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Creatine Kinase in Veterinary Medicine

Creatine kinase (CK) is an analyte that is highly prevalent in skeletal muscle.
Creatine kinase (CK) is an analyte that is highly prevalent in skeletal muscle.
September 2, 2022

A long-term wild turkey patient of yours presents due to acute onset ataxia and profound lethargy. Initially you worry about neurologic disease or infectious disease. However, during her physical exam you identify severe hyperthermia, pelvic limb paresis, and tachypnea. You've provided supportive care (sedation, fluids, external cooling) and obtained a blood sample for a serum chemistry.

You see that the CK is past the readable level of the chemistry analyzer, AST is supremely high, and uric acid (UA) is twice the upper limit of normal. Based on the patient's presentation and chemistry results, your top differential diagnosis is rhabdomyolysis.

How would you interpret the analytes present in this situation?

In our previous article, we reviewed AST and the difficulty of interpretation by itself due to the analyte's presence in many tissues. We decided that CK would be our second analyte to discuss since like AST, it is included in all of our chemistry panels and can be a helpful diagnostics tool when interpreted in context of other analytes like AST.

Since we already discussed how CK is used to determine if elevations in AST are of muscular or hepatic origin, here we discuss how CK can act as a sole indicator of diseases resulting in muscle damage.

As specific as it gets

CK, also known as creatine kinase, is one of the most organ-specific enzymes in the body.

CK is mostly found in skeletal muscle, cardiac muscle, and brain tissue, and it is considered an isoenzyme composed of three components: CK-BB (brain), CK-MB (heart), and CK-MM (muscles).

In most animals, the majority of CK activity is made up of CK-MM, then CK-BB, with CK-MB being of little influence.

Decreased CK levels are not clinically significant. However, increases in serum concentration  of CK are of importance and are a very sensitive indicator of striated muscle damage.1

Species variations

Although the CK enzyme is quite organ specific, species variations still exist. Therefore, careful consideration must be applied when evaluating the meaning of creatine kinase activity while working with various animals.

CK variation for reptiles

Snakes follow the mammal paradigm as large amounts of CK are found within myocytes and will increase with prolonged restraint or any other disease that results in increased catabolism.

Anecdotally, serum concentration of CK has been noted to increase with gastrointestinal disease in snakes.

In species that hibernate, CK levels are seen to significantly decrease.3

CK variation for birds

Birds are unique in that along with CK being identified in striated muscle, it is also found in the smooth muscle of the GI tract.

CK in birds will normalize in 72-96 hours after muscle injuries cease.

A study performed in red-tailed hawks reviewed the influence of exercise (flight) on CK levels where levels peaked 24 hours after activity and normalized within 48 hours.

Therefore, in flight trained red tailed hawks, a higher CK (1000mg/dL) may be considered normal within 24 hours of flight exercise.6

CK variation in mammals

The normal CK activity in dogs decreases with age, therefore normal activity in the serum in a puppy will be much higher than in an adult dog.1 At the same time, muscle disease in all dogs could be observed with persistent increases in CK.

Interestingly, CK serum concentrations will always be higher than plasma CK due to the release of CK from platelets during clot formation.1 CK in dogs with muscle damage normalizes within 72 hours of muscle injury abatement. Increases in CK have been seen in rabbits with handling, and often this elevation is accompanied by AST and LDH. 2,7

CK half-life

In addition to CK being organ-specific, there are also species-specific variations in half-life.4,8,9 Therefore, the time of diagnosis is another factor to consider when using CK as a part of evaluating a patient's health.

The known half-life of this analyte (in vivo) is depicted below for the following animals:

It is important to note that CK should decrease by half, but not necessarily normalize within these time periods. Depending on the species normalization of the value can take 2-3 days after the injury to the muscle has ceased. Values will remain elevated if injury still persists.

How to approach CK

So, what does all of this mean for our wild turkey above?

Since CK is very specific to striated muscle in the body, interpretation is relatively straightforward.

