Signs, Symptoms, and Diagnosis
Sherwood Animal Clinic
This topic is as
big as the states of Alaska and Texas combined. I really cannot do it justice in
a short essay, but I think it deserves some mention, if only to give the pet
owner some understanding as to the difficulties involved when a veterinarian is
faced with a case of possible liver failure.
If you asked ten people on the street what they knew about "liver", I would bet
that the only consistent answer you would get is that it tastes really bad
unless the cook really knows his stuff. The best description of the liver I can
give you is that this organ is the main industrial centre of the body. 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 e
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 it's 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 tumour, 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.
Because of the complexity of this topic, I am going to cover it using very
abbreviated point form. I will try to skip over the experimental theories and
the more esoteric points and keep to the meat of the topic.
Common Presenting Symptoms
All, some, or only one of these signs may be present.
Intermittent recurrent abdominal or gastrointestinal upsets. loss of appetite,
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
Pale gray feces. Bile pigments are what gives poop it's characteristic brown
colour and if the liver is not processing bile properly, the feces will not get
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.
Rarely: bleeding problems. Many of the proteins required for proper blood
clotting are created in the liver. Remove these proteins and blood clotting
Hepatic encephalopathy, or severe neurological signs. behavioural changes,
seizures, aimless pacing or circling, head pressing. May be associated with meal
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 (palpates) 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. May be behavioural too.
Points on notable symptoms.
1. Bile pigment processing. Bile is a complex mixture of organic and inorganic
compounds. It is primarily responsible for alkalizing the intestinal contents
(acidic from the stomach),emulsifying the dietary fat, and prevention of
putrefaction of digestive material.
Bilirubin, one of the bile pigments, is derived from the break down of
hemoglobin, the oxygen carrying molecule carried in our red blood cell.
Bilirubin is quite toxic, but it usually binds to a protein called albumin,
which harmlessly carries it to the liver for detoxification and excretion.
Albumin is made in the liver. Liver failure results in poor bilirubin processing
and decreased albumin manufacturing, which results in a dangerously high level
of free floating bilirubin.
The liver excretes the bilirubin after binding it to an amino acid into the bile
duct system. Eventually the conjugated bilirubin enters the digestive tract,
where the intestinal bacteria break it down to a harmless product called
urobilinogen. Urobilinogen, after complete digestion in the intestines, is
brown, therefore the feces tend to be brown.
Jaundice, also known as icterus, results from the accumulation of conjugated and
unconjugated bilirubin in the body tissues. This becomes visible to the
veterinarian, especially around the whites of the eyes and on the pale areas of
2. Important biological functions:
· a. hormone metabolism. The liver is both the target organ for many of the
body's hormones and the recycling centre for most of the hormones. Some of the
symptoms stemming from liver failure may mimic a major hormonal imbalance.
· b. vitamin metabolism. Practically all the vitamins consumed in our diets are
either directly involved in liver function or require liver aided transformation
to be used in the body. This includes Vitamin C, the B vitamins, Vitamins A, D,
E and K. Vitamin K is important to maintain blood clotting and requires hepatic
transformation from the inactive form to the active form.
· c. Red blood cell maintenance. In the mature dog the liver plays an active
role in the removal of aged or damaged red blood cells from circulation. It is
also active in the metabolism of hemoglobin and the storage of iron.
Abnormalities in red blood cell structure is one of the harbingers of liver
disease. Anemia may be present in chronic liver disease.
· d. Hemostasis or blood clotting ability. Most of the proteins involved in the
creation of a functional blood clot are made in the liver. The clotting system
is an extremely complex, interlocking system ; remove some of the factors
involved and you end up with a tendency to bleed or hemophilia.
· e. Carbohydrate and fat metabolism:
Sugars, or carbohydrates are the basic fuel of the body. The liver is the
primary centre for processing of the sugars into the form immediately required.
The liver is also responsible for the destruction of insulin, the hormone
directly involved with the cellular absorption of blood sugars. Alterations in
liver function often do not affect blood sugar levels until much of the liver
has been destroyed.
Fat metabolism is extremely complex due to the vast number of functions fat
carries out in the body. The liver sits at the centre of those many functions.
Cholesterol is probably the most common fat based product in the body, being the
major component in the cell wall, the basis for the steroid hormones and bile
pigments, and the precursor of vitamin D. Any disease in fat metabolism can
adversely affect the liver, and any disease in the liver can result in problems
in fat metabolism. An example of this is the "fatty liver syndrome" we see in
cats, whereas the rapid mobilization of fat stores during starvation results in
an overtaxed liver and eventually liver failure.
