CIMDA

Hello everyone

As we enter the year 2023, you and your dogs are wished the very best that life can bring including; lots of walks, lots of treats and most of all lots of love and good health.

Best wishes and Happy New Year to you all.

Jo and Sheila
xx

Wishing you  and your dogs a very Merry Christmas and a happy and healthy New Year.

Stay safe!

All the best

Jo

The Royal Veterinary College (RVC) is calling for owners of dogs in the UK with autoimmune diseases to take part in a vital piece of new research, which aims to gather data and insight into the diagnosis, treatment response and outcomes of these dogs. This information will then be shared with local veterinary practices and specialist hospitals to help owners and vets make well-informed decisions when dogs are diagnosed with one of these conditions.


https://www.rvc.ac.uk/small-animal-vet/news/the-rvc-invites-dog-owners-to-participate-in-the-largest-study-of-autoimmune-diseases-ever-conducted

Please consider taking part if your dog is newly diagnosed with one of the specified AI diseases, and also inform your vet of this study because the more dogs that take part the more the veterinary specialists will learn about autoimmune disease.


Thank you

Jo

More information from the RVC website:

Autoimmune diseases are encountered frequently in dogs, often causing severe illnesses that require intensive hospital care and prolonged treatment with immunosuppressive medications. The RVC alone sees between 50-100 dogs with immune-mediated diseases each year, with many more never being referred for treatment at specialist hospitals. In some cases, however, treatment causes side effects that can have a negative effect on quality of life. To address the current shortage of information and aid the veterinary community, researchers at the RVC have developed a new observational study, named ImmunoRegistry.

The registry will gather information about dogs that have been recently diagnosed with an autoimmune disease, following them in real-time over a one-year period to find out how they respond to treatment. Once enrolled, owners and vets will be contacted at regular intervals using emailed questionnaires to ask for detailed updates about their dog

Hi all

What a terrible year it has been for so many people around the world.  Despite this, with or without your loved ones present, I do wish you and your dogs a very happy Christmas and we can only hope that next Christmas will be much improved.

Best wishes to you all, and to your beloved dogs.

Love
Jo
xx

Hello Everyone

I have just heard the very sad news that Prof Michael J Day has recently passed away. 

Some of you may not know of this amazing gentleman's achievements, but the links below will give you some idea of the impact that he made on the veterinary world.


https://wsava.org/wp-content/uploads/2020/05/WSAVA-Pays-Tribute-to-Emeritus-Professor-Michael-Day.pdf

https://www.vettimes.co.uk/news/tributes-paid-following-death-of-michael-day/

Personally, I am truly saddened because Prof Day's immunosuppressive drug protocol has helped so many dogs with autoimmune disease, when their own vet had no previous knowledge of such treatments, and there is no doubt that his protocol has saved many, many lives that would have been lost.  It is the best immunosuppressive protocol that I have come across.  Many years ago, I emailed Prof Day to ask if I could pass on his protocol to those who may need it, and he replied straight away giving his permission but stressing that the protocol has to be tailored to the individual.  Now, I have no veterinary qualifications and yet this amazing man acknowledged that there was a need to get this specific treatment regimen out 'there' and he gave his permission with no hesitation.  I, and many, many others, will always  be truly grateful to him.

Prof Day, along with his colleagues at the WSAVA, is also the person who brought to the attention of the veterinary world that annual vaccination was not necessary and although it was important to vaccinate, to over vaccinate is potentially doing more harm than good.   

He has achieved so much more in his short life and you can read about him in the links, but I would like to say, Thank you Professor Day for all that you have done during your career and for going over and beyond to help individuals with your knowledge,  and the veterinary profession to understand more about immunology and these terrible diseases, and most importantly how to treat theses dreadful diseases and achieve remission, so that these dogs may have the chance of a happy and healthy life. 

Rest in Peace Michael J Day, and thank you from us all.  Your loss, to us in this world, is huge.

Jo

Hi  Everyone

I just thought I should let you know about recent warnings of a carcinogenic substance that has been detected in Zantac (Ranitidine) and many countries have withdrawn the product. 

Many dogs on immunosuppressive therapy have to use a gastroprotectant and up until now Ranitidine has been very widely used.

  It may be that the Ranitidine you use for your dog  is not affected.   If you have been buying over the counter tablets, then they say these are a not a problem.  It is only the prescription tablets that may have this carcinogen.   

I thought you might like to look into this and if you are unsure, please contact your vet.

https://www.dailymail.co.uk/health/article-7554005/Heartburn-drug-Zantac-recalled-WORLDWIDE.html

If your dog needs a gastroprotectant then there are others, such as Pepcid and Omeprazole. etc


Jo

P.S.  This is also relevant to any human users of Zantac or Ranitidine.

If anyone had any doubts about whether or not to vaccinate their dog for leptospirosis, take a read of this very interesting article.

Subject: The Problem With Leptospirosis vaccines:

http://www.thedogplace.org/VACCINES/Leptomania-10052-Jordan.asp

WHAT TO EXPECT ONCE IMMUNOSUPPRESSIVE TREATMENT HAS STARTED

If a dog has a serious autoimmune disease, then the sooner treatment commences the better chance the dog has of survival.  The main delay to starting treatment is obtaining a diagnosis or at least your vet being sure that he hasn't missed anything that could be made worse by giving high doses of steroids.  Achieving a diagnosis can be a fight against time. 

If your vet has decided that in all probabilities your dog has an autoimmune disease, then to a certain extent, which autoimmune disease your dog has, as far as treatment is concerned, is irrelevant because with the exception of a few diseases, they are all treated the same, that is, with immunosuppressive drugs.  The main objective is to 'knock out' the immune system and virtually stop it from working (or near enough) so the destruction will cease and give the body a chance to recover.  As previously stated, this treatment regime works in most cases, that is, if it has been given early enough and the dosage is correct.  All dogs are different and some can tolerate the drugs better than others. In proportion to their size, small dogs seem more able to tolerate higher doses of steroids than large ones. Some diseases are more serious than others and carry a poorer prognosis. So the initial crisis is a crucial time, however anecdotal evidence shows that many more dogs survive than die if correct treatment is administered in good time.
It is hoped that a positive response can be seen within 4-6 hours of starting treatment (depending on the disease), but in a serious, life threatening situation, the first 2-7-14 days can be a very worrying time.  Assuming the dog has stabilised he will quickly feel much better, and if he is in hospital may be allowed home within a week.

