Feline

Hypoadrenocorticism Refresher

By Lisa Murphy DACVECC

Primary hypoadrenocorticism (HA) is an uncommon disease in dogs and rare in cats.

Adrenal gland physiology

First, we’ll go over some basic adrenal gland physiology.

The adrenal cortex is primarily responsible for secreting several important hormones including cortisol and aldosterone. Cortisol has several functions including carbohydrate, lipid and protein metabolism, immune system modulation and proper catecholamine function. The amount of cortisol being released is determined by a negative feedback system:

  • The hypothalamus produces corticotropin releasing hormone (CRH) which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH).

  • ACTH stimulates the zona fasiculata and reticularis of the adrenal cortex to produce and release cortisol.

  • Increased serum cortisol inhibits the release of CRH and ACTH.

Aldosterone is also released from the cortex; however its release is stimulated by hypovolaemia which is recognised by the kidney. In times of hypovolaemia.

  • Angiotensin II is released via a hormonal cascade and stimulates the zona glomerulosa to release aldosterone.

  • Aldosterone stimulates cells in the renal collecting duct to resorb sodium (leading to secondary water retention and restoration of the effective circulating volume) and excrete potassium.

Causes of HA

Primary HA is caused by adrenal gland dysfunction. Although much more rare, secondary HA can also occur; this is caused by hypothalamic or pituitary dysfunction. Most cases of primary HA involve concurrent cortisol and aldosterone deficiency although atypical HA can also occur where only cortisol is deficient.

The typical signalment for HA is young-to-middle aged dogs with females more likely to be affected. Average age of onset is 4 years old.

The most commonly affected breeds include Portuguese water dogs, Great Danes, Westies, Standard Poodle, Wheaton Terrier and Rottweilers.

In cats there is no known sex or breed predisposition.

The exact cause of primary HA is unknown but is believed to be immune-mediated destruction of the adrenal cortex. Less common causes of primary HA include trauma, infiltrative disease or iatrogenic destruction due to mitotane or trilostane therapy for hyperadrenocorticism. In one study evaluating 156 dogs on chronic trilostane treatment for hyperadrenocorticism, the relative risk of developing HA was 15% at 2 years and 26% by 4 years.

Clinical presentation

The clinical presentation of typical HA can be vague and non-specific. We will focus on the emergent Addisonian crisis:

Common clinical signs of a crisis include lethargy or collapse, hypothermia, hypovolaemic shock and bradycardia. Much of these signs occur secondary to the electrolyte changes induced by this disease (mainly hyperkalaemia and hyponatraemia).

On blood work, common findings include hyponatraemia, hyperkalaemia, azotaemia with a concurrent inappropriately low urine specific gravity (typically < 1.030) and possible lack of a stress leucogram.

Most of these patients (> 90% in some studies) will also have a low sodium/potassium ratio, typically less than 28. Other differentials of this include any disease which leads to severe dehydration including renal failure, severe gastrointestinal disease, and body cavity effusions among others.

Other less common blood work findings include hypoglycaemia and hypercalcaemia. Cortisol promotes gluconeogenesis and glucogenolysis and calciuresis leading to these respective electrolyte derangements.

In cases of severe hyperkalaemia, patients can experience significant bradycardia and/or dysrhythmias. Common ECG changes noted include:

  • Bradycardia

  • Diminished/absent P waves

  • Tented T waves

  • Wide/bizarre QRS complexes

  • Ventricular tachycardia/fibrillation

Diagnosis

There are several ways to evaluate if a dog may have HA:

1. A screening test evaluating the resting cortisol can be performed initially with values less than 1 mcg/dl having excellent sensitivity (100%) and good specificity (98%) for HA in dogs.

Values < 2 mcg/dl were also 100% sensitive but only 78% specific for HA.

Dogs with values > 2 mcg/dl are very unlikely to have HA

2. A confirmatory ACTH stimulation test should be performed in all cases of suspected HA. This test is considered the gold standard.

