Gastroenterology 2008

G
Gastroenterology
Behzad Hassani, Ahmad Muinuddin and Vandana Pamandi, chapter editors
Lawrence Aoun and Sam Silver, associate editors
Jeremy Adams, EBM editor
Dr. Gabor P. Kandel, staff editor
Differential Diagnosis of Common
Presenting Complaints 2
NauseaNomiting
Dysphagia
Abdominal Distention
Acute Abdominal Pain
Chronic/Recurrent Abdominal Pain
Acute Diarrhea
Chronic Diarrhea
Constipation
Dyspepsia
Esophagus 3
Basic Anatomy Review
Dysphagia
Odynophagia
Dyspepsia
Gastroesophageal Reflux Disease (GERD)
Esophageal Motor Disorders
Esophageal Structural Disorders
Diverticula
Benign Stricture
Esophageal Cancer (see General Surgery. GS11)
Webs and Rings
Barrett's Esophagus
Infectious Esophagitis
Stomach and Duodenum 8
Gastritis
Peptic Ulcer Disease (PUD)
H. pylori-Induced Ulceration
NSAID-Induced Ulceration
Stress-Induced Ulceration
Zollinger-Ellison (ZE) Syndrome
Small and Large Bowel 12
Classification of Diarrhea
Acute Diarrhea
Traveller's Diarrhea
Chronic Diarrhea
Maldigestion and Malabsorption
Celiac Disease (Gluten Enteropathy/Sprue)
Bacterial Overgrowth
Inflammatory Bowel Disease (lBD)
Crohn's Disease (CD)
Ulcerative Colitis (UC)
Irritable Bowel Syndrome (lBS)
Constipation
Upper Gastrointestinal Bleeding
Bleeding Peptic Ulcer
Esophageal Varices
Mallory-Weiss Tear
Lower Gastrointestinal Bleeding
Colon Cancer
Toronto Notes 2008
Liver 30
Investigations of Liver Function
Hepatobiliary Disease Lab Tests
Hepatitis
Acute Viral Hepatitis
Fulminant Hepatic Failure
Chronic Hepatitis
Chronic Hepatitis C
Chronic Hepatitis B
Chronic Hepatitis B + D
Autoimmune Chronic Active Hepatitis
Drug-Induced Liver Disease
Wilson's Disease
Hemochromatosis
Alcoholic Liver Disease
Non-Alcoholic Fatty Liver Disease (NAFLD)
Cirrhosis
Hepatocellular Carcinoma
LiverTransplant
Hepatic Encephalopathy
Portal Hypertension
Ascites
Hepatopulmonary Syndrome
BiliaryTract 43
Jaundice
Gilbert's Syndrome
Crigler-Najjer Syndrome
Primary Biliary Cirrhosis (PBC)
Secondary Biliary Cirrhosis
Ascending Cholangitis
Sclerosing Cholangitis
Pancreas 47
Acute Pancreatitis
Chronic Pancreatitis
Clinical Nutrition 50
Determination of Nutritional Status
Enteral Nutrition
Parenteral Nutrition
Visualizing the GI Tract 52
Common Medications 53
Summary Key Questions 54
References 55
Gastroenterology Gl
G2 Gastroenterology Differential Diagnosis of Common Presenting Complaints Toronto Notes 2008
Differential Diagnosis of Common
Presenting Complaints
Table 1. Differential Diagnosis of Common Presenting Complaints
VOMITING With Abdominal Pain Without Abdominal PainINon-G1
Relieved by Vomiting Not Relieved by Vomiting HeadachelDizziness No Other Symptoms
Gastric outlet obstruction Gallbladder disease Cerebral tumour Drugs
..J ....'
Small bowel obstruction Pancreatitis Migraine Uremia
Myocardial infarction Vestibular Pregnancy
Hepatitis Cerebellar hemorrhage Metabolic
(e.g. hypercalcemia)
Gastroparesis
le.g. diabetesl
Ketoacidosis
DYSPHAGIA
Mechanical Motility Other
StricturelEsophagitis Achalasia Foreign body
Cancer Diffuse esophageal spasm
~ '
External compression Scleroderma
Schatzki ring/esophageal web Myasthenia gravis
Differential Diagnosis of
Zenker's diverticulum
Abdominal Distansion (6Fs):
ABDOMINAL Fluid Flatulence Feces Other
Fat
DISTENTION PortalHTN Normal Portal Pressure
Feces
Cirrhosis Cancer esp. ovarian Irritable bowel syndrome Colonic obstruction Pregnancy
Fetus
Flatus
Cardiac failure Pancreatitis IIBS) Obesity
Fluid Hepatic vein TB Diet le.g. lactose intolerance) Blood
Fatal Growth
thrombosis
ACUTE Generalized! RUQ RLQ LUQ LLQ
... ,,
9"\-------------, ABDOMINAL Periumbilical
PAIN
Acute Upper Abdominal Pain
Gastroenteritis Hepatitis Appendicitis Myocardial IBO
Remember to consider 'sounds
from the attic" (chest) e.g. myocar-
SBO Biliary colic IBD infarction (MI) Diverticulitis
dial infarction, pneumonia, dissect- Colonic obstruction Acute cholecystitis Ureteral stone Pancreatitis Sigmoid volvulus
ing aneurysm.
Mesenteric ischemia PUD Salpingitis Splenic infarction Ureteral stone
Peritonitis Pyelonephritis Ruptured corpus Pyelonephritis Salpingitis
Abdominal aortic aneurysm luteum cyst Ruptured corpus
Sickle cell crisis Ovarian torsion luteum cyst
Perforation Ruptured ectopic Ruptured ectopic
pregnancy pregnancy
CHRONICIRECURRENT
ABDOMINAL PAIN Inflammatory NeoplasticNascular Toxin Other
PUO Gastric cancer Lead poisoning Mittleschmertz
Biliary colic Recurrent bowel obstruction Endometriosis (see ~ GY171
IBO Mesenteric ischemia Porphyria
Chronic pancreatitis Sickle cell anemia ISS (functional)
Radiculopathy
ACUTE DIARRHEA Inflammatory Non-inflammatory
(see Infectious Diseases, Bacterial Bacterial Viral
1016) Shigella Salmonella enteritidis Rotavirus
Salmonella typhi Staphylococcus aureus Norwalk
Campy/obacter B. cereus Cytomegalovirus
Yersinia C. perfringens
E. coli (EHEC 0157:H7) Vibrio cholerae
C. difficile
Protozoal Protozoal Drugs
E. histolytica lamebiasis) Giardia lamblia Antacids
Strongyloides Antibiotics
Laxatives (Magnesium)
Colchicine
Toronto Notes 2008 Differential Diagnosis of Common Presenting ComplaintslEsophagus Gastroenterology G3
Table 1. Differential Diagnosis of Common Presenting Complaints (continued)
CHRONIC DIARRHEA Inflammatory Secretory Steatorrhea Osmotic
(a) ORGANIC
ISO Stimulant laxatives Celiac sprue Drugs/Laxatives
Ischemic Malignancy Giardia Lactose intolerance
Villous adenoma Chronic pancreatitis
Zollinger-Ellison (ZE)
Carcinoid
Addison's disease
VIP secreting tumour of
pancreas
Diabetes mellitus
Cryptosporidiosis
(bl FUNCTIONAL
ISS
Anal sphincter dysfunction
CONSTIPATION GI Systemic PsychlSocial
ISS Electrolytes (K, Cal Drugs
Colon cancer Hypothyroidism Voluntary retention
Anorectal pathology Scleroderma &other CTD Lifestyle/Diet
Mechanical obstruction Neurological diseases D e p r e s s i o ~
(e.g, neoplasm) (e,g. MS, Parkinson'sl Long car tripslTravel
DYSPEPSIA Common Uncommon Rare
Functional dyspepsia Angina Giardia
Drug side effect Crohn's disease Malabsorption (celiac sprue)
Peptic ulcer Cancer
GERD Gallstones
Aerophagia
Esophagus
______________-.1
mucosa: stratified squamous epithelium
submucosa: connective tissue, lymphocytes, plasma cells, nerve cells
muscularis propria: inner circular, outer longitudinal muscle
muscle: upper 1/3 striated muscle, lower 1/3 smooth muscle, separated by transition
zone comprised of both
blood supply:
thoracic part: esophageal arteries and terminal branches of bronchial arteries
abdominal part: left gastic artery, left phrenic artery
venous drainage:
thoracic part: esophageal veins ..... azygous system
abdominal part: left gastric vein ._+ portal system
lymphatic drainage: left gastric lymph nodes
innervation: vagus nerve
physiologic anatomic compressions (three): aortic arch, left main bronchus,
diaphragm
upper esophageal sphincter (DES)
cricopharyngeus + caudal fibers of inferior pharyngeal constrictor muscle
lower esophageal sphincter (LES)
internal muscles: intrinsic muscle of distal esophagus, sling fibers of
proximal stomach
external muscles: crural diaphragm
normal resting pressure = 15-30 mmHg above intragastric pressure
relaxes at onset of swallowing
contraction: cholinergic innervation (via vagus nerve)
relaxation: non-adrenergic, non-cholinergic input via nitric oxide and VIP
peristalsis: rhythmic contractions that propel solid contents onward
neuronal control via brainstem "swallowing center" (cranial nerve nuclei)
primary = induced by swallowing
secondary = induced by esophageal distention (e.g. during reflux)
tertiary = spontaneous (abnormal)
G4 Gastroenterology
,"'
Differential Diagnosis of Dysphagia:
Diffuse esophageal spasm
Intrinsic lesion
Scleroderma
Pharyngeal disorders
Heart (esp. LAE)
Achalasia
Goitre
Infections
American trypanosomiasis
o
Esophagus Toronto Notes 2008
D
Definition
difficulty swallowing, sensation of food "sticking" after swallowing
dysphagia: difficulty swallowing; sensation of food "sticking" after swallowing
I
I I
oropharyngeal (difficulty initiating swallowing esophageallinability to move food down esophagus!
coughing, nasal regurgitation!
I
r----I
neurological muscular structural solid food only solid and liquid food
conical muscular dystrophy Zenker's diveniculum
I I
bulbar polymyositis thyromegaly
peripheral myasthenia gravis cervical spur
mechanical obstruction neuromuscular disorder
cricopharyngeal I I
incoordination I I I I
progressive intermittent intermittent
I
age >50 heanburn lower diffuse
IWI lossl esophageal esophageal
I I
ringlweb spasm IDES!
carcinoma peptic [chest painl
Look for alarming features such as: age, weight loss, dementia history. stricture scleroderma achalasia
Figure 1. Approach to Dysphagia
Odynophagia
Definition
pain on swallowing
causes: usually due to ulceration of esophageal mucosa
infection: candida, herpes, CMV (common only in immunosuppressed patients,
especially AIDS)
inflammation/ulceration (e.g. caustic damage)
drugs: doxycycline, wax-matrix potassium chloride, quinidine, iron, vitamin C,
various antibiotics
radiation
Dyspepsia
Definition
intermittent epigastric discomfort, characteristically develops after eating
most common cause is functional dyspepsia (i.e. dyspepsia in which all
investigations fail to identify an organic cause)
causes: see Table 1
Gastroesophageal Reflux Disease (GERD)
Definition
reflux of gastric contents, especially acid, aborally toward the mouth, rather than
distally into duodenum
Etiology
LES relaxes inappropriately - most common
low basal LES tone (especially in scleroderma)
delayed esophageal clearance, delayed gastric emptying, increased intra-abdominal
pressure - contributing factors
acid hypersecretion (rare) - Zollinger-Ellison syndrome (gastrin secretory tumour)
hiatus hernia worsens reflux, does not cause it (see General Surgery, GSlO)
Epidemiology
most common condition affecting the esophagus
Toronto Notes 2008 Esophagus Gastroenterology G5
Clinical Features
most common symptom is heartburn (pyosis 80% sensitive and specific for reflux)
bitter regurgitation, water brash
feels as if there is too much acid, but the problem is that acid is in the wrong place
GERD signs/symptoms
I
non-esophageal
esophagaal
I I
I I I
respiratory non-respiratory
~
atypical
chronic cough sore throat heartburn chest pain
wheezing hoarseness acid regurgitation dysphagia lIatel
aspiration pneumonia dental erosions odynophagia (rare)
Figure 2. Signs and Symptoms of GERD
Investigations
usually a clinical diagnosis based on symptom history and relief following a
trial of pharmacotherapy (PP1: symptom relief 80% sensitive for reflux)
24-hour pH monitoring most accurate test but rarely used
gastroscopy: detects esophagitis but negative in non-esophagitis reflux disease
indicated if: chronic symptoms, age >50, to diagnose Barrett's esophagus
esophageal manometry may be done to diagnose abnormal peristalsis and/or
decreased LES tone, but cannot detect presence of reflux; must be done before surgery
add perfusion (Bernstein) test: attempt to reproduce symptoms; determines if reflux
causes symptoms
positive test when esophagus perfused with 0.1 normal HCl; no symptoms
if perfused with isotonic saline
barium swallow: to assess presence of strictures 'I-
Management
step-down approach: start with proton pump inhibitors (most effective therapy)
step-up approach: start with diet (more helpful in relieving symptoms), lifestyle
changes (elevate head of bed at night, tilt entire body)
main approach is three-phase management involving a combination of lifestyle
modification (Phase I), pharmacotherapy with H
2
blockers and proton pump
inhibitors (PP1s; Phase II), and maintenance therapy or surgery for refractory cases
(Phase III)
evidence based approach: proton pump inhibitors are most effective therapy,
usually need to be continued as maintenance therapy
Complications
reflux esophagitis: esophageal inflammation from prolonged acid regurgitation;
can progress to esophageal peptic stricture, bleeding
muscle spasm (DES) and/or stricture (scarring)
risk of Barrett's esophagus (columnar metaplasia) and esophageal adenocarcinoma
(0.4% risk per year), mandates surveillance gastroscopy
E s o ~ h a _ea. Motor Disorders
Symptoms
dysphagia with solids and liquids
chest pain
Diagnosis
esophageal motility study esophageal manometry
Causes (Table 2)
achalasia
diffuse esophageal spasm (DES)
scleroderma
idiopathic
Gastroesophagaal Raflux Disaasa IGERD)
gastroscopy
/ ~
non-erosive reflux disease esophagitis:
(NERD): aim to heal
aim for symptom relief only; inflammation;
proton pump inhibitor proton pump
PRN inhibitor indefinitely
or surgical
fundoplication
.... ' ,
1"
Esophageal damage from reflux
most severe at first gastroscopy;
therefore. necessary only once in a
lifetime.
o
G6 Gastroenterology Esophagus Toronto Notes 2008
o
Table 2. Esophageal Motor Disorders
Disorder Achalasia Scleroderma Diffuse Esophageal Spasm
Definition failure of smooth muscle see Rheumatology RH 11 normal peristalsis interspersed
relaxation at lower disease of collagen with frequent, repetitive,
esophageal sphincter spontaneous, high pressure,
ILES) non-peristaltic waves Itertiary
peristalsis)
Etiology usually idiopathic dysphagia: can be due to unknown
incomplete relaxation of reflux or dysmotility
LES with swallowing
high LES resting pressure
2to cancer
Chagas disease (I cruzi)
Pathophysiology' unknown (1' impaired blood vessel damage --> unknown
inhibition related to -.It NO intramural neuronal dysfunction -->
release) distal esophageal muscle
weakening --> aperistalsis and loss
of LES tone reflux --> stricture
--> dysphagia
Diagnosis chest x-ray: no air in -.ltpressure in LES barium x-ray: "Corkscrew pattern';
stomach, with dilated -.ltperistalsis in body of esophagus tertiary waves
esophagus
barium studies: esophagus
terminates in narrowing at
the sphincter, giving a
"bird's beak" appearance
endoscopy to rio malignancy
motility study for definitive diagnosis
Treatment dilatation of LES with balloon, medical: aggressive GERD reassurance
GERD prophylaxis, 50% therapy (proton pump medical: nitrates, calcium
good response, can repeat, inhibitors bid) channel blockers, anticholinergics
risk of perforation (5%) surgery: antireflux surgery have minimal benefit
injection of botulinum toxin (gastroplasty, last resort) surgical: lower esophageal
into LES (temporary) myomotomy if unresponsive
surgery (myomectomy) to above treatment
(rarely helpful); balloon dilatation
______________---J eal Structural Disorders
Diverticula
Definition
outpouchings of one or more layers of pharyngeal or esophageal wall
Clinical Features
commonly associated with motility disorders
dysphagia, regurgitation, retrostemal pain, intermittent vomiting, may be
asymptomatic
Classification
pulsion type: associated with high intraluminal pressures or mural muscular defect
traction type: esophageal wall pulled outward by inflamed peribronchial mediastinal
lymph nodes (not clinically significant)
classified according to location
pharyngoesophageal (Zenker's) diverticulum
most frequent form of esophageal diverticulum
posterior pharyngeal outpouching most often on the left side, above
cricopharyngeal muscle and below the inferior pharyngeal constrictor muscle
symptoms: dysphagia, regurgitation of undigested food, halitosis
treatment: myotomy of cricopharyngeal muscle excise or suspend sac
Toronto Notes 2008 Esophagus Gastroenterology G7
mid-esophageal diverticulum
secondary to mediastinal inflammation (traction type), motor disorders, or
endoscopic myotomy
usually asymptomatic: no treatment required
epiphrenic diverticulum
rare condition
distaJ esophagus, large, associated with motility disturbances (pulsion type)
symptoms: asymptomatic, dysphagia, regurgitation, angina-like chest pain
Benign Stricture
presents as progressive dysphagia in face of reflux symptoms
diagnose with barium study or endoscopy
Treatment
endoscopic dilatation and indefinite proton pump inhibitor
anti-reflux surgery if above unsuccessful
Esophageal Cancer ~ _ . ~ ~ -"u .....
(see General Surgery. GSll)
Webs and Rings
web = partiaJ occlusion (upper esophagus)
ring = circumferential narrowing (lower esophagus)
Clinical Features
asymptomatic with lumen diameter>12 mm
dysphagia with large food boluses
Plummer-Vinson or Patterson-Kelly syndrome
upper esophageal web with iron deficiency, plus cheilosis (dry scaling, and
fissuring of the lips) and koilonychia (concave outer nail surface)
usually in middle aged females (>40 years)
elevated risk of hypopharyngeal carcinoma
Schatzki ring
mucosal ring at squama-columnar junction above a hiatus hernia
causes intermittent dysphagia for solids
treatment involves shattering ring with bougie
Barrett's Esophagus
Definition
metaplasia of normal squamous epithelium to columnar epithelium
Etiology
usually acquired (long standing GERD)
Pathophysiology
endoscopy shows erythematous epithelium in distal esophagus
Significance
increased incidence of esophageal adenocarcinoma (1 in 250 patient years)
Treatment
proton pump inhibitor indefinitely
aggressive anti-reflux regimen
endoscopic surveillance every 3 years for dysplasia/cancer
G8 Gastroenterology Esophagus/Stomach and Duodenum Toronto Notes 2008
Infectious
Definition
severe mucosal inflammation and ulceration as a result of viral or fungal infection
Risk Factors
diabetes
malignancy (chemotherapeutic agents)
immunocompromised states
Symptoms
odynophagia, dysphagia
diagnosis is via endoscopic visualization and biopsy
Treatment
Candida (most common): nystatin swish and swallow, ketoconazole, fluconazole
Herpes (second most common): often self-limiting; acyclovir/vancyclovir/famciclovir
CMV: IV gancyclovir, famciclovir
Stomach and Duodenum
Stomach
chief function is enzymatic digestion of ingested material into chyme, and
propulsion of chyme into duodenum; see Table 3 and Figure 3 for a summary of
the gastric cell types and their products
consists of four parts:
cardia: adjacent to gastroesophageal junction
fundus: dilated superior part, related to the left diaphragm
body: lies between fundus and pylorus
pylorus: funnel-shaped, pyloric antrum leads to pyloric canal; distal part is
thickened to form the pyloric sphincter which controls discharge of stomach
contents into the duodenum
blood supply: arise from the celiac trunk and its branches - left gastric artery, right
gastric artery (branch of hepatic artery), right gastroepiploic artery (terminal
branch of gastroduodenal artery), left gastroepiploic artery (branch of splenic
artery), and short gastric arteries (branches of splenic artery)
venous drainage: gastric veins drain directly into portal vein, short gastric arteries
drain into the splenic vein which then joins the portal vein
lymphatics: drainage via gastric and gastroepiploic lymph nodes ---+ celiac nodes
innervation: parasympathetic innervation via vagus nerve; sympathetic supply via
celiac plexus (from T6-T9)
Duodenum
first part of small intestine
neutralize acidic components entering from stomach via secretin and bicarbonate
secretion
stimulation of bile secretion
blood supply: branches of celiac and superior mesenteric artery (SMA)
divided into 4 parts
Table 3. Cells of the Gastric Mucosa
Cell Type Secretory Product Important Notes
Parietal Cells Gastric acid (HCIl Stimulated by histamine, ACh, gastrin
Chief Cells Pepsinogen Stimulated by vagal input and local acid
G-cells Gastrin Stimulates H' production from parietal cells
Superficial Epithelial Cells Mucus, HC0
3
Protect gastric mucosa
Toronto Notes 2008 Stomach and Duodenum Gastroenterology G9
Gastric Interstitial
lumen fluid
cr
Figure 3. Stimulation of H+ secretion from the parietal cell
Gastritis
Definition
inflammation of the stomach; diagnosed by histology
Etiology
most common causes:
Helicobacter pylori infection
chronic NSAID use, ethanol use
physiological stress-related mucosal changes
other causes of gastritis (atrophic, lymphocytic, eosinophilic)
other infectious causes: TB, syphilis, CMV, fungal and parasitic infections
systemic diseases: e.g. sarcoidosis, Crohn's disease
Clinical Features
erosive: bleeding
non-erosive: asymptomatic (may rarely present with upper GI symptoms)
Table 4. Gastritis
Acute Chronic
Self-limited syndrome caused by irritation of Diagnosed via gastric biopsy: characterized by
gastric mucosa by alcohol, corrosives, food mononuclear and polymorphonuclear (PMN) cell
poisoning, etc. infiltration of mucosa, glandular atrophy and
intestinal metaplasia (occasionally)
Examples:
Chronic Fundal Gastritis
(etiology is pernicious anemia)
Chronic Antral Gastritis (etiology is H. pylon)
Peptic Ulcer Disease (PUD)
- _ - - : ; . . . . - - . ; ; . . . . - - - ~ - - - - - - -
Definition
erosion (superficial to the muscularis mucosa, thus no scarring) or ulcer (penetrates
the muscularis mucosa and can result in scarring)
Etiology
Table 5. Etiology of Peptic Ulcer Disease
Duodenal Gastric
H. pylori infection 90% 60%
NSAIDs 7% 35%
Physiologic stress-induced <3% <5%
Zollinger-Ellison (ZE) syndrome <1% <1%
NSAID negative, H. pylori negative ulcers becoming more commonly recognized
others: CMV, ischemic, idiopathic, diet (exact role not understood)
alcohol: damages gastric mucosa but only rarely causes ulcers
associated with cirrhosis of liver, COPD
o
~
o
.... ,,
9)-------------,
Gastric VB. Duodenal Uicen
Gastric ulcers must always be
biopsied to rule out malignan-
cies. Duodenal ulcers are rarely
malignant.
G10 Gastroenterology Stomach and Duodenum Toronto Notes 2008
Omeprazole and Mi,oproltol in NSAID-
Induced UlcerTreatment: OMNIUM
(NEJM 1998;338(11):727-34)
Study. Multicentre, randomized, double-
blinded study with 6months of follow-up,
Patients. 935 patients on NSAIDs who devel-
oped erosions or ulcers of the stomach or
duodenum and required continuing NSAID
therapy,
Infe/VIIRlion: 20 or 40 mg of omeprazole
daily, versus 200 of misoprostol four
times aday, Afollow-up study assessed
maintenance therapy with either omeprazole,
misoprostol, or placebo,
Main out_Treatment success defined
as: absence of ulcers, fewer than 5erosions,
and only mild dyspepsia,
RaultJ: 75% of patients in the misoprostol
groups and 71% of patients on omeprazole
remained in remission, While 48% of patients
on misoprostol did significantly beller than
the placebo group 127% in remission,
p<O.001), more adverse events were present
in the misoprostol group (59% versus 47% in
the omeprazole group.)
Conc/u.lon: Omeprazole and misoprostol
are equally effective in treating NSAID-
induced ulceration, with omeprazole superior
to misoprostol for maintenance. Omeprazole
is also better tolerated than misoprostol.
.... ' ,
.'"\-----------,
Approac:h to PUD
1. Stop NSAIOs
2. Acid neutralization
3. H. pylori eradication
4. Quit smoking
.... ' ,
.\-----------,
Risk Factors
Cigarette Smoking
'1' risk of ulcer
'1' risk of complications
''I' chance of death from ulcer
impairs healing rate
Clinical Features
dyspepsia is the most common presenting symptom; however, only 20% of patients
with dyspepsia have ulcers (see Table 1 for causes of dyspepsia)
may present with complications
bleeding 10% (severe if from gastroduodenal artery)
perforation 2% (usually anterior ulcers)
gastric outlet obstruction 2%
penetration (posterior) 2%; may also cause pancreatitis
duodenal ulcers present with 5 classical features:
epigastric location
pain described as burning that develops 1-3 hours after meals
relieved by eating and antacids
interrupts sleep
periodicity (tends to occur in clusters over weeks with subsequent
periods of remission)
gastric ulcers have more atypical symptoms; a biopsy is necessary to exclude
malignancy
Investigations
endoscopy (most accurate)
upper GI series
H. pylori tests (Table 6)
serum gastrin measurement if Zollinger-Ellison (ZE) syndrome suspected
Treatment
specific management depends on etiology; refer to H. pylori, NSAID and Stress
Induced Ulceration, GlO-G12
eradicate Helicobacter pylori if present, chief advantage is to lower ulcer
recurrence rate
stop NSAIDs if possible
proton pump inhibitor irreversibly inhibits parietal cell H+-K+ATPase pump
which secretes acid, heals most ulcers, even if NSAIDs are continued
other meds (e.g. histamine H2 antagonists) less effective
discontinue tobacco
no diet modifications required but logical to avoid foods which promote symptoms
H. Ulceration
------------------_---1
Pathophysiology
H. pylori is a gram-negative flagellated rod that resides on but does not invade the
gastric mucosa
acid secreted by parietal cell (stimulated by vagal acetylcholine, gastrin, histamine)
necessary for most ulcers
mucosal defenses moderated by PGF
2
and blood flow, mucus, etc.
theories of how H. pylori causes ulcers
toxin production: causes gastric mucosal inflammation and necrosis
interference with acid regulation: H. pylori blocks gastrin G cells in antrum
from sensing luminal acid -> increase serum gastrin -> increase gastric
acid -> ulcer
Epidemiology
H. pylori is found in 20-40% of all Canadians, highest prevalence in the generation
that grew up during the Depression
infection most commonly acquired in childhood, presumably by fecal-oral route
high prevalence in develuping countries, low socioeconomic status (poor sanitation
and crowding)
Symptoms
non-erosive gastritis in 100% of patients but this does not cause symptoms
peptic ulcer in 15% of patients, gastric malignancy (cancer and mucosal associated
lymphomatous tissue lymphoma = MALT lymphoma in 0.5% of patients)
most are asymptomatic but still worthwhile eradicating to a) lower future risk of
peptic ulcer/gastric malignancy and b) prevent spread to others (mostly children
<5 years of age)
Toronto Notes 2008 Stomach and Duodenum Gastroenterology Gll
Investigations
Table 6. Diagnosis of H. pylor; infection
Test Sensitivity Specificity Comments
Non-invasiveTests
Urea breath test 90-100% 89-100%
Serology 88-99% 89-95% Remains positive
InvasiveTests (require endoscopy)
Histology 93-99% 95-99% Gold standard
Rapid urease test (on biopsy) 89-98% 93-100% Rapid
Microbiology culture 98% 95-100% Research only
Treatment Eradication
H. pylori eradication (Canadian Consensus Guidelines, September 2004)
eradication upon documentation of H. pylori infection controversial since most
patients will not have peptic ulcer or cancer
however, empiric treatment suitable for patients <50 years old with mild
symptoms and no red flags
1st line triple therapy (Hp-packTM); >90% success rate
- (PPI + clarithromycin 500 mg + amoxidllin 1000 mg bid)
x 7-14 days
- (PPI + clarithromycin + metronidazole 500 mg) x 7-14 days
- ranitidine, bismoth-citrate + clarithromycin + amoxidllin
2nd line quadruple therapy
- PPI + BMT (bismuth + metronidazole + tetracycline) x 7 days
- lansoprazole 500 mg bid + amoxicillin 1 g bid + PPI bid
NSAID-Induced Ulceration
NSAIDs cause gastric mucosal petechiae in virtually all users, erosions in most users,
ulcers in some (25%) users; only ulcers cause significant clinical problems
most NSAID ulcers are clinically silent: dyspepsia is as common in patients with ulcers
as patients without ulcers
gastric ulcers more common than duodenal ulcers
may exacerbate underlying duodenal ulcer disease
Pathophysiology
direct: petechiae and erosions are due to local effect of drug on gastric mucosa;
drug is non-ionized (HA) in acidic gastric lumen, therefore enters gastric epithelial cell
where it becomes ionized (A-) at intracellular neutral pH, and damages cell
indirect: systemic NSAID effect (i.e NSAID absorbed in upper small bowel, reaches
gastric epithelial cells by arterial circulation); NSAIDs inhibit mucosal cyclooxygenase,
the rate-limiting step in the synthesis of prostaglandins, which are required for
mucosal integrity, leading to ulcers
Risk Factors
age
previous peptic ulcers/UGIB
high dose of NSAID/multiple NSAIDs being taken
concomitant corticosteroid use
concomitant cardiovascular disease/other Significant diseases
Treatment
lower NSAID dose, or stop all together
combine NSAID with PPI, or misoprostol
ECASA of little benefit (does not affect indirect effects)
Stress-Induced Ulceration
Definition
ulceration or erosion in the upper GI tract of ill patients, usually in ICU; lesions most
commonly in fundus of stomach
Pathophysiology
unclear: likely involves ischemia; may occur with CNS disease, acid hypersecretion
physiological stress causes ulcers and erosions
there is weak evidence linking psychological factors to ulcers
.... ' ,
,}--------------,
Helfcobllcte, pylori Manegement
AJM 1998; 105:424,
For patients with PUD and H, pylori
infection, treatment with aPPI, clar-
ithromycin 500 mg bid, and amoxicillin
19 bid x 14 days has approximately
90% success rate,
.... ' ,
,,}------------,
If at high risk for recurrence of
ulcers, lifelong prophylaxis with
PPI may be required,
G12 Gastroenterology Stomach and Duodenum/Small and Large Bowel Toronto Notes 2008
Risk Factors
mechanical ventilation
anti-coagulation
multiorgan failure
septicemia
severe surgery/trauma
CNS injury ("Cushing's ulcers")
bums involving more than 35% of body surface
Clinical Features
UGm (see Upper Gastrointf'stinal Bleeding, G26)
Treatment
prophylaxis with gastric add suppressants (PPI) decreases risk of UGm, but may
increase risk of pneumonia
treatment same as for bleeding peptic ulcer but often less successful
Zollinger-Ellison (ZE) Syndrome
~ - - - - - - - - - - - - - '
Definition
rare 1%) triad of gastric acid hypersecretion, severe ulcer disease, and gastrinoma
(gastrinoma: gastrin secreting tumour; most common in pancreas but 10-15%
occur in duodenum)
Clinical Features
"'. Recall MEN I (3 P',):
strong family history of ZE or multiple endocrine neoplasia (MEN-I)
1. Pancreas (ZE, insulinoma,
(1/3 of patients with ZE syndrome have MEN-I)
VIPoma)
unusually severe symptoms of POO
2. Pituitary
diarrhea and malabsorption
3. Parathyroid
multiple ulcers in unusual sites
refractory to treatment
Investigations
high gastric acid secretion + high serum gastrin level + positive "secretin" test
Treatment
high dose PPI
Small and Large Bowel
~ - - ~ - - ~ - - ~ - - - - - - - '
small bowel: jejunum, ileum
Table 7. Anatomical features of the Jejunum, Ileum, and Large bowel
Blood Supply Structural Features Functions
Jejunum SMA plicae circulares (circular folds absorption of food, salt, water
on the interior surface), which and nutrients (protein, CHO, fat,
have villi for absorption folic acid, Vit B, C, and Vit A,D,E,Kl
Ileum SMA plicae circulares absorption of water and water
soluble vitamins (incl. Vit B12)
absorption of bile
Large bowel branches of SMA starts at cecum, ends at rectum absorption of water (5-10% of total
and IMA tenia coli haustra water)
bacteria: further digestion of chyme,
and metabolization of undigested
CHO to short chain fatty acids
(SCFA); formation and storage of
feces
Toronto Notes 2008 Small and Large Bowel Gastroenterology G13
Classification of Diarrhea
Secretory (stool osmolality due entirely to Na, K and their accompanying
anions; diarrhea does not resolve with fasting but it can decrease)
bacterial toxins - cholera toxin, clostridial endotoxin
~ .
non-invasive gastroenteritis
bile salt malabsorption Think of Diarrhea in terms of:
neuroendocrine tumours - carcinoid syndrome (serotonin), pancreatic cholera
Secretory
syndrome (VIP), ZE syndrome (gastrin), thyroid cancer (calcitonin)
Osmatic
villous adenoma
Inflammatory
laxative abuse
Malabsorption
Addison's disease
Altered motility
Infectious
congenital electrolyte absorption defects
Osmotic (1'osmotic gap, resolves with fasting, watery stool, no blood or pus)
poorly absorbed carbohydrates in diet e.g. sorbitol or drugs (mannitol, lactulose)
pancreatic insufficiency
lactase deficiency
malabsorption - celiac sprue
Inflammatory (small infrequent stools with blood or pus)
ffiD - ulcerative colitis, Crohn's disease
ischemic colitis
radiation-induced enteritis
invasive gastroenteritis
Steatorrheal Causes (..v stool volume with fasting, l' fecal fat)
intraluminal maldigestion - pancreatic insufficiency, bacterial overgrowth, liver
disease
mucosal malabsorption - celiac sprue, Whipple's disease, infections
postrnucosal obstruction (primary or secondary lymphatic obstruction)
Altered Motility (variable presentation, related to malabsorption)
thyrotoxicosis
Irritable Bowel Syndrome
neurologic disease (DM associated enteropathy)
.-:... --1
Acute Diarrhea
0-,.[
o
Definition
passage of frequent unformed stools (>200 g of stoo1/24 hours) of <14 days duration
Etiology
most commonly due to infections, many as yet undetectable pathogens
most infections are self-limiting and resolve in less than 2 weeks
Risk Factors
food (sea food)
medications: antibiotics, laxatives
ThOle FacII Wilt
others
Travel
high risk sexual activity/homosexual contact
Homosexual contacts
outbreaks
Outbreaks

