Canine liver disease is among the top five leading causes of non-accidental death in dogs and as such should be taken seriously. The liver is responsible for a number of essential bodily functions, and if it is compromised in any way your dog’s overall health is in jeopardy.
Among the liver’s many responsibilities are blood detoxification, waste removal and bile production to aid digestion. This large gland is involved in just about every process in the body. As such, it is very resilient, with the ability to work even during the onset of liver disease in dogs.
It is involved with almost all of the biochemical pathways that allow growth, fight disease, supply nutrients, provide energy, and aid reproduction. Liver cells, which are called hepatocytes, go through thousands of chemical reactions every second in order to perform these myriad functions. Since the liver is involved with almost all biochemical processes it is no wonder that there are many different diseases that will affect it.
The liver processes raw materials, manufactures the building blocks of the body, recycles the old to make new, and detoxifies the industrial waste of the body. In short the liver is involved in just about every biochemical process required to run the body. As a result of this relationship, liver disease can affect just about any other part of the body and thus the symptoms of liver disease are typically unpredictable and non- specific. Furthermore, because the liver acts as a “biochemical cross roads” for the body, it is affected by a wide range of diseases, including viral and bacterial infections, degenerative and neoplastic disease, and toxic insults. It is estimated that three per cent of all disease seen by veterinarians is liver based.
The liver has a double edged nature which, while being life preserving, makes diagnoses and treatment of liver disease extremely difficult. The liver has a tremendous reserve capacity, which means that it can easily perform its duties with up to 70 to 80 per cent of the liver mass affected by disease. While it certainly is a benefit that our liver can keep us alive despite an overwhelming infection or a massive tumor, it also means that the disease is well advanced and possibly untreatable before any symptoms are noted. We all know that disease is most easily conquered early, but the very nature of the liver makes this an impossible task. One thing about livers though: they are the only organ in the body which is capable of complete regeneration and thus is we do manage to successfully treat the disease, there is a chance of complete recovery.
SPECIFIC LIVER FUNCTIONS
The liver is the organ that orchestrates the metabolism of fats, carbohydrates, and protein. It does this in conjunction with the circulatory system, the lymphatic system, and the endocrine (hormone) system. A healthy liver is critical to proper protein, carbohydrate, and fat metabolism.
The liver produces all of the proteins except for the proteins synthesized by the immune system. It does this by reassembling amino acids into protein. The main protein produced by the liver is called albumin.
Normal albumin in the bloodstream is important for many physiologic functions. One of these functions involves the normal maintenance of fluid pressure in the arteries and veins. When the protein level falls below a certain point the fluid in these vessels can leak out and pool in the abdominal or thoracic cavities. This fluid is called ascites when it occurs in the abdominal cavity, pleural effusion when it occurs in the thoracic cavity. Albumin also functions to “carry” other compounds through the bloodstream. These compounds include calcium, vitamins, hormones, fatty acids, many drugs, and bilirubin.
A consistent finding with liver disease is a low protein level (hypoproteinemia). This low level usually occurs only when the liver has been severely diseased for a prolonged period of time, because of the great reserve capacity of the liver to produce more albumin.
With the aid of the hormones insulin and glucagon, the liver maintains a normal blood glucose level. Abnormalities in blood glucose level can result from an insulinoma or diabetes mellitus (sugar diabetes).
Glucose that is stored in hepatocytes is called glycogen. It is used as a reservoir during times when carbohydrate intake is low (fasting or starvation). The liver can also manufacture glucose from proteins or fats.
In liver disease the body can have a difficult time regulating the blood glucose level, usually leading to hypoglycemia (low blood glucose). This is one of the reasons why caloric intake is an important aspect of treatment.
The liver regulates fats (called fatty acids) in the bloodstream. It does this by converting excess amounts of carbohydrates and proteins into fatty acids. The liver also manufactures cholesterol from this fat. Cholesterol is necessary for many functions, particularly the sex hormones and steroids like cortisone.
Drug detoxification is an important liver function. It is a complex process that occurs in the endoplasmic reticulum of the hepatocyte. Several phases are involved with this detoxification:
The offending drug is inactivated. This inactive drug is eliminated by the body, usually through the kidneys, or secreted into bile and passed out in the feces.
The drug is converted from an inactive drug to an active metabolite. This active metabolite circulates in the bloodstream and has an effect on the body.
The drug is converted from an active drug to an active metabolite.
In this phase biochemical processes occur that make these drugs more water soluble and thus easier to eliminate through the kidneys. They are excreted out of the body in the urine.
Another example of this detoxification process occurs with the compound ammonia. Ammonia is one of the by-products of the digestion and metabolism of protein into amino acids. Ammonia is detoxified by the liver and excreted by the kidneys. A diseased liver will not metabolize this ammonia to urea properly, leading to the disease called hepatic encephalopathy.
Bile is made up of electrolytes, cholesterol, bile acids, bilirubin, and globulins. It is produced by hepatocytes, secreted into channels in the liver called and stored in the gall bladder. Drugs are eliminated in the bile, red blood cells are re-circulated through the bile system, and fats are absorbed from the intestines into the bloodstream only in the presence of bile.
When red blood cells break down and are recycled they release bilirubin from their hemoglobin. The liver, along with spleen and bone marrow, recycle this bilirubin, salvaging some of the compounds and excreting the rest in the bile. Bilirubin, which is toxic, binds to albumin and is detoxified and excreted. This is eventually excreted into the intestines and broken down by intestinal bacteria, where it imparts the dark color to stool. If this bilirubin cannot be excreted from the gallbladder (when there is an obstruction in the bile duct) there will be very light colored stool. The excess amounts of bilirubin that build up in the bloodstream will cause jaundice, the yellow discoloration of the skin and mucous membranes that can occur with liver disease.
