Liver and Thyroid functions.

Today I am going to discuss liver function in greyhounds as well as thyroid function.

Let’s start with the liver.  The liver is an important organ in metabolism of food and drugs.  There are two main blood markers that we check for liver damage:  alanine aminotransferase (ALT) and aspartate aminotransferase (AST).  ALT is found in the liver and elevated levels are directly correlated with liver damage.  AST is found throughout the body in various cells.  AST can be elevated in hepatic injury but also for other reasons not related to the liver.

Greyhounds have elevated ALT without associated liver damage.  I was puzzled by this and could not find any data about why this would occur.   A genetic change is the most reasonable explanation of the greyhounds’ LTF abnormalities.  Again, selective breeding most likely caused this, and unlike the RBC changes that improve the greyhound’s athletic ability, this is just a side effect.

So if the greyhound has elevated ALT, is that why they cannot process drugs as quickly as non-greyhound dogs?  This is not the case.  In the livers of both humans and dogs there are enzymes called cytochrome P450 (CYP), and these are the liver’s metabolizers of drugs.  There are hundreds of these enzymes, all with different numbers.  Most if the information regarding this came from humans and has been used in dogs.  This area of study is booming and these researchers have found differences in this system between dogs and humans as well as between breeds.

Structure of the POR protein. Based on PyMOL rendering of PDB 1amo. Credit: Emw is licensed under CC-BY-SA 3.0

In particular the greyhounds CYP system is atypical from other dogs.  I am sure that you know greyhounds have issues with anesthesia and the anesthesia they receive should be different than other non-greyhound dogs.  This was originally thought to be from the lack of body fat in greyhounds.  This was found to be less likely after a series of studies looked at drug metabolism.  These studies found that if greyhounds were given a CYP inducer like phenobarbital, they could clear anesthesia agents more quickly; conversely, if a CYP inhibitor (chloramphenicol) was given prior to anesthesia, it would take longer for the drug to be cleared.  This points directly to the CYP system as the cause of delayed drug clearance and not the lack of body fat in the hound.

To sum it up, the changes in the liver enzymes seen in greyhounds does not cause the issues with drug metabolism in the greyhound.  However, the CPY system within the greyhound’s liver is unique and creates the changes in drug metabolism.

Now we have a better understanding of the liver function abnormalities seen in greyhounds, let’s talk about the thyroid valves.

There are four common thyroid tests completed when checking for disease in the thyroid.  They are total T4, free T4, T3, and thyroid stimulating hormone (TSH).  TSH is controlled by the pituitary gland in the brain; it controls the thyroid gland’s production of T3 and T4.  Thus, when TSH is elevated it means that there is not enough T4 or T3, and when the TSH is low it means that there is too much T4 or T3.  TSH and T3 play a large role in the diagnosis of hypothyroidism.  T3 is often more important in hyperthyroidism, as there is less of it made in the thyroid and oftentimes takes longer to become abnormal.

Greyhound’s T4 is oftentimes abnormally low; this has been well documented.  It is important to note that current racers or right-off-the-track retired racers have even lower T4 then non-racing greyhounds.

This posed the question about hypothyroidism in these dogs.  There was a study that gave greyhounds with low T4 synthetic thyroid stimulating hormone.  In a mammal with true hypothyroidism this should have elevated the T4, but this did not occur.

This furthered the idea that greyhounds have baseline low thyroid levels and prompted an additional study.  In this study a radioactive tracer was used to evaluate the thyroid function in greyhounds suspected of hypothyroidism.  The uptake of the tracer was within normal limits compared against dogs with normal thyroid function.  This indicated that hypothyroidism is extremely unlikely in greyhounds.

Greyhounds are different from other dogs for various reasons.  These variations in their lab values should be evaluated by someone who has experience with greyhounds.

I hope this series was helpful and you are more informed about why greyhounds’ lab valves are different from non-greyhound dogs.

