Gastroenterology

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Evaluate the extent (severity) of the bleeding and assess hemodynamic stability.

Locate the site of the bleeding:

• Upper GI bleeding (above the ligament of Treitz): PUD (40%-79%), gastritis/duodenitis (5%-30%), esophageal or gastric varices (6%-21%), Mallory-Weiss tears (3%-15%), tumors (2%-3%), AV (<1%) and aortoenteric fistulas (<1%)

• Lower GI bleeding (below the ligament of Treitz): Acute massive lower GI bleeding causes are diverticular disease (17%-40%), angiodysplasia (2%-30% of colonic bleeding, 70%-80% of small bowel bleeding), neoplasm (11%-14%), IBD (9%-21%), ischemic colitis (5%), solitary rectal ulcer (2%-5%), NSAID-induced colonic ulceration (1%), acute infectious colitis (1%), pseudomembranous colitis (1%), postpolypectomy bleeding (2%-5%), radiation colitis (2%-5%), hemorrhoids (1%), and anal fissures (1%).

Hx

Meds (ASA, steroids, “blood thinners,” NSAIDs)

Prior GI or vascular surgery

H/o GI dx or bleeding

Smoking

Alcohol intake (gastritis, esophageal varices)

Sx of PUD

Associated diseases (CAD, diabetes, HTN, hematologic disorders, renal failure)

Protracted retching and vomiting (consider gastric or gastroesophageal tear [Mallory-Weiss syndrome])

Weight loss, anorexia (consider carcinoma)

Color and character of stool (i.e., hematochezia or melena, constipation or diarrhea)

Presence or absence of hematemesis

PE

VS: tachycardia, hypotension, postural changes (orthostatic hypotension). A pulse ↑ >20 bpm or a postural ↑ in systolic BP >10 to 15 mm Hg indicates blood loss >1 L.

Pts taking β-adrenergic blockers may not demonstrate significant tachycardia w/volume depletion.

Cardiorespiratory exam: murmurs (↑ incidence of angiodysplasia in pts w/AS), pulmonary rales, JVD to determine rapidity of volume replacement

Abd exam:

• Observe for masses, tenderness, distention, ascites.

• Auscultate for bowel sounds or abd bruits.

• Look for evidence of liver disease (hepatomegaly, splenomegaly, abnl vascular patterns, gynecomastia, spider angiomas, palmar erythema, testicular atrophy).

DRE: Check for masses, strictures, hemorrhoids; test stool for occult blood and inspect it for abnormalities (tarry, blood streaked, bright red, mahogany color).

Skin: Check for jaundice (liver disease), ecchymoses (coagulation abnormality), cutaneous telangiectasia (Rendu-Osler-Weber disease), buccal pigmentation (Peutz-Jeghers syndrome), and other mucocutaneous changes (Ehlers-Danlos syndrome).

Look for evidence of metastatic disease (cachexia, firm nodular liver).

If the pt is not experiencing hematemesis and endoscopy is not immediately available, an NG tube may be placed for gastric lavage while awaiting endoscopy to determine whether the bleeding is emanating from the UGI tract (presence of bright red blood clots or coffee-ground–like guaiac (+) aspirate); however, the sensitivity and specificity of this process are limited. A (−) aspirate does not r/o upper GI bleeding because it could have subsided or the pt could be bleeding from the duodenal bulb w/o reflux into the stomach. Lavage w/500 mL of NS. Failure to clear blood w/gastric lavage indicates persistent bleeding and the need for more urgent endoscopy.

Initial Management

Stabilize the pt: Insert two large-bore (18-gauge) IV catheters and administer lactated Ringer’s solution or NS; the rate of volume replacement is based on the estimated blood loss, clinical condition, and h/o CVD, including CHF.

Type and crossmatch for 2 to 8 U of PRBCs, depending on the estimated blood loss, and transfuse as necessary. Aim for Hct >30 for elderly pts w/multiple comorbid conditions and ≥20 for young, healthy individuals.

Initial labs:

• Hgb/Hct

• Initial value should be considered erroneous until serum volume is replaced by crystalloid fluid.

• After bleeding ceases, the Hct may continue to ↓ for up to 6 hr, and full equilibration may require 24 hr. Follow the Hgb/Hct q6-8 hr while active bleeding is present.

• The Hct generally ↓ by 2 to 3 points and the Hgb falls by 1 point for every 500 mL of blood lost.

• BUN: In the absence of renal disease, the BUN level may help determine the severity of the bleeding; a simultaneous Cr level may also be of value because the disparity in the BUN/Cr ratio will reveal the extent of the bleeding more accurately; BUN/Cr >36 is suggestive of UGI bleeding. BUN levels can be confusing if the bleeding is insidious and may mark prerenal azotemia secondary to the bleeding.

• PT, APTT, and Plt count should be calculated to exclude bleeding disorders; other useful initial labs are LFTs, serum electrolytes, and glucose.

ECG: R/o myocardial ischemia secondary to severe anemia in patients with risk factors.

Endoscopic EzZvaluation

EGD is indicated when blood or guaiac (+) coffee ground–like material is obtained from the NG aspirate or if lower endoscopic findings are (−). It should be performed urgently in hemodynamically unstable pts or those found to still be actively bleeding by NG lavage or in those requiring blood transfusion. Otherwise, it should ideally be performed within 24 hr of the hospital admission. In addition, if a therapeutic procedure (e.g., bipolar heater probe, laser cauterization, injection scleroRx, or band ligation) is considered, endoscopy should be done on an emergency basis.

Colonoscopy should be performed initially if lower GI bleeding is suspected, generally within 24 hr of hospital admission after adequate bowel preparation.

Imaging

Arteriography can identify briskly bleeding sources. Overall diagnostic sensitivity of arteriography is 41%. Mesenteric arteriography is useful to identify bleeding from AV malformations.

Radionuclide scans may be used before angiography to determine which pts are bleeding sufficiently to make (+) angiographic result more likely. Bleeding at rates as low as 0.1 mL/min can be detected by radionuclide scans. A (+) “immediate blush” is a good indication for urgent angiography, whereas a (−) “delayed blush” is an indication for observation and elective colonoscopy.

Technetium-99m (^99mTc) pertechnetate scan (Meckel scan) selectively tags acid-secreting cells (gastric mucosa); it is used most often for unexplained bleeding in infants and young adults.

^99mTc-sulfur colloid scan is very sensitive in detecting lesions w/low bleeding rates; its major drawbacks are as follows:

• Short half-life (difficulty in detecting intermittent bleeding)

• Affinity of the colloid for liver and spleen (colonic bleeding may be missed if it originates in a region superimposed on areas of liver or spleen uptake)

^99mTc-labeled RBC scan: Its major advantage over the sulfur colloid scan is its long duration; it is useful for intermittent bleeding because the pt can be monitored for GI bleeding for 24 to 48 hr. Its disadvantage is that it has a high false-localization rate.

Selective angiography:

• On occasion, this is the first test ordered in actively bleeding pts, but in most situations, it is reserved for massive, ongoing bleeding, especially when endoscopy is not feasible or when endoscopic evaluation is unrevealing w/recurrent or persistent blood loss.

• Angiography may also be therapeutic because vasoconstrictors, autologous clots, or Gelfoam emboli can be administered intra-arterially at the time of angiography to occlude the bleeding vessel.

• Major drawbacks are the high rate of bleeding (>0.5 mL/min) necessary for dx and the risk of allergic reaction to the contrast dye.

• Advantages include the fact that no bowel preparation is required and anatomic localization is accurate.

• Enhanced helical CT scanning w/IV contrast material is used in selected cases.

Treatment

Correct bleeding abnormalities by administering FFP or vitamin K if the pt has a coagulopathy and Plt if the pt is severely thrombocytopenic.

IV PPIs in cases of probable peptic ulcer or gastritis. After endoscopic Rx of bleeding peptic ulcers, IV PPIs ↓ the risk of recurrent bleeding ↑ pH, ↑ platelet function.

Octreotide: IV bolus of 50 to 100 μg followed by IV infusion of 25 to 50 μg/hr is useful for acute variceal bleeding. Another useful agent is terlipressin.

Endoscopy:

• ScleroRx or endoscopic variceal ligation is used for bleeding varices.

• Injection Rx (e.g., epinephrine, saline), bipolar electrocoagulation, and heater-probe Rx are equally effective modalities in the Rx of bleeding peptic ulcer.

Balloon tamponade is indicated for severe bleeding from esophageal varices if octreotide or other endoscopic Rx modalities are ineffective.

Radiologic modalities include localized infusion of vasopressin, autologous clots, or foreign coagulating substances (e.g., Gelfoam) in the bleeding vessel during or after arteriography.

Surgery is indicated at the onset of dx of aortoduodenal fistula, but it is not suggested as the initial Rx in cases of other causes of GI bleeding until a definitive dx is made and other noninvasive modalities are tried. Surgical approach may be necessary in the following situations:

• Rebleeding in a hospitalized pt

• Bleeding episode that requires transfusion of >4 U of PRBCs in 24 hr or >10 U of PRBCs in total

• Endoscopic visualization of a “naked” vessel in a peptic ulcer unresponsive to injection or coagulation Rx

B. Disorders of the Esophagus

1. Dysphagia

a. Oropharyngeal Dysphagia

Inability to move food from oropharynx via UES → esophagus

Drooling, postnasal regurgitation, difficulty initiating swallowing, sialorrhea, sensation of food stuck in the neck, coughing/choking during swallowing, dysphonia, and dysarthria

Diagnosis

First test = modified barium swallow videofluoroscopy, then fiberoptic flexible nasopharyngeal laryngoscopy

b. Esophageal Dysphagia

Inability to move food from esophagus → stomach

Dysphagia to solids suggests mechanical obstruction.

Neuromuscular causes result in dysphagia to both solids and liquids.

Sx intermittent in pts with esophageal dysphagia from benign causes of structural obstruction or diffuse esophageal spasm; sx progressive in pts with peptic stricture, esophageal carcinoma, scleroderma, and achalasia

Luminal diameter >18 to 20 mm (rarely sx); diameter <13 mm (sx)

Diagnosis

Esophageal dysphagia: first test = barium esophagography, then EGD

Treatment

Goal is airway protection and nutrition maintenance.

Consider consultation with ENT, head and neck surgeon, radiologist, speech pathologist, physical therapist, dietitian, gastroenterologist, physical medicine and rehabilitation specialist, dentist, neurologist, etc., because nursing home pts with oropharyngeal dysphagia and hx of aspiration have 45% mortality rate over 1 yr

2. Esophageal Motility Disorders

Table 6-1 compares esophageal motor disorders.

TABLE 6-1

Esophageal Motor Disorders

	Achalasia	Scleroderma	Diffuse Esophageal Spasm
Symptoms	Dysphagia Regurgitation of nonacidic material	Gastroesophageal reflux disease Dysphagia	Substernal chest pain (angina-like) Dysphagia with pain
Radiographic appearance	Dilated, fluid-filled esophagus Distal bird-beak stricture	Aperistaltic esophagus Free reflux Peptic stricture	Simultaneous noncoordinated contractions
Manometric Findings
Lower esophageal sphincter	High resting pressure Incomplete or abnormal relaxation with swallow	Low resting pressure	Normal pressure
Body	Low-amplitude, simultaneous contractions after swallowing	Low-amplitude peristaltic contractions or no peristalsis	Some peristalsis Diffuse and simultaneous nonperistaltic contractions, occasionally high amplitude

From Andreoli, T E, Benjamin IJ, Griggs RC, Wing EJ: Andreoli and Carpenter’s Cecil Essentials of Medicine, 8th ed. Philadelphia, Saunders, 2010.

3. GERD

Motility disorder caused by the reflux of gastric contents into the esophagus

Etiology

Incompetent LES

Medications ↓ LES pressure (CCBs, β-blockers, theophylline, anti-AChs)

Foods ↓ LES pressure (chocolate, yellow onions, peppermint)

Tobacco abuse, alcohol, coffee

Pregnancy

Gastric acid hypersecretion

Hiatal hernia (present in 70% w/GERD ); however, most w/hiatal hernia asx

Diagnosis

H&P

Heartburn, dysphagia, sour taste, regurgitation of gastric contents into mouth, chronic cough/bronchospasm, chest pain, laryngitis, early satiety, abd fullness and bloating w/belching, dental erosions in children

Additional Testing

EGD = document type/extent tissue damage; r/o potential malignancy (Barrett’s esophagus)

24-hr esophageal pH monitoring: generally not done; useful in atypical manifestations of GERD (chest pain and chronic cough)

Esophageal manometry: useful in refractory reflux pt w/surgical Rx planned

Upper GI series: identify ulcerations/strictures; may miss mucosal abnormalities. Only one third of pts w/GERD have radiographic signs of esophagitis.

Treatment

Lifestyle change (wt loss, ↓ fat intake)/avoidance of exacerbating factors: EtOH, tobacco, citrus/tomato–based products, caffeine, β-blockers, CCBs, α-agonists, theophylline

↑ Head of bed 4 to 8 in. Avoid lying supine directly after late/large meals.

Avoid wearing clothing that is tight around the waist.

PPIs: preferred Rx (H₂ blockers less effective)

Antacids: relief of mild sx; ineffective in severe cases

Prokinetic agents (metoclopramide): indicated if PPIs not fully effective. May be used in combination Rx; however, side effects limit use.

Nissen fundoplication (refractory cases)

Endoscopic radiofrequency heating of GE-jxn (Stretta procedure): pts unresponsive to traditional Rx

4. Barrett’s Esophagus

Squamous lining of lower esophagus replaced by intestinalized metaplastic columnar epithelium; predisposing to neoplasia

H&P

Sx ranging from heartburn → dysphagia → nl PE

Diagnosis

EGD with biopsy

Treatment

Control GERD sx; maintain healed mucosa via PPI

Monitoring

Relative risk of adenocarcinoma is 11.3 compared with general population.

Pts should undergo surveillance EGD and systematic four-quadrant biopsy at intervals determined by the presence and grade of dysplasia.

Pts who have had two consecutive EGDs showing no dysplasia should have follow-up every 3 to 5 yr.

Pts with low-grade dysplasia should have extensive mucosal sampling within 6 mo and follow-up every 6 to 12 mo.

Pts with high-grade dysplasia should have expert confirmation and extensive mucosal sampling. High-grade dysplasia with visible mucosal irregularities should be removed by endoscopic mucosal resection.

Consider intensive surveillance every 3 mo for patients with focal high-grade dysplasia. Patients with multifocal high-grade dysplasia or carcinoma should be considered for resection or ablation if not an operative candidate.

5. Esophageal Tumors

15% in proximal third esophagus, 50% in middle third, 35% in lower third

Risk factors: EtOH, smoking, achalasia (7× > risk), chronic GERD, HPV (types 16, 18), obesity/hiatal hernia/low-vitamin high-fat diet, ingested carcinogens (nitrates, smoked opiates, fungal toxins [pickled vegetables], betel nut chewing), mucosal damage (long-term exposure tea >70° C, lye ingestion), radiation-induced stricture

H&P

Dysphagia (74%): initially with solid foods; gradually → semisolids/liquids

Unintentional weight loss; losing >10% of body mass = poor outcome

Hoarseness (recurrent laryngeal nerve involvement)

Cervical adenopathy; usually supraclavicular lymph nodes

Diagnosis

EGD

Endoscopic U/S: locoregional staging (depth of invasion/lymph assessment)

Chest/abd CT and/or integrated CT-PET scans (tumor spread for preop staging)

Staging laparoscopy may alter Rx plans (20%-30% cases) by more accurately staging regional lymph nodes/detecting occult peritoneal mets.

Treatment

Surgical resection of squamous cell carcinoma and adenocarcinoma of lower esophageal third indicated for local, resectable disease in the absence of widespread mets detected by CT-PET. Gastric pull-through/colonic interposition is typically used to provide luminal continuity.

Squamous cell carcinoma is more radiosensitive than adenocarcinoma; used as palliative monoRx of obstructive sx in unresectable/advanced cases.

