Liver Curs 2009

LIVERLIVER

LABORATORY TESTS IN LIVER DISEASES1. 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. TRANSAMNINASESALANINE TRANSFERASE (A. L. T.) N. V.=8-20 u/lASPARTATE 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 cirrhosis5.TESTS FOR VIRAL INFECTION6. HEMATOLOLOGY7. LIVER BIOPSY8. IMAGING TEHNIQUE (ULTRASONOGRAPHY, COMPUTERTOMOGRAPHY, SCINTIGRAPHY, ARTERIOGRAPHY

UltrasonographyUltrasonography»

Imaging techniques

CTCT

MRIMRI

scintigscintigraphyraphy (Tc99). (Tc99).

Imaging techniques

» LaparoscoLaparoscopypy

» Liver biopsy/fine needle aspirationLiver biopsy/fine needle aspiration

RADIOLOGY– Hepatic arteriographyHepatic arteriography

– SplenoportoSplenoportographygraphy

– ERCPERCP

Imaging techniques

other» EndoscopyEndoscopy

» paracparacentesisentesis

Physical examPhysical exam

Telangiectasia / spider naevi

Skin– jaundicejaundice

– hipopilosityhipopilosity

– ginecomastiaginecomastia

– Xantelasmas, xantomasXantelasmas, xantomas


Skin– Palmar eritemaPalmar eritema

– colateral venous circulasioncolateral venous circulasion

– purpurepurpure- Spider naevi- Spider naevi

– White nailsWhite nails

– Red tonqueRed tonque

– Dupuytren;Dupuytren;

– hipocratic fingershipocratic fingers

– Hepatic edemaHepatic edema


NutritionNutrition


INSPECTION


PALPATION

LIVER PALPATION



PERCUTION-UPPER MARGIN

- V ic space - mid axilar line-VII ic space- anterior axilar line-X ic – space scapular line.


ASCULTATION – – hepatic artery murmer in hepatic artery murmer in liver cancerliver cancer

HepatomegalyHepatomegaly

Def Def lower margin mid clavicular line : lower margin mid clavicular line : costal ribcostal rib

upper margin : percusion 5upper margin : percusion 5 thth intercostal space mdi clavicular line; 8intercostal space mdi clavicular line; 8 thth ic ic space mid axila space mid axila


Inflammation – acute hepatitis, chronic hepatitis Inflammation – acute hepatitis, chronic hepatitis autoimune hepatitis, alcoholic liver disease, tuberculosis, autoimune hepatitis, alcoholic liver disease, tuberculosis, liver abces, liver cirrhosis, liver abces, liver cirrhosis,

Metabolic disorders – steatosis, Metabolic disorders – steatosis, Biliarry diseases primary billiary cholangitis, biliarry Biliarry diseases primary billiary cholangitis, biliarry

obstructionobstruction Vascular disorders heart failure, chronic pericarditisVascular disorders heart failure, chronic pericarditis Tumors, liver metastasisTumors, liver metastasis Congenital disorders hemocromatosis, Wilson disease, Congenital disorders hemocromatosis, Wilson disease,

glicogenosisglicogenosis Hematological disorders chornic leukemia, lymphomasHematological disorders chornic leukemia, lymphomas


Liver cirrhosis; not painful, high Liver cirrhosis; not painful, high consistency, nodularconsistency, nodular

Liver tumors; painful, irregular Liver tumors; painful, irregular Heart failure: painful, regular, mobile, Heart failure: painful, regular, mobile,

hepato-jugular reflexhepato-jugular reflex

JAUNDICEJAUNDICE

DDEFINITIONEFINITION

clinicclinicalal evidentevident- bilirub - bilirub > 2,5 mg%, > 2,5 mg%, Sub jaundice Sub jaundice == bilirubin > 1,8 mg%, bilirubin > 1,8 mg%,

“scleral jaundice”“scleral jaundice” simptom not disease simptom not disease

PREHEPATICPREHEPATIC JAUNDICE JAUNDICE

HEPATOCELULARHEPATOCELULAR JAUNDICE JAUNDICE

POSTHEPATICPOSTHEPATIC JAUNDICE JAUNDICE

Jaundice type CAUSES

PrehepaticPrehepatichemolisishemolisis

Gilbert syndromeGilbert syndrome

Crigler-Najjar sdrCrigler-Najjar sdr

HepaticHepatic

hepatitis A, B, C, Ehepatitis A, B, C, E

Autoimune hepatitisAutoimune hepatitis

Alcohol (toxic)Alcohol (toxic)

cirrhosiscirrhosis

Wilson DWilson D

Dubin-Johnson sdrDubin-Johnson sdr

Rotor sdrRotor sdr

PosthepaticPosthepatic

Primary biliary cirrhosisPrimary biliary cirrhosis

toxictoxic

gallstonesgallstones

Cancer of head pancreasCancer of head pancreas

PREHEPATICPREHEPATIC JAUNDICE JAUNDICE

Simptoms• No itching

• Hipercromic feces • normal hipercromic urines• palor• splenomegaly.

LAB•Unconjugated bilirubin •stercobilinogen •urobilinogenurie•Normal liver tests •Elevated reticule cell count, •Normocrom normocitic anemia,

HEPATOCELULARHEPATOCELULAR JAUNDICE JAUNDICE

Simptoms• variable jaundice

• ± signs of liver disease

•

Lab• Unconjugated and conjugated Bilirubin

• ± citolysis

• ± Hipocolesterolemia, hipoalbuminemia , hipergamaglobulinemia

POSTHEPATICPOSTHEPATIC JAUNDICE JAUNDICE

Tablou clinic itchingitching jaundicejaundice acolicacolic feces feces hipercromhipercromicic urines urines diareea diareea ((steatoresteatoree)e);; Liposoluble vitamines malabsortions Liposoluble vitamines malabsortions

Lab Conjugated hyperbilirubine, Conjugated hyperbilirubine, hipercolesterolemia, hipercolesterolemia, Alcaline PhosphataseAlcaline Phosphatase , GGT, GGT Normal liver tests at the biginingNormal liver tests at the bigining PP index index - -corected corected with with K1 K1

!!!

US

MRI

ERCP

ASCITESASCITES

BACKGROUNDBACKGROUND The word ascites is of Greek origin (The word ascites is of Greek origin (askosaskos) )

and means bag or sac. and means bag or sac. Ascites describes the condition of pathologic Ascites describes the condition of pathologic

fluid accumulation within the abdominal fluid accumulation within the abdominal cavity. cavity.

Healthy men have little or no intraperitoneal Healthy men have little or no intraperitoneal fluid, but women may normally have as much fluid, but women may normally have as much as 20 mL depending on the phase of the as 20 mL depending on the phase of the menstrual cycle. menstrual cycle.

PATHOPHYSIOLOGYPATHOPHYSIOLOGYThe pathogenesis of ascites in patients with cirrhosis involves The pathogenesis of ascites in patients with cirrhosis involves

several mechanisms. several mechanisms. Portal hypertension results in decreased perfusion of hepatocytes Portal hypertension results in decreased perfusion of hepatocytes

with portal blood. This leads to increased reabsorption of sodium with portal blood. This leads to increased reabsorption of sodium and water by the kidney resulting in increased plasma volume and and water by the kidney resulting in increased plasma volume and increased portal flow. increased portal flow. Portal inflow increases but resistance within the liver is relatively fixed Portal inflow increases but resistance within the liver is relatively fixed

secondary to underlying hepatic fibrosis. This too results in portal secondary to underlying hepatic fibrosis. This too results in portal hypertension. hypertension.

Hepatic fibrosis also results in sinusoidal hypertension altering starling forces 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 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. perisinusoidal space into which microvilli of the hepatocytes protrude.

Patients with cirrhosis are often hypoalbuminemic and Patients with cirrhosis are often hypoalbuminemic and hypoalbuminemia also works to promote this movement of hypoalbuminemia also works to promote this movement of fluid into the Space of Disse. This fluid is removed by fluid into the Space of Disse. This fluid is removed by hepatic lymphatics. hepatic lymphatics.

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Hepatic lymph flow increases dramatically in response to Hepatic lymph flow increases dramatically in response to tissue edema. tissue edema. Normal thoracic duct lymph flow is 800-1000 cc per day. In patients Normal thoracic duct lymph flow is 800-1000 cc per day. In patients

with cirrhosis, hepatic lymph flow may approach 20 liters per day with cirrhosis, hepatic lymph flow may approach 20 liters per day exceeding the capacity of the thoracic duct and percolate from the exceeding the capacity of the thoracic duct and percolate from the liver capsule into the peritoneal cavity. liver capsule into the peritoneal cavity.

Also as a result of decreased perfusion of hepatocytes, Also as a result of decreased perfusion of hepatocytes, splanchnic vasodilation occurs. splanchnic vasodilation occurs.

This triggers the release of sympathetic neurotransmitters This triggers the release of sympathetic neurotransmitters further activating the renin-angiotensin-aldosterone axis. further activating the renin-angiotensin-aldosterone axis. This further stimulates sodium and water retention by the This further stimulates sodium and water retention by the kidney. It is important to note that renal function in kidney. It is important to note that renal function in patients with cirrhosis is disturbed long before ascites patients with cirrhosis is disturbed long before ascites forms.forms.

PATHOPHYSIOLOGYPATHOPHYSIOLOGYPortal Hypertension

7 Direct Reflex

Compensatory Pathways

Portosystemic CollateralsNitric Oxide Stimulation

Hyperdynamic State

Underfill Physiology, ↓ SVR

Overflow Physiology Plasma Volume Expression

Renal Na and Impaired Water Excretion

Lymphatics Overwhelmed(Hepatic, Planchnic, and Peritoneal)

Ascites

Hepatorenal Syndrome

7 Trigger

Portal Hypertension Process

Facilitating and opposing forces in ascites formation

Ambulatory patients with an episode of Ambulatory patients with an episode of cirrhotic ascites have a 3-year mortality rate cirrhotic ascites have a 3-year mortality rate of 50%. The development of refractory of 50%. The development of refractory ascites carries a poor prognosis, with a 1-year ascites carries a poor prognosis, with a 1-year survival rate of less than 50%.survival rate of less than 50%.