The fat soluble vitamins, A, D, E, and K, require bile for proper absorption from the intestines. These vitamins are stored in the liver, and are converted to active compounds as the liver maintains normal physiology.
The proteins that initiate and maintain clotting of blood are synthesized by the liver. These proteins go through very complex biochemical processes to achieve this vital function. A diseased liver is unable to synthesize these proteins, leading to a potential bleeding problem. Vitamin K is also an essential component of these clotting mechanisms.
Red Blood Cell System
The liver removes old or damaged red blood cells from the circulation, and is involved with the storage of iron and the breakdown of hemoglobin. Because of this, chronic liver disease could cause anemia. The liver (along with the spleen), is a storage organ for blood. If there is a severe blood loss the liver expels this blood into the bloodstream to help make up for the loss.
Specific cells called Kupffer cells line the inside of the liver. These cells are part of the immune system. They eliminate and degrade the substances that are brought into the liver by the portal vein. Some of these substances are bacteria, toxins, nutrients, and chemicals. A diseased liver will not filter these compounds normally, resulting in toxic accumulations of drugs, chemicals, or bacteria. Excess accumulation of bacteria in the bloodstream is called septicemia, and is one of the reasons that antibiotics are commonly used in liver disease.
Many vitamins are stored in the liver, and perform their functions only when activated by the liver, and are degraded by the liver. These include some of the B vitamins and Vitamin C, along with A, D, E, and K previously described.
The pictures in this section are reprinted with permission by the copyright owner, Hill’s Pet Nutrition, from the Atlas of Veterinary Clinical Anatomy. These illustrations should not be downloaded, printed or copied except for personal, non-commercial use
The liver is a multi-lobed organ that is located at the most forward part of the abdomen. It is so far forward that it lays up against the diaphragm, the muscle that aids in breathing in mammals. The liver is the largest organ that is located in the body, a testament to its importance. It has 6 distinct lobes organized into 3 regions. Like the kidneys, 25% of the blood ejected with each beat of the heart goes to the liver.
The liver is supplied with nutrients from the hepatic artery and the portal vein, which is different from other internal organs. Blood from the heart goes through the aorta and into the hepatic artery. The hepatic artery supplies a large amount of the oxygen and nutrients the hepatocytes use during metabolism. Approximately 1/3 of the blood that flows into the liver comes from this artery.
The other source of blood for the liver is the portal vein, supplying 2/3 of the blood that flows into the liver. The nutrients in the portal vein originate from the digestive tract, this time, not the heart, like the hepatic artery does. In essence, raw food that is absorbed from the intestines flows directly to the liver. This exposes the liver to toxins and bacteria, which are metabolized and detoxified by a normal liver before they leave the liver and enter the general circulation via the heart. This detoxification process protects other organs, particularly the brain, from bacteria and toxins that could injure brain cells. When this system fails, which happens in liver shunts, excess ammonia will build up in the bloodstream and affect the brain.
**Information from this section was compiled from the following sources:
We cannot stress enough that the symptoms of liver disease are VERY subtle and your dog may be acting normal other than a few small differences in behavior. DO NOT WAIT TO CONSULT YOUR VETERINARIAN. Often times, by the time the symptoms below are present, the disease is quite advanced. Early detection is the KEY for treatment and survival.
Pets with liver disorders can show a variety of physical symptoms. Very few of the symptoms are specific for liver disease, but can be signs of multiple diseases and conditions. Symptoms of liver disease are variable and subtle in the early stages of the problem. All, some, or only one of these signs may be present:
Loss of appetite – Anorexia (Most Common) – THIS IS VERY IMPORTANT AND ANY EATING CHANGES SHOULD BE REPORTED TO YOUR VETERINARIAN!!!
Intermittent recurrent abdominal or gastrointestinal upsets; vomiting, diarrhea, constipation
Progressive depression or lethargy; does not want to play anymore or refuses to go for walks.
Swollen belly with a “fluid filled” look. This is also known as ascites and is actually fluid accumulation in the belly due to circulation alterations in the abdomen.
Pale gray feces. Bile pigments are what give feces it’s characteristic brown color and if the liver is not processing bile properly, the feces will not get their color.
Orange urine. The improper processing of bile results in the excretion of bilirubin in the urine in high amounts, thus orange urine.
Jaundice, also known as icterus. Any pale or white skin or visible tissue takes on a yellow hue. Again the biliary pigments are accumulating in the body because the liver is not processing them.
Bleeding problems. Many of the proteins required for proper blood clotting are created in the liver. Remove these proteins and blood clotting decreases.
Hepatic encephalopathy, or severe neurological signs; behavioral changes, seizures, aimless pacing or circling, head pressing.
Pain associated with the abdomen. This is due to the stretching of the liver capsule. May be noted when the dog is lifted around the belly or when the veterinarian probes the abdomen. The veterinarian may also notice a swollen liver while palpating with some of the more acute liver diseases
Chronic weight loss or wasting. The liver processes all the building blocks. If it fails to process, the body fails to maintain itself.
Increased water consumption and urination. Most likely due to dramatic shifts in serum and kidney salt balances.
In a recent study it was found that dogs with liver disease can also have high blood pressure. This is called hypertension, and should be monitored to see if therapy is needed
If you notice any of the above symptoms, make sure you consult your veterinarian as soon as possible. Because the liver is able to function effectively even at 70-80% capacity, the disease may be in its advanced stages by the time the condition manifests itself.
