You are on page 1of 215

LIVER

LABORATORY TESTS IN LIVER DISEASES


1. BILIRUBIN (Normal value (N. V)= 0.3-1.0 mg %)
causes of > bilirubin levels:
-increased production (hemolysis)
-decreased clearance: colestazis(acute hepatitis,
chronic hepatitis,liver cirhosis)biliary obstruction
(choledocolitiazis)inherited diseases (Gilbert d.,
Dubin-Johnson d)

2. TRANSAMNINASES
ALANINE TRANSFERASE (A. L. T.) N. V.=8-20 u/l
ASPARTATE TRANSFERASE (A. S. T.) N. V.-10-30 u/l
causes of >transaminase
-acute viral or alcoholic hepatitis
A. L.T. >200 U/L
-chronic hepatitis or liver
cirrhosis
3. PROTHROMBIN TIME ( P. T.) (N. V.=18-22"); Prothrombin index
>90%)
(is influenced by the level of prothrombin, cloting factors: V, VII,
IX, fibrinogen)
-causes of < P. T.
-liver cirrhosis
-vitamine K deficiency
4. PROTEIN ELECTROPHORESIS
-serum albumine (35-50 gr/l) decresed in liver cirrhosis
-serum globulines (ă=8-16 gr/l) incresed in chronic hepatitis,
liver cirrhosis
5.TESTS FOR VIRAL INFECTION
6. HEMATOLOLOGY
7. LIVER BIOPSY
8. IMAGING TEHNIQUE (ULTRASONOGRAPHY, COMPUTER
TOMOGRAPHY, SCINTIGRAPHY, ARTERIOGRAPHY
Imaging techniques

Ultrasonography
»
Imaging techniques

 CT

 MRI

 scintigraphy (Tc99).
» Laparoscopy

» Liver biopsy/fine needle aspiration


Imaging techniques

RADIOLOGY
– Hepatic arteriography

– Splenoportography

– ERCP
 other
» Endoscopy

» paracentesis
Physical exam

Telangiectasia / spider naevi


Physical exam
 Skin
– jaundice
– hipopilosity
– ginecomastia
– Xantelasmas, xantomas
 Skin
– Palmar eritema
– colateral venous circulasion
– purpure
- Spider naevi
Physical exam

– White nails
– Red tonque
– Dupuytren;
– hipocratic fingers
– Hepatic edema
Physical exam

Nutrition
Physical exam
 INSPECTION
Physical exam
 PALPATION
Physical exam

 LIVER PALPATION
Physical exam

PERCUTION
-UPPER MARGIN
- V ic space - mid axilar line
-VII ic space- anterior axilar line
-X ic – space scapular line.
Physical exam
 ASCULTATION – hepatic artery murmer in
liver cancer
Hepatomegaly
 Def lower margin mid clavicular line :
costal rib
upper margin : percusion 5th
intercostal space mdi clavicular line; 8th ic
space mid axila
Hepatomegaly
 Inflammation – acute hepatitis, chronic hepatitis
autoimune hepatitis, alcoholic liver disease, tuberculosis,
liver abces, liver cirrhosis,
 Metabolic disorders – steatosis,
 Biliarry diseases primary billiary cholangitis, biliarry
obstruction
 Vascular disorders heart failure, chronic pericarditis
 Tumors, liver metastasis
 Congenital disorders hemocromatosis, Wilson disease,
glicogenosis
 Hematological disorders chornic leukemia, lymphomas
Hepatomegaly
 Liver cirrhosis; not painful, high
consistency, nodular
 Liver tumors; painful, irregular
 Heart failure: painful, regular, mobile,
hepato-jugular reflex
JAUNDICE
DEFINITION

 clinical evident- bilirub > 2,5 mg%,


 Sub jaundice = bilirubin > 1,8 mg%,
“scleral jaundice”
 simptom not disease
PREHEPATIC JAUNDICE
HEPATOCELULAR JAUNDICE
POSTHEPATIC JAUNDICE
Jaundice type CAUSES
hemolisis
Prehepatic Gilbert syndrome
Crigler-Najjar sdr

hepatitis A, B, C, E
Autoimune hepatitis
Alcohol (toxic)
Hepatic cirrhosis
Wilson D
Dubin-Johnson sdr
Rotor sdr
Primary biliary cirrhosis
toxic
Posthepatic gallstones
Cancer of head pancreas
PREHEPATIC JAUNDICE

Simptoms LAB
•Unconjugated bilirubin
• No itching
•stercobilinogen 
•urobilinogenurie
• Hipercromic feces
•Normal liver tests
• normal hipercromic urines
•Elevated reticule cell count,
• palor
•Normocrom normocitic anemia,
• splenomegaly.
HEPATOCELULAR JAUNDICE

Simptoms Lab
• variable jaundice • Unconjugated and conjugated Bilirubin
• ± signs of liver disease • ± citolysis
• • ± Hipocolesterolemia, hipoalbuminemia ,
hipergamaglobulinemia
POSTHEPATIC JAUNDICE
Lab
 Conjugated hyperbilirubine,
 hipercolesterolemia,
 Alcaline Phosphatase , GGT
 Normal liver tests at the bigining
Tablou clinic  P index  -corected with K1
 itching
 jaundice
 acolic feces
 hipercromic urines
!!!
 diareea (steatoree);
US
 Liposoluble vitamines malabsortions
MRI
ERCP
ASCITES
BACKGROUND
 The word ascites is of Greek origin (askos)
and means bag or sac.
 Ascites describes the condition of
pathologic fluid accumulation within the
abdominal cavity.
 Healthy men have little or no
intraperitoneal fluid, but women may
normally have as much as 20 mL
depending on the phase of the menstrual
cycle.
PATHOPHYSIOLOGY
The pathogenesis of ascites in patients with cirrhosis
involves several mechanisms.
Portal hypertension results in decreased perfusion of
hepatocytes with portal blood. This leads to increased
reabsorption of sodium and water by the kidney resulting in
increased plasma volume and increased portal flow.
Portal inflow increases but resistance within the liver is relatively
fixed secondary to underlying hepatic fibrosis. This too results in
portal hypertension.
Hepatic fibrosis also results in sinusoidal hypertension altering starling
forces and driving fluid into the Space of Disse. Recall that the Space
of Disse is a perisinusoidal space into which microvilli of the
hepatocytes protrude.
 Patients with cirrhosis are often hypoalbuminemic and
hypoalbuminemia also works to promote this
movement of fluid into the Space of Disse. This fluid
is removed by hepatic lymphatics.
PATHOPHYSIOLOGY
 Hepatic lymph flow increases dramatically in
response to tissue edema.
Normal thoracic duct lymph flow is 800-1000 cc per day. In
patients with cirrhosis, hepatic lymph flow may approach 20
liters per day exceeding the capacity of the thoracic duct and
percolate from the liver capsule into the peritoneal cavity.
 Also as a result of decreased perfusion of
hepatocytes, splanchnic vasodilation occurs.
 This triggers the release of sympathetic
neurotransmitters further activating the renin-
angiotensin-aldosterone axis. This further stimulates
sodium and water retention by the kidney. It is
important to note that renal function in patients with
cirrhosis is disturbed long before ascites forms.
PATHOPHYSIOLOGY
Portal Hypertension
Portosystemic Collaterals
Nitric Oxide Stimulation
7 Direct Reflex
Hyperdynamic State
Underfill Physiology, ↓ SVR

Compensatory Pathways

Overflow Physiology Plasma Volume Expression

Renal Na and Impaired Water Excretion

Lymphatics Overwhelmed
(Hepatic, Planchnic, and Peritoneal)

