2. Structure of presentation
Information supplied
Interpretation of findings
Pathophysiology and differential exclusions
Diagnosis and case management
3. Background
Signalment: 3YO, Male entire, DSH cat
History: Acute lethargy, vomiting and anorexia
Clinical exam: Obese and almost comatose
Essentially I am going to aim to work through this case exactly how I did from start to finish. I hope to, in the end, have explained thoroughly the pathophysiology of the aetiological cause and appropriate treatment of such cases in practice - both from my own experience and using appropriate references.
Even from the brief signalment it’s clear to see that this is an extreme case. Such acute onset and severe levels of clinical signs need prompt, thorough investigation. It’s likely that if therapy is pursued then it’s going to be intensive.
In a first opinion setting I think that it’s important to realise that the decisions you make early in the approach to a critical patient can lead to huge variations in the level of success. This isn’t an “admit it and see it in a few hours” sort of case. This patient needs attention and lack of haste or inappropriate interpretation of the blood results that follow could prove fatal.
We have a mild polycythemia, moderate leukocytosis characterised by a neutrophilia (no evidence of a left shift) and a lymphopenia.
Thinking about the Polycythemia we instinctively should be seeing our Absolute/ Relative/ Primary or Secondary mind map and quickly ruling out specific causes of erythrocytosis. We know PCT occurs in response to hypoxia at the level of the JGA and results from a release of EPO, stimulating BM production of erythrocytes.
This cat ain’t at altitude, where a low PaO2 is the trigger.
No evidence of respiratory disease and consequent lack of oxygenation.
No murmur, so less likely of CardioVascular origin.
I mean it could be shock so keep that in our mind.
Polycythemia vera – not likely in such a young animal not to mention it’s not as extreme as we would expect in a true PCV.
But look – when we take a look at the leukocytes in conjunction its clear to see the most likely cause is a combined stress leukogram. Remember – SMILED. Okay, it’s not the most textbook but I think at this point it’s something we should hav up there. I guess we could always test again in an hour to monitor the PCV etc because we understand that the Adrenilin induced stress leukogram is transient. If I was comatosed – I’d be stressed.
So this is a lot to take in. This is where the interpretation and understanding of your pathophysiology is critical. It was here my differential list was formed and focussed.
Glucose – moderate hyperglycaemia 15. 5mmol/l – Stress is our main differential here. Of course, with this patient being a cat and a blood glucose surpassing the renal threshold of 12nmol/l we would be looking out for a glucosuria. Other differentials for hyperglycaemia would be things like diabetes mellitus, DKA, hyperadrenocorticolism, glucogonoma, liver tumours (although more commonly hypoglycaemia)
Azotemia – At this stage don’t know if it’s pre renal/renal or post renal for sure. But when we look through the other bloods and take into account the comatosed (and likely dehydrated) presentation of the patient - it’s likely multifactorial (pre renal components and renal). We will go onto confirm it with a USG.
Hypocalcaemia – It’s a significant finding. Hypoparathyroidism, chronic renal disease either by diuresis effects or consequent to the increased phosphate bound protein. Often though most chronic patients aren’t clinical with it because after all only 5% of calcium is bound to phosphorous. Or Hyperphosphotaemia causing disease - diabetic ketoacidosis, rhabdomyolysis, overwhelming systemic infections, and tumor lysis syndrome)
The Total protein is increased with albumin being the main reason, as globulins are set steady. 40-50% of calcium is bound to Albumin in circulation so we need to pay even more attention to it when there is paradoxical movement in their parameters. I came to the conclusion that although the albumin may actually be low, it’s depicted as a hyperalbuinaemia because of dehydration, not hepatocellular tumour, the only other known cause.
Now here is where it gets interesting. Again reinstating acute renal disease, but we have never really been taught much about anion gap so I had to do some reading. It proved useful because the specific results illustrate a particular type of acidosis that helps pin point the diagnosis. I’ll come back to this though.
This is all well and great pointing us to acute renal disease of the sort but still no diagnosis. There are lots of causes from infection with leptospirosis to urethral obstruction but we can’t make a proper assesment without one important thing – Yip Urine analysis. If anything we need to know both the hydration status and USG to assess any form of azotemia. But there is also gross and microscopic examination that can highlight disease.
We do have glucose in the urine but no presence of ketones ruling out DKA.
The likelihood of a diabetic patient only having a qualitive result of 1+ on the dipstick is unlikely plus the fact the presentation doesn’t pair with DM in any way shape or form other than the hyperglycaemia.
Of course there has got to be a stress component – it’s a cat! But if we now look now with a mildly concentrated urine (heading towards isothynuriec). All in all renal dysfunction is now a pertinent issue. Glomerular disease could lead to increased filtration and without functioning proximal tubules glucose would be reabsorbed less efficiently. Obviously an infection could be present but looking at the big image overall I think the protein is either blood contamination or simply as a result of leaky damaged glomerulus.
EGT!
Taking into account all the findings; the presentation – acutely sick cat, with vomiting (likely some component of uraemia but also just nausea and pain), not wanting to eat. The comatose appearance a combination of the CNS effects as well as the fast ensuing renal failure. Bloods showing renal damage with associated acidosis.
One thing I found that was interesting was that in matter of fact, these crystals aren't the most common form seen with EGT. As matter of fact….The monohydrate crystals are the most common, not these dihydrate ones. A tad confusing because they look like struvite crystals – Mg crystals.
This is the key understanding of this toxicity. A really easy pathway to understand and learn but doing so provides an overall understanding of the pathophysiology and clinicians approach to therapy.
Talk through the pathway.