The liver manufactures many of the proteins involved in the body functions. The
major protein is albumin, which is required for transport of many nutrients and
toxins (i.e. bilirubin). Albumin is also responsible for keeping the serum
concentration constant, which is important with regards to serum fluid and salt
balance. (also known as "oncotic pressure") Also synthesized in the liver is the
globulin series, which are responsible for numerous biochemical reactions
throughout the body. Elevations of select globulins may indicate a particular
The building blocks of proteins are the amino acids. The liver is also primarily
involved in processing of dietary amino acids to modify them into required or
Some of the amino acids require direct hepatic metabolism, while others can be
used by the body unchanged. Experimental efforts have been made to diagnose and
track liver disease based on the relative proportion of the various amino acids
to each other. In liver failure the amino acids requiring hepatic alterations
prior to use should climb in concentration as compared to those amino acids
unaffected by the liver.
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 in the dog and cat. Cell damage
will cause elevations of A-LT 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.
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.
Alkaline Phosphatase. This enzyme is present in many tissues, therefore it is
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. A similar sensitivity has not been noted in the cat..
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.
Gamma Glutamyltransferase GGT: This enzyme is has it's 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
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 form 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
Ammonia and Urea:
Ammonia is a by product of digestion of protein in food and the catabolism of
nitrogen based organic materials in the body. Eighty per cent of ammonia is
delivered to the liver and converted to urea. In patients with liver
insufficiency the ammonia is not detoxified to urea, but enters the circulation
to act as a central nervous system depressant.
In patients with a severely reduced liver function we may see a true intolerance
of ammonia and thus neurological signs after a heavy protein meal or we may see
substantially reduced urea levels. This is a late sign in liver disease, only
seen after 60 to 70 per cent of the liver function is gone.
This is the accumulation of fluid in the abdominal cavity and results from
several factors. Simply put liver disease tends to alter the blood pressure in
the portal system, the albumin and salt concentration in the serum, the water
retention in the body, the function of the surrounding organs and the
permeability of the portal vessels. As a result of all these factors, fluid
tends to build up in the abdomen and the animal gets a big, swollen, fluid
Electrolyte and Acid-Base disorders.
Common side effect of liver disease due to a multiple of factors leading from
metabolic disorders. Enough said.
Gastrointestinal Ulceration and Hemorrhage:
Again a sequellae to liver disease which may confuse the veterinarian. He may
think he is treating a simple ulcer and miss the liver disease.
Simply described as severe neurological dysfunction due to advanced liver
disease. Has been linked to the accumulation of biological toxins, including
ammonia, alterations in the blood brain barrier, alterations in the
neuroreceptors in the brain, and decreased blood sugar.
Diagnosis of Liver Disease
Having gone into such detail prior to this, I hope this section will be short
and to the point. I hope most of my statements here will naturally flow from
points made above.
1. Examination, specifically noting signs which may indicate liver disease.
Periodic ascites, intolerance of a high protein diet, icterus, chronic weight
loss, abnormally coloured feces or urine, bleeding disorders, chronic illness,
and all that has been mentioned above. Sometimes urinary crystals formed from
the improperly metabolised proteins and amino acids may indicate liver disease.
2. Extensive blood work:
· A complete blood count to check for anemia and blood cell abnormalities.
· 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 a 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.
· A complete urine analysis. Check urobilinogen levels, bilirubin levels,
glucose levels, protein levels. Again all this is usually on a standard
· 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
· Biopsy of the liver. While this is a surgical technique, it is the ultimate
for diagnoses, since it allows us to directly examine and test liver tissue,
give an absolute diagnoses 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 removed,
therefore liver biopsy is usually a low risk procedure in capable hands.
Specific Diseases of the Liver
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 characterised 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.
Another syndrome has been seen in England called Canine Acidophil hepatitis.
Typical signs of hepatitis are present, but the case may take a very chronic
course, lasting over a period of years. No specific viral organism has been
identified, therefore no vaccine or treatment is available.
No specific virus causes hepatitis in cats, but the feline corona virus
responsible for Feline Infectious Peritonitis will cause a hepatitis in some
cases. Diagnoses by biopsy. No treatment. Mediocre vaccine.
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.
Blastomycosis, histoplasmosis and coccidiomycosis are fungal infections seen in
various parts of the country (usually associated with river systems) Difficult
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.
Tuberculosis is still around and is considered transmissible to humans.
Certain parasites will infect the liver. Typically the likelihood of parasitic
infestation depends on the area you live in. Diagnoses is often based on
symptoms, fecal examination, and standard diagnostic techniques for liver
disease. Treatment is the use of appropriate parasiticides.
Liver Disease Secondary to other Disease
Acute pancreatitis: 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
c bowel disease: the chronic inflammation of the bowel allows portal absorption
of toxic intestinal products and bacteria. treat the colitis.
Shock, anemia, and congestive heart failure. All these result in severe loss of
blood circulation to the liver and lack of oxygen. The liver disease is rarely
of primary concern as the primary causes of the problem are most likely going to
kill the animal prior to liver failure.
