GASTROENTEROLOGY
DEFINITIONS
 Essential: cannot be produced in body so must be
acquired from diet
 Microcolon: radiographic feature of low intestinal
obstruction before colon from intrauterine
underutilization or ‘unused colon’
 Meconium ileus: in neonates, one of earliest
manifestations in patients with cystic fibrosis
o Inspissated meconium (thick, adhesive,
desiccated first fecal excretion of newborn)
o Obstructs small intestine at terminal ileum,
proximal dilates with meconium, gas, fluid
 Pathognomonic: characteristic of a condition
 Normal stool: 1-2 times per day, soft and formed
(like soft serve ice cream), not black (internal
bleeding), white (lack of bile), or red (lower or anal
bleeding)
o Builds up in frequency from 1 time in 24
hours to 6 times/day
o Meconium – black or dark green, thick,
sticky, lasts for 24-48 hours
o Between 3-6 day – change into greenish-
brown-yellow transitional
o After 6th day – milk stools that are yellow in
colour because processing bilirubin
o Will settle around 1-2 times per day, but
normal frequency varies widely
 Height and weight milestones:
o Birth-4 days: average 19.5 inches long and
7.25lb
o Don’t lose more than 10% within 5 days; if
keep losing after 5, or haven’t regained
within 2 weeks, then consider supplements
o 1 year: length increases by 50% and
birthweight triples
o Early-late childhood: yearly gain of about
5.1-7.6cm in height and 2.3kg in weight
o ((3 year: 7-8 more inches and quadrupled
birthweight
o 3-4 year: grow about 3 inches and 4 pounds
per year
o 5+ year: ~2 inches and 4 pounds each year
until puberty))
 Variant of unknown significance: follow up with
variant of unknown significance later on because
might have more information
 Colicky: fussy baby (uncertain pathogenesis), 3
days to 3 months, cries 3 times a day
 Laparoscopic cholecystectomy: minimally
invasive
 Multiple small incisions with ports to perform
surgery with specialized instruments
o Indications: cholecystitis, biliary
dyskinesia, acalculous cholecystitis,
gallstone pancreatitis, gallbladder
masses/polyps
o Contraindications: inability to tolerate
pneumoperitoneum or general anesthesia,
uncorrectable coagulopathy, metastatic
 Laparotomy: single large incision in abdomen
o Indications: lack of access and/or risk of
injury to vital structures outweighs benefits
(e.g. multiple dense adhesions from
previous surgery or inflammatory
conditions, grossly distended intestines,
massive ascites with end-stage liver or
cardiac, emergency, elective that involves
large specimen)
o Contraindications: unfit for general
anesthesia due to co-morbidities, sepsis,
hemodynamic instability, metastatic
malignant disease
 Biliary sludge: mixture of particulate solids
(cholesterol crystals, calcium bilirubinate pigment,
other calcium salts) that have precipitated from bile
o Stasis or slowed movement
 Constipation: Rome IV criteria when >=2 present
for at least 1 month (<4 years) or 2 months (>4
years)
o Two or fewer BM/week
o At least one episode of fecal
incontinence/week after child has acquired
complete bowel control
o History of extensive fecal retention or
withholding behavior by child
o Having hard and painful stools
o Large fecal mass on digital rectal exam
o Large in diameter of stools that cause rectal
outlet obstruction
ANATOMY
 Two groups of organs:
 GI or alimentary tract
o Oral cavity  pharynx  esophagus 
stomach  duodenum, jejunum, ileum 
cecum, ascending colon, transverse colon,
descending colon, sigmoid colon  rectum
 anal canal  anus
o State of tonus (sustained contraction)  5-
7m in living, 7-9m in cadaver
 Accessory digestive organs
o Teeth in physical breakdown
o Tongue in chewing and swallowing
o Salivary glands (parotid, sublingual,
submandibular), liver, gallbladder, and
pancreas produce or store secretions for
chemical digestion
BASIC PROCESSES
 Ingestion: taking foods and liquids into mouth
 Secretion: release of water, acid, buffers, and
enzymes into lumen of GI tract
 Motility: alternating contractions and relaxations of
smooth muscles of tract mix food and secretions
and propel them toward anus
 Digestion: process of breaking down ingested food
into small molecules that can be used by cells
o Mechanical: teeth grinds, stomach and
small intestines churn
 Food dissolved, mixed with
enzymes
 o Chemical: carbs, lipids, proteins, nucleic
acids split into smaller molecules by
hydrolysis
 Absorption: movement of products of digestion
from lumen of GI tract in blood or lymph
o Substances not requiring digestion:
vitamins, ions, cholesterol, water
 Defecation: wastes, indigestible or unabsorbed
substances, bacteria, cells sloughed from tract lining
leave anus as feces/stool
LAYERS OF THE GI TRACT
 GI tract has same 4-layered arrangement starting
from lower esophagus
 Deep to superficial: mucosa, submucosa,
muscularis, serosa/adventitia
MUCOSA
 Composed of epithelium, lamina propria, and
muscularis mucosae
 Epithelium: simple columnar for secretion and
absorption in stomach and intestines,
nonkeratinized stratified squamous everywhere else
o Between epithelial are exocrine cells that
secrete mucus and fluid, and
enteroendocrine that secrete hormones
 Lamina propria: areolar connective containing
blood and lymphatic vessels
o Contains majority of mucosa-associated
lymphatic tissue (MALT)
 Muscularis mucosae: ensures all absorptive cells
exposed to contents of lumen
SUBMUCOSA
 Areolar connective containing blood and lymphatic
vessels and submucosal plexus
MUSCULARIS
 Skeletal muscle in:
o Mouth, pharynx, superior and middle
esophagus for voluntary swallowing
o External anal sphincter for voluntary
defecation
 Smooth muscle everywhere else
o Inner sheet circular fibers
o Outer sheet longitudinal fibers
 Between muscle layers is myenteric plexus
SEROSA/VISCERAL PERITONEUM
 Specific to parts in the abdominal cavity
 Simple squamous (mesothelium) and serous
membrane of areolar connective underneath
 Named adventitia in esophagus
PLEXI
 Myenteric plexus between serosa and muscularis
 Submucosal plexus between muscularis and
submucosa
PERITONEUM
 Parietal peritoneum lines wall, visceral lines organs,
peritoneal cavity in between
 Retroperitoneal organs only has peritoneum on
anterior surfaces
 Unlike pericardium and pleurae, peritoneum has
large folds weaving between viscera that 1) binds
and 2) blood vessels, lymphatic, nerve supply
o Greater and lesser omentum, falciform
ligament, falciform ligament, mesentery,
mesocolon
MOUTH OR ORAL/BUCCAL CAVITY
 Cheeks:
o Mucous membrane consisting of
nonkeratinized stratified squamous
o Buccinator muscles and connective tissue
between skin and mucous membranes
 Lips:
o Similar layers as cheeks but has orbicularis
oris muscle
o Muscles together keep food between teeth
while chewing and assist in speech
 Palate:
o Hard palate in anterior, soft palate in
posterior roof of mouth
o Possible to eat and breathe simultaneously
 Tongue:
o Skeletal muscle covered by mucosa
 Extrinsic muscles (attach to bones)
move tongue side to side and in and
out for chewing, moving food
 Intrinsic muscles (insert to
tongue’s connective tissue) alter
shape and size of tongue for speech
and swallowing
o Median septum extending entire length
o Upper and lateral surfaces covered with
papillae, projections of lamina propria
covered by stratified squamous
 Main contain taste buds
 Some lack but have
mechanoreceptors
SALIVARY GLANDS
 Three major pairs: parotid (parotid duct),
submandibular (submandibular duct), and
sublingual (lesser sublingual ducts)
 Minor: labial (lips), buccal (cheeks), palatal
(palate), lingual (tongue) glands
 Acinus is ‘grape’ at end of branching duct system
 Acinar cells produce initial saliva
 Passes through intercalated duct then striated duct
 Ductal cells in striated which alter concentrations
of various electrolytes into final saliva
 Myoepithelial cells in acini and intercalated
contract to eject saliva into mouth
PHARYNX
 Skeletal muscle encased by mucosa
 Nasopharynx only in respiration
 Both oropharynx and laryngopharynx also have
digestive functions  propel food into esophagus
ESOPHAGUS
 Inferior end of laryngopharynx  mediastinum
anterior to vertebrae  pierces diaphragm through
esophageal hiatus
 Superior third skeletal, intermediate skeletal and
smooth, inferior third smooth
 Upper esophageal sphincter skeletal and controls
food from pharynx to esophagus, prevents air
 Lower esophageal sphincter smooth and controls
food from esophagus into stomach, prevents acid
STOMACH
 Lesser curvature = concave medial border; greater
curvature = convex lateral border
  Cardia surrounds opening of esophagus into
stomach
 Fundus superior and to left of body
 Body inferior of fundus, central portion
 Pyloric antrum connects to body, pyloric canal
leads to pylorus, which connects to duodenum via
the smooth muscle pyloric sphincter
 Differences in motility:
o Orad proximal and thin walled
o Caudad distal and thick walled to generate
stronger contractions
GASTRIC GLANDS
 Gastric pit  epithelial cells extend into lamina
propria  gastric glands  muscularis mucosae
 Three kinds of exocrine gland cells:
o Mucous neck cells secrete mucous, HCO3-
o Parietal cells produce intrinsic factor (for
vit B12 absorption) and HCl
o Chief cells secrete pepsinogen and gastric
lipase
PYLORIC GLANDS
 Similar configuration but deeper pits, in antrum
 Mucous neck cells secrete mucous, HCO3-
 Enteroendocrine cell G cell secretes gastrin not into
pyloric ducts but circulation
PANCREAS
 Head near curve of duodenum, central body, tail
 Pancreatic duct combines with common bile duct
 hepatopancreatic ampulla surrounded by
sphincter of hepatopancreatic ampulla  major
duodenal papilla
 Accessory duct directly into duodenum superior to
hepatopancreatic ampulla
EXOCRINE GLANDS (99%)
 Organized similar to salivary glands
 Unique that ductal cells extend into acinus as
centroacinar cells
o Both secrete HCO3-
ENDOCRINE GLANDS (1%)
 Islets of Langerhans
LIVER
 Divided into right and left lobe by falciform
ligament, fold of mesentery
 Left and right coronary ligaments are extensions
of parietal peritoneum suspending liver from
diaphragm
 Ligamentum teres (round ligament) remnant of
umbilical vein in free border of falciform
HISTOLOGY
 Hepatocytes: specialized epithelial with 5-12 sides
 Hepatic laminae: plates of hepatocytes one cell
thick, highly branched and irregular
 Hepatic sinusoids: endothelial-lined vascular
spaces that border hepatic laminae
o Contains fixed phagocytes, stellate
reticuloendothelial cells, which destroy
WBC and RBCs, bacteria, other foreign
 Bile canaliculi: small ducts in the grooves between
adjacent hepatocytes
o  bile ductule  bile duct  right and left
hepatic ducts  common hepatic duct +
cystic duct  common bile duct
Portal triad: bile duct, branch of hepatic artery,
branch of portal vein
ORGANIZATION
 Hepatic lobule: centre is central vein, sinusoids
radiate outwards, three corners portal triad
o Difficult to see in human liver
 Portal lobule: portal triad is centre, triangle
connecting three central veins
 Hepatic acinus: preferred functional/structural unit
o Short axis by portal triad of hepatic lobule
o Long axis by curves between central veins
o Divided into zones with no sharp
boundaries:
 Zone 1 closest to portal triad (first
to receive nutrients, first to take up
glucose or break down glycogen,
first to show morphological
changes to obstruction or toxin, last
to die, first to regenerate)
 Zone 2 middle (intermediate)
 Zone 3 farthest (last to show
impaired circulation, first to show
fat accumulation)
BLOOD SUPPLY
 Receives blood from 1) oxygenated hepatic artery
and 2) deoxygenated hepatic portal vein with
newly absorbed nutrients, drugs, toxins
o 2) comes from spleen, stomach, pancreas,
small intestine, and colon
 1) and 2) drain into sinusoids  central vein 
hepatic vein  IVC
GALLBLADDER
 Pear-shaped sac in depression of posterior liver
 Consists, from inferior to superior: fundus, body,
neck
 Mucosa is simple columnar epithelium arranged in
rugae resembling stomach
 Contraction of smooth muscle fibers in muscular
coating ejects contents into cystic duct
 Innervated by phrenic so get radiation to shoulder
SMALL INTESTINE
 Epithelial layer:
o Absorptive cells contain enzymes that
digest and microvilli that absorb
o Goblet cells secrete mucous
 Intestinal glands: deep crevices of epithelium
o Paneth cells secrete lysozyme
(bactericidal) and can phagocytose
o Enteroendocrine cells (S, I, K)
 Secrete secretin, cholecystokinin,
and GIP respectively
 Lamina propria:
o MALT
o Solitary lymphatic nodules, groups called
aggregated lymphatic follicles, abundant in
ileum
 Submucosa:
o Duodenal glands secrete alkaline mucous
ORGANIZATION
 Circular folds are folds of mucosa and submucosa
that end in midportion ileum
o Increases SA for absorption
o Causes chyme to spiral
  Villi are fingerlike projections of mucosa
o Embedded within are arteriole, venule, and
blood capillary network, and lacteal
 Microvilli on absorptive by 20-30 actin filaments
o Create fuzzy line brush border on
microscope
LARGE INTESTINE
 Attached to posterior abdominal wall by
mesocolon, double layer of peritoneum
