Bile acid response testing for possible PSS
Question: Hi Dr. Richards, I was wondering if you could review the below info and give me your opinion.
I have a 4 and 1/2 year old Australian Shepard pure breed named Mojo. He is the best dog and I love him. I got him from a reputable breeder when he was a puppy. Not to long after we brought him home did he start vomiting and having diarhea that looked like yellow gel (yuk). Anyway I tried many vets who did not know what was wrong..SO, i switched his food a couple of times and came up with one (solid gold) that stopped the diarhea all together and made his vomiting stop for the most part. So over the next couple of years he seemed to do pretty good except for occasional boughts with vomiting (usually once or twice a month). About nine months ago he got a hold of a cheese sandwich, ate it and I fed him his regular food the very next day and he threw up blood. I am very careful not to give him treats, just his food. This was very scary to me I took him to the vet and they said he looked fine, said to watch him if he did it again to come in and sent him home. Then we moved back to Ohio and he seemed to be doing ok and he threw up blood again one early morning . This was about two months after first episode so we took him to very well respected vet hospital in the area and they did blood work, xrays and stomach biopsy as well as ultra sound and said everything turned out ok except white blood cell count was slightly elevated and they found one very small bladder stone. So they gave us Amoxicillan and metronidazole and sent us home. Off and on for the next month or so Mojo kept vomiting not blood just yellow and food. Then one day over a weekend when he was due back for a checkup i noticed his eyes and skin looked yellow, and he would not eat, and was leaking urine. I took him to the vet right away and his billirubin was like 17! Which was weird to me because his blood work had been fine the last two times they took it. They put him on IV, and his blood work slowly returned to basically normal. They said that he had pancreatitis and cholangiohepatitis. They put him on baytril, clavamox and metronidazole for like eight weeks, and we switched his food to IVD Venison can food. He has been back for check ups and done well only one value is slightly high on his blood tests and that is GGT. It has been 5 1/2 months since then and he is like a new dog, running, playing and no vomiting..Except last two days I noticed he is leaking urine again and last night he was moving his head kinda weird i think you called it head pressing..They have never removed the bladder stone and they said last time they checked they could not even find it.
My question is, do you think he may have a PSS? Could they have missed that on liver xrays and ultrasound? I had been doing some reading on your site and i noticed one person brought up Cryptorchidism and PSS link..His testicles never did fall and i had them remove them when he was 2.
Please give me your advice..We have spent much time and money caring for our little Mojo and I am afraid that maybe we did not get to the bottom of his problem.
Thank you so very much, Debbie
It sounds like it would be a good idea to do bile acid response testing. This is done after at least a twelve hour fast. Blood is then drawn for a baseline value for bile acids. A small meal is fed right away and then blood is drawn again in two hours. If the bile acids are elevated significantly on either test, or if there is a significant rise in bile acids between the first and second blood samples then it is likely that there is a decrease in the functional capacity of the liver. Portosystemic shunts are one reason for elevations in bile acids but they can also occur with chronic liver diseases in which there is ongoing damage. Sometimes, when the damage is progressing slowly the other liver values will stay normal because the liver is being damaged so slowly and they really only elevate when there is active damage to liver cells. The bile acid test actually measures the functional capacity of the liver indirectly.
If the bile acid response test is normal there isn't much chance of PSS and there is a good chance that there is enough liver capacity to allow for a good response to treatment for other liver diseases. If the bile acid test is abnormal then it would be a good idea to re-evaluate the liver using ultrasound examination, rectal scintigraphy or other testing as seems appropriate based on the results.
It might also be a good idea to do a trypsin-like immunoreactivity (TLI) test to try to rule out pancreatic insufficiency, or lack of production of digestive enzymes. This can happen with chronic pancreatitis. Usually there is continuous diarrhea, weight loss and a general unthriftiness with pancreatic insufficiency but we have seen some milder cases in which intermittent diarrhea occurred.
I think that I would want to deworm with fenbendazole in this situation, even in the absence of any evidence of worms, because both whipworms and roundworms can cause intermittent problems and are hard to diagnose if eggs are not being shed when fecal examinations are checked.
It really does seem like you have made good decisions and that your vets have done the same but these are just some additional things to consider that may or may not be helpful.