Palliative radiation Rx for bone mets

Preoperative chemoradioRx + surgery in late stage I (T2,3N0), stage II or III ↑ tumoricidal effects

5-yr survival 13% (37.3% [local], 18.4% [regional], 3.1% [distant] disease)

C. Disorders of Stomach and Duodenum

1. Peptic Ulcer Disease

Etiology/Epidemiology

H. pylori infection (70%-90% duodenal ulcers)

NSAIDs (40%-50% gastric ulcers)

Cigarette smoking, EtOH

Neoplasia: gastrinoma (ZE syndrome), carcinoid, mastocytosis

Diagnosis

EGD (preferred), UGI barium studies

H. pylori testing by endoscopic biopsy (gold standard), urea breath test (dx active infection >90% sens/spec), stool antigen test (useful for follow-up s/p Rx), or serology (shows hx but not necessarily current infection, false-[+] possible s/p Rx)

Treatment

Eradicate if (+) H. pylori infection (Table 6-2).

Lifestyle change: d/c smoking/EtOH.

Add PPI to ↓ acid secretions.

TABLE 6-2

Overview of Antibiotics Used for Helicobacter Pylori Eradication

Drug Class	Drug	Triple Therapy^∗ Dose	Quadruple Therapy^† Dose	Sequential Therapy^‡ Dose
Acid suppression	Proton pump inhibitor	20-40 mg bid^§	20-40 mg bid^§	20-40 mg bid^§
Standard antimicrobials	Bismuth compound^\|\|	2 tablets bid	2 tablets bid
	Amoxicillin	1 g bid		1 g bid
	Metronidazole^¶	500 mg bid	500 mg tid	500 mg bid
	Clarithromycin	500 mg bid		500 mg bid
	Tetracycline		500 mg qid
Salvage antimicrobials	Levofloxacin	300 mg bid	300 mg bid
	Rifabutin	150 mg bid
	Furazolidone	100 mg bid
	Doxycycline		100 mg bid
	Nitazoxanide		1 g bid

^∗ Triple therapy consists of a proton pump inhibitor or bismuth compound, together with two of the listed antibiotics, usually given for 7-14 days.

^† Quadruple therapy consists of a proton pump inhibitor plus either the combination of a bismuth compound, metronidazole, and tetracycline given for 4-10 days, or the combination of levofloxacin, doxycycline, and nitazoxanide for 10 days.

^‡ Sequential therapy consists of 10 days of proton pump inhibitor treatment, plus amoxicillin during days 1-5 and a combination of clarithromycin and an imidazole (when available, tinidazole; otherwise, metronidazole) during days 6-10.

^§ Proton pump inhibitor dose equivalent to omeprazole 20 mg bid.

^|| Bismuth subsalicylate or subcitrate.

^¶ An alternative is tinidazole 500 mg bid.

From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, Elsevier, 2012.

2. Gastroparesis

Sx impaired gastric emptying in absence of mechanical obstruction

Differential Diagnosis and Clinical Pearls

Diabetes mellitus gastroparesis (HBA_1c, fasting glucose)

Gastric surgery

Pregnancy

Hypothyroidism (TSH)

Cannabinoid hyperemesis syndrome (hx of use; hx of relief of N/V with hot baths/showers)

Rumination syndrome (hx of passive regurgitation of pleasant tasting food w/o nausea)

Management

Prokinetic agents (e.g., metoclopramide)

Refractory cases (↑ risk malnutrition), gastroduodenal manometry to distinguish myopathic from neuropathic process

3. Gastric Cancer

Adenocarcinoma; mostly antral (35%)

Male-to-female ratio 3:2

Familiar diffuse gastric cancer (autosomal dominant, mutation E-cadherin gene CDH1 = cancer at young age)

Physical Exam and Labs

Wt loss (70%-80%), N/V (20%-40%), dysphagia (20%)

Dyspepsia (unrelieved by antacids, worse w/food), epigastric/abd mass (40%)

Microcytic anemia, hemoccult (+) stools

Hypoalbuminemia

Diagnosis

Upper endoscopy with biopsy (staging via abd CT scan ± lymph node dissection)

Treatment

If curable: gastrectomy with regional lymphadenectomy

• Perioperative epirubicin, cisplatin, and infused fluorouracil (ECF) ↑ survival

• Gastrectomy pts require vitamin B₁₂ replacement

D. Disorders of the Pancreas

1. Acute Pancreatitis

Inflammatory process w/intrapancreatic enzyme activation possibly also involving peripancreatic tissue/remote organ systems

Etiology

>90% of cases: biliary tract disease (calculi or sludge) or EtOH

Drugs: thiazides, furosemide, corticosteroids, tetracycline, estrogens, valproic acid, metronidazole, azathioprine, methyldopa, pentamidine, ethacrynic acid, procainamide, sulindac, nitrofurantoin, ACEIs, danazol, cimetidine, piroxicam, gold, ranitidine, sulfasalazine, isoniazid, acetaminophen, cisplatin, opiates, erythromycin

Abd trauma, surgery, ERCP, viral infections, PUD, pancreas divisum (congenital failure to fuse of dorsal or ventral pancreas), pregnancy, vascular (vasculitis, ischemic), hypolipoproteinemia (types I, IV, and V), hypercalcemia, pancreatic carcinoma (primary/mets), renal failure, hereditary pancreatitis, occupational exposure (methanol, cobalt, zinc, mercuric chloride, creosol, lead, organophosphates, chlorinated naphthalenes)

Others: scorpion bite, obstruction at ampulla region (neoplasm, duodenal diverticula, Crohn’s disease), hypotensive shock, autoimmune pancreatitis

Scoring System

Table 6-3 describes various scoring systems to assess severity of acute pancreatitis.

BUN most accurate in predicting severity

TABLE 6-3

Scoring Systems to Assess Severity of Acute Pancreatitis

System	Criteria
Ranson	At admission Age >55 yr WBC >16,000/μL Glucose >200 mg/dL LDH >350 IU/L AST >250 IU/L Within next 48 hr Decrease in hematocrit by >10% Estimated fluid sequestration of >6 L Serum calcium <8.0 mg/dL Pao₂ <60 mm Hg BUN increase >5 mg/dL after hydration Base deficit >4 mmol/L
APACHE-II	Multiple clinical and laboratory factors. Calculator available at www.mdcalc.com/apache-ii-score-for-icu-mortality
BISAP	BUN >25 mg/dL Impaired mental status Presence of SIRS Age >60 yr Pleural effusion
CT	A: Normal pancreas B: Focal or diffuse enlargement of pancreas C: Grade B plus pancreatic and/or peripancreatic inflammation D: Grade C plus a single fluid collection E: Grade C plus two or more fluid collections or gas in pancreas
CT severity index	CT grade A = 0 B = 1 C = 2 D = 3 E = 4 Plus necrosis grade No necrosis = 0 <30% necrosis = 2 30-50% necrosis = 4 >50% necrosis = 6

APACHE-II, Acute Physiology and Chronic Health Evaluation II; BISAP, bedside index of severity in acute pancreatitis.

From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, Elsevier, 2012.

“Severe Acute Pancreatitis”

The presence of any of the following 4 criteria:

1. Organ failure w/one or more of the following: shock (systolic BP <90 mm Hg), pulmonary insufficiency (Pao₂ <60 mm Hg), renal failure (serum Cr >2 mg/dL after rehydration), and GI bleeding (>500 mL/24 hr)

2. Local complications such as necrosis, pseudocyst, or abscess

3. At least 3 of Ranson’s criteria

4. At least 8 of the APACHE II criteria

Diagnosis

H&P

Fever, epigastric tenderness/guarding; sudden severe pain (peak intensity 10-30 min; lasting several hr w/o relief)

Hypoactive bowel sounds (secondary to ileus)

Tachycardia, shock (secondary to ↓ intravascular volume)

Confusion (secondary to metabolic disturbances)

↓ Breath sounds (atelectasis, pleural effusions, ARDS)

Jaundice (secondary to obstruction or compression of biliary tract)

Ascites (secondary to tear in pancreatic duct, leaking pseudocyst)

Palpable abd mass (pseudocyst, phlegmon, abscess, carcinoma)

Hypocalcemia (Chvostek’s sign, Trousseau’s sign)

Intra-abd bleeding (hemorrhagic pancreatitis):

• Gray-blue discoloration around umbilicus (Cullen’s sign)

• Bluish discoloration involving flanks (Grey Turner’s sign)

Tender SC nodules (SC fat necrosis)

Labs

↑ Serum amylase (initial 3-5 days), ↑ serum lipase, ↑ serum trypsin

Rapid urinary trypsinogen-2; useful screening test in pts w/abd pain; (−) dipstick r/o acute pancreatitis w/high degree of probability; (+) test result indicates need for further evaluation.

CBC: leukocytosis; ↑ Hct (secondary to hemoconcentration); ↓ Hct may indicate hemorrhage/hemolysis.

↑ BUN (secondary to dehydration)

↑ Serum glucose; in previously nl pt correlates w/pancreatic malfunction

↑ AST/LDH (tissue necrosis); ↑ bili/alk phos (CBD obstruction); ≥3 ↑ ALT = biliary pancreatitis (95% probability)

↓ Serum Ca (saponification, precipitation, and ↓ PTH response)

ABGs: Pao₂ may be ↓ secondary to ARDS, pleural effusions; pH may be ↓ secondary to lactic acidosis, respiratory acidosis, and renal insufficiency.

Serum electrolytes: K⁺ may be ↑ secondary to acidosis/renal insufficiency; Na⁺ may be ↑ secondary to dehydration.

Imaging

Abd plain film: r/o perforated viscus; may reveal localized ileus (sentinel loop), pancreatic calcifications (chronic pancreatitis), blurring of left psoas shadow, dilation of transverse colon, calcified gallstones

CXR: elevation of one or both diaphragms, pleural effusions, basilar infiltrates, platelike atelectasis

Abd U/S: gallstones (sensitivity 60%-70%), pancreatic pseudocysts; limited in presence of distended bowel loops overlying pancreas

CT abd: superior to U/S in dx extent; also able dx pseudocysts (well-defined area surrounded by high-density capsule); GI fistulation or infection of a pseudocyst (gas within pseudocyst)

Contrast-enhanced CT (pancreatic necrosis): severity graded by CT scan (see Table 6-3)

MRCP: useful if surgical procedure not anticipated

ERCP: avoided during acute stage, unless to remove impacted stone

Treatment

General Measures

Maintain intravascular volume (vigorous IV hydration).

NPO until clinically improved, stable, and hungry; enteral feedings preferred to TPN; PN necessary if unable to tolerate enteral/adequate infusion rate cannot be reached within 2 to 4 days.

NG suction is used to decompress abd in pts w/ileus.

Control pain with IV morphine or fentanyl.

Correct metabolic abnormalities (replace Ca, Mg).

Specific Measures

Pancreatic/peripancreatic infection in 40% to 70% pts w/pancreatic necrosis; prophylactic IV abx (5-7 days) justified if septicemia, pancreatic abscess, or pancreatitis secondary to biliary calculi. Cover Bacteroides fragilis/anaerobes (cefotetan, metronidazole, clindamycin, + AG) and enterococcus (ampicillin).

Surgical Rx indicated: gallstone-induced pancreatitis (cholecystectomy when acute phase subsides), perforated peptic ulcer, excision/drainage necrotic/infected foci w/placement of wide-bore drains for continuous postop irrigation

Complications

Pseudocyst (dx: CT scan or U/S) Rx: CT scan or U/S-guided percutaneous drainage w/pigtail catheter for continuous drainage (↑ recurrence rate); conservative approach to reevaluate (w/CT scan or U/S) after 6 to 7 wk and surgically drain if no ↓ in size. Pseudocysts <5 cm generally reabsorbed w/o intervention; those >5 cm require surgery after wall maturation.

Phlegmon (dx: CT scan or U/S) Rx: supportive care

Pancreatic abscess (dx: CT scan-retroperitoneal bubbles, Gram staining and cultures of fluid from percutaneous biopsy) Rx: surgical/catheter drainage + IV abx (imipenem-cilastatin)

Pancreatic ascites (dx: paracentesis-amylase/lipase level in fluid, ERCP) Rx: surgery if exudative/does not resolve spontaneously

GI bleeding: via EtOH gastritis, varices, stress ulcer, or DIC

Renal failure: via hypovolemia (oliguria or anuria), cortical or tubular necrosis (shock, DIC), or thrombosis of renal artery or vein

Hypoxia: via ARDS, pleural effusion, or atelectasis

2. Chronic Pancreatitis

Recurrent/persistent inflammatory process characterized by chronic pain and pancreatic exocrine/endocrine insufficiency

Etiology

Chronic EtOH, obstruction (ampullary stenosis, tumor, trauma, pancreas divisum, annular pancreas), hereditary pancreatitis, severe malnutrition, untreated hyperparathyroidism (hypercalcemia), mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene (TF genotype)

Autoimmune (sclerosing) pancreatitis (5% cases): manifests w/jaundice (63%) + abd pain (35%). CT = diffusely enlarged pancreas, enhanced peripheral rim of hypoattenuation “halo,” and low-attenuation mass in head of pancreas. Labs = ↑ serum IgG4, serum Ig or γ -globulin level, + antilactoferrin Ab, anti–carbonic anhydrase II level, ASMA, or ANA.

Diagnosis

H&P

Persistent/recurrent epigastric + LUQ pain, may radiate to the back

Tenderness over the pancreas, muscle guarding

Significant weight loss, epigastric mass (10%), jaundice (5%-10%)

Bulky/greasy, foul-smelling stools

Labs

↑/Nl serum amylase and lipase

↑ Glucose, bili, alk phos, glycosuria

72-hr fecal fat determination (rarely performed) = excess fecal fat. Fecal elastase test requires 20 g of stool.

Secretin stimulation test (dx pancreatic exocrine insufficiency)

Lipid panel: ↑↑ TGs can cause pancreatitis.

Serum Ca: hyperparathyroidism (rare cause of chronic pancreatitis)

↑ Serum IgG4 (sclerosing pancreatitis and autoimmune pancreatitis)

↑ Serum Ig or γ-globulin level, antilactoferrin Ab, anti–carbonic anhydrase II level, ASMA, or ANA in autoimmune pancreatitis

Imaging

Plain abd radiographs: may reveal pancreatic calcifications (95% spec)

U/S abd: duct dilation, pseudocyst, calcification, presence of ascites

Contrast-enhanced abd CT scan: calcifications, evaluate ductal dilation, r/o pancreatic cancer

EUS (97% sens, 60% spec)

FNAB combined w/EUS = preferred evaluation of modality to r/o malignant cystic/mass lesions

MRCP (preferred to ERCP)

Treatment

Steatorrhea Rx w/pancreatic supplements (e.g., pancrease, pancrelipase [Creon] PRN on basis of steatorrhea/weight loss)

Glucocorticoids (autoimmune pancreatitis)

Surgical intervention if duct obstruction

Transduodenal sphincteroplasty/pancreaticojejunostomy if intractable pain

Clinical Pearls

50% of pts die within 10 yr of chronic pancreatitis or malignant neoplasm.

3. Pancreatic Adenocarcinoma

Risk Factors

Smoking, chronic EtOH, genetics (5%-10% pts have family hx), dipeptidyl peptidase-4 inhibitors, incretin mimetics

Diagnosis

Labs: ↑ alk phos, bili, amylase

H&P

Jaundice, abd pain (dull upper abd pain/vague abd discomfort), wt loss

Imaging

Multidetector helical CT with IV contrast (imaging procedure of choice)

Endoscopic ultrasonography: useful if no identifiable mass on CT + ↑ clinical suspicion

Treatment

Surgery

Curative cephalic pancreatoduodenectomy (Whipple’s procedure) in 10% to 20% pts whose lesion <5 cm, solitary, and without metastases. Surgical mortality rate is 5%.

Palliative surgery (for biliary decompression/diversion)

Palliative therapeutic ERCP with stents

Celiac plexus block = pain relief in 80% to 90% of cases

ChemoRx

Gemcitabine given alone or + platinum agent (erlotinib or fluoropyrimidine)

Combination consisting oxaliplatin, irinotecan, fluorouracil, and leucovorin (Folfirinox)

Radiation

External-beam radiation for palliation of pain

4. Neuroendocrine Pancreatic Neoplasms

a. Gastrinoma

ZE syndrome: hypergastrinemic state via pancreatic/extrapancreatic non–β islet cell tumor (gastrinoma) resulting in peptic ulcer disease

2/3 gastrinomas (sporadic), 60% assoc (MEN-1; AD including hyperparathyroidism, pituitary tumors)

60% gastrinomas = malignant (mets to liver, regional lymph nodes)

Neuroendocrine tumors = 1.3% of all cases of pancreatic cancer

Diagnosis

Gastric acid secretion: serum gastrin level (fasting) >1000 pg/mL

Provocative gastrin level tests:

• Secretin stimulation

• Ca²⁺ stimulation

Gastrinoma localization via arteriography, abd U/S or CT scan or MRI

• Selective portal vein branch gastrin level

• Octreotide scan

H&P

95% sx of peptic ulcer, 60% sx related to GERD, 33% diarrhea, steatorrhea

Treatment

Surgical resection; total gastrectomy/vagotomy (palliative in some pts)

Medical Rx: PPIs, somatostatin or octreotide, chemo (mets)

b Insulinoma

Diagnosis

H&P

Sx typically in AM before meal; fasting hypoglycemia versus reactive hypoglycemia (which is not commonly associated w/insulinoma)

Labs

Overnight fasting blood sugar level + simultaneous plasma insulin, proinsulin, and/or C peptide level will establish existence of fasting organic hypoglycemia in 60% of pts.