Ascites
7 Trigger

Portal Hypertension
Hepatorenal Syndrome
Facilitating and
opposing forces in
 Ambulatory patients with an episode of
cirrhotic ascites have a 3-year mortality rate
of 50%. The development of refractory
ascites carries a poor prognosis, with a 1-year
survival rate of less than 50%.
HISTORY
 Most cases of ascites are due to liver disease. Patients often state that their
increasing abdominal girth has been noted for a short period.
 Patients with ascites should be asked about risk factors for liver diseases. These
include the following:
› Alcohol use and duration of use
› Chronic viral hepatitis or jaundice
› Intravenous drug use
› Sexual promiscuity
› Sexual orientation
› Transfusions: Hepatitis C has been linked to transfusions occurring before 1980.
› Tattoos
› Habitation or origination from an area endemic for hepatitis
 Patients with alcoholic liver disease who intermittently cease or reduce alcohol
consumption may experience ascites in a cyclic fashion. When the patient has a
very long history of stable cirrhosis and then develops ascites, the possibility of
superimposed hepatocellular carcinoma should be considered.
 Obesity, hypercholesterolemia, and type 2 diabetes mellitus are now recognized
causes of nonalcoholic steatohepatitis, which can progress to cirrhosis.
 Patients with a history of cancer, especially gastrointestinal cancer, are at risk for
malignant ascites. Malignancy-related ascites is frequently painful, whereas
cirrhotic ascites is usually painless.
 Patients who develop ascites in the setting of known diabetes or nephrotic
syndrome may have nephrotic ascites.
PHYSICAL EXAMINATION
 The physical examination should focus on the signs of portal
hypertension and chronic liver disease.
 Physical findings suggestive of liver disease include jaundice, palmar
erythema, and spider angiomas.
 The liver may be difficult to palpate if a large amount of ascites is
present, but often, the liver is enlarged. The puddle sign indicates that as
little as 120 mL of fluid is present. When peritoneal fluid exceeds 500
mL, ascites may be demonstrated by the presence of shifting dullness or
bulging flanks. A fluid-wave sign is notoriously inaccurate.
 Elevated jugular venous pressure may suggest a cardiac origin of ascites.
A firm nodule in the umbilicus, the so-called Sister Mary Joseph nodule,
is not common but suggests peritoneal carcinomatosis originating from
gastric, pancreatic, or hepatic primary malignancy.
 A pathologic left-sided supraclavicular node (Virchow node) suggests
the presence of upper abdominal malignancy.
 Patients with cardiac disease or nephrotic syndrome may have anasarca.

CAUSES OF ASCITES
 Normal peritoneum
› Portal hypertension (serum-ascites albumin gradient [SAAG]
>1.1 g/dL)
Hepatic congestion, congestive heart failure, constrictive
pericarditis, tricuspid insufficiency, Budd-Chiari syndrome
Liver disease, cirrhosis, alcoholic hepatitis, fulminant hepatic
failure, massive hepatic metastases
› Hypoalbuminemia (SAAG <1.1 g/dL)
Nephrotic syndrome
Protein-losing enteropathy
Severe malnutrition with anasarca
› Miscellaneous conditions (SAAG <1.1 g/dL)
Chylous ascites
Pancreatic ascites
Bile ascites
Nephrogenic ascites
Urine ascites
Ovarian disease
CAUSES OF ASCITES
› Diseased peritoneum (SAAG <1.1 g/dL)
› Infections
Bacterial peritonitis
Tuberculous peritonitis
Fungal peritonitis
HIV-associated peritonitis
› Malignant conditions
Peritoneal carcinomatosis
Primary mesothelioma
Pseudomyxoma peritonei
Hepatocellular carcinoma
› Other rare conditions
Familial Mediterranean fever
Vasculitis
Granulomatous peritonitis
Eosinophilic peritonitis
IN VARIOUS DISEASE STATES
Condition Gross Protein, Serum- Cell Count Other
Appearanc g/L Ascites Red Blood White Blood Tests
e Albumin Cells, Cells, per L
Gradient, >10,000/L
Cirrhosis Straw-colored <25 (95%) g/dL
>1.1 1% <250 (90%)a;
or bile-stained predominantly
mesothelial
Neoplasm Straw-colored, >25 (75%) <1.1 20% >1000 (50%); Cytology, cell
hemorrhagic, variable cell block,
mucinous, or types peritoneal
Tuberculous chylous
Clear, turbid, >25 (50%) <1.1 7% >1000 (70%); biopsy
Peritoneal
peritonitis hemorrhagic, usually >70% biopsy, stain
chylous lymphocytes and culture for
Pyogenic Turbid or If purulent, <1.1 Unusual Predominantly acid-fast
Positive
peritonitis purulent >25 polymorphonu bacilli
Gram's stain,
clear culture
Congestive Straw-colored Variable, 15– >1.1 10% leukocytes
<1000 (90%);
heart failure 53 usually
mesothelial,
Nephrosis Straw-colored <25 (100%) <1.1 Unusual mononuclear
<250; If chylous,
or chylous mesothelial, ether
mononuclear extraction,
Pancreatic Turbid, Variable, often <1.1 Variable, may Variable Increased
Sudan staining
ascites hemorrhagic, >25 be blood- amylase in
(pancreatitis, or chylous stained ascitic fluid
DIFFERENTIAL DIAGNOSES
ASCITIC LIQUID
paracentesis
LABORATORY STUDIES
› Total protein:
› In the past, ascitic fluid has been classified as an exudate if the protein
level is greater than or equal to 2.5 g/dL. However, the accuracy is only
approximately 56% for detecting exudative causes. The total protein
level may provide additional clues when used with the SAAG. An
elevated SAAG and a high protein level are observed in most cases of
ascites due to hepatic congestion. Those patients with malignant ascites
have a low SAAG and a high protein level
› Culture/Gram stain:
› The sensitivity with bedside inoculation of blood culture bottles with
ascites results in 92% detection of bacterial growth in neutrocytic
ascites. Gram stain is only 10% sensitive for helping visualize bacteria
in early-detected spontaneous bacterial peritonitis. Approximately
10,000 bacteria/mL are required for detection by Gram stain; the median
concentration of bacteria in spontaneous bacterial peritonitis is 1
organism/mL.
› Cytology:
› Cytology smear results are reported to be 58-75% sensitive for helping
detect malignant ascites.
IMAGING STUDIES
 Chest and plain abdominal films
› Elevation of the diaphragm, with or without sympathetic
pleural effusions (hepatic hydrothorax), is visible in the
presence of massive ascites. More than 500 mL of fluid
is usually required for ascites to be diagnosed based on
findings from abdominal films.
› Many nonspecific signs indicate ascites, such as diffuse
abdominal haziness, bulging of the flanks, indistinct
psoas margins, poor definition of the intra-abdominal
organs, erect position density increase, separation of
small bowel loops, and centralization of floating gas
containing small bowel.
Abdominal ultrasound
IMAGING STUDIES
 Ultrasound
› Real-time sonography is the easiest and most sensitive
technique for the detection of ascitic fluid.. Free ascites does
not displace organs but typically situates itself between them,
contouring to organ margins and demonstrating acute angles
at the point at which the fluid borders the organ.
› The smallest amounts of fluid tend to collect in the Morison
pouch and around the liver as a sonolucent band. With
massive ascites, the small bowel loops have a characteristic
polycyclic, "lollipop," or arcuate appearance because they
are arrayed on either side of the vertically floating
mesentery.
› Certain sonographic findings suggest that the ascites may be
infected, inflammatory, or malignant...
› Most patients (95%) with carcinomatous peritonitis have a
gallbladder wall that is less than 3 mm thick. The thickening
of the gallbladder is primarily a reflection of cirrhosis and
portal hypertension.
IMAGING STUDIES
 CT scan:
Ascites is demonstrated well on CT scan images. Small amounts
of ascitic fluid localize in the right perihepatic space, the
posterior subhepatic space (Morison pouch), and the Douglas
pouch. A number of CT features suggest neoplasia. Hepatic,
adrenal, splenic, or lymph node lesions associated with masses
arising from the gut, ovary, or pancreas are suggestive of
malignant ascites. Patients with malignant ascites tend to have
proportional fluid collections in the greater and lesser sacs;
whereas, in patients with benign ascites, the fluid is observed
primarily in the greater sac and not in the lesser omental bursae.
PROCEDURES
 Abdominal paracentesis: Abdominal paracentesis is
the most rapid and perhaps the most cost-effective
method of diagnosing the cause of ascites
formation. Therapeutic paracentesis may be
performed for refractory or tense ascites. The
removal of 5 L of fluid is considered large-volume
paracentesis. Total paracentesis, ie, removal of all
ascites (even >20 L), can usually be performed
safely. Recent studies demonstrate that
supplementing 5 g of albumin per each liter over 5
L decreases complications of paracentesis, such as
electrolyte imbalances, and increases in serum
creatinine secondary to large shifts of intravascular
volume.
STAGING
 Ascites may be semiquantified using the
following system:
– Stage 1+ is detectable only after careful
examination.
– Stage 2+ is easily detectable but of relatively
small volume.
– Stage 3+ is obvious ascites but not tense ascites.
– Stage 4+ is tense ascites.
Paracentesis
Introduction

