Universitatea Titu Maiorescu

Liver
 Motion and Activity

• The position of the liver in the body is not

static.
– moves up and down with the diaphragm and
rotates during respiration.
– rotates backward when an individual lies down in
the supine position.
• The upper surface of the liver can move upward from
1 cm to 10 cm when full expiration follows deep
inspiration.
The Anatomy of the Liver
 LIVER Histology

• lobules >> roughly

hexagonal structures
consisting of
hepatocytes. Radiate
outward from a central
vein.
• At each of the six
corners of a lobule is a
rtal po
• PORTAL triad
p.arteriole,
•p.venule &
•bile duct)
•Between the
hepatocytes sinusoids.
Normal Liver - Microscopy
 Liver Functions:
• Metabolism – Carbohydrate, Fat &
Protein
• Secretory – bile, Bile acids, salts &
pigments
• Excretory – Bilirubin, drugs, toxins
• Synthesis – Albumin, coagulation
factors
• Storage – Vitamins, carbohydrates etc.
• Detoxification – toxins, ammonia, etc.
 Hepatic Physiology

• Liver:
• Largest solid organ in the body
• Performs over 500 chemical processes
• Produces over 160 different proteins
• Makes clotting factors for the blood
• Stores & releases sugar as glycogen
• Metabolizes, detoxifies, synthesizes
5-Detoxification – Hepatic Physiology 1- homeostasis;
toxins, ammonia, etc glycogenolysis & gluconeogenesis
Catabolism of hormones
and other serum proteins

Chronic Liver
Disease

4-Synthesis:
- Albumin
- Coagulation factors
1-Storage:
3-Secretory - Glycogen
– bile, Bile acids, salts & pigments - Iron
Bile excretion - Cu, Iron, vitamins
-2-Metabolism – Carbohydrate, Fat & Protein

.
 1-SYNTHETIC FUNCTIONS
• production and release of circulating factors critical to the
coagulation cascade

• the single most sensitive tests of liver function are measures of

coagulation function—International Normalized Ratio (INR)
and factor VII and factor V levels.

• synthesizes a wide variety of plasma proteins, the most

important of which is albumin.

• variety of acute-phase proteins and cytokines that have

important interactions with a variety of inflammatory,
infectious, and regulatory processes.
 2-Metabolism
• Carbohydrate Metabolism
– critical storage site of glycogen and is essential to the maintenance of
systemic glucose homeostasis through a complex process involving broad
interactions with lipid metabolism.
– The liver also metabolizes lactate, and the Cori cycle is important in
maintaining peripheral glucose availability in the setting of anaerobic
metabolism.
• Lipid Metabolism
– modulator of lipid metabolism, critical role in the synthesis of lipoproteins,
triglycerides, gluconeogenesis from fatty acids, and cholesterol metabolism.
– cholesterol is synthesized in the liver and is used most importantly for bile
salt synthesis.
• Bilirubin Metabolism
– Bilirubin circulates bound to albumin in the blood.
– It is actively taken up by hepatocytes, where it is glucuronidated and
actively secreted into bile.
– Benign disorders of bilirubin metabolism include:
• conjugated (direct) hyperbilirubinemia.
• Dubin-Johnson and Rotor's syndrome, which produce conjugated (direct)
hyperbilirubinemia.
• Unconjugated hyperbilirubinemia is seen in Crigler-Najjar type II and
Gilbert's
 3-Bile and the Enterohepatic
Circulation
• Bile is a mixed micelle composed of bile
• 1- acids and pigments, 2-phospholipids and cholesterol, 3-proteins,
and electrolytes.

• The volume of bile secreted in an adult ranges from 500 to 1000

mL/24 h.

Electrolyte composition of bile is similar to plasma, intravenous

volume replacement of a high-volume biliary fistula output can be made
milliliter for milliliter with lactated Ringer's solution.

• Role of the distal ileum in the reabsorption of bile salts became clear
when patients undergoing resection of the ileum for Crohn's ileitis
developed malabsorption and steatorrhea.

• It was also noted that such patients had lower serum cholesterol levels,
ultimately found to be a result of increased hepatic metabolism of
cholesterol to bile acids to replace the bile acids not absorbed and
recirculated.
.

Traditional LFT’s (Liver Functional Test)

Traditional LFT’s (Liver Functional
Test)
• ALT: alanine aminotransferase (SGPT)

• AST: aspartate aminotransferase (SGOT)

• Alkaline Phosphatase & Bilirubin

Traditional LFT’s (Liver Functional
Test)
ALT: GPT alanine aminotransferase (SGPT)

• Found primarily in hepatocytes

• Released when cells are hurt or destroyed
• Normal levels depend on the reference range which
actually differs lab to lab
• Considered normal between 5-40 U/L
• Probably should be half of this (5-20?)
 Traditional LFT’s

AST:GOT aspartate aminotransferase

• Found in many sources, including liver, heart,

muscle, intestine, pancreas
• Not very specific for liver disease
• Often follows ALT to a degree
• Elevated 2 or 3:1 (vs. ALT) in alcoholics
• Normal range: 8-20 U/L
 Traditional LFT’s

Alkaline Phosphatase:

• Found in liver (especially biliary tract), bones,

intestines, & placenta
• “Fractionated” or “isoenzymes” to source
• Liver AP rises with obstruction or
infiltrative diseases (i.e., stones or tumors)
• Normal range: 20-70 U/L
 Traditional LFT’s

• Bilirubin: two primary sources

• Indirect (unconjugated): old red cells, removed by

the spleen, sent to the liver

• Direct (or conjugated) Liver “adds” glucuronic

acid, making these cells water soluble for excretion;
now called direct (or conjugated)
Normal range: less than 0.8 mg/Dl

• Total bilirubin includes both direct and indirect

types
 Patterns of Abnormal

• Elevations in ALT & AST only: suggests cellular

injury

• Elevations in Alk Phos & Bilirubin: suggests

cholestasis or obstruction

• Mixed pattern: ALT, AST, AP & Bili: probably the

most common scenario
LIVER DISEASE
Viral Hepatitides
 Viral Hepatitides

• Hepatitis A, B, C, D, E, G

• Cytomeglovirus (CMV)

• Herpes Virus (HSV)

Chronic Hepatitis
 Chronic Hepatitis
Overview

• Progression to cirrhosis over 20 years2

– 18% to 26% in liver clinic series
– 1% to 10% in community cohort series

• Leading cause of chronic liver disease,

cirrhosis, HCC, and liver transplantation
(40%)4
 Four subtypes
are recognized, but the clinical utility of distinguishing
subtypes is limited.
1-Positive ANA (antinuclear antibody ) and smooth
muscle antibody (SMA) raised immunoglobulin G
(classic form, responds well to low dose steroids)

– 2-Positive LKM-1 (Liver/kidney microsomal antibody)

– typically female children and teenagers; disease can be
severe)

– 3-All antibodies negative, positive antibodies against

soluble liver antigen (SLA) (now designated SLP/LP).
This group behaves like group 1.

– 4-No autoantibodies detected (~13%)

 CLD Aetiology

Surgical Sieve
• Viral
• Autoimmune –
• Autoimmune hepatitis, PBC, PSC
• Genetic –
• Wilson’s, Haemochromatosis, Alpha 1
antitrypsin deficiency
• Toxic / Drugs – alcoholic, paracetamol

• Non-alcoholic fatty liver (DM / metabolic syndrome,

pregnancy, idiopathic)
 Differential Diagnoses

• 1-(Decompensated) Alcoholic liver disease

• 2-Viral liver disease
• 3-Autoimmune liver disease, Wilson’s, HH etc
• 4-Hepatocellular Carcinoma
• 5-Pancreatic Cancer
• 6-Cryptogenic Liver Cirrhosis

What further history would be needed?

What signs would you look for on examination?
 Chronic HCV Infection
Natural History
Exposure
(Acute Phase)
Primary Point
55-85% of Intervention
15-45%

Resolved Chronic 5%-25% over 20-30 years

75-95%

Stable Cirrhosis5%/yr decompensation

2-8%/yr HCC

Liver Decompensation
Hepatocellular Carcinoma
Poynard T. Lancet. 1997 349:825-832.
Mathurin P. Hepatology. 1998 27:868-872.
Benhamou J. Hepatology. 1999 30:1054.
 What is your management plan?
Conservative
• Alcohol abstinence, optimise nutrition, low salt diet, fluid
restriction
Medical
• Vitamin B supplementation (IV/PO), chlordiazepoxide
• Diuretics
• Paracentesis (give albumin)
• NG feeding
• Antibiotics (? SBP)
• Steroids + albumin (N.B. avoid NaCl)
• Lactulose (in hepatic encephalopathy)
Surgical
• Liver transplantation
Autoimmune Hepatitis
 What is autoimmune hepatitis?

• Autoimmune hepatitis is a disease in which the

body’s own immune system attacks the liver and
causes it to become inflamed.

• The disease is chronic, meaning it lasts many

years. If untreated, it can lead to cirrhosis and
liver failure.

.
 Autoimmune Hepatitis

• Autoantibodies against hepatocytes

• Young/middle age, mainly women
• Presentation: jaundice, RUQ pain, systemic symptoms
• May be associated with other autoimmune conditions
• Investigations
- Type 1: anti-smooth muscle antibodies (80%), anti-
nuclear antibodies (10%)
- Type 2 (children): anti-liver/kidney microsomal type 1
antibodies
- Liver biopsy
• Rx: immunosuppressant's (steroids, azathioprine),
transplant
 How is autoimmune hepatitis
diagnosed?
• Autoimmune hepatitis often occurs suddenly. Initially, you may feel like
you have a mild case of the flu. As PE does not often offer the examiner
much information to confirm a diagnosis of autoimmune hepatitis, your
doctor will need to use…blood tests and a liver biopsy

– antinuclear antibody (ANA),

– smooth muscle antibody (SMA),
– Liver/kidney microsomal antibody (LKM-1)
– and anti-mitochondrial antibody (AMA)

• are all of use, as is finding an increased Immunoglobulin G level.

• However, the diagnosis of autoimmune hepatitis always

requires a liver biopsy.

• In complex cases a scoring system can be used to help determine if a

patient has autoimmune hepatitis, which combines clinical and laboratory
features of a given case.
 What causes autoimmune
hepatitis?
• Your immune system normally attacks bacteria,
viruses and other invading organisms. It is not
supposed to attack your own cells; if it does, the
response is called autoimmunity.

• In autoimmune hepatitis, your immune system

attacks your liver cells, causing long-term
inflammation and liver damage.

• Scientists don’t know why the body attacks itself

in this way, although heredity and prior infections
may play a role.
 What are the symptoms and
complications of autoimmune
hepatitis?
Often, the symptoms of autoimmune hepatitis are minor.
When symptoms do occur, the most common are

fatigue
abdominal discomfort
aching joints
jaundice
enlarged liver
nausea
Liver biopsy histology at initial presentation showing peri-portal
lymphocytic infiltration and extensive peri-portal fibrosis.
 How is autoimmune hepatitis
treated?
• The goal of treatment is to stop the body’s attack on itself
by suppressing the immune system.
– prednisone,,
– azathioprine (Imuran)

• Treatment starts with a high dose of prednisone. When

symptoms improve, the dosage is lowered and azathioprine
may be added.In most cases, autoimmune hepatitis can be
controlled but not cured. That is why most patients will
need to stay on the medicine for years, and sometimes for
life.

