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Liver
Disease
Introduction
The largest organ in the
body is the liver, an indication of its importance in health.
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 complex biochemical
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. This
page will cover some of the more important ones we see in
animals. The beginning of this page will discuss liver anatomy
and physiology, eventually leading to detailed explanations of
the more common liver diseases we encounter. This complex
organ does not lend itself to easy classification or
understanding. Many of the functions of the liver overlap with
other organs, and some of the liver's functions involve
complicated biochemical pathways.
Even though it makes for
good reading, you can skip the anatomy and physiology section
and go right to the section on specific diseases if that is
all that interests you:
We have a very short
Quicktime movie of a liver ultrasound that shows a stone in
the gall bladder. Make sure you have Quicktime on your
computer to view it. You can get it at www.apple.com
Terminology
It is helpful to be exposed
to several medical terms that will be used later in this page:
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hepatic- having
to do with the liver
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icterus
(jaundice) - yellow discoloration of skin or mucous
membranes
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hepatocyte-
individual liver cell
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hypertrophy-
increased size of an organ
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hypoalbuminemia -
low albumin
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polyuria-
excess urinating
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hypoproteinemia-
low protein
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polydypsia-
excess drinking
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polyphagia-
excess appetite
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PU/PD-
polyuria and polydypsia
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ascites-
fluid buildup in the
abdominal cavity
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gluconeogenesis- the
manufacture of glucose
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hypertension-
increased blood pressure
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iatrogenic-
caused by something a person does as opposed to
happening naturally.
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euglycemia-
normal blood glucose (sugar) level
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homeostasis-
normal physiology
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hepatomegaly-
enlarged liver
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septicemia-
excess accumulation of bacteria and toxins in the
bloodstream
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hepatitis-
a general term for inflammation of the liver
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parenchyma-
the internal anatomy of
an organ
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encephalopathy-
chemicals, like ammonia, that depress the brain
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laparotomy-
exploratory surgery of
the abdomen
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anorexia- poor
appetite
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H.E.- hepatic encephalopathy
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metastatic-
a tumor that has spread
from elsewhere in the body
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microhepatica-
abnormally small liver
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cholestasis -
excess bile accumulation in the liver
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Anatomy
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 (birds and
reptiles
do not have a diaphragm).
This
autopsy picture of a cat shows the gallbladder in green, with
several lobes of the liver laying right up against the
diaphragm (towards the top of the picture). On the other side
of the diaphragm is the chest cavity containing the lungs and
heart.

This
close-up of the gallbladder and one of the lobes of the liver
gives you a feel for what a normal liver lobe looks like in a
cat.
For
fun comparison purposes, this is the gallbladder from an
Iguana. It is also surrounded by liver lobes. Notice the
difference in color from the cat liver above?

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. Of tremendous significance is the
fact that a healthy liver has great reserve power, using only
a small amount of its full potential at any one time.
Unfortunately, this great reserve power means that diseases
that affect the liver can be well entrenched and not show
symptoms of disease before a diagnosis is made. This obviously
makes the prognosis worse. The liver does have an advantage
though. Liver cells (hepatocytes) can regenerate themselves.
This regenerative ability allows a diseased liver to return to
normal function in some cases. Very few organs in the body
have this ability.
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. You will
learn more about this when we discuss porto-systemic shunts
later.
The
extensive blood supply to the liver is apparent in this
picture. The large blue vessels are part of the portal vein.

Functional Unit
At the cellular level the liver has a basic functional unit call
the acinus. This consists of hepatic sinusoids (areas of blood
pooling), liver cells (hepatocytes), central vein and the
portal triad. Blood from the portal triad flows into the
hepatic sinusoids that surround the hepatocytes. This blood
then exits through the central vein and back into the general
circulation.
Biliary
System
The
biliary system consists of the gallbladder, bile ductules,
hepatic ducts, and the common bile duct.
The
gallbladder is located between two of the liver lobes. It
stores bile that is made by the liver, and secretes this bile
through the common bile duct into the beginning of the small
intestine (duodenum). The bile that is secreted into the
duodenum aids in the digestion of many compounds, especially
fat.
This
is a picture of a greatly enlarged gall bladder and common
bile duct in a cat.
BD-
Bile duct
GB-
Gall Bladder
L-
Liver

