HEPATOBILIARY DISEASE

Dr Mohd Firdaus Mohd Aslam

Common presenting complaints

1.Abdominal pain Frequency and duration-acute or chronic Site:Right hypocondrium region Radiation-acute cholecystitis may radiate to right side and referred to right shoulder Character and pattern of pain -colicky in nature(gallstone)/ -dull (cirrhosis, tumour, hepatitis) Aggravating and relieving factor-after eating fatty food

2.Appetite or weight change Indicate malignancy Liver disease a/w disturbsance of taste 3.Nausea and vomiting Acute hepatobiliary disease and alcoholism

4.Diarrhoea May occur in viral hepatitis steatorrhoea causes: chr pancreatitis 5.Jaundice-progression 6.pruritis 7.Abdominal swelling 8.lethargy

Other history
Symptoms : -pale stool and tea coloured urine ( obstructive jaundice) -easy bruising -fever -Chills and rigors -haematemesis and malaena -altered mood and behaviour,confusion, disorientation,slurred speech(hepatic encephalopathy)

Past medical history

Any liver test?liver biopsy?x-ray/ultrasound of gallbladder? Previous history of recurrent RUQ paincholelithiasis Any operation on biliary tract? Any blood transfusion? Hypercholestrolemia-fatty liver disease

Drug history
NSAID isoniazid

Family history
Liver disease-heriditary cause : wilsons ds, alpha-1-antitrypsin deficiency, hemochromatosis Jaundice-rule out other cause of jaundicehaemolytic jaundice,hereditary spherocytosis

Social history
Alcohol IVDU Sexual history Occupation-health care worker has high risk of hepatitis B History of travelling-Hep A.Hep D in mediterranean countries

Physical examination
General examination: cachexic, hepatic encephalopathy: grade1:altered mood and behaviour grade 2:confusion, disorientation,slurred speech grade3:restlessness, stupor grade4:coma Hand: -clubbing -palmar erythema -Leukonychia(hypoalbuminemia) -Dupuytrens contracture -flapping tremor Forearm -scratch mark -tatoo(viral hep) -bruising(coagulopathy)

 Face -sclera jaundice -xanthelasma -parotid swelling Neck -lymph node Chest -spider naevi -absent of axillary hair -gynecomastia

 Abdomen -Hepatomegaly -splenomegaly -ascites -liver bruit -caput medusa Leg -ankle edema Genitalia

hypogonadism

INVESTIGATION

 Urine FBC Serum haptoglobin, reticulocyte count & Coombs test LFT Coagulation profile Viral studies US abdomen Special Ix: ERCP, CT abd, liver biopsy

Liver function test

Serum albumin- marker of synthetic function &
severity of chronic liver disease

Prothrombin time- same as above,

sensitive indicator for acute & chronic liver disease (short half life),12-16s Vitamin K deficiency should be excluded (giving of iv bolus 10mg vitamin K)

Liver biochemistry
Bilirubin
<17 um/L 2 types- unconjugated and conjugated raised in certain pathology ( prehepatic, hepatic and post hepatic)

Aminotransferase
presence in hepatocytes (leak into blood when there is liver damage) 1) AST- Mitochondrial enzyme heart, kidney, muscle and brain 2) ALT- cytosol enzyme & specific to liver

 Alkaline phosphatase (ALP)

39-117 U/L presence in canalicular and sinusoidal membrane of liver also presence in bone, intestine and placenta electrophoresis or bone specific monoclonal antibodies marked raised together with -glutamyl transpeptidase in cholestasis indicate hepatic and post hepatic disease Cholestasis disease- raised 4-6 times Cirrhosis and metastases raised ( in the absence of jaundice)

Y-glutamyl transpeptidase microsomal enzyme in many tissue raise together with ALP in cholestasis induced by alcohol and phenytoin if ALP is normal and Y-GT increase indicate alcohol intake (screening test) sensitive test for alcohol intake A/G

raised globulin fraction seen in liver disease dt raised circulating immunoglobulin

OTHERS
Hematological - Full blood count - Peripheral blood film - Coombs test - RBC fragility test Biochemical - 1- antitrypsin >> deficiency cause liver cirrhosis - fetoprotein >> indicate hepatitis, cirrhosis teratoma (mild increase) and HCC (marked increase in adult) - Serum and urinary cooper and serum caeruloplasmin wilsons disease - Serum iron, transferrin saturation, serum ferritin hereditary haemachromatosis Tumor markers : Ca 19-9, CEA

Jaundice

Definition
Yellow discolouration of the sclera, skin and mucous membranes due to increase plasma bilirubin. Normal serum bilirubin is < 17 mol/L Levels of clinically apparent bilirubin is > 35 mol/L

Bilirubin Metabolism
In Circulation New RBCs (120 days) Senescent RBCs 1 RES Hb Globin + Haem Haem Iron + Bilirubin Unconjugated bilirubin bound to albumin