When he comes home he will probably have a 'goody bag' full of drugs.  He will be on a high dose of steroid, usually prednisolone, and he may also be on another immunosuppressive drug, such as Azathioprine.  Your dog will be weaned off in a controlled manner according to his wellness and clinical observations. 

Note: High doses of steroids must not be stopped abruptly.  Your dog could go into an adrenal crisis if the medication is withdrawn too quickly.

In addition to immunosuppressive drugs he should have something to protect his stomach from excess acid.  The last thing your dog needs when he is feeling poorly is a bleeding stomach ulcer caused by the drugs.  Sometimes, Antepsin is given to coat and protect the stomach (but this must not be given within two hours of other medication otherwise it will stop the drugs from being absorbed).  Zantac (Ranitidine) may also be prescribed to take away the excess acid. Another gastroprotectant used is Omeprazole. To minimise irritation to the stomach it is usual for the daily dose of steroid to be split into two doses and given with food, one dose in the morning with breakfast and the other dose with his evening meal. I have known several dogs, who did not receive a gastroprotectant as a part of their treatment regime, and went on to develop anaemia. This is not autoimmune haemolytic anaemia but iron deficiency anaemia caused by bleeding stomach ulcers. Using a gastroprotectant is a good preventative measure. When the steroids have been significantly reduced to a low dose, a gastroprotectant may not be necessary.

Excess acid, produced because of the drugs, may make a dog prone to developing pancreatitis. A dog with pancreatitis will appear in pain and his back may be arched as if he can't straighten up.  He may be lethargic, seem bloated and have a tender abdomen. Dogs usually go off food and water, may vomit and look depressed.  If you suspect that your dog has pancreatitis, don't try to feed him because it will make the condition worse. Take him to the vet as soon as possible as he may require treatment or need to go on an intravenous drip to stop him dehydrating.  Again, the risk of pancreatitis should be minimal once the dog is on a lower dose of steroids.   A low fat diet is best when your dog is on high dose steroids or prone to pancreatitis. 
As your dog's immune system is being significantly suppressed, he will be more likely to pick up infections, and will not have the ability to fight against them.  As a precaution a broad spectrum antibiotic is often prescribed. Also it is sensible not to exercise him in areas where he is more likely to encounter infections, for example, a park or a popular dog walking area. 

Whilst your dog is on high dose steroids he will want to eat and drink excessively. However, this also means that he will want to urinate more and this can sometimes cause temporary incontinence.  You may have to get up to let him out during the night and if you leave the garden door open during the day, it may save some mopping up!  He cannot help it and won't like it either, so don't be too hard on him, it's only temporary. You will notice as he is weaned off the drugs the unwanted side effects will subside and he should return to normal habits and behaviour.  Urinary tract infections and/or bacterial skin pustules are not uncommon when a dog's immune system is suppressed, and this is often the reason for a dog to be off colour during this time.  Note: Always consider a urine infection if your dog seems under par.  A course of antibiotics will usually sort this out quickly.

Depending on what autoimmune disease your dog has, he will probably need to have regular blood tests.  Biochemical blood tests will also keep an eye on other body functions, such as those of the liver and kidneys, which is important at this stage.
Assuming good progress is being made, the clinical signs of his illness are diminishing and positive signs of improvement are apparent, your vet will want to start weaning him down from the high doses of steroid.  This process can take 3-6 months or more, and usually begins any time after 10 - 28 days from the start of treatment, depending on the results of his blood tests and his clinical signs.

Relapses are not uncommon, especially in diseases that are difficult to control, for example SLE.  A relapse may mean that initially, your dog needed to be on a higher dose of immunosuppressive drugs for a longer period of time, or your dog may have been weaned off a little too quickly and then the dose withdrawn too soon.
If a relapse occurs he will probably show similar clinical signs to his initial crisis.  He will have to go back on an immunosuppressive dose of prednisolone, but it may not have to be quite as high as before. A combination drug may need to be added at this stage. The weaning process will then have to start all over again. Returning to an immunosuppressive dose will mean that he has to go back on a gastroprotectant.

Side Effects of the Drugs – Iatrogenic Cushing's Syndrome
Iatrogenic Cushing's syndrome is a side effect of high dose steroids and is caused by too much corticosteroid in the body. To a lesser extent, the immediate side effects observed when the dog initially goes on steroids eg., drinking, eating and urinating excessively is a mild example of Cushing's syndrome.  Personally I like to see dogs responding to high doses of prednisolone in this way, as it means that they are responding to the drugs as they should.

Usually, Cushing's syndrome only becomes a real problem when exceptionally high doses, or prolonged high doses of steroids are administered, maybe due to a relapse, or in some cases where the vet is inexperienced in reducing steroid doses and keeps the dog on a high dose for longer than necessary; or when the dog is not responding to treatment and higher doses are necessary to control the disease.  This is where the cytotoxic drug Azathioprine is very useful. 

All drugs carry side effects and Azathioprine is no exception, but it does not carry the same side effects as prednisolone, therefore by using this drug in combination with prednisolone it reduces the risk of iatrogenic Cushing's syndrome.  As Azathioprine takes at least 10 days to take effect, starting the 'combination' therapy at the beginning of treatment may enable the prednisolone to be lowered within the 10-28 day band and still maintain a good level of immunosuppression. If your dog is not responding to treatment then your vet may consider changing his treatment to other immunosuppressive drugs.

How Can I Tell if My Dog Develops Iatrogenic Cushing's Syndrome?
Iatrogenic means 'drug induced'.  Clinical signs of Iatrogenic Cushing's syndrome are the same as primary Cushing's syndrome but can present with acute clinical signs. It reflects the level of corticosteroid in the body.

The most notable side effects are, heavy panting, some hair loss, and an increase in drinking and urinating, excessive pigmentation.  This is something everyone seems to be aware of and accepts as normal when a dog is on high dose steroids. Very often the dog will be weaned down to a low dose before any major problems arise. 