 

Court, M. H. (2013). Canine cytochrome P450 (CYP) pharmacogenetics. The Veterinary Clinics of North America. Small Animal Practice43(5), 1027–1038. http://doi.org/10.1016/j.cvsm.2013.05.001
Zaldívar-López, S., Marín, L. M., Iazbik, M. C., Westendorf-Stingle, N., Hensley, S., & Couto, C. G. (2011). Clinical pathology of Greyhounds and other sighthounds. Veterinary Clinical Pathology / American Society for Veterinary Clinical Pathology40(4), 10.1111/j.1939–165X.2011.00360.x. http://doi.org/10.1111/j.1939-165X.2011.00360.x

WBCs and platelets in greyhounds

We discussed the differences in greyhound RBCs and non-greyhound RBCs.  There are two other types of blood cells that are different in greyhounds vs. non-greyhound dogs, the White Blood Cell (WBC) and the platelet. 

RBCs, WBCs, and platelets are made in the bone marrow.  After they are mature they are sent into the blood stream.  As discussed previously, the RBC carries oxygen to the tissues.  The WBC’s job is more complex; lets look at it first. 

WBCs are immune cells.  They fight off viral, bacterial, parasitic, and fungal infections.  This is an important job, and there are multiple cells types and they each specialize on a certain intruder. 

I am going to break down WBCs cells lines as simply as possible.  I want this to be easy to understand for everyone!  If there are any questions please comment or email and I will be happy to address this further. 

There are five main types of WBCs.  Some of them are granulated and have a nucleus or control center (RBCs do not have this).  These granulations are particularly important.  The granules are enzymes within the cell that improve cellular function—i.e. they are the marinade on the foreign evader the WBC is going to destroy.  These are the types of WBCs found in the body:

1.     Neutrophils: most numerous WBC.  Nucleated and have granules.  Responsible for ridding the body of bacterial and fungal infections.

2.     Eosinophils: nucleated with granules.  Responsible for ridding the body of parasites.  Assist in allergic reactions.  Help destroy cancer cells. 

3.     Basophils: nucleated with granules.  Basophils control the histamine response in inflammation.

4.     Lymphocytes: Multiple subsets (T and B cells) of the lymphocyte—complex cell with very important functions.  Some subsets have granules others do not.  All have nuclei.  Help the body rid itself of viral and bacterial invaders and also create memory cells so that when the same infection enters the body again, it will be prepared. 

5.     Monocytes: nucleated without granules.  They have longer lives than the other WBCs.  When mature they migrate to the tissues and organs and hang out there to take care of any potential bacterial evaders. 

With all of this complexity it is hard to believe the immune system does not go haywire more often!

Now lets look at the differences in greyhound labs values vs. non-greyhound dogs. Lower WBC counts are often seen in greyhounds.  This has been well defined and is currently not a point of concern, as it is considered a breed trait.  The eosinophil of the greyhound has been widely studied.  Beginning in the 1960s the greyhound was discovered to have a vacuolated eosinophil, meaning that the granules within the cell would not stain for microscopic examination (FYI staining is a method of putting a dye into cells allowing them to be better evaluated by microscope).  This was odd, as non-greyhound dogs’ eosinophils will stain orange with a quick stain method.  The lack of the staining was concerning, as it appeared to be a toxic cell.  The concern for abnormalities prompted large work-ups looking for a source of the inflammation.  Fortunately, these changes were not pathologic.  This prompted more studies.  In 2005, there was a study published in Veterinarian Clinical Pathology.  This study looked a 49 greyhound blood smears and compared them to 200 non-greyhound dog blood smears.  A more advanced staining method was used than in the 1960’s study.  This study showed that structurally and chemically, the greyhound’s eosinophil was the same as the non-greyhound dogs.  This suggests that there were different staining properties in the greyhound eosinophil but overall it was the same cell seen in non-greyhound dogs.  The cell was deemed not pathologic.

In addition to the changes in the WBC there are also changes in the platelet counts of greyhounds.  First things first, what is a platelet? Platelets are tiny blood cells that are made in the bone marrow with RBCs and WBCs.  They are responsible for blood clotting.  