This
"inside" lining view of the small intestine gives
you a great view of bile as it is being secreted from the gall
bladder into the duodenum.
Physiology
It is an understatement to
say that the liver is an important organ. Every second the
liver cells go through thousands of complex biochemical
interactions that influence all of the other organs in the
body. Its complexity precludes us from discussing all of its
functions, so we will limit the physiology section to some of
its more important functions.
The liver has reserve
functional power and can operate effectively when most of the
hepatocytes are not working well. In addition, diseased hepatocytes can actually regenerate and return to normal
function.
Metabolism
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.
Protein Metabolism
The
liver produces all of the proteins except for the proteins
synthesized by the immune system (called gammaglobulins or
immunoglobulins). 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. (A more detailed explanation of
ascites will follow). 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.
Carbohydrate Metabolism
With
the aid of the hormones insulin
and glucagon, the liver maintains a normal blood glucose level
(euglycemia). 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.
Lipid Metabolism
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. Excess fatty acid accumulation in the hepatocytes
is called lipidosis. This is a disease that occurs mainly in
cats, which you will learn more about later.
Detoxification
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:
Phase
I
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 to an active
metabolite. This active metabolite circulates in the
bloodstream and has an affect on the body. An example is the
conversion of prednisone, an inactive compound, to
prednisolone, and active form of cortisone.
The
drug is converted from an active drug to an active metabolite.
A great example of this is antifreeze
poisoning (ethylene oxide).
Phase
II
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 into a compound called urea., which
is excreted by the kidneys.
A diseased liver will not metabolize this ammonia to urea
properly, leading to the disease called hepatic encephalopathy.
This disease is explained in more detail later.
Bile Metabolism
Bile
is made up of electrolytes, cholesterol, bile acids, bilirubin,
and globulins. It is produced by hepatocytes, secreted by
hepatocytes into channels in the liver called bile cannaliculi,
and stored in the gall bladder. Drugs are eliminated in the
bile, red blood cell are recirculated 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 (iron) 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 into urobilinogen, where it
imparts the dark color to stool. If this bilirubin can not be
excreted from the gallbladder (when there is an obstruction in
the bile duct) there will be very light colored (acholic)
stool. The excess amounts of bilirubin that build up in the
bloodstream will cause icterus. Icterus is more commonly known
as 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 form the intestines. These vitamins are stored in
the liver, and are converted to active compounds as the liver
maintains normal physiology (homeostasis).
Coagulation
Factors
The
proteins that initiate and maintain clotting of blood are
synthesized by the liver. These proteins go through very
complex biochemical processes to achieved 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. When rat
poison (warfarin poisoning) is ingested it interferes with the
ability of vitamin K to perform this vital function.
This
is a Coagulation Panel from a 15 year old dog with liver
disease. The arrows point to elevations that show the blood is
not clotting in a normal amount of time. In addition, the
platelets are low.

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 these is a severe blood loss
the liver expels this blood into the bloodstream to help make
up for the loss.
Reticuloendothelial
System
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.
Vitamins
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.
Did you make it through the
physiology section? If that seemed a little complex keep in
mind we only glossed over a small fraction of liver
physiology. You can spend a lifetime studying the liver and
still not understand all of its physiology.
Pathophysiology
Icterus
Icterus (jaundice) can have a pre-hepatic, hepatic, or post-hepatic
cause:
Pre hepatic
Diseases that cause extensive red blood cell destruction (immune
mediated hemolytic anemia, for example) can overload the
liver's ability to metabolize bilirubin. The liver is not
diseased in this situation, it is just being overloaded with
work to do. This is not to say there isn't a problem because
the anemia that causes this overload is a sign of a problem
somewhere in the body. It usually takes a severe anemia to
cause this problem.
Hepatic
Icterus can also be caused by impaired excretion of bilirubin in a
diseased liver. These animals do not usually have a severe
anemia, what they have is inflammation in the liver and
biliary system. This swelling, known also as
cholangiohepatitis, impairs the liver's ability to excrete
bilirubin in the digestive system. The bilirubin builds up and
eventually spills over into the bloodstream, causing the
yellow discoloration.
Post hepatic
Obstruction of bilirubin flow out of the liver, which is a more
extreme version of impaired excretion above, can also cause
icterus. An obstruction of the gall bladder or common bile
duct can cause this. These animals will have light colored
feces because no bile pigment is being excreted into the
digestive system to give stool its dark color. Bilirubin that
is retained in the liver is toxic and will add to the liver
problem that is already present.
Ascites
This is an accumulation of fluid in the abdominal cavity. It is
more common in dogs vs. cats when liver disease is the cause
of ascites (heart disease, kidney diseas,
and abdominal tumors
can cause it also). Ascites due to liver disease occurs when
there is impairment of blood flow through the portal vein.
This impairment leads to increased blood pressure
(hypertension) which causes fluid to leak out of the portal
vein and into the abdomen. The low albumin level (hypoalbuminemia)
that sometimes accompanies liver disease adds to this problem
because albumin helps retain fluid inside the blood vessels.
Ascites is diagnosed by abdominal palpation, although in large pets
it can be difficult to feel the fluid. You can see a fluid
wave when you gently tap the abdomen of a pet with ascites.
Ascites is also diagnosed by radiography. In this situation
the fluid obscures the normal organs like kidney and
intestines. There are other diseases that can cause abdominal
enlargement and mimic ascites. These include obesity, pregnancy,
urinary
obstruction,
enlarged spleen, uterus, or
stomach.
This
radiograph illustrates ascites. The fluid that has built up
makes it difficult to distinguish individual organs. Emaciated
animals with no body fat, or young animals with minimal
abdominal fat accumulation, can look like they have ascites,
when in reality they are perfectly normal.

