PATHOPHYSIOLOGY

MODULE 7 OUTLINE o pale stools and dark urine 1-5 days

prior to icteric phase
I. Hepatobiliary Tree Disorders o hepatomegaly plus RUQ pain
a. Hepatitis o splenomegaly and cervical
i. Viral lymphadenopathy (10-20% of cases)
ii. Drug – induced
b. Cholelithiasis - hepatic enzymes
c. Cholecystitis o hepatocellular necrosis which
i. Acute causes increased AST, ALT > 10-20X
ii. Chronic normal
II. Disorders of the Stomach o ALP and bilirubin minimally
a. Gastritis increased
i. Peptic Ulcer Disease o WBC normal or slightly decreased
ii. H. Pylori associated initially,
III. Disorders of the Pancreas
a. Acute Pancreatitis Viral Hepatitis - (A&E=Acute, B&D=Acute &
IV. Disorders of the Intestines Chronic, C=Chronic)
a. Gastroenteritis
i. Bacterial a. HEPATITIS A VIRUS (Acute):
ii. Viral Etiology
b. Constipation - Hepatitis A Virus (Most Common Viral
V. Parasitic Gut Infections Hepatitis Worldwide)

I. HEPATOBILIARY TREE DISORDERS Pathogenesis:

- Fecal-Oral Transmission
a. Hepatitis - 2-6wk Incubation
- liver inflammation - Virus is Directly Cytopathic to the Liver -
Etiology But Does NOT lead to Cirrhosis
- viral infection
- toxins Clinical Features:
- drugs - Acute Symptoms ONLY; No Chronic.
- other (immune mediated - Viremia > Fever, Malaise, Anorexia, Nausea,
Arthralgia
i. Viral Hepatitis Signs:
- Jaundice (After 1-2wks) (Due to
ACUTE VIRAL HEPATITIS Intrahepatic Cholestasis)
Definition o Inc Conjugated Bilirubin
- viral hepatitis lasting < 6 months  > Pale Stools
 > Dark Urine
Clinical Features - +/- Hepatomegaly
- most are subclinical - +/- Splenomegaly
- prodrome (flu-like illness) may precede - +/- Tender Lymphadenopathy
jaundice by 1-2 weeks - Rarely - Hepatic Encephalopathy & Death.
- nausea, vomiting, anorexia, taste/smell
disturbance (aversion to cigarettes) Investigations
headaches, fatigue, malaise, myalgias - LFTs - (Everything Raised)
- low-grade fever may be present - Hep A Serology
arthralgia and urticaria (especially hepatitis - Hep A PCR
B)
Prognosis
- clinical jaundice (icteric) phase (50% of - Usually Self-Limiting with Supportive
cases) lasting days to weeks Treatment Only.

