Evaluation of the Liver Patient

Roles of the Protein synthesis / proteolysis

liver Factors for the coagulation cascade
Acute phase reactants
Major source of glucose production and release in the body
Provides a defense against colonic bacteria (Koupper Cells)
Clears & metabolizes ammonia
Colonic bacteria
Enterocyte metabolism of glutamine

Definitions Cholestasis: Impaired bile flow

Intrahepatic cholestasis: Impaired bile flow within the liver
Extrahepatic cholestasis: Impaired bile flow in bile ducts outside the liver
Cholangitis: Bile duct inflammation
Bacterial, viral, parasitic, autoimmune
Hepatitis: Necrosis and inflammation of the liver
***Not all hepatitis is viral hepatitis!!

Symptoms of Right upper quadrant pain

Liver Disease Dark urine and light stools (bile gets stuck in the blood = loses color)
if Pruritus
symptomatic! Anorexia (loss of appetite)
Nausea and vomiting
Alteration of taste - dysgeusia
Fever and chills

Pruritus Rule of Intrahepatic cholestasis causes pruritus as an early symptom

Thumb Primary biliary cirrhosis and early itching
Itch first, jaundice later
Extrahepatic cholestasis results in pruritus as a late symptom
Bile duct obstruction may not even cause itching
Jaundice first, itch later

Scleral Icterus ICTERUS preceeds jaundice

*Sclera has a high affinity for bilirubin

Spider End-stage liver disease

Angiomata Pregnancy
Use of birth control pills
Hyperthyroidism
Signs and
symptoms

*Palmar
Erythema
*Clubbing
*Caput Medusa
-back up of
blood flow
*Gynecomastia
*Ascites

ASCITES = Bulging flanks

Collection of Right flank dullness
fluid around the Fluid wave
organs Shifting dullness
SOUNDS DULL Associated with peripheral edema

Exam Findings Hepatomegaly

Hepatosplenomegaly
Small liver on percussion / palpation
RUQ tenderness
Hepatic bruit
-Alcoholic hepatitis
-Hepatocellular carcinoma
-Arterio-venous malformation (AVM)
Hepatic = LIVER CONFUSION
Encephalopathy A neuropsychaitric syndrome
encompassing a wide spectrum of mental
and motor disorders
Gut-derived toxins are shunted from
the digestive tract, around the
liver, and affect the brains functioning
Predominantly ammonia derived
from bacterial production and
entrocyte metabolism of glutamine
Results in low-grade cerebral edema

Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span;

impaired performance of addition or subtraction
Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle
personality change; inappropriate behaviour
Grade 3 - Somnolence to semi-stupor, but responsive to verbal stimuli; confusion;
gross disorientation
Grade 4 - Coma (unresponsive to verbal or noxious stimuli)

Asterixis (during
Encephalopathy
)

Definition of Liver tests, not liver function tests

Terms: Sound Transaminitis - not a thing
Smart Melena is a noun BLACK STOOL
Saying melanotic stools is like saying poopy poop

When Should Screening for liver disease

You Order Liver Confirmation of possible liver disease
Tests? Differential diagnosis of liver disease
Prognosis of liver disease
Prothrombin time, bilirubin, albumin, factor V
Monitoring progression of liver disease
Monitoring therapy
Aminotransfer Aspartate aminotransferase (AST) (A Shot of Tequila - elevated in Alcoholic
ases Hepatitis) MITOCHONDRIA
Previously called SGOT
*enzymes in the Location is principally sub-cellular
HEPATOCYTES
(released in Alanine aminotransferase (ALT) (hALT viral hepatitis)
RESPONSE to Previously called SGPT
damage) Location is principally cytosolic

INCREASE IN AST/ALT Hepatocellular damage ACUTE or CHRONIC

Detection of hepatocellular (liver cell) injury
Monitoring resolution of hepatocellular injury
*and allow measurement for improvement

*BUT AST/ALT does not provide PROGNOSTIC INFO on someones outcome in liver
disease

Results in rise of aminotransferases

Elevation of both occurs
AST typically rises and peaks first
ALT is often the last to return to normal
Level of elevation may be a clue to the etiology of liver injury

Elevation of Marked elevation (up to 20+ fold)

Aminotransferas Acute hepatitis due to viruses, ischemia, or drugs
es
Moderate elevation (up to 8 fold)
Chronic hepatitis, cirrhosis, cholestatic diseases, and replacement
disease

Minimal elevation (up to 2+ fold)

Non-alcoholic liver disease, chronic viral hepatitis (C and B),
alcoholism, obesity, celiac sprue
*the elevation doesnt tell you the PROGNOSIS but gives you an idea about what
may be going on

Ratio of AST to Normally the ALT is slightly > AST

ALT Ratio typically near 1 to 1 in most liver cell injury
When AST/ALT > 1, consider
Alcoholic hepatitis
Occasionally NASH (non-alcoholic steatohepatitis)

Work-up of Most importantly, conduct a thoughtful H&P

Aminotransferas If you find signs of liver disease, evaluate on that basis
e Elevation If other non-liver signs (e.g. cardiac S 3 gallop), evaluate on that basis
If a history of ethanol, medications, drug abuse, or toxins, eliminate
them and repeat the liver tests in the future
Hemolysis With Wilsons disease
Liver Disease Alcoholic hepatitis
Autoimmune hepatitis
Drug-induced liver disease

Enzymes of Gamma glutamyltranspeptidase (GGT) SPECIFIC

Cholestasis Hepatobiliary disease
Replacement disease
Enzyme induction

Alkaline Phosphatase Elevation less specific (can be elevated via bone
reabsorption etc.)
Hepatobiliary disease
Replacement disease
Enzyme induction
Bone disease
Idiopathic

**Serum Bilirubin
Van den Bergh reaction separates bilirubin into
Conjugated fraction = direct
Unconjugated fraction = indirect (UN is an IN)

Hyperbilirubine Unconjugated hyperbilirubinemia not taking bilirubin into the liver and
mia with Normal excreting it SO the bilirubin just builds up in the blood.
Liver Tests Gilberts mild elevation, worst when fasting or sick
Crigler-Najjar complete deficiency of glucuronyl transferase,
incompatable with life liver transplant
Hemolysis and ineffective erythropoiesis

Conjugated hyperbilirubinemia
Dubin-Johnson syndrome
Rotors syndrome
Cholestasis of pregnancy

Gilberts Often college aged

Syndrome Unconjugated hyperbilirubinemia
Direct fraction does not usually exceed 0.3 mg/dL
Total bilirubin does not usually exceed 3 mg/dL
Aminotransferases often normal
Bilirubin elevation aggravated by:
Fasting
Stress
Crigler-Najjar Glucuronyl transferase deficiency
Syndrome Type 1 = no enzyme (fatal)
Type 2 = some enzyme (may be treatable may respond to
PHENOBARBITOL WHY? b/c it induces the Gluc. Transferase
enzyme)
Results in marked hyperbilirubinemia
May develop kernicterus
Type 2 may respond to phenobarbital and decrease unconjugated bilirubin
level
Liver transplantation will cure the disease

Dubin-Johnson Conjugated hyperbilirubinemia

Syndrome Secretion defect
Gallbladder does not visualize with oral
cholecystography
Melanin-like pigment accumulates within
centrilobular liver cells have BLACK LIVERS

Tests of Acute Hepatitis A

Viral Hepatitis IgM anti-HAV (ACUTE think IgM)
Hepatitis B
HBsAg, IgM anti-HBc, HBV DNA
Hepatitis C
HCV RNA
Others
HDV, HEV, EBV, CMV, HSV, adenovirus

Tests of Chronic Hepatitis B

Viral Hepatitis HBsAg, IgG anti-HBc, HBV DNA
Hepatitis C
Anti-HCV antibody and HCV RNA
Hepatitis D
Anti-HDV and HDV Ag
Hepatitis A and E
Chronic hepatitis does not occur
Hemochromatos *one of the most COMMON
is AUTOSOMAL RECESSIVE diseases
MOA = DEFECT in the ability to SHUT
OFF the absorption of IRON in the
duodenum resulting in excessive
iron absorption and subsequent
deposition of iron into the tissues
(HEART, SPLEEN, PANCREAS)
Clinical manifestations
Liver disease
Cirrhosis
Hepatocellular
carcinoma (HEP B
and
Hemochromatosis)
Diabetes mellitus
Cardiomyopathy
Osteoporosis-like disease and arthropathy
Disease expression more common in men (bc of menses women lose the
iron)

Diagnostic features
Transferrin saturation > 45% (Serum Iron / TIBS) 1st test
Ferritin > 400
HFE gene studies
C282Y/C282Y
Remember, only 90% of clinical hemochromatosis
patients will be homozygous C282Y
C282Y/H63D heterozygote (5% clinical expression)
Hepatic iron concentration > 20,000 mcg/g dry weight
Hepatic iron index > 1.9

What do you Hyperpigmentation

see clinically
with
Hemochromatos
is?
Wilsons *Abnormal COPPER METABOLISM
Disease Autosomal recessive inheritance
Disease stages
Hemolysis
Typically the first manifestation in
childhood SEE ANEMIA
Liver disease
Presents as liver disease up to the age of 25 years
Neurologic disease
Basal ganglia dysfunction with choreoathetoid movements
Laboratory
Ceruloplasmin typically low (cant be excreted from the liver)
Can be normal in 5% of patients
Spontaneous urine copper levels high
Therapy
Use of copper binding substances like penicillamine or trientine
Low copper diets and zinc therapy
Kayser-Fleischer Rings
- Seen with slit-lamp exam

Alpha-1- Autosomal recessive

Antitrypsin Liver injury results from accumulation of improperly
Deficiency glycosylated A1AT within liver cells
Liver disease in 10% in those with Protease inhibitor
(Pi) type ZZ (PiZZ)
Can rarely occur in MZ heterozygotes
Diagnosis is by protease inhibitor (Pi) typing
Associated diseases
Neonatal hepatitis
Emphysema in the 4th decade of life
End stage liver disease in the 7th and 8th decades
Chronic pancreatitis may occur
Hepatocellular carcinoma has been reported in both ZZ and MZ
phenotypes

Elevated: Hepatocellular carcinoma (HCC)

Alpha- 30% of HCC is fibrolamellar type no elevation of AFP
Fetoprotein Hepatic regeneration / inflammation
Testicular tumors
Neonates

Acute Liver Failure

Acute Liver Acute Liver Failure
Failure Rapid deterioration of liver function in people without known pre-existing
liver disease
Altered mentation and coagulopathy
Rare: 2000 cases per year in the U.S.
Before liver transplantation: less than 15% survival
Currently, one-year survival of 65% (including those undergoing liver
transplantation)

Definition of Acute Liver Failure

Terms INR > 1.5
Encephalopathy
Without known pre-existing cirrhosis
Illness < 26 weeks duration (6 months)
Pre-existing, yet unknown: Wilson disease, vertically acquired Hep B,
autoimmune hepatitis

Viral Hepatitis *acute = hep B 85% will clear

*most chronic is hep C only 15% will
clear

Symptoms of Viral Hepatitis

Flu-like symptoms
Malaise and fatigue- RUQ pain
Anorexia
Alteration of taste
Dark urine and light stools
Pruritus
Serum sickness

Signs of Viral Hepatitis

Hepatomegaly
Splenomegaly in 25%
Signs of portal hypertension (ascites or encephalopathy) suggest massive
necrosis or another diagnosis
Ascites or encephalopathy in viral hepatitis suggests a poor
prognosis
Such patients should be evaluated for liver transplantation
What is Hepatitis is a medical condition defined by the inflammation of the liver and
hepatitis? characterized by the presence of inflammatory cells in the tissue of the organ. The
name is from the Greek hepar (), the root being hepat- (-), meaning liver,
and suffix -itis, meaning "inflammation" The condition can be self-limiting (healing
on its own) or can progress to fibrosis (scarring) and cirrhosis.

