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GASTROENTEROLOGY

DIARRHEA, CONSTIPATION AND ILEUS

ACUTE DIARRHEA (<4 wk)

Evaluation (NEJM 2009;361:1560; Gastro 2009;136:1874)

•  Hx: stool freq, bloody, abd pain, duration of sxs [~1 wk for viral & bacterial (except C. diff), >1 wk for parasitic], travel, food, recent abx

•  PEx: vol depletion (VS, UOP, axillae, skin turgor, MS), fever, abd tenderness, ileus, rash

•  Further evaluation if warning signs: fever, signific abd pain, blood or pus in stools, >6 stools/d, severe dehydration, immunosupp, elderly, duration >7 d, hosp-acquired

•  Etiology established in only ~3% of community-acquired diarrhea

•  Laboratory: fecal WBC (high false  & ; ✓ fecal calprotectin or lactoferrin Se/Sp >90%), stool cx, BCx, lytes, C. diff (if recent hosp or abx), stool O&P (if >10 d, travel to endemic area, exposure to unpurified H2O, community outbreak, daycare, HIV  or MSM)

± stool ELISAs (viruses, CryptoGiardia), serologies (E. histolytica), special stool cx

•  Imaging/endoscopy: CT/KUB if ? toxic megacolon; sig/colo if immunosupp or cx 

•  Ddx: infxn vs. preformed toxin vs. med-induced vs. initial presentation of chronic diarrhea

Treatment

•  If none of the above warning signs and Pt able to take POs → supportive Rx only: oral hydration, loperamide, bismuth subsalicylate (avoid anticholinergics)

•  If moderate dehydration: 50–200 mL/kg/d of oral solution (1/2 tsp salt, 1 tsp baking soda, 8 tsp sugar, & 8 oz OJ diluted to 1 L w/ H2O) or Gatorade, etc. If severe, LR IV.

•  For traveler’s diarrhea, bismuth or rifaximin useful for prophylaxis & empiric Rx

•  Empiric abx for non–hospital-acquired inflammatory diarrhea reasonable: FQ × 5–7 d

abx rec for Shigella, cholera, Giardia, amebiasis, Salmonella if Pt >50 y or immunosupp or hospitalized, ? Campylobacter (if w/in 4 d of sx onset)

avoid abx if suspect E. coli O157:H7 as may ↑ risk of HUS

CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA (CDAD)

Pathogenesis

•  Ingestion of C. difficile spores → colonization when colonic flora Dd by abx or chemo → release of toxin A/B → colonic mucosal necrosis & inflammation → pseudomembranes

•  ↑ toxigenic strain (NAP 1/027) ↑ mort. & length of hosp (esp. in elderly) (NEJM 2008;359:1932)

•  Additional risk factors: elderly, nursing home residents, IBD, PPI (CID 2011;53:1173)

Clinical manifestations (a spectrum of disease)

•  Asx colonization: <3% healthy adults; ~20% in hospitalized patients on antibiotics

•  Acute watery diarrhea (occ bloody) ± mucus, often w/ lower abd pain, fever, ↑↑↑ WBC

•  Pseudomembranous colitis: above sx + pseudomembranes + bowel wall thickening

•  Fulminant colitis (2–3%): toxic megacolon (colon dilatation ≥6 cm on KUB, colonic

atony, systemic toxicity) and/or bowel perforation

Diagnosis

•  Only test if symptomatic; test liquid stool (unless concern for ileus)

•  Stool EIA: detects toxin B and/or A (1–2% strains make A); fast (2–6 h); most often used

•  PCR: quick, becoming test of choice (Mayo 2012;87:643)

•  Alternative is 2-step method: ✓ glutamate dehydrogenase (GDH) EIA (high Se,  even if no toxin production), then if , ✓ cytotoxin assay or toxigenic cx

•  Consider flex sig if dx uncertain and/or evidence of no improvement w/ standard Rx

Treatment (Infect Control Hosp Epidemiol 2010;31:431)