family history (inflammatory bowel disease) Seafood

diet (poor, changes) Extra-intestinal signs of IBD
immunosuppression Family history
weight loss Antibiotics

malignancy
Diet

Steatorrhea
Weight loss
Classification
Immunosuppressed
broadly.divided and classified into inflammatory and non-inflammatory diarrhea
Laxatives
mecharusms
Tumour history
in both, the diarrhea is due to mplecules stimulating intestinal water secretion/
inhibiting water absorption (i.e. secretory problem)
in inflammatory diarrhea, organisms and cytotoxins invade mucosa, killing
mucosal cells, further perpetuating the diarrhea
G14 Gastroenterology
~ .
Inf8ctioul EtloIogy of Inflammatory
Diarrhea - Think "EE-CYSTS"
E. coli (EHEC 0157:H7)
E. histolytica
Campylobacter/C. difficile
Yersinia
Shigella
Salmonella typhi
Strongyloides
Must rule out infection in all
patients with diarrhea.
",' ,
. ~ - - - - - - - - - . . . ,
Stool 0Im0tic Gep
Normally, and in secrel01Y diarrhea, stool
osmolality (as measured by freezing
point depression; almost always about
290 mOsmlkg) is same IS calculated
stool osmolality (2 xstool (Na +K)) (mul
tiplied by 2to account for anions). In
osmotic diarrhea, measured stool osmo
Iality
Small and Large Bowel Toronto Notes 2008
Table 8. Classification of Acute Diarrhea
Inflammatory Non-Inflammatory
Definition Disruption 01 intestinal mucosa No disruption of intestinal mucosa
Site Usually colon Usually small intestine
Sigmoidoscopy Usually abnormal mucosa seen Usually normal
Symptoms Bloody Inot always) Watery, little or no blood
Small volume, high frequency Large volume
Often lower abdominal cramping Upper/periumbilical pain/cramp
with urgency tenesmus
May have fever shock
Investigations Fecal WBC and RBC positive Fecal WBC negative
Etiology Infectious Infectious
- Bacterial - Bacterial
Shigella Salmonella enteritidis
Salmonella typhi S. aureus
Campy/obaeter B. cereus
Yersinia C. perfringens
E. coli (EHEC 0157:H7) E. eo/i (ETEC, EPECI
C. diffieile Vibrio molerae
- Protozoal - Protozoal
E. histo/ytiea (amebiasis) - Giardia /amblia
Strongyloides -Viral
Rotavirus
Norwalk
CMV
Drugs
Antacids (Mg: Makes you Go)
Antibiotics
Laxatives, lactulose
Colchicine
Differential diagnosis Mesenteric ischemia Chronic diarrheal illness IIBS, dietary intolerance)
Radiation colitis
Chronic diarrheal illness IIBD, celiac)
Significance Higher yield with stool C&S Lower yield with stool C&S
Can progress to life-threatening Chief life-threatening problem is fluid depletion and
megacolon, perforation, hemorrhage electrolyte disturbances
Investigations
stool cultures/microscopy (C&S/O&P) are not cost-effective in acute diarrhea unless
inflammation (fecal WBC) present
diagnostic tests
stool WBC: stool smeared on slide and methylene blue drops added
postive test: >3 PMNs in 4 high power fields (HPFs)
usually positive for infectious but also IBD and radiation
culture: routinely onJy for Campylabaeter, Salmonella, Shigella, E. Coli
if you want others, order them specifically
ova and parasites (O&P): may need more than one sample because of sporadic
passage, but higher yield in first specimen
flexibfe sigmoidoscopy: useful if inflammatory diarrhea suspected
biopsies useful to distinguish idiopathic inflammatory bowel disease (Crohn's
disease and ulcerative colitis) from infectious colitis or acute self-limited colitis
C. difficile toxin: indicated when recent/remote antibiotic use, hospitalization, nursing
home or recent chemotherapy
Treatment
fluid and electrolyte replacement: note that, except in extremes of age and coma, it is
electrolyte repletion wfuch is most important, as patient will drink
antimotility agents: diphenoxylate, loperarnide (ImodiumTM); contraindicated in
mucosal inflanunation
side effects: abdominal cramps, toxic megacolon
absorbants: kaolin/pectin (Kaopectate), methylcellulose, activated attapulgite
act by absorbing intestinal toxins/micro-organisms, or by coating/protecting
intestinal mucosa
much less effective than antirnotility agents
modifiers of fluid transport: may be helpful, oismuth subsalicylate (Pepto-BismoI)
antibiotics: rarely indicated
risks
prolonged excretion of enteric pathogen
drug side effects (including C. difficile infection)
develop resistant strains
Toronto Notes 2008 Small and Large Bowel
indications for antimicrobial agents in acute diarrhea
septicemia
prolonged fever with fecal blood or leukocytes
clearly indicated: Shigella, Cholera, C. difficile, Traveller's Diarrhea
(Enterotoxigenic E. coli (ETEC)), Giardia, Entamoeba histolytica,
Cydospora
indicated in some situations: Salmonella, Campylobacter, Yersinia,
non-enterotoxigenic E. coli
Salmonella: always treat Salmonella typhi (typhoid or enteric fever);
treat other Salmonella only if there is underlying
immunodeficiency, hemolytic anemia, extremes of age, aneurysms,
prosthetic valve grafts/joints
Traveller's Diarrhea
Definition
3 unformed stools in 24 hours nausea, vomiting, abdominal pain, tenesmus,
blood/mucus in stool
Etiology
up to 50% of travellers to developing countries affected in first 2 weeks and 10-20%
after retuming home
80% bacterial, E. coli most common
ETEC, other E. coli, Campylobacter, Shigella, Salmonella, Vibrio
(non-cholera)
viral: Norwalk and Rotavirus account for about 10%
rarely protozoal (giardiasis, amebiasis)
Treatment
usually self-limited, 90% last less than 1 week; antibiotics shorten duration
can use bismuth subsalicylate (Pepto-Bismol), empiric quinolone such as
ciprofloxacin, TMP/SMX, or rifaximin for either treatment or prophylaxis
(although not useful for invasive bacteria)
if diarrhea persists after returning horne, think of Giardia, Entamoeba histolytica,
post-infectious IBS
Chronic Diarrhea
Definition
passage of frequent unformed stools (>200 mL of stool water/24 hours) for> 14 days
duration
differential is similar to that of acute diarrhea, except the majority of cases are
non-infectious
Investigations
fecal fat, fecal leukocytes, C&S, O&P
stool osmotic gap = OSM
stool
(usually 290) - [2 x (Na
s
ool
+ 1<,;'001)]
Etiology/Classification
see Classification of Diarrhea section, G14
Investigations
stool analysis for
WBC
sudan stain
O&P
blood for
CBC
chemistry
C-reactive protein
TSH
sigmoidoscopy with biopsy
small bowel biopsy
wireless small bowel endoscopy capsule
trial of lactose free diet
Gastroenterology GIS
",,' ~
~ . ) - - - - - - - - - - - ,
s. typhi has arose spot rash (transient
macolopapular rash on anterior thorax,
upper abdomen).
G16 Gastroenterology Small and Large Bowel Toronto Notes 2008
Maldigestion and Malabsorption
-'''-----------.....
maldigestion: inability to break down large molecules in the lumen of the intestine into
their component small molecules
malabsorption: inability to transport molecules across the intestinal mucosa to the
body fluids
malassimilation: encompasses both maldigestion and malabsorption
chief complaint abnormal
(weight loss, change in bowel habits) blood tests

