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Chronic Diarrhea?&?Malabsorption by TZA

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Chronic Diarrhea
&
Malabsorption
Dr. Thant Zin Aung
PG 2nd Year
NORMAL PHYSIOLOGY
• The main function of SI is digestion and assimilation of nutrients
• The small intestine and colon together
• regulate the secretion and absorption of water and electrolytes,
• transport of intraluminal contents aborally, and
• the salvage of some nutrients that are not absorbed in the small intestine
Alterations in fluid and electrolyte handling contribute significantly to diarrhea.
Alterations in motor and sensory functions of the colon result in highly prevalent syndromes s/a irritable bowel syndrome
(IBS), chronic diarrhea, and chronic constipation
the ascending and transverse colon function as reservoirs (average transit time, 15 h)
the descending colon acts as a conduit (average transit time, 3 h).
NEURAL CONTROL
• intrinsic and extrinsic innervation.
• The intrinsic innervation comprises
• myenteric,
• submucosal, and
• mucosal neuronal layers.
• The myenteric plexus regulates smooth-muscle function
• The submucosal plexus affects secretion, absorption, and mucosal blood flow.
• The extrinsic innervations are part of the autonomic nervous system
• The parasympathetic nerves.
• via the vagus nerve reach the small intestine and proximal colon along the
branches of the superior mesenteric artery.
• The distal colon is supplied by sacral nerves (S2–4) via the pelvic plexus;
• The sympathetic nerve
• reaches the small intestine and colon alongside their arterial vessels.
• generally excitatory to sphincters and
• inhibitory to non-sphincteric muscle.
• Normally, 9-10 liters of fluid
composed of ingested fluid and
secretions from the salivary glands,
stomach, pancreas, bile ducts and
duodenum enter the GIT
• The jejunum absorbs approximately
6L and the ileum 2.5L
• ~1 L of residual fluid reaches the
colon
• Normally, the colon removes 90% of
this load
• so stool water represents only about
1% of the fluid entering the gut each
day
Reduction of water absorption by as little as 1% can result in diarrhea.
SMALL-INTESTINAL MOTILITY
• During the fasting period, the motility of the small intestine is
characterized by a cyclical event called the migrating motor complex
(MMC), which serves to clear nondigestible residue from the small
intestine (the intestinal “housekeeper”).
Rapid transit prevents adequate time for absorption:
• This organized, propagated series of contractions lasts, on average, 4
Diarrhea or constipation may result from alteration in the reservoir
min, occurs every 60–90 function
min of the proximal colon or the propulsive function of the left colon
Diarrhea results despite intact mucosal absorptive capacity.
• After food ingestion, the small intestine produces irregular, mixing
Intestinal hurry has been linked to post-vagotomy diarrhea, diarrhea
contractions of relativelypredominant
low amplitude
Irritable bowel syndrome and diabetic diarrhea
ILEOCOLONIC STORAGE AND SALVAGE
• The distal ileum acts as a reservoir, &empty the ileum by bolus transfers.
• Segmentation by haustra compartmentalizes the colon and facilitates
mixing, retention of residue, and formation of solid stools.
• The resident microorganisms, predominantly anaerobic bacteria, in the
colon are necessary for the digestion of unabsorbed carbohydrates that
reach the colon even in health, thereby providing a vital source of
nutrients to the mucosa.
COLONIC MOTILITY AND TONE
• The small-intestinal MMC only rarely continues into the colon.
• However, short duration or phasic contractions mix colonic contents
and high-amplitude (>75 mmHg) propagated contractions are
sometimes associated with mass movements through the colon and
normally occur approximately five times per day, usually on
awakening in the morning and post-prandially.
• Increased frequency of HAPCs may result in diarrhea or urgency. The
predominant phasic contractions in the colon are irregular and
nonpropagated and serve a “mixing” function.
DEFECATION
What is diarrhea?
Definition
• Patients may describe diarrhea as bowel movements that are
increased in frequency, larger in size, loose in consistency, or
associated with urgency or incontinence.
• The normal daily stool weight is 100-200 g, although individuals on
high-fiber diet may pass 500 g/day.
