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“The only thing necessary for these diseases to the triumph is for good people and governments to do nothing.”

 
    

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:

hepatic- having to do with the liver

icterus (jaundice) - yellow discoloration of skin or mucous membranes

hepatocyte- individual liver cell

hypertrophy- increased size of an organ

hypoalbuminemia - low albumin

polyuria- excess urinating

hypoproteinemia- low protein

polydypsia- excess drinking

polyphagia- excess appetite

PU/PD- polyuria and polydypsia

ascites- fluid buildup in the abdominal cavity

gluconeogenesis- the manufacture of glucose

hypertension- increased blood pressure

iatrogenic- caused by something a person does as opposed to happening naturally.

euglycemia- normal blood glucose (sugar) level

homeostasis- normal physiology

hepatomegaly- enlarged liver

septicemia- excess accumulation of bacteria and toxins in the bloodstream

hepatitis- a general term for inflammation of the liver

parenchyma- the internal anatomy of an organ

encephalopathy- chemicals, like ammonia, that depress the brain

laparotomy- exploratory surgery of the abdomen

anorexia- poor appetite

H.E.- hepatic encephalopathy

metastatic- a tumor that has spread from elsewhere in the body

microhepatica- abnormally small liver

cholestasis - excess bile accumulation in the liver

 

 

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