Saturday, December 5, 2009

Jaundice – when your furry fellow turns bright yellow.

Introduction
Yesterday, I examined a cat name Pan who came in for weight loss and poor appetite. On physical examination, the cat was visibly jaundiced. In honor of Pan (who's getting an ultrasound-guided liver biopsy at my hospital on Friday), I'm posting this article to my blog.
If there was one thing Minka Esbensen could count on, it was her cat’s appetite. Kitty, a 9-year old male sealpoint Himalayan, has had his minor illness throughout his life – a little colitis here, a sprained paw there – but through it all, one thing remained consistent: the enthusiastic appetite. When the famous appetite disappeared for three days late last February, he was in my office in a flash.

According to Ms. Esbensen, Kitty had showed minimal interest in his food over the past three days. He could be coaxed to eat a few treats, and was still drinking normally, but he simply would not eat his regular food. He was a little lethargic, and had vomited twice two days prior, and twice the day before. On physical examination he checked out fine, except for some mild weight loss (10 ounces). Bloodwork was offered, but was declined by Ms. Esbensen. The plan was to offer him a variety of different yummy foods, and see how he did over the weekend. I thought that was reasonable.

On Monday, he was back. Kitty had absolutely zero interest in food, including people food. In the exam room he was bright and alert, but he had lost another four ounces. On examination, a new finding had emerged: the skin inside Kitty’s ears had a faint yellow appearance, as did the whites of his eyes and his gums. Kitty had developed jaundice.

Jaundice 101


“Jaundice (also called icterus) is a yellow discoloration of the tissues. It is most visible in the skin, the mucous membranes (for example, the gums), and the whites of the eyes. The yellow coloration is due to an excessive amount of a substance called bilirubin in the bloodstream”, says Dr. Michael Stone, a board-certified internist at Cummings School of Veterinary Medicine at Tufts University.

To understand the phenomenon of jaundice, a brief explanation of normal bilirubin metabolism is in order. Bilirubin is an orange-yellow pigment that comes from the breakdown of hemoglobin. The primary source hemoglobin is from old red blood cells. When red blood cells become old, most of them are removed from the circulation by cells called macrophages, which reside mainly in the spleen and liver. Once the red blood cells are gobbled up by the liver and spleen macrophages, the hemoglobin inside the red blood cells is metabolized to produce bilirubin. This bilirubin is then released into the circulation, where it binds to a protein called albumin. The albumin then transports the bilirubin to the liver.

Once the albumin-bilirubin arrives at the liver, the liver cells extract the bilirubin from the albumin, and then secrete the bilirubin into the biliary system (the gall bladder and the bile ducts). Eventually, bilirubin is released, along with bile, into the small intestine, where it plays an important role in digestion.

The feline liver is very good at taking bilirubin out of the bloodstream and delivering it to the biliary system, maintaining the serum bilirubin level in a pretty well-controlled range. To figure out why the bilirubin level in the bloodstream might become elevated, we need to examine the three traditional categories of jaundice.


Classifying the jaundice

Knowing the physiology of bilirubin metabolism allows us to understand the mechanisms by which excessive levels of bilirubin might develop. “One way bilirubin levels could build up is if too much bilirubin is being produced because of rapid red blood cell destruction” says Dr. Stone. “Another explanation for too much bilirubin in the blood stream would be an inability of the liver cells to properly remove it from the bloodstream. A third reason would be an impaired ability to release bilirubin from the biliary system into the intestine. These three explanations correspond to the traditional, shorthand way veterinarians classify jaundice: pre-hepatic, hepatic, and post-hepatic.” Although there is considerable overlap between the categories, this simplistic classification system allows for a clearer understanding of why cats turn yellow.

The literal translation of the word “pre-hepatic” would be “before the liver”. Indeed, pre-hepatic jaundice has nothing to do with the liver. The liver is fine. The problem has to do with excessive bilirubin production as a result of hemolysis - undue destruction of red blood cells. As mentioned above, bilirubin is derived from hemoglobin contained in red blood cells. The spleen and liver constantly monitor the circulation, removing old, damaged, or abnormal red blood cells from the circulation. If the liver and spleen remove too many red blood cells from the circulation, too much bilirubin will be produced. The liver will shift into overdrive, removing as much of the bilirubin as it can. Eventually, the liver’s capacity to remove this excessive amount of bilirubin is exceeded, and bilirubin levels build up in the bloodstream, staining the tissues yellow.

