Problem 3 GI

Olivia paulus
Anatomy of Lower GI Tract
 SMALL INTESTINE
• Extends from pylorus to
ileocecal junction
• ~6m long, ÷ to 3 parts:
duodenum, jejunum, ileum
• Proximal: ~25 cm duodenum,
fixed part
• Remaining long part freely
mobile: ÷2 jejunum & ileum
• Jejunum + ileum = principally
concerned w/ digestion &
absorption of digested food =
small intestine proper
Arterial Supply
• Jejunal & ileal branches of superior mesenteric
artery (12-15 in #)
• Arise from left side of superior mesenteric artery
& enter mesentery to reach intestine
• Terminal part of ileum supplied by ileal branches
of ileocolic branch of superior mesenteric artery
• Enters mesentery  break up into smaller
branches anastomosing w/ each other  arterial
arcades  terminal arcades  small parallel
straight vessels vasa recta  opposite surface of
small intestine
Venous Drainage
• Correspond to branches of superior mesenteric artery 
drain to portal vein  carries products of proteins & carbs to
liver
Lymphatic drainage
• Pass through mesenteric nodes  drain to superior
mesenteric nodes around origin of artery
Nerve supply
• Sympathetic supply: T10-T11 spinal segment through
splanchnic nerves & superior mesenteric plexus
– Pain from jejunum & ileum reffered to umbilical region
– Motor to gut sphincter
• Parasympathetic: vagus nerve through celiac & superior
mesenteric plexuses
– Stimulate peristalsis & inhibitory to sphincter
 Mesentery of Small Intestine
• Broad fan-shaped fold of
peritoneum
• Suspend small intestine
(jejunum & ileum) from
posterior abdominal wall
• Root (attached margin) and
free margin (intestinal margin)
• Root attached to oblique line
across posterior abdominal
wall extending from duodenal
flexure  ileocecal junction
– Duodenal flexure: left side of
L2
– Ileocecal junction: right
sacroiliac joint
 Development
• Jejunum & ileum dev from U-
shaped midgut loop w/
cephalic & caudal limbs
– Cephalic  jejunum & upper
part of ileum
– Caudal  lower part of ileum
• Apex midgut loop
communicates w/ yolk sac
through vitello-intestinal
duct
• Vitelline duct fenerally
obliterated by 6th wk of
intrauterine life
Meckel’s diverticulum (ileal diverticulum)
• Persistent prox part of embryonic vitello-intestinal duct
Normal: symptomless
May cause clinical problems:
• Intestinal obstruction
• Ectopic gastric mucosa or pancreatic tissue  may
ulcerate, perforate, bleed (mimic acute abdomen)
 LARGE INTESTINE
• ~1.5 m long
• Extends from caecum in right iliac fossa to anus in
perineum
• Apart from transverse & sigmoid colon, it is more
fixed in position than small intestine
• Parts:
– Caecum & appendix
– Colon
– Rectum
– Anal canal
DISTINGUISHING FEATURES OF
COLON:
• Taenia coli
– Ribbon-like bands of longitudinal
muscle coat
– Distally become continuous w/
longitudinal muscle coat of
rectum
– ✓ until caecum
• Appendices epiploicae
– Small bags of visceral
peritoneum = fats
– ✗ in appendix, rectum & anal
canal
– Most on side of sigmoid colon &
posterior surface of transverse
colon
• Sacculation (haustrations)
– Pouches/dilatation in walls of
cecum & colon b/w taenia
– Due to length of taenia that is
shorter
– Puckered appearance in LI
 CAECUM
• Large dilated blind sac at proximal end of LI
• Location: Right iliac fossa above lateral ½ of
inguinal ligament
• At birth: conical in shape, vermiform appendix
attached at its apex  growth results in 2
saccules  right saccule > left  apex of caecum
& base of appendix pushed toward left & nearer
to ileocaecal junction  base of appendix is
attached at posteromedial wall of caecum
• On basis of growth, 4 types of caecum maybe found in
adult:
– Conical type/fetal type (2%)
• Conical & appendix attached in apex
– Infantile type (3%)
• Quadrate shape (right = left saccule) & appendix attached at
depressed bottom
– Normal type (80-90%)
• Right > left appendix on posteromedial ~2cm below ileocaecal
junction
– Exaggerated type (4-5%)
• Right >>> (exaggerated growth), left saccule ✗
• Appendix attached just below ileocaecal junction
INTERIOR OF CAECUM
• 2 orifice: ileocecal orifice (prominent feature)
& appendicular orifice
– Valve of Gerlach: semicircular fold of mucous
membrane guarding appendicular orifice
Blood supply & Lymphatic Drainage
• Caecum: anterior & posterior
caecal branches of ileocolic artery
 branch of superior mesenteric
artery
• Vein: follow arteries  superior
mesenteric vein  portal system
• Lymph vessels caecum  ileocolic
lymph nodes  sueprior
mesenteric of pre-aortic lymph
nodes
Nerve supply
• Sympathetic nerve: T11-L1
through sup mesenteric plexus
• Parasympathetic nerve: vagus
nerve
 Vermiform Appendix
• Narrow worm-like
diverticulum arise from
posteromedial wall of
caecum ~2cm below
ileocaecal junction
– Length: children > adults
• Surface anatomy:
– 2 cm below intersection b/w
transtubercular plane & right
midclavicular line
– Clinicians equate surface
marking of appendix to
McBurney’s point
Arterial Supply
• Appendicular artery, branch of inferior division of ileocolic artery
– Passes behind terminal part of ileum  enters
mesoappendix runs in free margin to reach tip of appendix
(least vascular part)
– Appendicular artery = end artery; in appendicitis: artery
thrombosed  gangrenous change in tip may perforate
Venous drainage
• Correspond to artery  superior mesenteric vein  portal vein
Lymphatic drainage
• Ileocolic lymph nodes  appendicular nodes in mesoappendix
Nerve supply
• Sympathetic; carries pain sensation: T10 via splanchnic & sup
mesenteric plexus  umbilical region
• Parasympathetic: vagus nerve
Histology of Lower GIT
 SMALL INTESTINE
3 Segments: Duodenum, Jejunum, Ileum
MUCOSA
• Permanent Circular folds (plicae circulares Kerckringi)
– Consisting mucosa & submucosa
– Best developed in jejunum
• Simple columnar epithelium of absorptive cells: enterocytes w/ many
goblet cells
• Villi projecting to lumen covering entire mucosal outgrowth
– Finger or leaff-like projections
• Each villus has core:
– Loose connective tissue from lamina propria
– Contain: fibroblast, Smfibers, lymphocytes, plasma cells, fenestrated
capillaries, central lymphatic (lacteal)
• b/w vili: openings of short tubular gland (crypts of Lieberkuhn)
Each villus continuous w/ intervening glands &
pluripotent stem cells:
• Enterocytes:
– absorptive cells, tall columnar w/ oval
nucleus in basal
– Apical end w/ brush border (microvilli
covered w/ glycocalyx) = nutrients taken
into cells
• Cylindrical protrusion
• Contain actin filaments & enclosed
by cell membr
Villi, microvilli, plicae =  mucosal surface area 
important for absorption
• Goblet cells:
– Interspersed among absorptive
enterocytes
– Secrete glycoprotein mucins  hydrated
 mucus  protect & lubricate lining of
intestine
• Paneth cells:
– Basal portion of intestinal crypts below
stem cells
