aproach to disease managment Flashcards
resourses for intoxication cases
Veterinary Poison Information Service (VPIS)
BSAVA/VPIS guide to common canine and feline poisons.
Ingredient lists/data sheets
Phone triage for toxcity case
Information to acquire:
Signalment- size??
Suspected toxicant, timing of ingestion/exposure, suspected dose.
Likely time of arrival.
Instructions for owner:
Prevent further exposure- dont let animal lick toxins off coat
Bring any packaging of the suspected toxicant.
Preparation by the team:
Set up necessary medication, supportive care etc.
Contact VPIS if required
Decontamination for intoication
Topical-
Rinse eyes with tap water or sterile water
Wash skin/coat with a mild detergent
Emesis-
General rule: Sooner = better.
Solid toxins (grapes/raisins, chewing gum, chocolate) stay in the stomach longer than liquids (ethylene glycol) and powders (lily pollen).
Emesis contraindications:
Non-toxic/very low toxicity substance or dose.
Patients that have already vomited
Caustic/corrosive agent
Volatile agent e.g. petroleum products
High risk of aspiration - megaoesophagus, comatose ect
Respiratory distress
Severe acid-base or electrolyte derangements
agents for inducing emisis in toxicity cases
Inducing emesis:
Apomorphine – licensed for dogs
No licensed options for cats – xylazine preferred.
Soda crystals – care
Examine the vomitus to check the toxin has been expelled
Gastric lavage may be considered where emesis is contraindicated
activated charcoal for decontamination
Adsorbant – bind to toxins to prevent absorption
Alcohol and xylitol do not bind to activated charcoal
Repeated doses recommended
Feed as a slurry with food if possible
May affect the efficacy of orally administered medications – give drugs parenterally while giving charcoal if possible.
emergency stabalisation for toxicity
Primarily of the neurological, cardiovascular, and respiratory system.
See specific lectures for more details.
General advice:
Control seizures- rectal diaxopam
Provide oxygen
Get an IV line
baseline tests for toxicity
Haematology and biochemistry-
Often normal, especially in acute, asymptomatic cases.
Most useful for monitoring and symptomatic cases.
Urinalysis-
Especially useful for suspected ethylene glycol toxicity to look for calcium oxalate crystals.
Coagulation profiles-
Where anticoagulant rodenticide intoxication is suspected
Toxic metabolites:
It is possible to check stomach contents and blood/urine samples for a great number of toxins
Mostly used for forensic work (e.g. wildlife crime) and in zoos and other very valuable animals.
supportive care for toxicity
Intravenous fluid therapy-
Replace fluid loses e.g. from vomiting
Maintain renal perfusion and diuresis
Analgesia-
Opioids preferred over NSAIDs in most cases
Antiemetics-
Maropitant and ondansetron preferred options
Gastroprotectants-
H2 blockers- ranitidine, famotidine
Proton pump inhibitors - omeprazole
Sucralfate
Common Intoxications
Alliums
Anti-parasiticides
Avocado
Chocolate
Ethylene glycol
Grapes/raisins
Herbicides and fertilisers
Lilies
Metaldehyde
NSAIDs
Rodenticides
Teflon
Xylitol
Alliums as intoxicants
The allium family includes onions, garlic, and leeks as well as ornamental varieties.
Cats more sensitive than dogs (5 g/kg for cats; 15 to 30 g/kg for dogs).
Toxicology: Contain organosulphoxides -> organic sulphur compounds -> oxidative damage to erythrocytes -> Heinz body anaemia.
Clinical effects: Inappetence, vomiting, diarrhoea, Heinz body anaemia, methaemoglobinaemia and/or jaundice.
Treatment:
Decontamination (if possible)
Fluid therapy
Symptomatic and supportive care.
Prognosis: Favourable
Anti-parasiticides for toxicities- Pyrethroids:
Cats and snakes
Toxicity: Prevents closure of voltage-dependent sodium channels in nerve membranes, -> repetitive membrane depolarization.
Cats: Vomiting, hypersalivation, ataxia, dilated pupils, tachycardia, hyperexcitability, hyperaesthesia, hyperthermia, tachypnoea, twitching, convulsions and respiratory distress.
Reptiles: Loss of coordination, loss of righting response, sensitivity to bright light, and muscle spasms and panic.
treatment-
Active cooling
Lipid infusion
Decontamination
Seizure control – (diazepam, midazolam, pentobarbital, phenobarbital, propofol, or levetiracetam).
Fluid and nutritional support
prognosis- gaurded to poor
Anti-parasiticides for toxicities- Fipronil
frontline
Rabbits
Toxicity: Blocks GABA receptors in the CNS -> prevention of chloride ion uptake -> excessive CNS stimulation.
Fipronil: Seizures, tremors,
anorexia, lethargy, and death
treatment-
Stasis treatment if needed
Decontamination
Seizure control – (diazepam, midazolam, pentobarbital, phenobarbital, propofol, or levetiracetam).
Fluid and nutritional support
prognosis- gaurded to poor
Anti-parasiticides for toxicities- Ivermectin
Chelonia- can use in low doses
Toxicology: Binds to GABA-gated chloride channels, -> increased chloride ion uptake -> hyperpolarization and flaccid paralysis
Flaccid paralysis and death
treatment-
respiritory support
Decontamination
Seizure control – (diazepam, midazolam, pentobarbital, phenobarbital, propofol, or levetiracetam).
Fluid and nutritional support
prognosis- gaurded to poor
Avocado as an intoxicant
Toxic compound = persin
Birds are the most commonly affected species in small animal practice.
Toxicology: Myocardial necrosis in birds and mammals; mammary necrosis and haemorrhage in mammals.
Clinical effects: GI signs (anorexia, vomiting, diarrhoea,), mastitis, cardiac insufficiency.
Treatment:
Decontamination (if possible)- gastric lavage necessary in birds and horse
Symptomatic and non-specific
Prognosis: Poor if cardiac signs have developed
Chocolate as intoxicant
Toxic compound = theobromine
Cocoa powder = highest concentration of theobromine; white chocolate contains negligible amounts.
Toxicology:
Antagonism of cellular adenosine receptors -> CNS stimulation
Inhibition of cellular calcium reuptake -> increased muscle contractility in cardiac and skeletal muscle.
Clinical effects: Vomiting
Treatment:
Decontamination
Fluid therapy
Anti-emetics e.g. maropitant
Sedation e.g benzodiazepines
Beta-blockers (e.g. atenolol, propranolol)
Prognosis: Good
Ethylene glycol as an intoxicant
Antifreeze; used in screen wash, brake fluid, fountains over winter etc.
Cats more sensitive than dogs.
Toxicology: Converted by alcohol dehydrogenase to various toxic metabolites -> renal damage and hypocalcaemia.
Clinical effects:
cannot decontaminate once symptoms show
Stage 1: Non-specific signs (vomiting, ataxia, tachycardia, weakness, PU/PD) + CNS signs in cats (convulsions, rapidly progressing to coma)
Stage 2: Cardiopulmonary signs
Stage 3: Renal signs
Clinical pathology: Metabolic acidosis, oxaluria, hyperglycaemia, hyperkalaemia and hyperphosphataemia
Treatment:
Decontamination rarely useful
Ethanol = specific antidote- competes for metabolites in liver and stops toxins being metabolised from the ethalyene glycol
Fomepizole = a competitive inhibitor of alcohol dehydrogenase
Sodium bicarbonate
Intensive fluid therapy and monitor renal enzymes
Prognosis:
Good in dogs if presented at time of ingestion, guarded to poor in all cats, and dogs once signs of renal failure have developed.
Grapes/raisins as an intoxicant
Dried fruit appears to be a greater risk than fresh fruit.
There is no apparent correlation between dose ingested and the incidence of toxicity.
Primarily canid species affected, cats tend to show GI rather than kidney signs.
Toxicology: Toxic mechanism unknown
Clinical effects: Vomiting and diarrhoea (both +/- blood), hypersalivation, ataxia, weakness, and lethargy, progressing to renal failure over 24-72 hours.
Treatment:
Decontamination (if possible)
Aggressive fluid therapy
Supportive care- very expensivve and possibly not needed! onwer needs to choose
Prognosis: Good to poor. much wosr once renal signs show
Herbicides and fertilisers as intoxicants
Herbicides:
Phenoxyacetic acid derivative herbicide – very common lawn weed killers, very acidic and volatile.
Diquat/diquat dibromide
Glyphosate
Moss killer is often iron based – treat as for iron toxicity
Most clinical signs are associated with irritation caused by the products, but renal and hepatic toxicity may occur with some products.
Fertilisers:
Most very low toxicity; clinical effects due to irritation
Clinical effects: Variable, but many are related to irritation (hypersalivation, vomiting, diarrhoea, ulceration of mucous membranes)
Treatment:
Decontamination – NOT EMESIS- topical, fairy liquid
Supportive care – fluid therapy, analgesia, GI protectants.
Feeding tube in severe cases.
Prognosis: Favourable
Lilies as an intoxicant
True lilies (Lilium spp.) and day lilies (Hemerocallis spp.) are the toxic species.
All parts of the plant are toxic.
Even very small amounts e.g. grooming pollen from fur can -> toxicity
Toxicity: Mechanism unknown, causes necrosis of renal tubular epithelial cells
Clinical effects: Vomiting, anorexia, depression, PU/PD and renal failure.
Treatment:
Decontamination – topical, emesis and activated charcoal
Fluid therapy and close monitoring of renal function
Supportive care
Prognosis: Favourable if treatment is started before onset of renal damage
Metaldehyde as an intoxicant
Outdoor use of metaldehyde slug baits has been banned in the UK from 31 March 2022.
Toxicology: Not fully understood; possibly due to decreased inhibitory GABA concentrations.
Clinical effects: CNS signs (hyperaesthesia, muscle spasm/rigidity, tremors, twitching, convulsions), hyperthermia, tachycardia, tachypnoea or respiratory depression, and cyanosis
Treatment:
Decontamination (gastric lavage)
Diazepam to control twitching/convulsions, with escalation to full GA if required.
Active cooling
Supportive care – fluid therapy, liver support if needed.
Prognosis: Favourable if mild signs, poor once covulsions develop.
aspirin as an intoxicant
Stimulates the respiratory centre -> hyperventilation and respiratory alkalosis, ->metabolic acidosis over time.
Depression, vomiting, anorexia, hyperthermia, tachypnoea, haematemesis, melaena, abdominal tenderness and anorexia.
treatment-
Decontamination
Fluid therapy
Oxygen therapy (if required)
Antiemetics (if required)
Gastroprotectants e.g. sucralfate, ranitidine or famotidine, omeprazole
Monitor renal and hepatic enzymes, electrolytes, and acid-base changes.
paracetamol as an intoxicant
Toxic metabolite which induces cellular necrosis, methaemoglobin, and Heinz body formation.
three pathways it can be metabolised- third pathway is the toxic one, this kicks in once overdosed- cats hae limited ability to use first tow pathways so no safe dose like there is for dogs
Depression, vomiting, anorexia, hyperthermia, tachypnoea, haematemesis, melaena, abdominal tenderness and anorexia.
