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

VI. Diagnostic Laboratory Methods for the Evaluation of Neuromuscular Disorders
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correlates with the evidence that type 1 and type 2a myofibers
are activated first and their metabolic orientation is
toward aerobic pathways. With workloads approaching
maximal O 2 utilization and beyond, the sources of energy
are derived principally from anaerobic pathways through
glyco(geno)lysis. Type 2x (IIB) myofibers are recruited
with increased workload intensities, and their metabolic
energy derivation is mainly by anaerobic pathways.
VI . DIAGNOSTIC LABORATORY
METHODS FOR THE EVALUATION OF
NEUROMUSCULAR DISORDERS
Neuromuscular diseases are classified, whenever possible,
as to the origin or site of the primary lesion. Myopathies
are those diseases in which the primary defect or disease
process is considered to be limited to the myofibers, and
neuropathies are those diseases of muscle that are secondary
changes resulting from defects or diseases of the neuron
(e.g., denervation).
Muscular weakness, abnormal muscle contraction,
and stiffness or muscular pain are principal clinical signs
of neuromuscular disorders. Manifestations of muscular
weakness may be functional (e.g., paresis, paralysis,
gait abnormalities, exercise-related weakness, dysphagia,
regurgitation, dyspnea, and dysphonia) or physical (e.g.,
gross atrophy, hypotrophy, hypertrophy, and skeletal deformities).
Abnormal muscle contraction may be a functional
disturbance of neuronal or muscular excitation/conduction.
Muscle pain is often the result of physical disruption of
muscle cells or sustained muscle contractions.
Instituting measures of prevention or therapy for neuromuscular
disorders depend on an accurate definition of the
functional and physical manifestations of muscle weakness/contraction/pain
and the identification of the specific
pathoanatomic motor unit component(s) involved (i.e.,
neurons in neuropathies, neuromuscular junctions in disorders
of neuromuscular transmission, or myofibers in myopathies)
and, when possible, identification of the specific
cellular dysfunctions underlying the muscular dysfunction.
The evaluation of neuromuscular disorders requires a
coordinated approach and special examinations, some of
which fall outside the scope of this chapter. This approach
involves the neurological examination and includes the signalment
(e.g., species, breed, age, sex), history (e.g., congenital
or acquired, course of the disease, exposures, and
responses to treatment), clinical findings (e.g., presence and
distribution of signs, neurological deficits, and abnormal
reflexes) and electrodiagnostic tests that involve electromyography
(EMG), and the evaluation of sensory and motor
nerve conduction velocity measurements and evoked MAPs.
Standard hematological and clinical chemistry panels are
indicated to provide general screening that would suggest
possible infectious, immune, or metabolic abnormalities.
Exercise testing may be revealing in cases of exertional
myopathies or exercise intolerance. In addition to these
evaluations, there are some more specific tests that provide
insight into the pathoanatomic involvement and in some
instances specific identification of the etiology and pathogenesis
of the muscular weakness.
A . Muscle-Specific Serum Enzyme
Determinations Used in the Diagnosis
of Neuromuscular Disorders
A valuable adjunct to the clinical diagnosis of neuromuscular
diseases has been the utilization of serum enzyme
determinations. The activities or concentrations of the
enzymes are usually low in serum or plasma because they
are normally located within healthy myofibers. Necrosis
of myofibers is a primary example of a process by which
serum activities of intracellular enzymes are elevated, and
the elevations are roughly proportional to the mass of tissue
involved. Elevations in serum enzyme activities may
also occur in association with increased cell permeability
(leakage), increased enzyme production by the parenchymal
cells, obstructions to normal enzyme excretory routes,
increased amount of enzyme-forming tissue, delayed
removal, or inactivation of enzyme ( Cornelius et al. , 1959 ;
Dawson and Fine, 1967 ).
The initial examination of a patient with muscle disorders
should always include the measurement of muscle-specific
enzyme activities. This provides immediate
information concerning the possible presence of muscle
necrosis and provides a course-grain analysis for distinguishing
between myopathies and neuropathies.
1 . Creatine Kinase
The most widely used serum enzyme determination in
neuromuscular diseases of domestic animals is creatine
kinase (CK), previously designated creatine phosphokinase
(CPK). In muscle, this enzyme provides ATP for contraction
by phosphorylation of ADP from creatine phosphate
( Fig. 15-2 ). Analysis of tissues from humans indicates that
significant CK activities are present in skeletal muscle,
myocardium, and brain, with lesser amounts in the gastrointestinal
tract, uterus, urinary bladder, kidney, and thyroid
( Dawson and Fine, 1967 ). The diversity of organs tested in
other animals is not as broad, but those tested correlate well
with these findings. The liver has negligible amounts of CK
( Dawson and Fine, 1967 ). Normal values for CK activity
vary with physical activity, restraint, age, and sex ( Anderson,
1975 ; Blackmore and Elton, 1975 ; Heffron et al. , 1976 ;
Tarrant and McVeigh, 1979 ). Intramuscular injections may
also increase CK activities because of local areas of muscle
necrosis ( Steiness et al. , 1978 ). The amount of CK liberated
following intramuscular injection of a drug depends on