Animals that receive a severe and blunt blow to the front of the abdomen can suffer from liver disease. The most common cause of this type of blow is being hit by a car. A liver lobe can be fractured and bleed into the abdomen, even leading to death. A more common occurrence is a bruise (contusion) that heals itself. Heatstroke, diaphragmatic hernia and liver lobe torsion can also cause liver problems.
The severe inflammatory process that occurs with digestive enzymes can spill over into the liver and cause severe disease. The close proximity of the pancreas to the liver and the bile ducts results in some degree of hepatitis whenever there is a case of pancreatic inflammation. Treat the pancreatitis and the liver disease will regress.
Hemolytic anemia can decrease the oxygen available to liver cells and lead to their death.
An inflamed liver is called hepatitis.
Trauma can cause this, along with drugs, viruses, bacteria, bile, and toxins
Typically caused by either an adenovirus or a herpes virus. Transferred from dog to dog by oral contact and ingestion. Usually only causes a transient non specific illness characterized by lethargy, vomiting, diarrhea and fever. Sometimes develops into a full blown case of severe hepatitis with many of the symptoms previously noted. Treatment is geared to support while the body fights off the bug. Prevention is by vaccination.
Bacteria, viruses, and fungi can all cause liver disease.
Since bacterial infection is common in many liver problems it is routine to use antibiotics when treating liver problems. Specific diseases include Infectious canine Hepatitis, canine Herpesvirus, Leptospirosis, abscesses, histoplasmosis, coccidiomycosis, and Toxoplasmosis.
Several bacterial causes of hepatitis are known. Treatment is based on a proper diagnoses and appropriate antibiotic use. There is good proof that the bacteria is a normal inhabitant of the liver and only becomes a problem when the liver is injured form other causes. There are notable exceptions.
*Leptospirosis is a bacterial infection common in wildlife and transferable to domestic animals and
people through contaminated water. Dangerous, possible fatal, but the vaccine is quite good for prevention.
Certain parasites will infect the liver.
Typically the likelihood of parasitic infestation depends on the area you live in. Diagnosis is often based on symptoms, fecal examination, and standard diagnostic techniques for liver disease. Treatment is the use of appropriate parasiticides.
*Copper storage Diseases
Primarily found in Bedlington Terriers, Doberman Pinschers, and
West Highland White Terriers. These are all genetically inherited diseases
which result in abnormal and toxic levels of copper to be stored in
the liver. The course of the disease is variable, some presenting with
acute hepatitis, many presenting in end stage cirrhosis of the liver.
Diagnosis is based on liver biopsy. Treatment requires the use of copper
binding drugs, anti inflammatory to decrease liver inflammation, dietary
modification to limit copper uptake.
Chronic Active Hepatitis
In humans there is a chronic form of hepatitis characterized by chronic elevation of liver enzymes and biopsy samples showing scarring and active inflammation. The underlying cause for this entity falls into one of three categories: viral induced, toxin induced, and immune mediated. There is some question as to whether a similar syndrome exists in dogs.
There has been cases which did show chronic elevation of the liver enzymes over weeks to months), symptoms characteristic of liver disease ill defined malaise), and a response of anti inflammatory treatment to limit the ongoing inflammation and scarring of the liver. At this time recommendations
for treatment are that moderate or intermittent disease should only receive supportive therapy or basic nursing, while deteriorating chronic cases should receive steroid based anti inflammatory. If the case shows poor response, biopsies should be referred to a pathologist for evaluation in an attempt to find the underlying cause. In some cases it may be necessary to use strong immune suppressant drugs to stop the destruction of the liver.
Disease primarily of the blood supply to the liver. Diagnosed by very specialized radiograph techniques which measure and visualize the blood flow through the liver; Biopsy critical for diagnosing location
These worms can block blood flow into the liver and cause liver failure. Any disease that can cause failure of the right side of the heart can also cause liver problems.
Primary disease is caused by the ingestion, injection, or inhalation of a toxic substance which adversely affects the liver. Due to the central nature of the liver with regards to detoxification of chemicals, it is no surprise that many are harmful to the liver. Factors contributing to the disease are: Gender (females more susceptible), fatty diets more dangerous, continuous exposure, high levels of exposure to toxins. Exposure results in death and inflammation of the liver cells, followed by replacement of damaged tissue by fibrous scarring. This can be a self perpetuating cycle, resulting in cirrhosis of the liver.
Toxins include many common drugs, such as acetaminophen, ASA, anabolic steroids, chemotherapy drugs, some antibiotics, glucocorticoids, anaesthetics, parasite control drugs, and phenylbutazone.
Some of the drug induced hepatitis is a predictable side effect of the drug, while other incidences of hepatitis are considered an unpredicted or abnormal side effect of the drug. This is difficult to diagnose unless there is a known exposure to the drug or toxin and the appropriate tests are taken. Biopsy will confirm liver destruction, inflammation, and fibrosis, but it will not single out the causative agent.
Dogs seem abnormally sensitive to glucocorticoid drugs (“cortisone”) and will develop typical lesions in the liver after multiple dose therapy or long term over production of intrinsic cortisone by the adrenal gland (Cushing’s disease). Lesions are fairly typical and the rare animal which shows liver associated symptoms during glucocorticoid therapy will improve with the removal of the steroids. Liver associated lesions may take weeks to months to heal.
Anticonvulsant Associated Hepatopathy
Phenobarbital, primidone, phentoin, May cause liver disease in 6 to 15 % of all dogs on anti-convulsant therapy. Inflammation seems related to dose. Degree of disease is variable and unpredictable. Diagnoses based on history, symptoms, laboratory tests, and biopsy. Treatment is removal of offending agent.