Good luck with this.
Mike Richards, DVM 2/20/02
Question: We have a 4 year old female minature schnauzer named Jammer weighing 12 lbs. She is our fourth miniature schnauzer. We took her to the vet 4 months ago because she couldn't eat and lost nearly 2 lbs in 10 days. Addisons was the diagnosis. She was treated with florinef 1/2 mg 3 times daily, and 1 mg of prednisone each day.
She got better and regained her weight. We now only give her a prednisone on stress days (haircuts/vet visits). She is active and as loving as ever.
It was the blood tests that were given over time that alarmed us to yet another problem. Her liver levels were elevated. Her electrolytes were high and her bile levels high. The vet said her liver is not functioning properly. We then took her in for an x-ray. This produced nothing. No tumors were located. It was noted, however, that she has a small liver for her size.
The vets advice was to treat her for a systemic infection. We gave her an antibiotic, denosyl, and a vitamin E (100 mg water soluble) daily. The next blood test produced no improvement. Actually, the levels were higher.
We are continuing the DenoSyl and the Vitamin E hoping it will help. Our next recourse was an ultrasound and/or biopsy. We opted for the ultrasound because of the risk involved with a biopsy. The ultrasound produced no significant evidence. No tumors, shunts or other abnormalities other than a small liver. The ultra sound did find a small crystal in her kidney (something to watch for).
After the ultrasound the vet said that without a biopsy it would be difficult to make a positive diagnosis, however, the ultrasound specialist and the vet thought that Jammer had chronic active hepatitis. She said the treatment for such was massive doses of prednisone (15 mg per day) or, actigal.
Our vet looked at other chronic active hepatitis cases and found that the actigal made no significant effect. Is this true? Actigal or prednisone or yet something else we haven't thought of? We want to treat her before her liver scars. We want to make the right decisions because we love her so much.
What treatment can you suggest we try? Do you have any other suggestions that would be helpful. Our Jammer is most dear to us. She is family. She is us.
I really think that it would be a good idea to get a more definite diagnosis in a dog of Jammer's age. It is likely that you will be treating her condition for a long time and knowing exactly what it is, if that is possible to determine, would be really helpful in designing the best long term treatment. Sometimes biopsies do not produce a diagnosis but they are the best tool for getting one and so I really would recommend taking this step.
It may be possible to get a diagnostic sample using fine needle aspiration. This procedure is pretty safe, since a regular hypodermic needle is placed through the skin and into the liver and a small sample sucked into the needle for evaluation. The sample size is small enough that it is often not helpful, though. We often try this as a first step, though. When it works it saves a lot of further effort.
When fine needle aspirate won't work, or just doesn't seem appropriate, then the choices are ultrasound guided biopsy and surgical biopsy. I am comfortable with surgical biopsy and have no problems taking this approach but ultrasound guided biopsy can eliminate the need for an incision the resultant healing and recovery time. Once in a while ultrasound guided biopsies miss an important lesion just because it doesn't show up well on the ultrasound but this is also true for surgical biopsy if the surgeon can't see where lesions are on the liver. It is best to have biopsies examined by a pathologist and evaluated for copper accumulation, too. If there is only enough tissue for histopath examination the pathologist can estimate the amount of copper with special staining procedures.
If you opt not to have a biopsy done then you have to make some educated guesses about what is best. I personally favor the use of ursodiol (Actigal Rx) but I will try to check on your vet's concerns and get back with you if I find something to indicate it may not be effective. Prednisone use is somewhat controversial for chronic active hepatitis (chronic canine inflammatory hepatic disease), with some veterinarians thinking it is very helpful and others thinking that it doesn't help or may cause harm. The usual recommended starting dosage is 1mg/kg (or about 5mg for a 12 lbs dog) and then tapering to 0.25 to 0.5mg/kg every other day, if possible.
Colchicine is recommended by some vets to fight fibrin formation but I haven't used this much and can't give a personal perspective on it. The dosage is 0.03mg/kg per day. Zinc supplementation is reported to help some dogs, as well. I am not sure if there is any research to support this, though.
I really do think that a biopsy would be the best approach for most dogs in Jammer's age range due to the potential need for life long medications and the potential for starting the most appropriate medications as early as possible.