consider 72-hour fecal
fat collection

ethanol abuse diarrhea
abdominal pain flatulence
t t
plain view ot suspect pancreatic suspect small ----.. duodenal
abdomen disease bowel disease biopsy

pancreati( normal abnormal
calcifications t

ERCP or MRCP bile acid +hydrogen treat
breath test (looking for
bacterial overgrowth)
I \
normal abnormal
/
t
normal
pancreatic /
insufficiency
small bowJvisualization
(Looking for Crohn's disease, lymphoma, etc.)
Figure 4. Approach to Malabsorption
Etiology
maldigestion
inadequate mixing of food with enzymes (e.g. post-gastrectomy)
pancreatic exocrine deficiency
primary diseases of the pancreas (e.g. cystic fibrosis, pancreatitis)
bile salt deficiency
terminal ileal disease (impaired recycling), bacterial overgrowth
(deconjugation of bile salts), rarely liver disease (cholestatic)
specific enzyme deficiencies
e.g. lactase
malabsorption
inadequate absorptive surface (e.g. bowel resection, extensive Crohn's disease)
specific mucosal cell defects (e.g. abetalipoproteinemia)
diffuse disease
immunologic or allergic injury (e.g. celiac disease)
infections/infestations (e.g. Whipple's disease, giardiasis)
infiltration (e.g. lymphoma, amyloidosis)
fibrosis (e.g. systemic sclerosis, radiation enteritis)
drug-induced
cholestyramine, ethanol, neomycin, tetracycline and other antibiotics
endocrine
e.g. diabetes
Clinical Features
symptoms usually vague unless disease is severe
weight loss, diarrhea, steatorrhea, weakness, fatigue
manifestations of malabsorption/deficiency (Table 9)
Table 9. Absorption of nutrients and fat soluble vitamins
Deficiency
Iron
Calcium
Folic acid
Vitamin 8'2
Carbohydrate
Protein
Fat
Vitamin A
Vitamin 0
Vitamin E
Vitamin K
Absorption
duodenum, upper jejunum
duodenum, upper jejunum
(binds to Ca binding-protein
in cells; levels l' by Vit D)
jejunum
see Figure 5
complex polysaccharides
hydrolyzed to oligosaccharides
and disaccharides by salivary
and pancreatic enzymes
monosaccharides absorbed in
duodenUm/jejunum
digestion at stomach, brush
border, and inside cell
absorption occurs primarily
in the jejunum
Signs and Symptoms
hypochromic, microcytic
anemia, glossitis, koilonychia
(spoon nails), pica
metabolic bone disease,
may get tetany and paresthe-
sias if serum calcium falls
(see Endocrinology, E39)
megaloblastic anemia, glossitis
~ red cell folate
(but may see l' folic acid
with bacterial overgrowth)
subacute combined
degeneration of the spinal
cord, peripheral/optic
neuropathy, dementia, mega-
loblastic anemia, glossitis
generalized malnutrition,
weight loss, flatus and
diarrhea
general malnutrition and
weight loss
amenorrhea and ~ libido if
severe
lipase, colipase, phospholipase A generalized malnutrition,
(pancreatic enzymes) and bile weight loss, and diarrhea
salts needed for digestion
products of lipolysis form
micelles which solubilize fat
and aid in absorption
fatty acids diffuse into cell
cytoplasm
from plants
skin (via UV light)
or diet
from food
synthesized by intestinal flora
l' risk of deficiency after
prolonged use of broad
spectrum antibiotics
foul smelling feces
night blindness
dry skin
keratomalacia
osteomalacia in adults
rickets in children
retinopathy, neurological
problems
prolonged INR causes bleeding
Investigations
~ Hb, ~ serum Fe, ~ serum ferritin
~ serum calcium, serum magnesium,
and ALP
evaluate for ~ bone mineralization
radiographically (DEXA)
.j, serum folic acid
differentiate causes by Schilling test
(see Figure 6)
D-xylose test
hydrogen breath test
trial of CHO-restricted diet
.j, serum albumin (low sensitivity)
quantitative stool fat test (72 hr)
sudan stain of stool
C-triolein breath test
Small bowel biopsy
MRCp, ERCP, pancreatic function tests
..... ,,
.l-----------,
Fat Soluble Vitamins: ADEK
..... ' ,
.l------------,
Vitamin Kdependent coagulation
factors: II, VII, IX, X, protein C, protein S
GI8 Gastroenterology Small and Large Bowel Toronto Notes 2008
Salivary
Gland
sJ

p\ancreas
G)
8'2 ingested and bound to R
proteins mainly from salivary
glands
I

f::\ Stomach secretes Intrinsic
o Factor (IF) in acidic medium
o
In basic medium,
proteases from the pancreas
cleave R protein, and 8'2 - IF
lIeunn
complex forms, protecting
8'2 from further protease
attack
8'2 absorbed in ileum and
binds to transcobalamin (Te)
Figure 5. 8'2 Absorption
Investigations (in malassimilation syndromes)
72 hour stool collection (weight, fat content)
stool fat globules on fecal smear, low serum carotene, folate, Ca, Mg, vitamin BlOt
albumin, ferritin, serum iron solution, elevated INR/PTf
other tests specific for etiology
radiolabeled B12 PO +
unlabeled B121M to replenish stores (Stage I)
,
measure 24 hour urine excretion of labeled B12
normal ...... r---------- decreased
intfficient dietary intake radio!beled B12 +
achlorhydria (gastric acid required to liberate intrinsic factor (IF) (Stage III
vitamin B12 from food)
falsely low serum B'2(normal tissue levels; measure
serum homocysteine, methyl malonic acid}
normal ........ measure 24 hour urine excretion of labeled B12