• In the United States, a daily stool weight of more than 200 g is
considered abnormal
• Diarrhea can be
1. Acute if <2 weeks
2. Persistent if 2-4 weeks
3. Chronic if > 4 weeks duration
Causes of diarrheas by predominant
pathophysiological mechanisms
The classification of chronic diarrhea by pathophysiologic mechanism facilitates a
rational approach to management, although many diseases cause diarrhea by
more than one mechanism & direct the evaluations in meaningful ways
Iatrogenic Causes
• Cholecystectomy
• Ileal resection
• Bariatric surgery
• Vagotomy,
Factitial Causes
• Munchausen
• Eating disorders
Dysmotile Causes
• Irritable bowel syndrome (including postinfectious IBS)
• Visceral neuromyopathies
• Hyperthyroidism
• Drugs (prokinetic agents)
• Postvagotomy
Secretory diarrheas
• are due to derangements in fluid and electrolyte transport across the
enterocolonic mucosa.
• They are characterized clinically by watery, large-volume fecal
outputs that are typically painless and persist with fasting.
MEDICATIONS
• Surreptitious or habitual use of
stimulant laxatives (e.g., senna,
cascara, bisacodyl, ricinoleic
acid [castor oil)
• Chronic ethanol consumption
• Inadvertent ingestion of certain
environmental toxins (e.g.,
arsenic) may lead to chronic
diarrhea
BOWEL RESECTION, MUCOSAL DISEASE, OR
ENTEROCOLIC FISTULA
• inadequate surface for reabsorption of secreted fluids and
electrolytes.
• Unlike other secretory diarrheas, it tends to worsen with eating.
• Crohn’s ileitis
• resection of <100 cm of terminal ileum
HORMONES
• The carcinoid syndrome due to the release of potent intestinal secretagogues
including serotonin, histamine, prostaglandins, and various kinins.
• Gastrinoma due to pancreatic enzyme inactivation by low intraduodenal pH.
• Non-β cell pancreatic adenoma, a VIPoma, that secretes VIP and a host of other
peptide hormones including pancreatic polypeptide, secretin, gastrin, gastrininhibitory polypeptide, neurotensin, calcitonin, and prostaglandins.
• The secretory diarrhea is often massive with stool volumes >3 L/d;
• daily volumes as high as 20 L have been reported.
• Life- threatening dehydration; neuromuscular dysfunction from associated
hypokalemia, hypomagnesemia, or hypercalcemia; flushing; and hyperglycemia
may accompany a VIPoma.
• Medullary carcinoma of the thyroid may present with watery diarrhea
caused by calcitonin, other secretory peptides, or prostaglandins.
• Systemic mastocytosis, which may be associated with the skin lesion
urticaria pigmentosa, may cause diarrhea that is either secretory and
mediated by histamine or inflammatory due to intestinal infiltration by
mast cells.
• Large colorectal villous adenomas may rarely be associated with a
secretory diarrhea that may cause hypokalemia, can be inhibited by
NSAIDs, and are apparently mediated by prostaglandins
Osmotic Causes
• 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.
stool osmotic gap (>50 mosmol/L): serum osmolarity (typically 290 mosmol/kg) − (2 × [fecal sodium + potassium concentration
Measurement of fecal osmolarity is no longer recommended because, even when measured immediately after evacuation, it
may be erroneous because carbohydrates are metabolized by colonic bacteria, causing an increase in osmolarity.
OSMOTIC LAXATIVES
• Magnesium-containing antacids,
• Health supplements, or
• Laxatives
CARBOHYDRATE MALABSORPTION
• due to acquired or congenital defects in brush-border disaccharidases
and other enzymes leads to osmotic diarrhea with a low pH.
• lactase deficiency,
• Some sugars, such as sorbitol, lactulose, or fructose, are frequently
malabsorbed, and diarrhea ensues with ingestion of medications, gum, or
candies sweetened with these poorly or incompletely absorbed sugars.
WHEAT AND FODMAP INTOLERANCE
• non-celiac gluten intolerance and
• intolerance of fermentable oligosaccharides, disaccharides,
monosaccharides, and polyols (FODMAPs).
Steatorrheal Causes
1. Intraluminal maldigestion,
2. mucosal malabsorption, or
3. lymphatic obstruction may produce Fat malabsorption
• Increased fecal output due to osmotic effects of fatty acids
• greasy, foul-smelling, diicult-to-flush diarrhea
• Quantitatively, steatorrhea is defined as stool fat exceeding the
• normal 7 g/d;
• mild steatorrhea of up to 14 g/d can be produced by maldigestion from rapid transit alone
• In the presence of diarrhea, value more than 14 g/d is considered significant
• daily fecal fat averages 15–20 g with small-intestinal diseases and
• is often > 20 g with pancreatic exocrine insuiciency.
INTRALUMINAL MALDIGESTION
• Due to pancreatic exocrine insuiffciency,
• Chronic pancreatitis, cystic fibrosis, pancreatic duct obstruction,
somatostatinoma.
