Approach to a patient with
jaundice
Dr chuku.c.chika
Introduction
• Jaundice is the yellowish discoloration of the sclera, skin, and
mucous membranes caused by accumulation OR deposition of
bilirubin, a pigmented metabolite of heme.
• Normal levels of bilirubin in blood are below 1.0 mg/dl (17 μmol/L)
• Clinically apparent jaundice in children and adults occurs when the
serum concentration of bilirubin reaches 2-3 mg/dL (34-51 µmol/L);
• Neonate might not appear jaundiced until the bilirubin level is
>5 mg/dL (>85 µmol/L).
INTRODUCTION
• Jaundice may be the earliest and only sign of hepatic dysfunction.
• Jaundice in adults is rare however, Under the five year DISCOVERY
programme in the UK, annual incidence of jaundice was 0.74 per 1000
individuals over age 45,
• Risk factors associated with high serum bilirubin levels include male
gender, white ethnicities, and active smoking.
• The prevalence of jaundice in adults is rare, while jaundice in babies is
common, with an estimated 80% affected during their first week of life.
Introduction
• jaundice is due to bilirubin overproduction, impaired
bilirubin conjugation, biliary obstruction, and hepatic
inflammation.
TYPES OF JAUNDICE
• (1) Hemolytic/pre hepatic: results from increased bilirubin
production from excessive breakdown of red cells.
• (2) Hepatocellular: results from disease of the liver parenchyma,
sometimes referred to as “nonobstructive jaundice” or “medical
jaundice”
• (3) Obstructive /post hepatic: results from mechanical obstruction
of the biliary ducts outside the liver, sometimes referred to as
“surgical jaundice”.
Types of jaundice
• The most common causes of hepatocellular jaundice are viral
hepatitis and alcoholic cirrhosis;
• The most common causes of obstructive jaundice are gallstone
disease choledocholithiasis and pancreatic carcinoma or biliary-
tract obstruction.
Prehepatic causes
• Prehepatic jaundice is most commonly caused by a pathological
increased rate of red blood cell (erythrocyte) hemolysis.
• The increased breakdown of erythrocytes → increased unconjugated
serum bilirubin → increased deposition of unconjugated bilirubin into
mucosal tissue .
• Hemoglobinopathies: Sickle-cell anemia/thalassemias/spherocytosis
• Pyruvate kinase deficiency
• Glucose-6-phosphate dehydrogenase deficiency
• Microangiopathic hemolytic anemia
• Hemolytic-uremic syndrome
• Severe malaria (in endemic countries)
Hepatocellular causes
• Hepatic jaundice is due to significant damage to hepatocytes
• Acute hepatitis/Chronic hepatitis
• Cirrhosis
• Drug-induced hepatitis
• Alcoholic liver disease
• Gilbert's syndrome (found in about 5% of the population, results in
induced mild jaundice)
• Crigler-Najjar syndrome, type I/II
• Leptospirosis
• Metabolic :wilsons disease, haemochromatosis
Drug induced jaundice
• Hemolysis : Antimalarial (dapsone)
• Hepatitis :Paracetamol overdose, Rifampicin, Pyrazinamide
• Monoamine oxidase inhibitors
• Flucloxacillin
• Cholestasis: fusidic, co amoxiclav, nitrofurantoin, steroids.
• Others; sodium valproate, halothane, statins, sulfonylureas,
prochlorperazine, chlorpromazine.
Posthepatic causes ctd…….
• Primary biliary cholangitis
• Pancreatic pseudocysts
• Mirizzi’s syndrome
Etiology summary
Forms of Bilirubin
• Bilirubin exists in two forms; unconjugated and conjugated.
• Unconjugated bilirubin is insoluble in water. This means it can only
travel in the bloodstream if bound to albumin and it cannot be
directly excreted from the body.
• conjugated bilirubin is water soluble. This allows it to travel
through the bloodstream without requiring transport proteins like
albumin, can also be excreted out of the body.
Bilirubin Metabolism
• Bilirubin breakdown
• Reticuloendothelial cells are macrophages which are responsible for
the maintenance of the blood, through the destruction of old or
abnormal cells. They take up red blood cells and metabolise the
haemoglobin present into haem and globin. Globin is further broken
down into amino acids which are subsequently recycled.
