Evaluation of the Liver Patient

Roles of the
liver

Definitions

Protein synthesis / proteolysis

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
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
Liver Disease
if
symptomatic!

Right upper quadrant pain

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

Pruritus Rule of
Thumb

Intrahepatic cholestasis causes pruritus as an early symptom

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
Angiomata

End-stage liver disease

Pregnancy
Use of birth control pills
Hyperthyroidism

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

ASCITES =
Collection of
fluid around the
organs
SOUNDS DULL

Exam Findings

Bulging flanks
Right flank dullness
Fluid wave
Shifting dullness
Associated with peripheral edema

Hepatomegaly
Hepatosplenomegaly
Small liver on percussion / palpation
RUQ tenderness
Hepatic bruit
-Alcoholic hepatitis
-Hepatocellular carcinoma
-Arterio-venous malformation (AVM)

Hepatic
Encephalopathy

= LIVER CONFUSION
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
Terms: Sound
Smart

Liver tests, not liver function tests

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

When Should
You Order Liver
Tests?

Screening for liver disease

Confirmation of possible liver disease
Differential diagnosis of liver disease
Prognosis of liver disease
Prothrombin time, bilirubin, albumin, factor V
Monitoring progression of liver disease
Monitoring therapy

Aminotransfer
ases
*enzymes in the
HEPATOCYTES
(released in
RESPONSE to
damage)

Aspartate aminotransferase (AST) (A Shot of Tequila - elevated in Alcoholic

Hepatitis) MITOCHONDRIA
Previously called SGOT
Location is principally sub-cellular
Alanine aminotransferase (ALT) (hALT viral hepatitis)
Previously called SGPT
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

Elevation of
Aminotransferas
es

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

Marked elevation (up to 20+ fold)

Acute hepatitis due to viruses, ischemia, or drugs

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
ALT

Normally the ALT is slightly > AST

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
Aminotransferas
e Elevation

Most

importantly, conduct a thoughtful H&P

If you find signs of liver disease, evaluate on that basis
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
Liver Disease

Enzymes of
Cholestasis

Hyperbilirubine
mia with Normal
Liver Tests

Gilberts
Syndrome

Wilsons disease
Alcoholic hepatitis
Autoimmune hepatitis
Drug-induced liver disease

Gamma glutamyltranspeptidase (GGT) SPECIFIC

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)

Unconjugated hyperbilirubinemia not taking bilirubin into the liver and

excreting it SO the bilirubin just builds up in the blood.
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

Often college aged

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
Syndrome

Dubin-Johnson
Syndrome

Tests of Acute
Viral Hepatitis

Tests of Chronic
Viral Hepatitis

Glucuronyl transferase deficiency

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

Hepatitis A
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
Hepatitis B
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
is

*one of the most COMMON

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
see clinically
with
Hemochromatos
is?

Hyperpigmentation

Wilsons
Disease

Alpha-1Antitrypsin
Deficiency

*Abnormal COPPER METABOLISM

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

Elevated:
AlphaFetoprotein

Autosomal recessive
Liver injury results from accumulation of improperly
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
Hepatocellular carcinoma (HCC)
30% of HCC is fibrolamellar type no elevation of AFP
Hepatic regeneration / inflammation
Testicular tumors
Neonates
Acute Liver Failure

Acute Liver
Failure

Definition of
Terms

Acute Liver 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)

Viral Hepatitis

Acute Liver Failure

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

*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?

