Icterus

Description

Icterus refers to the staining of tissues by bilirubin pigment or bilirubin complexes. Bile pigments such as bilirubin have particular affinity for elastic tissues and the typical yellow/orange colour of icterus is therefore evident in the slcera and mucous membranes in life and in the tunica intima of the aorta at post mortem examination.

Bilirubin is a pigment of red blood cells which is released into plasma cells when these cells are degraded in the monocytic phagocyte system (MPS). This unconjugated bilirubin is transported in plasma bound to albumin and taken up into hepatocytes where it is conjugated with glucuronic acid. The resultant conjugated bilirubin is secreted into bile which then moves into the small intestine. The conjugated bilirubin is degraded to urobilinogen by gastro-intestinal bacteria and a small proportion of this product is reabsorbed and excreted in the urine. The remaining urobilinogen is further degraded to stercobilinogen, a brown pigment which contributes to the colour of faeces. Therefore, in animals with complete biliary obstruction, urobilinogen is absent from the urine and the faeces have a white/grey 'acholic' colour due to the absence of stercobilinogen. Small quantities of conjugated bilirubin are found in the urine of normal dogs because it has a low renal threshold.

The serum bilirubin concentration of an animal indicates the degree of icterus and the condition only becomes clinically evident at levels above 2 mg/100 ml (normal range below 0.5 mg/100 ml). Bilirubin should be measured by a technique which measures the large proportion which is bound to plasma albumin.

Causes of Icterus

Prehepatic Jaundice

This condition results from increased red blood cell destruction, overwhelming the capacity of the liver to conjugate and excrete the bilirubin which is released into the plasma. The majority of the bilirubin is therefore unconjugated and, unlike the conjugated form, this cannot be excreted by the kidney. Possible causes of haemolysis and prehepatic jaundice include:

• Haemolytic bacteria, including Clostridium haemolyticum in cattle and Leptospires in various species.
• Haemolytic parasites, including Babesiosis in cattle and dogs
• Immune reactions to red blood cells, including:
  • Neonatal isoerthryolysis, resulting from the production of antibodies by the dam which are ingested by the neonate in colsotrum and subsequently cause destruction of red blood cells. Bilirubin is able to cross the immature blood brain barrier and cause direct damage to the neurones of the brain, a phenomenon called kernicterus.
  • Autoimmune haemolytic anaemia or Immune-mediated haemolytic anaemia
  • Destruction of red blood cells of lambs fed with colostrum from certain cattle
• Hypophosphataemia, which may occur in Post-parturient Haemoglobinuria of cattle, rapid stabilisation of animals suffering from diabetic ketoacidosis with insulin and refeeding syndrome
• Inherited defects of red blood cell enzymes, including phosphofructokinase and pyruvate kinase
• Microangiopathic damage to red blood cells as they pass through narrow or damaged blood vessels, as in haemangiosarcomata, disseminated intravascular coagulation (DIC) or vasculitis
• Oxidant damage to red blood cells, caused by paracetamol in cats, onion poisoning in dogs and copper toxicity in many species. Ingestion of red maple leaves may also cause haemolysis in horses, as may brassicas (such as rape and kale) in cattle and sheep.

Haemolysis which is sufficiently severe to cause icterus is likely to be life-threatening due to the reduction in oxygen-carrying capacity of the blood. Animals affected acutely may require transfusions of whole blood, packed red blood cells or synthetic bovine haemoglobin and it may be advisable to provide oxygen by nasal catheter, flow-by or mask. In addition, the presence of large amounts of haemoglobin may cause acute intrinsic renal failure (in addition to the pre-renal failure caused by the reduced oxygen delivery to the kidneys) and neonates may suffer from kernicterus, direct damage to the central nervous system by bilirubin.

Hepatic Jaundice

two factors are concerned in the production of jaundice following liver cell damage

• damage to liver cells can interfere with the passage of bile along the bile capillaries
  • eg intrahepatic obstruction
• Liver cell damage may cause failure of conjugation and therefore excretion failure of bile pigment

Obstructive jaundice

• due to bile duct obstruction
• accumulation of conjugated bilirubin
• bile pigment is excreted in the urine
• bile pigment will be diminished in the faeces
• diseases
  • carcinoma involving the head of the pancreas