Enterohepatic circulation Hepatocytes Kidneys Urobilinogen Small bowel Conjugated bilirubin

Bacteria

Bilirubin 3
Glucoronyl transferase

Urobilinogen Urobilinogen Stercobilinogen in faeces

Conjugated bilirubin (bilirubin glucoronide)

in urine

Aetiology of jaundice
Jaundice

Pre-hepatic Hepatic

Obstructive

 Pre-hepatic
Haemolytic anemia: hereditary spherocytosis, sickle cell disease, G6PD deficiency, thalassaemia Congenital hyperbilirubinaemia: Gilberts Syndrome Autosomal dominant glucuronyl transferase, bilirubin uptake Mild jaundice, especially with fasting Crigler-Najjar syndrome Autosomal dominat/recessive Absent/ glucuronyl transferase Present in neonate, rapid death if untreated

 Hepatic
Hepatocellular damage liver unable to conjugate bilirubin efficiently accumulation of both conjugated & unconjugated bilirubin Infection(hepatits)
Viral (HAV, HBV, HCV) Leptospirosis, glandular fever

Cirrhosis Drugs (chlorpromazine) Toxin(PCM, CCl4, chloroform, halothane, phosphorus, aflatoxin) Liver tumours

Test Urine Serum bilirubin ALT AST ALP Blood glucose Reticulocyte count Haptoglobin Prothrombin

Pre-hepatic Urobilinogen , no bilirubin Unconjugated bilirubin Normal Normal Normal Raised in haemolysis Low due to haemolysis Normal

Hepatic Urobilinogen, bilirubin Conjugated and unconjugated Raised Normal or moderately raised Low if liver failure Normal Normal Prolonged dt poor synthetic function even after vitamin K correction May be abnormal liver texture, e.g cirrhosis

Post-hepatic No Urobilinogen, bilirubin Conjugated bilirubin Normal or moderately raised Raised with -GT raised also Sometimes raised if pancreatic tumour Normal Normal Prolonged due to vitamin K malabsortion; corrects with vit K Dilated bile ducts

Ultrasound

Normal

Obstructive jaundice-causes
Intraluminal
Gallstones,parasitic infection

Mural
Benign
Post instrumentation stricture(ERCP,surgery) Strictures from other causes(gallstones,chronic pancreatitis) PSC Choledochal cyst

Malignant
cholangiocarcinoma

 Extramural
Benign
Mirizzi syndrome

Malignant
Head of pancreas tumor Periampullary carcinoma Enlarged porta hepatis LN

Complications
Symptoms of cholangitis: Charcots triad/Reynauds pentad Fat malabsorption: steatorrhea, fat soluble vitamin deficiency --> coagulopathy Liver decompensation: encephalopathy Pruritus: bile retention

 Courvoisier's law
states that in the presence of an enlarged gallbladder which is nontender and accompanied with mild jaundice, the cause is unlikely to be gallstones.

Exceptions to Courvoisier's Law

1. Oriental cholangiohepatitis 2. Double stone impaction (one in cystic duct, other in Common Bile Duct) 3. a pancreatic calculus obstructing ampulla of vater 4. Mucocele of gall bladder due to an impacted stone at neck of gall bladder.

 Murphys sign
performed by asking the patient to breathe out and then gently placing the hand below the costal margin on the right side at the mid-clavicular line (the approximate location of the gallbladder). The patient is then instructed to inspire (breathe in). Normally, during inspiration, theabdominal contents are pushed downward as the diaphragm moves down (and lungs expand). If the patient stops breathing in (as the gallbladder is tender and, in moving downward, comes in contact with the examiner's fingers) and winces with a 'catch' in breath, the test is considered positive.

 Boass sign- Increased sensitivity below the right scapula (also due to phrenic nerve irritation). Ortner's sign - tenderness when hand taps the edge of right costal arch. Georgievskiy - Myussi's sign (phrenic nerve sign) - pain when press between edges of sternocleidomastoid

Acute cholecystitis
Pathophysiology
Gallstone gets stuck in the cystic duct, causing obstruction of biliary flow distended and inflammed

USG features of cholecystitis

Presence of gallstones in biliary system( acoustic shadow) Contracted gallbladder(chronic) Pericholecystic fluid

Management
Resuscitate Septic workout Bowel rest, IV fluids Analgesia Empirical antibiotics- IV Ceftriaxone, Metronidazole Plan for op

Complications
Hydrops Cystic duct obstruction leads to a tense gallbladder filled with mucus May lead to gallbladder wall necrosis if pressure exceeds capillary blood pressure Empyema Gallbladder is filled with pus due to bacterial infection of the stagnant bile Gangrene and perforation Cholecystenteric fistula Gallstone ileus

Acalculous cholecystitis
Occurs in very ill pt with prolonged stay in icu,prolonged fasting, poor nutition, labile blood pressure,sepsis Poor nutrition leads to biliary stasis, while dehydration and hypotension leads to formation of viscous bile and gallbladder ischemia bile infected cholecystitis

Choledocholithiasis
p/w obstructive jaundice Mx:
If unsure of presence of stone: MRCP/EUS If likelyhood of stone high ERCP

If ERCP successful, plan for cholecystectomy If failed ERCP, if pt well and can tolerate another ERCP for repeat ERCP(+/- stent in between to drain bile) or operative removal( open/lap CBD exploration)

When to do operative removal of stones?