Hepatitis is a medical condition defined by the inflammation of the liver and

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
Values in Viral
Hepatitis

Hepatitis A

Aminotransferase elevation (ALT & AST)

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

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

Serology of
Acute HBV
Infection

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.
can smolder for decades
present in 20-30s
Clinically more severe illness in
acute infection
Carrier rate is 5 to 10%
Treat with IFN-

*note the WINDOW = the time before the

CONVERSION PROCESS has occurred = surface
antigen and surface antibody negative

Pre-exposure prophylaxis
HBV vaccine
Post-exposure prophylaxis
Hyperimmune B immunoglobulin
(HBIG)

Asia,
and

Hepatitis C
Virus

Hepatitis C 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 E

Hepatitis D and 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
Chronic
Hepatitis

Autoimmune (chronic) hepatitis

Types 1 and 2
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
Hypertension

*blood flows through the portal vein into

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
c Varices

Causes of
Ascites

Liver disease related

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

Cirrhosis
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
Bacterial
Peritonitis

Hepatorenal
Syndrome

More common in cirrhosis as ascites etiology

Develops in 10% of those with ascites
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

Definition
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
Liver
(AST
ELEVATED!!)

Alcoholic
Hepatitis

Alcoholic
Cirrhosis

Nonalcoholic
Fatty Liver
Disease
(NAFLD)

Primary Biliary
Cirrhosis

Most common histologic abnormality

Symptoms/signs may be absent or minimal
RUQ abdominal pain
Hepatomegaly
Ultrasound may suggest fatty change
Aminotransferases normal to slightly increased
Therapy is abstinence from ethanol
Only 10-20% of chronic alcoholics develop alcoholic 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
Laennecs 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
Fatty liver in the absence of significant alcohol intake
Common associations
Type 2 Diabetes, hyperlipidemia, obesity
Symptoms and signs
May be asymptomatic
May have fatigue, weakness, RUQ pain
Normal or minimally increased aminotransferases
Therapy is to control the cause
An autoimmune disease characterized by lymphocytic destruction of
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
Hyperplasia

Hepatic
Adenoma

Hepatocellular
Carcinoma

A hyperplastic response to a portal artery-tovenous 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
Benign neoplasm composed of hepatocytes without accompanying liver
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
Associations
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
oma

Associations
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
center is the portal area = hepatic artery and vein
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

the
is

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

Ito Cell stores

vit A and can
produce
collagen

*Cell of ITO store

VITAMIN A produce
collagen are the source of
abberant collagen production
ITO CELL = STELLATE CELL
*located in the space of disse
*major cell type involved in
LIVER FIBROSIS
*fxn store Vit A

Hepatic Injury-5
patterns

Jaundice

*when the liver is damaged

the Stellate Cells are
ACTIVATED secrete
COLLAGEN creating scar
tissue which can lead to CIRRHOSIS.
1. Degeneration and intracellular accumulation cells have metabolic probs
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

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
Hyperbilirubine
mia

Cholestasis =
buildup of bile
acids

Hepatic failure

Crigler-Najjar syndrome-genetic lack of bilirubin UGT

Gilbert syndrome-autosomal dominant-reduced expression of UGT-6% of
population
Dubin-Johnson syndrome-autosomal recessive-impaired biliary excretion
of bilirubin glucuronides
Rotor syndrome-recessive-defects in hepatocyte uptake and excretion

Biliary obstruction-intrahepatic or
extrahepatic
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

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

Cirrhosis
Etiology-in U.S.

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

Alcoholic liver disease

Viral hepatitis (C)
Biliary disease
Hemochromatosis
cardiomyopathy)
Wilson disease
1-Antitrypsin deficiency
Cryptogenic cirrhosis
*morbid obesity

60-70%
10%
5-10%
5% - (iron is toxic to the hepatocyte
rare
rare (lung or liver)
10-15%

Pathogenesis of
Cirrhosis

Progressive fibrosis continual degeneration

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
of Cirrhosis

Portal
hypertension

Viral hepatitis A
*acute SELF
LIMITED
(wimpiest form)

Silent for a long time

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

Increased resistance to portal flow at the level of the sinusoids and

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
Infectious hepatitis-no chronic hepatitis form CLEAR THE DISEASE
Low fatality rate
Single stranded RNA picornavirus
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
(serum)
hepatitis

HBV

Note

Acute hepatitis, non progressive chronic hepatitis, progressive hepatitis,

fulminant 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
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

