Hepatic Encephalopathy In Your Dog And Cat
AKA: Portosystemic Encephalopathy
Ron Hines DVM PhD
Hepatic encephalopathy describes a situation in your dog or in your cat that is the result of a failing liver. When you pet’s liver is no longer healthy, it looses its ability to detoxify waste materials (eg ammonia, glutamine, ɣ-aminobutyric acid agonists, benzodiazepine-like substances as well as proinflamatory cytokines). Ammonia levels becoming too high in your dog or cat’s blood stream are a major marker for this problem. Ammonia is normally produced by the bacteria in your pet’s intestines and as a normal byproduct of everyday metabolism within your pet’s body. Its the liver’s job to convert that ammonia into less toxic urea. The traditional explanation of HE is that ammonia buildup in you pet’s blood stream affects the animal’s brain, leading to confusion and mental dysfunction.
The most common cause of HE in younger dogs and cats is an abnormal blood flow from the veins that drain their intestines. The major vein that does that (the pet’s portal vein) normally leads to the animal’s liver where these wastes are detoxified or re-excreted into the pet’s bile for elimination. These abnormal vein channels that circumvent the liver are called portosystemic shunts. You can read my rather complex article through the link at the top of this page or just look at a simplified diagram of the problems here. Most are birth defects, but some occur as a result of chronic liver inflammation. Hepatic encephalopathy can also occur when the pet’s liver has been damaged by medications such as Tylenol® (acetaminophen), sulfa antibiotics, moldy food, toxic mushrooms, artificial sweetener (just xylitol) and a number of poisonous plants. Hepatic encephalopathy can also result from liver damage caused by canine hepatitis, FIP in cats, toxoplasmosis, leptospirosis and neospora infections. It is also occasionally seen in very severe cases or the end-stage results of hepatic microdysplasia. In many older dogs and cats, HE is just another sign of age-related liver failure.
In dogs, heavy burdens of heartworms (caval syndrome) have been known to cause HE. In cats, HE has been associated with abnormally low levels of the amino acid arginine. In some dog breeds HE is due to a genetically based problem in storing copper. (copper storage disease. (read here & here) In pets with copper storage disease, restricting dietary copper sources can slow the disease’s progression.
If you want to read an extensive review of the many things that can cause sudden liver failure in dogs and cats resulting in HE, ask me for Weingarten2015.pdf
Hepatic encephalopathy is somewhat more common in the breeds of dogs and cats that are most prone to liver problems. Liver shunts (portosystemic shunts) are also a predisposing factor for HE in toy and small breeds of dogs as well as Persian cats. English cockers, Labrador retrievers, Westies and Dobies appear to be at greater risk for HE because of their increased susceptibility to liver disease in general. Us humans suffer from hepatic encephalopathy too. The most common cause in humans is cirrhosis of the liver brought on by alcoholism.
What Signs Would I See If My Cat or Dog Had Hepatic Encephalopathy?
Hepatic encephalopathy is a disease that usually begins gradually. Generally, the first sign that owners notice is the pet’s lack of interest – a sort of preoccupation or fog – as if the dog or cat was contemplating things far away. That can progress to confusion when decisions need to be made and even snappiness when urged to move or perform some task.
Because you know your pet so well, none of these early signs are likely to be apparent to visitors or even to your veterinarian. But as liver damage increases, some pets become unsteady on their feet and disoriented or “spacey”. That can progress to getting trapped in corners, pressing their heads against objects, blindness, drooling, and even aggression when handled or disturbed. In middle-aged to old dogs and cats, those signs need to be sorted out from early onset dementia aka CCDS. Other owner descriptions of their pet’s changed behavior with HE include wandering, circling, stargazing, pacing, sleepiness, apathy, dementia and compulsiveness.
Your pet’s symptoms can progress to prolonged seizures/ convulsions and even a semi-comatose condition. Dogs and cats with these more critical signs are approaching the end of life. In a few, heroic emergency treatments might restore a semblance of normalcy and gain a bit of time. But in the majority of cases they will not.
In some cats with HE, the color of the iris of their eyes is said to assume a lighter metallic color.
Near-to-normal liver function is essential for many of your dog and cat’s critical body functions; so a lot of other, non-specific symptoms such as poor hair coat, diarrhea, weight loss, unsteady gait and vomiting might occur as well.