 Joins small intestine at smooth muscle sphincter
ileocecal sphincter  cecum (attached is
appendix)  colon  rectum  anal canal with
internal (involuntary) and external anal sphincter
(voluntary)
 Ascending colon  right colic (hepatic) flexure 
transverse colon  left colic (splenic flexure) 
descending colon  sigmoid colon
o Ascending/descending are retroperitoneal;
transverse/sigmoid not
 Anal canal mucosa arranged in anal columns
 Epithelium:
o Long tubular crypts of Lieberkuhn contain
absorptive (water) and goblet cells
(mucous)
o Absorptive cells have microvilli
 Lamina propria:
o Solitary lymphatic nodules
 Muscularis
o Unique to large intestine, portions of
longitudinal muscles are thickened, forming
three bands called teniae coli
 Separated by less or no longitudinal
muscle
o Attached to teniae coli are pouches of
visceral peritoneum filled with fat, omental
(fatty) appendices
o Tonic contractions of teniae coli gather
colon into pouches called haustra
IMMUNITY
 Lipopolysaccharide from bacteria and Th2
cytokines are goblet cell stimulants
 Mucous is physical barrier to motility and feeding
of pathogens
 IgA in mucous can trap invading bacteria
 Defensins, both a- and B-, kills wide spectrum of
pathogens in vitro
 Tissue-resident macrophages, eosinophils, mast
cells can phagocytose, release toxic + inflammatory
mediators such as N radicals and histamine
 Pathogen recognition receptors normally
expressed on basal side of epithelium or
intracellularly to avoid activation by normal flora
o TLR and NOD families
o Initiates powerful inflammatory response
MOTILITY
 Contraction and relaxation of walls and sphincters
o Grinds, mixes, and moves food
 All contractile tissue in GI tract except pharynx,
upper third of esophagus, and external anal
sphincter, which are striated, is smooth
o Unitary smooth muscle  electrically
coupled via gap junctions
 Circular smooth muscle decreases diameter
 Longitudinal smooth muscle decreases length
 Plastic contractions: periodic contractions
followed by relaxation (action potentials)
o Esophagus, gastric antrum, and small
intestine
 Tonic contractions: constant level of tone without
regular periods of relaxation (subthreshold slow
waves produce weak contraction)
o Upper region of stomach, lower
esophageal, ileocecal, and internal anal
sphincters
SLOW WAVES
 Not action potentials
 Oscillating depolarization and repolarization of
membrane potential of smooth muscle cells
o Depolarize: Ca channels inward
o Repolarize: K channels outward
 If at peak the membrane potential depolarized to
threshold, group of action potentials generated
 Frequency changes based on part, stomach lowest
(3/min) and duodenum highest (12/min)
 Interstitial cells of Cajal are pacemakers
CHEWING
 1) Mixes food with saliva to lubricate
 2) Reduces size of food to facilitate swallowing
 3) Mixes carbohydrates with salivary amylase
 Both voluntary and involuntary components
SWALLOWING
 Initiated voluntarily but thereafter involuntary
 Somatosensory receptors in pharynx  vagus and
glossopharyngeal nerves  medullary swallowing
centre  striated muscle in pharynx/upper
esophagus
 A. Oral phase
o Tongue forces bolus of food toward
pharynx
 B. Pharyngeal phase
o Soft palate upward, epiglottis closes, upper
esophageal sphincter relaxes
o Peristaltic wave of contraction propels food
into esophagus
 C. Esophageal phase
o Swallowing reflex closes sphincter and
sends another peristaltic wave down
esophagus
o If primary wave does not clear food,
secondary peristaltic wave initiated by
continued distention of esophagus (enteric)
ESOPHAGEAL MOTILITY
 Sequential contractions create area of high pressure
behind bolus, pushing it continuously
 At lower esophageal sphincter:
o Peptidergic fibers in vagus nerve release
VIP which produces relaxation of sphincter
and receptive relaxation of stomach
GASTRIC MOTILITY
 1) relaxation of orad region to receive bolus
 2) contractions reduce size of bolus and mix with
gastric secretions
 o Wave of contraction begin in middle of
body and move distally along caudad
 3) gastric emptying propels chyme into duodenum
o Retropulsion: but most propelled
backward because contraction closes the
pylorus
 Contracts 3-5 times per minute because 3-5 slow
waves per minute:
o Parasympathetic by gastrin and motilin
increase frequency  stronger contractions
o Sympathetic by secretin and GIP decrease
frequency  weaker contractions
 Migrating myoelectric complexes are 90min
interval gastric contractions mediated by motilin
during fasting that clears stomach of residue
GASTRIC EMPTYING
 Rate closely regulated for neutralization of gastric
H+ in duodenum and digestion and absorption
 Inhibited by:
o Fat in duodenum causes secretion of CCK
o H+ in duodenum via enteric nervous
system
SMALL INTESTINE
 ~12 slow waves/min in duodenum, ~9 in ileum
o Parasympathetic by vagus increases
contraction (ACh, peptidergic: VIP,
enkephalins, motilin)
o Sympathetic by fibers from celiac and
superior mesenteric ganglia decreases
 Migrating myoelectric complex clears residual
chyme
 Two types of contractions coordinated by enteric
NS
SEGMENTATION CONTRACTIONS
 Mix chyme and expose to mucosa for absorption
 Section of small intestine contracts, splitting chyme
 Then relaxes, merging bolus back together
PERISTALTIC CONTRACTIONS
 Propel chyme toward large intestine
 Simultaneously contraction at point orad to (behind)
chyme and relaxation at point caudad to (in front
of)
 Circular and longitudinal reciprocally innervated
o Orad: circular contracts, longitudinal
relaxes
o Caudad: circular relaxes, longitudinal
contracts
 Peristalsis: bolus sensed by ECL cells of intestinal
mucosa  release 5-HT  5-HT binds to receptors
in primary afferent neurons  initiate peristaltic
reflex in that segment  orad excitatory
transmitters (ACh, substance P, neuropeptide Y)
released in circular muscle, inhibited in longitudinal
muscle, caudad inhibitory pathways (VIP, NO)
activated in circular but excitatory in longitudinal
VOMITING
 Vomiting centre in medulla receives input from
vestibular system, back of throat, GI tract, and
chemoreceptor trigger zone in fourth ventricle
LARGE INTESTINE
GASTROILEAL REFLEX
 Immediately after meal intensifies peristalsis in
ileum and forces chyme into cecum
 Gastrin also relaxes sphincter
MOVEMENTS
 Segmentation contractions/haustral churning:
o In cecum and proximal colon
o Haustra remain relaxed  become
distended  once threshold, contract and
squeeze into next haustrum
 Mostly churning, less advancement
 Peristalsis:
o 3-12 contractions per minute
 Mass movements:
o Strong peristaltic wave that begins in
middle of transverse colon and quickly
drives contents of colon into rectum, where
stored until defecation
o 1-3 times/day
o Water absorption in distal colon makes
fecal contents of large intestine semisolid
and difficult to move
GASTROCOLIC REFLEX
 Distention of stomach  parasympathetic nervous
system  CCK and gastrin release  increased
motility of colon (increased frequency of mass
movements)
DEFECATION
 Rectum fills and distended  sensory nerve
impulses to sacral spinal cord  motor impulses
along parasympathetic to desc/sigmoid colon,
rectum, anus  contraction of longitudinal rectal
muscles shortens rectum and increases pressure
inside  pressure, contractions of abdominal
muscles, and parasympathetic opens internal anal
sphincter
o Rectosphincteric reflex
 If external anal sphincter not relaxed  feces back
up into sigmoid colon until next mass peristalsis
 Urge to defecate when rectum 25% filled
 Intra-abdominal pressure created for defecation can
be increased by Valsalva maneuver (expiring
against a closed glottis)
SECRETION
 Addition of fluids, enzymes, and mucous to lumen
by salivary glands, gastric mucosa, pancreas, liver
SALIVARY SECRETION
 Composition of saliva:
o Initial approximately same electrolyte
composition as plasma and isotonic
o Ductal cells have Na-H, Cl-HCO3, and H-K
transporters on luminal  net absorption
of Na, Cl and excretion of K, HCO3- but
impermeable to water
o Final is hypotonic, composed of -amylase,
lingual lipase, kallikrein, mucous, mucin
glycoproteins, IgA, and electrolytes
o At higher flow rates, less time in contact
with ductal cells, most like plasma
 Functions:
o 1) Initial digestion of starches and lipids
o 2) Dilution and buffering of ingested foods
o 3) Lubrication to aid movement
  Kallikrein cleaves HMW kininogen
to bradykinin  local vasodilation
 high blood flow
 Regulation:
o Exclusively neural without hormonal
control
o Both sympathetic and parasympathetic
stimulates saliva production and secretion
GASTRIC SECRETION
 Composition of gastric juice:
o HCl, pepsinogen, intrinsic factor, mucous
 Functions:
o 1) initiate process of protein digestion
o 2) absorption of vit B12 in ileum
o 3) protect from corrosive HCl and lubricate
gastric contents
HCl SECRETION MECHANISM
 Apical: H-K ATPase and Cl- channels
 Basolateral: Na-K ATPase and Cl-HCO3
exchangers
 1. Intracellular CO2 from aerobic metabolism
combines with H2O to form H2CO3 which
dissociates into H+ and HCO3-
 2. Apical, H+ secreted into lumen against
electrochemical gradient and Cl- diffuses
 3. Basolateral, HCO3- exits into blood and Cl- enters
SUBSTANCES THAT ALTER HCl SECRETION
 Histamine:
o Released from ECL cells in gastric mucosa
o Binds to H2 receptors on parietal cells  Gs
 AC  cAMP  PKA  secretion of
H+
o Cimetidine blocks H2 receptors
 ACh:
o Released from vagus nerves
o Binds to muscarinic (M3) receptors on
parietal cells  Gq  phospholipase C 
diacylglycerol, IP3 from membrane
phospholipids  diacylglycerol and Ca2+
from intracellular stores activate protein
kinases  secretion of H+
 Also stimulates ECL cells (indirect)
o Atropine blocks muscarinic receptors
 Gastrin:
o Released by G cells (endocrine mechanism
instead of paracrine like histamine)
o Binds to cholecystokinin B (CCKB)
receptors on parietal cells  IP3/Ca2+
system
 Also stimulates ECL cells (indirect)
o Gastrin release triggered by distention of
stomach, presence of small peptides and
amino acids, and stimulation of vagus
nerves
 Potentiation because of relationships between
substances  consequences for drugs except
omeprazole, which counteracts H-K ATPase
 Vagal stimulation both ACh on parietal and GRP
on G cells  atropine will block direct effect but
not indirect gastrin-mediated effect
STIMULATION OF H+ SECRETION
 Three phases:
 Cephalic phase: ~30% total HCl
o Stimuli: smelling, tasting, chewing,
swallowing, and conditioned reflexes in
anticipation of food
o Mechanisms: direct (ACh) and indirect
(GRP) stimulation by vagus nerve
 Gastric phase: ~60% total HCl
o Stimuli: distention of stomach, presence of
breakdown products of protein (amino
acids and small peptides)
o Mechanisms: distention  vagus effects |
distention of antrum  local reflex 
gastrin release | protein products stimulate
G cells
 Intestinal phase: ~10%
o Mediated by protein products
INHIBITION OF H+ SECRETION
 When food moves to small intestine  less
buffering  lower pH  inhibits gastrin secretion
 Somatostatin is major inhibitory mechanism:
o Released by D cells
o Direct: receptors on parietal cells and Gi
protein to counteract histamine
o Indirect: inhibit histamine and gastrin
release
 Prostaglandins inhibit via Gi on parietal cells
PANCREATIC SECRETION
 ~1L into duodenum per day
 Aqueous component high in HCO3- (neutralize) and
enzymatic component (digestion of macro)
 Formation of enzymatic:
o Acinar cells: synthesized on RER  Golgi
complex  condensing vacuoles 
zymogen granules until stimulus triggers
secretion  apical membrane via
cytoskeletal network  fusion and release
o Amylases and lipases secreted as active
forms, proteases in inactive
 Formation of aqueous:
o Initial secretion by ductal and centroacinar
followed by modification in ductal
 Cl-HCO3- exchanger in apical
 Na-H exchanger in basolateral
 Net: secretion of HCO3, absorption
of H, so pancreatic venous acidic
o Isotonic containing Na, Cl, K, HCO3-
 Only Cl and HCO3- vary with flow
rate due to exchanger
 Higher = more HCO3-, less Cl-
 Regulation:
o Sympathetic by postganglionic from celiac
and superior mesenteric plexuses
o Parasympathetic by vagus which synapse in
enteric NS and postanganglionic on
pancreas
o Sympathetic decreases, parasympthateic
increases secretion
STIMULATION OF PANCREATIC SECRETION
 Cephalic phase:
o Same stimuli and mediated by vagus nerve
o Mainly enzymatic secretion
 Gastric phase:
o Distention of stomach and vagus nerve
o Mainly enzymatic secretion
  Intestinal phase: ~80%
o Both enzymatic and aqueous secretions
stimulated
o Acinar cells (enzymatic): CCKA and
muscarinic (ACh) receptors
 Amino acids, small peptides, FAs
 I cells secrete CCK  CCK on
acinar via IP3/Ca  enzymes
 ACh stimulates potentiates
o Ductal (aqueous): CCK, ACh, and secretin
receptors
 H+  S cells secrete secretin 
secretin on ductal via cAMP 
aqueous secretion
 ACh, CCK potentiates
INHIBITION OF PANCREATIC SECRETION
 Presence of fat in distal small intestine signals
intestinal phase concluding
 Inhibitors peptide YY secreted by endocrine of
ileum and somatostatin
LIVER AND GALLBLADDER PHYSIOLOGY
LIVER
 1) processing of absorbed substances
 2) synthesis and secretion of bile acids