• long-term use of steroid can cause serious side effects

including diabetes, osteoporosis, high blood pressure,
glaucoma, weight gain and decreased resistance to
infection.
Conventional Treatment
Regimens
CIRROSIS OF THE LIVER
 Description

• A chronic, progressive disease of the liver

– Extensive parenchymal cell

degeneration
– Destruction of parenchymal
cells
 Definition - Cirrhosis

 End stage of chronic

hepatitis
 conversion of normal
architecture to
abnormal nodules
 nodular regeneration
 fibrosis
Cirrhotic Liver
.

• ,
Liver cirrhosis
 Description

• Regenerative process is
disorganized
• , resulting in abnormal blood vessel
and bile duct relationships from
fibrosis
 Description

• Normal lobular structure distorted by

fibrotic connective tissue

• Lobules are irregular in size and

shape with impaired vascular flow

• Insidious, prolonged course

Etiology and Pathophysiology

• Cell necrosis occurs

• Destroyed liver cells are
replaced by scar tissue
• Normal architecture becomes
nodular
Etiology and Pathophysiology
• Four types of non viral cirrhosis:

– 1-Alcoholic (Laennec’s) cirrhosis

– 2-Postnecrotic cirrhosis

– 3-Biliary cirrhosis

– 4-Cardiac cirrhosis
 Etiology and Pathophysiology

• 1-Alcoholic (Laennec’s)
Cirrhosis
– Associated with alcohol abuse
– Preceded by a theoretically
reversible fatty infiltration of the
liver cells
– Widespread scar formation
 Etiology and Pathophysiology

• 2-Postnecrotic Cirrhosis

– Complication of toxic or viral

hepatitis
– Accounts for 20% of the cases of
cirrhosis
– Broad bands of scar tissue form
within the liver
 Etiology and Pathophysiology

• 3-Biliary Cirrhosis

– Associated with chronic biliary

obstruction and infection
– Accounts for 15% of all cases of
cirrhosis
 Etiology and Pathophysiology

• 4-Cardiac Cirrhosis

– Results from longstanding severe

right-sided heart failure
Histopathology
Histopathology
Histopathology
Hepatitis C
 Morphologic Classification
• 1-Micronodular cirrhosis
– Nodules less than 3 mm in diameter
– Believed to be caused by alcohol,
hemochromatosis, cholestatic causes
of cirrhosis, and hepatic venous outflow
obstruction

– 2-Macronodular cirrhosis
 Diagnostic Studies

• Liver function tests

• Liver biopsy
• Liver scan
• Liver ultrasound
Signs of CLD
Manifestations of Liver Cirrhosis
 Clinical Manifestations
Early Manifestations

• Abdominal pain
• Fever
• Lassitude (laziness)
• Weight loss
• Enlarged liver or spleen
 Clinical Manifestations
Late Manifestations

• Two causative mechanisms

–Hepatocellular failure
–Portal hypertension
 Clinical Manifestations
Jaundice

• Intermittent jaundice is characteristic

of biliary cirrhosis
• Late stages of cirrhosis the patient
will usually be jaundiced
..

• .
Jaundice or Scleral Icterus
 Clinical Manifestations
Jaundice

• Occurs because of insufficient

conjugation of bilirubin by the liver
cells, and local obstruction of biliary
ducts by scarring and regenerating
tissue
 Clinical Manifestations

Skin

• Spider angiomas (telangiectasia,

spider nevi)
• Palmar erythema
 Clinical Manifestations
Endocrine Disturbances

• Steroid hormones of the adrenal

cortex (aldosterone), testes, and
ovaries are metabolized and
inactivated by the normal liver
 Clinical Manifestations
Endocrine Disturbances

• Alteration in hair distribution

– Decreased amount of pubic hair
– Axillary and pectoral alopecia
 Clinical Manifestations

Hematologic Disorders

• Bleeding tendencies as a result

of decreased production of
hepatic clotting factors (II, VII, IX,
and X)
 Clinical Manifestations
Hematologic Disorders

• Anemia, leukopenia, and

thrombocytopenia are believed
to be result of hypersplenism
 Clinical Manifestations
Peripheral Neuropathy

• Dietary deficiencies of thiamine, folic

acid, and vitamin B12
Spider Angiomata
Spider Nevi
Nail Clubbing
.
,
Ascites
.

• .
 Ascites

• The most successful therapeutic

regimen is the combination of single
morning oral doses of Spironolactone
and Furosemide, beginning with 100 mg
and 40 mg
• Two major concerns with diuretic
therapy for cirrhotic ascites:
– Overly rapid removal of fluid
– Progressive electrolyte imbalance
Imaging techniques in liver disease
• Ultrasonography
• CT
• MRI
• Angiography
• Fibroscan
 Today: useful with other parameters
Clinical signs

Blood sample
Biomarkers

Liver biopsy Stiffness

Imaging
(US, MRI, endoscopy)
Ultrasound: periportal fibrosis
Ultrasound and liver scan: hepatic
Hemangioma
Ultrasound: periportal fibrosis
MRI: macronodulaer cirosis
Ascites
MRI for cirosis
FibroScan (Vibration-
Controlled Transient
Elastography
 Which method: blood sample or liver
stiffness?

• Hepascore
• Fibrotest
• Fibrometer

 Liver stiffness
(FibroScan)
Liver stiffness measurement using
FibroScan.
 Liver stiffness
Portal fibrosis

Cholestasis
Centrolobular fibrosis

Sinusoidal fibrosis Stiffness

Steatosis?
Portal blood flow

Inflammation

104
 FibroTest=FibroScan

• FibroTest
• was first described for patients with HCV infection in
This test uses five serum markers, Apo A1, Hap, a-2-
M, c-glutamyl transpeptidase (cG

• FibroMeter
• This is a new serum model that is claimed to
outperform other models. The six parameters
required to calculate FibroMeter are platelets, PT
index, AST, a-2-M, HA, and urea levels
Transient elastography (FibroScan)

FibroScan
is a non-invasive method for measuring liver
stiffness. An ultrasound transducer probe is
mounted on the axis of a vibrator.
Vibrations of mild amplitude and low frequency are transmitted
from the vibrator to the tissues
via the transducer,thereby inducing an
elastic shear wave that propagates through the tissue.
 New methods-FibroScan

• Liver biopsy

• Elastography (Fibroscan (F,N,I,S)

• Scarring has 4 stages: •

• F0 means no scarring •
• F1 is mild fibrosis •
• F2 is moderate fibrosis •
• F3 is severe fibrosis •
• F4 is cirrhosis or advanced fibrosis
Normal liver (A) and changes in the hepatic architecture
associated with advanced hepatic fibrosis (B)5
Liver biopsy
A, Prominent portal inflammation and occasional
Peripheral
piecemeal necrosis.
Hepatic encephalopathy
.
Complications
 Complications

• Other Pulmonary syndromes

– Hepatic hydrothorax
– Portopulmonary HTN
• Hepatic Encephalopathy
• Hepatocellular carcinoma
 Complications
Portal Hypertension
Internal Hemorrhoids

• Occurs because of the dilation of

the mesenteric veins and rectal
veins
 Complications
Portal Hypertension
Caput Medusae

• Collateral circulation involves

the superficial veins of the
abdominal wall leading to the
development of dilated veins
around the umbilicus
 Complications
Peripheral Edema and Ascites

• Ascites:
- Intraperitoneal accumulation of
watery fluid containing small
amounts of protein
 Complications
Peripheral Edema and Ascites
• Factors involved in the pathogenesis of ascites:

- Hypoalbuminemia
-  Levels of aldosterone
-  Portal hypertension
Major Complications of Cirrhosis

Jaundice
Portal hypertension
Variceal bleeding
Ascites
Spontaneous bacterial peritonitis
Hepatorenal syndrome
Hepatic encephalopathy
 CIRROSIS OF THE LIVER
Complications

• 1-Portal hypertension and esophageal

varices
• 2-Peripheral edema and ascites
• 3-Hepatic encephalopathy
• 4-Hepatorenal syndrome
 Hepatorenal syndrome

• acute renal failure coupled with advanced

hepatic disease (due to cirrhosis or less often
metastatic tumor or severe alcoholic hepatitis)
• characterized by:
– Oliguria
– benign urine sediment
– very low rate of sodium excretion
– progressive rise in the plasma creatinine
concentration
 Hepatorenal Syndrome

• Reduction in GFR often clinically

masked
• Prognosis is poor unless hepatic
function improves
• Nephrotoxic agents and
overdiuresis can precipitate HRS
 Hepatopulmonary syndrome

• Hepatopulmonary syndrome
– Liver disease
– Increased alveolar-arterial gradient while
breathing room air
– Evidence for intrapulmonary vascular
abnormalities, referred to as intrapulmonary
vascular dilatations (IPVDs)
 Hepatic Hydrothorax

• Pleural effusion in a patient with cirrhosis and

no evidence of underlying cardiopulmonary
disease
• Movement of ascitic fluid into the pleural
space through defects in the diaphragm, and
is usually right-sided
• Diagnosis -pleural fluid analysis
– reveals a transudative fluid
– serum to fluid albumin gradient greater than 1.1
 Hepatic hydrothorax

• Confirmatory study:
– Scintigraphic studies demonstrate tracer in the chest cavity
after injection into the peritoneal cavity
• Treatment options:
– diuretic therapy
– periodic thoracentesis
– TIPS
 Portopulmonary HTN

• Refers to the presence of pulmonary hypertension

in the coexistent portal hypertension
• Prevalence in cirrhotic patients is approximately 2
percent
• Diagnosis:
– Suggested by echocardiography
– Confirmed by right heart catheterization
 Hepatic Encephalopathy

• Spectrum of potentially reversible neuropsychiatric

abnormalities seen in patients with liver dysfunction
– Diurnal sleep pattern pertubation
– Asterixis
– Hyperactive deep tendon reflexes
– Transient decerebrate posturing
 Complications
Peripheral Edema and Ascites

• Ascites:
- Intraperitoneal accumulation of
watery fluid containing small
amounts of protein
 Complications
Portal Hypertension

• Primary mechanism is the increased resistance

to blood flow through the liver
 Portal Hypertension

Arteriovenous
Esophagea shunting
l
Hypersplenism
Varices
Caput Moderate anemia
medusae Neutropenia
(dilated abd.
veins) Thrombocytopeni
a
Hemorrhoids

Marked ascites
 Complications
Portal Hypertension

• Characterized by:
– Increased venous pressure in
portal circulation
– Splenomegaly
– Esophageal varices
– Systemic hypertension
 Portal Hypertension
• Normal pressure ranges from 7 to 10 mm Hg.

• In portal hypertension, pressure exceeds 10 mm Hg,

averaging around 20 mm Hg and occasionally rising
as high as 50–60 mm Hg.

• In extrahepatic portal vein thrombosis (without liver

disease), collaterals in the diaphragm and in the
hepatocolic, hepatoduodenal, and gastrohepatic
ligaments transport blood into the liver around the
occluded vein (hepatopetal).