HISTORYHISTORY Most cases of ascites are due to liver disease. Patients often state that their increasing Most cases of ascites are due to liver disease. Patients often state that their increasing

abdominal girth has been noted for a short period.abdominal girth has been noted for a short period. Patients with ascites should be asked about risk factors for liver diseases. These include Patients with ascites should be asked about risk factors for liver diseases. These include

the following: the following: › Alcohol use and duration of use Alcohol use and duration of use › Chronic viral hepatitis or jaundice Chronic viral hepatitis or jaundice › Intravenous drug use Intravenous drug use › Sexual promiscuity Sexual promiscuity › Sexual orientation Sexual orientation › Transfusions: Hepatitis C has been linked to transfusions occurring before 1980. Transfusions: Hepatitis C has been linked to transfusions occurring before 1980. › Tattoos Tattoos › Habitation or origination from an area endemic for hepatitis Habitation or origination from an area endemic for hepatitis

Patients with alcoholic liver disease who intermittently cease or reduce alcohol 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 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 history of stable cirrhosis and then develops ascites, the possibility of superimposed hepatocellular carcinoma should be considered. hepatocellular carcinoma should be considered.

Obesity, hypercholesterolemia, and type 2 diabetes mellitus are now recognized causes of Obesity, hypercholesterolemia, and type 2 diabetes mellitus are now recognized causes of nonalcoholic steatohepatitis, which can progress to cirrhosis. nonalcoholic steatohepatitis, which can progress to cirrhosis.

Patients with a history of cancer, especially gastrointestinal cancer, are at risk for Patients with a history of cancer, especially gastrointestinal cancer, are at risk for malignant ascites. Malignancy-related ascites is frequently painful, whereas cirrhotic malignant ascites. Malignancy-related ascites is frequently painful, whereas cirrhotic ascites is usually painless. ascites is usually painless.

Patients who develop ascites in the setting of known diabetes or nephrotic syndrome may Patients who develop ascites in the setting of known diabetes or nephrotic syndrome may have nephrotic ascites.have nephrotic ascites.

PHYSICAL EXAMINATIONPHYSICAL EXAMINATION

The physical examination should focus on the signs of portal The physical examination should focus on the signs of portal hypertension and chronic liver disease.hypertension and chronic liver disease.

Physical findings suggestive of liver disease include jaundice, palmar Physical findings suggestive of liver disease include jaundice, palmar erythema, and spider angiomas. erythema, and spider angiomas.

The liver may be difficult to palpate if a large amount of ascites is 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 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 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 mL, ascites may be demonstrated by the presence of shifting dullness or bulging flanks. A fluid-wave sign is notoriously inaccurate. bulging flanks. A fluid-wave sign is notoriously inaccurate.

Elevated jugular venous pressure may suggest a cardiac origin of ascites. Elevated jugular venous pressure may suggest a cardiac origin of ascites. A firm nodule in the umbilicus, the so-called Sister Mary Joseph nodule, A firm nodule in the umbilicus, the so-called Sister Mary Joseph nodule, is not common but suggests peritoneal carcinomatosis originating from is not common but suggests peritoneal carcinomatosis originating from gastric, pancreatic, or hepatic primary malignancy. gastric, pancreatic, or hepatic primary malignancy.

A pathologic left-sided supraclavicular node (Virchow node) suggests A pathologic left-sided supraclavicular node (Virchow node) suggests the presence of upper abdominal malignancy. the presence of upper abdominal malignancy.

Patients with cardiac disease or nephrotic syndrome may have anasarca. Patients with cardiac disease or nephrotic syndrome may have anasarca.

CAUSES OF ASCITESCAUSES OF ASCITES Normal peritoneum Normal peritoneum

› Portal hypertension (serum-ascites albumin gradient [SAAG] >1.1 Portal hypertension (serum-ascites albumin gradient [SAAG] >1.1 g/dL) g/dL) Hepatic congestion, congestive heart failure, constrictive pericarditis, Hepatic congestion, congestive heart failure, constrictive pericarditis,

tricuspid insufficiency, Budd-Chiari syndrome tricuspid insufficiency, Budd-Chiari syndrome Liver disease, cirrhosis, alcoholic hepatitis, fulminant hepatic failure, massive Liver disease, cirrhosis, alcoholic hepatitis, fulminant hepatic failure, massive

hepatic metastaseshepatic metastases› Hypoalbuminemia (SAAG <1.1 g/dL) Hypoalbuminemia (SAAG <1.1 g/dL)

Nephrotic syndrome Nephrotic syndrome Protein-losing enteropathy Protein-losing enteropathy Severe malnutrition with anasarcaSevere malnutrition with anasarca

› Miscellaneous conditions (SAAG <1.1 g/dL) Miscellaneous conditions (SAAG <1.1 g/dL) Chylous ascites Chylous ascites Pancreatic ascites Pancreatic ascites Bile ascites Bile ascites Nephrogenic ascites Nephrogenic ascites Urine ascites Urine ascites Ovarian diseaseOvarian disease

CAUSES OF ASCITESCAUSES OF ASCITES› Diseased peritoneum (SAAG <1.1 g/dL) Diseased peritoneum (SAAG <1.1 g/dL) › Infections Infections

Bacterial peritonitis Bacterial peritonitis Tuberculous peritonitis Tuberculous peritonitis Fungal peritonitis Fungal peritonitis HIV-associated peritonitisHIV-associated peritonitis

› Malignant conditions Malignant conditions Peritoneal carcinomatosis Peritoneal carcinomatosis Primary mesothelioma Primary mesothelioma Pseudomyxoma peritonei Pseudomyxoma peritonei Hepatocellular carcinomaHepatocellular carcinoma

› Other rare conditions Other rare conditions Familial Mediterranean fever Familial Mediterranean fever Vasculitis Vasculitis Granulomatous peritonitis Granulomatous peritonitis Eosinophilic peritonitisEosinophilic peritonitis

CHARACTERISTICS OF ASCITIC FLUID CHARACTERISTICS OF ASCITIC FLUID IN VARIOUS DISEASE STATES IN VARIOUS DISEASE STATES

ConditionCondition Gross Gross AppearancAppearancee

Protein, Protein, g/Lg/L

Serum-Serum-Ascites Ascites Albumin Albumin Gradient, Gradient, g/dLg/dL

Cell CountCell Count Other Other TestsTestsRed Blood Red Blood

Cells, Cells, >10,000/L>10,000/L

White Blood White Blood Cells, per LCells, per L

CirrhosisCirrhosis Straw-colored Straw-colored or bile-stainedor bile-stained

<25 (95%)<25 (95%) >1.1>1.1 1%1% <250 (90%)<250 (90%)aa; ; predominantly predominantly mesothelialmesothelial

NeoplasmNeoplasm Straw-colored, Straw-colored, hemorrhagic, hemorrhagic, mucinous, or mucinous, or chylouschylous

>25 (75%)>25 (75%) <1.1<1.1 20%20% >1000 (50%); >1000 (50%); variable cell variable cell typestypes

Cytology, cell Cytology, cell block, block, peritoneal peritoneal biopsybiopsy

Tuberculous Tuberculous peritonitis peritonitis

Clear, turbid, Clear, turbid, hemorrhagic, hemorrhagic, chylouschylous

>25 (50%)>25 (50%) <1.1<1.1 7%7% >1000 (70%); >1000 (70%); usually >70% usually >70% lymphocyteslymphocytes

Peritoneal Peritoneal biopsy, stain biopsy, stain and culture for and culture for acid-fast acid-fast bacillibacilli

Pyogenic Pyogenic peritonitisperitonitis

Turbid or Turbid or purulent purulent

If purulent, If purulent, >25>25

<1.1<1.1 UnusualUnusual Predominantly Predominantly polymorphonupolymorphonuclear clear leukocytesleukocytes

Positive Positive Gram's stain, Gram's stain, culture culture

Congestive Congestive heart failure heart failure

Straw-coloredStraw-colored Variable, 15–Variable, 15–5353

>1.1>1.1 10%10% <1000 (90%); <1000 (90%); usually usually mesothelial, mesothelial, mononuclearmononuclear

NephrosisNephrosis Straw-colored Straw-colored or chylousor chylous

<25 (100%)<25 (100%) <1.1<1.1 UnusualUnusual <250; <250; mesothelial, mesothelial, mononuclearmononuclear

If chylous, If chylous, ether ether extraction, extraction, Sudan stainingSudan staining

Pancreatic Pancreatic ascites ascites (pancreatitis, (pancreatitis, pseudocyst)pseudocyst)

Turbid, Turbid, hemorrhagic, hemorrhagic, or chylousor chylous

Variable, often Variable, often >25>25

<1.1<1.1 Variable, may Variable, may be blood-be blood-stainedstained

VariableVariable Increased Increased amylase in amylase in ascitic fluid ascitic fluid and serumand serum

DIFFERENTIAL DIAGNOSESDIFFERENTIAL DIAGNOSES

ASCITIC LIQUIDASCITIC LIQUID

paracentesisparacentesis

LABORATORY STUDIESLABORATORY STUDIES› Total proteinTotal protein: :

› In the past, ascitic fluid has been classified as an exudate if the 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 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 approximately 56% for detecting exudative causes. The total protein level may provide additional clues when used with the SAAG. An level may provide additional clues when used with the SAAG. An elevated SAAG and a high protein level are observed in most cases of elevated SAAG and a high protein level are observed in most cases of ascites due to hepatic congestion. Those patients with malignant ascites ascites due to hepatic congestion. Those patients with malignant ascites have a low SAAG and a high protein levelhave a low SAAG and a high protein level

› Culture/Gram stainCulture/Gram stain: : › The sensitivity with bedside inoculation of blood culture bottles with The sensitivity with bedside inoculation of blood culture bottles with

ascites results in 92% detection of bacterial growth in neutrocytic ascites results in 92% detection of bacterial growth in neutrocytic ascites. Gram stain is only 10% sensitive for helping visualize bacteria ascites. Gram stain is only 10% sensitive for helping visualize bacteria in early-detected spontaneous bacterial peritonitis. Approximately in early-detected spontaneous bacterial peritonitis. Approximately 10,000 bacteria/mL are required for detection by Gram stain; the median 10,000 bacteria/mL are required for detection by Gram stain; the median concentration of bacteria in spontaneous bacterial peritonitis is 1 concentration of bacteria in spontaneous bacterial peritonitis is 1 organism/mL. organism/mL.