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[MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD
 PATHOPHYSIOLOGY
b. HEPATITS E VIRUS (Acute):
- (Very Similar to Hep A; But HIGH
MORTALITY in PREGNANCY [20% > DIC in
3rd Trimester])
Etiology
- Hepatitis E Virus (A Herpesvirus)
Pathogenesis
- Virus is Directly Cytopathic to the Liver
Clinical Features
- Fecal-Oral Transmission (Incl. Vectors:
Dogs/Pigs/Rodents)
Clinical Picture - (Same as Hep A)
Investigations
- LFTs ʹ (Everything Raised)
- Hep E Serology
- Hep E PCR
Prognosis
- 1-2% Mortality (From Fulminant Hepatic
Failure)
- 20% Mortality in Pregnancy (From DIC in
3rd Trimester)
ACUTE AND CHRONIC VIRAL HEPATITIS
a. HEPATITIS B VIRUS (HBV)
- transmission via parenteral route or
equivalent
- vertical transmission
o occurs during 3rd trimester or early
post-partum
o HBsAg +ve, HBeAg +ve mothers ––>
90% of infants infected
o HBsAg +ve, anti-HBe +ve mothers ––
> 10-15% infected
o give HBIG and full HBV vaccination
to newborns of HBsAg +ve mothers
(90% effective)
- incubation period 6 weeks to 6 months
- infectivity: during HBsAg positivity
- high-risk groups
o neonates of carriers (“vertical
transmission”)
o partners of acutely and chronically
infected individuals, with male
homosexuals at particular risk
o IV drug users
o hospital employees
o patients from endemic country
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[MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD
Hepatitis B serology (Refer to PowerPoint)
- HBsAg: surface antigen
- HBeAg: e antigen (a component of HBV
core); marker of viral replication
- HBcAg: core antigen (cannot be measured
in serum)
- Both HBsAg and HBeAg are present during
acute hepatitis B
- Anti-HBs follows HBsAg clearance and
confers long-term immunity
- Anti-HBe and anti-HBc appear during the
acute and chronic phases of the illness but
do not provide immunity!
- Anti - HBe indicates low infectivity
Prevention
- HBV vaccine = recombinant HBsAg
- Seroconversion rates about 94% after 3
injections
- Hepatitis B immune globulin (HBIG) = anti-
HBs
o for needle stick, sexual contact, and
neonates born to mothers with
acute or chronic infection
b. HEPATITIS C VIRUS (HCV)
- Transmission is chiefly parenteral
o Transfusions (HCV is the most
common cause of post-transfusion
hepatitis)
o IV drugs use
o Sexual transmission occurs but risk
is less than with HBV
o 40% of cases have no risk factors
- Clinical incubation period 5-10 weeks
- AST and ALT levels fluctuate (unlike Hep A
or B)
- More than half progress to chronic liver
disease (see below)
- Serology
o HCV RNA (detected by PCR assay)
o anti-HCV
o develops in 6-8 weeks in 85% of
patients
o persists in chronic infection and
does not confer immunity
Prevention: no accepted vaccine for HCV
c. HEPATITIS D (HDV)
- infectious only in the presence of HBV
because HBV surface antigens are required
for replication
 PATHOPHYSIOLOGY
- 2 patterns of transmission
o nonparenteral transmission by close
personal contact in endemic areas
(Mediterranean)
o transmission by blood products in
non-endemic areas (IV drugs, blood
transfusions)
- Types of infection
o coinfection: simultaneous HBV and
HDV infection
o superinfection: appears as clinical
exacerbation in a chronic HBV
patient
- predisposes to severe or fulminant course