: Brown mucous membranes, hypothermia, and facial and paw oedema (mainly cats)
owners may be reluctant to tell about giving paracetamol- tell by clinical sigsn- face and paw oedema
treatment-
Specific antidote:
N-Acetylcysteine
Methaemoglobinaemia treatment:
Vitamin C
Methylene blue- very carcinogenic! be careful
Decontamination
Fluid therapy
Oxygen therapy (if required)
Antiemetics (if required)
Gastroprotectants e.g. sucralfate, ranitidine or famotidine, omeprazole
Monitor renal and hepatic enzymes, electrolytes, and acid-base changes.
ibupropen as an intoxicant
Non -selective COX inhibitor; toxicity due to COX-1 inhibition
Depression, vomiting, anorexia, hyperthermia, tachypnoea, haematemesis, melaena, abdominal tenderness and anorexia.
treatment-
Decontamination
Fluid therapy
Oxygen therapy (if required)
Antiemetics (if required)
Gastroprotectants e.g. sucralfate, ranitidine or famotidine, omeprazole
Monitor renal and hepatic enzymes, electrolytes, and acid-base changes.
Prostaglandin analogue (misoprotol)
Rodenticides as an intoxicant
Usually anticoagulants, occasionally vitamin D is used.
1st generation anticoagulant rodenticides are less toxic than second generation.
Toxicology:
Anticoagulants: Competitively inhibit hepatic vitamin K1 epoxide reductase -> depletion of clotting factors (II, VII, IX and X); impairment of hepatic prothrombin synthesis.
Vitamin D: Hypercalcaemia -> tissue mineralisation and renal failure
Clinical effects:
Non-specific: Lethargy, weakness, depression
Other signs will depend on the site of bleeding – petechiation, abdominal distension, cough/respiratory distress etc
Prognosis:
Favourable in mild and asymptomatic cases; poor where uncontrolled haemorrhage is present.
Treatment:
Decontamination
Anticoagulant:
Chronic/symptomatic cases = start vit K immediately.
Acute/asymptomatic cases = wait and check PT after 48-72 hours.
Severe anaemia = Blood transfusion.
Vitamin D:
Promote diuresis - fluid therapy and diuretics (e.g. furosemide)
Promote calcium excretion - bisphosphonates or calcitonin.
Polytetrafluoroethylene as an intoxicant
AKA Teflon; used in non-stick coatings, especially on cookware.
Primarily effects birds; humans can also be affected but symptoms tend to be self-resolving.
Toxicology: Overheated PTFE releases fumes which, when inhaled, -> alveolar congestion and pulmonary oedema.
Clinical effects: Respiratory distress, acute death.
Treatment:
Decontamination not possible
Supportive care only – oxygen supplementation, NSAIDs and diuretics, fluid therapy, and supplemental heat
Consider antibiosis
Prognosis: Guarded to poor
Xylitol as an intoxicant
Artificial sweetener, commonly found in chewing gum.
Toxicology: Stimulates insulin release in dogs -> severe, rapid-onset hypoglycaemia; hepatotoxic.
Clinical effects: vomiting, tachycardia, ataxia, depression, eventually coma, convulsions and collapse; signs of liver failure and coagulopathy less common.
Treatment:
Decontamination – emesis and activated charcoal
IV dextrose CRI where hypoglycaemia is present
Liver support (SAMe, silybin)
Prognosis:
Favourable if caught early, poor where liver failure has developed.
NEOPLASIA
–> the uncontrolled, abnormal growth of cells
Benign neoplastic masses do not spread (metastasize) - Examples include lipomas and sebaceous adenomas
Malignant neoplasia frequently invade locally and metastasize “cancer” – Examples include lymphoma and carcinomas
Both benign and malignant disease are commonly seen in practice
Cancer is the cause of death in approximately 47% of dogs >10 years of age
What type of neoplasia is it? -We cannot treat it effectively if we do not know what it is
Is it benign or malignant? -Benign disease may not always need treatment
If malignant, has it spread? “Staging” - Important for prognosis and treatment
Are there any paraneoplastic effects? -High calcium with anal sac adenocarcinoma
Does the patient have co-morbidities that could impact on treatment?
Consider whole patient welfare and what is appropriate for the pet and owner
cytology for neoplasia
FINE NEEDLE ASPIRATE – For solid tumours or enlarged lymph nodes – External and internal via ultrasound guided FNA
FLUID CYTOLOGY – Abdominal & thoracic effusions, prostatic wash etc. – Make a fresh smear and put some into EDTA
(care some neoplastic effusions may not have detectable neoplastic cells on cytology)
BONE MARROW ASPIRATE –
Indications – Cytopenia - especially when multiple cell lines are affected (anaemia, thrombocytopaenia) Unexplained big increase in cell lines – lymphocytosis, neutrophilia etc. Hyperglobulinaemia (multiple myeloma)
Slides are best sent to the lab in my opinion
fine needle asprirate for neoplasia
Pros:
Simple, quick and non-invasive
Quick turnaround for results
Lower cost than surgical biopsy and histopathology
Performed awake in most cases unless:
-Fractious
-The mass in near a delicate structure
-Abdominal mass
Cons:
Smaller sample so may not be representative
Some masses such as sarcomas do not exfoliate well
Masses cannot always be graded
Contraindications:
Bleeding disorders- If no gross bleeding disordersexternal FNA is fine. For internal FNA’s check the PLT count first. (Clottingprofile if unsure)
Bladder tumours- Risk of seeding tumour cells
Immobilise the mass/or lymph node with your non dominant hand
Needleonly: -Introduce a 21 or 23g needle into the mass and move the needle back and forth several times
Suction:
-Useful for masses that do not exfoliate well
-Attach a syringe and apply suction whilst moving the needle back and forth. Release suction prior to needle removal
Attach an air-filled syringe and spray onto the slide
Make a smear
Costs: £120 FNA plus consult fee £50 (local Staffordshire practice 11/23)
Managing owner expectations -Important in all aspects of veterinary care:
Make owners aware of the cost and the benefits of the procedure
That samples may come back inconclusive or that further testing may be required
That their pet may yelp or have minor bleeding from the procedure
histopathology for neoplasia
Various methods -Incisional, excisional, pinch, Tru-Cut….
Pros:
Larger sample so increased chance of diagnosis
Architecture can be assessed, and masses graded
Provides more prognostic info
Cons:
More invasive
GA or deep sedation required
Takes more time to get results
Increased cost
Risks:
Bleeding, seeding, compromising future surgery
Contraindications:
Bleeding disorders, co-morbidities increasing the risk of GA
In practice cytology and histopathology arecomplimentary:
FNA’s are often performed first todistinguishbetweeninflammatory/hyperplastic andneoplasticlesions
Biopsy and histopathology is used if the FNA is inconclusive
Otherwise,histopathology is performed after full mass excision toconfirm the diagnosis, allow full grading and to assess surgical margins
INCISIONAL WEDGE BIOPSY-
For solid tumours and LN
Choose an appropriate location
Avoid infected, haemorrhagic or necrotic regions
Inclusion of a normalarea of tissue can beuseful,as long asthe whole biopsysite can be fully removed at follow up surgery
Be aware of local anatomy – avoid important structures!
Surgery
If subcutaneous incise overlying skin and blunt dissect down to the mass or LN
Cut a wedge out of the mass – routine closure
Place in formalin
Do not includeformalin histo samples in the same package as slides
Excisional biopsy - removing the entire mass
FNA advised first ideally. Excisional biopsy can potentially be used without FNA in:
Mammary masses
Haemorrhaging splenic masses – emergency
Deep pulmonary tumours (FNA superficial ones – syringe on!)
In some cases, for dog masses wherefunds are limited
60% skin masses benign in dogs vs only 20% in cats
Not appropriate for:
Masses of an unknown diagnosis
Poorly defined masses
Inflamed or oedematous masses (e.g. MCT)
Rapidly growing masses (feature of malignancy)
Ulcerated masses
HEAT DIFFUSING IMAGING for neoplasia
Cancer cells have different thermal properties than normal tissue. Heat waves (visible blue light) are sent into the mass and are read by a thermal sensor. This is thenassessed by AI and a numerical value is generated:
1 – 4 increased risk of malignancy, further testing recommended (FNA)
5 – 10 the mass appears to be benign (98% certainty)
It cannot diagnose the mass, only give an indication of benign vs malignant
Limitations:
Deep s/c masses
Large masses
Some cysts
False positives can occur in some of the above cases. Further testing would then be advised which would then identify that they areactually benign
Interesting novel, non-invasive technique. Likely further research is required
Cost:
£80/mass local Staffordshire corporate 11/23
TUMOUR STAGING – HAS IT SPREAD? TNM
T – Tumour – What is the primary tumour? - Grade?
N – Nodes – Has it spread to the local lymph node? – FNA, biopsy
M – Mets – Has it spread to distant sites? – Imaging – Thoracic radiographs and abdominal ultrasound vs CT
pulmonary mets diagnostics
Nodular interstitial pattern
Always take 3 inflated views:
R lateral
L lateral
VD or DV
THORACIC RADIOGRAPHS:
Pulmonary METS under 3 – 5mm are not visible
CT
Preferred to radiographs where possible
Able to detect pulmonary masses as small as 1 – 2mm
Even CT has limitations:
Osteosarcoma -the chestCT may benormal, but around95% of dogs havemicrometastasesat thetime of presentation
Abdominal ultrasonography for METS
Can be limited by patient size and equipment/operator- Even specialist diagnostic imagers often CT abdomens of large dogs >30kg beforeultrasound
Ultrasound cannot distinguish between benign and malignant nodules just on appearance-
The exception are targetnodules - 81% predictor of malignancy wherethere are multiple in oneorgan
FNA’s of nodules. Benign regenerative liver nodules are common in olderdogs so a dog should notbe suspected of havingMETS (and then euthanised) just off ultrasound
A liver and spleen can also have MCT METSand look normal on scan!
ONCOLOGICAL SURGERY
KNOW WHAT IT IS BEFORE YOU ATTEMPT TO REMOVE IT!-
With diagnosis and staging you can provide the owner with all the necessary information to make their decision
You do not need to know all the median survival times and treatments off the top of your head, this can be researched once a diagnosis is achieved
IS SURGERY EVEN APPROPRIATE?-
What is the prognosis with or without surgery?
What is the expected benefit?
Will surgery be curative?
What will the impact of surgery be? (to the patient and owner finances)
SURGICAL PREP-
Gentle surgical prep to reduce the risk of tumour seeding
Strict asepsis due to the higher risk of post op infections in cancer patients
SURGICAL MARGINS-
The amount of normal tissue around the tumour that is resected
Narrow surgical margins can be obtained in benign masseslimiting morbidity
If narrow margins are obtained in malignant disease, it is likely to result in treatment failure
The aim is to fully remove the tumour with appropriate margins on the first surgery to get the best chance of a cure-
Tumours are more active at their edges. Partial resection leaves the most aggressive cells behind
There will be less tissue available for closure second time round. A wider resection is also needed second time round which can compoundthe problem.
SURGICAL MARGINS for neoplasia
Narrow margins – up to 1cm – Suitable for benign masses
Wide excision- 2cm+ depending on grade, plus a fascial plane-
-Low – intermediate grade MCT -2 cm and one fascial plane (1cm for low grade)
-High grade MCT – 3 – 4 cm and one fascial plane
Radical excision – The removal of the tumour with extensive margins (includes limb amputation)
CAN YOU GET THE REQUIRED MARGINS?