 Paracentesis is a procedure in which a


needle or catheter is inserted into the
peritoneal cavity to obtain ascitic fluid for
diagnostic or therapeutic purposes.
Indications

 Diagnostic tap
– New onset ascites: Evaluate fluid to help determine
etiology, to differentiate transudate versus exudate,
to detect the presence of cancerous cells, or to
address other considerations.
– Suspected spontaneous or secondary bacterial
peritonitis
 Therapeutic tap
– Respiratory distress secondary to ascites
– Abdominal pain or pressure secondary to ascites
Contraindications
Absolute
 Acute abdomen that requires surgery
Relative Severe thrombocytopenia (platelet count <20 X 103/μL),
coagulopathy (international normalized ratio [INR] >2.0), or both
– Patients with an INR greater than 2.0 should receive fresh frozen plasma (FFP) prior
to the procedure. One strategy is to infuse one unit of fresh frozen plasma before the
procedure and then perform the procedure while the second unit is infusing.
– Patients with platelet counts less than 20 X 103/μL should receive an infusion of
platelets prior to performing the procedure.
 In patients without clinical evidence of active bleeding, routine labs such
as prothrombin time (PT), activated partial thromboplastin time (aPTT),
and platelet counts may not be needed prior to the procedure.5 In these
patients, pretreatment with FFP, platelets, or both before the paracentesis is
also probably not needed.
 Pregnancy
 Distended urinary bladder
 Abdominal wall cellulitis
 Distended bowel
 Intra-abdominal adhesions
Treatment and Medication
 Anesthesia
 Local anesthesia is used.
 Equipment
 Disposable paracentesis/thoracentesis kits
 Antiseptic swab sticks
 Fenestrated drape
 Lidocaine 1%, 5-mL ampule
 Syringe, 10 mL
 Injection needles, 22 gauge (ga), 2
 Injection needle, 25 ga
 Scalpel, No. 11 blade
 Eight-French catheter over 18 ga x 7 1/2" needle with 3-way stopcock, self-sealing
valve, and a 5-mL Luer-Lock syringe
 Syringe, 60 mL
 Introducer needle, 20 ga
 Tubing set with roller clamp
 Drainage bag or vacuum container
 Specimen vials or collection bottles, 3
 Gauze, 4 x 4 inch
 Adhesive dressing
Positioning
 The two recommended areas of
abdominal wall entry for paracentesis
are as follows (see photo):
– Two centimeters below the umbilicus in
the midline (through the linea alba)
– Five centimeters superior and medial to
the anterior superior iliac spines on either
side
 Recommended routine use of
ultrasonography to verify the presence
of a fluid pocket under the selected
entry site in order to increase the rate
of success.6 The ultrasound also helps
the physician avoid a distended • Patients with severe ascites can be
urinary bladder or small bowel positioned supine. Patients with mild
adhesions below the selected entry
point. To minimize complications, ascites may need to be positioned in the
avoid areas of prominent veins (caput lateral decubitus position, with the skin
medusa), infected skin, or scar tissue. entry site near the gurney. The lateral
decubitus position is advantageous because
air-filled loops of bowel tend to float in a
distended abdominal cavity.
Technique
 Apply a sterile fenestrated drape to create a sterile
field.

• Use the 5-mL syringe and the 25-ga needle


to raise a small lidocaine skin wheal around the
skin entry site. Switch to the longer 20-ga
needle and administer 4-5 mL of lidocaine
along the catheter insertion tract. Make sure to
anesthetize all the way down to the
peritoneum. The authors recommend
alternating injection and intermittent
aspiration down the tract until ascitic fluid is
noticed in the syringe. Note the depth at which
the peritoneum is entered. In obese patients,
reaching the peritoneum may involve passing
through a significant amount of adipose tissue.
 Use the No. 11 scalpel blade to make a small
nick in the skin to allow an easier catheter
passage.

 Insert the needle directly perpendicular to the


selected skin entry point. Slow insertion in
increments of 5 mm is preferred to minimize the
risk of inadvertent vascular entry or puncture of
the small bowel.
 Continuously apply negative pressure to the syringe
as the needle is advanced. Upon entry to the
peritoneal cavity, loss of resistance is felt and ascitic
fluid can be seen filling the syringe. At this point,
advance the device 2-5 mm into the peritoneal
cavity to prevent misplacement during catheter
advancement. In general, avoid advancing the
needle deeper than the safety mark that is present on
most commercially available catheters or deeper
than 1 cm beyond the depth at which ascitic fluid
was noticed in the lidocaine syringe.
 Use one hand to firmly hold the needle
and syringe in place to prevent the needle
from entering further into the peritoneal
cavity.