› CytologyCytology: : › Cytology smear results are reported to be 58-75% sensitive for helping Cytology smear results are reported to be 58-75% sensitive for helping

detect malignant ascites. detect malignant ascites.

IMAGING STUDIESIMAGING STUDIES

Chest and plain abdominal films Chest and plain abdominal films › Elevation of the diaphragm, with or without sympathetic pleural Elevation of the diaphragm, with or without sympathetic pleural

effusions (hepatic hydrothorax), is visible in the presence of effusions (hepatic hydrothorax), is visible in the presence of massive ascites. More than 500 mL of fluid is usually required massive ascites. More than 500 mL of fluid is usually required for ascites to be diagnosed based on findings from abdominal for ascites to be diagnosed based on findings from abdominal films. films.

› Many nonspecific signs indicate ascites, such as diffuse Many nonspecific signs indicate ascites, such as diffuse abdominal haziness, bulging of the flanks, indistinct psoas abdominal haziness, bulging of the flanks, indistinct psoas margins, poor definition of the intra-abdominal organs, erect margins, poor definition of the intra-abdominal organs, erect position density increase, separation of small bowel loops, and position density increase, separation of small bowel loops, and centralization of floating gas containing small bowel. centralization of floating gas containing small bowel.

Abdominal ultrasound

IMAGING STUDIESIMAGING STUDIES Ultrasound Ultrasound

› Real-time sonography is the easiest and most sensitive technique Real-time sonography is the easiest and most sensitive technique for the detection of ascitic fluid.. Free ascites does not displace for the detection of ascitic fluid.. Free ascites does not displace organs but typically situates itself between them, contouring to organs but typically situates itself between them, contouring to organ margins and demonstrating acute angles at the point at which organ margins and demonstrating acute angles at the point at which the fluid borders the organ. the fluid borders the organ.

› The smallest amounts of fluid tend to collect in the Morison pouch The smallest amounts of fluid tend to collect in the Morison pouch and around the liver as a sonolucent band. With massive ascites, and around the liver as a sonolucent band. With massive ascites, the small bowel loops have a characteristic polycyclic, "lollipop," the small bowel loops have a characteristic polycyclic, "lollipop," or arcuate appearance because they are arrayed on either side of the or arcuate appearance because they are arrayed on either side of the vertically floating mesentery. vertically floating mesentery.

› Certain sonographic findings suggest that the ascites may be Certain sonographic findings suggest that the ascites may be infected, inflammatory, or malignant... infected, inflammatory, or malignant...

› Most patients (95%) with carcinomatous peritonitis have a Most patients (95%) with carcinomatous peritonitis have a gallbladder wall that is less than 3 mm thick. The thickening of the gallbladder wall that is less than 3 mm thick. The thickening of the gallbladder is primarily a reflection of cirrhosis and portal gallbladder is primarily a reflection of cirrhosis and portal hypertension. hypertension.

IMAGING STUDIESIMAGING STUDIES CT scan: CT scan:

Ascites is demonstrated well on CT scan images. Small amounts Ascites is demonstrated well on CT scan images. Small amounts of ascitic fluid localize in the right perihepatic space, the of ascitic fluid localize in the right perihepatic space, the posterior subhepatic space (Morison pouch), and the Douglas posterior subhepatic space (Morison pouch), and the Douglas pouch. A number of CT features suggest neoplasia. Hepatic, pouch. A number of CT features suggest neoplasia. Hepatic, adrenal, splenic, or lymph node lesions associated with masses adrenal, splenic, or lymph node lesions associated with masses arising from the gut, ovary, or pancreas are suggestive of arising from the gut, ovary, or pancreas are suggestive of malignant ascites. Patients with malignant ascites tend to have malignant ascites. Patients with malignant ascites tend to have proportional fluid collections in the greater and lesser sacs; proportional fluid collections in the greater and lesser sacs; whereas, in patients with benign ascites, the fluid is observed whereas, in patients with benign ascites, the fluid is observed primarily in the greater sac and not in the lesser omental bursae. primarily in the greater sac and not in the lesser omental bursae.

PROCEDURESPROCEDURES Abdominal paracentesis: Abdominal paracentesis is the Abdominal paracentesis: Abdominal paracentesis is the

most rapid and perhaps the most cost-effective method most rapid and perhaps the most cost-effective method of diagnosing the cause of ascites formation. Therapeutic of diagnosing the cause of ascites formation. Therapeutic paracentesis may be performed for refractory or tense paracentesis may be performed for refractory or tense ascites. The removal of 5 L of fluid is considered large-ascites. The removal of 5 L of fluid is considered large-volume paracentesis. Total paracentesis, ie, removal of volume paracentesis. Total paracentesis, ie, removal of all ascites (even >20 L), can usually be performed all ascites (even >20 L), can usually be performed safely. Recent studies demonstrate that supplementing 5 safely. Recent studies demonstrate that supplementing 5 g of albumin per each liter over 5 L decreases g of albumin per each liter over 5 L decreases complications of paracentesis, such as electrolyte complications of paracentesis, such as electrolyte imbalances, and increases in serum creatinine secondary imbalances, and increases in serum creatinine secondary to large shifts of intravascular volume. to large shifts of intravascular volume.

STAGINGSTAGING Ascites may be semiquantified using the Ascites may be semiquantified using the

following system: following system: – Stage 1+ is detectable only after careful Stage 1+ is detectable only after careful

examination. examination. – Stage 2+ is easily detectable but of relatively Stage 2+ is easily detectable but of relatively

small volume. small volume. – Stage 3+ is obvious ascites but not tense ascites. Stage 3+ is obvious ascites but not tense ascites. – Stage 4+ is tense ascites.Stage 4+ is tense ascites.

ParacentesisParacentesis

IntroductionIntroduction

Paracentesis is a procedure in which a Paracentesis is a procedure in which a needle or catheter is inserted into the needle or catheter is inserted into the peritoneal cavity to obtain ascitic fluid for peritoneal cavity to obtain ascitic fluid for diagnostic or therapeutic purposes.diagnostic or therapeutic purposes.

IndicationsIndications

Diagnostic tap Diagnostic tap – New onset ascites: Evaluate fluid to help determine New onset ascites: Evaluate fluid to help determine

etiology, to differentiate transudate versus exudate, to etiology, to differentiate transudate versus exudate, to detect the presence of cancerous cells, or to address detect the presence of cancerous cells, or to address other considerations. other considerations.

– Suspected spontaneous or secondary bacterial Suspected spontaneous or secondary bacterial peritonitisperitonitis

Therapeutic tap Therapeutic tap – Respiratory distress secondary to ascites Respiratory distress secondary to ascites – Abdominal pain or pressure secondary to ascitesAbdominal pain or pressure secondary to ascites

ContraindicationsContraindicationsAbsoluteAbsolute Acute abdomen that requires surgeryAcute abdomen that requires surgeryRelativeRelative Severe thrombocytopenia (platelet count <20 X 10 Severe thrombocytopenia (platelet count <20 X 1033/μL), coagulopathy /μL), coagulopathy

(international normalized ratio [INR] >2.0), or both(international normalized ratio [INR] >2.0), or both– Patients with an INR greater than 2.0 should receive fresh frozen plasma (FFP) prior to 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 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. procedure and then perform the procedure while the second unit is infusing.

– Patients with platelet counts less than 20 X 10Patients with platelet counts less than 20 X 1033/μL should receive an infusion of /μL should receive an infusion of platelets prior to performing the procedure.platelets prior to performing the procedure.

In patients without clinical evidence of active bleeding, routine labs such as In patients without clinical evidence of active bleeding, routine labs such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet counts may not be needed prior to the procedure.platelet counts may not be needed prior to the procedure.5 5 In these patients, In these patients, pretreatment with FFP, platelets, or both before the paracentesis is also pretreatment with FFP, platelets, or both before the paracentesis is also probably not needed. probably not needed.