- Serology: HBsAg, anti-HDV IgM or anti-HDV
IgG
Prevention: HBV vaccine
d. HEPATITIS E VIRUS (HEV)
- fecal-oral transmission occurring in
epidemics in Asia, Africa, Central America
- most have mild disease, but in 3rd
trimester of pregnancy 10-20% have
fulminant liver failure
- serology: anti-HEV
Prevention: no vaccine available
ii. Drug induced liver disease / Drug induced
hepatitis
SPECIFIC DRUGS
I. Acetaminophen
- metabolized by hepatic cytochrome P450
system
- can cause fulminant hepatic failure
(transaminases > 1,000 U/L)
- requires 10-15g in normals, 4-6g in
alcoholics/anticonvulsant users
- Mechanism:
o high acetaminophen dose saturates
glucuronidation and sulfation
elimination pathways, therefore a
reactive metabolite is formed which
covalently binds to hepatocyte
membrane
- Presentation •
o first 24 hrs.: nausea and vomiting
usually within 4-12 hours
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[MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD
o next 24-48 hrs.: hepatic necrosis
resulting in increased
aminotransferases, jaundice,
possibly hepatic encephalopathy,
acute renal failure, death
o after 48 hrs: continue hepatic
necrosis/resolution
o note: potential delay in
presentation in sustained-release
products
- Blood levels of acetaminophen correlate
with the severity of hepatic injury
- Therapy
o Gastric lavage/emesis (if < 2 hrs
after ingestion)
o Oral charcoal
o N-acetylcysteine PO/IV within 8-10
hours of ingestion, most effective
for up to 72 hours (promotes
hepatic glutathione synthesis)
II. Chlorpromazine
- Cholestasis in 1% after 4 weeks; often with
fever, rash, jaundice, pruritus and
eosinophilia
III. INH
- 20% develop elevated transaminases but <
1% develop clinically significant disease
- susceptibility to injury increases with age
IV. Methotrexate
- May rarely cause cirrhosis, especially in the
presence of obesity, diabetes, alcoholism
- Scarring develops without symptoms or
changes in liver enzymes, therefore biopsy
may be needed in long-term treatment
V. Amiodarone
- can cause same histology and clinical
outcome as alcoholic hepatitis
b. Cholelithiasis
Pathogenesis
- Imbalance of cholesterol and its solubilizing
agents, bile salts and lecithin
concentrations
- If hepatic cholesterol secretion is excessive
then bile salts and lecithin are
 PATHOPHYSIOLOGY
“overloaded”, supersaturated cholesterol
precipitates and can form gallstones
Types of Stones
- Cholesterol (80%) = mixed (> 70%
cholesterol by weight), radiolucent
o risk factors
 female, fat, fertile, forties
 North American First Nations
peoples have highest
incidence
 diabetes mellitus (DM),
pancreatitis
 malabsorption, terminal ileal
resection or disease (e.g.
inflammatory bowel
diseases
- Pigment stones (20%), may be radio-
opaque
o smooth green/black to brown:
 composed of unconjugated
bilirubin, calcium, bile acids
o black pigment stones
 associated with cirrhosis,
chronic hemolytic states
o calcium bilirubinate stones
 associated with bile
stasis, (biliary
strictures, dilatation
and biliary infection
(Clonorchis sinensis)
Natural History
- 80% are asymptomatic
- 18% develop symptoms over 15 years
Clinical Presentation (in severity of increasing
order)
- asymptomatic stones
o most asymptomatic gallstones do