Plasma proinsulin, C-peptide, antibodies to insulin, and plasma sulfonylurea levels to r/o factitious insulin use/hypoglycemic agents/autoantibodies against the insulin receptor or insulin. Refer to Table 5-5 in Chapter 5.

Imaging

Abdominal CT scan or MRI

Octreotide scan

Treatment

Enucleation of single insulinoma

Partial pancreatectomy for multiple adenomas

E. Disorders of Small and Large Bowel

1. Diarrhea

↑ Frequency (>200 g/24 hr) of stool w/ ↓ consistency compared with baseline; if lasting >3 wk = chronic diarrhea

Diagnosis

Hx

Travel hx (traveler’s diarrhea)

Short duration (1-3 days) assoc w/mild sx usually viral (rotavirus, Norwalk virus); >3 wk probably not bacterial or viral

Nocturnal diarrhea (common w/diabetic neuropathy)

Onset within minutes: scombroid poisoning (tuna, mahi-mahi, mackerel) (N/V, flushing, diarrhea)

Onset within hr: toxins (Staphylococcus aureus, toxigenic Escherichia coli, Clostridium perfringens, Bacillus cereus, Vibrio parahaemolyticus, [barracuda, grouper, red snapper: ciguatera toxin, causing paresthesia, weakness])

Diarrhea secondary to Salmonella, Shigella, Campylobacter, Yersinia = longer incubation period.

Stress: “functional” diarrhea, IBS

Diarrhea alternating w/constipation: IBS

Foods containing sorbitol/mannitol (osmotic diarrhea), fried rice (B. cereus), undercooked hamburger (E. coli 157:H7), poultry, eggs (Campylobacter, Salmonella, S. aureus), diarrhea after dairy ingestion (lactose intolerance)

Shellfish ingestion (Norwalk virus, Vibrio cholerae, Vibrio mimicus, V. parahaemolyticus, Plesiomonas shigelloides)

Long-distance runners (bloody diarrhea secondary to bowel ischemia)

Daycare centers (rotavirus, Giardia, Salmonella, Shigella, Cryptosporidium, Campylobacter)

Medications: (common agents: Mg-containing antacids, misoprostol, PPIs, methylxanthines [caffeine, theophylline], laxatives, lactulose, colchicine, antiarrhythmic agents (quinidine, digitalis, propranolol), metformin, thyroxine). Abx-induced pseudomembranous colitis should be suspected in any pt receiving abx: (+) Clostridium difficile toxin w/the stool assay, cytotoxin test.

Sexual habits: male homosexuals ↑ incidence of (Giardia, E. histolytica, Cryptosporidium, Salmonella, Neisseria gonorrhoeae, Campylobacter).

Relevant medical hx

• Surgical hx (ileal resection, gastrectomy, cholecystectomy), abd irradiation, DM, hyperthyroidism, watery diarrhea in elderly pts w/chronic constipation via fecal impaction/obstructing carcinoma

• AIDS: Cryptosporidium, Salmonella, CMV, Mycobacterium avium-intracellulare, Kaposi’s sarcoma involving the gut, AIDS enteropathy, Cyclospora spp (cyanobacterium-like bodies)

• Proteinuria, neuropathy: amyloidosis, DM

• Organ transplantation, cancer chemoRx, steroid Rx

Associated sx

• Tenderness, fever, weight loss (IBD, amebiasis, lymphoma, tuberculosis)

• Abd pain + weight loss (carcinoma of pancreas/malignant neoplasia)

• Weight loss despite good appetite (malabsorption, hyperthyroidism)

• Diarrhea and PUD (ZE-syndrome, gastrinoma, gastrocolic fistula)

• Flushing and bronchospasm (carcinoid syndrome)

• LLQ pain, fever and/or bloody diarrhea (diverticulitis)

• Arthritis (IBD, Whipple’s disease)

• Bloody diarrhea, HUS, thrombocytopenic purpura (E. coli O157:H7)

Characteristics of the stool (from pt’s hx)

• Large, foul smelling (malabsorption)

• ↑ Mucus (IBS)

• Watery stools (psychosomal disturbances, fecal impaction, colon carcinoma, IBD or IBS, Cyclospora infection, pancreatic cholera [vasoactive intestinal peptide])

PE

Rectal fistulas, RLQ abd mass (Crohn’s disease)

Arthritis, iritis, uveitis, erythema nodosum (IBD)

Abd masses (neoplasms of colon, pancreas, or liver; diverticular abscess [LLQ mass], IBD)

Flushing, bronchospasm (carcinoid syndrome)

Buccal pigmentation (Peutz-Jeghers syndrome)

Pigmentation (Addison’s disease)

Ammoniac/urinary breath odor (renal failure)

Ecchymosis (vitamin K deficiency secondary to malabsorption, fat-soluble vitamins, celiac)

Fever (IBD, infectious diarrhea, lymphoma)

Goiter, tremor, tachycardia (hyperthyroidism)

Lymphadenopathy (neoplasm, lymphoma, tuberculosis, AIDS, Whipple’s disease)

Macroglossia (amyloidosis)

Kaposi’s sarcoma (AIDS)

Initial Evaluation

Labs (may not be necessary in pts not appearing ill/dehydrated)

• CBC: ↑↑ WBCs w/left shift (? infection); ↓ Hb/Hct levels (? anemia via blood loss); ↑ Hct (? dehydration)

• Serum electrolytes: hypokalemia (diarrhea), hypernatremia (dehydration), hyponatremia (ADH compensation)

• BUN, Cr may be ↑ via dehydration.

• ELISA stool antigen test if suspect Giardia

• Stool evaluation: most cases self-limited generally not necessary; stool cultures considered if pt febrile + bloody diarrhea or immunocompromised. If obtaining stool sample, consider:

• Occult blood ([+] IBD, bowel ischemia, some infection)

• Löffler’s alkaline methylene blue stain for fecal leukocytes ([+] inflammatory diarrhea via Salmonella, Campylobacter, Yersinia, Shigella, invasive E. coli, although low sensitivity).

• Bacterial cultures if bloody stool w/suspected infection (Salmonella, Shigella, Campylobacter, Yersinia, E. coli O157:H7); culture for N. gonorrhoeae active male homosexual pts

• Examine O&P; indirect hemagglutination test (Entamoeba histolytica) if suspect amebiasis and stool exam inconclusive.

• C. difficile toxin: r/o pseudomembranous colitis if receiving abx

• Modified Ziehl-Neelsen stain, acid-fast, or auramine stain in immunocompromised pts w/suspected Cryptosporidium infection

Abd x-rays indicated if abd pain or evidence of obstruction (r/o toxic megacolon, bowel ischemia; pancreatic calcifications = pancreatic insufficiency)

Treatment

NPO, IV hydration, electrolyte abnl correction, d/c possible causative agents (antacids containing Mg, abx)

Antiperistaltic agents (diphenoxylate) used w/caution in pts suspected of IBD or infectious diarrhea; loperamide/bismuth subsalicylate helpful in mild cases

Persistent diarrhea + bacterial/parasitic organism ID, start abx:

• Giardia: metronidazole, 250 mg tid × 7 to 10 days, or tinidazole, quinacrine

• E. histolytica: metronidazole, 750 mg tid × 10 days, + either iodoquinol (650 mg tid × 20 days) or paromomycin

• Shigella: ciprofloxacin (Cipro) 500 mg bid × 3 days, or azithromycin 500 mg qd × 3 days

• Campylobacter: azithromycin 500 mg qd × 3 days or erythromycin 500 mg qid × 3 days

• C. difficile: PO metronidazole or vancomycin

• Cyclospora: TMP-SMX-DS bid × 7 days

• Salmonella (in pts w/sickle cell, HIV, uremia, malignancy, prosthetic device, age <6 mo or >50 yr): Cipro 500 mg bid × 5 to 7 days or TMP-SMX 160 mg/800 mg bid × 5 to 7 days. Mild cases + low-risk pts = no Rx

• V. cholerae O1/O39: Cipro 750 mg × 1, or doxycycline 300 mg × 1, or TMP-SMX 160 mg/800 mg bid × 3 days

• Cryptosporidium: paromomycin 500 mg tid × 7 days (severe)

• Yersinia species: Cipro 500 mg bid × 7 days or TMP-SMX 160 mg/800 mg × 7 days

• Isospora species: TMP-SMX 160 mg/800 mg qid × 10 days, then bid × 3 wk

• Microsporidium species: albendazole 400 mg bid × >3 wk

• Salmonella HIV pts: amoxicillin 1 g tid × 3 to 14 days, Cipro 500 mg bid× 7 days, or TMP-SMX bid × 14 days

IBS Rx: psyllium (fiber products) + ↓ caffeine, chocolate, EtOH, stress; antispasmodics (dicyclomine, hyoscyamine) if resistant cases

Evaluation of Pt w/Chronic or Recurrent Diarrhea

Etiology

Drug induced (including laxative abuse), IBS, lactose intolerance, IBD, malabsorption (mucosal/pancreatic insufficiency, bacterial overgrowth), parasitic infections (giardiasis, amebiasis), functional diarrhea, postsurgical (partial gastrectomy, ileal resection, cholecystectomy)

Endocrine disturbances: DM (↓ sympathetic input to the gut), hyperthyroidism, Addison’s disease, gastrinoma (ZE syndrome), VIPoma (pancreatic cholera), carcinoid tumors (serotonin), medullary thyroid carcinoma (calcitonin)

Pelvic irradiation, colonic carcinoma (villous adenoma)

Collagenous colitis (middle-aged woman, nl endoscopy, subepithelial acellular collagen band on sigmoid bx or right colon; sx resolution w/sulfasalazine alone or steroid combination)

Lymphocytic colitis (lymphocytic infiltration w/o collagen band)

Diagnosis

H&P/initial labs same as new-onset diarrhea; additional labs:

• Sudan III stool stain: presence of fat droplets and meat fibers = malabsorption

• CBC = macrocytic, obtain vitamin B₁₂ + RBC folate levels to r/o megaloblastic anemia secondary to malabsorption

• Mg-induced diarrhea dx w/quantitative fecal analysis for soluble Mg

• 24-hr urine for 5-HIAA if suspected carcinoid syndrome; serum gastrin level if suspected ZE syndrome

• Stool osmolality to evaluate for factitial diarrhea; hypotonic stools (? Munchausen syndrome/malingering because the colon does not excrete free water, hypotonicity indicates addition of water/urine/hypotonic fluid)

Secretory diarrhea from impaired absorption/excessive secretion of electrolytes via enteric infection, neoplasms of exocrine pancreas (VIP, GIP, secretin, glucagon), bile salt enteropathy, villous adenoma, IBD, carcinoid tumor, celiac, cathartic agent ingestion

Osmotic diarrhea from impaired water absorption secondary to osmotic effect of nonabsorbable intraluminal molecules via lactose and other disaccharide excess, pancreatic insufficiency, lactulose/sorbitol/sodium sulfate/antacid induced, postop (gastrojejunostomy, vagotomy, pyloroplasty, intestinal resection)

Dx “osmotic gap” in stool analysis = measured osmolality –2([Na⁺] + [K⁺])

Difference between calculated and actual Osm >50 = osmotic diarrhea

2. Constipation

DDx: metabolic (hypercalcemia, DM, pregnancy, hypothyroidism), structural (colorectal cancer, strictures, hernias, adhesions, endometriosis, rectocele, diverticular disease, volvulus, intussusception, IBD, hematoma of bowel wall secondary to trauma or anticoagulants), drug induced (opiates, anti-Ach, iron, CCB, antipsychotics, antacids w/aluminum, verapamil), neurologic/psychological (IBS, anorexia, depression, MS), neonatal (Hirschsprung’s disease, meconium ileus, atresia), insufficient bulk in diet, travel, old age, spinal cord injury

Treatment

Fiber (25-30 g/day) and fluid intake essential

Physiologic testing (DRE, anorectal manometry, rectal balloon expulsion colonic transit) provides insight/possible indication for MR defecography

Pts >50 yr old or have alarm sx (wt loss, rectal bleeding, change in bowel habits, FHx colon cancer) should undergo colonoscopy

3. Malabsorption

Generalized loss of nutrients, fat, carbohydrates, or protein in digestive tract

Differential Diagnosis

Celiac disease (diarrhea, bloating, wt loss)

• Rx: gluten-free diet

Lactose malabsorption (osmotic diarrhea, bloating, excess flatus)

• Dx: hydrogen breath test (>20 pp million)

• Rx: asx up to 12 g lactose ingestion, dietary diligence

Short-bowel syndrome (<200 cm of small bowel, nl 600 cm) from Crohn’s disease, ischemia, volvulus, desmoid tumors, trauma

• Rx: dietary/electrolyte monitoring, gastric acid control (PPI), hydration

Small intestinal bacterial overgrowth: bacterial overgrowth from change in colonic flora via dysmotility (scleroderma, amyloidosis), altered secretion/anatomy

• Dx: upper endoscopy with culture >10⁵ organisms/mL

• Rx: abx (amoxicillin-clavulanate, fluoroquinolones, tetracyclines, metronidazole)

4. Celiac Disease

Chronic disease characterized by malabsorption and diarrhea precipitated by ingestion of food products containing gluten. Celiac sprue is considered an autoimmune-type disease, with TTG suggested as a major autoantigen. It results from an inappropriate T-cell–mediated immune response against ingested gluten in genetically predisposed individuals who carry either HLA-DQ2 or HLA-DQ8 genes. There is sensitivity to gliadin, a protein fraction of gluten found in wheat, rye, and barley. In patients with celiac disease, immune responses to gliadin fractions promote an inflammatory reaction, mainly in the upper small intestine, manifested by infiltration of the lamina propria and the epithelium with chronic inflammatory cells and villous atrophy.

Diagnosis

H&P

Weight loss, pallor (from anemia), dyspepsia, short stature, and failure to thrive in children and infants

Weight loss, fatigue, pallor, and diarrhea in adults

Angular cheilitis, aphthous ulcers, atopic dermatitis, and dermatitis herpetiformis frequently associated w/celiac disease

Labs

IgA TTG antibody by enzyme-linked immunosorbent assay (TTG test) is the best screening serologic test for celiac disease.

Iron deficiency anemia (microcytic anemia, ↓ ferritin level)

Folic acid deficiency

Serum I_fA (small % of patients are I_fA deficient)

Vitamin B₁₂ deficiency, ↓ Mg, ↓ Ca

Treatment

Gluten-free diet (avoidance of wheat, rye, and barley). Safe grains (gluten free) include rice, corn, oats, buckwheat, millet, amaranth, quinoa.

Correct nutritional deficiencies w/iron, folic acid, Ca, vitamin B₁₂ as needed.

Prednisone 20-60 mg qd gradually tapered is useful in refractory cases.

Clinical Pearls

Celiac disease should be considered in pts w/unexplained metabolic bone disease or hypocalcemia, especially because GI sx may be absent or mild. Clinicians should also consider testing children and young adults for celiac disease if unexplained weight loss, abd pain or distention, and chronic diarrhea are present.

Pts w/celiac disease have an overall risk of cancer that is almost 2× that in the general population: risk of adenocarcinoma of the small intestine and non-Hodgkin’s lymphoma, especially of T-cell type and primarily localized in the gut.

Screening for celiac disease is recommended in first-degree relatives. It should also be considered in type 1 DM and autoimmune disorders such as PBC, primary sclerosing cholangitis, autoimmune hepatitis, IBD, thyroid disease (hypothyroidism occurs in up to 15% of patients with celiac disease), SLE, RA, and Sjögren’s syndrome because of the increased risk of celiac disease in these populations. Screening persons with Down’s syndrome or Turner’s syndrome for celiac disease has also been recommended.

