What is a Liver Shunt:

A Liver Shunt is a condition in which a portion of the blood in the body by-passes the liver and goes directly to the heart. Toxins especially ammonia build up in the blood stream and the dog has seizures due to increased ammonia levels. The liver is usually smaller than normal and will have decreased liver function. Secondary liver infection can occur but this plays a minimal role in the liver shunt syndrome. It is the bypassing of the blood thru the liver that is the major problem.

The symptoms of liver shunt can start to appear at almost any age. Dogs with a liver shunt are usually very thin dogs who pick at food. They not only have a poor appetite but they can become lethargic, dizzy, and stagger. They may try to climb out of their pen, climb higher on you and cry and throw their head far back after eating, and they may go into convulsions.

Many breeders feel that it is an inherited disease and that the only way to eliminate that disease is to cull those dogs who are affected and producing this disease from their breeding program.

Treatment
This disease usually goes hand in hand with a kidney disorder and it seems that a special diet can sometimes keep it under control with some dogs for a time. Surgery sometimes works depending on where the "shunt" is.

[ Some of this information here was taken from the book "How to Buy and Raise Your Toy Dog" by Terri Shumsky copyrighted 1993, with the authors permission. ]

Acquired vs. Congenital

Acquired shunts are caused by high blood pressure in the liver. When the pressure in the liver gets too high, the blood has to find a new way back to the heart. It does this by the opening of dozens or even hundreds of tiny and small blood vessels that hook the flow from the intestines, spleen and stomach to the great vein in the belly (the caudal vena cava), bypassing the liver. You may recognize some of the syndrome in people: a person that drinks too much gets "hardening" (cirrhosis) of the liver, and forms these little shunts around the esophagus and upper stomach. Then the person drinks more, gets ulcers, and starts to bleed into the stomach, perhaps even vomiting blood. Those people have formed multiple acquired shunts from high pressure in the liver, and have the unfortunate problem of the shunts bleeding into the stomach. Dogs usually don't drink alcohol excessively, but can get extensive liver damage from poisons, hepatitis, bacterial infections, inflammation, and high blood pressure in the heart. The shunts then form. Because the pressure in the vessels is high, fluid tends to leak through the walls of organs and vessels, filling the belly with ascites.

There is no way to tell before surgery which dogs have only a congenital shunt, and which dogs have both diseases. If we fix the shunt and the bile acids return to normal, we assume they don't have HMD/MVD. If we fix the shunt and the bile acids remain high, then they could have both diseases.

When we see persistently high bile acids 6 or more months after surgery, we think of the following possibilities:

1. The ameroid constrictor ring didn't close. This can happen in 1% of dogs, especially dogs that do not make enough scar tissue (for example a dog on steroids or with an adrenal gland problem).

2. The dog has a second congenital shunt. This can happen in 1% of dogs.

3. HMD/MVD

4. Multiple acquired shunts that developed because there were not enough normal microscopic vessels within the liver (probably MVD) , or because the dog had other liver diseases at the same time.

5. Presence of another liver disease.

We recommend repeating the scintigraphy.

For a positive scintigraphy: If another shunt is present, we place a second constrictor ring. If the first shunt is still open, we tie it off. If multiple acquired shunts are present, we recommend biopsying the liver to determine if it is MVD (which is treated with low protein diet, lactulose, and milk thistle) or another liver disease that might require a different treatment.

For a negative scintigraphy: We recommend repeating a liver biopsy to determine if the bile acids are high from MVD or from a different liver disease that might require other treatment.

Dr. Tobias

What is the prognosis for dogs diagnosed with multiple acquired PSS?

Multiple acquired shunts are diagnosed by ultrasound, CT, scintigraphy, or surgery. Dogs develop multiple acquired shunts for a variety of reasons, including severe liver inflammation or infection, liver cancer, biliary disease, heart disease, and other conditions that increase blood pressure within the liver. On rare occasions, dogs with PVH-MVD will also develop multiple acquired shunts, if they are born with very few, or no, small portal venules within their livers. Prognosis for multiple acquired shunts depends on whether the underlying cause can be corrected (for instance, infection or heart disease treated) and the type and severity of the liver’s reaction to that cause. If the liver has hardened from scar tissue (“cirrhosis’) or there are few portal vessels within the liver (severe PVH-MVD), the liver may never recover. A liver biopsy helps veterinarians determine the underlying cause and the prognosis and differentiate congenital and acquired causes.

Medical management of dogs with multiple acquired shunts includes the same supportive and nutritional care described for CPSS and hepatic encephalopathy, in addition to the use of medications that reduce the risk of gastrointestinal ulcers (e.g., omeprazole) or decrease fluid accumulation of abdominal fluid (diuretics such as furosemide and spironolactone).

What nutritional and medical management is recommended for dogs with congenital PSS?

Diet The most important treatment of dogs with congenital PSS is an appropriate diet. The liver is responsible for removing the toxic products of protein metabolism. When the liver is not functioning correctly, ammonia and other waste products accumulate; in addition, proteins broken down by bacteria in the colon can release toxins into the bloodstream. Therefore, liver diets tend to be moderately restricted in protein. Protein sources should be high quality and readily digestible, and they may contain higher concentrations of branched chain amino acids (e.g., vegetable and dairy sources of protein). Dogs with liver disease also need higher levels of zinc, vitamin E, vitamin K, and omega-3 fatty acids and reduced levels of manganese and copper compared with normal dogs. What brands of diet are recommended for dogs with liver disease?

