CLINICAL APPROACH TO

JAUNDICE
Dr. J.K.S.L.S.Perera
MBBS, MRCGP (INT)
 Jaundice

• The word “jaundice” comes from the French word jaune,

which means yellow.
• jaundice is a yellowish discoloration of the skin, sclera, and
mucous membranes by bilirubin.
• The discoloration typically is detected clinically once the
serum bilirubin level rises above 3mg/dL
• Bilirubin metabolism takes place in three phases—prehepatic,
intrahepatic, and posthepatic. Dysfunction in any of these
phases may lead to jaundice.
•The overall incidence of jaundice in primary care in
the UK is estimated to be about 56 per 100,000
people.

•Although jaundice is not a particularly common

presentation in general practice, it usually indicates
a serious underlying condition and requires urgent
investigation. Malignancy, alcohol, and gallstone
disease are important causes of jaundice in the UK
Jaundice :- background
 Jaundice is defined as a serum bilirubin level exceeding 19 μ mol/L. (1.1Mg/dl)
 Clinical jaundice manifests only when the bilirubin level exceeds 50 μ mol/L.
(3 mg/dl) However, jaundice is difficult to detect visually below 85 μ mol/L
(5 mg/dl) if lighting is poor.
 It can be distinguished from yellow skin due to hypercarotenaemia (due to dietary
excess of carrots, pumpkin and mangoes) and hypothyroidism by involving the
sclera.
 The most common causes of jaundice recorded in a general practice population are
(in order) viral hepatitis, gallstones, pancreatic cancer, cirrhosis, pancreatitis and
drugs.
 Always take a full travel, drug and hepatitis contact history in any patient presenting
with jaundice.
 Acute hepatitis is usually self-limiting in patients with hepatitis A and in adults with
hepatitis B , but progresses to chronic infections with hepatitis C and children with
hepatitis B.
 A fatty liver (steatosis) can occur not only with alcohol excess but also with obesity,
diabetes and starvation. There is usually no liver damage and thus no jaundice
Hepatobilliary system :- overview
 Production of
bilirubin

Hepatic/biliary
removal
 Jaundice

unconjugated
Pre-hepatic
hyperbilirubinemia

Conjugated
hepatic Post-heptic
hyperbilirubinemia
Unconjugated hyperbilirubinemia
Conjugated hyperbilirubinemia
 A diagnostic approach
• Probable diagnosis depends on the age and social grouping of the patient, especially
if the patient practice risk taking behavior or has travelled overseas.

• Viral hepatitis A, B or C account for the majority of cases of jaundice.

• In the middle-aged and elderly group, a common cause is obstruction from gallstones or
cancer.
It is common for older people to have painless obstructive jaundice;
bear in mind that the chances of malignancy increase with age.

• Alcoholic liver disease is common and may present as chronic alcoholic cirrhosis with liver
failure
or as acute alcoholic hepatitis. It is worth emphasizing that such patients can make a
dramatic recovery when they cease drinking alcohol.

• In family practice we encounter many cases of drug-induced jaundice,

especially in the elderly.
Serious disorders not to be missed

• Malignancy must always be suspected, especially in the elderly patient and those with a
history of chronic active hepatitis (e.g. post hepatitis B or C infection). The former is more likely
to have a carcinoma of the head of the pancreas and the latter,
• hepatocellular carcinoma (hepatoma). Metastatic cancer must be kept in mind, especially in those with a
history of surgery, such as large bowel cancer, melanoma and stomach cancer. An enlarged, knobby, hard
liver is a feature.

• Hepatic failure can be associated with severe systemic infection (eg. septicemia and pneumonia),
and after surgery in critically ill patients. A patient who has the classic Charcot triad of
upper abdominal pain, fever (and chills) and jaundice should be regarded as having
Ascending cholangitis until proved otherwise.
• Wilson syndrome, although rare, must be considered in all young patients with acute hepatitis
 Pitfalls
• Gallstones, especially in the absence of upper abdominal pain, can be overlooked, so this possibility
should be kept in mind in the elderly

• Gilbert syndrome is worth considering, especially as it is the commonest form of unconjugated

hyperbilirubinaemia. It affects at least 3% of the population.

