Hyperkalemic Periodic Paralysis (HYPP)

Hyperkalemic periodic paralysis, better known in the horse world as HYPP, can be a devastating disease. There are horses that have it that never show a symptom a day in their life, and horses that have repeated severe episodes, to the point that their owners choose to humanely euthanize them instead of watching them suffer.

A large part of the management of hyperkalemic periodic paralysis is based around the diet, so we are going to discuss today what aspects of the HYPP horse's diet are most important.

However, to understand how this diet helps the HYPP-positive horse, its essential to understand how this disease works, and what it does to the horse.

HYPP: The Genes Behind It

In big words, hyperkalemic periodic paralysis is a co-dominant single autosomal gene disorder. In easier-to-understand language, this means that:
  • It's genetic
  • It is located on one single autosomal gene
  • It is co-dominant

(more on these last two in a minute!)

Now for a very basic genetic lesson:

Genes are made up of parts called "alleles"...each horse has one from its sire and one from its dam for each gene.

So, in respect to hyperkalemic periodic paralysis, a horse could be N/N, which is two normal alleles on the gene...this horse would not have HYPP, and could not possibly pass it on to its foals. These horses are HYPP negative.

Or, the horse could be N/H...this is where the co-dominance comes in. In a gene that is not co-dominant, either the animal has the disease, or he doesn't. However, with co-dominance, there is an "intermediate" which is different from the positive and negative.

Horses that are N/H have one affected allele, and one normal allele. They can show symptoms of the disease, but they are less likely to show symptoms than horses that have two affected alleles. However, it can still happen, and they CAN still pass it on to their foals.

For all intents and purposes, these horses should be treated and managed as if they have hyperkalemic periodic paralysis. These horses are often referred to as HYPP "carriers" because they carry the disease in their genes, but they don't always exhibit symptoms.

And lastly, horses can be H/H. These horses have two copies of the problematic allele, and are considered HYPP positive. These horses are most prone to HYPP attacks, and need to be managed very carefully.

H/H horses will ALWAYS pass on an affected gene to their foals. This means that if they are bred to a N/N horse, all of their foals will be N/H (carriers). If they are bred to a N/H horse, their foals will all be N/H (carriers) or H/H (positive).

HYPP: Abnormal Muscle Cells

In a normal muscle cell, there is an electrical gradient across the cell membrane when sodium is pumped out of the cell and potassium is pumped in. This gradient is usually around 85 millivolts (mV)

This gradient is able to be maintained because the only way sodium can get into a cell is through the sodium channels. However, these channels are not always open. In fact, most of the time they are closed -- they are only opened when a nerve impulse is received by the cell.

When the sodium channel is closed, sodium collects outside the cell while potassium collects inside the cell. As long as the electrical gradient remains close to 85 mV, the cell will stay at rest and the muscle will not contract.

When a nerve impulse is received by the cell, the sodium channel changes shape and allows sodium to rush into the cell. At the same time, potassium rushes out, because both ions are positive, so potassium moves to the more negatively charged area, which is outside the cell.

As the sodium rushes in and potassium rushes out, the electrical gradient gets close to 0 mV. This is called an action potential and causes calcium to be released from storage sites in the cell. The calcium then binds with areas on the muscle fibers called myosin. Once the calcium is bound, the muscle contracts and stays contracted until the calcium pump in the cell gets all the calcium put back into the storage site.

Then the entire process starts over again with another nerve impulse.

That is how it is supposed to work. However, in horses that have hyperkalemic periodic paralysis, the sodium channels are "leaky". They are not able to completely close, thus sodium is constantly leaking into the cell.

All this leaking of sodium causes the electrical gradient to be repeatedly brought close to 0mV, which causes the muscles to release the calcium and it to bind. This happens over and over, causing the muscles to repetitively contract.

Large muscles

All of the repetitive contractions of the muscles works the muscles even when the HYPP horse is at rest. Because a muscle grows the more it is worked, any muscles that are being affected will grow larger than normal.

However, not every HYPP positive horse has visibly large muscles. Likewise, not every horse will abnormally large muscle groups will have HYPP. There is absolutely NO way to tell if a horse has HYPP just by looking at it.