Hepatitis may occur with limited or no symptoms, but often leads to jaundice,
anorexia (poor appetite) and malaise. Hepatitis is acute when it lasts less than six
months and chronic when it persists longer. A group of viruses known as the
hepatitis viruses cause most cases of hepatitis worldwide, but hepatitis can also be
caused by toxic substances (notably alcohol, certain medications, some industrial
organic solvents and plants), other infections and autoimmune diseases

Laboratory Aminotransferase elevation (ALT & AST)

Values in Viral Cholestasis
Hepatitis Especially in hepatitis A and hepatitis E
Hyperbilirubinemia
Elevation of total IgM
Non-organ specific autoantibodies in low titer

Hepatitis A Hepatitis A
RNA virus (picornavirus)
Short incubation
*15 to 50 days
Transmission
*Fecal-oral (day care centers,
travelers, gays)
*Cases may be sporadic or common
source
TRAVEL?
Illness is typically mild and may not be recognized as viral hepatitis
May have clinical and biochemical relapse during recovery
Hepatitis B Hepatitis B
DNA virus (hepadnavirus family)
Longer incubation period
30 to 180 days
Transmission
Sexual (blood is the main way
spread high incidence previously
assoc. blood trans)
Parenteral
Vertical especially E. Asia,
can smolder for decades and
present in 20-30s
Clinically more severe illness in
acute infection
Carrier rate is 5 to 10%
Treat with IFN-

Serology of *note the WINDOW = the time before the

Acute HBV CONVERSION PROCESS has occurred = surface
Infection antigen and surface antibody negative

Pre-exposure prophylaxis
HBV vaccine
Post-exposure prophylaxis
Hyperimmune B immunoglobulin
(HBIG)
Hepatitis C Hepatitis C Virus
Virus RNA virus
Long incubation period
15 to 180 days
Transmission
Parenteral IVDU, tattoos, inhaled
cocaine
Inapparent parenteral (blood
transfusions)
Typically a mild clinical acute illness
Once infected, the carrier rate > 65%

*Hep C w/ CIRROSIS = at a very high risk for hepatocellular carcinoma

*Pre-exposure prophylaxis, No vaccine is available, Post-exposure prophylaxis,

Immune globulin is not effective

Hepatitis D and Hepatitis D and Hepatitis E

Hepatitis E
Hepatitis D must have preexisting HEP B to have D
Incubation 28 140 days
Transmission
Parenteral
Inapparent parenteral
Requires simultaneous presence of HBV
Co-infection
Super-infection
Hepatitis E
Incubation 28 40 days
Transmission
Fecal-oral
Associated with:
Cholestasis
High mortality during pregnancy
Causes of Autoimmune (chronic) hepatitis
Chronic Types 1 and 2
Hepatitis Type 1
Typically occurs in Women
Peri-pubertal and post-menopausal
age groups
Systemic manifestations, Fatigue,
Hashimotos thyroiditis
Pleuritis, pericarditis, arthralgias
Malar rash
Striae on the abdomen and legs (if acute ascites / edema)
Signs of chronic liver disease
Spiders angiomas, palmar erythema
Hepatosplenomegaly
Jaundice
Marked elevation of aminotransferases
Usually 10-fold elevation
Autoantibodies present = Antinuclear (ANA) and smooth muscle
antibody (SMA) positive (90% +)
Hyper-gammaglobulinemia
In those with hemolysis = Coombs-positive
Eosinophilia
Chronic viral hepatitis
Associations
HBV, HCV, and HBV/HDV
HAV and HEV never cause chronic hepatitis
Autoimmune markers typically absent or in low titer
No other autoimmune manifestations
Chronic Hep B
Men > women
Carrier defined as HBsAg + > 6 months
Associations
Glomerulonephritis, polyarteritis nodosa, cryoglobulinemia
Therapy
Pegylated or conventional interferon alfa Tenofovir, Entecavir
Lamivudine, adefovir, telbivudine are less potent and associated with
increased resistance
Chronic Hep C
Up to 65% become chronic carriers of HCV
Disease manifestations
Healthy carrier, chronic hepatitis, cirrhosis, hepatocellular carcinoma
Associations
Cryoglobulinemia, rarely polyarteritis nodosa
Therapy
Pegylated interferon alfa and ribavirin coupled with boceprevir or
telaprevir
Drug-induced chronic hepatitis
Alpha-methyldopa
Antibiotics such as nitrofurantoin, isoniazid, and sulfas
Propylthiouracil
Dantrolene
Cirrhosis A diffuse liver process with fibrosis
and nodule formation

If fibrosis without nodule

formation = not cirrhosis
If nodule formation without
fibrosis = not cirrhosis
End result of fibrogenesis caused by
chronic liver injury

*MUST BIOPSY to truly dx Cirrhosis

*NODULES are liver tissue that is trying to survive lost orientation are in
random orientations

Can get MICRO or MACROnodular

Cirrhosis

Portal *blood flows through the portal vein into

Hypertension the liver space of disse and is
processed by the hepatocytes

**in cirrhosis get STELLATE CELLS that

start laying down scar tissue and the
endothelial cells lose their fenestrations
PHYSICAL OBSTRUCTION but the liver
wants more blood flow so it sends out
messengers to increase flow NO etc.
but scar tissue is blocking no matter what
BUT the VASOACTIVE substances are
circulated an begin to affect other local
vasculature such as the SPLENIC VEIN and the small collateral vessels are
beginning to swell due to the NO stimulus = results in dilations = VARICIES
Esophagogastri Liver disease related
c Varices Cirrhosis
Non-cirrhotic liver conditions
Volume overload
Pregnancy
Congestive heart failure
Constrictive pericarditis
SVC occlusion
*Formation of superficial veins in the
esophagus or stomach
*Develop from the shunting of blood from the
portal circulation around the liver to the heart

Causes of Cirrhosis
Ascites Severe acute liver injury such as fulminant hepatitis
Peritoneal disease such as tuberculosis, mesothelioma, or metastases
Ovarian tumors (Meigs syndrome)
Hepatic vein occlusion (Budd-Chiari)
Veno-occlusive disease

CAUSES Liver, lover, tumor, tuber(culosis) (also the kidneys, note lover =
heart)
*do paracentesis on ALL patients with ascites (do cell count, albumin, gm stiain)

Spontaneous More common in cirrhosis as ascites etiology

Bacterial Develops in 10% of those with ascites
Peritonitis Most common in alcoholic cirrhosis ascites
Suspect in anyone with ascites
May be asymptomatic
Up to 50% also have bacteremia
Possible symptoms and signs of SBP
Encephalopathy, nausea-vomiting, increasing ascites, azotemia, fever,
or hypotension
MANY ARE ASYMPTOMATIC

Hepatorenal Definition
Syndrome Progressive oliguria and progressive azotemia in a patient with
advanced liver disease, either acute or chronic
Precipitating events
Gastrointestinal bleeding, sepsis
Large volume paracentesis, vigorous diuresis
Hyponatremia

*kidney get confused by the elevated VASOACTIVE substances getting released
the kidney responds to the low BP via +RAS which puts the kidneys in a
profound state of HYPOPERFUSION
Alcoholic Fatty Most common histologic abnormality
Liver Symptoms/signs may be absent or minimal
RUQ abdominal pain
(AST Hepatomegaly
ELEVATED!!) Ultrasound may suggest fatty change
Aminotransferases normal to slightly increased
Therapy is abstinence from ethanol

Alcoholic Only 10-20% of chronic alcoholics develop alcoholic hepatitis

Hepatitis Concomitant HCV infection may be present
Cholestasis and AST:ALT > 2:1
May mimic a surgical abdomen
Prednisone and pentoxifylline therapy may benefit those with
concomitant hepatic coma
Liver transplantation is not indicated

Alcoholic Laennecs Cirrhosis

Cirrhosis Initially develops as a micronodular cirrhosis and transforms to a
macronodular form with time and abstinence
Up to 30% will develop hepatocellular carcinoma
Median to onset in 4.5 years after the diagnosis of cirrhosis
Therapy is control of complications and alcohol cessation

Nonalcoholic Fatty liver in the absence of significant alcohol intake

Fatty Liver Common associations
Disease Type 2 Diabetes, hyperlipidemia, obesity
(NAFLD) Symptoms and signs
May be asymptomatic
May have fatigue, weakness, RUQ pain
Normal or minimally increased aminotransferases
Therapy is to control the cause

Primary Biliary An autoimmune disease characterized by lymphocytic destruction of

Cirrhosis bile ducts
Women:men = 9:1
Typically a disease of middle age presenting between age 30 and 55 years
Presentation
Pruritus and excoriations
RUQ pain
Jaundice or weight loss
Abnormal liver tests
Laboratory findings
Elevated alkaline phosphatase
Typically 2 to 20 times elevated
Aminotransferases 1 to 5 times elevated
Anti-mitochondrial antibody (AMA) positive in > 90%
Elevated IgM in > 80%
Hypercholesterolemia without increased risk of heart disease (HDL
elevated too)
Hemangioma Abnormal collection of endothelial lined, blood filled spaces
Most common benign lesion of the liver
Present in 1-2% of individuals
Typically in the right lobe
Solitary
Multiple in 10%
Technetium RBC scan, ultrasound, CT and MRI can be used for diagnosis

*DONT DO ANTHING to them

Focal Nodular A hyperplastic response to a portal artery-to-

Hyperplasia venous shunt
*excessive tissue growth
Imaging studies and histology show a central
scar
Background hepatic histology is normal
Second most common benign liver lesion
Most are found incidentally at surgery
Can present as a RUQ mass
Rarely presents with intra-abdominal bleeding
Typically solitary
Therapy can be observation

Hepatic Benign neoplasm composed of hepatocytes without accompanying liver

Adenoma structures
Oral contraceptives frequently associated
Presentation
RUQ mass or pain
Intra-abdominal hemorrhage
Therapy
If less than 5 cm diameter, stop OCPs and observe if asymptomatic
If greater than 5 cm diameter, consider resection

Hepatocellular Associations
Carcinoma Hemochromatosis
All forms of cirrhosis esp. Hep C
Less common in Wilsons disease and PBC
HBV with or without cirrhosis and HCV with cirrhosis
A1AT deficiency and tyrosinemia
Drugs and toxins (e.g. anabolic steroids), IVC webs
**recall see inc. -Fetal Protein
Cholangiocarcin Associations
oma Sclerosing cholangitis
Choledochal cyst
Carolis disease
Biliary atresia
Toxins
Thorium, arsenicals,
vinyl chloride
Liver flukes

Disorders of the Liver I

*blood supple from the PORTAL

VEIN and HEPATIC ARTERY
PENETRATING VESSELS to the
SINUSOIDS the central artery

*Classic Lobule from portal triad to

portal triad no fibrous tissue between so
the lobules are virtual
*Terminal Hepatic Vein (THV) terminiolgy
replaced the central vein

*Can use the THV to THV = Liver ACINUS in the

center is the portal area = hepatic artery and vein is
subdivided into 3 ZONES on O2 levels
*hepatocytes are very metabolically active
*zone 1 = MOST metabolically active
*zone 3 = is the MOST hypoxic area
*becomes more hypoxic w/ rt. Heart faiure
Structure *sinus lined with
endothelial cells loose
connections RBC just
percolate thought until the
reach the THV.

