Diarrheal Diseases

Presented by Dr. Kapil Dhingra

Diarrhea

• Diarrhea is defined as passage of abnormally liquid or unformed stools at an increased frequency.

• For adults on a typical Western diet, stool weight >200 g/d can generally be considered diarrheal.

• Diarrhea may be further defined – acute if <2 weeks,– persistent if 2–4 weeks, – chronic if >4 weeks

Acute Diarrhea

• >90% caused by infectious agents.

• Remaining 10%– medications,– toxic ingestions,– ischemia

Infectious Agents– feco-oral transmission – five high-risk groups

1. Travelers - enterotoxigenic or enteroaggregative Escherichia coli, Campylobacter, Shigella, Giardia

2. Consumers of certain foods - – Salmonella, Campylobacter, or Shigella from chicken– enterohemorrhagic E. coli (O157:H7) from undercooked

hamburger– Bacillus cereus from fried rice or other reheated food– Staphylococcus aureus or Salmonella from mayonnaise or

creams– Salmonella from eggs– Listeria from uncooked foods or soft cheeses– Vibrio species, Salmonella, or acute hepatitis A from seafood,

especially if raw.

3. Immunodeficient persons– primary immunodeficiency (e.g., IgA deficiency, common variable

hypogammaglobulinemia, chronic granulomatous disease)– secondary immunodeficiency states (e.g., AIDS, senescence,

pharmacologic suppression)4. Daycare attendees and their family members5. Institutionalized persons

Pathogen Incubation PeriodBacillus cereus, Staphylococcus aureus 1-8 hr

Clostridium perfringens 8-24 hr

Vibrio cholerae, enterotoxigenic Escherichia coli, Klebsiella pneumoniae, Aeromonas species

8–72 h

Enteropathogenic and enteroadherent E. coli, Giardia organisms

1-8 days

C. difficile 1–3 d

Hemorrhagic E. coli 12–72 h

Rotavirus and norovirus 1–3 d

Salmonella, Campylobacter, and Aeromonas species, Vibrio parahaemolyticus, Yersinia

12 h–11 d

• Infectious diarrhea may be associated with systemic manifestations– Reiter's syndrome - arthritis, urethritis, and

conjunctivitis may accompany or follow infections by Salmonella, Campylobacter, Shigella, and Yersinia.

– Hemolytic-uremic syndrome - enterohemorrhagic E. coli (O157:H7) and Shigella

Other Causes• Medications –

antibiotics, cardiac antidysrhythmics, antihypertensives, nonsteroidal anti-inflammatory drugs (NSAIDs),antidepressants, chemotherapeutic agents, bronchodilators, antacids, laxatives

• Ischemic colitis – – acute lower abdominal pain preceding watery,

then bloody diarrhea; – acute inflammatory changes in the sigmoid or left

colon while sparing the rectum • Toxins – – organophosphate insecticides– amanita and other mushrooms;– arsenic

Approach to the Patient: Acute Diarrhea

• Most episodes of acute diarrhea are mild and self-limited and do not justify the cost and potential morbidity rate of diagnostic or pharmacologic interventions.

• Indications for evaluation include – profuse diarrhea with dehydration, – grossly bloody stools, – fever 38.5°C (101°F), – duration >48 h without improvement, – recent antibiotic use, – new community outbreaks, – associated severe abdominal pain in patients >50 years, – elderly (70 years) – immunocompromised patients.

Investigations• The cornerstone of diagnosis in those

suspected of severe acute infectious diarrhea is microbiologic analysis of the stool.

• Workup includes a) cultures for bacterial and viral pathogens,b) direct inspection for ova and parasitesc) immunoassays for certain bacterial toxins (C.

difficile), viral antigens (rotavirus), and protozoal antigens (Giardia, E. histolytica).

• If stool studies are unrevealing, flexible sigmoidoscopy with biopsies and upper endoscopy with duodenal aspirates and biopsies may be indicated.

• Structural examination by sigmoidoscopy, colonoscopy, or abdominal CT scanning (or other imaging approaches) may be appropriate in patients with uncharacterized persistent diarrhea to exclude IBD or as an initial approach in patients with suspected noninfectious acute diarrhea caused by ischemic colitis, diverticulitis, or partial bowel obstruction.

Treatment: Acute Diarrhea

• Fluid and electrolyte replacement are of central importance to all forms of acute diarrhea.

