Laboratory Testing for the Exocrine Pancreas

Chapter 135

Laboratory Testing for the Exocrine Pancreas

Diseases of the exocrine pancreas are important and occur frequently in dogs and cats. Recent studies that established a far higher prevalence of exocrine pancreatic disease in both species than was estimated about 30 years ago suggest that exocrine pancreatic disease in general, and more specifically pancreatitis, have long been underdiagnosed in both species. Because of the relative inaccessibility of the pancreas, the diagnosis of exocrine pancreatic disease can pose a challenge and requires a combination of patient history, thorough clinical examination, evaluation of biochemical markers that are highly sensitive and specific for exocrine pancreatic disease, and the use of diagnostic imaging techniques.

Laboratory Tests for Pancreatitis

Pancreatitis is a common and important disease in dogs and cats; antemortem diagnosis of pancreatitis can be challenging. Depending on the severity, patients may or may not exhibit classical clinical signs, nonspecific signs, or signs of severe systemic complications. Particularly cats often show only mild clinical signs that can be masked by other disease processes commonly associated with feline chronic pancreatitis (i.e., cholangitis and or inflammatory bowel disease). Thus the diagnosis of pancreatitis can be elusive, and probably a significant number of especially mild or subclinical cases remain undiagnosed.

Clinical pathology findings (e.g., leukocytosis or leukopenia, hyper- or hypoglycemia, hypocalcemia and hypophosphatemia, increased liver enzyme activities, hypercholesterolemia) are seen commonly but are nonspecific and do not help to arrive at a diagnosis of pancreatitis. However, routine blood work is essential to rule out major differential diagnoses and to assess the patient with pancreatitis for systemic complications. Abdominal radiography is not useful for diagnosing patients with pancreatitis but, like routine laboratory data, abdominal radiographs are important in ruling out other differential diagnoses. Abdominal ultrasonography can be useful for diagnosing pancreatitis, but stringent diagnostic criteria are crucial (see Chapter 137).

For many years, serum amylase activity alone or in combination with serum lipase activity was used as an indicator for acute pancreatic acinar cell damage and biomarker for pancreatitis. Today more sensitive and specific laboratory tests for diagnosing pancreatitis, most importantly pancreatic lipase immunoreactivity (Spec cPL, Spec fPL), are available.

Other tests that have been evaluated for the diagnosis of pancreatitis include systemic and urinary concentrations of trypsinogen-activation peptide (TAP), a by-product of the activation of trypsinogen that is undetectable in the circulation unless trypsinogen is activated prematurely within the pancreas because of pancreatitis. However, TAP is not clinically useful for the diagnosis of pancreatitis in dogs and cats. The concentration of serum trypsin-alpha1-proteinase inhibitor (α1PI) complex, derived from prematurely activated trypsin leaking from the inflamed pancreas and scavenged by α1PI, and serum α2-macroglobulin as a scavenger for prematurely activated trypsin are also not useful for the diagnosis of pancreatitis. Serum C-reactive protein (CRP), an acute-phase protein, has been measured in dogs with acute pancreatitis. Because CRP is not specific for the pancreas and may increase with any inflammatory disease, infection, or trauma, CRP is not useful to diagnose pancreatitis but may be useful as a marker of disease severity.

Serum Amylase and Lipase Activities

Amylase and lipase are digestive enzymes produced by pancreatic acinar cells. Damage to these cells as occurs with pancreatic necrosis and inflammation during pancreatitis leads to increased amounts of both enzymes in the systemic circulation. Because many different lipases and amylases originate from a wide range of tissues, their activities that are measured by catalytic assays are not pancreas specific. An increased serum amylase activity can be found in patients with conditions other than pancreatitis; conversely, a normal serum amylase activity does not rule out pancreatitis. Similarly, the sensitivity and specificity of serum lipase activity for canine pancreatitis are low. To be suggestive of pancreatitis in dogs, serum amylase or lipase activities must be increased at least threefold to fivefold above the upper limit of the reference range, but both are of low diagnostic value. In cats, serum amylase and lipase activities have a very low sensitivity for pancreatitis and thus are of no diagnostic value in this species.

Serum Trypsin-like Immunoreactivity

Assays for serum trypsin-like immunoreactivity (TLI) measure cationic trypsinogen, trypsin (if present), and some trypsin molecules complexed with proteinase inhibitors. Serum TLI reflects the amount of functional pancreatic tissue present and is highly sensitive and specific for the diagnosis of exocrine pancreatic insufficiency (see later) but lacks sensitivity in the diagnosis of pancreatitis in dogs and cats.

