Page 938 - Small Animal Internal Medicine, 6th Edition

910 PART VII Metabolic and Electrolyte Disorders

downregulates the hepatic LDL receptor, which increases the hypertriglyceridemia (levels exceeding 1000 mg/dL) has
concentration of circulating LDL and HDL cholesterol–rich been associated with insulin resistance, pancreatitis, lipemia
VetBooks.ir particles. retinalis, seizures, cutaneous xanthomas, peripheral nerve
Insulin deficiency (diabetes mellitus) reduces the produc-
paralysis, and behavioral changes. Cutaneous xanthomas,
tion of lipoprotein lipase, which contributes to decreased
are the most common manifestation of hypertriglyceride-
clearance of triglyceride-rich lipoproteins. Furthermore, which represent lipid-laden macrophages and foam cells,
insulin deficiency activates HSL, causing the release of large mia in the cat. Severe hypercholesterolemia has been asso-
quantities of free fatty acids into the blood. These free fatty ciated with arcus lipoides corneae, lipemia retinalis, and
acids are ultimately converted by the liver into triglycerides, atherosclerosis (not severe enough to cause myocardial
packaged into VLDL particles, and secreted back into the infarction).
circulation. Therefore the hypertriglyceridemia seen with In addition to the clinical manifestations, hypertriglyceri-
diabetes mellitus is attributed to both reduction of lipopro- demia may interfere with the results of several routine bio-
tein lipase and increased production and decreased clear- chemical tests (Table 52.2). The degree of interference
ance of VLDL particles. Insulin deficiency increases the depends on the specific assay used by the laboratory, the
synthesis of cholesterol in the liver. The increased intra- species (canine versus feline), and the severity of the hyper-
hepatic cholesterol concentration downregulates the hepato- triglyceridemia. In addition, hyperlipidemia may cause
cyte LDL receptor, consequently reducing the clearance of hemolysis, which in turn can interfere with the results of
circulating LDL and HDL particles, which in turn causes some biochemical assays. Alternatively, hyperbilirubinemia
hypercholesterolemia. may cause the cholesterol concentration to be falsely lower.
The mechanism of hypertriglyceridemia associated with These potential alterations in biochemical data must be con-
hyperadrenocorticism is probably due to stimulation of HSL sidered when results of testing in animals with hyperlipid-
with release of free fatty acids into the circulation. Similar to emia are interpreted. Fortunately, many laboratories will
the situation with diabetes mellitus, excess free fatty acids are attempt to clear the hypertriglyceridemia by ultracentrifuga-
converted into VLDL particles. In addition, glucocorticoids tion before performing biochemical assays.
inhibit lipoprotein lipase activity, thereby reducing the clear-
ance of triglyceride-rich lipoproteins. Diagnosis
The presence of grossly lipemic serum suggests that the
Clinical Features animal is hypertriglyceridemic. Lactescence refers to the
Waxing-and-waning vomiting, diarrhea, and abdominal opaque, milk-like appearance of serum samples that occurs
discomfort are the most common clinical presentations with sufficiently severe elevation of the triglyceride concen-
associated with hypertriglyceridemia (Table 52.1). Severe tration. Animals with lactescent serum typically have triglyc-
eride concentrations that exceed 1000 mg/dL; samples with
a less opaque character than that of nonfat milk may corre-
TABLE 52.1 spond to elevated lipid content but visual inspection is not a
reliable indicator of severity. Conversely, animals that are
Clinical Signs and Potential Consequences of purely hypercholesterolemic do not exhibit lipemic or lactes-
Hypertriglyceridemia and Hypercholesterolemia cent serum because the cholesterol-rich LDL and HDL par-
ticles are too small to refract light. Blood samples to confirm
HYPERTRIGLYCERIDEMIA HYPERTRIGLYCERIDEMIA
CLINICAL SIGNS CONSEQUENCES hyperlipidemia should be obtained after a fast of at least 12
hours. A serum sample rather than whole blood or plasma
Seizures Seizures should be submitted for assessment. The sample can be
Blindness Pancreatitis refrigerated or frozen for several days with no effect on the
Abdominal pain Lipid-laden aqueous humor: assays. When assessing the sample for hypertriglyceridemia,
Anorexia uveitis, blindness the technician should not clear the sample before determin-
Vomiting Lipemia retinalis ing the triglyceride concentration. Clearing lipemic samples
Diarrhea Xanthomas by centrifugation removes chylomicrons, and this will artifi-
Behavioral changes cially lower the triglyceride result. Reference intervals for
Lipemia retinalis
Uveitis serum triglyceride concentration are typically 50 to 150 mg/
dL for the adult dog and 20 to 110 mg/dL for the adult cat.
HYPERCHOLESTEROLEMIA HYPERCHOLESTEROLEMIA Reference intervals for serum cholesterol concentration are
CLINICAL SIGNS CONSEQUENCES typically 125 to 300 mg/dL for the adult dog and 95 to
130 mg/dL for the adult cat.
Xanthoma formation Corneal arcus lipoides
Peripheral neuropathy Lipemia retinalis The chylomicron test can be helpful in delineating whether
Horner’s syndrome Atherosclerosis (not severe lipemia is predominantly a chylomicron or a VLDL defect.
Tibial nerve paralysis enough to cause fatal The test is performed by refrigerating a serum sample for 12
Radial nerve paralysis myocardial infarction) hours. Chylomicrons are less dense than the other particles
and hence will float to the top of the sample to form an