The drug used in this test (cortisyn) is very expensive and recent studies have shown that the low dose ACTH (5 mcg/kg) stimulation test is as effective as the standard dose (using a 250 mcg vial in a dog or 125 mcg vial in a cat).

3. In cases where primary vs. secondary HA needs to be differentiated or to diagnose atypical HA, endogenous ACTH levels can be measured.

Animals with atypical HA (cortisol deficiency without concurrent aldosterone deficiency), should have normal electrolyte values and an elevated endogenous ACTH level.

4. Evaluation of a dog’s cortisol/ACTH ratio: in one study, all dogs with HA had ratios < 0.17 vs. healthy dogs who had values > 0.79 (reference range 1-1.26).

5. Urine sodium levels: in a recent study dogs with HA had significantly higher urine sodium levels when compared to dogs with non-adrenal illness

While there are several tests that may increase suspicion for HA, the ACTH stimulation is the gold standard confirmatory test.

It is important to note that most exogenous glucocorticoids can interfere with adrenal function tests; therefore tests should be delayed if the patient has recently received steroids. Of all types of glucocorticoids dexamethasone has the least effect on testing. In a true Addisonian crisis, fluid resuscitation is the most important first step so delaying steroid administration until after the ACTH stimulation test likely does not have a significant impact on survival.

Treatment

Volume resuscitation:

Intravenous fluids are the mainstay of therapy in a crisis. Despite their potassium content, a balanced electrolyte solution is recommended over 0.9% sodium chloride solution. This is because the latter could increase the patient’s blood sodium levels too quickly which can cause neurological complications. Once the effective circulating volume is restored, kidney function and GFR will increase leading to kaliuresis; this negates the risk of using fluids with low potassium levels in a hyperkalaemic patient.

Hyperkalaemia:

Patients who have life-threatening hyperkalaemia require rapid intervention.

In animals that are experiencing significant cardiotoxic effects, calcium gluconate can be administered. This will not lower potassium levels and its cardioprotectant effects last approximately 15-20 minutes so more definitive treatments need to be instituted following calcium administration.

Treatments to lower plasma potassium levels include fluid resuscitation as well as administration of substances which shift potassium from the extracellular compartment into the intracellular compartment:

  • The most commonly used is 50% glucose solution and regular (neutral, soluble) insulin (0.1 u/kg with concurrent glucose supplementation to avoid hypoglycaemia)

  • Sodium bicarbonate is used less commonly as this drug carries significant risks due to several possible side effects and should only be considered a last resort.

Following adrenal function testing, patients with typical HA can be started on mineralocorticoid and glucocorticoid supplementation:

  • Mineralocorticoids can be given daily in tablet form or as an injection given approximately every 25-30 days.

  • Glucocorticoids are typically administered intravenously to begin with and then per os. They are usually weaned off over time.

  • The timeline for clinical recovery is different for every patient although it can be anywhere from hours following supplementation to 3-5 days.

  • Animals with atypical HA (singular glucocorticoid deficiency) only require glucocorticoid supplementation.

  • Cats typically take longer to respond than dogs.

The prognosis for this disease is quite good, especially in those who survive the initial crisis. However they do require lifelong monitoring and treatment. This is typically long-term mineralocorticoid administration with intermittent glucocorticoid administration at times of physiological stress or illness.

Monthly Journal Round-Up - July/August 2018

Thanks as always to Lara Brunori DVM CertAVP MRCVS

Clinical review:

  • Nafe, L.A. et al. (2018) ‘Aspiration-related respiratory disorders in dogs’ Journal of the American Veterinary Medical Association, 253(3), pp. 292-301. See below.

Clinical studies:

Prospective:

  • Darnis, E. et al. (2018) ‘Establishment of reference values of the caudal vena cava by fast‐ultrasonography through different views in healthy dogs’. Journal of Veterinary Internal Medicine, 32(4), pp. 1308-1318.