• In cirrhosis, collateral vessels circumvent the liver

and deliver portal blood directly into the systemic
circulation (hepatofugal); these collaterals give rise
to esophageal and gastric varices.
 Portal Hypertension
• Isolated thrombosis of the splenic vein causes
localized splenic venous hypertension and gives rise to
large collaterals from spleen to gastric fundus.
• From there, the blood returns to the main portal system
through the coronary vein.
• In this condition, gastric varices are often present without
esophageal varices.
• spontaneous bleeding is relatively uncommon except
from those at the gastroesophageal junction;
spontaneous bleeding from gastric varices can
sometimes occur.
• Compared with adjacent areas of the esophagus and
stomach, the gastroesophageal junction is especially rich
in submucosal veins, which expand disproportionately in
patients with portal hypertension.
• The cause of variceal bleeding is most probably
rupture due to sudden increases in hydrostatic
pressure.
 Complications
Portal Hypertension
Splenomegaly

• Back pressure caused by portal hypertension  chronic

passive congestion as a result of increased pressure in
the splenic vein
 Complications
Portal Hypertension

Esophageal Varices
• Increased blood flow through the
portal system results in dilation
and enlargement of the plexus
veins of the esophagus and
produces varices
 Collaborative Care
Esophageal Varices

• Endoscopic sclerotherapy or ligation

• Balloon tamponade
• Surgical shunting procedures (e.g., portacaval
shunt, TIPS)
Treatment of esophageal varices
Active bleeding
• Central line & pulmonary artery pressures
• Blood transfusions & fresh frozen plasma for
clotting factors
• Somatostatin or Vasopressin – constrict gut
vessels
• Nitroglycerin- to counter negative affects of
vasopressin
• Airway/trach
Later prevention of re-bleeding
• Beta-blockers
• Long-acting nitrates
• Soft food, chew well, avoid intra-abdominal
pressure
• Protonix (pantoprazole)
Rapid Endoscopy!
Sclerotherapy:

• A sclerosant solution
(ethanolamine oleate or
sodium tetradecyl
sulphate) is injected into
the bleeding varix or the
overlying submucosa

• Complications can
include fever, dysphagia
and chest pain,
ulceration, stricture, and
(rarely) perforation.
Band ligation:

• Band ligation is
achieved by a
banding device
attached to the tip of
the endoscope
Balloon Tube Tamponade:

•
 Drug Therapy

• There is no specific drug

therapy for cirrhosis
• Drugs are used to treat
symptoms and
complications of advanced
liver disease
 Collaborative Care
Ascites

• High carbohydrate, low

protein, low Na+ diet
• Diuretics
• Paracentesis
Paracentesis

• To treat respiratory
distress
• Pt will loose 10-30 grams
of protein
• Pt in sitting position
• Empty bladder first
• Post--watch for
hypotension, bleeding,
shock & infection
Peritoneovenous Shunt
Portosystemic Shunts
 Complications
Hepatic Encephalopathy

• Liver damage causes blood to

enter systemic circulation
without liver detoxification
 Complications
Hepatic Encephalopathy

• Main pathogenic toxin is NH3

although other etiological factors
have been identified
• Frequently a terminal complication
 Collaborative Care
Hepatic Encephalopathy
• Goal: reduce NH3 formation

– Protein restriction (0-40g/day)

– Sterilization of GI tract with antibiotics (e.g.,

neomycin)

– lactulose (Cephulac) – traps NH3 in gut

– levodopa
 Treatment Options

• The major goals of treating the cirrhotic patient

include:
– Slowing or reversing the progression of liver disease

– Preventing superimposed insults to the liver

– Preventing and treating the complications

– Determining the appropriateness and optimal timing for liver

transplantation
 Liver Transplantation

• Liver transplantation is the definitive treatment for

patients with decompensated cirrhosis
• Depends upon the severity of disease, quality of life
and the absence of contraindications
 Liver Transplantation

• Minimal criteria for listing cirrhotic patients on the liver

transplantation list include
– A child-Pugh score 7
– Less than 90 percent chance of surviving one year without a
transplant
– An episode of gastrointestinal hemorrhage related to portal
hypertension
– An episode of spontaneous bacterial peritonitis
 Vaccinations

• Hepatitis A and B
• Pneumococcal vaccine
• Influenza vaccination
 Surveillance

• Screening recommendations:
– serum AFP determinations and ultrasonography every six
months
 Cholestatic
Liver Diseases
 Primary Biliary Cirrhosis
• Differential diagnosis
– Sarcoidosis
– Granulamatous hepatitis
– Hepatitis C
– Drug induced hepatitis
– PSC
– Alcoholic liver disease
– Idiopathic adult onset ductopenia
– Autoimmune hepatitis
 Features of PBC
• Clinical Features • Laboratory
• Sicca syndrome
50% features
• Thyroid disease • AMA positive
15% (95%)
• Arthritis 10% OR
• Less Common <5% • ANA positive
– Raynaud’s • ASMA positive
– Breast cancer • Elevated
– Scleroderma cholesterol
– Renal stones • Elevated IgM level
Histologic Staging of PBC

.
• .

CholangioCarcinoma:
 Liver biopsy in a patient with a large, right lobe hepatic mass. Only a small area of the
slide contains hepatocytes. The remainder of the biopsy reveals an infiltrating

neoplasm typical of cholangiocarcinoma. The abnormal

adenocarcinoma-like proliferation of tubo-ductular structures, largely seen in the
upper left hand corner of the photograph, may be impossible to differentiate from
Image courtesy Dr. Chris Pappas
metastatic adenocarcinoma.
 CholangioCarcinoma:
Epidemiology
• Malignant bile duct cancer arising from
epithelial cells of the intra/extrahepatic bile
ducts
• Rare…but lethal
• 3% of all GI malignancies
• Increases with age (50-70 years old)
 Molecular Pathogenesis

• Malignant transformation incompletely

understood
• Molecular defects involving oncogenes and tumor
suppressor genes
• 70-80% overexpress p53
• Mutations in oncogenes K-ras, c-myc, c-neu, c-erB-2
• Overexpression of MET, hepatocyte growth factor,
common feature
• Share molecular features of hepatocellular carcinoma
 Treatment
Surgical

Intrahepatic cholangiocarcinoma
• Hepatic resection
– 61 patients: 60% 3 year survival
– 30 patients: 86/63/22% survival
Perihilar cholangiocarcinoma:
• 20-40% potentially resectable
• Aggressive resection of bile duct, liver resection, and
caudate lobectomy
 .

Primary Sclerosing Cholangitis

(PSC)
 .
Primary Sclerosing Cholangitis
(PSC)

• Associated with ulcerative colitis (UC)

• Incidence of colitis 90%
• 30% of CC diagnosed in UC and PSC
• Annual incidence 1.5/year
• Lifetime risk of 10-15%
• Autopsy studies: 30% CC
• More difficult to diagnose in PSC
• 1/3 cases of CC made within 2 years of
diagnosis
 .
Primary Sclerosing Cholangitis (PSC)

• Smokers and former smokers had

higher rates of cancer
• Alcohol consumption
• Role of CEA, CA-19-9, CA-50, and
CA-242 of limited value
 Risk Factors

• Parasitic infections
• Hepatolithiasis
• Toxic exposures: Thorotrast (20-30
years), auto/rubber/wood-finishing
• Li-Fraumeni syndrome
• Biliary Papillomatosis
Budd-Chiari syndrome
 Mechanism Hepatic vein outflow obstruction:
hepatic vein thrombosis (Budd-Chiari syndrome)
o Original description: fatal acute thrombosis
o Expanded definition: acute, subacute, or chronic
occlusions of hepatic vein
o Signs/symptoms: hepatomegaly, pain, ascites
o Causes (most frequent to less frequent)
o Polycythemia vera (myeloproliferative diseases)
o Pregnancy or post-partum state
o Oral contraceptives
o Paroxysmal nocturnal hemoglobinuria
o Cancers, especially hepatocellular carcinoma
o Idiopathic (10%, presumably undiagnosed
thrombogenic disorder)
 Budd-Chiari syndrome: pathology

Severe centrilobular congestion & necrosis; degree of

necrosis depends on degree of hepatic outflow occlusion
 Budd-Chiari syndrome: treatment

o Address underlying cause; high mortality

without treatment
o Acute interventions:
o Surgical creation of portal-systemic shunt (portal vein to
systemic circulation), which allows reverse flow through
portal vein, but hepatic artery inflow preserved to prevent
infarction
o Angiographic thrombectomy and/or dilation of hepatic vein
Universitatea Titu Maiorescu
Bucuresti

GASTROENTEROLOGY
Liver Disorders and Biliary Tract Disease

Lecture III

Prof Univ Dr Ion C. Țintoiu

.
CIRROSIS OF THE LIVER
Universitatea Titu Maiorescu
LIVER TUMORS
Benign liver tumors
 Basic workup

• Differentiate between
• primary hepatic malignancy vs.
• metastatic disease vs. benign
 Hepatic abscess

• Pyogenic
• Amebic
• Fungal
• Echinococcal
 Pyogenic abscess

• Cholangitis is the most common cause of liver

abscesses
• Patient usually present with variable
constitutional symptoms
• US, CT, and MRI are all sensitive modalities for
identifying an abscess, however they do not
differentiate between pyogenic and amebic
 Pyogenic abscess
-- Pyogenic Liver Abscess Microbiology
Gram-negative Gram-positive
Anaerobes
Aerobes Aerobes
Staphylococcus
Escherichia coli
aureus
Common (≥10%) Enterococcus spp. Bacteroides spp.
Klebsiella Viridans
streptococci
Pseudomonas
Fusobacterium
Proteus
Uncommon (1%– β-hemolytic Anaerobic
Enterobacter
10%) streptococci streptococci
Citrobacter Clostridium
Serratia Lactobacilli
 Pyogenic abscess

• Treated with
• -antibiotics

• - percutaneous drainage

• -Open surgical drainage

• is reserved for patients with concurrent

gastrointestinal disease processes that require
surgery or those patients who have failed
percutaneous drainage.
 Pyogenic abscess

• .
 Fungal abscess

• Fungal liver abscesses are being recognized with

increased frequency and currently account for
approximately 10% of hepatic abscesses

• Candida albicans and other Candida species are

found in approximately 80% of cases
• Fungal liver abscesses are usually multiple and
usually occur in immunocompromised patients.
 Fungal abscess

• Fungal liver abscesses are treated with systemic

antifungal therapy and drainage of the abscess cavity
or cavities by simple aspiration, percutaneous
drainage, or open surgical drainage
• Amphotericin B is the first-line drug of choice for
systemic antifungal therapy because of its broad
fungal efficacy
• Voriconazole or Caspofungin may be used to treat
patients who are not responding to Amphotericin B or
who have aggressive infections caused by other
fungal species
 Echinococcal disease

• Echinococcus is a flat tapeworm

• Human infestation occurs with
• consumption of contaminated vegetables or through
contact with infected animals or soil

• E. granulosus forms cysts that are constituted by an

external acellular layer and an inner cellular germinal
layer that produces the brood capsules containing
protoscolicies, hydatid sand, or daughter cysts
 Echinococcal disease