• Cardiac failure can present as jaundice with widespread tenderness under the right costal
margin. It can be insidious in onset or manifest with gross acute failure. It can be confused
with acute cholecystitis. The biochemical abnormalities seen are very variable. Usually there is
a moderate rise in bilirubin and alkaline phosphatase and sometimes, in acute failure, a marked
elevation of transaminase may occur, suggesting some hepatocellular necrosis.
General pitfalls
• Excluding jaundice by examining the sclera in artificial light

• Not realizing that the sclera in elderly patients often have an icteric appearance (without jaundice)

• Omitting to take a careful history, including illicit drugs

• A liver biopsy is essential in all patients with chronic hepatitis

Red flag pointers for jaundice
• Unexplained weight loss

• Progressive jaundice including painless jaundice

• Oedema

• signs of hepatic encephalopathy (such as confusion , somnolence)

 hepatic dysfunction (such as bruising),

 gastrointestinal blood loss and sepsis; marked abdominal pain or tenderness,

vomiting, weight loss,

 of paracetamol overdose.
Evaluation:

History of
Past medical
presenting
history
illness

Physical
Investigations
examination
History

The history should include questioning about the

following:

• any episodes of jaundice • dietary history—shellfish, drinking water

• change in color of feces and urine • sexual history—evidence of promiscuity
• anorexia, sore throat, weight loss, pruritus • drug history, including alcohol, paracetamol
• abdominal pain • recent medical history, including surgery
• residence and members of household • family history—family contacts who have had
contact with patients with hepatitis or jaundice jaundice, haemolytic disease and other genetic
• recent overseas travel liver diseases
• exposure to blood or blood products • ethnic history—liable to haemolytic disease,
• needle-stick injuries or exposure to needles, such contact with hepatitis B
as acupuncture, tattooing and intravenous drugs • occupational history—exposure to hazards
 Past medical history:
• Hepatobiliary disease: gallstones, hepatitis, cirrhosis

• Disorders that could cause hemolysis:

• hemoglobinopathy ,

• G6PD deficiency.
• Infiltrative disorders:
• amyloidosis, sarcoidosis , lymphoma

• Drug history

• Vaccination against hepatitis

 Significance of various symptoms
• Pain in the right hypochondrium:
— gallstones
— acute hepatitis (a constant ache)
— cholecystitis
• Anorexia, dark urine, fever:
— viral hepatitis probable
— alcoholic liver disease possible
— drug-induced hepatitis possible
• Pruritus:
— cholestasis probable
— possible with all liver diseases
• Arthralgia, rash:
— viral hepatitis
— autoimmune hepatitis
Examination
The abdominal examination is very important.

 liver :- Enlargement, Consistency and Tenderness

 gall bladder
enlargement
 Spleen

• Signs of sepsis — fever, tachycardia, and hypotension.

• A palpable gall bladder indicates extra hepatic biliary obstruction,
• splenomegaly may indicate hemolytic anemia, portal hypertension or viral hepatitis.
• Test for ascites.
• Skin excoriation :- pruritus, associated with cholestatic jaundice
• Look for evidence of chronic liver disease
• palmar erythema, easy bruising, spider naevi and muscle wasting, testicular atrophy gynaecomastia.
• hepatic flap (asterixis) and fetor :- liver failure
• Lymphadenopathy:- indicative of malignancy. :- Enlargement of the left supraclavicular lymph nodes
Investigations