5. Inflammatory Bowel Disease

a. Crohn’s Disease

Inflammatory disease most commonly involving the terminal ileum. Table 6-4 compares Crohn’s disease with ulcerative colitis.

TABLE 6-4

Differentiating Features of Ulcerative Colitis and Crohn’s Disease

	Ulcerative Colitis	Crohn’s Disease
Site of involvement	Involves only colon Rectum almost always involved	Any area of the gastrointestinal tract Rectum usually spared
Pattern of involvement	Continuous	Skip lesions
Diarrhea	Bloody	Usually nonbloody
Severe abdominal pain	Rare	Frequent
Perianal disease	No	In 30% of patients
Fistula	No	Yes
Endoscopic findings	Erythematous and friable Superficial ulceration	Aphthoid and deep ulcers Cobblestoning
Radiologic findings	Tubular appearance resulting from loss of haustral folds	String sign of terminal ileum RLQ mass, fistulas, abscesses
Histologic features	Mucosa only Crypt abscesses	Transmural Crypt abscesses, granulomas (about 30%)
Smoking	Protective	Worsens course
Serology	p-ANCA more common	ASCA more common

From Andreoli, T E, Benjamin IJ, Griggs RC, Wing EJ: Andreoli and Carpenter’s Cecil Essentials of Medicine, 8th ed. Philadelphia, Saunders, 2010.

Diagnosis

H&P

Sx intermittent w/episodic remission:

• Abd tenderness/mass/distention

• Chronic or nocturnal diarrhea, wt loss, fever, night sweats

• Hyperactive bowel sounds (if partial obstruction), bloody diarrhea

• Delayed growth and failure to thrive in children

• Perianal and rectal abscesses, mouth ulcers, atrophic glossitis

• Extraintestinal manifestations: joint swelling and tenderness, hepatosplenomegaly, erythema nodosum, clubbing, SI joint tenderness to palpation

Labs

↓ Hgb/Hct (chronic blood loss, bone marrow inflammation, and vitamin B₁₂ malabsorption)

↓ K, Mg, Ca, alb in pts w/chronic diarrhea

Vitamin B₁₂ and folate deficiency

↑ ESR, (+) ASCA, (−) ANCA

Imaging

Endoscopy: transmural asymmetric/discontinued disease w/deep longitudinal fissures (“cobblestone appearance via submusocal inflammation”), strictures, crypt distortion + inflammation, possible noncaseating granulomas + lymphoid aggregates on bx

Barium imaging (rarely indicated): deep ulcerations (often longitudinal/transverse) and segmental lesions (skip lesions, strictures, fistulas); “thumbprinting” is common; “string sign” in terminal ileum

CT abd: helpful in identifying abscesses/complications

See Table 6-4.

Treatment

Figure 6-1 describes a treatment algorithm for Crohn’s disease.

b. Ulcerative Colitis

Diagnosis

H&P

Abd distention and tenderness

Bloody diarrhea, fever, evidence of dehydration

Extraintestinal manifestations (25% pts): liver disease, sclerosing cholangitis, iritis, uveitis, episcleritis, arthritis, erythema nodosum, pyoderma gangrenosum, aphthous stomatitis

Labs

Anemia, ↑ ESR

↓ K, Mg, Ca, alb

If persistent diarrhea: Consider stool exam O&P, stool culture, and testing for C. difficile toxin.

(−) ASCA (anti-Saccharomyces cerevisiae Ab), (+) p-ANCA (>45% pts; p-ANCA assoc w/relative resistance to medical Rx)

FIGURE 6-1 Crohn’s disease treatment algorithm. (From Goldman L, Schafer AI [eds]: Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)

Imaging

Generally not indicated; double-contrast barium enema w/small bowel follow-through used if colonic strictures prevent evaluation, may reveal continuous involvement (including rectum), pseudopolyps, ↓ mucosal pattern, and fine superficial ulcerations.

Treatment

Rx is based on disease activity. According to Hanauer and Sanborn, disease activity can be defined as follows:

• Mild to moderate disease: The pt is ambulatory and able to take oral alimentation. There is no dehydration, high fever, abdominal tenderness, painful mass, obstruction, or weight loss of >10%.

• Moderate to severe disease: Either the pt has not responded to treatment for mild to moderate disease or has more pronounced symptoms, including fever, significant weight loss, abdominal pain or tenderness, intermittent nausea and vomiting, or significant anemia.

• Severe fulminant disease: Either the pt has persistent symptoms despite outpt steroid Rx or has high fever, persistent vomiting, evidence of intestinal obstruction, rebound tenderness, cachexia, or evidence of an abscess.

TPN in patients with advanced disease

Oral salicylates, such as mesalamine (Asacol, Rowasa)

Corticosteroids have been the mainstay for treating moderate to severe active Crohn’s disease. Prednisone 40 to 60 mg/day is useful for acute exacerbation. Steroids are usually tapered over approximately 2 to 3 mo. Some patients require a low dose for a prolonged period of maintenance.

Steroid analogues are locally active corticosteroids that target specific areas of inflammation in the gastrointestinal tract. Budesonide is available as a controlled-release formulation and is approved for mild to moderate active Crohn’s disease involving the ileum and/or ascending colon.

Immunosuppressants such as azathioprine 150 mg/day, methotrexate, or cyclosporine can be used for severe, progressive disease. In pts with Crohn’s disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission.

Metronidazole 500 mg qid may be useful for colonic fistulas and treatment of mild to moderate active Crohn’s disease. Ciprofloxacin 1 g qd has also been found to be effective in decreasing disease activity.

TNF inhibitors: Infliximab can induce clinical improvement in 80% of pts with Crohn’s disease refractory to other agents. It can be used in combination with other medications such as azathioprine in patients with severe Crohn’s disease. Adalimumab and certolizumab are also effective in inducing remissions and may be useful in adult patients with Crohn’s disease who cannot tolerate infliximab.

Natalizumab effective in increasing the rate of remission and response in pts with active Crohn’s disease.

Hydrocortisone enema bid or tid is useful for proctitis.

Most patients who have anemia associated with Crohn’s disease respond to iron supplementation. ESAs are useful in patients with anemia refractory to treatment with iron and vitamins.

6. Microscopic Colitis

Painless, watery diarrhea without bleeding via drugs/idiopathic

High likelihood (acarbose, ASA, PPIs, NSAIDs, ranitidine, sertraline, ticlopidine)

Intermediate (carbamazepine, lisinopril, simvastatin, paroxetine, flutamide)

• Dx: colonic biopsy (lymphocytic or collagenous colitis)

• Rx: drug cessation, antidiarrheal agents, systemic corticosteroids

7. Irritable Bowel Syndrome

Rome III dx criteria for IBS:

Recurrent abd pain/discomfort ≥3 days/month in past 3 mo (with onset >6 mo prior) associated w/2/3 of the following:

• Pain relived/improved with BM

• Pain onset assoc with changed frequency of BM

• Pain onset assoc with changed stool form/appearance

Risk factors: physical/sexual abuse, infectious gastroenteritis, somatization/psychological traits

Alarm sx (onset age >50 yr, anemia, nocturnal sx, wt loss, bleeding, FHx colon cancer) should prompt further testing tailored to the clinical scenario.

Rx: high-fiber diet and PO linaclotide if constipation IBS, SSRIs, loperamide if diarrheal IBS, behavioral + psychoRx

8. Appendicitis

Etiology

Obstruction of appendiceal lumen w/subsequent vascular congestion, inflammation, and edema; common causes of obstruction are

Fecaliths: 30% to 35% of cases (most common in adults)

Foreign body: 4% (fruit seeds, pinworms, tapeworms, roundworms, calculi)

Inflammation: 50% to 60% of cases (submucosal lymphoid hyperplasia [most common etiology in children, teens])

Neoplasms: 1% (carcinoids, metastatic disease, carcinoma)

Diagnosis

H&P

Abd pain: initially may be epigastric/periumbilical (50%) → localizing to RLQ within 12 to 18 hr. Pain can be found in back/right flank if retrocecal or malrotated appendix.

(+) psoas sign: pain w/right thigh ext, low-grade fever: Temperature may be >38°C if appendiceal perforation.

(+) obturator sign: pain w/internal rotation of flexed right thigh

(+) Rovsing’s sign: RLQ pain on palpation of the LLQ

PE may reveal right-sided tenderness in pts w/pelvic appendix.

Point of maximum tenderness = RLQ (McBurney’s point).

N/V, tachycardia, cutaneous hyperesthesias at the level of T12

Labs

CBC w/diff: leukocytosis w/a left shift (>90%). WBC count generally <20,000/mm³. Higher counts indicative of perforation. ↓ Hgb and Hct in older pt ↑ suspicion of cecal carcinoma.

Imaging

CT abd/pelvis (sens >90%): distended appendix, periappendiceal inflammation, and thickened appendiceal wall

U/S (sens 75%-90%): useful in younger/pregnant women if dx unclear. Anl U/S should not deter surgery if H&P suggest appendicitis.

Treatment

Urgent appendectomy (laparoscopic or open), IV hydration/electrolyte replacement

IV abx prophylaxis to cover gram(−) bacilli and anaerobes (ampicillin-sulbactam 3 g IV q6h or piperacillin-tazobactam 4.5 g IV q8h in adults)

Clinical Pearl

Perforation is common (20% adult pts): sx perforation = pain >24 hr, leukocytosis >20,000/mm³, temp >102° F, palpable abd mass, and peritoneal findings

9. Diverticular Disease

Definitions

Colonic diverticula: herniations of mucosa + submucosa through muscularis along the colon’s mesenteric border at anatomic weak point (site where vasa recta penetrates the muscle wall)

Diverticulosis: asx presence of multiple colonic diverticula

Diverticulitis: inflammatory process/localized perforation of diverticula

Diagnosis

H&P

Painful diverticular disease can manifest w/LLQ pain, relieved by defecation; location of pain may be anywhere in lower abd due to redundant sigmoid colon.

Diverticulitis can cause muscle spasm, guarding, and rebound tenderness predominantly affecting the LLQ.

Diverticular bleed: painless and stops spontaneously in 60% of pts; 70% occurs in right colon

Labs

WBC w/left shift: diverticulitis

Microcytic anemia (chronic bleeding); MCV may be ↑ acute bleeding secondary to reticulocytosis.

Imaging

CT of abd: (sens of 93%-97%, spec ∼100%) for diverticulitis. Typical findings = bowel wall thickening, fistulas, and abscess formation. May also reveal (appendicitis, tubo-ovarian abscess, Crohn’s disease) accounting for lower abd pain.

If bleeding suspected:

• Arteriography if the bleeding >1 mL/min

• ^99mTc sulfa colloid

• ^99mTc-labeled RBC (detect rates as low as 0.12-5 mL/min)

Treatment

Diverticulosis

↑ Fiber intake + regular exercise

Diverticulitis

Mild: Cipro 500 mg PO bid (aerobic colonic flora) + metronidazole 500 mg q6h (anaerobes) + liquid diet for 7 to 10 days

Severe: NPO + aggressive IV abx

• Ampicillin-sulbactam 3 g IV q6h or Piperacillin-tazobactam 4.5 g IV q8h or Cipro 400 mg IV q12h + metronidazole 500 mg IV q6h or (cefoxitin 2 g IV q8h + metronidazole 500 mg IV q6h)

Life-threatening: imipenem 500 mg IV q6h or meropenem 1 g IV q8h

Surgical: resection of involved area + diverting colostomy w/reanastomosis performed when infection controlled

Diverticular Hemorrhage

Blood replacement/correction of volume and clotting abnl

Colonoscopic Rx w/epinephrine injection and/or bipolar coagulation, may prevent recurrent bleeding and ↓ need for surgery.

Surgical resection if bleeding does not stop spontaneously after administration of 4 to 5 U of pRBCs or recurs w/severity within days; if localization attempts unsuccessful → total abd colectomy w/ileoproctostomy.

10. Small Bowel Obstruction

Etiology

Adhesions from prior surgery (60%)

Hernias (25%)

Malignant tumors (15%)

Diagnosis

H&P

Colicky abd pain, N/V, abd distention

Failure to pass gas/feces

Tachycardia, hypotension, dehydration, fever (if strangulation present)

Distended abd, tenderness w/ or w/o palpable mass, hyperactive bowel sounds initially followed by ↓ bowel sounds late in obstruction

Labs

Electrolytes, BUN, Cr, ALT, amylase (generally not helpful)

Imaging

Plain abd films: dilated loops of small intestine w/o evidence of colonic distention, air-fluid levels

CT: sensitive for dx complete or high-grade obstruction (less sensitive for partial obstruction); may also ID cause (abscess, neoplasm).

Barium studies: enteroclysis (PO insertion of a tube into the duodenum and instillation of air and barium) may be useful for low-grade or intermittent obstruction.

Treatment

IV fluid resuscitation, NG suction to empty stomach

Prophylactic broad-spectrum abx

Operative management

11. Adynamic Ileus

Abdominal trauma

Infection (retroperitoneal, pelvic, intrathoracic)

Laparotomy

Metabolic disease (hypokalemia)

Renal colic

Skeletal injury (rib fracture, vertebral fracture)

Medications (e.g., narcotics)

12. Ischemic Bowel Disease

a. Mesenteric Ischemia

Sudden-onset intestinal hypoperfusion via emboli, a/v thrombosis, or vasoconstriction (low-flow states)

Etiology

Mesenteric arterial embolism: usually LA, LV, or cardiac valves (superior mesenteric artery)

Mesenteric arterial thrombosis: hx progressive atherosclerotic stenoses, w/superimposed abd trauma or infection

Mesenteric venous thrombosis: hypercoagulable states, blunt trauma, abd infection, portal HTN, pancreatitis, and portal malignancy

Nonocclusive mesenteric ischemia: atherosclerotic vascular disease, pt treated w/drugs ↓ intestinal perfusion (recent cardiac surgery/dialysis); cocaine use

Diagnosis

H&P

Rapid onset of severe periumbilical pain out of proportion to PE findings

N/V

Initial abd exam may be nl, w/no rebound or guarding, or show minimal distention or occult blood (+) stool.

Later in course, may present w/gross distention, absent bowel sounds + peritoneal signs (in elderly change in mental status).

Labs

Nonspecific (early); later may reveal leukocytosis, acidosis, and ↑ Hct (hemoconcentration).

Protein C/S, AT III, FV Leiden (? hypercoagulable state)

Imaging

Mesenteric angiography (gold standard)

Plain films: nl 25% in early stages; may include ileus, bowel wall thickening, intramural gas.

Doppler U/S evaluation of intestinal blood flow: often limited by air-filled loops of bowel

CT scan: nonspecific. Portal venous/intramural gas possible if development of gangrene. CT more useful if mesenteric vein thrombosis causing acute mesenteric ischemia (90% sens).

Treatment

Rapid blood flow restoration before infarction; correct acidosis, broad-spectrum abx, NG tube decompression

If peritonitis: laparotomy + infarcted bowel resection

SMA embolus: embolectomy. Depending on location/degree of occlusion, surgical revascularization, intra-arterial thrombolytic infusion or vasodilators, or systemic anticoagulation may be considered.

SMA thrombosis: emergent surgical revascularization

Mesenteric venous thrombosis: if peritoneal sx (laparotomy + infarcted bowel resection), if no peritoneal sx (anticoagulate-heparin)

b. Mesenteric Thrombosis

Thrombotic occlusion of the mesenteric venous system involving major trunks or smaller branches and leading to intestinal infarction in its acute form

Etiology

Hypercoagulable states

Portal HTN

Inflammation (pancreatitis, peritonitis [appendicitis, diverticulitis, perforated viscus], IBD, pelvic/intra-abd abscess)

Intra-abd cancer

Postop state or trauma

Thrombosis may begin in small mesenteric branches (e.g., in hypercoagulable states) and propagate to the major venous mesenteric trunks or begin in large veins (e.g., in cirrhosis, intra-abd cancer, surgery) and extend distally. If collateral drainage is inadequate, the intestine becomes congested, edematous, cyanotic, and hemorrhagic and eventually may infarct.