Acute Cushing's syndrome due to overdosing of cortiocoid steroids can be very serious.  Blood results will reflect this, especially the liver enzymes which may be extremely high. Red blood cells and blood platelets may also be high and blood clotting may be a risk.
So when should you alert your vet to suspected, unacceptable level of corticosteroid?  The owner should take note when other clinical signs occur, such as: Depression, anorexia, muscle wasting and extreme weakness, continuous panting, lethargy - unwillingness to exercise, skin lesions and thinning of the skin, excessive hair loss, pot-bellied appearance and sagging back, behavioural changes (aggression).

If your dog is showing these signs it will probably mean that the dose of steroids needs to be lowered. It is important that it is not confused with a relapse of the dog's condition or an infection. The dilemma is that steroids must not be withdrawn too quickly otherwise the dog may go into an adrenal insufficiency crisis.  If the clinical signs of iatrogenic Cushing's syndrome is intolerable, it is hoped that the high dose of steroids that he has been on will have already done their job and that his autoimmune disease will be stable. As long as the steroids are lowered in a controlled manner and in time, all the symptoms of Cushing's will subside and your dog will return to normal, but extreme signs must not be ignored.

How Do I Know if My Dog Will Relapse?
Until you have attempted to wean your dog off of the tablets for the first time you will not know if he is likely to relapse or not.  Sometimes during the weaning off process, before you even get down to an every other day dose, he may relapse.  If this happens then the drug dosage has to be raised, probably up to the last dose before the relapse (maybe a little higher, depending on the severity of the relapse) and then start the weaning process again.  If this happens again, then you and your vet may have to settle for keeping him on a low maintenance dose to achieve a good quality of life. A low, every other day maintenance dose of prednisolone is preferred to enable the dog's liver to rest in between doses. There are many autoimmune diseases that carry a good, drug free prognosis.  The more common, serious autoimmune diseases that may not need long term steroid therapy are: primary immune-mediated polyarthritis, autoimmune haemolytic anaemia and thrombocytopenia. However, as previously stated, all dogs are different and it very much depends on the individual dog, the severity of the disease, the experience of the vet and the vigilance and compliance of its owner.

If a relapse occurs whilst the dog is still being treated then true remission has not been achieved.  If the dog has achieved remission and has enjoyed a period without drugs or is on EOD maintenance drugs, when a relapse occurs or he develops another autoimmune disease, he has encountered a 'trigger factor' which has induced this change.

Wishing you and your dogs a very happy and healthy New year.

All the best

Jo

Christmas greetings to you all.

Wishing you and your dogs a merry Christmas and a happy and healthy New Year.

Jo

Focal GME  or  Granulomatous Meningo-Encephalitis (GME) or MUO (MENINGO-ENCEPHALO-MYELITIS of Unknown Origin)

TYPES OF MUO
There are several different of MUO which tend to be breed related. The main types are:
• Granulomatous Meningo-Encephalitis (GME)
• Necrotising Meningo-Encephalomyelitis (NME)
• Necrotising Leuco-Encephalitis (NLE)
• Idiopathic Tremor Syndrome (ITS)



Case history of  Focal GME

24 Feb a totally normal dog and had just started agility 

26 February woke up not responding to voice or touching, eyes wide open no response straight to the vets, bloods taken only thing they found was a very high fat in the blood he started to look a bit normal and sent home no injection just advices to put him on a low fat diet and treatment him like a normal dog, a bit odd but it was the advice

28 February another episode this time he woke up looking out off it and wobbled down the stairs and stopped in the kitchen non responsive staring at nothing and not hearing me or even being touched luckily I took a video of this as how could I explain it to the vets as he was also when I got him to move he was walking into things door frame kitchen bin... off to the vets

On examination he was walking in circles, bumping into things and a head tilt, more bloods again nothing abnormal Just high fat.  The vet scratched his head went off and called the vet who we saw days before.

A referral to Andersonmoore for the next day as they thought it wasn't an emergency.

Arrived at Andersonmoore and met the vet from Internal Medicine show the videos and history given, they then mentioned his blindness in his left eye news to me.. now feeling worried after more tests they suspect Liver Shunt!

He gets admitted for more bloods etc etc

Next day get a call it's not Liver Shunt and hes transferred to Neurology for MRI and CSF.. now feeling very sick myself.


Next day the MRI scan comes back abnormal changes and CSF sent away results came back 6 days later.

He was started on antibiotics and prednicare 30 mg per day as a starter till the CSF results arrive. Go and collect him 2 days later and he's ok just very sleepy. Results back they mentioned Atopica for life or a course of chemotherapy 4 in total, which meant a 2 night stay and every 4 weeks and 4 injections.

I opted for tablets thinking easy option, 75 mg twice a day, this medication was very regimented around an empty stomach and given 12 hrs apart long with 30 mg steroids. But we just got on with it. He to be honest didn't do much just sleep and being made to being walked.

Next chapter

23 March, back the vets as he's now being sick and had diarrhoea more antibiotics and sent home

5 April, back to the vets not drinking sent home with a vit b injection and don't worry he's just hot but what about the blood in his urine as I thankfully got a sample from him, other advice if hes not better by Monday call Andersonmoore

6 April not drinking or eating called Andersonmoore spoke to his specialist and was advised to rush him back to the vets.... It's nothing to do with his MUO

Arrive with only what I can describe as a very ill dog showing signs of jaundice admitted and put on a drip and a referral back to Andersonmoore luckily they are only 45 mins away and off we go back this time with Pancreatitis and a 6 night stay and they found a grade 2 heart murmur after his heart scan just to be on the safe side before starting chemotherapy

Everyone put there thinking chaps on scratched their heads and argue over reduce his Atopica start chemotherapy ,

10 April his 1st chemo

12 April came home and drop down to 75 mg Atopica per day

15 April steroids drop to 15mg per day

1 May 2nd chemo and drop down to 10 mg steroids per day

16 May Atopica stopped thank god

29 May last chemotherapy

So far the vet bill is £6500 for the MUO and have £1000 left till next Jan and the chemotherapy on average is £550 per go hence only having 3

His pancreatitis bill was £3750


Happy days 27 June back to Andersonmoore they are over the moon with him and in remission and another drop 5 mg steroids per day

Back on the 9th August and fingers crossed another steroids drop.