Increased serum TLI concentrations can be measured in dogs and cats with pancreatitis, presumably because of leakage of trypsinogen and prematurely activated trypsin from the inflamed pancreas. However, the half-life of TLI in serum is thought to be very short, and a significant degree of inflammation is required for serum TLI concentrations to be increased. In dogs, the sensitivity and specificity of serum cTLI concentration for pancreatitis have been reported as less than 40% and 65% to 100%, respectively. In cats, serum fTLI concentration appears to be more useful clinically, but the increase of serum fTLI above the diagnostic cutoff value used for pancreatitis was of much shorter duration than that of serum fPLI in mild experimentally induced feline pancreatitis. The sensitivity and specificity of serum fTLI concentration for the diagnosis of pancreatitis in cats range between 33% and 86% and 56% and 90%, respectively. TLI also may be increased in patients with renal failure, and thus a serum chemistry profile and urinalysis should be performed to rule out renal disease if the serum TLI concentration is increased. With the availability of newer, more sensitive and specific diagnostic tests (Spec cPL and Spec fPL), serum TLI concentration should no longer be employed for the diagnosis of pancreatitis in either species.

Serum Pancreatic Lipase Immunoreactivity

In contrast to serum lipase activity, immunoassays for pancreatic lipase immunoreactivity (PLI) measure lipase that originates exclusively from the exocrine pancreas. Increased amounts of pancreatic lipase escape into the systemic circulation during pancreatic inflammation and necrosis and can be measured using species-specific immunoassays.

Sensitivities of 82% to 94% have been reported for the diagnosis of clinically significant pancreatitis by serum cPLI concentration. In a study that evaluated the sensitivity of various serum markers in dogs with less severe pancreatitis, measurement of serum cPLI concentration showed the highest sensitivity of any diagnostic test evaluated with 64% (Steiner et al, 2008). However, a single measurement of cPLI in serum cannot predict the histopathologic severity of pancreatitis. In cats, sensitivities of serum fPLI for diagnosing patients with pancreatitis range from 54 (subclinical or mild disease) to 100% (moderate to severe pancreatitis). Unlike serum fTLI, serum fPLI was increased persistently in cats with experimentally induced pancreatitis, presumably because of a delayed renal elimination of the larger negatively charged protein measured.

Measurement of serum PLI is a practical test that requires a serum sample after withholding food for 8 to 12 hours. Commercially available tests that measure PLI in dogs (Spec cPL) and cats (Spec fPL) are reported to perform similarly to the originally developed assays. Concentrations of at least 400 µg/L (Spec cPL) in dogs and at least 5.4 µg/L (Spec fPL) in cats are consistent with a diagnosis of pancreatitis. Equivocal test results (Spec cPL: 201 to 399 µg/L; Spec fPL: 3.6 to 5.3 µg/L) require further evaluation of the patient or repeated testing. Recently, patient side tests (SNAP cPL and SNAP fPL) for use in the clinic have been introduced. In these tests, a color intensity of the sample spot that is lighter than the reference spot indicates that pancreatitis is very unlikely and other differential diagnoses should be considered. In contrast, a sample spot that is equal to or darker than the reference spot indicates an abnormal cPL or fPL concentration, suggesting pancreatitis. As a positive SNAP cPL/SNAP fPL indicates a Spec cPL/Spec fPL in the equivocal or diagnostic range for pancreatitis, Spec cPL/Spec fPL should be measured to verify the diagnosis of pancreatitis and to obtain a baseline concentration that then can be used to monitor the progression of disease in the patient.

Studies in dogs and cats with induced chronic renal failure (CRF) suggest that serum cPLI and fPLI can be used as diagnostic tests in patients with CRF because serum PLI is either not affected or only minimally affected. Also serum cPLI was not affected by long-term administration of prednisone (Steiner et al, 2009). Serum PLI is specific for the exocrine pancreas and is the most sensitive serum test that currently is available for the diagnosis of pancreatitis in dogs and cats. However, as for other diseases, the integration of all clinically available data, especially abdominal ultrasonography and serum PLI, are expected to yield the best diagnostic accuracy.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Laboratory Testing for the Exocrine Pancreas

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