*KUPFFER CELLS
macrophages, clean up
depris, apotosis, CD68+
(endothelial cells CD34+)

SPACE OF DISSE area

has plasma that takes up
nutrients

*Cell of ITO store

VITAMIN A produce
collagen are the source of
abberant collagen production
Ito Cell stores ITO CELL = STELLATE CELL
vit A and can *located in the space of disse
produce *major cell type involved in
collagen LIVER FIBROSIS

*fxn store Vit A

*when the liver is damaged

the Stellate Cells are
ACTIVATED secrete
COLLAGEN creating scar
tissue which can lead to CIRRHOSIS.
Hepatic Injury-5 1. Degeneration and intracellular accumulation cells have metabolic probs
patterns a. Fatty change-steatosis
2. Necrosis and Apoptosis-zonal (zone 1,2 or 3)
3. Inflammation = hepatitis can be in the portal or lobular areas
4. Regeneration
5. Fibrosis = cirrhosis

Jaundice Normal bilirubin 0.3 to 1.2mg/dL

Jaundice evident 2.0 to 2.5 mg/dL but can be hard to see subtle changes
Excessive production of bilirubin
Reduced hepatocellular uptake
Impaired conjugation
Decreased hepatocellular excretion
Impaired bile flow
Hereditary Crigler-Najjar syndrome-genetic lack of bilirubin UGT
Hyperbilirubine Gilbert syndrome-autosomal dominant-reduced expression of UGT-6% of
mia population
Dubin-Johnson syndrome-autosomal recessive-impaired biliary excretion
of bilirubin glucuronides
Rotor syndrome-recessive-defects in hepatocyte uptake and excretion

Cholestasis = Biliary obstruction-intrahepatic or

buildup of bile extrahepatic
acids Pruritus-increased bile acids
Skin xanthomas
Elevated serum alkaline phosphatase
Intestinal malabsorptiion + deficiencies of
A,D, K
Distention of upstream bile ducts-leads to
proliferation of ducts, inflammation and portal tract fibrosis

Hepatic failure Endpoint-loss of 80-90% of hepatic activity

Massive hepatic necrosis
Fulminant viral hepatitis, drugs (acetaminophen), chemicals &
mushroom poisoning
Chronic liver disease-most common route to failure-hepatitis or alcohol
Hepatic dysfunction without overt necrosis-Reyes syndrome

See clinically?
Jaundice
Hypoalbuminemia
Hyperammonemia one of the most damaging consequences =
encephalopathy
Fetor hepaticus- musty sweet & sour
Impaired estrogen metabolism-palmar erythema, spider angiomas and
gynecomastia
Coagulopathy-(II, VII, IX & X)
Hepatic encephalopathy due to hyperammonemia

Cirrhosis Bridging fibrous septa-from portal area to portal area and/ central vein
Regenerating parenchymal nodules regenerative nodules in areas of
hepatocellular necrosis but dont form the proper connections
Disruption of the architecture of the entire liver increase in pressure in
portal hypertension, vascular architecture is reorganized

Cirrhosis Alcoholic liver disease 60-70%

Etiology-in U.S. Viral hepatitis (C) 10%
Biliary disease 5-10%
Hemochromatosis 5% - (iron is toxic to the hepatocyte
cardiomyopathy)
Wilson disease rare
1-Antitrypsin deficiency rare (lung or liver)
Cryptogenic cirrhosis 10-15%
*morbid obesity
Pathogenesis of Progressive fibrosis continual degeneration
Cirrhosis Hepatic stellate cells (Ito cell) the source of collagen
Normally store Vit. A, transform into myofibroblasts
Chronic inflammation produces cytokines-(TNF)-(TGF) ITO cells are
stimulated to lay down collagen
Cytokine production stimulated by endogenous cells
Extracellular matrix disrupted
Stellate cells (AKA ITO cells) stimulated = lay down collagen, ZONE 3
(surrounding the central vein (i.e. THV) is affected first most vulnerable to
alcohol b/c the cells are already stressed being in a low oxygen area.

*normal liver = 1400 grams if an alcoholic ~ = 2400 g with most of the weight
as FAT with slow progression of fibrosis
*eventually alcohol taste bad the liver begins to shrink

Clinical features Silent for a long time

of Cirrhosis Anorexia, weight loss, to overt
hepatic failure
Portal hypertension
Development of
hepatocellular carcinoma

Portal Increased resistance to portal flow at the level of the sinusoids and
hypertension compression of central veins by perivenular fibrosis
Ascites-excess fluid in the peritoneal cavity
Sinusoidal hypertension
Increased lymphatic flow-up to 20L/day
Intestinal fluid leakage
Renal retention of sodium and water due to 2 hyperaldosteronism
Porto-systemic shunts
Splenomegly

Viral hepatitis A Infectious hepatitis-no chronic hepatitis form CLEAR THE DISEASE
*acute SELF Low fatality rate
LIMITED Single stranded RNA picornavirus
(wimpiest form) Fecal-oral spread flies
IgM antibody against HAV-present at time of symptoms
IgG antibody persists for years providing protective immunity
Hep A incubation period 2 weeks 3 months
-most have symptoms malaise most common
by the time jaundice develops ususally
cleared the virus
Hepatitis B Acute hepatitis, non progressive chronic hepatitis, progressive hepatitis,
(serum) fulminant hepatitis
hepatitis * I.E. has both ACUTE and CHRONIC PHASES (incorporates into our genome
= persistent hepatitis), was frequently associated with blood transfusions
DNA virus
Nucleocapsid core proteins(HBcAg) and HBeAg
Envelope glycoprotein(HbsAg)-hepatocytes can synthesize massive
quantities of this protein
A DNA polymerase (reverse transcriptase activity)
A protein from the X region (HBX)-necessary for viral replication
Proliferative phase-HBV DNA is present in episomal form-complete virions
Leads to activation of cytotoxic CD8+T lymphocytes and hepatocyte
destruction.
Integrative phase-viral DNA is incorporated into the host genome in
hepatocytes not destroyed
CREATES IMMUNE COMPLEXES polyarteritis nordosa
HBV serologic diagnosis
Long asymptomatic 4 to 26 week incubation
HBsAg appears before the onset of symptoms
HBeAg, HBV- DNA and DNA polymerase-signify active viral replication
IgM anti-HBs-detectable just before symptoms
Anti-Hbe-detectable shortly after the disappearance of HBeAg-meaning
infection has peaked
IgG anti-HBs comes months after disappearance of HBsAg

Note Hep A think Acute and self limited

Hep B think Blood (was associated with blood and since from others BLOOD which
has DNA think DNA its the only hepatitis that is a DNA virus (others are all
RNA viruses)
Hep C think Chronic
Hep D think, B loves DDs i.e. Hep D is only in the presence of Hep B
Hepatitis C virus Small enveloped single stranded RNA virus (Flaviviridae)
HCV has a high rate of progression to chronic hepatitis, eventual
cirrhosis->50%
2 to 26 weeks incubation-HCV-RNA is detectable in blood
Clinical course milder than HBV

Hep C risk factors

IV drug abuse (54%)
Multiple sex partners (36%)
Surgery within last 6 months (16%)
Needle stick injury (10%)
Multiple contacts with an HCV-infected person (10%)

*mild flu-like symptoms, mild increase in transaminases progress to CHRONIC

*if stable then unlikely to progress to cirrhosis

*stable cirrhosis can be managed

Acute viral Incubation period-peak infectivity occurs during the

hepatitis last days of the incubation period
HIGH AST will have a coagulopathy therefore DO
NOT BIOPSY
Preicteric phase-nonspecific constitutional symptoms,
some immune complex symptoms ( esp HBV)
Icteric phase-may be absent in 50% of cases,
beginning of convalescence phase

Chronic viral Symptomatic, biochemical or serologic evidence of

hepatitis continuing disease for more than 6 months
Most have persistent transaminase elevations
Vasculitis, glomerulonephritis , cryoglobulinemia
Diffuse swelling of hepatocyte
Cholestasis
Clumps of macrophages-areas of hepatocyte drop out
Apoptosis-eosinophilic councilman bodies
Kupffer cell hypertrophy
Portal tracts infiltrated by inflammatory cells
Chronic hepatitis morphology
Smoldering hepatocyte necrosis, Inflammation in portal tracts, Bridging
fibrosis, Regenerative nodule formation, Cirrhosis
Fulminant Rapid onset of hepatic insufficiency(within 2 weeks)
hepatitis Fulminant viral hepatitis in 50-65% of cases
Drugs (#1) and chemical toxicity -next-
acetaminophen, isoniazid, anti-depressants,
halothane, amanita phalloides (MUSHROOM
HUNTERS)
Acute yellow atrophy-small flabby liver

Autoimmune Chronic & progressive hepatitis of unknown etiology

Hepatitis Cell mediated autoimmunity injury caused by IFN-g produced by CD4 & CD8
t-cells
?triggered by viral infections, certain drugs, other autoimmune diseases
Women, ANA, anti-smooth muscle, anti-microsome
Clusters of plasma cells in portal areas with interface hepatitis

Alcoholic liver disease

Alcoholic liver Ingestion of up to 80 gm of ethanol (8 beers) produces mild reversible fatty

disease change
Daily ingestion of 80 gm or more increase risk of severe liver disease
Only 10% of alcoholics develop cirrhosis

EFFECT OF ALCOHOL:
Fatty change results from shunting of normal substrates away from
catabolism and toward lipid biosynthesis, impaired assembly of lipoproteins
and increased peripheral catabolism of fat
Induction of cytochrome P-450-transform other drugs into toxic metabolites
Free radicals found react with cellular membranes
Alcohol affects microtubular and mitochondrial function
Acetldehyde induces lipid peroxidation
Alcohol induces immunologic attack on hepatic neoantigens

Morphology of Fatty change-

alcoholic liver microvesicular/macrovesicular
disease lipid
Alcoholic hepatitis-acute hyaline
sclerosis
Hepatocyte swelling and
necrosis NEUTRO/LYMPHS
Mallory bodies - clumps
of cytokeratin filiments,
due to damage to the
hepatocyte
Neutrophilic reaction
Fibrosis-starts around central vein via ITO CELLS
Alcoholic cirrhosis-irreversable
Nonalcoholic Hepatic steatosis who dont drink alcohol (<20g of ethanol/week)
Fatty Liver Becoming more common (decrease in alcoholic liver disease)
Disease Obese METABOLIC SYNDROME, DM, post gastric banding
(NAFLD) & Leads to NASH & cirrhosis (crytogenic cirrhosis no alcohol involved)
NASH
2 Biliary *is the most common obstruction is due to some other NON-BILIARY CAUSE
cirrhosis Obstruction of extrahepatic biliary tree
Cholelithiasis
Malignant neoplasms of biliary tree or pancreas (most common)
Strictures from previous surgical procedures
Yellow-green pigmentation of liver bilirubin is CONJUGATED = water
soluble, accumulates in the liver no true cirrhosis
Hard finely granular appearance, Portal fibrosis with distended small and
large bile ducts

Primary biliary Chronic progressive cholestatic liver disease

cirrhosis (PBC) Destruction of intrahepatic bile ducts AUTOIMMUNE DISEASE
Portal inflammation and scarring
Non-suppurative, granulomatous destruction of medium-sized intrahepatic
bile ducts
Middle aged women(6:1), alkaline phosphatase, Antimitochondrial
antibodies

Primary VS
Secondary
BILIARY
CIRRHOSIS
Primary Inflammation, obliteraive fibrosis and segmental
sclerosing constriction of the intrahepatic and extrahepatic bile
cholangitis ducts
Seen in association with inflammatory bowel disease
Males(2:1) 3 -5 decades, Onion-skin fibrosis,
Autoantibodies in less than 10% of cases

Other odds and Bacteria: Staph, S. typhi, tertiary syphilis

ends Liver flukes- Fasciola hepatica, Clonorchis sinensis, Opisthorchis viverrini
Malaria, schistosomiasis, strongyloidiasis, cryptosporidiosis, leishmaniasis
Von Meyenburg complexes
Bile duct hamartomas-benign
Polycystic Liver disease
Simple cysts (usually asymptomatic recall only need 10% of liver to
fxn)
Many have polycystic kidney disease
Congenital hepatic fibrosis
Caroli disease
Larger ducts of the intrahepatic biliary tree segmentally dilated

Passive Right sided heart failure leads to chronic passive

congestion congestion(CPC)
May cause centrilobular necrosis-nutmeg liver
Sustained failure can cause cardiac sclerosis (rare)

*outflow obstruction =
BUDD-CHIARI
SYNDROME

Peliosis hepatis Sinusoidal dilation, Associated with anabolic steroids,In HIV patients seen
mostly with infection by Bartonella henselae