Tumour location may make it difficult or impossible to get appropriate margins (for example – distal limb)
Advanced surgical skills may also be required to close deficits created by these surgeries (surgical flaps etc.)
Referral may be required
Even in referral hands margins may be impossible to achieve due to tumour size and location
This is where adjunctive treatments play a role
Chemotherapy to shrink a tumour pre surgery
General surgical principles for malignant neoplasia:
Be careful with tumour manipulation during surgery as this could seed cells – use atraumatic forceps rather than rat-tooth’s
Ligate vascular supply to the tumour as early as possible
If there are any adhesions to the tumour remove these with the mass as they could have tumour cell invasion
Remove local LN if staging has shown them to be affected or if they appear grossly abnormal during surgery. Biopsy normal appearing local LN
Lavage the op site post excision and change, drape, kit and gloves prior to closure
Adhere to normal surgical principles of closing dead space and reducing tension
Avoid chemotherapy 7 days prior to surgery and 7 days post-surgery – can affect wound healing
Approximate first opinion costs of GA, surgery, histology
£600 - 800 for an average size mass
£1000+ for more involved surgery
Cost could be reduced where needed, depending on the case,as long as the potential impacts are discussed:
No pre-GA blood – save £65
No IVFT – save £110
No histology – save £165
CHEMOTHERAPY
The use of cytotoxic drugs to kill tumour cells
Chemo drugs target rapidly dividing cells:
Tumours with a high growth rate (high grade and mitotic index)
GI tract and bone marrow- Diarrhoea and myelosuppression
The dose and frequency used aims to balance effective tumour kill whilst minimising side effects by allowing time for normal tissue to recover
Lower dosages are used in veterinary medicine compared to human oncology. We want to improve median survival times in our patients whilst limiting any negative side effects
As the main treatment for conditions such as lymphoma/leukaemia andmetastatic neoplasia
After the surgery of tumours with a high risk of metastasis- Intermediate grade MCT with a high mitotic index, high grade MCT, osteosarcoma,haemangiosarcoma
Neoadjuvant chemo to reduce a non-operable tumour into a smaller operable size
For in-operable chemo-sensitive tumours
There are published protocols for a variety of neoplasticconditions, but in an ever-evolving field it can be useful to contact an oncologist for advice
Chemopetis an oncologist led business that provides expert advice and pre prepared chemotherapeutics to first opinion practices
Cytotoxic drugs are carcinogenic, mutagenic, teratogenic, abortifacient and increase the risk of stillbirth.
At risk people should avoid administering chemotherapy and being around patients posttreatment
At risk groups:
Pregnant, lactating or people trying to conceive
Young children and elderly people
Immunocompromised people
Safe handling is essential to reduce the risk to staff and owners
Appropriate PPE:
Thicker nitrile gloves
Gown
Face shield/eye protection
Mask
Use PPE when handling patient urine, faeces, saliva or vomit.
Drug residues can be found in the urine and faeces for around 7 days
Double bag faeces
Pour water over the site of urination/defecation
CHEMOTHERAPUTICS Safety considerations
Safe administration of injectable chemotherapeutics
PPE
Low risk staff
Safe handling using a needle free closed system to reduce the risk of spillage
Appropriate disposal of materials contaminated with cytotoxic residues
miroclave extentsion set
syringe with spyros attached
CHEMOTHERAPY – PATIENT CONSIDERATIONS
Chemotherapy drugs have a narrow therapeuticindex so accurate dosing is essential:- Use mg/m^2 rather than mg/kg for most dosages (table in the back of the formulary)
Save peripheral veins for chemotherapy – take bloods from the jugular
“One-stick” technique when placing IV catheters- Avoids multiple punctures of the vein that could lead to chemo drugs leaking perivascular
Draw back to demonstrate a “blood flash”
Vincristine, vinblastine and doxo/epirubicinare vesicants – local tissue necrosis can occur if the chemo leaks outside the vein
Early signs of extravasation:
Pain, swelling and redness at the catheter site
If extravasation is suspected:
Stop the chemo
Attach a new syringe and try to aspirate as much as possible
Cold and warm compresses – contact an oncologist for specific treatments where available
iv protocall-
Pre-procedure checks – Appropriate neutrophil count - >1.5 × 10^9/L - if less, delay treatment (2 – 7 days) & reduce dosage (10 – 20%)
Maropitant
First stick catheter
Attach extension set with the clave port
Saline flush and demonstrate “blood flash”
Put on PPE
Attach the chemo syringe Spirosto the clave port
Administer the chemo at an appropriate rate
Monitor for signs of extravasation
Flush 10 – 15ml saline through to clear drug residue from the catheter lockoff and do not disconnect
Remove the IV, extension set and syringe as one and put into cytotoxic bin
Apply dressing – remove PPE and wash hands
CHEMOTHERAPY – PATIENT SIDE EFFECTS
GASTROINTESTINAL-
Diarrhoea, nausea/loss of appetite
Pre-treatment with maropitant – oral for home use
Delayed ileus with vincristine – metoclopramide and supportive treatment
MYELOSUPPRESSION-
Takes time for max suppression – monitor the neutrophilnadir(peak of suppressiom) – around 7 days (5-10)
Risk of sepsis if the neutrophil count drops <0.75 × 109/L- Prescribe prophylactic potentiated amoxicillin
Febrile neutropaeniais an emergency – isolation, IV broad spectrum AB including a fluroquinolone
STERILE HAEMORRHAGIC CYSTITIS-
Cyclophosphamide
RENAL TOXICITY-
Carboplatin and cisplatin
CARDIOTOXICITY-
Doxo/epirubicin
HEPATOTOXICITY-
Lomustine
ELECTROCHEMOTHERAPY (ECT) for neoplasia
Electrical pulses are administered to a mass after an IV or local dose of chemotherapy
The electrical pulses make the tumour cells more permeable to the chemotherapy drug allowing greater uptake and increased sensitivity to the drug- may decrease dose needed
Side effects are generally low but can include local inflammation and myelosuppression
Whilst general chemotherapy for conditions such as lymphoma can be performed in general practice ECT typically requires referral
Treatment is administered under GA/sedation and often two treatments are used two weeks apart
Indications:
Tumours that are inoperable
As part of palliative care in advanced disease
Typical tumours treated:
Carcinomas such as nasal squamous cell carcinomas in cats
Mast cell tumours
Melanomas, sarcomas
radiotherapy for neoplasia
High energy x-rays from a linear accelerator can beused to killcancer cells
Indications:
Tumours of the nasal cavity (carcinoma, lymphoma)
Brain neoplasia – Meningioma
Palliative pain relief of bone tumours such as osteosarcomas
Palliative care of inoperable tumours e.g. oral malignant melanoma that is not amenable to surgery
After the surgical removal of invasive tumours (mast cells tumours, soft tissue sarcomas) to reduce the risk of regrowth
Acute:
Inflamed skin, hair loss etc.
Reversible
Late:
Damage to vascular and connective tissue
Cataracts, retinal issues,skin & joints etc.
Rarely neoplasia
Irreversible
CANCER TREATMENT- PAIN
The control of pain is essential in all aspects of veterinary care to ensure patient welfare
Sources of pain in oncology patients:
The cancer itself – bone neoplasia is notoriously painful
The treatment – surgery etc.
Pre-empting pain and multi-modal analgesia is essential. Chronic pain is often underestimated
Multi-modal analgesia-
NSAIDs – Ensure no contraindications and do not give to patients having corticosteroids as part of their treatment
Paracetamol – Dogs only
Gabapentin – Good for neuropathic pain
Monoclonal antibodies targeting nerve growth factor (Librela/solensia)
Amantadine – Good for pain refractory to NSAIDs but could be restricted
Ketamine – Low dose subcutaneously – monthly to weekly
Antidepressants
CANCER TREATMENT- EUTHANASIA
One of the options to alleviate pain and suffering in our patients
It must be approached with great care and empathy
In our patients it could be due to welfare of the patient and/orcost concerns
We need to be compassionate and ensure the process goes as smoothly as possible
lead with open questions. “Have you thought about euthanasia” is too direct and can be jarring
“How is Kevin getting on?”
“How are you feeling about his treatment?”
If open questions do not prompt the discussion and you are concerned about the patient’s quality of life a delicate more direct approach can be considered:
“We always have to be mindful of how happy our pets are. Are we having more bad days than good days?”
“I’m worried Kevin is not doing as well on treatment anymore. What do you think?”
Quiet private room and where possible ensure there is enough time
Ensure consent and understanding
“Put to sleep term”
Options for their pets afterwards
Signed consent form
Discuss the procedure and whether owners would like to stay
Most do but never assume
SEBACEOUS ADENOMAS
Benign
Raised pink to pigmented lobulated masses – “wart like” – “brains”
Common in middle aged to older dogs – terriers, poodles, cocker spaniels
The appearance is fairly typical but ddx can include:
Viral papilloma
Dermal MCT
Melanoma
Basal celltumour
Squamouscellcarcinoma
Melanoma
Diagnosis:
High suspicion on gross appearance – definitive by FNA/histo
Treatment:
Not required if not causing a problem – just cosmetic
Surgical excision if bothering the dog
Common neoplastic conditions of the skin
SEBACEOUS ADENOMAS
BENIGN CUTANEOUS CYSTS
HISTIOCYTOMAS
LIPOMAS
CANINE MAST CELL TUMOURS (MCT)
BENIGN CUTANEOUS CYSTS
Multiple types which can be considered under the umbrella term of cyst
Follicular cysts – Dermal raised masses filled with a thick keratinaceous material (cheese/paste like on gross FNA) – dilated hair follicles
Sebaceous cysts – look similar – develop in and around the sebaceous gland
Both can rupture generating an inflammatory response and secondary infection
Common in multiple breeds of dog including Shih Tzus, Hounds, Schnauzers and Boxers
Ddx – dermal MCT, deep pyoderma – can look similar to a ruptured cyst
Diagnosis:
Suspicion on appearance and paste like gross FNA material
Benign on heat imaging although false malignancies can occur
Definitive on FNA/histo
Treatment:
Monitor vs surgical excision
Excision recommended for cysts that are prone to rupture
HISTIOCYTOMAS
Benign small pink-red domed cutaneous mass, often found on the limbs, ears or head/neck
Common in young dogs <2 years but can be seen in middle aged dogs too
They can ulcerate -> self-trauma
Ddx
Dermal MCT, Ulceratedmelanoma, Cutaneous lymphoma
Non neoplastic lesion – inflammation, FB, insect bite
Diagnosis:
Suspicion on appearance in a young dog on the limbs
Benign reading on heat imaging
Definitive on FNA (ideal)
Treatment:
May regress spontaneously in a month or so
If not and/or bothering the dog – surgical excision is curative
LIPOMAS
LIPOMAS
Subcutaneous mass made up of fat cells, normally soft and mobile on palpation (occasionally can be found internally)
Very common in middle aged to senior dogs
Gross oily fat on slide after FNA
Ddx:
S/c MCT, soft tissue sarcoma, liposarcoma
Diagnosis:
“Targeted” FNA
Cytology will come back as “lipid”, but this could be just subcutaneous fat, so the clinician needs to ensure the FNA was directly from the mass
Treatment:
None required unless growing in an areas that could cause a problem – axillae - surgical excision
Is it appropriate to diagnose a lipoma based off the exam and demonstrating a fatty oil-like appearance on gross FNA?