normalizes with antibiotics p!creatic enzymes does not normalize

(Stage III) (Stage IV) I
pernicious anemia b ' , I h actena overgrow! .. ffi' pancreatic Insu IClency 'I It Iea ulsease
Figure 6. Schilling Test
Treatment (of malassimilation syndromes)
dependent on underlying etiology
Celiac Disease (Gluten EnteropathYlSprue)
Definition
abnonnal small intestine mucosa due to intestinal reaction to a-gliadin antigen in
gluten
Etiology
associated with other autoimmune diseases
gluten, a protein in cereal grains, is toxic factor
HLA-DQ2 (chromosome 6) found in 80-90% of patients compared with 20% in general
population; also associated with HLA-DQ8
Epidemiology
more common in women
family history: 15% of first-degree relatives
may present any time from infancy (when cereals introduced), to elderly
peak presentation in infancy and old age
Clinical Features
classically: diarrhea, weight loss, anemia, symptoms of vitamin/mineral deficiency,
failure to thrive; now more commonly bloating, gas, iron deficiency
improves with gluten-free diet, deteriorates when gluten reintroduced
disease is usually most severe in proximal bowel; therefore iron, calcium, and folic acid
deficiency common
gluten enteropathy may be associated with dennatitis herpetiformis skin eruption,
epilepsy, myopathy, depression, paranoia, infertility, bone fractures/metabolic bone
disease
Investigations
small bowel mucosal biopsy (usually duodenum) is usually diagnostic, abnonnalities
seen include:
villous atrophy and crypt hyperplasia
increase number of plasma cells and lymphocytes in lamina propria
similar pathology in: small bowel overgrowth, Crohn's, lymphoma, Giardia
small bowel follow through to exclude lymphoma
evidence of malabsorption (localized or generalized)
steatorrhea
low levels of ferritin/iron saturation, Ca, Fe, albumin, cholesterol, carotene, 8
12
absorption
improvement with a gluten-free diet
serological tests
anti-endomysial antibody (EMA) or ELISA for IgA tissue transglutaminase
(TIC)
anti-TIC test is 90-98% sensitive, 94-97% specific
IgA deficient patients have false-negative IgA anti-EMA and anti-TIC so
measure serum IgA concomitantly
antigliadin antibodies may be measured
fecal fat >7% over 72 hrs
Treatment
dietary counselling
gluten restricted diet: avoid barley, rye, wheat, maybe oats
rice and com flour are acceptable
iron, folate supplementation
in the event of treatment failure, consider
incorrect diagnosis
non-adherence to gluten-free diet
unsuspected concurrent disease (e.g. pancreatic insufficiency)
development of intestinal (enteropathy-associated T-cell) lymphoma
(abdominal pain, weight loss, palpable mass)
development of diffuse intestinal ulceration, characterized by aberrant
intraepithelial T-cell population, precursor to lymphoma
presence of non-granulomatous ulcerative jejunoileitis
presence of diffuse collagen deposits ("collagenous sprue")
presence of lymphocytic (microscopic) colitis
Prognosis
associated with l' risk of lymphoma, carcinoma including small bowel and colon
majority of patients have nonnallife expectancy
o
Gluten found in "BROW"
Barley
Rye
Oats (controversiall
Wheat
Bacterial Overgrowth
Definition
syndrome caused by proliferation of bacteria in small bowel to concentrations >1Q4
bacteria/mL of bowel tissue
Etiology
anatomic factors
jejunal diverticulae
surgical blind loop
Crohn's & fistulas
strictures (regional enteritis, radiation injury)
obstruction
surgical damage to the ileocecal valve
-.It motility
scleroderma
diabetes, hypothyroid
intestinal pseudo-obstruction
achlorhydria
described in elderly patients: unknown etiology
Clinical Features
steatorrhea: bacteria deconjugate bile salts impairing micellar lipid formation
diarrhea: bowel mucosa damaged by bacterial products, impairing absorption; altered
gut motility, free bile acids stimulate colon water secretion
megaloblastic anemia due to vitamin B]2 malabsorption
may be asymptomatic
Investigations
gold standard: mixed bacterial cultures of>1Q4 CFU/mL jejunum
72-hour fecal fat collection
bile acid breath test (l4C-cholyglycine) misses 1/3 of cases
hydrogen breath test or 14C-xylose breath test
positive three stage Schilling test (Figure 6) if done before and after treatment can
be diagnostic
low serum Bjz, high serum folate (since folate synthesized by GI bacteria)
small bowel follow through to look for underlying cause
consider small bowel biopsy to rule out primary mucosal disease as cause of
malabsorption
Treatment
treat underlying etiology if possible (e.g. prokinetic agents for small bowel motility
disorder)
symptoms relieved by a 10-14 day trial of antibiotics (best if based on culture results)
broad-spectrum antibiotics, killing anaerobes and aerobes
e.g. amoxicillin + clavulinic acid 250-500 mg PO tid
patients may need to be treated with intermittent antibiotics indefinitely
discontinue acid reducing agents if possible
consider supplemental Vit A, D, E, K, B
12
Inflammatory Bowel Disease (lBD)
Definition
Crohn's Disease, Ulcerative Colitis, and Indeterminate Colitis
Pathophysiology
poorly understood
mappropriate response of the immune system to enteric flora in a genetically
preillsposed individual
current hypothesis emphasizes that the chief problemis lack of appropriate down
regulation of immune responsiveness
Genetics
increased risk of both ulcerative colitis and Crohn's disease in relatives of patients with
either disease, especially siblings, early onset disease. Familial risk greater if proband
has Crohn's than ulcerative colitis
probably polygenomic pattern
9 gene loCI described to be associated
CARD15 gene mutation associated with Crohn's (relative risk in heterozygote is 3, in
homozygote is 40), especially Ashkenazi Jews, early onset disease, ileal involvement,
fistulizmg and stenotic disease
CARD15 gene product modulates NFkB, which is required for the innate immune
response to microbial pathogens, best expressed in monocytes-macrophages
other gene associations described but even less well understood
Clinical Features
Table 10. Clinical Differentiation of Ulcerative Colitis from Crohn's Colitis
Crohn's Disease Ulcerative Colitis
Location Any part of GI tract Isolated to large bowel
small bowel +colon: 50% Always involves rectum
small bowel only: 30%
colon only: 20%
Rectal Bleeding Uncommon Very common (90%)
Diarrhea Less prevalent Frequent small stools
Abdominal Pain Post-prandial/colicky Pre-defecatory urgency
Fever Common Uncommon
Palpable Mass Frequent, RLQ Rare
Recurrence After Surgery Common Rare
Endoscopic Features Discrete aphthous ulcers, patchy lesions Continuous diffuse inflammation,
erythema, friability, loss of normal
vascular pattern, pseudopolyps
Histologic Features Transmural distribution with skip lesions Mucosal distribution
Focal inflammation Granulomas absent
Noncaseating granulomas, deep fissuring Gland destruction, crypt abscess
& aphthous ulcerations, strictures
Glands intact
Radiologic Features Cobblestone mucosa Lack of haustra
Frequent strictures and fistulae Strictures and fistulae rare
XR: Bowel wall thickening "string sign"
Complications Strictures, fistulae, perianal disease, abscess Stricture, toxic megacolon
Colon Cancer Risk 3 x that of general population 7-30 x that of general population
Crohn's Disease
Definition
chronic inflammatory disorder potentially affecting the entire gut "from gum to bum"
Epidemiology
incidence 1-6/100,000; prevalence 10-100/100,000
bimodal: onset before 30 years, second smaller peak age 60
incidence of Crohn's increasing (relative to DC) especially in young females
more common in Caucasians, Ashkenazi Jews
M=F; smoking incidence in Crahn's patients is higher than general population
Clinical Features
most often presents as recurrent episodes of mild diarrhea (more common with
involvement of colon), abdominal pain, and fever
ileitis may present with post-prandial pain, vomiting, RLQ mass mimics acute
appendicitiS
fistulae, fissures, abscesses are common
extra-intestinal manifestations (Table 11) are more common with colonic involvement
natural history unpredictable
linear ulcers leading to mucosal islands and "cobble-stoning"
deep fissures with risk of perforation into contiguous viscera (leads to fistulae
and abscesses)
enteric fistulae may communicate with skin, bladder, vagina, and other parts of bowel
granulomas are found in 50% of surgical specimens, 15% of mucosal biopsies
Investigations
endoscopy with biopsy to diagnose
barium studies
bacterial cultures, 0 & P, C. diffici/e toxin to exclude other causes of inflammatory
diarrhea
o
nutrition
symptomatic therapy
(e.g. loperamide, acetaminophen)
~
5-ASA (rnesalamine)
antibiotics (FlagylTM, Cipro"')
~
corticosteroids (e.g. budesonide)
~
immunosuppression
(e.g. azathioprine, 6-Mp,
methotrexate)
~
immunomodulators
(e.g. infliximab - TNF-antagonistsl
~
experimental therapy or surgery
Figure 7. GradedApproachTo
Induction Therapy In Crohn's
Gn Gastroenterology
Medical Management of Crohn's
Induced Maintenance
Remission
5ASA
Steroids
Immunosuppressive
Antibiotics
MTX
Infliximab
,,' ,
.l-------------,
Principles ofThenlpy in 180
Aim more for clinical than histolog-
iclendoscopic radiologic remission
.Treatment has so many side effects that,
usually one disease (180) ends up being
replaced with another (iatrogenicl
Spend the time to lower expectations,
discuss risks and expected benefits of Rx
Don't use corticosteroids for mainte-
nance therapy
" ' ,
.l------------,
Many patients with Crohn's suffer from
vague abdominal pain and diarrhea for
years before adiagnosis of Crohn's dis
ease is considered.
InIIbiimab fur induction of I1mission in Crohn's
DiMae
Cochrane Database of Systemic Reviews
2003, Issue 4. Art. No.: CD003574.DDI:
10.1002/14651858.CD003574.pub2.
Study: Meta-analysis of TNF blocking agents in
the induction of remission of Crohn's disease.
ConUlsionl: There is evidence to suggest that
infliximab is effective in inducing remission in
patients when compared to placebo.
Infliximab fur maintaining remission in Crohn's
disaasa: tha ACCENT ITriel
The Lancet 2002. 359l9317): 15411549
Study: Multicentre double blind RCT evaluating
the efficacy of maintenance infliximab for Crohn's
Disease in patients who initially responded to
infliximab.
Methods: 573 patients with active CD received an
injection of 5mg/kg at week 0of the sudy.
Responders were then randomized to three
groups: I) placebo infusions, III infliximab infu
sions of 5mg/kg at 2, 6and 8weeks and then q8
weeks until week 46, 11115 mg/kg infliximab at 2
and 6weeks and then 10 mg/kg thereafter.
Rea: Patients in groups II and III were 11 more
likely to have sustained clinical remission
throughout the 54 week trial, and 2) had signifi-
cantly lower rates of corticosteriod usage during
the trial. Rates of infection and serious adverse
events were similar across treatment groups.
Conclusions: Infliximab is effective in maintaining
remission and reducing corticosteroid use in
patients who initially respond to infliximab.
Small and Large Bowel Toronto Notes 2008
Management (see Figurc 7)
Medical management (most uncomplicated cases can be managed medically)
Diet
fluids only during acutc exacerbation
elemental diets may aid in remission but are not palatable
TPN and bowel rest only of transient benefit
those with extensive small bowel involvement need electrolyte, mineral and
vitamin supplements (Vit D, Ca, Mg, zinc, Fe, Bul
5-ASA
efficacy controversial, most evidence for efficacy is for mild, colonic disease
block arachidonic acid metabolism to prostaglandins and leukotrienes
often limited by side effects and intolerance
e.g. sulfasalazine (SalazopyrinTM) =a compound composed of 5-ASA bound to
sulfapyridine
hydrolysis by intestinal bacteria releases 5-ASA, the active component
effectiveness is related to dose, best at >4 gld
others include PentasaTM, SalofalkTM, AsacoFM, Mesasal =5-ASA
(mesalamine) with different coatings to release 5-ASA in the ileum and colon
Steroids
prednisone 20-40 mg OD for acute exacerbations (but use only if symptoms are
severe)
no proven role for steroids in maintaining remissions, masks intra-abdominal
sepsis
complicatiuns of steroid therapy (dose and duration dependent):
common early in therapy - insomnia, emotional lability, weight
gain/enhanced appetite
common if underlying risk factors - hypertension, diabetes, POO, acne
prolonged use - Cushing's habitus, impaired wound healing, adrenal
suppression, infection diathesis, osteonecrosis, myopathy
insidious - osteoporosis (recent evidence suggests this starts early, and
can be prevented with calcium, Vitamin D or bisphosphonates), skin
atrophy, cataracts, atherosclerosis, growth retardation, fatty liver
unpredictable and rare - glaucoma, pseudotumour cerebri
Note: budesonide has fewer side effects than prednisone
Immunosuppressives
e.g. 6-mercaptopurine (6-MP), azathioprine (Imuran); cyclosporine and
methotrexate used less often
used to treat active inflammation and to maintain remission
most commonly used as steroid-sparing agents, i.e. to lower risk of relapse as
corticosteroids arc withdrawn
requires >3 months to have beneficial effect (methotrexate works faster than
azathioprine); usually continued for several years
probably help to heal fistulae, -.j., disease activity
have important side effects (pancreatitis, bone marrow suppression, l' risk of
cancer)
Antibiotics
e.g. metronidazole (20 mglkg/d, bid or tid dosing)
decreases disease activity and improves perianal disease
side effects are common and reversible for metronidazole (50% have peripheral
neuropathy after 6 months of h-eatment, may not be reversible)
use of ciprofloxacin + metronidazole may be beneficial in Crohn's disease
Antidiarrheal agents
loperamide (lmodium rM) > diphenoxylate (Lomotil) > codeine (cheap but
addictive)
all work by decreasing small bowel motility
use with caution (if colitis is severe, risk of precipitating toxic megacolon); avoid
in flare-ups
Cholestyramine
a bile salt binding resin
for watery diarrhea with less than 100 em of terminal ileum diseased or resected
(see below)
lmmunomodulators
infliximab (Remicade) = antibody to tumour necrosis factor (TNFa),
subcutaneously
proven effective for treatment of fistulae and patients with medically refractory
Crohn's
often effective within days, generally well tolerated allergic reactions
side effect -> reported cases of reactivated TB, PCP, other infections
Surgical treatment (see General Surgery, GS25)
surgery generally reserved for complications such as fistulae, obstruction,
abscess, perforation, bleeding, and rarely for medically refractory disease
at least 50% clinical recurrence within 5 years; 85% within 15 years; endoscopic
recurrence rate even higher
40% likelihood of second bowel resection
30% likelihood of third bowel resection
complications of ileal resection
<100 em resected ---> watery diarrhea (impaired bile salt absorption)
- treatment: cholestyramine
>100 em resected ---> steatorrhea (bile salt deficiency)
- treatment: fat restriction, medium chain triglycerides
Prognosis
highly variable course
10% ---> chronic, relapsing
10% disabled by the disease eventually
increased mortality, especially with more proximal disease, greatest in the first
4-5 years
intestinal obstruction due to edema, fibrosis
fistula formation
intestinal perforation characteristically contained (free perforation uncommon)
malignancy: l' risk especially with colonic involvement, but not as high as ulcerative
colitis
Ulcerative Colitis (UC)
Definition
inflammatory disease affecting colonic mucosa anywhere from rectum to cecum, but
always starting in rectum
Epidemiology
incidence 2-10/100,000; prevalence 35-100/100,000 (more common than Crohn's)
2/3 onset by age 30 (with second peak after 50); M=F
small hereditary contribution (15% of cases have 1st degree relative with disease)
risk is less in smokers
disease limited to reetum/left colon is more common than pancolitis
Pathology
disease can involve any portion of lower bowel from rectum only (proctitis) to entire
colon (pancolitis)
rectum always involved
inflammation diffuse, continuous, and confined to mucosa
Clinical Features
chronic disease characterized by rectal bleeding and diarrhea, prone to remissions
and exacerbations
severity of colonic inflammation correlates with symptoms (stool volume, amount of
blood in stool)
diarrhea, rectal bleeding most frequent, but can also have abdominal cramps/pain
(especially with defecation)
tenesmus, urgency, incontinence
systemic symptoms: fever, anorexia, weight loss, fatigue
extra-intestinal manifestations (Table 11)
characteristic exacerbations and remissions; 5% of cases are fulminant
Investigations
sigmoidoscopy with mucosal biopsy (to exclude self limited colitis) without bowel
prep to diagnose (often sufficient for diagnosis)
colonoscopy contraindicated in severe exacerbation; helpful to determine extent of
disease
barium enema (not during acute phase or relapse)
stool culture, microscopy, C. difficile toxin assay necessary to exclude infection
no single confirmatory test
Management
mainstays of treatment: 5-ASA derivatives and corticosteroids, with azathioprine used
in steroid-dependent or resistant cases
Diet - of little value in decreasing inflammation but may alleviate symptoms
Antidiarrheal medications - generally not indicated in DC
5-ASA drugs
topical (suppository or enema): very effective for distal disease (no further than
splenic flexure), preferable to corticosteroids
oral: effective for mild to moderate, but not severe colitis
e.g. sulfasalazine (Salazopyrin) 3-4 g/d; mesalamine (Salofolk, Pentasa,
AsacoJTM) 4 g/d
Intliximab for m.intlining remission of Croh!I',
Disease in patilnlJ with dreining fisbJalaa: 1IIe
ACCENT II Trial
NEJM 2004; 350 191876-896
Study. Multi-centre, double blind RCT of 306
patients with Crohn's Disease and one or more
draining perianal fistulas. Atotal of 195 patients
who responded to treatment were randomized to
received placebo or 5mg/kg of infliximab.
RNuIll: Mean time to loss of response was sig-
nificantly longer in the group that received inflix-
imab compared to placebo (40 weeks compared
to 14 weeksl p<O.OOI.
Conclusions: Infliximeb is effective in the mainte-
nance of remission for Crohn's patients with
draining abdominal or parianel fistulas. Note:
What has not been precisaiy defined is the infec-
tion risk associatad with infliximab.
Medical Management of Ulcerative Colitis
Induced Maintenance
Remission
5-ASA
Steroids
Immunosuppressive
Intliximab for induction of remission in UC
Cochrane Database of Systematic Reviews
2OlXi, Issue 3. Art. No.: CDOO5112. DOl:
lo.1002/14651858.CD005112.pub2.
Conclusions: Infliximab is more useful in induction
of remission Iboth clinical and endoscopic remis-
sion) of active UC than placebo in UC that hes
been refrectory to BOTH corticosteriods and anti-
immune medications.
....' ,
.')------------,
In UC's initial presentation, nonb/oody
o\annea isnequen\\"-i seen. It will
however, eventually progress to bloody
diarrhea.
CCIIlIidering complications of
lBO, dlink:
UlCERATIVE COU11S
Urinary Calculi
Liver problems
Cholelithiasis
Epithelial problems
Retardation of growth/sexual maturation
Arthralgias
Thrombophlebitis
Iatrogenic complications
Vitamin deficiencies
Eyes
Colorectal cancer
Obstruction
Leakage (perforationl
Iron deficiency
Toxic megacolon
Inanation (wasting)
Strictures, fistulae
useful only for mild to modE'rate disease, not for severe disease
more use in maintaining rE'mission (decreases yearly relapse rate from
60% to 15%)
may decrease rate of colorectal cancer
Steroids
best drugs to remit acute disease, especially if severe or first attack (e.g.
prednisone 40 mg PO OD)
limited role as maintenance therapy
use suppositories for proctitis, enemas for proctosigmoiditis
less toxic topical steroids (e.g. tixocortol enemas) have been shown to be
equally effective when used as enemas/suppositories
Immunosuppressants (steroid sparing)
if severe DC is refractory to steroid therapy, add IV cyclosporine: rapidly
effective but has many side effects
azathioprine: is too slow to rapidly resolve acute relapse but is helpful in
inducing remission and sparing steroids in refractory cases
may be added to steroids when steroids fail, but most commonly used to
maintain remission as corticosteroids withdrawn
Surgical treatment
early in fulminant cases and toxic megacolon
aim for cure with colectomy
indications: failure of adequate medical therapy, toxic megacolon, bleeding,
pre-cancerous, dysplastic changes picked up with screening endoscopic biopsies
(dysplasia)
Complications (Table 11)
like Crohn's, except for the following:
more liver problems (especially primary sclerosing cholangitis (PSC) in men)
greater risk of colorectal cancer
risk increases with duration and extent of disease (5% at 10 years, 15% at
20 years for pancolitis; overall RR is 8%)
risk also increases with presence of sclerosing cholangitis, family history
of colorectal cancer
therefore, regular screening colonoscopy and biopsy in pancolitis of
8 years or more is indicated
toxic megacolon (transverse colon diameter >6 cm on abdominal x-ray) with
immediate danger of perforation
Prognosis
chronic relapsing pattern in most patients
10-15% chronic continuous pattE'rn
>1 attack in almost all patients
more colonic involvement in the 1st year correlates with increased severity of attacks
and increased colectomy rate
colectomy rate = ] % for all patients after the 1st year; 20-25% eventually undergo
colectomy
normal life expectancy
proctitis only, usually benign course
Table 11. Extraintestinal Manifestations of IBD
System Crohn's Disease Ulcerative Colitis
Dennatologic
Erythema Nodosum 15% 10%
Pyoderma Gangrenosum 10% Less common
Perianal skin tags 75-80% Rare
Psoriasis 5-10% of those with IBD
Oral mucosal lesions Common Rare
Rheumatologic
Peripheral arthritis 15-20% of those with IBD (CD>UCI
Ankylosing Spondylitis 10% of those with IBD ICD>UCj
Sacroiliitis Occurs equally in CD and UC
Ocular 1-10% of IDD)
Uveitis (vision threatening)
Episcleritis (benign) 3-4% of IBD patients (CD>UC)
Hepatobiliary
Cholelithiasis 15-35% of patients with ileal Crohn's
Primary sclerosing cholangitis IPSCI 1-5% of IBD cases involving colon
Fatty liver
Urologic
Calculi most common in CD, especially following ileal resection
Ureteral obstruction
Fistulas characteristic of Crohn's
Others
Thromboembolism
Vasculitis
Osteoporosis
Vitamin deficiencies IB", Vit ADEKj
Cardiopulmonary disorders
Pancreatitis (rare)
Irritable Bowel Syndrome (lBS)
------"---...;..--------_...
o
Definition
a form of functional bowel disease; considered a disease, not just a label for all CI
symptoms that are unexplained after investigation
Epidemiology
20% of North Americans
onset of symptoms usually in young adulthood
F>M
Pathophysiology
normal perception of abnormal gut motility
abnormal perception of normal gut motility
psychological: "socially acceptable vehicle for accepting care"
behavioural: symptoms of illS common in general population; l' physician seeking
behaviour and expectations in small percentage reaching medical attention
Diagnosis
Table 12. Rome III Criteria for Diagnosing Irritable Bowel Syndrome
In the absence of structural or metabolic abnonnalities to explain the symptoms:
At least 3months, with onset at least 6 months previously of recurrent abdominal pain or discomfort associated with
2 or more of the following:
improvement with defecation; and/or
onset associated with achange in frequency of stool; and/or
onset associated with achange in form (appearance) of stool
Symptoms that cumulatively support diagnosis of 185:
abnormal stool frequency (i.e. >3 bowel movements/day, and <3 bowel movements/wk)
abnormal stool form lIumpy/hard/looselwateryl
abnormal stool passage (straining, urgency, feeling of incomplete evacuation)
passage of mucus
bloating or feeling of abdominal distention
Absence of Negative Features/"Alarm" Features
weight loss fever
nocturnal defecation anemia
blood or pus in stool abnormal gross findings on flexible sigmoidoscopy
Nonnal Physical Exam
Investigations
use discretion: the more history resembles Rome III criteria or younger the patient, the
less number of investigations required
aim is to rule out:
enteric infections e.g. Giardia
lactose intolerance/other disaccharidase deficiency
Crohn's disease
celiac sprue
drug-induced diarrhea
diet-induced (excess tea, coffee, colas)
CBC, TSH, albumin, C-reactive protein, TIC and serology
stool for C&S, O&P, fat excretion if diarrhea present
sigmoidoscopy
Management
reassurance, realistic goals, education
relaxation therapy, biofeedback, hypnosis, stress reduction
no therapeutic agent effective
bran or psyllium for constipation, loperamide for diarrhea
consider use of tricyclic antidepressants
symptom-guided treatment
pain predominant
antispasmodic medication before meals, e.g. hyosine
change diet (anticholinergic diet)
tricyClic compounds (TCA)
selective serotonin reuptake inhibitors (SSRI)
visceral antinociceptive agent
diarrhea predominant
change diet
loperamide 2-4 mg t i d / ~
diphenoxylate (Lomotil )
cholestyramine 4 g qid
constipation predominant
exercise and adequate fluid intake
add fibre
osmotic or other laxatives
5-HT
4
receptor agonist where available (e.g. tegaserod)
G26 Gastroenterology Small and Large Bowel Toronto Notes 200S
Prognosis
80% improve over time
most have intermittent episodes
normal life expectancy
'I)' Cauae. of Constipation
"DOPED":
Drugs
Obstruction
Pain
Endocrine dysfunction
Depression
...... ' ,
.1-----------,------,
WJ% of upper GI bleeds stop sponta
neously or need only supportive therapy.
Constipation
-------------------_......_....
Definition
passage of infrequent or hard stools with straining (stool water <50 mL/day); bowel
frequency <3 times per week
Epidemiology
increasing prevalence with age; F>M; rare in Africa and India where stool weight is
3-4 x greater than in Western countries
Etiology
in the absence of other clinical problems, most commonly due to lack of fibre in diet,
change of diet, or poorly understood gut motility changes
organic causes
medication side effects (antidepressants, codeine) most common
intestinal obstruction, left sided colon cancer (consider in older patients);
fecal impaction
metabolic
diabetes mellitus (DM)
hypothyroidism
hypercalcemia, hypokalemia, uremia
neurological
intestinal pseudo-obstruction
Parkinson's disease
multiple sclerosis (MS)
collagen vascular disease
scleroderma
amyloid
Clinical Presentation
illS, depression, anorexia
painful anal conditions (e.g. hemorrhoids)
abdominal pain relieved by defecation, hard stools, straining and pain with defecation,
flatulence, overflow diarrhea, sense of incomplete evacuation, abdominal distension
<3 BM/week
Investigations
swallow radio-opaque markers to quantify colonic transit time (normal: 70 hours)
normal = misperception of normal defecation
prolonged = "colonic inertia"
prolonged plus abnormal anal manometry =outlet obstruction
Treatment (in order of increasing potency)
surface acting (soften and lubricate)
docusate salts, mineral oils
bulk forming
bran 30 gld (effective within 1 week), psyllium seed (metamucil), wheat fibre,
sterculin, methylcellulose (ensure adequate hydration)
osmotic agents (effective in 2-3 days)
lactulose, sorbitol, magnesium citrate, magnesium sulfate, magnesium
hydroxide, sodium phosphate, lactitol
cathartics (effective in 24 hrs)
castor oil, senna (watch out for melanosis)
enemas and suppositories (e.g. saline enema, phosphate enema, glycerin suppository)
note: avoid senna and anthracena (..J... colon motility when used chronically)
er Gastrointestinal Bleeding
_._"'__ _-=, __~ ~ ~ ~ ~ ~ ~ - - J
Definition
bleeding proximal to the ligament of Treitz (75% of GI bleeds)
Ligament of Treitz; suspensory ligament in the third and fourth portions of the
duodenum
Clinical Features
in order of decreasing severity of the bleed: hematochezia > hematemesis > melena>
occult blood in stool
Etiology
above the GE junction
epistaxis
esophageal varices (10-30%)
esophagitis
esophageal cancer
Mallory-Weiss tear ( 10%)
stomach
gastric ulcer (20%) (see Peptic Ulcer Disease, G9)
gastritis (e.g. from alcohol or post surgery) (20%)
gastric cancer
duodenum
ulcer in bulb (25%)
aortoenteric fistula: usually only if previous aortic graft
coagulopathy (drugs, renal disease, liver disease)
vascular malformation (Dieulafoy's lesion, AVM)
Management (initial)
stabilize patient (IV fluids, cross and type, 2 large bore IVs, monitor)
send blood for CBC, platelets, PI, PTt, electrolytes, BUN, Cr, LFTs
keepNPO
NG tube to determine upper vs. lower GI bleeding (except in variceal bleeding)
endoscopy (OGD): establish bleeding site + coagulate leslOn
if stable non-variceal bleed and endoscopy is not available then PPI either IV or high
dose PO
for variceal bleeds, octreotide 50 flg loading dose followed by constant drip of
50 flg/hr is helpful prior to endoscopy
consider IV erythromycin prior to gastroscopy to remove clots from stomach
Prognosis
80% stop spontaneously
petic ulcer bleeding: low mortality (2%) unless rebleeding occurs (25% of patients,
10 Yo mortality)
endoscopic predictors of rebleeding: spurt or ooze, visible vessel, fibrin clot
H
2
antagonists have little impact on rebleeding rates and need for surgery
esophageal varices have a high rebleeding rate (55%) and mortality (29%)
tic Ulcer
------------------'
Clinical Features
seePUD, G9
Treatment
see Figure 8
judge risk of rebleeding or continuous bleeding
clinically on basis of
age
bleeding diathesis
volume of blood loss Iclinical measurementl
previous history of PUD
comorbid disease
high risk low risk
adt to ICU adm!to ward
------""endoSCOPY
acflve bleeding tspot base
or nonbleeding I Ino bljedingulcer)
visible vessel t ,
1. therapy: observe for discharge
electrocoagulation 3days
heater probe oral PPI
injection of epinephrine, sclerosing agents, etc.
band ligation, clips
2.ICU
3. IV PPI
..... ' ,

Aortoenteric F"lItula is arare and lethal
cause of GI bleed, most common in
patients with ahistory of aortic graft sur-
gery. Therefore, perform endoscopy or
surgery if suspicion arises.
Note:The window of opportunity is nar
row. Act fast to prevent death.
..... ' ,
.l----------,
Always ask about NSAJDlaspirin intake or
anticoagulant therapy in GI bleed.
IntrMnouI 0mepnIz0Ie VI. Placebo for BIeecing
PeplIc Ulcellllquiring EndoscGpic
TI8IlIIIent
NEJM 2000; 343:310-316
Slvdy. Randomized, doublHllind placebo controlled
trial.
1IIIIBntI: 240 patients wittl actively bleeding ulcers or
ulcers wittl noll-bleeding visible vessels treated by
endoscopic injectioo plus coagulation.
1ntInwrIilHr IV omeprazole lKl mg followed by
constant infusion 8mghllor nhours vs. placebo.
IIain 0fIll:0lnIs: Recurrent bleeding.
IIrrIa/ls: 0mepraz0Ie decreased rates of recurrent
bleeding (7% vs. 22%1. surgetV (jl<1l.OO1I. alkause
mortality (jl<1l.OO1), but no statistically
dlange in surgel'f or death.
CortduIion: Intravenous omeprazoIe reduces realr-
rent bleeding alter endoscopic treatment of bleeding
peptic ulcer.
Figure 8. Approach to Management of Suspected Bleeding Peptic Ulcer
SdInlthenpy IIId Oetnlotide for Acute Variceal
.....
NfJM
Sludy. Randomi2ed, double-blind, prospective trial.
I'Illenu: 199 patients with cirrhosis and aetrte variceal
bllffiding
ItItInInIioII: Sclerotherapy with continuous
octreolide infusion VI. sclerothernpy and
MI/n Outcome: SUI'lival wnhout rebllffiding 5d after
sclerotherapy
,..After 5d, a lJI0p0rtion of patients sur
vived without rebleeding in the octreotide group 187%
vs 71%, poO,OOOI and required less blood transfusKlnS
111 vs 2,0 units, poO,OOO},The mean 15d cumulative
survival rate was equal in both groups.
ConduIiorr In patients with cirrhosis, sclerotherapy
and odreotide were more effective than sclerotherapy
aloM in controlling acute variceal bleeding, but there
was no difference in overall mortality rnles.
v.iceII Ligation VI. Sclerotherapy for
Acute Vlrice8l1IleedIng
J Hepato/2006; 45{41:560-7
SIudy. Randomized controlled trial,
PJtienm 179 patients with acute esophageal
variceal bleeding and suspected cirrhosis,
1nt8Iwntion: Sclerotherapy wnh continuous
somatostatin infusion vs. variceal ligation with
oontinuous somatostatin infusion,
MIin Outcom Therapeutic failure - failure to
oontrol acute bleeding episode or early rebleed-
ing,
Ilelulll:Therapeutic failure occumed in 24% of
patients treated with sclerotherapy compared
to 10% of those treated with ligation (RR=2,41,
Failure 10 oontrol bleeding higher in scIerother
apy group 115% vs, 4%; p:O,02I, Higher propor
tion of patienls with sclerotherapy had serious
side effects 113% vs. 4%; p=O.01I,
e-JuIiotr. The use of variceal ligation, com
pared to sclerotherapy as emergency endo
scopic therapy for the treatment of acute
variceal bleeding, significantly improves the
efficacy and safety,
Esophageal Varices
Clinical Features
characteristically massive upper GI bleeding
Etiology
almost always due to portal hypertension
often accompanied by varices in stomach
Investigations
endoscopy
Treatment
see Figure 9
al resuscitation: ABC's history
b) start octreotide/somatostatin
elective/urgent
endoscopy and
endoscopic variceal ligation (EVU
stable?
---
.............

follow-up transjugular intrahepatic
(P-blocker, EVL, portosystemic shunt (TIPS)
ES, nitrates, etc,) available/succesfu I?

