DIARRHEA  Enterocytes

- Dr Go  Myofibroblasts
 Blood hormones
Major cause of worldwide morbidity & mortality  Capillary blood flow
 3-5 Billion Episodes per Year  Lymphatics
 5 million Deaths per year, 80% under 1 yr of age  Immune cells
 A major cause of work absenteeism  Enteric neurons
 A major economic burden, particularly in  Smooth muscle
developing nations
As a symptom Mucosal endocrine cells regulate intestinal ion
 ↑ Frequency transport by paracrine action
Prosecretory Proabsorptive
 ↑ Volume Neurotensin Somatostatin
 ↓ Consistency Serotonin (5HT)
As a sign Substance P
Secretin
 Stool Weight >150 to 200 g per 24 hr
 Stool water > 150 to 200 mL per 24 hr
Daily intake & endogenous secretions are efficiently  Luminal stimuli   5 HT   Net secretion
absorbed by the gastrointestinal tract
 Oral intake = 2000 The intestinal mucosa changes with nutrient
 Endogenous secretions: 7000 availability & disease
 Salivary glands = 1500 Normal mucosa Villus atrophy Villus
 Stomach = 2500 Hypertrophy
 Bile = 500 Starvation Diabetes, short
 Pancreas = 1500 bowel syndrome
 Intestine = 1000 Nutrient & ↓ ↑
electrolyte
 Total presented to intestines = 9000
absroptive
 Absorbed = 8800 (%absorbed = 98%)
capacity per unit
 Net Balance (2000 - 200 = 1800) area
 Stool 200
Intestinal Epithelial layer has many functions: There are two major pathophysiological mechanisms
 Barrier and Immune defense for diarrhea
 Fluid & electrolyte absorption  Decreased absorption of fluid & electrolytes
 Protein synthesis & secretion  Inhibited or defective absorption of fluid &
 Nutrient digestion & absorption electrolytes
 Fluid & electrolyte secretion & IgA secretion  Luminal presence of osmotically active
 Mediator production agents
 Increased propulsive activity causing
The intestine has a very large surface area for decreased contact time
absorption  Increased secretion of fluid & electrolytes
Type of surface Amplification Surface Area  Stimulated anion secretion
Factor (cm2)  Secretion from crypts
Mucosal cylinder 1 3,300 Some diarrheal pathogens are not invasive, but may
Fold of Kerkring 3 10,000 cause alterations in microvillus function & structure
Villi 10 100,000  Examples:
Microvilli 20 2,000,00  Enteroadherent E Coli
 Giardia lamblia
Total surface area = 200 m2  Cryptosporidia
Double Tennis Court = 175 m2  Possible actions
 Increased mucosal permeability
Intestinal epithelial cells are continually renewed:
 Inhibition of nutrient & electrolyte
 Turnover time ~ 48 – 72 hrs absorption
 Normally: # Cells entering villus = # of Cells dying  Stimulation of anion secretion
 Villus Region = Cell death & sloughing Some secretory diarrheas are caused by hormone
 Crypt Region = Dividing cells & Paneth Cells producing tumors
Hormone producing tumor Putative secretagogue
Digestive & Transport properties of villus & crypt Carcinoid Serotonin, PG, bradykinin,
regions differ tachykinin
Brush Nutrient Net Permeability VIPoma VIP & others
border transport water/ ion Gastrinoma Gastrin
hydrolases transport Medullary Carcinoma of the Calcitonin, PG
Villus ↑ ↑ Absorption ↓ thyroid
Crypt ↓ ↓ Secretion ↑ Ganglioneuroma Probably VIP

Many factors regulate or modulate intestinal water & Inflammation-induced diarrhea results from several
electrolyte transport mechanisms
 Luminal stimuli
 Mucosal endocrine cells
 ⊕ secretion &  absorption
  ⊕ of enteric nerves causing propulsive  Salmonella colitis --> ???
contractions & ⊕ secretions  Ulcerative colitis --> ???