Hepatomegaly
Enlargement
of the liver can be from several different causes:
·
Passive
congestion of blood flowing through the liver
·
Inflammation or
infection
·
Cysts
·
Increased size of
individual hepatocytes
·
Infiltrative
disorders
Microhepatica
·
Hypotension
·
Fibrosis
·
Hepatocyte
atrophy
Anemia
Improper utilization of iron in the bone marrow, decreased
appetite, and less nutrients from a liver with abnormal
metabolism all can cause anemia. Gastric ulcers and clotting
problems will cause bleeding and exacerbate anemia.
Hepatic Encephalopathy (HE)
In severe liver disease or porto-systemic shunts the flow of blood
through the liver is abnormal. This leads to a buildup of
ammonia levels with a deleterious effect on the brain.
Cause of Liver
Disease
In many cases
the liver is ill secondarily to a problem elsewhere in the
body.
Trauma
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.
Inflammation
An inflamed liver is called hepatitis. Trauma can cause this, along
with drugs, viruses, bacteria, bile, and toxins.
Pancreatitis
The severe inflammatory process that occurs with digestive enzymes
can spill over into the liver and cause severe disease.
Anemia
Hemolytic anemia can decrease the oxygen available to liver cells
and lead to their death.
Infection
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, Feline
Infectious Peritonitis (FIP),
Leptospirosis, abscesses, histoplasmosis, coccidiomycosis, and
Toxoplasmosis.
Heartworms
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.
Toxins
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) in Labradors
·
Thiacetarsamide
(heartworm treatment)
·
Ketaconazole
(fungal treatment)
·
Tylenol
(acetaminophen)
·
Glucocorticoids
(cortisone)
·
Anthelmintics
(worming medication)
·
Parasiticides
·
Phenobarbital
(epilepsy medication)
Cancer
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:
Primary
·
Lymphosarcoma
·
Hemangiosarcoma
Metastatic
·
Adenocarcinoma
·
Leiomyosarcoma
·
Mammary tumors
·
Oral carcinoma
·
Lymphosarcoma
·
Hemangiosarcoma
Metabolic
diseases that cause secondary liver problems:
·
Hypothyroidism
·
Diabetes
Mellitus
·
Pancreatitis
·
Hyperthyroidism
·
Cushing's
·
Inflammatory
Bowel Disease
·
Hypoadrenocorticism
·
Protein-losing
enteropathy
Symptoms
Symptoms of
liver disease are variable and subtle in the early stages of
the problem. The classic symptoms are:
Poor appetite
(anorexia)- This is a common symptom
Weight loss- The poor appetite that occurs in liver disease
eventually leads to loss of weight. Improper metabolism of
fat, carbohydrates, and proteins complicates the situation
also.
Polyuria/polydypsia (PU/PD)- This is excess urinating and excess
drinking of water. This can occur in liver disease, although
several other important diseases cause these symptoms also,
notably, Kidney disease,
Cushing's
disease, pyometra, and sugar diabetes.
Lethargy- Poor appetite and disruption in normal physiologic
processes leads to this symptom. Anemia adds to this lethargy,
along with ascites due to the discomfort it causes.
Anemia- Improper nutrition from a poor appetite, along with disease
in the hepatocytes will cause this.
Light colored stool- If the
biliary tree is prevented from secreting normal bile pigments
into the intestine the stool will lack pigmentation and appear
lighter in color.
Bleeding disorders- The normal clotting system is impaired since it
depends on a healthy liver.
Distended abdomen due to ascites or hepatomegaly. If the distention is severe enough breathing might be
labored from pain or the pressure on the diaphragm.
Vomiting (emesis), nausea, or diarrhea. Sometimes blood is present
in the vomitus (hematemesis), especially if a gastric ulcer is
present. The ulcer comes from a complex interaction of
histamine, nitrogen, bile acids, Gastrin, portal hypertension,
and an altered mucous membrane lining the inside of the
stomach.
Pain due to distention of a diseased liver.
Orange colored urine or mucous membranes due to jaundice.
Behavioral changes- circling, head tilt, heap pressing, and
seizures, particularly right after a meal.
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.
Diagnosis
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.
1. Signalment
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, or FIP in cats. 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
terrier's, 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.
2. History
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. In cats with hepatic lipidosis the history