 3) bilirubin production and excretion
o Hemoglobin degraded by RES  biliverdin
byproduct (green)  bilirubin (yellow) 
bound to albumin in circulation  taken up BILIARY SYSTEM
by hepatocytes  conjugated with
glucuronic acid by UDP-glucuronyl
transferase in hepatic microsomes 
now water soluble  excreted in urine and
secreted into bile
o Conjugated bilirubin in bile  terminal
ileum and colon  deconjugated by
bacterial enzymes  metabolized to
urobilinogen
 Some absorbed by enterohepatic
circulation and delivered to liver,
some to systemic and kidney
 Remainder converted to urobilin
(urine) and stercobilin (feces)
o Jaundice: yellow discoloration of skin or
sclera due to accumulation of free or
conjugated bilirubin
 Increased destruction of RBCs,
obstruction of bile ducts, liver
disease
 Conjugated bilirubin, if cannot go
into bile (clay stool), goes into
urine (dark) and blood (jaundice)
 4) metabolism of key nutrients
o Carbohydrates: GNG, converts to
glycogen and triglycerides, releases stored
glucose when needed, convert certain aa,
lactic acid, and other monosaccharides to
glucose
o Proteins: synthesizes nonessential aa,
deaminates aa so can be used for ATP
production or converted to carbohydrates or
fats, converts ammonia (byproduct of
catabolism) to urea in urine
o Lipids: FA oxidation, synthesizes
lipoproteins (transport FAs, TGs, and
cholesterol to and from body cells), store
some TGs, synthesize cholesterol, use
cholesterol to make bile salts
 5) synthesize proteins
o Synthesize almost all plasma proteins
including albumin, clotting factors
 6) storage
o Primary storage site for certain vitamins (A,
B12, D, E, K) and minerals (iron and
copper)
 7) activation of vitamin D
o Involved in synthesis of active vitamin D
 8) detoxification and excretion of waste products
o ‘First pass metabolism’ so little substances
make into systemic circulation
o Eg) bacteria phagocytized by hepatic
Kupffer cells (in addition to aged RBCs and
WBCs)
o Eg) enzymes modify endogenous and
exogenous toxins to render water soluble
and capable of being excreted in bile or
urine
o Phase I reactions: catalyzed by
cytochrome P450
o Phase II: conjugate with glucuronide,
sulfate, amino acids, or glutathione
 1. Hepatocytes continuously synthesize and secrete
constituents of bile
 2. Flows through cystic duct and
stored/concentrated in gallbladder
 3. Contraction of gallbladder secretes bile through
hepatopancreatic ampulla
 4. Bile salts emulsify lipids and solubilize products
of lipid digestion in micelles
 5. Bile salts recirculated to liver via enterohepatic
circulation
o Na-bile salt cotransporters
o Mostly at ileum so high bile salt
concentrations throughout small intestine
 6. Bile salts extracted from portal vein by
hepatocytes to bile salt/acid pool
o Liver must replace only the small
percentage of bile salt excreted in feces
 Fecal loss is about 600mg/day out
of total bile salt pool of 2.5g
o Negative feedback mechanism with bile
salts inhibiting RLS cholesterol 7a-
hydroxylase
 7. Choleretic effect: recirculation of bile salts to
liver stimulates biliary secretion
BILE SALTS (50%)
 Hepatocytes : cholesterol  7a-hydroxylase 
cholic and chenodeoxycholic acid (primary bile
acids)
 Intestinal bacteria: cholic and chenodeoxycholic 
7a-dehydroxylase  deoxycholic and lithocholic
acid (secondary bile acids)
  Hepatocytes: conjugates bile acids w/ aa glycine or o Trehalose  trehalase  glucose
taurine  eight bile salts (e.g. glycocholic acid)ABSORPTION:
o Primary bile salts have more hydroxyl  Glucose and galactose
groups and better at solubilizing lipids o Na-dependent cotransport (SGLT1) in
 Solubility: intestinal luminal membrane
o Bile acids pKa~7, bile salts pKa~1-4  Sugar uphill, Na downhill
o At duodenal pH 3-5, bile acids HA while  Na gradient maintained by Na-K
bile salts ionized A-  more soluble pump in basolateral membrane
 Amphipathic: o Then facilitated diffusion (GLUT2) into
o Bile salts have hydrophilic and blood
hydrophobic  Fructose
 Functions: o Transported exclusively by facilitated
o Emulsify lipids: negatively charged bile diffusion, so cannot be absorbed against
lipids surround lipids but repel each other, concentration gradient
causing droplets to disperse rather than PROTEINS
coalesce DIGESTION:
o Micelles: inner products of lipid digestion  Can absorb amino acids, dipeptides, and tripeptides
are dissolved in aqueous intestinal lumen  Endopeptidases hydrolyze interior peptide bonds
PHOSPHOLIPIDS AND CHOLESTEROL (40% AND  Exopeptidases hydrolyze one aa at a time from C-
4%) terminus of peptides
 Phospholipids are amphipathic and line micelles  Pepsin (endo):
 Cholesterol included in micelles o Secreted as pepsinogen by chief cells of
BILIRUBIN (2%) stomach and activated by H+ from parietal
 Major bile pigment o Optimal pH 1-3, denatured when >5
 Liver conjugates to bilirubin glucuronide, secreted o HCO3- in pancreatic fluids of duodenum
into bile and gives yellow colour inactivates pepsin
IONS AND WATER  Pancreatic proteases:
 Secreted by epithelial cells lining bile ducts o Secreted in inactive forms and activated in
 Secretory mechanisms same as pancreatic ductal, sequence in small intestine
and also stimulated by secretin o Trypsinogen activated to trypsin by brush
GALLBLADDER border enzyme, enterokinase
 1) Storing bile o Trypsin converts more trypsinogen,
o Smooth muscle relaxes and sphincter of chymotrypsinogen, proelastase,
Oddi is closed procarboxypeptidase A and B to active
 2) Concentrating bile o Pancreatic proteases degrade each other and
o Epithelial cells of gallbladder absorb ions absorbed with dietary proteins
and water in isosmotic fashion similar toABSORPTION:
PCT  Free amino acids:
 3) Ejecting bile into small intestine o Na-dependent luminal cotransport followed
o Begins within 30 minutes of ingestion by facilitated diffusion into blood
o Major stimulus is CCK, 1) contracts (analogous)
gallbladder and 2) relaxes sphincter of Oddi o Four separate carriers for neutral, acidic,
o Pulsatile spurts because rhythmic basic, and imino amino acids
contractions of duodenum (when relaxed,  Dipeptides and tripeptides:
duodenal pressure is lower) o H-dependent luminal cotransport, faster
than amino acids
DIGESTION & ABSORPTION OF MACRONUTRIENTS o Cytoplasmic peptidases hydrolyze to amino
acids then facilitated diffusion into blood
CARBOHYDRATES LIPIDS
DIGESTION: DIGESTION:
 Only monosaccharides are absorbed so must digest  Stomach:
carbs to glucose, galactose, and fructose o Mixing breaks lipids into droplets to
 -amylase (salivary and pancreatic) hydrolyze 1,4- increase SA for pancreatic enzymes
glycosidic bonds o Lingual lipases digest minority of TG to
o Starch  maltose, maltotriose, -limit monoglycerides and FAs
dextrins o CCK slows gastric emptying  adequate
 Maltase, -dextrinase, and sucrase (intestinal time for digestion/absorption in intestine
brush border) then hydrolyze oligosaccharides   Small intestine:
glucose o Bile acids emulsify lipids to increase SA
 Lactase, trehalase, sucrase hydrolyze AND solubilize hydrophobic products of
disaccharides  monosaccharides digestion into micelles
o Lactose  lactase  glucose and galactose o Pancreatic lipases hydrolyze lipids to FAs,
o Sucrose  sucrase  glucose and fructose monoglycerides, cholesterol, lysolecithin
  Pancreatic lipase, cholesterol ester
hydrolase, phospholipase A2
ABSORPTION:
 1. Micelles bring products into contact with
intestinal surface
 2. FAs, monoglycerides, cholesterol diffuse into
cell
o Glycerol is hydrophilic, not in micelles
 3. Products of lipid digestion reesterified to TGs,
cholesterol ester, and phospholipids
 4. Form chylomicrons with apoproteins
 5. Chylomicrons transported out of intestinal cells
by exocytosis
 6. Enter lacteal because too big for capillaries 
lymph vessels  thoracic duct  blood
ENERGY METABOLISM
 Energy required for maintenance of ionic and
osmotic gradients, cell transport, nerve conduction,
intermediary metabolism, biosynthesis, heat
generation, and performance of mechanical work
 Supply largely from mitochondrial production of
high-energy phosphate bonds generated by
oxidation of fat, carbohydrate, and protein
 1. Hydrolysis of carbohydrates  simple sugars,
fats  fatty acids and glycerol, proteins  amino
acids
 2. Used immediately or stored endogenously
o Largest source of endogenous energy is TG
in adipose tissue  high energy density
o Glycogen, the other largest source, in liver
and muscle tissue as a gel  less dense
 3. Most of these small molecules converted to
acetyl unit of acetyl-CoA
o Many amino acids enter citric acid cycle as
α-ketoglutarate or oxaloacetate instead
 4. Citric acid cycle and oxidative phosphorylation
o As acetyl-CoA oxidized, reduced NADH
and FADH2 transfer electrons to respiratory
chain in inner mitochondrial membrane
o Transfer of electrons down electron
transport chain coupled to generation of
ATP
MEASURING ENERGY
 Portion of energy produced is dissipated as heat
 One kcal, or 4.184 kilojoules, is amount of heat
required to raise temperature of 1kg of water by 1C
 Direct calorimetry: transfer of heat from body to
water in chambers or suits
 Indirect calorimetry: measure CO2 production and
O2 consumption
PROTEINS
 Definition: amino acids joined by peptide bonds
 Essential amino acids: histidine, isoleucine, leucine, VITAMINS
lysine, methionine, phenylalanine, threonine,
tryptophan, valine, possibly arginine
 Metabolism: >75% of aa from protein breakdown
reused for synthesis of new proteins (also glucose,
ketone bodies, FAs), remaining oxidized
 Liver is main site of catabolism for essential amino WATER-SOLUBLE
acids with exception of branched-chain aa
Branched-chain aa leucine, isoleucine, valine taken
up by skeletal muscle, undergo transamination,
yielding alanine, glutamine, branched-chain keto
acids
o Keto acids used as fuel
o Alanine and glutamine go to liver and
intestine, respectively
LIPIDS
 Definition: soluble in organic solvents, include TG,
sterols, glycolipids, phospholipids, vitamins
o In diet mostly TGs, saturated and
unsaturated long-chain FAs
 Essential fatty acids: those with n-3 double bond
and n-6 double bond, e.g. linoleic and oleic acid
 Metabolism: hormone-sensitive lipase in adipocytes
hydrolyzes adipose tissue TG, lipoprotein lipase at
capillary endothelium hydrolyzes plasma TG
o Former releases free FAs into bloodstream,
latter releases free FAs for local tissue
uptake
 In mitochondria, FAs degraded by β-oxidation to
acetyl-CoA
 Ketone bodies produced by partial oxidation of FAs
in liver increases with rate of FA production >>>
rate of FA oxidation, e.g. starvation or DM
o Ketone bodies cross BBB and spares
glucose for other tissues
 FA production by fatty acid synthase
o Acetyl-CoA carboxylase regulates rate-
limiting step, formation of malonyl-CoA
o Stimulated by citrate, abundant when ATP
and acetyl-CoA abundant
o Antagonized by palmitoyl-CoA, end
product
CARBOHYDRATES
 Definition: contain carbon, hydrogen, oxygen atoms
 Metabolism: undergo hydrolysis to yield glucose,
other simple sugars, and short-chain FAs
o Some cells, such as RBCs, WBCs, renal
medulla, eye tissues, peripheral nerve
tissue, cannot perform citric acid cycle so
requires glucose for anaerobic glycolysis
 Glucose can be stored as glycogen or fat, glycogen
in skeletal muscle for itself, in liver for rest of body
 Glycolysis is conversion of glucose to pyruvate that
generates ATP but does not require oxygen
o Only 2 ATPs /glucose vs. 36 ATPs in
Krebs
 Hepatic glycogenolysis most endogenous glucose
production, hepatic gluconeogenesis from lactate,
glycerol, and most amino acids (principally alanine)
ABSORPTION OF NON-MACRONUTRIENTS
 Coenzymes or cofactors not synthesized in body
FAT-SOLUBLE (A, D, E, K)
 Processed same as lipids
 Micelles  diffuse across apical membranes 
incorporated into chylomicrons  lymph
 In most cases Na-dependent cotransport
 Exception is vitamin B12
 o Released from foods by pepsin in stomach
 binds to R proteins from salivary juices
 proteases degrade R proteins in
duodenum, so B12 transferred to intrinsic
factor  complex resistant to degradative
actions and travels to ileum for absorption
CALCIUM
 Dietary vitamin D3 or cholecalciferol is inactive
o Converted to another inactive form in liver, ABSORPTION
which is primary circulating form
o Activated by 1-hydroxylase in kidney
PCT
 Induces synthesis of vitamin D-dependent Ca 2+-
binding protein (calbindin D-28K) in intestinal
epithelial cells  promotes absorption of Ca2+
IRON
 Absorbed either as free iron (Fe2+) or heme iron
(iron bound to hemoglobin or myoglobin) in
duodenum
o Heme iron digested by lysosomal enzymes
in absorptive cells to release free iron
 Most non-heme iron bound to transferrin in plasma
o Transferrin transfers iron from enterocytes ILEUM
and storage pools (macrophages of RES
and hepatocytes) to RBC precursors in BM
 Hepcidin is hormone produced by hepatocytes
o Binds to iron exporter ferroportin on
duodenal enterocytes and RES cells 
induces degradation  diminished
absorption of iron and trapping in RES 
less in serum
o Increased in states of iron overload and
inflammation (anemia of chronic inflamm.)