Diagnosis

H&P

Sx: abd pain (90%), typically out of proportion to the physical findings; N/V (50%), GI bleeding (50% occult, 15% gross)

Early: abd tenderness/distention, ↓ bowel sounds

Later: guarding and rebound tenderness, fever, and septic shock

Labs

CBC (leukocytosis), electrolytes (metabolic acidosis [lactic] indicates bowel infarction), amylase

Hypercoagulable state evaluation: PT, PTT, protein C/S, factor V Leiden, antithrombin III

Imaging

Abd CT (diagnostic in 90%): bowel wall thickening, venous dilation, venous thrombus

Treatment

Anticoagulation or thrombolytic Rx

Laparotomy if intestinal infarction is suspected

• Short ischemic segment: resection

• Long ischemic segment:

• Nonviable: resection or close

• Viable: intra-arterial papaverine or thrombectomy followed by “second-look” intervention

13. Colorectal Neoplasia

a. Colorectal Carcinoma

Descending colon (40%-42%), rectosigmoid and rectum (30%-33%), cecum and ascending colon (25%-30%), transverse colon (10%-13%)

Etiology

CRC arises via mutations in microsatellite/chromosomal instability, in germline mutations (basis of inherited syndromes), and in accumulation of somatic mutations in cells (basis of sporadic colon cancer).

Classification and staging

Dukes’ and UICC classification for CRC:

• A: Confined to the mucosa-submucosa (I)

• B: Invasion of muscularis propria (II)

• C: Local node involvement (III)

• D: Distant mets (IV)

Diagnosis

H&P

Presentation initially nonspecific (weight loss, anorexia, malaise)

Right-sided sx:

• Anemia (iron deficiency secondary to chronic blood loss)

• Dull, vague, uncharacteristic abd pain or pt asx

• Rectal bleeding often missed as blood mixed w/feces (occult blood)

• Obstruction/constipation unusual (large lumen)

Left-sided sx:

• Change in bowel habits (constipation, diarrhea, tenesmus, pencil-thin stools)

• Rectal bleeding (bright red blood coating the surface of the stool)

• Intestinal obstruction is frequent because of small lumen.

Labs

+ Fecal occult blood test

Microcytic anemia

↑ Plasma CEA (poor screening test for CRC as may be ↑ in pts w/ [smoking, IBD, alcoholic liver disease]); normal CEA level does not r/o CRC; main use is to monitor CRC recurrence.

LFTs

Imaging

Colonoscopy w/bx (primary assessment tool)

Virtual colonoscopy (sens/spec detection of polyps >10 mm = 70%-96%, 72%-96%, respectively)

CT of abd, pelvis, chest (preoperative staging)

PET scan: accurate in detection of CRC + distant mets; combined PET/CT optimal (colonography) can provide whole-body tumor staging in a single session.

Treatment

Surgical resection: 70% resectable for cure at presentation; 45% of pts are cured by primary resection.

Rx mainstay = fluorouracil; addition of leucovorin (folinic acid) enhances fluorouracil effect

Radiation Rx = useful adjunct to fluorouracil + leucovorin (stage II or III rectal cancers)

For pts w/standard-risk stage III tumors (e.g., involvement of 1-3 regional lymph nodes), both fluorouracil alone and fluorouracil w/oxaliplatin are reasonable choices. Capecitabine is an alternative to IV fluorouracil as adjuvant Rx for stage III CRC.

Irinotecan can be used to treat metastatic CRC refractory to other drugs.

Oxaliplatin, a third-generation platinum derivative, can be used in combination w/fluorouracil and leucovorin for pts w/metastatic CRC whose disease has recurred or progressed despite Rx w/fluorouracil and leucovorin + irinotecan. Fluorouracil + oxaliplatin should be considered for high-risk pts w/stage III cancers (e.g., >3 involved regional nodes [N2] or tumor invasion beyond the serosa [T4 lesion]).

The monoclonal Abs cetuximab, panitumumab, and bevacizumab can be used for advanced CRC.

The liver is generally the initial and most common site of CRC mets. Resection of mets limited to the liver is curative in more than 30% of selected pts. In pts who undergo resection of liver mets, postoperative Rx w/a combination of hepatic arterial infusion of floxuridine and IV fluorouracil improves the outcome at 2 yr.

CRC Screening

Table 6-5 describes CRC screening and surveillance recommendations.

Table 6-6 shows hereditary colorectal cancer syndromes.

F. Disorders of the Liver

1. Approach to the PT with Abnormal Liver Enzymes

Table 6-7 describes typical liver test patterns in hepatocellular necrosis and biliary obstruction.

2. Viral Hepatitis

a. Hepatitis A

Infection by HAV (27-nm, nonenveloped, icosahedral, [+]-stranded RNA virus) transmitted interpersonally via fecal-oral route (contact w/poorly purified food/water); IV transmission rare; vertical transmission also reported.

TABLE 6-5

Colorectal Cancer (CRC) Screening and Surveillance Recommendations^∗

Indication	Recommendations
Average risk	Beginning at age 50 yr: colonoscopy every 10 yr, CT colonography every 5 yr Flexible sigmoidoscopy every 5 yr Double-contrast barium enema every 5 yr (stool blood testing annually or stool DNA testing acceptable but not preferred)
One or two first-degree relatives with CRC at any age or adenoma at age <60 yr	Colonoscopy every 5 yr beginning at age 40 yr, or 10 yr younger than earliest diagnosis, whichever comes first
Hereditary nonpolyposis colorectal cancer	Genetic counseling and screening^† Colonoscopy every 1 to 2 years beginning at age 25 yr and then yearly after age 40 yr^‡
Familial adenomatous polyposis and variants	Genetic counseling and testing^† Flexible sigmoidoscopy yearly beginning at puberty^‡
Personal history of CRC	Colonoscopy within 1 yr of curative resection; repeat at 3 yr and then every 5 yr if normal
Personal history of colorectal adenoma Inflammatory bowel disease	Colonoscopy every 3 to 5 yr after removal of all index polyps Colonoscopy every 1 to 2 yr beginning after 8 yr of pancolitis or after 15 yr if only left-sided disease

^∗ Recommendations proposed by the American Cancer Society and U.S. Multi-Society Task Force on Colorectal Cancer; recommendations for average-risk patients also endorsed by the American College of Radiology.

^† Whenever possible, affected relatives should be tested first because of potential false-negative results.

^‡ Screening recommendation for individuals with positive or indeterminate tests, as well as for those who refuse genetic testing.

From Andreoli, T E, Benjamin IJ, Griggs RC, Wing EJ: Andreoli and Carpenter’s Cecil Essentials of Medicine, 8th ed. Philadelphia, Saunders, 2010.

TABLE 6-6

Hereditary Colorectal Cancer Syndromes

Type	Trait	Gastric	Small Bowel	Colon	Histology	GI Malignancy	Extraintestinal
Familial polyposis	AD	<5%	<5%	100%	Adenoma	100%	—
Gardner	AD	5%	5%	100%	Adenoma	100%	Osteoma, others^∗
Peutz-Jeghers	AD	25%	95%	30%	Hamartoma	Rare	Perioral pigmentation
Juvenile polyposis	AD	—	—	100%	Inflammatory	?	—
Turcot	AR	—	—	100%	Adenoma	100%	Glioma
Cronkhite-Canada	Nonhereditary	100%	50%	100%	Inflammatory	None	Ectodermal changes
Cowden^†	AD	—	—	—	Hamartoma	None	Oral papilloma^‡
Ruvalcaba-Myhre^†	AD	Yes	Yes	Yes	Hamartoma	None	Macrocephaly, penile macules, mental retardation, SC lipomas

^∗ Soft tissue tumors, sarcomas, ampullary carcinoma, ovarian carcinoma.

^† Extremely rare.

^‡ Gingival hyperplasia, breast cancer, thyroid cancer.

From Weissleder R, Wittenberg J, Harisinghani M, Chen JW: Primer of Diagnostic Imaging, 5th ed. St. Louis, Mosby, 2011.

Diagnosis

H&P

Infection w/HAV may have acute or subacute presentation, icteric or anicteric. Severity of illness ↑ w/age (90% infections in children <5 yr may be subclinical).

A preicteric, prodromal phase (1-14 days); 15% no prodrome. Sx onset usually abrupt and may include anorexia, malaise, N/V, fever, headache, abd pain, chills, myalgias, arthralgias, URI sx, constipation, diarrhea, pruritus, urticaria (less common).

Jaundice (>70%); icteric phase is preceded by dark urine.

Bilirubinuria is followed a few days later by clay-colored stools and icterus.

FIGURE 6-2 Serologic test in hepatitis A virus infection. (From Goldberger E: Treatment of Cardiac Emergencies, 5th ed. St. Louis, Mosby, 1990.)

TABLE 6-7

Typical Liver Test Patterns

Test	Hepatocellular Necrosis			Biliary Obstruction
Test	Toxic or Ischemic	Viral	Alcohol	Chronic Complete	Chronic Partial	Acute Complete (first 24 hr)	Infiltration (Chronic)
Aminotransferases	50-100×	5-50×	2-5×	1-5×	1-5×	1-50×	1-3×
Alkaline phosphatase	1-3×	1-3×	1-10×	2-20×	2-10×	May be nl	1-20×
Bilirubin	1-5×	1-30×	1-30×	1-30×	1-5×	Usually nl	1-5×
PT	Prolonged in severe cases, unresponsive to vitamin K			May be prolonged, responsive to vitamin K	Usually nl	Usually nl	Usually nl
Albumin	Nl in acute illness, may be ↓ in chronic illness			Usually nl, but may be ↓ in biliary cirrhosis		Usually nl	Usually nl
Typical disorders	Acetaminophen toxicity, shock liver	Acute hepatitis A or B	Alcoholic hepatitis	Pancreatic carcinoma	Sclerosing cholangitis	Choledocholithiasis	Primary or metastatic carcinoma, Mycobacterium avium-intracellulare infection

Labs (Fig. 6-2)

Dx confirmed by IgM anti-HAV; detectable in almost all infected pts at presentation and remains (+) for 3 to 6 mo.

4× ↑ titer of total Ab (IgM + IgG) to HAV confirms acute infection.

HAV detection in stool and body fluids by EM

HAV RNA detection in stool, body fluids, serum, and liver tissue

↑ ALT AST (usually >8× nl in acute infection)

↑ Bili (usually 5-15× nl)

Alk phos minimally ↑ but higher level in cholestasis

Alb and PT generally nl; if ↑ may herald hepatic necrosis

Imaging

U/S (r/o obstructive jaundice)

Treatment

Self-limited (supportive care; activity as tolerated)

Advise to avoid alcohol and hepatotoxic drugs

Pts w/fulminant hepatitis may require hospitalization/assessment for liver transplantation.

Clinical Pearls

Reported to public health authorities

Common illness in internationally traveled/developing countries; preexposure prophylaxis if travel to endemic area (IG 0.02-0.06 mL/kg IM); Lower dose = effective up to 3 mo; higher dose = effective up to 5 mo.

Postexposure prophylaxis (IG 0.02 mL/kg given IM) if exposure within 2 wk + no previous vaccination; high-risk pts, may vaccinate with immunoglobulin

Inactivated vaccines HAVRIX or VAQTA safe/immunogenic in adults/children >12 mo w/protective Ab levels reached 94% to 100% 1 mo combined HepA/HepB vaccine TWINRIX also available

b. Hepatitis B

Infection by HBV (42-nm hepadnavirus w/an outer surface coat [HBsAg], inner nucleocapsid core [HBcAg; HBeAg], DNA polymerase, and partially double-stranded DNA genome) with transmission via parenteral (needle use, tattooing, piercing, acupuncture, blood transfusion, hemodialysis, sexual contact) and perinatal routes

Diagnosis

H&P

Often nonspecific sx, malaise

Prodrome:

• 15% to 20% serum sickness (urticaria, rash, arthralgia) during early HBsAg

• HBsAg-Ab complex disease (polyarteritis nodosa–arthritis, arteritis, GN)

• Hepatomegaly (87%) w/RUQ tenderness

• Hepatic punch tenderness

• Splenomegaly (10%-15%)

• Jaundice, dark urine, w/occasional pruritus; fever (when present, precedes jaundice and rapidly declines after icteric phase onset)

• Spider angiomas: rare; resolve during recovery

• Rare polyarteritis nodosa, cryoglobulinemia

Labs (Fig. 6-3)

Acute HBV infection is best confirmed by IgM HBcAb in acute or early convalescent serum or by HB DNA.

• Generally, IgM present during onset of jaundice

• Coexisting HBsAg

HBsAg and IgG-HBcAb during acute jaundice are strongly suggestive of remote HBV infection and another etiology for current illness.

HBsAb alone is suggestive of immunization response.

W/recovery, HBeAg is rapidly replaced by HBeAb in 2 to 3 mo, and HBsAg is replaced by HBsAb in 5 to 6 mo.

In chronic HBV, HBsAg and HBeAg are persistent w/o corresponding Ab.

In chronic carrier state, HBsAg is persistent, but HBeAg is replaced by HBeAb.

HBcAb develops in all outcomes.

HBeAg correlation w/highest infectivity; appearance of HBeAb heralds recovery.

LFTs:

• ALT and AST: usually >8× nl at onset of jaundice (low acute ALT/AST ↑ often followed by chronic hepatitis or HCC)

• ↑ Bili: variably ↑ in icteric viral hepatitis

• Alk phos: minimally ↑ (1-3× nl) acutely

Alb and PT: generally nl; if abnl, possible harbinger of impending hepatic necrosis (fulminant hepatitis)

WBC and ESR: generally nl or mildly ↑

Imaging

U/S to r/o obstructive jaundice

Treatment

Acute Hepatitis B

90% of adults spontaneously clear infection; avoid hepatic metabolized drugs; IV hydration if severe vomiting

Hospitalization if pt risk dehydration via poor PO intake, PT ↑, bili level >15 to 20 μg/dL, or if hepatic failure

FIGURE 6-3 Serologic and clinical patterns observed during acute hepatitis B virus infection. Patients in whom the hepatitis B infection does not resolve (chronic carrier state) will demonstrate persistence of HBsAg and will not have an elevation of anti-HBs. (From Ravel R: Clinical Laboratory Medicine, 6th ed. St. Louis, Mosby, 1995.)

Chronic Hepatitis B

Rx: determined by e antigen status and viral qualification

• HbeAg (+): HBV DNA ≥20,000: Rx if ALT ↑ or if biopsy abnl

• HbeAg (−) : HBV DNA ≥2000: Rx if ALT ↑ or if biopsy abnl

Documented cirrhosis [(+) or (−) HBeAg] with

• HBV DNA ≥2000: adefovir 10 mg PO daily or entecavir 0.5 mg PO daily

• HBV DNA <2000: observe

• Decompensated cirrhosis (regardless of HBV DNA level): (lamivudine 100 mg PO daily or entecavir 0.5 mg daily) + tenofovir 300 mg PO daily (∗dosages for non–HIV-infected pt)

Clinical Pearls

Virus and HBsAg are present in high titers in blood for 1 to 7 wk before jaundice and for a variable time thereafter.

Transmission is possible during entire period of HBsAg (and especially during HBeAg) in serum.

Prevention after exposure:

• HBV hyperimmune globulin (HBIG) is given immediately after needle stick, within 14 days of sexual exposure, or at birth, followed by HBV vaccination.

• Standard immune globulin is nearly as effective as HBIG.

Preventive Rx w/lamivudine for pts who test (+) for HBsAg and are undergoing chemoRx may ↑ the risk for HBV reactivation and HBV-associated morbidity and mortality.

c. Hepatitis C

Infection via HCV (single-stranded RNA flavivirus) is mostly via the parenteral route (IV drug use 60% new cases, 20%-50% chronic cases). Occupational needle stick exposure from an HCV(+) source has a seroconversion rate of 1.8% (range, 0%-7%).

Diagnosis

H&P

Sx usually develop 7 to 8 wk after infection (2-26 wk), but 70% to 80% of cases are subclinical.

10% to 20% report acute illness w/jaundice and nonspecific sx (abd pain, anorexia, malaise).

Fulminant hepatitis may rarely occur during this period.

After acute infection, 15% to 25% have complete resolution (absence of HCV RNA in serum, nl ALT).

Progression to chronic infection is common (50%-84%); 74% to 86% have persistent viremia; spontaneous clearance of viremia in chronic infection is rare. 60% to 70% of pts will have persistent or fluctuating ALT levels; 30% to 40% w/chronic infection have nl ALT levels.

15% to 20% of those w/chronic HCV will develop cirrhosis during a period of 20 to 30 yr; in most others, chronic infection leads to hepatitis and varying degrees of fibrosis.

