3. small Anim. Pruct.
(1976) 17, 119-129.
Jaundice in the dog D . B. M U R D O C H Leahurst Veterinary Field Station, University of Liverpool, Neston, Wirral, Merseyside
ABSTRACT Jaundice or icterus is the clinical manifestation of an increase in the concentration of bilirubin in serum. The aetiology, clinical signs and the use of ancillary aids in the diagnosis of the conditions giving rise to jaundice in the dog will be discussed.
INTRODUCTION Jaundice in the dog has been sadly neglected in veterinary literature, although individual conditions giving rise to jaundice have been described by numerous authors. The first step towards an understanding ofjaundice is to consider the production and excretion of bile pigments by the body. This process begins with the breakdown of haemoglobin in the spleen and other reticulo-endothelial tissues to produce bilirubin which then circulates in the plasma, loosely linked to albumen. Bilirubin is then conjugated with glucuronic acid by the liver to enable it to be excreted into the bile canaliculi. This water-soluble form then passes along the bile ducts to the intestine and is eventually excreted as stercobilin, the pigment responsible for the brown appearance of faeces. The above description is an over-simplification of a more complicated process, but an understanding of the basic pathway greatly facilitates accurate diagnosis.
A E T I O L O G Y OF J A U N D I C E Whatever the reason for the increased concentration of serum bilirubin, the jaundice which follows is a staining of the mucous membranes, skin and other tissues by the excess circulating bilirubin. If we consider the pathway outlined 119
120
D . B. M U R D O C H
earlier, it can be seen that this excess of bilirubin in plasma and serum may develop at four points.
(1) Excessive breakdown of red blood cells (intravascular haemolysis) This situation arises when there is massive destruction of red blood cells producing large quantities of haemoglobin and, consequently, bilirubin. As the liver cannot clear this increased amount of bilirubin from the blood stream quickly enough, clinical jaundice develops. I n the dog this is an uncommon form of jaundice. Leptospira icterohaemorrhagiae produces a toxin causing some haemolysis of red blood cells but in these cases, the concomitant hepato-cellular damage will contribute to the jaundice for reasons outlined below. Anomalous antigen-antibody reactions also produce this form of jaundice, the commonest being incompatible blood transfusions. With the increasing use of blood in veterinary practice, transfusion reactions will become more common. Sixty per cent of all dogs are A+ve and are classed as ‘universal recipients’. Thus a transfusion reaction will only occur with the 40% of dogs which are A-ve and then only on second transfusion (Owen & Glen, 1972). The resulting jaundice is not clinically appreciable until several days after the transfusion. Haemolytic disease of the newborn is extremely rare in the dog as it only occurs when a pregnant A-ve bitch is transfused with A+ve blood (Young et al., 1951). Auto-immune haemolytic anaemia in the dog is associated with clinical jaundice. I n this condition, antibodies act against the host’s own red blood cells to produce intravascular haemolysis (Jones & Darke, 1975). Lewis et al. (1965), McKenzie (1969) and Dear (1970) all described the clinical signs of anaemia, splenomegaly and jaundice but in the author’s experience, jaundice is not a common clinical sign with this condition. Other instances of haemolytic jaundice which have been recorded in Britain are with Haemobartonella canis infection and Piroplasmosis, but these are extremely rare.
(2) Failure
oj. the liver to excrete bilirubin Many conditions produce generalized hepato-cellular damage. If this is severe enough to interfere with uptake, conjugation and excretion of bilirubin by the liver, then clinically detectable jaundice may develop. As hepato-cellular damage may also distort the bile canaliculi, there is always a certain degree of biliary obstruction present (see below). This explains why icteric dogs with hepatocellular damage will show elevations in both unconjugated and conjugated bilirubin because the liver is having difficulty in conjugating and excreting the bilirubin. Conjugated bilirubin reacts directly with the Van den Bergh reagent and hence is described as ‘direct’ reacting, whereas the unconjugated, which has not passed through the liver, only reacts after the addition of an uncoupling agent and is known as ‘indirect’ reacting bilirubin.
