EVALUATION OF JAUNDICE IN ED

 

 

Jaundice is the yellow discoloration of body tissues caused by an excess accumulation of bilirubin, also referred to as hyperbilirubinemia. 

Normal bilirubin levels are less than 1mg/dL, while scleral icterus, a sign of jaundice, is observed when levels exceed 3mg/dL.

 Jaundice is classified into two main types.

1.       Unconjugated hyperbilirubinemia 

2.       Conjugated hyperbilirubinemia

Forms of Bilirubin	Characteristics
Unconjugated	- Insoluble in water. - Travels in the bloodstream bound to albumin. - Cannot be directly excreted from the body.
Conjugated	- Water-soluble. - Travels freely in the bloodstream. - Excreted in bile and urine

      Pathophysiology of jaundice

• metabolism of bilirubin occurs in 3 phases.

1. Prehepatic phase
2. Hepatic phase
3. Post hepatic phase.

1.       

2.       

Conjugated Hyperbilirubinemia	Unconjugated Hyperbilirubinemia
Defects in canalicular transport Dubin-Johnson syndrome	·       Excess production of bilirubin Haemolytic anaemias    ·       Dyserythropoiesis    ·       Extravasation of blood into tissues)
Defects in sinusoidal reuptake Rotor Syndrome	Reduced hepatic uptake.    ·       Gilbert syndrome    ·       Heart failure    ·       Portosystemic shunts    ·       Certain drugs - Rifampin, probenecid, flavaspadic acid, bunamiodyl
Intrahepatic Cholestasis ·       Viral hepatitis (A, B, D, EBV, CMV, HSV) ·       Wilson ·       Autoimmune ·       Alcoholic hepatitis, cirrhosis ·       Non-alcoholic steatohepatitis ·       Primary biliary cholangitis, Primary sclerosing cholangitis ·       Infiltrative diseases (amyloidosis, lymphoma, sarcoidosis, tuberculosis) ·       Pregnancy ·       Sepsis and hypoperfusion states, Total parenteral nutrition ·       Drugs and toxins (eg, alkylated steroids, chlorpromazine, herbal medications, arsenic) ·       Hepatic crisis in sickle cell disease	Impaired conjugation       ·       Crigler–Najjar syndrome     ·       Gilbert syndrome     ·        Hyperthyroidism     ·       Oestradiol /Oestrogen     ·       Neonates     ·       Liver Diseases- Cirrhosis
Extrahepatic cholestasis ·       Choledocholithiasis ·       Tumours (cholangiocarcinoma, pancreatic cancer) ·       Pancreatitis ·       Strictures ·       Parasitic infections like Ascaris, liver flukes

In ED emergency evaluation is usually not required except for the following three conditions which are life threating and require early identification and treatment.

Jaundice – Medical Emergencies
Massive Haemolysis	Clostridium perfringens sepsis or falciparum malaria
Ascending Cholangitis	That can lead to sepsis and liver abscesses if not treated promptly. It often requires emergency antibiotic treatment and sometimes surgical intervention.
Fulminant Hepatic Failure	A rapid deterioration of liver function, typically associated with encephalopathy and coagulopathy. It is a life-threatening condition that requires immediate medical attention, often in an intensive care unit.

Diagnostic Approach

diagnosis of jaundice is based on- 

1.Focused History

2.Physical examination

3.Laboratory Evaluation

1 Focused History

History Information	Possible diagnosis
Use of medications, herbal medications, dietary supplements, recreational drugs	·        Drug-induced hyperbilirubinemia
Hepatitis risk factors	·        Viral hepatitis
History of abdominal operations	·        Post-surgical complications
Inherited disorders	·        Genetic liver diseases
HIV status	·        HIV-associated liver disease
Exposure to toxic substances	·        Toxic liver injury
Development/worsening of jaundice during stress	·        Gilbert syndrome
Fever with chills or right upper quadrant pain	·        Acute cholangitis
Anorexia, malaise, myalgias	·        Viral hepatitis
Right upper quadrant pain	·        Extrahepatic biliary obstruction
Acholic stool (Clay coloured stool)	·        Biliary obstruction     ·        Although rare, it can also be seen in the acute cholestatic phase of viral hepatitis

