Hepatic microvascular dysplasia
Question: DEAR DOC, MY 8 MONTH OLD TOY FOX TERRIER HAS BEEN DIAGNOSED WITH MICROVASCULAR DYSPLASIA. COULD YOU PLEASE GIVE ME ANY INFO YOU HAVE ON TX, ALTERED LIFE EXPECTANCY, ETC. THANKS, DONNA
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 crystals 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.
I hope that this is helpful.
Mike Richards, DVM 9/14/2001
Question: Hello Dr. Richards, My standard poodle, Angel 16 months appears active and healthy aside from some itching and rapid breathing-all she has had since we owned her at 3 months. We found out she has some form of Liver Disease when she was spayed. She had elevated Liver enzymes. She has been seen by University of Wisconsin(and currently still in contact with) but questions seem to arise. It was decided after liver biopsies and removal of her gallbladder (which was abnormal) to start her on ursidiol and colchicine,Vit E(water soluble). Colchicine as I understand is to minimize fibrosis thereby minimizing cirrhosis. The ursidiol I'm not sure I understand -I think it's a good bile acid. Her liver enzymes are all coming down, I don't have them currently. So the thought is the colchicine is working. However her Bile acid test which had been a high normal before starting ursidiol is now 300 pre and 125 post. (These are approximate numbers) The strange thing is they are the reverse-high pre and lower post. I am told this is a phenomena when the gallbladder is removed. The Dr. at Madison is trying to talk with some Clinical Pathologist at Cornell about her Bile acid test. Is the Bile acid test effected by ursidiol and or no gallbladder? You made reference in response 7/26/2000 Vet info digest to monitor use of ursidiol in a dog with no gallbladder. How do you monitor it? Her tests have us stumped because the Liver enzymes are lowest ever, while the Bile Acid is high. Bleeding time, NH3, Bilirubin remain normal. The albumin has dropped slightly to 2, so we have added 1/2 c. cottage cheese to her current LD diet. Any information would be greatly appreciated. My vet and the vets at the University are excellent, but I am finding that Liver disease in dogs is difficult to understand and manage. Meanwhile, Angel plays alot, loves to swim, eats heartily- and appears normal. I'm trying to keep it this way. Do you have any info on Sam-E and Milk weed extract? Why do dogs get Liver fibrosis?(I feel she was born with it)
Thank you, Kim
Ursodiol (Actigal Rx) is a naturally occurring bile acid, although I think that the pharmaceutical is a synthetically produced duplicate. I do not understand the exact mechanism for why it is beneficial when some other bile acids are considered to be harmful. However, it lowers cholesterol in the bile by decreased synthesis of it in the liver and absorption of it in the intestines. This helps keep the bile flowing. In addition to this effect, ursodiol seems to have a direct stimulatory effect on bile flow and to protect liver cells from the detrimental effects of bile salts which are also a component of bile. These are all beneficial effects that help both dogs and cats when they have chronic liver disease.
Ursodiol is a bile acid, so it does contribute to the measured levels of bile acids when a bile acid test is performed. For this reason, it is recommended that it be discontinued about 3 days prior to performing a bile acid response test or measuring serum bile acid levels. I do not know if anyone has developed a formula for compensating for ursodiol administration so that it could be continued despite testing but it is possible that this has been done or will be done in the future. I know of no problems with the use of ursodiol in patients without a gall bladder. Since bile flows continuously in this case (no storage facility for it), it makes sense that free flow would continue to be important but that is just my own logic, not something I have found in the literature.
SAM-e (Denosyl SD4 tm) is S-adenosylmethionine. This is also a naturally occurring compound that can be synthesized for pharmaceutical use. It is supposed to help stabilize liver cell membranes and when broken down also provides essential nutrients for repair and maintenance of the liver. It seems to be very safe. Several of the leading experts on liver disease in the US have been endorsing the use of this medication for liver disease and there are now a small number of studies that also support its use. The tablets should not be broken, so if the 20mg/kg dose doesn't match the tablet size it is best to round the dosage up to the next whole tablet dosage.
Milk thistle contains a compound, silymarin, that also seems to help protect liver cells and to stimulate cell healing. This compound is an anti-oxidant and that may be part of its effect but I am not sure what the mechanism for the whole effect is. Milk thistle can be overdosed, so it has to be used in a appropriate manner. There are many available formulations so giving exact dosing information is difficult. One approach is to use about 1/4th of the adult human dosage for a 50lb dog and to adjust that up or down some based on the size of the dog that the milk thistle is being given to. I have not seen any reports of incompatibility with other liver medications.
I think that I understand how bile acid measurement works enough to explain what might be happening. Bile acids are contained in the biliary system (the bile ducts and the gall bladder) most of the time. They are released into the intestine when the gall bladder is stimulated to contract by the presence of food or liquid in the intestine. They are absorbed from the intestinal tract into the blood stream where they can be measured and the liver recaptures them. So, bile acids are normally low when the gall bladder has not contracted and when the liver is functioning properly. After a meal, the bile acid levels increase temporarily due to the release of bile containing them from the gall bladder and biliary system. This means that in a "normal" bile acid response test, the levels of bile acids should be higher in the sample taken after feeding a small meal, rather than the sample taken after a twelve-hour fast prior to the test. Unfortunately, it is not possible to stop the dog from secreting liquid from the stomach into the small intestine or from stimulating gall bladder contractions for other reasons. So in about 25 to 35% of the bile acid response tests the pre-feeding sample is higher than the post-feeding sample. Usually both samples are pretty close in value in this case but not always.