There are literally thousands of chemicals that could be toxic to the liver. A few examples of these chemicals that are commonly used to treat ill animals include:
Rimadyl (arthritis treatment)
Thiacetarsamide (heartworm treatment)
Ketaconazole (fungal treatment)
Anthelmintics (worming medication)
Phenobarbital (epilepsy medication)
Portal Vascular Abnormalities
Usually occurs when a portal-systemic shunt allows blood to pass from the digestive tract directly into the general circulation without being detoxified by the liver first. Usually a congenital defect restricted to young dogs and puppies, but can be the result of hepatic cirrhosis. Symptoms are never consistent, but many dogs are young, malnourished, chronically sick, poorly tolerant of toxins, drugs, and anesthetics, and tending to eat strange items (pica). Diagnosis is based on physical exam, history, laboratory tests, and specialized X-rays showing blood flow through the liver. Treatment is surgical correction of the circulatory abnormality to force the blood into the liver prior to it entering the general circulation.
Cancer can arise directly within the liver (primary) or spread from elsewhere (metastatic or secondary) through the circulatory or lymphatic systems. In the anatomy section we mentioned the dual blood supply to the liver; the portal vein and the hepatic artery. This extra blood supply increases the chance that a tumor in a different organ that has spread into the bloodstream will end up in the liver. As mentioned in the physiology section, liver cancer is usually detected only after the disease is well established, since functional reserve capacity allowed the liver to function normally for a prolonged period of time.
Some of these liver cancers include:
Metabolic diseases that cause secondary liver problems:
Inflammatory Bowel Disease
Cirrhosis of the liver can occur as the end result of several liverdiseases, which may be why it is hard to find information on this condition as a separate entity. Cirrhosis can occur in copper storage diseases of the liver, as the end result of idiopathic chronic hepatitis (also called chronic active hepatitis, chronic canine inflammatory hepatic disease and probably other names), as a breed related disorder (several terrier breeds, Dobermans, Labs, cockers and standard poodles), due to anti-seizure medications and possibly due to carprofen and oxibendazole (a dewormer). It is sometimes the end result of infectious illnesses, especially leptospirosis and infectious canine hepatitis (pretty rare now).
Of these conditions, the one that usually shows up without much warning is the idiopathic chronic hepatitis. This condition can sometimes go on for long periods of time with no really obvious clinical signs and affected patients may have markedly decreased liver size and function when the condition finally causes clinical signs. Even at this point it is often possible to help make patients feel better for some time, though. The usual recommendations are to use a low to moderate protein diet to try to decrease the liver’s work load, use metronidazole or neomycin orally if there are signs of central nervous system disturbance, to give lactulose for the same reason, to consider the use of cholchicine, ursodiol (Actigal Rx), SAMe (Denosyl SD-4 Rx), copper chelating agents if necessary and to provide general supportive care, such as gastrointestinal protects if GI ulceration occurs, fluid therapy if there is dehydration, Vitamin K if blood clotting problems occur, and possibly Vitamin E as an anti-oxidant. In liver disease, at least if copper toxicosis is possible, it is best to avoid Vitamin C supplementation as it can make the copper toxicity worse.
As the diseases mentioned above progress, they slowly destroy liver cells, resulting in scarring and an increase in fibrosis in the liver, or cirrhosis. Some patients live for extended periods of time even after it is clear that they have reached the stage that liver cirrhosis is occurring. It can be pretty hard to go back at the time that there is cirrhosis and to figure out why it occurred, so when the liver disease is discovered at this stage, it may not be possible to give you information on the underlying disease and thus the diagnosis of cirrhosis, rather than a more specific diagnosis.
New and Emerging Liver Diseases
Also Known As: necrolytic migratory erythema, superficial necrolytic dermatitis, and metabolic epidermal necrosis
Transmission or Cause: Hepatocutaneous syndrome is a disease characterized by degeneration of the skin cells likely as a consequence of a nutritional imbalance, resulting from metabolic abnormalities caused by severe liver dysfunction or a pancreatic tumor.
Affected Animals: Hepatocutaneous syndrome is a disease that generally affects older dogs with no consistent breed predisposition. There have been very few reports of cats affected by hepatocutaneous syndrome.
Clinical Signs: Skin disease is the usual presenting complaint, although some dogs will exhibit systemic illness (lethargy, poor appetite, weight loss) prior to the skin eruptions. The skin lesions frequently occur in areas of trauma such as the muzzle, lower legs, and footpads. Lesions can also affect the mouth, ear flaps, elbows, and genitalia. Most lesions consist of crusting, erosions or ulcerations, but blisters may also occur. Footpads are often severely thickened and fissured and are often painful.
Diagnosis: Diagnosis is based on supporting history, physical examination, bloodwork abnormalities (such as elevated liver enzymes and low protein levels), and skin biopsy results. Abdominal ultrasonography frequently reveals a pathognomonic “honeycomb” pattern of the liver (due to liver degeneration) or less commonly a pancreatic tumor. In cats, the most common finding is a pancreatic tumor.
Treatment: If a pancreatic or liver tumor is identified and able to be surgically excised, the skin lesions may normalize for an extended period of time, but because these tumors metastasize (spread to other areas of the body) quickly, surgery is not curative. In cases of end stage liver disease, surgery is not possible, and the goal of therapy is to increase quality of life and decrease uncomfortable skin lesions with supportive care and addressing the nutritional abnormalities. Supportive care includes supplementing protein and necessary minerals and enzymes through the diet and oral supplements or by weekly intravenous amino acid infusions that are performed in the hospital on an outpatient basis until improvement in the skin is noted. Unfortunately, despite the supportive care, the disease will progress.