They have said because the pancreatitis got involved the treatment plan is "bespoke" and as he is young poor boy is only 20 months and fit in his body they thought it was worth trying.

They have given us the provisional diagnoses of Focial GME (as they can never be for sure unless a brain biopsy is done which can't be) as he hasn't had another episode in for months and they say it's the best of the worst condition

I'm happy with that and thank god he's insured I thought £7500 was a lot of money and have only £1000 left but with fingers crossed we won't need it.

Laters,

Keeper the crazy cocker spaniel X



Note from Jo:  For further reading:  http://www.wear-referrals.co.uk/factsheets/GME&Meningitis.pdf

Some useful links:

https://www.petmd.com/dog/conditions/neurological/c_dg_myasthenia_gravis

http://cal.vet.upenn.edu/projects/saortho/chapter_72/72mast.htm

http://vetneuromuscular.ucsd.edu/cases/2017/january.html

https://www.vin.com/apputil/content/defaultadv1.aspx?meta=Generic&pId=11157&id=3857014

Hello.
I have just joined the CIMDA forum. I hope you can advise me please. I have two toy poodles. Coco is 10 and Candy is 8. Coco is well . Last summer Candy was diagnosed with SLO but the treatment almost killed her. She was on a drip for 2 days. I ceased all meds and she is fine now except for deformed nails.
She is now due annual vaccinations but I am very worried that she may react as she has this autoimmune disease.
The vet advised that she has the Leptospirosis vaccine as this only lasts a year and I  live in the middle of the Norfolk Broads. Apparently the teter  test does  not reveal the lepto situation in a dog.
I am struggling to know what to do.
What do you think?
Regards Glynis

At the moment there seems to be a problem authorising people who want to join the forum.  I apologise for the inconvenience and hope this will be resolved very soon.

Jo

HEALTH SEMINAR

for The East of England Afghan Club.

To be held at:      Dick White Referral Specialists, Six Mile Bottom, Newmarket.

Saturday 25th November, 2017

These topics are not breed specific, so could be of interest any breed owner.

Tickets cost £15 & can be booked through the club secretary Lynn Hewson at  rekaylahn@hotmail.com. telephone 01536 267892.

Programme:

10.00 – 10.15   Arrival, Registration and Coffee

10.15 – 10.30  Welcome - Who we are and what Dick White Referral Specialists do  by Rob Foale

10.30 – 11.15  Soft tissue surgery  -  Laryngeal paralysis by Georga T Karba

11.15 – 11:30  Coffee break

11:30 – 12.15   Neurology  -  Investigation and treatment of seizures  by  Giunio Bruto Cherubini

12.15 – 13.00  Respiratory medicine  -  Lung lobe torsion and chylothorax  by  Chiara de Gennaro,  Jon Wray

13.00 - 14:00  Lunch and DWR Tour  by Rob Foale

14:00 – 14:35  Cardiology:  Diagnosis and treatment of canine cardiomyopathy  by Ruth Willis

14.35 -  15.15  Soft Tissue Surgery -  Current thoughts on canine GDV by Fransisco Silviera

15:15 – 15:30  Coffee break

15.30 – 16.15  Internal Medicine - Diagnosis and treatment of hypothyroidism  by Simon Tappin

16:15 – 16:45  Internal Medicine  - Diagnosis and management of insulinomas by  Rob Foale

16.45  - Closing Comments  by Rob Foale

Glossary

Acidosis – A disturbance of acid base balance leading to an excessive accumulation of acids or loss of bicarbonate.
Anaphylactic (shock) – State of collapse resulting from injection of a substance to which the animal has been sensitized can be deliberate injection or insect sting.
Anorectic/Anorexia – Having no appetite/Loss of appetite.
Ascites – Abnormal accumulation of serous fluid in the abdominal cavity due to interrupted return of blood to the heart, obstruction of the vena cava or portal vein, obstruction of lymphatic drainage or electrolyte imbalance.
Corticosteroids – Any steroid hormone from the cortex of the adrenal gland, or a synthetic drug that mimics their function such as prednisolone.
Edema – Local or generalized abnormal accumulation of fluid in tissues (oedema in the UK).
Ehrlichiosis – Infection with Ehrlichia canis (a rickettsial bacteria) carried by the brown dog tick that attacks the white blood cells (monocytes).
Endo – A prefix that means inside.
Endotoxins – A toxin confined within a bacterium and only released when the bacterial wall is breached.
Enzymes – Complex proteins that act as catalysts and are produced by living cells.  They speed up biochemical reactions without being changed in the process.  They are found most often in digestive fluids. 
Hyper – A prefix that means above hence an excess or higher than normal.
Hypo – A prefix that means under indicating less than or below normal - a deficiency.
Immune-mediated disease – Diseases that are mediated through the immune system.  Either this over-reacts to an external threat (contact dermatitis) or the immune system fails to distinguish self from non self, and attacks the animal's own body – autoimmune disease eg., autoimmune hemolytic anemia (AIHA) or Addison's disease.
Immune-mediated thrombocytopenia (ITP) – Autoimmune destruction of the blood platelets a.k.a as idiopathic (of unknown cause) thrombocytopenia (low platelets).
Ischemia/ischemic  - A restriction of blood supply leading to a local and temporary anemia.
Ketones – The end products of fat metabolism.  Their levels will be high when carbohydrates are scarce or not properly used – diabetes mellitus, starvation, high fat diet, pregnancy or after anesthesia.
Ketosis – Significant accumulation of ketones in the body and urine.
Lactic acid – A substance formed by the break down of carbohydrate in the body.  It accumulates in working muscles when production exceeds removal.
Leukemia – Cancer resulting in unrestrained production and growth of white cells and their precursors in the bone marrow and tissues.
Lipemia – An excess of fat in the blood.
Lymph – A normally clear, colorless fluid – becomes milky when laden with fat – similar to blood without red cells, and formed in tissue spaces throughout the body.  It flows through vessels that collect into the thoracic or right lymph ducts and enters the blood in the neck.  It passes through the lymph nodes which remove foreign particulate material especially bacteria from the lymph.  They may also filter out cancer cells.  Lymph is used to carry fat and also protein that is absorbed from the intestines.
Lymph system- Lymphatic system is a network or organs, lymph nodes, ducts and vessels that transport lymph.  Organs include tonsils, thymus gland and spleen.  Its major role is in providing immunity.
Mast cells – These are connective tissue cells containing anticoagulant heparin and histamine granules.  They are part of the normal body defense system against infection and help blood coagulation in injury.
Metabolism/Metabolic -  The sum of all the physical & chemical changes that take place in a living organism,  all the energy and material transformations that occur within living cells./Relating to metabolism.
Microbes – Bacteria, germs producing fermentation, putrefaction and disease.
Morphology – The science of structure and form without regard to function. 
Morphologically – Relating to morphology.
Myopathy – Any striated muscle disease or abnormal condition.
Myositis – Inflammation of the muscle tissue.
Necrosis – Death of tissue or bone surrounded by normal structures, or mass death of tissue as opposed to gradual destruction.  The result of insufficient blood supply, trauma, radiation, chemical agents or toxins.
Nephron – The structural and functional unit of the kidney that achieves filtration, selective secretion and reabsorption to finally produce urine.  There are about a million nephrons in a kidney.
Parvovirus – Viral infection spread by direct or indirect fecal contact.  It primarily affects dogs under a year of age and those that are immunocompromised.  Usually it produces gastrointestinal disease, and destroys the absorptive surface of the intestinal tract.  It also attacks the immune system – lymph nodes, bone marrow.  Bacteria can freely cross the damaged intestinal wall and enter the circulation leading to sepsis.  It is frequently fatal.  A rarer form of the disease attacks the heart muscle of puppies in utero and neonates.and usually results in sudden death.  Still rarer, all of the organs in the neonate or fetus can be destroyed by the virus. 
Peptide – Compounds of two or more amino acid molecules. About twenty amino acids – organic compounds containing both amino and carboxyl radicals - combine to make all the proteins found in the body.  Some amino acids can be made by the body, but some "essential" amino acids have to be consumed in the diet.   
Petechiae/petechiation – small, purplish hemorrhagic spots that appear in skin or mucus membrane due to abnormalities in blood clotting or high fevers./The presence of petechiae.
Portal blood – Blood from the capillaries in the intestinal walls drains into the portal vein and is taken first to the liver.  There nutrients are removed and processed and any toxins absorbed from the digestive system and detoxified and metabolized. 
Pyometra – Infection of the uterus, literally pus in the uterus.
Sepsis – Disease resulting from the presence of microorganisms or their poisonous products in the blood stream.  Usually results in fever.
Urease – An enzyme that catalyzes the breakdown of urea.
Uremia – Toxic condition due to insufficient kidney function and resulting in the retention of nitrogenous waste in the body that would normally be excreted.
Venipuncture – puncture of a vein for any purpose, often used synonymously for phlebotomy - the withdrawal of blood from the vein.