– Exocrine cells
– Large eosinophilic secretory granules in
apical cytoplasm
– Release lysozome, phospholipase A2,
hydrophobic peptides defensins  break
down bacterial cell walls
– Innate immunity & regulate
microenvironment of crypts
• Enteroendocrine cells:
– Secrete peptide hormones
– Has chemoreceptor similar to taste buds
• M (microfold) cells
– Specialized epith cells in mucosa of ileum
overlying lymphoid follicles of Peyer
patches
– Basal membrane invaginations or
pockets containing many intraepithelial
lymphocytes & APC
– Endocytose Ag & transport them to
underlying lymphocytes & dendritic cells
 lymph nodes  immune response
MUCOSAL LAMINA PROPRIA
• Contains extensive BV & LV, nerve fibers, SMC,
diffuse lymphoid tissue
• SM fibers extending from muscularis mucosae
 produce rhythmic movements of vili  
absorption efficiency
• Produce local movements of plicae circulares
propel lymph from lacteals to submucosal &
mesenteric lymphatics
SUBMUCOSA
• Larger BV & LV & diffuse interconnected
neurons = Meisnner nerve plexus
• Proximal duodenum: Brunner glands
• In ileum, both lamina propria & submucosa
contain well dev MALT (mucosa-associated
lymphid tissue) of lymphoid aggregates Peyer
patches underlying M cells
 LARGE INTESTINE
• Absorption of H2O & electrolytes from
indigestible materials to feces
• Regions:
– Short cecum w/ ileocecal valve & appendix
– Ascending, transverse, descending, sigmoid colon
– Rectum to store feces for defecation
• ✗ villi in mucosa
• Rectum ✗ major folds
• <1/3 lonf from SI, diameter: 6-7 cm
• Wall of colon puckered to large sacs: haustra
MUCOSA significant component of MALT
• Tubular intestinal gland Muscularis of colon
• Lumen lined by goblet + absorptive • Taenia coli: muscularis; fibers of
cells outer layer gathered in 3 separate
•  # of enteroendocrine cells longitudinal bands
• Columnar absorptive cells • Serosa
colonocytes • Descending colons are tunica
adventitia
• Goblet cells produce mucus  #
along colon & rectum DISTAL GI TRACT
• Epith stem cells in 1/3 bottom each Anus: distal end of GI tract (3-4 cm)
gland • Rectoanal junction: simple
Lamina propria columnar  stratified squamous
• Rich lymphoid cells & lymph epithelium
nodules extending to mucosa • Circular layer of rectum’s
•  MALT due to  bacteria # muscularis  internal anal
Appendix ✗ absorptive function but sphincter
Physiology of Lower GIT
 SMALL INTESTINE
• Most digestion & absorption takes place
– In large intestine ✗ further digestion; only small # absorption of H2O
& salt
• Lies coiled w/in abdominal cavity
• Divided to 3 segments:
– Duodenum
• 1st portion: duodena cap/bulb
• At ligament of Treitz (in duodenojejunal flexure) bends
– Jejunum
• Upper 40% SI below duodenum
– Ileum
• Lower 60%
• Shorter during life than cadavers
• Mucosa contains solitary lymphatic nodules (esp ileum); Peyer’s patch
• Brunner’s gland in duodenum & goblet cells in mucosa secrete intestinal
mucus throughout GIT
Motility, 3 types
• Segmentation
– Mixes & slowly propels chyme
– Oscillating
• Ring like contraction along length w/in
seconds
• Contracted segment relax & previously
relaxed area contract  mixing chyme w/in
SI lumen
• Initiation: BER (basic Electrical rhythm)
• Slightly/asent b/w meals, vigorous
immediately after meal
– Duodenum & ileum start to segment
simultaneously when meal 1st enter SI
• Focal distention by chyme  duodenum
starts to segment
– Ileum: gastrin secreted in response to
chyme in stomach (gastroileal reflex)
– Extrinsic nerve:
• Parasymphatics  segmentation
• Symphatics  segmentation
Function of segmentation
– Mixing chyme & digestive juices
– Exposing chyme to all absorptive surfaces of SI
mucosa
– Freq of segmentation  along length of SI
– Pacemaker in duodenum spontaneous depol
faster than farther down
• Duodenum: 12/min
• Ileum: 9/min
⌃chyme pushed forward
Slow movement: allows digestive & absorptive processes
Content move ~3-5 hrs through SI
• Migrating Motility Complex (MMC)/Intestinal
housekeeper
– b/w meals
– Weak, repetitive peristaltic wave starting at
stomach  intestine
– ~100-150 min
– Sweeps remnants of preceding meal +mucosal
debris & bacteria  colon
– End of SI  cycle begins again until next meal
– Regulated by hormone Motilin, secreted during
unfed state by SI mucosa endocrine cells
ILEOCECAL JUNCTURE
• b/w SI & LI, last part of ileum
empties to cecum
• Region as a barrier. 2 factors
contributing:
– Valve-like folds of tissue; protrude
from ileum  lumen of cecum
• Ileal contents pushed  ileocecal
valce easily opened
• Folds forcibly closed when cecal
content attempt to move
backwards
– Smooth muscles w/in several cm
of ileal wall thickened  sphincter
under neural & hormonal control
• Ileocecal sphincter remains mildly
constricted (intrinsic plexus)
• Distention ileal side  sphincter
relax
• pressure in cecal side  contract
more
Primary role of SI: ABSORPTION
• Most in duodenum & jejunum, little in ileum
• 50% SI can be removed w/out interference in
absorption except:
– Terminal ileum removed  vit b12 & bile salts ✗
abs
• Transport mechanism is here
• Special absorptive function:
– Large surface area
– Epithelial cells have variety or specialized
transport mech
• Adaptation  SI SA:
– Inner surface: circular folds (3x )
– Finger like villi (10x )
– Smaller hairlike projection: brush
border/microvilli (20x )
– 3000-6000 microvilli/epith cells
– Enzymes w/in brush border
DIARRHEA Causes:
• Secretion & absorption ✗ • Excess SI motility:
parallel each other – irritation of gut wall by
• Acid – base abnormalities infections or emotional
stress
• Loss of fluid
– ✗ time for adequate
• ly fluid fecal matter ( absorption of fluid
freq of defecatio) • Excess osmotically active
• Beneficial: rapid particles;  fluidity of
emptying/elimination of feces
harmful materials in body • Toxins of bacterium
• Excessive loss: V.cholera  excess # of
dehydration,  nutrients, fluid by mucosa
metabolic acidosis (loss Th/: oral rehydration
oh HCO3-)
 LARGE INTESTINE
• Consist of: colon, rectum, cecum, appendix
– Cecum: forms blind-end pouch at ileocecal valve
– Appendix: fingerlike projection: lymphoid tissue
– Colon: not coiled, 3 straight parts
• End part: S shaped: sigmoid  straightened  rectum
• Primarily a drying & storage organ
COLON
• Main function of colon: absorption of H2O, Na+, minerals
• Receives ~500 mL chyme from SI/day
• Consist of: indigestible food residues (cellulose), unabsorbed biliary
components, remaining fluid
• Main motility: haustral contraction initiated by autonom rhythmicity of
colon SMC (~30 min b/w contraction)
• MASS MOVEMENT
– 3-4x/day after meals
 motility during
drive feces 1/3 – ¾ Distal part of LI,
contraction of ascending
length of colon in few materials stored until
& transverse colon
seconds defecation
simultaneously