Prognosis: As this disease is a cutaneous marker for serious internal disease, the prognosis is poor with a survival time of less than a year in most cases.
Idiopathic Vacuolar Hepatopathy
This is a diagnosis frequently observed in older dogs. These cases appear typical of steroid hepatopathies based on histopathologic examination and abnormal serum ALP, but without clinical or laboratory evidence of hyperadrenocorticism. The liver of these dogs contains excess glycogen, and they have laboratory findings of predominately G-ALP isoenzymes. One is unable to make the diagnosis of hyperadrenocorticism based on lack of typical clinical signs and normal conventional adrenal testing (i.e., ACTH stimulation or low-dose dexamethasone suppression test). Several dogs recently discovered having vacuolar hepatopathy and increased serum ALP without overt hyperadrenocorticism have abnormal concentrations in some of the other adrenal steroids (i.e., sex hormones such as progesterone and 17alpha-hydroxy-progesterone). It has been documented that progestin steroids bind to hepatic glucocorticoid receptors and will induce a steroid hepatopathy when given orally to dogs. There is now speculation that increases in progestin steroid hormones may result in the hepatic changes and serum ALP increase. It appears that most, if not all, of these dogs live a prolonged life without adverse consequences from their liver disease. The reason for abnormal progestin levels may be secondary to adrenal adenomas, adrenal enzyme deficiency for converting precursors to cortisol or inapparent adrenal masses. Adrenal adenomas have been shown to secrete high levels of 17-hydroxyprogesterone in dogs.
Recently a disproportionate number of Scottish terriers have elevated serum ALP and hepatic vacuolar changes, suggesting a breed predisposition for this condition. They may have a genetic defect in ALP production.
Hepatic Nodular Hyperplasia
Nodular hyperplasia is a benign process causing an increase in serum hepatic values and histomorphologic changes that include macroscopic or microscopic hepatic nodules containing vacuolated hepatocytes. Liver function remains unchanged. Grossly, the appearance may be suggestive of chronic hepatitis or neoplasia. The cause is unknown but appears to be an aging change in dogs; most of those affected are older than 10 years of age. Laboratory findings include a serum ALP increase, but some may have mild increases in serum ALT and AST concentrations as well. Ultrasound study may be normal or may demonstrate larger nodules (many can be only microscopic and not observed on ultrasound study). Biopsy confirms the diagnosis; however, a wedge section is preferred, as a needle biopsy may not demonstrate the nodules. There is no specific therapy.
Gallbladder mucocele is seen in an enlarged gallbladder with immobile stellate or finely striated patterns within the gallbladder on ultrasound study. Changes often result in biliary obstruction or perforation. Smaller breeds and older dogs were over-represented, with Cocker Spaniels being most commonly affected. Most dogs are presented for nonspecific clinical sign,s such as vomiting, anorexia and lethargy. Abdominal pain, icterus and hyperthermia are common findings. Most have serum elevations of total bilirubin, ALP, GGT and variable ALT. Ultrasonographically, mucoceles are characterized by the appearance of stellate or finely striated bile patterns (wagon wheel or kiwi fruit appearance) and differ from biliary sludge by the absence of gravity-dependent bile movement. The gallbladder-wall thickness and wall appearance are variable and nonspecific. The cystic, hepatic or common bile duct may be of normal size or dilated, suggesting biliary obstruction. Gallbladder-wall discontinuity on ultrasound study indicates rupture, whereas neither of the bile patterns predicted the likelihood of gallbladder rupture. Mucosal hyperplasia is present in all gallbladders examined histologically, but infection is not present with all cases, suggesting biliary stasis and mucosal hyperplasia as the primary factors involved in mucocele formation. Cholecystectomy is the treatment for mucoceles.
*New and Emerging Liver Diseases taken from DVM360
Dr. Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail: email@example.com
A thorough approach is needed for a correct diagnosis of any liver problem. An organ like the liver that
is so intimately involved with other important organs will exhibit symptoms that mimic disease in these other organs. Also, what initially might appear as a diseased liver is in reality a disease elsewhere in the
body that is involved with the liver secondarily. This is why it is crucial to follow a thorough and methodical approach called the diagnostic process.
Specifically noting signs which may indicate liver disease. Periodic ascites, intolerance of a high protein diet, icterus, chronic weight loss, abnormally colored feces or urine, bleeding disorders, chronic illness, and all that has been mentioned above. Sometimes urinary crystals formed from the improperly metabolized proteins and amino acids may indicate liver disease.
Liver disease can occur in pets of any age. If it occurs in young animals we tend to think more of toxicity, a liver shunt or a viral disease like adenovirus in dogs. In older pets we tend to think more of inflammation and cancer as the cause of the liver problem.
Several canine breeds are prone to getting liver disease:
Bedlington terriers, Skye terriers, Doberman pinschers, and West Highland White terriers get a
problem with excessive copper accumulation that results from failure of normal biliary excretion of copper. Cocker spaniels have an increased incidence of chronic hepatitis
Early signs of liver disease are subtle, and might exhibit as some of the symptoms described above. It is important to remember that some pets do not show any symptoms early in the course of the disease. This is another reason for yearly exams, along with blood and urine samples in dogs and cats 8 years of age or more. Even though many cancers do not show up in a blood sample, we can sometimes get indirect evidence there is a problem, leading to additional diagnostic tests that might find cancer.