The Biochemistry Profile[/b]
The levels of a variety of enzymes, electrolytes and other substances are measured in the blood serum.  Serum is the clear (hopefully) fluid left after the blood cells have been allowed to clot.  Together with urinalysis it provides an overview of the health and function of many of the body organs.  The tests included in the profile can vary.  Idexx, the laboratory I use, offers a wellness check of 11 substances, but also offers tests or 21, 25 and 27 substances as well as a multitude of add-on tests.  Common tests are presented here.

Albumin is a small protein produced by the liver. Albumin helps to hold water in the blood vessels; if albumin levels drop, fluid leaks out of the blood as it is pumped through the body and accumulates in body cavities (e.g. ascites) or in tissues as edema. Albumin is decreased due to intestinal malabsorption or malnutrition; exocrine pancreatic insufficiency (EPI) which results in fewer enzymes to digest protein; or chronic liver disease.  Reduced levels also occur if protein is lost through kidney disease or hemorrhage.  Burns and certain other skin diseases can cause loss of protein through the skin. Increased albumin is the spurious result of dehydration.

Total protein includes albumin, fibrinogen and globulins. Fibrinogen is involved in the formation of blood clots and levels increase in inflammation or neoplastic disease.  It may also be increased mildly if the animal is dehydrated.  It can be, but is not normally, measured separately as part of the profile.  Globulins are larger proteins commonly referred to as antibodies.  Often globulin is listed as total protein minus albumin, more accurate assays separate not only albumin from globulin but alpha, beta and gamma globulins from each other.  Alpha globulins are acute reacting antibodies responding to tissue injury and inflammation, beta globulins are associated with acute liver disease, and gamma globulins are associated with chronic inflammatory diseases, immune mediated diseases and some lymph based cancers.  Some reports will include the ratio of albumin to globulin. 

Alkaline phosphatase (ALP) is a group of enzymes that originates from every tissue in the body.  High activities occur in liver, bone, intestine, kidney, placenta and white blood cells.  Although not normally done, the enzymes from the various organs can be isolated and measured.  In healthy animals most ALP is of liver origin.  Increased ALP can indicate liver disease (due to interruption of bile flow), bone disease (osteosarcoma, bone healing or hyperparathyroidism) or increased blood cortisol either because corticosteroids have been given or due to Cushing's disease (hyperadrenocorticism).  Other drugs especially phenobarbital can also increase ALP.  In acute liver disease, ALP may remain normal while other liver enzymes rise, but ALP levels may continue to rise during recovery.  In geriatric dogs certain malignant cancers (mammary, squamous cell carcinoma and hemangiosarcoma) may produce a very high ALP.

Alanine aminotransferase (ALT) {aka as glutamic pyruvic transaminase (SGPT)} is an enzyme considered liver specific in the dog. Liver damage – sublethal damage or necrosis - causes ALT to increase in the bloodstream. The level of increase reflects the number of cells that have been damaged.  In acute disease a reduction in ALT is favorable, but in chronic cases may just reflect that most of the liver is already compromised.  Elevation in ALT does not provide information as to whether the liver disease is reversible or not.

Aspartate aminotransferase (AST) {aka glutamic oxaloacetic transaminase (SGOT)} occurs in most cells but is considered diagnostic of liver and muscle disease. It is less specific and less sensitive to liver damage than ALT. 

Other enzymes used to detect liver injury include gamma glutamyl transferase (GGT) and sorbitol dehydrogenase (SDH).

