Daisy and Nipper

Nipper

Daisy

This is even a record for me, adding 2 ferrets to my web page after they have both died...

Daisy and Nipper belonged to friends of mine, Alan and Jane. I used to look after them when Alan and Jane went on holidays so I was quite fond of them. Nipper was very laid back and cuddly, Daisy was a bit more cheeky but also very lovable.

In the summer of 2007, Alan and Jane decided to sell up and move to England to be close to Jane's mother. I was hoping they would take Nipper and Daisy along with them but one night early October I got a phone call to say that they weren't taking the ferrets with them and would I take them. I said yes because what else could I have done. They had become like my own and if I hadn't taken them, I don't think they would have gone to a good home. But still I felt very low, I was already struggling with 5 groups and really did not want a 6th group.

So Daisy and Nipper arrived on the 15th of October 2007. Nipper was 7 at the time, Daisy, his daughter, was 6. Not wanting to have a 6th group, I decided to try and put Daisy and Nipper in a group with Ruby and Honey. It worked out okay, they squabbled a bit at first but in the end Nipper was the alpha ferret.

Honey and Nipper

Honey, Nipper and Daisy

Nipper was already ill when he arrived. He'd had some breathing problems for the last year and sounded to me like he had some fluid on his lungs. So by November I took him to the vets because he was coughing. His heart rate was fast at the vets and sounded muffled so he was put on Fortekor heart tablets and I started him on Furosemide that I already had for Bobby.

April '08, Nipper started showing signs of insulinoma, I measured his BG and it was pretty low at around 40. He'd hidden it well, he'd become quiet over the last few months and wouldn't play much or be active much at all but I never saw the tell tale signs of insulinoma. Then one night I wanted to encourage him to play in the garden and he stood there and stared into space and was unsteady on his feet, swaying from side to side, so that is when I did the test. Since he's being treated for cardiomyopathy but hasn't actually had an x-ray, I wanted him to have one now to see whether the heart is enlarged and also wanted Michaela to listen to his chest again to see what the heart is like and also fluid in his lungs. He always sounds fluidy but it's controlled by Furosemide... Obviously it's not a very good idea to give prednisolone to a ferret that has cardiomyopathy so I wanted to know whether he does indeed have cardiomyopathy. The x-ray showed that he had chronic lung disease and cardiomyopathy so the pred needed to be given not only for the insulinoma but also the chronic lung disease/ bronchitis. He was also started on the broncho dilator Theophylline. All the medications worked very well and Nipper became quite active again.

Daisy also started having problems early April, she was unsteady on her feet and walked like she was drunk. She would veer to the right, she'd be walking along and all of a sudden she'd loose her balance and veer to the right. She had some hind leg weakness but was able to get up the stairs at this point in time. She did not act sick in any other way. She happily ran and stumbled around like nothing was wrong. Her ears are clean and Michaela couldn't find anything wrong so we decided that I was going to do some blood glucose tests because Daisy went quite quiet and limp after the stress of having her heart listened to and temperature taken. I did the test when I got home and it was 72 mg/dl so not horrendously low but also not normal and maybe the glucose normalised on the way home.

Daisy leaning to right

Daisy low on ground to steady herself

Beginning of June, Daisy suddenly got worse and was stumbling a lot to the left and right. She had an x-ray 3rd June which showed enlarged lymph nodes in her abdomen and chest. She got progressively worse over the next week, developed a severe head tilt to the right, could eventually barely get around so I had her put to sleep on the 10th of June. It was hard because she was not really suffering and wasn't in pain. She wasn't discouraged by her balance problems and still wanted to run and would eventually get to where she wanted to be but in the end there was no point. Her chest was in a bad way and I think very soon she would have developed serious problems breathing if I had let her go on. Her chest already looked so bad that we were surprised she didn't have problems breathing. She did have some fluid in her lungs and the last week she was on a low dose Furosemide because she was coughing occasionally. Anyway, Michaela said vestibular syndrome/ disease when she saw the head tilt and I believe it can be caused by cancer as well as inflammation/ infection. Of course when I heard vestibular disease I felt shocked and thought what if it was only an infection and we could have cured it with antibiotics. Completely forgot about all the tumours we'd seen...

Daisy head tilt, not focused unfortunately



Daisy's histopathlogy report


DESCRIPTION:

Slide #1

Liver no major changes. In several portal areas small round nuclear infiltrates.