• Use the other hand to hold the stopcock


and catheter and advance the catheter over
the needle and into the peritoneal cavity all
the way to the skin. If any resistance is
noticed, the catheter was probably
misplaced into the subcutaneous tissue. If
this is the case, withdraw the device
completely and reattempt insertion. When
withdrawing the device, always remove the
needle and catheter together as a unit in
order to prevent the bevel from cutting the
catheter.
 While holding the stopcock, pull the needle out. The
self-sealing valve prevents fluid leak.
 Attach the 60-mL syringe to the 3-way stopcock and
aspirate to obtain ascitic fluid and distribute it to the
specimen vials. Use the 3-way valve, as needed, to
control fluid flow and prevent leakage when no
syringe or tubing is attached.
 Connect one end of the fluid collection tubing
to the stopcock and the other end to a vacuum
bottle or a drainage bag.
 The catheter can become occluded by a loop of
bowel or omentum. If the flow stops, kink the
tubing to break the vacuum and try to slightly
change the patient's position. Then undo the
kink in the tubing to see if the flow resumes.
 Remove the catheter after the desired amount
of ascitic fluid has been drained. Apply firm
pressure, as necessary, to stop bleeding, if
present. Place a bandage over the skin puncture
site.
Complications
 Failed attempt to collect peritoneal fluid
 Persistent leak from the puncture site
– In cases with a persistent leak, a single skin suture might solve the problem.
– The application of an ostomy bag around the puncture site keeps the leak contained until it is
eventually sealed off.
 Wound infection
 Abdominal wall hematoma
 Spontaneous hemoperitoneum: This rare complication is due to mesenteric variceal
bleeding after removal of a large amount of ascitic fluid (>4 L).
 Hollow viscous perforation (small or large bowel, stomach, bladder)
 Catheter laceration and loss in abdominal cavity
 Laceration of major blood vessel (aorta, mesenteric artery, iliac artery)
 Postparacentesis hypotension
– This delayed complication may occur more than 12 hours after a procedure in which large
volumes are taken off.
– Patients can be pretreated with a colloid solution, such as albumin, to decrease the frequency of
this complication, though no difference in survival has been noted relative to other plasma
expanders.8
 Dilutional hyponatremia
 Hepatorenal syndrome
Laboratory
 Depending on the clinical situation, fluid may be sent for the
following laboratory tests:
 Gram stain
 Cell count (elevated counts may suggest infection)
 Bacterial culture
 Total protein level
 Triglyceride levels (elevated in chylous ascites)
 Bilirubin level (may be elevated in bowel perforation)
 Glucose level
 Albumin level, used in conjunction with serum albumin levels
obtained the same day (used to calculate serum-ascitic albumin
gradient [SAAG])
 Amylase level (elevation suggests pancreatic source)
 LDH level
 Cytology
Laboratory
 Depending on the clinical situation, fluid may be sent for the
following laboratory tests:
 Gram stain
 Cell count (elevated counts may suggest infection)
 Bacterial culture
 Total protein level
 Triglyceride levels (elevated in chylous ascites)
 Bilirubin level (may be elevated in bowel perforation)
 Glucose level
 Albumin level, used in conjunction with serum albumin levels
obtained the same day (used to calculate serum-ascitic albumin
gradient [SAAG])
 Amylase level (elevation suggests pancreatic source)
 LDH level
 Cytology
 A variety of approaches may be utilized for
obtaining a liver tissue specimen.
 These include a blind percutaneous
approach after percussion of the chest wall,
biopsy under ultrasound or CT guidance,
intravascular tissue sampling via the hepatic
vein, and intra-abdominal biopsy at
laparoscopy or laparotomy.
 Although liver biopsy is generally safe and is
currently considered the criterion standard for
the evaluation of hepatic inflammation and
fibrosis, sampling error, rare complications,
and occasionally significant patient anxiety do
occur.
 These factors have led to keen interest in the
development of noninvasive tests of hepatic
fibrosis.
 Several modalities of these tests are currently
under investigation, and 2 serum tests are now
commercially available in the United States.
 Complications of liver biopsy are rare but
potentially lethal.
 A thorough understanding of the
indications, contraindications, techniques,
and common complications and their
management is imperative.
 Liver biopsy, in combination with history and physical
examination data, is a powerful clinical tool for
diagnosing and treating liver disease. Indications for
obtaining a biopsy specimen are listed in as follows.
These are divided according to the type of clinical
question framed.
– Evaluation of abnormal hepatic laboratory test results
– Confirmation of diagnosis and prognostication
– Suspected hepatic neoplasm
– Diagnosis of cholestatic liver disease
– Evaluation of infiltrative or granulomatous disease
– Following a case of liver transplantation to evaluate and
manage rejection
– To evaluate unexplained jaundice or suspected drug
reactions
 The biopsy specimen may be used to identify
or exclude possible etiologies for physical or
laboratory abnormalities.
 various disease states may present similarly,
diagnostic histologic patterns exist when used
in the context of clinical presentation.
 Infiltration of the hepatic parenchyma by fat
may exist in diseases due to alcohol abuse,
hepatitis C, diabetes, and/or obesity. For each
disease state, histologic clues exist that
distinguish one from the other.
 Another indication for biopsy is the determination of the
extent of histologic change present in a biopsy specimen.
 This involves scoring systems for the degrees of
inflammation and fibrosis noted by the pathologist.
 Many systems exist for describing the microscopic
findings, ranging from simplistic to complex.
 The majority of scoring systems report the degree of
inflammation as the grade of the disease and the amount
of fibrosis as the stage.
 An example here would be the finding of moderate
inflammation (grade 3) in a specimen from a cirrhotic
(stage 4) liver.
 The third set of indications is the monitoring of
the progression of disease or of treatment
efficacy.
 For example, liver biopsy specimens
frequently are used to evaluate and treat
rejection following liver transplantation.
 Repeated biopsies are used less frequently to
monitor progression of diseases such as
primary biliary cirrhosis, chronic hepatitis C,
or alcoholic liver disease.
 Contraindications to percutaneous liver biopsy are
relatively few, but identifying contraindications is
important to avoid the major complications associated
with the procedure. Contraindications to liver biopsy
include the following:
– Increased prothrombin time, international normalized ratio
(INR) greater than 1.6
– Thrombocytopenia, platelet count less than 60,000
– Ascites (transjugular route preferred)
– Difficult body habitus (transjugular route preferred)
– Suspected hemangioma
– Suspected echinococcal infection
– Uncooperative patient
 A variety of needle types is
available for obtaining a
liver biopsy specimen.
 Needles may be divided
into 3 broad categories—
suction needles (Jamshidi,
Klatskin, and Menghini),
cutting needles (Tru-cut and
Vim-Silverman), and
spring-loaded cutting
needles.
 Each needle type has
proposed advantages and
disadvantages.
 Patient preparation prior to undertaking a liver biopsy is essential.
 Ideally, education should begin during an office visit prior to the
biopsy.
 Explain the procedure in sufficient detail, with careful attention to
anxiety and pain management issues.
 Discontinue aspirin 1 week prior to the procedure.
 Nonsteroidal anti-inflammatory drugs should be stopped 3 days prior
to the biopsy procedure.
 The patient may, or may not, be asked to complete an overnight fast.
 Eating prior to the procedure allows for gallbladder contraction,
reducing the risk of gallbladder puncture.
 An empty stomach may decrease the likelihood of postprocedure
nausea and vomiting, however. T
 his is an important consideration because many biopsies are preformed
under light sedation.
 The patient must remain within 30 minutes of the facility at which the
biopsy was performed.
 The patient must be accompanied by a reliable person the first night
after the procedure.
 The patient should have no contraindications or conditions that
increase the risk associated with the procedure.
 The facility where the biopsy is performed should have an approved
blood bank, laboratory, inpatient bed, and personnel available to the
patient for at least 6 hours postprocedure. (Note: Many centers
routinely observe patients for only 2-4 hours postbiopsy, and recently
published data indicate that discharge following 1 hour of observation
does not appear to affect patient safety. If this results in a change in
practice habits, it may significantly lower costs associated with
percutaneous liver biopsy.)
 Hospitalization should accompany evidence of bleeding, bile leak,
pneumothorax, or pain requiring more than one analgesic dose.
 On the day of the biopsy, review recent laboratory evaluation of
prothrombin time and complete blood count, including platelets.
Explain the procedure to the patient and obtain informed consent.
 Place the patient supine, remove pillows, and elevate the right arm
behind the head. The legs and feet may be angled to the left to
further open the right intercostal spaces.
 Percuss the right trunk to the point of maximum dullness during
both inspiration and expiration.
 This frequently corresponds to a point along the midaxillary line at
the second or third intercostal space above the costal margin. Mark
this location with a surgical pen or other method.
 Ultrasound or CT imaging may be useful, particularly if obtaining a
biopsy of a particular region or mass within the liver is desired.
Some have advocated that all biopsies be performed under
ultrasound guidance; however, whether this reduces procedure-
related morbidity or is cost effective is controversial.
 Once a suitable site has been identified, sterile technique is
employed. Prepare the field with Betadine solution and place sterile
drapes.
 Administer local anesthesia with 1% lidocaine in both superficial and deep
planes.
 Patients occasionally notice a pain described as burning or shooting in
quality that radiates either transversely or to the right shoulder region. This
pain is thought to represent contact of the anesthetic with the capsule of
the liver.
 Once adequate anesthesia has been obtained, a small nick in the skin is
made with a surgical blade to allow introduction of the biopsy needle.
 The biopsy needle is introduced within close proximity to the upper aspect
of the lower rib to avoid the intercostal nerve and vasculature. As the
needle is introduced, a series of several successive "pops" may be felt.
 Small amounts of saline contained in the syringe are flushed until
resistance is encountered. The resistance is the liver edge; at this point, the
needle is withdrawn slightly and flushed again to remove debris.
 Suction is applied to the syringe, and the patient is asked to expire and to
hold his/her breath. This shrinks the lung field and minimizes the risk of
perforating the gallbladder, while bringing the liver against the thorax
wall. The biopsy sample is obtained. Pressure is applied to the site,
followed by an adhesive bandage. The patient is rolled onto the right side
and instructed to remain in this position for 1 hour to help prevent
bleeding or bile leakage. Vital signs are obtained every 15 minutes for the
first hour, every 30 minutes during the second hour, and then hourly until
discharge.
 Complications of liver biopsy occur rarely but potentially are
lethal.
 The majority (60%) of complications occur within the first 2
hours, and 96% occur during the first 24 hours following the
procedure. Approximately 2% of patients undergoing biopsy
require hospitalization for the management of an adverse event.
Vasovagal episode and pain are the most common reasons for
admission.
 Pain occurs in approximately 30% of patients undergoing a liver
biopsy.
 It often is described as a dull ache in the right upper quadrant or
shoulder and typically is relatively short in duration, lasting less
than 2 hours.
 This pain often responds to analgesics. Unrelenting, severe
abdominal pain is alarming, possibly indicating a serious
complication such as intraperitoneal hemorrhage or biliary leak.
 Bleeding comprises a second group of complications.
Presentations include:
– subcapsular or parenchymal hematoma,
– hemobilia,
– free intraperitoneal hemorrhage.
 Intrahepatic or subcapsular hematomas are the most
common of the bleeding complications and are noted on
approximately 23% of ultrasound images obtained
following biopsy.
 Such findings often are incidental, without associated
clinical symptoms.
 They occur at similar rates after either blind or laparoscopy-
guided modalities, but incidence may be influenced by
needle type and imaging technique.
 Large hematomas are a rare cause of biliary obstruction.
 Symptomatic hematomas should be imaged by ultrasound
but usually respond to conservative treatment with
analgesics.
 Hemobilia presents as biliary colic, gastrointestinal bleeding, and
jaundice. It is a rare complication of biopsy; one study of 68,276
biopsies reported 4 instances of hemobilia.
 Clinical presentation ranges from chronic anemia to rapid
exsanguination. Hemobilia typically develops later than other
complications.
 The average time to onset of symptoms is 5 days following the
procedure, but onset may occur earlier. Conservative treatment often is
sufficient.
 Biliary peritonitis is another noteworthy complication, although rare.
 Severe abdominal pain and vasovagal hypotension herald its
occurrence. Analgesics and fluid management usually are sufficient,
but persistence of the condition may necessitate endoscopic retrograde
cholangiopancreatography with stent placement.
 Intraperitoneal hemorrhage is the most serious of the bleeding
complications. It is an early occurrence, most often observed during the
first few hours following the procedure, although reports of this
complication as long as 24 hours postprocedure have been noted.
 Late hemorrhage is associated with a poor outcome.
 Bacteremia, pneumothorax, and accidental biopsy of other organs are
rare complications. Their frequencies are outlined below.
 Pain (0.056-22%)
– Pleuritic
– Peritoneal
– Diaphragmatic
 Hemorrhage
– Intraperitoneal (0.03-0.7%)
– Intrahepatic and/or subcapsular (0.059-23%)
– Hemobilia (0.059-0.2%)
 Bile peritonitis (0.03-0.22%)
 Bacteremia
 Sepsis (0.088%) and abscess formation
 Pneumothorax and/or pleural effusion (0.08-0.28%)
 Hemothorax (0.18-0.49%)
 Arteriovenous fistula (5.4%)
 Subcutaneous emphysema (0.014%)
 Anesthetic reaction (0.029%)
 Needle break (0.02-0.059%)
 Biopsy of other organs
– Lung (0.001-0.014%)
– Gallbladder (0.034-0.117%)
– Kidney (0.096-0.029%)
– Colon (0.0038-0.044%)
 Mortality (0.0088-0.3%)
DISEASES
chronic hepatitis
ACUTE VIRAL HEPATITIS