Veterinary therapeutic liver diets such as Hill’s Prescription Diet l/d Canine Hepatic Health and Royal Canin Veterinary Diet Hepatic Formula provide quality proteins that are readily digestible in the small intestine, reducing ammonia and toxin production. Protein concentrations in these diets are higher than those in many of the kidney diets. This is important because animals with liver disease that receive too little protein will break down their own muscle tissue to make up for any deficiencies. These diets also have the appropriate balance of other nutrients critical for patients with liver disease, and they have been thoroughly tested to verify their quality. In fact, Hill’s l/d was developed under the supervision of one of our veterinarians at University of Tennessee. How much protein and fat does my dog need?

There is no one nutrient percentage that is good for all dogs with liver disease. Some dogs have severe liver dysfunction and can’t tolerate any extra protein; others need the extra protein. Some are fat, some are athletic, some are young, some are underweight. Based on research, however, we know that dogs with liver disease need at least 2.1 grams of crude protein per kg body weight each day. A good rule of thumb is to feed a diet that has a total of 40 to 50 grams of protein (including any yogurt or snacks!) for each 1000 Kcals. Dogs with liver disease do not need fat restricted, so they can receive normal or higher levels of fat in the diet.

How much protein is in veterinary therapeutic liver diets?

The following chart provides information about Science Diet l/d Hepatic Health and Royal Canin Hepatic veterinary therapeutic diets (chart to be added; currently they average 18% as a minimum content).

What about “over the counter” diets?

Most over-the-counter dog foods do not contain the proper balance and type of proteins, carbohydrates, fats, vitamins, and minerals for dogs with liver disease. Another concern is digestibility: while the pet food label can give us a rough idea of the contents, it provides no information about quality and digestibility of ingredients. Veterinary therapeutic diets have undergone rigorous testing and are therefore usually preferred for patients with liver disease. If owners are adverse to feeding the veterinary therapeutic diets, they can attempt to match the ingredients lists and nutrient content of the over-the-counter product to those of the veterinary diets; however, currently there are no over the counter diets appropriate for dogs with liver shunts. The best option for owners is to a consult with a veterinary nutritionist for advice on homemade diets or diet blends.

Why is it so hard to read pet food labels?

An excellent question! There seems to be no consistency among dog food companies in terms of the way they label their food. On the label, you will find the ingredients listed, in descending order, by weight. You may also see a guaranteed analysis, which shows the minimum (or maximum) of specific nutrients such as proteins, fats, carbohydrates, and minerals. These are not exact numbers because components change from batch to batch. For example, the label on Hill’s l/d Hepatic Health kibble lists a minimum of 14.5% crude protein, but it actually has more protein than that. Specifics about nutrients are usually not listed on pet food labels.

So how do I compare nutrients in diets?

Comparing nutrients themselves can be very confusing because there are several ways pet food companies report a diet’s nutritional contents: on an as fed basis, a dry matter basis, as percentage metabolizable energy, or as grams per 1000 Kcals. When veterinary nutritionists compare diets, they actually collect information from the company so they can determine the total amount of each nutrient per kg or 1000 Kcal of food. A pet owner would almost need a nutrition degree to do an accurate comparison; that’s why we leave it up to the experts! Information on preparing homemade diets.

Homemade diets formulated by veterinary nutritionists can be used for dogs that have congenital PSS or PVH-MVD. There is some risk to use of a homemade diet because changes in the diet content can make it unbalanced. This most often occurs when an owner decides to change the ingredients, but it can also occur if the quality of the dietary components change. For instance, diets that include chicken breast will have a different fat and calorie content than those made with the darker, thigh meat. Over several months, this could lead to nutritional imbalances. If you are interested in feeding a homemade diet, you will need to work closely with your veterinarian or a veterinary nutritionist to make a diet that is complete, balanced, and healthy for your pet. Pet owners can contact a board-certified veterinary nutritionist at www.acvn.org or consult with our nutritionists at the University of Tennessee (utvns@utk.eduor https://vetmed.tennessee.edu/vmc/SmallAnimalHospital/Nutrition/Pages/default.aspx)

Probiotics

Unfortunately, we don’t know whether dogs with shunts will respond to addition of probiotics, or “good bacteria”, to their diet, but it doesn’t hurt to try them. Probiotics have been shown to decrease inflammation and improve health for several conditions, including inflammatory bowel disease. The best source of probiotics is a packaged form such as VSL3 (1/10th of a sachet per 10 pound body weight per day) or Culturelle (1/2 an adult capsule or one child’s granule packet per 10 pounds body weight per day). Another option is to supplement the diet with yogurt with live, active cultures. Although yogurt doesn’t provide very many bacteria compared with prepackaged probiotics, it has been shown to reduce signs of hepatic encephalopathy in people, and it also provides soluble fiber and a high quality protein that is “liver friendly”.

Yogurt brand and amount

Look for a brand that has not been heat treated after addition of healthy bacteria; some brands will even have a “Live & Active Cultures” seal from the National Yogurt Association. Amounts are calculated based on the protein content of the yogurt and the total calories in the dog’s diet. For instance, 2.2 ounces of Activa vanilla yogurt can be added to each 1000 kcals of food, or 1 tsp of Chobani nonfat plain Greek yogurt for each 100 kcals. A rough dosage is 1-2 tsp of yogurt once or twice a day for a small Yorkie.

Lactulose

Lactulose syrup is a double sugar that is broken down by bacteria in the colon to two simple sugars. This reaction is beneficial in several ways. First, the reaction produces an acidic environment that reduces ammonia absorption and that may be unattractive to troublesome bacteria. Second, the resulting sugars cause an increase in fluid content in the feces, which makes them move out faster so there is less time for toxins to be produced or absorbed. Because of this second effect, lactulose must be dosed carefully: too much could result in diarrhea. In general, owners should give a dose that results in 2 to 3 soft-but-formed stools per day. For most Yorkshire terriers, that means 0.5 to 2 mls by mouth 2 to 3 times each day. The dose should be decreased if diarrhea or cow pie stools develop and increased for dogs with hard, dry feces. Dogs that vomit when given lactulose may do better with a powdered form.

