Author: Lindsay Reid / Editor: Janet Skinner / Reviewer: Michael Perry / Codes: CAP19 / Published: 20/10/2017 / Review Date: 20/10/2020
Jaundice is a physical finding, which emergency physicians see in patients who may present with jaundice alone or with other complaints and symptoms.
Alone, jaundice has no adverse effects, except in the neonate. It is the task of the emergency physician to evaluate the cause of jaundice by initiating appropriate investigations and making a decision regarding the need for in-patient admission for further investigation and management. Jaundice is not a disease but a clinical sign also known as icterus. It is yellow discolouration of the skin, sclerea and mucus membranes caused by deposition of bile pigments. Jaundice is often associated with pruritus.
Basic Science and Pathophysiology
In order to understand the physiology of jaundice, it is important to appreciate the normal physiology of Haem metabolism. Between 425 and 510 mmol of unconjugated bilirubin is produced from catabolism of haem every day. Red blood cells (RBC) pass through the reticuloendothelial system and, as they reach the end if their lifespan (120 days), they rupture and release their contents into the plasma.
Haemoglobin is the portion of the RBC that is involved in jaundice. Haemoglobin is broken down into haem and globin by macrophages. The globin portion is a protein broken down into Amino acids. The Haem portion is initially oxidised to biliverdin, which is then reduced to form bilirubin. At this point, the bilirubin is unconjugated or indirect. The majority of Bilrubin is created in this way but 20% comes from other haem sources, such as ineffective erythropoeisis, the break down of myoglobin in muscle and the break down of cytochromes and catalase.
Pre-hepatic causes of jaundice include
- Sickle cell anaemia
- Glucose 6-PD deficiency
- Transfusion reaction
Anything that causes increased rate of red cell breakdown (haemolysis) will lead to jaundice due to increased haem metabolism and saturation of enzymes
Unconjugated bilirubin travels to the liver bound to serum albumin where it is conjugated with glucuronic acid to form conjugated bilirubin.
Hepatic causes of jaundice include
- Drugs and toxins (Alcohol, paracetamol, anabolic steroids, isoniazid, amanita toxin, chlorpromazine, flucloxacillin, halothane)
- Infections (viral hepatitis, infectious mononucleosis, leptospirosis)
- Metabolic (Wilsons disease, Reyes disease, haemochromatosis)
- Granulomatous (Wegeners granulomatosis, lymphoma, sarcoidosis, mycobacterial
- Genetic (Gilberts syndrome, Crigler Najjar syndrome, Dubin-Johnson syndrome)
- Others (fatty liver of pregnancy, primary biliary cirrhosis, amyloidosis, metastatic carcinoma, neonatal jaundice)
Anything that impacts on the hepatic metabolism of bilirubin can cause jaundice
Conjugated bilirubin is excreted into biliary and cystic ducts as part of bile. In the small intestine it is converted by enzymes to urobilinogen. Urobilinogen can be further converted to stercobilinogen and passes out with faeces or reabsorbed by intestinal cells and transported in blood to the kidneys where it is oxidised to urobilin and passed out with urine. Stercobilin and urobilin are responsible for colouration of faeces and urine respectively.
Post-hepatic causes of jaundice include
- Obstructive causes due to inability to excrete bile
- Drugs (amitryptylline, prochlorperazine, verapamil, co-amoxiclav)
- Gallstones (cholecystitis alone does not produce jaundice)
- Pancreatic carcinoma
- Primary sclerosing cholangitis
- Biliary atresia
- Bile duct strictures
- Pancreatic pseudocyst
Any process which causes post-hepatic obstruction can result in jaundice
Clinical assessment should concentrate on taking an accurate history and examination looking for findings that will help differentiate the causes of jaundice.
The history should focus on questioning about risk factors as well as the onset of jaundice. Specifically, remember to ask about:
- Alcohol intake
- Transfusion of blood products
- Sexual contact with a person known to have hepatitis or promiscuous sexual activity
- Intravenous drug misuse
- Recent tattoos or body piercing
- Recent foreign travel
- Accidental needle stick injury
Questioning about colour of urine and stool, weight loss and family history of jaundice will also help formulate a differential diagnosis.