Blood
imaging
tests

Liver
biopsy
Blood tests

CBC
LFT
Viral serology
 LFT s are commonly ordered panel of blood tests that evaluate,
• Liver functions
• Liver damage
• Coagulation
• Billiary tree functions
• Nutrition
• Bone turnover
 Hepatic enzymes
 Alanine aminotransferase
 Aspartate aminotransferase
 Alkaline phosphatase
 Gamma glutamyltranspeptidase
 Synthetic function tests
 Serum albumin/total protein level
 PT/INR
 Billirubin
 Conjugated and unconjugated billirubin
First step
CAUSES OF ISOLATED UNCONJUGATED HYPERBILIRUBINEMIA

1. Indirect hyperbilirubinemia
1. Hemolytic disorders
1. Inherited
1. Spherocytosis, elliptocytosis
2. Glucose-6-phosphate dehydrogenase and
pyruvate kinase deficiencies
3. Sickle cell anemia
4. thalasemmia
2. Acquired
1. Microangiopathic hemolytic anemias
2. Paroxysmal nocturnal hemoglobinuria
3. Spur cell anemia
4. Immune hemolysis
5. Parasitic infections
1. Malaria
2. Babesiosis
2. Ineffective erythropoiesis
1. Cobalamin, folate, thalassemia, and severe iron
deficiencies
3. Drugs
1. Rifampicin, probenecid, ribavirin
4. Inherited conditions
1. Crigler-Najjar types I and II
2. Gilbert's syndrome
UNCONJUGATED HYPERBILURUBINEMIA

SBR rarely exceed 5mg/dl

Higher levels when there is coexistent renal or hepatic dysfunction or crisis.

Pigmented calcium bilirubinate gallstones and choledocholithiasis

Acquired-HUS, PNH, malaria

Ineffective erythropoiesis-cobalamin, folate deficiency or iron def.

Crigler najjar type I-rare

 GILBERTSYNDROME-1/3 UDPGTactivity ( about 3% of generalpopulation.)
 Some drugs : Rifampicin, probenicis, ribavirin
CONJUGATED HYPERBILIRUBINEMIA : (isolsted )

• Dubin-Johnson syndrome

• Rotor's syndrome
Elevation of serum bilirubin with other
LFT abnormalities
Hepatocellular type

Viral hepatitis Alcohol DRUGS

Wilson’s
TOXINS disease/Autoimmune
Hepatitis
*Patients with alcoholic hepatitis will have AST :ALT
ratio of 2:1
(AST rarely exceeds 300 U/L)

*Patients with hepatitis due to viral or

toxin-related will have
Aminotransferases > 500 U/L.
Further investigation of hepatocellular type jaundice

• Suspected hepatocellular injury:

Serologic tests for viral hepatitis (IgM HAV. Hbs Ag, IgM anti Hbc, HCV RNA,
Tests for EBV,CMV.)
• Measurement of antimitochondrial antibodies (for primarybiliary cirrhosis)

• Measurement of antinuclear anti-smooth muscle and liver-kidney

microsomal antibodies (for autoimmune hepatitis)

• Serum levels of iron, transferrin, and ferritin (for hemochromatosis)

• Serum and urinary copper , serum levels of ceruloplasmin (for Wilson disease)
 Cholistatic type jaundice

•Intrahepatic cholestasis Extra hepatic

• Primary biliary cirrhosis cholestasis
• Primary sclerosing
cholangitis • Benign
• Malignant
Suspected biliary obstruction or intrahepatic cholestasis:

Do an USG that will detect the presence of biliary dilatation.

 Biliary dilatation = extra hepatic cholestasis

 No Biliary dilatation = intrahepatic cholestasis

• Abdominal US: highly accurate in detecting extrahepatic

obstruction (gall stones)

• Distal CBD is an area that is difficult to be visualized by USG.

• CTscan: more accurate in pancreatic lesions.