The recent use of pesticides, insecticides, and drugs might give us a clue. Some Labradors are sensitive to the use of the arthritis medicine Rimadyl. These dogs should have a blood panel analyzed prior to initiating Rimadyl therapy. Every 6 months this panel should be repeated.
A history of poorly controlled diabetes mellitus might also clue us in to liver problems. Pets with
liver shunts might have stunted growth and become depressed right after eating.
Routine physical exam findings might include:
Distended abdomen due to enlargement of the liver (hepatomegaly) might be found. This can be palpated in some situations, especially in the smaller animals. an enlarged liver from a disease other than liver disease can cause hepatomegaly. This includes heart disease and Cushing’s Disease.
Enlarged lymph nodes due to secondary bacterial infections or spread of a primary or metastatic
Bruising (hematoma) might be observed under the skin, or when a blood sample is obtained. This is
due to the liver’s affects on the clotting mechanism
Fever- a rectal temperature of greater than 103 degrees F could accompany liver disease when inflammation or infection is present
Skin infections and wounds that do not heal, or recur after antibiotics are stopped
Yellowish discoloration (icterus or jaundice) of the ears, gums, or hairless areas of the skin
Anemia might be observed by checking the mucous membranes for a normal pink color
Extensive Blood Work and Diagnostic Testing
A complete blood count to check for anemia and blood cell abnormalities. A CBC (complete blood
count) and BCP (biochemistry panel) should be run on every pet 8 years of age or more, especially if they have any of the symptoms of liver disease. The CBC might show a decrease in the number of red blood cells (RBC’s). This decrease in RBC’s is called anemia. The white blood cell count (WBC) might be elevated (leukocytosis), normal, or decreased (leukopenia), mostly depending on the cause of the liver problem and how long it has been present. A change in the WBC’s does not necessarily indicate there is a liver problem.
A complete chemistry screen, including ALT, ALP, AST, bilirubin, glucose, urea, electrolyte levels,
albumin, globulin and bile acid levels. The bile acid levels should be checked on an empty stomach and two hours after feeding. All these values, with the exception of the bile acids, usually are included on
a standard Small Animal Data Base Screen.
Important Liver Enzymes
Traditionally the medical practitioner has measured the relative concentration of several enzymes which may indicate alterations in liver health. The following enzymes typically change values in the face of liver failure
Alanine Aminotransferase: ALT – Liver specific. Cell damage will cause elevations of ALT due to leakage. The elevation of the enzyme correlates with the number of cells damaged. Falling levels of ALT may indicate recovery or may indicate a failing number of functional liver cells. Rapid increases in ALT may indicate an acute process, while slow increases may indicate bile duct obstruction.
Normal Test Range: 10-100 U/L*
Aspartate Aminotransferase: AST - an enzyme seen in the liver, heart, kidney, skeletal muscle and brain. The half life of the AST in the blood stream is much shorter than that of ALT, therefore the values of AST tend to drop more rapidly once liver function is resumed. AST elevations and ALT elevations should parallel each other in liver disease
Normal Test Range: 5-55 U/L*
Alkaline Phosphatase: ALKP/ALP – This enzyme is present in many tissues, therefore it not very specific in liver disease, but it appears very early in the progress of liver disease, therefore it is considered quite sensitive. ALP tends to be slightly more specific in the cat, but not quite as sensitive. A similar enzyme or isoenzyme is secreted as a result of high levels of cortisone, therefore an effort must be made to separate Cortisole induced ALP or CALP and normal ALP. Liver ALP is released from the liver when many anticonvulsant drugs are administered to the dog. This must be taken into account when evaluating ALP levels. ALP levels typically are greatly elevated in the young, growing animal and therefore a veterinarian should not mistake any elevations as disease in a young animal.
Normal Test Range: 23-212 U/L*
Gamma Glutamyltransferase: GGT – This enzyme is has its highest concentration in the kidneys and pancreas, but it is also found in the liver and other organs. The major proportion of GGT in the serum seems to come from the liver. Elevations of GGT in disease seem to stem from new synthesis rather than leakage, therefore the changes seen due to disease are not spectacular. Large elevations of GGT are more commonly associated with pancreatitis and bile duct obstruction.
These series of organic acids circulate almost entirely in the localized blood flow between the intestines
and the liver (a.k.a. the Portal system). The flow is typically from the liver, into the bile duct system, then excretion into the intestines to aid digestion after a meal, to be re- absorbed into the portal system and recycled by the liver. Very little of the bile acids escape from the portal circulation system into the rest of the body. Leakage is considered abnormal and is a sure sign of a liver abnormality. This is one of the most sensitive tests available to diagnose liver disease. While the liver does actually manufacture this product, it has tremendous reserve capacity and can easily meet the bodies demand for bile acids despite severe disease. As a result of this reserve, the bile acid levels do not typically drop due to liver disease.
Normal Test Range: Pre = Less than 7.0 umol/L, Post = Less than 15.0umol/L*
A complete urine analysis
Check urobilinogen levels, bilirubin levels, glucose levels, protein levels. Again all this is usually on a standard urinalysis panel.
Radiograph the abdomen
X rays can show increased liver size, decreased liver size liver abscesses, abnormal mineralization , and circulatory abnormalities (using special dyes).
Ultrasound the liver
Perfect technique for visualizing the circulation of the liver, the bile duct system, the density of the liver tissue, the size of the liver. Ultrasound is highly beneficial in the diagnosis of liver disease. We recommend ultrasounding a liver when the liver enzymes tests are elevated over time, or the bile acids test is abnormal. The internal structure (called parenchyma) can be analyzed, and post-hepatic liver disease can be differentiated from hepatic liver disease. This can be very important because disease in the liver can often be diagnosed with a biopsy during the ultrasound. Post-hepatic liver disease cannot easily be diagnosed in this matter. Instead it is diagnosed and treated with an exploratory surgery (called a laparotomy).
