★— D ermatitis (photosensitive, pigmented, pellagra), D iarrhea, D ementia, D eath 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 vitamin B1 ( thiamine ) deficiency —Wernicke syndrome, Korsakoff syndrome, Leigh’s syndrome (subacute necrotizing encephalomyopathy) vitamin B3 ( niacin , nicotinic acid ) deficiency ★ DDDD ★— D ermatitis (photosensitive, pigmented, pellagra), D iarrhea, D ementia, D eath 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