The first of two steps is the production of glycoaldehyde from EG by the enzyme alcohol dehydrogenase. Glycolaldehyde is then rapidly metabolized to glycolic acid. The oxidation of glycolic acid to glyoxylic acid is which allows glycolic acid to accumulate, resulting in acidosis and nephrotoxicosis. REFER to pH and acidosis.
Glyoxylic acid is rapidly metabolized to formic acid, carbon dioxide, glycine, serine, and oxalate. Oxalate is not further metabolized and is cytotoxic to the renal tubular epithelium and exacerbates the metabolic acidosis. Glycolic acid and oxalate are the metabolites thought to be most responsible for acute tubular necrosis associated with EG ingestion.
Oxalate also combines with calcium to form a soluble complex that is excreted via glomerular filtration. Calcium oxalate crystals form within the lumina of tubules as water is reabsorbed from the glomerular filtrate and the pH decreases (smaller numbers of calcium oxalate crystals may also be observed in the adventitia of blood vessel walls throughout the body).
It’s this oxalic acid that precipitates with free Calcium giving rise to the crystal deposition and decimates the nephron.
Something that I found interesting was that there tends to be a period of in-between the initial vomiting following ingestion and the full blown Renal failure whereby a lot of patients almost look clinically normal. This is thought to be believed by the two step pathway forming the glycoaldehyde and it’s major rate limiting step. So example of cat ingesting it outside – owner doesn’t see it initially vomit…then boom – it’s dead.
Lethal dose - 1.4 mL/kg body wt in cats, 4.4 mL/kg in dogs
3 hours till peak blood concentration! <treatment implications regarding haste of therapy.
multisystemic signs CNS disease or trauma, gastroenteritis, pancreatitis, ketoacidotic diabetes mellitus, and acute renal failur. If ingestion of EG is not witnessed, diagnosis is usually based on a combination of history, physical examination, and laboratory data.
Normochloremic metabolic acidosis with an increased anion gap,
minimally concentrated or isosthenuric urine with an acidic pH
marked serum hyperosmolality with an increased osmolal gap. Serum osmolality can be increased as much as 100 mOsm/kg above normal (280–310 mOsm/kg) within 3 hr of EG ingestion.
Flick back to BIOCHEM - The difference between measured and calculated (1.86 [Na+ + K+] + glucose/18 + BUN/2.8 + 9) osmolality is referred to as the osmolal gap. The gap is caused by the presence of osmotically active particles (eg, ethylene glycol) in the serum that are not factored into the above equation.
Calcium oxalate crystalluria - 3 and 6 hr after ingestion in cats and dogs, respectively. Monohydrate calcium oxalate crystals (clear, 6-sided prisms) are more common than dihydrate calcium oxalate crystals (maltese cross or envelope-shaped).
EG concentrations in serum and urine are detectable by 1–2 hr after ingestion. Commercial test kits can detect serum EG concentrations of ≥50 mg/dL. Good tests; sensitive and specific.
Some antifreeze preparations contain fluorescein, which appears bright yellow-green when viewed under a Wood's lamp. Urine fluorescence has been used as a qualitative adjunctive test in suspected EG ingestions in people and may be of value in veterinary medicine.
Hyperphosphatemia - commercial antifreeze solutions that contain phosphate rust inhibitors. This hyperphosphatemia resolves before the onset of EG-induced acute renal failure and azotemia, then recurs when the animal becomes azotemic.
Euthanasia – a reasonable choice in majority of these cases. Most clinicians who I have worked with in the past say that if the animal is already demonstrating clinical signs of acute renal failure and shows blood work changes by the time of presentation they advise euthanasia because of the seriously grave prognosis.
However if treatment is sought after decontamination and supportive therapy is the mainstay of the therapeutics.
Emesis using any potent emetic agent – most commonly xylazine in cats – has been used. But cast your mind back to the rate of absorption. It takes a mere 2 – 3 hours for EG to reach peak serum concentrations following rapid absorption from the GI tract. So is it worth it? And is it safe? If we have a patient that is comatosed and showing neurologic signs then not likely. Don’t want an aspiration pneumonia on our hands as well as EGT.
Activated charcoal – We all love it. It is genuinely the backbone of emergency critical care medicine but in fact – something I learned whilst watching online webinars is that “Activated charcoal does not bind to Ethylyene Glycol”. Or any other “Ol” for that matter. So propylene glycol – nope.
Gastric lavage is the preferred mode of decontamination. As well as washing the patient to rid it of cutaneous contamination < Did you know that EGT has been reported in pour on accidents via cutaneous absorption.
Fluid therapy – People assume its to flush out the crystals/ toxins or the sorts. No. It’s to combat the dehydration by increasing perfusion to the kidneys. And we need to balance the ins and outs. In acute renal failure we all know the animals can develop post obstructive diuresis following a period of anuria. Gold standard would be to catheterize and measure hourly output.
The dose of 4-MP (5% solution [50 mg/mL]) is 20 mg/kg body wt, IV, initially, followed by 15 mg/kg, IV, at 12 and 24 hr, and 5 mg/kg, IV, at 36 hr. If 4-MP is not available, an ethanol regimen. This doesn’t mean downing alchohol straight from the bottle! (5.5 mL of 20% ethanol/kg body wt IV every 4 hr for five treatments and then every 6 hr for four additional treatments) is recommended.
There is a dosage regme for bicarbonate but most clinicians don’t touch it and I have been told by vets before that if you haven’t been shown then don’t try. But it is an option none the less. I think most attempts of treatment are happy to try with spiked fluid bags.
Overall EGT leads to severe acute renal disease. Perhaps the most striking thing is the speed of absorption and how it does not give much time for clinical intervention.
It’s something to always be on the look out for in the ECC + OOH setting but overall it’s not that common as people think, more common in colder climates where the use of such chemicals are daily.
Hope they enjoyed it.