Pregnancy Pregnancy Distended urinary bladder Distended urinary bladder Abdominal wall cellulitis Abdominal wall cellulitis Distended bowel Distended bowel Intra-abdominal adhesionsIntra-abdominal adhesions

Treatment and MedicationTreatment and Medication

AnesthesiaAnesthesia Local anesthesia is used.Local anesthesia is used. EquipmentEquipment Disposable paracentesis/thoracentesis kitsDisposable paracentesis/thoracentesis kits

Antiseptic swab sticks Antiseptic swab sticks Fenestrated drape Fenestrated drape Lidocaine 1%, 5-mL ampule Lidocaine 1%, 5-mL ampule Syringe, 10 mL Syringe, 10 mL Injection needles, 22 gauge (ga), 2 Injection needles, 22 gauge (ga), 2 Injection needle, 25 ga Injection needle, 25 ga Scalpel, No. 11 blade Scalpel, No. 11 blade Eight-French catheter over 18 ga x 7 1/2" needle with 3-way stopcock, self-sealing 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 valve, and a 5-mL Luer-Lock syringe Syringe, 60 mL Syringe, 60 mL Introducer needle, 20 ga Introducer needle, 20 ga Tubing set with roller clamp Tubing set with roller clamp Drainage bag or vacuum container Drainage bag or vacuum container Specimen vials or collection bottles, 3 Specimen vials or collection bottles, 3 Gauze, 4 x 4 inch Gauze, 4 x 4 inch Adhesive dressingAdhesive dressing

PositioningPositioning The two recommended areas of The two recommended areas of

abdominal wall entry for paracentesis abdominal wall entry for paracentesis are as follows (see photo):are as follows (see photo):– Two centimeters below the umbilicus in Two centimeters below the umbilicus in

the midline (through the linea alba) the midline (through the linea alba) – Five centimeters superior and medial to Five centimeters superior and medial to

the anterior superior iliac spines on either the anterior superior iliac spines on either sideside

Recommended routine use of Recommended routine use of ultrasonography to verify the presence ultrasonography to verify the presence of a fluid pocket under the selected of a fluid pocket under the selected entry site in order to increase the rate entry site in order to increase the rate of success.of success.6 6 The ultrasound also helps The ultrasound also helps the physician avoid a distended the physician avoid a distended urinary bladder or small bowel urinary bladder or small bowel adhesions below the selected entry adhesions below the selected entry point. To minimize complications, point. To minimize complications, avoid areas of prominent veins (caput avoid areas of prominent veins (caput medusa), infected skin, or scar tissue.medusa), infected skin, or scar tissue.

• Patients with severe ascites can be positioned supine. Patients with mild ascites may need to be positioned in the lateral decubitus position, with the skin 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.

TechniqueTechnique

Apply a sterile fenestrated drape to create a sterile field.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 Use the No. 11 scalpel blade to make a small nick in the skin to allow an easier catheter nick in the skin to allow an easier catheter passage.passage.

Insert the needle directly perpendicular to the Insert the needle directly perpendicular to the selected skin entry point. Slow insertion in selected skin entry point. Slow insertion in increments of 5 mm is preferred to minimize the increments of 5 mm is preferred to minimize the risk of inadvertent vascular entry or puncture of risk of inadvertent vascular entry or puncture of the small bowel.the small bowel.

Continuously apply negative pressure to the syringe as Continuously apply negative pressure to the syringe as the needle is advanced. Upon entry to the peritoneal the needle is advanced. Upon entry to the peritoneal cavity, loss of resistance is felt and ascitic fluid can be cavity, loss of resistance is felt and ascitic fluid can be seen filling the syringe. At this point, advance the seen filling the syringe. At this point, advance the device 2-5 mm into the peritoneal cavity to prevent device 2-5 mm into the peritoneal cavity to prevent misplacement during catheter advancement. In general, misplacement during catheter advancement. In general, avoid advancing the needle deeper than the safety mark avoid advancing the needle deeper than the safety mark that is present on most commercially available that is present on most commercially available catheters or deeper than 1 cm beyond the depth at catheters or deeper than 1 cm beyond the depth at which ascitic fluid was noticed in the lidocaine syringe.which ascitic fluid was noticed in the lidocaine syringe.

Use one hand to firmly hold the needle Use one hand to firmly hold the needle and syringe in place to prevent the needle and syringe in place to prevent the needle from entering further into the peritoneal from entering further into the peritoneal cavity.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-While holding the stopcock, pull the needle out. The self-sealing valve prevents fluid leak. sealing valve prevents fluid leak.

Attach the 60-mL syringe to the 3-way stopcock and Attach the 60-mL syringe to the 3-way stopcock and aspirate to obtain ascitic fluid and distribute it to the aspirate to obtain ascitic fluid and distribute it to the specimen vials. Use the 3-way valve, as needed, to control specimen vials. Use the 3-way valve, as needed, to control fluid flow and prevent leakage when no syringe or tubing fluid flow and prevent leakage when no syringe or tubing is attached.is attached.

Connect one end of the fluid collection tubing to Connect one end of the fluid collection tubing to the stopcock and the other end to a vacuum bottle the stopcock and the other end to a vacuum bottle or a drainage bag.or a drainage bag.

The catheter can become occluded by a loop of The catheter can become occluded by a loop of bowel or omentum. If the flow stops, kink the bowel or omentum. If the flow stops, kink the tubing to break the vacuum and try to slightly tubing to break the vacuum and try to slightly change the patient's position. Then undo the kink in change the patient's position. Then undo the kink in the tubing to see if the flow resumes. the tubing to see if the flow resumes.

Remove the catheter after the desired amount of Remove the catheter after the desired amount of ascitic fluid has been drained. Apply firm pressure, ascitic fluid has been drained. Apply firm pressure, as necessary, to stop bleeding, if present. Place a as necessary, to stop bleeding, if present. Place a bandage over the skin puncture site.bandage over the skin puncture site.

ComplicationsComplications Failed attempt to collect peritoneal fluid Failed attempt to collect peritoneal fluid Persistent leak from the puncture site Persistent leak from the puncture site

– In cases with a persistent leak, a single skin suture might solve the problem. 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.The application of an ostomy bag around the puncture site keeps the leak contained until it is eventually sealed off.

Wound infection Wound infection Abdominal wall hematoma Abdominal wall hematoma Spontaneous hemoperitoneum: This rare complication is due to mesenteric variceal bleeding after removal Spontaneous hemoperitoneum: This rare complication is due to mesenteric variceal bleeding after removal

of a large amount of ascitic fluid (>4 L). of a large amount of ascitic fluid (>4 L). Hollow viscous perforation (small or large bowel, stomach, bladder) Hollow viscous perforation (small or large bowel, stomach, bladder) Catheter laceration and loss in abdominal cavity Catheter laceration and loss in abdominal cavity Laceration of major blood vessel (aorta, mesenteric artery, iliac artery) Laceration of major blood vessel (aorta, mesenteric artery, iliac artery) Postparacentesis hypotension Postparacentesis hypotension

– This delayed complication may occur more than 12 hours after a procedure in which large volumes are taken off. 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, 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.though no difference in survival has been noted relative to other plasma expanders.8 8

Dilutional hyponatremia Dilutional hyponatremia Hepatorenal syndromeHepatorenal syndrome

LaboratoryLaboratory Depending on the clinical situation, fluid may be sent for the following Depending on the clinical situation, fluid may be sent for the following

laboratory tests:laboratory tests:

Gram stain Gram stain Cell count (elevated counts may suggest infection) Cell count (elevated counts may suggest infection) Bacterial culture Bacterial culture Total protein level Total protein level Triglyceride levels (elevated in chylous ascites) Triglyceride levels (elevated in chylous ascites) Bilirubin level (may be elevated in bowel perforation) Bilirubin level (may be elevated in bowel perforation) Glucose level Glucose level Albumin level, used in conjunction with serum albumin levels obtained Albumin level, used in conjunction with serum albumin levels obtained

the same day (used to calculate serum-ascitic albumin gradient [SAAG]) the same day (used to calculate serum-ascitic albumin gradient [SAAG]) Amylase level (elevation suggests pancreatic source) Amylase level (elevation suggests pancreatic source) LDH level LDH level CytologyCytology

A variety of approaches may be utilized for A variety of approaches may be utilized for obtaining a liver tissue specimen. obtaining a liver tissue specimen.

These include a blind percutaneous These include a blind percutaneous approach after percussion of the chest wall, approach after percussion of the chest wall, biopsy under ultrasound or CT guidance, biopsy under ultrasound or CT guidance, intravascular tissue sampling via the hepatic intravascular tissue sampling via the hepatic vein, and intra-abdominal biopsy at vein, and intra-abdominal biopsy at laparoscopy or laparotomy.laparoscopy or laparotomy.

Although liver biopsy is generally safe and is Although liver biopsy is generally safe and is currently considered the criterion standard for currently considered the criterion standard for the evaluation of hepatic inflammation and the evaluation of hepatic inflammation and fibrosis, sampling error, rare complications, and fibrosis, sampling error, rare complications, and occasionally significant patient anxiety do occasionally significant patient anxiety do occur. occur.

These factors have led to keen interest in the These factors have led to keen interest in the development of noninvasive tests of hepatic development of noninvasive tests of hepatic fibrosis. fibrosis.

Several modalities of these tests are currently Several modalities of these tests are currently under investigation, and 2 serum tests are now under investigation, and 2 serum tests are now commercially available in the United States.commercially available in the United States.

Complications of liver biopsy are rare but Complications of liver biopsy are rare but potentially lethal. potentially lethal.

A thorough understanding of the A thorough understanding of the indications, contraindications, techniques, indications, contraindications, techniques, and common complications and their and common complications and their management is imperative.management is imperative.

Liver biopsy, in combination with history and physical Liver biopsy, in combination with history and physical examination data, is a powerful clinical tool for diagnosing examination data, is a powerful clinical tool for diagnosing and treating liver disease. Indications for obtaining a and treating liver disease. Indications for obtaining a biopsy specimen are listed in as follows. These are divided biopsy specimen are listed in as follows. These are divided according to the type of clinical question framed.according to the type of clinical question framed.– Evaluation of abnormal hepatic laboratory test results Evaluation of abnormal hepatic laboratory test results – Confirmation of diagnosis and prognostication Confirmation of diagnosis and prognostication – Suspected hepatic neoplasm Suspected hepatic neoplasm – Diagnosis of cholestatic liver disease Diagnosis of cholestatic liver disease – Evaluation of infiltrative or granulomatous disease Evaluation of infiltrative or granulomatous disease – Following a case of liver transplantation to evaluate and Following a case of liver transplantation to evaluate and

manage rejection manage rejection – To evaluate unexplained jaundice or suspected drug reactionsTo evaluate unexplained jaundice or suspected drug reactions

The biopsy specimen may be used to identify The biopsy specimen may be used to identify or exclude possible etiologies for physical or or exclude possible etiologies for physical or laboratory abnormalities. laboratory abnormalities.

various disease states may present similarly, various disease states may present similarly, diagnostic histologic patterns exist when used diagnostic histologic patterns exist when used in the context of clinical presentation. in the context of clinical presentation.