It is common for the signs of hepatic encephalopathy in your pet to come and go – becoming more pronounced at one time of day or days, getting better at another. That is a key sign. Come-and-go symptoms are not the case with other things that affect the brain – things like brain tumors, brain deterioration (=encephalomalacia) or hydrocephalus, toxic exposure or drug overdose – all of which can result in symptoms quite similar to HE.
Sometimes pet owners notice that symptoms of HE are at their the worst soon after their dog or cat has eaten. As I mentioned earlier, a recent meal sometimes triggers an episode – perhaps because the pet’s body has to deal with more free ammonia released (indirectly) from the food it ate. Ammonia ions are liberated through the breakdown (hydrolysis) of the digested amino acids in the proteins your dog or cat consumes as well as during the construction and deconstruction of its own body proteins. (read here) Ammonia (NH3) at low levels is a normal constituent of all your pet’s body fluids. Ammonia’s ionized form, ammonium (NH4+), is most prevalent in your dog or cat’s muscles – the chief non-dietary source of free ammonia in its body.
Are There Other Things That Might Make The Symptoms Of Hepatic Encephalopathy Worse From Time To Time?
Any form of stress tends to make the symptoms of hepatic encephalopathy worse.
What Test Will My Veterinarian Suggest To Diagnosis This Disease?
As I mentioned earlier, there are a number of non-liver health problems that could explain some or all of your pet’s symptoms. Some of the tests your veterinarian might suggest are designed to rule those other issues out. Abnormal behaviors that you describe to your veterinarian might also bring the chance of HE to your veterinarian’s mind. Another clue for your veterinarian is a history of unusually strong or persistent effects of tranquilizers and anesthetics (prolonged recovery) or a sensitivity to flea and tick products, or to medications used to control epilepsy. That is because many of those (and other) medications are eliminated/detoxified by your dog or cat’s liver and a weakened liver is inefficient in doing so.
Liver function tests (ALT, Total bilirubin, Alkaline Phosphatase, GGT ) are indicated. But normal results do not rule out HE. Those tests tend to be high early in liver disease when liver cells are inflamed (leaking) or destroyed, but the test results might be normal when liver problems are long-standing.
Many dogs and cats with failing livers also have lower than normal blood albumin levels because their liver can no longer synthesize sufficient albumin which is one of the liver’s jobs. Some pets with HE have reduced blood-clotting abilities in tests that measure the speed at which blood clots (CT, PT, CTG , etc.). That is because compounds required for blood to clot require a healthy liver.
Measuring your pet’s blood ammonia levels directly might be helpful in diagnosing hepatic encephalopathy. However the test is quite difficult to perform because ammonia is so volatile (evaporates quickly). Results vary from laboratory to laboratory. So it is a test best performed at advanced institutions familiar with this difficult assay procedure. Even then, the test suffers from poor repeatability (two identical samples sent to different labs give different results). When your pet’s plasma ammonia level is substantially elevated, it is a suggestion that HE underlies your pet’s problems. But some pets with normal blood ammonia reading still have hepatic encephalopathy. Also, the degree (amount above normal) that your dog or cat’s ammonia level is above the laboratory’s normals does not appear to directly influence the severity of the symptoms your pet is experiencing. (read here) I mentioned earlier that failing livers allow multiple toxic products to enter your pet’s circulation. HE is not just about high blood ammonia. Because of the difficulties in accurately testing for elevated blood ammonia, most veterinarians rely on high blood bile acid levels levels to diagnose HE instead. However, like ammonia, normal bile acid results do not entirely rule out HE either.
X-ray, Ultrasound And Other Imaging Techniques
Many pets with HE have a smaller-than-normal liver or liver tissue that has an abnormal texture (increased or heterogenic echogenicity) (read here) when viewed with an ultrasound machine. That is due to fibrosis (scaring). There are advanced imaging methods that are excellent for identifying abnormal liver blood flow (such as portosystemic shunts) which account for a very large portion of the younger pets with HE. You can read about them here.
Dogs and cats with HE are also at an increased risk of developing urinary tract stones and crystals composed, in part, of ammonia compounds (ie ammonium biurate urolithiasis = calculi = “stones”). Although not as dense as other urinary tract stones, they can sometimes be detected and are generally checked for during ultrasound or x-ray imaging exams whenever chronic liver disease is suspected.