  • Hogen, T. et al. (2018) ‘Evaluation of end‐tidal carbon dioxide as a predictor of return of spontaneous circulation in dogs and cats undergoing cardiopulmonary resuscitation’. Journal of Veterinary Emergency and Critical Care (Early view).

Retrospective:

  • Skulberg, R. et al. (2018) ‘Description of the Use of Plasma Exchange in Dogs With Cutaneous and Renal Glomerular Vasculopathy’. Frontiers in Veterinary Science, https://doi.org/10.3389/fvets.2018.00161

  • Ohad, D.G. et al (2018) ‘Constant rate infusion vs. intermittent bolus administration of IV furosemide in 100 pets with acute left-sided congestive heart failure: A retrospective study’. The Veterinary Journal, 238, pp.70-75.

  • Ruiz, M.D. et al. (2018) ‘Characterization of and factors associated with causes of pleural effusion in cats’. Journal of the American Veterinary Medical Association, 253(2), pp. 181-188.

  • DePompeo, C.M. et al. (2018) ‘Intra-abdominal complications following intestinal anastomoses by suture and staple techniques in dogs’. Journal of the American Veterinary Medical Association, 253(4), pp. 437-443.

  • Lux, C.N et al. (2018) ‘Factors associated with survival to hospital discharge for cats treated surgically for thoracic trauma’. Journal of the American Veterinary Medical Association, 253(5), pp. 598-605.

  • Walton, K.L. & Otto, C.M. (2018) ‘Retrospective evaluation of feline rodenticide exposure and gastrointestinal decontamination:146 cases (2000-2010)’. Journal of Veterinary Emergency and Critical Care (Early view).

Case series:

  • Teh, H. et al. (2018) ‘Medical management of esophageal perforation secondary to esophageal foreign bodies in 5 dogs’. Journal of Veterinary Emergency and Critical Care (Early view).

Case reports:

  • Bellamy, E.J. & Steele, H. (2018) ‘Abdominal wall rupture with gastric herniation in an 8‐week‐old puppy’. Journal of Small Animal Practice (Early view).

For a copy of any of the papers mentioned in this post (personal education purposes only), please email lara.brunori@gmail.com.

Pick of the Month

‘Aspiration-related respiratory disorders in dogs’

Nafe, L.A. et al. (2018) Journal of the American Veterinary Medical Association, 253(3), pp.292-300

Aspiration is defined as the intake of solid or liquid material into the airways and pulmonary parenchyma. The term aspiration is often used interchangeably with aspiration pneumonia, however other aspiration-related respiratory disorders exist and have been well characterised in human medicine.

This paper offers a comprehensive overview of all aspiration-related disorders involving canine patients based on the parallels recognised in human medicine.

An anatomical approach has been adopted to classify these disorders:

Airways

Upper-airway disorder secondary to gastroesophageal reflux (GER)

Repeated micro-aspiration of gastric contents in the upper airways can result in oropharyngeal, nasopharyngeal, laryngeal and proximal tracheal inflammation.

In humans clinical signs of reflux (heartburn, belching and nausea) in combination with visible evidence of laryngeal or oropharyngeal inflammation are often enough to make a diagnosis and institute treatment.

In dogs, however, diagnosis can prove challenging. Laryngeal dysfunction and hyperaemia are unspecific signs amongst the canine population and GER can act both as a cause and a consequence in the perpetuation of laryngeal disease.

Therapeutic trials with proton pump inhibitors resolving upper respiratory signs have been considered diagnostic for laryngeal dysfunction secondary to GER in dogs.

Alternatively, CT examination of the head often shows thickening of the soft palate without evidence of a nasal or nasopharyngeal mass and tracheoscopy might reveal a specific demarcation between an hyperaemic proximal tracheal region and a normally appearing mucosa in the distal portion.

