Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 12 Diagnostic Enzymology of Domestic Animals
has been most useful for the detection of canine exocrine
pancreatic insufficiency (EPI). In a group of 25 dogs with
EPI, serum cTLI concentrations were all less than 1.9 μg/l
(reference interval 5.2–34μ g/l), resulting in a test sensitivity
of 100% ( Williams and Batt, 1988 ). In 50 dogs with
small intestinal disease, there was no difference in the cTLI
values from normal dogs, suggesting a specificity of 100%.
The high degree of sensitivity and specificity of cTLI for the
diagnosis of EPI is supported by a more recent study ( Steiner
et al. , 2006 ). Hence, cTLI has become the gold standard for
the diagnosis of EPI in dogs. Serum cTLI may also increase
in acute pancreatitis, as evidenced by the observation in one
study that, following pancreatic duct ligation of eight dogs,
cTLI increased within 24 h and remained increased above
control values in six of the eight for 5 days ( Simpson et al. ,
1989 ). Serum cTLI also decreased more rapidly than amylase
and lipase activity. In spontaneous pancreatitis, only
6 of 10 dogs with severe pancreatitis and 2 of 5 dogs with
mild pancreatitis had serum cTLI greater than the reference
range ( Mansfield et al. , 2003 ). Because trypsinogen is
cleared by the kidneys, decreased glomerular filtration rate
may result in increased cTLI ( Geokas et al. , 1982 ). The relative
lack of sensitivity and the historically longer turnaround
time for cTLI determination compared to serum lipase and
amylase has made cTLI of little value for determination of
pancreatitis in dogs.
When serum fTLI has been evaluated for the diagnosis
of pancreatitis in cats, the results have been variable
depending on the study. Reported reference ranges have
been variable resulting in reported sensitivities ranging
from 33% when the cutoff is 100 μ g/l to 86% when the cutoff
is 49 μ g/l ( Gerhardt et al. , 2001 ). Although specificity
was not reported in this study, an overlap in TLI values in
cats with confirmed pancreatitis and cats without pancreatitis
are reported ( Forman et al. , 2004 ; Swift et al. , 2000 ).
Increased serum fTLI concentration may be associated
with azotemia, inflammatory bowel disease, and gastrointestinal
lymphoma ( Simpson, 2001 ; Swift et al. , 2000 ).
To improve specificity, higher cutoff values must be used,
which reduces sensitivity. Even at lower sensitivity, the
fTLI concentration was considered a useful diagnostic test
in cats because clinical signs in cats are less specific and
other minimally invasive tests such as serum amylase and
lipase, ultrasonography, and contrast-enhanced computed
tomography were insensitive or of no value ( Gerhardt
et al. , 2001 ; Simpson, 2001 ; Steiner, 2003 ). However, a
more recent study has demonstrated a higher sensitivity
of fPLI (67%) in the diagnosis of feline pancreatitis along
with a higher specificity, suggesting that fPLI may supplant
determination of fTLI in the diagnosis of pancreatitis
in cats ( Forman et al. , 2004 ).
Although fewer data are available compared to that for
dogs, there is evidence that determination of fTLI concentration
is useful for the diagnosis of EPI in cats as well.
Of 20 cats with f TLI of 8 μ g/l (controls 17–49 μ g/l),
17 had compelling evidence of EPI ( Steiner and Williams,
2000 ).
J . Creatine Kinase
Creatine kinase (CK) (EC 2.7.3.2) catalyzes the exchange
of a phosphate moiety between creatine phosphate and
ATP. In myocardial and skeletal muscle, CK allows energy
storage as creatine phosphate when demand is low, but
when energy is needed for muscle contraction, CK catalyzes
the transfer of the high-energy phosphate from creatine
phosphate to ADP to form ATP. A small amount of
CK activity is associated with the mitochondria, where it
is responsible for transfer of high-energy phosphate to creatine,
the cytosolic carrier.
The greatest amount of data for CK in domestic species
is available for dogs, as this species has often been used as
an experimental model for myocardial disease in humans.
Canine CK is reviewed in depth elsewhere ( Aktas et al. ,
1993 ).
CK activity is in greatest concentration in skeletal
muscle followed by heart muscle, diaphragm and smooth
muscle, and then brain ( Keller, 1981 ). In most species,
the amount of activity is two- to four-fold greater in skeletal
muscle than heart muscle, although in cats it is nearly
equal ( Boyd, 1983 ). The CK activity in brain tissue is
approximately 10% of that in skeletal muscle. CK is primarily
found in the cytoplasm; however, there is a mitochondrial
form that makes up a small percentage of the
total CK activity of the cell. There is evidence of breed
differences, with higher skeletal muscle CK activity in
greyhounds than mongrels and more CK activity in fastacting
than in slow-twitch muscles ( Guy and Snow, 1981 ;
Lindena et al. , 1982 ).
There are two distinct subunits of CK, referred to as the
M (muscle) and B (brain) subunits. These combine randomly
to form three isoenzymes of CK: CK-MM, CK-BB,
and CK-MB. Skeletal muscle of most species has nearly
100% CK-MM ( Aktas et al. , 1993 ; Boyd, 1983 ). Heart
muscle has primarily CK-MM, and a variable amount of
CK-MB, with dogs and horses having approximately 3%
and 10% CK-MB, respectively. The brain has primarily
CK-BB with a small percentage of CK-MB and CK-MM.
In dogs, intestine and spleen have predominantly CK-BB,
followed by CK-MB and then CK-MM. The normal distribution
of serum CK isoenzymes in dogs is approximately
50% CK-MM and 40% CK-BB with the remaining being
CK-MB ( Aktas et al. , 1993 ). Although CK isoenzyme analysis
is of great importance in human medicine as an indicator
of myocardial infarction, the need for CK isoenzyme
analysis in veterinary species has not been demonstrated.
However, experimentally induced left ventricular hypertrophy
in dogs resulted in a 50% reduction in CK-MM
and a 10-fold increase in CK-MB ( Ye et al. , 2001 ).