Budd-Chiari *Occlusion of the IVC or hepatic veins with centrolubular

syndrome congestion and necrosis, leading to
congestive liver disease. Associated with;
HYPERCOAGABLE STATE, PCV, PREGNANCY,
HCC, OCP
Pregnancy Preeclampsia and eclampsia-HELLP syndrome-(hemolysis, elevated liver
enzymes, low platelets)
Fibrin into space of Disse, leading to periportal hepatocytic necrosis
Acute fatty liver of pregnancy

Neoplasms

Focal nodular Well demarcated nodule, Central gray-white stellate scar,

hyperplasia Young women

Malignant 0.5% to 2% of cancers in U.S.-but up to 20% of cancers in areas endemic for

tumors hepatitis
Hepatoblastoma-young children
Angiosarcoma-associated with vinyl chloride, arsenic or Thorotrast
Primary carcinoma of the liver
Hepatocellular carcinoma
Cholangiocarcinoma bile duct

Hepatocellular Aflatoxins, hepatitis B Virus, cirrhosis

carcinomas Most unifocal mass in a background of cirrhosis (PRECURSOR)
May be multifocal
Most paler than surrounding liver
Well-differentiated to highly anaplastic lessions
Fibrfibrolamellar variant seen in young adult
No association with HBV or cirrhosis risk factors

Hepatic Drug toxicity after Bone Marrow transplantation can have a lot of post-
complications of transplant LIVER probs
Organ or Bone Quite common- up to 50%
Marrow Tender hepatomegaly, hyperbilirubinemaia, centrilobular necrosis and
Transplantatio inflammation
n May get a veno-occlusive process

Graft-versus host disease and liver rejection

Can be attacked by both graft-versus-host and host-versus-graft
mechanisms
But are reasonably well tolerated perhaps because the liver contain a large
number of lymphocytes, establishing a chimerism in the recipient.
Acute graft-versus-host disease after BM
10 -50 days after transplant
Hepatitis & necrosis
Chronic: >100 days portal inflammation & bile duct destruction

Liver Transplant Acute-within 2 weeks-mixed inflammatory cell infiltrate in portal tracts and in
pathology the endothelial layer of portal and hepatic vein branches
Chronic-cell mediated destruction of intrahepatic bile ducts(vanishing bile
ducts) and occlusion of hepatic arteries
 Pathology of the Large Bowel

Hirschsprung Absence of ganglion cells DUE TO FAILURE OF NC MIGRATION in the

Disease- muscle wall (Auerbach plexus) and submucosa (Meissner) of the effected
Congenital segment
Aganglionic Rectum always involved
Megacolon Short segment also involves sigmoid
Long segment beyond sigmoid, rarely entire colon
Proximal (normal) colon dilates and hypertrophies
May lead to megacolon

Diarrhea-an increase in stool mass, frequency or fluidity

Dysentery - low volume, painful bloody diarrhea
Diarrhea-daily stool >250 gm containing 70 to 95% H 2O
Secretory = >500 ml fluid, isotonic
Osmotic = Excessive osmotic feces
Exudative = Mucosal destruction (i.e. C. diff)
Malabsorption = Improper absorption, excess stool fat
Deranged = Improper gut neuromuscular function

Infectious Viral - usually mild to moderate gastroenteritis with diarrhea and vomiting
Enterocolitis Rotavirus - 6 to 25 months old
Norwalk virus - older, adults, epidemic outbreaks (cruise ships)
Adenovirus - 2nd most common in children

Bacterial Mechanisms
Preformed toxin ingested in contaminated food - Staph
Infection by toxigenic organism which grow in gut and produce toxin-
E.coli
Infection by enteroinvasive organism which invades epithelial cells
-Shigella

Infectious Shigella - distal colon, acute mucosal inflammation and exudate

Enterocolitis Bloody diarrhea
Invasive Person to person spread
organisms
(Dysentery) Campylobacter jejuni: villous blunting, superficial ulcers, exudate
Bloody diarrhea
Animal contact or poultry puppies

Salmonella: ileum & colon: blunted villi, congestion, linear ulcers

Dysentery and bacteremia
Milk, beef, eggs, poultry

Y. entercolitica: ileum, appendix, colon, mucosal hemorrhage and ulcers

Lymphadenopathy with necrotizing granulomas (more systemic than
others)
Milk, pork
Infectious V. cholerae: small intestine - intact mucosa
Enterocolitis Massive watery diarrhea loss of fluids and electrolytes = arrhythmias
toxin Shellfish, water, person to person
organisms
Clostridium perfringens: small intestine and colon - congestion, some
epithelial damage
Watery diarrhea
Meat, fish

Staph Aureus
Enterotoxin present in food
Symptoms come and go quickly

Clostridium botulinum (botox)

Toxin causes muscle weakness which can progress to respiratory
failure

Cholera Toxin *chloride gets pumped into the

lumen water follows =
WATERY DIARRHEA = RICE
WATER STOOL

E. coli Enterotoxigenic E.coli (ETEC)

Cholera-like toxin, no invasion, watery diarrhea

Enterohemorrhagic E. coli (EHEC)

Shiga-like toxin, bloody diarrhea
E. coli O157:H7 Hemolytic uremic syndrome
Just give supportive treatment

Enteropathogenic E. coli (EPEC)

Watery diarrhea in infants and toddlers

Enteroinvasive E. coli (EIEC)

Invade enterocytes bloody diarrhea
Parasitic Ascaris lumbricoides - lives in the intestine, larva penetrate the mucosa
Enterocolitis and migrates to liver & lung eggs in intestine
Stongyloides in ground soil, penetrate intact skin, migrates trough the
lungs and resides in the intestine
Necator duodenale and ancylostoma duodenale - penetrate skin, lungs
& intestine, attach to mucosa & sucks blood
Enterobius vermicularis - fecal oral, migrate to anus at night & deposit
eggs
Trichuris trichiura- whipworms, does not penetrate mucosa, some may
cause bloody diarrhea and rectal prolapse
Schistosomiasis live in the portal vasculature, progressive seeding w/
eggs
Intestinal cestodes (tape worms)
Diphyllobothrium latum
Taenia solium
Hymenolepsis nana
Entamoeba histolytica- flask shape ulcer, liver abscesses
Giardia lamblia- malabsorbtion, diarrhea
Crytosporidium immunosuppressed patients

Necrotizing Acute necrotizing inflammation of neonates

Enterocolitis Premature or low birth weight neonates are at highest risk
Immaturity of the gut immune system
Initiation of oral feeding releasing cytokines
Gut colonization, Mucosal injury, Possible derange blood flow

Antibiotic- *when giving broad spectrum antibiotics, frequently you wipe out the NORMAL
Associated FLORA but not the C. DIFFICILE = and therefore unchecked the C. diff OVERGROWS
Colitis (unopposed by the normal flora)
C. difficile
Known as pseudomembranous colitis
Psuedo Membrane forms on the surface of the colon usually from
the rectum to some point proximally
Idiopathic Spectrum from Ulcerative colitis to
Inflammatory Crohn disease
Bowel Disease Chronic relapsing inflammatory
disorders of obscure origin
Genetic predisposition: HLA
Dr1/DR1/DQws in 27% of white pts
with CD
HLA-DR2 is increased in pts with UC
Infectious causes - mycobacterium?
Measles virus, need bacteria
Abnormal Host Immunoreactivity-
abnormal T-cell responses -- too
much T-cell activation and too little
control by regulatory T-cells
P-ANCA is positive in 75% of UC
(but only 11% of those with CD)
Inflammation of the GI tract
Simmering chronic inflammation
Bouts of acute inflammation = activity (neutrophils in crypts)
*model of IBD Pathogenesis 1.) driven by bacteria 2.) T-cell activation excessive
activation
Crohn Disease
Sharply
Crohns is to delimited and
the CORE transmural- full
(extends thickness- skip
deeply) lesions can
get random
lesions with
normal bowel in-
between
Noncaseating
granulomata
Fissuring (narrow
ulcers) with
fistulas can
cause loops of
bowel to stick
together
Anywhere in the gut- but most common in terminal ilium
3/100,000 - smoking a risk factor
Intestinal wall thick, edematous
Creeping fat
Linear ulcers, cobblestone pattern
Inflammation through wall
Granulomata
Aphthous ulcers

Ulcerative Literally Ulcers in the Colon

Colitis- Only the mucosa is involved -- not deep!
contrast with Continuous from rectum-- no skip lesions!
CD Involves only the colon (maybe a little
spill over into the ileum)
Systemic symptoms
Primary sclerosing cholangitis and
pericholangitis (more common in UC
but can occur in CD)
Usually begins in rectum
Extensive broad based ulceration
Pseudopolyps (cobblestoning)
Crypt abscesses, only mucosa
Bloody diarrhea
Extensive ulceration may lead to Toxic megacolon
Long term complication is cancer (adenocarcinoma)- if not treated & severe
colitis 20 to 30 increased risk
Crohns vs.
Ulcerative
Cholitis

Chronic colitis Diversion colitis due to surgical diversion

Microscopic colitis
Collagenous colitis thickening of the collagen plate
Lymphocytic colitis lymph infiltration
Non-bloody watery diarrhea
Endoscopy normal
Graft-versus-host disease

Diverticular Acquired, common

Disease Secondary to increased
luminal pressure (low
fiber diet)
Inflammation-scarring
Leading to obstruction
Diverticulosis presence of
diverticula
Diverticulitis diverticula with
inflammation, rupture, often
abscess formation

*DIVERTICULITIS think LEFT

LOWER QUADRANT PAIN

Pathology of the Large Bowel II Neoplasms

Polyp Mass that protrudes into the lumen of the

gut
Sessile = no stalk
Pedunculated = stalked
Some non-neoplastic - hyperplastic or
metaplastic
True neoplasm tubular adenoma
Non Neoplasitic Hyperplastic-small <5mm-low malignant potential most common in rectum
Polyps Juvenile polyps-hamartomatous malformation sporadic or HNPCC
Peutz-Jeghers polyps-harmartomatous

Neoplastic Tubular ademonas-pedunculated-malignant potential depends on size

Adenomas Villous adenomas-sessile and large-malignant potential high
Tubulovillous adenoma-large and in between malig potential

Familial Familial adenomatous polyposis-hundreds of adenomatous polyps

Polyposis prophylactic cholectomy
Syndrome Gardner Syndrome-polyps, osteomas, epidermal cysts
Turcot Syndrome-polyps, CNS tumors (gliomas)
Hereditary nonpolyposis colorectal cancer (Lynch Syndrome)
serrated pathway

Hereditary Autosomal dominant

nonpolyposis Increased colon ca & endometrium
colorectal Adenomas tend to be few and flat but occur early
cancer (Lynch Cancers may be multiple & not associated with adenomas
Syndrome Mutations in DNA repair genes leading to microsatellite instability
MISMATCH REPAIR probs

Adenoma *initial mutation in the APC

carcinoma gene- develop an adenoma
sequence increase in abnormalities
serrated = carcinoma
pathway

Microsatelite
instabilty/HNPC
C

SMALL BOWEL Adenomas

Tumors Adenocarcinoma (rare in small bowel)
Carcinoid (very rare in colon)
Stromal tumors
Lymphoma
Carcinoid Appendix(distal tip) > ileum > rectum > stomach > colon
Stomach tend to be multicentric
Usually incidental but.
Carcinoid syndrome if active and metastasis to liver (rare to met)
*Can produce SEROTININ

Intestinal Stomach > Small > Large

Lymphoma MALToma:
H pylori associated
t(11:18), c-myc
B cell
Celiac Sprue
T Cell Lymphoma
Mediterranean type - rare
Plasma Cell, IgA
Children, young adults
Plaques to fungating tumors
Variety of histologic subtypes

Colon Cancer Most 60 to 80 years

High rate in U.S. and Eastern European countries
Dietary
Excess energy intake relative to requirements
A low content of unabsorbable vegetable fiber
High content of refined carbohydrates
High intake of red meat
Iron deficiency anemia in older male patients necessitates a workup for
occult colon cancer

Right sided lesions- polypoid, exophytic masses

Left sided lesions- annular, constricting lesions (napkin ring lesion)

Colon if invasion into the lamina still considered in situ if it breeches past the
basement membrane = invasive carcinoma

Tumors of the *transition from colonic epithelium squamous epithelium

Anal Canal 3 patterns - rectal, transitional, squamous
Tumors may have a basaloid pattern nuclei are darker
Pure squamous carcinoma associated with HIV and chronic HPV
infection.

