Clinical Case: Diarrhea

Plan
Section (1):
Importance, normal function, and defining the
subject
Section (2):
The subject and its various implication
(pathophysiology, classification, differential,
treatment etc.)
Section (3):
Case discussion on the subject, and attempting to
answer the relevant questions
Importance, normal function, and
defining the subject

Importance
Very common
1 billion suffer from an episode of acute
diarrhea worldwide each year
250,000 require hospitalization
5000 die (mostly elderly)
Economic burden may exceed $20 billion
Infectious and acute most common
Mostly developing countries, contrary to
constipation, mostly developed counteries.
Importance - 2
Can be a mere nuisance symptopms at one
extreme
On another, they can be life-threating.
Mild symptoms can signal serious underlying illness
Colorectal cancer
Thyroid disease
Imperative for clinicians to appreciate the
pathyophysiology, etiologic classification, and
diagnostic strategies, as well as principles of
management
Normal Physiology
Small intestines digest and assimilate food
Colon + Intestine do also:
secretion + absorption of water & electrolyte
Storage & transport of intraluminal contents aborally
Salvage of nutrients after bacterial metabolism that are not
absorbed in small intestines.
Alterations in fluid and electrolyte handling contribute
significantly to diarrhea.
Alterations in motor + sensory functions of colon
result in highly prevalent syndromes such as IBS,
chronic diarrhea, and chronic constipation.
Functional level at different sites
Stomach and small bowel:
Synchronized MMC in fasting
Accommodation, trituration, mixing, transit
Stomach 3h
Small Bowel 3 h
Illeal Reservoir empties boluses
Colon: irregular mixing, fermentation, absorption,
transit
Ascending + transverse: resvervoirs
Descending: Conduit
Sigmoid/rectum: volitional reservoir
Neural control
Intrinsic innervation (Enteric nervous system):
Myenteric, submucosal, and mucosal neuronal layers
They modulate the action of neurostransmiters (eg., Ach,
VIP, Opoids, NE, SE, ATP, and NO)
Myenteric smooth muscle
Submucosal plexus absorption + secretion
Mucosal - blood flow
Extrinsic: ANS: Vagus Small intestine+ proximal
colon; pelvic parasympathetic (S2-4) distal
colon; major substance: Ach, and Substance P.
Sympathetic = excite sphincter + inhibit nonsphinteric
muscles
Its normal function
Visceral afferents convey sensation from the gut
to CNS:
Course along sympathetic fibres
Go to cell bodies in DRG (in spinal cord)
Go to dorsal horn of spinal cord
Conveyed to brain along the lateral spinothalamic
tract + nocireceptive dorsal column pathway
Projected after thalamus to insula + cerebral cortex to
be perceived.
Others are just afferent synapses in prevertebral ganglia and
reflexly modulate intestinal motility
Intestinal Fluid Absorbtion and
Secretion
Daily average 9 L of fluid in GI tract
1 L reaches colon as residual
Stool excretion of fluid is about 0.2 L/d
Colon has large capacitance and functional reserve
Can recover four times its usual volume of 0.8 L/d
Very helpful in intestinal absorptive or secretory disorders
Sodium absorption in colon, electrogenic @ apical
membrane.
Neural plus non neural mediators affect the colon, such as
cholinergic, adrenergic and serotonergic mediators
Can be affected by angiotensin + aldostrone secretion
Due to Renal tubules have similar embryologic origin of distal
colon

Motility of Small Intestine
cyclical event migrating motor complex MMC
serves as a housekeeper to clear nondigestiable
residues
Occurs while fasting
On average 4 mins of propagation and contraction
Occurs every 60-90 minutes.
If you eat: small intestine produce irregular
mixing contraction of low amplitude
Except at distal illium where powerful intermittent
contraction occur to empty illeum by bolus transfers
Ileocolonic Storage and Salvage
Distal ileum acts as a reservoir and emptying place for bolus movements
intermittently
Allows time to salvage of fluid + nutritents + electorlytes
Segmentation by haustra in colon
Compartmentalises food + facilitate mixing
Rentention of residue + forms stools
Resident bacteria in colon
Digest unabsorbed carbohydrates
Provides nutrients to mucosa
Diarrhea happens due to alteration of
its reservoir function @ proximal site
Or Propulsive function @ left colon
Contstipation happen as a result of disturbance of
Rectal or segmoidal resoirvoir
Dysfunction of pelvic floor
Coordination of defecation