What about treats?

Treats are okay if they are safe for pets and do not add additional protein. However, treats should not make up more that about 10% of a dog’s diet. For example, if you have dog that eats 200 calories per day, it shouldn’t have more than 20 calories per day from sources other than a liver diet. One treat that should never be given to dogs with liver disease is rawhide bones, which are chock full of non-digestible or poor quality proteins.

Is it okay to add fish oils?

Prescription liver diets already have high levels of EPA/DHA - the good fats in fish oil. However, if dog is not on a liver diet, our nutritionist recommends supplementing with fish oils at about 250-300mg of EPA/DHA per 10 pounds of body weight.

Other Supplements

Some veterinarians will prescribe supplements that reduce inflammation of the liver, such as denosyl (“SAM-E”) and silymarin (milk thistle). While these supplements can be purchased over the counter, their content and manufacturing are not regulated by the FDA. Therefore, use of veterinary products is recommended, since these have been appropriately tested for active ingredients. Denamarin (Nutramax Laboratories) is a common brand; the chewable form is preferred because it has greater absorption and causes less stomach upset. Use of these nutriceuticals in dogs with congenital PSS or PVH-MVD has not been studied, so no one knows whether they make any difference in these dogs. Owners should never give any supplements that could have negative effects on their pet’s liver, nor should they use any chemical products around their house that have risks of toxicity.

Antibiotics

Antibiotics are prescribed for animals with active infections (for instance, urinary tract infections) or those with neurologic signs. Certain antibiotics will kill off the bacteria in the colon that are causing ammonia production. Antibiotics are not used routinely, however, because of potential side effects.

Surgery for Liver Shunts

A new method may improve rate of success
By September Morn

Rita Gray of Bellingham, Wash., became concerned when her Yorkshire Terrier, Ellie, vomited twice in one day. Effie, 5, had vomited occasionally, but this time the material was a peculiar brown color, and she was lethargic.

A check of her urine at the veterinary dinic revealed a urinary tract infection, her second. The doctor suspected more might be going on and drew blood for analysis. The test results were alarming.

“Ellie’s bile acids were through the roof,” Gray said. She was referred to the Washington State University College of Veterinary Medicine, where an ultrasound examination showed Ellie had kidney stones. X-rays yielded an even more alarming discovery — a severely undersized liver.

Blood Supply

Ellie’s liver had apparently never received enough blood to grow. “It was so small the radiologist looking at the X-ray first thought they were looking at the liver of a newborn pup,” Gray said.

The cause of Ellie’s urinary tract infections and other health problems turned out to be a portosystemic shunt (PSS), an abnormal blood vessel that rerouted most of her blood around the liver instead of through it as required for proper development and good health.

Though relatively uncommon, PSS can occur in any breed but seems more prevalent in small dogs, especially Yorkshire Terriers and Cairn Terriers. It’s also seen fairly often in Miniature Schnauzers, Maltese, Cocker Spaniels, Dachs­hunds, Jack Russell Terriers, Shih Tzus, Lhasa Apsos and Poodles. Large breeds also can have PSS. Irish Wolihounds are the most likely to develop shunting and, less commonly, Australian Shepherds, Australian Cattle Dogs, Golden Retrievers, Labrador Retrievers and Samoyeds.

A portosystemic shunt will make a dog chronically ill. It can lead to death if left untreated, so a dog showing dinical signs of liver dysfunction should be checked for this disorder particularly if he’s one of the more commonly affected breeds.

Dietary management and oral antibiotics can help, but surgery is the only way to correct PSS. It’s the first line of treatment, said John Berg, DVM, Dip. ACVS, Chair of the Department of Clinical Sciences at Tufts University School of Veterinary Medicine. “Historically, only dogs with shunts outside the liver have been good candidates for surgery, but a new breakthrough involving a thrombogenic [clot-forming] metal coil may change that,” Dr. Berg said. “Intrahepatic shunts - those within the liver — have often been difficult to treat surgically, but theoretically, the coil can treat any dog.”

Improved Chances

The new surgical procedure may improve chances for successful repair of intrahepatic shunts. A catheter carrying a tiny compressed metal coil is placed into a leg vein then moved through that vein to the liver while the process is observed by fluoro­scope. ‘When the catheter reaches the shunt, the coil is inserted into the vein where it springs out to the walls of the vessel. Attached Dacron fibers then cause a clot to form, gradually blocking the shunt.

Karyn Briggs, DVM, at Washing­ton State performed surgery to close Ellie’s shunt. The Yorkie was placed on a special prescription diet to ease the workload on her tiny liver and oral antibiotics to heal her urinary tract infection. She recovered and quickly became healthier.

Blood normally flows from the intestines to the liver. This is called the portal circulatory system. Portal blood is rich in dissolved nutrients and full of bacteria and digestive waste. In the normal liver, toxins are removed, proteins are formed and sugar stored. The cleaned blood flows to the heart via a large vessel called the vena cava. The heart then pumps the filtered blood around the body through the systemic circula­tory system.

With portosystemic shunt, instead of flowing through the liver for filtering, abnormal vessels reroute — or shunt — the blood directly into the vena cava. Improper nutrient absorption causes low energy and poor growth. Improper removal of wastes allows toxins to accumulate in the blood, causing illness, abnormal behavior and impaired neurological function. Depending on the severity of the shunt, various degrees of damage to the liver will occur. If untreated, damage will be progres­sive and health will deteriorate, often resulting in serious illness and premature death.