Spleen shows severe congestion with foci of EM erythropoesis (splenomegaly). The white pulp consists of proliferations monomorphic, large cleaved and non-cleaved lymphoblasts, only in some centres with a few smaller, more well-differentiated cells.

Kidney shows no histological visible changes.

Slide #2

Lymph node (3x) filled with nodular proliferating monomorphic lymphoblasts, filling the complete lymph node. Only small enclaves of more mature lymphocytes, especially under the capsule. In the surrounding fat tissue idem small foci with lymphoblasts.

Ilium with at least one proliferation of lymphoblasts and more areas with mature lymphocytes (normal GALT).

Pancreas (exo- and endocrine) no changes.

Duodenum with in the submucosa small areas with more mature lymphocytes and one larger follicle (GALT).

Slide #3

Kidney no changes.

Colon (large lumen) no changes.

Connected to it in fat tissue a cystic lymph node with a "cortex" of lymphoblastic cells.

Slide #4

Another 3 massive lymph nodes and one more cystic with the same lymphoblastic proliferations.

Lungs collapsed (PM atalectase?) showing some hyperaemia and possible small amount of oedema and some alveolar ectasie.

Slide #5

Fat tissue with many small lymphoblastic "lymph nodes".

Another massive lymphoblastic lymph node.

Slide #6

Heart muscle without visible changes.

MORPHOLOGICAL DIAGNOSIS:

Generalized lymphoblastic lymphadenopathy

COMMENTS:

With the age of 8 years it cannot be called the juvenile lymphoblastic sarcoma, which is considered to be present in ferrets up to 2 years old, but the changes are similar as seen in this animal. The main difference is that in this case liver and kidney are not involved.

Daisy


Nipper did okay for a while. He was still in a group with Ruby, Honey and Snoopy (who had joined the group in May). He hadn't really bonded with any of them but enjoyed the company and sleeping with them. Nipper went through a spell of diarrhoea, occasional vomiting, and lack of appetite when some of the ferrets had diarrhoea in June/ July. But after 2 weeks he was back to normal, eating fine again.

Nipper sleeping with Honey

He even had a weird looking skin tumour taken off on 14/08/08 and was fine while under anaesthetic.

Nipper with warty growth on the right side of his face

But what was to come was one of the most awful things I'd ever seen. I wasn't sure whether to write about it in detail because it is upsetting but I just want people to be aware of what can happen. I wrote to the Ferret Health List about it, especially Dr. Ruth Heller helped me through it, and I will add some of her comments (with permission). I'm not going to write about it, I'm just copying what I wrote to the FHL as it is painful enough to deal with this again.

Post to FHL 30 September 2008

I'll try to make this as short as possible. Please remember I'm German and I can't think straight after this afternoon so my grammar may be a bit haphazard.

Nipper, 8 1/2, last year he was diagnosed with chronic lung disease and cardiomyopathy. He got Fortekor (Benazepril) and a few months ago we started Theophylline. He was already on Prednisolone because of insulinoma and the pred was needed for the lung condition, too. And 4-5 or so months ago we started Furosemide because he started coughing with fluid in his lungs. He did quite well until recently.

Beginning of July he went through a phase where he had some diarrhoea and occasional vomiting for 2 weeks. He went off his food and got one shot of Metocloperamide which got him eating again and after 2 weeks he was okay. Then recently, the last 2 weeks or so, he slowly went off his food again. Some mucous diarrhoea at times. The last few days it was a real struggle to get him to eat, he eats ground meat and didn't like the tiny pieces of bone in it. Last night there was no way he would finish his portion, he looked okay before food but in pain and miserable after his half portion. This morning I didn't feed him because I didn't want to upset him. He only had his Furosemide, no heart tablet, no pred. With the discomfort after eating I thought of stomach ulcer so I got some Carafate from the vets. I gave this to him and tried to feed him 3/4 hour later. He had a few mouthfulls and then started to do something that seemed to me like a mix of coughing and trying to vomit/ retching/ gagging. I don't know how to describe it, it sounded like he had suddenly become very congested. I put him back to bed because this was horrible to watch and that's when he started this weird cough, it sounded hollow, like a bark almost, he started to wheeze and I imagine whooping cough to be like his coughing was. His mouth was wide open, he seemed rigid, it seemed he had problems breathing, it also sounded like his lungs were full of mucous. I phoned the vets and rushed him there to be put to sleep.