0.4% to 2.5% of pts w/chronic infection develop HCC.

25% of pts w/chronic infection continue to have an asymptomatic course w/nl LFTs and benign histology.

In chronic HCV infection, extrahepatic sequelae include a variety of immunologic and lymphoproliferative disorders (e.g., cryoglobulinemia, membranoproliferative GN, and possibly Sjögren’s syndrome, autoimmune thyroiditis, polyarteritis nodosa, aplastic anemia, lichen planus, porphyria cutanea tarda, B-cell lymphoma, others).

Labs (Fig. 6-4)

Dx is often by exclusion because it takes 6 wk to 12 mo to develop anti-HCV Ab (70% + by 6 wk, 90% + by 6 mo).

Diagnostic tests include serologic assays for Abs and molecular tests for viral particles.

Enzyme immunoassay is the test for anti-HCV Ab:

• The current version can detect Ab within 4 to 10 wk after infection.

• False (−) rate in low-risk populations is 0.5% to 1%.

• False (−) also in immune-compromised persons, HIV-1, renal failure, HCV-associated essential mixed cryoglobulinemia

• False (+) in autoimmune hepatitis, paraproteinemia, and persons w/no risk factors

Recombinant immunoblot is used to confirm + enzyme immunoassays: recommended only in low-risk settings

Qualitative and quantitative HCV RNA tests using PCR:

• Lower limit of detection is <100 copies HCV RNA/mL.

• It is used to confirm viremia and to assess response to Rx.

• Qualitative PCR is useful in pts w/(−) enzyme immunoassay in whom infection is suspected.

• Quantitative tests use either branched-chain DNA or reverse transcription PCR; the latter is more sensitive.

Viral genotyping can distinguish among genotypes 1, 2, 3, and 4, which is helpful in choosing Rx; most of these tests use PCR. (Genotypes 1, 2, 3, and 4 predominate in the United States and Europe [1 is especially common in North America].)

FIGURE 6-4 Hepatitis C virus antigen and antibody. (From Hollinger FB, Dienstag JL. In Murray PR, et al [eds]: Manual of Clinical Microbiology, 6th ed. Washington, DC, American Society for Microbiology, 1995.)

LFTs:

• ALT and AST may be ↑ > 8× nl in acute infection; in chronic infection, ALT may be nl or fluctuate.

• Bili may be ↑ 5 to 10× nl.

• Alb and PT are generally nl; if abnl, may be harbinger of impending hepatic necrosis.

• WBC and ESR are generally nl.

Imaging

U/S is useful to r/o obstructive jaundice and to evaluate rapid liver size ↓ during fulminant hepatitis or mass in HCC.

Treatment

Acute Hepatitis C

HCV PCR detected within 13 days (antibody in >36 days)

If clear HCV viral load via PCR within 3 to 4 mo (no Rx-supportive care)

Chronic Hepatitis C (persistent HCV viral load)

Rx duration depends on HCV RNA level:

Null: no ↓ of 2log10 by wk 12

Partial: 2log10 ↓ by wk12 but detectable by wk 24

Nonresponsive: HCV RNA not cleared by wk 24

Early Virologic Response (EVR): >2log10 ↓ by wk 12, undetectable by wk 24

Complete EVR: undetectable by wk 12 and 24, but not at wk 4

Rapid Virologic Response (RVR): undetectable by wk 4, no change during Rx

Extended Virologic Response (eRVR): undetectable by wk 4 (telaprevir) or wk 8 (boceprevir) and wks 12 and 24

Relapse: undetectable at Rx end, but detectable within 24 wk s/p Rx

Sustained Virologic Response (SVR): cure; undetectable s/p 24 wk Rx

Rx options depend on Genotype:

• FOR ALL genotypes, primary Rx: (PEG-IFN Alfa 2a 180 μg SC/wk or PEG-IFN Alfa 2b 1.5 μg/kg SC/wk) + (ribavirin 400 mg qAM + [if < 75 kg: 600 mg qPM; if >75 kg: 600 mg bid])

• Genotype 1

• Add: telaprevir 750 mg (2 tab) PO tid w/food first 12 wk, then continue without telaprevir for duration of Rx or boceprevir 800 mg (4 cap) PO tid w/food 4 wk after starting primary Rx continued for duration of Rx

• Never combine telaprevir/boceprevir or use either as monoRx

• If eRVR: Continue Rx 24 wk (telaprevir) or 28 wk (boceprevir); check SVR 48 wk (telaprevir), 52 wk (boceprevir).

• If not eRVR: Continue Rx 48 wk (telaprevir 12 wk + PEG-IFN/RBV 48 wk) (boceprevir 44 wk + PEG-IFN/RBV 48 wk); check SVR 72 wk.

• If partial/null response, d/c Rx (failure)

• Genotypes 2/3

• If RVR: May shorten Rx 16 to 24 wk; check SVR wk 40 to 48.

• If EVR: Rx 24 wk; check SVR wk 48.

• If partial/null response: d/c Rx wk 12 (failure).

• Genotype 4

• Rx 48 wk; check SVR at wk 72.

• If null or partial response, d/c Rx wk 12 or 24, respectively.

When Rx HIV-HCV dually infected pt, monitor interactions between direct-acting antivirals (DAAs) and antiretroviral drugs. Rx duration will likely be the full 48 wk.

Liver transplantation: May be only option if HCV-related deteriorating cirrhosis exists.

d. Hepatitis D

Incomplete virus requiring presence of HBV for replication; thus, resolution of HBV infection will result in resolution of HDV infection.

e. Hepatitis E

Similar to HAV (enteric transmission, acute infection only)

Despite low overall mortality, infection during third trimester mortality rate ≥25%

Prevention via good hygiene; avoid dirty water/poorly cooked food.

3. Autoimmune Hepatitis

Diagnosis

H&P

Can manifest asymptomatically → fulminant hepatic failure; most commonly fatigue, pruritus, jaundice, hepatomegaly/splenomegaly

TABLE 6-8

Simplified Diagnostic Criteria for Autoimmune Hepatitis

Variable	Cutoff	Points	Cutoff	Points
ANA or SMA	≥1:40	1	≥1:80	2
LKM			≥1:40	2
SLA			Positive	2
IgG	≥ULN	1	≥1.1 × ULN	2
Histology	Compatible with AIH	1	Typical of AIH	2
Absence of viral hepatitis			Yes	2
Maximum number of points for all antibodies = 2, total = 8.
Probable AIH ≥6 points, definite AIH ≥7 points.

AIH, Autoimmune hepatitis; LKM, liver/kidney microsomes; SLA, soluble liver antigen; SMA, smooth muscle antibody; ULN, upper limit of normal.

From Ferri F: Ferri’s Clinical Advisor: 5 Books in 1. 2013 edition. Philadelphia, Mosby, 2012.

Autoimmune findings: arthritis, xerostomia, keratoconjunctivitis, cutaneous vasculitis, and erythema nodosum

Labs

↑ ALT and AST (both 2-10× nl)

Women 4× > risk than men

Bili and alk phos moderately ↑/nl

↑ γ-Globulin (>2.0 g/dL)

Serum ANA + anti–smooth muscle Ab (64% cases); if (−), p-ANCA helpful

Liver bx = interface hepatitis (lymphoplasmacytic inflammatory infiltrate extending from portal tract → lobule)

Table 6-8 describes simplified diagnostic criteria for autoimmune hepatitis.

Imaging

U/S of liver and biliary tree: r/o obstruction or hepatic mass

Indications for Treatment

AST >10× nl

AST >5× nl, w/↑ γ-globulin 2× nl

Fever, N/V, jaundice

Histologic features of bridging necrosis or multiacinar necrosis

Treatment

Prednisone 60 mg PO/day or (prednisone 30 mg + azathioprine 50 mg PO/day); both achieve remission in 80% pts w/combo Rx = less steroid SE

Taper based on lab response striving for minimum dose needed for maintenance Rx (same regimen 12-18 mo) to ↑ remission rate.

If liver transplant necessary, 10-yr survival rate 75%

4. Cholestatic Liver Disease

a. Primary Biliary Cirrhosis (PBC)

Diagnosis

H&P

Typical pt middle-aged female (50 yr); most asx but develop fatigue, pruritus, dry eyes/mouth over 10-yr period

Labs

(+) Antimitochondrial Ab titer >1:40 (if undetectable, need biopsy)

↑ alk phos >1.5× nl (with nl total bili); ↑ AST/ALT <5× nl possible

Histology: florid duct lesion (duct obliteration w/granuloma formation = pathognomic)

Treatment

Pruritus: cholestyramine (8-24 g qd), sertraline, rifampin

Hyperlipidemia/malabsorption of fat-soluble vitamins via cholestasis: statin Rx + wt loss and vitamin (especially vitamin D) replacement

Asymptomatic stage: Follow LFTs q3-4 mo; if alk phos and/or AST >1.5× nl start ursodeoxycholic acid 12 to 15 mg/kg/day (UDCA).

Liver transplant is only definitive Rx.

b. Primary Sclerosing Cholangitis (PSC)

Diagnosis

H&P

Mean age 40 yr; 60% men (most asymptomatic, but may have pruritus, abd pain, jaundice)

↑ risk cholangiocarcinoma; 2% to 4% pts with IBD develop PSC.

Labs/Imaging

↑ Alk phos (3-10× nl); ↑ ALT/AST (2-3× nl); (+) ANA, smooth muscle abs (20%-50%)

“Beads on a string” (segmental bile duct fibrosis w/saccular dilatation of nl areas)

Cholangiography: MRCP (gold standard); if obstruction, ERCP

Liver bx: periductal fibrosis, fibro-obliterative cholangiopathy

Staging

See Table 6-9.

TABLE 6-9

Staging of Primary Sclerosing Cholangitis

Stage	Description
I: Portal	Portal edema, inflammation, ductal proliferation; abnormalities do not extend beyond the limiting plate
II: Periportal	Periportal fibrosis with or without inflammation extending beyond the limiting plate
III: Septal	Septal fibrosis, bridging necrosis, or both
IV: Cirrhotic	Biliary cirrhosis

From: Cameron AM: Current Surgical Therapy, 10th ed. Philadelphia, Saunders, 2011.

Treatment

Sx relief; liver transplantation

5. Complications of Liver Disease

a. Cirrhosis

Defined histologically as the presence of fibrosis/regenerative nodules in the liver

Etiology

EtOH abuse, secondary to biliary cirrhosis/obstruction of the CBD (stone, stricture, pancreatitis, neoplasm, sclerosing cholangitis), drugs (acetaminophen, INH, MTX, methyldopa), hepatic congestion (CHF, constrictive pericarditis, tricuspid insufficiency, hepatic vein thrombosis, vena cava obstruction), PBC, PSC, chronic hepB/C, Wilson’s disease, α₁-antitrypsin deficiency, infiltrative diseases (amyloidosis, glycogen storage diseases, hemochromatosis), jejunoileal bypass, parasitic infections (schistosomiasis), idiopathic portal HTN, congenital hepatic fibrosis, systemic mastocytosis, autoimmune hepatitis, hepatic steatosis, IBD

Diagnosis

H&P

Jaundice; spider angiomas; ecchymosis; gynecomastia in men; small, nodular liver; ascites; hemorrhoids; testicular atrophy

Labs

Alcoholic hepatitis and cirrhosis: mild ↑ ALT, AST, usually <500 IU; AST > ALT (ratio >2:3)

Extrahepatic obstruction: moderate ↑ ALT/AST to levels <500 IU

Viral, toxic, or ischemic hepatitis: ↑↑ (>500 IU) ALT, AST

↑ Alk phos: extrahepatic obstruction, PBC, and PSC

↑ Serum LDH: liver mets, hepatitis, cirrhosis, extrahepatic obstruction, congestive hepatomegaly

↑ Serum GGTP: alcoholic liver disease, PBC, PSC

↑ Serum bili + urinary bili: hepatitis, hepatocellular jaundice, biliary obstruction

↓ Serum alb: significant liver disease

↑ PT: severe liver damage and poor prognosis

(+) HBsAg: acute or chronic hepatitis B

(+) Antimitochondrial Abs: PBC, chronic hepatitis

↑ Serum copper, ↓ ceruloplasmin: Wilson’s disease

↓ α₁-Globulins (α₁-antitrypsin deficiency), ↑ IgA (alcoholic cirrhosis), ↑ IgM (PBC), ↑ IgG (chronic hepatitis, cryptogenic cirrhosis)

↑ Serum ferritin, ↑ transferrin saturation: hemochromatosis

↑ Blood ammonia: hepatocellular dysfunction

(+) ANA: autoimmune hepatitis

Imaging

U/S: detection of gallstones and dilation of CBDs

CT abd: detection of mass lesions in liver/pancreas; hepatic fat content; identification of idiopathic hemochromatosis; early dx of Budd-Chiari syndrome, dilation of intrahepatic bile ducts; and detection of varices and splenomegaly

Percutaneous liver bx: evaluation of hepatic filling defects; dx of hepatocellular disease or hepatomegaly; evaluation of persistently abnl LFTs; and dx of hemochromatosis, PBC, Wilson’s disease, glycogen storage diseases, chronic hepatitis, autoimmune hepatitis, infiltrative diseases, alcoholic liver disease, drug-induced liver disease, and primary or secondary carcinoma

Scoring system: Table 6-10

Treatment

Variable w/etiology. Figure 6-5 summarizes the management of compensated and decompensated cirrhosis.

Liver transplantation: indicated in otherwise healthy pts (age <65 yr) w/sclerosing cholangitis, chronic hepatitis, cirrhosis, or PBC, w/prognostic information suggesting <20% chance of survival w/o transplantation. Contraindications to liver transplantation are AIDS, most metastatic malignant neoplasms, active substance abuse, uncontrolled sepsis, and uncontrolled cardiac or pulmonary disease.

FIGURE 6-5 Summary of the management of compensated and decompensated cirrhosis. (From Goldman L, Schafer AI [eds]: Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)

TABLE 6-10

The Two Most Commonly Used Scoring Systems in Cirrhosis

1. Child-Turcotte-Pugh (CTP) Score (Range, 5-15)
Parameters	Points Ascribed
Parameters	1	2	3
Ascites	None	Grade 1-2 (or easy to treat)	Grade 3-4 (or refractory)
Hepatic encephalopathy	None	Grade 1-2 (or induced by a precipitant)	Grade 3-4 (or spontaneous)
Bilirubin (mg/dL)	<2	2-3	>3
Albumin (g/dL)	>3.5	2.8-3.5	<2.8
PT (seconds > control) or INR	<4	4-6	>6
PT (seconds > control) or INR	<1.7	1.7-2.3	>2.3
CTP classification: Child A: score of 5-6; Child B: score of 7-9; Child C: score of 10-15
2. Model of End-Stage Liver Disease (MELD) Score (Range, 6-40)
[0.957 × LN (creatinine in mg/dL) + 0.378 × LN (bilirubin in mg/dL) + 1.12 × LN (INR) + 0.643] × 10

From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.

Rx of complications of portal HTN (ascites, esophagogastric varices, hepatic encephalopathy, and HRS)

b. Ascites/Paracentesis

Paracentesis

Indications

Ascites of undetermined etiology

Evaluation for possible peritonitis

Relief of abd pain and discomfort caused by tense ascites

Relief of dyspnea caused by ↑ diaphragm (from ascites)

Evaluation of possible intra-abd hemorrhage in a pt w/blunt abd trauma

Institution of peritoneal dialysis

Contraindications

Bleeding disorders, thrombocytopenia (relative contraindication)

Bowel distention

Infection or surgical scars at the site of needle entry

Acute abdomen

Distended bladder that cannot be emptied w/Foley catheter

Procedure

1. Have the pt empty the bladder (insertion of a Foley catheter is not recommended but may be necessary in certain pts).

2. To identify the site of paracentesis, first locate the rectus muscle; a good site is approximately 2 to 3 cm lateral to the rectus muscle border in the lower abd quadrants. Avoid the following:

a. Rectus muscles (↑ risk of hemorrhage from epigastric vessels)

b. Surgical scars (↑ risk of perforation caused by adhesion of bowel to the wall of the peritoneum)

c. Areas of skin infection (↑ risk of intraperitoneal infection)

d. Note: An alternative site is on the linea alba 3 to 4 cm below the umbilicus.