Food enters Triggers mass

stomach; stimulate movement in colon New foods enters
Urge to defecate
gastrin & extrinsic (GASTROCOLIC DT
autonomic nerves REFLEX)

Defecation reflex Reflexes initiated

Make way for
(distention of to move content
Rectum incoming new
rectum  receptor further along down
foods
in rectal wall) tract

Internal & external

anal sphincter
relax; rectum, Defecation
sigmoid colon
contract vigorously
 Inhibit Distended
Tightening of
Circumstances defecation; rectal wall
external
are unfavorable despite the gradually
sphincter
reflex relaxes

Next mass
movement
Urge  Urge 
propels more
feces to rectum

• During inactivity, both anal sphincters

remain contracted to ensure fecal
continence
• Defecation:
– Assisted by voluntary straining movements:
• Contraction of abdominal muscles
• Forcible expiration against closed glottis
•  Intraabdominal pressure
• Constipation:
– Defecation delayed too long
– >H2O # absorbed from feces  dry & hard
• Possible causes for delayed
defecation:
– Ignoring urge to defecate
–  colon motility: aging,
emotion, low bulk diet
– Obstruction of fecal movement
due to tumor or colonic spasm
– Impairment of defecation reflex
(injury of nerve pathway)
 INTESTINAL GASES
• Flatus – gas, primarily driven by 2 sources:
– Swallowed air
• (500 mL air during meal)
– Gas produced by bacterial fermentation in colon
• Presence of gas percolating through luminal contents  gurgling sound
(borborygmi)
• Eructation (burping) removes most of swallowed air from stomach, some
passes to intestine
• Little # of gas present in SI absorbed or passes on to colon + bacterial
products from undigested KH  expelled through anus
– Abdominal contraction  pressure against contracted anal sphincter
 ΔP forces air out at  velocity through slit like opening  edge of
anal opening vibrates  low pitched sound
Biochemistry of Lower GIT
Secretions Source Function & pH
Saliva Salivary gland Moistens & lubricates
pH 6.5-7.5
Lysozyme Salivary gland Kills bacteria
Mucus Foveolar (surface mucous) cells in Protects stomach wall
stomach
Chymosin/Rennin Chief cells of stomach Coagulates milk
pH: 3.5
HCl acid Parietal cells of stomach Kills bacteria
Activates pepsinogen  pepsin
Denatures proteins aiding prot
digestion
pH 1-2
Intrinsic Factor Parietal cells of stomach Assist absorption of vit B12 by
(enzyme/glycoprot) protecting acid-intolerant
substance as it goes to stomach
pH: 7
Bile (bile salts + billirubin) Hepatocytes of liver; secreted by Assist digestion of lipids
gallbladder pH 7.5-8.8
Bicarbonate ions Pancreas Alkaline, employed to control pH
lvl
 PANCREAS
• Elongated gland behind & below stomach; above 1st loop of
duodenum
• Mixed gland
– Exocrine (predominant); grape-like cluster of sensory cells
forming sacs (acini)  connect ducts  duodenum
• Pancreatic enzymes
– Proteolytic enzymes: prot digestion
» Trypsinogen, chymotrypsinogen, procarboxypeptidase
– Pancreatic amylase: carbs digestion
– Pancreatic lipase: fat digestion
• Aqueous alkaline solution (NaHCO3)
– Endocrine (smaller); isolated island (islets of Langerhans)
dispersed throughout pancreas
• Insulin
• Glucagon
Role of hormones in pancreatic secretion
LIVER & GALLBLADDER
 Nutrition, Digestion, Absorption
Biomedical importance
• Diet must provide metabolic fuels
– Carbohydrates & Lipid
• For growth & turnover of tissue
– Protein
• Bulk in the intestinal lumen
– Fibers
• Elements w/ specific metabolic function
– Minerals
• Needed in low # for metabolism & physiologic function
– Essential fatty acid (FA) & vitamin
 Polysaccha
rides
Triacylglyc
erol

Protein

Monosaccharide, Fatty acids,

Amino Acids

Absorption
&
Utilization
 CARBOHYDRATES
• By hydrolysis
– Liberate oligo/polysaccharide  di/monosaccharide
• Amylase catalyzes hydrolysis of starch
– Salivary & pancreatic amylase
• Hydrolysis of α(1  4) glycoside bonds
• Dissaccharidase are brush border enzyme
– Dissacharidase, maltase, sucrase/isomaltase (hydrolysis of sucrose &
isomaltose), lactase, trehalase (located in brush border of intestinal
mucosal cells)  resultant: monosaccharide are absorbed
• Lactose gradually  through adolescence  lactose
intolerance
– Lactose remains in interstitial lumen as substrate for bacterial fermentation to
lactate  discomfort + diarrhea
2 Mechanism of absorption of Monosaccharide
in small intestine
• Glucose & galactose
absorption by Na-dependent
process
 Transport prot: SGLT1,
competing w/ each other
for intestinal absorption
• Other monosaccharide
absorbed by carrier-mediated
diffusion
 ✗ actively transported,
eg: fructose & alcohols
only absorbed down the
[] gradient after
moderately  intake
 Some remains in lumen
(substrate for bacterial
fermentation)
 Indigestible Carbohydrates
• Fiber, some oligosaccharides and resistant starch
– Resistant starch: escaped digestion in small intestine
of healthy individual due to cooking & process altering
its digestibility
• Foods high in starch:
– Legumes, unripe bananas, cold cooked potatoes, rice,
pasta
• Affects GI motility, type of intestinal microflora,
nutrient absorption & # of intestinal gas
• Stimulate GI motility
–  vol of material in lumen of intestine   bulk of
material in feces
– + water from soluble fibers & resistant stach to intestine =
easier evacuation of stool
–  healthy bowel function: extra bulk stimulates peristalsis
 muscle of colon works extra, becomes stronger,
function better
• Promote healthy microflora
– Serve as food source for microflora
– Breakdown of these carbs  SCFA + acidification of colonic
contents  SCFA as fuel source for cells in colon & body
tissues  regulates cellular process
• Acid inhibits growth of undesirable bacteria & favor growth of
Lactobacili & Bifidobacteria
– SCFA help prevent & treat inflammation in bowel (causes
of diarrhea) & protect against colon cancer
 • Slow nutrient absorption
–  vol of intestinal contents & absorb water 
viscous solutions  slow nutrient absorption 
 # of contact b/w nutrients & absorptive surface
of SI & enzymes and foods
– Fiber causes distention & slows emptying in
stomach
– Slows absorption of glucose   fluctuation in
blood glucose in SI
– Binds cholesterol & bile   absorption  
blood cholesterol &  risk of CVD
•  Intestinal Gas

Carbohydrates in Digestive Tract. http://www.wiley.com/college/sc/smolin/pdf/chapter4.pdf

 Indigestible Carbohydrates

http://www.cmrinstitute.org/nni/content/module2/groups/44.html
 LIPIDS
• Major lipids in diet: Triacylglycerol,
phospholipids (lesser in extent)
• Hydrophobic mol., therefore have to be
emulsified to very small droplets (micelles)
before they can be absorbed
• Fat sol., vits & other lipids (chol.) are absorbed
dissolved in micelles
– Absorption of vitamins are impaired on a very low
fat diet
• Hydrolysis of triacylglycerol initiated by lingual &
gastric lipases
– Attack sn-3 ester bond forming (C1 & C3)  1,2-
diacylglycerol + F.A (aiding emulsification)
• Pancreatic lipases secreted to small intestine, then
requires further pancreatic proteins (colipase) for
activity
– Specific for primary ester link position 1 & 3 in
triacylglycerol  2-monoacylglycerol & FFA (major end
product)
– Monoacylglycerol (poor substrates for hydrolysis), so <25%
of ingested triacylglycerol is completely hydrolyzed to
glycerol + F.A
• Bile salts by liver, secreted in bile
– Permits emulsification of products of lipid digestion into
micelles (together w/ phospolipid & chol. from bile)
 Diffusion
Allow Permit close
(transported
Because product of contact w/ Allow uptake
thru aq.
micelles are digestion brush border into
Environment
soluble (includes of mucosal epithelium
of intestinal
vitamin) cells
lumen

• Bile salts pass on ileum (most are absorbed to enterohepatic circulation)