In the case of a dog without a gall bladder, there is no place to store the bile and so a big release of bile and bile acids after feeding doesn't occur like it would in a dog with a gall bladder. I am actually not sure if there is a great deal of value in doing pre and post feeding blood tests in a dog without a gall bladder for this reason but that is probably something that should be determined by testing a number of dogs without gall bladders and if that work has been done I couldn't find it.
In any case, values in both the 125 and 300 range do indicate a decrease in liver function. However, as you are discovering, this doesn't always translate into serious clinical signs. Some dogs with really serious liver failure still feel great and act like normal dogs. By doing the things you are doing to slow the progression of this disease, hopefully Angel will be able to feel good for a long time.
Mike Richards, DVM 7/20/2001
Question: Dear Dr. Richards, I am a new subscriber, and I emailed you a week ago tomorrow about my 3 year old Shiba Inu. I am not sure if you are going to reply to my email address or put your answer on the website (or both). In any case, there is now more information on Sasi's condition which somewhat outdates my original questions. SaSi has now had some bloodwork done which indicates that she probably has some sort of liver disease. They took a blood sample after fasting, fed her some puppy food (because of the high protein content) and took a second blood sample. I don't have the numbers but I understand they were very high. Our vet said the results were likely indicative of liver disease, and if not, then inflammatory bowel disease. We are booked to have an ultrasound in a specialist clinic Feb.2. My questions remain along the same lines. What might the ultrasound tell us? And what happens next? There is also talk of doing a liver biopsy depending on the results of the ultrasound. What does the liver biopsy tell us? Thank you. Dianne
Ultrasound examination can sometimes detect portosystemic shunts, gall bladder stones, bile obstructions and tumors in the liver (and probably some other things that aren't coming to mind right now). Liver biopsy allows specific diagnosis of conditions that affect most of the liver, such as cholangiohepatitis and chronic active hepatitis. In addition, biopsy can allow a specific diagnosis of the type of tumor present if there is liver cancer (not too likely in your dog). Very high bile acid levels are most commonly associated with portosystemic shunts (where blood flow that should go through the liver bypasses it instead) but can occur with any liver condition in which liver function is significantly decreased.
The advantage of ultrasound exam is that it is less invasive than exploratory surgery and it allows guided biopsy, in which the operator can aim for a structure showing in the ultrasound picture. The disadvantages are additional cost is surgery is necessary later, anyway and smaller sample size when doing needle biopsies, which can make it hard for the pathologist to be sure of the problem, in some cases. We send some patients for ultrasound and do exploratory surgery on others, based on how we feel about the odds for successful anesthesia and surgery and how the client feels about surgery versus ultrasound (do they wish to avoid surgery or is cost more important?)
We see many instances of liver disease that are acute insults to the liver, such as bacterial infections, blood clots, trauma or toxin exposure. In these cases there is usually a good recovery, so even when liver related blood values seem really bad we try to keep on treating until we either have a definite diagnosis that discourages us or until it is obvious that the problem is not going to clear up and the patient is becoming debilitated.
Good luck with this.
Mike Richards, DVM 4/4/2001
Question: Dear Dr. Richards, SaSi's ultrasound showed a smaller than normal liver, (so small the internist said he would not be able to do a biopsy under ultrasound), and some evidence of scar tissue, but otherwise normal. (I believe he said that the liver was about the size of thumbnail. Is this possible?) He did a very thorough exam and checked out all the other organs and everything seemed normal. Since that time SaSi has stabilized on a low protein hypoallergenic diet, (the Canadian VMD MediCal), and has even gained two pounds. Our veterinarian is planning to retest SaSi's liver function in a month or so, and probably proceed with a liver biopsy if the enzymes are elevated again. I guess my problem is I am trying to avoid the trauma of both the liver enzyme test and the biopsy, hoping to get a diagnosis, or at least rule out some possibilities, from behavioral clues. She was put on the low protein diet about three days after she was fed the puppy food to get the blood test showing the elevated enzymes. For about six weeks after that her stools were very yellow and formed but very soft, and she continued to have an odor that I noticed when she was so sick at Christmas, kind of an acrid smell from her breath. Then overnight and for no apparent reason her stools became a more normal brown colour and held their shape when I picked them up. This lasted for about a week and I noticed that the disturbing odor was gone, and even briefly noticed her breath was back to a normal not unpleasant slightly sweet doggie breath. But now we seem to be deteriorating again and also for no apparent reason. Her stools are softening up, and are a mixture of brown and yellow. She does not show any sign of wanting to vomit but the last two or three days she has wanted to eat grass, usually a sign that her tummy is upset. During all this time I have been watching her very carefully and do not think she has been able to eat too much crap on our walks, although I cannot say for sure that she hasn't picked up some tidbits. So are these yellow stools and acrid breath indicative of liver disease? And does the fact that both are normal at times mean anything? If the liver is really small already, won't taking a biopsy compound the problem? If we were to assume that she had a liver shunt (at the cellular level) could we treat her with some of the drugs you have recommended in your emails to see what effect they have and perhaps gather more information that way leading to a diagnosis? There is no heartworm disease where we live but we plan to travel across the continent this summer and will be wanting to protect her from fleas and ticks and heartworm. Should we be concerned about any detrimental effect of these medications on a weak liver and are there alternatives? And for dogs with liver disease, is it important to minimize stress. (SaSi is aggressive with other dogs so I take her walking with other dogs and she gets very anxious at first. We also do agility training and I am not sure she is crazy about that either!) There are two other issues I am not sure are related. Sasi never seems to need to drink water. She likes to drink it outside in muddy puddles but from her bowl in the house almost never unless she has been running hard. Also she seems to do an abnormal amount of licking her chops and slurping and gulping. Our veterinarian has checked her mouth and throat and they seem normal. Are either of these behaviors potentially indicative of anything in particular? Thank you very much for your support. Regards, Dianne
I have to think that the description of the liver as being as big as a thumbnail would have to be an exaggeration. Livers can be pretty small in some cases, though.