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
hepatitis

Chronic viral
hepatitis

Incubation period-peak infectivity occurs during the

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

Symptomatic, biochemical or serologic evidence of

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
hepatitis

Autoimmune
Hepatitis

Rapid onset of hepatic insufficiency(within 2 weeks)

Fulminant viral hepatitis in 50-65% of cases
Drugs (#1) and chemical toxicity -nextacetaminophen, isoniazid, anti-depressants,
halothane, amanita phalloides (MUSHROOM
HUNTERS)
Acute yellow atrophy-small flabby liver
Chronic & progressive hepatitis of unknown etiology
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
disease

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

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
alcoholic liver
disease

Fatty changemicrovesicular/macrovesicular
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
Fatty Liver
Disease
(NAFLD) &
NASH
2 Biliary
cirrhosis

Primary biliary
cirrhosis (PBC)

*is the most common obstruction is due to some other NON-BILIARY CAUSE
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 VS
Secondary
BILIARY
CIRRHOSIS

Hepatic steatosis who dont drink alcohol (<20g of ethanol/week)

Becoming more common (decrease in alcoholic liver disease)
Obese METABOLIC SYNDROME, DM, post gastric banding
Leads to NASH & cirrhosis (crytogenic cirrhosis no alcohol involved)

Chronic progressive cholestatic liver disease

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
sclerosing
cholangitis

Other odds and

ends

Passive
congestion

Inflammation, obliteraive fibrosis and segmental

constriction of the intrahepatic and extrahepatic bile
ducts
Seen in association with inflammatory bowel disease
Males(2:1) 3 -5 decades, Onion-skin fibrosis,
Autoantibodies in less than 10% of cases

Bacteria: Staph, S. typhi, tertiary syphilis

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

Right sided heart failure leads to chronic passive

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
syndrome

*Occlusion of the IVC or hepatic veins with centrolubular

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
hyperplasia

Malignant
tumors

Well demarcated nodule, Central gray-white stellate scar,

Young women

Hepatocellular
carcinomas

Hepatic
complications of
Organ or Bone
Marrow
Transplantatio
n

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

hepatitis
Hepatoblastoma-young children
Angiosarcoma-associated with vinyl chloride, arsenic or Thorotrast
Primary carcinoma of the liver
Hepatocellular carcinoma
Cholangiocarcinoma bile duct
Aflatoxins, hepatitis B Virus, cirrhosis
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
Drug toxicity after Bone Marrow transplantation can have a lot of posttransplant LIVER probs
Quite common- up to 50%
Tender hepatomegaly, hyperbilirubinemaia, centrilobular necrosis and
inflammation
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
pathology

Acute-within 2 weeks-mixed inflammatory cell infiltrate in portal tracts and in

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
DiseaseCongenital
Aganglionic
Megacolon

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

muscle wall (Auerbach plexus) and submucosa (Meissner) of the effected
segment
Rectum always involved
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
Enterocolitis

Infectious
Enterocolitis
Invasive
organisms
(Dysentery)

Viral

- usually mild to moderate gastroenteritis with diarrhea and vomiting

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 toxinE.coli
Infection by enteroinvasive organism which invades epithelial cells
-Shigella

Shigella - distal colon, acute mucosal inflammation and exudate

Bloody diarrhea
Person to person spread

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
Enterocolitis
toxin
organisms

Cholera Toxin

E. coli

V. cholerae: small intestine - intact mucosa

Massive watery diarrhea loss of fluids and electrolytes = arrhythmias
Shellfish, water, person to person

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

*chloride gets pumped into the

lumen water follows =
WATERY DIARRHEA = RICE
WATER STOOL

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
Enterocolitis

Necrotizing
Enterocolitis

AntibioticAssociated
Colitis

Ascaris lumbricoides - lives in the intestine, larva penetrate the mucosa

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
Acute necrotizing inflammation of neonates
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