In exotic species like the wild turkey, rhabdomyolysis (capture myopathy) is of significant concern during immobilization for physical examination. Severely elevated CK along with AST are commonly identified and indicate significant muscle injury. The muscle tissue damage produces breakdown products directly affecting renal function resulting in elevations of blood urea nitrogen and creatinine or uric acid depending on the species.

In our wild turkey patient, CK, AST, and UA were highly abnormal. Despite aggressive supportive care, rhabdomyolysis often has a grave prognosis, no matter the species.

In companion species, remember that age can play a part in what is normal for that species. It's also important to note that CK elevations are of clinical significance whereas low values are not.

CK testing methodology

The International Federation of Clinical Chemistry (IFCC) recommends measuring CK via the catalytic concentration of the enzyme.10 The rate of increase of absorbance is directly proportional to the activity of CK in the sample.10

Analyte interferences

For optimal stability, CK specimens should be protected from light whenever possible. CK values will be falsely elevated with the presence of hemolysis. Care should be taken during the phlebotomy event and shipping to avoid hemolysis in blood cells. Plasma samples may occasionally produce unpredictable rate reactions resulting in false low results.10

Next month’s analyte

Next month we will review BUN (Blood Urea Nitrogen) in more detail. We're also working on producing a pocket reference document with analyte information for each species, so stay tuned for that downloadable document coming soon.

See what analytes we test for in our chemistry profiles

Learn more about CK and other analyte testing with Moichor here.  

References

1. Chapman SE. Duncan & Prasse’s Veterinary Laboratory Medicine: Clinical Pathology, 5th EditionEditor: KennethS. LatimerPublisher: Wiley-Blackwell, Ames IA, ISBN: 978-0-8138-2014-9hardcover: 524 pages, 2011,Veterinary Clinical Pathology. 2013;42(2):246-246. doi:10.1111/vcp.12042

2. Jill Heatley J, Russell KE. Exotic Animal Laboratory Diagnosis. John Wiley & Sons; 2020.

3. Oguni. Mader’s reptile and amphibian medicine and surgery: Stephen J. Divers and Scott Stahl, eds. Elsevier; 2019, 1511 pages. J Exot Pet Med.

4. Divers S. , Stahl S.  Mader’s reptile and amphibian medicine and surgery: Stephen J. Divers and Scott Stahl, eds. Elsevier; 2019, 1511 pages. J Exot Pet Med

5. Speer B. Current Therapy in Avian Medicine and Surgery. Elsevier Health Sciences; 2015.

6. Knuth’ ST, Chaplin SB. THE EFFECT OF EXERCISE ON PLASMA ACTIVITIES OF LACTATE DEHYDROGENASE AND CREATINE KINASE IN RED-TAILED HAWKS Buteo jamaicensis). Accessed June 21, 2022. https://biostor.org/pdfproxy.php?url=https%3A%2F%2Farchive.org%2Fdownload%2Fbiostor-215636%2Fbiostor-215636.pdf

7. Quesenberry K, Mans C, Orcutt C, Carpenter JW. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. Elsevier; 2020.

8. Melillo A. Rabbit Clinical Pathology. J Exot Pet Med. 2007;16(3):135-145.

9. Ettinger SJ, Feldman EC, Cote E. Textbook of Veterinary Internal Medicine - eBook. Elsevier Health Sciences; 2017.

10. Hørder M, Elser RC, Gerhardt W, Mathieu M, Sampson EJ. International Federation of Clinical Chemistry (IFCC): Scientific Division, Committee on Enzymes. IFCC methods for the measurement of catalytic concentration of enzymes. Part 7. IFCC method for creatine kinase (ATP: creatine (N-phosphotransferase, EC 2.7.3.2). IFCC Recommendation. Journal of Automatic Chemistry. 1990;12(1):22-40. doi:10.1155/s1463924690000049

Education
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/

Creatine Kinase in Veterinary Medicine

Creatine kinase (CK) can be used to determine if elevations in AST are of muscular or hepatic origin, and in this article we discuss how CK can act as a sole indicator of diseases resulting in muscle damage.

September 2, 2022
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