,
balloon tamponade ----. surgery
(confirmed varix)
Figure 9. Management of Bleeding Esophageal Varices
Mallory-WeissTear
o

Definition
longitudinal laceration in gastric mucosa on lesser curvature near GE junction (20%
straddle junction, 5% in distal esophagus)
Etiology
due to rapid increasf>s in gastric pressure (i.e. retching-vomiting against a
closed glottis)
most patients abuse alcohol
usually hiatus hernia present
Clinical Features
hematemesis melena, classically following an episode of retching
can lead to fatal hematemesis
Management
90% stop spontaneously; NG (if needed) and replacement of lost volume
if persistent: endoscopy with electrocautery or surgical repair
Lower Gastrointestinal Bleedin
Definition
hleed distal to ligament of Treitz
Clinical Features
hematochezia (see Figure 10)
anemia
occult blood in stool
rarely melena
Toronto Notes 2008 Small and Large Bowel
Etiology
rule out upper source
vascular
angiodysplasia
hemorrhoids
neoplasm
cancer
polyps
inflanunation
colitis
infection
Resuscitate
consider upper GI source Iclinical suspicion', NG aspirate,
bloody, increased BUN/creatinine ratio)
lower GI source likel upper GI source likely
sigmodoscopyon
unprepared bowel'
/ ~
bleed in bleeding source bleeding source bleeding source
lumen found not found found
t
t t t
follow in treat lower source treat
hospital
(ABP, pulse, Hbl
bleeding stops bleeding continues bleeding continues
rate <0.5 mUh rate >0.5 mUh
t
colonic lavage radionIleotide angiogram
then colonoscopy labelled red cell scan
1Clinical suspicion of upper source if bleeding hemodynamically significant, ASAiNSAID use, previous upper GI bleed, known
portal hypertension/liver disease/upper GI tract disease.
2 Look for diffuse mucosal inflammation, active bleeding from hemorrhoid, mass.
Figure 10. Approach to Hematochezia
Colon Cancer
(see General Surgery. GS29)
EtiologylEpidemiology
environmental influences (presumed)
high dietary fat consumption
low dietary fibre consumption
genetic influences
all colorectal cancers considered to have genetic component, to varying degrees
familial syndromes (see Risk Factors section)
multiple "step-wise" somatic mutations, contributed by environment, have been
implicated
genetic changes implicated are
activation of proto-oncogenes (K-ras)
loss of tumour-suppressor gene activity (APC, DCC, p53)
abnormalities in DNA repair genes (hMSH2, hMLHl),
especially HNPCC syndromes (see Risk Factors, GS30)
Pathophysiology
normal colon -> hyperproliferative epithelium -> adenoma -> carcinoma
Gastroenterology G29
.... ' ~
.)-------------,
When suspecting lower GI bleed, first
and foremost exclude upper GI bleeding
before localizing the site of the lower GI
bleed.
Lower GI Bleed
Most common cause of LGIB 'CHAND':
Colitis (radiation, infectious. ischemic,
IBD [UC> COil
Hemorrhoids
Angiodysplasia
Neoplastic
Diverticular disease
.... ' ~
.l---------------,
Some colon cancers may bleed intermit
tently or not at all.
No bleeding ~ no cancer.
.... ' ~
.l---------------,
Melena more often seen with rightsided
tumours.
HematodIeziI more often seen with
leftsided tumours.
.... ,,
~ " } - - - - - - - - - - - .
, msterdam' Criteria for
HNPCC diagnosis:
3 relatives with colorectal cancer,
where 1 is 1st degree relative of
other 2
2 generations of colorectal cancer
.1 colorectal cancer before age 50
..... ' ,
~ } - - - - - - - - - - - . . . ,
ColoI8CtaI Cancer Screening
Canadian Association of Gastroenterology, Can
JGastroenterol2004;1812).
People at average risk
>50, no family histol'( should undergo one o ~
FOBT evel'( 2years
Flexible sigmoidoscopy eve!'( 5years
Combined FOBT and flex sig every 5years
Double contrast barium enema evel'( 5years
Colonoscopy evel'( 10 years
People at above-average risk;
HNPCC - Genetic testing +colonoscopy
q2years beginning at age 20
FAP - Genetic testing +sigmoidoscopy
annually beginning at age 1lJ.12
Fam Hx of cancer/polyps but does not fit
criteria for HNPCClFAP - colonscopy q5years
beginning at age 40, or 10 years earlier than
the youngest diagnosed polyp/cancer in the
family.
.... ' ,
~ . ) - - - - - - - - - - - - - - ,
Note that rectal cancers have ahigher
recurrence rate and lower 5-year survival
rate than colon cancers.
\ .
Therefore, do arectal exam.
.... ' ,
~ } - - - - - - - - - - - - ,
Liver Functions
glucose homeostasis
plasma protein synthesis
lipid and lipoprotein synthesis
bile acid synthesis and secretion
vitamin A,D,E,K,B'2 storage
biotransformation, detoxification,
excretion of endogenous and
exogenous compounds
Small and Large BowelfLiver Toronto Notes 2008
Risk Factors
75% of new cases are in people with no known RF
age
90% of cancers in people >50 years old
person 50 years old has 5% chance of developing colorectal cancer by 80 years
old
adenomatous polyps
family history
sporadic cancer
risk increases 1.8 times for those with one affected relative, 2-6 times with
two affected relatives
risk is greater if relative has cancer diagnosed <45 years old
familial adenomatous polyposis and Gardner's syndrome
autosomal dominant, inactivated APC gene on 5q
over 100 adenomatous polyps develop in colon and rectum, starting at
age 15-20 years old
if colon is not removed, risk of cancer is 100%
Gardner's syndrome is a variant, with polyposis plus extracolonic
manifestations (osteomas, soft tissue tumours, congenital hypertrophy of
retinal pigmented epithelium)
hereditary nonpolyposis colorectal cancer (Lynch syndrome, or HNPCq
autosomal dominant (hMSH2, hMLH1)
compared to sporadic cancer, requires more extensive surveillance
(colonoscopy q 2 years if polyp)
more extensive surgery if cancer found (subtotal segmental rather than
colectomy) and more extensive screening of family members
occurs earlier, age 40-50 years, often proximal in location and multiple,
can be associated with other malignancies (especially ovarian
and uterine)
mucinous or poorly differentiated because no preceding polyp stage;
cancers are often diagnosed late in disease
Inflammatory Bowel Disease (IBD)
ulcerative colitis (UC) - after 10 years with the disease, cancer risk l' by 1% for
each additional year; Crohn's disease - exact risk of cancer remains unclear
Prevention
some evidence to support:
increase fibre in diet, decrease animal fat and red meat, decrease smoking and
EtOH, increase exercise and decrease BMI
Prognosis
actuarial survival
stage I (limited to wall of bowel - 95%)
stage 2 (through wall of bowel- 80%)
stage 3 (into lymph nodes - 50%)
Treatment (see General Surgery, GS29)
Liver
..!r. Basic Anatomy Review .....
Anatomy and Physiology
composed of 4 lobes (left, right, caudate, quadrate) and divided into 8 segments
the liver performs several important functions including:
carbohydrate/lipid metabolism
coagulation factor production (excluding factor VIII)
bile production
drug metabolism/detoxification
blood supply
arterial supply:
hepatic artery (from celiac artery)
portal vein (from splenic vein and superior mesenteric vein)
venous supply:
hepatic veins (left, middle, right which drain to inferior vena cava)
Toronto Notes 2008 Liver Gastroenterology G31
Middle hepatic
vein
I - Posterior (caudate) segment v -Right anterior medial segment
II - Left posterior lateral segment VI - Right anterior lateral segment
III - Left anterior lateral segment VII . Right posterior lateral segment
IV - Left medial segment VIII - Right posterior medial segment
@Jodi Crossingham 2007
Figure 11. Liver Anatomy
Investigations of Liver Function
ProthrombinTime (PT)
daily marker of hepatic protein synthesis
must exclude co-existent vitamin K deficiency
Serum Bilirubin
product of heme metabolism in the liver
must exclude extrahepatic causes of hyperbilirubinemia
Serum Albumin Level
detects prolonged (weeks) hepatic dysfunction
must exclude malnutrition and renal or GI losses
Hepatobiliary Disease LabTests ________~ ~ - . a
l' AST, ALT = hepatocellular damage
sensitive but not specific for Iiver damage
implies hepatitis (inflammation) or vascular injury (ischemia)
if AST, ALT >1000, think of common bile duct stone, virus, drugs, ischemia,
autoimmune hepatitis
l' ALP with l' 5-NT' and/or GGT = cholestatic disease
biochemical cholestasis (drugs, primary biliary cirrhosis)
systemic disease (e.g. sepsis), pregnancy
infiltrative disease (tumour, fat, lymphoma)
mass lesions (stone, tumour, abscess)
Hepatitis
Etiology
viral infection
toxins
drugs
immune-mediated
Acute Viral Hepatitis
Definition
viral hepatitis lasting < 6 months
Clinical Features
most are subclinical
prodrome (flu-like illness) may precede jaundice by 1-2 weeks
nausea, vomiting, anorexia, taste/smell disturbance (aversion to cigarettes)
headaches, fatigue, malaise, myalgias
low-grade fever may be present
arthralgia and urticaria (especially hepatitis B)
All clotting factors except factor VIII are
exclusively synthesized in the liver.
" ' ,
.}------------,
Order of deterioration of Liver Function
Tests: 1. tPTnNR 2, t bilirubin
3. -l-Albumin
,,' ,
.')-------------,
Serum transaminases >1000 due to
- viral hepatitis
drugs
common bile duct stone
hepatic ischemia
rarely immune hepatitis
G32 Gastroenterology Liver Toronto Notes 2008
icteric (clinical jaundice) phase (50% of cases) lasting days to weeks
pale stools and dark urine 1-5 days prior to icteric phase
hepatomegaly plus RUQ pain
splenomegaly and cervical lymphadenopathy (10-20% of cases)
Investigations
hepatocellular necrosis which causes t AST, ALT >1O-20x normal
ALP and bilirubin minimally t
WBC normal or slightly decreaSf'd initially, followed by relative lymphocytosis with
atypicallyrnphocytes (similar to mononucleosis)
Treatment
supportive (hydration, diet)
indications for hospitalization: encephalopathy, coagulopathy, severe vomiting,
hypoglycemia
treat acute hepatitis C with interferon ribavarin if HCY-RNA persists after
8 weeks, especially if asymptomatic
Prognosis
90% resolve spontaneously, - 1% fulminant
chronic
hepatitis C 80%
hepatitis B5%
hepatitis A never becomes chronic
poor prognostic indicators
comorbidities
persistently high bilirubin (>340 mmol/L; 20 mg/dL), t rNR, -!- albumin,
hypoglycemia
cholestasis - most commonly during hepatitis A virus (HAV) infection
Symptoms
~ - - - anti-HBs
anti-HBc IgG
------ anti-HBc IgM
2 3 4 5 6 12 24
months after inoculation
Figure 12. Time Course of Acute Hepatitis BInfection
Fu minant Hepatic Failure
(1) rapid (characteristically less than 8 weeks) development of hepatocellular
dysfunction (usually including high bilirubin, INR)
(2) encephalopathy (due to cerebral edema)
(3) no prior history of liver disease
causes: drugs, especially acetaminophen, hepatitis B (ask for serum HBV-DNA
because sometimes HBsAg rapidy becomes negative), hepatitis A, exacerbation of
chronic disease (Note: hepatitiS e is rare in this setting)
management: usually in reu, correct hypoglycemia, monitor level of consciousness
(some centres still use intracranial pressure monitoring), prevent Gl bleeding with
proton pump inhibitor, vigilant for infection and multiorgan failure
consider liver biopsy before INR becomes too high; chief value is to exclude chronic
disease, less helpful for prognosis
liver transplant: consider early, especially if 1) rapid deterioration, 2) age <10 or >40,
cause is drug or unknown, bilirubin >400, INR >3.5, creatinine >200
Ctironic Hepatitis
Definition
an increase in serum transaminases for >6 months; requires a liver biopsy to
determine severity/need of treatment
Etiology
viral (8, B+O, C not A or E)
drugs (methyldopa, INH, nitrofurantoin, amiodarone)
autoimmune
-------------
genetic (Wilson's disease, (Xl-antitryrsin deficiency)
metabolic (nonalcoholic steatohepatitis: NASH)
Clinical Features
often asymptomatic, detected incidentally
constitutional symptoms
fatigue, malaise, anorexia, weight loss
signs of chronic liver disease
hepatomegaly (firm) and splenomegaly
l' ASI, ALI
Chronic Hepatitis C (HCV)
diagnosis: anti-HCY positive in most cases (exception: immunosuppression such as
HIV, post renal transplant) used for screening, positive serum HCV-RNA establishes
diagnosis
accounts for at least 50% of chronic hepatitis in USA
80% of acute hepatitis C becomes chronic, especially if acute infection is anicteric,
asymptomatic
20% of chronic HCY progresses to cirrhosis, especially if high alcohol intake
3% of cirrhotics develop hepatocellular carcinoma (HCC), especially in Japan
in contrast to hepatitis B which predisposes to HCC even in the absence of
cirrhosis
Iime course:
chronic hepatitis at 10 years
cirrhosis at 20 years
HCC at 30 years
Treatment
minimize alcohol intake
strict blood precautions (but risk of sexual transmission low)
vaccinate for hepatitis A, B unless already immune
HCC screening with ultrasound and serum alpha fetoprotein if cirrhosis present
peglyated interferon alpha 2b or 2a plus ribavarin - clearest indication is for those with
high ALI + liver biopsy showing scarring; overall sustained remission rate of 40%,
especially if non-la/lb genotype, absence of cirrhosis, low HCY-RNA, high ALI;
multiple side-effects, including depression, flu-like symptoms, bone marrow
depression from interferon, anemia from ribavarin
commonest indication for liver transplant in North America even though recurrence of
HCY infection universal after transplant
Chronic Hepatitis B (HBV)
Table 13. Hepatitis B Serology
HBsAg Anti-HBs HBeAg Anti-HBe Anti-HBc
Acute HBV + + IgM
C h r o ~ i c HBV (high infectivity)
+ + IgG
Chronic HBV (low infectivity)
+ + IgG
Recovery + + IgG
Immunization
+
Epidemiology
develops in 1-2% of healthy adults with acute hepatitis B, higher if immunosuppressed
(HIV, renal dialysis, post transplant, cancer chemotherapy), very high (90%) ifiitfected
at birth
4 Patterns: all have positive HBsAg
(a) active virus replication with high HBY-DNA, HBeAg positive, but normal
ALI/AST, characteristic of perinatal infection
(b) active virus replication, HBeAg positive, HBY-DNA >100,000 copies/ml,
characterized by progressive disease without treatment, sometimes to
cirrhosis and/or hepatocellular carcinoma
(c) virus slowly replicating with HBY-DNA <100,000 copies/ml, HBeAg
negative, ALI/ASI normal, risk of reactivation to pattern (b) especially
with immunosuppression such as corticosteroids, lymphoma, reactivation
clinically resembles acute hepatitis B
(d) "core or precore mutant" = active virus replication with HBY-DNA >100
copies/m1, HBeAg negative because of promoter gene mutation, ALI/ASI
high, tends to progress, treatment difficult therefore prognosis poor
IFN 8I1d Ribavirin for Hepatitis C
NEJM 1998;339(211: 1485-92
Study. Randomized efficacy trial.
1'lItier/l$. 912 patients with dlronic hepatitis C,
InterwNrtion: IFN a-2b alone or in combination
with ribavirin for 24 or 48 weeks.
M.in IItItcomes: Efficacy as assessed by
serum HCV RNA, AST/AlT, and liver biopsy,
IlftuJts: The rate of sustained virologic
response (undetectable HCV RNA level 24 wks
after treatment completion1was higher in the
IFN +ribavirin group (31% vs, 6%, p<1J,0011,
Drug doses had to be reduced and treatment
discontinued more often in patients on combi-
nation therapy,
ConduIIon: In patients with dlronic hepatitis
C, initial treatment with IFN +ribavirin was
more effective than treatment with IFN alone,
o
Liver Enzymes
ALl; AST elevated
ALl; AST normal
lamivudine for chronic hepatitis B
(NEJM 1999;341(17):1256-631
Study. Multicentre, randomized, double-
blinded, placebo-controlled trial.
Patients. 143 patients with HBsAg positive,
HBeAg positive, All elevated chronic hepati-
tis Binfection. Also had chronic hepatitis on
liver biopsy and detectable serum levels of
HBV DNA.
Intervention: 100 mg orallamivudine daily
for 1year.
Main outcomes. Histologic response at 1
year (a decrease of 2points on the histologic
activity index), HBeAg seroconversion (loss
of HBeAg, presence of HBeAb, and unde-
tectable HBV DNA levels), All normalization.
Ruults. 52% of patients in the lamivudine
group experienced ahistologic response,
17% experienced HBeAg seroconversion, and
41% of patients had normalized All levels,
compared to 23%, 6%, and 7% respectively in
the placebo group (p<O.OO1, p=O.04, and
p<O.001 respectively).
Conclusion: lamivudine treatment
improves histologic, virologic, and biochemi-
cal features of chronic hepatitis Binfection.
.... ,,
9\-----------.
HDV increases severity of hepa-
titis but does not increase risk of
progression to chronic hepatitis.
.... ' ,
9)----------...,
Causes of a Spike in Serum
Transaminases in Chronic
Hepatitis B
Reactivation (anti-HBe convert-
ing to HBeAg; occurs especially
with immunosuppression)
5eroconversion (HBeAg con-
verting to antiHBe; especially
with Rx such as interferon)
Hepatitis D
Hepatocellular carcinoma
Liver insult (alcohol, drugs,
hepatitis A)
Progression of disease
Liver Toronto Notes 200S
Pathophysiology
generally liver damage is caused more by the immune response to the hepatitis B virus
than from the virus itself
2 phases of viral replication
replicative phase (HBeAg +ve)
high infectivity: 1'liver injury
associated with more severe"hepatitis (e.g. chronic active hepatitis)
non-replicative phase (anti-HBe +ve)
10w infectivity and minimal liver injury
associated with milder disease (e.g. chi-onic persistent hepatitis)
distinctions in replicative phase and histological classification do not
always coincide
Treatment
limit alcohol intake, blood and sex precautions, vaccinate close contacts, give immune
globulin immediately after birth if mother has high serum HBV-DNA, hepatoma
screening with abdominal ultrasound every 6 to 12 months and perhaps serum
alpha-fetoprotein (although evidence for screening is poor, risk fughest in males,
HBV-DNArositive), if HBV-DNA negative warn about possibility of reactivation
(especially i on corticosteroids, immunosuppressive illness), if HEV-DNA positive
warn about possibility of progression into cirrhosis
pharmacological options:
interferon (6 month course leads to remission in 25% of cases), lamivudine (few
side effects but high likelihood of virus resistance developing within 3 years of
starting the drug), adefovir (can cause renal failure), entecaVlr (available soon),
telbiruaine (more potent than larnivudine), tenofivir (also effective against HN)
RISE IN ALT/AST IN A PATIENT WITH CHRONIC HEPATITIS B
hepatocellular carcinoma, hepatitis D, reactivation if known to be anti-HBeAg, flare if
known to be HBeAg positive, progression of disease, superimposed acute hepatitis
from drugs, alcohof, viruses such as A, C, Epstein-Barr
Hepatitis D
defective RNA virus requiring HBsAg for enry into hepatocyte, therefore infects only
patients with hepatitis B, causes more aggreSSIve disease than hepatitis B virus alone
Chronic Hepatitis B + D
low-dose interferon has limited impact, high-dose under investigation
liver transplant more effective than in HBV alone
liver transplant for end stage disease (reinfection rate 100% but infection usually mild)
Autoimmune Chronic Active Hepatitis
can be severe: 40% mortality at 6 months without treatment
diagI!osis of exclusion: rule out viruses, drugs, metabolic or genetic derangements
extrahepatic manifestations
amenorrhea, rashes, ame, thyroiditis, Sjogren's
immune complex disease: arthritis, GN, vasculitis
antibodies
hypergammaglobulinemia
ANA (antinuClear antibody homogenous), RF (rheumatoid factor),
anti-smooth muscle, anti-lKM (liver kidney microsome)
can have false positive viral serology (especially anti-HeY)
management: steroids (80% respond) azathioprine
Drug-Inaucea
Table 14. Classification of Hepatotoxins
Direct Indirect
Example Acetaminophen, CCI. Phenytoin, INH
Dose-dependence Usual Unusual
Latent Period Hours-days Weeks-months
Host Factors Not important Very important
Predictable Yes No
Specific Drugs
Acetaminophen
metabolized by hepatic cytochrome P450 system
can cause fulminant hepatic failure (transaminases >1,000 U/L)
....
....,
Table 15. Characteristics of the viral hepatitides
Virus Transmission Incubation Communicability Serology Management Prognosis Complications
0
a
::;
6"
Z
Hepatitis A Fecal-oral 2-6 weeks 2-3 weeks in late incubation
to early clinical phase
acute hepatitis in most adults,
10% of children
General hygiene
Treat close contacts
lanti-HAV Ig, 0,02 mg/kg ASAP)
Prophylaxis for high-risk groups
0
;:0
en
N
8
ex>
IHAV vaccine HAV Ig)
unless immune
Hepatitis B Parenteral or equivalent 6weeks - 6months During HBsAg+ state SeeTable 13 HBV vaccine ami/or Chronicity in 5% Serum sickness-like syndrome
Vertical Highly communicable HBeAg+ state Hepatitis BIg IHBIG): for Glomerulonephritis
1'duringT3 or early post-partum needlestick, sexual contact, infants Cryoglobulinemia
of infected mothers unless already Polyarteritis nodosa
immune Porphyria cutanea tarda
Hepatitis C Parenteral (transfusion, 5-10 weeks HCVRNA Prevention Ino vaccine) Chronicity in 80%
IVOU, sexual <HBV) (detected by PCRI Rx: IFN +ribavirin
40% have no known Anti-HCV (lgG/lgMI
risk factors
Hepatitis D Non-parenteral Infectious only in presence HBsAg Prevention Predisposes HBV carriers to severe fulminant course
Iclose contact in of HBV (HBsAg required for Anti-HDV ( l g G ~ g M ) HBV vaccine
endemic areas) replication) ,.....
Parenteral
Iblood products, IVDU)
=t
'"
...
Hepatitis E Fecal-oral (endemic: 2-6 weeks Anti-HEV ( l g G ~ g M ) Prevention (no vaccinel Mild, except in third trimester (10-20% fulminant liver failure)
Africa, Asia, central
America, India, Pakistan)
C"l
'"
I
'"
~
~
C"l
~
~ '
Clinical manifestions of
Wilson's disease: ABCD
Asterixis
Basal ganglia degeneration
Ceruloplasmin .Jt
Cirrhosis
Corneal deposits (KF ringl
Copper l'
Choreiform movements
Carcinoma (HCCI
Dementia
Liver Toronto Notes 2008
requires 10-15 g in normals, 4-6 g in alcoholics/anticonvulsant users
recent studies have emphasized liver disease in chronic users >4 glday
mechanism: high acetaminophen dose saturates glucuronidation and sulfation
elimination pathway -+ reactive metabolite is formed --> covalently binds to
hepatocyte membrane
presentation
first:24 hrs: nausea and vomiting usually within 4-12 hours
next :24-48 hrs: hepatic necrosis resulting in l' aminotransferases,
jaundice, possibly hepatic encephalopathy, acute renal failure, death
after 48 hrs: continued hepatic necrosis/resolution
note: potential delay in presentation in sustained-release products
blood levels of acetaminophen correlate with the severity of hepatic injury,
particularly if time of ingestion known
therapy
gastric lavage/emesis (if <2 hrs after ingestion)
oral charcoal
N-acetylcysteine can be given PO or IV, most effective within 8-10
hours of ingestion, but should be given no matter when time of
ingestion; promotes hepatic glutathione synthesis
Chlorpromazine
cholestasis in 1% after 4 weeks; often with fever, rash, jaundice, pruritus and
eosinophilia
INH
20% develop elevated transaminases but <1% develop clinically significant
disea&e
susceptibility to injury increases with age
Methotrexate
may rarely cause cirrhosis, especially in the presence of obesity, diabetes,
alcoholism
scarring develops Witllout symptoms or changes in liver enzymes, therefore
biOpsy may be needed in long-term treatment
Amiodarone
can cause same histology and clinical outcome as alcoholic hepatitis
Others
azoles, statins, methyldopa, phenytoin, PTU, rifampin, sulfonamides,
tetracycline&
Wilson's Disease
Definition
autosomal recessive defect in copper metabolism
Clinical Manifestations
slow accumulation of copper with deposition in tissues
liver: cirrhosis, chronic active hepatitis, acute hepatitis, fulminant liver failure,
low risk of HCC
eyes: Kayser-Fleischer rings (copper in Descemefs membrane); more common in
patients with CNS involvement
CNS: basal ganglia (wing flapping tremor, Parkinsonism), cerebellum (dysarthria,
dysphagia, incoordination, ataxia), cerebrum (psychosis, affective disorder)
kidneys: Fanconi's syndrome (proximal tubule transport defects) and stones
blood: intravascular hemolysis: may be initial presentation in fulminant hepatitis
joints: arthritis, bone demineralization, calcifications
Investigations
suspect if increase liver function test (LFTs) with clinical manifestations
requires 2 of the following 3 for diagnosis:
1. reduced total serum copper (and low serum ceruloplasmin)
2. l' liver copper on biopsy
3. Kayser-Fleischer rings
other tests
radiocopper incorporation study: diagnostic
urine copper 1': non-specific
molecular (gene) analysis, usually liver tissue required
Treatment
d1elators (penicillamine, trientine): l' urinary excretion of copper
zinc acetate: l' absorption of copper in diet and enterohepatic circulation
screen relatives
liver transplant in severe cases
Toronto Notes 2008 Liver
Hemochromatosis
Definition
excess iron storage, which causes multiorgan system dysfunction with total body
stores of iron t to 20-40 g (normal 19)
Etiology
may be primary or secondary
primary hemochromatosis
due to common recessive gene (5%); 1/400 patients are homozygotes
results in t gut absorption of iron
secondary hemochromatosis
parenteral iron overload: transfusion
chronic hemolytic anemia: thalassemia, pyruvate kinase deficiency
excessive iron intake
Clinical Features
usually presents with trivial elevation in serum transaminases or during screening
liver: cirrhosis; 30% get HCC (200x t risk); most common cause of death (1/3 of
patients)
pancreas: "bronze" diabetes, chronic pancreatitis
skin: bronze or grey (due to melanin, not iron)
heart: dilated cardiomyopathy
pituitary: hypogonadotropic hypogonadism (impotence, .J, libido, amenorrhea)
joints: arthralgia (especially MCP joints of hands), chondrocaldnosis
Investigations
screening for individuals with clinical features and/or family history (1/4 chance of
sibling having the disease)
transferrin saturation (free Fe/TIBC) >50%
serum ferritin >400
HFE gene analysis: 90% of idiopathic hemochromatosis have Cys 282 Tyr (C282Y) gene
mutation, or less frequently His 63 Asp (H63D)
liver biopsy (to define degree of iron overload and to detect cirrhosis)
hepatoma screening if cirrhosis
Treatment
phlebotomy: once or twice weekly until anemia develops or serum iron and ferritin
normalizes; then lifelong maintenance phlebotomies q 2-6 months
deferoxamine if phlebotomy contraindicated (e.g. cardiomyopathy, anemia)
primary hemachromatosis responds well to phlebotomy (secondary hemochromatosis
responds poorly)
Prognosis
normal life expectancy if treated before the development of cirrhosis or diabetes
Alcoholic Liver Disease
Types of Lesions
fatty liver (all alcoholics): always reversible
alcoholic hepatitis (35% of alcoholics): usually reversible
cirrhosis (10-15% of alcoholics): irreversible
Pathophysiology
several mechanisms that are incompletely understood
fatty liver related to t NADPH ---> fatty acid and triglyceride formation
EtOH impairs release of triglycerides causing accumulation in the liver
acetaldehyde is probably a direct toxin
combines with hapten ---> immunological damage
alcohol metabolism causes
relative hypoxia in liver zone III > zone I
necrosis and hepatic vein sclerosis
alcohol causes liver cells to swell
turbulence in sinusoids
deposition of collagen in the space of Disse
portal hypertension
Gastroenterology G37
o
~
..... ,,
9.)---------------,
..... ' ,
9.)---------------,
GI Complications of Alcohol Abuse
Esophagus:
Mallory-Weiss tear
Esophageal varicies (secondary to portal
hypertension)
Pancreas:
Acute pancreatitis
Liver:
Alcoholic hepatitis
Fatty liver
Cirrhosis
Hepatic encephalopathy
Portal hypertension (secondary to cirrhosisI
Ascites Isecondary to cirrhosisl
..... ' ~
9}-----------,
Biopsy +histology of alcoholic hepatitis
(triad)
hepatocyte necrosis with surrounding
inflammation in zone III
Mallory bodies (intracellular
eosinophillic aggregates of
cytokeratins)
spider fibrosis (network of intralobular
connective tissue surrounding cells
and venulesl
[
o
..... ' ~
9}-------------,
In fatty liver, distinguish between
microvesicular (early) and macro-
vesicular (late).
..... ' ~
9)-------------,
Most Common Cause of Liver
Diteale
t TG. eIlol, insulin resistance
tAlT
Liver bx diagnostic
a
Clinical Features
threshold for cirrhosis is 40 g EtOHiday in females or >80 g EtOH/day in males
x 10-20 years
clinical findings do not predict type of liver involvement
fatty liver
mildly tender hepatomegaly; jaundice rare
mildly l' transaminases <5x normal
alcoholic hepatitis
variable severity: mild to fatal liver failure
clinically similar to viral or toxic injury
constitutional symptoms fever, abdominal distention, jaundice, tender
hepatomegaly, splenomegaly (1/3)
blood tests are non-specific, but in general
AST:ALT > 2:1 (transaminases rarely >600, usually <300)
l' GGT, l' triglycerides, l' INR
l' mean corpuscular volume (MeV), l' platelets (suggests alcohol abuse)
Treatment
alcohol cessation (see Psychiatry, PS20)
Alcoholics Anonymous, disulfuram, lithium, naltrexone
multivitamin supplements (with extra thiamine)
caution giving drugs metabolized by the liver
prednisone
has been shown to decrease mortality in a severely ill subgroup with alcoholic
hepatitis characterized by 1'bilirubin, 1'INR, encephalopathy, but no GI
bleeding
pentoxyphilline decreases TNF, shown in one article to reduce mortality in alcoholic
hepatitis, now widely used because so few side effects
Prognosis
fatty liver: rapid and complete resolution with cessation of EtOH intake
alcoholic hepatitis mortality
immediate: 5%
with continued alcuhol: 70% in 5 years
with cessation: 30% in 5 years
Non-Alcoholic Fatty Liver Disease (NAFLD)
Etiology
macrovesicular fat: most common is "NASH" = non-alcoholic steatohepatitis
commonest cause of liver disease in North America
characteristically develops in middle-aged, over-weight women with type II diabetes,
but increasingly recognized in all populations especially young men
associated with elevated serum tryglyceride/cholesterollevels and insulin resistance
presents as echogenic liver texture on ultrasound, elevated serum ALT (exclude other
causes of l'ALT)
losing body weight might be of benefit
has been described to progress to cirrhosis especially if inflammation/scarring on liver
biopsy or if obese
microvesicular fat: jejuno-ileal bypass, fatty liver of pregnancy, Reye's syndrome
fat in liver also recognized from drugs e.g. methotrexate, tetracycline, amiodarone,
valproic acid
liver biopsy diagnostic but often necessary only for prognosis
Cirrhosis
Definition
diffuse, irreversible fibrosis plus hepatocellular nodular regeneration
decompensated cirrhosis: means ascites has developed
Etiology
alcohol (85%)
viral (B, B+D, C but not A nor E)
autoimmune
hemachromatosis
a-I-antitrypsin deficiency
drugs and toxins
methotrexate
biliary cirrhosis
primary
secondary
chronic hepatic congestion
cardiac cirrhosis (chronic right heart failure, constrictive pericarditis)
hepatic vein thrombosis (Budd-Chiari)
idiopathic
rare - Wilson's disease, Gaucher's
Diagnosis
blood work: liver enzymes, bilirubin, PT/pTI, l' gamma globulin
imaging: DIS is the primary imaging modality, then CT
liver biopsy: the onTy way to definitely diagnos(' cirrhosis
Management
treat underlying disorder
alcohol cessation
follow patient for complications (see below)
colchicine may be of some benefit
prognostic factors include (see Table 16)
nutrition (EtOH consumption)
ascites
varices
encephalopathy
labs: albumin, INR, bilirubin
liver transplantation for end-stage disease
Complications
hematologic changes in cirrhosis
pancytopenia from hypersplenism
'V clotting factors
fibrin, thrombin, I, II, V, VII, IX, X
renal failure in cirrhosis
classifications
pre-renal
acute tubular necrosis (ATN)
hepatorenal syndrome
hepatorenal syndrome can occur at any time in severe liver disease,
especially after:
overaggressive diuresis or large volume paracentesis
GI bleeding
sepsis
differentiate hepatorenal syndrome from pre-renal failure
prerenal azotemia =hepatorenallab findings (see Nephrology, NP30)
clinical (very difficult)
intravenous fluid challenge (giving volume expanders improves
prerenal failure but not hepatorenal syndrome)
pulmonary capillary wedge pressure measurements (PCWP)
(preferable)
differentiate hepatorenal syndrome from ATN
treatment for hepatorenal syndrome is generally unsuccessful
- vasopressin, octreotide, midodrine
(1' renal blood flow by l' systemic vascular resistance)
definitive treatment is liver transplant
Effects of Portal Hypertension
esophageal varices
/' gastric varix --> melena
splenomegaly
caput medusa, paraumbilical hernia
ascites
hemorrhoids
loss of sexual hair, testicular atrophy