*when giving broad spectrum antibiotics, frequently you wipe out the NORMAL
FLORA but not the C. DIFFICILE = and therefore unchecked the C. diff OVERGROWS
(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
Inflammatory
Bowel Disease

Spectrum from Ulcerative colitis to

Crohn 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 Immunoreactivityabnormal 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

Crohns is to
the CORE
(extends
deeply)

Ulcerative
Colitiscontrast with
CD

Sharply
delimited and
transmural- full
thickness- skip
lesions can
get random
lesions with
normal bowel inbetween
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

Literally Ulcers in the Colon

Only the mucosa is involved -- not deep!
Continuous from rectum-- no skip lesions!
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

Diverticular
Disease

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
Acquired, common
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
Polyps

Hyperplastic-small <5mm-low malignant potential most common in rectum

Juvenile polyps-hamartomatous malformation sporadic or HNPCC
Peutz-Jeghers polyps-harmartomatous

Neoplastic
Adenomas

Tubular ademonas-pedunculated-malignant potential depends on size

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

Familial
Polyposis
Syndrome

Familial adenomatous polyposis-hundreds of adenomatous polyps

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

Hereditary
nonpolyposis
colorectal
cancer (Lynch
Syndrome

Adenoma
carcinoma
sequence
serrated
pathway

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

*initial mutation in the APC

gene- develop an adenoma
increase in abnormalities
= carcinoma

Microsatelite
instabilty/HNPC
C

SMALL BOWEL
Tumors

Adenomas
Adenocarcinoma (rare in small bowel)
Carcinoid (very rare in colon)
Stromal tumors
Lymphoma

Carcinoid

Intestinal
Lymphoma

*Can

Colon Cancer

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)
produce SEROTININ
Stomach > Small > Large
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
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
Anal Canal

Mucocele and
pseudomyxoma
peritonei

*transition from colonic epithelium squamous epithelium

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

Most a simple mucinous cystadenoma

20% perforate producing localized collections of mucus around the
appendix and in the peritoneal cavity
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
Pseudomyxoma
Peritonei?

PMP is not a
single entity

The name given by Werth in 1884 tells us

that it is not a myxomatous degeneration of
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!

1. Low grade Largely pools of mucin with scattered benign

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
Malformations

Meckel Diverticulum
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
Malformations

Malabsorption

Malrotation
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

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
Symptoms
(rrhea, rhhea,
and sons)

Celiac Sprue

Tropical
(infectious)
Sprue

Steatorrhea
Diarrhea
Abdominal pain
Weight loss
Vitamin deficiencies
Vit D, calcium
Vit A, B12

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

In the tropics
Endemic and epidemic forms
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
Disease

Disaccharidase
(Lactase)
deficiency

PAS positive macrophages (the material is the

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 +)

Intestinal
Obstruction

Located on the apical cells of the small bowel

Congential or acquired
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
Results from a variety of causes
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
disease

Vascular
disorders of the
bowel

Small bowel
malignancies

GI Lymphoma

Arterial thrombosis-ASVD,
systemic vasculitis
Dissecting aneurysm,
etc.
Arterial embolismvegetations, 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
Angiodysplasia- tortuous dilations of submucosal and mucosal blood
vessels
Account for 20% of significant lower gut hemorhage
Hemorrhoids- dilations of anal venous plexuses
Rare overall with tumors in the small bowel when compared to stomach and
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
1-4% of GI malignancies
Helicobacter gastritis
Natives of Mediterranean region
Congenital immunodeficiency states
HIV infective individuals
Patients with sprue

Mesenchymal
Tumors

Lipoma
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
atresia with or
without a
tracheoesophag
eal fistula (TEF)

1/3000 births
Proximal esophagus ends in a blind pouch
Most have an associated fistula to trachea
(exam)**MOST COMMON esophageal atresia with distal
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
(no esophageal
atresia)

These are diagnosed later in life with recurrent pneumonia or

persistent cough
*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
Diaphragmatic
Hernia