• w/in intestinal epithelium,
• 1-MAG  hydrolyzed  FA + glycerol
• 2-MAG  re-acylated  Triacylglycerol via monoacylglycerol pathway
• Glycerol released in intestinal lumen ✗ reutilized but passes into portal vein
• Glycerol released w/in epithel is reutilized for triacylglycerol synthesis via
normal phosphatidic acid pathway
• Long chain FA are esterified to yield triacylglycerol in mucosal cells & together
w/ other product of Lipid digestion  secreted as chylomicrons  lymphatics
 thoracic duct  blood stream
• Short & medium chain FA mainly absorbed to hepatic portal vein as FFA
Transport of lipid across Intestinal Epithelium
 PROTEINS
2 main classes of proteolytic digestive enyzmes (proteases):
Endopeptidase & Exopeptidase
– Endopeptidase – Exopeptidase
• Hydrolyze peptide of
• Hydrolyze peptide bond peptide bond one at a time
b/w specific AA through from the ends of peptide
out molecule – CARBOXYPEPTIDASE
» Secreted in PJ, release
• 1st enzyme to act, yield AA from free carboxyl
 # of smaller terminal
– AMINOPEPTIDASE
fragments » Secreted in intestinal
• pepsin, trypsin, mucosal cells, release
AA from amino
chymotrypsin, elastase terminal
– DIPEPTIDASE
» In brush border of
intestinal mucosal cells,
hydrolyzes of
dipeptides
• Proteins are zymogen (inactive)
– Pepsinogen  gastric acid & activated pepsin
(autocatalysis)  pepsin
– Trypsinogen (in small intestine) 
enteropeptidase by duodenal epithelial cells 
trypsin
– Chymotrypsinogen  trypsin  chymotrypsin
OU Human Physiology: Chemical Digestion and Absorption: A Closer Look. Available from: http://archive.cnx.org/contents/47e14543-2793-
423b-baa4-dc0e4548245f@1/ou-human-physiology-chemical-digestion-and-absorption-a-closer-look
• Inhibitor protein:
– Serin:
• Inhibits activation of premature pancreatic zymogen
• Inhibits trypsin  inh activation of proteases in tissue,
especially during:
– Growth
– Wound healing
– Infection
Needs more /  # of protein
 Vitamins & Minerals
• H2O-soluble vitamins & most mineral salts 
absorbed from small intestine through active
transport or carrier mediated diffusion 
binding to intra cell protein to achieve []ve
uptake
– Vit B12 absorption: requires Intrinsic Factors (IF)
– Ca2+: vit D dependent
– Zn: Zn binding ligand by exocrine pancreas
– Fe: limited
• Ca2+
– Regulated by PTH
– Calbidin (Ca binding prot) required for absorption
• Induced by vit D (affects permeability of mucosal cells to Ca2+)
– Phytic acids (inositol hexaphosphate) in cereals bind Ca2+
in Intestinal lumen – inh/prevent absorption
– Zn are also chelated by phytate
– Whole wheat products;
• yeast contains enzyme phytase (dephosphorylation of phytate)
–  [] FA in intestinal lumen  impaired fat absorption, 
Ca2+ absorption by forming insoluble Ca2+ salts
– intake of oxalate  deficiency (Ca oxalate is insoluble)
 • Most effective compound to  absorption of
Fe: vit C (40-80 mL/day)
– 25-20 mL/meal  iron absorption
• Alcohol & fructose  iron absorption
• Absorption of iron (inorganic or heme) is
impaired by Ca2+
10% dietary
absorption due
Ferritin
Transferrin in to mucosal
Inorganic iron (intracell
plasma barrier (1-5%
protein)
from plant
foods)
 Electrolytes
• Most ions are actively absorbed along length
of small intestine
– Na+ coupled w/ absorption of glucose + AA
– Anions passively follow electrical potential
established by Na+
– K+ diffuses across Intestinal mucosal due to
osmotic gradient
Typhoid Fever
 The Organism
• Salmonella typhi, a Gram-negative bacterium
• Less severe disease: Salmonella serotype paratyphi A.
• S. typhi has several unique features:
– several unique clusters of genes known as pathogenicity
islands (PAIs)
– S. typhi can be identified in the laboratory by several
biochemical and serological tests
– Most specific is that of polysaccharide capsule Vi
• present in about 90% of all freshly isolated S. typhi and has a
protective effect against the bactericidal action of the serum of
infected patients.
• Provides the basis for one of the commercially available vaccines

Background document: The diagnosis, treatment and prevention of typhoid fever. Communicable Disease Surveillance & Response Vaccines & Biologicals. WHO
 The Disease
typhoid organisms
S. typhi multiplies in
Ingestion in food or pass through the
mononuclear
water pylorus and reach the
phagocytic cells.
small intestine

rapidly penetrate the

rapidly elicit an influx arrive in the lamina mucosal epithelium
of macrophages (Mp) propria via microfold cells or
enterocytes

Some bacilli remain

ingest the bacilli but
within Mp of the
do not generally kill
small intestinal
them.
lymphoid tissue
 typhoid bacilli reach
Other typhoid bacilli
the bloodstream
are drained into further multiplication
principally by lymph
mesenteric lymph and ingestion by Mp.
drainage from
nodes
mesenteric nodes,

pathogen reaches an
intracellular haven
(resides) within 24
hours after ingestion general circulation 
enter the thoracic
throughout the silent primary
duct
organs of bacteraemia
reticuloendothelial
system (spleen, liver,
bone marrow, etc.)

• The incubation period in a particular individual depends on

the quantity of inoculum
it resides during the • i.e. it decreases as the quantity of inoculum increases,
incubation period, ~8 and on host factors.
to 14 days.
• Incubation periods ranging from 3 days to more than 60
days have been reported.

Inoculation: the introduction of a pathogen or antigen into a living organism to stimulate the production of antibodies
 Symptoms & Factors
• Mild illness with low-grade fever, malaise, and slight dry cough  Severe clinical
picture with abdominal discomfort and multiple complications

Factors influencing severity & overall clinical outcome of the infection:

• duration of illness before the initiation of appropriate therapy
• choice of antimicrobial treatment
• age,
• previous exposure or vaccination history
• virulence of the bacterial strain
• quantity of inoculum ingested
• host factors (e.g. HLA type, AIDS or other immunosuppression)
• taking other medications such as H2 blockers or antacids to diminish gastric acid
• HIV  significantly increased risk of clinical infection with S. typhi & S. paratyphi
• Helicobacter pylori infection  increased risk of acquiring typhoid fever
 Acute non-complicated disease
• Prolonged fever
• disturbances of bowel function
– constipation in adults
– diarrhoea in children
• headache
• Malaise
• anorexia
• Bronchitic cough: common in the early stage of the illness.
• During the period of fever, up to 25% of patients show
exanthem (rose spots), on the chest, abdomen and back.
 Complicated disease
• Occult blood is a common finding in the stool of 10-20% of
patients, and up to 3% may have melena.
• Intestinal perforation
• Abdominal discomfort develops and increases.
– It is often restricted to the right lower quadrant but may be
diffuse.
• The symptoms and signs of intestinal perforation and
peritonitis sometimes follow + sudden rise in pulse rate,
hypotension, marked abdominal tenderness, rebound
tenderness and guarding, subsequent abdominal rigidity.
• Rising WBC count with a left shift
• Free air on abdominal radiographs are usually seen
• Typhoid meningitis
• encephalomyelitis,
• Guillain-Barré syndrome
• cranial or peripheral neuritis
• psychotic symptoms,
although rare, have been reported.

Other serious complications documented with typhoid fever include:

• haemorrhages (causing rapid death in some patients)
• hepatitis,
• myocarditis,
• pneumonia,
• disseminated intravascular coagulation,
• Thrombocytopenia
• Haemolytic uraemic syndrome
• Prolonged persistent fever and diseases for no clear reason.
• Genitourinary tract manifestations or relapse, and/or a chronic carrier
state may develop.
– Carrier state: 15% of patients, depending on age, become chronic carriers
harbouring S.typhi in the gallbladder.
 Contamination & Transmission
• Human: only natural host & reservoir
• By Ingestion of food or water contaminated w/
feces
• Ice cream  significant risk for transmission
• Shellfish from contaminated water, raw fruit, vegs
fertilized w/ sewage  sources of past outbreaks
• Dev countries: transmitted when chronic carriers
contaminate food (unsatisfactory food-related
hygiene)
 Diagnosis
• Definitive: isolation of S.typhi from blood,
bone marrow, specific anatomical lesion
• Presence of clinical symptoms characteristics
• Detection of specific Ab response 
suggestive but not definitive
• Blood culture  mainstay of diagnosis
• Ox bile medium (Oxgall) recommended for
enteric fever pathogens (S.typhi & S.paratyphi)
• Failure to isolate organism may be caused by
several factors:
– Limitation of lab media
– Presence of AB
– Vol of specimen cultured
– Time of collection
– Patients w/ history of fever for 7-10 days
• Bone marrow aspirate: GOLD STANDARD for
diagnosis of typhoid fever
• Duodenal aspirate culture also proved highly
satisfactory diagnostic test
 Ideal specimen
• 1st wk = blood (culture)
– 10-15 mL adults & adolescents
– 2-4 mL in children
• 2nd wk = serum (Ab)
• 3rd wk = stool
• 4th wk = urine
 Colony Characteristics
• Blood agar
– Non-hemolytic smooth white colonies
• MacConkey agar
– Lactose non-fermenting smooth colonies
• SS agar
– Lactose non-fermenting colonies + black centers
*except S.paratyphi A
Biochemical identification
 Serological Procedures
• Characterized by their somatic (O) & flagellar (H) Ag
– O: w/ slide agglutination test w/ group specific antiserum +
agglutination w/ factor antiserum
– H: tube agglutination test
• Organism should be motile & from a liquid culture
• Envelop Ag = Vi (virulence)
• Felix-Widal test
– Measures agglutinating Ab lvl against O & H Ag
– Doubling dilution of sera in large test tubes
– O = appear on days 6-8 after onset – disc-like pattern
– H = 10-12 after onset of disease – loose, cotton wooly clumps
– Performed on acute serum (at first contact w/ pts)
– At least 1 ml blood should be collected/time
– Moderate sensitivity & specificity
 New diagnostic test
• IDL Tubex test
– Simple (1 step test) & rapid (~2
mins)
– Slide latex agglutination test
– O9 Ag – highly specific for S.typhi
(immunodominant epitope)
– Not positive for S.Paratyphi
– Detects IgM Ab
• Typhidot test
– Simple, speed,
economical
– Sensitivity 85.9%,
specificity 96.7%
– Detect IgM & IgG to
S.typhi
• IgM dipstick test
– Detect IgM Ab in serum
& whole blood
 DD
• Malaria
• Amebiasis
• Viral illnesses: dengue or EBV infection,
infection w/ non-Salmonella bacterial
pathogens (Yersinia, Campylobacter,
Pseudomonas)
THERAPY
• Fluoroquinolones  DOC
– More rapidly effective
– Lower rates of relapse & stool
carriage >> chloramphenicol,
ampicillin, TMP-SMX
– More effective than ceftriaxone •
• Strain sensitive to nalidixic acid:
– Ciprofloxacin 5-7 days
• Uncomplicated disease
– Effectiveness of oral th/ =
parenteral th/
• Infected by strains w/ intermediate
resistance minumum inhibitory
concentration (MIC) to
ciprofloxacin 0.125 – 1 μg/mL
– Higher doses of cipro for 10-14
days
Pts w/ S.typhi strains w/ MIC value
2 μg/mL or >>
– 3rd generation cephalosporin or
– Azythromycin
 Prevention
• Relies on proper food handling & sanitation
• Dev countries: careful attention to separation of raw &
cooked foods; awareness to multiple ways in which
cross-contamination can occur in food preparation
areas
• Monitor children to insure hand hygiene after contact
w/ reptiles & fowl
• Travel to dev countries: vaccine or parenteral capsular
polysaccharide vaccine
– 1st line: care in consumption of food & water.
• Avoid tap water, salads, uncooked vegs, unpasteurized milk & milk
products
Diarrhea
 Gastroenteritis
• Gastroenteritis is an inflammation of the lining
of the intestines caused by a virus, bacteria or
parasites.
• When you have diarrhea and vomiting, you
may say you have the "stomach flu." What it's
really called is gastroenteritis.
• Viral gastroenteritis is the second most
common illness in the U.S. The cause is often a
norovirus infection.