o Decreased in states where erythropoiesis
increased (e.g. hemolysis) or O2 tension
low
 Storage
o Ferritin: ferric iron complexed to
apoferritin (liver, spleen, bone marrow
main ferritin storage sites)
 Also an acute phase reactant
o Hemosiderin: aggregates or crystals of
ferritin with apoferritin partially removed
(macrophage-monocyte system main
storage)
 Anemia would show low serum iron, low serum
ferritin, high total iron binding capacity (indirect
measure of total amount of transferrin in blood)
COLON
 Bacteria:
o Ferment remaining carbohydrates 
release H, CO2, methane gases
o Convert proteins  aa  indole, skatole,
HS, fatty acids
o Produce some B vitamins and vitamin K
 Some indole and skatole eliminated in feces, some
absorbed and transported to liver where converted
to less toxic and excreted in urine
INTESTINAL FLUID AND ELECTROLYTE
TRANSPORT
 Small and large absorb ~9L of fluid daily
 Composed of ~2L diet and ~7L salivary, gastric,
pancreatic, biliary, and intestinal secretions
 100-200mL not absorbed excreted in feces
 Permeability of tight junctions determines
whether fluid and electrolytes move para- or
transcellularly
o Tight junctions in small are leaky and
permit paracellular, but in large are tight
 By cells lining villi
 Absorbate always isosmotic, solute and water
absorption occur in proportion
JEJUNUM
 Identical to kidney PCT
 Apical:
o Na-monosaccharide and Na-amino acid
cotransporters
o Na-H exchanger, H comes from carbonic
anhydrase in cell
 Basolateral:
o Na-K ATPase
o HCO3- channel from carbonic anhydrase
 Same as jejunum but additional Cl-HCO3- exchange
in apical AND Cl- instead of HCO3- transporter in
basolateral
 Net absorption of NaCl instead of NaHCO3-
COLON
 90% of water absorbed in small intestine
 Similar to principal cells of late DCT and collecting
 Apical:
o Na channel absorption
o K channel secretion
o Aldosterone increases synthesis of Na
channels and secondarily K secretion (more
K enters via Na-K ATPase and more
secreted)
 Basolateral:
o Na-K ATPase
 Other ions (e.g. chloride)
SECRETION
 By cells lining intestinal crypts
 Apical:
o Cl- channel
 Basolateral:
o Na-K-2Cl- cotransporter bringing all into
the cells
o Na-K ATPase
 **Na+ follows Cl- passively paracellular, and water
follows NaCl
 Normally Cl- channels closed
o Open to substances such as ACh and VIP
via cAMP
o Normally excreted electrolytes and water
absorbed by intestinal villi, but when
maximally stimulated  diarrhea
NUTRITIONAL PRINCIPLES
INFANTS
 Feed every 1-3 hours
 At birth:
 o Low secretion of digestive enzymes 
cannot digest solid foods or cow’s milk
o Low renal capacity  high protein intake
overloads and induces osmotic diuresis
 At 1 year:
o Can chew and swallow soft foods
o Gastric, pancreatic, intestinal secretions
permits efficient digestion of solid foods
o Kidneys can handle high solute loads
 Fluids:
o Term infants highly sensitive to fluid
deprivation and overhydration
o Adequate intake (AI) for is 0.7L/day at 0-6
months, from breast milk
o Do not need water until solid foods
 Macronutrients:
o Fats: 31 g/day
 Brain and organ growth, energy
source, absorption of fat-soluble
vitamins and essential FAs
o Carbohydrate: 60g/day
 Primary energy, glucose/ketones
for brain, lactose/oligosaccharides
promote growth of acidifying
bacteria (low pH reduces risk of
infection and increases absorption
of Ca and Mg)
o Protein: 9.1g/day (1.5g/kg/d)
 Synthesis of enzymes, hormones
 Intake of about 150mL/kg/day of breastmilk or
infant formula will satisfy all requirements
CHILDREN
 Iron, choline, DHA for CNS, fat and fat-soluble
vitamins for adipose tissue, protein and vitamin C
for muscle, Ca, P, and vitamin D for bone
mineralization, zinc for sexual maturation, iron,
folate, and B12 for blood formation
 Children has higher relative (per kg) but lower
absolute requirements than an adult, declining untilCLINICAL PRESENTATION
steady state at adulthood
GUIDELINES
 1) maintain calorie balance over time to achieve and
sustain healthy weight
 2) focus on consuming nutrient-dense foods and
beverages
INFANT FEEDING
 Breastfeeding: preferred because optimal nutrition,
reduces risk of infections and food allergies,
improves cognitive and visual development
o Exclusive breastfeeding 4-6 months
o Antibodies, hormones, stem cells, WBCs
beneficial bacteria, many enzymes in breast
o Nutrients, probiotics in formula
 Infant formulas: soy-based, with partial
hydrolysates, hypoallergenic, medical formulas,
preterm formulas, modular formulas
 Cow’s milk: high protein content causes protein
overload  interferes with digestion, metabolism,
fluid balance  not appropriate for <1 year
 ****Iron-fortified infant formulas only acceptable
human milk substitutes
 Follow up with variant of unknown significance
later on because might have more information
CYSTIC FIBROSIS
ETIOLOGY
 Mutation in gene on chromosome 7 that codes for
CF transmembrane conductance regulator protein
PATHOPHYSIOLOGY
 CFTR is cAMP-activated chloride channel
 Mutation causes decreased secretion of chloride 
increased resorption of sodium and water 
thickened mucous secretion in nearly every system
 In sweat glands, chloride is reversed (reabsorbed
into body), so unable to leads to sodium and fluid
loss
 Most commonly affects sinuses, lungs, pancreas,
biliary and hepatic systems, intestines, sweat glands
 Pancreatic insufficiency:
o Largely by obstructing pancreatic ductules
o Decreased sodium bicarbonate composition
 less neutralization of stomach chyme 
lower pH degrades leftover enzymes
o Chyme is not enzymatically processed 
pathognomonic steatorrhea, colicky
abdominal pain, malabsorption of nutrients,
specifically fat-soluble vitamins
 Meconium ileus due to dehydration and
constipation, change in luminal contents from
pancreatic insufficiency
o Leads to chronic inflammation and scarring
which increases susceptibility to intestinal
obstruction later in life
 Essentially all have severe nutritional impairment
EVALUATION
 Sweat chloride test > 60mEq/L on two occasions
 Confirmatory genetic testing if two disease-causing
CFTR mutations
TREATMENT
 Consume high-fat, high-calorie diet
 Pancreatic enzyme supplements and fat-soluble
vitamins (A, D, E, K)
PEPTIC ULCER DISEASE (PUD)
DEFINITION
 Defects in gastric or duodenal mucosa that
penetrate muscularis mucosa and cause scarring
o Defects superficial to muscularis are
erosions and do not cause scarring
ETIOLOGY
  Damaging factors: Helicobacter pylori, NSAIDs,
stress, smoking, alcohol consumption
 May also be ischemic, idiopathic
 Associated with COPD, cirrhosis, CKD
PATHOPHYSIOLOGY
 Mucous from neck cells (protective barrier) and
HCO3- from epithelial cells (neutralize incoming
pepsin or proton)
o Prostaglandin E2 stimulates HCO3- and
mucous secretion
o Other protective factors: mucosal blood
flow (epithelial cell growth) and growth
factors
o Restitution: mucous moves to areas that
has been harmed, aided by prostaglandins
 Gastric ulcers:
o Primarily because mucosal barrier problem
o H. pylori colonizes mucus (often antrum),
attaches to epithelial, releases cytotoxins
that break down mucous and underlying
cells
 Survives because urease converts
urea to NH3, alkalinizes
environment
 Duodenal ulcers:
o Excess H+ secretion
o H. pylori can inhibit somatostatin secretion
 increased gastrin OR spread and inhibit
duodenal HCO3- secretion
 NSAIDs:
o More commonly cause gastric ulcers
o Direct effect on gastric mucosa 
erosions/petechiae
o Indirect systemic effect and inhibits
mucosal COX  decreased prostaglandin
synthesis
CLINICAL PRESENTATION
 Cardinal:
o Dyspepsia (epigastric pain/burning for at
least 1 month)
 Duodenal:
o Epigastric pain, burning, develops 1-3h
after meals, relieved by eating and antacids,
interrupts sleep, periodicity (clusters of
weeks with subsequent period of remission)
 Gastric:
o More atypical symptoms
EVALUATION
 Endoscopy (most accurate)
 Upper GI series (X-ray examination)
 H. pylori tests
TREATMENT
 Treat H. pylori if present with bismuth quadruple
therapy for 10-14 days
 Stop NSAIDs and smoking
 PPI (H2, antacids less effective)
GASTRO-ESOPHAGEAL REFLUX DISEASE (GERD)
DEFINITION
 Retrograde movement of gastric content into
esophagus that elicits 1) tissue injury or 2)
symptoms
ETIOLOGY
 Risk factors: age, pregnancy, H. pylori, certain
medications (nitrates, calcium channel blockers,
anticholinergics)
PATHOPHYSIOLOGY
 Mechanisms of reflux:
o Anatomic distortion of esophagogastric
junction, hypotensive lower esophageal
sphincter, transient LES relaxations
 Impaired esophageal clearance of reflux:
o Impaired peristalsis and re-reflux associated
with larger hiatal hernias
 Epithelial tissue injury:
o Luminal acid damages intercellular
junctions - H+ penetration 
acidification of intercellular space  buffer
capacity of this space overwhelmed 
acidification of cell cytosol via basolateral
membrane  cell edema and death
CLINICAL PRESENTATION
 Cardinal symptoms:
o Heartburn, esp. after eating, during
exercise, lying recumbent, that relieves
with water or antacid
o Regurgitation: without nausea or retching
 Esophageal symptoms:
o Dysphagia: may be caused by peptic
stricture, weak peristalsis, or mucosal
inflammation
o Chest pain
o Odynophagia (rare)
 Extradigestive:
o Respiratory: chronic cough, wheezing,
aspiration pneumonia
o Non-respiratory: sore throat, hoarseness,
dental erosions, water brash, frequent
belching
EVALUATION
 Usually clinical diagnosis based on symptom
history and relief following trial of
pharmacotherapy
 Gastroscopy absolute indications:
o Heartburn accompanied by red-flags
(bleeding, weight loss, dysphagia,
persisting vomiting, fhx of GI cancer, etc.)
o History suggests esophageal stricture
o High risk for Barrett’s
 Repeat endoscopy after 6-8 weeks of PPI if:
o Severe esophagitis because can mask
Barrett’s esophagus or symptoms
 Esophageal manometry indicated if:
o Normal gastroscopy but with chest pain
and/or dysphagia
 24h pH monitoring: most accurate test for reflux but
not required or performed in most cases
TREATMENT
 PPIs most effective and usually maintenance
therapy
o Non-erosive reflux disease: symptom relief
with antacids, H2-blockers, or PPIs
o Esophagitis: PPI indefinitely or surgical
fundoplication (wrap fundus around lower
end of esophagus)
 Lifestyle: weight loss and avoid alcohol, coffee, o Works best in children who have less sugar
spices, tomatoes, citrus juices absorption in colon
COMPLICATIONS  Abnormal findings suggest sugar malabsorption,
 Reflux esophagitis, Barrett metaplasia, peptic rarely used except in resource poor settings
stricture, esophageal adenocarcinoma CELIAC SPRUE/CELIAC DISEASE
 Autoimmune destruction of small intestinal villi
MALABSORPTION GLUTEN
 Gliadin and glutenin found in wheat
 Malabsorption of nutrients due to intestinal process  Combined to gluten when baking bread with water
 General symptoms:  Disease is triggered by gluten exposure
o Diarrhea, weight loss, vitamin and mineral GLIADIN
deficiencies  Glutamine residues on gliadin deamidated by tissue
CLINICAL MANIFESTATIONS transglutaminase (tTG)  COOH group
FAT MALABSORPTION  Deamidated gliadin consumed by APCs 
 Steatorrhea, voluminous stool, float, greasy and presented to T cells  type IV hypersensitivity
foul smelling o T-cell mediated tissue damage
 Loss of fat soluble vitamins o Unknown how antibodies contribute to
 Pale if bile is absent because no bilirubin disease
CARBOHYDRATE MALABSORPTION  Associated with HLA-DQ2 and HLA-DQ8
 Water diarrhea due to osmotic effect of sugar RISK FACTORS
molecules  Common in whites of northern European descent
PROTEIN MALABSORPTION (all Scandinavian countries)
 Don’t absorb enough sufficient amino acids  loss DIAGNOSIS
of albumin  edema  Serum antibodies:
DIARRHEA WORKUP o Anti-gliadin (rarely tested, poor accuracy)
 Steatorrhea (as above) o Endomysium is smooth muscle connective
 Watery tissue but unclear how involved
o Secretory: classically cholera, toxin o IgA endomysial (more specific) and tTG
stimulates secretion of chloride and water (more sensitive) highest accuracy
 Persists with fasting o IgA tTG is automated, used for screening
o Osmotic: classically lactose intolerance, o IgG can also be done
lactose not absorbed and draws fluid  Some patients have IgA deficient
 Stops with fasting  Negative tTG plus low IgA level =
 Inflammatory (RBCs/WBCs on stool microscopy) check IgG
o Infection, IBD  Confirmatory duodenal biopsy:
STOOL OSMOTIC GAP o Duodenum is most commonly involved
 Osmotic gap = 290 – (2[Na]+2[K])stool because first encounters gluten
 If only water drawn in, will dilute Na, K o Three key features:
 If water and Na, K secreted, will concentrate Na, K  Blunting of villi, crypt hyperplasia,
o Gap > 50 in osmotic causes lymphocytes in lamina propria
o Gap < 50 in secretory causes  Screening:
SUGAR AND FAT TESTS o Patients with first-degree relatives, T1 DM,
FECAL FAT TEST Down Syndrome, autoimmune (IBD,
 Collect stool over 1-3 days rheumatoid arthritis)
 Measure fat: <7g/day CLINICAL FEATURES
 Increased in fat malabsorption:  Unlike tropical sprue, which affects entire small
o Loss of bile (liver, biliary disease) intestine
o Loss of pancreatic enzymes  Flatulence, bloating, chronic diarrhea (steatorrhea
o Loss of small bowel (resection) and all of its features)
D-XYLOSE TEST  Children: failure to thrive; adults: unexpected
 After testing, ingests D-xylose weight loss
 Monosaccharide absorbed in small intestine only  Lethargy, iron deficiency anemia
requiring intact mucosa TREATMENT
 Measure D-xylose in serum/urine: normal rise  Gluten-free diet, avoid wheat
o Small intestinal bacterial overgrowth  Avoiding gluten is difficult because many packaged
o Whipple’s disease foods include gluten
OTHER TESTS COMPLICATIONS
 Stool pH  Increases risk of small bowel malignancy (rare
o Most sugars cause pH<6 compared to gastric and colon) AND
 Clinitest adenocarcinoma AND T-cell lymphoma
o Detects undigested sugars o Enteropathy-associated T-cell lymphoma
(EATL)
 oPresentation: patient adherent to gluten- o Lactase non-persistence most common
free diet with worsening symptoms  Enzyme falls with aging
 Dermatitis herpetiformis  Fallts too low is non-persistence
o Herpes-like lesions on skin  Lowest prevalence European
o Caused by IgA deposition in dermal Americans; highest among African
papillae  inflamed  formation of Americans, Native Americans,
vesicles Asians
o Resolves with gluten free diet o Secondary deficiency
TROPICAL SPRUE  Mucosal injury due to bacterial
 Etiology: overgrowth, viral infection,
o Malabsorption due to unknown infectious Giardiasis, Celiac, IBD
agent (responds to antibiotics)  Lactase usually first disaccharidase
o Traveler to tropics, especially Caribbean lost due to distal location on villi
 Pathophysiology: o Congenital lactase deficiency (rare)
o Key difference is intestinal location:  Pathophysiology:
o Because tropical affects entire small bowel, o Lack of lactase  lactose remains in small
often associated with folate/B12 deficiency bowel  osmotic effect
 Clinical features: o Normal histology
o Chronic diarrhea can be steatorrhea (fat) or  Clinical features:
watery (sugar malabsorption) o Symptoms with lactose ingestion: milk,
o Symptoms of malabsorption dairy
 Megaloblastic anemia due to folate o Bloating, abdominal pain, watery diarrhea
 Diagnosis:  Diagnosis
o Similar to celiac sprue with histology but o Often clear from history
serum antibodies will be negative o Lactose breath hydrogen test
 Treatment:  Ingest lactose  if undigested,
o Antibiotics (responds well to tetracycline) bacteria ferment lactose to
and supplement folate hydrogen  measure exhaled
WHIPPLE’S DISEASE hydrogen level
 Etiology: o Lactose tolerance test (rarely done)
o Infection with Tropheryma whipplei, gram-  Monitor blood glucose after lactose
positive rod related to actinomycetes consumption  tiny rise <20mg/dL
PANCREATIC INSUFFICIENCY
o Most common among white, European
males  Loss of pancreatic lipase, colipase, etc.
