Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 86

Haematological changes include mild to moderate microcytic, normochromic nonregenerative anaemia. Serum biochemistry abnormalities include decreased albumin, urea, glucose and cholesterol levels. In animals with parenchymal hepatic disease, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin are often elevated and vitamin K-dependent clotting factor levels may be decreased. Ammonium biurate crystals can be identified in the urine sediment in approximately half of the dogs with HE (Rothuizen, 2009).

Box 4.2. Theories on hepatic encephalopathy pathophysiology (Maddison, 1992; Rothuizen, 2009; Bismuth et al., 2011; Poh and Chang, 2012; Kilpatrick et al., 2014).

• Neurotoxic effect of ammonia and other substances (e.g. phenols, mercaptans and short-chain fatty acids) derived from intestinal degradation;

• Impairment of cerebral energy metabolism possibly due to excess amount of neurotoxic substances;

• Astrocyte swelling due to:

i. intra-astrocytic accumulation of glutamine as a result of hyperammonaemia;

ii. hyponatraemia, inflammatory cytokines and benzodiazepines;

• Increased cerebral concentrations of endogenous benzodiazepine-like substances;

• Up-regulation of the translocator protein (formerly referred to as the peripheral benzodiazepine receptor), which results in increased cholesterol uptake and synthesis of neurosteroids (e.g. allopregnanolone and tetrahydradeoxycorticosterone) which have potent positive allosteric modulator properties on the GABAA receptor system;

• Imbalance between excitatory amino acid neurotransmission mediated by glutamate, and inhibitory amino acid neurotransmission mediated by gamma-aminobutyric acid;

• Alterations in monoamine neurotransmission as a result of perturbed plasma amino acid metabolism;

• Manganese-induced neurotoxicity resulting in astrocyte dysfunction, neuronal loss and gliosis;

• Formation of reactive oxygen species and reactive nitrogen species;

• Increased circulating levels of tumour necrosis factor (TNF)-alpha, interleukins 1 and 6.

Box 4.3. Factors that can precipitate or exacerbate neurologic signs of HE.

• Feeding (particularly food rich in protein and fatty acids);

• Bacterial production of ammonia in large intestine (e.g. following constipation);

• Gastrointestinal haemorrhage;

• Hypokalaemia (due to diarrhoea, anorexia, vomiting, salivation, ascites);

• Hypovolaemia;

• Alkalosis;

• Fever;

• Infection;

• Renal disease resulting in reduced excretion of ammonia;

• Administration of CNS depressant undergoing hepatic metabolism.

The diagnosis of hepatobiliary disease can be confirmed by the presence of increased levels of fasting plasma ammonia and fasting (e.g. 12-h) and post-prandial (e.g. 2-h) total serum bile acid concentrations. The sensitivity and specificity of fasting ammonia in the diagnosis of portosystemic shunts has been reported as 91% and 84% in dogs and 83% and 86% in cats, respectively (Ruland et al., 2010). The sensitivity and specificity of serum bile acids in the diagnosis of portosystemic shunts has been reported as 78% and 87% in dogs and 100% and 84% in cats, respectively (Ruland et al., 2010). Dogs and cats with congenital urea-cycle enzyme deficiencies have hyperammonaemia and low bile acid concentrations (Rothuizen, 2009).

Definitive diagnosis of portal vascular anomalies requires ultrasonography (Figs 4.3a–c), portovenography, scintigraphy (transcolonic or trans-splenic), computed tomographic angiography or magnetic resonance angiography (d’Anjou et al., 2004; Sura et al., 2007; Berent and Tobias, 2009; Mai and Weisse, 2011; Nelson and Nelson, 2011). Liver biopsy is required for confirmation of parenchymal hepatic disease. MRI of the brain of dogs and cats with portosystemic shunts may reveal cerebral cortical atrophy characterized by widened sulci and hyperintensity of the lentiform nuclei on T1-weighted images (Torisu et al., 2005). In addition, bilateral diffuse hyperintensity predominately of the parietal and occipital cortex grey matter on T2-weighted MR images has been reported in a dog with portosystemic shunt. The authors suggested that the signal changes represented cerebral oedema associated with cortical laminar necrosis caused by acute hyperammonaemia (Moon et al., 2012).