Conditions of the liver, spleen and pancreas



Conditions of the liver, spleen and pancreas



Developmental disorders


There are no clinically significant common congenital splenic, pancreatic or peritoneal abnormalities of the horse. Congenital hepatic abnormalities include rarely reported portosystemic shunts, biliary atresia and hyperammonemia of Morgans. Increases in liver enzymes and bilirubin concentration without overt hepatic insufficiency can frequently be seen in septicemic neonates.



Hepatic disorders


Portosystemic shunt


Congenital portosystemic shunts in foals are rare. Clinical signs are most commonly seen at 2–6 months of age when the foals have a higher dietary intake of protein, but in some cases may be noted soon after birth. Shunts may be single or multiple, intrahepatic or extrahepatic. The vascular shunts allow blood within the portal system to bypass the liver and drain into the systemic circulation. The signs seen are mostly a result of hepatoencephalopathy and include depression, recurrent seizures, ataxia and cortical blindness. These signs may wax and wane and affected foals are often unthrifty.



Diagnosis and treatment



• The diagnosis may be difficult in some cases since liver enzymes and serum bilirubin are usually normal and any condition resulting in abnormal behavior and poor growth is a differential. Markedly elevated serum bile acids and blood ammonia with normal serum hepatic enzymes are highly supportive of the diagnosis. The diagnosis can be confirmed by a portogram or by nuclear scintigraphy.


• Differential diagnosis: The main clinical signs are abnormal behavior and poor growth. Therefore any condition producing this combination of signs could be considered as a differential. This would include: brain abscesses, mesenteric/lung abscesses, microencephaly or hydrocephalus and chronic intestinal inflammation. Morgan foals with hyperammonemia can also have similar signs.


• Surgical repair has been performed in one foal. Single extrahepatic shunts would have a better prognosis than multiple or intrahepatic shunts.




Hyperammonemia of Morgan foals


This is presumed to occur because of an inherited abnormality in hepatic ammonia metabolism. Based on abnormal serum and urine amino acid concentrations it is theorized that this condition is similar to the hyperornithinemia, hyperammonemia and homocitrullinemia (HHH) syndrome in man. HHH is a rare autosomal recessive disorder that results in abnormal ornithine transport into mitochondria with subsequent ornithine accumulation and a reduced ability to clear ammonia through the urea cycle.


Affected Morgan foals are usually 4–7 months old and have an acute onset of signs caused by cerebral dysfunction. These signs include blindness, head pressing, circling and seizures. In some cases, there is hemoglobinuria.




Hepatic insufficiency


Hepatic disease in the horse is a relatively common occurrence, but only those with either biliary obstruction or extensive hepatic parenchymal disease (or both) will exhibit easily identifiable signs of hepatic failure.


The wide range of disorders of the liver reflects the diversity of its metabolic functions and the clinical signs of hepatic failure may, in turn, reflect the loss of one or more of these. In some cases, specific metabolic processes are deranged and this results in conspicuous clinical signs which may not immediately be attributable to the liver.


The onset of clinical signs attributable to liver disease is invariably acute, as the liver has a large functional reserve and normally greater than 75% of the liver mass must be functionally lost before clinical signs are apparent (see Table 2.1). Thus when signs of hepatic failure become obvious damage is usually severe, whether this is of chronic or acute onset. The organ does, however, have some regenerative capacity and may regain some, if not all, of its complex functions even after severe acute insults. Acute hepatic damage therefore provides the clinician with therapeutic opportunities while chronic severe changes are usually frustratingly unmanageable.





Icterus (Figs. 2.1 & 2.2)


Icterus (jaundice) is caused by hyperbilirubinemia with subsequent deposition of the pigment in tissues causing a yellow discoloration. It is most apparent in the mucous membranes and non-pigmented skin. It may be particularly difficult to assess accurately in the horse; 10–15% of normal horses have slightly yellow discoloration of mucous membranes and inherently high blood concentrations of natural, harmless carotenes can be found in some grazing horses.




Hyperbilirubinemia may result from:



1) Increased production of bilirubin



2) Impaired hepatic uptake or conjugation of bilirubin result in increased levels of unconjugated bilirubin.