NOT require treatment
o consider operating if calcified
"porcelain" gallbladder, sickle cell
disease (15-20% associated cancer),
DM, history of biliary pancreatitis
- biliary colic
- cholecystitis - acute and chronic
- complications of cholecystitis
- choledocholithiasis (CBD stones)
- cholangitis
- biliary induced pancreatitis
- biliary induced ileus
c. Cholecystitis
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[MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD
A. ACUTE CHOLECYSTITIS
Mechanism
- Inflammation of gallbladder resulting from
sustained obstruction of cystic duct by
gallstone (80%)
- No cholelithiasis in 20% (acalculous)
Signs and symptoms
- Often have history of biliary colic
- Severe constant epigastric or RUQ pain –
- Anorexia, nausea and vomiting are
common
- Systemic signs – low grade fever (>38.5
degC); tachycardia
- Focal peritoneal findings
o Murphy's sign (sudden cessation of
inspiration with deep RUQ
palpation)
- Palpable gallbladder in one third of patients
Differential diagnosis
- Perforated or penetrating peptic ulcer, MI,
pancreatitis, hiatus hernia, right lower lobe
pneumonia, appendicitis, hepatitis, herpes
zoster
Diagnostic investigation
- elevated WBC, left shift
- mildly elevated bilirubin, ALP
- sometimes slight elevation AST, ALT
- U/S shows distended, edematous
gallbladder, pericholecystic fluid, large
stone stuck in gallbladder neck,
sonographic Murphy's sign (maximum
tenderness elicited by probe over site of
gallbladder)
II. DISORDERS OF THE STOMACH
a. Gastritis
GASTRITIS:
- Inflammation of the Stomach Lining
Etiology & Pathogenesis
- Acute:
o 15% Alcohol
o NSAIDs > Inhibits COX > dec
Prosƚaglandin > Hyperacidity >
Inflammation
o Severe Burns > dec Plasma Volume
> Sloughing of Stomach Mucosa
 PATHOPHYSIOLOGY
- Chronic:
o **80% Bacterial - Helicobacter
Pylori (Most Common)
- Atrophic:
o Autoimmune ʹPernicious Anemia ʹ
(Antibodies against Parietal Cell & IF
> B12 Deficient)
Clinical Features:
- Symptoms:
o Abdo Pain, Dyspepsia, Bloating,
Nausea/Vomiting, +/- Hematemesis
(if PUD), +/- Anemia (If Pernicious
B12 Deficiency)
Investigations:
- **C13 Urea Breath Test - (H.Pylori)
- Serology (IgG) - (H.Pylori)
- H.pylori Fecal Antigen Test - (H.Pylori)
- Endoscopy + Gastric Biopsy - (H.Pylori
Microscopy + ?Gastric Cancer)
Treatment:
- Conservative
o (Avoid Precipitating Factors
(Alcohol/NSAIDs))
o Antacids
o PPIs - (Omeprazole) or H2-
Antagonists - (Ranitidine)
o H.Pylori Triple Eradication Therapy
 (Clarythromycin +
Amoxicillin +/-
Metronidazole)
o If Pernicious ʹ (B12 Injections)
PEPTIC ULCER DISEASE:
Etiology: Either
- inc. Attack (Hyperacidity, Zollinger Ellison
Syndrome) Or
- dec Defense (**H.Pylori, Stress, Drugs
[NSAIDs & Corticosteroids], Smoking)
Morphology:
- Small, Single, Round, Punched out Ulcer
- 90% in Duodenum or Lesser-Curve of
Stomach.
- Healing Peptic Ulcers have Radiating
Mucosal Folds due to scar contraction.
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[MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD
Clinical Features:
- Burning Epigastric Pain; (Most Severe when
Hungry. Relieved by Food)
- Nausea & Vomiting
- Anorexia & Weight Loss
- Hematemesis/Melena
- (Perforation > Acute Peritonitis)
Investigation:
- Clinical History
- Endoscopy + Biopsy (Ulcer? H. Pylori?