Portosystemic shunts can be congenital — present at birth — as Ellie’s probably was or acquired later in life as the result of liver disease. Congenital shunts are fetal develop­mental defects that usually involve only one abnormal vessel. Acquired shunts often involve a number of vessels and are generally seen in older dogs with livers damaged by disease.

Shunts are classified according to location in relation to the liver. Extrahepatic shunts, those outside the liver, are the more common. They’re typically seen in small or toy breeds. About one third of large dogs with shunts have extrahepatic shunts.

Intrahepatic shunts are found more often in large and giant breeds. Most intrahepatic shunts result from the embryonic connection between the umbilical vein and the vena cava remaining open. This connection normally closes within three days after birth, but for unknown reasons it sometimes stays open, resulting in intrahepatic shunt.

Hepatic microvascular dysplasia is a form of intrahepatic shunt, where some of the vessels are very tiny, while others multiply in an attempt to improve blood supply and drainage. Hepatic microvascular dysplasia usually has milder clinical signs than other forms of PSS.

By hampering the liver’s ability to filter the blood, a shunt disrupts functions of the gastrointestinal and urinary tract, and central nervous system. Most dogs show signs before 6 months of age, but about one-quarter of them with PSS show no signs until they’re older and can no longer compensate for a low grade congenital shunt.

Dogs with acquired shunts show signs similar to those with congenital shunts. Clinical signs of PSS are often vague and may come and go but usually worsen after meals high in protein. Among the signs:

~ Gastrointestinal: Because the liver doesn’t properly process nutrients, a pup with PSS may grow more slowly than littermates and have poorer coat and less muscle mass. The dog may be weak, disinterested in food and prone to intermittent diarrhea or vomiting.

~ Urinary Tract: As the liver fails to detoxify ammonia and uric acid — the byproducts of protein digestion — the substances must be excreted in the urine. The abnormally high concentration of ammonia encour­ages formation of mineral salts, which can crystalize into rough­~ surfaced calculi, or stones. These calculi obstruct and irritate the kidneys, bladder or urethra, making urination painful and difficult, sometimes resulting in blood in the urine. Some dogs develop recurrent urinary tract infections, as Ellie did. Dogs with PSS tend to drink large amounts of water and urinate a lot.

~ Central nervous system: Digestion of protein increases intesti­nal production of neuro­toxins, which the brain absorbs from the unfil­tered blood. This can cause a diseased state of the brain called hepatic encephalopathy. Neuro­logical signs can be hyperactivity or lethargy, weakness, excessive salivation, poor balance, seizures, temporary blindness and sometimes coma.

Common behavioral signs are depression and loss of appetite, but some peculiar behaviors may also occur — head pressing and cir­cling. “Head pressing is when the animal walks into a corner or an object and just stands there pressing its head into the object,” said Mary Labato, DVM, Clinical Associate Professor at Tufts.

Circling isn’t like tail chasing or getting ready to lie down, Dr. Labato said. “It’s usually not as frantic as tail chasing. It’s more like constantly walking in wide, slow circles, usually in the same direction, and being disoriented instead of being able to walk in a straight line or in a specific direction?’

Congenital shunt may be suspected if a dog of a predisposed breed shows signs of liver dysfunction. The dog’s urine may be dilute or infected, and may contain spiky crystals. In many cases, prolonged recovery from anesthesia or sedation is the first indication, because the liver can’t break down and excrete the drugs so they continue circulating.

Blood tests for bile acid show high levels about two hours after a meal. Bile acids are produced in the liver and stored in the gallbladder until needed to help digest fats. They’re released into the intestines when needed, then reabsorbed through the liver and stored again in the gallbladder. Liver shunts cause bile acids to accumulate because the liver can’t reabsorb them.

Blood and urine tests indicate problems with the liver, but advanced diagnostic techniques are needed to conflim or rule out PSS. Among these are ultrasound, CT scan, Magnetic Resonance Imaging (MRI) and contrast X-ray. Abdominal ultrasound and MRI are non-invasive imaging techniques that can detect abnormal blood vessels, though not every shunt will show up. In Ellie’s case, ultra­sound detected kidney stones but missed the shunt.

Veterinarians may also use scintigraphy, a technique that records the distribution of a radioactive substance in the body. The substance is introduced into the colon, then scanned with a special camera. If a dog has a shunt, most of the chemical bypasses the liver and is carried to the heart. A computer measures and compares the amount of radioactive blood in the heart and liver. Contrast scintigraphy doesn’t show the location of a shunt but does indicate the degree of shunting, which helps the veterinarian decide on the most successful manage­ment options.

Contrast X-ray is the most accurate diagnostic tool but is usually used only if ultrasound is inconclusive. A marker dye is injected into a vein draining the intestine and X-rays are taken. When there is shunting, the dye goes to the abnormal vessel instead of the liver, and the X-ray shows where the problem is. This is an invasive procedure performed under anesthe­sia. It’s usually done in combination with corrective surgery so the dog needs to be anesthetized only once.

Special Diet

Medical management and special diet are usually recommended for dogs with shunts, whether or not surgery is performed. “Early detec­tion of PSS can make dietary and medical management more effective by helping control the toxic proper­ties the malfunctioning liver can’t deal with,” Dr. Labato said.

Prescribed diets for PSS limit the amount and quality of protein so less ammonia is produced. Lactulose, a stool softener, is used to reduce buildup of waste in the intestines. Oral antibiotics minimize urinary tract infections and reduce bacteria in the intestine that produce neuro­toxins. These management strategies lighten the liver’s workload and usually improve the dog’s physical well being and quality of life.

Dietary and medical management alone are not as effective as when combined with surgery. Surgery can range from $1,500 to $2,000, how­ever, and sometimes poses risks. Some owners elect to manage the disorder solely with diet and antibiotics.