• The outer acellular layer is usually 2 to 5 mm thick

and is composed of fibroblasts that produce a
capsule of fibrous connective tissue called the
pericyst. The pericyst is calcified in approximately
half of patients.
• The symptoms associated with hepatic E. granulosus
can vary considerably
• specific enzyme-linked immunosorbent assay
(ELISA) and hydatid antigen immunobinding assays
yield a sensitivity and specificity up to 95% and 90%,
respectively
 Echinococcal disease

• .
 Echinococcal disease

• Chemotherapy with
• benzimidazole compounds
• (mebendazole and albendazole) is the medical
treatment of choice
• More recently, praziquantel, a synthetic isoquinoline-
pyrazine derivative, has been used in combination
with albendazole
• with medical treatment alone, only 30% of patients
can expect clinical and radiographic resolution.
Medical treatment therefore should be used primarily
in conjunction with percutaneous drainage or surgery
 Benign Hepatic Masses

• The differential diagnosis of the benign solid hepatic

hepatic adenoma,
• focal nodular hyperplasia (FNH),
• focal fatty infiltration,
• cavernous hemangioma, and other rare neoplasms
(e.g., mesenchymal hamartoma and teratoma)
• Benign hepatic lesions are common, with an
estimated incidence of 7% to 9%, and in one autopsy
series, up to 20% of the population
 Simple Cysts

• Simple cysts are solitary more than 50% of the time

and asymptomatic more than 90% of the time.
• Size can range up to 20 cm, although most are less
than 5 cm
• Asymptomatic simple cysts less than 8 cm require no
intervention but should be observed
 Simple Cysts

• .
 Simple Cysts

• Any symptoms are usually related to mass effect,

causing pain in the right upper quadrant and
occasionally early satiety. Rarely, intracystic
hemorrhage and infection may develop
• patients with symptomatic cysts (>5 cm) should
undergo laparoscopic or open cyst unroofing.
 Complex cysts

• If multiple simple cysts are seen, consider polycystic

liver disease
• This is an inherited condition (autosomal dominant),
often found in association with renal cysts
• the majority of patients with polycystic liver disease
remain asymptomatic with preserved liver function
and do not require surgical intervention
 Complex cysts

• .
 Complex cysts

• Biliary cystadenomas are uncommon, slow-growing

complex cysts measuring up to 20 cm in size. They
are benign but have malignant potential to transform
into cystadenocarcinoma and thus should be
surgically removed whenever recognized
• The diagnosis is made by the presence of
mesenchymal tissue
 Complex cysts

• Radiologically, internal septations are almost always

seen in cystadenomas on contrast-enhanced CT or
MRI. Cystadenomas have irregular borders and a
thick stromal layer, and calcifications and mural
nodules can occasionally be seen in the walls
 Complex cysts

• .
 Hemangioma

• Autopsy series report prevalances from 0.5% to as

high as 20.0%. The female-to-male ratio is between
5:1 and 6:1. Hemangioma is usually found between
the ages of 30 and 70 years
• tumors arise from the endothelial lining of blood
vessels as vascular ectasias and have been
associated with high estrogen states including
puberty, pregnancy, oral contraceptive use, and
androgen treatment
 Hemangioma

• Most tumors are less than 5 cm and asymptomatic

• Contrast-enhanced CT with delayed venous
examination will demonstrate peripheral nodular
enhancement and progressive centripetal fill-in
 Hemangioma

• .
 Hemangioma

• Hemangiomas almost never require surgical

resection after the diagnosis is secure because most
lesions are asymptomatic, and risk of spontaneous
rupture is extremely small.
• For symptomatic lesions, simple enucleation is
recommended because it preserves the maximal
amount of functional liver
 Focal nodular hyperplasia (FNH)

• Focal nodular hyperplasia (FNH) is the second

most common benign solid hepatic tumor (behind
hemangioma), comprising 8% of all primary hepatic
tumors.
• Prevalence of FNH is estimated to be 3% of the
general population, predominantly in women in their
third to fifth decades.
• The female-to-male ratio is between 6:1 and 8:1
 Focal nodular hyperplasia- FNH

• FNH consists of benign-appearing hepatocytes with

cords of fibrous septae radiating from a central
scar, which comprises biliary structures of
hepatocellular origin
• Most patients present with an asymptomatic, solitary
tumor of less than 5 cm near the hepatic surface.
Only 10% of patients have clinical symptoms
 Focal nodular hyperplasia -FNH

• On contrast-enhanced multiphasic CT imaging,

lesions are usually homogenous and isoattenuating
to liver parenchyma before contrast injection. Lesions
are bright, hypervascular with hypodense central
scarring on arterial phase examination. If present,
radiating hypodense fibrous bands and septa that
arise from the scar are characteristic findings
 Focal nodular hyperplasia -FNH

• .
 Focal nodular hyperplasia -FNH

• Nuclear medicine imaging can sometimes be helpful

to distinguish FNH from hepatic adenoma
because sulfa-colloid is taken up by Kupffer cells
(present in FNH), which are usually absent in
adenoma
 Focal nodular hyperplasia -FNH

• Treatment strategy is heavily influenced by the

certainty of diagnosis. In asymptomatic patients with
a clear diagnosis, no further treatment is
necessary, and the patient may be observed. In
equivocal cases in which all imaging modalities fail to
establish a firm diagnosis, biopsy is warranted for
histologic examination
 Hepatic adenoma

• Hepatic adenoma (HA) is a rare hepatic tumor that

occurs predominantly in women aged 20 to 40 years,
with a female-to-male ratio of at least 4:1 and
reportedly as high as 11:1.
• It has a strong association with oral contraceptive
use, with an incidence of 3 to 4 in 100,000 oral
contraceptive users versus 1 in 100,000 nonusers
 Hepatic adenoma

• HAs are mostly solitary (70%–80%), well

circumscribed, round, and unencapsulated. A
pseudocapsule is often present
• Larger HA tumors (>5 cm) can be associated with
right upper-quadrant pain, fullness, or discomfort.
Because of its hypervascular nature and lack of a
capsule, HA carries a moderate to high risk of
spontaneous rupture, associated with increasing size
(>5 cm). When rupture occurs, it is intratumoral in
one third of cases and intraperitoneal in two thirds of
cases.
 Hepatic adenoma

• On CT, adenomas often appear heterogeneous

because of their mixed components of fat,
hemorrhage, and necrosis. On portal venous
examination or delayed images, they may appear
isodense. HAs are contrast enhancing because of
their rich vascular supply and often show peripheral
enhancement with centripetal progression, indicating
the presence of large subcapsular feeding vessels
and early draining veins
 Hepatic adenoma

• .
Liver Cancer
 Malignant Liver Tumors

1. Hepatocellular carcinoma (HCC)

2. Fibro-lamellar carcinoma of the liver
3. Hepatoblastoma
4. Intrahepatic cholangiocarcinoma
5. Others
 Risk Factors - HCC

• Chronic HBV and HCV

• Cirrhosis

• Chronic underlying liver disease.

 Risk Factors - cholangioCA

• Infrequently associated with cirrhosis.

• Primary sclerosing cholangitis

• Widespread infection with liver flukes (Clonorchis

sinensis
HEPATOCELLULAR CARCINOMA
HCC
 HCC: Incidence
• The most common primary liver cancer
• The most common tumor in Saudi men
• Increasing in US and all the world
 HCC: Risk Factors
The most important risk factor is cirrhosis from any
cause:
1. Hepatitis B (integrates in DNA)
2. Hepatitis C
3. Alcohol
4. Aflatoxin
5. Other
 HCC: Metastases
• Rest of the liver
• Portal vein
• Lymph nodes
• Lung
• Bone
• Brain
HCC: Systemic Features
• Hypercalcemia
• Hypoglycemia
• Hyperlipidemia
• Hyperthyroidism
 Signs & symptoms
• Nonspecific symptoms
– abdominal pain
– Fever, chills
– anorexia, weight loss
– jaundice

• Physical findings
– abdominal mass in one third
– splenomegaly
– ascites
– abdominal tenderness
 HCC: Diagnosis
• Clinical presentation
• Elevated AFP
• US
• Triphasic CT scan: very early arterial perfusion
• MRI
• Biopsy
 HCC: labs
• Labs of liver cirrhosis

AFP (Alfa feto protein)

• Is an HCC tumor marker
• Values more than 100ng/ml are highly suggestive of
HCC
• Elevation seen in more than 70% of pt
 Diagnosis
(b) what investigations are required to make a definite
diagnosis

1) AFP produced by 70% of HCC

> 400ng/ml
AFP over time

2) Imaging
- focal lesion in the liver of a patient with cirrhosis is highly
likely to be HCC

- Spiral CT of the liver

- MRI with contrast enhancement

 Diagnosis

3) Biopsy is rarely required for diagnosis

seeding
in 1–3%.
Biopsy of potentially operable lesions
should be avoided where possible
US: HCC
CT: Venous Phase
CT: Arterial Phase
 Diagnosis
.
Cirrhosis + Mass < 2 cm

Raised Normal
AFP AFP
CT, MRI

Assess for
surgery lesion by exam

Confirmed FNAC or biopsy

diagnosis
Liver Cancer Treatment
 Treatment (Surgery)

• The only proven potentially curative therapy for HCC

• Hepatic resection or liver transplantation

• Patients with single small HCC (≤5 cm) or up to three lesions ≤3 cm

• Involvement of large vessels (portal vein, Inferior vena cava) doesnt

automatically mitigate against a resection; especially in fibrolamellar
histology

• No randomised controlled trials comparing the outcome of

surgical resection and liver transplantation for HCC.
 Treatment (Surgery)

• Hepatic resection should be considered in HCC and a non-cirrhotic

liver (including fibrolamellar variant)

• Resection can be carried out in highly selected patients with cirrhosis

and well preserved hepatic function (Child-Pugh A) who are
unsuitable for liver transplantation. It carries a high risk of
postoperative decompensation.

• Perioperative mortality in experienced centres remains between 6%

and 20% depending on the extent of the resection and the severity of
preoperative liver impairment.

• The majority of early mortality is due to liver failure.

 Treatment (Surgery)
• Recurrence rates of 50–60% after 5 years after resection are usual
(intrahepatic)

• Liver transplantation should be considered in any patient with

cirrhosis

• Patients with replicating HBV/ HCV had a worse outlook due to

recurrence and were previously not considered candidates for
transplantation.

• Effective antiviral therapy is now available and patients with small

HCC, should be assessed for transplantation
 Treatment (non-Surgical)
should only be used where surgical therapy is not possible.