3) Impaired excretion of bilirubin through a blockage of bile flow results in regurgitation icterus with an increase in the conjugated bilirubin (>25%). This can be seen with:



The establishment of the cause of icterus is obviously important and biochemical analysis of the proportions of conjugated and non-conjugated bilirubin in circulating blood may be required to accurately identify the type of icterus which is present and thereby provide indications as to its origin.



Hepatic encephalopathy (HE) (Figs. 2.32.6)


This is a complex syndrome of abnormal mental status resulting from increased neuronal inhibition that accompanies severe hepatic insufficiency. There are no specific features of HE that allow it to be distinguished from other causes of cerebral dysfunction and a diagnois is usually made based on abnormalities of serum liver enzymes or the accompaniment of other clinical signs of liver disease. HE has been divided into four clinical stages (Table 2.2).



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Figure 2.3 Hepatoencephalopathy (head pressing). This horse had serum sickness (Theilers disease, see p. 93). Although head pressing may rarely be seen in a number of other neurological conditions, it is very characteristic of hepatic insufficiency.
Differential diagnosis of abnormal behavior patterns: neurological disorders.




The pathogenesis of HE is most likely multifactorial and has not been clearly defined. Proposed mechanisms which may all play a role to a greater or lesser degree are:



1) Gastrointestinal-derived neurotoxins, e.g. ammonia



2) False neurotransmitter accumulation following plasma amino acid imbalance



3) Augmented activity of γ-aminobutyric acid (GABA) in the brain



4) Increased permeability of the blood–brain barrier.




Colic, diarrhea, edema, tenesmus, ascites and steatorrhea (Fig. 2.8)


Abdominal pain associated with hepatocellular disease may result from acute hepatic swelling or biliary obstruction.



Diarrhea may occasionally accompany chronic hepatic insufficiency. The pathogenesis of this diarrhea is thought to include alterations in intestinal microflora, portal hypertension and deficiency of bile acids.


Failure of the anabolic functions of the liver is reflected in a depression of glucose and albumin synthesis. While the reduced blood glucose shows few specific signs, reductions in circulating albumin have distinctive clinical signs. Significant hypoalbuminemia results in peripheral and ventral edema. Gross abnormalities of albumin synthesis and portal hypertension, arising as a result of hepatic fibrosis, can lead to increased hydrostatic and oncotic pressure in the intestinal mucosa with a resultant loss of water and proteins into the bowel lumen (diarrhea) and peritoneal cavity (ascites). Horses with significant ascites have a pot-bellied appearance and it may be possible to percuss a fluid thrill across the abdomen.


Tenesmus is thought to be a sign of HE but may also result from constipation.


Steatorrhea with excessive amounts of fat in the feces results from lipid malabsorption secondary to decreased excretion of bile. This is a rare sign in horses as the equine diet is normally low in fat.



Hepatogenic photosensitization (Figs. 2.9 & 2.10)


Horses lacking the normal detoxification capacity as a result of hepatic insufficiency become excessively sensitive to ultraviolet light. Photodynamic agents are derived endogenously as a result of metabolic processes (particularly in the intestine), or from ingested chemicals, including phenothiazine, and some plants, including Hypericum peroratum (St John’s wort), Polygonum fagopyrum (buckwheat) and Lolium perenne (perennial ryegrass). Failure to detoxify these photodynamic agents including phylloerythrin (a product of bacterial degradation of the plant pigment chlorophyll) results in accumulation in the circulation. In normal animals any absorbed photodynamic agents are removed from the portal circulation and excreted in bile, precluding the general distribution of the agents to the skin and other organs. Ultraviolet radiation in sunlight causes activation of electrons within the molecules of the photodynamic agent resulting in local free radical formation with subsequent cell membrane damage and necrosis. Unpigmented areas of skin absorb UV light more efficiently and thus are more severely affected. It is not always only the obvious areas of unpigmented skin which become affected, but the restriction to white skin is almost pathognomonic for photosensitization. The skin first appears erythematous and edematous. Pruritis, pain, vesiculation, ulceration, necrosis and sloughing may occur.





Hemorrhagic diathesis


The liver is also responsible for the synthesis of a wide range of important metabolic proteins including clotting factors, amino acids and other nutrients required for red cell and hemoglobin production. Particularly sensitive to hepatic disease is the synthesis of fibrinogen and the vitamin-K-dependent factors (II, VII, IX, X and protein C), which have short half lives. Vitamin K requires bile acids for proper absorption from the intestinal tract. Hepatic failure then results in a number of related clinical signs, including hemorrhagic diatheses and anemia. Although overt spontaneous hemorrhage is not a common sign associated with hepatic failure, bleeding into the intestine or into the major conducting airways and prolonged or excessive bleeding from wounds or following venipuncture may be encountered.