Eliciting an accurate history is vital when looking for the cause of jaundice in a patient
A full examination should follow accurate history taking. Focus on the GI system as a whole may provide clues as to the cause of jaundice. A hard nodular liver on a background of known malignancy may indicate metastatic disease. Signs such as palmar erythema, spider naevi, proximal muscle wasting/weakness, hepatic flap, fetor hepaticus, cerebellar signs or encephalopathy may indicate alcoholic liver disease. Fever and right upper quadrant tenderness in association with jaundice are known as Charcots Triad, characteristic of acute cholangitis. Painless jaundice and cachexia and an epigastric mass suggests biliary obstruction due to malignancy.
Jaundice will be apparent when the serum bilirubin is 3x above normal. (The normal value of bilirubin is
Pre-hepatic hyperbilirubinaemia Unconjugated bilirubin is bound to Albumin and is not water-soluble therefore cannot appear in the urine.
Post-hepatic hyperbilirubinaemia Conjugated bilirubin is water-soluble and therefore appears in the urine. Urobilinogen is absent due the inability of conjugated bilirubin to be excreted in to the small intestine.
The findings in the urine should then be confirmed by measuring direct (conjugated) and total bilirubin levels
Liver Function Tests
Liver function tests (LFTs) are the central test when investigating jaundice and often point towards the cause.
Other blood tests include:
- Full blood count Reticulocyte count/film haemolysis indicated by raised reticulocyte count and schistocytes on blood film. Coombs test will be positive.
- Amylase If raised may indicate pancreatitis
- Hepatitis serology Hepatitis serology for viral hepatitis
- Autoimmune markers Autoimmune markers such as anti-nuclear antibodies and anti-smooth muscle antibodies. The majority of patients with primary biliary cirrhosis are positive for anti-mitochondrial antibody. Up to 85% of patients with primary sclerosing cholangitis are positive with perinuclear staining anti-nuclear cytoplasmic antibody
- Alpha 1 antitrypsin Deficiency may proceed to liver cirrhosis.
- Copper/ceruloplasmin if low may indicate Wilsons Disease.
- Ferritin/transferring saturation Ferritin levels >1000ng/ml and transferring saturations > 50% will indicate Haemochromatosis.
LFTs are the key investigation in a patient with jaundice
The MRCP or Magnetic Resonance Cholangiopancreatography is a useful non invasive, radiation free diagnostic test. It is useful for evaluating the biliary tree, pancreas and liver. The findings of the MRCP will aid the decision on whether proceeding to the more invasive ERCP is required.
The majority of diagnostic imaging in patients with jaundice will be performed out with the ED if the patient is stable.
Abdominal USS Abdominal USS is useful as an initial radiological test to distinguish between hepatocellular and extra-hepatic causes. It is cheap, readily available, lacks radiation and is more sensitive than CT at detecting stones in the gallbladder. The drawback of USS is that it is not good at detecting intraparenchymal disease of the liver or pancreas.
CT CT is better at determining intraparenchymal liver/pancreas disease. Neither Ultrasound nor CT is good at delineating intraductal gallstones
ERCP endoscopic retrograde cholangiopancreatography (ERCP) may be required and is particularly useful to detect disease in the biliary and pancreatic ducts, which may be missed on CT and USS. As well as a diagnostic adjunct it may be used therapeutically to remove gallstones from the biliary tract or place stents across narrow ducts. The most common and serious complication of ERCP is pancreatitis.
Liver Biopsy Liver biopsy is useful if serum and radiological investigations have not suggested a firm diagnosis. Liver biopsy is particularly useful in diagnosing Autoimmune Hepatitis or biliary tract disorders such as primary biliary cirrhosis or primary sclerosing cholangitis
abdominal USS is the most useful first-line imaging investigation in a patient with jaundice
Often the course of jaundice will be indolent and therefore the emergency physician may only be involved in facilitating the initial investigations and management with a decision as to whether the patient should be admitted or discharged. However, it is important to remember that jaundice can reflect a medical emergency. These cases include:
- Ascending cholangitis
- Fulminant hepatic failure
- Massive haemolysis
- Neonatal jaundice
Timely diagnosis, resuscitation and initiation of therapy in these situations should occur. Patients with jaundice and anaemia due to haemolysis require admission.