palmar erythema, ------,
Dupuytren's contracture, asterixis
anemia
Figure 13. Clinical Features Of Liver Disease
..... ' ,
.'}----------,
Causes of HCC
Cirrhosis due to:
Hep B=most common
Alcohol abuse
Hemochromatosis
a-' anti-trypsin
~ i
Precipitating Fector. for Hepetic
Encephelopllthy:
Hemorrhage in GI tractIHyperkalemia
Excess dietary protein
Paracentesis
Acidosis/Anemia
Trauma
Infection
Colon surgery
Sedatives
Hepatocellular Carcinoma
characteristically underlying liver disease - cirrhosis of any cause, or hepatitis Bof any
severity
usually presents as apparent worsening of underlying liver disease (increased ascites,
variceal bleed, jaundice, alkaline phospnatase) or upper abdominal pain
imaging shows focal mass in liver with arterial hypervascularity, in underlying
cirrhosis this is often sufficient for diagnosis, obviating need for biopsy, especially if
nodules >2 cm + serum alpha fetoprotein >400 nglmL
treatment: hepatic resection if normal liver, liver transplant if cirrhosis plus solitary
nodule <5 em, or less than 3 nodules each <3 cm (Milan criteria)
non-surgical candidates: ultrasound guided tumour thermoablation, or injection with
ethanol, acetic acid
LiverTransplant
early referral for transplant should be considered for all patients with progressive liver
disease not responding to medical therapy, especially decompensated cirrhosis,
unresectable primary fiver cancers, and fulminant hepatic failure
hepatitis B virus prophylactic medical therapy is usually effective in preventing
recurrence in graft; h.epatitis C anti-recurrence therapy IS less effective but recurrence is
usually controllable medically
most common indications: chronic hepatitis C, alcoholic liver disease, chronic heaptitis B,
cryptogenic cirrhosis, primary biliary cirrhosis
contraindications: sepsis, extrahepatic malignancy, AIDS, active alcoholism/substance
abuse, advanced cardiac or pulmonary disease
priority for transplantation dependent upon MELD (Model for End Stage Liver Disease)
score, a mathematical formula incorporating serum bilirubin, INR and creatinine
choice between cadaver donor and liver donor
5 year survival rate following transplant is 40% to 80%, depending upon age,
pretransplant bilirubin and creatinine
Hepatic Encephalopathy
~ - - - - - - - - - - - - - -
Definition
acute neuropsychiatric syndrome secondary to liver disease
Pathophysiology
porto-systemic snunt around hepatocytes increases toxins (believed to be ammonia
from gut, mercaptans, fatty acids, ammo acids) to brain
Precipitating Factors
nitrogen load (GI bleed, protein load from food intake, renal failure, constipation)
drugs (narcotics + CNS depressants)
electrolyte disturbance (hypokalemia, alkalosis, hypoxia, hypovolemia)
infection (Le. spontaneous bacterial peritonitis)
deterioration in hepatic function or superimposed liver disease
Stages
I: apathy, restlessness, reversal of sleer rhythm, slowed intellect, impaired
computational abilities, impaired hanawnting
II: asterixis, lethargy, drowsiness, disorientation
III: stupor (arousable), hyperactive reflexes, extensor plantar responses
N: coma (response to painful stimuli only)
Investigations
distinguish from non-liver-related neuropsychiatric disease in a patient with liver
problems (e.g. alcohol witl1drawal or intOXICation, sedatives, subdural hematoma,
metabolic encephalopathy)
diagnosis chiefly clinical, supported by laboratory findings, exclusion of other
neuropsychiatrIc diseases
only pathognomonic finding is fetor hepaticus
characteristic EEG findings: diffuse (non-focal), slow, high amplitude waves
Treatment
treat underlying liver disease and precipitating factors
decrease generation of nitrogenous compounds
oJ, dietary protein to 50 glday; vegetable protein is better tolerated than animal
protein
lactulose
prevents diffusion of NH
3
(amononia) from the colon into blood by
lowering pH and forming non-diffusible NH
4
+ (ammonium)
serves as a substrate for incorporation of ammonia by bacteria, promotes
growth in bowel lumen of bacteria which produce minimal ammonia
also acts as a laxative to eliminate nitrogen-producing bacteria from colon
if inadequate response with lactulose, may try antibiotics
broad-spectrum antibiotics (tetracycline, metronidazole, neomycin) eliminate
ammorua-producing bacteria from bowel lumen
neomycin IS less effective than lactulose plus more side effects (ototoxicity,
nephrotoxicity)
combination of the two may be more effective
Portal Hypertension
Pathophysiology
pressure =flow x resistance
Unlikely that l' flow alone can cause portal hypertension (although described in
AV-fistula or massive splenomegaly)
3 sites of l' resistance
pre-sinusoidal (e.g. portal vein thrombosis, schistosomiasis, sarcoidosis)
sinusoidal (e.g. cirrnosis, alcoholic hepatitis)
post-sinusoidal (e.g. right-sided heart failure, hepatic vein thrombosis,
veno-occlusive disease, constrictive pericarditis)
signs of portal hypertension: see sidebar
Management
(propanolol, nadolol) and nitrates decreases risk of bleeding from varices
shunts
goal: decrease portal venous pressure
transjugular intrahepatic portosystemic shunt (TIPS): interventional radiologist
creates a shunt between portal and hepatic vein via a catheter placed in the liver
can be used to stop acute bleeding or prevent rebleeding
shunt usually remains ORen for no longer than up to one year
other (rare): portocaval, Clistal spleno-renal (Warren shunt)
Table 16. Child-Pugh Classification .... ,
.l-----------,
2 3
Portal Hypertension
Serum bilirubin <34 34-51 >51
Cause =l'flow AND l'resistance
Serum albumin (giLl >35 28-35 <28
Signs
Presence of ascites Absent Controllable Refractory
Esophageal varices
Encephalopathy Absent Minimal Severe
Melena
INR <1.7 1.7-2.3 >2.3 Splenomegaly
Ascites
Score: 5-6 (Child's Al. 7-9 (Child's Bl. 10-15 (Child's C)
Hemorrhoids
'Note: Child's classification is rarely used for shunting, but is still useful to quantitate the severity of cirrhosis
Management
Left gastric vein