Early detection of PSS is benefi­cial for another reason, Dr. Labato said. “Should the shunt be one that is [surgically] correctable, the sooner more normalized blood flow returns to the liver, the greater the likelihood the liver will be able to regenerate, function and grow.”

Though surgery isn’t indicated in every case of PSS, it usually provides the best chance for a dog to live a healthy life. Because it’s best done by an experienced surgeon, your regular veterinarian may refer you to a specialist.

Easiest to Correct

Extrahepatic shunts are the easiest to correct, said Dr. Berg. “Virtually every dog discovered to have an extrahepatic shunt is a good candidate for ligation surgery.” It involves partially or completely closing off the shunt. In the past, ligation surgery involved suturing the blood vessel closed, but that method was risky. Now surgeons close an extrahepatic shunt by placing a ring around it that gradually constricts the shunt and sends blood through the liver.

The ring is shaped like a tiny donut with a slit through one side so it can be slipped around the shunt. The ring is usually made of clay, which slowly swells as it absorbs fluid from the abdominal cavity. This narrows the “donut hole” around the blood vessel and eventu­ally closes it off. A new ring now available is made of polymer protein. It also closes the vessel slowly so the liver becomes gradually accustomed to increased blood flow. Correcting intrahepatic shunts is more difficult, Dr. Berg said. “It isn’t easy to treat surgically because it’s inside the liver, and we can’t see the vessel, unlike extrahepatic where you can look right at it.” About 20-50 percent of intrahepatic shunts aren’t repa­rable and must be managed with diet and antibiotics. Dogs with intrahepatic shunts are more likely to have complications after surgery, usually requiring more time in intensive care.

The first 48 hours after surgery are the most critical. A dog’s hospital stay is usually a minimum of three or four days. During that time, staff members monitor the dogs for portal hypertension, a pressure buildup within the liver and small intestines from increased blood flow. The condition is painful and potentially fatal. Signs are vomiting, diarrhea, abdominal pain and shock.

Once a shunt is corrected, the liver can start functioning normally. Digestion becomes more efficient and toxins in the blood decrease. The dog feels better and behavior changes accordingly. Ellie’s case is an example. The Yorkie now has more energy, drinks less water and vomits less frequently. “There’s a calm over her now,” Gray said. She calls Ellie her miracle dog.

September Morn, a dog trainer and free­lance writer in Bellingliam, Wash.,is the author of “Training Your Labrador Re­triever” (Barron’s).

D08CA-001: Genetics of Portosystemic Vascular Anomalies & Microvascular Dysplasia
in Small Breed Dogs, Sharon A. Center, DVM

3/3/2012
PROGRESS UPDATE: Portosystemic vascular anomalies (PSVAs) and microvascular dysplasia (MVD) are related genetic disorders where blood returning from the intestines bypasses the liver instead of being filtered through the liver. This disease is common in small terrier breeds where the prevalence ranges from 30 to 80 percent. To identify genetic mutations underlying PSVA and MVD, researchers from Cornell University, funded by Morris Animal Foundation, compared DNA from PSVA affected Cairn Terriers, Yorkshire Terriers, Tibetan Spaniels, and Norfolk Terriers, with their unaffected siblings. They found that PSVA/MVD syndrome is the result of more than one mutation. Using genetic mapping, the research team has tentatively identified several regions of interest which are common to several breeds, as well as a few breed-specific regions that are associated with PSVA/MVD. Since the last report, researchers have expanded their analysis to include a larger population of Cairn and Yorkshire Terriers afflicted with PSVA or MVD. Cairn Terriers are representative of breeds like Tibetan spaniels and Miniature Schnauzers with lower genetic trait prevalence (approximately 30 to 35%); Yorkshire Terriers are representative of breeds like Norfolk Terriers, Maltese, Havenese and Papillion with higher genetic trait prevalence (approximately 65 to 90%). Preliminary data from this expanded mapping has confirmed a common but expansive disease-risk region and has also identified several additional regions with potential candidate genes (genes with known functions that may play a role in the disease process). Once genetic mutations responsible for PSVA and MVD are identified, the investigators plan to develop genetic tests that can identify carrier animals. These tests could be used to make breeding decisions which could reduce and eventually eliminate the occurrence of these disorders. This study is providing a research associate and an assistant professor, both of whom are in the early stages of their scientific careers, with valuable training in veterinary molecular genetics and in the mapping of complex traits.

What is Hepatic Microvascular Dysplasia or Portal Atresia (HMD):

Overview of the condition
The liver performs an incredible number of functions to maintain health of animals, including filtering out toxins, storing sugar, and making proteins. Most of the blood that is carried to the liver for these processes arrives via the portal vein, which drains the intestines, stomach, pancreas, and spleen. Within the liver, the portal vein branches into smaller and smaller vessels so that the blood can percolate throughout the tissues to each liver cell. When these microscopic vessels are abnormal on liver biopsy, the condition is called "hepatic microvascular dysplasia (HMD or MVD)" or "portal atresia". When the microscopic vessels within the liver are underdeveloped or absent, the liver becomes small ("atrophied") and the animal can no longer process toxins or make proteins necessary for growth and normal function. Hepatic microvascular dysplasia (HMD) or portal atresia is a histologic diagnosis, meaning it only describes the biopsy findings. In fact, there are many conditions that can cause these findings, including congenital portosystemic shunts; however, when the diagnosis is made without evidence of a congenital shunt, then the dogs are often given the diagnosis of HMD as a specific disease.