Gastric Cancer?)
- **C13 Urea Breath Test - (H. Pylori? The
Best NON-Invasive Diagnosis)
- Serology (IgG) - (H. pylori)
- H. Pylori Fecal Antigen Test - (H.pylori)
Treatment:
- Conservative - (Avoid Precipitating Factors
(Alcohol/NSAIDs)
- Antacids
- PPIs - (Omeprazole) or H2-Antagonists -
(Ranitidine)
- H. Pylori Triple Eradication Therapy ʹ
(Clarithromycin + Amoxicillin +/-
Metronidazole)
- *Emergency Surgery ʹ (If Hematemesis /
Rupture / Peritonitis / CANCER
Complications:
- GI Bleeding > Anemia
- Perforation > Hemorrhage/Shock,
Peritonitis, or Into Pancreatitis.
- Pyloric Stenosis (Scarring) > Gastric Outlet
Obstruction > Vomiting
- **GASTRIC CANCER (NB: H. Pylori > 6x Risk
of Cancer)
III. DISORDER OF THE PANCREAS
a. ACUTE PANCREATITIS:
Etiology:
- 50% - Gallstones (Cholelithiasis) >
Ampulla/Common Bile Duct Obstruction
- 40% - Alcohol Abuse
- 10% Infections/Metabolic (inc. Ca in
hyperparathyroidism) DKA͕, Uremia͕
 PATHOPHYSIOLOGY
Pregnancy/ Trauma/ Ischemia /Duodenal
Ulcer/Scorpion Venom/Drugs/Unidentified
Pathogenesis:
- Autodigestion of Pancreas > Reversible
Inflammation > +/- Necrosis
- Can lead to Systemic Inflammatory
Response Syndrome
o > Shock
o > Acute Renal Failure
o > Acute Respiratory Distress
Syndrome
Clinical Features:
- An Acute Medical Emergency:
- Signs/Symptoms:
o Epigastric/Abdo Pain
o Precipitated by Large Meal OR
Alcohol
o Peritonitis - (Guarding + Rigidity)
o Vomiting
o If Hemorrhage > Hypotension &
Shock > Grey Turner’s and Cullen
sign
o Local Complications:
 Pancreatic Abscess/Infection
 Pseudocysts
 Duodenal Obstruction
o Systemic Complications:
 Jaundice
 DIC (Diss.Iv.Coag)
 ARDS (Resp. Distress)
 Acute Renal Failure
Diagnosis:
- Rule out Other Causes of Acute Abdomen͟
o Appendix/#Diverticulitis/#Peptic
Ulcer/#Cholecystitis/Isch.Bowel/
Bowel Obstruction.
- Inc Serum Amylase (Within 24hrs)
- Inc Serum Lipase (After 72hrs/3days)
- CBC - Neutrophil Leukocytosis
- Inc Alkaline Phosphatase ;If Biliary StasisͿ
- Inc Bilirubin
- (ERCP/MRCP if Indicated)
- !!NOT Biopsy!!! ʹ HAZARDOUS
Prognosis:
- 80% - Self-Limiting with Supportive
Treatment
- 20% - Life Threatening & 1/More-Organ
Failure (Requires ICU)
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[MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD
IV. DISORDERS OF THE INTESTINES
a. GASTROENTERITIS
(Bacterial Gastroenteritis) (Food Poisoning):
1. TOXIGENIC DIARRHEA (FOOD POISONING):
Etiology:
- Staph Aureus (Poor Food Handling)
- Bacillus Cereus (Mostly found in cereal
Symptoms:
- Onset Within 4hrs
o *Vomiting, *Stomach Cramps,
Diarrhea
Pathogenesis:
- Toxigenic Diarrhea
- (NB: Some toxins are Heat Stable)
Diagnosis:
- History + Clinical Course
- Retrospective Epidemiology > Find
Common Denominator. (Who ate what??)
- Stool OCP if worried.
Treatment:
- Supportive Treatment - (Fluid & Electrolyte
Replacement)
- Anti-Diarrheal Controversial > Symptomatic
but decreases toxin expulsion
2. ESCHERICHIA COLI – (“TRAVELLER’S
DIARRHEA”):
- ETEC: (Enterotoxigenic E. coli)
o Produces Toxins:
o Travelers Diarrhea
- EIEC: (Enteroinvasive E. coli)
o Active Intestinal
Invasion/Destruction
o Traveller͛s Dysentery
- EPEC: (Enteropathogenic E. coli)
o Sporadic disease in babies and
children
- EHEC: (Entero-Hemorrhagic E. coli)
o The Serious One:
 PATHOPHYSIOLOGY