Mucocele and Most a simple mucinous cystadenoma

pseudo- 20% perforate producing localized collections of mucus around the
myxoma appendix and in the peritoneal cavity
peritonei A few of these are malignant mucinous cystadenocarcinomas and seed
diffusely causing jelly-belly -pseudomyxoma peritoneii
Sometimes these tumors develop from the mesothelial surface
What is The name given by Werth in 1884 tells us
Pseudomyxoma that it is not a myxomatous degeneration of
Peritonei? peritoneal connective tissue (a belief of
early XIX century pathologists), but mucin
spilled into the peritoneal cavity from an
(ovarian) neoplasm.
Gelatinous ascites
Jelly-belly!

PMP is not a 1. Low grade Largely pools of mucin with scattered benign
single entity appearing mucosa
a. Arises from low grade process in appendix single
layer

2. High grade Morphologically similar to metastatic adenocarcinoma with

invasive glands and cells
a. Arises from carcinoma

Peritonitis
Infectious
Sterile chemical (bile or pancreatic enzymes)
Sclerosing retroperitonitis
Tumors (Metastatic vs. primary)
Non-tumoral conditions (e.g. endometriosis)

Small bowel pathology/Pathology of Malabsorption

Small Bowel Meckel Diverticulum

Malformations Most common congenital anomaly
Rule of 2s
Most within 2 feet of ileocecal valve
2 inches in length
2% of population
If symptomatic, symptoms by age 2
(95% asymptomatic)
2 x as common in males

Failure of the vitelline duct to involute
True diverticulum as it involves all three layers of bowel wall
Ectopic gastric/pancreatic tissue producing gastric acid or pancreatic
enzymes in the termiminal ileum nothing to neutralize
Antimesenteric aspect of the small bowel
Symptoms related to obstruction or bleeding
Small Bowel Malrotation
Malformations Asymptomatic usually, gut fails to rotate embryologically
Duplication
Cylindrical cysts which run parallel to the normal gut
Heterotopia
Ectopic pancreas, occasionally gastric
Symptoms if functional
Omphalocele
Failure of abdominal musculature to properly develop
Abdominal contents in a hernia sac
40% with additional congenital defects
Diaphragmatic hernia and cardiac defects
Gastroschisis
Complete failure of abdominal wall formation
Abdominal contents completely exposed
Atresia
Complete blockade of bowel lumen
Most common in duodenum
Stenosis
Narrowed segment of bowel
Less common

Malabsorption Suboptimal processing of food

Can be fat, protein, carbs, water, salt
Since digestion begins in the mouth and continues to the colon, the culprits
can be anywhere
Presenting signs/symptoms may be seen in another system
Due to disturbance of:
Intraluminal digestion
Pancreatic insufficiency, ileal resection or dysfunction
Terminal digestion
Bacterial overgrowth, loss of flora Vitamin K deficiency
Transepithelial transport
Celiac sprue (decreased surface area) loss of microvilli
becomes a flat epithelium (like the colon)
Additional Examples:
Pancreatic insufficiency, eg. Cystic Fibrosis
Biliary obstruction
Bacterial overgrowth - antibiotics
Reduced surface area
Lymphatic obstruction (e.g. TB)
Infection
Tumor
Malabsorption Steatorrhea
Symptoms Diarrhea
(rrhea, rhhea, Abdominal pain
and sons) Weight loss
Vitamin deficiencies
Vit D, calcium
Vit A, B12

Celiac Sprue aka Gluten sensitive enteropathy, non-tropical

sprue
Patient is sensitive to gluten
Strong association with HLA DQw2 and B8
? Adenovirus type 12
Can appear at birth or later
Diarrhea, weight loss watery diarrhea
Diagnosis
Malabsorption
Serology-antigliadin or anti-endomysial ab
Biopsy to see the VILLI ATROPHY
Removing gluten improves symptoms
?Gluten challenge has someone become
tolerant?
Prognosis
Excellent if remove gluten
2 fold increase in lymphoma (T cell)
Histopathology
Diffuse enteritis, worse in the duodenum
Villous atrophy but thickness the same due to corresponding crypt
hyperplasia
Small bowel mucosa resembles normal colonic mucosa
Lymphocytes, eosinophils, mast cells

Tropical In the tropics

(infectious) Endemic and epidemic forms
Sprue Diarrhea, malabsorption
Variable histology but usually more diffuse than Celiac Disease
Involves distal small bowel as much as proximal small bowel
Treat with antibiotics
Whipple PAS positive macrophages (the material is the
Disease partially digested material of WD), small intestine, CNS,
joints
Tropheryma whippelii
Males, whites
Malabsorption, diarrhea, CNS, joints
Lymphadenopathy
Rx with antibiotics (TMP)
Histopathology
Expansion of the small bowel lamina propria with sheets of macrophages
containing PAS positive material
Material is partially digested organisms
Mycobacterium avium-intracellulare is an important differential in immune
compromised patients can look like WD must do acid-fast stain to
distinguish (MAI will be +)

Disaccharidase Located on the apical cells of the small bowel

(Lactase) Congential or acquired
deficiency Congenital presents at start of breast feeding
Acquired is much more common
Osmotic diarrhea
Partially breakdown of lactose leads to unabsorbed sugar being broken down
by gut flora resulting in hydrogen formation

Intestinal Results from a variety of causes

Obstruction 80% from hernia, adhesions, volvulus, and
intussusception
Less commonly results from a tumor
Symptoms:
Abdominal pain
Distention
Constipation
Vomiting
May require immediate surgical intervention
ADHESIONS most common, bowel sticks
together, due to prior surgery
INTUSSESSCEPTION common in kids, bowel folds in upon itself
Hernias Hernias
Weakness or defect in the
peritoneal wall
Viscera, most often small
bowel, protrudes into the sac
formed by the defect
Usual sites
Inguinal or femoral
canal
Umbilicus
Surgical scar
Complications
Incarceration:
permanent trapping of
sac contents
Strangulation: infarction of the entrapped bowel

Adhesions Adhesions
Fibrous bands which connect loops of bowel to one another,
surrounding organs or abdominal wall
Secondary to:
Surgery, Infection, Endometriosis

Intussusception Intussusception
One segment of bowel
telescopes into the immediately
distal segment
Children
Otherwise healthy
No point of traction
Adults
Results from some mass
or tumor acting as a point
of traction

Volvulus Volvulus
Twisting of a loop of bowel around its mesenteric base
Most often occurs in sigmoid colon
Occurs rarely
Ischemic bowel Arterial thrombosis-ASVD,
disease systemic vasculitis
Dissecting aneurysm,
etc.
Arterial embolism-
vegetations, angiographic
procedures
ASVD
Venous thrombosis-hypercoagulable states, oral contraceptives
Non-oclusive ischemia-cardiac failure, vasoconstrictive drugs
Miscellaneous-radiation

Can involve any segment of bowel

Splenic flexure of colon is at greatest risk due to watershed location
between inferior and superior mesenteric arteries
More common in older individuals and those with risk for obstruction
Varies in severity and involvement of bowel wall layers

Complications if transmural
Perforation
Vascular collapse and shock
50-75% death rate
Mucosal and Mural
Nonspecific abdominal complaints, Bloody diarrhea
All types are easy to confuse with other entities

Vascular Angiodysplasia- tortuous dilations of submucosal and mucosal blood

disorders of the vessels
bowel Account for 20% of significant lower gut hemorhage
Hemorrhoids- dilations of anal venous plexuses

Small bowel Rare overall with tumors in the small bowel when compared to stomach and
malignancies colon
75% of the length of the GI tract but 3-6% of tumors
Benign tumors
Adenomas and mesenchymal tumors
Malignant tumors
1% of GI malignancies
Adenocarcinoma and carcinoid
Lymphoma

GI Lymphoma 1-4% of GI malignancies

Helicobacter gastritis
Natives of Mediterranean region
Congenital immunodeficiency states
HIV infective individuals
Patients with sprue
Mesenchymal Lipoma
Tumors Stromal tumors
Leiomyoma
GIST- gastrointestinal stroma tumors- CD-117 or c-KIT positive
Leiomyoma
May be the site for itussusception or obstruction

Gastrointestinal problems in infancy

Esophageal 1/3000 births

atresia with or Proximal esophagus ends in a blind pouch
without a Most have an associated fistula to trachea
tracheoesophag
(exam)**MOST COMMON esophageal atresia with distal
eal fistula (TEF)
TEF
Is DISCOVERED within the first 24 hours

Polyhydramnios (excessive amniotic fluid b/c baby cant swallow)

and preterm delivery are increased if fetus has esophageal atresia because fetus
cannot swallow amniotic fluid
*stretches the UTERUS and can cause PREMATURE delivery

*How to diagnose? - Place a ORAL GASTRIC TUBE and it stops MID THORAX and on
XR see AIR IN STOMACH = DISTAL TEF (only cause for air to be in stomach)

H-typed TEF These are diagnosed later in life with recurrent pneumonia or
(no esophageal persistent cough
atresia) *baby can swallow but reflux secretions will go into lungs will
eventually cause pheumonia note the angle, so will be minimal
flow but eventually becomes symptomatic

Congenital *left lung hypoplasia

Diaphragmatic *bowel gas in thorax
Hernia *babies present with a SUNKEN ABDOMEN the
intestines are in the chest
Pyloric stenosis Hypertrophy of pylorus
Projectile non-bilious (i.e is above the liver)
vomiting
3-6 weeks old is not a
condition that is congenital,
develops
Male > female
Erythromycin can cause

Hypertrophy and hyperplasia of muscular layers of pylorus leads to gastric outlet

obstruction

firm, nontender, mobile hard pylorus that is 1-2 cm in

diameter, described as an "olive," in the right upper quadrant
best palpated after the infant has vomited and when calm

Pyloric stenosis diagnosed by UGI

String sign: elongated narrowed pyloric canal (short
arrow)
Shoulder sign: hypertrophied muscle (long arrow)

*Or can be dx via ultrasound

Classic serum Repeated vomiting results in loss of HCl

electrolytes Hypochloremic (low Cl-)
in pyloric Hypokalemic (low K+)
stenosis
Metabolic alkalosis (high HCO3-)

Duodenal Complete obliteration of duodenal lumen

atresia Failure of recanalization of duodenal lumen
Polyhydramnios and premature delivery are common
Trisomy 21 is common
Bilious vomiting b/c the obstruction is distal to the ampulla of Vader

Duodenal DUODENAL ATRESIA think DOWN SYNDROME and on XR

atresia DOUBLE BUBBLE which is referring to air in the DUODENUM
Xray: double & STOMACH
bubble
Intestinal interruption of normal intestinal rotation and fixation
malrotation during fetal development
cecum is normally located in right lower quadrant of the
abdomen
in malrotation, the cecum stay in the upper right side of
the abdomen
bands of tissue called Ladd's bands form between the
cecum and the intestinal wall and can create a blockage
in the duodenum *see BILIOUS VOMITING

40% present by age 1 week

50% of patients by age 1 month
75% by age 1 year
remaining 25% present after age 1 year and into late adulthood
**Present with: bilious vomit
**If a baby has bilious emesis you must rule out an intestinal malrotation:
do an upper GI MUST DO ASAP
WHY? b/c when you are MALROTATED normal peristalsis can cause a MID GUT
VULVULUS

midgut volvulus A patient with malrotation of intestines can

suddenly develop a complication called a midgut
volvulus the TWISTING cuts off circulation to the
intestines is a MEDICAL EMERGENCY