• haem is then broken down into iron and biliverdin, a process which
is catalysed by the enzyme haem oxygenase. The iron gets recycled,
while biliverdin is reduced to create unconjugated bilirubin.
Bilirubin metabolism
• Bilirubin Conjugation:
• In the bloodstream, unconjugated bilirubin binds to albumin to
facilitate its transport to the liver.
• Once in the liver, glucuronic acid is added to unconjugated bilirubin
by the enzyme glucuronyl transferase.
• This forms conjugated bilirubin, which is soluble.
• This allows conjugated bilirubin to be excreted into the duodenum
in bile.
Bilirubin metabolism
• Bilirubin excretion:
• Conjugated bilirubin is deconjugate by colonic bacteria into
urobilinogen.
• Around 80% of this urobilinogen is further oxidised by intestinal
bacteria and converted to stercobilin and then excreted through
faeces. It is stercobilin which gives faeces their colour
• Around 20% of the urobilinogen is reabsorbed into the bloodstream
as part of the enterohepatic circulation.
• It is carried to the liver where some is recycled for bile production,
while a small percentage reaches the kidneys. Here, it is oxidised
further into urobilin and then excreted into the urine.
History
1.Age
• In neonates, common causes include physiological jaundice, Rh incompatibility, and biliary
atresia
• In children one of the common causes of obstructive jaundice is a choledochal cyst.
• In young adults, common causes of jaundice are hepatits, parasitic infections, trauma, and
gall stones.
• In older adults, malignancies should be considered.
1.Gender
• Males may have an X-linked disease causing jaundice (G6PD deficiency).
• Obstructive jaundice due to pancreatic cancer is commoner in males.
• A female predominance is seen in choledocholithiasis.
• Females may also suffer from cholestasis in pregnancy.
History
1.Occupation.
• Sex workers are at risk of hepatitis, HIV infection. Healthcare workers may
acquire hepatitis B or C from a needle prick injury or from other occupational
exposure.
• Workers in chemical factories may be exposed to hepatotoxic agents like
carbon tetrachloride, lead.
1.Race, country, neighborhoods
• Thalassemias are commoner in Chinese and Mediterranean regions.
• G6PD deficiency tends to occur in African-americans.
• Cholangiocarcinoma is common in southeast asia.
• Also check for cases of jaundice in the neighborhood.
History
1.Duration of jaundice
• A more recent jaundice may indicate acute hepatitis;
• longer duration in benign strictures and chronic liver disease.
1.Onset of jaundice
• Rapidity of onset is quick in obstructive jaundice due to gallstone disease
• In hepatitis, it is sudden in onset and fades slowly in days.
• Hemolysis is associated with a steady increase with a slow rise. The onset is
the most gradual in obstruction due to cancer of the pancreatic head
• It tends to be slower in obstructive jaundice
• Who noticed it first? Patient? Relative? Doctor?
HISTORY
1.Progression/ periodicity of jaundice
• Progressively worsening jaundice will occur in untreated obstruction as in
tumour, stone.
• It may be getting better, as in an inflammation that is subsiding, e.g. hepatitis.
• Periodicity. Fluctuating obstructive jaundice occurs with intraluminal lesions
like
• a). bile duct stones,
• b). cholangiocarcinomas, and
• C). ampullary cancer.
• Progressive obstructive jaundice occurs with a, b, and c above, and also
lesions that invade the bile duct from outside: pancreatic cancer, gall bladder
cancer, tumours at the porta that press on both hepatic ducts.
• Hepatocellular defects like Gilbert’s and Dubin-Johnson syndromes may be
associated with recurrent jaundice that precipitates during physiological stress
HISTORY
• Urine color
• Urine is “tea colored” in jaundice associated with conjugated
hyperbilirubinemia.
• In hemolysis, urine color is normal, because the
hyperbilirubinemia is unconjugated. Unconjugated bilirubin
does not appear in the urine.
• Stool color
• Pale stools indicate obstructive jaundice.
• Itching
• Itching is typical of obstructive jaundice.
HISTORY
1.Pain
• Painful jaundice: think of choledocholithiasis.
• Painless jaundice: think of cancer.
1.Gastrointestinal disturbances
• Gastrointestinal disturbance include anorexia, nausea, vomiting, altered bowel
habit.