Bilirubin is produced by the liver, spleen and bone marrow as they recycle old red blood cells.  Most bilirubin is conjugated in the plasma with proteins although some will be free.  In the case of hemolytic anemia or internal hemorrhage most of the increase will be free bilirubin.  Blockage of bile flow – either in the liver of gallbladder leads to an increase in conjugated bilirubin.   Acute and chronic liver disease usually produces a combined response with increases in both types.  Large amounts of bilirubin in the bloodstream will give a yellow color to the mucus membranes, inside the ears and eye whites.  This is called icterus or jaundice. Bilirubin is further broken down and eliminated in both the urine and stool.  In dogs increases in bilirubin in urine precedes that in the serum.

Bile acids Cholic acid and chenodeoxycholic acid are produced by the liver, combined with amino acids glycine and taurine and secreted into the bile to assist in fat digestion and absorption as well as absorption of the fat soluble vitamins.  They are stored in the gall bladder.  A bile acid test is used to evaluate the function of the liver and its blood flow to the liver, and to diagnose dogs with portosystemic, shunt, where blood from the intestines by-passes the liver and goes straight to the general circulation. The bile acid test measures a fasting blood sample and a blood sample two hours after eating.  In normal dogs, bile acids released to digest a meal are recovered into the portal blood and returned to the liver.  If the dog has a portosystemic shunt the bile acids enter the general circulation and will be dramatically elevated.

Blood Urea Nitrogen (BUN) Only small amounts of urea are ingested, most is made from ammonia – either from the break down of protein or absorbed from the large intestine – in the liver.  Urea is excreted by the kidneys.  Increased protein breakdown due to increased protein in the diet, hemorrhage, necrosis, starvation, prolonged exercise, infection, fever or corticosteroids causes a mild increase in BUN.  Decreased perfusion of the kidneys caused by dehydration, shock or cardiovascular disease can also increase BUN.  In dogs with kidney disease approximately 75% of the kidneys are nonfunctional before BUN will increase. BUN doubles approximately each time the remaining number of nephrons is halved. 

Creatinine A small amount of creatinine may be ingested from diets rich in muscle meats.  Most, however, comes from the conversion of energy stores of phosphocreatine in the muscles to creatinine - a waste product that is eliminated from the body by the kidneys.  The creatinine pool is influenced by muscle mass, which in turn can be affected by muscle disease, wasting and training.  Unlike BUN, creatinine is less influenced by diet or urine flow, and elevation of creatinine is the result of kidney disease or dehydration.
 
Amylase is an enzyme produced by the pancreas, small intestine and liver. Amylase helps the body break down sugars. In healthy animals serum amylase is non-pancreatic in origin.  In pancreatitis (inflammation of the pancreas) or pancreatic cancer amylase can leak into the lymph system and from there to the blood.  The higher the level (3 to 4 times normal) the more likely the source is the pancreas.  Kidney disease and intestinal obstruction can also increase amylase; corticosteroids can increase it or decrease it.  Occasionally, animals with pancreatitis can have normal serum levels of amylase.   Because pancreatic disease isn't the only cause of increased amylase, levels are assessed in conjunction with those of lipase.

Lipase is another pancreatic enzyme which is responsible for the breakdown of fats.  It takes longer to get a lipase measurement than that of amylase.  A two-fold or greater increase in lipase indicates acute pancreatic disease, and it is almost never normal if the dog has pancreatitis.   However, increase can occur in kidney or liver disease or with corticosteroids.

Creatine phosphokinase (CK, CPK) CK is an enzyme that helps store and release energy from muscle.  In healthy dogs levels vary considerably with age, at one day old puppies have 5 times the activity of adults.  Adult levels are reached at 7 months of age.  Old dogs may have lower levels.  Levels may be artificially increased by hemolysis, excess bilirubin or muscle derived from difficult or repeated venipuncture.  Elevation may indicate infection; myositis; trauma; degenerative, metabolic, ischemic or nutritional myopathy and involve heart muscle as well as skeletal muscle.  The increase does not correlate to the extent of the damage. Even minor insignificant damage can cause elevation in CK.  Two other enzymes -lactate dehydrogenase (LDH) and aspartate amintransferase (AST, GOT) - may also be measured to determine muscle function.  Results tend to mirror CK, but they are less sensitive.

Glucose is blood sugar. Its level is regulated by the pancreatic hormones insulin and glucagon.  Insulin increases the uptake of glucose by liver, skeletal muscle and fat primarily, as well as uptake of some other simple sugars, amino acids, fatty acids, potassium and magnesium.  Glucagon is released in response to low blood sugar and causes the liver to convert stored glycogen into glucose.  Corticosteroids antagonize insulin's effects.  Glucose is increased in dogs and cats with diabetes mellitus – lack of insulin. It may be mildly increased in dogs with Cushing's disease. (Glucose can temporarily increase in the blood if the dog is stressed by having blood drawn or the general examination.  If glucose is also elevated in the urine, the blood glucose elevation is not transient.)  Low blood sugar occurs less commonly and can be indicative of pancreatic cancer or overwhelming infection (sepsis) or administration of excessive insulin.  It may also indicate improper handling of the sample.  An animal with low blood sugar will be depressed, seizuring or even in a coma.   

Cholesterol There are four major fats in plasma; the two most often measured are cholesterol and triglycerides.  They travel bound to peptides in complexes called lipoproteins.  Cholesterol levels are usually inversely related to thyroid hormone activity, and it is one of the best indicators of thyroid disease. Liver disease, acute pancreatitis, diabetes mellitus, and kidney disease (nephritic syndrome) and corticosteroid drugs, but not Cushing's disease, can also elevate cholesterol.  High cholesterol does not predispose dogs to cardiovascular disease.

The Electrolytes usually measured include sodium (Na+), potassium (K+), chloride (Cl-) and TCO2 - which is primarily a measure of bicarbonate HCO3-).  The sum of positive ions minus the sum of negatively charged ions is called the anion gap, and is used to determine acid base abnormalities.  It increases in such diseases as lactic acidosis, diabetes mellitus, ketosis, renal insufficiency and some toxicities like ethylene glycol (antifreeze) poisoning.  A decrease is rare.