•  Start contact precautions; if possible d/c abx ASAP; stop antimotility agents

•  Mild-Moderate (WBC <15k, Cr <1.5 × baseline, age <65 y and no peritoneal sx): MNZ 500 mg PO tid × 10–14 d

•  Severe (WBC >15k or Cr >1.5× baseline or age ≥65 y): vanco 125 mg PO qid × 10–14 d

•  Complicated (ileus, malabsorption, shock, megacolon, peritonitis): vanco 500 mg PO q6h and MNZ 500 mg IV q8h; PR vanco if ileus, but avoid if evidence of toxic megacolon; abd CT & urgent surg consult re: colectomy; ? IVIG fidaxomicin 200 mg bid noninferior to vanco PO & ↓ rate of recurrence (NEJM 2011;364:422)

•  If Pt needs to stay on original abx, continue C. diff. Rx for ≥7 d post-abx cessation

•  Stool carriage may persist 3–6 wk postcessation of sx and should not trigger further Rx

•  Recurrent infection: 15–30% risk after d/c of abx, most w/in 2 wk of stopping abx

1st relapse: if mild; repeat 14-d course of MNZ or vanco

2nd relapse: PO vanco taper for 6 wk

>2 relapses: vanco taper & adjunctive Rx such as S. boulardii, probiotics, rifaximin, nitazoxanide, fidaxomicin or cholestyramine (binds vanco so cannot take concurrently)

Fecal transplant in refractory disease appears safe and effective (Clin Gas Hep 2011;9:1044; NEJM 2013;368:407)

•  Probiotics may prevent CDAD by 66% in non-immunosuppressed Pts (Annals 2012;157:878)

CHRONIC DIARRHEA (>4 wk; Gastro 2004;127:287)

Medications (cause ↑ secretion, ↑ motility, Δ flora, ↑ cell death or inflammation)

•  PPI, colchicine, abx, H2RA, SSRIs, ARBs, NSAIDs, chemo, caffeine

Osmotic (↓ diarrhea with fasting,  fecal fat, ↑ osmotic gap)

•  Lactose intolerance: seen in 75% nonwhites & in 25% whites; can be acquired after gastroenteritis, med illness, GI surgery. Clinical: bloating, flatulence, discom- fort, diarrhea. Dx: hydrogen breath test or empiric lactose-free diet. Rx: lactose- free diet, use of lactose-free dairy products and lactase enzyme tablets.

•  Other: lactulose, laxatives, antacids, sorbitol, fructose

Malabsorption (↓ diarrhea with fasting, ↑ fecal fat, ↑ osmotic gap)

•  Celiac disease (NEJM 2012;367:2419)

Immune rxn in genetically predisposed Pts (~1% pop) to gliadin, a component of gluten (wheat protein) → small bowel inflammatory infiltrate → crypt hyperplasia, villus atrophy → impaired intestinal absorption

Other s/s: Fe/folate defic anemia; osteoporosis; dermatitis herpetiformis (pruritic papulovesicular); ↑ AST/ALT

Dx: IgA tissue transglutaminase or endomysial Abs ~90% Se & >98% Sp (JAMA 2010;303:1738). Small bowel bx and clinical/serologic response to gluten-free diet definitive.

Rx: gluten-free diet; 7–30% do not respond to diet → ? wrong dx or noncompliant

Complic: ~5% refractory (sx despite strict dietary adherence), risk of T-cell lym- phoma and small bowel adenocarcinoma

•  Whipple’s disease: infxn w/ T. whipplei (NEJM 2007;365:55)

Other s/s: fever, LAN, edema, arthritis, CNS Ds, gray-brown skin pigmentation, AI & MS, oculomasticatory myorhythmia (eye oscillations + mastication muscle contract)