3. Cleanse the area w/povidone-iodine and drape the abd.

4. Anesthetize the puncture site w/1% to 2% lidocaine.

5. Cautiously insert the needle (attached to a syringe) perpendicular to the skin; a small “pop” is felt as the needle advances through the anterior and posterior muscular fascia, and entrance into the peritoneal cavity is evidenced as a sudden “give” (use caution to avoid the sudden thrust forward of the needle). Some physicians use the Z technique to minimize leaks—the needle is inserted through the skin, then moved laterally before entering the peritoneal cavity to avoid a straight shot from skin to peritoneal cavity that is better for leaking fluid.

6. Remove the necessary amount of fluid (generally not more than 1 L, particularly in cirrhotic pts). If it is a therapeutic paracentesis w/plans to remove a significant amount of fluid, one can use an angiocatheter (basically just an IV) to cover the sharp needle during the procedure and to allow the operator to move the catheter around at will (in small increments) to try to restart flow when it stops. Transfusion of alb may be necessary with >4 to 5 L of paracentesis to avoid hemodynamic deterioration.

7. If it is a diagnostic paracentesis, process the fluid as follows:

a. Tube 1: LDH, glucose, alb levels

b. Tube 2: protein level, specific gravity

c. Tube 3: complete blood cell count and diff

d. Tube 4: save until further notice

8. Draw serum samples for measurement of LDH, protein, and alb.

9. Gram stain, AFB stain, bacterial and fungal cultures, amylase, and TGs should be ordered only when clearly indicated; bedside inoculation of blood culture bottles w/10 to 20 mL of ascitic fluid improves sensitivity in detecting bacterial growth in suspected cases of bacterial peritonitis.

10. If malignant ascites is suspected, consider ascertaining a CEA level on the paracentesis fluid and a cytologic evaluation.

Interpretation of Results

Peritoneal effusion, like pleural effusion, can be subdivided into exudative or transudative on the basis of its characteristics (Fig. 6-6).

The serum-ascites alb gradient (SAAG) (serum alb level–ascitic fluid alb level) correlates directly w/portal pressure and can also be used to classify ascites (Table 6-11). Pts w/gradients of ≥1.1 g/dL or higher have ascites secondary to portal HTN, and those w/gradients <1.1 g/dL do not; the accuracy of this method is >95%.

FIGURE 6-6 Diagnostic algorithm for ascites. (From Ferri FF: Ferri’s Best Test: A Practical Guide to Clinical Laboratory Medicine and Diagnostic Imaging, 2nd ed. Philadelphia, Mosby, 2010.)

TABLE 6-11

Causes of Ascites Based on Normal or Diseased Peritoneum and Serum-to-Ascites Albumin Gradient (SAAG)

Normal Peritoneum
Portal Hypertension (SAAG >1.1 g/dL)	Hypoalbuminemia (SAAG <1.1 g/dL)
Hepatic congestion	Nephrotic syndrome
Congestive heart failure	Protein-losing enteropathy
Constrictive pericarditis	Severe malnutrition with anasarca
Tricuspid insufficiency
Budd-Chiari syndrome
Liver disease	Miscellaneous Conditions (SAAG <1.1 g/dL)
Cirrhosis	Chylous ascites
Alcoholic hepatitis	Pancreatic ascites
Fulminant hepatic failure	Bile ascites
Massive hepatic metastases	Nephrogenic ascites
	Urine ascites
	Ovarian disease
Diseased Peritoneum (SAAG <1.1 g/dL)
Infections	Other Rare Conditions
Bacterial peritonitis	Familial Mediterranean fever
Tuberculous peritonitis	Vasculitis
Fungal peritonitis	Granulomatous peritonitis
HIV-associated peritonitis	Eosinophilic peritonitis
Malignant Conditions
Peritoneal carcinomatosis
Primary mesothelioma
Pseudomyxoma peritonei
Hepatocellular carcinoma

From Vincent JL, Abraham E, Moore FA, et al (eds): Textbook of Critical Care, 6th ed. Philadelphia, Saunders, 2011.

Complications

Persistent leakage of ascitic fluid

Hypotension and shock

Bleeding

Perforated bowel

Abscess formation in area of puncture site

c. Varices

Dilated submucosal veins via portal vein HTN (>10-12 mm Hg), functioning as a shunt between portal and systemic venous circulation; result in severe upper GI hemorrhage (25%-40% cirrhotic pts)

Diagnosis

EGD (Esophagography with barium noninvasive option)

Labs and W/up

Anemia (blood loss, nutritional deficiencies, alcohol myelosuppression)

Thrombocytopenia (hypersplenism, alcohol myelosuppression)

BUN: often ↑ in setting of upper GI bleeding

Cr: often ↑ by hypovolemia, monitor for hepatorenal syndrome

Na⁺: dilutional hyponatremia

Heme (+) stools (type/crossmatch: in preparation for blood transfusion)

INR/PT and PTT: may be ↑ in liver disease or impairment

LFTs: ALT/AST may be nl in cirrhotic pts because of fibrosis, ↑ alk phos, direct hyperbilirubinemia possible if cholestatic liver disease

Serum alb: Severe liver disease results in hypoalbuminemia.

Treatment

Hemorrhage: acute hemodynamic resuscitation (pRBC transfusion, correct coagulopathy/thrombocytopenia), SBP prophylaxis (ceftriaxone or norfloxacin), octreotide 2 to 5 days in conjunction with endoscopic Rx

Ligation (if ↑ risk hemorrhage: Child Pugh B/C or red wale markings on EGD)

Follow-up surveillance EGD 1 to 3 mo s/p obliteration, then q6-12mo indefinitely

Primary prophylaxis: nonselective β-blockers (propranolol 20 mg bid or nadolol 40 mg daily)

d. Portal Hypertension

Portal vein pressure >10 mm Hg

Etiology

↑ Resistance to flow (portal/splenic/hepatic vein thrombosis, cirrhosis, schistosomiasis)

↑ Portal blood flow (splanchnic arterial vasodilation, arterial-portal venous fistulae)

Imaging

Duplex-Doppler U/S (CT/MRI/MRA scanning if results unclear)

Treatment

↓ HTN directly, minimize volume overload, correct underlying disorders, and prevent complications (most notably SBP and variceal bleeding).

e. Hepatic Encephalopathy (HE)

Cognitive disturbance via hepatic insufficiency and portosystemic shunting

Etiology

Precipitating factors in pts w/underlying cirrhosis (UGI bleeding, hypokalemia, hypomagnesemia, analgesic and sedative drugs, sepsis, alkalosis, dietary protein), acute fulminant viral hepatitis, drugs and toxins (INH, acetaminophen-Reye’s syndrome, diclofenac, statins, methyldopa, loratadine, propylthiouracil, lisinopril, labetalol, halothane, carbon tetrachloride, erythromycin, nitrofurantoin, troglitazone), shock or sepsis, fatty liver of pregnancy, metastatic carcinoma, HCC, other (autoimmune hepatitis, ischemic veno-occlusive disease, sclerosing cholangitis, heat stroke, amebic abscesses)

Diagnosis

Requires r/o other causes (medications, metabolic disorders, infectious diseases, intracranial lesions/events). Clinical stages of hepatic encephalopathy are described in Table 6-12. The West Haven criteria is noted here.

West Haven Criteria for Classification of Hepatic Encephalopathy

Stage 0: nl cognitive function/no abnl detected

Stage 1: lack of awareness, euphoria/anxiety, ↓ attention/concentration

Stage 2: lethargy/apathy, altered personality, inappropriate behavior, time disorientation

Stage 3: somnolence to semistupor, confusion, gross disorientation, bizarre behavior

TABLE 6-12

Clinical Stages of Hepatic Encephalopathy

Stage	Asterixis E	EEG Changes	Clinical Manifestations
I (prodrome)	Slight	Minimal	Mild intellectual impairment, disturbed sleep-wake cycle
II (impending)	Easily elicited	Usually generalized	Drowsiness, confusion, coma/inappropriate behavior, disorientation, mood swings
III (stupor)	Present if patient cooperative	Grossly abnormal slowing of rhythm	Drowsy, unresponsive to verbal commands, markedly confused, delirious, hyperreflexia, positive Babinski’s sign
IV (coma)	Usually absent	Appearance of delta waves, decreased amplitudes	Unconscious, decerebrate or decorticate response to pain present (stage IVA) or absent (stage IVB)

From Fuhrman BP, Zimmerman JJ, Carcillo JA, Clark RS, et al (eds): Pediatric Critical Care, 4th ed. Philadelphia, Saunders, 2011.

Stage 4: Coma, unable to test mental state

PE

Variable w/the stage and may reveal the following abnormalities:

• Skin: jaundice, palmar erythema, spider angiomas, ecchymosis, dilated superficial periumbilical veins (caput medusae) in pts w/cirrhosis

• Eyes: scleral icterus, Kayser-Fleischer rings (Wilson’s disease)

• Breath: fetor hepaticus

• Chest: gynecomastia in men w/chronic liver disease

• Abd: ascites, small nodular liver (cirrhosis), tender hepatomegaly (congestive hepatomegaly)

• Rectal exam: hemorrhoids (portal HTN), guaiac + stool (alcoholic gastritis, bleeding esophageal varices, PUD, bleeding hemorrhoids)

• Genitalia: testicular atrophy in men w/chronic liver disease

• Extremities: pedal edema from hypoalbuminemia

• Neurologic: flapping tremor (asterixis), obtundation, coma w/ or w/o decerebrate posturing

Labs

ALT, AST, bili, alk phos, glucose, Ca, electrolytes, BUN, Cr, alb

CBC, Plt count, PT, PTT

Serum/urine toxicology screen (suspected medication/illegal drug use)

Blood/urine cultures, U/A

Venous ammonia level (no correlation w/stage HE but helpful in initial evaluation)

ABGs

Treatment

Identification and Rx of precipitating factors

Restriction of protein intake (30-40 g/day) to ↓ toxic protein metabolites

↓ Colonic ammonia production:

• Lactulose 30 mL of 50% solution qid (dose adjusted via clinical response). Ornithine aspartate 9 g tid is also effective.

• Neomycin 1 g PO q4-6h or given as a 1% retention enema solution (1 g in 100 mL of isotonic saline solution); neomycin should be used w/caution in pts w/renal insufficiency. Metronidazole 250 mg qid may be as effective as neomycin and is not nephrotoxic; however, long-term use can be associated w/neurotoxicity. Rifaximin 1200 mg/day is a viable alternative to metronidazole.

• Lactulose + neomycin are used when either agent is ineffective alone.

Rx of cerebral edema: Cerebral edema is often present in pts w/acute liver failure, and it accounts for nearly 50% of deaths. Monitoring of ICP by epidural, intraparenchymal, or subdural transducers and Rx of cerebral edema w/mannitol (100-200 mL of 20% solution [0.3-0.4 g/kg of BW]) given by rapid IV infusion is helpful in selected pts (e.g., potential transplantation pts). Dexamethasone and hyperventilation (useful in head injury) are of little value in treating cerebral edema from liver failure.

f. Hepatorenal Syndrome (HRS)

Intense renal vasoconstriction resulting from loss of renal autoregulation occurring as a complication of severe liver disease. HRS has 2 types:

Type 1: progressive renal function impairment (doubling of initial serum Cr >2.5 mg/dL or 50% reduction initial 24-hr CrCl to <20 mL/min in <2 wk)

Type 2: stable/slowly progressive renal function impairment (assoc w/refractory ascites)

Etiology

HRS may occur after significant ↓ effective blood volume (paracentesis, GI bleeding, diuretics) or in absence of any precipitating factors.

Diagnosis

Serum Cr >1.5 mg/dL; with no improvement (↓ ≤1.5 mg/dL) after 2 days diuretic withdrawal + albumin volume expansion

Absence of shock, infection, fluid loss, or current Rx w/nephrotoxic drugs

Absence of proteinuria (<500 mg/day) or hematuria (<50 RBC/hpf)

Absence of U/S evidence of obstructive uropathy/parenchymal renal disease

Urinary Na <10 mmol/L

Treatment

Volume challenge (↑ MAP) then large-volume paracentesis (↑ CO, ↓ renal venous pressure) recommended to distinguish HRS from prerenal azotemia in pts w/Fe_Na <1% [if prerenal azotemia the ↑ renal perfusion pressure/renal blood flow results in prompt diuresis]; volume challenge can be accomplished by 100 g albumin in 500 mL isotonic saline.

Vasopressin analogues may ↑ renal perfusion by reversing splanchnic vasodilation (hallmark HRS); IV NE + albumin and furosemide may also be effective.

Rx w/vasoconstrictors 5 to 15 days in attempt to ↓ serum Cr to <1.5 mg/dL:

• Norepinephrine (0.5-3.0 mg/hr IV)

• Midodrine (7.5-12.5 mg tid) + octreotide (100 μg SC tid)

• Terlipressin (0.2-2.0 mg IV q4-12h)

• Add albumin (1 g/kg IV on day 1, then 20-40 g qd)

Liver transplantation (most effective Rx) may be indicated pts (<65 yr) w/sclerosing cholangitis, chronic hepatitis w/cirrhosis, or PBC. Contraindications include AIDS, metastatic disease, substance abuse, uncontrolled sepsis, and uncontrolled cardiac/pulmonary disease.

g. Spontaneous Bacterial Peritonitis

Ascitic fluid bacterial culture (+) with absolute polymorphonuclear count ≥250 cells/μL

Management and Treatment

Third-generation cephalosporin given until culture report finalized

If SBP + hepatorenal syndrome, concomitant IV alb ↑ survival rate

Repeat paracentesis (48 hr) should reveal ↓ PMN count, will be ↑ if secondary peritonitis

Rx secondary peritonitis with norfloxacin (TMP-SMX if fluoroquinolone allergy)

Prophylaxis with norfloxacin warranted if low-protein ascitic fluid <1 g/dL (10 g/L)

h. Hepatocellular Carcinoma (HCC)

Malignant tumor of the hepatocytes; third leading cause of cancer-related death worldwide (80% HCCs occur in cirrhotic pts; other risk factors = male sex, chronic HepB/C, hemochromatosis, α₁-antitrypsin deficiency)

Diagnosis

H&P

33% asx at dx; Abd pain may be initial presentation.

Sx underlying cirrhosis often present; new ascites, encephalopathy, jaundice/bleeding, paraneoplastic syndromes (hypoglycemia, erythrocytosis, hypercalcemia, severe diarrhea) may be present.

Labs

↑ LFTs

↑ AFP 70% pts (sens 40%-65%; spec 80%-94%)

Paraneoplastic syndromes associated w/HCC may cause hypercalcemia, hypoglycemia, and polycythemia.

HBV DNA level (>10,000 copies/mL) is a strong risk predictor of HCC independent of HBeAg, serum aminotransferase level, and liver cirrhosis.

Imaging

U/S (optimal for screening q6mo if ↑ risk), CT scan, or MRI

Percutaneous bx under U/S or CT scan usually is diagnostic. Tissue dx (gold standard); However, HCC reliably diagnosed if

• Mass >2 cm that shows characteristic arterial vascularization is seen on 2 imaging modalities or

• Single (+) imaging method w/AFP >400 μg/mL

Staging and Treatment

According to the Barcelona Clinic Liver Cancer staging classification, Rx is determined according to stage.

Early stage: Liver transplantation is the most effective Rx.

Ablation (via radiofrequency, transarterial hepatic artery chemoembolization, percutaneous ethanol injection) can be used as bridge to transplantation.

Nonresectable HCC: sorafenib

i. Fulminant Hepatic Failure (FHF)

Hepatic encephalopathy + jaundice without preexisting liver disease

Classification:

• Hyperacute = failure within 1 wk

• Acute = failure 1 to 4 wk

• Subacute = failure 4 to 12 wk

Etiologies: acetaminophen overdose (most common cause), infectious (HepA-E, HSV, CMV, EBV, PB19, varicella), drugs (INH, sulfa, NSAIDs, MDMA, cocaine), autoimmune hepatitis

Rx: Recognition should prompt immediate referral to liver transplantation center (1-yr survival 73%). Table 6-13 summarizes the management of fulminant hepatic failure.

j. Liver Abscess

Necrotic infection of the liver, usually classified as pyogenic or amebic.

Etiology

Pyogenic abscess: polymicrobial (streptococcal species [37%], E. coli [33%], Klebsiella pneumoniae [18%], Pseudomonas, Proteus, Bacteroides)

Sources of pyogenic abscess: biliary disease w/cholangitis, gallbladder disease, diverticulitis, appendicitis, penetrating wounds, hematogenous

Amebic abscess: E. histolytica. Transmission is through fecal-oral contamination w/invasion of intestinal mucosa and portal system.