Infiltration of the hepatic parenchyma by fat Infiltration of the hepatic parenchyma by fat may exist in diseases due to alcohol abuse, may exist in diseases due to alcohol abuse, hepatitis C, diabetes, and/or obesity. For each hepatitis C, diabetes, and/or obesity. For each disease state, histologic clues exist that disease state, histologic clues exist that distinguish one from the other.distinguish one from the other.

Another indication for biopsy is the determination of the Another indication for biopsy is the determination of the extent of histologic change present in a biopsy specimen. extent of histologic change present in a biopsy specimen.

This involves scoring systems for the degrees of This involves scoring systems for the degrees of inflammation and fibrosis noted by the pathologist. inflammation and fibrosis noted by the pathologist.

Many systems exist for describing the microscopic Many systems exist for describing the microscopic findings, ranging from simplistic to complex. findings, ranging from simplistic to complex.

The majority of scoring systems report the degree of The majority of scoring systems report the degree of inflammation as the grade of the disease and the amount inflammation as the grade of the disease and the amount of fibrosis as the stage. of fibrosis as the stage.

An example here would be the finding of moderate An example here would be the finding of moderate inflammation (grade 3) in a specimen from a cirrhotic inflammation (grade 3) in a specimen from a cirrhotic (stage 4) liver.(stage 4) liver.

The third set of indications is the monitoring of The third set of indications is the monitoring of the progression of disease or of treatment the progression of disease or of treatment efficacy. efficacy.

For example, liver biopsy specimens frequently For example, liver biopsy specimens frequently are used to evaluate and treat rejection following are used to evaluate and treat rejection following liver transplantation. liver transplantation.

Repeated biopsies are used less frequently to Repeated biopsies are used less frequently to monitor progression of diseases such as primary monitor progression of diseases such as primary biliary cirrhosis, chronic hepatitis C, or alcoholic biliary cirrhosis, chronic hepatitis C, or alcoholic liver disease.liver disease.

Contraindications to percutaneous liver biopsy are Contraindications to percutaneous liver biopsy are relatively few, but identifying contraindications is relatively few, but identifying contraindications is important to avoid the major complications associated important to avoid the major complications associated with the procedure. Contraindications to liver biopsy with the procedure. Contraindications to liver biopsy include the following:include the following:– Increased prothrombin time, international normalized ratio Increased prothrombin time, international normalized ratio

(INR) greater than 1.6 (INR) greater than 1.6 – Thrombocytopenia, platelet count less than 60,000 Thrombocytopenia, platelet count less than 60,000 – Ascites (transjugular route preferred) Ascites (transjugular route preferred) – Difficult body habitus (transjugular route preferred) Difficult body habitus (transjugular route preferred) – Suspected hemangioma Suspected hemangioma – Suspected echinococcal infection Suspected echinococcal infection – Uncooperative patientUncooperative patient

A variety of needle types is A variety of needle types is available for obtaining a available for obtaining a liver biopsy specimen. liver biopsy specimen.

Needles may be divided Needles may be divided into 3 broad categories—into 3 broad categories—suction needles (Jamshidi, suction needles (Jamshidi, Klatskin, and Menghini), Klatskin, and Menghini), cutting needles (Tru-cut and cutting needles (Tru-cut and Vim-Silverman), and Vim-Silverman), and spring-loaded cutting spring-loaded cutting needles. needles.

Each needle type has Each needle type has proposed advantages and proposed advantages and disadvantages.disadvantages.

Patient preparation prior to undertaking a liver biopsy is essential. Patient preparation prior to undertaking a liver biopsy is essential. Ideally, education should begin during an office visit prior to the Ideally, education should begin during an office visit prior to the

biopsy. biopsy. Explain the procedure in sufficient detail, with careful attention to Explain the procedure in sufficient detail, with careful attention to

anxiety and pain management issues. anxiety and pain management issues. Discontinue aspirin 1 week prior to the procedure. Discontinue aspirin 1 week prior to the procedure. Nonsteroidal anti-inflammatory drugs should be stopped 3 days prior Nonsteroidal anti-inflammatory drugs should be stopped 3 days prior

to the biopsy procedure. to the biopsy procedure. The patient may, or may not, be asked to complete an overnight fast. The patient may, or may not, be asked to complete an overnight fast. Eating prior to the procedure allows for gallbladder contraction, Eating prior to the procedure allows for gallbladder contraction,

reducing the risk of gallbladder puncture. reducing the risk of gallbladder puncture. An empty stomach may decrease the likelihood of postprocedure An empty stomach may decrease the likelihood of postprocedure

nausea and vomiting, however. Tnausea and vomiting, however. T his is an important consideration because many biopsies are preformed his is an important consideration because many biopsies are preformed

under light sedation.under light sedation.

The patient must remain within 30 minutes of the facility at which the The patient must remain within 30 minutes of the facility at which the biopsy was performed. biopsy was performed.

The patient must be accompanied by a reliable person the first night The patient must be accompanied by a reliable person the first night after the procedure. after the procedure.

The patient should have no contraindications or conditions that The patient should have no contraindications or conditions that increase the risk associated with the procedure. increase the risk associated with the procedure.

The facility where the biopsy is performed should have an approved The facility where the biopsy is performed should have an approved blood bank, laboratory, inpatient bed, and personnel available to the blood bank, laboratory, inpatient bed, and personnel available to the patient for at least 6 hours postprocedure. (Note: Many centers patient for at least 6 hours postprocedure. (Note: Many centers routinely observe patients for only 2-4 hours postbiopsy, and recently routinely observe patients for only 2-4 hours postbiopsy, and recently published data indicate that discharge following 1 hour of observation published data indicate that discharge following 1 hour of observation does not appear to affect patient safety. If this results in a change in does not appear to affect patient safety. If this results in a change in practice habits, it may significantly lower costs associated with practice habits, it may significantly lower costs associated with percutaneous liver biopsy.) percutaneous liver biopsy.)

Hospitalization should accompany evidence of bleeding, bile leak, Hospitalization should accompany evidence of bleeding, bile leak, pneumothorax, or pain requiring more than one analgesic dose.pneumothorax, or pain requiring more than one analgesic dose.

On the day of the biopsy, review recent laboratory evaluation of On the day of the biopsy, review recent laboratory evaluation of prothrombin time and complete blood count, including platelets. prothrombin time and complete blood count, including platelets. Explain the procedure to the patient and obtain informed consent.Explain the procedure to the patient and obtain informed consent.

Place the patient supine, remove pillows, and elevate the right arm 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 behind the head. The legs and feet may be angled to the left to further open the right intercostal spaces. further open the right intercostal spaces.

Percuss the right trunk to the point of maximum dullness during Percuss the right trunk to the point of maximum dullness during both inspiration and expiration. both inspiration and expiration.

This frequently corresponds to a point along the midaxillary line at This frequently corresponds to a point along the midaxillary line at the second or third intercostal space above the costal margin. Mark the second or third intercostal space above the costal margin. Mark this location with a surgical pen or other method.this location with a surgical pen or other method.

Ultrasound or CT imaging may be useful, particularly if obtaining a Ultrasound or CT imaging may be useful, particularly if obtaining a biopsy of a particular region or mass within the liver is desired. biopsy of a particular region or mass within the liver is desired. Some have advocated that all biopsies be performed under Some have advocated that all biopsies be performed under ultrasound guidance; however, whether this reduces procedure-ultrasound guidance; however, whether this reduces procedure-related morbidity or is cost effective is controversial. related morbidity or is cost effective is controversial.

Once a suitable site has been identified, sterile technique is Once a suitable site has been identified, sterile technique is employed. Prepare the field with Betadine solution and place sterile employed. Prepare the field with Betadine solution and place sterile drapes. drapes.

Administer local anesthesia with 1% lidocaine in both superficial and deep Administer local anesthesia with 1% lidocaine in both superficial and deep planes. planes.

Patients occasionally notice a pain described as burning or shooting in Patients occasionally notice a pain described as burning or shooting in quality that radiates either transversely or to the right shoulder region. This 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 pain is thought to represent contact of the anesthetic with the capsule of the liver.the liver.

Once adequate anesthesia has been obtained, a small nick in the skin is 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. made with a surgical blade to allow introduction of the biopsy needle.

The biopsy needle is introduced within close proximity to the upper aspect 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 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. needle is introduced, a series of several successive "pops" may be felt.

Small amounts of saline contained in the syringe are flushed until Small amounts of saline contained in the syringe are flushed until resistance is encountered. The resistance is the liver edge; at this point, the resistance is encountered. The resistance is the liver edge; at this point, the needle is withdrawn slightly and flushed again to remove debris. 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 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 hold his/her breath. This shrinks the lung field and minimizes the risk of perforating the gallbladder, while bringing the liver against the thorax perforating the gallbladder, while bringing the liver against the thorax wall. The biopsy sample is obtained. Pressure is applied to the site, 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 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 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 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 first hour, every 30 minutes during the second hour, and then hourly until discharge.discharge.

Complications of liver biopsy occur rarely but potentially are lethal. Complications of liver biopsy occur rarely but potentially are lethal. The majority (60%) of complications occur within the first 2 hours, The majority (60%) of complications occur within the first 2 hours,

and 96% occur during the first 24 hours following the procedure. and 96% occur during the first 24 hours following the procedure. Approximately 2% of patients undergoing biopsy require Approximately 2% of patients undergoing biopsy require hospitalization for the management of an adverse event. Vasovagal hospitalization for the management of an adverse event. Vasovagal episode and pain are the most common reasons for admission.episode and pain are the most common reasons for admission.