Pre-hepatic (hemolytic) causes of jaundice is less common in cats, compared to dogs. The most common cause for hemolysis in cats is Mycoplasma haemofelis (formerly called Hemobartonella felis), a red blood cell parasite. These parasites cling to the surface of the red blood cells. Macrophages in the liver and spleen recognize these cells as being abnormal, and they dutifully remove them from the circulation, releasing bilirubin into the bloodstream. There other causes for hemolysis in cats, as well.


Hepatic jaundice, as the name implies, is jaundice that develops as a result of liver impairment. Severe liver disease, such as cholangiohepatitis (inflammation of the liver and bile ducts), hepatic lipidosis (fatty liver disease), or liver cancer may impair bilirubin metabolism, preventing the liver from processing the bilirubin effectively. As a result, the bilirubin levels become elevated, leading to visible jaundice.

The third category, post-hepatic jaundice, is said to occur when the primary abnormality is an impaired ability to excrete the bilirubin due to an obstruction of the flow of bilirubin and bile through the major bile ducts. Common causes of bile duct obstruction include cancer and gallstones.

Of the types of jaundice, hepatic causes are the most common. Common signs of liver disease in cats include poor or absent appetite, lethargy, weight loss, vomiting, diarrhea, dehydration, unusual behavior, and prolonged bleeding.


Diagnostic approach to a cat with jaundice

With Kitty showing signs of jaundice, it was time to do a little investigating. The first step in evaluating the cause of feline jaundice is to rule out any pre-hepatic causes. In other words, is the high bilirubin level due to excessive destruction of red blood cells? This is easily determined by measuring the hematocrit – the percentage of the blood that consists of red blood cells. This test can be readily performed in-house in all veterinary hospitals. The normal hematocrit for a cat is somewhere between 29 and 48%. If a jaundiced cat has a hematocrit that falls in this range, then red blood cell destruction is unlikely to be the culprit. If, however, the hematocrit is low (less than 20%), hemolysis is likely to be the cause of the increased bilirubin levels, and further evaluation for causes of hemolysis is warranted. A complete blood count was performed on Kitty, and his hematocrit was a robust 41%. No anemia.

Once pre-hepatic causes have been eliminated, the cat should be evaluated for causes of liver disease (see sidebar). Liver diseases that frequently cause jaundice in cats include cholangiohepatitis, hepatic lipidosis, lymphoma, feline infectious peritonitis, and toxic liver disease. Evaluation for liver disease should include a complete blood count, serum chemistry panel, urinalysis, and blood clotting evaluation. Kitty’s complete blood count was normal, however, the chemistry panel and urinalysis told a different story.

Increased liver enzymes are expected in most cats with jaundice. Most biochemistry panels report the activity of four liver enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT). Elevations of the first two, ALT and AST, reflect damage to the liver cells. Elevations of the second two, ALP and GGT, reflect an impairment of bile flow within the tiny bile channels between liver cells. In most cases, all four enzymes are elevated. Bilirubin levels are also reported on the chemistry panel, and of course these levels will be elevated, confirming and quantifying the jaundice. Not surprisingly, Kitty had elevated ALT, AST, and ALP levels. His GGT level was normal. The bilirubin level was markedly elevated, approximately 15 times the normal value.

The urine of jaundiced cats will often be a bright, almost fluorescent orange, due to increased bilirubin levels. “While it may be normal for dogs to have a small amount of bilirubin in their urine, the presence of bilirubin in feline urine is always an abnormal finding”, notes Dr. Stone. Indeed, Kitty’s urine specimen glowed a bright orange. The complete blood count in cats with liver disease may be normal, as it was with Kitty, or it may show an elevated white blood cell count in cases of liver infection. Abnormally shaped red blood cells (called poikilocytes) are a common finding in cats with liver disease. Other laboratory tests may be warranted, depending on circumstances.

Post-hepatic causes of jaundice, i.e. obstruction of bile flow from the gall bladder and/or common bile duct, is much less common than jaundice due to primary liver disease. Diagnosis of bile flow obstruction, due to cancer, gallstones, etc. is best diagnosed via ultrasound.