1) Percutaneous ethanol injection (PEI)

• has been shown to produce necrosis of small HCC.
• It is best suited to peripheral lesions, less than 3 cm in
diameter

2) Radiofrequency ablation (RFA)

• High frequency ultrasound to generate heat
• good alternative ablative therapy
• No survival advantage
• Useful for tumor control in patients awaiting liver transplant
 Treatment (non-Surgical)

3) Cryotherapy
• intraoperatively to ablate small solitary tumors outside a
planned resection in patients with bilobar disease

4) Chemoembolisation
• Concurrent administration of hepatic arterial chemotherapy
(doxirubicin) with embolization of hepatic artery
• Produce tumour necrosis in 50% of patients
• Effective therapy for pain or bleeding from HCC
• Affect survival in highly selected patients with good liver
reserve
• Complications: (pain, fever and hepatic decompensation)
 Treatment (non-Surgical)

5) Systemic chemotherapy
– very limited role in the treatment of HCC with poor
esponse rate
– Best single agent is doxorubicin (RR: 10- 20%)
– Combination chemotherapy didn’t response but
survival
– should only be offered in the context of clinical trials

6) Hormonal therapy
- Nolvadex, stilbestrol and flutamide

7) Interferon-alfa
8) retinoids and adaptive immunotherapy (adjuvant)
 HCC: Local Ablation
• For non resectable pt
• For pt with advanced liver cirrhosis
• Alcohol injection
• Radiofrequency ablation
• Temporary measure only
Radio Frequency Ablation
Ethanol Injection
 HCC:
Chemoembolization
• Inject chemotherapy selectively in hepatic artery
• Then inject an embolic agent
• Only in pt with early cirrhosis
• No role for systemic chemotherapy
Chemoembolization
 HCC: Prognosis
• Tumor size
• Extrahepatic spread
• Underlying liver disease
• Pt performance status
 HCC: Liver
Transplantation
• Best available treatment
• Removes tumor and liver
• Only if single tumor less than 5cm or less than 3
tumors less than 3 cm each
• Recurrence rate is low
• Not widely available
 Selection of agents for targeted
therapy in HCC
Name Target
Gefitinib EGFR
Erlotinib EGFR
Lapatanib EGFR
Cetuximab EGFR
Bevacizumab VEGF
Sorafenib (Nexavar) Raf1, B-Raf, VEGFR , PDGFR
Sunitinib PDGFR, VEGFR, c-KIT, FLT-3
Vatalanib VEGFR, PDGFR, c-KIT
Cediranib VEGFR
Rapamycin mTOR (mammalian target of rapamycin)
Everolimus mTOR
Bortezomib (Velcade) Proteasome
 Clinical Importance of Early Detection
& Precise staging of HCC

•T1: Resection
Ablation
•T2: Transplant

• 5-yr survival rates

50 – 70%

• HCCs detected in T1 & T2 stages show much better survival

• Sensitive imaging modalities to detect HCCs in its early stages
El-Serag HB, et al. Gastroenterology 2008; 134:1752-1763.
Liver Failure
 Liver failure:

• Liver failure:
Clinical syndrome: sudden loss of
liver
parenchymal and metabolic function
Manifest as coagulopathy and
encephalopathy
 Liver failure
Hyper - acute liver failure
Acute liver failure
Greatest risk of cerebral
oedema, CVS failure
Greatest chance of
spontaneous survival

Sub - acute liver failure

Lowest risk of cerebral
oedema/ encephalopathy
Easily confused with CLD
Ascites
Lowest chance of spontaneous
survival
 Multi system
disease
Coagulopathy
• INR important prognostic indicator in established ALF
• Platelet dysfunction DIC - rare
Metabolic
• Insulin resistance : Clarke et al Hepatology
• Hyperlactataemia :Bernal et al Lancet 2002 : useful to track
• Liver net producer of lactate Murphy et al Crit Care Med
2001
• P04, Mg, Na, glucose, K, pH
• High incidence of pancreatitis
Nutrition
• Frequent poor recent oral intake ± vomiting
• No evidence for protein restriction in either acute or
CLD
• Gastric prophylaxis
 Acute liver failure

• Acute liver failure :

Defined as interval between onset of the illness and

appearance of encephalopathy < 8 weeks
 Acute liver failure

• Uncommon causes:
Wilson’s disease, other infections (CMV, HSV,
EBV), vascular abnormality, toxin, acute fatty liver
of pregnancy, antoimmune hepatitis, ischemia,
malignant infiltration
 Acute liver failure

• Symptoms and signs:

Jaundice, altered mental status, nausea/
vomiting, anorexia, fatigue, malaise,
myalgia/arthralgia
Most of them present hepatoencephalopathy
and icteric appearance.
 Non-specific Management

Hypoglycemia
Encephalopathy
Infections
Hemorrhage
Coagulopathy
Hypotension(hypovolemia, vascular
resistance ↓)
Respiratory failure
Renal failure
Pancreatitis
 Non-specific Management

• Hypoglycemia: monitoring blood glucose, IV glucose

supplement.
• Infection: aseptic care, high index of suspicion,
preemptive antibiotic.
• Hemorrhage (i.e. GI): NG placement, H2 blocker or
PPI.
• Hypotension: hemodynamic monitoring or central
pressures, volume repletion
 Non-specific Management

• Respiratory failure (ARDS): mechanical ventilation.

• Renal failure (hypovolemia, hepatorenal syndrome,

ATN): hemodynamic monitor, central pressure,
volume repletion, avoid nephrotoxic agent
 Encephalopathy

• major complication
• precise mechanism remains unclear

• Hypothesis: Ammonia production

• Treatment toward reducing ammonia production
• Watch out airway, prevent aspiration
 Encephalopathy Portal Systemic Encephalopathy
Portal systemic shunt
– spontaneous collateral
– Surgical
– TIPPS
Not at risk of cerebral oedema

Precipitating factors
– Sepsis
• SBP Rx fluids ++
• Albumin
HE of Acute Liver Failure • Avoid renal failure
Hepatocellular failure – CNS active drugs
Rapid onset – Electrolyte abnormalities
Cerebral oedema
– Diuretics - over use
Myoinositol levels not reduced
– Gastrointestinal bleeding
Cytotoxic and vasogenic
 Encephalopathy

TX upon ammonia hypothesis

• Correction of hypokalemia
• Reduction in ammoniagenic substrates: cleansing
enemas and dietary protein restriction.
• Lactulose: improved encephalopathy, but not
improved outcome.
Dose 2-3 soft stools per day
 Encephalopathy

• Oral antibiotics: neomycin  lack of evidence

nephrotoxicity  limited use.
 Hepatic Encephalopathy

• Stage 1: shorted attention span, reversal of sleep-wake

cycle, subtle personality changes (anxiety, irritability)
• Stage 2: lethargy, personality change, disorientation.
Asterixis.
• Stage 3: stupor but responsive, severe confusion and
disorientation, abnormal behaviour, incomprehensible
speech
• Stage 4: coma
 Cerebral Edema

• Cerebral edema develops in 75 - 80 % of patients

with grade IV encephalopathy.
• precise mechanism : not completely understood
• Possible contributing factor:
1-osmotic derangement in astrocytes
2-changes in cellular metabolism
3-alterations in cerebral blood flow
 Coagulopathy

• diminished capacity of the failing liver to synthesize

coagulation factors.
• The most common bleeding site: GI tract.
• Prophylactic administration of FFP: not
recommended.
 performed before transplant or invasive procedure
 Liver transplant

• Liver transplant: remain backbone of treatment of

fulminant hepatic failure
reliable criteria to identify these patients who really
need transplant.
 remain unresolved in fulminant hepatic failure.
 Liver support system

• Non-cell-based:
• plasmapheresis and charcoal-based
hemoabsorption

• Cell-based systems :
• known as bioartificial liver support systems
• Non-cell-based: not improved survival.
Available systems:
• (MARS) Molecular Adsorbents Recirculation
System
 Liver Dialysis

• Bridge to transplant
• Dialyze 6 hours at a time
Molecular Adsorbents
Recirculation System

(MARS) …
 MARS
Molecular Adsorbents Recirculation System
Therapy

, encephalopathy
• Controls: biochemistry static, worsening
encephalopathy

Coagulopathy and
MARS treatment in CLD

Single Pass Albumin Dialysis (SPAD)

Clearance of bilirubin, bile acids, NH4 : improved

 MARS

• Significant improvement in encephalopathy

• No change in renal function or creatinine

• No change in ammonia or cytokine levels (TNF, IL-6, IL-10, IL-8),

MDA, MELD fell in both groups

No differences in survival
LIVER TRANSPLANT
 Liver Transplantation
for
Liver
Alcoholic Liver Disease
Transplantation
Live Donor Liver Transplant
 Liver transplant complications
• Rejection. About 70% of all liver-transplant patients
have some degree of organ rejection prior to
discharge.

• Anti-rejection medications are given to ward off the

immune attack.
• Infection

• Most infections can be treated successfully as they

occur.
• Cancer
 Biliary Complications
“The Achilles heel of liver
transplantation”
• Early (< 30 days) • Late (> 30 days)

Anastomotic bile leak Anastomotic stricture

Anastomotic stricture Nonanastomotic
Bile leak at T tube exit strictures
Obstruction of T tube Bile leak on T tube
Sphincter of Oddi removal
dysfunction Sphincter of Oddi
dysfunction
QUESTIONS

PAUZA !!!!!!!---GATA ????

Gallbladder
Disorders
 ANATOMY & PHYSIOLOGY
BILIARY SYSTEM
a. Canaliculi – the smallest bile ducts located
between liver lobules, receive bile from
hepatocytes. The canaliculi form larger bile
ducts, which lead to hepatic duct.
b.Hepatic duct – from the liver joins the cystic
duct from the gallbladder to form the common
bile duct, which empties into the duodenum.
c. Sphincter of Oddi – controls the flow of bile
into the intestine.
d.Gallbladder – is a hollow pear-shaped organ
that is 30-40mm long. Normally holds 30-
50mL of bile and can hold up to 70mL when
fully distended.
CHOLELITHIASIS
 CHOLELITHIASIS

• Refers to formation of calculi (ie,

gallstones in the bladder.

• Predisposing Factors:
1.Obese
2.Female
3.>40 yrs
4.OC, Estrogen, intake
5.Fair
 CHOLELITHIASIS
Supersaturated bile, Biliary stasis

Stone formation

Blockage of Gallbladder

Inflammation, Mucosal Damage and WBC infiltration

CHOLECYSTITIS
Gall Stones
 CHOLECYSTITIS/
CHOLELITHIASIS
Signs and Symptoms:
• Severe Right abdominal pain radiating to the
back
• Fever
• Fat intolerance
• Anorexia, n/v
• Jaundice
• Pruritus
• Easy bruising
• Tea colored urine
• Steatorrhea
Cholecystitis & Cholelithiasis
by: Gari Glaser
 What is it?
• By definition,
cholecystitis is an
inflammation of the
gallbladder wall and
nearby abdominal
lining.

Abdomi
nal wall Gallbl
adder
 Etiology / Pathophysiology
• Can be caused by an obstruction, gallstone or a tumor.
• 90% of all cases caused by gallstones.
• The exact cause of gallstone formation is unknown.

When there is an obstruction, gallstone or

tumor it prevents bile from leaving the
gallbladder.
 Bile gets trapped and acts as an irritant which causes
cellular infiltration within 3 – 4 days.
• This infiltration causes an
inflammatory process – the
gallbladder becomes
enlarged and edematous.
• Eventually this
occlusion along with
bile stasis causes the
mucosal lining of the
gallbladder to become
necrotic.
• Bacterial growth
occurs due to
Necrotic
ischemia. Gallbladder
 • Rupture of the gallbladder becomes a danger, along with spread
of infection of the hepatic duct and liver.
• If the disease is severe and interferes with the blood supply it
can cause the gallbladder to become gangrenous.

Gang
Gallst
renou
ones
s
gallbl
 Gallstones . .