Immediate Stabilization For Pets With Hepatic Encephalopathy
Dog and cats brought to their veterinarian in hepatic encephalopathy crisis often need intravenous fluids to rehydrate them. They may also need products to coat inflamed intestines – another common finding. Any other life threatening symptoms will be addressed appropriately. Some dogs and cats with HE are thought to have increased pressure upon their brain. If that is suspected, those pets might be given mannitol in an attempt to alleviate that.
Dogs experiencing seizures are often given levetiracetam or potassium bromide. Both are anti-epileptic drugs. Unlike diazepam and phenobarbital which also help to break seizures, levetiracetam and potassium bromide metabolism does not require a healthy liver. Both medications tend to have the potential to cause more worrisome side effects when given to cats than when given to dogs.
If constipation is thought to be a contributing factor (and even if it is not), enemas are useful to solve that immediate problem. Some ammonia can leave the body in the stool and some ammonia is also produced by the microbes that normally inhabit your pet’s colon. That exit rout for ammonia needs to be preserved and fully utilized.
What Long Term Treatments Might Help My Dog Or My Cat?
The best hope for dogs and cats with hepatic encephalopathy are for those in which the underlying cause of their problem is a surgically-correctable hepatic shunt. That surgery is quite expensive. It can only be performed by a limited number of trained veterinary surgeons. It is not always successful and some cases do not lend themselves to surgical correction. Read about that in another article of mine I mentioned before. (read here)
If your veterinarian suspects that a liver infection might be the cause of your pet’s liver failure, antibiotics are indicated. Antibiotics ( metronidazole or perhaps neomycin) are also thought to be helpful in HE even when no liver infection exists because they reduce the number of ammonia-forming bacteria in your dog or cat’s intestine. So in almost every suspected case of hepatic encephalopathy, antibiotics will be part of your veterinarian’s long-term treatment plan.
Pets with hepatic encephalopathy should avoid medications used to sedate them or they should be given those drugs in reduced doses and the pets then closely monitored. Those medications include benzodiazepines (like Valium®), barbiturates (like phenobarbital given for epilepsy or various compounds used to anesthetize or tranquilize pets) as well as narcotics and pain-control medications of any kind. Bouts of constipation, dehydration or prolonged fasting can precipitate (cause) an HE attack in dogs confirmed to have the problem.
Lactulose, a non-absorbable sugar, is one of the most widely used medications to lessen the symptoms of hepatic encephalopathy. An alternative is lactitol. Both work only in the pet’s intestine and are not absorbed. Added dietary fiber (soluble and insoluble) is also thought to be beneficial. Fiber and fiber fermentation in the dog or cat’s intestine might allow more ammonia to leave as ammonium via the feces. Be prepared for looser stools and/or bloating on all three of these products. Oral neomycin might reduce any bloating and/or diarrhea problems.
Folks generally believe that neomycin is not absorbed into the body when it is given orally…. But that is not entirely correct. Drugs of that class have the potential to cause kidney harm as well as hearing problems. So pets on long-term neomycin need to be monitored (kidneys, hearing, etc.). When neomycin can not be given, long-term metronidazole (Flagyl®) at a reduced dose has been used to keep intra-intestinal bacterial ammonia production as low as possible. In humans, rifaximin (Xifaxan®) is sometimes given for HE (rifampin as well). I am told that rifaximin has been given successfully to dogs and cats when neither neomycin nor metronidazole were effective in keeping the pet’s blood ammonia levels under control.
Some veterinarians give or suggest a zinc supplements or additional l-carnitine in your dog or cat’s diet. The benefits of both are uncertain. Others suggest probiotics that they dispense or suggest for a wide array of health issues including hepatic encephalopathy. Although they are not harmful, there is very little science to suggest that they will be helpful either. You are certainly welcome to give live-culture yogurt to your pet if it handles it well.
Omega-3 polyunsaturated fatty acids (PUFAs) are thought by some to reduce inflammation throughout the body. (read here) In experimental systems, these PUFAs also appeared to protect liver cells from the toxic damage caused by the abnormally high bile acid levels found in many liver diseases. So a krill or cold water fish oil supplement, marketed for humans, might be a helpful addition to your pet’s diet – particularly if its bile acid test results are high.