Pain occurs in approximately 30% of patients undergoing a liver Pain occurs in approximately 30% of patients undergoing a liver biopsy. biopsy.

It often is described as a dull ache in the right upper quadrant or It often is described as a dull ache in the right upper quadrant or shoulder and typically is relatively short in duration, lasting less shoulder and typically is relatively short in duration, lasting less than 2 hours. than 2 hours.

This pain often responds to analgesics. Unrelenting, severe This pain often responds to analgesics. Unrelenting, severe abdominal pain is alarming, possibly indicating a serious abdominal pain is alarming, possibly indicating a serious complication such as intraperitoneal hemorrhage or biliary leak.complication such as intraperitoneal hemorrhage or biliary leak.

Bleeding comprises a second group of complications. Bleeding comprises a second group of complications. Presentations include:Presentations include:– subcapsular or parenchymal hematoma, subcapsular or parenchymal hematoma, – hemobilia, hemobilia, – free intraperitoneal hemorrhage. free intraperitoneal hemorrhage.

Intrahepatic or subcapsular hematomas are the most Intrahepatic or subcapsular hematomas are the most common of the bleeding complications and are noted on common of the bleeding complications and are noted on approximately 23% of ultrasound images obtained approximately 23% of ultrasound images obtained following biopsy. following biopsy.

Such findings often are incidental, without associated Such findings often are incidental, without associated clinical symptoms. clinical symptoms.

They occur at similar rates after either blind or laparoscopy-They occur at similar rates after either blind or laparoscopy-guided modalities, but incidence may be influenced by guided modalities, but incidence may be influenced by needle type and imaging technique. needle type and imaging technique.

Large hematomas are a rare cause of biliary obstruction. Large hematomas are a rare cause of biliary obstruction. Symptomatic hematomas should be imaged by ultrasound Symptomatic hematomas should be imaged by ultrasound

but usually respond to conservative treatment with but usually respond to conservative treatment with analgesics.analgesics.

Hemobilia presents as biliary colic, gastrointestinal bleeding, and Hemobilia presents as biliary colic, gastrointestinal bleeding, and jaundice. It is a rare complication of biopsy; one study of 68,276 jaundice. It is a rare complication of biopsy; one study of 68,276 biopsies reported 4 instances of hemobilia. biopsies reported 4 instances of hemobilia.

Clinical presentation ranges from chronic anemia to rapid Clinical presentation ranges from chronic anemia to rapid exsanguination. Hemobilia typically develops later than other exsanguination. Hemobilia typically develops later than other complications. complications.

The average time to onset of symptoms is 5 days following the The average time to onset of symptoms is 5 days following the procedure, but onset may occur earlier. Conservative treatment often is procedure, but onset may occur earlier. Conservative treatment often is sufficient.sufficient.

Biliary peritonitis is another noteworthy complication, although rare.Biliary peritonitis is another noteworthy complication, although rare. Severe abdominal pain and vasovagal hypotension herald its Severe abdominal pain and vasovagal hypotension herald its

occurrence. Analgesics and fluid management usually are sufficient, occurrence. Analgesics and fluid management usually are sufficient, but persistence of the condition may necessitate endoscopic retrograde but persistence of the condition may necessitate endoscopic retrograde cholangiopancreatography with stent placement.cholangiopancreatography with stent placement.

Intraperitoneal hemorrhage is the most serious of the bleeding Intraperitoneal hemorrhage is the most serious of the bleeding complications. It is an early occurrence, most often observed during the complications. It is an early occurrence, most often observed during the first few hours following the procedure, although reports of this first few hours following the procedure, although reports of this complication as long as 24 hours postprocedure have been noted. complication as long as 24 hours postprocedure have been noted.

Late hemorrhage is associated with a poor outcome.Late hemorrhage is associated with a poor outcome. Bacteremia, pneumothorax, and accidental biopsy of other organs are Bacteremia, pneumothorax, and accidental biopsy of other organs are

rare complications. Their frequencies are outlined below.rare complications. Their frequencies are outlined below.

Pain (0.056-22%) Pain (0.056-22%) – Pleuritic Pleuritic – Peritoneal Peritoneal – DiaphragmaticDiaphragmatic

Hemorrhage Hemorrhage – Intraperitoneal (0.03-0.7%) Intraperitoneal (0.03-0.7%) – Intrahepatic and/or subcapsular (0.059-23%) Intrahepatic and/or subcapsular (0.059-23%) – Hemobilia (0.059-0.2%)Hemobilia (0.059-0.2%)

Bile peritonitis (0.03-0.22%) Bile peritonitis (0.03-0.22%) Bacteremia Bacteremia Sepsis (0.088%) and abscess formation Sepsis (0.088%) and abscess formation Pneumothorax and/or pleural effusion (0.08-0.28%) Pneumothorax and/or pleural effusion (0.08-0.28%) Hemothorax (0.18-0.49%) Hemothorax (0.18-0.49%) Arteriovenous fistula (5.4%) Arteriovenous fistula (5.4%) Subcutaneous emphysema (0.014%) Subcutaneous emphysema (0.014%) Anesthetic reaction (0.029%) Anesthetic reaction (0.029%) Needle break (0.02-0.059%) Needle break (0.02-0.059%) Biopsy of other organs Biopsy of other organs

– Lung (0.001-0.014%) Lung (0.001-0.014%) – Gallbladder (0.034-0.117%) Gallbladder (0.034-0.117%) – Kidney (0.096-0.029%) Kidney (0.096-0.029%) – Colon (0.0038-0.044%)Colon (0.0038-0.044%)

Mortality (0.0088-0.3%)Mortality (0.0088-0.3%)

DISEASESDISEASES chronic hepatitischronic 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 HepatitisChronic Hepatitis

Chronic viral hepatitis B (B+D),CChronic viral hepatitis B (B+D),C Toxic induced (drugs,..)Toxic induced (drugs,..) Alcohol liver disease (steatosis, hepatitis, Alcohol liver disease (steatosis, hepatitis,

cirrhosis)cirrhosis) Autoimune hepatitisAutoimune hepatitis Wilson diseaseWilson disease HemocromatosisHemocromatosis

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 CIRRHOSISLIVER 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+ KayserFleyscher ring

-Congestive change- Right heart failure

-Obstruction- Secundary biliary cirrhosis

Simptoms & Signs1. Enlargement of liver: -pain

-revealed at physical exam2. Portal hypertension:

-bleeding varices + hemoroids-splenomegaly + hipersplenism-ascites-colateral superior abdominal circulation-hepatic encephalopaty

personality change, stupor, coma3. Hepatocelular failure

- serum albumine ascites, edema- excretion of bilirubine jaundice- fibriongen, store vitamine K bleeding- detoxication:

oestrogen spider naevipalmar erythemagynecomastialoss of body hairtesticular athrophy

aldosterone edemanitroso 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 lymphoma

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 hypertensionPortal hypertension

The portal venous system

Def : permanent increase of portal presure Def : permanent increase of portal presure (NV – 5-12 mmHg) or portal gradient > 7 (NV – 5-12 mmHg) or portal gradient > 7 mmHg (wedged hepatic pressure - free mmHg (wedged hepatic pressure - free hepatic presiure); > 20 mmHg PP determine hepatic presiure); > 20 mmHg PP determine collateral venous circulationcollateral venous circulation

Measurement of portal hypertension

Causes of PHTCauses of PHT

Post hepatic – portal thrombosis, extrinsic Post hepatic – portal thrombosis, extrinsic compressions on portal vein : pancreatic compressions on portal vein : pancreatic tumors, adenopatytumors, adenopaty

Hepatic cause: liver cirrhosis, sarcoidosis, Hepatic cause: liver cirrhosis, sarcoidosis, hepatic lymphoma, hepatic lymphoma,

Prehepatic: Inf Venae Cavae thrombosis, Prehepatic: Inf Venae Cavae thrombosis, Budd- Chiari sdrBudd- Chiari sdr

Consequence Consequence

Esophageal and Gastric varicesEsophageal and Gastric varices HemorrhoidsHemorrhoids Collateral abdominal circulation (caput Collateral abdominal circulation (caput

medusae)medusae) Splenomegaly (and hypersplenism)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 gallbladderFigure 1.13 - The gallbladder

©Copyright Science Press Internet Services

Figure 1.15a - Luminal surface of rabbit gallbladder Figure 1.15a - Luminal surface of rabbit gallbladder mucosamucosa


Figure 7.15 - The cycle of cholesterol gallstone Figure 7.15 - The cycle of cholesterol gallstone pathogenesispathogenesis

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

TABLE 7-34. CLINICAL RISK FACTORS FOR CHOLESTEROL GALLSTONE 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 GALLSTONESTABLE 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 gallstonesFigure 7.2b - Appearance of gallstones


Figure 7.2c - Appearance of gallstonesFigure 7.2c - Appearance of gallstones


Figure 7.2d - Appearance of gallstonesFigure 7.2d - Appearance of gallstones


Figure 7.2f - Appearance of gallstonesFigure 7.2f - Appearance of gallstones


TABLE 8 - 3. CHARACTERISTICS OF TABLE 8 - 3. CHARACTERISTICS OF CHOLESTEROL GALLSTONESCHOLESTEROL 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


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

TABLE 8-8. CHARACTERISTICS OF BLACK PIGMENT GALLSTONES

Usually less than 1 cm in diameter

Often irregular contour

Not floatable on oral cholecystography

May be radiolucent on plain film

Radiopaque on CT scan

Figure 8.10 - Typical black pigment stones are Figure 8.10 - Typical black pigment stones are irregular in contourirregular in contour


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


Litiaza biliaraLitiaza biliara

Figure 8.4b - Visual identification of cholesterol Figure 8.4b - Visual identification of cholesterol stonesstones


Figure 8.11 - Pigment stones are usually detectable Figure 8.11 - Pigment stones are usually detectable on CT scanon CT scan


Acute pancreatitisAcute pancreatitis

AnatomyAnatomyThe 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 duodenumStomach empties liquids and partly digested food. The pancreatic duct runs through the middle of the gland and carries pancreatic juice to the intestine. This duct joins with the bile duct and they open into the duodenumthrough the ampulla of Vater.