Polydipsia, polyuria and the hepatorenal system


Alterations in renal function, serum sodium concentrations, impaired water excretion and urine concentrating ability may accompany severe liver disease.


The heporenal syndrome characterized by acute azotemia and anuria may occur in ponies with hyperlipemia and hepatic lipidosis. The pathogenesis is unclear but may include such factors as reduced effective circulating volume, decreased hepatic inactivation of renin and endotoxemia.



Diagnosis of liver disease

The diagnosis of acute or chronic hepatic failure in the horse is largely based upon the detection of these characteristic, but non-specific, signs and confirmation usually relies heavily upon laboratory studies involving concentrations of hepatic enzymes and plasma proteins. The release of enzymes into the circulating blood from damaged hepatocytes is an index of the extent of the cell damage, although the magnitude of the enzyme concentration increase does not always correlate closely with the degree of hepatic dysfunction.


Liver biopsy, which is a relatively safe and simple procedure, provides definitive histological evidence of the type and extent of the pathological process. As almost all the significant hepatic disorders occurring in the horse are diffuse, biopsy is a most useful aid to their diagnosis. Although chronic hepatic failure may be accompanied by blood clotting disorders the procedure is seldom accompanied by dangerous blood loss. Some of the more common means of assessment of liver pathology are shown in Table 2.3.




Treatment of hepatic insufficiency

The basic goal of therapy is to maintain the animal until the liver regenerates enough to function sufficiently. Thus horses with severe fibrosis often respond poorly as the required regeneration is not possible. In this respect early biopsies are often useful prognostic indicators as therapy may be prolonged in many cases.



• Sedation. Horses with HE are often difficult to control and sedation is often required to allow for other treatment, avoid self-inflicted injury and provide safety for the nursing staff. Many tranquilizers are metabolized by the liver and should therefore be used cautiously. Xylazine or detomidine in small doses are safest. Diazepam should be avoided as it enhances the effect of GABA and may exacerbate signs.


• Fluid therapy. Fluid deficits and acid–base imbalances should be addressed. Extreme caution should be taken if administering bicarbonate- or lactate-containing fluids as they may result in elevations of blood ammonia levels. Hypokalemia or alkalosis result in increased renal production of ammonia with a corresponding increase in diffusion of ammonia into the CNS, thus treatment with potassium or acidifying fluids may be necessary. As many affected horses are anoretic, continuous infusion of dextrose 5% at a rate of 2 ml/kg/h may be beneficial.


• Reducing toxic metabolites. Reducing the production or decreasing the absorption of toxic protein metabolites is also an important part of therapy. Methods to reduce production include the oral administration of antibiotics (e.g. neomycin) or lactulose (a syrup containing lactose and other disaccharides). A disadvantage of both is that they may produce diarrhea. Lactulose is also expensive for long-term therapy. Other means of reducing production include alteration of intestinal flora by administration of pro-biotics such as Lactobacillus acidophilus. Administration of a low-protein diet (see below) is also advised although this has not consistently reduced signs of HE in humans. Zinc is an important co-factor in many urea cycle enzymes and supplementation may be warranted. Decreasing absorption of toxic metabolites is achieved through the administration of mineral oil or magnesium sulfate.


• Dietary management. Once horses with hepatic insufficiency become appetent they can be best managed by dietary control. Diets high in carbohydrates, low in protein and rich in BCAAs (branch chain amino acids) should be fed. Oat or other types of grass hay are best. Alfalfa and legumes should be avoided. Grazing should be encouraged. Small feeds several times a day are best because of impaired gluconeogenesis. Vitamin B1, K1 and folic acid should be administered weekly.


• Other treatments. Anti-inflammatory drugs may be beneficial and include flunixin meglumine, dimethyl sulfoxide and pentoxifylline. Other experimental drugs have been used in human and small animal medicine and may have a future role for management of hepatic insufficiency in horses.

Feb 27, 2017 | Posted by in EQUINE MEDICINE | Comments Off on Conditions of the liver, spleen and pancreas
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