Defining it: Diarrhea
Loosely defined as:
Passage of abnormally liquid or unformed stools
@ increased frequency
For weight > 200 g/d
Acute < 2 weeks, persistant 2-4 weeks
Chronic > 4 weeks in duration
< 200 g/d stool weight
1) Pseudodiarrhea frequent urgency of passage of small volumes of
stool ( IBS or Proctits)
2) Fecal incontinence, involuntary discharge of rectal contents
caused, often, by neuromascular or antorectal problems
They should be always investigated in patients complaining of
diarrhea
Overflow Diarrhea due to fecal impaction happens in nursury
homes mostly
Acute Diarrhea
90% infectious agents
Accompanied by:
Fever Vomitting Abdominal pain
Remaining 10%:
Medication Toxins Ischemia Others
Infectious agents: Fecal-oral transmission
Infected food or contaminated water
Disturbed flora by Antibiotics (C.dif.)
Bypassing immune + non-immune defense mechanism
Five high-risk group in US: Travelers, Food consumers,
Immunodeficient, daycare attendee and their family members, and
institutionalised patients.
Clincial features: Profuse watery diarrhea secondary to intestinal
secretion.
Treatment: Fluid and electrolyte replacement, maybe Antibiotics

The subject and its various
implication (pathophysiology,
classification, differential,
treatment etc.)

Chronic diarrhea
Lasting > 4 weeks warrants evaluation
To exclude underlying pathology
Mostly, noninfectious
Classified into 7 causes:
1) Secretory
2) Osmotic
3) Steatorrheal
4) Inflammatory
5) Dysmotile
6) Factitial causes
7) Iatrogenic
Secretory causes
Exogenous Stimulant Laxatives
Chronic Ethanol Ingestions
Other drugs and toxins
Endogenous laxatives (dihydroxy bile acids)
Idiopathic secretory diarrhea
Certain bacterial infection
Bowel resection
Hormone producing tumors (VIPOMA, carcinoid, medullary
cancer of thyroid, mastocytosis, gastrinoma, colorectal
villous adenoma)
Addisons disease
Congenital Electolyte absorption defect
Secretory causes
Due to derangements in fluid and electrolyte
transport across the enterocolonic mucosa
Characterised clinically by:
Watery, large volume fecal utputs
Typically painless and persist with fasting
Thereis no malabsorbed solute
Stool osmolality is accounted for by normal
endogenous electrolite with no fecal osmotic gap.
Medication
Side effects from ingestion of drugs and toxins
Most common secretory cause
Over the counter medications
Habitual use of stiumulant laxitives[e.g., senna, cascara]
Chronic Ethanol consumption Enterocyte injury
Impaired sodium and water absorption
Inadvertant ingestion of certain toxins (e.g., arsenic)
Bacterial infections occassionally persist and cause it
Bowel Resection, Mucosal Disease, or
Entercolic Fistula
Inadquate surface for reabsorption of secreted fluids +
electrolyte
Unlike other subsets:
They tend to be worse while eating
With disease states e.g., Chrons ileitis or resection of <100 cm of
terminal illium
Dihydroxy bile acids may escape absorption and stimulate colonic secretion
(Cholorrheic diarrhea)
Called Idiopathic secretory diarrhea
Idiopathic bile acid malabsorption 40% of unexplained chronic
diarrhea
Fibroblast growth factor (FGF) 19 produced by eneterocyte results
in synthesis of excessive bile acids too much to be reabsorbed by
ileal function.
It causes bile acids diarrhea
Partial bowel obstruction, ostomy striction, or fecal impaction
Can lead to paradoxically increased fecal output due to fluid hyper secretion
Hormones
Uncommon, yet classic example for secretory.
Metastatic Carcinoid tumors
Produce watery diarrhea alone or as part of carcinoid sx
Episodic flushing, Wheezing, Dysnea, Rt sided vavular heart dx
Intestinal secretagogues (SE, Hista., PGC)
Pellagra-like skin lesion, rarely happen due to serotonin with niacin depletion
Gastrinoma (neuroendocrine tumor)
Refractory peptic ulcer and diarrhea due to fat mal-abs.
Watery diarrhea hypokalemia achlorhydria syndrome (Pancreatic cholera)
Due to non-B cell pancreatic adenoma or VIPOMA
Secretion of VIP and a host of other peptides.
Often massive stool volume >3 L/d; daily, up to 20 L can be.
Life threatening complications: dehydration, neuromascular dysfunction from electrolyte imbalance. Flushing, and
hyperglycemia may accompany VIPOMA
Medullary carcinoma of thyroid
Watery diarrhea due to calcitonin
Systemic mastocytosis
Associated with skin lesion, urticaria pigementosa
Cause diarrhea that is secretory by histamine due to intestinal infiltration of mast cells
Large colorectal villous adenoma
Rarely associated with secretory diarrhea
May cause hypokalemia, and can be inhibited by NSAID, and mediated by PGC
Congenital Defects in Ion Absorption
Rarely, can cause diarrhea from birth.
Include:
Defective CL/HCO3 exchange (congenital chloridorrhea)
With alkalosis (results from a mutated DRA [down regulated
adenoma] gene)
Defective Na/H exchange (congenital sodium diarrhea)
Results from a mutation in NHE3 (sodium hydrogen exchanger
gene
Results in acidosis
Adrenocortical insufficiency (addisons disease)
Can be accompanied with skin hyperpigmentation
Osmotic Cause
Osmotic Diarrhea occurs when ingested, poorly
absorbably, osmotically active solutes draw enough fluid
into lumen to exceed the re-absorptive capacity of the
colon. Fecal water output increases in propotion to such
solute load. Ceases with fasting or with stopping
causative agents
Examples:
Osmotic laxatives (Mg, PO4, SO4)
Lactase and other disacchride defeciency
Nonabsorbable carbohydrates (sorbitol, lactulose,
polyethylene glycol)
Osmotic laxatives
Ingestion of magnesium contaning antacid
Typified by as tool of osmotic gap >50 mosmol/L
Serum Osmolarity (typically, 290 mosmol/kg) [2 x(fecal
sodium + potassium concentration)]
Measurement of fecal somolarity is no longer
recommended
cause even when measured immediately after
evacuation
maybe erroneous because carbohydrates are
metabolized by clonic bacteria causing increase in
osmolarity
Carbohydrate malabsorption
Acquired or congenital defects
@ Brush border disaccharides
Other enzymes
Leading to osmotic diarrhea with low pH
Common cause:
Lactase deficiency
Learn to avoid milk (3/4 of non-whites worldwide affected)
Sugars: sorbitol, lactulose, or fructose Freq. mal-abs
Ingestion of medications, gum, or candies sweetened
Steatorrheal causes
Fat malabsorption may lead to:
Greasy, foul smelling, difficult to flush diarrhea
Associated with: Weight loss + nutritional loss
Increased fecal output due to osmotic effect of fatty
acids. Quantitatively, steatorrhea is:
Stool fat exceeding the normal 7 g/d
Daily fecal fat averages 15-25 g with small intestine, and >
35 with pancreatic exocrine dysfunction. Its types:
1. Intraluminal maldigestion (pancreatic exocrine insufficiency,
bacterial overgrowth, bariatric surgery, liver disease)
2. Mucosal malabsorption (celiac sprue, Whipple's disease,
infections, abetalipoproteinemia, ischemia)
3. Postmucosal obstruction (1 or 2 lymphatic obstruction)