Necrotizing Problem of premature infants

Enterocolitis Ischemia of intestine that leads to intestinal necrosis
(NEC) Baby develops: abdominal distension, bloody stools and
abdominal discoloration
Dx via XR:
Xray hallmark: Pneumotosis intestinalis = air that is in the
WALL of the intestine dissected though an ischemic area of
the intestine

*stop feedings put the baby on antibiotics

Occaionally the bowel can PERFORATE =

pneumoperitoneum
(free air in abdomen) means bowel perforation visualize with Left lateral
decubitus Xray
Meconium intestinal obstructive variant of cystic fibrosis
ileus (= 15% of infants with cystic fibrosis (AR, D508, Ch 17)
Cystic present with intestinal obstruction related to meconium
Fibrosis) ileus
EXAM
MI MOA - distal ileum obstructed by small, round waxy rabbit
pellets and more proximal obstructed by thick green
meconium

Meconium ileus: contrast enema shows the dried out

pebbles (red arrow) of meconium in ileum

Gastroschisis Abdominal wall defect located to right of

umbilical cord in the involution process
hole develops
Usually isolated defect
No other anomalies
No membrane surrounds bowel

Omphalocele Intestine herniated within umbilical cord

Intestine covered by a membrane
Increased incidence of other anomalies
Beckweedamin Syndrome profound
hypoglycemia

Hirschsprungs absence of ganglion cells and myenteric plexus, secondary

Disease to failure of neuroblastic migration
absent ganglion cells start at the anus and progresses
cephalad for varying lengths
70% affects only the distal sigmoid and the rectum
15% affects bowel proximal to the splenic flexure

*present with abdominal distention - diagnosis is frequently made because of

failure of the child to pass meconium within the first 48 hours
Imperforate
Anus

Diarrhea, Constipation, Malabsorption

200 g/d, Decrease in form, consistency, >4 stools/day

Incontinence (not diarrhea)
Functional vs. organic (nocturnal, incontinence, weight loss)
Osmotic vs. secretory
Duration (Chronic = 2wks), meds (alternative Rxs), diet, travel, immune
compromise

Diarrhea Types SECRETORY

large volume/watery
little response to fasting
cholera, VIPoma
bile salts, fatty acids (ileal resection)

OSMOTIC
improves with fasting
lactose intolerance, CHO malabsorption, fructose intolerance, Mg+ laxatives,
lactulose, PEG
increased solute gap

Simplified 5- 1. Does the patient really have diarrhea? Beware of fecal incontinence
Step Approach and impaction.
to Diarrhea 2. Rule out medications as a cause of diarrhea (drug-induced diarrhea).
EXAM 3. Distinguish acute from chronic diarrhea.
4. Categorize the diarrhea as inflammatory (BLOODY), fatty (OIL
DROPLETS), or watery.
5. Consider factitious diarrhea (LAXITIVES)

Secretory *vibrio, laxative abuse, VIPoma

diarrhea
C.difficile: Carrier State
manifestations C.difficile-associated diarrhea (CDAD)
C.difficile colitis
(not test Qs) Pseudomembranous colitis
Fulminant Colitis/Toxic Megacolon can present atypically
Atypical (e.g., sepsis, ascites)
Recurrent disease
*can treat empirically b/c can be such a serious infection

Collagenous Collagenous colitis has recently

Colitis been recognized as a principal cause
of sudden profuse, chronic, watery
diarrhea, predominantly in woman
over the age of 50. The diarrhea is
not bloody and the endoscopic
appearance is usually normal, but
colonoscopic biopsies will reveal an
infiltration of lymphocytes and
plasma cells in the lamina propria as
well as a marked excess of
intraepithelial lymphocytes. A
thickened subepithelial layer of
collagen may sometimes be recognized as a pink band on routine hematoxylin and
eosin staining, but whenever the diagnosis is suspected, special stains for collagen
such as Massons trichrome or toluidine/alcyon blueshould be performed.

Constipation < two stools per week, Straining, Hard stools

Rome III
10% of US population
Inadequate fiber, Meds
Systemic disorders
Endocrine
Neurologic
Rheumatologic
Dyssynergic defecation
Slow transit (nl=72hr)

Red flag Recent onset of constipation in older age (> 50 years) = Obstruction?
features in Rectal bleeding, Weight loss
chronic Family history of colon cancer
constipation Iron deficiency anaemia
Haem positive stool
Pooping

Epidemiology of o 3-20% of U.S. population

IBS o Women 2x men
Exam o Age 15-34 years (early 20s)l
o 5009 people, 14% incidence of IBS (77% undiagnosed)
AlimentPharmTher2005
o People with IBS have OTHER FUNCTIONAL PROBLEMS Fibromyalgia,
chronic fatigue syndrome, depression, anxiety, panic disorder

Pathophysiology Visceral hypersensitivity

of IBS Abnormal colonic motility
Abnormal brain-GI tract interactions
Immune activation
Small bowel bacterial overgrowth

*SYNDROME exists bc the patient decided to go to the doc = IBS (i.e. lots of
people have GI probs)
*IBS patients just see the doc more frequently, the controls had the same incidence
of probs
*WHY are some people hyper vigilant in seeing the doc? SEXUAL ABUSE,
TRAUMATIC EXPERIENCES (KOSOVO WAR), PSYCHOSOCIAL COMPONENTS = IBS
*SPRUE is increasing in incidence, check with the ANTIBODY TEST (much
better than biopsy)
How do you Psychotherapy - Interpersonal
treat IBS? Treatment
PSYCHOTHERAP One well-designed study using
Y!! psychotherapy (interpersonal
treatment) was able to show that
the active therapy was superior to
medical treatment in reducing
diarrhea, abdominal pain,
physician visits and symptoms of
anxiety and depression. The
improvement in bowel symptoms
paralleled the psychological
treatment. Since no physiological
studies were done, it is not known
whether the psychotherapy improved bowel physiology or just the cognitive
interpretation or degree of coping with the symptoms.

*50% PLACEBO effect just talk to the patient

IBS = personality disorder, its a psychosocial syndrome

Mechanisms of Luminal
Malabsorption Pancreatic insufficiency
chronic pancreatitis
Improper mixing, rapid transit, bacterial overgrowth, ZE
Bile salt deficiency
Bacterial overgrowth
Increased losses (terminal ileum)
Reduced synthesis, secretion (liver disease)
Mucosal
Diffuse disease (sprue)
Resection
Transport
Lymphatic conditions

Malabsorption Pancreatic insuffiency presenting pattern

Suspected Protein/calorie malnutrition
Normal CBC, protime, serum chemistry profile
Image the pancreas
No clues
H2 breath test
QUALITATIVE stool fat, giardia
Serum tests for sprue
Small bowel SPRUE (if suspected get an antibody test)
Vitamin, mineral deficits
Fe deficiency, Elevated protime, Night blindness, Vit D
deficiency
Hypocalcemia, Hypophosphatemia
Pancreatic Loss of 80-90% of exocrine function before you start to SPILL FAT INTO
Insufficiency STOOL
Fecal fat >8-10 g/d (>3 is normal)
TREAT WITH Pancreatic supplement (30,000 lipase units per meal)
May need acid suppressant ACID INACTIVATES pacreatric enzymes

Celiac Sprue Inappropriate T-cell mediated immune response

Gluten-sensitive Inflammatory injury to small bowel
enteropathy Wheat gluten (rye, barley)
1:300 North America, Europe
Rare in Chinese, Japanese, African
Sxs may be mildiron defic, osteoporosis
Assoc with autoimmune diseases (5% of diabetics)
Serologic tests; small bowel biopsy
IgA deficiency in 2-3% - therefore test IgA levels
*About 1% of the population

Interaction of Gluten with

Environmental, Immune, and
Genetic Factors in Celiac Disease.
Gluten is digested by luminal and
brush-border enzymes into amino
acids and peptides. The gliadin
peptides induce changes in the
epithelium through the innate
immune system and, in the lamina
propria, through the adaptive
immune system. In the epithelium,
gliadin damages epithelial cells,
resulting in increased expression of
interleukin-15, which in turn
activates intraepithelial
lymphocytes. These lymphocytes
become cytotoxic and kill
enterocytes that express MIC-A (a
stress protein) on their surface.
During infections or as the result of
permeability changes, gliadin enters
the lamina propria, where it is
deamidated by tissue transglutaminase, allowing interaction with HLA-DQ2 (or HLA-
DQ8) on the surface of antigen-presenting cells. Gliadin is presented to gliadin-
reactive CD4+ T cells through a T-cell receptor, resulting in the production of
cytokines that cause tissue damage. This leads to villous atrophy and crypt
hyperplasia, as well as the activation and expansion of B cells that produce
antibodies.
Deamatitis
Herpetiformis
Celiac Sprue

Celiac Lifelong gluten-free diet

Treatment An expert dietitian
Initially, other dietary modifications may be necessary, including a low-
lactose diet and nutritional supplements
Lack of response to a gluten-free diet should signal the physician to look for
intentional or inadvertent gluten ingestion
Incorrect initial diagnosis, and complications of celiac disease
True refractory celiac disease or lymphoma (due to chronic inflammation)

EXAM QS *know 5 strep approach for diarrhea

*(nothing on diarrhea)
*IBS, epidemiology in US
*diff mechanisms that make IBS an ORGANIC DISEASE (bacterial overgrowth etc.)
*psychosocial factors IBS
*broad mechanisms of malabsorption LUMENAL, MUCOSAL, LYMPHATIC

Nutrition

Metabolic Android (abdominal) obesity

Syndrome Hypertension
Insulin resistance
Hyperuricemia
Dyslipoproteinemia
High waist-to-hip ratio
>1.0 in men
>0.6 in women

Diets Atkins 4.7 kg low at 1 year also better BP, HDL, TG BUT the type of diet
doesnt matter its about # CALORIES in

EXAM When can you

operate?
-BMI > 40
-less than 40 if also
have obesity related
disease
 *addressing the stimulus for food intake new drugs
will target serotonin or leptin (FYI)

Bariatric More effective than nonsurgical Rx

Surgery BMI >40 kg/mm (less if obesity related disease)
Wt loss of 20-30 kg
more wt loss with gastric bypass rather than gastroplasty
mortality <1%
morbidity 20% (better with laparoscopy)

GASTRIC BYPASS make the stomach smaller and INDUCE

malabsorption, early satiety

LAP BAND port on the stomach, allows tightening/loosening

Complications Perioperative infection

of Bariatric Anastomotic leak
Surgery Anastomotic stricture
EXAM Diarrhea
Fe deficiency (Roux-en-Y)
B12 deficiency
30% gallstones
Osteoporosis
Alcohol use disorders (alcohol abuse etc.)