• Profoundly dehydrated patients, especially infants and the elderly, require IV rehydration.

• WHO ORS Sodium chloride 2.6 gm/ltGlucose, anhydrous 13.5 gm/ltPotassium chloride 1.5 gm/ltTrisodium citrate, dihydrate 2.9 gm/dl

Antibiotics

• Reduce severity and duration of diarrhea.

– Treat empirically without diagnostic evaluation

using a quinolone, such as ciprofloxacin (500 mg

bid for 3–5 d).

– Empirical treatment can also be considered for

suspected giardiasis with metronidazole (250 mg

qid for 7 d).

• Antibiotic coverage is indicated, whether or not a causative organism is discovered, in patients who are immunocompromised, have mechanical heart valves or recent vascular

grafts, or are elderly.

• In moderately severe nonfebrile and nonbloody diarrhea, antimotility and antisecretory agents such as loperamide can be useful adjuncts to control symptoms.

• Such agents should be avoided with febrile dysentery, which may be exacerbated or prolonged by them.

Chronic Diarrhea

• Diarrhea lasting >4 weeks

• In contrast to acute diarrhea, most of the causes of chronic diarrhea are noninfectious.

Causes of chronic diarrhea

Secretory causes

Osmotic causes

Steatorrheal causes

Inflammatory causes

Dysmotile causes

Factitial causes

Iatrogenic causes

• Secretory Causes– due to derangements in fluid and electrolyte

transport across the enterocolonic mucosa. – characterized clinically by watery, large-volume

fecal outputs – typically painless – persist with fasting

1. Medicationsantibiotics, cardiac antidysrhythmics, antihypertensives, nonsteroidal anti-inflammatory drugs (NSAIDs),antidepressants, chemotherapeutic agents, bronchodilators, antacids, laxativesChronic ethanol consumption

2. Bowel Resection, Mucosal Disease, or Enterocolic Fistula– inadequate surface for reabsorption of secreted fluids

and electrolytes. – tends to worsen with eating.– With disease (e.g., Crohn's ileitis) or resection of <100

cm of terminal ileum, dihydroxy bile acids may escape absorption and stimulate colonic secretion (cholorrheic diarrhea).

– may contribute to so-called idiopathic secretory diarrhea, in which bile acids are functionally malabsorbed from a normal-appearing terminal ileum.

3. Hormones– Metastatic gastrointestinal carcinoid tumors • watery diarrhea ,episodic flushing, wheezing,

dyspnea, and right-sided valvular heart disease. • Diarrhea is due to the release into the circulation of

potent intestinal secretagogues serotonin, histamine, prostaglandins, and various kinins.

– Gastrinoma• diarrhea due to fat maldigestion owing to pancreatic

enzyme inactivation by low intraduodenal pH

– VIPoma• watery diarrhea hypokalemia achlorhydria syndrome,

also called pancreatic cholera, • due to a non- cell pancreatic adenoma, referred to as a

VIPoma, • secretes VIP and a host of other peptide hormones

pancreatic polypeptide, secretin, gastrin, gastrin-inhibitory polypeptide ,neurotensin, calcitonin, and prostaglandins

– Medullary carcinoma of the thyroid • watery diarrhea caused by calcitonin, other secretory

peptides, or prostaglandins

– colorectal villous adenomas

4. Congenital Defects in Ion Absorption

• defects in specific carriers associated with ion absorption • defective Cl–/HCO3

– exchange (congenital chloridorrhea) with alkalosis (which results from a mutated DRA [down-regulated in adenoma] gene) and

• defective Na+/H+ exchange (congential sodium diarrhea), which results from a mutation in the NHE3 (sodium-hydrogen exchanger) gene and results in acidosis.

• hormone deficiencies such as occurs with adrenocortical insufficiency (Addison's disease) that may be accompanied by skin hyperpigmentation.

• Osmotic Causes– ingested, poorly absorbable, osmotically active

solutes draw enough fluid into the lumen to exceed the reabsorptive capacity of the colon.

– characteristically ceases with fasting or with discontinuation of the causative agent.