There does seem to be a correlation between liver function and breath odor. Several of my clients have mentioned this and have even been able to use this symptom to evaluate how treatment was going to some degree. The buildup of toxins in the blood stream is probably responsible for this effect. A lot of dogs with liver disease lick their lips a lot and I have always assumed that this probably related to the taste or feeling of the toxins that build up, as well.
It is usually necessary for me to track liver enzymes or to do periodic bile acid response testing in order to feel really comfortable about when to make changes in liver therapy. There is some evidence that low protein diets are not optimal when the liver disease is compensated (when the patient is doing well), so choosing when to stick with a low protein diet is part of the reason that we try to monitor patients as time goes on. When liver values are not good, we also try to add lactulose and neomycin or metronidazole to the treatment effort, so it is important to know when things are going well and when they are not. Once we reach a point where we know that the liver function is going to remain depressed, we often opt to cut back on the lab work and monitor just when clinical signs seem to indicate a need.
Biopsy of the liver is often the only way to be really certain what is happening with the liver. It is most important to have a diagnosis when something treatable seems like it is a strong possibility. Your vet has to make that judgment based on the lab work, the physical exam findings and a subjective opinion about how SaSi feels, based on your opinion and your vet's experience with her in the office. It is hard to decide whether or not to pursue a biopsy in a patient whose liver is very small, because the odds of discovering something that will change that situation are not very good but it is the best test available.
If you are going to travel into heartworm endemic areas you should use heartworm prevention. It is important to remember that the monthly heartworm prevention medications are not time release. They do not protect for the month AFTER administration of the pills, they kill heartworms that have been acquired in the month BEFORE administration. It is really important to give 1 heartworm preventative pill at least a month after the last possible exposure to heartworms. We have used these medications in a number of dogs with liver disease, since we live in a heartworm endemic area and so far, we have not been able to detect problems with either ivermectin (Heartgard 30 Rx) or milbemycin (Interceptor or Sentinel Rx).
Some dogs with small livers do very well with medical management so I hope that is your experience with SaSi, as well.
Mike Richards, DVM 4/4/2001
Question: Dear Dr. Richards,
I have a beautiful little Min Pin who will be two years old on December 26th. She has always been a very fun and energetic dog to say the least. She is very well taken care of because she is hard of hearing in one ear. Because of that she is always walked on a lead.
On November 3rd Callie had her first episode of lethargic behavior. I had never seen this with her before. She was fine in the morning but by 5pm she was depressed with no appetite. By the next day though she was better. 5 days later we were going out of town and decided not to bring Callie since she seemed depressed again. We left her for the weekend at the vets. I really have great confidence in our vet. Callie boards there when we travel and they are very familiar with Callie's normal behavior. They ran blood work and everything looked normal except one of her liver enzymes were slightly elevated. By the time we got back two days later she was back to her happy self. But 5 days later, she had a bad episode of throwing up, not eating, etc. On Saturday morning we brought her back to the vet and she saw the Jr vet. With Callie's history of allergies he said it sounded like that could be the culprit. She got a cortisone shot and we changed her diet to z/d. She was fine all of Saturday, eating etc. but by Monday she was bad again so we left her at the vets for more blood work. Her liver enzymes were off the chart! They put her on an IV with fluids and vitamins. An x-ray showed no signs of any obstructions. Her white blood cell cut was slightly elevated but her billy rubens were normal. By Wednesday she was almost back. Eating l/d and taking an antibiotic. The vet gave her fluids under her skin and sent us home. Callie got better every day--no throwing up and almost back to her crazy hyper self. By Saturday she was back!! Saturday night we were at a friends house and there were a lot of children who had dropped a French fry on the ground and before we could grab her, she had scarfed it down. She was also sniffing around the carpet and probably got a few other tid bits. She was sick by 4am Sunday morning--throwing up, etc. Sunday night we went to the vet and they gave her fluids and send us home. By 10pm she would eat a little. Yesterday they did another set of blood tests which showed one of her enzymes down to 1534 but the other one is still off the charts. Her white blood cells and her billy rubens were normal. They gave her fluids and sent us back home. Last night was her worst night. By then she had not eaten anything but a tablespoon of l/d since Saturday night. She was lethargic, in some pain, couldn't even handle the smell of food. All she wanted was to sleep and be held. But like before by 1am she popped up and wanted to go out, At 2am she was hungry--scratching at her dish and sniffing the floor for food. I gave her food and she kept it down. The morning she is better again. She is back at our vets now for a bile acid test and a copper toxicity test. The vet has also put a call into NC State's Vet Hospital. They said that it sounded more routine but they could take her on December 13th. If our vet felt it was an emergency they could take her sooner. There is a good person in Chesapeake, VA that could do the Ultra sound/biopsy on the liver sooner but can not offer all the services the the hospital can. Callie was weighing 6.4-6.8 pounds. She now weighs 5.8 pounds. My questions are these:
1. What could this possibly be in a healthy, two year old dog? It is so hard to understand why she is so suddenly up and down. 2. Should I decide my self this is an e,emergency and try to get her to Raleigh sooner or should I take her to Chesapeake for the ultra sound and go from there? 3. Could there be any connection between her partial deafness and her liver problems? 4. Why would the technition at NC State say that her condition sounds routine? If you need Callie's specific numbers from her blood work I can get them this afternoon. We love this little dog so much. She is loved by everyone who meets her partly because of how friendly and small she is. I want to do the best I can for her. I really appreciate your help.