Anorexia Prevalence 0.5-1% primarily adolescent and young women

Nervosa Female/male : 10/1
Exam 5-15% of women evaluated for amenorrhea
Preoccupation with thinness (some binge then compensate)
Mortality rate 6% per decade due to the ELECTROLYTE ABNORMALITIES
Hypo K+, Phos-, Mg++
alkalosis
Family-based therapy
20% chronicity
Bulimia Nervosa Lifetime prevalence 1.1% fem, 0.1% male
Women aged 16-22 yrs
Binge/purge (secretive behavior)
Rarely crosses over to A. Nervosa
Normal or high BMI
Parotid gland enlargement, elevated salivaryamylase, enamel erosion,
Russell sign (finger calluses from inducting vomiting)
Hypo K+, Mg++
alkalosis
Behavioral Rx, high relapse
Alcohol/drug dependency
Binge eating; Night Eating Syndrome; w/o purging - obesity

Starvation Increased fat metabolism to conserve lean mass

changes can be reversed by appropriate feeding
Reduced Basal Energy Expenditure
Die from PNEUMONIA
Cachexia Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue,
(EXAM Diff weakness, and significant loss of appetite in someone who is not actively trying to
b/t cachexia lose weight. The formal definition of cachexia is the loss of body mass that cannot
and be reversed nutritionally: Even if the affected patient eats more calories, lean body
starvation) mass will be lost, indicating a primary pathology is in place.
Cachexia is seen in patients with cancer, AIDS,[2] chronic obstructive lung disease,
multiple sclerosis, congestive heart failure, tuberculosis, familial amyloid
polyneuropathy, mercury poisoning (acrodynia) and hormonal deficiency.
It is a positive risk factor for death, meaning if the patient has cachexia, the chance
of death from the underlying condition is increased dramatically. It can be a sign of
various underlying disorders; when a patient presents with cachexia, a doctor will
generally consider the possibility of cancer, metabolic acidosis (from decreased
protein synthesis and increased protein catabolism), certain infectious diseases
(e.g., tuberculosis, AIDS), chronic pancreatitis, and some autoimmune disorders, or
addiction to amphetamine. Cachexia physically weakens patients to a state of
immobility stemming from loss of appetite, asthenia, and anemia, and response to
standard treatment is usually poor.

redistribution of bodys
protein content
depletion of skeletal muscle
increased synthesis of
acute-phase proteins i.e.
part of the STRESS RESPONSE
increased Basal Energy
Expenditure
hypercaloric feeding doesnt
reverse loss of lean mass
Energy-intensive
High rates of hepatic protein
synthesis require large quantities of essential AAs
Need for AAs drives loss of skeletal muscle
Adaptive over the short term (muscle replaced rapidly after recovery)

*point of the graph = CACHEXIA = trauma, infection etc results in a

GREATLY ELEVATED energy expenditure especially when compared to
just STARVATION

Nutritional *the best is SUBJECTIVE GLOBAL ASSESSMENT i.e. the basic H&P
Assessment

ENERGY Harris-Benedict with stress factor

REQUIREMENTS Direct calorimetry heat produced in water bath
Indirect calorimetry calculated from VCO2, VO2, and nitrogen excretion

Nitrogen Balance (grams) = 24hr protein intake(gm)/6.25 - 24hr uun(gm) + 4 gm

Is there a blood = YES, its the PREALBUMIN

test?
How do we feed Enteral = feeding into the gut assumes the GI TRACT IS
a patient? FUNCTIONAL less expensive, more complete nutrient profile,
fewer complications.

Parenteral = IV feedings higher complications

Go to Jejunal
feedings if
worried about
gastroparesis,
and reflux
REFEEDING *As you start refeeding patients
SYNDROME and if it occurs TOO FAST the
EXAM following are possible, all leading to
CARDIORESPIRATORY FAILURE

*increased workload must blow off

more CO2 can go into respiratory
distress

EXAM Qa When to operate for obesity

Clinical patterns of anorexia/bulimia
Starvartion Cachexia
How to do a nutritional assessment = Subjective Global Assessment
Refeeding Syndrome

Drugs Used in Gastrointestinal Disorders

Drugable Pharmacologically treatable impairments to normal motility, digestion, secretion

Targets and absorption processes of the stomach/intestinal tract include: Peptic Ulcers,
GERD, Gastroparesis, Diarrhea and Nausea & Vomiting

Drugs for the Peptic Ulcer: lesion of gastric or duodenal mucosa occurring at a site where the
Treatment of mucosal epithelium is exposed to acid and pepsin. (generally NOT a disease of
Peptic Ulcers EXCESSIVE ACID but a disease of loss of STOMACH DEFENSE MUCOSAL BARRIER
is disrupted)

GOAL #1 is to reduce the PAIN, can promote HEALING by treating the cause = H.
Pylori

Therapeutic Overview of the Treatment of Peptic Ulcer

A. Neutralize Acid/Pain & Healing
B. Block Acid Secretion/Pain & Healing
C. Repair Mucosal Barrier/Healing
D. Eradicate Helicobacter Pylori
Rationale *Superficial Epithelial
Underlying Drug Cell secretes mucus
Treatment for MAINTAINS the
Peptic Ulcers MUCOSAL BARRIER
*right hand side faces
(EXAM the stomach lumen
understand) *Proton Pump
transports acid into the
lumen
-PPIs Omeprazole

*Have ANTIACIDS
(bismuth simple bases
that chelate acids in the
lumen)

*Sucraifate bind to the ulcer lesion (proteins) and protects

On the basolateral side

*Muscarinic Antagonists Ach when released by vagal nerves = + acid
production
*Gastirin circulating polppeptide hormone = +acid
*can bind to enterochromafin cells activates the release of HISTAMINE H2
receptors
*PG are locally produced they inhibit acid production, and stimulate MUCUS
secretion
*M2/3 are = Gs coupled recetors which function to ACTIVATE the H+ pump via
cAMP
*G (gastrin) Receptors = work though a Gq pathway = + Ca+2 dependent
pathway is less efficacious then the cAMP pathway
*Histamine which goes directly to activate the H+ pump and do so more
strongly than the other activators i.e. is the primary driving force for H+
production.

*NSAIDS inhibit PG function PG function to stimulate the production of the

mucosal barrier hence the inhibitor results in a decrease in the mucosal
protection

Acid Weak bases that react with HCl to form salt + H 2O

Neutralizers - [Tums] CaCO3 + 2 HCl = CaCl2 + H2CO3
Antacids [Milk of Magnesia] Mg(OH)2 + 2 HCl = MgCl2 + 2 H20
[Alka-Selzer] NaHCO3 + HCl = NaCl + H2O + CO2
Gastric H2 Histamine Receptor (competitive) Antagonists very selective - MOA is
Antisecretory they block histamines abilitiy to increase cAMP and phosphorylate the H+/K+
Drugs ATPase.

Cimetidine (Tagamet) first one developed, should not be used, INHIBITS P450s
therefore has significant D-D INTERACTIONS, and has ANTIANDROGENIC EFFECTS
Ranitidine (Zantac)
Famotidine (Pepsid)
Nizatidine (Axid)
*best to take drugs PRIOR to BEDTIME leads to the greatest change in ULCER
HEALING

Gastric Proton Pump Inhibitors are PRO drugs that undergo bioacitvation occurs AT
Antisecretory THE SITE OF ACTION they are all WEAK BASES and therefore PROTINATED in the
Drugs stomach = +activated and bind to and PERMINATELY INHIBIT the pump.
*best to take IN THE MORNING PRIOR TO MEAL get large premeal acid rush
and the acid pump is inhibited
*are not useful for immediate relief takes several days for the pumps to be
inhibited- once active they inhibit 90-100% of H+ PUMPS are highly efficacious,
with limited adverse effects
*raise the pH BUT why do we have acid what is the LONG TERM effect of PPI?
no evidence of tumor formation, BUT have seen reduce defenses against
bacterial infections, Ca+2 absorption is reduced (higher fractures),
hypomagnesiuma.

Omeprazole (Prilosec) (Nexium is the stereoisomer of Omeprazole)

Lansoprazole (Prevacid)
Rabeprazole (Aciphex)
Pantoprazole (Protonix)

Drug with BOTH Prostaglandin (PGE1) Analogs

Misoprostol agonists at the prostaglandin receptor both inhibits via cAMP at
ANTISECRETO the H+ Pump AND activates the release of MUCOSA (see diagram) only approved
RY and for the use of NSAID induced ulcer very rarely used.
MUCOSAL *SEs causes uterine contraction pains (can induce abortion)
PROTECITVE
PROPERTIES
Mucosal Sucralfate - Aluminum Salt of Sucrose Octasulfate MOA has zero systemic
Protective uptake (NO ABSORBED) and it fxns by BINDING to and COVERING the lesion (i.e.
Agents the ulcer) forms a barrier protecting from the endogenous acid.
*major use is in INTENSIVE CARE patients under significant stress
Polytherapy to
eradicate H.
pylori

Drug Therapy Antisecretory Drugs

for the
Treatment of Prokinetic Drugs
GERD and *Tegaserod/Zelnorm
Gastroparesis
*GERD + Gastroparesis can co-exists,
delay in emptying can cause the extra gastric
contents to reflux

*can use drugs to increase the motility =

PROKINETIC DRUGS
*METOCLOPRAMIDE C dopamine 2
receptor antagonists it increases the TONE
of the LES and it ALSO stimulates intestinal motility (prokinetic)
therefore is ONLY used when patient has BOTH GERD and Gastroparesis.

Rational Basis Cisapride = 5-HT4 Agonists

for Using enhanced Ach release
Prokinetic Drugs
to Treat GERD & Erythromycin = + MOTILIN
Gastroparesis which + GI motility therefore
can be used to treat
gastroparesis (short term)
(hence one of the side effects of
Erythromycin is diarrhea)

METOCLOPRAMIDE = DA is an
Ach ANTAGONISTS therefore by inhibiting DA then get an increase in the release
of Ach = INC. GUT MOTILITY
*may be used in nausea/vomiting i.e. as an antiemetic
*SEs can cross the BBB and block D2 receptors in the brain can cause
tardive dyskinesia
Antidiarrheal Opioid Agonists:
Drugs Codeine only need low doses to achieve
- antidiarrheal effect
Morphine
Loperamide (Imodium) does not cross the BBB
less efficacious
Diphenoxylate semiperminant in the BBB is combined with ATROPINE = slows
motility but is combined to limit its abuse potential b/c get atopine SEs at high
concentrations blurry vision, inability to poop etc.

*recall the SE of CONSTIPATION OPOIDS fxn via INHIBITING

NEUROTRANSMISSION (increases the transit time paralyze the gut)

Bismuth Subsalicylate i.e. is Pepto BIsmal not absorbed orally therefore can
create a BLACK STOOL

Pharmacologist *if you ingest something

s View of Emetic that is toxic = is detected
Stimuli by the CHEMO-RECEPTOR
(produces TRIGGER ZONE which
vomiting) then can activate the
EMETIC CENTER to induce
vomiting

*Blood Born Emetics i.e.

OPOIDS activate the
CHEMO-R ZONE and cause
vomiting
*when cells in the gut
are irritated = +serotonin
release = vomiting
Antiemetic Metoclopramide/Domperidone - Dopamine receptor (D2) antagonists (above)
Drugs
Chlorpromazine/Prochlorpromazine/Haloperidol/Droperidol - Antagonists
at dopamine, muscarinic and histamine receptors

*Ondansetron/Granisetron - Serotonin receptor (5HT3) antagonists

*post-surgical anesthesia use, post chemotherapy

Dimenhydrinate/Diphenhydramine/Meclizine, Promethazine and

Scopolamine -Histamine (H1) and muscarinic receptor blockers
*use in MOTION SICKNESS
*many have anticholinergic activity sleep aids (blocking of H1)

Dronabinol - Cannabanoid receptor (CB1) agonist

*antiemedic effects pill form of THC
*oral bioavailability is UNPREDICTABLE

Lorazepam/Alprazolam Benzodiazepine receptor agonists

*treating anticipatory dread i.e. chemotherapy, anterograde amnesia

Dexamethasone/Methylprednisilone Glucorticoid receptor agonists

*have mood elevating effects

Gastrointestinal Bleeding

GI Bleeding Upper 75%

LGIB
*80% of the time the bleeding will stop

Etiology of Non Variceal: 86%

Upper GI Ulcerations: about 50%
Bleeding Mallory-Weiss Tear: 4-8%
Erosive esophagitis: 1-13%
Neoplasia: 2-7%
Vascular ectasia: 0-6%
Variceal: 14%

Gastric Ulcer *like a pot-hole in the gastric mucosa

Risk of NSAID-Related Ulcer Bleeding
Dose dependent
Concomitant steroid and NSAID use doubles risk of ulcer
complications

Gastric Cancer
Mallory-Weiss *excessive wretching

Upper GI Hematemesis (30%)

Bleeding Melena (20%) = upper GI bleed until proven otherwise
Presentation Both
Up to 15% of all patients present with hematochezia bright red blood in
stool due to high volume GI bleed