• Bacterial overgrowth in the small intestine may deconjugate bile
acids and alter micelle formation, impairing fat digestion; blind-loop,
small-bowel diverticulum or dysmotility
• cirrhosis or biliary obstruction may lead to mild steatorrhea due to
deficient intraluminal bile acid concentration.
MUCOSAL MALABSORPTION
• Celiac disease
• Tropical sprue
• Whipple’s disease,
• Mycobacterium avium- intracellulare infection in patients with AIDS.
• Giardiasis
• Abetalipoproteinemia
• Medications (e.g., olmesartan, MMF, colchicine, cholestyramine,
neomycin),
• amyloidosis, and
• chronic ischemia.
POSTMUCOSAL LYMPHATIC OBSTRUCTION
• congenital intestinal lymphangiectasia
• acquired lymphatic obstruction secondary to trauma, tumor, cardiac
disease or infection,
Inflammatory Causes
• generally accompanied by pain, fever, bleeding, or other
manifestations of inflammation.
• The mechanism of diarrhea may not only be exudation but,
depending on lesion site, may include fat malabsorption, disrupted
fluid/electrolyte absorption, and hypersecretion or hypermotility
from release of cytokines and other inflammatory mediators.
• Stool Analysis  leukocytes or leukocyte-derived proteins such as
calprotectin.
• With severe inflammation, exudative protein loss can lead to anasarca
(generalized edema)..
IDIOPATHIC INFLAMMATORY BOWEL DISEASE
• Crohn’s disease and ulcerative colitis
• Microscopic colitis, including both lymphocytic and collagenous
colitis, especially in middle-aged women and those on NSAIDs,
statins, proton pump inhibitors (PPIs), and selective serotonin
reuptake inhibitors (SSRIs);
• It typically responds well to anti-inflammatory drugs (e.g., bismuth),
the opioid agonist loperamide, or to budesonide.
EOSINOPHILIC GASTROENTERITIS
• Eosinophil infiltration of the mucosa, muscularis, or serosa at any
level of the GI tract may cause diarrhea, pain, vomiting,
• Affected patients often have an atopic history, Charcot-Leyden
crystals due to extruded eosinophil contents may be seen on
microscopic inspection of stool,
• peripheral eosinophilia is present in 50–75% of patients.
Dysmotility Causes
• Rapid transit may accompany many diarrheas as a secondary or
contributing phenomenon
• Stool features often suggest a secretory diarrhea,
• Hyperthyroidism, carcinoid syndrome, and certain 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.
Factitial Causes
• Factitial diarrhea accounts for up to 15% of unexplained diarrheas
referred to tertiary care centers.
• Either as a form of Munchausen syndrome or eating disorders, selfadminister laxatives or surreptitiously add water or urine to stool
sent for analysis.
How will you approach to a
patient with chronic diarrhea?
APPROACH TO THE PATIENT
• Assess the patient’s fluid/electrolyte and nutritional status
• Diagnostic evaluation must be rational
• Directed by a careful history, and physical examination
• When this strategy is unrevealing, simple triage tests are often
warranted to direct the choice of more complex investigations
Algorithm for management of chronic
diarrhea.
• In an estimated two-thirds of cases, the cause for chronic diarrhea
remains unclear after the initial encounter, and further testing is
required.
TREATMENT
• Fluid and electrolyte repletion
• Replacement of fat-soluble vitamins may also be necessary in patients
with chronic steatorrhea.
• Treat specific underlying etiology
• Induction and maintenance of remission is the main goal of therapy in
patients with inflammatory bowel disease. This goal can be achieved by
using 5-ASA (aminosalicylates) and immunosuppressant drugs
• Gluten free diet is the main therapeutic measure in patients with celiac
disease.
• Role of long-term antibiotics in management of tropical sprue is yet
not proved, but limited studies showed that 6 months treatment
using doxycyclin and folic acid improved diarrhea frequency and
malabsorption.
• The somatostatin analogue, octreotide, is of proven effectiveness in
carcinoid tumors and other peptide-secreting tumors, dumping
syndrome, and chemotherapy-induced diarrhea
• Patients with gastrinoma, and VIPoma can be treated by surgical
removal.
• Empiric therapy can be provided:
a) as a temporizing measure during evaluation,
b) when there is a failure to reach a diagnosis in a patient with
chronic diarrhea,
c) when a diagnosis is made, but is not specifically treatable.
9/11/2019
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Thank You!