1. Osmotic Laxatives– Ingestion of magnesium-containing antacids,

health supplements, or laxatives

2. Carbohydrate Malabsorption– acquired or congenital defects in brush-border

disaccharidases and other enzymes– Ex. lactase deficiency • sugars, such as sorbitol, lactulose, or fructose, are

malabsorbed, and diarrhea ensues with ingestion of medications, gum, or candies sweetened with these poorly or incompletely absorbed sugars

• Steatorrheal Causes– Fat malabsorption – greasy, foul-smelling, difficult-to-flush diarrhea

often associated with weight loss and nutritional deficiencies due to concomitant malabsorption of amino acids and vitamins

– Quantitatively, defined as stool fat exceeding the normal 7 g/d

Causes of steatorrhea1. Intraluminal Maldigestion– most commonly results from pancreatic exocrine

insufficiency– Other causes include • cystic fibrosis; • pancreatic duct obstruction;• somatostatinoma.

– Bacterial overgrowth in the small intestine may deconjugate bile acids and alter micelle formation, impairing fat digestion• occurs with stasis from a blind-loop, • small-bowel diverticulum or • dysmotility

2. Mucosal Malabsorption– most commonly occurs from celiac disease• characterized by villous atrophy and crypt hyperplasia • proximal small bowel • fatty diarrhea associated with multiple nutritional

deficiencies

– Tropical sprue • a similar histologic and clinical syndrome • occurs in residents of or travelers to tropical climates

– Whipple's disease, • due to the bacillus Tropheryma whipplei • histiocytic infiltration of the small-bowel mucosa, • typically occurs in young or middle-aged men; • frequently associated with arthralgias, fever,

lymphadenopathy, and extreme fatigue, and it may affect the CNS and endocardium

3. Postmucosal Lymphatic Obstruction– congenital intestinal lymphangiectasia – acquired lymphatic obstruction secondary to

trauma, tumor, cardiac disease or infection– unique constellation of fat malabsorption with

enteric losses of protein (often causing edema) and lymphocytopenia.

• Inflammatory Causes– accompanied by pain, fever, bleeding, or other

manifestations of inflammation– The unifying feature on stool analysis is the

presence of leukocytes or leukocyte-derived proteins such as calprotectin

– Any middle-aged or older person with chronic inflammatory-type diarrhea, especially with blood, should be carefully evaluated to exclude a colorectal tumor.

Idiopathic Inflammatory Bowel Disease―Crohn's disease ―ulcerative colitis

Distinguishing characteristics of CD and UCUC CD Feature

Only colon SB or colon Location Continuous,

begins distally

Skip lesions Anatomic distribution

Involved in >90%

Rectal spare Rectal involvement

Universal Only 25% Gross bleeding

Rare 75% Peri-anal disease

No Yes Fistulization No 50-75% Granulomas

Endoscopic features of CD and UCUC CD Feature

Continuous Discontinuous

Mucosal involvement

Rare Common Aphthous ulcers

Abnormal Relatively normal

Surrounding mucosa

Rare Common Longitudinal ulcer

No In severe cases

Cobble stoning

Common Uncommon Mucosal friability

distorted Normal Vascular pattern

Pathologic features of CD and UC

UC CD Feature

Uncommon

Yes Transmural inflammation

No 50-75% Granulomas

Rare Common Fissures

No Common Fibrosis

Uncommon Common Submucosal inflammation

Radiologic features of CD and UC

UC CD

Collar button ulcers

Nodularitygranularity

cobble stoningstring sign of SB

Primary or Secondary Forms of ImmunodeficiencyEosinophilic Gastroenteritis

o Eosinophil infiltration of the mucosa, muscularis, or serosa at any level of the GI tract may cause diarrhea, pain, vomiting, or ascites.

o atopic history, o Charcot-Leyden crystals due to extruded eosinophil

contents may be seen on microscopic inspection of stool, and

o peripheral eosinophilia

• Dysmotility Causes– Hyperthyroidism, – carcinoid syndrome, – drugs (e.g., prostaglandins, prokinetic agents)– Primary visceral neuromyopathies or idiopathic acquired intestinal

pseudoobstruction may lead to stasis with secondary bacterial overgrowth causing diarrhea.

– Diabetic diarrhea, often accompanied by peripheral and generalized autonomic neuropathies, may occur in part because of intestinal dysmotility.

– The exceedingly common IBS characterized by disturbed intestinal and colonic motor and sensory responses to various stimuli. Symptoms of • stool frequency cease at night, • alternate with periods of constipation• accompanied by abdominal pain relieved with defecation, • rarely result in weight loss.