o Produce Verotoxin > Destroys o Still infective for = 2 days after

Platelets & RBCs > HEMOLYTIC- symptoms subside.
UREMIC SYNDROME > Kidney - Any kid with vomiting/diarrhea should stay
Failure + Bleeding + Dysentery home for >1wk to minimize transmission

3. SALMONELLA; TYPHOID͟ Symptoms:

Etiology: - Vomiting (projectile)
- Salmonella typhi: - Diarrhea
- + Flu-Like Illness - (Fever, Irritability, Poor
Pathogenesis: Feeding, Myalgia)
- > Dysentery
- Can cause Septicemia Diagnosis:
- Also, Fever - rose spots - delirium - - Clinical Diagnosis of Gastroenteritis
perforation of bowel - Definitive Diagnosis via Stool Sample
Management: o Enzyme Immunoassay
- Ceftriaxone +/- Ciprofloxacin o Or RT-PCR
Management:
4. LISTERIOSIS (LISTERIA): - Supportive Mx
Etiology: - FLUID REPLACEMENT!
- Listeria Monocytogenes – (G-Pos) - Quarantine (Especially for
- (Soft Cheeses & Cold Deli Meats) Immunocompromised/Chemo Pts!)

Risk to Pregnant Women & Immunocompromised b. Constipation

5. CHOLERA: - The passage of infrequent or hard stools

Etiology: Vibrio Cholerae with straining (<50 ml per day)
Symptoms: Profuse Rice-Water Stools o Etiology
Management: - In the absence of other clinical problems,
- Fluid Replacement o Prognosis: Self- most commonly due to lack of fiber in the
Limiting diet, change of diet, or poorly understood
gut motility problems
NB: DYSENTERIC ORGANISMS: o Salmonella, - Organic causes include:
Shigella, Entamoeba Histolytica o Medication side effects
(antidepressants, codeine)
Viral o Left sided colon cancer (consider in
older patients)
Etiology: o Metabolic
- 80% Norovirus (Adult Diarrhea)  DM
- Rotavirus (Kid Diarrhea <3 y/o); usually  Hyperthyroidism
from Day Care Centers  Hypercalcemia
- Fecal-Oral Transmission o Collagen vascular diseases
 Scleroderma
Pathogenesis:  Amyloidosis
- Destruction of Enterocytes > o Neurological
Gastroenteritis  intestinal pseudo-
- Produces ͚Toxic Rotavirus Protein͛ - NSP4 > obstruction
Induces Chloride Secretion > Inhibits Water  Parkinson’s disease
Absorption in gut  Multiple sclerosis
Investigations:
Clinical Features: - Swallow radio opaque markers to
- Timeframe: quantitate colonic transit time (normal: 70
o Incubation Period = 2 days hours)
o Duration of Symptoms = 6 days Treatment: (in increasing order of potency)
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[MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD
 PATHOPHYSIOLOGY

- Surface acting (soften and lubricate) - Ingestion of oocysts (Contaminated

o Docusate salts and mineral oils
- Bulk forming
o Bran, psyllium seeds
- Osmotic agents
o Lactulose, sorbitol, magnesium
citrate, magnesium sulfate,
magnesium hydroxide, sodium
phosphate
- Cathartics
o Castor oil, senna (watch out for
melanosis coli)
Drinking Water/Public Pools)
- Can survive Chlorination
Pathogenesis is mostly unknown.
- Possibly induces inflammatory response >
Disrupts absorptive surface
- Damages Villi > Crypt Cells Replicate faster
to replace them > Immature cells in the
villus > Poor absorption.
Treatment:
- Nitazoxanide (Normally Self-Limiting if
Immunocompetent)

V. PARASITIC GUT INFECTIONS Long term Effects:

- AIDS PATIENTS DO NOT RECOVER > Chronic
PARASITIC GUT INFECTIONS Infection
(Protozoa & Helminths):
Diagnosis:
Transmission: - Cysts in Stools
- Fecal-Oral - (Ingestion of Dormant Cysts in
Contaminated Food/Water) c. ENTAMOEBA HISTOLYTICA
(The Amoebic Dysentery):
Diagnosis:
- Stool Samples (Looking for cysts) under Transmission:
Direct Microscopy - Ingestion of oocysts (Fecal Oral)
- Antigen Testing Pathogenesis:
- Intestinal Invasions > Ulcerations >
Prevention: Dysentery (Bloody Diarrhea)
- Boiling Water to Eliminate Cysts Diagnosis:
- Good Hygiene - Cysts in Stools
- Avoiding Fecal Contact Management:
- Metronidazole

HELMINTHIC INFECTIONS
- clinically significant helminths are “soil
transmitted”
a. GIARDIA
Pathogenesis: 1. Infection via swallowing infected eggs
- Not Toxigenic; Rather, it covers the brush a. Ascaris lumbricoides (roundworm)
border > Malabsorption b. Trichuris trichiura (whipworm)
Diagnosis: 2. Infection via Active skin penetration
- Cysts in Stools a. Strongyloides stercoralis (threadworm)
Complications: b. Ancylostoma duodenale (hookworm) -
- Chronic Infection
- Malabsorption Management:
o > Malnutrition - Albendazole
o > Fatty Stools
Treatment: ********END OF MODULE 7********
- Metronidazole

b. CRYPTOSPORIDIUM:

Transmission:
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[MODULE 7 – GASTROINTESTINAL] Handout Prepared by: Michael Angelo Sumugat RMT, MD