o 86% men, average age onset 49 years  Cystic fibrosis, chronic pancreatitis, obstruction
 Pathophysiology:  Fat malabsorption  steatorrhea and deficiencies of
fat-soluble vitamins
o Systemic infection involving small BACTERIAL OVERGROWTH
intestine, any portion
 Small intestine should be nearly sterile
o Involves joints, brain, heart
 Small number of organisms can be present
 Clinical features:
 Etiology:
o Four cardinal: diarrhea (malabsorption of
fats and sugars), abdominal pain, weight o Altered motility
loss, joint pains (migratory arthralgias large  DM (enteric nerve damage)
joints)  Scleroderma
o Mesenteric lymphadenopathy may cause o Partial/intermittent obstruction
abdominal distention  Adhesions from prior surgery
 Crohn’s disease
o Hyperpigmentation (darkened skin)
 Pathophysiology:
o CNS disease: confusion
o Significant bacteria  excessive
o Endocarditis: culture negative because fermentation, inflammation, malabsorption
Tropheryma is difficult to grow
 Presentation:
 Diagnosis:
o Bloating, flatulence, abdominal discomfort
o Biopsy of small intestine
o Chronic diarrhea (watery or steatorrhea),
 PAS-positive foamy macrophages vitamin deficiencies
seen in lamina propria of small
intest.  Diagnosis:
 Treatment: o Jejunal aspirate (gold standard) and
measure how much bacteria present
o Antibiotics (responds well to ceftriaxone)
o Different tx for extra-intestinal disease o Lactulose test and measure hydrogen
LACTOSE INTOLERANCE  Laxative as sugar molecule not
absorbed, bacteria will metabolize
 Lactose made of galactose and glucose some of it to hydrogen
 Digested by brush border enzyme lactase  Treatment:
 Etiology: o Antibiotics
CAUSES OF DIARRHEA
 Acute inflammatory:
o Bacterial, protozoal
o NSAIDs, IBD, ischemic
 Acute non-inflammatory:
o Bacterial, protozoal, viral
o Drugs: antibiotics, colchicine, laxatives,
antacids (Mg)
 Chronic inflammatory:
o IBD, infectious, ischemic bowel, radiation
colitis, neoplasia
 Chronic secretory:
o Stimulant laxatives, post-ileal resection,
bacterial toxins, neoplasia, Addison’s
disease
 Chronic steatorrhea:
o Giardia lamblia, celiac sprue, chronic
pancreatitis or cholestasis
 Chronic osmotic:
o Osmotic laxatives, lactose intolerance,
chewing gum (sorbitol, mannitol)
 Chronic functional:
o IBS, constipation (overflow diarrhea), anal
sphincter dysfunction
ACUTE DIARRHEA/GASTROENTERITIS
 Word: inflammation of stomach (gastro) and small
intestine (entero)
 Medical: increase in bowel movement frequency
with or w/o vomiting, abdominal pain, fever
o Three or more watery or loose bowel
movements in 24 hours
o OR at least 200g stool/d for >2d but <14d
 Acute: <14 days
 Persistent: 14-30 days
 Chronic: >30 days
ETIOLOGY
 Mostly infections: viral, bacterial (associated with
more severe), parasitic, fungal
 Most infections caused by viruses
 Viruses: rotavirus (dsRNA), norovirus (ssRNA),
adenovirus, sapovirus, astrovirus
PATHOPHYSIOLOGY
BACTERIAL
 Adherence, mucosal invasion, toxin production
o Enterotoxins stimulate secretory
mechanisms on mucosa
o Cytotoxins destroy mucosal cells and cause
inflammation
 Different mechanisms  malabsorption + fluid
excretion  loose stools
VIRAL
 Uses enterocyte to replicate  interference with
brush border enzyme production  malabsorption
 Viral toxins  direct damage and cell lysis 
transudative loss of fluid
CLINICAL PRESENTATION
 Nausea, vomiting, diarrhea, abdominal pain, fever
 Potentially signs of dehydration
Exam: soft abdomen but may have voluntary
guarding
 Most self-limiting and resolve within 7d
INFLAMMATORY ACUTE DIARRHEA
 Organisms and cytotoxins invade mucosa and kill
mucosal cells
o Usually colon
 Bacterial: shigella, salmonella, campylobacter,
yersinia, EHEC 0157:H7
 Protozoal: E. histolytica, stronglyoides
 Others: NSAIDs, IBD, ischemic
 Bloody (not always), small volume, high frequency,
may have fever +- shock
 Fecal WBC and RBC positive
 Chief life-threatening megacolon, perforation,
hemorrhage
NON-INFLAMMATORY ACUTE DIARRHEA
 Stimulation of water secretion and inhibition of
water resorption with intact mucosa
o Usually small intestine
 Bacterial: S. aureus, C. perfringens, B. cereus, E.
coli (enterotoxigenic, enteropathogenic), salmonella
enteritidis, virbio cholera
 Protozoal: giardia lamblia
 Viral: rotavirus, Norwalk, CMV
 Drugs: antibiotics, colchicine, laxatives, antacids
(Mg)
 Little to no blood, large volume,
upper/periumbilical pain/cramp +- shock
 Fecal WBC negative
 Chief life-threatening fluid depletion and electrolyte
disturbances
RISK FACTORS
 Food (raw, undercooked, contaminated)
 Sexual activity, outbreaks, occupational exposures
SCREENING
BACTERIA
 Fecal occult blood, leukocytes, lactoferrin,
calprotectin
 Positive tests increase yield of stool culture
 Negative tests not predictive for exclusion
EVALUATION
 Tests costly and warranted in specific criteria
 C&S/O&P if diarrhea inflammatory, severe (fever,
abdominal pain, dehydration), epidemiological
purposes (outbreak)
 Flexible sigmoidoscopy if inflammatory suspected
to distinguish from idiopathic IBD
BACTERIA
 1) Plating stool specimens on selective and
differential agar plates
o Selective: diminishing or preventing
growth of non-target organisms
o Differentiating: exploiting phenotype of
target organism to identify it among flora
 2) Inoculate into various broths
 Routine: salmonella, shigella, campylobacter
 Special requests: vibrio, yersinia, E. Coli O157:h7,
other shiga toxin-producing E. coli
 Persistent: ova and parasite testing
VIRAL
 Rare, mostly clinical diagnosis
 Antigen detection by special request
 o Identification may reduce need to
investigate other etiologies or lead to
specific therapy
PARASITE
 1) Microscopy of wet mount specimens
 2) additional stained slides of fresh or preserved
specimens
 Antigen for C. parvum and G. lamblia
 Microscopy: C. parvum, G. lamblia, entamoeba
histolytica, hymenolepsis nana, isospora,
microsporidia
ADDITIONAL TESTS
 Chemistry: electrolytes in dehydrated patients
 Blood count: potential complications
 Blood culture: bacterial suspected + high fever,
severe constitutional symptoms, extremes of age,
immunocompromised
 Imaging:
o Air or barium contrast enema or CT to
exclude lesion such as intussusception
o Diffusely inflamed colon in infectious
colitis
 Urinalysis: UTI in febrile infants with diarrhea
 Surgical consult: if signs of appendicitis
TREATMENT
 Most are self-limited
 Rehydration preferably by oral route then IV
 Antiemetic to control nausea/vomiting
 Antidiarrheals debate
o Antimotility agents (e.g. loperamide) and
modifiers of fluid transport (e.g. bismuth
subsalicylate) contraindicated in inflamm.
o Absorbants (e.g. kaolin/pectin) much less
effective than antimotility
 Antibiotic (bacterial): rarely indicated
o Side effects, renal failure, resistant strains
o Indications: septicemia, prolonged fever
with fecal blood or leukocytes,
immunocompromised, specific types
(salmonella typhi, shigella, V. cholerae, C.
difficile, ETEC, giardia, entamoeba
histolytica, Cyclospora)
IRRITABLE BOWEL SYNDROME
 Presence of abdominal pain or discomfort with
altered bowel habits
o IBS-D: predominant diarrhea
o IBS-C: predominant constipation
o IBS-M: mixed (each >25% of abnormal
BM)
o IBS untyped: insufficient abnormality in
stool
PATHOGENESIS
 Unclear combination of motility, visceral sensation,
brain-gut interaction, psychosocial distress
 Environmental contributors: life stressors, food
intolerance, antibiotics, enteric infection
 Altered gut immune activation
CLINICAL PRESENTATION
 Diagnosis by Rome IV criteria: recurrent
abdominal pain for >6 months, at least 1/d/wk in
last 3 months, associated with 2 of following:
oRelated to defecation, change in frequency
of stool, change in appearance of stool
 Supportive but not essential to diagnosis:
o Abnormal stool frequency (>3/d or
<3/wk); stool form
(lumpy/hard/loose/watery) >1/4
defecations; stool passage (straining,
urgency, feeling of incomplete evacuation)
>1/4 defecations
o Passage of mucous >1/4 defecations
o Bloating
EVALUATION
 Diagnosis less likely when red flags:
o Weight loss, fever, nocturnal defecation,
blood or pus in stool, abnormal gross
findings on flexible sigmoidoscopy, anemia
o Colonoscopy when red flags, family hx
IBD, or age>50
 Rule out similar diseases, esp. celiac and IBD
o No family history of IBD or colorectal
cancer
o CBC, inflammatory markers, celiac
serology
o Consider TSH, stool cultures metabolic
panel
TREATMENT
 No therapeutic agent effective, drug should be
‘wanted, not needed’
o Pain-predominant: antispasmodic meds
before meals, tricyclic antidepressants
o IBS-D: increase fibre, gluten avoidance,
loperamide, diphenoxylate
o IBS-C: increase fibre, linaclotide, osmotic
or other laxatives
 Diet: low FODMAP (fermentable oligo-, di-,
monosaccharides and polyoyls)
o Helps pain, bloating gas, irregular BM
 Education, relaxation therapy
ACUTE PANCREATITIS
 Acute inflammation of pancreas
 Liquefactive necrosis and hemorrhage
ETIOLOGY
  Can be idiopathic or any of the following
GALLSTONES (COMMON)
 Shows dilated bile ducts
ALCOHOL (COMMON)
 Exact mechanism unclear
 Usually apparent from history
 Alcohol can trigger release of pancreatic enzyme
TRAUMA
 Blunt or penetrating  damage to pancreas
 Sometimes occurs in children restrained by
seatbelts
 Rare because pancreas retroperitoneal location
INFECTION
 Viruses more common than bacteria/parasites
 Mumps (also causes inflammation of parotid gland)
DRUGS
 Many drugs so need review of medication lists
 GLP-1 agonists (diabetes)
o Exenatide, liraglutide
 Sulfa drugs
 6-mercaptopurine (6-MP)
o Chemotx and immunosuppressant
TOXINS
 Venom of arachnids and reptiles
 Brown recluse spider, some scorpions, Gila monster
lizard
AUTOIMMUNE PANCREATITIS
 Chronic abdominal pain
 Recurrent attacks of acute pancreatitis
 Diffusely enlarged pancreas on imaging
 IgG4+ plasma cells
o Identified in pancreas
o Serum IgG4 will be elevated
 Responds to treatment with steroids
HYPERCALCEMIA
 Calcium may deposit in pancreatic ducts and
activate trypsinogen
HYPERTRIGLYCERIDEMIA (>1000)
 Exact mechanism unclear
 May involve chylomicrons in plasma
o Usually formed after meals and cleared
o Always present with TG > 1000
o May obstruct capillaries  ischemia 
vessel damage exposes TGs to pancreatic
lipases  TGs break down  free FAs 
tissue injury  pancreatitis
DUODENAL ULCERS
 Pancreas sits behind posterior duodenum
 Rupture of posterior duodenal ulcer may lead to
acute pancreatitis
PATHOPHYSIOLOGY
 Blocked flow of enzymes while ongoing synthesis
 Large amounts of trypsin activated
o Activates trypsin and all other proteases:
phospholipase, chymotrypsin, elastase
o Normally trypsinogen activated at brush
border enterokinase
 “Auto-digestion” of pancreas and self-perpetuating
CLINICAL FEATURES
 Epigastric pain, classically radiating to back
 Nausea, vomiting
PHYSICAL EXAM
 Usually mild abdominal tenderness but non-specific
 Rare findings: periumbilical or flank hemorrhage
o Spread of necrosis/blood from enzyme-
induced damage
o Cullen’s sign (hemorrhage under skin of
umbilicus)
o Grey Turner’s sign (hemorrhage under skin
in area under flank)
o Also seen in ruptured ectopic pregnancy
DIAGNOSIS
 Serum:
 Elevated serum pancreatic enzyme levels
o Increased amylase and lipase (lipase more
specific)
o Both elevated in conditions other than
pancreatitis
 Liver function tests
o May be abnormal if gallstones are cause
o Cholestatic picture: increased AlkP >>
AST/ALT, increased conjugated bilirubin
 Leukocytosis (elevated WBC)
 Imaging:
 US and CT may show gallstones or bile duct
dilation
 CT may show pancreatic edema/necrosis
 Formal criteria (need 2/3):
 1) epigastric pain; 2) elevated amylase/lipase > 3x
normal; 3) abnormal pancreatic imaging (CT/MRI)
STAGING
RANSON’S CRITERIA
 Scoring system based on criteria at admission AND
at 48 hours to indicate if patient will be ill