The only way to tell for sure is to have the horse tested. UC Davis is the most well known place to have a horse tested for HYPP...you simply send a hair sample in and they send you the results after it has been tested.

You can also tell if a horse is definitely negative if he has two parents that have been tested and are both N/N.

The Impressive Disease

Hyperkalemic Periodic Paralysis is often known as the "Impressive" disease because it is thought that the gene mutation that causes it started with the famous Quarter Horse stallion named Impressive.

However, there are some people in the horse world that believe it may go back further than Impressive.

I've heard accounts of at least 2 horses that tested positive for Hyperkalemic Periodic Paralysis at UC Davis without having Impressive in their pedigree. However, both mares that did test positive (UC Davis tested 3 different samples from each mare and all came back positive) did have Impressive's dam, Glamour Bars, in their pedigree. These mares just happened to be tested because they were part of a good-sized breeding operation that tests all of their horses regardless of bloodlines, before sale.

There is speculation that the gene mutation goes back further in Glamour Bars' pedigree, probably carried through the dams. This is rational, as mares usually average 10-15 foals throughout their lifetime at most, so the chances of them having large amounts of offspring affected would be minimal. Even if half the foals from one mare carried the disease or were afflicted by it, news about it would not spread much further than the foal's immediate locale, thus a problem like this carried through the dam's line would probably not be caught.

Regardless of how far the HYPP mutation does go back, research has proven that it goes back to Impressive for sure. Thus every horse that has Impressive in his pedigree has a chance of carrying the disease (unless his parents have been tested negative) and should be tested.

Nutritional Management of HYPP

The overall goal of treatment and management of Hyperkalemic Periodic Paralysis is to limit increases in serum potassium levels. This is done by a combination of:

  • Limiting dietary potassium intake
  • Promoting entry of potassium into cells
  • Eliminating excess potassium from the body through urine

The single most important aspect of treatment is limiting dietary potassium intake. If a Hyperkalemic Periodic Paralysis-positive horse consumes a diet that is more than 1% potassium, clinical signs, or "attacks" are more common.

However, if the diet is maintained below 1% potassium, the disease can often be managed without any other preventative measures.

The largest source of potassium in a horse's diet is his hay. In general, grass hays tend to have less potassium than legumes such as alfalfa. However, the potassium content of hay depends on where it was grown, when it was cut, and conditions during growth and harvest, as well as the grass fertility and moisture content. Due to this great variation, it is imperative that if you are managing a HYPP horse, you have your hay tested at a laboratory for potassium content.

It is usually a good idea to maintain an HYPP horse on grass hays such as timothy, Bermudagrass, or prairie hay. If legumes such as alfalfa must be included in the diet, it may be necessary to use other measures to control the disease.

Inclusion of larger amounts of cereal grains in the HYPP horse's diet is also a way to decrease the potassium level, as cereal grains are fairly low in potassium.

Not only will the intake of cereal grains decrease the potassium content of the diet, but it may also increase the uptake of potassium into cells by promoting insulin release, which promotes uptake of potassium into cells.

However, intake of commercial mixes that contain molasses, soybean meal, or dehydrated alfalfa should be monitored, as these feeds can contain large amounts of potassium.

Management beyond nutrition

In cases where nutritional management is not enough to control Hyperkalemic Periodic Paralysis, a few other options are available.

Mild exercise, insulin release, and administration of other cations have all been shown to increase potassium uptake.

Insulin release can be achieved by feeding cereal grains high in starch, or administering glucose either IV or orally.

Sodium or calcium administered through IV will increase potassium uptake as they are both cations.

Another prevention method that can be used under the supervision of a veterinarian is the administration of acetazolimide, which is a diuretic that increases the excretion of potassium in the urine.

You cannot tell if a horse has HYPP by looking at it.

Hyperkalemic Periodic Paralysis is a scary disease to have to deal with. Thankfully it can usually be managed through dietary changes. If dieatary changes are not sufficient to manage the disease, there are other options available.

Knowledge of what the disease does, how it is passed on, and what causes it all help you be prepared should you end up with a HYPP positive horse in the future.

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