Jaundice

Yellow discoloration of sclera, skin, mucous membranes due to deposition of bile pigment

Clinically detected with serum bilirubin 2-2.5mg/dL or (2 times normal)

What causes bilirubin?

Prehepatic Unconjugated

Hepatic mixed

Post-hepatic conjugated

Causes

Hepatocellular diseaseViral infections (hepatitis A, B, and C)Chronic alcohol useAutoimmune disordersDrugsPregnancy

Causes

Parenteral nutritionSarcoidosis Dubin-Johnson syndromeRotor's syndromePrimary biliary cirrhosis Primary sclerosing cholangitis

Drugs that may cause liver damageAnalgesicsParacetamolAspirinNon-steroidal anti-inflammatory drugsCardiac drugsMethyldopaAmiodaronePsychotropic drugsMonoamine oxidase inhibitorsPhenothiazines (such as chlorpromazine)OthersSodium valproateOestrogens (oral contraceptives and hormone replacement therapy)

Symptoms

Yellow discoloration of the skin, sclerae and mucous membranes

Itching (pruritus) due to deposits of bile salts on the skin

Stool becomes light in color

Urine becomes deep orange and foamy

Clinical Features

Careful history and examination

Family history (Gilbert, Rotor, Crigler-Najjar, Dubin-Johnson, Sickle Cell)

Healthy young person with fever, malaise, myalgias = viral hepatitis (try to locate source)

Gradually develops symptoms = hepatic/bile duct obstruction (consider liver disease/cirrhosis)

Develops acutely with abdominal pain = acute cholangitis sec to choledocholithiasis

Clinical Features

Painless jaundice in older person with epigastric mass & weight loss = biliary obstruction from malignancy

Hepatomegaly with pedal edema, JVP, and gallop = CHF

Duration of jaundicePrevious attacks of jaundicePainChills, fever, systemic symptomsItchingExposure to drugs (prescribed and illegal)Biliary surgeryAnorexia, weight lossColour of urine and stoolContact with other jaundiced patientsHistory of injections or blood transfusionsOccupation

History that should be taken from patients presenting with Jaundice

Examination of patients with Jaundice

Depth of jaundiceScratch marksSigns of chronic liver diseasePalmar erythemaClubbingWhite nailsDupuytren’s contractureGynaecomastia

LiverSizeShapeSurfaceEnlargement of gall bladderSplenomegalyAbdominal massColour of urine and stools

Laboratory Tests

Pigment studies Serum bilirubin, direct Serum bilirubin, total Urine R/E for bilirubin and urobilinogen

Alkaline PhosphataseLiver aminotransferrase levels

AST ALT

Elevated levels usually indicate cellular damage to the liver

> 70% of liver cells may be damaged before LFT’s become elevated

Blood Studies

Serum Ammonia Liver converts ammonia to urea. Ammonia

rises in liver failureProtein Studies Serum albumin

Low levels seen with liver disease Serum Globulin

Elevated levels with advanced cirrhosis and chronic active hepatitis

CBC

PT

Other labs pertinent to history

Coombs test

Hb electrophoresis

Viral hepatitis screen

ULTRASOUND

Tumor Marker Alpha-fetoprotein (AFP) Increased levels are seen with hepatic

carcinomaProthrombin Time (PT) Time required for a firm fibrin dot to form In liver dysfunction, increase clotting time

with increased risk of bleeding

Liver Biopsy

Used to obtain a specimen of liver tissueDone under local anesthesia

Autoantibody and immunoglobulin characteristics in liver disease Liver disease Auto antibodies Immunoglobulin