-Causes: hepatic virus: A, B, C, D, E


-Onset: -anorexia
-nausea
-vomiting
-Physical exam:
-jaundice
-liver +/- spleen enlargement
-Laboratory findings:
-A. L. T >10X N. V.
-serum bilirubin increase
-positive viral marker
Pathogenesis of liver injury
Chronic Hepatitis
 Chronic viral hepatitis B (B+D),C
 Toxic induced (drugs,..)
 Alcohol liver disease (steatosis, hepatitis,
cirrhosis)
 Autoimune hepatitis
 Wilson disease
 Hemocromatosis
Modes of transmission
Risk factors for hepatitis C
Parenteral Sexual Perinatal

Intravenous drug abuse Multiple partners High viral load


Nasal cocaine Traumatic sex HIV-positive mother
Transfusions HIV-positive partner
Needle-stick injury Prostitute use
Tattoos
Body piercing
Manicures
Household items
Differential diagnosis of histologically documented chronic hepatitis
Chronic viral hepatitis (B, C, D)

Autoimmune hepatitis

Drug-induced chronic hepatitis

Wilson's disease
Outcomes of drug metabolism
Clinical manifestations of hereditary hemochromatosis
Common physical findings in hereditary hemochromatosis
Findings Occurrence, %

Hepatomegaly 60–85
Cirrhosis 50–95
Skin pigmentation 40–80
Arthritis (second and third metacarpophalangeal joints) 40–60
Clinical diabetes 10–60
Splenomegaly 10–40
Loss of body hair 10–30
Testicular atrophy 10–30
Dilated cardiomyopathy 0–30
Wilson's disease pathophysiology
Chromosome 13
Copper transport protein
Membrane-spanning p-type ATPase protein
Decreased hepatic excretion of copper into bile
Clinical manifestations of Wilson's disease
Diagnosis of wilson's disease
Serum ceruloplasmin
Urinary copper
Hepatic copper
Hepatic histology
Glucosuria, hemolysis
LIVER CIRRHOSIS
-Definition:
Necrosis of liver cells followed by fibrosis, nodular regeneration
-Causes:
-Toxins: - Alcohol
- Drugs (metil dopa, tuberculostatic drugs)
-Infection- Hepatic virus B, C
-Autoimune reaction
- Primary biliary cirrhosis
-Metabolic- Haemochromatosis: iron deposits in liver
cirrhosis+ diabetes+ pigmentation
- Wilson Disease: copper deposits in liver
cirrhosis + neurological abnormalities+ Kayser
Fleyscher ring
-Congestive change
- Right heart failure
-Obstruction
- Secundary biliary cirrhosis
Simptoms & Signs
1. Enlargement of liver: -pain
-revealed at physical exam
2. Portal hypertension:
-bleeding varices + hemoroids
-splenomegaly + hipersplenism
-ascites
-colateral superior abdominal circulation
-hepatic encephalopaty
personality change, stupor, coma
3. Hepatocelular failure
- ↓ serum albumine →ascites, edema
- ↓ excretion of bilirubine →jaundice
- ↓ fibriongen, store vitamine K →bleeding
- ↓ detoxication:
oestrogen → spider naevi
palmar erythema
gynecomastia
loss of body hair
testicular athrophy
aldosterone → edema
nitroso products from the gut
→ neurological abnormalities
Development of ascites
Early signs of ascites
Abdominal ultrasound
Indications for diagnostic paracentesis
At first presentation of ascites
Alteration of the patient's clinical state
Sudden increase in ascites
Worsening of hepatic encephalopathy
Presence of fever
Differential diagnosis of ascites
Cirrhosis Constrictive pericarditis

Hepatoma Nephrotic syndrome

Tuberculous peritonitis in the malnourished alcoholic Pancreatitis

Peritoneal carcinomatosis Malignant chylous ascites, especially lymphom

Right-sided cardiac failure


Ascitic fluid analysis
Polymorphonuclear count

> 250/μL is diagnostic of spontaneous bacterial peritonitis

Ascitic fluid albumin concentration

Serum-ascitic fluid albumin gradient > 11 g/L is suggestive of cirrhotic,

rather than malignant, ascites


Active hemorrhage from an esophageal varix
Assessing asterixis
Portosystemic encephalopathy
The relative frequency of various tumors of the liver
Imaging modalities in diagnosis of hepatocellular cancer
Ultrasound examination of the liver
Contrast-enhanced CT scan
Spontaneus peritonitis
Table 10-73. Clinical Features of Spontaneous Bacterial
Peritonitis
Significant fever Worsening encephalopathy
Chills Worsening of ascites
Abdominal pain Hypotension
Abdominal tenderness Asymptomatic
Reduced bowel sounds
Pathogenesis of Spontaneous Bacterial Peritonitis
Table 10-74. Diagnosis of Spontaneous Bacterial
Peritonitis
Standard criterion-PMN cell count > 250/μL
Culture negative neutrocytic ascites = SBP
Monomicrobial non-neutrocytic bacterascites-positive
culture + PMN count < 250μL
Portal hypertension
The portal venous system
 Def : permanent increase of portal presure
(NV – 5-12 mmHg) or portal gradient > 7
mmHg (wedged hepatic pressure - free
hepatic presiure); > 20 mmHg PP determine
collateral venous circulation
Measurement of portal hypertension
Causes of PHT
 Post hepatic – portal thrombosis, extrinsic
compressions on portal vein : pancreatic
tumors, adenopaty
 Hepatic cause: liver cirrhosis, sarcoidosis,
hepatic lymphoma,
 Prehepatic: Inf Venae Cavae thrombosis,
Budd- Chiari sdr
Consequence
 Esophageal and Gastric varices
 Hemorrhoids
 Collateral abdominal circulation (caput
medusae)
 Splenomegaly (and hypersplenism)
Natural history of esophageal varices
Large varices of stigmata of recent bleeding (A)
Classification of gastric varices (A)
GALLBLADDER & BILLIARY TRACT DISEASES