• Anorexia and nausea are common in acute hepatitis.
• Vomiting may occur from a tumour, e.g. pancreatic cancer, that causes
intestinal obstruction.
• Altered bowel habit may occur if the lesion causing jaundice is invading the
small bowel or colon. Absence of bile salts in the stool can lead to steatorrhea.
HISTORY
1.Fever
• fever may indicate the development of cholangitis in a patient with
obstructive jaundice. Cholangitis is characterized by a triad of fever,
abdominal pain, and jaundice.(CHARCOT TRIAD)
1.Weight loss, lethargy
• Weight loss is common in most causes of jaundice: tumors, hepatitis,
chronic hemolysis.
• If the patient has lethargy, consider anemia caused by hemolysis, or by
malnutrition resulting from a tumor.
HISTORY
1.Past history
• Ask about surgery and transfusion; past/ current illness; tattoos and
inoculations
• Surgery: Operative trauma to the bile duct may cause a bile duct stricture and
jaundice. This is particularly common after gall bladder surgery. Also
• A blood transfusion during surgery may have transmitted hepatitis B or C..
• Tattoos and inoculations: Punctures with contaminated needles transmit
hepatitis B and C.
• Ask about a history of tattoos and of possible inoculations in less-than-ideal
circumstances
HISTORY
• Past or current illness:
• Does the patient have a known liver disease, or any condition that may
explain jaundice?
• Did the patient have acute hepatitis, and is possibly developing chronic
hepatitis or cirrhosis?
• An inquiry into illnesses may also uncover medications that the patient
is taking, one or more of which may explain the jaundice.
• Family history
• Look for the evidence of a similar disorder among the family
members. Gilbert’s, Rotor, Dubin-Johnson’s syndromes run in
families.
HISTORY
• Personal history
• Recent travel: In travelers returning from endemic areas, the
following should be considered if jaundice develops: Viral
hepatitis, malaria, dengue fever, yellow fever.
• Smoking: Smoking is a risk factor in pancreatic cancer
• Alcohol: is a risk factor for chronic liver disease.
• Drug history: Many drugs cause cholestasis, hepatitis, or both.
Drugs causing jaundice include rifampicin, erythromycin, INH,
anabolic steroids, carbamazepine, and others.
General physical exam
• Jaundice
• skin, palms, nail bed, eyes, nasal tip, lips, on the undersurface
of the tongue, and on the soft palate
• In hepatocellular jaundice, the patient appears more acutely ill
than a patient with obstruction
• Is the patient cachexic? This might be the indicator of a cancer
causing the jaundice.
• Check for tattoos. If present, inquire if the jaundice started a
few months after the tattoo was applied. This might point
towards a needle-transmitted hepatitis.
Examination ctd……
• Pedal or generalized edema may indicate hypoalbuminemia as
in cirrhosis.
• supraclavicular lymphadenopathy may represent a metastasis
from a pancreatic cancer.
• Stigmata of chronic liver disease
Investigations in a jaundiced patient
• FULL BLOOD COUNT
• LIVER FUNCTION TEST
• E/U/CR
• COAGULATION PROFILE
• URINALYSIS
• STOOL ANALYSIS
• BIOMARKERS FOR CA/AUTOIMMUNE DISEASE
• ABDOMINAL SCAN
• CT/MRI ABDOMEN
• MRCP/ERCP
• LIVER BIOPSY
TREATMENT
• Treatment is fully dependent on the cause
• Alcoholic hepatitis, firstly cessation of alcohol usage.
• Drug-induced hepatitis, firstly focus on withdrawal of the
suspected drug.
• viral hepatitis, antivirals are the method of choice.
• primary biliary cholangitis, treatment of choice UDCA.
• End-stage liver disease, liver transplantation is the only
method of choice.
Treatment
• Obstructive jaundice: ERCP is done to remove or relieve the
obstruction, This method relies on sphincterotomy, balloon
dilatation, and stent placement.
• Malignant obstruction, surgery remains the method of choice.
Conclusion
• In every patient with suspected jaundice,
• Detailed history, laboratory, and imaging examinations are needed in
order to establish the etiology and accordingly determine the adequate
treatment.
•Thanks for listening