Signs/Clinical presentation
Dogs with HMD can present with signs similar to dogs with congenital portosystemic shunts; however, many dogs have no clinical signs at all. Often affected dogs are 3 to 4 years old before they have clinical signs. Some affected dogs are smaller than normal, with poor muscle development. They may seem less intelligent or quieter because of the toxins that depress their brains. They may have a loss of appetite or occasional bouts of vomiting and diarrhea. Some dogs may have a greater risk of infections or develop bladders stones. Severely affected dogs may be wobbly or act drunk or blind and can even seizure. Rarely, dogs will develop fluid filled bellies from liver failure.

Risk Factors
Yorkshire terriers and Cairn terriers are most commonly affected, but the condition is also seen in many other small breeds, including Maltese, dachshund, miniature poodles, Shih tzu, Lhasa apso, cocker spaniel, and West Highland white terriers.

Diagnostic tests
In dome dogs, basic biochemical tests are normal. Severely affected dogs may have low blood protein, albumin, glucose, and urea nitrogen levels because their livers are not making enough of these chemicals. Some dogs have increased liver enzymes. Urine is evaluated for evidence of infection and crystals; rarely, dogs with HMD will develop ammonium biurate crystals in the urine that look like spiky balls or starfish.

Bile acids are measured after an overnight fast ("preprandial" or fasting) and then 2 hours after eating ("postprandial"). In dogs with HMD, one or both sets of bile acids are increased. Bile acids can increase with any liver disease, so high bile acids are not specific to congenital portosystemic shunts or HMD.

A definitive diagnosis of HMD is made by proving that the dogs do not have any shunts but that they do have changes on their liver biopsies. Dogs with HMD have normal portal blood flow on scintigraphies (nuclear scans of liver blood flow), portograms (x-ray studies of liver blood flow), and CT angiograms (Cat scans of liver blood flow), but they have abnormal portal blood vessels on liver biopsy. The liver biopsy is usually taken surgically through a belly incision or with a laparoscope so that enough liver tissue can be obtained to evaluate the blood vessels. Needle biopsy using ultrasound may not provide enough tissue to make the diagnosis.

Differential diagnoses
HMD must be differentiated from congenital portosystemic shunts; unfortunately some dogs can have both diseases, and this cannot be determined before surgery. If a dog undergoes surgical closure of a congenital portosystemic shunt and its bile acids remain high 3-6 months after surgery, it is quite possible it also had congenital HMD. Dogs with HMD are usually older than dogs with shunts when they are diagnosed (2 to 5 years instead of less than one year), and often their blood work changes are less severe than dogs with shunts. They may even have normal fasting bile acids, but usually their postprandial bile acids are increased. HMD must also be differentiated from other conditions that cause seizures (epilepsy, hydrocephalus, toxins, etc.) or liver disease (viral or bacterial infections, chronic active hepatitis).

Treatment Options
There is no surgical treatment for HMD. Dogs with the condition are managed medically, and treatment is based on the severity of the condition. In some dogs no treatment is needed. The mainstay of medical management is to reduce the amount of protein in the diet. Specific veterinary diets such as Hill's L/d have been formulated for dogs with liver disease. The protein is highly digestible (often milk based or soy) and is only mildly protein restricted. Diets for dogs with HMD should contain about 15-20% protein (roughly 2 g/kg per day of protein), 15-30% fat, and 30-50% highly digestible carbohydrates on a dry matter basis. They should also be high in zinc and Vitamin E and low in manganese. Most dogs with HMD do well on diet change alone.

Changing the type of bacteria that live in the intestines can also decrease toxin production and absorption. This can be accomplished by giving lactulose syrup or yogurt. Some veterinarians may prescribe antibiotics for a short time as well. Nutriceuticals- compounds that are not considered "drugs"- can also improve liver function. Milk thistle ("silymarin") can help improve liver function and regeneration. Because the government does not regulate over-the-counter compounds, purchase of specially formulated veterinary supplements is recommended. Two veterinary companies that sell milk thistle include Nutrimax ("Marin") and RxVitamins ("Hepatosupport"). Veterinarians may also prescribe Denosyl (SAM-e) to improve liver function.

When to seek referral
Specialized tests that are used to diagnose HMD and rule out portosystemic shunts are often not available in general veterinary practices. Your veterinarian may consider referral for scintigraphy, portography, ultrasonography, or surgical or laparoscopic liver biopsies to rule out other liver diseases. Additionally, dogs that do not improve with dietary management (reduced protein in the diet), particularly dogs with seizures or vomiting and diarrhea, may have other conditions that are actually causing the clinical signs. These veterinarians should be seen by and ACVIM Veterinary Internist or Neurologist for further evaluation.

Prevention and prognosis
Hepatic microvascular dysplasia or portal atresia is a hereditary condition. Dogs with abnormal bile acids should not be bred, and dogs that come from parents with abnormal bile acids should also not be bred. Prognosis is good for most dogs with HMD. Most dogs are clinically normal with medical management and many have normal life spans. Dogs with gastrointestinal signs or partial or focal seizures, however, may show no improvement, possible because they have other diseases besides HMD. Occasionally dogs with HMD can progress to liver failure, and a few dogs will die within 4-6 months of diagnosis because of the severity of their liver disease.

Milk Thistle dosage: Dried herb: 15-20mg/poun once a day; concentrated or alcohol extract: 2-5 mg/pound every 8-12 hours. See manufacturer recommendations for veterinary-formulated supplements.

What is Protein Losing Enteropathy:

Excessive loss of plasma and proteins into the gastrointestinal (GI) tract is called protein-losing enteropathy. It can result from any condition that damages the lining of the GI tract. Protein-losing enteropathies that are thought to have an inherited component include intestinal lymhangiectasia, immunoproliferative enteropathy , and protein-losing enteropathy and nephropathy in the soft-coated wheaten terrier. The latter condition is thought to be related to adverse food reactions, and there is also loss of protein from the kidney (see also familial renal disease).