1.GALLSTONES
-90% ASYMPTOMATIC
-biliary colic
-pain in right upper quadrat
-nausea
-vomit
-Murphy sign
-diagnosis
-ultrasonography
2. ACUTE COLECISTITIS
-biliary colic +
-fever + chills +
-jaundice +
-tendernes
Figure 1.13 - The gallbladder

©Copyright Science Press Internet Services


Figure 1.15a - Luminal surface of rabbit gallbladder
mucosa

©Copyright Science Press Internet Services


Figure 1.13 - The gallbladder

©Copyright Science Press Internet Services


Figure 7.15 - The cycle of cholesterol gallstone
pathogenesis
Figure 1.13 - The gallbladder

©Copyright Science Press Internet Services


TABLE 7 - 34. CLINICAL RISK FACTORS FOR
CHOLESTEROL GALLSTONE FORMATION

TABLE 7-34. CLINI CAL RISK FACTORS FOR CHOLESTEROL GALLSTO NE FORMATION

Estrogens:

Pregnancy, Female Sex, Exogenous Administration

Age

Ethnic Origin: Native American

Obesity and Rapid Weight Loss

Hypertriglyceridemia

Gallbladder Stasis:

Spinal Cord Injury, Increased Somatostatin Levels, Vagotomy


TABLE 7 - 1. TYPES OF GALLSTONES

TABLE 7-1. TYPES OF GALLSTONES

Cholesterol Black pigment Brown pigment

Location Gallbladder Gallbladder Bile ducts

Pathogenesis Physical-Chemical Physical-Chemical Infectious

Composition: Cholesterol +++ + ++

Calcium and Bilirubin Content + +++ ++

©Copyright Science Press


Figure 7.2b - Appearance of gallstones

©Copyright Science Press Internet Services


Figure 7.2c - Appearance of gallstones

©Copyright Science Press Internet Services


Figure 7.2d - Appearance of gallstones

©Copyright Science Press Internet Services


Figure 7.2f - Appearance of gallstones

©Copyright Science Press Internet Services


TABLE 8 - 3. CHARACTERISTICS OF
CHOLESTEROL GALLSTONES

TABLE 8-3. CHARACTERISTICS OF CHOLESTEROL GALLSTONES

80% Radiolucent on plain film Usually smooth contour

50% Radiolucent only on CT scan May float in contrast

©Copyright Science Press Internet Services


TABLE 8 - 8. CHARACTERISTICS OF BLACK
PIGMENT GALLSTONES
TABLE 8-8. CHARACTERISTICS OF BLACK PIGMENT GALLSTONES

Usually less than 1 cm in diameter

Often irregular contour

Not floatable on oral cholecystography

Ma y be radiolucent on plain film

Radiopaque on CT scan
Figure 8.10 - Typical black pigment stones are
irregular in contour

©Copyright Science Press Internet Services


Figure 8.47c - Optimal results with solitary stones 2
cm or less in diameter

©Copyright Science Press Internet Services


Litiaza biliara
Figure 8.4b - Visual identification of cholesterol
stones

©Copyright Science Press Internet Services


Figure 8.11 - Pigment stones are usually detectable
on CT scan

©Copyright Science Press Internet Services


Acute pancreatitis
Anatomy
The pancreas is a solid gland
situated at the back of the
abdominal cavity behind the
stomach.
25 cm in length and 4-6 cm in
width.
The gland is divided into 5 parts –
Head
Uncinate process
Neck
Body
Tail
Attached to the duodenum
Stomach empties liquids and Vascularisation:
partly digested food. Artery supplying blood to the
The pancreatic duct runs through lower abdomen and legs (the aorta)
the middle of the gland and carriesVein which returns blood from these areas
pancreatic juice to the intestine. (the inferior vena cava).
This duct joins with the bile duct
 The pancreas is made up of two types of tissue:
 exocrine tissue
The exocrine tissue secretes digestive
enzymes. These enzymes are secreted into a
network of ducts that join the main pancreatic
duct, which runs the length of the pancreas.
 endocrine tissue
The endocrine tissue, which consists of the
islets of Langerhans, secretes hormones into
the bloodstream.
Function
 The pancreas has digestive and hormonal functions:
 The enzymes secreted by the exocrine tissue in the
pancreas help break down carbohydrates, fats, proteins,
and acids in the duodenum.
 These enzymes travel down the pancreatic duct into the
bile duct in an inactive form. When they enter the
duodenum, they are activated.
 The exocrine tissue also secretes a bicarbonate to
neutralize stomach acid in the duodenum.
 The hormones secreted by the endocrine tissue in the
pancreas are insulin and glucagon (which regulate the
level of glucose in the blood), and somatostatin (which
prevents the release of the other two hormones).
Pancreatitis
 Introduction:
Pancreatitis is an inflammation of the pancreas. The
pancreas is a large gland behind the stomach and close to
the duodenum. The duodenum is the upper part of the
small intestine. The pancreas secretes digestive enzymes
into the small intestine through a tube called the pancreatic
duct. These enzymes help digest fats, proteins, and
carbohydrates in food. The pancreas also releases the
hormones insulin and glucagon into the bloodstream.
These hormones help the body use the glucose it takes
from food for energy.
• Acute Pancreatitis: Def and Causes:
• Acute pancreatitis occurs suddenly and lasts for a short period of time
and usually resolves.
• Acute pancreatitis is usually caused by gallstones or by drinking too
much alcohol.
• Biliary stone Disease ( Cholelithiasis, Choledocholithiasis )
• Medications like azathioprine, corticosteriods, sulphonamides,
NSAIDS, Methyldopa, thiazides, fruosemides, mercaptopurines,
tetracyclines.
• ERCP
• Hypertriglyceridemia ( when TG levels > 1000mg/U )
• Peptic ulcer disease
• Abdominal or cardiopulmonary bypass surgery
• Trauma to the abdomen or back
• Carcinoma of the pancreas
• Viral infections like coxsackie, CMV, hepatitis, EBV & rubella.
• Ischemia or vasculitis
Summary of main etiologies for acute pancreatitis
TABLE 3 - 14. PATHOGENESIS OF ACUTE
PANCREATITIS: INITIATING EVENT
UNKNOWN
? Intra - acinar activation of trypsin, which in turn
activates chymotrypsin, elastase, and
phospholipase A2
? Accumulation of lipase in interstitium, which
leads to peripancreatic fat necrosis
Possible pathogenetic sequence of acute pancreatitis
SIMPTOMS & SIGNS

-pain -severe, epigastric, radiating to back or transverse


+ nausea
+ vomiting
-fever
-tachypnea
-tachycardia
-low blood pressure
-ileus
-epigastric tendernes
-ecchymosis in the flank (Gray-Turner sign)
-ecchymosis umbilical (Cullen's sign)
• PHYSICAL FINDINGS:

•Fever (76%) and tachycardia (65%) are common abnormal vital


signs.

•Abdominal tenderness, muscular guarding (68%), and distension


(65%) are observed in most patients. Bowel sounds are often
hypoactive.

•A minority of patients exhibit jaundice (28%).

•Some patients experience dyspnea (10%), which may be caused


by irritation of the diaphragm (resulting from inflammation) or by
a more serious condition, such as respiratory distress syndrome.

•In severe cases, hemodynamic instability is evident (10%) and


A few uncommon physical findings are associated with severe necrotizing
pancreatitis:

• The Cullen sign is a bluish discoloration around the umbilicus


resulting from hemoperitoneum.

• The Grey-Turner sign is a reddish-brown discoloration along the


flanks resulting from retroperitoneal blood dissecting along tissue
planes.