 Mortality increases with higher score
TREATMENT
 1. NPO
o Nil per os (no food or liquid)
o “rests” the pancreas bc prevents stimulation
 2. IV fluids
o Fluid loss to pancreatic edema
o Inflammation leads to diffuse vascular leak
o Maintain BP and renal perfusion, esp. NPO
 3. Pain control
 Most patients with mild disease improve in 2-3
days
COMPLICATIONS
SYSTEMIC INFLAMMATORY RESPONSE
SYNDROME
 Clinical syndrome of dysregulated inflammation
o Temperature >38.3C or <36C
o Heart rate >90bpm
o RR >20 breaths/min
o WBC > 12,000
 Can occur from many causes:
o Trauma, severe pancreatitis
o Sepsis = SIRS + infection
DISSMINATED INTRAVASCULAR COAGULATION
 Diffuse activation of clotting factors 
“consumption coagulopathy”  prolonged
PT/PTT, thrombocytopenia, vascular occlusion
 Vascular occlusion  microangiopathic hemolytic
anemia (hematocrit low) + ischemic tissue damage
 Can present as bleeding
ACUTE RESPIRATORY DISTRESS SYNDROME
 Damage to capillary endothelium and alveolar
epithelium  protein escapes from vascular space
 fluid pours into interstitium
 Looks like pulmonary edema on CXR but
pulmonary capillary wedge pressure normal
 Presents as respiratory failure with hypoxemia
 Many patients end up ventilated, and pneumonia
develops
PSEUDOCYST
 Walled-off collection of edema/fluid
o Contain minimal or no necrosis in contrast
to walled-off pancreatic necrosis
 “Psuedo” because no epithelium
o Granulation/fibrous tissue surrounds
 Usually outside pancreas, most common is lesser
sac (posterior to stomach and front of pancreas)
 Course:
o Takes 4 weeks to ‘mature’ (10% of patients
in chronic pancreatitis)
o Often resolve without intervention
o Sometimes requires drainage
 Complications:
o Rupture  peritonitis
o Also can lead to fistulas, obstruction
o Can become infected  abscess
 Diagnosed by CT or MRI imaging
PANCREATIC ABSCESS
 Infection of pancreatic pseudocyst
 Usually late (~10 days) into acute pancreatitis
 Commonly caused by intestinal bacteria:
o E. coli (common), pseudomonas,
Klebsiella, Enterococcus
 Presents as fever, failure to improve clinically
FAT NECROSIS
 Inflammation involves fat surrounding pancreas
 Can lead to hypocalcemia/hypomagnesemia
o Enzymes (lipase) may release FFAs into fat
 FFAs bind electrolytes like calcium
“saponification”  pulls out of serum
 Low calcium is poor prognostic indicator because
suggests extensive involvement of fat
MULTI-ORGAN FAILURE
 Complication of pancreatitis  requires life-
supportive treatment often required in ICU
o Mechanical ventilation, vasopressors,
dialysis
 Can progress to multi-system failure and death
o Persistent hypotension despite vasopressors
o Failure to wean from ventilator
o Renal failure requiring dialysis
CHRONIC PANCREATITIS
 Much less common than acute pancreatitis
 Recurrent bouts of acute pancreatitis 
fibrosis/calcification of pancreas
ETIOLOGY
 Commonly recurrent acute pancreatitis from:
o Alcohol in adults
o Cystic fibrosis in children
 Most causes of acute not recurrent
DIAGNOSIS
 Serum:
 Amylase/lipase
o May be mildly elevated or normal
o Fibrosis may lead to loss of production
 Imaging:
 CT scan: classic finding calcified pancreas
CLINICAL FEATURES
 Chronic abdominal pain is hallmark
o May wax and wane
o May be worse after meals  fear of eating
and weight loss
 Often present to doctor asking for more narcotics to
mitigate abdominal pain
TREATMENT
 Eating small, frequent low-fat meals
 Replacement of fat-soluble vitamins and pancreatic
enzymes
 Cease alcohol and smoking
 Non-opioid regimens before trial of opioids
COMPLICATIONS
SPLENIC VEIN THROMBOSIS
 Portal vein drains blood from intestine (superior
and inferior mesenteric veins), splenic (splenic
vein), stomach (left gastric/coronary vein)
 Pancreas runs below splenic vein  inflammation
can involve vein  can cause thrombosis  dilate
short gastric veins (connect left gastric and splenic
vein)  gastric varices
 Present as patient with chronic pancreatitis who
develops upper GI bleed
o Enlarged spleen on physical exam and
gastric varices
 Treatment: splenectomy
PANCREATIC INSUFFICIENCY
 No exocrine due to destruction of parenchyma
 Fat malabsorption and steatorrhea
 Fat-soluble vitamin deficiencies
 Diabetes (loss of insulin)
PANCREATIC CANCER
Adenocarcinoma
More common at head of pancreas and so often will
obstruct flow of bile
ETIOLOGY
 K-RAS gene (chromosome 12p)
o Seen in 90% of pancreatic cancers
o Most frequently mutated gene
o Also part of adenoma-carcinoma sequence
for colon cancer
 SMAD4 gene (chromosome 18q)
o Tumor suppressor gene
o Inactivated in 60%
 BRCA2 mutations:
o BRCA1/BRCA2 encode DNA repair
proteins
o Associated with breast/ovarian cancer
o BRCA2 also associated with pancreatic
cancer, especially true among Ashkenazi
Jews
 Strongest risk factors: age >50 years old, smoking
  Other: diabetes, chronic pancreatitis (>20 years)
o NOT strongly associated with alcohol
CLINICAL FEATURES
 Often causes vague abdominal pain, weight loss
 Classically ‘painless jaundice’
o Slow growth of tumor blocks bile flow and
gradually leads to jaundice
o No pain due to absence of abrupt
obstruction/inflammation
 May see other signs of pancreatic-biliary
obstruction
o Dark urine, clay stools, steatorrhea
PHYSICAL EXAM
 Courvoisier’s sign:
o Enlarged, non-tender gallbladder + jaundice
 Trousseau’s syndrome/migratory superficial
thrombophlebitis:
o Redness and induration on (below) skin that
migrates
o Thrombosis/inflammation of veins due to
hypercoagulable state
DIAGNOSIS
 Tumor markers:
 Ca-19-9 (cancer-associated antigen 19-9)
o Not useful for diagnosis because sens/spec
o Can measure baseline and follow after
treatment to assess recurrence
 Carcino-embryonic antigen (CEA)
o Can be elevated but poor sens/spec
o Largely replaced by Ca-19-9
TREATMENT
 Chemotherapy, radiation, or surgery
 Classic surgery is Whipple
procedure/pancreatoduodenectomy
o Remove head of pancreas
o Rest of pancreas, bile duct, and stomach
connected directly to small intestine
PROGNOSIS
 Very poor prognosis
 Usually metastatic at presentation
 5-year survival node-positive: 10%
 5-year survival node-negative: 25%
EXTRA
ETIOLOGY
 Acute pancreatitis:
o Alcohol, gallstones most common
o Hyperlipidemia, autoimmune, trauma,
smoking, hypercalcemia, renal disease
 More common in chronic:
o Alcohol (most), CF in children (thick
mucous blocking pancreatic duct)
hypercalcemia, hyperlipidemia, obstruction
PATHOPHYSIOLOGY
 Acute pancreatitis:
 1. Premature activation of trypsinogen to trypsin
within acinar cell as opposed to duct lumen
o Can be caused by elevated ductal
pressures (e.g. obstruction); problems with
calcium homeostasis and pH;
predisposition involving genes related to
trypsin activation
o Toxins (e.g. alcohol) suspected to involve
ATP depletion  elevated intra-acinar
calcium
 2. Trypsin activates enzymes such as elastase and
phospholipases
 3. Localized tissue damage and release of Damage
Associated Molecular Patterns (DAMPs)
 4. DAMPs recruit neutrophils and initiate
inflammatory cascade
 5. Systemic manifestations
 6. Eventually damage of endothelium with
microvascular thrombosis causing multiorgan
dysfunction syndrome (MODS), main morbidity
and mortality
 Chronic pancreatitis:
 Bicarbonate theory: impaired bicarbonate
secretion cannot respond to increased secretion of
pancreatic proteins  abundant proteins form plugs
within lobules and ducts  calcification and stone
formation
 Intraparenchymal activation theory: genetics or
substances such as alcohol  intraparenchymal
activation of digestive enzymes  same as acute
CLINICAL PRESENTATION
 Acute pancreatitis:
o Acute onset abdominal pain radiating to
back
 Chronic pancreatitis:
o May be asymptomatic for a long time
o Exocrine affected: pancreatic insufficiency,
steatorrhea, weight loss
o Endocrine affected: pancreatogenic
diabetes
APPROACH TO DYSPHAGIA
 Dysphagia = difficulty swallowing
LIVER DISEASE
LIVER ‘DYSFUNCTION’ TESTS
 Serum aspartate aminotransferase (AST):
o Transfers nitrogen group from aspartate
o Located in mitochondria, liver most, then
muscle, kidneys, brain, pancreas, lungs
o Normal 10-40IU/L (labs differ)
  AST:ALT > 2 suggestive of
alcoholic liver disease, hepatitis,
cirrhosis
 Alcohol is mitochondrial toxin
 Serum alanine aminotransferase (ALT):
o Transfers nitrogen group from alanine
o Located in cytoplasm, primarily liver
o Normal 10-40IU/L (labs differ)
 ALT increase > AST increase in
most hepatocellular disorders
 >500IU in acute, <300IU in
chronic
 AST/ALT ratio:
o Normal to moderate elevation in hemolysis,
Gilbert’s syndrome, intra- and extrahepatic
cholestasis, obstructive jaundice, infiltrative
diseases
 Serum alkaline phosphatase (AlkP):
o Enzyme from liver, bones, GI tract
o Precise function unknown
o Increased synthesis x4 by bile ductal
epithelium with cholestasis
o Can also occur in non-liver conditions
 Pregnancy (placenta), thyroid
disease, bone disease
 Serum gamma-glutamyl transpeptidase (GGT):
o Similar to AlkP but not elevated in bone
disease
o Also elevated after heavy alcohol
consumption
o Similar enzyme: 5’-nucleotidase rarely
elevated in conditions other than liver
disease
 Abnormalities indicate some degree of dysfunction
LIVER FUNCTION (SYNTHETIC) TESTS
 Serum bilirubin:
o Unconjugated (indirect): water-insoluble
and bound to albumin
 Suggestive of hemolytic disorder
not of liver disease
o Conjugated (direct): water-soluble
 Upper limit 0.3mg/dL
 Almost always implies disease
because rate-limiting step of
bilirubin metabolism is transport of
conjugated into bile canaliculi
o Total: 1-1.5 mg/dL
 Platelets fall:
o TPO
 Albumin low
o In hepatitis, <3g/dL raises possibility of
chronic liver disease
 PT/PTT increased
o Can look at any clotting factor except
FVIII, which is produced by endothelial
cells
 Glucose falls
 Abnormalities indicate severe liver disease
ALCOHOLIC LIVER DISEASE
 Three ways alcohol can damage liver:
o Alcoholic fatty liver disease
o Acute hepatitis
o Cirrhosis
ALCOHOLIC FATTY LIVER DISEASE
 Accumulation of fatty acids in liver (fatty
infiltration)
o Begins in zone III (centrilobular zone)
o Also first to get affected in fibrosis
 Usually asymptomatic among heavy drinkers
o May cause hepatomegaly on exam
o AST>ALT
 Often reversible with cessation of alcohol
 Higher risk of developing cirrhosis
 Viral hepatitis tends to affect zone I first
NON-ALCOHOLIC FATTY LIVER DISEASE
 Fatty infiltration of liver not due to alcohol
o NAFL: fatty liver
o NASH: steatohepatitis (fat and
inflammation)
 Associated with obesity
 Often asymptomatic but:
o ALT>AST
 May improve with weight loss
 May progress to cirrhosis
ACUTE HEPATITIS
 Classically after heavy, binge drinking on top of
long history of alcohol consumption
 Toxic effects from acetaldehyde on hepatocytes
 Presents with fever, jaundice, RUQ pain/tenderness
 Histology:
o Mallory bodies, cytoplasmic inclusions
representing damaged intermediate
filaments
BUDD CHIARI SYNDROME
 Thrombosis of hepatic vein
 Zone 3 congestion, necrosis, hemorrhage
 Common causes:
o Myleoproliferative disorder (P. vera, ET,
CML), hepatocellular carcinoma,
OCP/pregnancy, hypercoagulable states
 Presents with abdominal pain, ascites (pressure in
portal system gets high, pushes fluid into peritoneal
cavity), hepatomegaly
RIGHT HEART FAILURE
 Blood backed up in IVC  liver edema  “cardiac
cirrhosis” (rare)
 Results in netmeg liver
o Mottled appearance, not smooth
o Can also be seen in Budd Chiari
REYE’S SYNDROME
 Children with viral infections who take aspirin
o Classically chicken pox (varicella zoster) or
influenza B
 Rapid severe liver failure and encephalopathy
o Evidence that aspirin inhibits beta oxidation
 mitochondrial damage seen
o Fatty changes in liver (hepatomegaly)
o Vomiting, coma, and death
 Avoid aspirin in children (except Kawasaki’s)
A1-ANTITRYPSIN DEFICIENCY
 Autosomal co-dominant inheritance
 Decreased or dysfunction AAT