No – some neoplasia such as MCT can appear fatty
Yes & no – Where funds are limited, or surgery would never be considered
As long as the limitations are discussed with the owners and documented in the clinical notes
CANINE MAST CELL TUMOURS (MCT)
Mast cells have an important role in inflammatory, immune and allergic reactions
They are present in most tissues in the body and malignant transformation leads to MCTs
7 – 21% of call canine skin tumours
Majority are dermal but they can be subcutaneous
Predisposition:
Any breed but particularlyBulldogs, Staffordshire bull terriers, Boston terriers, Boxers, Pugs, Beagles, Lab/Golden Retrievers, Dachshunds, Shar-peis, Rhodesian Ridgebacks, Weimeraner
Pugs are prone to getting multiple low grade MCT
Shar-peis tend to get high grade metastatic disease
Appearance - Variable – why FNA is so important
Approx 2/3rds of masses may show benign behaviour and present as a slow growing cutaneous lesion
Subcutaneous masses are often less aggressive and may appear like lipomas – FNA’s are very important
Masses can be inflamed from histamine release and can wax and wane in size (vomiting, diarrhoea/melaena)
Rapid growth and mass ulceration can be seen in high grade MCT
MCT diagnosis
FNA -fine basophilic cytoplasmic granules
The Camus grading system and 2022 Paes adaptation were developed to try and give an indication of grade based off cytology
The study showed a high correlation between cytological and histopath grade so it can give a good initial indication
Cytology can overestimate the grade compared to histo
MCT Grading from Histopathology:
Currently only apply to cutaneous MCT’s not s/c ones although dogs with s/c MCT’s tend to have a longer survival time
Various grading systems -Patnaik orKuipel
Grade correlates to prognosis
OTHER PROGNOSTIC INDICATORS-
Size and growth rate – High growth is a sign of malignancy, larger MCTs are harder to remove
Appearance – Inflammation, ulceration and pruritus = poorer prognosis
Systemic signs – vomiting and melaena = poorer prognosis
Breed- pug low grade, sharpei high grade
Location – In some but not all studies, preputial, muzzle, nail bed, perineal and those in mucocutaneous areas = a poorer prognosis
Grade is the most important prognostic indicator
The histology report will come back with the grade and the option of further testing - proliferation markers. These can provide more prognostic information
Ki67 – identifies the growth fraction (activelydividing cells)
AgNOR– identifies the generation time (speed ofcell cycle progression
They can cost an extra £300 odd to test
SHOULD WE TAKE AN INCISIONAL BIOPSY AFTER FNA OF EVERY MCT TO ALLOW FULL GRADING?
Historically yes – before the cytological grading system was developed this was the only way to establish the MCT grade to then know what surgical margins to take
Today with a good cytological grading system we often decide on appropriate staging and treatment based off the FNA grade and other prognostic indicators
Patnaik Grading
CANINE MCT - GRADING
Grade 1 (low grade, well differentiated)– no mitotic figures
Grade 2 (Intermediate)
0 – 2 mitotic figures per hpf, some pleomorphic cells- variation in size
Areas of oedema and necrosis
Infiltration of lower dermis/subcutaneoustissue
Grade 3 (high grade, poorly differentiated)- multiple abnomal cells
3 – 6 mitotic figures per hpf, sheets of pleomorphic cells
Odema/necrosis/haemorrhage and ulceration is common,
Infiltration of lower dermis/subcutanous tissue
KuipelGrading
Low grade
High grade-
7 or more mitotic figures
Generally low mitotic index and well differentiated = lower grade and better prognosis
High mitotic index (>5) and poorly differentiated = higher grade and worse prognosis
Canine MCT – Proliferation markers
Ki67 from immunohistochemistry:
A high Ki67 expression = increasedrate oflocalrecurrence, metastasisand mortality
This can be useful for intermediate grade MCT as around 30% of these are found to be more aggressive when Ki67 tested(Van Erp, M et al)
HigherAgNORcounts are also associated with an increasedrate of localrecurrence, metastasisand mortality
CANINE MCT – APPROACH TO STAGING AND TREATMENT when FNA suggests a low-intermediate grade + no other negative prognostic indicators
FNA the local LN
LN positive for METs-
Full staging
Abdominal ultrasound
FNA lesions
FNA liver and spleen even if they look normal
Lung METs are very rare
–>
LOW – INTERMEDIATE GRADE WITH METS
2cm margin, 1 facial plane excision
Remove the metastatic LN
Grade the mass and assess margins
Chemotherapy
OR
LN negative-
Surgical excision
2cm* margin & one facial plane
Biopsy the local LN if the FNA was inconclusive
Grade
Assess margins
–>
LOW – INTERMEDIATE GRADE CLEAN MARGINS (no METS)
No further treatment
Consider proliferation markers for intermediate grade
Monitor the site
For low grade reoccurrence risk is low
For intermediate grade this risk is slightly higher (up to 23%)
consider the implications of histamine release during surgery
Chlorphenamine is used pre-op alongside omeprazole which is continued post operatively
CANINE MCT – HIGH GRADE
Referral where possible – they are very difficult to manage
Wide excision + post op radiotherapy + chemotherapy (regardless of margins achieved)
High grade MCT median survival time (MST) with surgery = 3.5 months
Surgery + radiotherapy = 20 months
Surgery + radiotherapy + chemotherapy = 65% of patients alive at 3 years
CHEMOTHERAPY FOR CANINE MCT’S – WHAT AND WHEN?
INDICATED POST SURGERY FOR DOGS WITH POOR PROGNOSTIC INDICATORS:
High grade III MCT
High mitotic index
Intermediate grade with high prognostic indicators
METs
Other factors such as tumour location and malignant features
Chemo is often started around 2 weeks post op to allow time for wound healing
Typical first line protocol
IV vinblastine – 8 doses – weekly for the 1st 4 then every 2 weeks
Oral prednisolone
In cases wheregross disease is present this protocol may be continued weekly until full effect is seen then the frequency decreased. In some cases, lomustine is used
Contacting an oncologist is advised!
MCT location (such as on the distal limb) can make it impossible to achieve the desired surgical margins.
Options for these cases:
Referral
Pre op (neo-adjuvant) chemo can shrink some non-operable masses down to an operable size
1 – 2mg/kg prednisolone for 7 – 10 days prior to surgery +/- vinblastine
Pre op radiotherapy
Tigilanol Tiglate (Stelfonta®) intra-tumour injection
TigilanolTiglate
(Stelfonta®) - A natural molecule extracted from the seed of an Australian plant. Injected intra-tumour
Itbreak down the tumour cell walls and blocks blood vessels to the mass –> inflammation, tumour necrosis & drop off –> wound healing
For non-resectable, non-metastatic mast cell tumours of the following types in dogs:
- Cutaneous mast cell tumours (located anywhere on the dog)
- Subcutaneous mast cell tumours located at or distal to the elbow or the hock.
Tumours must be less than or equal to 8 cm3in volume and be intact/non ulcerated to avoid product leakage
Local LN must be FNA’d or biopsied first
Prednisolone and H1/H2 receptor blocking agents are neededboth before and aftertreatment
Sedation can be required along with a 2nd injection in 4 weeks
Cost £400 per vial
TYROSINE KINASE INHIBITORS
CANINE MCT
Anti-cancer and anti-angiogenic properties
Toceranib is licensed for use in recurrent, non-resectable intermediate or high-grade MCTs
Masitinib is licensed for use in non-resectable intermediate or high-grade MCTs with demonstrable c-KIT mutations.
Not first line therapy - reserved for masses where clean surgical excision is not possible, or where surgical excision to microscopic disease followed by radiation is also not possible
Mammary neoplasia
In dogs – approximately 50% are benign, 50% are malignant
Malignant transformation of benign mammary masses can occur with time
Entire bitches and those neutered late are predisposed
Can present as a single mass or multiple along the chain
Smaller mobile masses <3cm are more likely to benign vs larger masses which can grow rapidly and ulcerate
In cats’ mammary masses are rarer but up to 95% are malignant
MAMMARY MASS DIFFERENTIALS-
Ductal and lobular hyperplasia – can be influenced by oestrus
Mastitis
Mammary enlargement related to oestrus
Pregnancy or pseudopregnancy
DIAGNOSIS-
FNA-
Not commonly performed as it normally cannot distinguish between benign vs malignant
Benign mammary masses should be removed anyway to avoid malignant transformation
Could be used to rule out other differentials such as ductal hyperplasia
EXCISIONAL BIOPSY-
Removing the entire mass and then sending for histo is performed most commonly
Cases with small solitary mobile lesions <3cm are more likely to be benign
These cases could be taken straight to surgery and the mass assessed on histo post excision
If benign – no further staging or treatment if needed
If it was malignant –> full staging
This approach can save client funds and reduce the length of GA
Full staging should be performed on all cases with larger or multiple mammary masses
This helps with prognosis and decision making
Is it fair to do two mammary strips in a dog with pulmonary METs?
The surgical approach depends on the case
Neutering has no effect on future malignant mammary tumour development, or on incidence of metastatic spread
It can be considered in entire bitches however to eliminate the future risk of pyometra
Mammary neoplasia - Surgery
Single or regional (more than one gland) mastectomy is generally indicated
2cm margin and one facial plane
Mammary strips (radical mastectomy) +/- local LN are used when multiple masses are found along the mammary chain
Surgery is normally staged in bilateral disease
Mammary neoplasia ->Further treatment
Repeat surgery for dirty margins or for very narrow margins in high grade disease
Chemotherapy is debatable but normally recommended for high grade tumours or if there is evidence of LN METs
Various protocols:
Single agent carboplatin
Single agent doxi/epirubicin
They are given once every 3 weeks for 4 – 6 treatment
If chemo is declined for personal or cost reasons ongoing NSAIDs (meloxicam) could be considered as they have some anti-neoplastic properties with carcinomas
Neutering before the first season drops the risk to 0.5%
Note - this must be balanced against the behavioural impact of early neutering and the increased risk of joint disease and bone neoplasia seen with neutering before the first season in some larger breeds of dog
For this reason, neutering is often advised to be performed around 3 months after the first season
Neutering after the first season, prior to the second – 8%
Neutering after the second season, prior to the third – 26%
GENERALISED LYMPHADENOPATHY
Multicentric lymphoma
Reactive
Infectious-
Severe generalised pyoderma
Leishmania, Ehrlichia,Babesia (important in travelled dogs)
Brucellosis
Aspergillus
Inflammatory
Mineral associated lymphadenopathy
Leukaemia
Secondary to METs from other neoplasia
Canine lymphoma
Neoplasia arising from lymphoid tissue
7 – 24% of all canine malignant neoplasia
Various forms
Cutaneous
Alimentary
Thymic
Hepatic etc
We will be focusing on the most common form
Multicentric lymphoma (around 70% of all lymphoma cases)
Any breed can be affected, higher incidences in:
Golden Retrievers
GSD
Boxers
Cocker spaniels
Basset Hounds
Scottish terriers
Rottweilers
Affected dogs are normally middle aged but younger patients can be affected too.
Most dogs are well on presentation with no clinical signs other than the generalised peripheral lymphadenopathy, normally affecting all peripheral LN.
