Systemic Diseases Involving The Liver

For the majority of the diseases described in the following sections, the presenting signs are usually not those of liver disease. However, the presenting signs are often vague and there may be indications of liver involvement. Cases which present for obvious liver disease are unlikely to be experiencing these systemic disease processes without exhibiting accompanying signs of the underlying disease process. In considering a diagnostically challenging case presenting with only low yield problems, it is advisable to consider the whole animal and systemic or widespread involvement in the pathophysiology of the presenting signs.

Feline Infectious Peritonitis (FIP)

FIP is a systemic disease associated with a mutation of the feline enteric coronavirus. The disease is most commonly recognized in cats less than five years of age, although the greatest incidence of disease in cats less that one year of age. There is reported to be a higher incidence of FIP in purebred cats, however this may be related to an increased exposure rate in high density housing situations such as catteries. FIP can occur in two forms: wet (effusive) FIP is characterized by peritoneal effusion, and dry (non-effusive) FIP typically has granulomatous lesions and no effusion. Cats with FIP usually present for anorexia, fever, malaise, dehydration and weight loss.

Clinically, cats with the wet form of FIP have signs of multi-organ inflammatory disease including: icterus, ascites, abdominal distension, lymphadenopathy, irregular liver borders (+/- hepatomegaly), abdominal masses, pleural effusion, dyspnea, pericardial effusion, splenomegaly, and neurologic deficits. An experienced clinician may be able to palpate discrete nodules on the serosal surfaces, especially in the kidneys and the spleen.

The dry form of FIP tends to be much more difficult to diagnose due to the vagueness of its presentation both in clinical signs and laboratory data. Persistent fever of unknown origin, pyogranulomatous hepatitis, anterior uveitis, ataxia, seizures, vestibular deficits, and other CNS dysfunction are frequently reported in cases of dry FIP. In either form, hepatic manifestation of this disease is consistent with immune-complex vasculitis or pyogranulomatous/granulomatous hepatitis secondary to viremia.

Wet FIP (above left)

Dry FIP (above right)

FIP Kidney (below right)

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Congestive Heart Failure

Hepatomegaly, due to chronic passive congestion of the liver, often occurs secondary to right-sided or generalized heart failure. The condition ultimately stems from a decrease in cardiac output. This results in increased caudal vena cava pressure thereby producing a functional post hepatic blood flow obstruction followed by portal hypertension, passive congestion, and dilation of the hepatic sinusoids. Grossly, the liver will appear swollen, dark in color, and bloody when cross sectioned. Periacinar congestion and sinusoidal dilation are the two most common histological findings in acute passive congestion. In more chronic cases, hepatic fibrosis combined with sinusoidal congestion and dilation produce a "nutmeg" appearance to the liver parenchyma. Both acute or chronic passive congestion can result in mild to moderate changes in alkaline phosphatase, however serum bile acid levels are usually unaffected. Changes in coagulation times, serum albumin, and serum bilirubin have not been reported in either the dog or cat. Animals experiencing congestive heart failure are likely to present with such low yield problems as weakness, syncope, dyspnea, cyanosis, and ascites.


Passive congestion in a cow.	Chronic passive congestion with fibrosis (aka nutmeg liver).
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Hyperthyroidism

    Hyperthyroidism is a commonly reported disease in older cats. It most frequently occurs secondary to bilateral multinodular adenomatous hyperplasia of the thyroid gland. Seventy percent of reported cases of hyperthyroidism in cats are bilateral. Cats with hyperthyroidism typically present for polyuria, polydipsia, weight loss, and hyperactivity. Many cats also present with gastro-intestinal signs such as vomiting and diarrhea.

    The mechanisms for hepatic changes secondary to hyperthyroidism are not well defined. Histological examination of affected tissues reveals centrilobular vacuolization, however liver function is rarely significantly impaired. Mild to moderate elevations in serum liver enzymes (primarily AP and ALT) and serum total bilirubin may be noted. Based upon biochemical and histological changes, it has been proposed that malnutrition, hypoxia, or direct toxicity due to excessive thyroid hormone may best explain secondary hepatic changes associated with hyperthyroidism in cats.

Nodular hyperplastic thyroid glands (cat). The bottom gland is close to normal size, whereas the upper gland is significantly enlarged. On both of these glands, the nodular changes can be appreciated. These glands are palpably large on cats affected with hyperthyroidism.