Large airway obstructions

These are usually due to a foreign body inhalation and can represent a potentially life threatening situation. Common foreign bodies in dogs include food, plant material and various chewed objects.

Radiography can be a useful diagnostic tool, however its sensitivity is impaired when the aspirated object is radiolucent.

Evidence of atelectasis and air trapping in the lung tissue could be additional indicative findings. CT scan, although not always readily available provides a more reliable option.

Tracheoscopy with a flexible endoscope is likely the most effective diagnostic and therapeutic tool applicable in these situation. The foreign body can usu-ally be easily identified and subsequently removed via the additional use of alligator forceps.

Bronchiectasis

This is a structural change affecting the elastic and muscular components of the bronchi which leads to an irreversible widening of the airways. In dogs, aspiration pneumonia has been shown to be the most likely underlying cause of this pathological process.

Diagnosis can be achieved via thoracic radiography, CT and bronchoscopy. X-rays typically show a multifocal unstructured interstitial pattern with thickened bronchial walls and bronchi with a wide diameter that does not taper down to the periphery. CT scan provides a superior sensitivity and in some circumstances can even identify the presence of a well-circumscribed foreign material within a bronchus.

Other differentials for bronchiectasis are bacterial infections, eosinophilic infiltrate and ciliary dyskinesia.

Diffuse aspiration bronchiolitis (DAB)

DAB represents a chronic inflammation of the small airways caused by re-current aspiration. Diagnosis include the identification of a predisposing factor (i.e. megaesophagus) and the evidence on CT scan of bilateral diffuse bronchiolocentric lesions.

Since there are no available therapies able to specifically address small airway inflammation, treatment is focused on addressing the underlying causes.

Parenchyma

Aspiration pneumonia and pneumonitis

Aspiration pneumonia is the most commonly recognised pathological manifestation of aspiration disorders in veterinary medicine.

In human medicine there is an interesting distinction between aspiration pneumonia and aspiration pneumonitis.

The first one involves a bacterial infection and it’s usually associated with the aspiration of high pH (>2.5) material containing bacteria from the oropharyngeal or upper gastrointestinal tract. It has a slow and progressive development and it’s associated with a chronic predisposing condition (i.e. laryngeal paralysis).

Aspiration pneumonitis on the other hand is characterised by an hyperacute onset of hypoxia, pyrexia and radiographical changes occurring within hours from a major aspiration event. This presentation is due to the inflammatory reaction associated with the chemical damage caused by the aspirated material and it’s independent from bacterial infections.

This distinction in veterinary medicine is still not clearly recognised. How-ever the more extensive use of CT scans might enhance the specificity of diagnosis and could consequently help implementing more adequate treatments. This is particularly relevant in regards of a more cautious use of antimicrobials. Aspiration pneumonitis in humans is treated mainly with supportive care measures and does not require any antimicrobial interventions.

Acute respiratory distress syndrome (ARDS)

A recognised common consequence of aspiration pneumonitis in humans is ARDS. This is a syndrome defined by an acute onset of impaired gas exchanges and pulmonary vessels leakage without pulmonary hypertension. The radiographical evidence of bilateral infiltrates involving more than one lobe/quadrant is usually considered as a diagnostic confirmation.

This syndrome carries an extremely high mortality with pulmonary protective ventilation identified as the only therapeutic option.

Exogenous lipid pneumonia

This is very rarely described in veterinary medicine and it occurs when there’s inhalation/aspiration of animal, vegetable or mineral oil. Usually the history is quite indicative and radiographically it shows as a patchy pneumonic consolidation. Cytological evidence of lipid-laden macrophages is considered the definitive diagnostic evidence.

Interstitial lung diseases

This is a group of inflammatory disorders affecting the space between the pulmonary and vascular epithelium. Repetitive micro-aspiration is a recognised cause for this presentation in human medicine. In veterinary medicine this cause-effect relationship is still under investigation. However, if confirmed treatment at-tempts to reduce chronic micro-aspiration could prove very useful in slowing down the inevitable decline in lung function connected with these diseases.