Vascularisation:Artery supplying blood to thelower abdomen and legs (the aorta)Vein which returns blood from these areas(the inferior vena cava).

The pancreas is made up of two types of tissue:The pancreas is made up of two types of tissue: exocrine tissueexocrine tissue

The exocrine tissue secretes digestive The exocrine tissue secretes digestive enzymes. These enzymes are secreted into a enzymes. These enzymes are secreted into a network of ducts that join the main pancreatic network of ducts that join the main pancreatic duct, which runs the length of the pancreas. duct, which runs the length of the pancreas.

endocrine tissueendocrine tissueThe endocrine tissue, which consists of the The endocrine tissue, which consists of the islets of Langerhans, secretes hormones into islets of Langerhans, secretes hormones into the bloodstream. the bloodstream.

FunctionFunction

The pancreas has digestive and hormonal functions:The pancreas has digestive and hormonal functions: The enzymes secreted by the exocrine tissue in the The enzymes secreted by the exocrine tissue in the

pancreas help break down carbohydrates, fats, proteins, pancreas help break down carbohydrates, fats, proteins, and acids in the duodenum. and acids in the duodenum.

These enzymes travel down the pancreatic duct into the These enzymes travel down the pancreatic duct into the bile duct in an inactive form. When they enter the bile duct in an inactive form. When they enter the duodenum, they are activated. duodenum, they are activated.

The exocrine tissue also secretes a bicarbonate to The exocrine tissue also secretes a bicarbonate to neutralize stomach acid in the duodenum. neutralize stomach acid in the duodenum.

The hormones secreted by the endocrine tissue in the The hormones secreted by the endocrine tissue in the pancreas are insulin and glucagon (which regulate the pancreas are insulin and glucagon (which regulate the level of glucose in the blood), and somatostatin (which level of glucose in the blood), and somatostatin (which prevents the release of the other two hormones). prevents the release of the other two hormones).

Pancreatitis Pancreatitis

Introduction: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.

1. 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

• Bacterial infections such as mycoplasma

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: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 hematemesis or melena sometimes develops (5%).

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. It may cause temporary or permanent blindness

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

Ileus Metabolic–hypocalcemia, hyperglycemia

Fistulization Coagulopathy–disseminated intravascular coagulation

Gastrointestinal hemorrhage–pseudoaneurysm

Scan of pancreas indicating gas bubbles within pancreas

An example of colonic obstruction due to pancreatitis

Chronic pancreatitisChronic pancreatitis

Classification by etiology

Diagnostic tests

TABLE 4 - 7. DIAGNOSTIC TESTS Function Structure

Direct hormonal stimulation tests Endoscopic retrograde pancreatography

Bentiromide test Computed tomography Serum trypsin - like immunoreactivity

Endoscopic ultrasound

Fecal chymotrypsin or fecal elastase

Magnetic resonance imaging

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).


Diffusely dilated pancreatic duct due to 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


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.


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.


(a)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.

(b)(b) This spiral CECT shows an irregularly dilated pancreatic duct (arrow) associated with calculi and pancreatic atrophy.

Cancer of pancreasCancer of pancreas

IntroductionIntroduction

Over 90% of pancreatic cancers are ductal Over 90% of pancreatic cancers are ductal adenocarcinomas of the exocrine pancreas. adenocarcinomas of the exocrine pancreas.

These tumors occur twice as frequently in the These tumors occur twice as frequently in the pancreatic head compared to the rest of the pancreatic head compared to the rest of the organ, and tend to be aggressive, often organ, and tend to be aggressive, often presenting when locally inoperable or after presenting when locally inoperable or after distal metastases have occurred. distal metastases have occurred.

Patients with pancreatic cancer have a poor Patients with pancreatic cancer have a poor prognosis, with a 5-year survival of only 5%. prognosis, with a 5-year survival of only 5%.

EpidemiologyEpidemiology

The lifetime risk of being diagnosed with pancreatic cancer The lifetime risk of being diagnosed with pancreatic cancer in the United States is 1.27%. in the United States is 1.27%.

In the United States, it is estimated that approximately In the United States, it is estimated that approximately 37,170 people will be diagnosed with pancreatic cancer in 37,170 people will be diagnosed with pancreatic cancer in 2007. 2007.

Consistent with its associated poor prognosis, 33,370 are Consistent with its associated poor prognosis, 33,370 are expected to die from this disease in the same year, making expected to die from this disease in the same year, making it the fourth leading cause of cancer-related death. it the fourth leading cause of cancer-related death.

Median age of diagnosis of pancreatic cancer is 72 years, Median age of diagnosis of pancreatic cancer is 72 years, – peak incidence of diagnosis between the ages of 65 and 84; peak incidence of diagnosis between the ages of 65 and 84; – rarely diagnosed in those below the age of 50. rarely diagnosed in those below the age of 50.

The incidence is slightly higher in men than women, and it The incidence is slightly higher in men than women, and it is also higher in African Americans than in Caucasians.is also higher in African Americans than in Caucasians.

EtiologyEtiology

Cigarette smoking, obesity, and nonhereditary chronic Cigarette smoking, obesity, and nonhereditary chronic pancreatitis appear to be risk factors for the development of pancreatitis appear to be risk factors for the development of pancreatic cancer. pancreatic cancer.

With smoking, the risk seems to increase with the number of With smoking, the risk seems to increase with the number of cigarettes consumed and decreases with smoking cessation. cigarettes consumed and decreases with smoking cessation.

An epidemiologic association between diabetes mellitus and An epidemiologic association between diabetes mellitus and pancreatic cancer has also been demonstrated; however, it is pancreatic cancer has also been demonstrated; however, it is uncertain if diabetes is a precedent of, or consequence of, uncertain if diabetes is a precedent of, or consequence of, pancreatic cancer.pancreatic cancer.

Chronic pancreatitisChronic pancreatitis Less clear, and sometimes conflicting associations, have been Less clear, and sometimes conflicting associations, have been

observed for other environmental factors such as diet, coffee observed for other environmental factors such as diet, coffee and alcohol consumption, previous partial gastrectomy or and alcohol consumption, previous partial gastrectomy or cholecystectomy, and cholecystectomy, and Helicobacter pyloriHelicobacter 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 StudiesImaging Studies Ultrasound is often used as an initial investigation for patients with Ultrasound is often used as an initial investigation for patients with

jaundice, or with less-specific symptoms such as upper abdominal jaundice, or with less-specific symptoms such as upper abdominal discomfort, and is able to assess the biliary tract, gall bladder, discomfort, and is able to assess the biliary tract, gall bladder, pancreas, and liver. pancreas, and liver.

Computed tomography (CT) scanning is preferable to ultrasound even Computed tomography (CT) scanning is preferable to ultrasound even though it is more costly, as it is less operator-dependent, more though it is more costly, as it is less operator-dependent, more reproducible, and less susceptible to interference from intestinal gas. reproducible, and less susceptible to interference from intestinal gas.

CT may show a pancreatic mass, dilatation of the biliary system or CT may show a pancreatic mass, dilatation of the biliary system or pancreatic duct, or distal spread to the liver, regional lymph nodes, or pancreatic duct, or distal spread to the liver, regional lymph nodes, or peritoneum (and/or associated ascites). peritoneum (and/or associated ascites).

When helical CT is combined with the use of intravenous contrast, it When helical CT is combined with the use of intravenous contrast, it may also help determine resectability by providing information on the may also help determine resectability by providing information on the involvement of important vascular structures such as the celiac axis, involvement of important vascular structures such as the celiac axis, superior mesenteric or portal vessels. 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 StudiesImaging Studies Endoscopic retrograde cholangiopancreatography (ERCP) is also Endoscopic retrograde cholangiopancreatography (ERCP) is also

widely used in the diagnosis of pancreatic cancer, particularly when CT widely used in the diagnosis of pancreatic cancer, particularly when CT and ultrasound fail to show a mass lesion, and may reveal either and ultrasound fail to show a mass lesion, and may reveal either stricture or obstruction in either the pancreatic or common bile duct. 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 ERCP can also be used to obtain brushings of a stricture for cytology or for placing stents in order to relieve obstructive jaundice. for placing stents in order to relieve obstructive jaundice.

Endoscopic ultrasound (EUS) may be useful in the diagnosis of small 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 lesions (<2–3 cm in diameter) and, in some cases, for local staging as well as evaluating invasion of major vascular structures.well as evaluating invasion of major vascular structures.

Magnetic resonance imaging (MRI) does not offer any advantages over Magnetic resonance imaging (MRI) does not offer any advantages over CT in the routine evaluation of patients with possible pancreatic cancer, CT in the routine evaluation of patients with possible pancreatic cancer, magnetic resonance cholangiopancreatography (MRCP) may be better magnetic resonance cholangiopancreatography (MRCP) may be better than CT for defining the anatomy of the pancreatic duct and biliary tree, 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. being able to image the ducts both above and below a stricture.

The sensitivity of MRCP is comparable to ERCP, but does not require The sensitivity of MRCP is comparable to ERCP, but does not require contrast administration to the ductal system, so that there is less contrast administration to the ductal system, so that there is less associated morbidity. associated morbidity.