Rx: (PCN + streptomycin) or 3rd-gen ceph × 10–14 d → Bactrim for ≥1 y

•  Small Intestinal bacterial overgrowth (SIBO; Inf Dis Clin 2010;24:943): ↑ SI bacteria from incompetent/absent ileocecal valve, s/p RYGB, scleroderma, diabetes, s/p vagotomy → fat & CHO malabsorption. Dx:  14C-xylose & H+ breath tests; Rx: cycled abx (eg, MNZ, FQ, rifaximin)

•  Pancreatic insufficiency: most commonly from chronic pancreatitis or pancreatic cancer

•  ↓ bile acids due to ↓ synthesis (cirrhosis) or cholestasis (PBC) → malabsorption

•  Other: s/p short bowel resection (short bowel syndrome), Crohn’s disease, chronic mesenteric ischemia, eosinophilic gastroenteritis, intestinal lymphoma, tropical sprue

Inflammatory ( FOB, fever, abd pain,  fecal WBC or lactoferrin or calprotectin)

•  Infections: particularly parasitic (incl above pathogens & Strongyloides), CMV, TB

•  Inflammatory bowel disease

•  Radiation enteritis, ischemic colitis, neoplasia (colon cancer, lymphoma)

Secretory (nocturnal diarrhea freq described, no Δ diarrhea after NPO, normal osmotic gap)

•  Hormonal: VIP (VIPoma, Verner-Morrison), serotonin (carcinoid), thyroxine, calcitonin (medullary cancer of the thyroid), gastrin (Zollinger-Ellison), glucagon, substance P

•  Laxative abuse

•  Neoplasm: carcinoma, lymphoma, villous adenoma

•  ↓ bile acids absorption (s/p ileal resection, Crohn’s) → colonic exposure & ↑ secretion

•  Lymphocytic colitis, collagenous colitis (may be a/w meds, including NSAIDs)

Motility (normal osmotic gap)

•  Irritable bowel syndrome (10–15% of adults; BMJ 2012;345:e5836; NEJM 2012;367:1626)

Due to altered intestinal motility/secretion in response to luminal or environmental stimuli w/ enhanced pain perception and dysregulation of the brain–gut axis

Rome III criteria: recurrent abd pain ≥3 d/mo over last 3 mo plus ≥2 of following: (i) improvement w/ defecation, (ii) onset w/ Δ freq of stool, (iii) onset w/ Δ in form of stool

Rx sx-guided (AJG 2009;104:51)
Pain: antispasmodics, TCA, SSRI
Bloating: rifaximin (NEJM 2011;364:22), probiotics
Diarrhea: loperamide, alosetron (5-HT3 antagonist) for women (↑ risk of ischemic colitis), rifaximin

Constipation: ↑ fiber 25 g/d, lubiprostone (Cl channel activator)

•  Scleroderma; diabetic autonomic neuropathy; hyperthyroidism; amyloidosis; s/p vagotomy

Figure 3-2 Workup of chronic diarrhea

CONSTIPATION & ADYNAMIC ILEUS

Constipation (Gastro 2013;144:211 & 218)

•  Definition (Rome III): ≥2 of the following during last 3 mo at least 25% of time: straining, lumpy/hard stools, incomplete evacuation, sensation of anorectal obstruction, manual maneuvers to facilitate defecation, stool frequency <3 per wk

•  Etiology

Functional: normal transit, slow transit, pelvic floor dysfunction, constipation-predom IBS

Meds: opioids, anticholinergics (TCAs & antipsychotics), Fe, CCB, diuretics, NSAIDs

Obstruction: cancer, stricture, rectocele, anal stenosis, extrinsic compression

Metabolic/endo: DM, hypothyroid, uremia, preg, panhypopit, porphyria, ↑ Ca, ↓ K, ↓ Mg

Neuro: Parkinson’s, Hirschsprung’s, amyloid, MS, spinal injury, autonomic neuropathy

•  Diagnosis: H&P w/ DRE. Labs: consider CBC, electrolytes w/ Ca, TSH

Colonoscopy if alarm sx: wt loss,  FOBT, fever, FHx of IBD or colon cancer. Sigmoidoscopy if no alarm sx & <50 y