Abdominal trauma: tears, bruising, biliary leakage, hepatic bleeding. Correction
of these problems would require surgical intervention, assuming a timely
diagnoses. Simple bruising of the liver will heal unaided, with only a transient
increase in the hepatic enzymes.
Feline Hyperthyroidism: many of the symptoms of hyperthyroidism and hepatitis
are the same and in fact the hyperthyroidism will cause elevations in the liver
enzymes. The thyroid level of any cat presenting with symptoms suggestive of
liver failure should be checked. The hepatitis will resolve once the
hyperthyroidism is treated.
Copper storage diseases in Beddlington 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. Diagnoses 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
characterised 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.
Leptospirosis associated chronic hepatitis: An example of bacterial infection
leading to chronic disease. Diagnoses by biopsy and identification of the
pathogen. Treatment by antibiotics.
Infectious Canine Hepatitis associated chronic hepatitis. Exposure to the virus
responsible for ICH leads to chronic active hepatitis due to an ongoing immune
system malfunction. Diagnoses by biopsy and the use of special stains to
demonstrate the viral antigens in the liver.
Lobular dissecting hepatitis: rare disease diagnoses by biopsy.
Hepatoportalfibrosis: 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 of
Toxic liver injury: 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: 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.
Glucocorticoid Hepatopathy 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
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.
Cirrhosis: This is the end point of chronic, active hepatitis. The cycle is one
of liver cell death (due to insult, either toxic, viral, or immune mediated),
followed by inflammation and scarification. The end [[[[ requires all previously
noted techniques. No treatment is possible and ongoing palliative and dietary
care is the only treatment option..
Noninflammatory Liver Diseases
Portal vascular abnormalities Usually a portal-systemic shunt which 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 anaesthetics, and tending to eat strange
items (pica). Diagnoses 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.
Hepatic Lipidosis Most common form of severe liver disease in cats. Most often
seen in obese cats suddenly subjected to dietary deprivation. May also be
associated with diabetes mellitus, drug injury and toxicity. Thedisease seems to
result from the sudden mobilisation of the bodies fat stores which quickly
overwhelms the liver's ability to process the raw fat into useful nutrients. The
fat accumulates in the liver rapidly and causes acute liver failure. The end
result is a swollen, greasy liver which is fragile and yellow to see. The cats
present with complete lack of appetite and many signs of acute liver failure.
Treatment is based on the provision of a highly nutritious diet to provide the
energy required to run the body, stop the ongoing mobilisation of the fat
stores, and drive the liver to decrease the fatty accumulation in the liver.
Treatment is difficult and a long process.
Hepatic Cancer (Neoplasm) Falls into two categories: primary or originally
stemming from liver tissue or secondary; originating in some other part of the
body and spreading to the liver through the circulation system.
Primary liver cancers can stem from exposure to toxins (oncogenic compounds)
which attack the liver full strength, since the liver is the primary
detoxification centre of
Secondary cancers may stem from any part of the body, but the liver is a
favourite destination for metastatic cancer because of it's central function in
the body and the micro- capillary network which makes up the circulation passing
through the liver.
Primary liver cancer is usually quite advanced prior to diagnoses and tends to
metastasize to the rest of the body very early in the course of the disease.
Keep in mind the liver can function with less than one third of it's volume
still operating, therefore liver cancer can be very advanced before any symptoms
Treatment is usually pointless, but would be based on diagnoses of the specific
cancer and the use of appropriate chemotherapy agents.
Basic Points for Treatment of Liver Disease
1. Removal of toxic agents. Identify and remove any drug or toxin which may
potentially hurt the liver.
2. Rest and confinement. This will help divert body resources to the healing
process at the liver and reduce discomfort caused by inflammation of the liver
such as painful belly, nausea, malaise.
3. Dietary management: Extremely important. The goal is to provide all the
necessary nutrients which may be lost due to failure of liver processing without
overtaxing the liver with regards to processing of dietary intake. High levels
of top quality protein to provide the essential amino acids in an easily
digestible carrier which will not produce high levels of ammonia during
digestion. Cottage cheese is good, meat tends to produce high levels of ammonia.
High level carbohydrates to drive the metabolism of the body, essential fatty
acids not less than 6% of the daily intake, and a good mineral and vitamin
supplement. Force feeding may be necessary.
4. Control of ascites and water retention. Reduce sodium intake. Diuretics will
help in resistant cases.
5. Control concurrent infections with antibiotics.
6. Deal with the concurrent medical problems as they crop up. Remember that the
dog may develop bleeding problems, malabsorption problems, and neurological
problems. Each separate problem has to be dealt with both individually and as a
part of the whole disease entity. Neurological symptoms such as coma need to be
addressed aggressively with a combination of therapies.
I realise that this is a long, possibly boring paper that is far from complete.
I cannot emphasize too strongly how difficult this topic is. I gleaned this
information from a single source Textbook of Veterinary Internal Medicine edited
by Stephen J. Ettinger 1989.