Harrison's 18th
 Epidemiology
• Acute gastroenteritis is a common cause of morbidity and mortality
worldwide.
• Diarrhea is in the top 5 causes of deaths worldwide, with most occurring
in young children in nonindustrialized countries.
• In industrialized countries, diarrheal diseases are a significant cause for
morbidity across all age groups.
• Etiologies include bacteria, viruses, parasites, toxins, and drugs.
(Viruses are the most often, in all ages)
• Sporadic gastroenteritis in infants, which most frequently is caused by
rotavirus.
• Epidemic gastroenteritis, which occurs either in semiclosed communities
(eg, families, institutions, ships, vacation spots) or as a result of classic
food-borne or water-borne pathogens. Most of these infections are
caused by caliciviruses.
• Sporadic acute gastroenteritis of adults, which most likely is caused by
caliciviruses, rotaviruses, astroviruses, or adenoviruses.

Harrison's 18th
 Diarrhea Classification
• Acute Diarrhea
– lasts two weeks or less
– self-limited
– requiring no diagnostic work-up
– symptomatic treatment only (fluids)
– Acute diarrhea should be investigated only if there is
• evidence of tissue invasion such as blood or pus in the stool
• fever
• leukocytosis
• severity that produces significant fluid and electrolyte loss�
• Chronic diarrhea
– lasts longer than two weeks
– or is intermittent over months or years
– This form requires a diagnostic work-up and a treatment strategy
 Pathophysiology of Diarrhea
• Osmotic diarrhea
– Diarrheal stools promptly regress with discontinuation of the offending nutrient, and the
stool ion gap is high, exceeding 100 mOsm/kg.
– The fecal osmolality in this circumstance is accounted for not only by the electrolytes
but also by the unabsorbed nutrient(s) and their degradation products.
• Secretory diarrhea
– The epithelial cells’ ion transport processes are turned into a state of active secretion.
– The most common cause of acute-onset secretory diarrhea is a bacterial infection of the
gut.
– Colonization  enteric pathogens may adhere to or invade the epithelium  produce
enterotoxins or cytotoxins  trigger release of cytokines attracting inflammatory cells &
prostaglandins or platelet-activating factor.
– Features of secretory diarrhea include a high purging rate, a lack of response to fasting,
and a normal stool ion gap (ie, 100 mOsm/kg or less), indicating that nutrient absorption
is intact.
 Etiology
Viruses : Enterovirus, adenovirus, rotavirus
Enteral Infection
Bacteria : Vibrio, E. coli, Shigella,
Salmonella, Campylobactr,
Yersinia, Aeromonas
Infection Protozoa : G. Lamblia, E.
Histolitica, Isospora belli
Helmin : Ascaris,
Parasites
Trichuris, Oxyyuris,
Caused of Strongyloides
diare
Fungal : Candida albicans

Parenteral Infections : OMA, Tonsilofaringitis,

Bronkopneumonia, Morbilli
Malabsorption : Carbohydrate, Lipid, Protein
Food : out-of-date, poisonous
Allergic
Immunodeficiency
Phsycology : afraid, worried
 Etiology
• Viruses
– Norwalk virus, cytomegalovirus and viral hepatitis. Rotavirus is a common
cause of acute childhood diarrhea.
• Bacteria and parasites.
– Contaminated food or water can transmit bacteria and parasites to your body.
– Parasites such as Giardia lamblia and cryptosporidium can cause diarrhea.
– Common bacterial causes of diarrhea include campylobacter, salmonella,
shigella and Escherichia coli.
– Diarrhea caused by bacteria and parasites can be common when traveling in
developing countries and is often called traveler's diarrhea.
• Medications
– The most common are antibiotics.
– Antibiotics destroy both good and bad bacteria, which can disturb the natural
balance of bacteria in your intestines. This disturbance sometimes leads to an
infection with bacteria called Clostridium difficile, which also can cause
diarrhea.
• Lactose intolerance.
– Your body makes an enzyme that helps digest lactose, but for most
people, the levels of this enzyme drop off rapidly after childhood. This
causes an increased risk of lactose intolerance as you age.
• Fructose, can cause diarrhea in people who have trouble digesting
it.
• Artificial sweeteners.
• Surgery. Some people may experience diarrhea after undergoing
abdominal surgery or gallbladder removal surgery.
• Other digestive disorders.
– Chronic diarrhea has a number of other causes, such as Crohn's
disease, ulcerative colitis, celiac disease, microscopic colitis and
irritable bowel syndrome.
 Bacterial Gastroenteritis
• Bacterial Gastroenteritis is a very common
disorder
• Usually self-limited
• The most common complication is
dehydration
 Etiology
1. Salmonella sp.
2. Shigella sp.
3. Campylobacter sp.
4. Aeromonas sp.
5. Escherichia sp.
 Durati
Incubation Associated Laboratory
Etiology Sign and Symptom on of Treatment
Period Foods Testing
Illness
Supportive care for
raw and Routine stool
severe cases,
undercooked, culture;
Watery diarrhea, antibiotics such as
poultry, Campylobacter
Campylobacter cramps, fever and 2-10 erithromycin,
2-5 days unpasturized requires special
jejuni vomiting, diarrhea days quinolones early in
milk, and medium and
may be bloody the diarrhea
contaminated incubation at
disease. GBS can
water 42C to grow
be a sequela.
water or food Supportive care ,
watery diarrhea,
Enterotoxigenic 3 to >7 contaminated antibiotics, include
1-3 days abdominal cramps, stool culture
E. coli ( ETEC ) days with human TNP-smx and
some vomiting
feces quinolones
Supportive care
with aggressive oral
Conaminated and IV rehydration;
Profuse watery
water, fish, tetracyclin,
diarrhea with
shellfish, doxycyclin is
vomiting, wihich can 3-7
Vibrio Cholerae 24-72 hours street-vended Stool culture recommended for
lead to severe days
food typically adult, and TMP-
dehydration and
from latin smx is
death within hours
america recommended for
children ( < 8 years
old )
Unrefrigerate
Normally a
d or
Sudden onset severe clinical
improperly
nausea and diagnosis.
refrigerated
Staphylococcus vomiting. Abdominal 24-48 Stool, vomitus,
1-6 hours meats, Supportive care
aureus cramps, diarrhea, hours and food can be
potato, and
and fever may be tested for toxin
egg salads.
present and culture if
Cream
indicated
pastries.
Algorithm for
the
management of
acute diarrhea