Greyhounds are known to have low platelet levels.  This is considered to be a breed trait as long as the count is not below 100,000/μL.  Again, I ask why is the greyhound’s platelet different from non-greyhound dogs?  Well there are multiple theories about this.  The first came about in 1994 by PS Sullivan.  This theory has been supported multiple times since and focuses on stem cell competition.  Do you remember the RBCs we talked about a few days ago?  Well, Sullivan posited that when the bone marrow begins creating the building blocks of blood, there is a competition between the cells destined to be platelets and the cells destined to be RBCs.  Due to the need for more RBCs in the greyhound, the poor platelets lose this fight—leading to lower platelet counts.  Another theory focuses on the mature RBCs—due to the amount of oxygen molecules on the RBC, there is a mild loss of oxygen overall when the RBCs release the oxygen into the tissues, and this mild hypoxemia causes an increase in the production of RBCs, thus causing a decreased production of platelets—remember these cells are in competition.  Both of these studies show that the competition between the RBC and the platelet either in the blood or the bone marrow is most likely why greyhounds have lower platelet counts. 

Naturally one would think that greyhounds would be “easy bleeders” due to their low platelet counts.  Well, they are “easy bleeders” but it is not due to the lack of platelets.  Actually, the time it takes for a greyhound to create a platelet plug or the “closing time” is very similar to non-greyhound dogs.  This suggests that greyhounds’ platelets are more active than non-greyhound dogs.  These researchers also looked at the risk for bleeding disorders in greyhounds, but this was very rare and not related to their “easy bleeding” tendencies.  However, the clot strength in the greyhound was weaker than non-greyhound dogs—this most likely is the cause of the “easy bleeding” in greyhounds.  

So why would the greyhound be able to clot quickly with a low platelet count but then create a substandard clot? Aging that points back to the high level of RBCs in the blood.  Due to the high RBC mass in the blood, the plasma (fluid in the bloodstream after removal of RBCs, WBCs, and Platelets) has less Fibrinogen (a protein that aids in clotting).  This is the confusing part; there is actually no difference in the fibrinogen levels in greyhounds vs. non-greyhounds.  The mass of the RBCs within the blood is to blame for the pseudo hypofibrinogenemia.  Additionally, it is thought that greyhounds have enhanced fibrinolysis (the ability to break down clots).  This would keep the greyhound from clotting, as they are at risk due to the increased viscosity of blood during exercise. 

Photo Credit: Cindy Frezon

 To sum up the bleeding tendency of the greyhound goes something like this: greyhounds have low platelet numbers but active platelets and these platelets create clots quickly but the clots lack stability due to low levels of fibrinogen due to elevated RBCs in the blood.  Furthermore, is has been theorized that greyhounds have active fibrinolysis and can break up clots quicker than non-greyhound dogs. 

Whew! Now we have looked at the RBCs, WBCs, Platelets, and hemostasis in the greyhound.  It has been great for be to learn more about this.  I now have an understanding of why these levels are different from non-greyhound dogs and I think this adds to the undeniable coolness of the greyhound! The last series on labs will be next week and it will focus on liver and thyroid functions.  Hope you check it out!  

Iazbik MC, Couto CG. Morphologic characterization of specific granules in Greyhound eosinophils. Vet Clin Pathol. 2005; 34:140–143.
Feature image credit: Cindy Frezon
Sullivan PS, Evans HL, McDonald TP. Platelet concentration and hemoglobin function in greyhounds. J Am Vet Med Assoc. 1994; 205:838–841. [PubMed: 7829376]
Zaldívar-López, S., Marín, L. M., Iazbik, M. C., Westendorf-Stingle, N., Hensley, S., & Couto, C. G. (2011). Clinical pathology of Greyhounds and other sighthounds. Veterinary Clinical Pathology / American Society for Veterinary Clinical Pathology40(4), 10.1111/j.1939–165X.2011.00360.x. http://doi.org/10.1111/j.1939-165X.2011.00360.x

What is up with lab values and Greyhounds?

Like I have said previously, I am a nurse and a researcher.  I like to figure out why things do what they do.  When I got Jethro I was amazed by the difference in laboratory (lab) valves in greyhounds and non-greyhound dogs. 

I searched the Internet looking for studies to show why the difference existed.  I recently found a literature review that does a good job with this but it is very science driven and not accessible to most greyhound owners.

Due to the numerous differences in the greyhound and non-greyhound labs, I am going to do a lab series on the blog looking into the different abnormalities. 