How is protein-losing enteropathy and nephropathy inherited? The inheritance may be autosomal recessive.

What breeds are affected by protein-losing enteropathy and nephropathy? soft-coated wheaten terrier

What does protein-losing enteropathy and nephropathy mean to your dog & you? Your dog may fail to gain weight or may progressively lose weight. The loss of protein into the bowel causes loss of fluid from the circulation into the limbs, the abdomen, or the chest. Your dog's legs and/or abdomen may appear swollen and he/she may have trouble breathing. There may be a chronic persistent or intermittent diarrhea due to the loss of protein, fluid and fat into the bowel. Loss of protein from the kidney will cause increased urination and drinking in your dog.

How is protein-losing enteropathy and nephropathy diagnosed? If your dog has the signs described above, your veterinarian will likely suspect one of the diseases that result in loss of proteins into the gut. Laboratory tests and an intestinal biopsy are necessary to diagnose the specific cause.

How is protein-losing enteropathy and nephropathy treated? This condition can not be cured but it can generally be well-managed by you and your veterinarian. The major goal of therapy is to reduce the loss of proteins into the intestine, to restore normal protein levels in your dog. This is done through diet, and medication to reduce inflammation in the intestinal wall. An ideal diet for dogs with protein-losing enteropathy contains minimal fat, and an ample quantity of high-quality protein. There are commercial prescription diets available which fulfill these requirements, or your veterinarian can give you information to prepare a low-fat diet at home. In either case, you will need to supplement your dog's diet with fat-soluble vitamins, due to the poor absorption of fat that occurs with this condition. Corticosteroids may help to reduce inflammation, and thereby reduce loss of protein and associated diarrhea.

Breeding advice
Affected dogs should not be used for breeding. Given that the inheritance is thought to be autosomal recessive, parents (considered carriers) and siblings (suspect carriers) should not be used for breeding either.

FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources
Burrows, C.F., Batt, R.M., Sherding, R.G. 1995. Diseases of the small intestine. In S.J. Ettinger and E.C. Feldman (eds.) Textbook of Veterinary Internal
Medicine. p. 1224-1225. W.B. Saunders Co., Toronto.
Williams, D.A. 1998 Protein-losing enteropathy Proc. 16th ACVIM Forum pp 419-421
Copyright C 1998 Canine Inherited Disorders Database. All rights reserved. Revised:
This database is a joint initiative of the Sir James Dunn Animal Welfare Centre at the Atlantic Veterinary College, University of Prince Edward Island, and the Canadian Veterinary Medical Association.

What is MVD?

When the Liver Isn’t Getting Enough Blood

August 07, 2000
Written by: Celeste A. Clements, DVM, Diplomate ACVIM

Veterinarians and owners of small breed dogs are on the lookout for signs of a liver problem that has been recognized by pathologists for some 15 years, but only recently by veterinary internists.

Hepatoportal microvascular dysplasia, or MVD, is a congenital disorder of the liver’s blood supply. Dogs that inherit this problem may become quite ill: coma, seizures, and bizarre behavior are among the more extreme manifestations of the disease. The problem is especially prevalent in Cairn and Yorkshire terriers.

Dogs that have MVD don’t get an adequate supply of blood to the liver. A healthy liver detoxifies and purifies blood returning from the abdominal organs. Blood enters the liver through the portal vein, which branches throughout the liver lobes via seven major tributaries. If blood supply to the liver is abnormal or insufficient, the liver will not grow properly, and its function will be affected—and how bad the problem is really depends on the extent of the deformity. Blood that fails to enter the liver properly is diverted or "shunted" through alternate routes.

An elusive disease

MVD isn’t the only type of congenital liver abnormality resulting from improper blood supply. With a portosystemic vascular anomaly—or PSVA—the blood supply may be visibly abnormal because it bypasses all or a portion of the liver. The difference with MVD is that the abnormality is apparent only at the microscopic level—which is why veterinarians sometimes have a hard time tracking it.

The disease is so subtle that the veterinarian may not be able to detect it. If the dog does show signs of illness, they usually include increased thirst and urination, intolerance of food, or changes in behavior that may reflect the influence of dietary toxins and byproducts of metabolism on the brain. Hepatic encephalopathy, a condition that results from an excessive blood level of metabolic byproducts that are normally filtered out by the liver, is observed in the majority of patients with substantial blood shunting.

Additional signs include depression or confusion, incoordination, apparent blindness, and even seizures and coma. Dementia or bizarre behavior after eating is a common occurrence in puppies with "shunts;" however, more subtle signs may be evident in canine patients with MVD.

Investigating MVD

Bile acid profiles have become a popular noninvasive test for detecting circulatory and other functional disturbances of the liver. The level of bile acids in the fasting and fed, or postprandial state, assessed together offer a useful prediction of clinically significant liver disease.

Bile acids are a component of bile, produced by the liver, and stored in the gallbladder. When the gallbladder empties, in response to chemical or hormonal signals stimulated by eating, bile enters the intestinal tract to aid in digestion. Along with other metabolic byproducts, a significant amount of the bile salts are reabsorbed into the bloodstream at the termination of the small intestine, the ileum. Subsequently, they pass into the portal circulation, destined for the liver.

In dogs with healthy livers, the bile salts are extracted from the blood and recirculated. However, the level of bile acids will be high if the patient has impaired hepatoportal circulation, reduced liver mass, or bile retention.

A high level of bile salts doesn’t mean the dog has MVD, though. There is considerable overlap between different liver diseases, so additional diagnostics are needed to differentiate between them, to include sonographic imaging, nuclear scintigraphy or dye studies, and, frequently, liver biopsy.