Harrison's 18th
 Treatment : Acute Diarrhea
• Fluid and electrolyte replacement.
– Oral sugar-electrolyte : severe
– IV rehydration : infants and elderly
• Moderately severe nonfebrile and nonbloody diarrhea 
loperamide
• Bismuth subsalicylate  reduce symptoms of vomiting and
diarrhea, may reduce frequency of travelers’ diarrhea
• Antibiotics
– Moderate-severe febrile dysentery  empiric  quinolone
– Suspect giardiasis  empiric  metronidazole
– AB prophylaxis  immunocompromise, IBD, hemochromatosis, gastric
achlorhydria
– Ciplrofloxacin anf rifaximin  reduce bacterial diarrhea in
uncomplicated travelers’ diarrhea

Harrison's 18th
 Prevention
• Preventing viral diarrhea
– Wash frequently.
– Use hand sanitizer when washing isn't possible.
• Preventing diarrhea from contaminated food
– Serve food right away or refrigerate it after it has been cooked or reheated.
– Wash work surfaces frequently to avoid spreading germs from one food item
to another.
– Use the refrigerator to thaw frozen items.
• Preventing traveler's diarrhea
– Watch what you eat. Eat hot, well-cooked foods.
– Watch what you drink.
• Drink bottled water, soda, beer or wine served in its original container.
• Avoid tap water and ice cubes.
• Use bottled water even for brushing your teeth. Keep your mouth closed while you
shower.
• Remember that alcohol and caffeine can aggravate diarrhea and dehydration.
– Ask your doctor about using antibiotics.
– Check for travel warnings.
Harrison's 18th
 Classification of Dehydration
Mild Dehydration Moderate Dehydration Severe Dehydration
Fluid loss (% from 2-5 % 5-8% 8-10%
body weight)
Symptoms Turgor <<, hoarse, Bad turgor, hoarse, Moderate
preshock preshock or shock dehydration + loss of
consciousness,
muscle stiffness,
cianosis
Plasma density 1.025-1.028 1.028-1.032 1.302-1.040

CVP CVP +4 to +11 cm H2O  N ; CVP < +4 cm H2O  shock or dehydration

Harrison's 18th
DIARRHEA
• Passage of abnormally liquid or unformed stools at  frequency
• Adults: stool weight >200 g/d  considered diarrheal
• Defined based on duration:
– Acute <2 wks
– Persistent 2-4 wks
– Chronic >4 wks
• Stool totaling <200 g/d = pseudodiarrhea: freq passage of small vol
of stools, associated w/ rectal urgency, tenesmus, or feeling
incomplete evacuation, & accompanies IBS or proctitis
• Fecal incontinece: involuntary discharge of rectal contents due to
neuromuscular disorders or strucutral anorectal problems
• Diarrhea & urgency if severe aggravate or cause incontinence
 ACUTE DIARRHEA
• >90% cases caused by infectious agents
– + fever, vomiting, abdominal pain
• 10% by non-infectious agents:
– Medications, toxic ingestions, ischemia, food
indiscretions
 GASTROENTERITIS
• Inflammatory process of stomach or intestinal
mucosal surface
• Refers to acute infectious diarrhea w/
syndrome of <2 wks duration + fever, nausea,
vomiting, abdominal pain, dehydration,
weight loss
• GIT: efficient at fluid reabsorption
– 1-2 L fluid ingested orally, 7 L enter upper tract from saliva,
gastric, pancreatic, biliary sources
– <200 mL fluid excreted in daily feces
Thus, small  in secretory rate or  in absorptive rate =
overwhelm intestinal absorptive capacity
• Diarrhea:  freq (>3 bowel movements) or  vol (>200
mL/day)
• Intestinal infection w/ bacteria, viruses, parasites 
gastroenteritis = fecal-oral transmission
– More commonly via ingestion of food or water
contaminated w/ pathogens from human or animal feces
• Acute infection occurs when ingested agent overwhelms
host’s mucosal immune & nonimmune (gastric acid,
digestive enzymes,mucus, peristalsis & suppresive resident
flora) defenses
PRINCIPAL HOST DEFENSES
• Gastric acidity
– <4.0  kill more than 99% ingested
organisms
– Rotavirus & protozoal cysts survive
– Achlorydia or hypochlorhydia  risk of dev
infectious diarrhea
• Physical barrier of mucosa
– Disruption; e.g mucositis  predispose pts
to gram 0ve bacteremia
•  peristalsis  propels organisms along GIT 
cough reflex  clearing w/ lungs
• Intestinal flora
– SI & colon ~104 – 1011 organisms/mL
respectively
– 99% anaerobes
– Production of fatty acids + acidic pH,
competition for mucosal attachment 
prevent colonization of invading organisms
– AB use & extremes of ages  alter flora 
risk for GE
 Virulence factors
Play complementary role in acute
infectious diarrhea
• Most organisms acquire an inoculum
of 105-108 = infection
– Except: Shigella, Giardia,
Cryptosporidium, Entamoeba  10
– 100 organisms ingested ✓
• Production of toxins  variety
clinical syndrome
– Enterotoxins: watery diarrhea
– Cytotoxins: dystentery
– Neurotoxins
• Botulinum toxin (classic example)
• Staph.auerus & Bacillus cereus 
neurotoxins  CNS  emesis
• Adherence & invasions factors
facilitate colonization  contribute
to virulence
 Infectious Agents
• Mostly acquired by fecal-oral transmission
• More commonly via ingestion of food or water
contaminated w/ pathogens from human or
animal feces
• Immunocompetent  resident fecal microflora
(>500 species) rarely cause diarrhea  actually
play role in  growth of ingested pathogen
– Disturbances of flora by AB  diarrhea by  digestive
function or allows overgrowth of pathogens
• E.g: Clostridium difficile
 Indicators of possible infectious
diarrhea
• Travel to dev. Areas
• Day-care center attendance or employment
• Consumption of unsafe foods (raw meats, eggs, shellfish, unpasteurized
milk or juices)
• Swimming in or drinking untreated fresh surface water from (e.g lake or
stream)
• Visiting a farm or petting zoo or having contact w/ reptiles or pets w/
diarrhea
• Knowledge of other ill persons (dormitory or office or social function)
• Certain recent or regular medications (AB, antacids, antimotility agents)
• Underlying medical conditions predisposing infectious diarrhea (AIDS,
medications, prior gastrectomy, extremes of age)
• Receptive anal intercourse or oral-anal sexual contact
• Occupation as food handler or care giver
 Clinical
Syndromes
• Acute infectious
diarrhea divided
into:
– Non
inflammatory
– Inflammatory
– invasive
 Epidemiology
• Gastroenteritis: major cause of global mortalilty & morbidity
among infants & children
– Peak attack rates: young school children & siblings
– Most case: viral agents
• Rotavirus 10-50%
• Norovirus 10-30%
• Enteric adenovirus 2-5%
– Bacterial <15% disease; severe in Campylobacter spp, E.coli spp,
Salmonella spp, Yersinia spp.
• EHEC O157:H7 = important cause of hemolytic uremic syndrome in
children
• Yersinia = watery diarrhea in children 1-5 yo, mimic appendicitis in older
children & adolescents
• World Health Organization (WHO) & UNICEF:
– ~2 billion cases of diarrheal disease worldwide
every year;
– 1.9 million children <5 years of age perish from
diarrhea each year, mostly in developing
countries.
– 18% of all the deaths of children under the age of
five
– more than 5000 children are dying every day as a
result of diarrheal diseases.
– Of all child deaths from diarrhea, 78% occur in the
African and South-East Asian regions.
• Each child <5 years of age experiences an average of 3
annual episodes of acute diarrhea.
• Globally in this age group, acute diarrhea is the second
leading cause of death (after pneumonia)
– both the incidence and the risk of mortality from diarrheal
diseases are greatest among children in this age group,
particularly during infancy – thereafter, rates decline
incrementally.
• Other direct consequences of diarrhea in children:
– growth faltering, malnutrition, and impaired cognitive
development in resource-limited countries.
 Causative agents & pathogenic mechanisms
BACTERIAL AGENTS
In dev countries, enteric bacteria & parasites > viruses
DIARRHEAGENIC E.COLI
• Enterohemorrhagic E.coli (EHEC O157:H7) cause disease more commonly
in dev countries
– Enterotoxigenic E.coli (ETEC)  traveler’s diarrhea
– Enteropathogenic E.coli (EPEC)  rarely cause disease in adults
– Enterohemorrhagic E.coli (EHEC)  bloody diarrhea, severe hemorragic colitis,
hemolytic uremic syndrome (cattle as predominant reservoir)
Pediatric details:
• Enteroaggregative E.coli (EAggEC)  watery diarrhea in young children &
persistent diarrhea in children w/ HIV
• Enterotoxigenic E.coli (ETEC)  diarrhea in infants & children in dev
countries
• Enteropathogenic E.coli (EPEC)  common in children <2 years, persistent
diarrhea in children
 Montezuma’s revenge: travelers' diarrhea or other sicknesses contracted by tourists visiting Mexico