You might recall that I mentioned that some veterinarians use high blood ammonia levels to confirm that your pet has HE – but that normal ammonia levels do not rule the disease out. I also gave you a link to a recent article that found that the level of ammonia detected in your pet’s blood stream does not correlate well with the severity of the symptoms the pet is experiencing. That led some of us to question if high blood ammonia was really the cause (or only cause) of the mental problems your pet is experiencing or if perhaps other toxic substances that build up in the blood stream of dogs and cats with failing livers might also be involved. One of those other substances are the bile acids your veterinarian used to confirm the diagnosis. Abnormally high blood bile acid levels are also toxic. An interesting experiment was performed in 2016. Mice were intentionally given compounds that caused their livers to fail. Some were fed supplemental bile acids and some where given medications that lowered blood bile acid levels. Those authors reported that the mice fed supplemental bile acids developed mental problems early than the mice that did not. They also reported that the medication (cholestyramine aka Questran®, Prevalite®) delayed or minimized those problems. ( read here ) Cholestyramine is one of a group of medications called bile acid sequestrants used in human medicine to lower cholesterol – but also to treat the itching that commonly occurs in chronic liver disease in humans. It has successfully lowered blood ammonia levels in dogs. (read here) I do not know of any veterinarians who have attempted to use cholestyramine or similar medications to lower high bile acid levels in HE pets or if they were helpful. If you do, please let me know.
There are other medications that sometimes help humans facing hepatic encephalopathy issues similar to those your pet is facing. You can read about some of those medications and suggestions here and here.
What Would Be The Best Long Term Diet For My Dog Or Cat With Hepatic Encephalopathy?
Many veterinarians believe that reducing your pet’s protein intake and upping its carbohydrate intake might reduce the symptoms of hepatic encephalopathy. That is because protein breakdown is the source of much of the blood ammonia that is thought to play a part in your dog or cat’s symptoms. But other veterinarians and human physicians avoid suggesting low protein diets because pets and humans have been known to develop malnutrition when fed significantly lower protein diets. The actual protein requirements of ill pets is sometimes even greater than the protein requirements of healthy ones. Those veterinarians simply suggest that your pet’s protein intake not be “excessive”. Your dog or your cat would probably also benefit from frequent small meals rather than one or two large ones. In theory, the reduced number of healthy cells in your pet’s liver might be able to manage the ammonia produced by small more frequent meals easier than by large less frequent meals. Once you dog or cat is on medications like lactulose, its ability handle protein should also improve. Physicians have observed that their human patients with hepatic encephalopathy seem to do better when plant protein rather than animal protein is the main source of protein in their diets. I have known that to be the case in some HE dogs as well.
Veterinarians will often also suggest you give your pet antioxidants, supplements with added vitamin E and/or C, silymarin (milk thistle) and/or s-adenosyl-methionine (SAMe). There is no harm in doing so, but there is minimal data at best to show that they are helpful. Since there are so few proven options, give these things a try long enough to see if they are beneficial.
Humans, in a similar hepatic encephalopathy situation to your dog or cat, would be place on a liver transplant waiting list . Your pet does not currently have that option. There are visionary veterinarians searching for other options for our pets. (read here)
My personal believe is that it is dishonest for anyone to offer to “regenerate” your pet’s liver with fat-derived stem cells. There are companies currently marketing those “treatments” for dogs and cats. Although stem cells are the current rage, others (including me) have no faith in those procedures. (read here)
What Is The Long Term Outlook For My Dog or Cat? What Does The Future Hold?
You have to realize that many of the suggested treatments for HE that we veterinarians have today are of unproven value in extending your pet’s life. Veterinarians and physicians of today have nothing that will regrow or regenerate a failing liver. When veterinarians locate a particular, correctable anatomical reason for your pet’s liver failure, its surgical options for a long life increase greatly. My favorite places to have those decisions made are the AMC in Manhattan (Dr. Chick Weisse), Angell Memorial in Boston, Penn Vet and the U. of C., Davis. In Europe, Utrecht, and in the UK, the RVC . I have had clients happy with the objectivity and surgical competence of all of them. Even if you utilize profit-driven corporate conglomerates like VCA or Blue Pearl, a second opinion from one of the above is prudent.
If you go to the human Wikipedia HE entry , you will see than several of the standard treatments we veterinarians still use in confirmed cases of HE were laid aside by human medicine long ago as being ineffective. But if you dog or cat can be stabilized, its time progression (speed) of liver function decline is quite variable. I have two of the more current diagnostic and treatment guidelines for dogs and cats with HE but I cannot post them here. In this article, I mentioned most, if not all, of the therapies they suggest. But email me if they are of interest to you and I will send them for you to read .
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