Owners typically noticed the enlarged submandibular LN
20 – 40% of cases present with additional clinical signs:
Lethargy
Anorexia
Weight loss
Vomiting
Dogs that present with these clinical signs typically have shorter survival times
Diagnosis is normally straightforward and involves FNA of the enlarged LN – sample multiple nodes - The
Once diagnosed we need to discuss with the owner the implications of this diagnosis
Rapid progression to death without treatment 4 - 6 weeks
Most patients however do well on treatment and whilst it cannot be cured, remission with a good quality of life can be achieved
Canine multicentric lymphomaImmunophenotyping & staging
We also need to discuss the costs and benefits of finding out the specific type of lymphoma (immunophenotyping) and disease staging
The form of lymphoma (B vs T cell) and whether it is low or high grade,has a big impact on prognosis and treatment
Most are intermediate to high grade and B-cell phenotype
High grades can be identifiedon cytology, but low grades may need LN biopsy and histopathology to identify- They are often resistant to doxorubicin (commonly used in lymphoma) so a different protocol should be used
B-cell lymphoma - the most common form (70% of cases)
High grade T-cell lymphoma – Aggressive and have a poorer prognosis
Low grade T-cell lymphoma (Indolent)
Better prognosis of around 2 years
Chemo does not affect prognosis and so may not be needed, only if the disease if progressing
NK-cell lymphoma – Like high grade T cell is associated with a shorter remissionand survival times
PARR CLONALITY-
You can ask the lab to run this PCR test on the FNA slide you already submitted
It identifies whether the lymphoma is T-cell or B-cell
Useful if the owner declines further sampling
FLOW CYTOMETRY-
Uses a liquid suspension of a fresh fine needle aspirate
More accurate than PARR
IMMUNOHISTOCHEMISTRY – On LN biopsy
BLOODWORK -Haematology, Biochemistry &Urinalysis
Needed to assess co-morbidities that could affect treatment, for screening of paraneoplastic disease (hypercalcaemia) and for staging
Further staging (ideal for unwell patients) involves imaging the thorax and abdomen +/- sampling (aspirating liver and spleen for example)
Always be mindful of costs and ensure this does not impact on treatment
Canine multicentric lymphoma-Treatment - chemotherapy
As a systemic disease chemotherapy is the treatment of choice
As a rough guide multidrug chemotherapy will induce remission (happy dog with no detectable disease) in 60 – 90% of patients
80% of patients live for a year, 20% of these up to 2 years
This does depend however on grade and phenotype
Treatment choices will be impacted by owner views, the individual dog (co-morbidities, bad at the vets etc.) and finances
Oral prednisolone only-
Remission achieved in 45 – 50% of cases
Remission lasts 60 – 90 days
Fairly common low-cost palliative option
Note – cannot start treatment with prednisolone alone and then decide to use a full chemotherapy at a later date as the efficacy will then be reduced
Canine multicentric lymphomaTreatment – B-cell lymphoma
CHOP PROTOCOL-
The most effective protocol currently for B-cell lymphoma (8K)
Vincristine (IV), Cyclophosphamide (PO), Epirubicin/doxorubicin (IV), Prednisolone (PO)
Weekly induction protocol, moving to every 2 weeks. 25-week duration – then stops
90% of dogs (with uncomplicated B-cell lymphoma) go into remission with this protocol
Duration of first remission is 10 – 12 months on average
There is no maintenance phase after this protocol.
When most patients come out of remission a rescue protocol can be considered
COP PROTOCOL INDUCTION
Shorter 8-week induction with Cyclophosphamide (PO), Vincristine (IV),Prednisolone (PO)
Then ongoing maintenance protocol – IV & oral protocols vs less expensiveoral only protocols
70% remission with B-cell lymphoma
Average first remission time of 5 – 6 months
Canine multicentric lymphomaTreatment – High grade T-cell
High grade T-cell lymphoma carries a worse prognosis
Shorter remission times are seen with “standard” lymphoma protocols, so the LOPP protocol is favoured
Includes alkylating agents such as lomustine and procarbazine alongside prednisolone and vincristine
Use for 6 months and then followed by a maintenance protocol
6 – 11 months median survival time
In cats and some dogs, sedation is used to facilitate the first stick catheter
This does require a lot of sedations depending on the protocol so this may not be appropriate in every case
Oral only palliative protocols could be used (which are also lower cost) such as prednisolone only or prednisolone in combination with other oral chemotherapy agents
Canine multicentric lymphomaTreatment – Low grade T cell
Low grade T-cell lymphoma is the least aggressive form
Median survival time of around 2 years
Treatment is not always needed unless there are clinical signs in which case prednisolone and chlorambucil tablets are the treatment of choice
Prednisolone every 48 hours and chlorambucil every 2 weeks
FELINE ALIMENTARY LYMPHOMA
Lymphoma is the most common neoplasia in the cat
Like the dog there are various types but, in the cat,alimentary lymphoma is the most common anatomical form
The median age of affected cats is 10 – 13 years
Cats may present with vomiting, diarrhoea, and weight loss
Low grade lymphoma leads to diffuse thickening of theintestinal tract, and it can be tricky to distinguish from inflammatory IBD
Intermediate to high grade lymphomas generally presentwith a palpable abdominal mass and often present moreacutely and severely than the low-grade form
Patients are more likely to present with GI obstructionwith the intermediate-high grade as the mass can block the bowel
FELINE ALIMENTARY LYMPHOMA (AL)Low grade AL (LGAL)
Cases present similarly to IBD with chronic gastrointestinal signs andweight loss. Appetite can be normal, reduced, or increased
Intestinal thickening and enlarged mesenteric lymph nodes may be palpable
differentails
Routine bloodwork, urinalysis and TT4
In limited finance cases biochemistry plus T4
If super limited just biochemistry (ALT is up in most hyperthyroid cats and there is often other clinical signs)- Other hyperthyroid clin sig:
Normal to PP appetite
Palpable goitre
Tachycardia/gallop/murmur
Dry, unkempt coat
Spicey
FPLi for pancreatitis where appropriate, FeLV/FIV
If all normal – imaging and cobalamin testing (B12)
Then diet trials, faecal testing, intestinal biopsy etc.
Rule out non-GI disease with bloodwork
Cobalamin (B12) bloods
Hypocobalaminemia can be present in up to 78% of cases
Abdominal ultrasonography
Could be normal!
Often seeintestinal thickening, especially of the muscularis layer+/- mesenteric lymphadenopathy
You also see this in IBD!
As the u/s appearance is not specific further testing is required
Fine needle aspiration of enlarged mesenteric LN and PARR clonality can be used to try and achieve a diagnosis of LGAL over IBD but this is not always possible
Gut biopsy
FOR DIFFUSE ALIMENTARY NEOPLASIA -Such as feline alimentary small cell lymphoma
Endoscopic pinch biopsy vs full thickness surgical
Endoscopic:
Less invasive – especially important in hypoproteinaemia – poor healing
Further equipment and expertise required
Smaller sample – less chance of diagnosis
Surgical:
Larger sample including all layers – increased chance of diagnosis
Multiple areas of the GI tract can be sampled
More accessible in first opinion practice
Ideal for ileal biopsy in low B12 cases as upper GI endoscopy cannot get to the ileum
Higher risk of complications which can be very serious – peritonitis
Dehiscence risk of 1.9% (Swinbourne et al. 2017 vs older report of 12%
FELINE IBD TREATMENT
Diet-
Hydrolysed/hypoallergenic (Purina HA),or novel
Pre and probiotics can play a role
Supplement B12
Faecal sample/fenbendazole trial
Prednisolone anti-inflammatory to immunosuppressive dosages
Chlorambucil if signs persist
FELINE ALIMENTARY LYMPHOMALGAL TREATMENT
B12
Prednisolone 2mg/kg then taper based on response and chlorambucil 20mg/m^2 every 2 weeks
Diet
Pre and probiotics
Supportive treatment
Mirtazapine appetite stimulation etc.
Prognosis – 70% chance of remission (95% partial response), 26 – 29-month median duration of remission
FELINE INTERMEDIATE-HIGH GRADE ALIMENTARY LYMPHOMA (I/HGAL)
Clinical signs are normally more acute, and cats are often unwell
Cats present with GI signs and a palpable abdominal mass in the majority of cases
GI obstruction or intussusception can occur in some cases
Ultrasound-
Identify the mass
FNA-
May require PARR testing ifinconclusive cases
Treatment-
Chemotherapy (e.g. COP)
MST 1 – 3.5 months
7 – 10 months in 33% of cases that fully respond
Palliative prednisolone
B12 supplementation if needed
IF THE CAT IS VOMITING AND HAS GI OBSTRUCTION:
Stabilisation and surgery is required – end to end anastomosis
CANINE OSTEOSARCOMA
The most common primary bone cancer in dogs
They are seen more often in larger breeds and cause significant pain, lameness and occasionally, pathological fractures
Microscopic METs are present in around 95% of cases at the time of diagnosis
Often larger breeds:
Dobermans
Greyhounds
Rottweilers
German Shepherd dogs
Golden Retrievers
Great Danes
Irish Setters
Irish Wolfhounds
Deerhounds
Saint Bernard
It can occur insmaller breeds, butit is rarer.
Progressive lameness-
Can become non weight bearing
Initially maybe partially analgesic responsive
Limb swelling/mass-
More obvious when the distal radius/tibia is affected
Pathological fracture-
Not as common a presentation but it is still seen
Any large breed dog presenting with a fracture should have the radiographs scrutinised closely for any traces of possible bone neoplasia
CANINE OSTEOSARCOMA - DIAGNOSIS
Radiographs-
Typical appearance on radiographs:
Single, aggressive bone lesion
Forelimb – Proximal humorous and distal radius
Hindlimb – Distal femur, proximal and distal tibia
(“away from the elbow and near to the knee”)
Areas of lysis
Periosteal reaction “sun-burst”
Radiographs are typical but full diagnosis requires cytology or histopath
FNA-
It is relatively non-invasive, quick and can be performed under sedation
A full osteosarcoma diagnosis is not always obtained but a diagnosis of a malignant mesenchymal neoplasia (that is most likely an osteosarcoma) is
Jamshidi needle
CANINE OSTEOSARCOMA - STAGING
Thoracic radiographs-
3 inflated views
CT is the preferred modality for a MET check-
Note - >40% of METS seen on CT are missed with radiographs
95% of cases have micro-METs at the time of diagnosis that will be missed by imaging
FNA local lymph nodes
CANINE OSTEOSARCOMA - Treatment
This depends on several factors including patient suitability, the presence of gross METS and owner opinion/finances. Euthanasia will be required in all cases at some point.