o Balances naturally occurring proteases,
especially in lung
 Lung:
 o Imbalance between neutrophil elastase
(elastin) and elastase inhibitor AAT 
autodigestion  emphysema
 Liver:
o Abnormal AAT builds up in ER of
hepatocytes  pathologic polymerization
 death of hepatocytes  cirrhosis
 Diagnosis:
o AAT polymers stain purple with PAS
(periodic acid shift stain)
o Glycogen also stains purple but will be
broken down by diastase; AAT resists
diastase
LIVER ABSCESS
 Walled-off infection of liver
 In the US usually bacteria:
o Bacteremia
o Cholangitis (climb up biliary tree)
 GN rods, Klebsiella
 Entamoeba histolytica (protozoa):
o Cysts in contaminated water  bloody
diarrhea (dysentery)  ascends biliary tree
 Echinococcus (helminth):
o Fecal-oral ingestion of eggs  massive
liver cysts
VIRAL HEPATITIS
 Hepatitis A, B, C, D, or E
 Most liver diseases start in zone III, this starts in
zone I
 Presents with hyperbilirubinemia and jaundice
o If severe, may see abnormal synthetic
function: hypoglycemia, elevated PT/PTT,
low albumin
 Very high AST/ALT (often >1000, >25x normal)
 Diagnosed via viral antibody tests
AUTOIMMUNE HEPATITIS
 Autoimmune inflammation of liver
 Most common in women 40s/50s
 Range of symptoms
o Asymptomatic  acute liver disease 
cirrhosis
 Diagnosis:
o Anti-nuclear antibodies (sensitive, not
specific)
o Anti-smooth muscle antibodies (more
specific)
 Treatment: steroids and immunosuppressants
TYLENOL OVERDOSE
 AKA acetaminophen, paracetamol, APAP
 Maximum recommended dose = 4g/24 hours
 Overdose causes acute liver failure (hepatic
necrosis)
o Extremely high AST/ALT (in 1000s)
 Three metabolites, but NAPQI is toxic to liver
o Glutathione metabolizes NAPQI to non-
toxic structure
 Treatment:
o Activated charcoal may prevent absorption
o N-acetylcysteine standard, usually oral
 Metabolized to cysteine which is
used to synthesize glutathione
 Used to replenish glutathione
SHOCK LIVER/ISCHEMIC HEPATITIS
 Diffuse liver injury from hypoperfusion
 Often seen in ICU patients with any form of shock
o Extremely high AST/ALT (1000s)
o >1000 in viral hepatitis, ischemic liver
injury, and toxin- or drug-induced liver
injury
 Zone III necrosis
 Usually self-limited
CIRRHOSIS
 Irreversible, end-stage liver disease
 Results from many causes of chronic liver disease:
o Viral hepatitis (usually B and C)
o Alcoholic liver disease
o Non-alcoholic fatty liver disease
 Shrunken liver and tissue replaced by fibrous
nodules
STELLATE CELL
 Perisinusoidal cell storage site for retinoids
(vitamin A metabolites)
 Activated and major contributor in liver disease
o Secrete TGF-B
o Proliferate and produce fibrous tissue
CLINICAL PATHOPHYSIOLOGY
 Jaundice
o Loss of bilirubin metabolism
 Hypoglycemia
o Loss of GNG
 Coagulopathy
o Loss of clotting factors
 Hyperammonemia
o Asterixis, confusion, coma
o Treatment:
o Low protein diet (not recommended
anymore because malnourishment)
o Lactulose
 Synthetic disaccharide (laxative)
 Colon breakdown by bacteria to
FAs  lowers colonic pH 
favors formation of NH4+ over NH3
 trapped in colon  patient has
more BMs  plasma ammonia
falls
 Elevated estrogen
o Usually removed by liver
o Amenorrhea in women
o Gynecomastia, spider angiomata (increased
number of blood vessels with unclear
mechanism), palmar erythema
 1) Hypoalbuminemia
o May cause low oncotic pressure 
decreased ECV
 2) Release of vasodilators
o Increase in vasodilators, especially NO 
increased splanchnic (abdomen)
vasodilation  decreased systemic vascular
resistance (SVR) and low BP  decreased
ECV
 oCompensation to decreased ECV: RAAS,
ADH  increased Na/H2O retention 
increased total body water
 3) Portal hypertension
o Cirrhosis causes obstructed blood flow
through liver
o Elevated TBW and decreased albumin
contributes to edema and ascites
o Portal hypertension contributes to ascites
 Patients with cirrhosis but no portal
HTN do not have ascites
 Venous collaterals/anastomoses from portal HTN
o Connections between portal veins and
systemic veins normally small and
collapsed
o Portal HTN makes these connections
dilated and engorged  named “venous
collaterals”
o Varices: dilated, tortuous blood vessels
o Esophageal varices
 Most esophageal venous drainage
via esophageal veins to SVC
 Small amount of superficial blood
via left gastric vein (coronary vein)
to portal vein
 Upper GI bleeding
o Gastric varices
 Short gastric veins drain connect
left gastric vein and splenic vein –
both part of portal system drain
fundus
 Upper GI bleeding
o Umbilicus
 Collaterals between paraumbilical
vein (portal) and epigastric veins
 Caput medusa – engorged veins
around umbilicus
o Internal hemorrhoids
 Above dentate line
 Collaterals between superior rectal
vein (portal) and middle/inferior
rectal veins
 Hemorrhoidal bleeding
 Hypersplenism from portal HTN
o Because spleen drains into portal via
splenic vein  spleen engorged  low
platelets
PORTAL VEIN THROMBOSIS
 Rare cause of portal HTN (no cirrhosis)
 Acute onset abdominal pain
 Splenomegaly (palpable spleen)
 May result in gastric varices with bleeding
 Liver biopsy will be normal
STAGING
 MELD score:
o For chronic liver disease or cirrhosis
o Point system using bilirubin, Cr, INR
o Estimates 3-month mortality from liver
disease (>40 = 71%, <9 = 2%)
 Child-Pugh classification:
o Five variables to predict risk/survival
o Points for encephalopathy, ascites,
bilirubin, albumin, PT
o 5-6: class A cirrhosis | 7-9: class B | 10-15:
class C (worst)
DIAGNOSIS
 Gold standard is livery biopsy
o Not required if diagnosis clear from history
o Only when biopsy will change management
 Imaging (US, CT, MRI)
o May show small, nodular liver
o Not sensitive or specific
o More helpful for detection of hepatocellular
carcinoma
 Clinical diagnosis (common)
o Presence of ascites, low platelet count,
spider angiomata
ASCITES
SERUM ASCITES ALBUMIN GRADIENT
 Two reasons for new/worsening ascites
o Portal HTN more common
o Malignancy (leaky vasculature)
 Sample of ascitic fluid via paracentesis
 SAAG = serum albumin – ascites albumin
o >1.1 g/dL
 Large difference indicates high
pressure driving fluid but no
albumin into peritoneum  portal
HTN
o <1.1 g/dL
 Similar levels indicates leaky
vasculature  malignant ascites
ASCITES TREATMENT
 Sodium restriction  volume contraction
 Diuretics:
o Spironolactone is drug of choice (K-
sparing, blocks aldosterone, most effective)
o Loop diuretics 2nd line (e.g. furosemide)
 Paracentesis
 Transjugular intrahepatic portosystemic shunt
o Creation of channel in liver that connects
portal vein to hepatic vein
SPONTANEOUS BACTERIAL PERITONITIS
 Bacteria in gut gain entry into ascitic fluid
 Usually E. coli and Klebsiella, rarely strep/staph
 In patients with known ascites has fever, abdominal
pain/tender
 Measure ascitic absolute PMNs (>=250 cells/mm 3)
 Treatment:
o 3rd gen cephalosporin (cefotaxime)
o Gram+ and gram- coverage
o Achieves good levels in ascitic fluid
ALCOHOLIC HEPATITIS AND CIRRHOSIS
PATHOPHYSIOLOGY
 Oxidative metabolism of alcohol increases
production of NADH from NAD
o Ratio inhibits oxidation of TGs and FAs
and promotes lipogenesis
 Nutritional deficiencies because alcohol provide a
lot of calories  directly impact liver or impact
other systems that damage liver
 Translocation of endotoxins as lipopolysaccharides
(LPS) from intestines to hepatocytes
 o In Kupffer cells, LPS binds to CD14 and  Y-glutamyl transpeptidase (yGT) to determine
TLR-4  ROS release  activates whether AlkP elevations due to liver disease
cytokines such as TNF-a, IL-8, MCP-1,  Hepatitis serology to determine type
PDGF  perpetuates Kupffer activation  Autoimmune markers for:
and accumulates neutrophils, macrophages o Primary biliary cholangitis –
o ROS and acetaldehyde-protein adducts antimitochondrial antibody
damage hepatocytes o Sclerosing cholangitis – peripheral
 Profibrogenic cytokines stimulate excess production antineutrophil cytoplasmic antibody
and deposition of collagen  connects portal triads o Autoimmune hepatitis – antinuclear,
forming nodules  combined with hepatocyte smooth-muscle, and liver-kidney
damage = shrunken liver with fibrous nodules microsomal antibody
TREATMENT  B) Imaging
 Abstinence is cornerstone of therapy o US, CT – sensitive for biliary duct dilation
 Adequate nutrition and ongoing management of o US, CT, MRI – fatty liver
complications (e.g. ascites, hemorrhage) o Spiral CT and MRI with contrast – hepatic
 Glucocorticoids (prednisolone) in severe alcoholic masses
hepatitis with or w/o hepatic encephalopathy o Magnetic resonance
o Don’t if GI bleeding, severe pancreatitis, cholangiopancreatography (MCRCP) –
uncontrolled DM, active infection visualization of biliary tree
 Oral pentoxifylline decreases production of TNF-a o Endoscopic retrograde CP: visualize with
and other proinflammatory cytokines camera and can take out stones
 C) liver biopsy for unclear diagnoses and for
APPROACH TO LIVER DISEASE staging of chronic

Generally present in distinct patterns:

Hepatocellular: liver injury, inflammation,
necrosis
o Viral hepatitis and alcoholic liver disease
 Cholestatic: inhibition of bile flow
o Primary biliary cholangitis, gallstone,
malignant obstruction
 Mixed: cholestatic forms of viral hepatitis and
many drug-induced liver diseases
 Presenting symptoms typically:
o Jaundice, fatigue, RUQ pain, nausea, poor
appetite, itching, abdominal distention,
intestinal bleeding
o Fatigue most common and characteristic
o Nausea indicates more severe
o Severe pain most typical of gallbladder
disease, liver abscess, and severe sinusoidal
obstruction syndrome
 Evaluation should:
o 1) establish etiologic diagnosis
o 2) disease severity – grading active or
inactive, mild, moderate, or severe
o 3) disease staging – point in course of
natural history of disease; pre, cirrhotic, or
end-stage
 Common causes:
o Chronic hepatitis C, alcoholic liver disease,
nonalcoholic steatohepatitis, chronic
hepatitis B, autoimmune hepatitis,
sclerosing cholangitis, primary biliary
cholangitis, hemochromatosis, and Wilson
disease
ALGORITHM
 A) Battery of serum ALT, AST, AlkP, direct and
total serum bilirubin and albumin, and PT
o Pattern points to 1) hepatocellular versus
cholestatic liver disease 2) whether acute or
chronic 3) whether cirrhosis and failure
  More likely to occur if excess cholesterol or
decreased bile acids from underproduction or poor
absorption from ileum (keep cholesterol emulsified
in bile)
o Nucleation (nydus to keep growing),
hypomotility
 1) Excess estrogen  increased cholesterol
synthesis
o Females
o Pregnancy, multiparity  estrogen +
progesterone (slows gallbladder emptying)
 Obesity  increased total body cholesterol
 Rapid weight loss  increased cholesterol
mobilization
 2) Cirrhosis  decreased synthesis of bile salts
 Crohn’s disease  inflammation of ileum
common and abnormal resorption of bile salts
 Cystic fibrosis  fat malabsorption  loss of bile
acids in stool
 Clofibrates and other fibrates  inhibit bile acid
synthesis
 Bile acid resins  prevent intestinal resorption of
bile acids and salts
o Old, rarely used cholesterol drugs
PIGMENT/BILIRUBIN GALLSTONES
 Composed of calcium bilirubinate, black or brown
 Can be seen on x-ray (radiopaque)
RISK FACTORS
 Rise in unconjugated bilirubin in bile (unconjugated
bilirubin insoluble in H2O)
 Extravascular hemolysis  excess bilirubin
 Cirrhosis or chronic liver disease  impaired
bilirubin conjugation
 Recurrent biliary tree infections  bacterial
glucuronidases convert conjugated bilirubin to
unconjugated
o Brown vs. black in hemolysis/liver disease
because more Ca2+ and some cholesterol
CLINICAL PRESENTATION
 Often asymptomatic
o Discovered incidentally on abdominal
imaging
 Can cause various clinical conditions:
BILIARY COLIC
 Gallbladder contracts against stone inside it, near
outlet but stone may move away
 Clinical features:
o Episodic RUQ pain often after eating, esp.