Intraluminal Maldigestion
Pancreatic exocrine insufficiency >90% of pancreatic
function is lost.
Chronic pancreatitis
Sequel to ethanol abuse
Cystic Fibrosis
Pancreatic duct obstruction
Rarely, somatostatinoma
Bacterial overgrowth deconjucating bile aciss and alter
micelle formation
Cirhossis or billiary obstruction leading to mild
steatorrhea due to deficient intraluminal bile acid
concentration
Mucosal Malabsorption
Commonly, Coeliac Disease:
Gluten sensitive enteropathy affects all ages
Characteristic: villous atropy + crypt hyperplasia in proximal small bower
Can present with fatty diarrhea associated with nutritional deficiency of varying severity
Frequently without steatorrhea, can mimic IBS
Tropical Sprue similar histology + clinical
Occur in residents or travellers to tropical climates
Whipples disease
Bacillus Tropheryma whipplei and histiocytic infiltration of small bowel mucosa
Less common, and mostly young or middle aged men.
Arthalgia, fever, lympadenopathy, and extreme fatigue
Can affect CNS and endocardium
Mycobacterium Avium intracellular infection in AIDS
Abetalipoproteinemia
Rare defect of chylomicron formation and fat malabsorption in children
Association: acanthocytic erthrocyte, ataxia, and retinitis pigementosa
Giardia: potozoal infection
Medications (e.g., colchicine, cholestryamine, neomycin
Amyloidosis
Chronic Ischemia
Postmucosal Lymphatic Obstruction
Rare: congenital intestinal lymphangiectasia
Acquired: lymphatic obstruction
Secondary to trauma, tumor, cardiac disease, or
infection
Leads to unique constellation of fat malabsorption
with enteric losses of protein
Lymphocytopenia
Inflammatory causes
Generally accompanied by pain, fever, bleeding or
other inflammatory manifestation
Mechanism depends on the lesion site which can be:
Fat malabsorption
Distrupted fluid/electrolyte absorption
Hypersecretion or hyper motility from cytokines release
Unifying features on stool analysis
Presence of leukocytes or leukocyte derived proteins such as
calprotectin
With severe inflammation: exudative protein loss can lead to
anasarca
Examples of Inflammatory causes
1. Idiopathic inflammatory bowel disease (Crohn's,
chronic ulcerative colitis)
2. Lymphocytic and collagenous colitis
3. Immune-related mucosal disease (1 or 2
immunodeficiencies, food allergy, eosinophilic
gastroenteritis, graft-vs-host disease)
4. Infections (invasive bacteria, viruses, and
parasites, Brainerd diarrhea)
5. Radiation injury Gastrointestinal malignancies