1) There are several possible problems.
A portosystemic shunt could be present. In this condition, blood bypasses the liver because a connection between the venous blood supply and the arterial blood supply develops (or is present congenitally). This decreases the functional capacity of the liver significantly. in most cases, signs of this disorder show up before dogs are a year of age, but sometimes clinical signs wait until later in life to show up. Dogs with this condition tend to have problems after eating. Surgical correction of the shunt is usually considered to be the best option for dealing with this problem, when it is present.
Microvascular dysplasia is another problem in which the blood supply is not properly routed, but in this case the shunting occurs at the cellular level. Dogs with microvascular dysplasia may be normal in appearance most of the time but have intermittent problems when the liver just can't react to an increased demand on it. Other times, the disorder is evident almost all the time. This problem is usually dealt with through dietary changes (lowering protein levels) and the use of lactulose and/or metronidazole or neomycin antibiotics. All of these treatments aim to lower the serum ammonia levels, which cause the clinical signs associated with the condition. Microvascular dysplasia can be subtle enough that clinical signs are not noticed until a dog is a young adult or may even be mild enough that they are never seen.
Chronic immune mediated hepatitis or chronic active hepatitis (probably different names for the same condition) may also be present. This disorder is most common in middle aged female dogs but can show up earlier than middle age. The only really good way to diagnose this condition is a liver biopsy and it is a good idea to check for copper accumulation in the biopsy sample, because copper may not be excreted properly when this disorder is present and can accumulate in the liver. This happens most commonly in dobermans. I do not know exactly how much correlation there is in problems between dobermans and miniature pinschers, if any, though.
Sometimes inflammatory bowel disease, pancreatitis, intestinal obstruction, gallstones, liver infection, blood clots or other problems lead to bile duct blockage or a sudden onset of hepatitis and these problems can occur in any age dog.
2) If you are worried about Callie and don't mind the possibility of having to pay for the ultrasound examination and/or liver biopsy twice, there is no reason not to go ahead and have the ultrasound done prior to the time it is possible to go to NC State. If it is suggestive of one of the above problems you may still need to go to the college for scintigraphy or other testing that is usually done mostly at universities.
3) I know of no connection between deafness and liver problems, except that liver disease can cause central nervous system disorders if they get severe. I haven't really heard of deafness from this problem, though.
4) The liver problems fall into two categories -- chronic conditions for which a couple of weeks of waiting isn't going to matter and acute conditions that will probably get better, with your usual vet's help, before you even get to the university. So that is probably why the tech feels that a routine visit is reasonable in this circumstance. If you feel otherwise, NC State seems reasonable about seeing patients on an emergency basis, based on our experiences with the school.
Good luck with this.
Mike Richards, DVM 12/4/2000
Question: Hi Dr Mike, This is my second letter to you about my Siberian Husky, Cody. I'm in total confusion now more than ever. She started out with ferocious water drinking and excessive urination particularly thru the night. My vet checked her urine for infection and he found a slight evidence of infection and so was put on anti biotics . She also was put on an acidifier because her ph level was off. It seemed to work for a while but eventually the problem returned. He checked for diabedes and found none. So he tested for Cushing's and he said that's what she's got. I did the 7dys Lysodren 2x/dy. On the 8th day she wilted and so my vet said to stop. She had a couple days of prednisone. She did not resume any Lysodren til 6 days later. By then she was frantic for water again and she got another Lysodren. That week she got a total of 4 Lysodren and the same the week after. The week after that only 2 and 1/2 pills; then she stopped eating. She also was not drinking or urinating excessively, either. She was retested and was not overdosed. ( she was retested a total of 3 additional times after the original diagnosis- she never was overdosed) She lost 3 lb in 10 dys. This dog is thin and does not have the pot belly they mention. And she has never been a big eater. I gave her a prednisone if she didn't eat anything by noon and usually within a couple hours she would eat something. My vet said it was time for a specialist as he didn't know what to suggest. ( she also has been on antibiotics most of the time) The specialist did an ultasound and said everthing looked normal but the liver looked raggedy. He did a liver function- the two hour test- before and after food. He came back and said she has liver failure and does not have Cushing's disease. He said with her numbers from all the retests, she would be a perfectly balanced Cushing patient and should have a good appetite . I was totally blown away and can't understand how that could be. Could she have both? He has put her on Actigal once a day but she's not eating. She's not drinking too much either, but she does have to go out a couple time at night and is prone to accidents . Today an hour after taking her pill and eating two little bites , she threw everything up. so, I gave her another actigal and did not try to feed her, not that she would eat anyway. It seems like she wants to eat but just can't bring herself to put it in her mouth. I thought she might be naseous and my reg vet said to try tagamet. What do you make of this? Are there any appitite stimulants for dogs that work until the medication has a chance to work? I'd appreciate any insight you have as my own vet is also at a loss as to what to do and he even questions the second diagnosis. Thanks Cody's mom, Carlye
I think that in most instances in which there is a disagreement between an internal medicine specialist and a general practitioner about interpretation of lab results for disorders such as hyperadrenocorticism (Cushing's disease), the specialist is most likely to be correct because they deal with these cases much more commonly than most general practitioners. This has happened in our practice and so far the specialists were right in all but two cases (based on my memory of events) --- over the course of twenty years.
Many dogs with liver disease have increased drinking and urinating, sometimes to the degree that it is very suggestive of Cushing's disease. The increased drinking and urinating are more likely to follow an on again, off again course with liver disease. Weight loss is a very consistent sign of chronic liver disease, so that also is highly suggestive.