Biopsy of the liver
While this is a surgical technique, it is the ultimate for diagnosis, since it allows us to directly examine and test liver tissue, give an absolute diagnosis and hopefully a final treatment regime. Biopsies can be taken by full laparotomy, where the surgeon actually looks at the liver and removes a small piece, or they can be done by a biopsy needle guided by ultrasound through the body wall. The liver will regenerate any piece that has been removed, therefore liver biopsy is usually a low risk procedure in capable hands.
*The ranges for the test results listed above are dependent on the lab, the testing done and are relative. Some specialist allow for a much larger range before they diagnose “true” Liver Disease. After receiving your test results, please consult with an internal specialist and have them explain the results to you.
The course of treatment required in a case of canine liver disease will depend upon the cause of the condition. For example, if trauma was the trigger, hospitalization while the dog recovers from the impact of the trauma may be all that is required. On the other hand, antibiotics may be needed if a bacterial infection is at the root of the disease. Furthermore, when liver disease is caused by another medical condition such as cancer or anemia, these additional medical circumstances will need to be taken into account.
In addition to certain medications, dietary adjustments and supplements can be very useful when attempting to treat canine liver disease. Dietary changes can include adjusting the amounts of proteins, vitamins, carbohydrates, fats, and minerals that a dog ingests. This will then ensure that the canine patient is receiving the nutrition it needs and will also help to decrease the stress and workload of the liver. Furthermore, vitamin K can be helpful with respect to controlling bleeding disorders while vitamin E, as an antioxidant, helps to remove free radicals and to prevent continued oxidative damaged to the canine’s liver.
Certain homeopathic remedies can also be very helpful when treating canine liver disease. Natural herbs and substances such as burdock and greater celandine have properties that assist with the purification of blood, the stimulation of digestive enzymes, and the protection of the liver from toxic substances. Also, some such substances have anti-inflammatory and antibacterial properties.
Milk thistle is another natural ingredient that is known to be very effective in cases of canine liver disease. This natural substance acts as an antioxidant like vitamin E, stimulates production of new liver
cells, and helps to prevent certain toxins from attaching to the liver.
Thus, many natural substances and remedies can be very beneficial for dogs suffering from liver disease. However, it is always important to carry out any form of treatment under the supervision of a qualified veterinary doctor.
SPECIFIC TREATMENTS AND PROGNOSES
Portal Vascular Abnormalities
Fluids and Electrolytes – This corrects the dehydration that occurs with a poor appetite and supplies needed sodium, potassium, and chloride. This fluid is usually given intravenously (IV) at first. Pets
that are severely ill from PSS should not be given anything orally initially.
Cleansing Enemas – Enema’s will decrease the bacterial count of the intestines, leading to less ammonia absorption.
Lactulose – Lactulose works in the large intestine to minimize the production of ammonia by bacteria. It does this by changing the pH and converting ammonia to a form that is not readily absorbed into the bloodstream. It also stimulates normal colon bacteria to absorb ammonia, which is then passed in the feces. Finally, it stimulates the intestines so that ammonia passes through faster, which means there is less time for absorption.
Antibiotics – These drugs are also administered, especially if mental depression is present. They minimize the bacteria count in the colon, thus reducing the amount of ammonia that is absorbed
from the intestines into the bloodstream. They work well with lactulose to decrease the ammonia level.
Dietary Modification – A diet that is restricted in protein may be beneficial because less ammonia is produced as a by-product of metabolism. This protein needs to be of high biological value, such as eggs and dairy products. Meat based proteins should be avoided since they can increase the chance of HE. Most of the caloric needs of a pet with PSS should be supplied with carbohydrates like rice and pasta. Higher fiber diets might also be helpful, as long as the dog or cat is not undernourished. They can act to minimize ammonia production and absorption in a manner that is similar to lactulose
Surgical – For many PSS cases surgery is the treatment of choice. The abnormal vessel that is shunting blood around the liver is identified and closed (ligated) to minimize blood flowing through it. When the abnormal blood vessel is ligated blood will now flow through the liver instead of around it. This is readily accomplished for solitary extrahepatic shunts. Intrahepatic shunts can be more difficult
to identify and ligate. Post surgical monitoring is important. If the pressure within the liver becomes too high due to the increased blood flow through the liver then the ligation on the shunting vessel(s) must be reduced or removed.
In some cases medical management must also be utilized to affect a cure. The final outcome of treatment depends on what age the PSS started, how long it has been present, and whether it is intrahepatic (worse prognosis) or extrahepatic in nature.
Long Term Monitoring – Pets on long term medical care need to be monitored carefully. Body weight, albumin, and total protein are watched to ensure adequate protein in the diet. Initially, these tests should be performed monthly, then every 3 months. In addition to the above tests, bile acids are monitored monthly, then every three months to assess the vitality of the liver. Blood ammonia levels are monitored monthly to assess effectiveness of treatment. When stable, ammonia levels can be monitored every 3 months.
Prognosis – Many pets with isolated extrahepatic shunts return to a normal life after surgery. There is no guarantee that surgery will correct the problem, especially those pets that develop the disease very early in life. Some of them will need medical management simultaneously. The prognosis for pets that are treated only medically varies.