Got there and he'd stopped coughing. My vet examined him, listened to his chest, she said his heart was racing, I mean *really really* fast, my vet palpated his abdomen which appeared to hurt him. She then tried to take his temperature which is when the distressing last moments started. He tried to cough again and then just collapsed, I think he started to suffocate, he was rigid, head bent back, eyes wipe open, mouth wide open, gasping for air, he tried to breath and cough but couldn't, I saw his tongue turned blue and I just became hysterical at this sight, my vet asked me to call a nurse for help and I didn't go back in. I don't know if Nipper just died or whether they managed to help him die. They said they did but it sort of looked like they just told me this to make it easier for me. The last moments of his life, the pictures in my head, are haunting me.

Please, if anybody knows what may have happened, please let me know so I understand. I think suffocation must be one of the worst ways to go and I don't know why he couldn't get air. Did the Carafate do this to him? Could he have had a heart attack or acute heart or respiratory failure? It was obviously the stress because he turned bad when my vet tried to take the temperature which I don't know why she did this when we had agreed to put him to sleep. I need to know whether he suffered as much as what it looked like.

We did a necropsy and sent tissue samples off, the heart was so soft and floppy, I've seen hearts of cardiomyopathy ferrets before but nothing like this. No muscle tone to it at all. Yet he didn't look this ill, I mean he had a lack of appetite and had been quiet but still had a walk around the garden and enjoyed rolling in the grass. He didn't look or act as ill as his heart looked. Also, I don't know if this is right, the vet nurse did the necropsy because my vet didn't have time and to me it looked like all organs were very vascular, lots of little blood vessels everywhere and I'm sure from what I remember, the organs from the other ferrets weren't covered with blood vessels like this. We think we found an enlarged right adrenal gland, it looked quite knobbly. Spleen and liver looked abnormal. Lungs were bad, especially the right side. Tissue samples were sent off.

Ulrike


In the meantime, I got the histopathology report back and sent it to the list, too:


Nipper's histopathlogy report


Diagnosis
Pathological changes in various tissues

Prognosis
No applicable

Sections from necropsy samples of various tissues from a Polecat Ferret, age and sex not specified, were examined microscopically.

LIVER: 3 samples received; 3 sections examined. One of these sections is largely unremarkable apart from a very small, single focus of hepatocytic vacuolar change. One section includes a large, cystic structure lined by a single layer of cuboidal epithelium, which I think is probably the distended gall bladder, but it is filled with blood and fibrinous clot material. The parenchyma surrounding this is markedly congested, the hepatocytes swollen and vacuolated and the portal areas inflamed and fibrosed, with moderate dilatation of bile ducts. In the third section, there is marked bile duct proliferation and marked peribillary, lymphoplasmacytic inflammation. The majority of the proliferated bile ducts are mildly distended with more or less amorphous debris, often admixed with a few neutrophils.

KIDNEY: 1 sample received; 1 section examined. A single area of interstitial fibrosis extends from the capsule down into the medulla and is associated with moderate tubular atrophy and dilatation and a minimal infiltrate of mononuclear inflammatory cells. The remainder of the section is histologically unremarkable.

SPLEEN: 1 sample received; 1 section examined. The splenic pulp is expanded by a combination of congestion and extramedullary haemopoiesis.

LUNG: 2 samples received; 2 sections examined. Microscopy reveals fairly marked congestion accompanied by slightly increased cellularity of the alveolar walls and slightly increased numbers of alveolar macrophages. A large plug of mucoid material admixed with a few neutrophils is present in one of the mainstem bronchi.

HEART: 1 sample received; 2 sections examined. Grossly, this appeared abnormally globose in shape and the lumen of the left ventricle was markedly dilated. Microscopy reveals patchy vacuolar degeneration of myocytes in the left ventricular wall, often accompanied by mild to moderate anisokaryosis and associated with mild interstitial fibrosis. There is minimal inflammation.

ADRENAL GLAND: 1 sample received; 1 section examined. The normal architecture of the gland is largely effaced by a cellular proliferation forming a mass that occupies almost the entire cortex in the section examined, expanding the gland markedly, crossing the capsule and growing into the adjoining adipose connective tissue. It consists of a mixture of cell types, including very large, ballooned cells with clear cytoplasm; medium-sized to large cells with fairly abundant, variably vacuolated, eosinophilic cytoplasm; and smaller cells with a small amount of amphophilic cytoplasm. There are also some interconnecting bands of spindloid cells coursing through the mass. There is little nuclear atypia and only occasional mitoses can be found.