When a dog has an abnormal circulation of blood to the liver, the presence of shunting can be assessed by noninvasive means, including nuclear scintigraphy. With this procedure, a radioisotope-labeled enema is administered. This radioisotope is taken up by circulation in the colon and the labeled blood is delivered to the liver in normal dogs and to the heart in dogs that have shunts. Computer technology allows for the comparison of labeled blood’s entry into the liver or the heart. Estimates of the shunt fraction are relatively reliable, but the technique rarely localizes the abnormal circulation. If the shunt fraction is less than or equal to 15 percent, then it’s unlikely that the portosystemic vascular anomaly is surgically correctable.

A dye study can provide a definitive diagnosis of a problem with circulation of blood to the liver. In the case of MVD, a dye study test will show uneven distribution of contrast within liver tissue, blunted branches of the portal vein, and persistence of contrast in the liver tissue. Such procedures are performed on an anesthetized patient, most commonly in connection with surgery to visualize or sample the liver. However, if an anomalous blood vessel is identified grossly, contrast studies, termed portography, are rarely performed.

Treatment options

Surgical correction of the shunting vessel, through banding or ligation, is successful in the majority of dog patients, if performed before two years of age. A more normal pattern of blood flow is achieved, with improved perfusion of liver tissue and improved liver function, but microscopic circulatory changes may persist in those patients, preventing establishment of a completely normal state.

Unlike dogs with PSVA, dogs with MVD cannot enjoy correction of the liver dysfunction. Treatment of dogs showing signs of disease focuses on feeding diets restricted in dietary protein, using oral antibiotics to curtail intestinal bacterial growth, and offering lactulose to reduce intestinal absorption of ammonia, one of the important contributions to hepatic encephalopathy. Effective control of signs should permit a good quality of life for most dogs. Some will still develop progressive liver dysfunction, though, with portal hypertension and subsequent accumulation of abdominal fluid.

No treatment is required for asymptomatic patients, but all dogs with MVD may be at higher risk for adverse reactions to medications processed by the liver. Discretion is wise when administering prescription or over-the-counter medications, and when planning for anesthesia. It is unclear whether MVD predisposes patients to other forms of liver disease, such as inflammatory conditions or infections.

Catching it early

Early identification of dogs with MVD is ideal. It’s important to prevent breeding and perpetuation of the disease and to distinguish the disorder from other diseases that might cause liver dysfunction in later life. Cairn terriers and Yorkshire terriers may be considered a high-risk population; MVD also has been documented in other small breeds, such as the miniature schnauzer, Lhasa apso, dachshund, Maltese, bichon frise, and poodle.

The problem should be suspected in pups or young small breed dogs that have repeatedly elevated serum bile acids but are otherwise well. Noninvasive scintigraphy makes sense for patients suspected of MVD or PSVA, although it may not be readily available in all locales. Further, the test cannot definitively verify or rule out microscopic abnormalities, only gross shunting. Only a liver biopsy of reasonable size and good quality can definitively diagnose MVD.

Liver biopsies are safely performed in the vast majority of patients, but the risks should be assessed for each patient and compared to the potential benefits. While a liver biopsy may be indicated for symptomatic patients with high bile acids, it is much more difficult to justify this procedure for dogs that have only abnormal test results. If spaying is planned for female dogs at risk, then a visual inspection of the liver and portal circulation and liver biopsy may be considered.

In some cases, MVD remains a tentative diagnosis, which seems reasonable provided no surgically treatable problem is overlooked. As one of many diseases that are hard to "pin down," MVD continues to be investigated by veterinary researchers.

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Hepatic Microvascular Dysplasia is a condition in which there is mixing of venous blood and arterial blood at the microscopic levels in the liver. If you search for information on this condition, it is also called hepatoportal microvascular dysplasia so you may find information using either name. This condition has been recognized in a number of small dog breeds but seems especially prevalent in Cairn terriers and Yorkshire terriers.

It is likely that most dogs with this condition have no readily apparent clinical signs associated with the microvascular dysplasia and are diagnosed when bile acid response testing is done to rule out liver disease for some reason. Unfortunately, some dogs with this condition do have clinical signs, which can include seizures or other central nervous system disorders, gastrointestinal problems or urinary tract disease associated with ammonium biurate cystals in the urinary tract, which form due to the liver problems.

Abnormal bile acid response testing usually provides the initial suspicion that this disease is present. High bile acid levels can occur with portosystemic shunts, as well. It is necessary to rule out that possibility when considering the possibility of hepatic microvascular dysplasia. Liver biopsy adds further evidence for the presence of this condition, in part by ruling out other liver diseases.

When dogs have microvascular dysplasia without clinical signs, their prognosis is very good. In many instances there is not a need for therapy. In dogs that are diagnosed because they have clinical signs, it is often possible to manage the signs through the use of dietary therapy and medications. The dietary therapy is aimed at reducing excess protein in the diet and the medications, including lactulose and antibiotics such as neomycin or metronidazole, which are used to lower ammonia levels in the digestive tract and thus in the body. The prognosis is variable for patients who have clinical signs from hepatoportal microvascular dysplasia. Some dogs do well with therapy and live normal, or nearly normal, life spans. Others have worsening of the clinical signs over time. I do not know of a method for predicting how well an individual patient will do.

There are a number of reduced protein diets that might be helpful, including Hills k/d (tm) and l/d (tm) diets, Purina's NF diet and others. Lactulose dosage is adjusted to individual patient's needs by using it to obtain a soft but formed stool. Neomycin is usually given at a dosage of 22mg/kg of body weight twice a day and metronidazole at 7.5mg/kg twice a day. This is a lower metronidazole dosage than is used for many other conditions. I have seen recommendations for the use of other antibiotics but these two are the most commonly mentioned ones.