Idiopathic Inflamatory bowel disease
Include: Chrons disaese + Ulcerative colitis
Range from mild to fulminant and life threatening
Associated: uveitis, polyarthralgias, cholestatic liver
disease (primary sclerosing cholangitis), and skin esions
(erythema nodosum, pyoderma gangrenosum)
Microscopic colitis: lymphocytic + collagenous collitis
Chronic cause of watery diarrhea, esp. middle aged
women and NSAID, statins, PPI, SSRI people
Biopsy of normal appearing colon is required for diagnosis
Can exist with IBS or celiac sprue
Responds wel to anti-infallmatory drugs e.g., bismuth, to opoid
agonist loperamide, or to budesonide
Others
Primary or secondary Immunodeficiency
Prolonged infectious diarrhea
Selective IgA deficency
Variable hypogammaglobulinemia
Often prevalent and result of Giardiasis, bacterial overgrowth, or sprue
Eosinophillic Gastroenteritis
Eosinophil infilteration of mucosa, muscularis, or serosa causing diarrhea,
pain, vomitting, or ascitis
Charcot leyden crystals due to extruded eosinophil contents on microscopic inspection of
stool
Peripheral eosinophilia present 50-70% of patients
Hypersensitivity to certain food can be present, but true allergy is rare
Chronic inflammatory diarrhea:
Radiation entercolitis
Chrnic graft versus host disease
Becht syndrome
Cronkhite canada syndrome
Dysmotlity
Rapid transit may accompany many diarrheas as a secondary or
contributing phenmnon.
Primary dysmotility is unusual etiology of true diarrhea
Stool features suggestion secretory diarrhea but mild steatorrhea of up to 14 g
of fat per day
Hyperthyroidism, carcinoid syndrome and certain drugs (PGC, prokinetic
agents)
Can produce hypermotility with resultant diarrhea
Diabetic diarrhea, accompanied by peropheral and generalised
autonomic neuropathies.
IBS is characterised by disturbed intestinal and colonic motor and
sensory responses to various stimuli.
Smptomps of stool frequency typically cease at nigh
Alternate with periods of constipation
Accompanied by abdominal pain relieved by defecation
Rarely, result in weight loss
Factitial causes
Accounts 15% of unexplained diarrhea referred to
tertirary care centres, can be:
Munchausen syndrome
Eating disorders
Self-adminstration of laxitatives or combination of
other medication (e.g., diuretics)
Hypotension and hypokalemia are common co-
presenting features.
History of psychiatric illness
Disproportionately from careers in health care
Approach to The Patient: Chronic
Diarrhea
Extensive workup, can be costly and invasive
Direct it to History and physical examination first
Hx + Px + Blood tests should attempt to characterize the
mechanism of diarrhea
Through identifying diagnostically helpfful association
Assess patients fluid/electrolte and nutrtional status
Questions to be asked: Onset; duration; pattern;
aggrevating, and relieving factors; also, stool
characterization of their diarrhea.
Presence of fecal incontinence, fever, weight loss, pain,
certain exposre (travel, medications, contacts with
diarrhea), and common extraintestinal manifestional (skin
changes, arthalgia, oral apthous ulcer)
Therapeutic trial = appropriate + effective + definitive
if we suspect a specific diagnosis
Eg, chronic watery diarrhea that ceases with fasting in a
young adult
DO LACTOSE RESTRICTED DIET
Bloating and diarrhea persisting since a mountain
backpacking trip
GIVE THEM METRNIDAZOLE for GIARDIASIS
Post prandial diarrhea persisting following resction of
terminal ileum
Maybe due to bile acid malabsorption
GIVE THEM CHOLESTYRAMINE OR COLESEVELAM
Yet persistant symptomops mean addition investigations
Additional investigation
Suspect IBS:
Evaluate with flexible sigmoidoscopy with colo-
rectal biopsy
Normal findings = reassurance and treat empirically
Antispasmodics, antidiarrhea, bulk agents, anxiolytic and
antidepressants.
Chronic Diarrhea and hematochezia
Evaluate with stool microbiologic studies and
colonscopy
We still we do not know..
Quantitative stool collection
Analayses yeild impottant objuctive data
If stool > 200 g/d
Do electrolyte concentration, pH, occult blood testing
Leukocyte inspection (or leukocyte protein assay)
Fat quantitation
Laxative screens
Secretory diarrhea (watery, normal osmotic gap)
Possible medication related side effects (lax?)
Microbiology for protozoas and parasites, Giardia antigen assay
Small bowel aspirates to exclude bacterial overgrowth# with
quantitative cultures, glucose, or lactulose breath test
Upper endoscopy and colonscopy with biopsies
Small bowel x-ray with barium swallow
Further evaluation of osmotic diarrhea
Include tests for lactose intolerance + mg ingestion
Low fecal pH suggests carbohydrate malabsorption
Lactose malabsorption by lactose breath testing
Fatty diarrhea
Endoscopy with small bowel biopsy (aspirate for Giradia)
Small bowel radiograph
Pancreatic direct tests (secretin cholecystokinin stimulation test)
Indirect tests such as assay of fecal elastase or chymotrypsin
Bentiromide test because it has fallen out of favor because of sensitivity and specificity
Chronic inflammatory-type diarrheas
Presence of blood or leukocyte in stool
Inspection for ova and parasites
C. Difficile toxin assay
Colonscopy with biopsy
Small bowel contrast studies
Treatment: Chronic Diarrhea
Depends on specific etiology
Three modalities of treatment: Curative, suppressive or
empiracal
Eradicated cause = Curative treamt eg., resection of a colonrectal
cancer or Antibiotics for Whipples disease
Suppression of underlying condition eg., elimination of dietary
lactose for lactase deficiency or gluten for celiarc sprue, or use
steriods for idiopathic IBD; absorptive agens for illeal bile acid
malabsorption (cholestryramine) PPI (omeprazole) for gastric
hypersecretion of gastrinoma
Empirical therapy beneficial for an evasive diagnosis
Mild opiates for moderate diarrhea diphenoxylate or lopermide
Codeine or tincture of opium for severe diarrhea
Avoid antimotility in severe IBD to avoid toxic megacolon
Clonidine, a2 adrengic agonist allow control for diabetic diarrhea
Remember, it is always fluid and electrolyte replacement first.
Fatty diarrhea, also replace them with fat soluble vitamins.
Case discussion on the subject, and
attempting to answer the relevant
questions