Mike Richards, DVM 9/9/2001Ultrasound liver biopsy
Q: Dr. Richards,
Thank you for the quick response. My vet wants a radiologist to do an ultrasound, needle biopsy on the liver this Thur.
Is this an invasive procedure? We seem to be making some progress and I'm hesitant to want to do anything that might set her back.
Are the blood clotting tests and bile acid tests recommended prior to a needle biopsy?
A needle biopsy is an invasive procedure. It is considered to be safer to do an ultasound guided biopsy than to do a "blind" biopsy -- but there is still some risk of hitting a blood vessel and it is best to know that the blood is likely to clot before taking that risk. I think that a mucosal bleeding time test, which can be done in the vet's office, is a reasonable choice for this test but some vets prefer to do more complex testing done through a reference lab. We rarely see clotting problems even with liver disease but it can happen and it is best to be cautious. We have never had a patient have a serious complication from liver biopsy that I can remember but we have elected not to do the procedure on at least one occasion when blood clotting problems were present.
Liver biopsies are often the only way to be sure what liver disease is present but I still think that it is reasonable to do bile acid testing first, just to be sure that there really is a change in liver function. This is one of those issues in which having the opportunity to actually see the patient can be a really big advantage so I can't say that your vet is wrong in this choice. He may have really good reasons to feel that liver biopsy is a better choice. Bile acid testing is not considered to be a prerequisite to liver biopsy as changes in the bile acid response would be a good reason to recommend liver biopsy and normal bile acid response testing does not rule out liver disease, it just makes it less likely that severe disease is present.
Hope that helps. It is always hard to figure out what to do in these kinds of cases. Clinical signs are important and if you are sure your dog is improving you have to consider that in your decision making.
Mike Richards, DVM 5/12/99
Q: Hi Dr Richards
We are at the next step with Roquefort and I need some help with decision making. He had the bile acid response test on April 16th. I don't have numbers in front of me but the test result was that the post-meal test showed a liver dysfunction. If it's important I can get the actual numbers.
What the vet is recommending now is a clotting panel ($75), then an ultrasound where a biopsy will be done at the same time ($375).
This is a tremendous amount of money for us but when I questioned the vet it sounds as if we should get these tests done as soon as possible.
Is there anything else we should consider and are we on the right path?
Many thanks Jane B
If there is a significant elevation in the postprandial (after eating) bile acid value, there is probably a significant decrease in liver function. It is a good idea to figure out what is going on. Before doing liver biopsies it is best to make sure that blood clotting is normal because the liver produces some of the clotting factors. If it is damaged to the point that it isn't doing that, severe bleeding and even death can result from attempting to biopsy the liver. If blood clotting is normal then ultrasound guided biopsy is safe enough to be a good choice for trying to determine the exact nature of the liver damage. In some cases there are problems that can be corrected surgically (some forms of portosystemic shunts) and in other cases knowing the cause of the liver damage can help in determining proper medical treatment. There are times when liver biopsies don't help much but they are the best way to determine what is happening when the liver is damaged.
If the biopsy is being done by a specialist in the area it would be worth asking them to review the lab results first. Bile acid tests have an overlap where values are normal in some pets and abnormal in others so if the elevation on the postprandial test is small it would be more important to have a second opinion on the need for ultrasound exam and biopsy. Sometimes we repeat the lab testing to see if the results are the same in these patients prior to moving on to more aggressive diagnostic procedures.
Mike Richards, DVM 4/20/99
Q: Dear Dr. Mike
Thank you so much for your evaluations. You cannot appreciate how important this resource is for me, and probably many many others. (I would certainly pay for each "consult," if you asked. I spent 10 days reading everything in your archives and other files before I wrote.
First question, is there a scientific or special name for a bile acid test? The vets down here don't seem to get it when I say bile acid test (in Spanish or English; that's why they did the bilirubin instead).
And, one other probably unimportant, question: Natasha's rectum. It looks perfectly normal (based on my experience with other dogs) most of the time, but when her bladder is almost full or she's considering defecating, there is a partial opening, like a little hole, until she decides to go, which could be an hour or two later. With other dogs the rectum usually just sort of bulges when they're full. Is this anything to be concerned about?