• Erythematous skin nodules may result from focal subcutaneous


fat necrosis.

• Rarely, abnormalities on fundoscopic examination may be seen


in severe pancreatitis. Termed Purtscher retinopathy, this ischemic
injury to the retina appears to be caused by activation of
complement and agglutination of blood cells within retinal vessels.
A middle-aged man with severe acute pancreatitis. He exhibits the
physical signs associated with Cullen and Grey Turner - namely bruising
around the umbilicus (Cullen) and in the flanks (Grey-Turner). These signs
are due to the extravasation of haemolysed fluids into the subcutaneous
tissues. These two signs are uncommon
LABORATORY FINDINGS

-↑serum amylase (25-125 U/l)


-↑urine amylase
-↑serum lipase (10-140 U/l)
-↑W. B. C. count
-↓serum Calcium
-↑serum trigliceride

-ULTRASONOGRAPHY EXAMINATION

-COMPUTER TOMOGRAPHY
Diagnosis of acute pancreatitis
Acute pancreatitis.

A 70-year-old man admitted with a short history of severe right upper


quadrant pain. Diagnosed as acute pancreatitis and the CT scan shows a
necrotic mass in the head of the pancreas. His condition deteriorated
and the patient underwent urgent laparotomy and pancreatic
necrosectomy.
Acute pancreatitis resulting in pseudocyst.

Spiral CECT in a patient several weeks after the onset of acute


pancreatitis. A small intrapancreatic pseudocyst is shown within the
neck (thin arrows), without any evidence of pancreatic-duct obstruction.
A larger, lesser-sac pseudocyst is also shown (large arrows).
Arrowheads, pancreatic duct.
Acute necrotizing pancreatitis.

The spiral CECT shows poor, uneven enhancement of pancreatic tissue


with massive diffuse swelling in keeping with oedema.
TABLE 3 - 29. COMPLICATIONS OF ACUTE
PANCREATITIS
Local Systemic
Necrosis Shock
Pseudocysts Respiratory failure
Abcess Renal failure
Metabolic–hypocalcemia,
Ileus
hyperglycemia
Coagulopathy–disseminated
Fistulization
intravascular coagulation
Gastrointestinal
hemorrhage–
pseudoaneurysm
Scan of pancreas indicating gas bubbles within pancreas
An example of colonic obstruction due to pancreatitis
Chronic pancreatitis
Classification by etiology
Diagnostic tests

TABLE 4 - 7. DIAGNOSTIC TESTS


Function Structure
Endoscopic retrograde
Direct hormonal stimulation tests
pancreatography
Bentiromide test Computed tomography
Serum trypsin - like
Endoscopic ultrasound
immunoreactivity
Fecal chymotrypsin or fecal
Magnetic resonance imaging
elastase
Quantitative fecal fat Ultrasonography
Blood glucose Plain abdominal radiography

Tests are listed in order of decreasing sensitivity.


Tests of structure: endoscopic retrograde pancreatography (B)
Tests of structure: computed tomography (A)
Tests of structure: ultrasonography (B)
Tests of structure: plain abdominal radiograph
Chronic pancreatitis.

Advanced chronic pancreatitis with strictures at the neck and body


(arrows), and a stone in the head (arrow head).
Chronic pancreatitis.

Diffusely dilated pancreatic duct due to chronic pancreatitis.


Chronic pancreatitis.

Percutaneous pancreatography
performed by direct puncture
under ultrasound guidance.
Dilated duct in chronic
pancreatitis.
Alcohol-induced chronic
pancreatitis.

A 54-year male with a 20-year


history of alcohol abuse
presented with jaundice.
Abdominal ultrasonography
revealed a dilated biliary tree.
ERCP confirmed this finding
and also showed a 'rat's tail'
type stricture in the distal
common bile duct. Then main
pancreatic duct is distended
with side radical changes
consistent with alcoholic
chronic pancreatitis
Chronic pancreatitis.

An ERCP in a patient with alcoholic liver disease and clinical features of


chronic pancreatitis, shows massive dilatation of the main pancreatic
duct, with a lack of filling of the tail of the gland. The duct measures
14mm between the arrowheads. There is marked deformity and dilatation
of multiple tributaries.
Chronic pancreatitis.

A 52-year-old male patient with a long history of alcohol abuse and


recurrent epigastric pain is shown to have widespread pancreatic
calcification on this unenhanced CT scan. Pancreatic calcification is rare
in gallstone-induced chronic pancreatitis.
Chronic pancreatitis.