Analgesia-
Bone neoplasia’s are very painful
Multi-modal analgesia is required
Most cases are euthanised within the first few weeks - months due to uncontrolled pain or occasionally from pathological fracture
Can be combined with bisphosphonates
Osteoclast inhibitors
Palliative radiotherapy-
Four treatments (fractions) given once a week under GA
Useful in patients that are not good surgical candidates
80 – 90% get a good analgesic response which can last up to 6 months
Unfortunately, pathological fracture or metastatic disease can affect them sooner, leading to a 3 – 4-month MST
AMPUTATION-
Fastest way to a pain free patient, if appropriate
Where gross METS are present the median survival time is 3- 4 months
Surgery where there are gross METS can be considered as part of palliative analgesia but should be carefully discussed with the owner before pursuing
Without gross METS the median survival time is:
6 months with limb amputation alone
Approximately 1 year if combined with chemotherapy, with 20% of patients living for 2 years
LIMB SPARING-
Aim to remove the bone neoplasia and preserve the limb
Higher risk of complications than limb amputation
Survival times are similar to limb amputation
As a highly aggressive malignant cancer chemotherapy following limb amputation is indicated
Various protocols
4 – 6 treatments of intravenous carboplatin every 21 days is used most often
Myelosuppression and GI side effects
The drug also reduces the glomerular filtration rate – watch the kidneys
canine transitional cell carcinoma
surgery not normally possible due to location-> urethral obstruction
chemotherapy main treatment- treat secondary utis: check sediement, bloods not reliable
Canine splenic masses
2/3 malignat
80% of cases presenting with haemoabdoent have mailgnant splenic tumour
acutr bleeds-
collapse, lethargy
pale mm
hypovolemia
pu/pd
gi dingd
mass may not be palpable in large dogs
enlarged abdomen
histeopath post splenectomy
non heamoabdomen cases- FNA and cytology
staging- abdo ultrasound
chest radiographs
chech right atrium if possible
individal factors effect treatment
treat hypovolemic shock-
fluid bolus
postop chemo if hsa
chemo- doxyrubicin
Main causes of foot pathology in adult sheep in UK/Ireland
Interdigital dermatitis (scald)
Footrot
Contagious ovine digital dermatitis (CODD)
Toe granuloma
Toe abscess
Shelly hoof (white line disease) – usually not lame
Non-infectious sheep lameness
Shelly hoof (white line disease)
Toe granulomas (‘strawberries’)
Foreign body penetration – thorns, sharp stones
Soil balling – mud stuck in the interdigital space causing inflamation
Hoof cracks – exposed corium
Overgrown, damaged or misshapen claws
Injuries to the limb
Dichelobacter nodosus
primary pathoges for scald and footrot
Primary aetiological agent of interdigital dermatitis (scald) and footrot
Gram negative rod – terminal swellings giving ‘dumbbell’ appearance; anaerobes
Can survive in a wet environment (soil) - reservoir for infection of other sheep – spreads in sheep in wetter conditions – esp. Spring and Autumn in UK
Persists long time on disease interdigital skin and in lesions within the hoof – need to isolate clinical cases – but can eliminate if remove these sheep as environmental reservoir will die out if not seeded repeatedly
Multiple strains – wide range of virulence – some extremely virulent, others benign
Theory: moist, softened or traumatised interdigital skin > inflammation and necrosis facilitates subsequent infections with D. nodosus > footrot develops as scald and can progress to full-blown footrot if not treated
Often also associated with presence of Fusobacterium necrophorum – regarded now to be a secondary pathogen in footrot (excreted in faeces by some sheep)
The microbiome on diseased feet also appears to play some role – some kind of bacterial dysbiosis = footrot
primary pathoges for scald and footrot
Dichelobacter nodosus
Often also associated with presence of Fusobacterium necrophorum – regarded now to be a secondary pathogen in footrot (excreted in faeces by some sheep)
Footrot – treatment
The research evidence base shows that:
Aiming to treat within 3 days of onset has the best outcome – inspect flock regularly and pick out anything lame
Treat with antibiotic injection (oxytet. LA) and spray i/d space and foot – don’t trim. Analgesic for pain.
Focus on individuals to reduce flock spread – aim to avoid whole flock treatment
Flocks where feet are never trimmed have the lowest prevalence of lameness
Sheep footrot vaccine – Footvax (MSD Animal Health)- Can be used for prevention or in the face of an outbreak
Sheep footrot vaccine – Footvax (MSD Animal Health)
‘For the active immunisation of sheep as an aid to the prevention of footrot and reduction of lesions of footrot caused by serotypes of Dichelobacter nodosus.’
Can be used for prevention or in the face of an outbreak
Thick, viscous vaccine (oil adjuvant) so hard to inject in cold weather, and can provoke skin reactions
footbaths for sheep
10% zinc sulphate solution (or copper sulphate) (frowned upon for heavy metal environmental contamination)
3% formalin solution (carcinogenic chemical for humans, granulomas)
Others: e.g. Digicur Advanced 2% - combination of glutaraldehyde, copper and zinc
Others: e.g. Hoofsure Endurance - organic acids, tea-tree oil and wetting agents
[Antibiotic footbath solutions] - (soluble antibiotics (e.g. lincomycin) licensed for chickens/pigs) - imprudent use and lacking evidence of efficacy!
Lot of vets will support their use, esp. for scald outbreaks in lambs
Evidence for the efficacy of footbaths? Limited actual scientific trial evidence, but very commonly used over the years
results suggest 2% Digicur is ineffective at reducing the load of D. nodosus when applied as a one off or weekly footbath, however sheep may act as a reservoir for multi-drug resistant bacteria creating opportunities to spread antimicrobial resistance to other sheep and their environment.’
Contagious ovine digital dermatitis (CODD)
First recorded in UK in 1997
Not quite as common as footrot, but still common in the UK (up to 58% flocks in UK)
Severe lameness and significant welfare issue on affected farms
Lesion at the coronary band and then extending under the horn down the toe – end up with avulsion of horn – exposes hoof laminae and affects pedal bone
Staton et al. (2021) found in an experimental study that 84% of lesions arose from existing scald/footrot lesions
Multiple bacteria present in CODD lesions – Treponema spp., D. nodosus, F. necrophorum
The treponemes: Treponema medium, Treponema phagedenis and Treponema pedis found
Can respond clinically to treatment with injectable LA amoxicillin (Betamox LA, Norbrook) or LA oxytetracycline; analgesics
Oxytetracycline injectables: licensed in sheep- Zoetis, Norbrook, MSD, Bimeda
Other antibiotic injectables: licensed in sheep- Norbrook (amoxicillin (not authorised for use in sheep producing milk for human consumption)
), Zoetis (– tulathromycin (macrolide)) , Boehringer Ingelheim (gamithromycin (macrolide))
Analgesia in sheep lameness
No licensed analgesics in sheep in UK
Use of NSAIDs under the cascade
Some farmers are seeing the benefits of analgesic use – persuaded by vets
Meloxicam most purchased NSAID in this sample of 52 N. Irish farms
More work for vets to do with sheep farmers to educate regarding the benefits for sheep welfare
Shelly hoof (white line disease)
Detachment of hoof horn wall from the underlying epidermis (often the abaxial wall)
The separation itself does not usually cause lameness, unless horn breaks off to expose sensitive laminae – very painful
Separation leaves a cavity – space for dirt to become impacted
Foreign body penetration easier into sensitive tissues - abscess formation and then severe lameness
risk facotors-
Reeves et al. (2019) found more likely in flocks that were footbathed in formalin compared with not footbathing (OR = 1.65; 95% CI 1.19–2.30)
It was less common in flocks that stocked ewes at higher stocking densities more than eight vs. four per acre (OR = 0.34; 95% CI 0.17–0.68) – why?
Found weak associations between shelly hoof and foot trimming
Reeves et al. (2019) proposed that flocks with shelly hoof would decrease incidence if farmers stopped footbathing (esp. with formalin), and avoided foot trimming whether as a therapeutic or routine practice
Toe granuloma (‘Stawberries’) in sheep
Granulation tissue in response to injury/untreated footrot
Usually caused by excessive trimming
Bleed profusely and painful
hard to fix- Regrow if removed
Nursing care, analgesia, cull
Footbathing in formalin appears to predispose
Toe abscess in sheep
Occurs when infection gets into the white line – e.g. stone or thorn penetration – abscess develops under the wall or sole horn
Pus from the coronary band once bursts
Smelly
Hoof likely to be hot to the touch and painful before pus becomes visible
Very painful = acutely lame
Can often see the penetration on white line on sole – gentle paring may reveal
Post-dipping lameness in sheep
Caused by Erysipelothrix rhusiopathiae (also causes dimond marks in pigs)
Typically, in sheep that have been dipped in a dip that was used the day before and allowed to stand overnight
E. rhusiopathiae contamination from soil the previous day multiplies overnight and enters small skin abrasions – bacterial soup!
Dull, lame and pyrexic within next few days
Can have sizeable proportions of the flock affected, esp. lambs
Treat with injectable penicillin; avoid keeping dip too long
Joint ill in lambs (infectious arthritis, polyarthritis)
Mainly Streptococcus dysgalactiae subsp. dysgalactiae
Lambs usually < 4 weeks old – clinical signs often at 10-14 days
Swollen, hot joints – lameness, recumbency – outbreaks possible
Thought to be acquired in first few hours of life – ewes, unsanitary conditions, lack of colostrum, untreated navel – umbilical entry, ear tag, tail dock, mouth
Procaine penicillin drug of choice, NSAIDs for pain
Joint pathology can be permanent if does not respond to treatment
Preventing infectious sheep lameness
Culling policy – breeding for genetic resilience (less susceptible ewes)
Biosecurity - closed flock (rams), quarantine and examine all incomers, prevent straying, transport vehicles, recognize contaminated pastures, move feed troughs, isolate infected sheep if possible
Vaccination – only one vaccine on the market – Footvax (MSD)
Treat individuals promptly and effectively for the benefit of the whole flock
The five-point plaN-
- Treat, quarantine and avoid contaminated pastures to reduce challenge
- Cull to build resilience
- Vaccinate to establish protection
Lameness treatment drives most of the antibiotic use in sheep
Emphasis must also be placed on the importance of long-term commitment to lameness control strategies, as there is no one, short-term panacea for controlling lameness
Cognitive Dysfunction Syndrome (CDS)
Known as well as Canine Cognitive dysfunction (CCD) in dogs, also affects cats (limited data).
Progressive neurodegenerative, linked to aging in dogs and cats and characterised by decline in cognitive performance and behaviour changes.
Risk factors identified in dogs – further research needed (MacQuiddy et al., 2022, Dewey et al., 2019)
Age
Anecdotally mentioned :
Female, neutered, Low BCS,
Diet? One study - high quality, controlled diet are 2.8 times less likely compared to uncontrolled low-quality diet.
Concomitant disease? One study on IE, more likely to develop at young age.
28% for dogs between 11–12 years old and 68% in dogs 15–16 years old. (Neilson et al., 2001)
8.1% in ages 8 to <11 years, 18.8% in ages 11 to <13 years, 45.3% in ages 13 to <15 years, 67.3% in ages 15 to <17 years, and 80% in ages >17 years (MacQuiddy et al., 2022)
14.2% for dogs between 8-19 years old, only 1.9% were diagnosed by a vet. (Salvin et al., 2010)
Cats: 36% 11-21y, 50% at 15+ and 28% 11-14y. (Moffat et al., 2003)
Pathophysiology - Pathologic features:
Perivascular and parenchymal neurotoxic amyloid beta (Aβ) protein accumulation into plaques that affect exchange at level of BBB.
Cerebrovascular diseases: decreased oxygenation to affected part of the brain.
Oxidative brain damage, due to decrease in endogenous antioxidants, leading to neuronal death and increase in free radicals. Reminder: brain tissues has high level of polyunsaturated FA, very sensitive to oxidative damage from free radicals.
Neuronal mitochondrial dysfunction
Decreased neuronal glucose metabolism
Glutamate-mediated excitotoxic neuronal damage
Decrease in catecholamine (Norepinephrine, dopamine), serotonin and GABA neurotransmitters and cholinergic system dysfunction, increase in monoamine oxidase B activity (MAOB)
Structural features:
Cerebrovascular disease: hemorrhages or infarcts
Meningeal calcification,
Reduction of overall brain mass (frontal and temporal lobes, hippocampus) with degeneration of white matter, demyelination,.
