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- 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 --> ???