DIARRHEA

Definition:
• Passage of abnormally liquid or unformed stools at an increased frequency
• stool weight >200 g/d - diarrheal.
• acute if <2 weeks, persistent if 2–4 weeks, and chronic if >4 weeks

Differential Diagnosis:
• Pseudodiarrhea – frequent passage of small volumes of stool,
o associated with
▪ rectal urgency,
▪ tenesmus,
▪ feeling of incomplete evacuation,
o accompanies IBS or proctitis
• Fecal incontinence – involuntary discharge of rectal contents
o neuromuscular disorders or structural anorectal problems

ACUTE DIARRHEA
Causes
• Infectious Agents –
o acquired by fecal-oral transmission
o ingestion of food or water contaminated with pathogens from human or animal feces
o immunocompetent person - resident fecal microflora >500 taxonomically distinct species
▪ actually, play a role in suppressing the growth of ingested pathogens
▪ Disturbances of flora by antibiotics can lead to diarrhea such as Clostridium difficile
o five high-risk groups
▪ Traveller’s diarrhoea –
• enterotoxigenic or enteroaggregative Escherichia coli, Salmonella. Shigella, Campylobacter,
Aeromonas, Coronavirus,
• Russia - Giardia-associated diarrhea
• Nepal - Cyclospora.
• Cruise ships - norovirus.
▪ Consumers of certain foods
• picnic, banquet, or restaurant
o chicken - Salmonella, Shigella , Campylobacter
o undercooked hamburger – enterohemorrhagic E. coli (O157:H7)
o fried rice or other reheated food – Bacillus cereus
o mayonnaise or creams - Staphylococcus aureus, Salmonella
o eggs – Salmonella
o fresh or frozen uncooked foods – Listeria
o seafood – Vibrio, Salmonella, or acute hepatitis A
▪ Immunodeficient persons -
• primary immunodeficiency
o IgA deficiency
o hypogammaglobulinemia,
o chronic granulomatous disease
• secondary immunodeficiency - AIDS,
• enteric pathogens – severe and protracted diarrheal
• opportunistic
o Bacteria – Mycobacterium
o Viruses – cytomegalovirus, adenovirus, and herpes simplex
o Protozoa - Cryptosporidium, Isospora belli
▪ Day-care attendees and their family members –
• Shigella, Giardia, Cryptosporidium, rotavirus
▪ Institutionalized persons –
• C. difficile

o Pathophysiology:
▪ preformed bacterial toxins, enterotoxin- producing bacteria,
• Diarrhea associated with marked vomiting and minimal or no fever
• within a few hours after ingestion
• secondary to small-bowel hypersecretion
▪ enteroadherent pathogens –
• watery diarrhea secondary to small-bowel hypersecretion
• vomiting is usually less, abdominal cramping or bloating is greater, and fever is higher
▪ bloody diarrhea –
• Invasive bacteria and Entamoeba histolytica
▪ diarrhea may be associated with systemic manifestations
 • Reactive arthritis, urethritis, and conjunctivitis - Salmonella, Campylobacter, Shigella, and Yersinia
• Yersiniosis may also lead to an autoimmune-type thyroiditis, pericarditis, and glomerulonephritis
• hemolytic-uremic syndrome - enterohemorrhagic E. coli (O157:H7) and Shigella

• Non-infectious agents –
o Side effects from medications most common
▪ antibiotics,
▪ cardiac antidysrhythmics, antihypertensives, n
▪ onsteroidal anti-inflammatory drugs (NSAIDs),
▪ antidepressants,
▪ chemotherapeutic agents,
▪ bronchodilators,
▪ antacids, and laxatives
o Ischemic colitis - >50 years
o Ingestion of toxins including
▪ organophosphate insecticides,
▪ amanita, mushrooms, arsenic

APPROACH TO THE PATIENT:

Indications for evaluation

o profuse diarrhea with dehydration,
o grossly bloody stools,
o fever ≥38.5°C (≥101°F),
o duration >48 h without improvement,
o recent antibiotic use,
o new community outbreaks,
o associated severe abdominal pain in patients aged >50 years, and
 o elderly (≥70 years) or immunocompromised patients.

o cornerstone of diagnosis in those suspected of severe acute infectious diarrhea is microbiologic analysis of the stool.
o cultures for bacterial and viral pathogens;
o direct inspection for ova and parasites; and
o immunoassays for certain bacterial toxins (C. difficile), viral antigens (rotavirus), and protozoal antigens (Giardia, E.
histolytica)
o Persistent diarrhea is commonly due to Giardia , additional causative organisms
o C. difficile (especially if antibiotics had been administered), E. histolytica, Cryptosporidium, Campylobacter
o Other test
o flexible sigmoidoscopy with biopsies
o upper endoscopy with duodenal aspirates and biopsies
o colonoscopy,
o abdominal computed tomography (CT) scanning
o Brainerd diarrhea is an increasingly recognized entity characterized by an abrupt-onset diarrhea that persists for at least 4 weeks,
but may last 1–3 years, and is thought to be of infectious origin