Increased in ventricular size
Generalised gliosis:
Microglial dysfunction: pro-inflammatory
Astrocyte dysfunction: increased neuroaxonal degeneration, decreased glutamate uptake, increase in free radicals.
Clinical signs of Cognitive Dysfunction Syndrome
Often unreported and missed by owners as thought to be part of the normal aging process, especially with mild signs (socialization and sleep changes in dogs, vocalization and house soiling in cats).
No apparent early clinical signs to owners, but cerebral changes will already be occurring.
Dogs (> 8yo), Cats (>10y approximately)
DISHAA (L)-
Disorientation
Alterations in social Interactions
Changes in Sleep-wake cycle
House soiling (part of it linked to memory)
Alterations in activity levels
Anxiety level changes
Learning and memory
Diagnostic approach:
Based on history, signalment and exclusion of other pathologies
Identification of stress factors (acute or chronic) that may impact wellbeing
Examination: general, neurological, orthopedic, pain assessment.
Use of scale / scoring tools:
Canine Cognitive Dysfunction Rating scale (CCDR) (Salvin et al., 2011)
CAnine DEmentia Scale (CADES) (Madari et al., 2015) - better at differentiating stages of CCD, identify earlier stages and follow progression
Cognitive Dysfunction Syndrome Management
Delay onset and progression – Uncurable currently
Early recognition and intervention is likely to lead to positive outcome.
Client education is paramount.
Preventative approach even in subclinical cases as patients no behavioral changes may still have pathological changes
Consistency at home is important to prevent increasing stress levels
diet and nurtritional suppiments
pharmcologic intervention
cognative and enviromental enrichmet
adjunctive therapies
CARE - Lack of clinical evidence in cats and many drugs are off licence.
cognative dysfuntion-
Increase and provide varied training, play and exercise time
Introduce new stimuli: toys, smells, sounds and touch.
Introduce hand or voice cues to palliate for sensory changes
Ensure positive and varied interactions (people and pets).
Ensure opportunities to explore new areas.
Cats: provide 3D environment and favours hunt-and-chase game.
soiling-
Increase frequency and safe proof access to outdoors
Add an indoor toilet area
Cats: provide low sides litter tray and add-in ramps
mobility-
Ramps
Ramps
Physical support devices: slings, cart, pram.
Facilitate access to ALL resources (outdoor, toileting area, sleep area, feeding area, toys)
sleep-
Provide a consistent day-night cycle: reduce exposure to artificial light during nighttime, increasing outdoor time
Reduce night disturbances
Provide a safe space for rest
Allow a final interactive and physical session before sleep
nutrition an ideat supliments–
Combination with behavioural enrichment would lead to a better cognitive performance compared to without (Milgram et al, 2004).
Provide antioxidants (AO, including vit B, C, E ), mitochondrial co-factors, phosphatidylserine and Omega-3 Fatty-acids to reduce the effects of free radicals and reduce Aβ deposits.
MCT (medium-chain Triglycerides, C8 and C10) - Provide alternative source of energy to palliate for deficient glucose metabolism.
Phosphatidylserine - neuronal membrane component and participating in synaptic processes.
Hill’s Prescription Diet b/d Canine - AO, omega-3
Purina One Vibrant Maturity 7+ Senior Formula (US) - MCT
Purina ProPlan Veterinary Diet NC NeuroCare - MCT
No current specific diets for Cats but Hill’s Prescription Diet Feline j/d – AO and omega-3
Coconut oil
Senilife®, Ceva - dogs/cat. Phosphatidylserine and AO
Aktivait®, Vet Plus – dogs/cats. Phosphatidylserine, AO and co-factors.
SAMe – increase AO production, improve catecholamine system performance. Care when use alongside serotonergic drugs.
Silymarin (milk thistle) – AO and anti-inflammatory properties.
medication for cognative dysfuntion syndrome
Selegiline-
Selective inhibitor of monoamine oxidase B (MAOI).
Enhance brain catecholamine activity and decrease free-radicals production and increase clearance.
Dogs– 0.5-1mg/kg SID in the morning. Improvement > 2 weeks.
Cats (off licence, anecdotal) - 0.5-1mg/kg SID
Should not be use alongside other serotonergic drugs (MAOIs, TCA and SSRIs - clomipramine, trazadone, fluoxetine and sertraline - tramadol)
Propentofylline-
Phosphodiesterase inhibitor.
Increase blood flow to CNS, muscle and heart. Inhibition of platelet aggregation and thrombus formation. Decreases free radical production.
Dogs – 2.5-5mg/kg PO BID 30min before food.
Cats (off licence, anecdotal) – 12.5mg SID
Bronchodilator, positive inotropic and chronotropic effects. Care in patient with cardiac disease and contraindicated in pregnant animals
Anxiolytic and behaviour modification drugs-
Memantine (POM off licence) – block activity of glutamate. Used in compulsive disorders in dogs – 0.3-1.0 mg/kg BID
Sertraline (POM) – SSRI. Used in compulsive disorders in dogs – 3mg/kg SID.
Fluoxetine (POM-V) – SSRI. Used in separation anxiety ad compulsive disorders. Dogs 1-2mg/kg SID, Cats 0.5-mg/kg SID
Clomipramine (POM-V) – TCA. Used in separation anxiety and inappropriate elimination, compulsive disorders. Dogs 1-2mg/kg BID, Cats (of Licences) 0.25-1mg/kg SID
Trazodone (POM) – antidepressant, sedative. Chronic anxiety. Dogs 2-5mg/kg up to TID
Gabapentin (POM) – GABA analogue. 10-30mg/kg TID to BID and Cats 5-10mg/kg TID to BID
Adjunctive therapies-
Sleep and stress -
Melatonin
Alpha-casozepine (Zylkene®, Vetoquinol) – dog and cat
Pheromones (Adaptil®,Feliway®, Ceva)- dog and cat
Anti-anxiety/compressive gear (Thundershirt®)
Situational use of sedative: inducer – phenobarbital, trazodone, benzodiazepine (clonazepam, lorazepam))
mobility-
Physiotherapy, hydrotherapy
Osteoarthritis treatment and management: NSAIDs, Paracetamol, Solensia®, Librella®, Tramadol, joint supplements
Selegiline
used for cognative dysdfunyion syndrome
Selective inhibitor of monoamine oxidase B (MAOI).
Dogs– 0.5-1mg/kg SID in the morning. Improvement > 2 weeks.
Cats (off licence, anecdotal) - 0.5-1mg/kg SID
Should not be use alongside other serotonergic drugs (MAOIs, TCA and SSRIs - clomipramine, trazadone, fluoxetine and sertraline - tramadol)
Propentofylline
used for cognative dysdfunyion syndrom
Phosphodiesterase inhibitor
Increase blood flow to CNS, muscle and heart. Inhibition of platelet aggregation and thrombus formation. Decreases free radical production.
Dogs – 2.5-5mg/kg PO BID 30min before food.
Cats (off licence, anecdotal) – 12.5mg SID
Bronchodilator, positive inotropic and chronotropic effects. Care in patient with cardiac disease and contraindicated in pregnant animals.
anatomial reasons for incontinence
Structural abnormalities -
Urethral length
Urethral diameter
Storage capacity-
Innervation
Detrusor atony
Urethral tone-
Bladder neck positioning
Neutering
Innervation
transitional cell carcinoma in th etrigone
Approaching Urinary Incontinence
Patient factors: Age, breed, sex, reproductive status (neutered or entire, age of neutering)
Description of the leaking: is it continuous or intermittent? Normal micturition in between episode? Episode information- time of day, progression over time & onset (acute, chronic, progressive, improving), association with stress, conscious or unconscious.
Other useful information: defecation patterns, back pain/history of neurological problems, PU/PD, abnormalities in normal urination (eg: stranguria, pollakiuria, haamaturia)
clinical exam-
Physical exam- full clinical examination. Specific areas of focus on:
Bladder size- normal/small or distended- obstruction? faulty innervation?
Neuro exam- proprioception, sensation and movement of the tail, perineal reflex, lumbar-sacral pain.
Genital exam- exteriorise penis, check for vulval dermatitis
Rectal examination- palpate urethra (stones or masses), check prostate in males, lymph nodes
Other indicators of conditions that maybe be associated with PU/PD for example: muscle wastage, alopecia in patient with hyperadrenocorticism
Diagnostics for urinary incontinance in the geriatric patient
Hematology, biochemistry and urinalysis
Radiographs – plain or contrast
Plain- abdominal radiograph without any contrast medium.
Retrograde urethrocystogram- contrast is administered via a urinary catheter and a series of radiographs are taken.
Aids identification of structural abnormalities in the bladder or urethral.
IV urethrography- contrast medium is administered IV and filtered out by the kidneys. Series or radiographs are taken. Helpful to identify pathologies associated with the ureters and kidneys.
Cystoscopy – endoscopic examination of the urethra and bladder.
Ultrasound
CT
Urethral Sphincter Mechanism Incontinence (USMI)
Reduction in the tone of the smooth and striated muscle comprising the internal and external sphincter respectively resulting involuntary urine leakage.
Why does it occur?
Anatomical abnormalities eg: short urethra and intra pelvic bladder position.
Hormonal changes associated with neutering eg: reduced circulating oestrogen.
Degenerative processes eg: loss of collagen
Other risk factors include breed and obesity- larger breeds
medical treatment of incontinance
Focus of treatment is to increase urethral sphincter tone.
Phenylpropanolamine (Propalin)
Mechanism of action: Adrenergic agonist that increases the contractility of the smooth muscle therefore resulting in a stronger close of the urethral sphincter.
1st line medical treatment in female and male dogs.
Estriol (Incurin)
Oestrogen replacement
Mechanism of action: increases the number of receptors responding to phenylpropanolamine.
2nd line medical treatment to be used in conjunction with phenylpropanolamine.
Contraindicated in male dogs as it is a oestrogen derivative.
surgical treatment of incontinance
You do not need to know how to perform each of the procedures just the principles of how they reduce incontinence by alternating urethral tone.
Reduce urethral diameter by injection agents such as collagen, vet foam into the urethra. Minimally invasive procedure performed by endoscopy- will need to be repeated every 6 to 18 minths
Increase urethral tone through surgical placement of a urethral cuff resulting in permanent narrowing of the proximal urethra- complex abdominal surgery, more invasive
In patients with anatomical abnormalities eg: short urethra and intra pelvic bladder position a surgical procedure to move the bladder neck and urethra cranially. This will reduce incontinence as the urethra will be subject to intra abdominal pressures.