Sodium is essential for proper kidney function and water retention.  The correct balance between sodium and potassium ions inside and outside nerve and muscle cells is essential for their proper function.  Low blood sodium is most commonly seen with Addison's disease (hypoadrenocorticism), but can also be seen in diabetes mellitus or an animal that has been vomiting.

Potassium is increased in the dogs with Addison's disease, as well as with acute kidney failure, and in animals with a ruptured or obstructed bladder.  Low potassium is associated with anorexia, vomiting, diarrhea, diabetes or the use of diuretics.  Many profiles calculate sodium potassium ratios.  If this number is less than 27 it indicates Addison's disease. 

Chloride changes tend to parallel those of sodium, but loss of stomach hydrochloric acid can result in low chloride and normal sodium. 

TCO2 Loss of bicarbonate can occur through diarrhea.  Loss can also be relative to a build up of lactic acid, ketones, or uremic acids in kidney failure.  Some organic poisons may also lower blood acidity.  In cases of loss of stomach acid, the kidneys may excrete more bicarbonate to compensate.   

Calcium The levels of calcium potassium and magnesium are regulated by parathyroid hormone, calcitonin from the thyroid and Vitamin D.  Serum calcium is a reflection of relative bone formation and resorption.  It is rarely affected by dietary intake.  High blood calcium is most commonly associated with cancer. Less common causes of elevated calcium are chronic kidney failure, primary hyperparathyroidism, poisoning with certain types of rodent bait and bone disease.  Low blood calcium may occur in bitches shortly before giving birth or during the early nursing period. This is called eclampsia.  It causes tetany, the muscles become rigid.  Hypofunction of the parathyroid will also result in low blood calcium.  Dogs poisoned with antifreeze may have very low blood calcium.

Phosphorus Levels will be higher in young animals than in adults.  Serum phosphorus is largely regulated by the kidneys, although parathyroid hormone can increase resorption.  Dietary intake can directly affect serum levels.  Phosphorus is increased in chronic kidney disease, as with BUN and creatinine, phosphorus increases in these patients when about 75 percent of both kidneys is damaged.

Blood serum as well as urine components can vary markedly throughout the day.  Taking blood from a fasted dog will minimize those variations, but fail to show nutrient sensitive diseases.  Blood glucose will be low, as will insulin, while glucagon secretion will be elevated.  In anorexic patients, or those fasted more than 24 hours, fat will start to break down excessively to provide energy and increase levels of ketones which might make the blood more acid.  In a dog that has been eating, elevated ketones would suggest it had diabetes or liver disease, however.  BUN and phosphorus decrease in anorexic patients, so that renal failure might be missed.  Fortunately creatinine levels will not be affected.  Fasting for 24 hours increases the resorption of sodium and excretion of potassium by the kidney.  More calcium, magnesium, uric acid and ammonia will also be excreted.  In general, fasting 6 to 12 hours before a blood draw is optimal.  If lipemia persists after fasting for 24 hours it indicates problems with fat metabolism.  If the purpose of the blood test is to evaluate the effect of dietary modification on a disease process, blood should be drawn 2 to 6 hours after food consumption.  If you are reevaluating the thyroid levels of a dog already receiving supplementation, blood should be drawn 4 to 6 hours after the morning pill.  At this point thyroid levels will be maximal, and should be in the upper 50% of lab normal to 150% of the upper limit. 

Linda Aronson DVM

Complete Blood Count
The CBC measures the number of cells of different types circulating in the blood.  There are three basic types, red cells, white cells and platelets.  Red cells are made in the bone marrow (the soft center of the bones).  Their function is to carry oxygen from the lungs to the cells throughout the body.  They are removed from the blood by the spleen and liver.  If a Beardie has too few red cells it is anemic, too many and it has a condition called polycythemia.  Anemia can occur if red cells are lost to either internal or external bleeding; or if they are destroyed earlier than normal (hemolysis). It may also be the result of insufficient production by the bone marrow.  Polycythemia is less common, and usually is the result of dehydration.  Animals living at higher elevations make more red cells to compensate for the lower amounts of oxygen in the air.  As well as the absolute number of red cells, the CBC will include the hematocrit (Hct) or packed cell volume (PCV) – the percentage of red cells in the blood sample.  Blood is spun in very thin tubes, and the red cells settle to the bottom.  Above them is the small "buffy" coat layer of white cells and above that the plasma which should be clear and colorless.  Clear yellow plasma indicates liver disease – jaundice, white opaque plasma indicates lipemia, and pink to red clear plasma the presence of hemoglobin from lysed red cells.  Hemoglobin concentration (Hb) is also measured.  Hemoglobin is the substance in the red cell that carries the oxygen.  Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) are all used to help classify anemia, albeit the most useful measure of anemia is the reticulocyte count.  Reticulocytes are immature red cells that still contain a nucleus.  In anemia they may be released prematurely to help meet the animal's need for oxygen.  You need the absolute reticulocyte count not the proportion.  As the numbers of adult red cells drop the proportion of reticulocytes will rise, and so be less informative. 

There are several different kinds of white blood cells or leukocytes.   The CBC will usually report the percentage as well as the absolute number.  The latter is always the more important number.  White cells are also made in the bone marrow. 

Neutrophils
The most numerous white cell group are the neutrophils.  They are phagocytes – cells that can engulf and digest foreign substances, and their primary function is to destroy microbes.  They secrete various substances to help with this, and can also pass through cell walls, attracted to the foreign invaders. Increased numbers of neutrophils indicate inflammation, infection by bacteria, distemper virus, fungi, some parasites, as well as immune mediated disease, necrosis, endotoxins, foreign bodies, hemorrhage, hemolysis and Rocky Mountain Spotted Fever.  Prednisone and other corticosteroid drugs can increase neutrophil numbers, by reducing their stickiness and random migration from blood to tissues.  In general, the response is greatest if the infection is localized (pyometra for example) rather than generalized.  Numbers are low if destruction exceeds production.  This can result from massive utilization but most often is due to decreased production or decreased survival.  Chemotherapy, leukemia, ehrlichiosis, parvovirus, immune mediated diseases, endotoxins or an overwhelming sepsis could cause this. 