Primary billiary cirrhosis

High titre of antimitochondrial antibody in 95% of

patients

Raised IgM

Autoimmune chronic active hepatitis

Smooth muscle antibody in 70%,

antinuclear factor in 60%, Low

antimitochondrial antibody titre in

20%

Raised IgG in all patients

Primary sclerosing cholangitis

Antinuclear cytoplasmic

antibody in 30%

SummaryAn isolated raised serum bilirubin concentration is usually due to Gilbert’s syndrome, which is confirmed by normal liver enzyme activities and full blood countJaundice with dark urine, pale stools, and raised alkaline phosphatase and gamma-glutamyl transferase activity suggests an obstructive cause, which is confirmed by presence of dilated bile ducts on ultrasonographyJaundice in patients with low serum albumin concentration suggests chronic liver diseasePatients with high concentrations of bilirubin (>100 micro mol/l) or signs of sepsis require emergency specialist referralImaging of the bile ducts for obstructive jaundice is increasingly performed by magnetic resonance cholangiopancreatography, with endoscopy becoming reserved for the therapeutic interventions

Pre-Hepatic Disorders

Gilberts Failure to

conjugate 2-5% Autosomal

recessive Asymptomatic Bilirubin

Unconjugated Normal ALT/ALP Worse if infection,

miss a meal

Haemolysis Excess bilirubin

production Unconjugated Bil

++ Normal ALP/ALT Low Hb/retics++ Splenomegaly Pigmented

gallstones

Hepatic Disorders & Hepatic Failure

Acute & Chronic Liver Disease

Acute Drugs Viral Alcohol Autoimmune

Chronic Biliary

Primary biliary cirrhosis

Primary sclerosing cholangitis

Liver cell damage (cirrhotic) Alcohol Autoimmune Viral* Haemochromatosis* Wilsons* A1AT*

Physical Findings

Acute Moderate liver

enlargement, tenderness, +/- jaundice

Chronic Sallow complexion,

extremity muscle atrophy, palmar erythema, spider nevi, testicular atrophy, gynecomastia, splenomegaly, ascites

Investigations

ACUTE LIVER INJURYLFTs

Hepatitic ALT/AST +++

Albumin Normal

FBC Normal

PT Mild elevation Exception-

paracetomol

CHRONIC LIVER DISEASELFTs

Hepatitic ALT/AST +++

Cholestatic ALP/GGT+++

Albumin Low

FBC Pancytopaenia Elevated wcc

PT Elevated

Blood tests for liver disease

Liver autoantibodies Anti-mitochondrial Anti-Smooth

muscle

Immunoglobulins IgM IgG IgA

Ferritin/TIBC

PBCAICAH

PBCAICAHAlcoholHaemochromatosis

Gross specimen of cirrhosis of the liver

Post-Hepatic Disorders

Intrinsic to the ductal system Gallstones Surgical strictures Infection (cytomegalovirus,

Cryptosporidium infection in patients with acquired immunodeficiency syndrome)

Intrahepatic malignancy Cholangiocarcinoma

Extrinsic to the ductal system Extrahepatic malignancy (pancreas,

lymphoma) Pancreatitis

CASE SCENARIO

A 54 years old female is presented in emergency department with complaints of low grade fever, nausea and loss of appetite for last 10 days. now she is worried because of yellow discoloration of sclera and dark colored urine for one day.

What physical signs you can suspect in this case?

, CASE SCENARIO

On examination, she has fever of 100-F.she is jaundiced and having tender hepatomegaly.

How will you investigate this case ?

CASE SCENARIOBilirubin 10mg/dlALT 1593IUAlkaline phosphatase 840IU

Hb 12.3TLC 8900Platelets 250000

PT 3 seconds prolongSerum albumin 3.6mg/dl

What is your likely diagnosis ?

CASE SCENARIO

Hepatitis AHepatitis BHepatitis CHepatitis D

CASE SCENARIO

How will you differentiate hepatitis A and hepatitis E infection ?

How will you manage this case ?

CASE SCENARIO

Bed restIncrease oral juices intake in anorexic patientsAnti emeticsParenteral feeding if severe anorexia and vomitingVitamin and liver supportive agents