Jaundice (icterus) is a moderately common finding on the physical examination of the emergency patient. It results from the accumulation of the pigment bilirubin in the plasma and tissues to the extent that a yellow discolouration becomes visible. Normal serum bilirubin levels should be less than ~ 6 µmol/L and jaundice only becomes visible when levels are around 35 µmol/L. Hyperbilirubinaemia thus has to be moderate or marked before jaundice is visible.
Clinical Approach to the Patient with Icterus
The key question that must be answered when evaluating an emergency patient where icterus is identified on initial physical examination is whether the jaundice is:
Determining between these categories is vital as it determines the differential diagnosis list and hence the diagnostic and treatment/stabilization plan.
Prehepatic icterus - Prehepatic icterus occurs when the rate of production of bilirubin exceeds the ability of the liver to excrete it. As the haemoglobin in red cells is the principle source of bilirubin, prehepatic icterus is seen with conditions where red cells are destroyed rapidly typically in an extravascular location; as such, prehepatic icterus is invariably associated with moderate-marked anaemia.
Hepatic icterus - Hepatic icterus occurs when liver function is compromised to the extent that it is no longer able to clear the normal daily bilirubin load. Icterus may be seen with both acute and chronic conditions that affect liver function and thus the differential list is long. Causes of acute onset hepatic icterus include hepatotoxins, infectious disease (e.g., leptospirosis), metabolic disease (e.g., hepatic lipidosis in cats), inflammatory disease (e.g., cholangiohepatitis in cats) and rarely infiltrative hepatic neoplasia such as lymphoma. The list of potential hepatotoxins is long but can include human foodstuffs (e.g., xylitol), prescribed medications (e.g., idiosyncratic valium toxicity in cats, paracetamol), biotoxins (e.g., aflatoxins, blue-green algae) and heavy metals (e.g., zinc, iron). Patients with chronic hepatic disease may occasionally present as emergencies with icterus due to acute deterioration of the chronic condition. If the animal has a long history of compatible clinical signs (e.g., PU/PD, weight loss, inappetence, vomiting, possibly abdominal distension) then this possibility should be strongly considered.
Posthepatic icterus - Posthepatic icterus occurs if the liver is able to clear the normal daily bilirubin load into the biliary system but the biliary system is unable to excrete it via the GI tract. This may be seen with biliary obstruction (e.g., severe pancreatitis) or biliary system rupture.
The first goal should be to determine if the icterus is prehepatic, hepatic or posthepatic. The diagnosis of prehepatic icterus is relatively straightforward as the patient will be at least moderately anaemic. A PCV is thus always the first test to prioritise in icteric patients. If the animal is moderately or markedly anaemic (approx PCV < 25% in dogs, PCV < 20% cats), then the icterus is very likely to be prehepatic in origin and differential list and work-up for haemolytic anaemia should be pursued. In patients with mild anaemia, the situation is less clear-cut as a mild anaemia may be associated with several causes of hepatic and posthepatic icterus. Clinical judgment must then be used but hepatic or posthepatic icterus is more likely.
If prehepatic icterus is ruled out, then a biochemistry panel and ultrasound imaging of the abdomen should be performed. The information gained from ultrasound imaging of the abdomen will be variable dependent on the skill of the ultrasonographer but at a minimum the animal should be assessed for the presence of free abdominal fluid and if present this should be sampled. With increasing skill level, the liver parenchyma should be examined and the pancreas, gall bladder and bile duct assessed. The diagnosis of obstructive cholestasis involves measurement of the diameter of the common bile duct with and identification of dilation - this requires a high level of skill.
The biochemistry panel should also be carefully evaluated for diagnostic information. Liver enzymes (ALT and AlkP) are both likely to be elevated with both hepatic and posthepatic disease although the magnitude of the increases may be helpful. ALT is a hepatocellular enzyme whereas AlkP is localized to the biliary endothelium. Thus with hepatic disease, the ALT tends to be proportionately higher than the AlkP and with posthepatic icterus, this is reversed. Other points it is important to remember are that neither ALT nor AlkP are reflective of liver function and in fact with some late stage chronic liver disease they may actually start to fall as the liver mass remaining to release them is so reduced.