fatty meals, due to CCK secretion
o May radiate to right shoulder blade
GALLSTONES o Pain lasts ~30 minutes then subsides
ACUTE CHOLECYSTITIS
CHOLESTEROL GALLSTONES  Stone obstructs cystic duct  gallbladder squeezes
 Most common type and constricts blood supply  ischemia 
 Usually not visible on X-ray (radiolucent) gallbladder dilates and becomes inflamed
o Not as important now because mostly use  Clinical features:
US o RUQ pain AND fever, elevated WBC
RISK FACTORS (from inflammation)
 Age: o May radiate to right scapula
o Classically occurs in 40s; rare  Other findings:
children/senior o Murphy’s sign: press RUQ, patient asked to
o Elderly patient with gallstone symptoms inspire, abruptly stops inspiring due to pain
could have cancer o Thickened gallbladder wall on imaging
  Risk of rupture/peritonitis
 Usually treated with urgent surgery
CHOLEDOCOLITHIASIS
 Stone obstructs common bile duct
 Clinical features:
o Liver stigmata such as jaundice, elevated
AlkP >> elevated AST/ALT
 May lead to cholangitis
ASCENDING CHOLANGITIS
 Stone blocks flow of bile  GI bacteria able to
‘ascend’ in biliary tree  cholestasis + infection
 Etiology:
o Gram negatives: E. coli, Klebsiella,
Enterobacter
o Clonorchis sinensis: rare Chinese liver
fluke, Helminth found in infected fish
 Will see peripheral eosinophilia
because helminth
 Clinical features:
o Charcot’s triad: fever, abdominal pain,
jaundice
o Reynold’s pentad: fever, abdominal pain,
jaundice, confusion, hypotension
 Indicates sepsis and shock from
infection
 Other findings:
o Elevated WBC, AlkP >> AST/ALT,
elevated conjugated and total bilirubin
 Treatment:
o Antibiotics: gram negative and anaerobic
coverage
 Ampicillin-sulbactam,
ciprofloxacin-metronidazole
o Biliary drainage: endoscopic
sphincterotomy with stone extraction
 Sometimes stent insertion
 Rarely surgery (replaced by
drainage)
GALLSTONE PANCREATITIS
 Obstruction of hepatopancreatic ampulla 
pancreatic enzymes autodigest parenchyma
GALLSTONE ILEUS
 Massive gallstone erodes through gallbladder and
intestinal wall  fistula (can be size of baseball
bat) between gallbladder and small intestine
o Usually bowel obstruction at ileocecal
valve
 Clinical presentation: bowel obstruction
 Key imaging finding on CT or X-ray:
o Air in biliary tree where should be all bile
CHRONIC CHOLECYSTITIS
 Long-standing, untreated cholecystitis
 Chronic inflammation causes calcium deposition
 Causes porcelain gallbladder (white in walls due
to calcium deposition)
 High risk of gallbladder carcinoma
 Surgery for symptoms and remove cancer risk
GALLBLADDER CARCINOMA
 Adenocarcinoma from chronic inflammation
 1) Untreated gallstone disease that progress to
porcelain gallbladder
 2) Chronic salmonella infection
o S. typhi can remain in gallbladder creating
carrier state
o In endemic countries 1-4% may be carriers
EVALUATION
 Initial labs include battery of liver disease tests,
CBC, comprehensive metabolic panel (CMP),
lipase, amylase, and urinalysis
 Imaging:
 1. Ultrasound is best modality
o Gallstones appear as hyperechoic structures
with distal acoustic shadowing
o Sludge also hyperechoic layering but no
acoustic shadowing
o Can measure common bile duct: 4mm in 40
years old + 1mm per additional decade
 2. If unequivocal US, nuclear medicine
cholescintigraphy scan (HIDA scan)
o Radioactive tracer in peripheral vein
circulated to liver where enters biliary tree
and gets taken up by gallbladder within 4h
o Obstruction will prevent from entering
gallbladder
 3. ERCP (requires contrast, invasive, but allows
intervention e.g. stenting, stone extraction, biopsy)
and MRCP (no dye and non-invasive)
TREATMENT
 Asymptomatic:
o Laparoscopic cholecystecomy
o Oral or parenteral analgesia
o Dietary and lifestyle changes
 Symptomatic:
o Laparoscopic cholecystectomy
o Body still able to absorb fats but much of
bile is removed
ERCP
 Endoscopic retrograde cholangiopancreatography
 In mouth, long endoscope  at duodenum, device
pokes into bile ducts and injects die  fluoroscope
detects dye for stones and strictures  tools can
remove stones
 Imaging and therapy of biliary disorders
URSODEOXYCHOLIC ACID
 A bile acid rarely used as medical therapy for
cholesterol stones
 Reduces cholesterol secretion into bile  less
cholesterol and increased ratio of bile
acids:cholesterol
 May dissolve gallstones
OTHER BILIARY DISORDERS
BILIARY ATRESIA (CLOSED OR ABSENT
ORIFICE)
 Idiopathic biliary obstruction in neonates
 Biliary ducts do not form or degenerate early in life
 no conduit to transmit bile from liver to intestine
 Clinical features:
o Jaundice, dark urine, pale “acholic” stools
 Imaging:
o US shows absent or abnormal gallbladder
o Absence of common bile duct
o No other causes such as stones/strictures
 Treatment:
 o Kasai procedure creates conduit for bile
drainage using small intestine
PRIMARY BILIARY CIRRHOSIS
 Biliary cirrhosis: old term for liver damage from
biliary obstruction (e.g. stone, stricture, pancreatic
cancer)
 Primary: without extra-hepatic obstruction
 Etiology:
o Associated with other autoimmune
disorders, most commonly Sjogren’s
 Autoimmune disorder mediated by T-cell attack on
small intralobular bile ducts
o Form of granulomatous inflammation
 Clinical features:
o More common among women
o Fatigue and pruritus most common initial
 Itching from increased bile acids in
serum/skin
 Itching often severe, worse at night
o Pruritus often precedes jaundice
 Diagnosis:
o Markedly elevated AlkP >> AST/ALT
o Anti-mitochondrial antibodies are hallmark
 ANAs in ~70%
o Serum lipids may be markedly elevated
with or without xanthomas
 Total cholesterol > 1000
o US shows absence of biliary obstruction
o Liver biopsy gold standard
o Elevated bilirubin occurs late  poor
prognosis
 Treatment:
o Ursodeoxycholic acid
 Only effective therapy
 Replaces endogenous bile acids
over time  decreases disease
progression because less
hepatotoxic
o Liver transplant
PRIMARY SCLEROSING CHOLANGITIS
 Etiology:
o Strongly associated with ulcerative colitis
(can think of complication of UC)
 Autoimmune disorder
 Inflammation, fibrosis, and strictures in biliary
tree
o Involves intra- AND extra-hepatic bile
ducts
 Clinical features:
o Sx of cholestasis: RUQ pain, fatigue,
jaundice
 Diagnosis:
o Elevated AlkP >> AST/ALT, conjugated
bili.
o Elevated IgM (~50%)
o Positive p-ANCA (~80%)
o Periductal (onion skin) fibrosis on
histopathology
o Confirmatory ERCP or MRCP
 Biliary strictures and dilations
creates ‘beading’ pattern
 Treatment:
o Endoscopic therapy
 Dilation or stenting of strictures
o Liver transplant
o Annual screening for cholangiocarcinoma
CHOLANGIOCARCINOMA
 Cancer of bile duct epithelial cells
 Sx usually from cholestasis
 Key risk factors:
o Anything that causes chronic biliary
inflammation
o E.g. primary sclerosing cholangitis and
Clonorchis sinensis
AIDS CHOLANGIOPATHY
 Rare complication of end-stage HIV infection
o Usually CD4< 100/mm3
 Chronic infection involving biliary tree from
cryptosporidium (most common) and
cytomegalovirus  biliary obstruction from
strictures of biliary tract
 Clinical features:
o RUQ pain, sometimes fever, jaundice
ACALCULOUS CHOLECYSTITIS
 Acute cholecystitis not due to gallstones
 Caused by gallbladder ischemia and bile stasis
 Usually occurs in critically ill patients (e.g. shock)
IBD
 Two chronic autoimmune bowel diseases with
unknown trigger  inflammation promotes leaky
epithelium  increased movement of pathogens
 Etiology:
o Slight female predominance
o Age of onset usually 14-50 years (possible
second spike 50-80)
o More common whites and Jewish
o Close relative, NSAIDs
o Smoking improve outcomes in UC,
worsens in Crohn’s (sometimes trigger
flare)
 Presentation:
o Classically white woman in 30s, Jewish
descent
o Similar symptoms:
 Recurrent episodes
 Abdominal pain, bloody diarrhea
 Course:
o Both have relapsing, remitting course
o Stable for period of time then ‘flare’ where
medication requirements go up
 Treatment:
o Mild to moderate disease: topical steroids
and/or sulfasalazine/5-ASA
 Can be combined with antibiotics
o Maintenance: 5-ASA drugs
o Flare-ups: corticosteroids
o Moderate to severe OR refractory: systemic
corticosteroid  if refractory 
immunosuppressants (methotrexate,
infliximab/adalimumab, azathioprine, 6-
MP)
o Surgery for complications (e.g. abscess,
perforation)
BLOODY DIARRHEA
 IBD is uncommon cause
 Many other causes, especially infection
 Typical studies sent:
o Stool cultures (salmonella, shigella,
campylobacter, yersinia)
o Testing for E. coli 0157:H7 (invasive form)
o Other stool studies (C. diff, Ova, parasites)
SULFASALAZINE
 Sulfasalazine  colonic bacteria  sulfapyridine
and 5-aminosalicylic acid (5-ASA)
o Not active until reaches colon
o 5-ASA works similarly to aspirin
 Side effects:
o GI upset (nausea, vomiting)
o Sulfonamide hypersensitivity
o Oligospermia in men
 Reversible when drug cessation
 Problem for men trying to conceive
on therapy
5-ASA/MESALAMINE
 Many side effects due to sulfa moiety
 Less side effects BUT absorbed in jejunum  less
delivery to colon
 Modified 5-ASA compounds to resist absorption:
o Coating or delayed release capsules
o Asacol, pentasa
ULCERATIVE COLITIS
PATHOPHYSIOLOGY
 Ulcers form in the colon only
 Th2-mediated inflammation of mucosa, sometimes
submucosa, NOT muscularis or serosa
 Always starts in rectum and works upward
o Always rectal involvement  left lower
quadrant pain common
 Never involves small intestine
GROSS MORPHOLOGY
 Pseudopolyps from healing of ulcers
o Scar tissue heaped up in ulcer and create a PATHOPHYSIOLOGY
raised portion of mucosa
 Loss of haustra (pouches on colon)  smooth,
straight lead pipe appearance on X-ray/CT
MICROSCOPY
 Crypt abscesses
o PMN infiltration of crypts
COMPLICATIONS
TOXIC MEGACOLON
 Rare complication of UC and infectious colitis
 Pathophysiology:
o Poorly understood  cessation of colon
contractions
o Evidence that NO synthesized and released
 inhibit smooth muscle tone  intestinal
dilation  rapid distention occurs  wall
thins  prone to rupture  perforation
 Presentation:
o Patient with UC develops abdominal pain,
distention, fever, diarrhea, shock
o Toxic = fever and shock
 Diagnosis:
o Flat-plate X-ray of abdomen
o Large, dilated loops of bowel
ADENOCARCINOMA
 Significant risk in UC but differs by patient
 Risk based on two key factors:
o Duration of disease (>10 years before most
cancers form)
o Extent of disease (more disease = more
risk)
 Extension from rectum into right or
descending colon = more risk
o “Right sided colitis” or “pancolitis” are risk
factors
 Screening colonoscopy recommended
o Multiple biopsies taken
 Colectomy sometimes required
EXTRA-INTESTINAL FEATURES
 Pyoderma gangrenosum
o Deep, necrotic skin ulceration
 Primary sclerosing cholangitis
 Ankylosing spondylitis
o Inflammation of spine
 Uveitis
o Inflammation of middle layer of eye
DIAGNOSIS
 Serum:
o p-ANCA
 Also seen in vasculitis syndromes,
e.g. Microscopic Polyangiitis,
elevated in UC
o Anti-saccharomyces cerevisiae antibodies
(ASCA)
 Type of yeast
 Elevated in Crohn’s
 Confirmatory:
o Colonoscopy or endoscopy and taking
biopsy of inflamed mucosa
CROHN’S DISEASE
 Th1-mediated granulomatous inflammation
 Entire wall affected (transmural)
 Any portion of GI tract can be affected
o Oral ulcers can even be seen
 Terminal ileum is common location
 Often spares rectum and ‘skips’ sections
GROSS MORPHOLOGY
 “Cobblestone mucosa”
o Stones are normal mucosa, fissures between
are formed by transmural inflammation
 Fistulas
o Transmural inflammation can spread to
nearby structure, forming connections
o Skin: peri-anal or abdominal opening
o Bladder: enterovesical fistula  feces or air
in urine
 Creeping fat
o Transmural inflammation heals 
condensed fibrous tissue pulls fat around
bowel wall
 Strictures
 o Healing  dense fibrous tissue narrows o Antimicrobial stewardship: control
lumen (string sign on imaging) antimicrobial resistance and reduce costs
MICROSCOPY
 Non-caseating granulomas
CLINICAL FEATURES
 Because terminal ileum
 Malabsorption:
o Vitamin deficiencies (B12), bile salt
deficiency (increased risk of gallstones,
secretory diarrhea, steatorrhea)
o May have non-bloody diarrhea due to
malabsorption
 Right lower quadrant pain
EXTRA-INTESTINAL FEATURES
 Migratory polyarthritis
o Most common
o Arthritis of large joints (knees, hips)
 Erythema nodosum
o Inflammation of fat under skin  red,
painful splotches on skin usually
 Calcium oxalate kidney stones
o Fat malabsorption  fat binds to calcium
 oxalate free to be absorbed in gut 
high oxalate in serum and urine
 Ankylosing spondylitis and uveitis (shared)
COMPLICATIONS
ADENOCARCINOMA
 Only when colon involved
 Surveillance colonoscopy to assess
MONITORING
 CRP, ESR: general inflammation
 Electrolyte: dehydration
 Vitamin B12: anemia
 Vitamin D: bone mineral status
 Stool calprotectin, lactoferrin: active intestinal
inflammation
 X-ray and CTs: perforations, blockages, abscesses
 MRCP, ERCP: pancreatic and bile ducts
PUBLIC HEALTH OUTBREAK
 By law, physicians and other practitioners must
report suspect or confirmed communicable disease
to local Medical Officer of Health
 Outbreak management team investigates reportable
diseases, identifies and manages contacts
 Also investigates outbreaks (sudden increase in # of
cases of infectious disease above expected)
 Infection control at hospitals:
o Precautions: standard (hand hygiene, PPE,
laundry, sharp disposal); contact
precaution (limit transport, disinfect or
dispose care equipment); droplet
precaution (mask on patient); airborne
precaution (isolated)
o Surveillance: assess rate of infections and
endemic likelihood
o Isolation: prevent transmission but
expensive and time-consuming
o Outbreak investigation and management:
pulsed-field gel electrophoresis or whole-
genome sequencing
o Education and employee health