Case
Abeer 23 year old female, Nurse
Watery diarrhea 5x a day for a year
Wake up at night abdominal cramps
Feeling need to empty her bowel (Tenismus)
No relief or aggrevating symptomps ( Fasting =
less frequent)
Past 6 months, she noticed weight loss of 5 kg
despite eating more
No blood or mucos in stool
No nausea, vomiting or fever

Px
Pale, mildly dehydrated, and underweight (46 kg), height
162 cm
BMI 17.5
Blood Pressure = 110/58 mm Hg
Pulse = 98 bpm
RR = 18 bpm
No clubbing, thyromegally, or lymphadenopathy
Abdominal pain shows soft and non-tender abdomen with
no detectable ascites or organomegally
Breast cardiovascular, chest, and neurological exam =
unremarkable
There was mild lower limb edema

Labs
CBC with renal function tests + electrolyte & serum protein
HB 102 g/L *LOW*
MCV 68 *LOW*
Platelets 499,000 *high*
WBC 7200 *normal*
Hepatic profile is notable for: AST = 40 U/L (1-40)
ALT = 49 U/L (10-40)
Alkaline phosphatase = 125 U/L (40-100 U/L)
Albumin = 28 g/L (35-50 g/L)
Total bilirubin = 13 umol/L (5-20 umol/L)
Calcium 1.8 mmol/L (2.2-2.4)

Questions - 1
1. What are the active problems in this patient?
The active problems are Chronic Diarrhea, abdominal pain,
urgency, chronic weight loss


2. What other information in the history and physical examination
you need to know to reach the correct diagnosis?


3. What is the definition of diarrhea? When you label patient to
have acute vs chronic diarrhea?

4. How can you categorize chronic diarrhea?


Questions - 2
5. What laboratory tests you need to order (blood and stool) to
reach the diagnosis?

6. What do you think this young patient has? (Our DDx)
IBS
IBD
Pancreatice insufficiency

7. What further test you need to do to confirm the diagnosis?

8. Name the complications of chronic diarrhea.

9. How to assess nutrition in patient with chronic diarrhea?