Appetite stimulation does not work as well for dogs as it does for cats. Prednisone is the most reliable appetite stimulant in dogs. Some forms of liver disease do respond to prednisone but other types of liver disease can get worse, so it is best to try to identify the exact cause of the liver disease, if possible, prior to using prednisone on a regular basis.
It can take some patience to get through the initial treatment for liver disease, since ursodiol (Actigal Rx) can take time to show beneficial effects. Many times there is a good long term outcome, though.
Question: I have a soon to be 13 year old Pattern White Australian Shepherd female, spayed. This past spring at her annual exam the doc noticed her liver enzymes specifically her ALKP, AST and ALT were slightly elevated, they were last year but now they were more so. Three months later we had her rechecked and found them to have risen even more so,,,,,,,,,ALKP 364, Alt 364 and Ast 60. He referred us to an internist who did an ultrasound and found a slightly mottled liver, enlarged adrenals and some gall bladder sluggishness. He also did a ACTH stim test that proved to be borderline high. He recommended we go through with the Low dex test, where she ended up being 95. A high dose was not indicated at that time. Last week my vet and the internist conference called and decided she was early stages of cushings, and that we should not start any meds at this time, but would redo any blood work in a month and see what her status is. In the meantime, I am wondering about vitamins, diet, supplements, water?? anything I can do to take care of her in the best way I know how. She is currently on Hills Science Diet and has been for three years. I bought some Milk Thistle to add one capsule to her food because I heard it will help with her liver. What is everyone else doing. If this is too cumbersome for the list you can privately email me if you chose, but I would love information on proper diet, and vitamins/supplements, and also if it could possibly be something else we are overlooking. Thanks so much in advance. Lisa
The typical dietary recommendations for liver disease are to use a low protein diet that has very good quality protein ingredients so that the liver doesn't have to do much work to convert the protein into forms the body can use. There are commercially available diets that help with this, including Hill's l/d (tm) and k/d (tm), Purina's NF diet and others.
Vitamin supplementation with B vitamins is often recommended for patients with liver disease, since these are important to liver function and because Vitamin B12 storage partly occurs in the liver. Vitamin K supplementation may be necessary at some time as liver disease progresses, as it may not be stored properly and blood clotting problems may develop. Vitamin C is sometimes recommended for its anti-oxidant properties and Vitamin E is sometimes recommended due to its anti-inflammatory effects.
SAMe (Denosyl SD4 tm) is commonly recommended for liver disease by some of the leading authorities on liver disease in veterinary medicine. The recommended dosage is 20mg/kg per day.
Ursodiol (Actigal Rx) is recommended to help with bile flow and protect the liver from the toxic effects of some bile acids. We use this medication frequently and I believe that it is helpful.
Hope this helps some.
Mike Richards, DVM 8/13/2000
Question: Dear Dr. Richards, My 12-yr-old neutered male Min. Schnauzer, Ruckus, had been "not himself" earlier this year (Feb-March). Urine and blood tests all came back normal. However, he then had a bout of pancreatitis and a second episode in late March that included severe abdominal pain, listlessness, and yes, elevated pancreatic enzymes. We did a sonogram on March 31st which showed gallstones and possible inflammation of the pancreas. Surgery on April 3rd removed his gallbladder, cut a 1 1/2" incision in his intestines to "clean out" the bile duct, and tissue samples were taken from the liver and spleen -- both of which appeared normal, visually. Subsequent lab biopsies of those tissues and the gallbladder and stones showed no abnormalities other than the gallbladder had stones and sludge, and there was a lot of infection within it. Ruckus recovered slowly, but that seemed 'normal' for such extensive surgery and for his age. About two or three weeks post-surgery, he had blood work done, and the ALT was 1354 and alkaline phosphate was 1057. This lab says the normal ranges are 5-60 for ALT and 10-150 for alk phosp. Since he had just come off of antibiotics following the surgery and the blood work did not show evidence of infection, we did not put him on antibiotics. He began acupuncture treatments (my primary vet also practices/advises on alternative medicine) on a weekly basis, a strong seeping of senna tea once/week for six weeks, and milk thistle -- approximately 15 mg of silymarin, three times/day. Ruckus appeared to be healthy -- good appetite, ormal feces and urine, etc. -- but his "sparkle" didn't seem to be back. On June 30, his ALT was 807 and alk phosp was 388 -- still not normal, but moving in the right direction. We have continued the acupuncture and milk thistle, and approximately two weeks ago, I switched him over to Ecliptex, 1/4 tab twice daily while still giving him 5-8 mg of the silymarin drops every day. We also put him on 14 days of Flagyl and Baytril, "just in case" there was an infection going on that wasn't giving indications in his blood work. About that same time, his sparkle seemed to be returning, and he is currently peppy, alert, and playful. (Earlier in July, we also did the blood test to rule out Cushing's, which he does not have.) On July 20, we did another blood workup -- expecting everything to be close to normal by now, especially given his improving behavior and "sparkle". Alarmingly, everything has worsened. The ALT is now 910 and alk phosp is 508. Admittedly, this lab says that the levels can be "three times or so the normal range" and still be considered OK, but these recent findings are now outside even that parameter and definitely moving in the wrong direction. My vet said the "only thing" he can suggest at this time is to do a needle biopsy during a sonogram. I don't want to do yet another invasive procedure, requiring sedation, if it can't tell me anything specific that can be treated. In other words, my sense is that cancer is about the only thing such a biopsy would show us, and given that liver cancer is fatal, there would be nothing to do about that so why put Ruckus through the procedure? Ruckus also has mild symptoms of sick sinus syndrome, and I am very reluctant to have him sedated needlessly. Is there anything else we should/could do? Are we missing something that should be looked at here? I've read some of the chain of e-mails on your site, and it looks as if there might be other things to consider. Any insight or recommendation you can give at this time would be very much appreciated. Thank you, Liz
I think that I'd consider the use of ursodiol (Actigal Rx) in this circumstance. This medication protects against toxic forms of bile acids and aids in bile flow. I do not know of a specific contraindication to the use of this medication in cases of surgical relocation of the bile ducts or removal of the gall bladder but it would be a good idea to monitor its use very carefully at first in this circumstance.
