Primary idiopathic hyperlipidemia has been reported to be familial in Miniature Schnauzers and Beagles, and some mixed breeds. It has been seen sporadically in other breeds, e.g. Poodles and Shelties, as well, Infrequently it has been reported in cats.
Secondary hyperlipidemia occurs as a result of another disease process. For example, it has been seen in association with diabetes, pancreatitis, hyperadrenocorticism and hypothyroidism.
Etiology:
This is a metabolically complex disease of lipid -lipoprotein metabolism and the exact etiology is not fully appreciated. The familial type in schnauzers may involve defects lipoprotein lipase and/or Apoprotein C-II, a required cofactor for lipoprotein lipase activity (see figure below for roles of enzyme and cofactors in lipid metabolism). This defect causes a failure to breakdown chylomicrons (most common) and/or VLDL, and results in excessive levels of circulating triglycerides. It is the elevated concentration of triglycerides that is responsible for the clinical signs.
Classification:
Lipids are derived from exogenous (dietary--> chylomicrons) and endogenous sources. Lipids have been classified as:
Chylomicrons: (see figure below for step-by-step...)
Are exclusively dietary in origin
transport triglycerides from the intestine to the capillaries of adipose and muscle tissue (routed via intestinal lacteals, thoracic duct, vena cava)
are converted in the capillaries to free fatty acids (FFAs) and the Chylomicron-remnant (rich is cholesterol esters).
pathways require lipoprotein lipase from endothelium
lipoprotein lipase activation requires heparin and Apoprotein C-II
the FFAs are transported into the adipocytes and skeletal muscle; the remnants are transported to the liver
Are the largest, and least dense of the lipoproteins
Are responsible for the post-prandial lipemia....where creamy white layer in plasma is seen approximately two hours after eating, and which persists for up to 10 hours.
Chylomicron Remnant:
Is the result of catabolism of chylomicons
Is rich in cholesterol, and is transported to the liver
Endogenous origin....synthesized in the liver from FFAs and carbohydrates
Rich in triglycerides, and metabolism is very similar to that of chylomicrons
Pure triglycerides from VLDL (or from chylomicron metabolism) do not form creamy white layer in plasma; circulating VLDL can result in persistent lipemia
LDL and HDL: (see figure below for step-by-step...)
These are byproducts of metabolism in extrahepatic and hepatic tissues
LDL (and to some extent, HDL) is rich in cholesterol, and serves as a bodily reservoir of this molecule; HDL is one source of cholesterol for the synthesis of LDL
Circulating cholesterol does not form creamy white layer or turbidity in plasma or serum
IDL:
In humans, an intermediate density lipoprotein (IDL) has been identified. The presence of the IDL in dogs is speculative, presently (but included in the metabolic pathway shown in the figure, below)
Metabolic Pathways:
Normal exogenous and endogenous biochemical lipid metabolism pathways, lipid composition and recommended diets for treatment are illustrated in the following figure ( Note...the first time you click the links in the image, it may take up to a minute to view the corresponding image):
Clinical Signs:
Usually occurs in middle-aged dogs (or cats)...(greater than 2-4yrs).
Clinical signs may occur intermittently, over many months or even years, with intermittent periods of complete resolution...or the patient may present in acute, severe distress.
Gastrointestinal Signs:
Vomiting and diarrhea
Non-localized abdominal pain
Pseudo-pancreatitis
clinical signs are similar to those of acute pancreatitis
laboratory and other diagnostics do not support the diagnosis of pancreatitis
Pancreatitis (sometimes withDiabetes):
however, sustained hypertriglyceridemia results in real pancreatitis, and, possibly diabetes as well
THUS, pancreatitis is the result of sustained hypertriglyceridemia, not its cause!
Laboratory and other diagnostics are consistent with (secondary) pancreatitis
Clinical signs do not improve (and may worsen) on commercial diets designed for general gastrointestinal (digestion/absorption) difficulties (because they contain moderate levels of fat....see Treatment, below)
Neurological Signs:
In the dog, the most common neurological manifestation of hypertriglyceridemia is seizures.
the pathophysiology is unclear, but hypertriglyceridemia may interfere with synthesis of myelin and other essential fatty portions of the CNS, resulting in conduction disturbances and seizures
In the cat, the most common neurological sign is a peripheral neuropathy.
tibial nerve paralysis and/or...
radial nerve paralysis and/or...
horner's syndrome
Cutaneous:
Primarily seen in cats
Xanthomas...result from the accumulation of lipid-laden macrophages in the skin.
