Page 903 - Equine Clinical Medicine, Surgery and Reproduction, 2nd Edition

878 CHAPTER 5

VetBooks.ir ute to HE, including ammonia, tumour necrosis in superficial blood vessels of non-pigmented skin
Many pathophysiological factors may contrib-
areas lead to skin injury. Hepatopathy should be
factor-alpha, aromatic amino acids, manganese,
copper, phenols, benzodiazepine-like substances, considered as a cause of all photodermatitis cases.
Interestingly, hepatic photosensitisation is sometimes
mercaptans, short chain fatty acids, monoamines, seen in the absence of other clinical or clinicopath-
neurosteroids, bilirubin and electrolytes. Ammonia ological signs of hepatic insufficiency so should not
undoubtedly plays a major role and although nearly be ruled out on the basis of detecting relatively mild
all HE cases have high plasma ammonia, there is hepatic disease.
generally a poor correlation between the concen- Following the release of haemoglobin during red
tration and severity of HE. However, increased blood cell degradation (normal turnover or haemoly-
blood–brain barrier permeability to ammonia is an sis), there is sequential enzymatic conversion of heme
important feature of HE and cerebral or cerebrospi- to biliverdin and bilirubin. Bilirubin is extracted from
nal fluid ammonia concentrations may correlate bet- the circulation by hepatocytes that conjugate the
ter with clinical signs. molecule before excretion into bile. Unconjugated
Histological examination of neurons in brains bilirubin (indirect Van den Berg reaction) tends to
affected by HE appear morphologically normal, bind to serum albumin in the circulation. It is non-
although astrocytes demonstrate nuclear enlarge- polar and insoluble with a high molecular weight
ment, peripheral chromatin margination and that prevents renal excretion, whereas conjugated
prominent nucleoli (Alzheimer type II degenera- (direct Van den Berg reaction) bilirubin is linked to
tion). Astrocytes are the sole source of glutamine glucuronic acid making it polar and soluble with a
synthetase in the brain, which catalyses the conver- smaller molecular weight that enables renal excre-
sion of ammonia to glutamine. The central patho- tion if present in plasma. Systemic accumulation of
logical feature of HE is disturbance of astrocyte bilirubin will lead to jaundice (Fig. 5.1). In cases of
cell volume homeostasis due to the osmotic effect of hepatic insufficiency, jaundice may develop due to
glutamine synthesised within the cells in response failure to clear unconjugated bilirubin from plasma
to high cerebral ammonia concentrations. Acute and/or due to failure to excrete conjugated bilirubin
hepatic insufficiency with HE is characterised by following biliary obstruction. Non-hepatic causes of
overt brain oedema, whereas chronic hepatic insuf- jaundice comprise: increased production of unconju-
ficiency with HE is associated with milder oedema, gated bilirubin as a result of haemolysis; and failure
astrocyte swelling and dysfunction. to extract normal amounts of unconjugated biliru-
Photosensitivity, or an increased susceptibility bin from plasma as a result of anorexia and catabo-
to photodermatitis, may occur when photodynamic lism, which may decrease the synthesis of hepatocyte
agents accumulate in the circulation and become receptors (‘rapid turnover proteins’) required to take
activated by exposure to ultraviolet light in super- up bilirubin from plasma. Rare cases of genetic
ficial vessels of non-pigmented skin. This results defects in bilirubin uptake or processing (Gilbert
in free radical production and oxidative damage to syndrome) might also explain occasional cases of
surrounding tissues. Pruritus may be an early feature, unconjugated hyperbilirubinaemia and jaundice in
followed by pain as the condition progresses. Typical horses. Urobilinogen is formed within the intestine
signs are erythema of exposed non-pigmented skin from excreted conjugated bilirubin and a little of this
with progression to serous exudation, local oedema, is absorbed into the circulation, filtered through the
crusting and necrosis (Figs. 5.3, 5.4). Hepatogenous kidneys and may appear normally in urine. Larger
(or secondary) photosensitisation results from failure amounts of urinary urobilinogen indicate excessive
of the liver to detoxify and excrete phylloerythrin, a hepatic bilirubin excretion as a result of increased
photodynamic agent absorbed from the colon follow- unconjugated bilirubin, usually from haemolysis.
ing bacterial enzymatic degradation of chlorophyll Hepatic insufficiency is associated with a decrease
contained in herbage. Increased circulating phylloer- in the synthesis and function of the majority of pro-
ythrin concentrations and consequent photoactivation coagulant, anticoagulant and fibrinolytic proteins,