LYMPHANGIECTASIA: AN IMPORTANT CAUSE OF INTESTINAL PROTEIN LOSS
WHAT IS A PROTEIN-LOSING ENTEROPATHY?
If the intestine is leaking nutrients out instead of absorbing them in, clearly the result is a nutritional disaster. In protein-losing enteropathy, that is exactly what is happening: the intestine and/or stomach is actually leaking out protein. This is obviously a serious problem as without protein coming in, the body's only choice for making the proteins it needs is breaking down existing proteins and reassembling their amino acids into new proteins. Muscle is broken down to make way for higher priority blood proteins. The immune system's ability to make antibody proteins may be compromised. Debilitation results from protein break-down and the intestinal disease that started it all facilitates this by creating diarrhea. Lymphangiectasia is one of several protein-losing enteropathies.
ALBUMIN LOSS IN PROTEIN-LOSING ENTEROPATHY
he main protein which one cannot afford to lose is called “Albumin.” This protein normally is produced by one’s liver and circulates in the bloodstream acting as a carrier for biochemicals that require transport but cannot actually dissolve in blood by themselves. Albumin can be considered sort of a mass transit system in the bloodstream, a bus or subway, if you will, carrying important biochemicals from one place to another.
|Normal small intestine under the microscope.
The finger-like projections are the "microvilli"
which are responsible for absorbing nutrients.
We want nutrients to be absorbed in,
not leaked out and lost.
(Photocredit: Nephron via Wikimedia Commons)
Albumin, by being the most prevalent blood protein, is also responsible (by virtue of the complicated concept of oncotic pressure) for actually keeping fluid in one’s bloodstream. When fluid cannot be held within the vasculature, it leaks out into body cavities as effusion or into tissue in general as edema.
Of course, in a protein-losing enteropathy, other proteins are lost, too. Antibodies, proteins of blood clotting, enzymes, etc. all leak out the intestine and are forever lost in the feces that exits the body.
The body tries hard to maintain its albumin level by extracting protein from other sources (like muscle), and having the liver make albumin from the components of these other proteins. This may help maintain a workable amount of albumin in the bloodstream but it comes at the expense of muscle tissue and other working proteins.
There are several described causes of protein-losing enteropathy:
- Inflammatory Bowel Disease
- Histoplasmosis (a fungal infection)
- Diseases associated with intestinal bleeding (parvovirus, intestinal parasites, cancers such as lymphoma)
- Breed Associated PLE (as in soft-coated wheaten terrier, shar pei, Maltese, and basenji)
- Crypt disease (where the intestinal crypts dilate and plug with mucus)
- Intestinal Lymphangiectasia
We will limit our discussion to lymphangiectasia.
WHAT IS INTESTINAL LYMPHANGIECTASIA?
Lymph is a fluid that circulates through the body similar to the way blood does; though blood is pumped actively through the body by the heart while lymph is pumped passively via the normal muscle activity of the body. Lymph consists of cells called “lymphocytes,” which are cells of the immune system as well as the fluid which collects from the tissues and shunts into lymphatic vessels which are similar to veins.
The word “lymphangiectasia” means “dilated lymph vessels.” In the intestinal tract, lymphangiectasia is usually caused by some kind of inflammation which puts back pressure on the lymph vessels leading them to dilate. Lymph flow may be blocked by the inflammatory events in the intestine or local structures.
Lacteals are special lymph vessels in the intestinal tract designed to absorb nutritional fats. The intestine is able to absorb our nutrients through small finger-like structures called "microvilli." Lacteals run though the center of the microvilli happily imbibing fats from the food we have eaten. When there is high pressure within the lymph vessels, the tender lacteals burst and instead of absorbing fats, the lymph inside them including cells, fats, and precious proteins are lost into the intestinal tract. The intestine may be able to reabsorb some of these valuable substances at other sites but if the inflammatory intestinal disease that started the problem in the first place is widespread, the balance may have shifted to nutritional loss rather than gain.
Small terrier breeds, particularly the Yorkshire terrier,
appear predisposed to the development of lymphangiectasia.
Lymphangiectasia is extremely rare in the cat.
WHAT DOES ONE SEE AT HOME?
Weight loss is the most consistent sign along with chronic diarrhea, vomiting, and, in more advanced cases, fluid accumulation in the abdomen creating a bloated appearance.
HOW DO WE MAKE A DIAGNOSIS?
In most cases, an obviously sick skinny dog is brought to the veterinarian. Sometimes the above classical signs are present but sometimes there is no specific hint of this condition until blood test results are in.
- Low Lymphocyte Count
Animals with lymphangiectasia have lymphocytes rolling out their lacteals and into their intestine to be lost forever. The low blood lymphocyte count is so consistent with lymphangiectasia that it is difficult to make this diagnosis if this finding is not present.
- Low Cholesterol
Cholesterol is part of the lymph fluid being lost.
- Low Albumin Level
Low blood albumin level is the most consistent finding in lymphangiectasia, though it is possible to have lymphangiectasia in a small portion of the intestine only and still maintain a normal albumin level. There are a limited number of conditions that can lead to a low albumin level: a protein-losing enteropathy, a protein-losing nephropathy (where the albumin is lost via leaking kidney membranes), reduced albumin production by a diseased liver, Hypoadrenocorticisim (a deficiency in cortisone), or serum leakage through extreme skin damage (such as third degree burns).