(b)A 52-year-old male patient


with a long history of alcohol
abuse and recurrent
epigastric pain is shown to
have widespread pancreatic
calcification on this
unenhanced CT scan.
Pancreatic calcification is
rare in gallstone-induced
chronic pancreatitis.
(c) (b) This spiral CECT shows
an irregularly dilated
pancreatic duct (arrow)
associated with calculi and
pancreatic atrophy.
Cancer of pancreas
Introduction
 Over 90% of pancreatic cancers are ductal
adenocarcinomas of the exocrine pancreas.
 These tumors occur twice as frequently in the
pancreatic head compared to the rest of the
organ, and tend to be aggressive, often
presenting when locally inoperable or after
distal metastases have occurred.
 Patients with pancreatic cancer have a poor
prognosis, with a 5-year survival of only 5%.
Epidemiology
 The lifetime risk of being diagnosed with pancreatic
cancer in the United States is 1.27%.
 In the United States, it is estimated that approximately
37,170 people will be diagnosed with pancreatic cancer in
2007.
 Consistent with its associated poor prognosis, 33,370 are
expected to die from this disease in the same year, making
it the fourth leading cause of cancer-related death.
 Median age of diagnosis of pancreatic cancer is 72 years,
– peak incidence of diagnosis between the ages of 65 and 84;
– rarely diagnosed in those below the age of 50.
 The incidence is slightly higher in men than women, and
it is also higher in African Americans than in Caucasians.
Etiology
 Cigarette smoking, obesity, and nonhereditary chronic
pancreatitis appear to be risk factors for the development of
pancreatic cancer.
 With smoking, the risk seems to increase with the number of
cigarettes consumed and decreases with smoking cessation.
 An epidemiologic association between diabetes mellitus and
pancreatic cancer has also been demonstrated; however, it is
uncertain if diabetes is a precedent of, or consequence of,
pancreatic cancer.
 Chronic pancreatitis
 Less clear, and sometimes conflicting associations, have been
observed for other environmental factors such as diet, coffee
and alcohol consumption, previous partial gastrectomy or
cholecystectomy, and Helicobacter pylori.
TABLE 7 - 4. PRESENTING SYMPTOMS IN PANCREATIC
CARCINOMA
Symptom Patients, %
Weight loss 91
Pain 83
Jaundice 71
Anorexia, nausea 44
Malaise 34
Vomiting 13
Imaging Studies
 Ultrasound is often used as an initial investigation for patients with
jaundice, or with less-specific symptoms such as upper abdominal
discomfort, and is able to assess the biliary tract, gall bladder,
pancreas, and liver.
 Computed tomography (CT) scanning is preferable to ultrasound even
though it is more costly, as it is less operator-dependent, more
reproducible, and less susceptible to interference from intestinal gas.
 CT may show a pancreatic mass, dilatation of the biliary system or
pancreatic duct, or distal spread to the liver, regional lymph nodes, or
peritoneum (and/or associated ascites).
 When helical CT is combined with the use of intravenous contrast, it
may also help determine resectability by providing information on the
involvement of important vascular structures such as the celiac axis,
superior mesenteric or portal vessels.
CT image of tumor within the pancreatic head. Note the stent
in the bile duct and the subtle low-density mass within the
head. The superior mesenteric artery (SMA) has a fat plane
completely surrounding it. This defines a potentially resectable
tumor.
Barium studies of the gastrointestinal tract not often used (A)
Computed tomography can also direct a needle aspiration (A)
Scans demonstrating common bile duct and gallbladder
dilatation (A)
Imaging Studies
 Endoscopic retrograde cholangiopancreatography (ERCP) is also
widely used in the diagnosis of pancreatic cancer, particularly when
CT and ultrasound fail to show a mass lesion, and may reveal either
stricture or obstruction in either the pancreatic or common bile duct.
 ERCP can also be used to obtain brushings of a stricture for cytology
or for placing stents in order to relieve obstructive jaundice.
 Endoscopic ultrasound (EUS) may be useful in the diagnosis of small
lesions (<2–3 cm in diameter) and, in some cases, for local staging as
well as evaluating invasion of major vascular structures.
 Magnetic resonance imaging (MRI) does not offer any advantages
over CT in the routine evaluation of patients with possible pancreatic
cancer, magnetic resonance cholangiopancreatography (MRCP) may
be better than CT for defining the anatomy of the pancreatic duct and
biliary tree, being able to image the ducts both above and below a
stricture.
 The sensitivity of MRCP is comparable to ERCP, but does not require
contrast administration to the ductal system, so that there is less
associated morbidity.
Pancreatic carcinoma that has grown into duodenum
Narrowed intrapancreatic segment of common bile duct (A)
Tissue diagnosis and Cytology
 Patients with disease that is potentially curable by surgery, and
in whom a highly suspicious lesion is seen on imaging, are often
taken directly to surgery without prior tissue confirmation of
cancer.
 This is because of theoretical concerns that a percutaneous fine-
needle aspiration may result in dissemination of cancer
intraperitoneally or along the track of the biopsy needle.
 In addition, negative cytology may not be sufficient evidence to
avoid surgery, particularly with small lesions.
 EUS-guided fine-needle aspiration is increasingly being used,
even in patients with potentially resectable disease, as there is
less risk of intraperitoneal spread of cancer. Other methods of
obtaining specimens for cytological analysis include sampling
of pancreatic juices or brushings of ductal lesions obtained by
ERCP.
Serum Markers
 The most widely used serum marker in pancreatic cancer is cancer-
associated antigen 19-9 (CA 19-9).
 It has a reported sensitivity and specificity of about 80–90%, and is
suggestive, rather than confirmatory, of the diagnosis of pancreatic
cancer.
 Serum levels of CA 19-9 can be elevated in patients with jaundice
without pancreatic cancer present. The level of CA 19-9 may have
prognostic implications, with very high levels sometimes found in
patients with inoperable disease.
 In advanced disease, patients treated with chemotherapy who had high
pretreatment levels of CA 19-9 have also been found to have a worse
survival, whereas those patients whose levels of marker fell with
treatment had a better outcome.
 In patients with cancers with elevated CA 19-9, serial evaluation of
this marker is useful for monitoring responses to treatment. In patients
with completely resected tumors, follow-up with CA 19-9 is useful for
detecting recurrence.
Tumour effect on Pancreas
 Most cancers of the pancreas are primary cancers which means
they arise from a group of cells within the pancreas itself.
 Commonest site is the head of the pancreas. The cause of
pancreatic cancer is unknown, but there may be some
association with tobacco smoking.
 There are two main effects of cancer of the pancreas
– cancer in the head of the pancreas blocks the bile duct, leading to
jaundice “going yellow”, dark urine, and pale stools. This is often
associated with itching of the skin which disappears once the
blockage is cleared.
– Bypassed - the cancer blocks the pancreatic duct leading to poor
digestion, loose motions and weightloss
– Diabetes may already be present in a number of patients prior to
developing the cancer, or become apparent soon after it is
diagnosed or following surgery.
Types of Tumours
 There are three common types of pancreatic cancer:
– Ductal adenocarcinoma - the commonest type is the cancer arising from the small
ducts of the pancreas. Most often it arises in the head of the gland and a principal
feature is the development of jaundice. This type often occurs in individuals over
the age of 60 years but it can affect younger people as well.
– Endocrine tumour less commonly tumours may arise from the islets of Langerhans
or other hormone producing cells. These tumours are often not malignant
– Tumours of the ampulla of Vater also present with jaundice, dark urine and pale
stools. Periampullary cancers can be broadly considered as those tumours arising
out of or within 1 cm of the papilla of Vater and include ampullary, pancreatic,
bile duct, and duodenal cancer. The cancer is often preceded by ampullary or
duodenal benign tumours or arise in an adenoma. Ampullary tumors are associated
with a good prognosis and if the tumor is limited to the duodenal mucosa without
any invasion into the adjacent pancreas then the five-year survival may be as high
as 90 percent. The 5-year survival rate refers to the percentage of patients who live
at least 5 years after their cancer is diagnosed. Some of these patients live much
longer than 5 years after diagnosis, and 5-year rates are used to produce a standard
way of discussing prognosis.

 The discussion of pancreatic cancer here will be limited to ductal


adenocarcinomas.
Ductal Endocarcinoma
 Normal:
– The normal ductal and ductular epithelium is a cuboidal to low-
columnar epithelium with amphophilic cytoplasm. Mucinous
cytoplasm, nuclear crowding and atypia are not seen.
 Squamous metaplasia
o represents a transitional morphology characterized by
replacement of normal cuboidal ductal epithelium by transitional
epithelium without atypia or by mature squamous epithelium.
 Pancreatic Intraepithelial Neoplasia 1-A (PanIN-1A)
– These lesions are described as flat, composed of tall columnar cells with
nuclei located basally and significant amounts of supranuclear mucin
(mucin refers to a family of heavily glycosylated proteins). Nuclei tend
to be small and round to oval. Oval nuclei are typically oriented
perpendicular to the basement membrane. Because of histological
uncertainty, the neoplastic character of many examples of PanIN-1A
remains unestablished.
 Pancreatic Intraepithelial Neoplasia 1-B (PanIN-1B)
– These epithelial lesions have a papillary, micropapillary or
basally pseudostratified architecture, but are otherwise
identical to PanIN-1A.
 Pancreatic Intraepithelial Neoplasia 2 (PanIN-2)
– are mucinous lesions appearing either flat or papillary.
Nuclear abnormalities may include some polarity loss,
nuclear crowding, enlarged nuclei, pseudo-stratification
and hyperchromatism. With hyperchromatism the nuclei
will tend to stain more intensely than normal. More nuclear
abnormalities are observed in PanIN-3. Mitoses occur
rarely.
 Pancreatic Intraepithelial Neoplasia 3 (PanIN-3)
– are usually papillary or micropapillary, rarely flat.
– Suggestive of the diagnosis of PanIN-3 include "true
cribriforming, budding off of small clusters of epithelial cells
into the lumen as well as luminal necrosis."
– These lesions show a loss of nuclear polarity, dystrophic goblet
cells ("goblet cells with nuclei oriented towards the lumen and
mucinous cytoplasm oriented towards the basement membrane")
as well as mitoses (sometimes abnormal), along with nuclear
irregularities with prominent nucleoli.
Staging
Stage Grouping TNM Staginga
Localized resectable I T1–2 N0 M0
II T3 N0 M0 or T1–3 N1 M0
Locally advanced III T4 N(any) M0
Metastatic IV T(any) N(any) M1
a
TNM, tumor, nodes, metastasis.

Note: T1, tumor limited to pancreas, 2 cm; T2, tumor


limited to pancreas, >2 cm; T3, tumor extends beyond
the pancreas but without involvement of celiac axis or
superior mesenteric artery; T4, tumor involves celiac axis
or the superior mesenteric artery (unresectable primary
tumor); N0, no regional lymph node metastasis (regional
lymph nodes are the peripancreatic lymph nodes,
including the lymph nodes along the hepatic artery, celiac
axis and pyloric/splenic regions); N1, regional lymph node
metastasis; M0, no distal metastasis; M1, distal
TABLE 7 - 6. DIAGNOSTIC WORK - UP FOR PANCREATIC
CANCER: LABORATORY FINDINGS
Elevated bilirubin
Elevated liver function tests
Elevated alkaline phosphatase
Elevated serum blood sugar
Elevated amylase
Occult blood in the stool
Low hemoglobin
Tumor markers
Gastrointestinal cancer - associated antigen (CA 19 - 9)
Carcinoembryonic antigen (CEA)
CA - 50
A - fetoprotein (AFP)
Pancreatic oncofetal antigen (POA)
Genetic markers
p52
K - ras
First diagnostic test the authors use