Conclusion

In conclusion aspiration can result in a broad range of clinical presentations. A better understanding of the types of aspiration-associated respiratory disorders in dogs will improve early recognition, optimise therapeutic protocols and provide better clinical outcomes.

For a copy of any of the papers mentioned in this post (personal education purposes only), please email lara.brunori@gmail.com.

Lara loves to hear from you!

Drowning Refresher

By Lisa Murphy DACVECC

Pathophysiology

Once the airway is below the surface of a liquid voluntary breath-holding occurs. This is then followed by involuntary laryngospasm as liquid enters the oropharynx and larynx. During both of these periods, the victim is not breathing gas and develops hypercapnia, hypoxaemia and acidosis. Once the arterial oxygen partial pressure drops sufficiently, laryngospasm stops and liquid is then actively aspirated. It is the hypoxaemia which leads to unconsciousness and apnea. 

Once aspirated, water leads to several severe side effects:

  • One of the most significant is surfactant dysfunction and washout which reduces lung compliance and leads to atelectasis.
  • Water also interferes with the normal osmotic gradient in the alveolar-capillary membrane thus directly injuring the pulmonary epithelium. Damage to these cells has several effects including the release of inflammatory mediators and increased membrane permeability worsening fluid accumulation in the lung parenchyma.

It was once believed that the type of water (salt versus fresh water) was a more important determinant of outcome than the volume aspirated, however, more recent studies have found this to be untrue. This is because it’s the volume of water which affects surfactant function regardless of the type aspirated. Pool water is interesting because it typically contains agents to limit bacterial growth so secondary pneumonia is uncommon with this type of aspiration. 

The temperature of the water aspirated can also play a role in survival. Cold water is associated with higher rates of survival. This is because it reduces cellular metabolism (and thus oxygen consumption) and activates the diving reflex (leading to bradycardia, hypertension, shunting of blood to the cerebral and coronary circulations). 

Diagnosis 

The history of a drowning episode is usually known. Common tests performed in these cases include:

  • Blood gas analysis (ideally arterial) – most cases have a mixed respiratory and metabolic acidosis
  • Thoracic radiography:
    • Pulmonary oedema is likely
    • In some cases, where the volume of water aspirated wasn’t large but they suffered a choking-like episode, non-cardiogenic pulmonary oedema (NCPO) may be identified. This is suspected where the pulmonary oedema is predominantly in the caudodorsal lung field.
    • In cases which don’t go on to develop pneumonia, there is usually radiographic resolution of oedema within 7-10 days.

Treatment

The focus should be on controlling the patient’s hypoxaemia.
The risk of pneumonia is low (estimated at 12% in humans) so empirical antibiotics are not recommended. In general, it is much more likely for these cases to develop pneumonia if they undergo mechanical ventilation.
Steroids also have not been shown to increase survival and their use is not recommended. 

Similarly, there is little evidence supporting the use of diuretics in cases of NCPO. Diuretics are most useful for hydrostatic oedema which is associated with congestive heart failure. In cases of NCPO, the oedema is due to changes in pulmonary epithelium permeability (permeability oedema). Fluid can still leak into the parenchyma despite diuretic use. And since diuretics have systemic effects, they put patients at risk of dehydration and potential renal compromise. 

There are several criteria that we can use to help identify those patients who could benefit from mechanical ventilation. The main indications are as follows:

  • Arterial partial pressure of carbon dioxide > 60 mmHg
  • Arterial partial pressure of oxygen < 60 mmHg despite non-invasive oxygen supplementation 
  • Excessive respiratory effort with impending respiratory fatigue

Prognosis is not known in veterinary medicine. In general, animals showing more organ systems negatively affected and those requiring positive pressure ventilation have a worse prognosis.