University of Endinburgh. Invasion of Eukaryotic cells by Bacteria (role of cytoskeleton). http://www.bms.ed.ac.uk/research/others/smaciver/Bacteria%20Inv.htm

Campylobacter
• Asymptomatic infection is very common in developing countries
• Associated with the presence of cattle close to dwellings
• Watery diarrhea; sometimes dysentery
• Poultry = source of Campylobacter infections in developed
countries & increasingly in developing countries (where poultry is
proliferating rapidly)
• The presence of an animal in the cooking area is a risk factor in
developing countries

Pediatric details:
• Campylobacter is one of the most frequently isolated bacteria from
the feces of infants and children in developing countries,
• peak isolation rates: 2 years of age and younger
SHIGELLA
• Hypoglycemia, occurs more frequently than in other types of
diarrheal diseases
• S. sonnei is common in developed countries, causes mild illness,
and may cause
• institutional outbreaks.
• S. flexneri is endemic in many developing countries and causes
dysenteric
• symptoms and persistent illness; uncommon in developed
countries.
• S. dysenteriae type 1 (Sd1) — the only serotype that produces Shiga
toxin, as
• does EHEC.

Pediatric details:
• An estimated 160 million episodes occur in developing countries,
primarily in children.
• common in toddlers and older children than in infants
 Clinical Microbiology Reviews. American Society for Microbiology. http://cmr.asm.org/content/21/1/134/F1.expansion.html

Cellular pathogenesis of Shigella spp.

• S. flexneri passes the EC barrier by transcytosis through M cells and encounters resident
macrophages.
• The bacteria evade degradation in macrophages by inducing an apoptosis-like cell death, which is
accompanied by proinflammatory signaling.
• Free bacteria invade the EC from the basolateral side, move into the cytoplasm by vectorial actin
polymerization, and spread to adjacent cells.
• Proinflammatory signaling by macrophages and EC further activates the innate immune response
involving NK cells and attracts PMN.
• The influx of PMN disintegrates the EC lining, which initially exacerbates the infection and tissue
destruction by facilitating the invasion of more bacteria.
• Ultimately, PMN phagocytose and kill Shigella, thus contributing to the resolution of the infection.
VIBRIO CHOLERAE
• All serotypes (>2000) are pathogenic for humans
• V. cholerae serogroups O1 & O139 are the only two
serotypes that cause severe cholera, and large outbreaks
and epidemics
• Absence of prompt and adequate rehydration  severe
dehydration  hypovolemic shock & death can occur
within 12–18 h after the onset of the first symptom
• Stools are watery, colorless, and flecked with mucus; often
referred to as “ricewatery” stools.
• Vomiting is common; fever is typically absent.

Pediatric details:
• In children, hypoglycemia can lead to convulsions and
death.
Salmonella
• Enteric fever — Salmonella enterica Typhi and Paratyphi A, B, or C
• (typhoid fever);
– fever lasts for 3 weeks or longer; patients may have normal bowel habits, constipation or
diarrhea.
• Animals are the major reservoir for salmonellae.
• Humans are the only carriers of typhoidal Salmonella.
• In non-typhoidal salmonellosis (Salmonella gastroenteritis):
– Acute onset of nausea
– vomiting,
– Diarrhea: watery
• The elderly & people with immune-compromised status (e.g., hepatic and
lymphoproliferative disorders, hemolytic anemia), appear to be at the greatest
risk.

Pediatric details:
• Infants and children with immune-compromised status (e.g., severe
malnourishment) appear to be at the greatest risk.
• Fever develops in 70% of affected children.
• Bacteremia occurs in 1–5%, mostly in infants.
 Viral Agents
In both industrialized and developing countries,
viruses are the predominant cause of acute
diarrhea, particularly in the winter season.

ROTAVIRUS
• 1/3 of diarrhea hospitalizations & 500,000
deaths worldwide
• each year
• Associated with gastroenteritis of above-
average severity.

Pediatric details:
• Leading cause of severe, dehydrating
gastroenteritis among children.
• Nearly all children in both industrialized and
developing countries get infected by the
time they are 3–5 years of age.
• Neonatal infections are common, but often
asymptomatic.
• The incidence of clinical illness peaks in
children b/w 4 and 23 months of age.
HUMAN CALICIVIRUSES (HUCVS):
• Family Caliciviridae—the noroviruses and sapoviruses (previously
• called “Norwalk-like viruses” and “Sapporo-like viruses.”
• Noroviruses: most common cause of outbreaks of gastroenteritis,
affecting all age groups.

Pediatric details:
• Sapoviruses primarily affect children. 2nd most common viral agent
after rotavirus, 4–19% of episodes of severe gastroenteritis in
young children

ADENOVIRUS
• Infections most commonly cause illnesses of the respiratory system.

Pediatric details:
• depending on the infecting serotype, this virus may cause
gastroenteritis especially in children.
 Parasitic Agents

http://www.uib.cat/depart/dba/microbiologia/ADSenfcomI/material_archivos/infeccion%20gastrointestinal.pdf
Hookworms can cause some of the
following symptoms:
• anemia (pale skin etc.) and protein
deficiency caused by blood loss
• constipation
• congestive heart failure
• decreased rate of growth and
mental development in children
(caused by protein and iron
deficiency)
• diarrhea
• dizziness
• dyspnea (shortness of breath)
• excessive coughing during larvae
migration
• fatigue (tiredness)
• fever
• loss of appetite
• nausea
• rash or sore and itchy feet after
larval invasion
• stomach or chest pain
• vomiting
• weight loss
Minor infections can be asymptomatic but usually
one or more of the following symptoms occur:
• anemia (for example, pale skin)
• constipation
• cough
• diarrhea
• eosinophilic pneumonitis (during larvae
migration through the lungs)
• nausea
• rashes in waist and buttocks
• stomach ache
• vomiting
• weight loss.

Immunosuppressed patients (immune system

weakened intentionally after an organ transplant
or suchlike) or immunocompromised patients
(immune system weakened by another disease
such as HIV) can have also some of the following
symptoms:
• death
• distension
• neurological and pulmonary complications
• septicemia
• shock.
 Giardiasis
Common giardiasis symptoms
include:
• bloating
• bad breath and farts
• dehydration
• diarrhea or greasy floating
stools
• fatigue
• loss of appetite
• nausea
• stomach ache
• weakness
• weight loss.
• Diarrhea can be fatal, if you
do not drink enough water
with salt and glucose.
• Lack of B12-vitamin. This is
due to the impaired
absorption (malabsorption)
in the damaged intestinal
wall.
Balantidiasis is
often
asymptomatic. But
in some cases the
patient might have
diarrhea, weight
loss and dysentery
Clinical manifestation of teaniasis solium: abdominal pain, nausea, diarrhea, weight loss, infection may by asymptomatic.
Clinical manifestation of cysticercosis in the brain: headache, meningoencephalitis, vomiting, and seizures; in the eyes:
uveitis, retinitis.
Clinical manifestation of teniasis saginata: abdominal pain, nausea, diarrhea, weight loss, infection may by
asymptomatic. In some, proglottids appear in the stools and may even protrude from the anus
Diphyllobothriasis is usually
asymptomatic.