• Factitial Causes– accounts for up to 15% of unexplained diarrheas

referred to tertiary care centers– Hypotension and hypokalemia are common co-

presenting features

APPROACH TO THE PATIENT: CHRONIC DIARRHEA

• History – onset – duration – pattern– aggravating (especially diet) and relieving factors – stool characteristics

• Other features– fecal incontinence– Fever– weight loss– Pain– exposures (travel, medications, contacts with diarrhea)– extraintestinal manifestations (skin changes, arthralgias, oral

aphthous ulcers) • Family history of IBD or sprue

• Physical findings– hemodynamic status– thyroid mass, – wheezing, – heart murmurs, – edema, – abdominal masses, – lymphadenopathy,– mucocutaneous abnormalities, – perianal fistulas, or anal sphincter laxity

• Peripheral blood leukocytosis, elevated sedimentation rate, or C-reactive protein suggests inflammation;

• anemia reflects blood loss or nutritional deficiencies;

• eosinophilia may occur with parasitoses, neoplasia, collagen-vascular disease, allergy, or eosinophilic gastroenteritis.

• Blood chemistries may demonstrate electrolyte, hepatic, or other metabolic disturbances.

• Measuring tissue transglutaminase antibodies may help detect celiac disease.

• Patients suspected of having IBS should be initially evaluated with flexible sigmoidoscopy with colorectal biopsies

• For secretory diarrheas medication-related side effects or laxative use should be reconsidered.

• Microbiologic studies should be done including – fecal bacterial cultures– inspection for ova and parasites, and – Giardia antigen assay (the most sensitive test for giardiasis).

• Small-bowel bacterial overgrowth can be excluded by intestinal aspirates with quantitative cultures or with glucose or lactulose breath tests

• Upper endoscopy and colonoscopy with biopsies and small-bowel barium x-rays are helpful to rule out structural or occult inflammatory disease.

• When suggested by history or other findings, screens for peptide hormones should be pursued (e.g., serum gastrin, VIP, calcitonin, and thyroid hormone/thyroid-stimulating hormone, or urinary 5-hydroxyindolacetic acid, and histamine).

• osmotic diarrhea should include tests for lactose intolerance and magnesium ingestion, the two most common causes.

• Low fecal pH suggests carbohydrate malabsorption;

• lactose malabsorption can be confirmed by lactose breath testing or by a therapeutic trial with lactose exclusion and observation of the effect of lactose challenge (e.g., a liter of milk).

• For those with fatty diarrhea, endoscopy with small-bowel biopsy (including aspiration for Giardia and quantitative cultures) should be performed

Tests for steatorrhea• Quantitative test– 72hr stool fat collection – gold standard

• > 7gm/day – pathologic• Qualitative tests– Sudan lll stain

• Detect clinically significant steatorrhea in>90% of cases

– Acid steatocrit – a gravimetric assay• Sensitivity – 100%, specificity – 95% , PPV – 90%

– NIRA (near infra reflectance analysis)• Equally accurate with 72hr stool fat test• Allows simultaneous measurement of fecal fat, nitrogen, CHO

• Chronic inflammatory-type diarrheas should be suspected by the presence of blood or leukocytes in the stool.

• Such findings warrant stool cultures; inspection for ova and parasites; C. difficile toxin assay; colonoscopy with biopsies.

Treatment: Chronic Diarrhea

• depends on the specific etiology • If the cause can be eradicated, treatment is

curative as with resection of a colorectal cancer, antibiotic administration for Whipple's disease or

tropical sprue, or discontinuation of a drug

• Suppression of the underlying mechanism elimination of dietary lactose for lactase deficiency

or gluten for celiac sprue, use of glucocorticoids or other anti-inflammatory

agents for idiopathic IBDs, adsorptive agents such as cholestyramine for ileal

bile acid malabsorption, proton pump inhibitors for the gastric

hypersecretion of gastrinomas,

somatostatin analogues such as octreotide for malignantcarcinoid syndrome,

prostaglandin inhibitors such as indomethacin for medullary carcinoma of the thyroid, and

pancreatic enzyme replacement for pancreatic insufficiency

• Replacement of fat-soluble vitamins may also be necessary in patients with chronic steatorrhea.

Thank you