_ Right gastric Nitrates
vein Shunts [e.g. Transjugular intrahepatic
Portal vein----+-'=,..L-----"O;
portosystemic shunt (TIPSIl

Splenic vein
mesenteric vei n
....... Inferior
mesenteric vein
U",l:cIi4-- Left colic vein
Ileocolic vei
Sigmoid and
rectosigmoid veins
Superior rectal vein

vein
Figure 14. Anatomy of Portal Venous System
o
..... ' ,
,\-----------.,
Secondary bacterial peritonitis (as
opposed to primary bacterial peritoni-
tis) usually results from aperforated
viscus or surgical manipulation.
Ascites
Definition
accumulation of excess free fluid in the peritoneal cavity
Etiology
Table 17. Serum-Ascites Albumin Ratio as an Indicator of the Causes of Ascites
serum [Albl . ascitic [Albl >11 gil serum [Albl . ascitic [Alb] <11 gil
Cirrhosis/severe hepatitis Peritoneal carcinomatosis
Chronic hepatic congestion TB
(right heart failure, Budd-Chiaril Pancreatic disease
Massive liver metastases Serositis
Myxedema Nephrotic syndrome"
" in nephrotic syndrome -J.. serum [Alb] to begin with therefore ratio not helpful
Pathogenesis of Ascites in Cirrhosis
normal physiology
intravascular hydrostatic pressure (HP) and oncotic pressure (OP) are balanced
(Starling forces) ---+ preventing accumulation of extravascular fluid into
peritoneal space
in cirrhosis, HI' and OP balance is disrupted, precipitating ascites by one or more
of the following mechanisms:
fibrotic constriction of sinusoids resulting in portal HTN and increased HP
---+ increased HP drives fluid lymphatic drainage into the abdomen via
hepatic capsules
renal hypoperfusion ---+ Na and H
2
0 retention
less important fact is hypoalbuminemia ---+ decreased OP
underfill theory
portal hypertension and hypoalbuminemia lead to transudation of Na and
water into peritoneum causing -It intravascular volume and secondary renal Na
and water retention
overflow theory
liver disease primarily causes renal retention of Na and water which then
"overflows" into peritoneal cavity
combined theory - incorporating both above theories is most popular
liver disease causes vasodilation, increasing vascular capacitance
-It effective intravascular volume (i.e. volume to capacitance ratio low,
but absolute volume is high)
secondary urinary Na and water retention
Diagnosis
clinically detectable when >500 mL
Investigations
diagnostic paracentesis - should be done on most patients:
cells and differential
chemistry (albumin, protein, amylase, TG)
C&S, gram stain
cytology (usually positive in peritoneal carcinomatosis)
Treatment
therapeutic paracentesis safe, especially if albumin infusion given concomitantly
medical
Na restriction
diuretics (spironolactone, furosemide)
aim for 0.5 kg loss per day to prevent ARF (this is maximum rate of ascitic fluid)
surgical
TIPS, liver transplantation (reserved for medically refractory cases)
Complication: Bacterial Peritonitis
primary/spontaneous bacterial peritonitis (SBP)
complicates ascites, does not cause it (occurs in 10% of cirrhotic ascites)
1/3 of patients arc asymptomatic, thus do not hesitate to do a diagnostic
paracentesis
fever, chills, abdominal pain, ileus, hypotension, worsening encephalopathy
gram compose 70% of pathogens: E. coli (most common pathogen),
Klebslcfla
-----
Toronto Notes 2008 LiverlBiliary Tract Gastroenterology G43
diagnosis:
absolute neutrophil count in peritoneal fluid >O.25x10
9
cellslL (250 cells/mm
3
)
or WBC count >O.5x10
9
cells/L (500 cells/mm
3
)
gram stain is positive in only 10-50% of patients
culture is positive in only 80% of patients (not needed for diagnosis)
treatment
IV antibiotics (cefotaxime is the treatment of choice until C&S is available) for
5-10 days; prophylaxis with daily norfloxacin or TMP-SMX for 5-7 days may
decrease the frequency of recurrent SBP, use if GI bleeding! previous SBP
IV albumin decreases mortality
Hepatopulmonary Syndrome
1) pulmonary vascular dilation 2) hypoxemia 3) underlying liver disease
serum p0
2
worse in standing position (orthodeoxia) perhaps because more
shunting at base of lung
diagnosis: established by contrast-enhanced echocardiography; microbubbles
("agitated saline") injected into peripheral vein normally filtered by pulmonary
circulation so not seen in left heart but in hepatopulmonary syndrome the
vascular dilation allows the bubbles to pass mto the left heart where they are
visualized by echocardiography (more than 4 heartbeats after bubbles seen in
right heart to distinguish from intracardiac shunt when bubbles seen <3 heartbeats)
BiliaryTract
Basic Anatom Review
consists of the hepatic ducts (intrahepatic, left, right and common), gallbladder,
cystic duct, common bile duct and ampulla of Vater
The general purpose of the gallbladder is to store and release bile that is produced in
the liver. Bire is used to emulsify fats and is composed of cholesterol, leCIthin, bile
acids and bilirubin. CholecystolGnin stimulates gallbladder emptying while trypsin
and chymotrypsin inhibit bile release
gallbladder blood supply: cystic artery (from the right hepatic artery) and cystic vein
Jaundice
o
see Table 18, Figures 15 and 16
Definition
yellow pigmentation of skin, sclerae and mucous membranes due to l' serum bilirubin
(3 mg!mL)
Signs and Symptoms
dark urine, pale stools - suggest that bilirubin elevation is from direct fraction
pruritus - suggests chronic problem
abdominal pain suggestive of biliary tract obstruction from stone or pancreatic
tumour (obstructive jaundice)
GM Gastroenterology Biliary Tract Toronto Notes 2008
Table 18. Classification of Jaundice
I. Predominantly OnconJugated Hyperbilirubinemia
RBe destruction (reticulo-endothelial system)
1. Overproduction
Hemolysis (spherocytosis, autoimmune disorders)

Ineffective erythropoiesis (megaloblas1ic anemias)
Hb ---.-globin
2. Decreased hepatic uptake
Gilbert's syndrome
Drugs (e.g. rifampin, radiographic contrast agents)
heme
3. Decreased conjugation
Drug inhibition le.g. chloramphenicol)
Crigler-Najjar syndromes type I and II
Neonatal jaundice
1
Gilbert's syndrome
bilirubin (unconjugatedl
II. Predominantly Conjugated Hyperbilirubinemia
1. Impaired hepatic secretion
Familial disorders (e.g. Rotor syndrome,
Bilirubin -Alb
Dubin-Johnson syndrome, cholestasis of pregnancy!
Hepatocellular disease - by far the most common

Drug-induced cholestasis le.g. oral contraceptives,
LIVER
chlorpromazine!
glucoronyl
Primary biliary cirrhosis IPBC)
transferase
conjugates
Sepsis
15-20%
bilirubin
Post-operative
reabsorbed
2. Extrahepatic biliary obstruction
via
Intraductal obstruction
entero-
Gallstones
hepatic
biliary excretion into duodenum
Biliary stricture
circulation
Infection
t intestinal flora
Malignancy (cholangiocarcinomal
Sclerosing cholangitis
Urobilinogen (010% -
Extraductal obstruction
I excreted via urine
Malignancy le.g. pancreatic cancer, lymphoma)
Inflammation (e.g. pancreatitis!
70-85%
stercobilinogen
Investigations
bilirubin (conjugated and unconjugated)
t
conjugated (direct) and unconjugated (indirect)
AST, ALT, GGT, ALP
stool
serologic tests for hepatitis, hemachrumatosis, autoimmune liver disease, Wilson's
disease
Figure 15. Production and
ultrasound for evidence of bile duct obstruction
Excretion of Bilirubin
direct duct visualization
endoscopic retrograde cholangiopancreatography (ERCP)
percutaneous transhepatic cholangiography (PTC) - only if obstruction is
suspected to be periportal rather than near sphincter or if previous gastric
surgery
magnetic reSOIldIlce cholangiopancreatography (MRCP) - non-invasive
liver biOpsy
Jaundice 1'serum bilirubin
fractionate bilirubin
""fly roro7 ,h',flY'""i".,,"
hemolysis hepatobiliary disease
Gilbert's syndrome abdominal ultrasound
bile duct normy duct dilated
hepatocellular disease bile duct obstruction
drugs visualize bile duct
alcohol endoscopic endoscopic
virus bile duct bile duct
autoimmune decompression decompression
hemochromatosis not likely likely to be
Wilson's disease etc. to be necessary
necessary
MRCP ERCP
Figure 16. Approach to Jaundice
--------------
Toronto Notes 2008 Biliary Tract Gastroenterology G45
Gilbert's Syndro_m_e ~ _
Definition
mild decrease in glucuronyltransferase activity leading to defective conjugation of
bilirubin
some patients have whepatobiliary uptake
affects 7% of population, especially males
autosomal dommant
Signs and Symptoms
presents in teens-20s, often as an incidental finding
only manifestation is intermittent jaundice with l' serum unconjugatcd bilirubin
developing most characteristically while fasting
no treatment indicated (entirely benign)
Crigler-Najjer Syndrome
Definition
deficiency in uridine diphosphate glycosyltransferase leading to defective
conjugation of bilirubin
Etiology
autosomal recessive
rare disorder - only few hundred cases reported
Signs and Symptoms
Type I: persistent neonatal jaundice
neurological symptoms (hypotonia, deafness, oculomotor palsy, lethargy)
due to kernicterus may develop if untreated
prompt treatment of hyperbilirubinemia (plasma exchange, long term
r
hototherapy) necessary as this can be fatal
Type I : milder form, patient less likely to develop neurological symptoms in
childhood
neurological symptoms can be precipitated by infection, anaesthesia or drug
use
treatment with phenobarbital occasionally used to decrease serum bilirubin
Primary Biliary Cirrhosis (PBC) L
o
Definition
chronic inflammation and fibrous obliteration of intrahepatic bile ductules
probably autoimmune (associated with Sjogren's syndrome, scleroderma, CREST
syndrome, RA, thyroiditis)
affects mainly middle-aged women (male:female ratio of 1:9)
Signs and Symptoms
often asymptomatic
earliest symptoms: pruritus, fatigue
after severalmonths-years: jaundice and melanosis (darkening skin) and other signs of
cholestasis
eventually: hepatocellular failure, portal hypertension, ascites
Investigations
l' ALP, GGT
positive anti-mitochondrial antibodies (98% specificity)
l' cholesterol --> xanthelasmas, xanthomas (mild increase in LDL, larger increase in
HDL)
1'lgM
diagnosis based on liver biopsy and normal ERCP
(i.e. rule out common bile duct (CBD) stones and sclerosing cholangitis)
Clinical Course
may be ultimately fatal although not all asymptomatic patients progress
Treatment
may treat with ursodiol, less frequently colchicine, methotrexate, cyclosporine,
cholestyramine (for pruritus ancfhypercholesterolemia), parenteral fat soluble
vitamins, Vitamin D and Ca supplements
only proven treatment is transplant
G46 Gastroenterology Biliary Tract Toronto Notes 2008
o
..... ' ,
.\--------------,
Charcot'sTriad
'RUa
Fever
'Jaundice
",,' ,
.\--------------,
Raynaud's Pentad
Charcot's triad
hypotension
delirium
l
o
..... ' ,
.'}-----------.,
PBC = intrahepatic bile duct
inflammation vs. PSC =inflamma-
tion in entire biliary tree
..... ' ,
.}-----------.,
ERCP
absence of narrowing in PBC
narrowing of intra and extrahepatic
ducts in PSC
Seconda Biliary Cirrhosis -' ...... -.l!:....
Definition
results from prolonged partial or total obstruction of major bile ducts
Etiology
acquired: post-op strictures, chronic pancreatitis, sclerosing cholangitis, rarely stone in
bile duct
congenital: cystic fibrosis (CF), congenital biliary atresia, choledochal cysts
Diagnosis
cholangiography and liver biopsy
Treatment
treat obstruction, give antibiotics for cholangitis prophylaxis
Ascendin Cholangitis __ ...... !rO..
Definition
infection of the biliary tree secondary to stasis
Etiology
stasis in the biliary tract due to obstruction or stricture (characteristically from previous
cholecystectomy)
infection by ascending from the duodenum or hematogenous spread from the portal
vein
bacteria
E. coli, Klebsiella, Enterobacter, Enterococcus
co-infection with Bacteroides and Clostridia can occur
Signs and Symptoms
Charcot's Triad: fever, RUQ pain, jaundice (50-70%)
Raynaud's Pentad in patients with suppurative cholangitis: fever, RUQ pain, jaundice,
hypotension, confusion
Diagnosis
1'WBC
1'ALP, 1'GGT, 1'bilirubin
l'AST, l'ALT
blood culture
abdominal U/S - CBD dilation and presence of stones
Treatment
ERCP - diagnosis and therapeutic sphincterotomy, stone extraction
antibiotic therapy - broad spectrum to cover gram negatives and enterococcus
ampicillin + gentamicin OR
3rd generation cephalosporin OR
imipenem
may consider metronidazole to cover anaerobes
Prognosis
good with effective drainage and antibiotics in mild to moderate cases
fugh mortality (-50%) in patients with Raynaud's Pentad
Sclerosing Cholangitis
Definition
inflammation of entire biliary tree (intra and extrahepatic bile ducts) leading to
scarring and obliteration
Etiology
primary/idiopathic
most common
associated with ulcerative colitis in up to 70% (usually male); associated with
AIDS (called "HN cholangiopathy")
one of the most common indications for transplant
secondary - less common
long-term choledocholithiasis
cholangiocardnoma
surgica1/traumatic injury (iatrogenic)
contiguous inflammatory process
post ERCP
Toronto Notes 2008 Biliary TractIPancreas Gastroenterology G47
Signs and Symptoms
often insidious, may present with fatigue and pruritus
may present with signs of episodic bacterial cholangitis secondary to biliary
obstruction
Diagnosis
l' ALP, bilirubin
minor l' in AST, usually <300
ERCP shows narrowing of bile ducts, both intrahepatic and extrahepatic bile ducts
p-ANCA (30-80%), elevated IgM (40-50%)
Treatment
prophylactic antibiotics for bacterial cholangitis
endoscopic sphincterotomy, biliary stent in selected cases of dominant CBD stricture
suppurative cholangitis requires emergency drainage of pus in CBD
liver trans.rlantation appears the best treatment for advanced sclerosing cholangitis
(nearly 90 Yo survive 1 year; mean follow-up from time of diagnosis to need for
transplant is 5 years)
Complications
repeated bouts of may lead to complete biliary obstruction with resultant
secondary biliary cirrhosIs and hepatic failure
increased incidence of cholangiocarcinoma, 10-15%, difficult to diagnose, even more
difficult to treat
Prognosis
unfavorable regardless of treatment
mean survival after diagnosis remains 4-10 years
Pancreas
Anatomy and Physiology
generally divided into 4 parts: head (includes uncinate process), neck, body, tail
blood supply:
anterior/posterior superior pancreaticoduodenal artery (from the celiac trunk)
anterior/posterior inferior pancreaticoduodenal artery (from the superior
mesenteric artery)
dorsal pancreatic artery (from the splenic artery)
pancreatic veins drain into the portal, splenic and superior mesenteric veins
endocrine function: Islets of Langerhans produce glucagon, insulin and somatostatin
(from the a, and /) cells respectively)
exocrine function: digestive enzymes are produced including amylase, lipase, trypsin,
chymotrypsin and carboxypeptidase
Causes of l' Serum Amylase
pancreatic disease
acute pancreatitis, chronic pancreatitis with ductal obstruction, pseudocyst,
abscess, ascites, trauma, cancer
.... ,,
.)------------,
non-pancreatic abdominal disease
biliary tract disease, bowel obstruction/ischemia, perforated or penetrating
Pancreatic Enzyme.
ulcer, ruptured ectopic pregnancy, aneurysm, chronic liver disease, peritonitis
non-abdominal disease
amylase
cancer (lung, esophagus, etc.), salivary gland lesions, bulimia, renal lipase
transplant/insufficiency, burns, ketoacidosis trypsin
macroamylasemia
when serum amylase >5 times normal, the cause is almost always pancreatitis
or renal disease
o