Predictors of Postural hypotension, Shock

Severity Red hematemesis significant GI bleed (if upper GI bleed and its reaching
of a Bleeding the end red = high volume/severe bleed active bleeding)
Episode: Hematochezia
Inability to clear the nasogastric (NG) lavage
Severe coagulopathy (taking anticoags)
Age > 60 years old
Inpatient hemorrhage
Presence of significant coexisting illness

Independent Use of NSAIDS or aspirin

Risk Factors for History of peptic ulcer disease more likely to have recurrent
Adverse Post op complications following urgent surgery
Outcomes Usually dont exsanguinate, die due to decompensation of other organs.
use to excessive blood loss, other organs suffer
Mortality of 5-10%

Initial *RESUSCITATION refers to the infusion of IV fluids and blood transfusion. Goal is
Resuscitation to prevent hypovolemaia and subsequent shock from occurring.
and Medical
Management Clinical Assessment
Hx (what is the source?)
PE vital signs (is the patient hypotensive due to blood loss?)
NGT aspirate
Admission to ICU or monitored bed
Resuscitation- doesnt matter what you use initially based on initial Hgb if
<7 then do blood transfusion
IVF
Transfusion of blood products (PRBC)
Endotracheal intubation
Ongoing hematemesis or altered MS
Correction of coagulopathy
Evaluation of Esophagogastroduodenoscopy (EGD)
UGI Tagged RBC scanning CTe, CTA, MRA noninvasive ways to look for
Hemorrhage bleeding
Arteriography
Surgery

Management of High dose PPI Rx

UGI Bleeding Endoscopic Modalities
Injection Rx
Thermal device
Mechanical

Endoscopic Thermally active

Methods of Heater probe
Hemostasis of APC
UGIB Injectable therapies
Epinephrine causes the vessels to stop bleeding
Glue
Mechanical
Endoscopic clips
Band ligation varicies
Combination Rx

Predictors of Active bleeding 55-90% likely to REBLEED

Early Visible vessel 43-50% 50% of the time there is 0 bleeding at
Rebleeding the base of an ulcer
Based on Adherent clot 12-33%
Endoscopic Clean ulcer base 3-5%
Findings
Retreatment Rebleeding after endoscopic Rx (10-25%)
Repeat endoscopic Rx is often warranted
signs of ongoing bleeding
Generally very effective

Two Strikes Rule 2 x that you failed time to look at open surgery

Surgical High risk of rebleeding

Consultation Ongoing bleeding despite endoscopic intervention

Angiographic Main role

Therapy When endoscopic localization of bleeding site has failed
If endoscopic hemostasis unsuccessful
Non-surgical candidate
Forms of therapy
Vasopressin infusion (rarely used now)
Embolization
Therapies For Medical therapies
Long-Term Acid suppression
Prevention of Prostaglandin analogs
Ulcer Mucosal protectants
Hemorrhage Helicobacter Pylori eradication heals an ulcer
NSAID discontinuation
Smoking cessation

Natural History *far left are large varices treat with successive banding
of Varices

Management of Varicele
Acute Variceal Resuscitation give blood, fluids
Bleeding Octreotide infusion decreases bleeding (mimics
somatostatin - +vasoconstriction and therefore
reduces portal vessel pressures in bleeding varices).
Antibiotics (quinolones)
Endoscopic Rx
Sclerotherapy
Band ligation
Balloon Tamponade extended in the esophagus, rarely used
Transjugular intrahepatic portosystemic shunt (TIPS) (see pic)
Beta-blockers when stable as primary or secondary prophylaxis

Lower GI bleeding

Lower GI Methods to distinguish types and location of LGIB

Bleeding Painful vs painless
Bright red blood (BRB) vs dark blood (or clots)
Blood on outside of stool vs mixed in stool
? Melena

Lower GI Diverticulosis
Bleeding Ischemic colitis
DIFFERENTIAL Colon polyp
Angiomas
Cancer
Hemorrhoids
Inflammatory bowel disease
Diverticular Brisk, abrupt onset, intermittent LGI bleeding
Bleeding Most common cause of severe hematochezia
Most frequently originates in right colon (70%)

*most of our diverticula are in the LEFT

COLON but the MAJORITY of bleeding occurs
in the RIGHT COLON

Ischemic Colitis *bright red bleed nausea, vomiting

Colonic VASCULAR ABNORMALITY

Angiodysplasia Most often in the right colon
Associated with
Advanced age
Comorbid illness
CRI, ESLD, CTD, valvular heart
disease, etc.
Precipitated with antithrombotics
Presentation
Usually mild and self-limited
Endoscopic Rx to obliterate multiple colonic angiomas
Rare hemicolectomy or transfusion dependency

Colonic Obscure more often than overt

Neoplasia May present as iron deficiency
Heme positive
Larger polyps bleed (but many colon cancers
dont bleed)
Intermittent
20% miss rate of colonoscopy
Precipitated with antithrombotics
Internal Presentation: mild to profuse bleeding
Hemorrhoids Active bleeding from internal hemorrhoids or stigma of hemorrhage
Typically painless hematochezia
BRBPR/clots
Therapies
Band ligation
Injection Rx
Excision
Coagulation

Severe, Acute Insertion of NGT for gastric lavage

Lower GI 10-15% of hematochezia secondary to UGI bleeding source
Bleeding: Bloody aspirate perform EGD 1st
General Aggressive resuscitative measures
Measures Lower endoscopic evaluation
Urgent colonoscopy
Scinitigraphy (Tc 99)
Angiography
IR/conventional selective visceral angio
CT angiography

Scinitigraphy = Bleeding rate > 0.1/cc/min (just tells you if there is bleeding not where it is
TAGGED RED from)
CELL SCAN Technetium-tagged RBC scan
Nonspecific localization and lack of etiologic diagnosis
Follow up with confirmatory angiography and/or endoscopy

Small Bowel EXAM MOST bleeding will be DIAGNOSED with UPPER or LOWER ENDOSCOPY
Bleeding but 3-5% in the small bowel
Proximal jejunum angioectasia (PROXIMAL J most common bleeding source)
Similar to right colon AVMs
Capsule endoscopy
Balloon assisted enteroscopy
Double balloon endoscopy
Single balloon enteroscopy
Intraoperative enteroscopy

Conclusions Medical stabilization must stabilize UPPER GI TRACT w/ hematochezia

may have a poorer out come
Signs and symptoms help to localize
Direct the investigation
 ABDOMINAL PAIN EVALUATION

*nerves that carry the pain sensory info? ALL AUTONOMIC

*Vagus
*Sacral Plexus
*Splanchnic Nerves (Greater, Less and the Least) from the thoracic ganglia

*get a dull poorly localized pain, in the midline

*how to differentiate? localization is due to the embryology

FOREGUT CILIAC (Distal Espohagus to Aumpilla of Vader) = dull EPIGASTRIC

PAIN
*i.e stomach ulcer or duodenal ulcer, HEPATITE

MIDGUT SMA = (Aumpilla of Vader to 2/3 down the transverse colon) =

PERIUMBILICAL PAIN
Ex. Bowel obstruceiong

HINDGUT IMA = (2/3 down the Transverse Colon to Rectum) = SUPRAPUBIC

PAIN
*rectal ca, diverticulitis

What is COLIC? Bockage creates an intermittent/cramp-like pain

Somatic Pain T6-12 = INTERCOSTAL NERVES they innervate the abdominal wall

Reterperitoneal Area behind the peritoneum pancreas, adrenals, kidneys,

abdominal aorta i.e kidney pain refers to the back

Pelvic Pain suprapubic radiates to the sacral area

Pain Duration important in distinguishing etiologies

ACUTE < 72 hours
SUBACUTE 3days 3 weeks
CHRONIC - > 3 weeks

Examine the patient yellow? = Jaundice = liver probs

Abdomen lookscars, discoloration
Hyperactive Bowel sounds OBSTRUCTION
NO Bowel sounds ileus
Look at the groin look for hernias, do a rectal exam

ACUTE PERITONITIS Peritonetum is irritated ruptured contents lethal =

Hippocratic Facies = patient looks like they are going to die
Abdomen is tender, GUARDING (involuntary tense as you approach area),
rigidity of the abdominal muscles
TENDERNESS, GUARDING, RIGIDITY

TESTS IN ABDOMINAL PAIN

-CBC, Serum Amylase (to check for acute pancreatitis), bHCG (r/o pregnancy), XR
(fluid)
 Patient has a GASTRIC ULCER?
**SEE = Foregut EPIGASTRIC PAIN, CHRONIC, is relieved by eating food

**Acute Alacoholic Pancreatis binge drinker, gets EPIGASTIRC PAIN elevated

serum amylase

Elderly Male with severe epigastirc pain to back mass in chest = LEAKING
ABDOIMINAL ANEURYSM

Patient 25 PERIUMBILICAL PAIN RLQ w/ vomiting rigidity = RUPTURED

APENDICITIS

Pain at the bladder area, tender in the LLQ = ACUTE DIVERTICULITIS

GI HISTOPATHOLOGY LAB

Acute *DISTAL TIP of Appendix where the CARCINIOID TUMORS occur

Appendicitis *neutrophil infiltration into the muscle wall = thinning (and potential perforation)

*clinical signs = fever, abdominal pain, RLQ

*diff DX abdominal perf, cholecystitis

Acute *necrosis diffuse, risk of rupture

Cholecystitis
Salivary Gland *PLEOMORPHIC TUMOR most common is a MIXED type tumor
Tumor *must remover the entire tumor have a significant capsule more common in
FEMALES

WARTHINS TUMOR MALES, SMOKERS, bilateral

Crohns Disease *dense chronic inflammation the submucosa deep FISSURE

*GRANULOMA

Ulcerative *involves the entire colon mucosa and submucosa only vary shallow
Colitis
Barretts *GOBLET CELLS intestinal metaplasia
Esophagus 30-40 x increase in ADENOCARCINOMA RISK

Colon Polyp - *can be a precursor for ADENOCARCINOMA

tubulovillous
adenoma

Alcoholic *fat accumulation, large vacuoles of fat (MACROVASICULAR STEOTOSIS), MALLORY

Hepatitis HYALINE eosinophilic granules, condensed cell fragments (degeneration)
*inflammation lots of NEUTROPHILS (acute like inflammatory look)
*alcohol is toxic to liver cells liver regenerates, progressively the fibrosis gets
worse cirrhosis

GI Histology Lab 3 - Small & Large Bowel

Pyloro-duodenal *pyloric epithelium to the duodenum MUCUS secreting glands SIMPLE
Junction GLANDS
-deeper glands in the duodenum = BRUNNERS GLANDS in the submucosa
are the HALLMARK of the duodenum
*folds (plica circularis) core is SUBMUCOSA villi off the folds - covered by
mucosa
*GALT see lots of random lymphocytes

Jejunum *MICROVILI on the enterocytes

*goblet cells
*see intraepithelial lymphocytes look for antigen if they do go and clone
themselves form PLASMA CELLS clock face nucleus secrete Igs
*see EOSINOPHILS bilobed cells & MAST CELLS single large nucleus (a lot in the
submucosa)
*can see LACTEALS at the tips of the VILLI
*Glands lined by ENTEROCYTES, GOBLET CELLS,ENTEROENDOCRINE CELLS,
PANETH CELLS, MITOTIC FIGURES of the STEM CELLS (are produced in the LOWER
1/3 OF THE GLAND in the Jejunum)
*parasympathetic neurons

ILEUM *cannot distinguish exact transiton point from the jejunum but generally see the
presence of PAYERS PATCHES lymphoid aggregates (M cells)

COLON *NO villi are projecting from the surface have TENAE COLI
*high # of GOBLET CELLS (gotta lube the POO!)

Appendix *accumulation of LYMPHOID TISSUE where activated lymphocytes are cloning

themselves

Rectum-Anus Colonic Epithelium wet stratified squamous epithelium

Junction *anal gland secretes mucus
*see SEVACEOUS GLANDS prevent chaffing
*APOCRINE SWEAT GLANDS