 mucosal destruction & ↑ permeability Sudan Fat stain

 nutrient maldigestion & malabsorption

Bile induced diarrhea results from ileal dysfunction

 The ileum is the only site of active bile
absorption
Diarrhea is a common manifestation of celiac sprue &
is caused by several different mechanisms (GLUTEN Stool analyses may be helpful in distinguishing
causing…) osmotic & secretory diarrhea
Stool Osmotic Diarrhea Secretory
 ↓ brush border hydrolases  unabsorbed osmols
measurement Diarrhea
 Villus atrophy (Fluid, nutrient & electrolyte Volume <200 mL/day > 200 mL/day
malabsorption)
Osmolality > [Na + K] x 2 </= [Na + K] x 2
 Crypt hyperplasia (↑ endogenous secretion) Sodium < 70 mEq/liter > 70 mEq/liter
 Inflammatory-induced secretion pH * <5 >6
Reducing (+) (-)
Duration of diarrhea helps guide evaluation substances *
Acute Chronic * applies to children under the age of 5
Duration <2-3 weeks >3 weeks
Etiology Usually Multiple Several approaches can be taken in the treatment of
infections diarrhea
Course Usually self Variable  Specific (e.g. lactase deficiency)
limited  Cure underlying disease
 Correct Pathophysiology
The management & treatment of acute diarrhea  Non-specific (e.g. chronic idiopathic)
depends on the patient’s hx & condition
Course Benign Dehydration &
 ↓ net fluid secretion
prior episode ↓ secretion, ↑ absorption
Aproach Observe Evaluate  modify motility
Recovery Spontaneous After appropriate ↓ propulsive contractions,
treatment
↑ mixing contractions
History is helpful in evaluating px w/ diarrhea
 Hx: duration, travel, Rx, age, diet Guideline for treatment of chronic diarrhea
 Character: freq, vol, blood, consistency  Specific diagnosis established--> eliminate cause
 Other: fever, wt loss, anorexia, n/v, dehydration --> if cause cannot be eliminated, treat specfic
Site of involvement: pathophysiological mechanism --> if specific
Small bowel & colonic Rectosigmoid treatment no available or successful -->institute
Large volume, Small amount of stool therapies to ↓ net secretion & propulsive
Moderate ↑ in # Frequency contractions
Minimal urgency Urgency
No tenesmus Tenesmus  Specific diagnosis NOT established --> institute
Mucus therapies to ↓ net secretion & propulsive
Little mucus
blood contractions

Disorder (examples) Treatment

Chronic & recurrent diarrhea should always be
investigated. Antibiotic associated Stop antibiotic or use
diarrhea (C. difficile) Vancomycin
 Hx PE
Giardiasis Metronidazole
 Stool Exam
VIP-secreting tumor Resection of Islet Cell
 Cultures, ova & parasites
adenoma
 Blood, leukocytes, microscopic fat
 Quantitative volumes & fat studies as Disorder Causative factor Treatment
indicated
Lactase Lactose Lactose-free diet
 Other studies: deficiency
 Endoscopic examinations with biopsy Ileal dysfunction Bile Acids Cholestyramine
 Absorption studies Pancreatic Fatty acids Low Fat Diet
 Special studies: imagins (CAT scan, insufficience and/or
ultrasound, etc.) Pancreatic
Barium studies Enzymes
Stool & urine analyses for laxative & Watery Diarrhea VIP Somatostatin
diuretics. syndrome analog
Ulcerative colitis Inflammation Steroids,
Fecal leukocytes from patients with bacterial colitis aminosalicylates
 Nani?
Oral rehydration solutions can correct metabolic
abnormalities:
L
D’O8
Plasma Values Untreated Treated
Na (mEq/L) 141 142
Cl 107 106
K 4.5 3.6
HCO3 9 21
Arterial pH 7.21 7.43
Plasma specific 1.05 1.026
gravity
Stool output 7.5 8.0
(liters/day

Somatostatin has several sites of antidiarrheal action

  of endocrine cell secretion (by hormone
producing tumor cells)
 ↓ propulsive & ↑ segmental contractions
 ↑ mucosal absorpton & ↓ secretion of water &
electrolytes
  of secreto-motor neurons
 modulation of immune cells
 modulation of blood flow
Diarrhea caused by arachidonic acid metabolites can
be treated with antinflammatory agents

Opiates prolong transit time & ↑ efficiency of

absorption