Today I am going to dive into the red blood cell values of the greyhound.

First, let’s talk about the red blood cell (RBC) or erythrocyte.  The RCB is the most common cell in the body.  It is disc-like cell that looks like a jelly doughnut with the jelly squeezed out.  RBCs are important because they house hemoglobin (Hgb), which carries oxygen to the body.  Hemoglobin is a protein within the RBC.  The hemoglobin molecule accepts oxygen from the lungs and carries it throughout the body, bringing nutrient rich blood to our organs.  The hematocrit (Hct) is a measurement of the volume of RBCs in the body—this value is needed to get an accurate hemoglobin measurement.  There are two additional RBC values that are different in non-greyhounds and greyhounds.  They are the Mean corpuscular volume (MCV) and the Mean corpuscular hemoglobin (MCH).  The MCV measures the size of the RBC and the MCH measures the color of the cell. 

Adult blood smear by scooterdmu

That is very basic RBC science.  Let’s now talk about the abnormalities in the greyhound’s valves and what they could mean.  Greyhounds have higher RBC counts.  The higher RBC cases an increase in Hgb concentrations and Hct.  These higher values allow for oxygen to reached stressed muscle cells quicker.  Initially selective breeding, training, and racing were deemed the cause of these changes; however, there are additional studies looking at other possible causes.

An argument against training and racing as a cause for these changes was completed looking at Hemoglobin and Hematocrit values in 5-6 month greyhounds and 9-10 month greyhounds.  This study showed that at 5-6 month the greyhound Hbg and Hct were not much different from non-greyhound dogs and much lower than the greyhounds in the 9-10 months group.  They then looked at the 9-10 month group vs. 12-13 month greyhounds. The differences in Hgb and Hct at 9-10 months vs. 12-13 months were statically insignificant, suggesting that at 9-10 months greyhounds have adult lab valves.

Sashi at 6 months by Cindy Frezon

On the other hand, there are studies to suggest that selective breeding is the cause for these changes.  The hemoglobin molecule in the greyhound has a higher affinity for binding to oxygen.  These studies also found unique amino acids mutations on the Hgb to allow for enhanced oxygen-binding capacity. 

You may be asking, how would breeders know this and know which greyhounds to breed?  Most likely the early dogmen breed greyhounds to be hearty, fast, and recovery quickly to hunt again whenever new quarry was seen.  This need for fast recovery influenced breeding practices, meaning that these hounds that were able to recover quickly again had higher RBC counts and more efficient hemoglobin.  These factors are still considered in breeding programs today – talk to any dogman or woman and they will tell you that test-mating or selecting a breeding pair is a time-consuming task with lots of consideration.  

Darla at the Christmas Cup 2015 by Cindy Frezon

Another interesting fact about greyhound RBC valves is the lives of their RBCs.  In non-greyhound dogs, the life of the RBC is around 100 days.  In Greyhounds the life of the RBC is about 50 days.  There are multiple theories about why this is.  Some believe that greyhounds trap their RBCs in their spleen; however, there is no proof to this theory.  Another theory is that the greyhound’s immune system selectively rids its self of older cells, but again this needs to be studied further for more clarity. 

Greyhound’s blood counts also show elevated MCV or large RBCs.  This was thought to be related to elevated reticulocytes (immature RBCs) in the blood but that is not the case. The increased size is breed specific and most likely due to the higher hemoglobin content within the RBC.  This would allow for more oxygen to reach the muscles and allow for continued activity. 

I hope that after this review you have a better understand of the RBC and why it is different in the greyhound.  As I had said before greyhounds are special dogs that do special things.  I think it is fitting that their labs are special too!  Check in later this week for differences in WBCs and Platelets in greyhounds.

 
Feature Photo Credit: Cindy Frezon
Zaldívar-López, S., Marín, L. M., Iazbik, M. C., Westendorf-Stingle, N., Hensley, S., & Couto, C. G. (2011). Clinical pathology of Greyhounds and other sighthounds. Veterinary Clinical Pathology / American Society for Veterinary Clinical Pathology40(4), 10.1111/j.1939–165X.2011.00360.x. http://doi.org/10.1111/j.1939-165X.2011.00360.x