CK is a "leakage" enzyme present in high concentration in the cytoplasm of myocytes and is the most widely used enzyme for evaluation of neuromuscular disease. In muscles, this enzyme functions by making ATP available for contraction by the phosphorylation of ADP from creatine phosphate by catalyzing the reversible phosphorylation of creatine by ATP to form phosphocreatine + ADP. Phosphocreatine is the major storage form of high energy phosphate in muscle. It is a dimeric molecule composed of two types of monomers, the M and B subunits. Routine assay measures total CK activity. Isoenzymes may be quantitated by electrophoretic or immunologic methods, but this is not commonly done in clinical veterinary medicine due to the infrequency of cardiac disease in domestic animals. In human beings, CK isoenzyme determination is being replaced by assay of more specific cardiac markers, such as cardiac troponin. There are four principle isoenzymes of CK:
- CK-1: BB isoenzyme, found mostly in the brain. Injury to brain tissue may increase CK-1 activity in CSF, but rarely results in raised total serum CK activity.
- CK-2: MB isoenzyme, highest concentration in cardiac muscle, with lesser amounts in skeletal muscle.
- CK-3: MM isoenzyme, found in skeletal muscle, with lesser amounts in cardiac muscle. This isoenzyme accounts for increased activity in most cases with raised total CK activity in animals.
- CK-Mt: Found in mitochondrial membranes, and comprises 15% of total cardiac CK activity.
CK has a very short half life, < 1 hour in horses. Activity increases quickly
(peaks at 6-12 hours) and returns to normal within 24-48 hours after
acute, transient muscle injury. Persistent or ongoing muscle injury
will maintain high CK concentrations. In contrast, AST (which has a
longer half-life) will increase more gradually after muscle injury and
stays elevated for a longer period of time than CK (see graph below).
CK activity is stable for 7 days at 4 C and 1 month at -25 C.
Causes of increased CK
|Figure reproduced with permission
from: Skeletal muscle function by Cardinet GH III in "Clinical
Biochemistry of Domestic Animals", 5th edition, Kaneko et
al, eds, pg 426, 1997; Copyright Elsevier.
- Artifact: Hemolysis will increase CK values as analytes in red blood cells (ADP or G-6-P) or their membranes (adenylate kinase) contribute to the enzymatic reaction for CK, artifactually increasing values. Inadvertant penetration of muscle during venipuncture
can cause 3- to 4-fold increases in CK activity in the sample and is a common cause of mildly increased CK values in healthy (or sick) animals.
- Physiologic: CK values in young puppies are higher than in adults. Moderate increases (2-3x) are possible in exercising horses. Post exercise increase is less in well conditioned animals although the baseline level is somewhat higher. Intramuscular injections will increase CK values (2-3x), dependent on the drug, muscle binding of drug, local blood flow. CK will especially increase if the injected compound is an irritant (e.g. tetracyclines).
- Muscle disease: Detection of increased activity in serum is useful as an indicator of muscle injury. The
assay is quite sensitive in this regard, but elevations are not specific as to cause
(e.g., trauma, inflammation, degeneration). High CK values are observed in inherited muscular dystrophies, exercise-induced rhabdomyolysis, polymyositis, vitamin E-selenium deficiency, snake bite poisoning, etc.
- Miscellaneous: Critically ill anorectic cats often have high CKs (median CK in one study was 2,500 U/L). The exact mechanism is uncertain, but it is thought to be due to increased muscle catabolism or membrane permeability.
Note that animals which are recumbent ("downer" cows or post-surgical patients) will have high CK values (up to 10 x normal) from muscle injury or ischemia. Similarly, horses and cattle after shipping have moderate increases in CK activity.