usually involves a lack of appetite (anorexia), especially if
the cat was previously obese.
3. Physical Exam
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 liver tumor.
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.
4. Diagnostic Tests
Several tests are used as an aid in making this diagnosis.
Blood
Panel
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 good way to diagnose liver disease is with the biochemistry
panel, abbreviated as BCP. There are several tests on the BCP
of dogs and cats that aid us in our diagnosis of liver
disease. Many of these are called liver enzyme tests, a few of
which we will discuss. When they are elevated it could be a
sign of liver disease, but not necessarily so. There are a
multitude of conditions that will cause an increase in these
enzymes even though the liver is not primarily diseased. (a
good example is Feline Hyperthyroidism). They need to be at least 1.5x normal to be of significance. If a
pet has significant elevations in the liver enzymes tests then
they should be repeated and trends noted. Only then can we get
an indication if the liver truly has a problem. To further add
to the complication, these tests can be normal in dogs and
cats that have severe liver disease.
Alkaline Phosphatase (Alk Phos)
This enzyme is found primarily in the cells of the biliary system.
It is also found in white blood cells, bone, kidney, and
intestines, so an elevation is not always an indication of
liver disease.
Anticonvulsant drugs and cortisone (more so in dogs than in cats)
can cause an increased Alk Phos even if there is no liver
problem. Normal young animals, especially in large breed dogs,
can have an increased Alk Phos. Older pets that have an
elevated Alk Phos should also be checked for Cushing's
disease.
Alanyl amino transferase (ALT)
This enzyme, also called SGPT (serum glutamate pyruvate
transaminase), is found primarily in the cytoplasm of the
liver cell. It is also found in small amounts in the heart,
kidneys, and muscles. When there is damage to the membrane of
the liver cell this enzyme leaks into the bloodstream. It is a
measure of the integrity of the hepatocyte, and correlates to
the number of hepatocytes affected. It does not tell us how
severe the injury is to the hepatocyte, and is not an
indication of the reversibility of the liver problem. In other
words, a high ALT indicates many liver cells are involved, but
it might be a minor problem that can correct itself with
supportive care. This is one of our more consistent enzyme
tests of the liver, yet an elevation here does not always
indicate liver disease.
GGT (Gamma glutamyltransferase)
This enzyme is also a part of the biliary system and correlates
with alkaline phosphatase. Highest quantities occur in the
kidneys and pancreas, with lesser quantities in the liver,
gallbladder, intestines, spleen, heart, lungs, and muscles.
Total Protein
Total protein is made up of albumin and globulin. Globulin's are
made by the immune system, the liver makes the rest of the
proteins in the body, the main one being albumin. A decrease
in total protein or albumin can occur in liver disease,
usually in chronic liver disease.
There are many factors that influence the level of total protein in
the bloodstream in addition to the liver. They include diet,
state of hydration, the ability to digest and absorb nutrients
through the intestines, and the normal functioning of other
organs like the kidney that normally excrete protein.
Bilirubin
We measure the amount of bilirubin in the bloodstream with this
test. We break it down into conjugated (direct) and
unconjugated (indirect). Even though this test is less
sensitive in detecting liver disease than the enzyme tests,
when it is elevated there is a greater chance the elevation is
indeed caused by liver disease. Anemia is another cause of
elevated bilirubin.
When bilirubin is significantly elevated a dog or cat usually has
jaundice (icterus). Sometimes bilirubin from the bloodstream
can spill over in a dogs urine. A small amount is normal in a
dogs urine. In the cat any bilirubin in the urine is a sign of
a liver problem.
BUN
This is one test where a low number is a sign of a liver problem.
If this test is normal there still could be a liver problem,
if elevated it is a sign of dehydration, a urinary
obstruction, or kidney
disease.
This
older cat with liver disease has a normal Alk Phos, only a
slightly elevated ALT and a normal GGT and albumin. The very
high Total Bilirubin (it is over 4x the highest normal) clues
us in to liver disease.