I would not automatically assume that cancer is present. I'd be more concerned about residual obstruction to bile flow, either from the original causes of the gallstones or from post-surgical complications.
If you want to do a non-invasive procedure to assess how the liver is functioning, a bile acid response test is simple and only involves drawing a couple of blood samples. If the function is good, I think it would ease your fears some. If it isn't so good, that would be stronger incentive to try the ursodiol or to consider a liver biopsy to try to get more specific information in case there are other options it might reveal.
Schnauzers are prone to hyperlipidemia, which can make pancreatitis more likely and possibly could be a contributing factor in the formation of cholesterol stones in the bile. If the blood work already done included cholesterol and triglyceride levels it might be worth rechecking to see if this is a problem, too. If so, controlling this might also help with the long term prognosis.
You and your vet have done well to get Ruckus to the point that you are at now. I am hopeful that your success in dealing with this situation will continue. The fact that he feels good is a very good sign and should be given strong weight in your evaluation of the need for further testing and lab procedures. There is often a lag time between when a dog or cat feels better and when the lab values reflect that improvement.
Mike Richards, DVM 7/26/2000
Question: Dr. Richards, I raise labs. My yellow lab was scheduled to be spayed last fall after having had four litters of puppies. After a routine blood test it was found that her Alt and liver enzymes were way up. We had biop done and ulta sound. Diagnoised with liver disease and we had her spayed. She is on medication and l/d diet and is doing wonderfully. We have a two year old pup out of her and another almost 1 year old. I'd like to bred both as the pedigree is extremely good. I have had prelim's done on the two year old's hips (excellent) and eye are due to be done. As precaution I had blood work run re liver problems. ALT came back at 110 additional blood work not back as of today. My vet (very) young, just out of vet school immediately said she's got liver disease. I called the specialist who did the bio and ultrasound on the dogs mother he says 110 ALT is not cause for alarm unless the rest of the tests come back bad. He suggested re-testing in a month and suggested using a different lab. I'm not into passing bad genes and would not hesitate to spay this dog or the pup if she tests badly however I'm concerned that this may be hereditery.
I will forward the results once I have them regarding the additional liver tests. Gayle-
Answer: I don't think that you should worry much about 1 blood test with an ALT value of 110. Different labs have different normal values for ALT, but our lab uses 118 as the high normal value, which would actually make this a normal value, for our particular laboratory. However, I do think that with the history of the mother and a lab value in the high end of normal that it does make sense to recheck the liver value in a month or so and perhaps even to monitor it over time. If an elevation in ALT does occur, it would be a good idea to pursue additional testing, such as bile acid response testing and liver biopsy before making a decision on breeding or not breeding, if this puppy has attributes that would improve the breed in general.
I am not aware of a liver disease that is known to be familial in Labradors but the reaction to Rimadyl (Rx) in which liver disease is induced by the medication, while rare, affects Labs more than other breeds based on the initial data. There are some instances of copper accumulation in the liver in Labs and they may be more prone to chronic active hepatitis than the average breed --- but none of these disorders has been proven to be genetic in origin, as far as I know.
If you do end up doing further testing and if the lab results do appear to be similar to her mother's it would be good to keep the specialist you have been conferring with informed, as that is the only way that genetic links can be recognized and identified.
Q: Dear Dr. Michael Richards; I have had a very confusing recent event regarding my 13 yr. old female dog come up and I will include the blood analysis for your evaluation also. First; my dog, Kahlua, is 13 yr. old, a little stiff due to old injury and arthritis. She eats very well, never vomits, no diarrea, norm stools. She plays in the evenings with us,and takes short walks during the day in her field. I placed her on Rimadyl a few months ago to help with her discomfort due to the arthritis. I took her to my vet to see if we should continue with the Rimadyl, and to have her checked. He also did blood work as he said she has not had any in a while. I also had them repeated on another visit. I will give you both results. May 18th test results; ALB = 4.29g/dl , ALKP = 867 U/L , ALT = 1095 U/L, (A DILUTION OF 1:1), CHOL = 520 mg/dl, GLU =126.7 mg/dl, Ca =12.24 mg/dl, K = 5.73, TBIL = .83 mg/dl. Bile acids; 18.l umol/L and bile acids post =31.2. Lipemia 2+.