The other parameters it is vital to assess on a biochemistry panel are those that are indicators of poor liver function notably blood glucose (low with hepatic failure as glucose is produced in liver via gluconeogenesis), BUN (low with hepatic failure as BUN is produced in liver from excess protein via urea cycle), cholesterol (low in hepatic failure as synthesized in liver) and albumin (low especially in chronic hepatic failure as synthesized in liver). If hepatic failure is suspected, clotting times (PT and PTT) should also be evaluated. Hepatic failure leads to prolongation of clotting times as most of the clotting factors are synthesized in the liver. Identification of prolonged clotting times will have implications for stabilization and further diagnostic decisions.
Finally if free abdominal fluid has been identified on ultrasound examination and sampled then a bilirubin should be run on this fluid. Biliary system rupture is diagnosed when the bilirubin in the free abdominal fluid is higher than the serum bilirubin. Although biliary rupture is very uncommon it is vital it is identified as urgent surgery is required whereas the therapy for almost all other causes of icterus is medical.
Any further diagnostic tests will be dependent on the refined prioritized differential list but may include full haematology panel, further imaging (thoracic imaging especially important if neoplasia is high on differential list), cPLI (if pancreatitis leading to obstructive cholestasis is high on differential list), infectious disease testing and sampling of the liver parenchyma (aspirate for cytology or biopsy). The first three are commonly performed on an emergency basis. If infectious disease is suspected (especially leptospirosis) then blood samples should be taken to submit to an external laboratory at the earliest possible opportunity. Sampling of the liver parenchyma is rarely performed on an emergency basis.
As with all emergency patients, initial stabilization should be based on the major body systems assessment. The range of diseases causing icterus is large and work-up may take a prolonged period of time, hence stabilization over the first few hours is likely to be empirical. Fluid therapy should be based on an assessment of whether the patient is hypovolaemic or dehydrated or both. Neurological abnormalities are relatively common in animals with severe liver disease. Seizures and abnormal mental status may occur secondary to hypoglycaemia or hepatic encephalopathy. Blood glucose should be checked as a priority and glucose supplemented if necessary (1 ml/kg of 50% dextrose solution diluted 50:50 with a replacement solution as an immediate bolus followed by supplementation at 2.5% or 5% glucose in the IV fluids). Hepatic encephalopathy is a complex metabolic disturbance that may be seen in patients with both acute and chronic liver disease. Signs may be fairly mild behavioural change through to seizures. Treatment involves oral lactulose and antibiosis such as ampicillin or metronidazole and in the longer term a low protein diet. If oral medications cannot be given due to the animal's neurological status, both lactulose and suitable antibiosis may be given rectally.
A more specific initial and longer term therapeutic plan will be dependent on the diagnosis or, if it is not possible to obtain a precise diagnosis initially, then the refined, prioritized differential diagnosis list.
Prehepatic icterus - Stabilization may include transfusion therapy with longer term treatment being tailored to the underlying cause of the haemolytic anaemia.
Hepatic icterus - If a toxic cause is suspected, treatment is principally supportive. The liver has a large capacity for regeneration thus even animals with severe clinical signs can recover. However, prolonged intensive (and expensive!) support may be required. If leptospirosis is on the differential list, therapy with intravenous ampicillin should be started at the earliest possible opportunity. It should also be remembered that leptospirosis is a zoonosis and can cause severe disease in people thus strict barrier nursing should be enforced. Other causes of hepatic icterus are likely to require a cytological or histopathological diagnosis and specific treatment will need to be delayed until these results are received. With all cases of hepatic icterus, clotting times should be evaluated and if prolonged administration of fresh frozen plasma should be considered - this is particularly important if the animal is going to undergo invasive sampling of the liver tissue.
Posthepatic icterus - If biliary rupture is diagnosed or marked extrahepatic biliary obstruction is present, then surgical treatment is required. As this surgery is not performed frequently and can be very complex, referral to a surgical specialist should be considered. Patients with pancreatitis should receive standard supportive and nutritional therapy; the icterus will resolve as the pancreatic swelling goes down.
References are available upon request.