Clinical approach to the icteric cat (Proceedings)

Icterus occurs when bilirubin accumulates in the plasma and tissues to the extent that it causes visible yellow discoloration of the sclera, mucous membranes, and skin. This occurs when:

     bilirubin > 2 mg/dl (Normal 0.0–0.3mg/dl)

     • Feline Bilirubin Metabolism

          o Bilirubin is a heme breakdown product, produced mostly in the spleen. Carrier proteins transport bilirubin into the liver, where it is conjugated and excreted in the bile.

          o Cats are deficient in glucuronyl transferase necessary for bilirubin conjugation

          o Anorexic cats develop deficiency in protein uptake carriers and intracellular protein ligands for bilirubine

          o Taurine is necessary for bile acid conjugation – deficiency results in cholestasis

          o Bilirubinuria is always significant because there is no renal conjugation of bilirubin in cats, and the renal threshold for bilirubin is higher than that of dogs.

Clinically, we divide causes of jaundice into three large categories – pre-hepatic, hepatic, and post-hepatic

     • Pre-hepatic causes

          o Excessive RBC hemolysis

          o Mycoplasma Haemophilus

          o Oxidative injury

     • Hepatic Causes

          o Hepatitis

          o Cholangiohepatitis

          o FIP

          o Toxoplasmosis

          o Lymphoma

          o Cellular stress

          o Hepatic necrosis

               • Methimazole therapy

     • Post-hepatic Causes

          o Pancreatitis

          o Neoplasia

          o Cholelithiasis

          o Liver flukes

          o Cholangitis

          o Ruptured gall bladder or bile duct

Most common causes of jaundice in cats

     • Hepatic lipidosis 50%

     • Inflammatory disease 25-40%

     • Lymphosarcoma 7%

     • FIP

     • Diagnosis

          o History

               • anorexia, medications, concurrent illness

          o Physical examination

               • Hypersalivation

               • Liver size

               • Hepatomegaly is common

               • Microhepatica is less common, but could be the result of chronic inflammation and cirrhosis (uncommon in cats)

               • Fundic examination to look for evidence of vasculitis associated with FIP

          o CBC

               • Look for anemia

               • Hemolytic anemia

               • Regenerative, Heinz bodies, mycoplasma, RBC fragments, spherocytes

               • Milder non-regenerative anemia in chronic disease

          o Serum chemistry

               • BUN is made in the liver, and low BUN can reflect hepatic failure

               • Glucose—gluconeogenesis is an important function of the liver, and hypoglycemia can accompany severe liver failure

               • Cholesterol – Liver disease can cause reduced excretion of cholesterol in the bile and can

               • Albumin – manufactured in the liver....is low in severe hepatic failure, and would be normal with hemolytic disease

               • Globulin – Can be elevated with chronic inflammation, and is typically elevated in cats with FIP

               • Bilirubin

               • ALT – A hepatocellular enzyme...elevation is associated with hepatocellular injury

               • ALP – A cholestatic enzyme...even mild elevations are important in cats because of the short half-life

               • GGT – Also a cholestatic enzyme...is sometimes (often) not elevated in hepatic lipidosis

               • Bile acids are probably not necessary because increased bilirubin indicated decreased hepatic function if pre- and post-hepatic causes have been investigated.

          o Urinalysis

               • Severe liver disease can cause isosthenuria

               • Bilirubinuria is never normal in cats

          o Coagulation profile –Necessary because coagulation factors are made in the liver.

          o T4 – hyperthyroidism alone would be unlikely to cause icterus

          o FeLV / FIV – May indicate lymphoma

          o Imaging

               • Radiographs can help assess liver size

               • Ultrasound can suggest (not confirm) lipidosis, neoplasia, cholestasis, pancreatitis

          o FNA cytology, culture

               • FNA results are inconsistent at best, and don't always correlate well with histopathology.

          o Liver biopsy

               • True cut

               • Surgical

               • Laparoscopic

               • Only after coagulation tests are known

Below are some liver profiles from icteric cats.

Yellow cat #1

This pattern is typical of cholangiohepatitis, but could occur with FIP as well. The pattern is more hepatocellular injury than cholestatic. In fact, there is no evidence of cholestasis.

Yellow cat #2

In this cat, the elevation in ALT is mild, but the highly elevated ALP suggests cholestatic disease. This cat had hepatic lipidosis with no other known disorder. Note the GGT, which is considered an indicator of cholestasis, is not elevated. This is sometimes seen in cats with hepatic lipidosis

Yellow Cat #3

This cat has evidence of cholestasis and hepatocellular injury. It could be consistent with several liver diseases, but this cat had infiltrative lymphoma in its liver.

Yellow cat #4

The only abnormality here is the elevated bilirubin. This cat had been anorexic for a couple of days.

Treatment

     • Nutrition

          o This is the most important aspect of therapy

          o Appetite stimulants and force feeding to not work as well as enteral feeding

          o Esophagostomy tubes work well for this

               • Start using tube 24 hours after placement

               • Most cats need 70 – 100 kcal/kg/day

               • For a sick cat recovering illness, you can calculate the need as 1.25 x basal energy requirement

                    √ BER = 30 x BW(kg) + 70

               • Commercial diets for use with feeding tubes are available

               • Start slow – first day's feedings should only be about 20 ml total

               • Always aspirate tube before feeding to make sure there is not food retention in the stomach

               • Always flush feeding tube with water before feeding

               • Maximum volume per feeding is 20 ml/kg

               • Most cats are fed 4 – 6 times a day

               • Cats should be offered food....and tube feeding can be skipped if the cat eats well.

               • Tube should be removed when the cat has been eating well for a couple of weeks and you have good evidence of resolving disease.

     • Fluid therapy

          o Necessary for the cat that is dehydrated

          o If a feeding tube is in place and the gut is working, use it for the daily fluid requirement

     • Antibiotics

          o May not be helpful

          o Beta lactams and metronidazole concentrate well in the bile

     • Corticosteroids

          o Can be useful in inflammatory disease

     • Vitamin K

          o Helps restore clotting function

               • Factors II, VII, IX, X are activated by vitamin K-dependent carboxylation reaction

     • Ursodiol (Actigall) - 10-15 mg/kg po sid

          o Bile acids are detergents designed to solubilize biliary lipids and to aid in absorption of fats from the intestine.

          o Hydrophobic bile acids are toxic

          o Solubilize cell membranes

          o Bile acids are pro-inflammatory

          o Major bile acids produced by the liver are cholic acid and chenodeoxycholic acid

          o ursodiol at therapeutic levels replaces normal bile acids

               • Bile is enriched in ursodiol

               • ursodiol replaces hydrophobic GCDCA in humans and protects hepatocyte membranes

               • Replacing taurocholate may not be of great benefit

          o ursodiol may inhibit the uptake of toxic bile acids at the intestinal level too

          o ursodiol increases flow of bile

          o Cholehepatic shunting

          o ursodiol is secreted into bile

          o ursodiol is an immunomodulator

          o Safety of ursodiol is fairly well established, but could potentially cause taurine deficiency

          o Therapeutic effects are completely unproven in dogs and cats

          o Potentially beneficial in inflammatory dz, hepatotoxicity, intrahepatic cholestasis

          o Contraindicated in extrahepatic biliary obstructio

Same, other antioxidants

     • Help restore glutathione, needed for detoxification reactions

     • Can protect from oxidant injury

Lactulose

     • Useful for treating hepatoencephalopathy

     • Traps ammonia in the gut