When thinking about the caus-
es of acute pancreatitis
remember:
I GET SMASHED
'" '
.
,
.)------------,
Increased amylase
sensitive. not specific
Increased lipase
higher sensitivity and specificity
stays elevated longer
Pancreas Toronto Notes 2008
Acute Pancreatitis
Etiology (mnemonic: I GET SMASHED)
Idiopathic: 3rd most common, thought to be hypertensive sphincter or microlithiasis
Gallstones (45%)
Ethanol (35%)
Tumours: pancreas, ampulla, choledochocele
Scorpion Stings
Microbiological
bacterial: mycoplasma, Cumpylobacter, TB, M. avium intracellolare, Legionella,
leptospirosis
viral: mumps, rubella, varicella, viral hepatitis, CMV, EBV, HIV, Coxsackie
virus, echovirus, adenovirus
parasites: ascariasis, clonorchiasis, echinococcosis
Autoimmune: SLE, polyarteritis nodosa (PAN), Crohn's
Surgery/trauma
manipulation of sphincter of Oddi (e.g. ERCP), post-cardiac surgery, blunt
trauma to abdomen, penetrating peptic ulcer
Hyperlipidemia (TG >11.3 mmol/L), hypercalcemia, hypothermia
Emboli or ischemia
Drugs/toxins: azathioprine, mercaptopurine, furosemide, estrogens, methyldopa, H
2
blOCKers, valproic acid, antibiotics, acetaminophen, salicylates, ethanol, methanol,
organophosphates, steroids
Differential Diagnosis
perforated peptic ulcer
biliary colic
acute acute cholecystitis
fatty infiltration of the liver (alcohol)
small bowel obstruction (5BO)
perforated/ischemic bowel
mesenteric infarction
dissecting aneurysm
nephrolithiasis
acute coronary occlusion/MI
Pathology
activation of proteolytic enzymes within pancreatic cells -> local + systemic
inflammatory response
mild
peripancreatic fat necrosis
interstitial edema
severe
extensive peripancreatic and intrapancreatic fat necrosis
parenchymal necrosis and hemorrhage -> infection in 60%
release of toxic factors into systemic circulation and peritoneal space (causes
multi-organ failure)
severity of clinical features may not always correlate with pathology
3 phases:
local inflammation + necrosis ->hypovolemia
systemic inflammation in multiple organs, especially in lungs, usually after IV
fluids given --> pulmonary edema
local complications 2 weeks after presentation -> pancreatic sepsis/abscess
Signs and Symptoms
clinical: patient can look well or pre-morbid
pain: epigastric, noncolicky, constant, can radiate to back, may improve when
leaning forward (Inglefinger's sign); tender rigid abdomen; guardmg
nausea and vomiting
abdominal distention from paralytic ileus
fever: chemkal, not due to ffifection
jaundice: compression or obstruction of bile duct
Cullen' s/Grey-Turners' signs
tetany: transient hypocalcemia
hypovolemic shock: can lead to renal failure
acute respiratory distress syndrome
breakdown of phospholipase A2
coma
Toronto Notes 2008 Pancreas Gastroenterology G49
Investigations
l' pancreatic enzymes in blood
l' amylase
l'lipase
ALT >100 ill a non-alcoholic patient strongly suggests biliary pancreatitis
l' WIlC
imaging
x-ray: "sentinel loop" (dilated proximal jejunem), calcification and
"colon cut-off sign' (colonic spasm)
VIS: best for evaluating biliary tree (67% sensitivity, 100% specificity)
CT scan with IV contrast: useful prognostic indicator because contrast seen only
in viable pancreatic tissue, non-viable areas can be biopsied percutaneously to
differentiate sterile from infected necrosis
ERCP or MRCP if no cause found, searching for duct stone, pancreatic or
ampullary tumour, pancreas division
Prognosis
usually a benign, self-limiting course, single or recurrent
occasionally severe leading to:
shock
pulmonary edema
pancreatic abscess
coagulopathy
hyperglycemia and hypoglycemia
GI ulceration due to stress
death
functional restitution to normal occurs if primary cause and complications are
eliminated (exception: alcohol)
occasional scarring and persistent pseudocysts
rarely leads to chronic pancreatitis
mortality: Ranson's:O; 2 criteria =5% mortality
3-4 criteria =15-20%
5-6 criteria =40%
z.7 criteria =99%
Treatment
goals: (1) hemodynamic stability
(2) analgesia
(3) stop progression of damage
(4) treat local and systemic complications
antibiotics controversial except in documented infection
aspirate necrotic areas of pancreas to diagnose infection; drain if infected
IV fluids (crystalloid or colloid)
NG suction (rests pancreas) if stomach dilated, inflammation severe or patient
vomiting
a n a l ~ e s i c s to control pain
nutritional support: nasoenteric jejunal feeding tube or TPN if cannot tolerate enteric
feeds
no benefit: glucagon, atropine, trasyJol, H
2
blockers, peritoneal lavage
follow clinically and with CT/ultrasound to exclude complications
drain abscesses (percutaneous vs. surgical)
drain pseudocysts if large, persisting or infected
embofize hemorrhagic vessels
surgery for infected pancreatic necrosis (try to delay for >2 weeks to allow
demarcation between viable and necrotic tissue)
Complications
pseudocyst (cyst-like structure encapsulated with fibrous material, not epithelium)
abscess
lungs: pleural effusion, atelectasis, pneumonia, acute respiratory distress syndrome (ARDS)
acute renal failure (e.g. ATN)
CVS: pericardial effusion, pericarditis, shock
antibiotics: especially quinolones (e.g. ciprofloxacin), irnipenem (other antibiotics do
not penetrate pancreas) may be useful as prophylaxis in severe pancreatitis
Chronic Pancreatitis
o
---------------_....
Definition
a continuing inflammatory disease of the pancreas characterized by irreversible
morphological changes
four manifestations: abdominal pain, diabetes, steatorrhea, calcification of pancreas
Etiology
nearly always alcoholic
alcohol increases viscosity of pancreatic juice
HlllIOn', criteria: pancreatitis not due
to gallllones lcriteria ,lightly different
for gallstone-induced pancreatitis)
At admiuion
G: blood glucose>11 mmollliwith no histo
ry of hyperglycemia)
A: age >55
L: serum LOH >350 lUll
A: AST >250 lUll
W: WBC >16 xllJ9/l
During fim 48 hours
C: serum calcium <2 mmolll
H: hematocrit drop>10%
0: arterial PO, <60 mmHg
B: base deficit >4 mmolll
B: BUN rise>1.8 mmolll
5: estimated fluid ,equestration >6 l
difficult course if 2+ present
high mortality if 3+ present
What is the evidence for utilization of Ranson's
Criterie?
Pancreas 2002; 2514): 331-335
Study. 153 patients with acute pancreatitis were
assessed using Ranson's Criteria, APACHE II, and
APACHE III scoring systems. ROC analysis was
performed for each scoring system.
R8SIl1ts: Sensitivity and Specificity for each scor-
ing system in identifying severe pancreatitis is
listed below:
Ranson Criteria: Sens: 82%, Spec: 74%, PPV: 48%,
NPV:93%
APACHE II: Sens: 58%, Spec: 78%, PPV: 42%,
NPV: 86%
APACHE III: Sens: 56%, Spec: 86%, PPV: 51 %,
NPV:89%
Conclusions: The principle utility of these scales
is to determine whether a patient needs to be
admitted to the ICU based on their presenting
characteristics. Both APACHE scoring systems
require 24 hrs observation to generate a score,
but Ranson criteria can be applied at the time of
admission, Moreover, the test characteristics of
the Ranson scale are equivalent, in some cases
superior, to the more complicated APACHE scale.
Of particular importance is the negative predica
tive value these scales (e.g. don't want to miss a
patient who will need an ICU admission).
Antibiotic therapy for prophylaxis egeinst infec-
tion of pancraetic necrosis in ecute pancreetitis
Cochrane Database of Systematic Reviews
2006 Issue 4. Art. No.: C0002941.001:
10.1002/148518581COOO2941.pub2.
Study. Meta-Analysis of 5RCTs which random-
ized 294 patients to either antibiotic prophylaxis in
acute pancreatitis or placebo.
Results: Signfficant decrease in all cause mortali-
ty in patients receiving antibiotic prophylaxis 16%
vs. 15.3%1. No signfficant difference between the
rates in infected pancreatic necrosis between the
two groups. In studies evaluating Beta-lactam
antibiotics, significant decreases in mortality
(6.3% vs. 16.7%) and infected necrosis (15.6% vs.
29.29%) were observed compared to placebo.
Studies that evaluated quinolones plus imidazole,
found no significant differences between mortali
ty or infected necrosis.
Conclusions: There was a significant degree of
heterogeneity between studies which makes
definitive conclusions challenging (different
antibiotics, dosing regimens, etc.). Therefore, the
alrthors do not recommend routine prophylaxis. If
prophylaxis is to be performed, the authors sug
gest starting as soon as possible and continuing
for one to two weeks.
.... ~ ~
,l------------,
Symptoms of Chronic Pancreatitis
Abdominal pain
Diabetes
Steatorrhea
Calcification of pancreas
Etiology =Almost Always Alcohol
Treatment
Alcohol abstinence
Pancreatic enzyme replacement
Analgesics
Pancreatic resection if ductular
blockage
.... ~ ~
,"l-------------,
Hypomagnesemia may be an initial
sign of short bowel syndrome in
patients who have undergone sur-
gical bowel resection.
Pancreas/Clinical Nutrition Toronto Notes 2008
decreases pancreatic secretion of pancreatic stone protein (lithostatin) which
normally solubilizes calcium salts --+ precipitation of calcium within
pancreatic dud
result is duct ubstruction and subsequent gland destruction
unusual causes:
cystic fibrosis
severe protein-calorie malnutrition
hereditary pancreatitis
never gallstones - cause acute pancreatitis
Pathophysiology
destruction of exocrine parenchyma
varying degrees of ductular dilatation and associated ductal strictures
protein plugs
calcification
Signs and Symptoms
early stages
recurrent attacks of severe abdominal pain (upper abdomen and back)
chronic painless rancreatitis: 10%
late stages: occurs in 15 Yo of patients
malabsorption syndrome when >90% of function is lost, steatorrhea
diabetes, calcification, jaundice, weight loss, pseudocyst, ascites, GI bleed
laboratory
increase in serum glucose
increase in ALP (portion of common bile duct within pancreas is narrowed by
pancreatic inflammation)
serum amylase + lipase usually normal
Investigations
flat plate (looking for pancreatic calcifications)
ultrasound (calcification, dilated pancreatic ducts, pseudocyst)
CT (calcification, dilated pancreatic ducts, pseudocyst)
MRCP or ERCP (abnormalities of pancreatic ducts-narrowing and dilatation)
p-aminobenzoic acid (PABA) test (exocrine function: reflects duodenal chymotrypsin
activity)
72-hour fecal fat test (exocrine function)
secretin test, CCK test (exocrine function)
fecal enzyme measurement
Management
general management
total abstinence from alcohol
enzyme. replacement may help pain by resting pancreas via negative feedback
analgeSICS
celiac ganglion blocks
pain decreases with time as gland bums out
steatorrhea
pancreatic enzyme replacement
diet: restricted fat and protein (may also decrease pain)
surgery
pancreatic resection if ductular obstruction (best seen on ERCP)
no surgical procedure can improve pancreatic function
endoscopic
remove pancreatic stone or insert stent if pancreatic duct obstructed
Clinical Nutrition
Determination of Nutritional Status _______~ __...J
Investigations
plasma proteins (alhumin, pr('-albumin, transferrin)
cfecrease may indicate -j, nutritional status (not very specific)
thyroid-binding pre-albumin, retinol-binding protein
too sensItive
small changes in nutritional status can result in large changes in the following indices:
hemoglobin levels
total lymphocyte count
cell-mediated immunity
muscle strength (hand-grip dynanometer, electrical stimulation of adductor
pollicis)
INR: measurt' of vitamin K status
creatinine-height index, compare to standard tables
other methods are available but mainly for research (underwater weighing, total
body water, total body potassium, total body nitrogen, etc.)
Toronto Notes 2008 Clinical Nutrition Gastroenterology G51
Table 19. Areas of Absorption of Nutrients
Fe CHO Proteins, Lipids Bile Acids Vit B'2
Na, H
2
O
Duodenum +++ +++ +++ +
Jejunum + ++ +
Ileum + ++ +++ +++
__________
Enteral Nutrition
Definition
enteral nutrition (tube feeding) is a way of proViding food throught a tube placed in
the nose, stomach or the smail intestine
Indications
oral consumption inadequate or contraindicated
appropriate enteral feeding formula is available
Relative Contraindications
vomiting and aspiration
intestina1 obstruction
small bowel ileus
enteroenteral or enterocutaneous fistulae
uncontrolled diarrhea
LiGI bleeding
Complications
aspiration
diarrhea
Enteral Nutrition: Advantages Over Parenteral Nutrition
fewer serious complications (especially sepsis)
nutritional requirements for enterally administered nutrition better understood
can supply gut-specific fuels such as glutamine and short chain fatty acids
nutrients m the intestinal lumen prevent atrophy of the gut and pancreas
prevents by stimulating gallbladder motility
less expenslVe
Parenteral Nutrition
Definition
parenteral nutrition is the practice of feeding a person intravenously, bypassing the
usual process of eating ana digestion
Indications
not well understood; only situations where total parental nutrition (TPN) has been
""', I
well shown to increase survival are after bone marrow transplant and in short bowel
syndrome, some evidence for benefit in cancer of stomach
preoperative: only useful in severely malnourished (i.e. lost more than 15% of Whenever possible, enteral nutri
premorbid weight, serum albumin <28 gIL) tion is ALWAYS preferable to TPNI
renal failure: TPN shown to increase rate of recovery from acute renal failure,
but not l' survival
liver disease: branched chain amino acids may shorten duration of encephalopathy,
but do not increase survival
IBD: TPN closes fistulae and heals acute exacerbations of mucosal inflammation, but
effect is transient
some evidence for efficacy, but convincing data not available for:
radiation/chemotherapy-induced enteritis
AIDS
severe acute pancreatitis
Indications for routine use ofTPN
patients with inability to absorb nutrients via the GI tract
small bowel resection (70% resected)
diseases of the small intestine (e.g. scleroderma, SLE, celiac, pseudo-obstruction,
multiple enterocutaneous fistulae and Crohn's disease) not responding to other
treatments
radiation enteritis, graft vs. host disease
chronic severe diarrhea (e.g. primary GI disease, viral or bacterial enteritis)
intractable and protracted vomiting
patients undergoing high-dose chemotherapy, radiation and bone marrow
transplantation with impaired gut function
G52 Gastroenterology Clinical NutritionlVisualizing the GI Tract Toronto Notes 2008
moderate to severe acute pancreatitis with GI symptoms associated with oral ingestion
of food
severe malnutrition in the face of a non-functioning GI tract
severely catabolic patients with or without malnutrition when GI tract is not usable
within 5 days; examples include:
>50% body surface area burn
multisystem trawna
extensive surgery
sepsis
severe inflammatory disease
Relative Contraindications
functional GI tract for enteral nutrition
active infection; at least until appropriate antibiotic coverage
inadequate venous access; triple-1umen central venous lines usually prevent this problem
unreliable patient or clinical setting
Complications ofTPN
sepsis: most serious of the common complications
mechanical pneumothorax from insertion of central line catheter migration and
thrombosis, air embolus
metabolic: CHF, hyperglycemia, gallstones, cholestasis
TPNburn
Visualizing the GITract
Esophagus, Stomach, Duodenum
gastroscopy under most circumstances
consider oarium swallow first if dysphagia, decreased level of consciousness,
(increases risk of aspiration), inability to cooperate (increases risk of pharyngeal
trauma during intubation)
endotracheal intubation first if massive upper GI bleed, acidosis, unable to
protect airway
Gastroscopy
NPO x 12 hours beforehand
can be used to band varices, cauterize/clip bleeding ulcers
Colon and Terminal Ileum
usually colonoscopy, with biopsy if required, but contraindicated in acute
diverticulitis, severe colitis (increased nsk of perforation)
barium enema more accurate in diagnosing diverticulosis, extrinsic pressure on
colon (e.g. ovarian cancer compressing sigmoid colon), fistulas
Small Bowel
most difficult to visualize
most accurate is wireless endoscopy capsule (26 x 11 mm capsule is swallowed,
transmits images to a computer; contramdicated if obstruction in bowel)
small bowel enema (enteroclysis) more accurate than small bowel swallow, but
both have low sensitivity
CT and MRI enteroclysis becoming more available
"double balloon" endoscopy (endoscope with balloons proximally and distally
to propel endoscope into jejunum from mouth, into ileum from anus) may be most
sensitive but currently available only in selected centres
Pancreatic/Biliary Duct
MRCP (magnetic resonance cholangiopancreatography = MRI of pancreas/bile
duct) as sensitive as ERCP (endoscopic retrograde cholangiopancreatography)
in determining if bile duct obstruction present, but less accurate in determining
cause of obstruction (tumour, stone, stricture)
use ERCP if endoscopic draining likely to be necessary, strong suspicion of
stone or ampullary tumour
MRCP has low sensitivity in sclerosing cholangitis
Toronto Notes 2008 Common Medications Gastroenterology G53
Common Medications
Table 20. Common Drugs prescribed in Gastroenterology
Class Generic Drug Name Canada Name Dosing Schedule Mechanism of Action Indications Contranindications Side Effects
Proton Pump omeprozole Losec IPriloseC 20 mg once daily Inhibits gastric enzymes hypersensitivity to drug dizziness, headache, duodenal ulcer,
Inhibitors H'-K' ATPase gastric ulcer, flatulence, abdo pain,
(H'-K'ATPase lansoprazole Prevacid oral therapy: (proton pump) NSAID-associated nausea, rash
inhibitors) 15-30 mg once daily gastric and duodenal
(before breakfast) ulcers; reflux esophagitis
IV therapy: symptomatic GERD
30 mg once daily dyspepsia
Zollinger Ellison syndrome
pantoprazole PantoloclProtonix@ eradication of H. pylori
Icombined with antibiotics)
rabeprazole Pariet /Aciphex 40 mg once daily
esomeprazole Nexium 20-40 mg once daily
Histamine ranitidine ZantaC 300 mg once daily inhibits gastric histamine hypersensitivity to drug confusion, dizziness, duodenal ulcer,
H
2
-receptor or 150 mg BID H
2
-receptors gastric ulcer, headache,
antagonists NSAID-associated arrhythmias,
famotidine Pepcid oral therapy: gastric and duodenal constipation, nausea,
duodenal/gastric ulcers: ulcers; ulcer prophylaxis, agranulocytosis,
40 mg qhs reflux esophagitis, pancytopenia
GERD: 20 mg BID symptomatic GERD,
IV therapy: Zollinger Ellison syndrome
20 mg BID
Stool Softener docusate sodium Colace 100-200 mg once daily promotes incorporation relief of constipation presence of abdo pain, throat irritation,
of water into stool, fever, nausea and abdo cramps,
resulting in softer stool vomiting rashes
Laxative lactulose Lactulose/ constipation: is poorly absorbed in GI chronic constipation patients who require flatulence, intestinal
Constulose ,5-30 ml once daily tract and is broken down prevention and alow galactose diet cramps, nausea,
to bid by colonic bacteria into treatment of portal- diarrhea if excessive
encephalopathy: lactic acid into colon. systemic dosage
20 ml bid to qid l' osmotic pressure encephalopathy
and acidification of colonic
contents, increase
stool volume
Peristaltic senna Senakot tablets: senna glycosides are relief of constipation patients with abdo cramps,
Stimulant 2-4 at bedtime converted into aglycones acute abdomen discolouration of
syrup: in the colon and function breast milk, urine,
10-15 ml at bedtime as laxative agents by feces, melanosis coli
altering colonic water and and atonic colon
electrolyte transport from prolonged use
Antidianbeal loperamide Imodium acute diarrhea: acts as antidiarrheal via adjunctive therapy for children <2 yrs, known abdo pain or
Agents 4mg initially, followed cholinergic, noncholingeric, acute non-specific hypersensitivity to drug discomfort,
by 2mg after each opiate and nonopiate diarrhea, chronic acute dysentery drowsiness or
unformed stool receptor-medicated diarrhea associated characterized by blood dizziness, tiredness.
mechanisms with IBD, and for in stools and fever, dry mouth, nausea
reducing the volume acute ulcerative colitis and vomiting,
of discharge for or pseudomembranous hypersensitivity
ileostomies, colitis associated with reaction
colonstomies and broad-spectrum
other intestinal antibiotics
resections
diphenoxylate/ Lomotil 5mg tid to qid inhibits GI propulsion adjunctive therapy hypersensitivity to dizziness, drowsiness,
atropine via direct action on for diarrhea diphenoxylate or insomnia, headache,
smooth muscle, atropine, jaundice nausea, vomiting,
resulting in adecrease in pseudomembranous cramps, allergic
peristaltic action and enterocolitis, diarrhea reaction
in transit time caused by enterotoxin
producing bacteria
G54 Gastroenterology Summary Key Questions Toronto Notes 2008
Summary Key Questions
Questions
1. What IS the most common cause of POD?
2. How is diarrhea classified?
3. What is the most common cause dyspepsia?
4. What is the most common cause of upper GI bleed?
5. What serological test is used to diagnose celiac disease?
6. Which type of inflammatory bowel disease is more
associated with rectal bleeding and increased colon
cancer risk?
7. What causes of hepatitis are associated with AST, ALT
>1000?
8. What is the serological profile for a patient who has
recovered from hepatitis Binfection?
9. What are the 3 most common causes of acute
pancreatitis?
10. What is the Raynaud's Pentad?
11. What is the most common cause of elevated ALT in
North America?
12. What is the genetic mutation in hemochromatosis
and how is it treated?
Answers
R. pylon
Secretory, osmotic, inflammatory,
steatorrheaI or altered motility
Functional
Peptic ulcer disease
Anti-tissue transglutaminase (TIG)
Ulcerative colitis
Common bile duct stone, virus, drugs,
ischemia, autoimmune hepatitis
Negative = HBsAg, HBeAg
Positive = anti-HBs
Gallstones, ethanol, idiopathic
Fever, RUG pain, jaundice, hypotension,
confusion
Non-alcoholic steatohepatitis (NASH)
C282Y or H63D in the HFE gene
Treated by phlebotomy or deferoxamine if
phlebotomy contraindicated
Toronto Notes 2008 References Gastroenterology G55
References
CD Atlas
Kandel, G., Division of Gastroenterology, SMH.
Olscamp, G., Division of Gastroenterology.
Saibil, E, Division of Gaslroenterology, SWCHSC.
Haber, G., Division of Gastroenterology, Lennox Hall Hospital, New York.
Esophageal and Gastric Disease
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Wilcox, C.M .. Karowe, MW.: Esophageal infections: etiology, diagnosis, and management. Gastroenterology. 2:188, 1994.
Stomach and Duodenum
American Gastroenterological Associ.tion Position statement: Evaluation of dyspepsia. Gastroenterology. 114:579-581, 1998.
Howden, C.W., Hunt,R.H.: Guidelines for the management of Helicobacter Pylori infection. Am J Gastroenterology. 93:2330-2338, 1998.
Hunt RH, Fallone CA, Thomson ABR.119991. Canadian Helicobacter pylori consensus conference update: infection in adults. J. Gastroenterol, 13:
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Laine, L., Petersonw.L.: Bleeding peptic ulcer. NEJM. 331:717-727, 1994.
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Small and Large Bowel
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Liver and BiliaryTract
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G

high risk sexual activity/homosexual contact

family history (inflammatory bowel disease) Seafood

weight loss Antibiotics

normalizes with antibiotics p!creatic enzymes does not normalize

Hemolysis (spherocytosis, autoimmune disorders)

Hepatocellular disease - by far the most common

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