TREATMENT
o Fluid and electrolyte replacement
o Oral sugar-electrolyte solutions
o In moderately severe nonfebrile and nonbloody diarrhea
o antimotility and antisecretory agents such as loperamide
o should be avoided with febrile dysentery, which may be exacerbated or prolonged by them
o Bismuth subsalicylate may reduce symptoms of vomiting and diarrhea
o not be used to treat immunocompromised patients or those with renal impairment because of the risk of bismuth
encephalopathy.
o moderately to severely ill patients with febrile dysentery
o empirically without diagnostic evaluation
▪ quinolone, such as ciprofloxacin (500 mg bid for 3–5 d)
o suspected giardiasis
▪ metronidazole (250 mg qid for 7 d).
o Because of resistance to first-line treatments, newer agents such as nitazoxanide may be required for Giardia and Cryptosporidium
infections.
o Antibiotic prophylaxis is only indicated for certain patients traveling to high-risk countries
o ciprofloxacin, azithromycin, or rifaximin
 CHRONIC DIARRHEA
o lasting >4 weeks
o causes –
o Secretory
o Osmotic
o Steatorrheal
o Inflammatory
o Dysmotile
o Factitial
o Iatrogenic
o
o Secretory Causes
o Derangements in fluid and electrolyte transport across the enterocolonic mucosa
o characterized clinically by watery, large-volume fecal outputs that are typically painless and persist with fasting
o stool osmolality – normal, no fecal osmotic gap.
o MEDICATIONS –
▪ most common secretory causes of chronic diarrhea
▪ stimulant laxatives - senna, cascara, bisacodyl, castor oil
▪ Chronic ethanol consumption- enterocyte injury with impaired sodium and water absorption
▪ Environmental toxins – arsenic
▪ angiotensin-receptor blocker – Olmesartan
o BOWEL RESECTION, MUCOSAL DISEASE, OR ENTEROCOLIC FISTULA
▪ Inadequate surface for reabsorption of secreted fluids and electrolytes
▪ worsen with eating
▪ disease - Crohn’s ileitis or resection of <100 cm of terminal ileum
• dihydroxy bile acids may escape absorption - stimulate colonic secretion (cholerheic diarrhea) may
lead to idiopathic secretory diarrhea or bile acid diarrhea (BAD)
• Reduced negative feedback regulation of bile acid synthesis in hepatocytes by fibroblast growth
factor 19 (FGF-19) produced by ileal enterocytes
• Leads to bile-acid synthesis producing BAD
• Alternative cause of BAD is a
o genetic variation in the receptor proteins on the hepatocyte for FGF-19
o genetic variation in the bile acid receptor (TGR5) in the colon, resulting in accelerated colonic
transit.
▪ Partial bowel obstruction, ostomy stricture, or fecal impaction – paradoxically increased fecal output
o HORMONES
▪ Metastatic gastrointestinal carcinoid tumors or, rarely, primary bronchial carcinoids –
• Produce watery diarrhea due to release into the circulation of potent intestinal secretagogues
including serotonin, histamine, prostaglandins and various kinins.
• Pellagra-like skin lesions - serotonin overproduction with niacin depletion
▪ Gastrinoma
• refractory peptic ulcers
• diarrhoea one-third of cases
• results from fat maldigestion owing to pancreatic enzyme inactivation by low intraduodenal pH
▪ VIPoma – watery diarrhea, hypokalemia achlorhydria syndrome
▪ Medullary carcinoma of the thyroid –
• Calcitonin - secretory peptides

o Osmotic Causes –
o Ingested, poorly absorbable, osmotically active solutes draw enough fluid into the lumen
o OSMOTIC LAXATIVES
▪ magnesium-containing antacids, health supplements, or laxatives
▪ stool osmotic gap (>50 mosmol/L) =
• serum osmolarity (typically 290 mosmol/kg) − (2 × [fecal sodium + potassium concentration])
o CARBOHYDRATE MALABSORPTION
▪ acquired or congenital defects in brush-border disaccharidases and other enzymes leads to osmotic diarrhea
with a low pH.
▪ most common causes - lactase deficiency
o WHEAT AND FODMAP INTOLERANCE
▪ fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs).