Stone > 25mm Intrahepatic stones Large number of stones Impacted stones Dual pathology Tortuous duct Previous Bilroth II(anatomy not suitable)

Mirizzi syndrome
Gallstone in the Hartmanns pouch compressing the common hepatic Compression effect from surrounding inflammation as well One of the exception to Courvoisier's law

Liver cirrhosis

Pathophysiology
Irreversible chronic injury of the hepatic parenchyma Extensive fibrosis - distortion of the hepatic architecture Formation of regenerative nodules

 Causes: 1. Chronic HBV, HCV infection 2. Chronic alcohol abuse 3. Autoimmune: autoimmune heptitis, primary biliary cirrhosis, primary sclerosing cholangitis 4. Metabolic: Wilson disease, haemachromatosis, alpha 1 antitrypsin 5. Drugs: methotrexate, methyldopa, amiodarone 6. Nonalcoholic steatohepatitis(NASH) 7. Others: Budd-Chiari syndrome

Investigations
FBC- low HB, platelet and WBC Liver function test
bilirubin or AST, ALT, ALP, gamma GT Albumin Cogulation profile: prothrombin time

Find the cause: Hb s Ag, Hb e Ag HCV Antibody AST:ALT> 2:1, gamma GT

Ferritin, serum iron, total iron binding capacity Serum and urine copper, ceruloplasmin Serum alpha 1 antitrypsin level Autoantibodies( AMA, ASMA, ANA, ANCA) Liver biopsy Ultrasound

Complications
Hepatic encephalopathy Portal hypertension-esophageal varices Ascites Hepatocellular carcinoma Spontaneous bacterial peritonitis Hepatorenal syndrome

Treatment Options
The major goals of treating the cirrhotic patient include:
Slowing or reversing the progression of liver disease Preventing superimposed insults to the liver Preventing and treating the complications Determining the appropriateness and optimal timing for liver transplantation

Ascites
Pathological accumulation of fluid in the peritoneal cavity Most common complication of cirrhosis Two-year survival of patients with ascites is approximately 50 percent

Causes

High gradient(SAAG=or 11g/L) Cirrhosis Alcoholic hepatitis Fulminant hepatic failure CCF, constrictive pericarditis Budd-Chiari synd, venoocclusive dis Myxoedema

Low gradient(SAAG < 11g/L) Peritoneal carcinomatosis TB Pancreatic /biliary ascites Nephrotic syndome

Pathogenesis
Dilatation of splanchic vascular beddecrease in effective central blood volumeactivation of reninangiotensin-aldosterone system increased sodium and water retention Portal hypertension
local hydrostatic pressure hepatic & splanchnic production of lymph transudate fluid into peritoneal cavity

Low serum albumin

Dt synthesis / excretion c fluid leakage

Investigations
Diagnostic paracentesis for proteins and malignant cells (cell count, cytology, biochemistry) US of abdomen Peritoneal biopsy or laparoscopy if cause remains unclear

Management
Monitor Se electrolytes, Cr, weight, urine output Dietary Na+ restriction Diuretics Paracentesis + admin of albumin

Spontaneous bacterial peritonitis

Infection of ascitic fluid Almost always seen in the setting of endstage liver disease The diagnosis is established by
A positive ascitic fluid bacterial culture Elevated ascitic fluid absolute polymorphonuclear leukocyte (PMN) count ( >500 cells/l)

Spontaneous Bacterial Peritonitis

Clinical manifestations:
Fever Abdominal pain Abdominal tenderness Altered mental status

Hepatorenal syndrome
acute renal failure coupled with advanced hepatic disease (due to cirrhosis or less often metastatic tumor or
severe alcoholic hepatitis)

characterized by:
Oliguria benign urine sediment very low rate of sodium excretion progressive rise in the plasma creatinine concentration

Hepatorenal Syndrome
Reduction in GFR often clinically masked Prognosis is poor unless hepatic function improves Nephrotoxic agents and overdiuresis can precipitate HRS

Pain & Drugs: Biliary Tract

Morphine used to be contraindicated. It is now known that all opiates create spasm of the Sphincter of Oddi Since the metabolite of Demerol has such negative side effects (CNS stimulant, seizures) it is no longer the drug of choice. Antacids: reduce gastric acid & associated pain. Histamine blockers: reduce gastric acid secretion, which stimulates pancreatic enzymes. Anticholenergics: reduce spasm of sphincter of ODDI
Gardner, A (2002) Meperidine: Time for a change. The Disatllate, 27 (4)

THANK YOU!!