Lymphocytes are found in lymph nodes, spleen, thymus, tonsils, lymphoid tissue in the gastrointestinal tract and respiratory system and bone marrow as well as the blood.  While they cannot be differentiated morphologically they are of two types T lymphocytes that mature in the thymus and are involved in cell-mediated immunity and B-lymphocytes that function as antibodies in the blood.  They are the most long lived white cells and are unique in that they recirculate back into the blood from the tissues.  Recirculation is the process most likely to influence the number of lymphocytes found in the blood.  Blood count correlates poorly with enlargement of the lymph nodes. Lymphocytosis (increased numbers) are occasionally seen during chronic infections.  Lymphopenia (low numbers) are relatively common in sick animals, however.  Stress mediated by corticosteroids (natural or drugs) causes lymphocytes to move from the blood into lymphoid tissue.  This effect is maximal 4 to 8 hours after the appearance of the corticosteroids.  Acute infection, immunosuppression, acquired deficiency as well as loss or damage to lymph tissue can all reduce lymphocyte numbers.  In puppies, lymphocytes may be elevated due to infection.

Monocytes usually parallel neutrophils and increase in infection as well as in response to corticosteroids.  Monocytes transform into macrophages after a time in circulation, these are large efficient macrophages with lots more granules and proteolytic enzymes than monocytes.  Macrophages clean out any foreign particles or dead cells, but are less responsive to infection than neutrophils.  They also present foreign substances to lymphocytes in a form more likely to elicit an immune response.  Reduced numbers of monocytes are not clinically significant.

Eosinophils are attracted to substances released by mast cells, and inhibit their further release limiting or delaying allergic or anaphylactic reactions.  Increased level is usually associated with parasitic infection or hypersensitivity.  Reduced numbers can be the result of an acute infection or the presence of corticosteroids. 

Basophils are usually quite rare.   Seeing them is therefore quite significant.  They tend to parallel eosinophils, and tend to increase in dirofilariasis the early stage of heartworm.  If eosinophil levels are normal but basophil levels are high, serious chronic disease should be investigated.

Platelets, also known as thrombocytes, stick to exposed collagen within seconds after injury and help to form clots to prevent internal and external bleeding.  Reduced numbers indicate either bone marrow damage or increased rate of destruction.  The two major causes of destruction are immune-mediated thrombocytopenia (ITP), which may be secondary to tick borne and other infections, or disseminated intravascular coagulation (DIC), a complex and usually terminal condition in which blood clots throughout the body as the result of a number of serious conditions.  Platelet numbers have to drop dramatically before you see spontaneous bruising – including pinpoint petechiation – and bleeding. 

A blood smear will be examined microscopically not only as confirmation of the machine generated cell numbers, but also to look for parasites, as well as abnormal cell shapes and arrangements.  Platelets may clump in samples giving false low readings and the blood smear will determine whether adequate numbers are indeed present.


Linda Aronson, DVM.   

Massive price rise for vital drug put pets' lives at risk

By Billy Kenber

If you are interested in the treatment of Addison's Disease, and the problems many people have had medicating their dogs over the past year then please take a look at this article.



https://www.thetimes.co.uk/article/massive-price-rise-for-vital-drug-put-pets-lives-at-risk-58clj6s63

IMHA STUDY

The AHT is the UK's leading veterinary and scientific research charity and we are working with other leading veterinary specialist centres on an exciting new project.
With your help, together we can not only save one animal's life, we can save thousands... 

The Condition

Immune-mediated haemolytic anaemia (IMHA)

This is a common haematological disease of dogs. The primary disease process involves destruction of a patient's red blood cells by their own immune system leading to the development of anaemia. Treatment involves immunosuppression of the patient to prevent this process. Until immunosuppression is effective, patients can be supported with a range of therapies including blood transfusion to treat the anaemia. Despite the increasing availability of transfusions, mortality for patients with IMHA remains high - reported to be between 30 and 70%.

Current Treatment and Research 

Despite the wide array of immunosuppressive treatment protocols that have been described for the treatment of IMHA, best practice remains highly controversial. It is typically accepted that corticosteroids are a mainstay of therapy, although evidence supporting this is lacking. Many additional immunosuppressive therapies have been used and described, including azathioprine, cyclosporine A and mycophenolate mofetil. Use of these has mainly been described in retrospective or non-randomized trials, making their benefit unclear. Where prospective, randomized trials have previously been conducted, investigating cyclophosphamide or human intravenous immunoglobulin, then these either showed no survival benefit or a disadvantage
associated with the use of these additional drugs.

Is there a more effective Treatment?

Intravenous immunoglobulins are thought to have many potential immunomodulatory effects, and these include inhibition of phagocytosis and inhibition of complement activation, meaning that this treatment may be relatively unique in its ability to accelerate remission in IMHA.

The Animal HealthTrust recently received a generous donation of Pentaglobin, an IgM enriched form of hIVIG from the family of a human patient. A study in new-born humans with haemolytic anaemia (Aqrabawi 2013) found that this drug was effective in rapidly inhibiting further haemolysis in most patients that received it.

Our Objective

To determine if administration of Pentaglobin at the time of initial diagnosis of IMHA in dogs is beneficial for their outcome.

Our Hypothesis

Pentaglobin administration will improve survival in dogs with IMHA when given in addition to conventional therapies, compared to dogs that do not receive pentaglobin. Pentaglobin will be associated with a more rapid remission in dogs with IMHA. Pentaglobin will be associated with a decreased transfusion requirement in dogs with IMHA.

How Can You Help?

As part of a multi-centre study, collaborating with Dick White Referrals, Davies Veterinary Specialists and Cambridge University, we need to test Pentaglobin's effect on dogs admitted to participating hospitals that have been diagnosed with IMHA.

Participation will be voluntary, with informed owner consent at the time of hospital admission, or once sufficient diagnostics are performed to meet the
inclusion criteria.

For more information about the study and what to do if you see a case suffering from IMHA, please contact your local study centre:

Animal Health Trust – Lead Investigators:

Mellora Sharman and
Mayank Seth

internalmedicine@aht.org.uk

Dick White Referrals

Simon Tappin

st@dwr.co.uk

Davies Veterinary Specialists

Nat Whitley

NWhitley@vetspecialists.co.uk

The Queen's Veterinary School Hospital
University of Cambridge

Barbara Skelly and
Mike Herrtage

medicine@vet.cam.ac.uk