Result from localized "mini"-trauma...so that blood (with chylomicrons/triglycerides?) leaks into the skin, and local macrophages phagocytose the irritating fats.
Other signs:
Lipemia retinalis
Lipemia acqueous
Diagnosis:
Laboratory:
A persistent lipemia after full twelve hour fast.
submit two serum samples....one to leave in the refrigerator and one to clear (of lipemia) for full panel analysis
one sample is placed in the refrigerator for 6-10 hour
if a creamy layer is seen at the top of the serum then there is a defect in chylomicron metabolism (most common abnormality)
if there is no creamy layer at the top but the sample is turbid, then there is a disorder of VLDL catabolism
second (cleared) sample is used for routine blood panel analysis
Other abnormalities reflective of secondary clinical signs (e.g. dehydration, electrolytes imbalances,other metabolic derangements), sometimes including diabetes and pancreatitis (secondary or primary pancreatitis???)
need to rule out possible secondary hyperlipidemia (e.g. endocrine disorders or primary pancreatitis (with secondary hyperlipidemia) discussed in the Introduction
Serum triglycerides:
normal is 100-150 mg/dl
hyperlipidemia frequently produces tiglycerides in excess of 1000 mg/dl
Lipoprotein serum electrophoresis:
lately the usefulness of electrophoresis has been degraded to "of dubious value".
Treatment:
Treat all secondary problems resulting from acute or chronic disease (e.g. diabetes, seizures)
The goal of treatment is to lower the fasting triglyceride levels to <500 mg/dl without incurring significant weight loss
Diet:
First (and maybe only) protocol is a low fat diet.
ideally, a diet with fat content of 7%-9% on dry matter basis, to start (see figure for examples of commercial diets)
recheck in 3-4 weeks
if no longer fasting lipemia (or triglycerides <500 mg/dl) and no weight loss, then continue current diet.
if no longer fasting lipemia (or triglycerides <500 mg/dl) but there is significant weight loss, then continue current diet but supplement with complex carbohydrate calories, e.g. pasta, potatoes.
if there is persistent fasting lipemia (or triglycerides > 500 mg/dl) then discontinue current diet, begin a NO fat diet and supplement diet with medium chain triglycerides (MCTs) at 0.11ml/kg/day (this assumes problem is with chylomicron assimilation)
Fish Oil supplement:
supplementation with omega-3 fatty acids may help to reduce serum triglycerides
one menhaden oil capsule per 10# body weight per day.
marine fish oil at 10mg-200mg/kg/day has also been recommended
Drugs:
Should be considered ONLY if dietary therapy, above, is not producing the desired results.
Niacin:
reduces the production of triglycerides from VLDL
dose is 25mg-100mg/dog/day
may result in pruritis
Gemfibrozil (Lopid ®)
increases level of lipoprotein lipase
use IF unresponsive to fish oil supplementation
Dose:
Dog: 100-300mg/DOG/12hr
Cat: 7.5-10mg/kg/12hr
Thyroxine:
has been recommended at dose of 0.1mg/10#/day
I question the wisdom of supplementing in the absence of hypothyroidism.....there may be "unhappy" side effects
Chitosan
Purpose is to reduce the absorption of fats from the intestine
A positively charged fiber derived from the chitin layer of shell fish
Interferes with the absorption of fat from the intestine by virtue of its surface charge with attracts and binds fat molecules within the intestinal lumen
A brand of Chitosan, from Nikken® is available as 150 mg tabs; the dose (for a Schnauzer-size dog) is 1-2 tablets 30 minutes prior to feeding
Cholesterol Lowering Drugs:
the need to control the cholesterol level in cases of hyperlipidemia is questionable
in cases of idiopathic hypercholesterolemia, (with potential cholesterol deposition in tissues, e.g. corneal deposits), cholesterol-lowering medication may be considered
drugs include bile acid sequestrants (lower enterohepatic circulation, thus promoting cholesterol secretion/elimination) and the HMG-Co-A reductase inhibitors (which block the hepatic synthesis of cholesterol)
Bile acid sequestrant Questran® (cholestyramine) can be used at 1-2 gm bid in dogs in cases of idiopathic hypercholesterolemia