These conditions can be easily ruled out one by one. It is obvious if there are third degree burns present. If there are none, a routine urinalysis will indicate if there is significant protein loss in the urine and if glomerular disease should be pursued. A liver function test such as a bile acids test will indicate whether or not there is liver failure latently present. Blood testing can be easily done to rule out Hypoadrenocorticism (also called "Addison's disease"). If none of these other conditions are present, then there must be a protein-losing enteropathy by exclusion. Biopsy will be needed to determine the nature of the intestinal disease causing the protein-losing enteropathy.
Sample from a human with Lymphangiectasia.
The villi are short and squat compared to the
normal finger-like villi shown at the top of this page.
Note the large white areas within the
intestinal microvillus shown.
These are dilated lacteals as described.
(Picture courtsey of The Scientific Electronic Library Online)
Tissue sampling is necessary to distinguish the intestinal diseases that cause protein-losing enteropathy. With most PLE patients being deficient in albumin, this means they are not in a good position to heal from a surgical biopsy so endoscopy is generally recommended as it is less invasive. With endoscopy a small camera on a long flexible scope travels down the mouth, through the stomach and into the intestine (or retrograde from the anus up past the large intestine and into the lower small intestine) where biopsy samples can be pinched off with a special grabber. The procedure requires general anesthesia but is otherwise low risk and most patients can go home the same day. Often the areas of intestinal disease are patchy and surrounded by large areas of normal intestine so it is important to biopsy the right area. Ultrasound of the abdomen prior to endoscopy is helpful in determining where to sample plus often a few spoons of corn oil or other fat are often fed a few hours prior to biopsy so that dilated lacteals with plump and leaking fat visibly in the best areas for biopsy. Because PLE patients often lose important vitamins and blood clotting factors, blood clotting tests are generally done just prior to endoscopy.
The image above is actually from a human with lymphangiectasia but the concept is the same. Note the large pale areas within the intestinal microvillus shown. These are dilated lacteals. (The small white areas in the layer of cells lining the villi are "goblet cell" which produce mucus. The dilated lacteals are the large expanses of white or lavender underneath the villus lining).
The first step in treatment is to address the underlying cause. In many cases of lymphangiectasia, there is an association with inflammatory bowel disease ("IBD"). Whether or not the IBD is actually causing the lymphangiectasia remains a matter of speculation but anti-inflammatories are often used aggressively in lymphangiectasia patients. Prednisolone has been the traditional immune suppressive medication in this situation but as it causes an increase in water consumption that can contribute to edema, other medications, particularly cyclosporine, have become more popular as it does not have steroid side effects.
Intestinal loss of a body protein called "anti-thrombin III" leads to a tendency to form abnormal blood clots which can lodge in inappropriate places (embolization). As prevention, anti-clotting medications are often used. Aspirin has been traditional but clopidogrel is gaining popularity.
Nutritional management of PLE is a bit tricky. The diet must be especially digestible and high in protein (20-25% protein on a dry matter basis) so as to replace all the protein being lost through the leaky GI tract. Further, the diet should be no more than 15% fat on a dry matter basis (lower for more severely affected patients). Reading a diet label shows percentages on an "as fed" basis, so to compare diets, it is necessary to convert values to a dry matter basis through knowing the moisture content. To see how this is done click here. There are prescription diets available for diseases like this one where fat restriction is crucial. Non-prescription diets are unlikely to meet the above criteria but if you know how to read the food label properly you may be able to find one. Injectable vitamin supplements are likely to be needed.
Severely affected dogs will find even the fat content of the prescription diets too high and may need to begin with what is called an "elemental diet." These are typically made for humans and are powders that can be mixed with water. They are not nutritionally balanced for dogs and can only be used for a few weeks. Alternatively, home cooked diets can be used but a professional veterinary nutritionist should be consulted to get a proper recipe. Again, because of intestinal absorption issues injectable vitamin supplements are likely to be needed. The goal is to eventually return to a standard commercial dog food.
If the underlying condition is treatable then prognosis for lymphangiectasia is good. It should be understood that lymphangiectasia is unlikely to be cured and at best can be managed.
This page is dedicated by Mark & Linda Welch to their Soft Coated Wheaten Terrier, Blarney. He was a high energy playful dog who lived for attention and play. He had more personality than you would expect in an animal. He was always happy and excited to just be there with us. He loved to fetch balls and chase deer, squirrels, birds and especially the laser pointer. When we talked on the phone or around the house he would join in (some day we expected him to talk). He knew the house rules and was very good. He would sneak off with our old dryer sheets just to get us to follow him and play. He never chewed up things he wasn’t supposed to. He wasn’t allowed on the furniture, so he would keep his back paws on the floor and the rest of him on your lap and snuggle with us and give kisses. At 4 years old he succumbed to aggressive form of intestinal Lymphangiectasia with Inflammatory Bowel Disease. He was a great part of our family and will missed more that words can express.
Page last updated: 5/31/2020