TABLE 6-13

Management of Fulminant Hepatic Failure

No Sedation Except for Procedures

Minimal Handling

Enteric Precautions Until Infection Ruled Out

Monitor

Heart and respiratory rate

Arterial BP, CVP

Core/toe temperature

Neurologic observations

Gastric pH (>5.0)

Blood glucose (>4 mmol/L)

Acid-base

Electrolytes

PT, PTT

Fluid Balance

75% maintenance

Dextrose 10%-50% (provide 6-10 mg/kg/min)

Sodium (0.5-1 mmol/L)

Potassium (2-4 mmol/L)

Maintain Circulating Volume with Colloid/FFP Coagulation Support Only If Required

Drugs

Vitamin K

H₂ antagonist

Antacids

Lactulose

N-acetylcysteine for acetaminophen toxicity

Broad-spectrum antibiotics

Antifungals

Nutrition

Enteral feeding (1-2 g protein/kg/day)

PN if ventilated

From Fuhrman BP, Zimmerman JJ, Carcillo JA, Clark RS, et al (eds): Pediatric Critical Care, 4th ed. Philadelphia, Saunders, 2011.

Diagnosis

H&P

RUQ abd pain, fever, nausea, cough w/pleuritic chest pain, anorexia, jaundice

Labs

Leukocytosis, + blood cultures (50%), ↑ INR (70%), ↑ alk phos (>90%), ↑ ALT/AST (50%), + stool samples for E. histolytica (10%-15%). Serologic testing for E. histolytica does not differentiate acute from prior infection.

Imaging

Abdominal CT (imaging study of choice)

CXR is abnl in 50% of cases: ↑ right hemidiaphragm, pleural effusion, subdiaphragmatic air fluid levels.

U/S (80%-95% sensitivity)

CT or U/S-guided aspiration (50% sterile) in suspected pyogenic abscess.

Treatment

Medical management (amebic liver abscess) versus percutaneous drainage under CT or U/S guidance + IV abx (pyogenic liver abscess)

Empiric broad spectrum abx recommended until culture results available:

• Piperacillin-tazobactam (4.5 g q6h), ticarcillin-clavulanate (3.1 g q4h), or ampicillin-sulbactam (3 g q6h)

• Imipenem (500 mg IV q6h), meropenem (1 g q8h), or ertapenem (1 g qd)

• If PCN allergy: clindamycin 600 to 900 mg IV q8h w/an AG

• Duration of abx Rx: 4 to 6 wk

• Pyogenic abscess: metronidazole (500 mg IV q8h) + quinolone (Cipro 400 mg IV q12h or levofloxacin 500 mg IV qd)

• Amebic abscess: metronidazole 750 mg PO tid × 10 days followed by paromomycin 500 mg tid × 7 days

• Dehydroemetine 1 mg/kg/day IM × 5 days then chloroquine 1 g/day × 2 days; then 500 mg/day for 2 to 3 wk (alternative to metronidazole)

6. Vascular Disorders of the Liver

a. Budd-Chiari Syndrome

Hepatic venous outflow obstruction anywhere from small hepatic veins to suprahepatic IVC in the absence of right-sided heart failure or constrictive pericarditis

Primary BCS = endoluminal obstruction (thromboses/webs)

Secondary BCS = obstruction from nonvascular invasion (malignant/parasitic masses) or extrinsic compression (tumor, abscess, cysts)

Etiology

Hypercoagulable state and/or underlying risk factor for thromboses (80%), myeloproliferative disease (50%), Behçet’s disease, infection, malignancy (<5%), PNH, abd trauma, UC, celiac disease, dacarbazine

Diagnosis

H&P

Fulminant/acute (uncommon): severe RUQ abd pain, fever, N/V, jaundice, hepatomegaly, ascites, ↑ serum aminotransferases, ↓ coagulation factors, and encephalopathy. Early recognition and Rx are essential to survival.

Subacute/chronic (more common): vague abd discomfort, gradual progression to hepatomegaly, portal HTN w/ or w/o cirrhosis; late-onset ascites, LE edema, esophageal varices, splenomegaly, coagulopathy, HRS; asx (15% cases)

Ascites protein content > 2.5 g/dL and SAAG ≥ 1.1 g/dL = BCS + cardiac disease

Imaging

Color and pulsed Doppler U/S: (sens >85%) first-line test

MRI w/gadolinium contrast (second-line test)

Venography (gold standard); useful if difficult case or precise delineation of venous stenoses required

Treatment

Lifelong anticoagulation INR 2 to 3 (LMWH → warfarin [Coumadin]) recommended for all

OCPs contraindicated

Hepatic vein/IVC angioplasty w/ or w/o stenting if refractory to anticoagulation

If unresponsive to medical Rx, TIPS insertion recommended

If unresponsive to TIPS, liver transplant indicated (5-yr survival 70%)

Rx underlying myeloproliferative or other liver dysfunction

b. Portal Vein Thrombosis

Etiology

In adults: cirrhosis (common cause), hypercoagulable states, inflammatory diseases, complications of medical intervention: ambulatory dialysis, chemoembolization, liver transplantation, partial hepatectomy, scleroRx, splenectomy, TIPS, infections (appendicitis, diverticulitis, cholecystitis)

In children: umbilical sepsis

Diagnosis

H&P

May result in portal HTN → esophageal/GI varices; upper GI hemorrhage (hematemesis or melena) can result from esophageal varices.

If abd pain is present, mesenteric venous thrombosis should be suspected.

Imaging

Abd U/S or MRI may show the portal vein thrombosis.

Esophagogastroscopy (esophageal varices)

Treatment

Anticoagulation

Variceal scleroRx or banding

Surgical mesocaval or splenorenal shunt

7. Hepatic Cysts

Simple cysts (uniform thin wall, no echoic structures) asx, usually occur more in women

Cysts <4 cm rarely of clinical significance

If sx (nausea/abd discomfort), r/o cystadenoma (irregularity/internal echoes) via U/S

Rx: Laparoscopic fenestration (simple needle aspiration assoc ↑ recurrence) if cystadenoma as malignant transformation to cystadenocarcinoma possible

8. Hepatic Adenoma (HA)

Sheets of benign hepatocytes without biliary structures/nonparenchymal liver cells

Assoc with use of OCPs

Rx: Resection of HA >5 cm or if pregnancy considered, discontinuation OCP with follow-up imaging if <5 cm

G. Metabolic Liver Disease

1. Alcoholic Hepatitis

Alcohol-induced liver disease: ranges from steatosis (fatty liver) → cirrhosis

• Steatosis: asx, resolves in 4 to 6 wk with abstinence; continued use (>40 g/day) ↑ risk cirrhosis by 30%

Labs

↑ AST (2-6× nl); [AST/ALT ratio 2:3 typical, AST >500/ALT >200 rare]

Alk phos nl to ↑, bili nl to ↑↑↑, ↑ PT, ↓ GGT

↑ CRP, hypophosphatemia, hypomagnesia, CBC (possible leukocytosis w/bandemia or anemia)

Carbohydrate-deficient transferring (CDT) = reliable marker chronic alcoholism

Screen to r/o: HbsAg, anti-Hep C, ferritin/transferrin sat, AFP, liver biopsy if necessary

Imaging

U/S (macrovascular steatosis, hepatocyte ballooning/necrosis, Mallory’s bodies, perivenular fibrosis, portal/lobular inflammation)

Prognosis

Maddrey discriminant function (MDF) score: 4.6× (prothrombin time [s] – control prothrombin time [s]) + total bili (mg/dL)

MDF ≥32 (severe alcoholic hepatitis): short-term mortality risk 50%

Model for End-Stage Liver Disease (MELD) score (prognostic index based on serum total bili, Cr, and INR): similar implications as MDF score

Treatment

Lifestyle change, d/c EtOH abuse, vitamin supplementation, caloric monitoring, protein 1.2 to 1.5 g/kg of ideal BW/day (except in encephalopathic pt)

Indications for initiating Rx (prednisolone 40 mg/day 28 days, 2-wk taper) include: MDF >30, MELD >20

2. Nonalcoholic Fatty Liver Disease (NAFLD)

Dx of exclusion resulting from insulin resistance/metabolic syndrome with presentation ranging from axs hepatic steatosis → cirrhosis. Pending inflammation and fibrosis is referred to as nonalcoholic steatohepatitis (NASH).

Diagnosis

Abdominal imaging via U/S, CT, MRI (reveal steatosis but not fibrosis)

Liver biopsy (confirms NASH)

Treatment

Lifestyle change, wt loss; monitor LFTs q3-6mo; metformin currently investigational Rx

3. Hereditary Hemochromatosis

Autosomal recessive disorder (chromosome 6, HFE gene missense mutations C282Y/H63D) characterized by ↑ iron accumulation in various organs (adrenals, liver, pancreas, heart, testes, kidneys, pituitary) with hepatic iron overload → organ dysfunction, cirrhosis, and hepatocellular cancer

Diagnosis

H&P

↑ Skin pigmentation, hepatomegaly, splenomegaly, hepatic tenderness, testicular atrophy (↓ libido 50% men), amenorrhea (25% women), alopecia, gynecomastia/ascites, fatigue, joint pain, new-onset diabetes, cardiomyopathy, arthropathy

Labs

Transferrin saturation (iron/TIBC) = best screening test; values >45% indicate need for further testing; values >52% in men and >50% in women suggest hemochromatosis. Serum ferritin is helpful but may be ↑ in inflammatory conditions or malignancy.

↑ AST, ALT, alk phos

Hyperglycemia

↓ testosterone, LH, FSH

Measurement of hepatic iron index (hepatic iron concentration divided by age) in liver bx specimen can confirm dx.

Genetic testing (HFE genotyping for C282Y/H63D mutations) useful in pts w/liver disease + suspected iron overload (transferrin saturation >40%). Genetic testing should not be performed as part of initial routine evaluation for hereditary hemochromatosis. Once pt confirmed, first-degree relatives should also be screened. Figure 6-7 describes an algorithm for evaluation of possible hereditary hemochromatosis in a person with (−) family hx.

FIGURE 6-7 Algorithm for elevation of possible hereditary hemochromatosis in a person with a negative family history. (From Goldman L, Schafer AI [eds]: Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)

Pts >40 yr old or serum ferritin level >1000 μg/L ↑ risk cirrhosis

Imaging

CT or MRI of the liver: useful to r/o other causes + may show iron overload in the liver

Treatment

Weekly phlebotomies of 1 to 2 U of blood (each w/ ≈250 mg iron) should be continued until ferritin level <50 ng/mL and transferrin saturation <30%. Subsequent phlebotomies PRN to maintain a transferrin saturation <50% and a ferritin level <100 ng/mL.

Deferoxamine 0.5 to 1 g IM qd or 20 mg SC constant infusion (iron chelating agent) is generally reserved for pts w/severe hemochromatosis w/diffuse organ involvement (liver disease, heart disease) and when phlebotomy is not possible.

4. α₁-Antitrypsin Deficiency

Autosomal codominant deficiency of protease inhibitor α₁-antitrypsin predisposing to early-onset emphysema + hepatic cirrhosis

Diagnosis

Serum α₁-antitrypsin level, genetic analysis for mutation/allele involvement PFTs (obstructive pattern)

CXR (emphysematous change at lung bases)

Chest CT (panacinar emphysema)

H&P

Early-onset, severe, lower-lobe predominant panacinar emphysema (± bronchiectasis)

Sx similar to “typical” COPD presentation (dyspnea, cough, sputum production)

Liver involvement (neonatal cholestasis, cirrhosis, primary hepatocarcinoma)

Dermatologic manifestation (panniculitis) to 85% deficit in plasma α₁-antitrypsin

Treatment

Manage acute exacerbations similar to “typical” COPD

Avoid smoking/factors that would worsen COPD

5. Wilson’s Disease

Rare (1/30,000 newborns) autosomal recessive ↑ hepatic uptake and ↓ biliary excretion of copper

Diagnosis

Usually pts < 45 yr old; ↓ ceruloplasmin, ↑ urinary copper excretion

↑ LFTs

Liver biopsy (excessive intrahepatic copper)

Kayser-Fleischer rings

Neuropsychiatric abnormalities (copper deposition in brain)

Treatment

Chelating agents (trientine, penicillamine) and low-copper diet

H. Disorders of Gallbladder

1. Cholelithiasis

Epidemiology and Demographics

Incidence ↑ with age (highest in 40s-50s)

Female sex, pregnancy, FHx, obesity, ileal disease, OCPs, DM

90% gallstones = cholesterol/mixed type, black-pigmented stones assoc with chronic hemolytic disease/cirrhosis, brown-pigmented stones assoc with biliary tract infection

Physical Exam and Clinical Findings

(60%-80%) asx

If biliary colic: episodic, cramping RUQ pain, may radiate to back/right shoulder

Diagnosis

Labs nl (unless obstruction: ↑ alk phos, ↑ bili)

U/S; if unclear HIDA scan (90% accuracy)

Treatment

Observation recommended for asx gallstones

If calcified “porcelain” gallbladder/stones >3 cm, consider cholecystectomy.

2. Acute Cholecystitis

Inflammation of the gallbladder

Etiology

Gallstones (>95% of cases), ischemic damage to the gallbladder, critically ill pt (acalculous cholecystitis), infectious agents (especially in AIDS pts [CMV, Cryptosporidium]), bile duct stricture, neoplasia

Diagnosis

H&P

Pain/tenderness of right hypochondrium/epigastrium; possibly radiating to infrascapular region. RUQ palpation elicits marked tenderness + stoppage of inspired breath (Murphy’s sign). Guarding, fever (33%), jaundice (25%-50%), palpable gallbladder (20%)

N/V (>70%), fever and chills (>25%), and ingestion of large, fatty meals before onset of pain in the epigastrium and RUQ

Labs

Leukocytosis (12,000-20,000) >70% of pts, alk phos, ALT, AST, bili; bili elevation >4 mg/dL is unusual and suggests presence of choledocholithiasis.

Imaging

U/S of gallbladder: presence of stones, dilated gallbladder w/thickened wall and surrounding edema, fluid stranding

HIDA scan: sensitivity and specificity >90% for acute cholecystitis. Test is reliable only when bili is <5 mg/dL. (+) Test = absence of gallbladder filling within 60 min after the administration of tracer.

CT of abd: in cases of suspected abscess, neoplasm, or pancreatitis

Treatment

Cholecystectomy

Conservative management w/IV fluids and abx (ampicillin-sulbactam 3 g IV q6h or piperacillin-tazobactam 4.5 g IV q8h) may be justified in some high-risk pts to convert an emergency procedure into an elective one w/lower mortality.

ERCP w/sphincterectomy and stone extraction can be performed in conjunction w/laparoscopic cholecystectomy for pts w/choledocholithiasis; 7% to 15% of pts w/cholelithiasis also have stones in the CBD.

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Gastroenterology

Hx

PE

Initial Management

Endoscopic EzZvaluation

Imaging

Treatment

B. Disorders of the Esophagus

1. Dysphagia

a. Oropharyngeal Dysphagia

Diagnosis

b. Esophageal Dysphagia

Diagnosis

Treatment

2. Esophageal Motility Disorders

3. GERD

Etiology

Diagnosis

H&P

Additional Testing

Treatment

4. Barrett’s Esophagus

H&P

Diagnosis

Treatment

Monitoring

5. Esophageal Tumors

H&P

Diagnosis

Treatment

C. Disorders of Stomach and Duodenum

1. Peptic Ulcer Disease

Etiology/Epidemiology

Diagnosis

Treatment

2. Gastroparesis

Differential Diagnosis and Clinical Pearls

Management

3. Gastric Cancer

Physical Exam and Labs

Diagnosis

Treatment

D. Disorders of the Pancreas

1. Acute Pancreatitis

Etiology

Scoring System

“Severe Acute Pancreatitis”

Diagnosis

H&P

Labs

Imaging

Treatment

General Measures

Specific Measures

Complications

2. Chronic Pancreatitis

Etiology

Diagnosis

H&P

Labs

Imaging

Treatment

Clinical Pearls

3. Pancreatic Adenocarcinoma

Risk Factors

Diagnosis

H&P

Imaging

Treatment

Surgery

ChemoRx

Radiation

4. Neuroendocrine Pancreatic Neoplasms

a. Gastrinoma

Diagnosis

H&P