*left lung hypoplasia

*bowel gas in thorax
*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
electrolytes
in pyloric
stenosis

Duodenal
atresia

Complete obliteration of duodenal lumen

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
atresia
Xray: double
bubble

Repeated vomiting results in loss of HCl

Hypochloremic (low Cl-)
Hypokalemic (low K+)
Metabolic alkalosis (high HCO3-)

DUODENAL ATRESIA think DOWN SYNDROME and on XR

DOUBLE BUBBLE which is referring to air in the DUODENUM
& STOMACH

Intestinal
malrotation

interruption of normal intestinal rotation and fixation

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

Necrotizing
Enterocolitis
(NEC)

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

Problem of premature infants

Ischemia of intestine that leads to intestinal necrosis
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
ileus (=
Cystic
Fibrosis)
EXAM

intestinal obstructive variant of cystic fibrosis

15% of infants with cystic fibrosis (AR, D508, Ch 17)
present with intestinal obstruction related to meconium
ileus

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

Omphalocele

Hirschsprungs
Disease

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

Intestine herniated within umbilical cord

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

absence of ganglion cells and myenteric plexus, secondary

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

Diarrhea Types

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

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 5Step Approach

to Diarrhea
EXAM

Secretory
diarrhea

1. Does the patient really have diarrhea? Beware of fecal incontinence

and impaction.
2. Rule out medications as a cause of diarrhea (drug-induced diarrhea).
3. Distinguish acute from chronic diarrhea.
4. Categorize the diarrhea as inflammatory (BLOODY), fatty (OIL
DROPLETS), or watery.
5. Consider factitious diarrhea (LAXITIVES)

*vibrio, laxative abuse, VIPoma

C.difficile:
manifestations
(not test Qs)

Collagenous
Colitis

*can

Carrier State
C.difficile-associated diarrhea (CDAD)
C.difficile colitis
Pseudomembranous colitis
Fulminant Colitis/Toxic Megacolon can present atypically
Atypical (e.g., sepsis, ascites)
Recurrent disease
treat empirically b/c can be such a serious infection

Collagenous colitis has recently

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
features in
chronic
constipation

Recent onset of constipation in older age (> 50 years) = Obstruction?

Rectal bleeding, Weight loss
Family history of colon cancer
Iron deficiency anaemia
Haem positive stool

Pooping

Epidemiology of
IBS
Exam

o
o
o
o
o

Pathophysiology
of IBS

3-20% of U.S. population

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

Psychotherapy - Interpersonal
Treatment
One well-designed study using
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
Malabsorption

Malabsorption
Suspected

Luminal
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
Pancreatic insuffiency presenting pattern
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
Insufficiency

Celiac Sprue
Gluten-sensitive
enteropathy

Loss of 80-90% of exocrine function before you start to SPILL FAT INTO
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

Inappropriate T-cell mediated immune response

Inflammatory injury to small bowel
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 HLADQ8) on the surface of antigen-presenting cells. Gliadin is presented to gliadinreactive 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
Treatment

EXAM QS

Lifelong gluten-free diet

An expert dietitian
Initially, other dietary modifications may be necessary, including a lowlactose 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)

*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
Syndrome

Android (abdominal) obesity

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
Surgery

More effective than nonsurgical Rx

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
of Bariatric
Surgery
EXAM

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

Anorexia
Nervosa
Exam

Prevalence 0.5-1% primarily adolescent and young women

Female/male : 10/1
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

Starvation

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

Increased fat metabolism to conserve lean mass

changes can be reversed by appropriate feeding
Reduced Basal Energy Expenditure
Die from PNEUMONIA

Cachexia
(EXAM Diff
b/t cachexia
and
starvation)

Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue,

weakness, and significant loss of appetite in someone who is not actively trying to
lose weight. The formal definition of cachexia is the loss of body mass that cannot
be reversed nutritionally: Even if the affected patient eats more calories, lean body
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
Assessment

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

ENERGY
REQUIREMENTS

Harris-Benedict with stress factor

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
test?