• If the results are positive forextrahepatic cholestasis, other tests may

be necessary to determine the cause: MRCP , ERCP
Extra hepatic Jaundice

*Malignant
* Cholangiocarcinoma
* Pancreatic cancer
* Gallbladder cancer
* Ampullary cancer
* Malignant involvement of the porta hepatis lymph
nodes

*Benign Choledocholithiasis
* Choledocholithiasis
* Postoperative biliary structures
* Primary sclerosing cholangitis
* Chronic pancreatitis
* AIDS cholangiopathy
* Mirizzi syndrome
* Parasitic disease (ascariasis)
• Liver biopsy:

• Not commonly required but can help in diagnosing autoimmune hepatitis or biliary
tract disorders (e.g., primary biliary cirrhosis, primary sclerosing cholangitis)
 When to refer
• All patients with fulminant hepatitis
• All patients with chronic liver disease
• Painless obstructive jaundice
• Evidence of malignancy
• Symptomatic gallstones
• Patients with cirrhosis
• Acute fatty liver of pregnancy (very urgent)
• Suspected rare conditions (e.g. Wilson syndrome)

Most adults presenting to primary care with jaundice should be

admitted or referred to secondary care
•People presenting with jaundice should be admitted for same-day assessment if:

•They are acutely unwell : Ex: encephalopathy is suspected or they have a fever.
•Cholangitis is suspected.
•Bilirubin is greater than 100 micromol/L.
•Renal function is abnormal or they are dehydrated.
•Clotting profile is abnormal.
•They are frail or have significant co-morbidities.
•Paracetamol overdose is suspected.

People presenting with jaundice who do not need admission should be referred to secondary care if:
•Malignancy is suspected (refer using a suspected cancer pathway, for an appointment within 2 weeks).
•Blood tests show a cholestatic or obstructive picture.
•Blood tests show a hepatitic picture.
•Alcohol-related liver disease is suspected.
•Inherited or autoimmune liver disease is suspected.
Practice tips

• All drugs should be suspected as potential hepatotoxins.

• With hepatitis A the presence of IgM antibodies reflects recent infection, and IgG antibody indicates past infection
and lifelong immunity.
• There is no chronic carrier state of hepatitis A and E.
• All patients with jaundice should be tested for hepatitis B surface antigen (HBsAg).
• Hepatitis B infection is usually benign and short-lived, but it can be fatal if chronic hepatitis develops, which may
lead later to cirrhosis and hepatocellular carcinoma.
• Up to 5% of patients with hepatitis B will become chronic carriers (especially drug addicts).
• Such carriers are identified by persistent titers of HBsAg and possibly HBeAg, the latter indicating the presence
of the whole virus, and active replication and high infectivity.
• A raised gamma glutamyl transferase accompanied by a raised MCV is a good screening test for alcohol abuse.
• A systolic murmur may be heard over the liver in alcoholic hepatitis and hepatoma.
• A distaste for smoking (with jaundice) suggests acute viral hepatitis.
Refferances

• NICE guidelines 2016 on jaundice on adults

• General practice by john murtagh 6th edition
• Approch to a patient with abnormal liver function tests by: - GI
Hepatology academy at the harward university
Investigations

First step

• Whether the hyperbilirubinemia is predominantly conjugated

or unconjugated in nature.

• Whether other biochemical tests are abnormal.

The main investigations are,

• CBC
• standard LFTs
• viral serology for the infective causes,
(particularly hepatitis A, B and C virus )
Intrahepatic Jaundice courses

1. Viral hepatitis
1. Fibrosing cholestatic hepatitis—hepatitis B and C
Hepatitis A, Epstein-Barr virus, cytomegalovirus
1. Alcoholic hepatitis
2. Drug toxicity
1.Pure cholestasis—anabolic and contraceptive steroids
2. Cholestatic hepatitis—chlorpromazine, erythromycin
2. 3.Chronic cholestasis—chlorpromazine and prochlorperazine
3. Primary biliary cirrhosis
4. Primary sclerosing cholangitis
5. Vanishing bile duct syndrome
1.Chronic rejection of liver transplants 2.Sarcoidosis