Patients with raised Alkaline Phosphatase and GGT are likely to have biliary tract obstruction and should have an USS requested in the ED and appropriate surgical/GI referral depending on the findings. Patients with raised AST/ALT have hepatocellular injury and should be admitted if there is evidence of:
- Altered mental status,
- Intractable pain/vomiting
- Otherwise outpatient investigation may be appropriate.
Acute Liver Failure
Patients with hepatocellular injury, coagulopathy and altered mental status may have acute liver failure and require admission to critical care area. The most common cause of fulimant hepatic failure (FHF) in UK is paracetamol poisoning but acute Hepatitis B is the most common cause worldwide due to its prevalence. Prior to liver transplantation, the mortality of FHF was greater than 80%. The most important aspect of managing FHF is good supportive care remembering that encephalopathy may lead to failure to protect and maintain an airway. Fluid resuscitation and haemodynamic monitoring are also important
The management of paracetamol poisoning depends upon when the patient presents to the ED and the estimation of quantity of paracetamol taken
Within 1 hour of overdose If the patient presents within 1 hours of overdose it is useful to give activated charcoal as decontamination, absorption from the gut is usually complete within 2 hours. If the quantity is potentially life threatening, gastric lavage is thought to be useful if it can be carried out within 1 hour of ingestion. Contraindications to lavage are patients who have a compromised, unprotected airway.
Within 8 hours of overdose If the patient presents within 8 hours, N-Acetyl Cysteine is proven to reduce the risk of serious hepatotoxicity, however when the patient presents as late as 48 hours, NAC is still beneficial. Indications for consideration of liver transplant are:
- Acidaemia (pH <7.3)
- Renal insufficiency
- Grade III or worse hepatic encephalopathy
- Elevated PT
Pregnancy and neonatal jaundice
Any pregnant jaundiced patient should be managed in conjunction with the obstetrician. Patients who present with jaundice in the third trimester may require delivery.
Well appearing neonates with a bilirubin <15mg/dL can safely be discharged home with close outpatient follow-up. Neonatal jaundice can often be physiological due to increased break down of premature erythrocytes and insufficient Glucuronyl Transferase in the newborn liver but jaundice persisting after 2 weeks requires investigation. Neonatal jaundice is treated with phototherapy. Quick and accurate treatment of neonatal jaundice reduces the risk of development of kernicterus, deposition of bilirubin in the basal ganglia. Exchange transfusion is an aggressive treatment to lower bilirubin levels.
Prognosis & Followup strategies:
Key Learning Points
- Understanding Haem metabolism is key to understanding jaundice.
- The differential diagnosis of jaundice is very wide.
- LFTs are the key Emergency department investigation in jaundice. (grade 4, recommendation D)
- Abdominal USS is useful and readily available as first line imaging in the ED. (grade 3, recommendation D)
- Patients with coagulopathy, sepsis or altered mental status must be admitted. (grade 4, recommendation D)
- Ascending cholangitis, fulminant hepatic failure, massive haemolysis and neonatal jaundice reflect medical emergencies (grade 4, recommendation D)
Safety pearls and Pitfalls:
- Assuming if USS is negative that there is no intraparenchymal disease of liver or pancreas.
- False negatives for bilirubin in the urine occur with Rifampicin.
- False positives for urinary urobilinogen occur in acute porphyria.
- Hypervitaminosis A or high levels of carotene can cause a paitent to appear jaundice but will have normal bilirubin levels
- Tintinalli Judith E, et al. Tintinallis Emergency Medicine: A Comprehensive Study Guide. 6th Edition, 2004, McGraw-Hill.
- Praveen Kumar and Michael Clark, Kumar and Clark Clinical Medicine, 2005, Elsevier Health Sciences