This
older dog with liver disease shows a normal Alk Phos, a
significantly elevated ALT, a normal GGT and a normal albumin
and Total Bilirubin.

This
older dog has all the classic blood parameters of a dog with
liver disease. The Alk Phos, ALT, GGT, and Total Bilirubin are
significantly elevated. Even the cholesterol is high, which
sometimes accompanies liver disease.

This
older cat does not have liver disease, even though the enzyme
levels are high. The lower arrow points to the real reason for
the high liver enzymes. This very elevated thyroid level is a
sign of Feline Hyperthyroidism.

After
2 weeks of treating for the thyroid problem the thyroid level
and the liver enzymes started returning to normal.

Bile Acids
This
is liver function test, not an enzyme test, and is not a
routine part of the BCP. We will request this test when we
suspect a liver problem, whether the enzyme tests are normal
or not. This test is performed by taking a blood sample,
giving a meal, then taking another blood sample 2 hours after
the meal. Comparing the pre-meal and post-meal blood results
gives us valuable information. The bile acids test is an
accurate measure of liver function.

Urinalysis
A urine sample can give us important clues as to the existence of
liver disease. The specific gravity might be below normal, an
indication that PU/PD is present. Bilirubin might be present,
a finding that is always abnormal in cats. There also might be
ammonium biurate crystals, a sign of improper ammonia
metabolism found in Hepatic Encephalopathy.
This
urine sample from a dog shows a trace amount of bilirubin,
which can be normal in a dog.

This
bilirubin in a urine sample from a cat is a sign of liver
disease or anemia.

Abdominocentesis
Analysis
of the fluid obtained from a pet with ascites can give
valuable clues as to its cause. There are numerous causes to
ascites, some of the more common ones are heart disease, liver
disease, and cancer.
Fluid
is removed from the abdomen with a special needle and syringe.

Liver
Biopsy
This
is a very valuable test in the diagnosis of liver disease. A
sample of the liver can be obtained during an exploratory
surgery or during an ultrasound procedure. The pathologist can
look at the hepatocytes microscopically and determine if
disease is present and what the cause is.
This
report is from a very ill cat.

It
is helpful to run a coagulation panel prior to any liver
biopsy. A diseased liver might not be able to clot
properly, and a
biopsy could cause hemorrhage into the abdomen.
Stool
A
dog that excretes stool without normal pigmentation could
indicate liver disease. It occurs when there is obstruction of
the biliary system and normal bile pigments are not secreted
to cause the normal dark color of stool.
Radiography
An enlarged liver on a radiograph is called hepatomegaly, an
abnormally small one is called microhepatica. Either one can
be a sign of a liver problem.
In addition to plain radiographs, contrast media can be put into
the arterial or venous system to help outline the liver. These
tests go by various names; cholecystography, portal venography,
and hepatic arteriography.
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.

This
radiograph also shows hepatomegaly, but in this case the
borders of the liver are not as sharp. This could be due to a
swelling of one of the lobes or fluid in the abdomen. An
enlarged spleen can look like this also.

Some
radiographs of a liver with hepatomegaly don't show the
routine shape of the liver lobes. This case of a liver cancer
has a very rounded appearance. A tumor of the stomach, spleen,
or intestines can also have this appearance.

Sometimes
we diagnose hepatomegaly or microhepatica indirectly by
looking at the angle of the stomach This picture shows the
angle of the stomach in a normal radiograph of the abdomen.
Compare it to the radiograph below.

This
abnormal liver is pushing the stomach (S) towards the rear, an
indication of hepatomegaly, even though it is difficult to
clearly see the liver.

Sometimes
we can not say for sure whether an enlarged organ on a
radiograph is the liver. This mass, located near the liver,
could also be an enlarged spleen, small intestine, lymph node,
stomach, or even pancreas.

Ultrasound
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).
This
liver ultrasound reveals a mass in the liver. Can you see its
circular appearance at the arrow? It also shows abdominal
effusion (this is the ascites described previously).

The
final report summarized the problems this dog has with its
liver and spleen:

The
gall bladder can be seen with ultrasound also. This is a
printout after an ultrasound has determined this dog indeed
has a stone in its gall bladder.

This
short Quicktime movie shows you how a stone in the gall
bladder looks during the actual ultrasound. You will have to
look fast, the stone is the whitish are in the center of the
movie. Double click on the movie and in a few seconds it will
play. This movie gives you an idea of the skill that is needed
by the ultrasonographer in making this diagnosis.
The
liver can get cysts, which are also diagnosed with ultrasound

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