Pancreatic carcinoma that has grown into duodenum

Narrowed intrapancreatic segment of common bile duct (A)

Tissue diagnosis and CytologyTissue diagnosis and Cytology

Patients with disease that is potentially curable by surgery, and Patients with disease that is potentially curable by surgery, and in whom a highly suspicious lesion is seen on imaging, are often in whom a highly suspicious lesion is seen on imaging, are often taken directly to surgery without prior tissue confirmation of taken directly to surgery without prior tissue confirmation of cancer. cancer.

This is because of theoretical concerns that a percutaneous fine-This is because of theoretical concerns that a percutaneous fine-needle aspiration may result in dissemination of cancer needle aspiration may result in dissemination of cancer intraperitoneally or along the track of the biopsy needle. intraperitoneally or along the track of the biopsy needle.

In addition, negative cytology may not be sufficient evidence to In addition, negative cytology may not be sufficient evidence to avoid surgery, particularly with small lesions. avoid surgery, particularly with small lesions.

EUS-guided fine-needle aspiration is increasingly being used, EUS-guided fine-needle aspiration is increasingly being used, even in patients with potentially resectable disease, as there is even in patients with potentially resectable disease, as there is less risk of intraperitoneal spread of cancer. Other methods of less risk of intraperitoneal spread of cancer. Other methods of obtaining specimens for cytological analysis include sampling obtaining specimens for cytological analysis include sampling of pancreatic juices or brushings of ductal lesions obtained by of pancreatic juices or brushings of ductal lesions obtained by ERCP.ERCP.

Serum MarkersSerum Markers The most widely used serum marker in pancreatic cancer is cancer-The most widely used serum marker in pancreatic cancer is cancer-

associated antigen 19-9 (CA 19-9). associated antigen 19-9 (CA 19-9). It has a reported sensitivity and specificity of about 80–90%, and is It has a reported sensitivity and specificity of about 80–90%, and is

suggestive, rather than confirmatory, of the diagnosis of pancreatic suggestive, rather than confirmatory, of the diagnosis of pancreatic cancer. cancer.

Serum levels of CA 19-9 can be elevated in patients with jaundice 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 without pancreatic cancer present. The level of CA 19-9 may have prognostic implications, with very high levels sometimes found in prognostic implications, with very high levels sometimes found in patients with inoperable disease. patients with inoperable disease.

In advanced disease, patients treated with chemotherapy who had high In advanced disease, patients treated with chemotherapy who had high pretreatment levels of CA 19-9 have also been found to have a worse pretreatment levels of CA 19-9 have also been found to have a worse survival, whereas those patients whose levels of marker fell with survival, whereas those patients whose levels of marker fell with treatment had a better outcome. treatment had a better outcome.

In patients with cancers with elevated CA 19-9, serial evaluation of In patients with cancers with elevated CA 19-9, serial evaluation of this marker is useful for monitoring responses to treatment. In patients this marker is useful for monitoring responses to treatment. In patients with completely resected tumors, follow-up with CA 19-9 is useful for with completely resected tumors, follow-up with CA 19-9 is useful for detecting recurrence.detecting recurrence.

Tumour effect on PancreasTumour effect on Pancreas

Most cancers of the pancreas are primary cancers which means Most cancers of the pancreas are primary cancers which means they arise from a group of cells within the pancreas itself. they arise from a group of cells within the pancreas itself.

Commonest site is the head of the pancreas. The cause of Commonest site is the head of the pancreas. The cause of pancreatic cancer is unknown, but there may be some pancreatic cancer is unknown, but there may be some association with tobacco smoking.association with tobacco smoking.

There are two main effects of cancer of the pancreasThere are two main effects of cancer of the pancreas– cancer in the head of the pancreas blocks the bile duct, leading to cancer in the head of the pancreas blocks the bile duct, leading to

jaundice “going yellow”, dark urine, and pale stools. This is often jaundice “going yellow”, dark urine, and pale stools. This is often associated with itching of the skin which disappears once the associated with itching of the skin which disappears once the blockage is cleared.blockage is cleared.

– Bypassed - the cancer blocks the pancreatic duct leading to poor Bypassed - the cancer blocks the pancreatic duct leading to poor digestion, loose motions and weightlossdigestion, loose motions and weightloss

– Diabetes may already be present in a number of patients prior to Diabetes may already be present in a number of patients prior to developing the cancer, or become apparent soon after it is developing the cancer, or become apparent soon after it is diagnosed or following surgery.diagnosed or following surgery.

Types of TumoursTypes of Tumours There are three common types of pancreatic cancer:There are three common types of pancreatic cancer:

– Ductal adenocarcinoma - the commonest type is the cancer arising from the small Ductal adenocarcinoma - the commonest type is the cancer arising from the small ducts of the ducts of the pancreaspancreas. Most often it arises in the head of the gland and a principal . 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 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.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 Endocrine tumour less commonly tumours may arise from the islets of Langerhans or other hormone producing cells. These tumours are often not malignantother hormone producing cells. These tumours are often not malignant

– Tumours of the ampulla of Vater also present with jaundice, dark urine and pale 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 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, 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 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 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 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. 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 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 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 after diagnosis, and 5-year rates are used to produce a standard way of discussing prognosis. prognosis.

The discussion of pancreatic cancer here will be limited to ductal The discussion of pancreatic cancer here will be limited to ductal adenocarcinomas.adenocarcinomas.

Ductal EndocarcinomaDuctal Endocarcinoma NormalNormal: :

– The normal ductal and ductular epithelium is a cuboidal to low-The normal ductal and ductular epithelium is a cuboidal to low-columnar epithelium with amphophilic cytoplasm. Mucinous columnar epithelium with amphophilic cytoplasm. Mucinous cytoplasm, nuclear crowding and atypia are not seen.cytoplasm, nuclear crowding and atypia are not seen.

Squamous metaplasia Squamous metaplasia o represents a transitional morphology characterized by represents a transitional morphology characterized by

replacement of normal cuboidal ductal epithelium by transitional replacement of normal cuboidal ductal epithelium by transitional epithelium without atypia or by mature squamous epithelium.epithelium without atypia or by mature squamous epithelium.

PanPancreatic creatic IIntraepithelial ntraepithelial NNeoplasia eoplasia 1-A 1-A (PanIN-1A)(PanIN-1A)– These lesions are described as flat, composed of tall columnar cells with These lesions are described as flat, composed of tall columnar cells with

nuclei located basally and significant amounts of supranuclear mucin nuclei located basally and significant amounts of supranuclear mucin (mucin refers to a family of heavily glycosylated proteins). Nuclei tend (mucin refers to a family of heavily glycosylated proteins). Nuclei tend to be small and round to oval. Oval nuclei are typically oriented to be small and round to oval. Oval nuclei are typically oriented perpendicular to the basement membrane. Because of histological perpendicular to the basement membrane. Because of histological uncertainty, the neoplastic character of many examples of PanIN-1A uncertainty, the neoplastic character of many examples of PanIN-1A remains unestablished.remains unestablished.

PanPancreatic creatic IIntraepithelial ntraepithelial NNeoplasia eoplasia 1-B 1-B (PanIN-1B)(PanIN-1B)– These epithelial lesions have a papillary, micropapillary or These epithelial lesions have a papillary, micropapillary or

basally pseudostratified architecture, but are otherwise basally pseudostratified architecture, but are otherwise identical to PanIN-1A. identical to PanIN-1A.

PanPancreatic creatic IIntraepithelialntraepithelial N Neoplasiaeoplasia 2 2 (PanIN-2)(PanIN-2)– are mucinous lesions appearing either flat or papillary. are mucinous lesions appearing either flat or papillary.

Nuclear abnormalities may include some polarity loss, Nuclear abnormalities may include some polarity loss, nuclear crowding, enlarged nuclei, pseudo-stratification nuclear crowding, enlarged nuclei, pseudo-stratification and hyperchromatism. With hyperchromatism the nuclei and hyperchromatism. With hyperchromatism the nuclei will tend to stain more intensely than normal. More nuclear will tend to stain more intensely than normal. More nuclear abnormalities are observed in PanIN-3. Mitoses occur abnormalities are observed in PanIN-3. Mitoses occur rarely.rarely.

PanPancreatic creatic IIntraepithelialntraepithelial N Neoplasia eoplasia 3 3 (PanIN-3)(PanIN-3)– are usually papillary or micropapillary, rarely flat. are usually papillary or micropapillary, rarely flat. – Suggestive of the diagnosis of PanIN-3 include "true Suggestive of the diagnosis of PanIN-3 include "true

cribriforming, budding off of small clusters of epithelial cells cribriforming, budding off of small clusters of epithelial cells into the lumen as well as luminal necrosis." into the lumen as well as luminal necrosis."

– These lesions show a loss of nuclear polarity, dystrophic goblet These lesions show a loss of nuclear polarity, dystrophic goblet cells ("goblet cells with nuclei oriented towards the lumen and cells ("goblet cells with nuclei oriented towards the lumen and mucinous cytoplasm oriented towards the basement membrane") mucinous cytoplasm oriented towards the basement membrane") as well as mitoses (sometimes abnormal), along with nuclear as well as mitoses (sometimes abnormal), along with nuclear irregularities with prominent nucleoli. irregularities with prominent nucleoli.

StagingStaging

Stage GroupingStage Grouping TNM StagingTNM Stagingaa

Localized resectableLocalized resectable II T1–2 N0 M0T1–2 N0 M0

IIII T3 N0 M0 or T1–3 N1 M0T3 N0 M0 or T1–3 N1 M0

Locally advancedLocally advanced IIIIII T4 N(any) M0T4 N(any) M0

MetastaticMetastatic IVIV T(any) N(any) M1T(any) N(any) M1

aTNM, 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 metastasis.

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

Liver Curs 2009

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