For functional constipation: Sitzmark study, anorectal manometry, defecography

•  Treatment: Bulk laxatives (fiber ~20 g/d) → osmotic laxative → stimulant laxative

Bulk laxatives (psyllium, methylcellulose, polycarbophil): ↑ colonic residue, ↑ peristalsis

Osmotic laxatives (Mg, sodium phosphate [avoid if CKD], lactulose): ↑ water in colon

Stimulant laxatives (senna, castor oil, bisacodyl, docusate sodium): ↑ motility & secretion

Enema/suppository (phosphate, mineral oil, tap water, soapsuds, bisacodyl)

Lubiprostone (see “IBS”). Methylnaltrexone and alvimopan for opioid-induced (AJG 2011;106:835)

Linaclotide ↑ stool freq, ↓ straining/bloating (NEJM 2011;365;6:527)

Acute pseudo-obstruction (adynamic ileus)

•  Definition: loss of intestinal peristalsis in absence of mechanical obstruction

Ogilvie’s = acute colonic adynamic ileus in presence of competent ileocecal valve

•  Precipitants: intra-abd process (surgery, pancreatitis, peritonitis); severe medical illness

(eg, PNA, sepsis); intestinal ischemia; meds (opiates, anticholinergics); electrolyte abnl

•  Clinical manifestations: abd discomfort, N/V, hiccups, abd distention, ↓ or absent bowel

sounds, no peritoneal signs (unless perforation); cecum ≥10–12 cm → ↑ risk of rupture

•  Dx: supine & upright KUB vs. CT→ gas-filled loops of small & large intestine. Must exclude mechanical obstruction (absence of gas in rectum).

•  Treatment: NPO, mobilize (walk, roll), d/c Rxs that ↓ intestinal motility, enemas; decompression (NGT, rectal tube, colonoscope); neostigmine (for colonic), methylnaltrexone (for small bowel, ? colonic)

NUTRITION IN HOSPITALIZED PATIENTS

Pathophysiology

•  When acutely ill, catabolism > anabolism, carbohydrates preferred due to ↓ fat metab

•  When recovering, anabolism > catabolism, so body restores protein and muscle loss

Critical illness (see “Mech Ventilation” for recs in that setting) (JPEN 2009;33:277)

•  Goals not well validated but 18–30 kcal/kg/d & 1.2–1.5g/kg/d protein

•  Enteral: start w/in 24–48 hrs of admission, trend toward ↓ infxns and mortality in early (<48 h) feeding in critically ill Pts who are adequately nourished at presentation Contraindic: inadequate volume resusc, intestinal obstruction, major GIB, severe vomiting, ischemic bowel

•  Parenteral: start if unable to tolerate enteral w/in 7 d or evidence of protein/cal malnutrition on admission; may be beneficial in those below calorie goal w/ enteral (Lancet 2013;381:385) Contraindic: hyperosmolality, severe electrolyte disturbances, severe hyperglycemia; sepsis is relative contraindication

End-stage liver disease (Clin Gastro & Hep 2012;10:117)

•  Nutrition status predicts morbidity/mortality; malnutrition in 50–90% of cirrhotics

•  Protein requirement higher than healthy adults (1–1.5 g/kg/d vs. 0.8 g/kg/d); protein restrict only if acute hepatic encephalopathy Supplement vitamins ADEK, zinc, selenium; do not carbohydrate restrict

Refeeding syndrome (BMJ 2008;336;1495)

•  Fluid/electrolyte shifts in malnourished Pts receiving artificial nutrition; hypophosphatemia is hallmark, but also ↓ K & Mg, hyperglycemia, ↓ thiamine, hypervolemia

•  Prevention: (1) thiamine 300 mg PO qd, vit B complex tid, MVI; (2) start feeding at ~10 kcal/kg/d (or 25% of estim goal) & ↑ over 3–5 d; advance only when electrolytes are w/in nl range; (3) follow electrolytes and volume status, rehydrating and repleting