May 29th test results; AlKP =1780 U/L, ALT =391 U/L, AST = 33 U/L, CHOL =575MG/DL, CALCIUM =11.7MG/DL, AMYLASE =1337 U/L, GGTP = 32, Platelet Count = 482, Tot. Protein = 7.4G/DL, Tbil = .1, K = 5.5 MEQ/L. I also had an ultrasound done and it was inconclusive as to what this might be. They did not several lesions, and suggested a biopsy. My question to the vet was to my concern about the Rimadyl and it's involvement-she stated that it only affects acutely in the first two weeks of treatment. I also have stopped the Rimadyl after the May 18th test. After the May 29th test- I have put her on Milk thistle 70G, Low Protein,Low Salt dry food, give Etogesic 300 mg 1 x day, give promethazine 1 x day, and also give her rec dosage of Hip Health-Glucosomine 1000mg+vit c 100mg. What do I do next? I am thinking of repeating the test with a question of bile duct blockage-she licks alot but had her anal glands removed years ago, and would also like to know if it sounds like I'm on the right track as far as meds and food go also. Again, she is not showing any symptoms of being ill at all. How can all this be happening and she is fine?? Thanks so much, Karen
The reactions to carprofen (Rimadyl Rx) that have been confirmed do seem to show up most frequently in the first few days to weeks of treatment. Despite that, I'd still be suspicious if a pet of mine had high liver enzyme levels and then I discontinued Rimadyl and the liver values improved. Since this is what happened to Kahlua, your suspicions seem reasonable to me --- just not certain.
We have seen several patients with sudden onset of illness in which the liver enzymes were elevated but later returned to normal (within a few weeks), or got close to normal, without us ever being able to figure out what happened. Most of these dogs have gone on to do fine despite the lack of a diagnosis. Since things are improving and since Kahlua feels OK, I don't see a problem with rechecking the liver values in a few days to a week or so and then basing the next diagnostic and treatment decisions on whether the enzyme levels continue to improve.
The calcium level on the first test was high enough to be worrisome. Hypercalcemia can indicate that neoplastic (malignant) cancer is present. Since it came down in the subsequent test this is less worrisome. It might still be worth carefully examining her lymph nodes for enlargement and rechecking the calcium level along with the liver enzymes.
With alkaline phosphatase levels in the 600 to 1000 range in an older dog, I always worry about the possibility of Cushing's disease (hyperadrenocorticism). This disorder sometimes causes elevations in cholesterol levels, too. Usually there is increased drinking and urinating associated with this problem but not always.
Your impression of how Kahlua feels is pretty important. In general, it is OK to be a little more cautious and take some time re-evaluating lab work when a patient is eating well and feels well. Our experience has been that a lot of the time these dogs are "telling" you the truth --- they are OK.
Mike Richards, DVM 6/1/99
Q: Dear Mike, having a sick dog has led me to search the net for answers and coming across your site has been great since it occupied my mind and gave me things to read that were related to my situation. After refusing to eat or drink from one day to the next and vomiting what I tried to coax her into, she was tested for possible obstructions as was extensive blood work done and a stool sample taken. There was no obstruction, the blood was normal, only slightly elevated pancreas numbers but they found a lot of coccidia in her stool. She was given Alban for the coccidia along with antibiotics. She continued to eat very little and threw up most of what she ate. Back to the vet for more blood work, now her liver numbers are all very high and the vet recommends, after doing an ultrasound where he sees no masses but a enlarged gallbladder, to do exploratory surgery. He opens her up but finds no obvious tumors, all her organs look good to the eye, just a very enlarged spleen. He takes biopsies of both liver and spleen. This dog has been in good shape, we walk daily and jog at times as well. She didn't show any signs of problems until she just stopped eating very suddenly. At the moment I have her at a university hospital because after taking her home on the second day following surgery she didn't do well, still refused to eat and just drank a lot of water and generally laid around. At the hospital they put her back on IV, gave her anti nausea pills so she now eats and at this point looks great again, except the urinates frequently and drinks lots of water which I am told is a sign of liver disease. We are desperately waiting for the results from the pathology report that my vet sent by REGULAR MAIL OUT OF STATE!! I was appalled by the way my vet treated the matter without any sense of urgency or compassion for the pet owner and wonder if this is general procedure. Her being ill started January 8, she was operated on Jan 20 and as of today Jan 25 the biopsy samples have not even arrived at the pathologist. I would be interests in your thoughts on the case and what other information I can give you besides of course the pathology report which I will e-mail after discussing it with the vet. Lydia
I am glad that you have taken your dog to a university veterinary hospital. That is usually a good way to get opinions from experts in several fields of study pretty quickly and complicated cases sometimes require that sort of collaboration. It is reasonable to suspect liver disease when a dog stops eating suddenly and even though it was an aggressive approach, exploratory surgery is a good option in these cases because it allows resolution of the worry over intestinal obstruction and gives the opportunity to take biopsies.
In patients in which I am worried about the progression of a disease or the time factors involved in getting lab samples I will usually send them by Federal Express or sometimes express mail through the post office in order to insure that they get to the lab quickly. Sending packages by Federal Express does cost a lot more and I do try to make a judgment call on the need to get the biopsy report quickly. I usually use a lab that is within the next day delivery area for U.S. mail and it takes at least a day or so for tissue to fix in formalin for examination so most of the time we aren't faced with worrying about a long delay. In retrospect, since your dog did experience progression of the clinical signs it probably would have been better to use a faster delivery service but that is still a judgment call.
We have experienced delays in mail and have had two lab samples simply disappear. After the first one we learned to keep a small section of most tissue samples we submit for biopsy (sometimes this isn't possible) just in case something goes wrong. It is worth asking your vet to do this in the future, just in case he or she hasn't had the bad experience we have had. We learned it the hard way.
I am assuming that there is lab work that supports the diagnosis of liver disease and am hopeful that means that the liver biopsy will turn out to be useful. It is possible to take a biopsy sample from an unaffected part of the liver even when disease is widespread but the veterinary school may be able to do an ultrasound guided needle biopsy if that problem occurs.
I will be glad to try to help you understand any diagnosis that is delivered via the biopsy sample. Hopefully you will get an answer soon on that.