In some cases it causes severe

vitamin B12 deficiency because D.
latum can absorb most of the B12
intake. It can lead to neurological
symptoms.

Diphyllobothriasis symptoms
include:
• constipation
• diarrhea
• fatigue
• obstruction of the bowel
• pernicious anemia (caused by
vitamin B12 deficiency) which
can lead to
• subacute combined
degeneration of spinal cord
• stomach pain
• vomiting
• weight loss.
• Migrating proglottids can
cause inflammation of the bile
duct or the gall bladder.
The first symptoms are a rash
or itch during the first few
days.

Within two months chills,

cough, diarrhea, fatigue, fever
and muscle aches can occur.

Usually however during the

first few weeks schistosomiasis
is asymptomatic.

The disease is worse for

children who can develop
anemia, learning difficulties
and malnutrition.

After years of infection eggs

inflame organs such as the
liver, bladder and lungs. If eggs
end up in the brain or spinal
cord, they can cause paralysis,
seizures or inflammation of
the spinal cord.

http://www.parasitesinhumans.org/
 Patient Evaluation
• Most cases of acute GE: self-limited
• Consultation is advised for pts w/
– fever >38.50C,
– dysentery,
– significant abdominal pain,
– dehydration,
– risk factors for disease requiring intervention
(Elder, pregnant, recent AB use)
INITIAL EVALUATION
• History should focus of:
– Severity of disease
– Risk factors for specific types of infectious diarrhea
– Symptoms, duration, fever, abd pain, tenesmus, dehydration
– Freq, vol, blood, pus, mucus in stools
– Diarrhea >2 – 4 wks  CHRONIC  fully investigated
– Inquiry made into factors at specific subgroup at  risk:
• >70 yo, pregnant, recent travel or camping, recent AB use,
immunosuppression (HIV, prednison th/, chemoth/), anal intercourse,
seafood consumption, household contacts of day-care workers or
children, potential common source (friends, realtives w/ similar sympts)
– Short incubation <6 hrs or 6-16 hrs
• enterotoxin S.aureus & B.cereus or Clostridium perfringens
– Vomiting
• dominant w/ viral infections & food poisoning  S.aureus, B.cereus, norovirus)
Physical examination
• Helpful to gauge severity of disease
• Orthostasis, Tachycardia,  skin turgor, Dry mucous
membranes  dehydration
• Fever, abdominal tenderness, skin rash  documented
• All patients should undergo rectal exam when rectal bleeding
reported
Screening stool examination
• Based upon history & physical exam
• Fresh-cup specimen – preferred
• Evaluate:
– Fecal leukocytes
• Staining or lactoferrin testing
• Methylene blue stain
• 3 or more leukocytes/high-powered field (at least 4 fields) = +ve
• Lactoferrin latex agglutination = more precise marker
– Fecal occult blood
– Organisms most common associated w/ +ve screening test:
Salmonella, Shigella, E.coli O157, Campylobacter, Yersinia, Aeromonas,
Vibrio, C.difficile
 Laboratory Evaluation
• Lab testing & antimicrobial th/ recommended underscored by
overall stool cultures +ve
• Indicated in pts w/ following findings or risks:
– Severe or persistent disease
• Fever >38.50C
• Dehydration
• Grossly bloody stools
• Duration >1 wk
• At risk subpopulations
• +ve stool screening exam
• Lab exam includes:
– CBC
– Serum electrolytes
– Stool processed for bacterial culture
• ✗ cost effective for ova & parasites
• Differentiation of pathogenic & non-pathogenic strains of
E.coli
– Specific serotyping
• Commercial enzyme immunoassay kits for detection of
rotavirus & enteric adenovirus
– Useful in pediatric population & elderly
• Colonoscopy rarely needed
– But appropriate where differential includes: ischemic
colitis, IBD, other etiologies requiring biopsies
(immunocompromised, concern for C.difficile w/ -ve stool
studies)
• Initial evaluation of AIDS-associated diarrhea:
– Stool exam for culture, ova, parasites, acid-fast stain
• Specialized stool studies
– detection of Cryptosporidium, Cyclospora,
microsporidiosis, Cystoisospora belli
• Mucosal biopsies
– diagnosis of CMV & Mycobacterium avium intracellulare
complex
• Sigmoidoscopy
– persistent or severe cases in pts w/ <100/μL CD4 counts &
weight loss
Pediatric details: Identification of a pathogenic bacterium, virus, or parasite in a stool
specimen from a child with diarrhea does not indicate in all cases that it is the cause
of illness.
 Management
REHYDRATION that are lost in diarrhea stool.
• Oral rehydration therapy (ORT) is
the administration of appropriate ORT consists of:
solutions by mouth to prevent or • Rehydration—water & electrolytes
correct diarrheal dehydration. administered to replace losses.
• Cost-effective method of managing • Maintenance fluid therapy to take
acute gastroenteritis care of ongoing losses once
• It reduces hospitalization rehydration is achieved (along with
requirements in both developed and appropriate nutrition).
developing countries
• Oral rehydration salts (ORS) contain
specific amounts of important salts
• ORT is contraindicated in:
– initial management of severe dehydration
– in children with paralytic ileus, frequent and persistent
vomiting (more than four episodes per hour)
– painful oral conditions such as moderate to severe thrush
(oral candidiasis)
Nasogastric administration of ORS solution is potentially
lifesaving if IV rehydration not possible & the patient is being
transported to a facility

• Rice-based ORS is superior to standard ORS for adults

and children with cholera
– Not superior to standard ORS in the treatment of children
with acute noncholera diarrhea, especially when food is
given shortly after rehydration, as is recommended to
prevent malnutrition.
Supplemental Zinc Th/, Multivitamins, Minerals in children
• Zinc deficiency is widespread among children in developing countries.
• Routine zinc th/ (adjunct to ORT): useful in modest reduction of the
severity; importantly reduce diarrhea episodes in children in developing
countries.
• Recommendation:
– Children + diarrhea: 20 mg of zinc/day for 10 days.
– Infants aged 2 months or younger should receive 10 mg/day for 10
days
• All children with persistent diarrhea should receive supplementary
multivitamins & minerals each day for 2 weeks:
– Including at least two recommended daily allowances (RDAs) of folate,
vitamin A, zinc, magnesium, and copper (WHO 2005).
 Diet
• Normal feeding should be continued for those with no
signs of dehydration
• Food should be started immediately after correction of
some (moderate) and severe dehydration (2–4 hours)
using ORT or IV rehydration

Pediatric details:
• Breastfed infants and children should continue
receiving food, even during the rehydration phase
• However, for non-breastfed, dehydrated children&
adults, rehydration is the first priority and that can be
accomplished in 2–4 hours
 Anti-diarrheal treatment
• Usually unnecessary in acute diarrhea
management, some have sedative effects 
ORT difficult
Pediatric details: antidiarrheals have no practical
benefits for children w/ acute or persistent
diarrhea
Doses shown are for oral administration
• Antimicrobials are reliably helpful; routine use is
recommended in the treatment of severe (clinically
recognizable):
– Cholera, shigellosis, typhoid and paratyphoid fevers .
– Dysenteric presentation of campylobacteriosis and
nontyphoidal salmonellosis when they cause persistent
diarrhea, and when host immune status is compromised
for any reason such as severe malnutrition, chronic liver
disease, or lymphoproliferative disorders.
– Invasive intestinal amebiasis
– Symptomatic giardiasis (anorexia and weight loss,
persistent diarrhea, failure to thrive).
• Consider antimicrobial treatment for:
– Shigella, Salmonella, Campylobacter (dysenteric form) or
parasitic infections.
– Nontyphoidal salmonellosis among at-risk populations
(malnutrition, infants and elderly, immunocompromised
patients, and those with liver diseases and
lymphoproliferative disorders), and in dysenteric
presentation.
– Moderate/severe traveler’s diarrhea or diarrhea with fever
and/or with blood stools.
– Antimicrobials are also indicated for associated health
problems such as pneumonia.
 Complications
DEHYDRATION
• Loses too much water & salt from the body
• Causes disturbance of electrolytes  affect vital organs
• Must be treated to help restore balance of water & salt
• Treated w/ ORS
Asses dehydration
• Restless or irritable
• Sunken eyes
• Skin loses elasticity
• Lethargic or unconcious (if continues)
Acute diarrhea in adults and children: a global perspective. World Gastroenterology organisation Global Guidelines 2012