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    Toxoplasma gondii is a coccidian protozoan infective to most vertebrates. The parasite's only definitive host appears to be members of the genus Felidae. Cats spread the disease by shedding oocysts in the feces. The infection rarely causes clinical disease in cats who generally acquire the parasite at a young age, shed for a period of time, and then remain seropositive for the parasite throughout their lives. In young or immunocompromised adult cats, an acute form of the disease can develop after overwhelming intracellular replication of the protozoan. These cats will present with depression, anorexia, fever followed by hypothermia, peritoneal effusion, icterus, dyspnea and death. Necropsies reveal hepatic, pulmonary, CNS, and pancreatic tissue involvement. The predominant gross pathological change revealed is multiple necrotic foci, primarily in the liver and spleen.   Histologically, toxoplasmic hepatitis appears as mononuclear cell infiltration and edema around portal triads and central veins.

    While fatal, toxoplasmosis may be regarded as rare within the population. Cats infected with FeLV, FIV, FIP, or those that are immunosuppressed due to drugs, are at increased risk for developing extraintestinal toxoplasmosis.

Diabetes Mellitus

Liver disease associated with diabetes mellitus in dogs, and especially cats, is usually in the form of hepatic lipidosis. Mild to moderate lipid deposition is a common sequela to diabetes mellitus. Liver enzymes will be increased mildly, and icterus may occur if involvement is severe. Hepatomegaly is the most consistent physical exam finding, besides icterus.

Diabetes also predisposes an animal to infection because of neutrophil dysfunction. High serum glucose concentrations cause failure of neutrophil adherence, allowing for bacteria to seed the organs of the body. Common bacterial infections for diabetic dogs and cats include urinary tract infections, bacterial dermatitis, bronchopneumonia, and less commonly hepatic abscessation. Diagnostic ultrasound is most commonly used in the assessment of hepatic abscesses. In reported cases of diabetic hepatic abscessation, ultrasonography revealed a mottled appearance to the parenchyma, and several poorly-defined hyperechoic areas. Clinical diagnosis is often complicated due to the nonspecific nature of presenting clinical signs. Typically, dogs present with anorexia, lethargy, weight loss, intermittent abdominal pain, and poor control of diabetes mellitus. The most consistent biochemical abnormalities include: hypoabluminemia, hypokalemia, hyperglycemia, and increased alkaline phosphatase activity.

Lipidosis_thumbnail.jpg (12512 bytes)

LEFT: Hepatic Lipidosis.
RIGHT: Abdominal radiographs illustrates hepatomegaly.

The liver in this radiograph is enlarged because the edge of the liver is protruding far beyond the last rib.
The edges of this liver are very sharp and clearly outline its borders.

Radiographic image and description courtesy of Carl Palazzolo, D.V.M

In dogs, hyperadrenocorticism usually develops in older animals (>6 yrs) with no apparent gender distribution. Affected animals will present with polyuria, polydipsia, polyphagia, panting, abdominal enlargement, endocrine bilateral alopecia, mild muscle weakness, and lethargy. Signs that may be confused with primary hepatobiliary disease include pendulous abdomen and hepatomegaly. AP and ALT will be elevated in the serum. The elevated cortisol levels associated with hyperadrenocorticism, leads to peripheral insulin resistance and secondary diabetes mellitus. The more easily recognizable clinical signs associated with diabetes may mask the underlying condition.

Hyperadrenocorticism is less common in cats than in dogs. In cats, the disease is seen in older mixed breed animals. Most of the common presenting signs of hyperadrenocorticism in cats are due to the presence of diabetes mellitus. The most common physical exam findings are pendulous abdomen and hepatomegaly as seen in dogs. Hepatomegaly is due to exaggerated hepatic glycogen deposition in response to serum adrenal steroid levels. Clinical signs include: polyuria, polydipsia, patchy alopecia, and unkempt hair coat. It is less common to see elevations in liver enzymes in cats affected with hyperadrenocorticism. Glucocorticoids are responsible for the induction of ALP, and therefore the observed elevations in hepatic enzymes is likely from this phenomenon rather than hepatocellular damage.


Adrenal tissue taken from dog with hyperadrenocorticism. Note the thickened adrenal cortex.	Bilaterally symmetrical alopecia and muscle wastage caused by hyperadrenocorticism.