• The presence of
gallstones in the
gallbladder is called
cholelithiasis.
 Signs and Symptoms.
• Complaints of indigestion after
eating high fat foods.
• Localized pain in the right-
upper quadrant epigastric
region.
• Anorexia, nausea, vomiting
and flatulence.

 Increased heart and respiratory rate –

causing patient to become diaphoretic
which in turn makes them think they
are having a heart attack.
 Signs and Symptoms.

• Low grade fever.

• Elevated leukocyte count.
• Mild jaundice.
• Stools that contain fat – steatorrhea.
• Clay colored stools caused by a lack of bile in the
intestinal tract.
• Urine may be dark amber- to tea-colored.
 Diagnostics.
• Fecal studies.

• Serum bilirubin tests.

• Ultrasound of the
gallbladder.
 Diagnostics.

• HIDA scan - imaging test used to

examine the gallbladder and the ducts
leading into and out of the gallbladder - also
referred to as cholescintigraphy.

• Oral cholecystogram - the patient

takes iodine-containing tablets by mouth -
iodine is absorbed from the intestine into the
bloodstream - removed from the blood by
the liver and excreted by the liver into the
bile – it is concentrated in the gallbladder -
outlines the gallstones that are radiolucent
(x-rays pass through them).

• Operative cholangiography –
common bile duct is directly injected with
radiopaque dye.
 Recap. Stages of Acute Cholecystitis.
- Gallbladder has a grayish
appearance & is edematous.
-There is an obstruction of the
cystic duct and the gallbladder
begins to swell.
- It no longer has the "robin
egg blue" appearance of a
normal gallbladder.
- As acute cholecystitis
progresses, the gallbladder
begins to become necrotic
and gets a speckled
appearance as the wall
begins to die.
- Gallbladder undergoes
gangrenous change and
the wall becomes very
dark green or black.
- This is the stage when
perforation occurs.
 Medical Management.
• Lithotripsy  If the attack of
• for patients with only cholelithiasis is mild –
a FEW stones.  bed rest is prescribed.
 patient is placed on
NPO to allow GI tract
and gallbladder to rest.
 an NG tube is placed
on low suction.
 fluids are given IV in
order to replace lost
fluids from NG tube
suction.
Medical Management.

Cholecystectomy
or
Laparoscopic Cholecystectomy
– removal of the gallbladder.

This is the treatment of choice.

The gallbladder along with the cystic
duct, vein and artery are ligated.
 Medical Management.
• If stones are present in the
common bile duct, an
• endoscopic sphincterotomy
• must be performed to remove
them BEFORE a
cholecystectomy is done.

• A number of various
instruments are inserted
through the endoscope in
order to "cut" or stretch the
sphincter.
• Once this is done, additional
instruments are passed that
enable the removal of stones
and the stretching of
narrowed regions of the
ducts.
• Drains (stents) can also be
used to prevent a narrowed
area from rapidly returning to
its previously narrowed state.
 Will you survive?

• Prognosis is usually excellent with prompt treatment.

• Laparoscopic surgery has decreased the number of

complications.

• Prognosis is NOT favorable for those who

develop pancreatitis. 
I’ll leave you with these. 

Eww!
.
QUESTIONS

LIVER DISEASE
Universitatea Titu Maiorescu
 PATHOLOGY OF THE

PANCREAS
1
 II. Detailed Anatomy

A. Landmark structures
1. Splenic Artery:
a. Branch of celiac
trunk
b. passes right to
left
c. Course is along
upper margin of
body and tail
 Arterial Supply to Pancreas

Proper Hepatic
Artery

Common
Hepatic Artery
Superior
Mesenteric
Artery
Detailed Anatomy continued
. Head of Pancreas
…

. Head , Body and Tail of Pancreas

1. Important clinically because:
a. Numerous ducts and vessels traverse it
b. Carcinoma usually located here
Duct of Wirsung (Main pancreatic duct)
 DISEASES OF THE
PANCREAS
• Congenital anomalies:
– Agenesis, hypoplasia, ectopia, duct anomalies
• Exocrine pancreas:
– Cystic fibrosis
– Acute pancreatitis
– Chronic pancreatitis
– Carcinoma of the pancreas
• Endocrine pancreas:
– Diabetes mellitus
– Islet cell tumors
 DISEASES OF THE EXOCRINE PANCREAS
ACUTE PANCREATITIS
• Inflammation of the pancreas, which is almost always
associated with acinar cell injury
• A clinical & histologic spectrum of severity & duration
• Etiologic factors:
– 1) Metabolic: alcohol, hyperlipoproteinemia,
hypercalcemia, drugs (e.g. thiazides), genetic
– 2) Mechanical: gallstones, traumatic & perioperative
injury
– 3) Vascular: shock, atheroembolism, polyarteritis
nodosa
– 4) Infections: Mumps, Coxsackie virus, Mycoplasma
– 5) Idiopathic : 10-20% ; ? Genetic basis
 DISEASES OF THE EXOCRINE PANCREAS
ACUTE PANCREATITIS
• Pathology:
– 4 basic alterations:
• 1) Proteolytic destruction of pancreatic substance
• 2) Necrosis of blood vessels & interstitial hemorrhage
• 3) Fat necrosis by lipolytic enzymes
• 4) Associated acute inflammatory reaction
– Pathologic lesions:
• a. Acute pancreatic necrosis
• b. Acute hemorrhagic pancreatitis
• c. Suppurative peritonitis
• d. Pancreatic pseudocysts
 DISEASES OF THE EXOCRINE PANCREAS
ACUTE PANCREATITIS
• Pathogenesis:
– Autodigestion of pancreatic tissue by inappropriately
activated pancreatic enzymes
– Trypsin has a major role:
• a. Activates other proenzymes (proelastase ,prophospholipase )
• b. Converts prekallikrein to kallikrein (Kinin system)
• c. Hageman factor is activated
– Mechanisms of pancreatic enzyme activation:
• 1) Pancreatic duct obstruction
• 2) Primary acinar cell injury
• 3) Defective intracellular transport of proenzymes within acinar cells
 DISEASES OF THE EXOCRINE PANCREAS
ACUTE PANCREATITIS
• Clinical features:
– Abdominal pain is the cardinal manifestation: epigastric, radiating
to back, variable in severity
– Shock: due to pancreatic hemorrhage & release of vasodilatory
agents (BK & PGs)
• Lab:  serum amylase and lipase;  Ca;
 bilirubin,  glucose & glycosuria
• CT scan: inflammation, pseudocysts
• Px: severe cases have high mortality rate (20-40%)
• Death due to: 1) shock, 2) secondary abdominal
sepsis, 3) adult respiratory distress syndrome
 DISEASES OF THE EXOCRINE PANCREAS
CHRONIC PANCREATITIS
• Repeated bouts of mild to moderate pancreatic
inflammation, with continued loss of pancreatic
parenchyma & replacement by fibrous tissue
• Distinction from acute pancreatitis may be
difficult; distinction is made if there is evidence of
previous attacks
• Middle-aged men, mostly in alcoholics but may
due to biliary tract disease, hyperlipoproteinemia
& hypercalcemia; no apparent cause in 50% of
cases
• Pathogenesis:
– Protein hypersecretion from acinar cells
– Precipitation of proteins forming ductal plugs
– Plugs enlarge forming laminar aggregates
 DISEASES OF THE EXOCRINE PANCREAS
CHRONIC PANCREATITIS
• Pathology:
– Hard organ with dilated ducts & calcified concretions
– Fibrosis, chronic inflammatory cells, obstruction of
ducts by protein plugs
– Extensive atrophy of exocrine glands
– Pseudocysts
• Clinical features:
– Repeated attacks of abdominal pain or may be silent
• Dx: clinical suspicion, lab & CT
• Px: chronic disabling disease due to its major
complications: pancreatic insufficiency & diabetes
mellitus
 …

G. Pancreatic Tumors

1. Malignant tumors usually arise

as adenocarcinomas
2. In head of Pancreas: Sx
a. Painless jaundice
b. Anorexia
 Pancreatic Tumors, In head, continued …

c. Nausea
d. Weight loss
e. Increased plasma amylase
f. Increased alkaline phosphatase
g. May involve compression of
pancreatic duct, CBD
 Pancreatic Tumors in the Head

• Tumors in the head

may compress
biliary ducts or
pancreatic ducts
 Pancreatic tumors, continued …

3. In Body of Pancreas: Sx
a. Gnawing pain radiating to back
b. Pain increases after eating or
lying down
c. Weight loss, anorexia
d. Large tumor may compress
IVC, portal vein
 Pancreatic tumors,
continued …

4. In Tail of
Pancreas: Sx
a. Often silent until
local metastasis occurs
b. May metastasize to:
1. para-aortic lymph
nodes
2. spleen
 Pancreatic tumors, continued …

5. Identified by organ enlargement,

subtle echo changes, irregular outline
6. Metastases to stomach, liver & lungs
are common
7. Often causes dilation of ducts
 Pancreatic Disorders, continued …

H. Fibrocystic Disease
1. Result of cystic fibrosis
2. Diagnosed by methods other than
ultrasound
 Pancreatic Disorders, continued …

I. Pancreaticolithiasis
1. Characteristic stone echoes in pancreatic
duct
2. May see atrophied pancreatic parenchyma
3. Associated with chronic alcoholic
pancreatitis
4. Contours of body, tail show irregularities
 Pancreatolithiasis, continued …

5. Incidence slightly higher in head

6. Associated with occult pancreatic
carcinoma
a. Mass < 2mm diameter
b. Seen with dilation of pancreatic
duct or CBD
FUNCTION/DYSFUNCTION OF
ENDOCRINE PANCREAS

Diabetes

344
345
 Endocrine Function :
Cells of the Islet of Langerhans
synthesize and release hormones into
the circulation.
Hormones travel through the bloodstream
to target tissues (especially liver and
muscle)
At the target cells, hormones bind specific
receptors and cause cell changes that
control metabolism
346
347
Pancreatic endocrine cells regulate
carbohydrate, fat, protein metabolism:

– Alpha cells – secrete the hormone

glucagon
– Beta cells – secrete the hormones
insulin and amylin
– Delta cells – secrete the hormones
gastrin and
somatostatin
– F cells - secrete hormone pancreatic
polypeptide 348
 Beta Cells

Synthesize pre-proinsulin, a protein

This is cleaved by enzymes →proinsulin,
then cleaved again → insulin

Insulin is the biologically active hormone

that is released into the bloodstream

349
 Insulin secretion is controlled
through several mechanisms:
• Chemically – high levels of glucose and amino acids
in the blood
• Hormonally – beta cells are sensitive to several
hormones that may inhibit or cause insulin secretion
• Neurally – stimulation of the parasympathetic
nervous system causes insulin to be secreted.