Mike Richards, DVM
Q: Dear Mike, thanks for the super fast reply. I have in the meantime forgiven my vet for delaying the prognosis since he seemed to be sorry at least, plus I feel I need to continue to work with him since he does know the case. I had him send me the report from the pathologist and here is his diagnosis: Liver: Severe, diffuse lymphoplamacytic and histiocytic portal hepatitis and hemosiderosis with associated, moderate, hepatocellular fatty change. Spleen: Red pulp hemosiderosis.
I was up at the university hospital today and my dog looked like her old self, I took her for a walk and she was peppy and ready to take on a German shepherd that we met. The jaundice in her eyes is gone and the university doctor seems very pleased. She will now however also read this report and I will hear from her tomorrow. I would appreciate your input and thoughts and particularly your prognosis. Lydia
It is sometimes hard to interpret the pathology reports from pathologists without their guidance. However, my interpretation of the report below is that a drug reaction would have to be considered if your terrier is on any drug with the potential to cause hepatitis -- these would include Filaribits Plus (Rx), phenobarbital, Rimadyl (Rx), enalapril and related heart medications, phenylbutazone and other medications.
In addition it may be a good idea to consider the possibility of copper toxicity as this has been seen in a number of terrier breeds, including Norwich terriers, wire-haired fox terriers, Bedlington terriers, Airedale terriers, bull terriers, West Highland white terriers and Kerry Blue terriers. While Tibetan terriers aren't on that list it seems reasonable to assume that they could also be affected and that it just hasn't been documented. Checking hepatic copper levels may give a clue if the pathologist thinks it is reasonable to suspect this.
There are probably viral and bacterial illnesses that could produce the changes noted in the biopsy, too.
I usually call the pathologist when I get a report like this, since the description of the changes seen in the liver aren't specific to a particular disease. Asking the pathologist what the possibilities are and what the next best diagnostic step can be helpful.
I also think it is really important to evaluate the dog when dealing with liver disease. They usually feel better before the lab work looks a lot better and they often recover from problems that seem really bad based on lab work and pathology reports. When things are looking good I am more hesitant to change treatments or to suggest further invasive testing.
Good luck with this.
Mike Richards, DVM
Liver disease - continued
Q: Dear Mike, I don't know whether you ever got my e-mail with all those numbers on the liver, but I have brought her home 2 days ago and she is doing really well. Amazingly well, considering the diagnosis. She is playful I go for walks with her she is eating and still drinking more than usual and with every day she is more the dog I know, tonight was the first time she was begging for dinner table scraps, which really made us thing she is back to normal. I was at a friends vet today, however, who was very surprised to see how perky she is and did a quick blood test. Her ALT was 545 that is down from 745 just two days ago. Do you suppose I should have hope again, it's almost that I am scared to do that. I have gone through an incredible emotional roller coaster and now it looks like she is recovering fast. Is that even possible with that diagnosis. They are also still talking about an outside change of some bacteria that deer etc. carry (I am sorry I don't know the medical term) but one of the things that result from that bacteria is acute hepatitis. We do live on a marsh and there is a lot of wildlife, we also have an incredible amount of canadian geese on our lawn all Summer and Fall. Your thoughts on this at least for me very complicated case would be highly appreciated. Lydia
I suspect that the bacteria being worried over is leptospirosis but I am not sure. There may be others that affect wildlife and domestic pets.
In any case, I think that you have good reason to believe that things will work out well at this time. While many times it is not possible to give a specific diagnosis, a lot of dogs with acute liver disease do recover fully and do not experience recurrences of the illnesses that affected them. I hope that this will be the case for your terrier, too.
I did get the email but I have just recently added a new computer and have managed to lose a few messages in the transition to it. If I remember correctly there was a slight downward trend in the numbers which appears to have been confirmed.
In liver disease, the attitude of the patient is often more indicative of how things are going than the lab work is. I really do think that it sounds like things will be OK, even if a diagnosis can not be confirmed.
Mike Richards, DVM
Q: My dog has been diagnosed with diabetis mellitus and shows symptoms of necrolytic mig. erythema on her feet. What is the recommended treatment for this condition. Any help would be appreciated. Currently using an antibiotic ointment and have considered trying Willard Water as a homeopathic remedy.
Thanks very much for your anticipated response.
A: Dear S-
Necrolytic migratory erythema (NME) is a disorder in which a primary disease in the liver, a glucagon producing tumor or diabetes causes secondary skin disease. The skin disease consists of sores on the face, ears, feet and sometimes other areas. There are usually significant changes in serum chemistry values correlating with the primary disease. In many dogs with this condition the NME shows up before the diabetes does.
I do not know if there is a definitive understanding of what causes this condition but the prevailing theory seems to be that it is partially caused by nutritional deficiencies induced by the underlying diseases. There are a number of suggested food additives, including essential fatty acids, amino acid supplements, zinc, and egg whites (presumably for their protein value). It doesn't appear that any of these things work really well based on the literature available to me at this time but they probably don't hurt. Treating for bacterial infection of the damaged skin with appropriate antibiotics or topical antiseptics may be helpful, too. Moderate to high fiber diets are often used to help control diabetes but in dogs with NME they may not be a good idea because the need for higher quality protein may over-ride the benefits of the fiber.
Most dogs with necrotizing migratory erythema do not do well over the long term. As far as I know there is no consistently
Michael Richards, D.V.M. co-owns a small animal general veterinary practice in rural tidewater Virginia. Dr. Richards graduated from Iowa State University's College of Veterinary Medicine in 1979, and has been in private practice ever since. Dr. Richards has been the director of the PetCare Forum...