o Steatorrheal Causes
o Fat malabsorption may lead to greasy, foul-smelling, difficult-to-flush diarrhea often associated with weight loss and
nutritional deficiencies
o Intraluminal maldigestion, mucosal malabsorption, or lymphatic obstruction may produce steatorrhea.
o Increased fecal output is caused by the osmotic effects of fatty acids
o Quantitatively,
▪ steatorrhea is defined as stool fat
 • exceeding the normal 7 g/d;
• rapid-transit diarrhea may result in fecal fat up to 14 g/d;
• daily fecal fat averages 15–25 g with small-intestinal diseases
• >32 g with pancreatic exocrine insufficiency.
o INTRALUMINAL MALDIGESTION
▪ pancreatic exocrine insufficiency
• Chronic pancreatitis
• cystic fibrosis,
• pancreatic duct obstruction
• somatostatinoma
▪ Bacterial overgrowth in the small intestine –
• deconjugate bile acids - alter micelle formation - impairing fat digestion
▪ cirrhosis or biliary obstruction may lead to mild steatorrhea –
• deficient intraluminal bile acid concentration
o MUCOSAL MALABSORPTION
▪ celiac disease
• gluten-sensitive enteropathy affects all ages
• villous atrophy and crypt hyperplasia in the proximal small bowel
• Fatty diarrhea associated with multiple nutritional deficiencies
▪ Tropical sprue
• residents of or travelers to tropical climates
• abrupt onset and response to antibiotics
▪ Whipple’s disease
• Tropheryma whipplei
▪ Mycobacterium avium-intracellulare infection in patients with AIDS
▪ Abetalipoproteinemia
• rare defect of chylomicron formation and fat malabsorption
• associated with acanthocytic erythrocytes, ataxia, and retinitis pigmentosa
o POSTMUCOSAL LYMPHATIC OBSTRUCTION
▪ rare congenital intestinal lymphangiectasia
▪ Aquired lymphatic obstruction secondary to trauma, tumor, cardiac disease or infection,
• fat malabsorption with enteric losses of protein

o Inflammatory Causes
o Crohn’s disease and chronic ulcerative colitis
o associated with uveitis, polyarthralgias, cholestatic liver disease (primary sclerosing cholangitis), and skin lesions
(erythema nodosum, pyoderma gangrenosum)
o PRIMARY OR SECONDARY FORMS OF IMMUNODEFICIENCY
▪ IgA deficiency
▪ Hypogammaglobulinemia
o EOSINOPHILIC GASTROENTERITIS
▪ Eosinophil infiltration of the mucosa, muscularis, or serosa at any level of the GI tract may cause diarrhea
o Dysmotility Causes
o Hyperthyroidism, carcinoid syndrome
o drugs (e.g., prostaglandins, prokinetic agents) may produce hypermotility with resultant diarrhea
o Primary visceral neuromyopathies or idiopathic acquired intestinal pseudoobstruction may lead to stasis with secondary
bacterial overgrowth causing diarrhea
o Diabetic diarrhea, often accompanied by peripheral and generalized autonomic neuropathies
o Factitial Causes
o Munchausen syndrome or eating disorders
▪ covertly self-administer laxatives alone or in combination with other medications (e.g., diuretics)
▪ Hypotension and hypokalemia are common co-presenting features.

TREATMENT

▪ chronic diarrhea - fluid and electrolyte

▪ elimination of dietary lactose for lactase deficiency
▪ elimination of gluten for celiac sprue
▪ use of glucocorticoids or other anti-inflammatory agents for idiopathic IBDs
▪ bile acid sequestrants for bile acid malabsorption
▪ PPIs for the gastric hypersecretion of gastrinomas
▪ somatostatin analogues such as octreotide for malignant carcinoid syndrome
▪ prostaglandin inhibitors such as indomethacin for medullary carcinoma of the thyroid
▪ pancreatic enzyme replacement for pancreatic insufficiency
▪ empirical therapy
o mild or moderate watery diarrhea - diphenoxylate or loperamide
o severe diarrhea - codeine or tincture of opium
o should be avoided with severe IBD, because toxic megacolon may be precipitated
 ▪ diabetic diarrhea - Clonidine, an a2-adrenergic agonist
o S/E causes postural hypotension
▪ 5-HT3 receptor antagonists- alosetron, ondansetron - may relieve diarrhea and urgency in patients with IBS diarrhea
▪ Other medications approved - diarrhea associated with IBS – rifaximin
▪ Replacement of fat-soluble vitamins may also be necessary in patients with chronic steatorrhea

APPROACH TO THE PATIENT