Diagnostic imaging of the liver is an important part of the diagnostic workup for jaundice. Liver size, and the presence of calcified gallstones, may be evaluated with abdominal x-rays. Ultrasound, however, is a more useful technique and provides a wealth of information. Ultrasonography is the technique most often employed to differentiate post-hepatic causes of jaundice (tumors, gallstones, etc.) from hepatic causes (primary liver diseases). Ultrasound usually allows identification of liver cancer, liver cysts, and/or liver abscesses. Abnormalities of the liver tissue itself, such as lipidosis (infiltration of the liver with fat), cholangiohepatitis (infiltration of the liver with inflammatory cells), and lymphoma (infiltration of the liver with cancerous lymphocytes) can sometimes be differentiated. Ultrasound of Kitty’s liver ruled out post-hepatic causes of his jaundice, supporting what we already suspected – that a liver disorder was his main issue. Indeed, the appearance of his liver on ultrasound suggested some type of cellular infiltrate. Was this a cancerous infiltrate, or was it an inflammatory disease, such as hepatitis?

While bloodwork and ultrasound provide an abundance of information regarding the liver and biliary system, a definitive diagnosis ultimately requires a liver biopsy. There are several ways of obtaining a liver biopsy, the two most common being needle biopsy and surgical biopsy. A needle biopsy is obtained by inserting a biopsy needle – either “blindly”, or using ultrasound guidance – into the liver and obtaining a small sample. Alternatively, a biopsy specimen can be obtained during exploratory surgery. The advantage of needle biopsy is that it is less invasive, and often only requires mild, short-acting anesthesia. With a needle biopsy, however, there is a risk that the specimen obtained may not be representative of the disease process that is present, especially if the disease is focal, involving a discrete portion of the liver. Exploratory surgery affords a better biopsy specimen, and allows the surgeon to visually assess and to feel the liver, as well as other abdominal organs, and take additional biopsy specimens if warranted. Of course, the disadvantage of exploratory surgery is that it is invasive, involving general anesthesia, and a longer hospital stay. It is also more costly. Ms. Esbensen elected for Kitty to have a surgical biopsy, to maximize the chances of obtaining a definitive diagnosis.

After a blood clotting profile confirmed that his blood clotting ability was unaffected, Kitty was taken to surgery, and a biopsy of his liver was obtained. The diagnosis: lymphocytic cholangiohepatisis, an inflammatory disorder. While Kitty was under anesthesia, a feeding tube was placed in his esophagus through a small incision in the left side of his neck. This allowed Ms. Esbensen to provide proper nutrition, as well as to provide him with the medications and supplements necessary to treat this disorder.

Kitty was faithfully given his medication through his feeding tube, and he began to gain weight and feel better. Most noticeable was the jaundice, or lack thereof. The yellow tinge to his skin, ears and gums was slowly dissipating. For three weeks, however, he refused to eat. Four weeks after his medical therapy was prescribed, a serum chemistry panel was obtained, and all of his liver parameters had returned to normal, including his bilirubin. During the fifth week, he began to eat a few treats on his own. Ms. Esbensen and I both suspected that the feeding tube had begun to annoy Kitty, and that removing the tube might actually spur him to eat on his own. With some trepidation, we removed the tube. Shortly afterward, Kitty began to eat on his own. Nearly two months after his initial bout of poor appetite, Kitty was now his usual, hungry self.

Conclusion

Jaundice is a common problem encountered in feline practice. Years ago, there was an old adage amongst veterinarians: “a yellow cat is a dead cat”. Thanks to numerous diagnostic and therapeutic advances, this is no longer the case. When faced with a jaundiced cat, the veterinarian’s challenge is to figure out where the derangement in bilirubin metabolism is occurring, and then formulate a proper diagnostic plan. Over the years, the prognosis for treating the diseases that cause jaundice have improved markedly, and many jaundiced cats recover and live long, healthy lives.


Signs of liver disease in cats

  • Decreased or absent appetite
  • Lethargy
  • Weight loss
  • Vomiting
  • Dehydration
  • Odd behavior
  • Prolonged bleeding
  • Ascites (fluid accumulation in the abdomen; less common in cats with liver disease, compared to dogs)


Common causes of liver disease in cats

  • Hepatic lipidosis (fatty liver disease)
  • Cholangiohepatitis (inflammation of the liver and bile ducts)
  • Lymphoma (a type of cancer)
  • FIP (Feline Infectious Peritonitis, a fatal viral disease)
  • Toxic hepatopathy (liver disease secondary to ingestion of a toxin or poison)
  • Hepatic amyloidosis (accumulation of amyloid, a type of protein, in the liver. Often seen in Oriental and Siamese breeds)

Read my article:
"Jaundice - when your furry fellow turns bright yellow."


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