= YES, its the PREALBUMIN

How do we feed
a patient?

Enteral = feeding into the gut assumes the GI TRACT IS

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
SYNDROME
EXAM

*As you start refeeding patients

and if it occurs TOO FAST the
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
Targets

Pharmacologically treatable impairments to normal motility, digestion, secretion

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

Drugs for the

Treatment of
Peptic Ulcers

Peptic Ulcer: lesion of gastric or duodenal mucosa occurring at a site where the
mucosal epithelium is exposed to acid and pepsin. (generally NOT a disease of
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
Underlying Drug
Treatment for
Peptic Ulcers
(EXAM
understand)

*Superficial Epithelial
Cell secretes mucus
MAINTAINS the
MUCOSAL BARRIER
*right hand side faces
the stomach lumen
*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
Neutralizers Antacids

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

[Tums] CaCO3 + 2 HCl = CaCl2 + H2CO3
[Milk of Magnesia] Mg(OH)2 + 2 HCl = MgCl2 + 2 H20
[Alka-Selzer] NaHCO3 + HCl = NaCl + H2O + CO2

Gastric
Antisecretory
Drugs

H2 Histamine Receptor (competitive) Antagonists very selective - MOA is

they block histamines abilitiy to increase cAMP and phosphorylate the H+/K+
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
Antisecretory
Drugs

Proton Pump Inhibitors are PRO drugs that undergo bioacitvation occurs AT
THE SITE OF ACTION they are all WEAK BASES and therefore PROTINATED in the
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

ANTISECRETO
RY and
MUCOSAL
PROTECITVE
PROPERTIES
Mucosal
Protective
Agents

Prostaglandin (PGE1) Analogs

Misoprostol agonists at the prostaglandin receptor both inhibits via cAMP at
the H+ Pump AND activates the release of MUCOSA (see diagram) only approved
for the use of NSAID induced ulcer very rarely used.
*SEs causes uterine contraction pains (can induce abortion)

Sucralfate - Aluminum Salt of Sucrose Octasulfate MOA has zero systemic

uptake (NO ABSORBED) and it fxns by BINDING to and COVERING the lesion (i.e.
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
for the
Treatment of
GERD and
Gastroparesis

Antisecretory Drugs
Prokinetic Drugs
*Tegaserod/Zelnorm
*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
for Using
Prokinetic Drugs
to Treat GERD &
Gastroparesis

Cisapride = 5-HT4 Agonists

enhanced Ach release
Erythromycin = + MOTILIN
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
Drugs

Opioid Agonists:
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
s View of Emetic
Stimuli
(produces
vomiting)

*if you ingest something

that is toxic = is detected
by the CHEMO-RECEPTOR
TRIGGER ZONE which
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
Drugs

Metoclopramide/Domperidone - Dopamine receptor (D2) antagonists (above)

Chlorpromazine/Prochlorpromazine/Haloperidol/Droperidol at dopamine, muscarinic and histamine receptors

Antagonists

*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

Etiology of
Upper GI
Bleeding

Gastric Ulcer

Gastric Cancer

Upper 75%
LGIB
*80% of the time the bleeding will stop
Non Variceal: 86%
Ulcerations: about 50%
Mallory-Weiss Tear: 4-8%
Erosive esophagitis: 1-13%
Neoplasia: 2-7%
Vascular ectasia: 0-6%
Variceal: 14%
*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

Mallory-Weiss

*excessive wretching

Upper GI
Bleeding
Presentation

Predictors of
Severity
of a Bleeding
Episode:

Postural hypotension, Shock

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

Independent
Risk Factors for
Adverse
Outcomes

Initial
Resuscitation
and Medical
Management

Hematemesis (30%)
Melena (20%) = upper GI bleed until proven otherwise
Both
Up to 15% of all patients present with hematochezia bright red blood in
stool due to high volume GI bleed