2 Physical examination

Physical Examination Finding	Potential Implication
Courvoisier sign (palpable gallbladder)	Obstruction distal to the cystic duct, often due to malignancy
Ascites	Chronic liver failure or portal hypertension
Splenomegaly	Portal hypertension or other hematologic conditions
Spider angiomata	Chronic liver disease
Gynecomastia	Hormonal imbalance often associated with liver disease
Hyperpigmentation	Hemochromatosis
Kayser-Fleischer rings	Wilson disease
Xanthomas	Primary biliary cholangitis

3 Laboratory Evaluation

 

·       Serum total and unconjugated bilirubin
·       Alkaline phosphatase
·       Aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT])
·       Prothrombin time/international normalized ratio (INR) – acute liver function
·       Albumin – chronic liver function
·       Urine Bilirubin

·       Hepatocellular workup: viral serologies, autoimmune antibodies, serum ceruloplasmin, ferritin.

      Cholestatic workup: Additional tests include abdominal ultrasound, CT, magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC), endoscopic ultrasound (EUS).

 

Interpretations

Test	Interpretation
AST (Aspartate Aminotransferase)	- Less specific to the liver than ALT - Non-hepatic sources: Skeletal muscle, Cardiac muscle, RBC, Brain, Kidney.
ALT (Alanine Aminotransferase)	- More specific to the liver than AST. - Non-hepatic sources: Skeletal muscle, Cardiac muscle, Kidney.
GGT (Gamma-Glutamyl Transferase)	- Specific to the liver. - Assists in liver specificity when combined with ALP.
AST/ALT Ratio	- AST/ALT > 2: Alcoholic hepatitis - AST/ALT < 1: NASH or Cirrhosis. - AST/ALT > 3: Acute muscle injury.
ALP (Alkaline Phosphatase)	- ALP > AST/ALT: Suggestive of cholestatic disease. - ALP elevation with Normal GGT and 5-Nucleotidase rules out hepatic causes.
	- ALP elevation with normal AST/ALT: Indicates infiltrative diseases.
Unconjugated Bilirubin	- If >90% of total bilirubin: Hemolysis or Gilbert’s syndrome.
AST and ALT values in 1000s	- Hepatocellular disease likely due to toxins (e.g., acetaminophen), ischemia, or viral infections.
Normal AST, ALT, and ALP	- Pre-hepatic causes: Inherited disorders of liver conjugation, blood disorders - Defects in hepatic excretion (e.g., Rotor syndrome, Dubin-Johnson syndrome).

 

R value 

 

The R value is a ratio used to interpret liver function tests, particularly in the context of liver injury.

It compares the levels of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) against their respective upper limits of normal (ULN).

 

Here’s how you can represent the R value formula:

This formula helps in differentiating between hepatocellular injury and cholestatic or obstructive patterns of liver disease.

 

·       R > 5 - suggests hepatocellular damage

·       R < 2 - suggests cholestatic or obstructive damage.

·       R 2-5 - may require further investigation or could be indicative of mixed liver injury.

 Remember to use the patient’s specific lab values and ULN for accurate calculation and interpretation.

Jaundice evaluation in ED

Remember that ALP is elevated not only in Obstructive jaundice it can also occur with intra hepatic cholestasis. The following flow chart helps in differentiate various causes of raised ALP.

Also moderate elevation of AST /ALT is not always due to Liver injury. AST ALT is not 100% specific to Liver as I discussed above the condtions with moderate elevation of AST/ALT are the following

1.Thyroid Disorders

2. Myocardial Infarction

3. Adrenal insufficiency

4. Muscle Injuries (as in Strenous exercise / Myopathy) 

5. Anorexia Nervosa / Celiac Disease

References

1.Guerra Ruiz AR, Crespo J, López Martínez RM, Iruzubieta P, Casals Mercadal G, Lalana Garcés M, Lavin B, Morales Ruiz M. Measurement and clinical usefulness of bilirubin in liver disease. Advances in Laboratory Medicine/Avances en Medicina de Laboratorio. 2021 Aug 4;2(3):352-61.

2.Uptodate -Evaluation of Jaundice

3.Schwarzenbach HR. [Jaundice and pathological liver values]. Praxis (Bern 1994). 2013 Jun  05;102(12):727-9. [PubMed]

4.

Leung TS, Outlaw F, MacDonald LW, Meek J. Jaundice Eye Color Index (JECI): quantifying the yellowness of the sclera in jaundiced neonates with digital photography. Biomed Opt Express. 2019 Mar 01;10(3):1250-1256. [PMC free article] [PubMed]

5.

Roche SP, Kobos R. Jaundice in the adult patient. Am Fam Physician. 2004 Jan