Thank you very very much.
I have been thinking Natasha's symptoms and labwork since you wrote. It may be simplest to just sum up my thought process and let you decide if any of it matters.
First, the labwork.
Bilirubin is a by-product of the breakdown of hemoglobin when red blood cells die. Since red blood cells are constantly dying and being replaced it has to be dealt with. The liver breaks it down. Bilirubin levels in the bloodstream rise for several reasons:
1) Breakdown of red blood cells in numbers sufficient to overwhelm the liver's ability to handle the bilirubin produced by breakdown of hemoglobin
2) Damage to liver cells so that they can not perform the task of bilirubin breakdown.
3) Blockage of bile ducts in any manner (gallstones, cancer, tissue swelling)
4) False elevations due to lipid levels in the blood stream being too high (Kirk's Current Therapy XII, page 737)
5) Lab error
A bilirubin level above 1.0 mg/dl usually will cause bilirubin to be present in the urine. Most urine test strips include bilirubin as one of the tests. Since you don't indicate the presence of bilirubin in the urine it is possible that there is a false reading in the blood OR that the level is just slightly below the level that spillover would occur. The lab values given left out two important clues to this mystery. If she is anemic that would make it easy to understand why her liver values appear to be normal but bilirubin is a little high. If she is not anemic it would be really helpful to know the serum alkaline phosphatase (ALKP, ALP) values because high ALKP levels can indicate bile duct blockage. The SGOT (also known as AST) value and SGPT (now known as ALT) value are normal indicating a lower probability of damage to the liver cells.
Bile acid testing. As far as I can determine this is the only name that is used for bile acid testing. Bile acids are produced by the liver from cholesterol. This is work. In general, animal bodies hate to do extra work. So bile acids are recycled in the body. They do their job (which I think is to stimulate bile transport) and are thus released into the intestinal tract. They are reabsorbed by the digestive tract and into the circulation. The liver recycles them rapidly. Therefore, there shouldn't be high levels in the blood stream at any time and there isn't much difference in levels before and after meals. High levels of bile acids indicate that the liver can't handle the recycling job due to damage or diminished capacity.
When do you need bile acid testing? If a dog has bilirubin levels above normal and is not anemic there is probably liver disease. If this is the case, then there isn't all that much need to run a bile acid test. When there is reason to be suspicious of liver disease but bilirubin levels are normal or close to normal, then bile acid testing can be very useful since it is a more sensitive indicator of diminished liver capacity.
Natasha has some signs consistent with chronic liver disease, including seizures, vomiting, slight elevation in bilirubin and tiring easily. Dobermans are prone to liver disease. So bile acid testing seems reasonable to pursue. If your vet's local lab doesn't run this test it is possible to send bile acid samples to labs in the U.S. by Federal Express or U.P.S. or by mail if it doesn't take too long. Checking on the other lab values (ALKP and the hematocrit, or percentage of red blood cells) may make this seem less important. If both are normal there isn't a whole lot of reason to worry too much.
I would also worry a little about bladder stones with the history given, since they can cause frequent urination, blood in the urine and because at least twice in my practice people have seen episodes that appeared to be seizures associated with bladder stones. I do not know if this was coincidence or if passing a small bladder stone is so painful that it looks like a seizure or perhaps even leads to one or to fainting resembling a seizure. Cystitis and incontinence both also seem possible. Even a disorder leading to increased drinking and urination (can occur with liver disease on occasion) may be causing incontinence that might not otherwise be present.
I would also worry about an orthopedic problem, such as hip dysplasia, with the reluctance to walk with you.
A lot of dobermans have the relaxation of the anal sphincter that you have noticed and I really think that is normal just based on my own observations of dogs.
Anyway, that is what I have been thinking about. As you can see, I think that there is reason to suspect several things and the only way to sort through them is to start somewhere. Hip X-rays and bladder X-rays may be worthwhile or bile acid testing may be an easier first step. You'll have to work with your vets there to decide what you and they think is the most likely first step to produce useful information. Sometimes you just have to keep looking until you find an answer or decide that there it doesn't look too likely that there is one. If you reach that point then you can worry about whether you worry too much.
Mike Richards, DVMLast edited 08/30/02
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...