Procedure name: colposuspension.
no garentied fix, may be used in combo with medical managemnt
primary hyperaldosteronism in cats
may present with-
tetraparesis
cervial ventroflexion
bilateral misdriasis
adrenal mass present on ultrasound
the zona glumerolosa in the cortex of the ad=lrenal gland produces aldosterone- mainains systemic blood pressure- RAAS
in this condition too much aldosterone is produced- more than 5 times normal range, ususlally due to functional mass
assosited with low circulating rnin concentration- RAAS neg feedback
causes hypocalemia which results in neuromuscular junction adn possible organ damage
retinal detachmet ot intraocular haemorages can also be present
can mimic other geriatric diorders- CKD, DM
palpable abdominal mass
systemic hypertension- coiuld presipitate renal disease
can mimic renal signs- azotemia, isosethenuria
diagnstics for primary hyperaldosteronism in cats
urinary aldosterone to creatanie ratio often used
dynamic testing with flufrocortisone- has no effect in cats with htis disease so diagnostic
abdominal ultrasound- not as specific, adrenals can be enlarged for other reasons
treatment for primary hyperaldosteronism in cats
unilateral adrenaectomy treatment of choice- contraindications?- bilateral presentation, other diseases
medical options-
ARB- spirolactone
potassium suplimentation
calcium blocker for hypertension-Amlodipine
hypersomatotropism in cats
causes acromegally
hepatomegally
uncontrolled diabetes- high dose of insulin >1.5, plantigrade stance from diabetic neuropathy
arythmia
broad facial fetures
Imaging- functional adenoma
imaging not diagnostic
overproduction og groth hormone-
organomegally
males more effected than females- domestic short hair
polyphagia may be increased
respiritory stridor - hyperglosia
mild cardiomegally
neuro signs form mass in later disease
diagnosed by testing for inusline like growth factor- can get false neg
repeat 6-8 weeks
short term fasting can lead to false neg
can test for growth hormone in a lab setting
hypersomatotropism treatment
durgical- transsphenoidal hypohyectomy
medical-
somatostatin analougs- pasireotide
radiation therapy- widley used
conservative options- high doses of insulin to control diabetes
primary hypoprathyroidism in dogs acute managment
slow bolus of Ca gluconate- 1ml/kg calium gluconate over 15-20 mins
administer IV through IV catheter
ECG attached
submit blood to regional laboratory for a PTH
diagnostic for hypoparathyroidism
decreased ionised calcium and parathyroid hormone
and absense of any other markers
primary hypoprathyroidism in dogs
results in electorlite imabalence
low ca high p
hyperexitability of cns and pns
idiopathic
primary hypoprathyroidism in dogs management
acute- iv calcium
chronic-
vitamin d- needs to be activated
calcitrol- activated vit d 3 gold standard
downside is short time to max effect
no vet formulations
cant split human capsuals
alfacidol- one alpha
best current option- not much literature
check tCa/iCa daily and adjust dose incramentally
Calcium distribution
99% of body calcium resides in the skeleton and is stored as hydroxyapatite
Most skeletal calcium is poorly exchangeable, and less than 1% is readily available
0.1%of total body calcium is in the extracellular fluid
The rest of the calcium is in the cells and its organelles
50% ionised calcium (diffusible)
E.g. Ca carbonate, Ca phosphate
Physiologically active
40% protein-bound (non-diffusable)
10% chelated calcium
Calcium pool-
Gains from:
GI absorption – 35% of ingested calcium is absorbed
Bone resorption
Loses to:
Endogenous faecal excretion ~ 90%
Urinary excretion ~ 10%
Milk
Bone formation
Calcium homeostasis
3 key components
Parathyroid hormone (PTH)
Calcitonin
Vitamin D (Calcitriol)
(also PTHrP)
important for-
Nerve Conduction
Neuromuscular transmission
Muscle contraction
Smooth muscle tone
Membrane stability
Membrane transport
Enzymatic reactions
Hormone secretion
Blood coagulation
Bone formation
Control of hepatic glycogen metabolism
Cell growth and division
Hypercalcaemia
Total Calcium >3mmol/L or iCa >1.5 mmol/L
Reference ranges vary between machines
Mild increases may not be relevant in juvenile dogs
High total calcium should prompt ionised calcium evaluation before further investigation
Clinical signs proportionate to:
Rate of increase
Magnitude of increase
Cause of hypercalcaemia
Increased calcium ions is toxic to cells:
affects membrane functionandmetabolism
ultimatelyends in cell death
HARD IONS
H – Hyperparathyroidism (primary vs secondary)
A – Addison’s
R – Renal disease (acute and chronic)
D – Vitamin D Toxicosis
I – Idiopathic (cats)
O – Osteolytic
N – Neoplastic (e.g., lymphoma, multiple myeloma, anal sac adenocarcinoma)
S – Spurious
G – Granulomatous disease (infectious)
Common Signs-
PU/PD
Anorexia
Dehydration
Lethargy
Weakness
Vomiting
Chronic renal failure
Uncommon Signs-
Constipation
Cardiac arrhythmia
Seizures
Twitching
Acute intrinsic renal failure
Calcium urolithiasis
Death
Hyperparathyroidism as a differential for hyper calcemia
Increased PTH increases calcium absorption-
Increased osteoclast activity –> increased calcium concentration in ECF
Increased calcium reabsorption from the renal tubules (less excretion)
Increased absorption of calcium from the GIT
Primary Hyperparathyroidism-
Parathyroid tumour – usually single parathyroid adenoma
Loss of normal negative feedback control
Uncommon in dogs, rare in cats
High calcium, low phosphate
Addison’s as a differential for hyper calcemia
30% of Addisonian dogs are hypercalcaemic
Rare in cats
Middle-aged dogs with Standard Poodles and PortugeseWater dogs being over-represented
Unknown mechanism
Vitamin D toxicosis as a differential for hyper calcemia
Relatively uncommon
Common examples:
Psoriasis cream (licking cream off the owner)
Vitamin D tablets
Nutraceuticals
Rodenticide
Plant ingestion e.g., nightshade, oatgrass, jasmine
Renal disease as a differential for hyper calcemia
CKD-
Azotaemia, hyperphosphataemia, normocalcaemia/hypocalcaemia, isosthenuria
Occasionally hypercalcaemia
31% of azotaemic cats, 10% of azotaemic dogs
Feeding early CKD cats severely-phosphate-restricted diets can cause them to develop hypercalcaemia
Renal disease due to other causes can also lead to hypercalcaemia
Idiopathic hyper calcemia
Cats not dogs
Most common cause of hyperCa in cats
Diagnosis of exclusion
50% don’t have clinical signs at time of diagnosis
10-15% have calcium oxalate uroliths
Osteolysis as a differential for hyper calcemia
Rare cause of hypercalcaemia
Usually secondary to other disease e.g., multiple myeloma, primary bone tumours
Neoplasia as a differential for hyper calcemia
Hypercalcaemia of malignancy
Typically driven by tumour PTHrP production-
Total calcium and ionised calcium increased
Phosphate normal/low
Low PTH, high PTHrP
Also, with tumour metastasis to the bone
Most common-
Lymphoma – especially T-cell lymphoma
AGASACA – rare in cats
Multiple myeloma
Less common-
Osteosarcoma
Metastatic bone tumours
Mammary carcinoma
Also reported in-
Thymoma, pulmonary carcinoma, nasal carcinoma, malignant melanoma
Spurious hypercalcemia
Acidosis
Lipaemia
Haemolysis
Young animal! (not spurious but also may be normal for them if mild)
Granulomatous disease (infectious) as a differential for hyper calcemia
Increased macrophages
Macrophages can synthesise calcitriol from calcidiol without negative feedback regulation
Macrophages may also synthesis PTH-rP which may activate PTH receptors
Granulomatous diseases-
Fungal (uncommon in the UK)
Schistosomiasis
Angiostrongylos vasorum
Nocardia
Mycobacteria
FIP in cats
approch to hypercalcemia- clinical exam
HARD IONS
Cat versus dog
Age of dog – is physiological likely?
Breed-
Large breed dogs <1 years old may have a mild hypercalcaemia
Keeshonds over-represented for primary hyperparathyroidism
Clinical signs-
Anorexia
Polydipsia/polyuria
Vomiting
Muscle weakness or twitching
Diet-
Raw diet
Toxin ingestion e.g., Vitamin D tablets, creams, rodenticide exposure
Supplements
Travel?
Palpate lymph nodes-
Submandibular, prescapular, axillae, inguinal, popliteal
FNA – can often reach diagnosis if lymphoma
Rectal Examination-
AGASACA – can be diagnostic with FNA
Sublumbar lymph node enlargement or urethral stones may be palpable
If not amenable, ensure do when asleep
Orthopaedic examination-
Bony swellings, pain
approch to hypercalcemia- diagnostics
initial blood tests-
Ionised calcium measurement-
Is hypercalcaemia true, repeatable especially if no clinical signs associated with this
CBC-
Lymphocyte count
Biochemistry-
Renal disease
Addison’s (Hyperkalaemia, hyponatraemia)
Phosphate
Basal Cortisol in dogs
PTH and PTHrP-
When to perform?
Is hypercalcaemia parathyroid dependent or independent?
Dependent – PTH is high normal or increased
Independent – PTH production is suppressed in response to the hypercalcaemia
Vitamin D analogues
Basal cortisol +/- ACTH stimulation if suspect Addison’s
FIV/FeLV in cats
Angiodetect
urinalysis-
Increased excretion of calcium in the urine of cats that are hypercalcaemic can predispose them to calcium oxalate urolith formation
Uroliths identified in 15% of hypercalcaemic cats – 73% calcium oxalate
Evaluation for underlying renal disease-
Protein
imaging-
Thoracic and abdominal radiographs-
Include bones!
Look at the spine
Abdominal ultrasound-
Kidneys
Lymph nodes
Neoplasia
Ultrasound of parathyroid glands
Soft tissue calcification-
Kidneys and gastric mucosa are the predominant organs to be affected
Uroliths, nephroliths, ureteroliths
Other-
Bone biopsy
FNA/biopsy masses
Dietary management – idiopathic hypercalcaemia in cats
Increased concentrations of fibre, sodium, water
Fibre binds to intestinal calcium thus reducing reabsorption
Decreased concentrations of calcium, vitamin D3, vitamin A (or a combination)
Diet options:
Hills Prescription diet w/d, or gastrointestinal biome
Psyllium husk
Chia seeds (controversial, but harmless?)
Treatment of hypercalcemia
Underlying disease dependent!
Treatment of underlying disease often can resolve hypercalcaemia
Depends on the aim-
Anaesthesia safety
Supportive treatment? e.g., seizures, arrhythmias,urolithiasis
Timing-
Will it influence diagnostics?
Steroids very effective but risks
How acute is the hypercalcaemia?
How unwell is the pet?
Saline 0.9%-
Increase calciuria
Na competes with Ca reabsorption so more Ca is excreted
Furosemide-
Increases diuresis because of increased lumen electronegativity
NaK2Cl transporter in the thick ascending loop of Henle aims to maintain electroneutrality
Ensure patient well hydrated before therapy
Glucocorticoid-
Reduce bone turnover and GI absorption
Also possibly increased renal excretion
Cytotoxic to lymphocytes so reducedPTHrP
Avoid use until definitive diagnosis reached
Bisphosphonates-
Inhibit osteoclast-mediated calcium mobilisation from bone
Risks include oesophagitis and mandibular necrosis(especially in cats)
e.g., Alendronate (give after fasting)
Emergency management of hypercalcaemia
Intravenous fluid therapy (0.9% NaCl) - for fluid deficits and promoting diuresis
Furosemide when well hydrated – promotes diuresis and rapid onset of action
Calcitonin – may be helpful in short-term
Oral bisphosphonates and oral
glucocorticoid therapy have a slower onset of action (1-2 days after administration) so are often not helpful in the acute setting