Use of NSAIDS or aspirin

History of peptic ulcer disease more likely to have recurrent
Post op complications following urgent surgery
Usually dont exsanguinate, die due to decompensation of other organs.
use to excessive blood loss, other organs suffer
Mortality of 5-10%
*RESUSCITATION refers to the infusion of IV fluids and blood transfusion. Goal is
to prevent hypovolemaia and subsequent shock from occurring.
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
UGI
Hemorrhage

Esophagogastroduodenoscopy (EGD)
Tagged RBC scanning CTe, CTA, MRA noninvasive ways to look for
bleeding
Arteriography
Surgery

Management of
UGI Bleeding

High dose PPI Rx

Endoscopic Modalities
Injection Rx
Thermal device
Mechanical

Endoscopic
Methods of
Hemostasis of
UGIB

Thermally active
Heater probe
APC
Injectable therapies
Epinephrine causes the vessels to stop bleeding
Glue
Mechanical
Endoscopic clips
Band ligation varicies
Combination Rx

Predictors of
Early
Rebleeding
Based on
Endoscopic
Findings

Active bleeding
55-90% likely to REBLEED
Visible vessel
43-50% 50% of the time there is 0 bleeding at
the base of an ulcer
Adherent clot
12-33%
Clean ulcer base 3-5%

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
Consultation

High risk of rebleeding

Ongoing bleeding despite endoscopic intervention

Angiographic
Therapy

Main role
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
Long-Term
Prevention of
Ulcer
Hemorrhage

Medical therapies
Acid suppression
Prostaglandin analogs
Mucosal protectants
Helicobacter Pylori eradication heals an ulcer
NSAID discontinuation
Smoking cessation

Natural History
of Varices

*far left are large varices treat with successive banding

Management of
Acute Variceal
Bleeding

Varicele
Resuscitation give blood, fluids
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
Bleeding

Methods to distinguish types and location of LGIB

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

Lower GI
Bleeding
DIFFERENTIAL

Diverticulosis
Ischemic colitis
Colon polyp
Angiomas
Cancer
Hemorrhoids
Inflammatory bowel disease

Diverticular
Bleeding

Brisk, abrupt onset, intermittent LGI 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
Angiodysplasia

VASCULAR ABNORMALITY
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
Neoplasia

Obscure more often than overt

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
Hemorrhoids

Presentation: mild to profuse bleeding

Active bleeding from internal hemorrhoids or stigma of hemorrhage
Typically painless hematochezia
BRBPR/clots
Therapies
Band ligation
Injection Rx
Excision
Coagulation

Severe, Acute
Lower GI
Bleeding:
General
Measures

Insertion of NGT for gastric lavage

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

Scinitigraphy =
TAGGED RED
CELL SCAN

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

Small Bowel
Bleeding

Conclusions

EXAM MOST bleeding will be DIAGNOSED with UPPER or LOWER ENDOSCOPY

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

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
Appendicitis

*DISTAL TIP of Appendix where the CARCINIOID TUMORS occur

*neutrophil infiltration into the muscle wall = thinning (and potential perforation)
*clinical signs = fever, abdominal pain, RLQ
*diff DX abdominal perf, cholecystitis

Acute
Cholecystitis
Salivary Gland
Tumor

*necrosis diffuse, risk of rupture

*PLEOMORPHIC TUMOR most common is a MIXED type 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
Colitis
Barretts
Esophagus

*involves the entire colon mucosa and submucosa only vary shallow

Colon Polyp tubulovillous

adenoma

*can be a precursor for ADENOCARCINOMA

Alcoholic
Hepatitis

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

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

*GOBLET CELLS intestinal metaplasia

30-40 x increase in ADENOCARCINOMA RISK

GI Histology Lab 3 - Small & Large Bowel

Pyloro-duodenal
Junction

*pyloric epithelium to the duodenum MUCUS secreting glands SIMPLE

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
Junction

Colonic Epithelium wet stratified squamous epithelium

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