350
Insulin secretion is decreased by:
• Decreased blood glucose
concentration
• Increased blood insulin
concentration
• Sympathetic stimulation

351
 Insulin
• Transported through the blood to target tissues where
it binds to specific receptors
• The binding of insulin to target cells:
– Acts as a biochemical signal to the inside of the cell
• Overall, cell metabolism is stimulated
• There is increased glucose uptake into the cell
• Regulation of glucose breakdown within the cell
• Regulation of protein and lipid breakdown within
the cell

352
 Disorder - Diabetes mellitus

• The single most common endocrine disorder – group

of glucose intolerance disorders
• Incidence is estimated at 1-2% of the North American
population
• Many of these cases are undiagnosed

353
 Diabetes mellitus

Historically - distinguished by weight

loss, excessive urination, thirst, hunger

Excessive urination = polyuria

Excessive thirst = polydipsia
Excessive hunger = polyphagia

Modern characterization is by
hyperglycemia and other metabolic
disorders
354
 Modern classifications (Table17.7)
Type 1 or IDDM - Insulin Dependent Diabetes
Mellitus

Type 2 or
NIDDM - Non-Insulin Dependent Diabetes
Mellitus

Other Types of Diabetes Mellitus

GDM - Gestational Diabetes Mellitus

355
 Clinical Manifestations:
Glucose in urine- Because when insulin is not present,
glucose is not taken up out of the blood at the target
cells.

So blood glucose is very highly increased → increased

glucose filtered and excreted in the urine (exceeds
transport maximum)

356
 Clinical Manifestations:
Weight loss - Patient eats, but nutrients are not taken up
by the cells and/or are not metabolized properly

Osmotic diuresis results in fluid loss

Loss of body tissue by metabolism of fats and proteins

357
 Polyuria, polydipsia, pholyphagia
Ketoacidosis
Fats and proteins are metabolized
excessively, and byproducts known as
ketone bodies are produced. These are
released to the bloodstream and cause:
Decreased pH (so increased acidity)
Compensations for metabolic
acidosis
Acetone given off in breath

358
 Treatment
1. Administer insulin
May be of animal or human origin
Cannot be given orally
Patient must monitor their blood
glucose concentration and
administer insulin with the correct
timing

359
 2. Control diet
Carbohydrates should make up
about 55-60% of patient’s total
calories
Fats should make up <30% of
patient’s total calories
Proteins should make up about 15-
20% of patient’s total calories

360
 3. Monitor exercise
Remember: muscles are a target tissue of
insulin, and metabolize much glucose for
energy

Sometimes exercise →irregular blood

glucose levels So diabetic patients should
be monitored when they are exercising

361
 Other:
Pancreatic transplant – so far not
successful
Experimental therapies – not as
successful as hoped

362
 Type 2 or NIDDM

More common than IDDM, often

undiagnosed
It has a slow onset
Most common in those > 40 years,
though children are being diagnosed
more regularly
May be genetic
Obesity is the greatest risk factor for
this disease
And is related to increased incidence
in children 363
NIDDM → insulin resistance in target cells
See decreased β cell responsiveness →
Decreased insulin secreted by β cells
Also abnormal amount of glucagon
secreted

364
 These effects may be due to:
1.Abnormally functioning β cells
2. Decreased β cell mass,
or a combination of the two
3. Target cell resistance to insulin
Due to:
Decreased number of insulin receptors
Postreceptor events may be responsible
Cells “burn out” and become insensitive

365
 Clinical manifestations
Overweight, hyperlipidemia common
(but these are precursors, not
symptoms)
Recurrent infections
Visual changes, paresthesias, fatigue

366
 Treatment
1. Weight loss
2. Appropriate diet (see IDDM above)
3. Sulfonyl ureas
stimulate β cells to increase insulin
secretion
Works only when β cells are still
functioning
→ An enhancement of insulin’s effect
at target cells
4. Exercise - promotes weight loss

367
Complications of Diabetes Mellitus
Acute:
Hypoglycemia = rapid decrease in plasma
glucose = insulin shock
Neurogenic responses – probably due
to decreased glucose to
hypothalamus.
Symptoms include:
Tachycardia, palpitations, tremor,
pallor
Headache, dizziness, confusion
Visual changes

368
 Treatment :
provide glucose (I.V. or subcutaneous if
unconscious)

Observe for relapse

369
Ketoacidosis – involves a precipitating event:
Increased hormones released w/ trauma 
increased glucose produced by the body’s cells
This “antagonizes” the effects of any glucose
present 
Increased ketones in blood
Acid/base imbalance
Polyuria, dehydration
Electrolyte disturbances
Hyperventilation (Kussmaul – deep,
gasping)
CNS effects
Acetone on breath
370
 Treatment:
- low dose insulin

Also, administer fluids, electrolytes

371
 Chronic Complications of DM
Neuropathies = nerve dysfunctions →
slowing of nerve conduction. In these
patients, see:
Degeneration of neurons
→Sensory, motor deficits →Muscle
atrophy, paresthesias
Depression
G.I. problems, as muscle motility
decreased
Sexual dysfunction

372
 Microvascular disease – chronic
diabetes w/ improper glucose
metabolism → thickening of the
basement membrane of capillaries,
particularly in the eye and the kidney.
As the capillary changes in this way, →
Decreased tissue perfusion
So ischemia → hypoxia

373
In the eye – the retina is metabolically quite
active, so hypoxia here is a big problem
So see:
Retinal ischemia→
Formation of microaneurisms, hemorrhage,
tissue infarct, formation of new vessels,
retinal detachment

374
375
In the kidney – diabetes is the most
common cause of end-stage renal
disease
Injured glomeruli
(glomerulosclerosis)
In these patients, see:
Proteinuria (protein is excreted into
the urine) → Generalized body
edema, hypertension

376
Macrovascular disease – atherosclerosis
Plaque formation increases→
Increased risk of coronary artery
disease, so increased risk of
myocardial infarction
Increased risk of congestive heart
failure
Stroke
Peripheral vascular disease
why diabetic patients face
problems with their lower legs and
feet
Increased risk of infections377
Endoscopic Stenting for
Pancreatic Diseases

1
Pancreatic Stents
• Shape
– Geenen - curve,
multiple side
holes/distal flaps
– Sherman - straight,
multiple side holes,
proximal flap/distal
pigtail
– Modified Cotton-Leung
stent – S-shaped with
distal flap
• Size 3,5,7 or 10 Fr
• Length 3,5,7,9,12 cm
Pancreatic Stents – Design and
Application
Optimal design of stents Common Indications
• Size (small) • Acute pancreatitis
• Material (soft) – Drainage to prevent
– Less irritation to ductal post ERCP pancreatitis
epithelium – Assist endoscopic
therapy
• Migrate out • Papillotomy
spontaneously • Leaks
• Malignancy
– Drainage to relief pain
• Chronic pancreatitis
– Adjuvant therapy for
stone and stricture
 Technique of Pancreatic Stent
Placement
• Deep cannulation
with guide wire
across papilla or
stricture
• + Pancreatic
papillotomy
• Stent inserted
over wire and
positioned with
pusher
 Post-ERCP Pancreatitis
Incidence Possible causes
• Most common • Acinarization –
complication of overfilling
ERCP • Hyperosmolarity /
• Incidence 5-10%, contrast allergy
1% severe, 0.1% • Trauma – guide wire
fatal • Coagulation injury
• Significant medical/ • Impaired drainage
social/economic and from pancreas
liability problem
• Bacterial
contamination
• Bile contamination
 Mechanism of Post ERCP
Pancreatitis
• Papillary manipulation results in edema and sphincter
spasm obstructing PD flow, leading to intracellular
activation of enzymes

• Improving drainage with PD stent may prevent post

ERCP pancreatitis
 PD Stenting Prevents PEP in
SOD Pts
• 80 Pts with pancreatic SOD after biliary EST were
randomized to PD stent or no stent
• Post ERCP pancreatitis occurred in
– 10/39 (26%) with “No stent”
– 1/41 (2.4%) with “Stent”
• 2 Pts (7%) developed PEP after stent removal

Tarnasky
Gastroenterol 1998
 PD Stenting for High Risk Patients
• 76 high-risk pts: SOM or difficult cannulation + EST were
randomized
• Post ERCP pancreatitis occurred in
– 10/36 (28%) with “No stent” (5 mild, 2 moderate, 3 severe)
– 2/38 (5%) with “Stent” (mild pancreatitis)
• PD cannulation failed in 2/40 pts (5%)

Fazel GIE 2003

 Is PD Stent Necessary for Every
ERCP?
Probably NOT
• Increased time and difficulty
• Increased risk
• Increased cost
• Risk of ductal changes from stent irritation
• Need follow–up to insure stent migration
• May need 2nd procedure for stent removal
 Who Will Benefit from PD Stenting?

Patient Factors Technical Factors

• Suspected SOD • Difficult cannulation
• Young female • Pre-cut sphincterotomy
• Prior post-ERCP
pancreatitis • Pancreatic
• Normal serum bilirubin sphincterotomy
• Ampullectomy
• Balloon
sphincteroplasty
 Potential Risks of Pancreatic
Stenting
Risks Dilemma
• Failed stent placement • To consider PD stent
• Proximal tip of stent placement in a “high-
damages PD risk” patient is a
• Stent occlusion serious decision
causing pancreatitis • If successful, risk of
• Chronic ductal PEP is reduced.
changes • However, failed
• Inward stent migration attempt INCREASES
the risks
Balloon Sphincteroplasty & Double
Stents
• Double wires
• Balloon
sphincteroplas
ty
• Double stents
for drainage
• PD stent for
prophylactic
drainage
 Pancreas Divisum
Minor Papillotomy with PD Stenting
Chronic Pancreatitis - Stone &
Stricture
EndoTherapy for Chronic
Pancreatitis
• Less invasive than
surgery
• Results comparable to
surgery
• Surgery is still possible
after failed
endotherapy
• ? Predicts outcome
after surgery
 Dilation/Stenting of Pancreatic
Stricture
• Guide wire (hydrophilic)
across stricture
• Dilators
– Graded dilators
– Pneumatic balloons (4-6
mm)
• Short-term pancreatic
stenting to insure drainage
Dilation of Tight PD Stricture with
Soehendra Stent Retriever
Dilation of Pancreatic Stricture
via Minor Papilla
 Pancreatic Stone Extraction
• Pancreatic sphincterotomy
• .035” guide wire
• Dilation of orifice/stricture
• Stone extraction with wire
basket (e.g. 22Q)
• ? Mechanical lithotripsy
– limitations
• PD stent for drainage
• ESWL to fragment large
(calcified) stone
 Summary

• Successful pancreatic stenting and drainage

prevents post ERCP pancreatitis
• Pancreatic stenting is a useful adjunct for assisted
papillotomy
• Pancreatic stenting provides drainage in patients
undergoing ESWL for stone obstruction
• Stenting helps to improve stricture post dilation and
provides short term pancreatic drainage
Pancreatic Neoplasm

1
 Types of Pancreatic Neoplasms

• Broadly speaking, there are three basic types:

• Ductal adenocarcinoma >90% of pancreatic
cancers with a 4% 5-year survival (worst of any
cancer)
• Neuroendocrine tumors aka islet-cell tumors, rare
• Cystic neoplasms account for <1% of pancreatic
cancers
 Clinical Scenario #1 –
Adenocarcinoma of the
Pancreas
• What are typical symptoms of pancreatic CA?
– Abdominal pain->pain can suggest neural plexus,
tail lesion, unresectability, poor prognosis
– Anorexia
– Weight loss
– Jaundice
– Pruritis ->biliary obstruction
– Steatorrhea->pancreatic duct obstruction
 Risk Factors for Pancreatic
Cancer?
• Firmly linked to cigarette smoking
• No clear dietary factors
• Increased BMI associated with increased risk
• Occupational exposures to amines (chemistry,
hairdressing, rubber work) associated with increased
risk
 Adenocarcinoma of the
•
Pancreas: CT scan
CT can confirm pancreatic cancer with a
sensitivity of 85-95% (sensitivity is limited by
smaller tumor size)
• Other than the presence of a pancreatic
mass, what else can you determine from CT
scan?
– PRESENCE of METASTASES (along with CXR)
– RESECTABILITY
 Adenocarcinoma of the
Pancreas: CT scan
• What makes a pancreatic mass likely resectable?
– No evidence of extrapancreatic disease
– Evidence of nonobstructive superior mesenteric-portal vein
confluence
– No evidence of direct tumor extension to the celiac axis and
SMA
– EUS, laparoscopy are universally regarded as useful
adjuncts to CT, not as essential however
 Adenocarcinoma of the
Pancreas: CT scan
• “Borderline” Resectable lesions include:
• SMV occlusion of a short segment (open vein
proximally and distally)
• Body and tail lesions with + celiac, para-aortic nodes
in the vicity
• Tumors briefly involving the IVC may be borderline
Adenocarcinoma of the Pancreas: CT scan
 Pancreatic Cancer: Endoscopic
Adjuncts
• ERCP can be utilized to:
– detecting small tumors not visualized on CT
(irregular solitary duct stenoses >1cm long, abrupt
cutoff of main pancreatic duct, or panc and bile
duct obstruction)
– palliating biliary obstruction
– brush cytology of the pancreatic duct has fair
sensitivity (70%) but excellent specificity
• EUS can be utilized to:
– aid in diagnosis and characterization of lesion
– obtain tissue biopsy; may be associated with lower
 Pancreatic Cancer: Serum Markers

• Is there a role for serum markers? If so, what?

– CA 19-9 is a sialylated Lewis A blood group
antigen commonly expressed and shed in
pancreatic and hepatobiliary disease, not tumor
specific
– This antigen, when significantly increased, can
assist in differentiating between pancreatic
adenocarcinoma and inflammatory pancreatic
disease
– decrease in serial CA 19-9 correlates with survival
of pancreatic patients after surgery or
chemotherapy
 Pancreatic Cancer: Neoadjuvant
Therapy
• This 70yo female has “borderline” resectable
features, has been stented to answer obstructive
jaundice via ERCP with EUS demonstrating a
positive adenocarcinoma
• Is there any role for neoadjuvant therapy for this
patient? If so, what sort of regimen and with what
objectives?
 Insulinoma

• Whipple’s Triad:
• symptoms of hypoglycemia during fasting or exercise
• serum glucose <45mg/dL during symptoms
• relief of symptoms with administration of glucose
• Definitive test is 72-hour fast with
measurement of insulin and glucose
• 75% of patients develop symptoms and GB<40 within 24
hours
• insulin:glucose ratio >0.4 is indicative of insulinoma
• Elevated c-peptide proinsulin levels are
confirmatory along with screening for
antiinsulin antibodies, sulfonylureas
 How are insulinomas localized?

• Non-invasive preoperative imaging studies fail to

localize 30-35% of insulinomas
• CT/MRI, etc. generally reserved by most endocrine
surgeons to r/o hepatic metastases
• Intraoperative U/S and palpation are the GOLD
standard for finding an insulinoma, 96-100%
sensitivity
 What is proper operation for
•
insulinoma?
Generally wide Kocher maneuver, superior and inferior
pancreatic border mobilization, medial reflection of the
spleen
• Bimanual palpation with U/S
• Enucleation of the lesion
• Secretin can assist in identifying pancreatic duct leak
after enucleation completed
• What about lesion in pancreatic head?
• Need to monitor glucose levels q15 minutes until lesion
out
Thank you
 Acute Cholecystitis

• Most common major

complication of
gallstones
– 90% associated with
obstruction of the
neck
• Gallbladder is
enlarged, tense, &
inflamed
• Persistent rather
mild RUQ pain to
very severe pain
Universitatea Titu Maiorescu
Bucuresti

GASTROENTEROLOGY

Liver Disorders and Biliary Tract Disease

Lecture III

Prof Univ Dr Ion C. Țintoiu

415
Gallbladder Disorders
 CHOLELITHIASIS/CHOLECYSTITIS

Post-operative nursing interventions

1. Monitor for surgical complications
2. Post-operative position after recovery from
anesthesia- LOW FOWLER’s
3. Encourage early ambulation
4. Administer medication before coughing and deep breathing
exercises
5. Advise client to splint the abdomen to prevent
discomfort during coughing
6. Administer analgesics, antiemetics, antacids
7. Care of the biliary drainageor T-tube drainage
8. Fat restriction is only limited to 4-6 weeks. Normal
diet is resumed
PATHOLOGY OF THE

PANCREAS
1
 II. Detailed Anatomy

A. Landmark structures
1. Splenic Artery:
a. Branch of celiac
trunk
b. passes right to
left
c. Course is along
upper margin of
body and tail
 Arterial Supply to Pancreas

Proper Hepatic
Artery

Common
Hepatic Artery
Superior
Mesenteric
Artery
Detailed Anatomy continued
. Head of Pancreas
…

. Head , Body and Tail of Pancreas

1. Important clinically because:
a. Numerous ducts and vessels traverse it
b. Carcinoma usually located here
Duct of Wirsung (Main pancreatic duct)
 DISEASES OF THE
PANCREAS
• Congenital anomalies:
– Agenesis, hypoplasia, ectopia, duct
anomalies
• Exocrine pancreas:
– Cystic fibrosis
– Acute pancreatitis
– Chronic pancreatitis
– Carcinoma of the pancreas
• Endocrine pancreas:
– Diabetes mellitus
– Islet cell tumors
 IV. Pancreatic Disorders
A. Pancreatitis: diagnosis depends on
clinical evidence
1. Usually secondary to biliary tract
disease
2. Surgery of biliary tract or stomach
alcoholism are other causes
 DISEASES OF THE EXOCRINE PANCREAS
ACUTE PANCREATITIS
• Inflammation of the pancreas, which is almost always
associated with acinar cell injury
• A clinical & histologic spectrum of severity & duration
• Etiologic factors:
– 1) Metabolic: alcohol, hyperlipoproteinemia,
hypercalcemia, drugs (e.g. thiazides), genetic
– 2) Mechanical: gallstones, traumatic & perioperative
injury
– 3) Vascular: shock, atheroembolism, polyarteritis
nodosa
– 4) Infections: Mumps, Coxsackie virus, Mycoplasma
– 5) Idiopathic : 10-20% ; ? Genetic basis
 DISEASES OF THE EXOCRINE PANCREAS
ACUTE PANCREATITIS
• Pathology:
– 4 basic alterations:
• 1) Proteolytic destruction of pancreatic substance
• 2) Necrosis of blood vessels & interstitial
hemorrhage
• 3) Fat necrosis by lipolytic enzymes
• 4) Associated acute inflammatory reaction
– Pathologic lesions:
• a. Acute pancreatic necrosis
• b. Acute hemorrhagic pancreatitis
• c. Suppurative peritonitis
• d. Pancreatic pseudocysts
 DISEASES OF THE EXOCRINE PANCREAS
ACUTE PANCREATITIS
• Pathogenesis:
– Autodigestion of pancreatic tissue by inappropriately
activated pancreatic enzymes
– Trypsin has a major role:
• a. Activates other proenzymes (proelastase
,prophospholipase )
• b. Converts prekallikrein to kallikrein (Kinin system)
• c. Hageman factor is activated
– Mechanisms of pancreatic enzyme activation:
• 1) Pancreatic duct obstruction
• 2) Primary acinar cell injury
• 3) Defective intracellular transport of proenzymes
within acinar cells
 DISEASES OF THE EXOCRINE PANCREAS
ACUTE PANCREATITIS
• Clinical features:
– Abdominal pain is the cardinal manifestation:
epigastric, radiating to back, variable in severity
– Shock: due to pancreatic hemorrhage & release
of vasodilatory agents (BK & PGs)
• Lab:  serum amylase and lipase;  Ca;
 bilirubin,  glucose & glycosuria
• CT scan: inflammation, pseudocysts
• Px: severe cases have high mortality rate (20-40%)
• Death due to: 1) shock, 2) secondary abdominal
sepsis, 3) adult respiratory distress syndrome
 DISEASES OF THE EXOCRINE PANCREAS
CHRONIC PANCREATITIS
• Repeated bouts of mild to moderate pancreatic
inflammation, with continued loss of pancreatic
parenchyma & replacement by fibrous tissue
• Distinction from acute pancreatitis may be
difficult; distinction is made if there is evidence of
previous attacks
• Middle-aged men, mostly in alcoholics but may
due to biliary tract disease, hyperlipoproteinemia
& hypercalcemia; no apparent cause in 50% of
cases
• Pathogenesis:
– Protein hypersecretion from acinar cells
– Precipitation of proteins forming ductal plugs
– Plugs enlarge forming laminar aggregates
 DISEASES OF THE EXOCRINE PANCREAS
CHRONIC PANCREATITIS
• Pathology:
– Hard organ with dilated ducts & calcified concretions
– Fibrosis, chronic inflammatory cells, obstruction of
ducts by protein plugs
– Extensive atrophy of exocrine glands
– Pseudocysts
• Clinical features:
– Repeated attacks of abdominal pain or may be silent
• Dx: clinical suspicion, lab & CT
• Px: chronic disabling disease due to its major
complications: pancreatic insufficiency & diabetes
mellitus
FUNCTION/DYSFUNCTION OF
ENDOCRINE PANCREAS

Diabetes

436
437
 Who Will Benefit from PD Stenting?

Patient Factors Technical Factors

• Suspected SOD • Difficult cannulation
• Young female • Pre-cut sphincterotomy
• Prior post-ERCP
pancreatitis • Pancreatic
• Normal serum bilirubin sphincterotomy
• Ampullectomy
• Balloon
sphincteroplasty
 Potential Risks of Pancreatic
Stenting
Risks Dilemma
• Failed stent placement • To consider PD stent
• Proximal tip of stent placement in a “high-
damages PD risk” patient is a
• Stent occlusion serious decision
causing pancreatitis • If successful, risk of
• Chronic ductal PEP is reduced.
changes • However, failed
• Inward stent migration attempt INCREASES
the risks
Balloon Sphincteroplasty & Double
Stents
• Double wires
• Balloon
sphincteroplas
ty
• Double stents
for drainage
• PD stent for
prophylactic
drainage
 Pancreas Divisum
Minor Papillotomy with PD Stenting
Chronic Pancreatitis - Stone &
Stricture
EndoTherapy for Chronic
Pancreatitis
• Less invasive than
surgery
• Results comparable to
surgery
• Surgery is still possible
after failed
endotherapy
• ? Predicts outcome
after surgery
 Dilation/Stenting of Pancreatic
Stricture
• Guide wire (hydrophilic)
across stricture
• Dilators
– Graded dilators
– Pneumatic balloons (4-6
mm)
• Short-term pancreatic
stenting to insure drainage
Radiofrequency Ablation