JAUNDICE IN THE DOG
121
Both cirrhosis and hepatic neoplasia which are the commonest causes ofjaundice in the dog in this country produce this type of lesion. These two forms of chronic liver damage are very difficult to differentiate although ascites occurs more commonly in cirrhosis than in hepatic neoplasms. Chronic hepato-cellular damage is a more frequent cause ofjaundice than acute hepato-cellular damage. As mentioned earlier, Leptospira icterohaemorrhagiae produces hepato-cellular jaundice but very few of the causes of hepatitis described in this country produce jaundice. Jaundice is uncommon in naturally occurring infectious canine hepatitis and the other infectious agents described in the literature, e.g. salmonellosis (Thompson & Wright, 1969) and toxoplasmosis (Frenkel, 1970). It is interesting to note that jaundice is commonly seen in acute necrotizing pancreatitis. This finding has been recorded by other authors (Holroyd, 1968; Greve et al., 1973) but whether the jaundice is due to hepatitis or pressure on the bile duct, has not been proved. The condition of myeloid leukemia presents many interesting features to the clinician. I t has been included in this discussion as jaundice is a presenting sign in many cases of myeloid leukemia due to the infiltration of hepatic parenchyma by large numbers of cells of the myeloid series. Although frequently incriminated by owners, the ingestion of toxic substances is rarely responsible for hepato-cellular jaundice. This is surprising as one of the liver’s principal functions is to remove circulating toxins. I n the dog, however, few toxic compounds exert their effect primarily on the liver. White phosphorous was used at one time as rat bait, but has now fallen out of favour. When chloroform was a popular anaesthetic, following prolonged administration, jaundice was occasionally recorded between 12 hours and 5 days later. Siebald & Bailey (1952) described an outbreak of toxic hepatitis in America (Hepatitis X) resulting from ingestion of proprietary foodstuffs containing peanut meal contaminated by the fungus, Aspergillusjams but the condition has not been recorded in this country.
( 3 ) Impaired excretion of bilirubin The conjugated bilirubin produced by the liver is excreted via the bile ducts to the duodenum. Any lesion which interferes with the patency of the bile duct, whether intra-ductal or extra-ductal, will cause retention of the bile. This explains why the excess bilirubin found in the plasma is principally the conjugated form of the pigment. This type of lesion gives rise to the most intense icteric staining of the mucous membranes seen in the dog. The bile duct enters the duodenum adjacent to the angle between the right and left lobes of the pancreas (Miller et al., 1965). Consequently, neoplasms of the pancreas, especially pancreatic carcinomata, can produce a severe obstructive jaundice. Holroyd (1968) states that in cases of obstructive jaundice in middleaged or old dogs, carcinoma of the pancreas should always be suspected.
122
D . B. MURDOCH
Cholelithiasis (gall-stones), a common cause of obstructive jaundice in man, is rarely associated with clinical disease in dogs (75 of the previously documented cases were discovered accidentally at post-mortem, Schall et al., 1973.) Bizarre cases of obstructive jaundice have been recorded as a sequel to intestinal obstruction with a foreign body (including a puppy with an acorn lodged over the duodenal papilla !) .
:
(1976) 17, 119-129.
Jaundice in the dog D . B. M U R D O C H Leahurst Veterinary Field Station, University of Liverpool, Neston, Wirral, Merseyside
ABSTRACT Jaundice or icterus is the clinical manifestation of an increase in the concentration of bilirubin in serum. The aetiology, clinical signs and the use of ancillary aids in the diagnosis of the conditions giving rise to jaundice in the dog will be discussed.
INTRODUCTION Jaundice in the dog has been sadly neglected in veterinary literature, although individual conditions giving rise to jaundice have been described by numerous authors. The first step towards an understanding ofjaundice is to consider the production and excretion of bile pigments by the body. This process begins with the breakdown of haemoglobin in the spleen and other reticulo-endothelial tissues to produce bilirubin which then circulates in the plasma, loosely linked to albumen. Bilirubin is then conjugated with glucuronic acid by the liver to enable it to be excreted into the bile canaliculi. This water-soluble form then passes along the bile ducts to the intestine and is eventually excreted as stercobilin, the pigment responsible for the brown appearance of faeces. The above description is an over-simplification of a more complicated process, but an understanding of the basic pathway greatly facilitates accurate diagnosis.
A E T I O L O G Y OF J A U N D I C E Whatever the reason for the increased concentration of serum bilirubin, the jaundice which follows is a staining of the mucous membranes, skin and other tissues by the excess circulating bilirubin. If we consider the pathway outlined 119
120
D . B. M U R D O C H
earlier, it can be seen that this excess of bilirubin in plasma and serum may develop at four points.
(1) Excessive breakdown of red blood cells (intravascular haemolysis) This situation arises when there is massive destruction of red blood cells producing large quantities of haemoglobin and, consequently, bilirubin. As the liver cannot clear this increased amount of bilirubin from the blood stream quickly enough, clinical jaundice develops. I n the dog this is an uncommon form of jaundice. Leptospira icterohaemorrhagiae produces a toxin causing some haemolysis of red blood cells but in these cases, the concomitant hepato-cellular damage will contribute to the jaundice for reasons outlined below. Anomalous antigen-antibody reactions also produce this form of jaundice, the commonest being incompatible blood transfusions. With the increasing use of blood in veterinary practice, transfusion reactions will become more common. Sixty per cent of all dogs are A+ve and are classed as ‘universal recipients’. Thus a transfusion reaction will only occur with the 40% of dogs which are A-ve and then only on second transfusion (Owen & Glen, 1972). The resulting jaundice is not clinically appreciable until several days after the transfusion. Haemolytic disease of the newborn is extremely rare in the dog as it only occurs when a pregnant A-ve bitch is transfused with A+ve blood (Young et al., 1951). Auto-immune haemolytic anaemia in the dog is associated with clinical jaundice. I n this condition, antibodies act against the host’s own red blood cells to produce intravascular haemolysis (Jones & Darke, 1975). Lewis et al. (1965), McKenzie (1969) and Dear (1970) all described the clinical signs of anaemia, splenomegaly and jaundice but in the author’s experience, jaundice is not a common clinical sign with this condition. Other instances of haemolytic jaundice which have been recorded in Britain are with Haemobartonella canis infection and Piroplasmosis, but these are extremely rare.