PANCREAS: 1 sample received; 1 section examined. In this section there is patchy, mild interstitial inflammation and fibrosis of the exocrine portion of the gland and there is marked vacuolation of the Islet cells.

DIAGNOSIS: Various pathological changes - see "Discussion" below.

DISCUSSION: There is evidence of fairly severe, chronic cholecystitis and cholangitis, which was probably sufficient to have been causing biochemical changes consistent with hepatic dysfunction. The cause is uncertain, but as there is also mild pancreatitis the possibility of infection ascending the biliary system from the intestine should be considered. Vacuolation of islet cells is often seen in animals with diabetes mellitus.

The heart showed gross and histological changes compatible with dilated cardiomyopathy and the congestion and mild interstitial pneumonia in the lungs may have been associated with this, although few pigmented macrophages ("heart-failure cells") were seen in the sections examined. Cardiomyopathy is fairly common in ferrets, but a definitive cause has not been identified, as far as I am aware. It is particularly common in some American lines, suggesting a possible genetic basis. Cardiomyopathy may also occur secondary to some myocardial infections, especially viruses, and some workers have suggested a dietary deficiency may be to blame. Clinical signs may be seen In animals as young as 1 year of age, but are more common between about 5 and 7 years.

Adrenal tumours of the type seen in this animal, comprising a pleomorphic population of cells, effacing the normal structure of the gland, have traditionally been diagnosed as carcinomas, but there is little published material correlating histological criteria used in diagnosis with clinical outcome and I suspect many such tumours are behaviourally benign and may be better classified as adenoma.

The combination of extramedullary haemopoiesis and congestion, as seen in the spleen of this animal, is a common cause of splenomegaly in ferrets but the cause remains uncertain, although there are many hypotheses.

There is also evidence of mild, patchy, chronic interstitial nephritis, which is unlikely to have been of any clinical significance at this level.

My own comments:

Nipper


Dr. Ruth Heller's comments after reading the report:

Dr. Ruth: LIVER: **This indicates some pretty significant liver issues. If that is not the gall bladder, it could have been a liver cyst or hematoma (and I have seen several encapsulated hematomas in ferret livers).**

Dr. Ruth: KIDNEY: **This is fairly mild kidney disease, IMO.**

Dr. Ruth: SPLEEN: **Which is very common in ferrets, and can be an indicator of chronic blood loss.**

Dr. Ruth: LUNG: **And that, unfortunately, is what he was choking on. The congestion in the lungs was making his breathing difficult. There still may have been clots there, that just didn't show up in the sections they looked at, but severe lung congestion prevents absorption of oxygen in and of itself.**

Dr. Ruth: HEART: **And this just confirms the diagnosis of heart disease.**

Dr. Ruth: ADRENAL GLAND: **So a fairly inactive looking mass, with no clinical signs of overproduction of adrenal hormones - I've seen this as an incidental finding in almost every ferret over seven that I've been allowed to do a post-mortem on, whether or not they were showing signs of adrenal disease.**

Dr. Ruth: **So overall, some real indication of the lungs/heart being the major problem, with the complication of the liver changes.**

Some more conversation:

Me: When he started coughing at home, it sounded like he had suddenly become very congested. It sounded like he was trying to cough mucus up. But at the vets he was better and then he just suddenly "collapsed", became rigid, mouth wide opened, gasping for air. I don't know anything about lungs, could the mucus have lodged in a way that it stopped air from getting into the lungs? It just happened so quickly and suddenly that I don't understand this.

Dr. Ruth: **Yes. The mainstem bronchi is one of the main airway passages. The trachea divides into bronchi, which further divide into the lung lobes to eventually become bronchioles and then alveoli, which is where the oxygen/carbon dioxide exchange occurs. A mucus plug in one of the mainstem bronchi will prevent air from getting to a significant portion (about half) of the lung tissue at all, and with already compromised oxygen exchange from lung congestion and heart disease, could easily have tipped him over the edge.

Also, that type of agonal breathing, posturing is very common. Poor guy.**

After seeing the post mortem pictures:

**The first picture is the spleen, I noticed that you have it questioned. Looks like a hematoma on the spleen to me. Heart definitely dilated, thin walled.**

Nipper

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