Chronic Active Hepatitis
Fluids and Electrolytes – This corrects the dehydration that occurs with a poor appetite and supplies needed sodium, potassium, and chloride. This fluid is usually given intravenously (IV) at first. It can be given subcutaneously (SQ) at home after the initial dehydration is corrected. B-Complex vitamins are routinely added to the fluid bag. Care must be taken not to give excessive amounts of fluids, especially if they contain sodium, in pets with fluid buildup in the abdomen (ascites).
Treating the Cause (when known) – Antibiotics are used to control bacterial infections and drugs that are suspected of causing this disease are stopped. We tend to use antibiotics that have minimal need for liver metabolism in order to minimize their toxic effects.
Rest – The liver has ability to heal itself if the disease is not too advanced. Rest can be a big aid, along with proper nutrition.
Ascites Reduction – Sodium restriction helps minimize fluid buildup (ascites) in the abdomen. This can be accomplished using Hills K/D Prescription Diet. Diuretics like Lasix are also used to help pull this fluid out of the abdomen.
Dietary Modification – Using a diet that is restricted in protein may be beneficial because less ammonia is produced as a by-product of metabolism. This protein needs to be of high biological value, such as eggs and dairy products. Meat based proteins should be avoided since they can increase the chance of HE. Higher fiber diets might also be helpful, as long as the dog or cat is not undernourished. This is the same basic diets as for pets with PSS (see above).
A diseased liver needs calories, which sometimes need to be supplied with a feeding tube.
Ulcer Treatment – This will make pets more comfortable, more inclined to eat, and prevent bleeding in the stomach.
Liver Specific Drugs:
Corticosteroids – Cortisone is used if there is evidence that the immune system is implicated as a cause
of the liver problem.
Ursodiol – This drug replaces toxic bile acids with a type of bile that is less toxic.
Zinc Supplementation – Might help reduce the effects of copper toxicity.
Long Term Monitoring – CCHID monitoring is similar to PSS (see above). In addition, repeating a liver biopsy 6 months after initiating therapy used.
Infectious Canine Hepatitis
Like most viral diseases therapy is directed towards symptoms. When symptoms are severe enough, intravenous fluids are administered. Since clotting factors can be disrupted particular attention needs to be paid to bleeding problems. If bleeding problems are severe enough, a whole blood transfusion must be administered. Dogs that are comatose may need intravenous glucose.
Copper Toxicosis (Copper Storage Disease)
Treatment has two goals – Enhance excretion of excess copper, and minimize further absorption of copper from the intestines.
Chelating agents – Drugs like penicillamine bind with copper to allow easier excretion.
Zinc – Zinc will help minimize further copper absorption from the intestines.
Supportive Care – Similar to other liver diseases previously described.
Long Term Monitoring – Serum, enzymes, and bilirubin should be monitored at least every 6 months.
Primary hepatic neoplasms are treated by removal of the affected liver lobe when possible. If multiple lobes are involved then surgery is usually not performed. Secondary hepatic neoplasms are treated with chemotherapy. The results vary, and depend on the duration, location, and degree of malignancy of the neoplasia.
The prognosis is poor for long term survival.
Supportive care that is similar to other liver diseases is also used in neoplasia.
**Information from this section was compiled from the following sources:
1. LISTEN TO YOUR INSTINCTS. You know your dog better than any vet or specialist. If there is something “not quite right”, encourage blood tests to see what is going on. The symptoms of canine liver disease are so subtle and can be mistaken for so many other things, ask for a liver panel test to rule it out.
2. Educate yourself about the signs/symptoms of canine liver disease so that you are able to recognize them if any are present in your dog.
3. Feed your dog a high-quality balanced diet with easily digestible protein (beef and fish are harder for dogs to digest), no animal by-products, fillers or allergens.
4. Know your dog’s normal body temperature and take it regularly and if/when they show behavior changes. Temperatures above 103F may be linked to internal infection and may be affecting the liver.
5. Know your dog’s eating and bathroom habits. If there are even slight changes that extend over a period of a week or so, seek out the advice of your veterinarian.
6. Do not allow dogs to roam freely where they can encounter animals or insects, standing water or poisonous plants.
7. Routinely vaccinate dogs for infectious canine hepatitis and leptospirosis.
8. Take your dog in for a yearly exam that should include blood, stool and urine samples in dogs 8 years of age or more. (Veterinarians will do these tests on dogs under the age of 8 as well.)
9. If tests are abnormal or presenting high range numbers, seek out the advice of an Small Animal Internal Medicine Specialist – your vet should be able to refer you to someone in your area.
10. Practice good dental hygiene for your dog. Brushing your dog’s teeth helps rid the gums and mouth of harmful bacteria that, if left unchecked, can spread to the heart, liver and other vital organs.
11. Avoid medications such as Cortisone, Rimadyl and Phenobarbital if at all possible. Also try to minimize exposure to flea and tick products, heartworm medication, anti-fungals, etc.
* If Rimadyl cannot be avoided:
A blood panel should be taken and analyzed prior to initiating Rimadyl therapy.
Every 6 months this panel should be repeated.
* If Phenobarbital cannot be avoided:
Have a chemistry panel with the liver enzymes ALT, GGT and alkaline phosphate
done every 3 to 4 months.
If all three liver enzymes are severely elevated (more than just a few points
above normal) then you should do a urine bile acid test or a pre- and post-meal
bile acid test to see what kind of damage has been actually done to the liver so you
can change the diet to the liver cleansing diet and/or reduce the Phenobarbital.
Monitor Phenobarbital levels every 6 months, more frequently if you do not have
seizure control or if there are any signs of toxicity like ataxia, wobbliness, and hind end
weakness (not after a seizure).