(2) Failure
oj. the liver to excrete bilirubin Many conditions produce generalized hepato-cellular damage. If this is severe enough to interfere with uptake, conjugation and excretion of bilirubin by the liver, then clinically detectable jaundice may develop. As hepato-cellular damage may also distort the bile canaliculi, there is always a certain degree of biliary obstruction present (see below). This explains why icteric dogs with hepatocellular damage will show elevations in both unconjugated and conjugated bilirubin because the liver is having difficulty in conjugating and excreting the bilirubin. Conjugated bilirubin reacts directly with the Van den Bergh reagent and hence is described as ‘direct’ reacting, whereas the unconjugated, which has not passed through the liver, only reacts after the addition of an uncoupling agent and is known as ‘indirect’ reacting bilirubin.
JAUNDICE IN THE DOG
121
Both cirrhosis and hepatic neoplasia which are the commonest causes ofjaundice in the dog in this country produce this type of lesion. These two forms of chronic liver damage are very difficult to differentiate although ascites occurs more commonly in cirrhosis than in hepatic neoplasms. Chronic hepato-cellular damage is a more frequent cause ofjaundice than acute hepato-cellular damage. As mentioned earlier, Leptospira icterohaemorrhagiae produces hepato-cellular jaundice but very few of the causes of hepatitis described in this country produce jaundice. Jaundice is uncommon in naturally occurring infectious canine hepatitis and the other infectious agents described in the literature, e.g. salmonellosis (Thompson & Wright, 1969) and toxoplasmosis (Frenkel, 1970). It is interesting to note that jaundice is commonly seen in acute necrotizing pancreatitis. This finding has been recorded by other authors (Holroyd, 1968; Greve et al., 1973) but whether the jaundice is due to hepatitis or pressure on the bile duct, has not been proved. The condition of myeloid leukemia presents many interesting features to the clinician. I t has been included in this discussion as jaundice is a presenting sign in many cases of myeloid leukemia due to the infiltration of hepatic parenchyma by large numbers of cells of the myeloid series. Although frequently incriminated by owners, the ingestion of toxic substances is rarely responsible for hepato-cellular jaundice. This is surprising as one of the liver’s principal functions is to remove circulating toxins. I n the dog, however, few toxic compounds exert their effect primarily on the liver. White phosphorous was used at one time as rat bait, but has now fallen out of favour. When chloroform was a popular anaesthetic, following prolonged administration, jaundice was occasionally recorded between 12 hours and 5 days later. Siebald & Bailey (1952) described an outbreak of toxic hepatitis in America (Hepatitis X) resulting from ingestion of proprietary foodstuffs containing peanut meal contaminated by the fungus, Aspergillusjams but the condition has not been recorded in this country.
( 3 ) Impaired excretion of bilirubin The conjugated bilirubin produced by the liver is excreted via the bile ducts to the duodenum. Any lesion which interferes with the patency of the bile duct, whether intra-ductal or extra-ductal, will cause retention of the bile. This explains why the excess bilirubin found in the plasma is principally the conjugated form of the pigment. This type of lesion gives rise to the most intense icteric staining of the mucous membranes seen in the dog. The bile duct enters the duodenum adjacent to the angle between the right and left lobes of the pancreas (Miller et al., 1965). Consequently, neoplasms of the pancreas, especially pancreatic carcinomata, can produce a severe obstructive jaundice. Holroyd (1968) states that in cases of obstructive jaundice in middleaged or old dogs, carcinoma of the pancreas should always be suspected.
122
D . B. MURDOCH
Cholelithiasis (gall-stones), a common cause of obstructive jaundice in man, is rarely associated with clinical disease in dogs (75 of the previously documented cases were discovered accidentally at post-mortem, Schall et al., 1973.) Bizarre cases of obstructive jaundice have been recorded as a sequel to intestinal obstruction with a foreign body (including a puppy with an acorn lodged over the duodenal papilla !) .
:
![[Slow infusion cholangiography in jaundice. An experimental study in the dog].](/assets/img/hold.png)
