The liver is a solid, voluminous organ, strategically placed between the digestive system and systemic circulation (Strombeck et al 1996).It is highly vascularised, notably through the portal vein carrying the blood of the abdominal viscera andd that produced by post-aortic circulation. Its roles are metabolic and synthetic, comprising detoxification, biotransformation, storage, body defence and homeostasis.
The liver represents roughly 3 to 4% of the overall body weight of an adult animal, and even more in young subjects.
Hepatic vascularisation is singular and produced by the hepatic artery (a branch of the celiac artery) AND by the portal veUl'
The portal vein transports blood from the viscera, such as the stomach, pancreas, spleen and intestines. This blood is very rich in nutrients but poor in oxygen. Because the portal vein has no valvula, any obstruction or hypertension will directly affect the surrounding blood stream.
The blood leaving the liver collects in the hepatic veins to return to the posterior vena. Thus, any hindrance to hepatic venous blood flow (of cardiac, pericardial or vena cava origin), jh will lead to passive venous congestion, hepatomegaly or the id production of ascitic fluid.
The liver is essential for the digestion, absorption, metabolism and storage of most nutrients. Another of the liver' s mam functions is as a secretory gland. Its functions also include y detoxification, the catabolization and excretion of numerous toxins, hormones and xenobiotics (substances with toxic ie properties, even at very low concentrations e.g. pesticides).
The liver is composed of cells called hepatocytes. Between the cells there are also bile capillaries which branch out to 1 as form bile ducts. Bile is secreted by the hepatocytes in the bile capillaries and flows into the bile ducts.
Bile contains bile acids. The latter have a detergent effect t and maintain non-miscible elements such as phospholipids and cholesterol in an aqueous milieu.
The liver is the main organ in which cholesterol is synthesised.In the event of acute liver failure or of portosystemic shunt, hypocholesterolemia can be observed, resulting in the reduced synthesis of bile acids, making them less available lin the intestine and leading to the malabsorption of fats.
Thus, the function of bile salts is to emulsify dietary fat (mix the fats with water to create a stable mixture) and to solubilize the products produced by their digestion.
The main bile pigment is bilirubin, which appears with redcorpuscles turnover in the liver (recycling). Thus, bilirubin isresponsible for the greenish colour so characteristic of bile.
Bile pigments also have a digestive function: bile serves 3to transport metabolic waste to the stool for final externalelimination.
The gall bladder is a small reservoir in which bile isconcentrated and stored between meals.
When there is little or no food in the intestinal lumen, theoddi sphincter is closed. This sphincter is located at the entranceto the bile duct in the duodenum, which is the first portion of thesmall intestine.
THE LIVER CONTROLS NUMEROUS METABOLICFUNCTIONS, CHIEF OF WHICH ARE:
- maintaininge homeostasis of glucose, amino acids and trace elements in the blood
- synthesizing albumin and clotting factors
- detoxifying and excreting endogenous and exogenouswaste e.g. NH3, medications and toxins
- regulating immunity
- regulating hormone balance
There are 3 major categories of circulatory disorders:
Congenital Porto-Systemic Shunts
Outflow disturbances affecting the heart, central vessels or the hepatic veins (examples: liver congestion due to cardiac failure; thrombosis, neoplasia, dirofilariasis)
Portal hypertension (persistent increase in pressure in the portal venous system)
Hepatic encephalopathy (HE) is a central nervous system dysfunction, with abnormal signs of behaviour, apathy or even convulsive fits in extreme cases. Although it is more common in dogs than in cats, HE is essentially the result of a portosystemic shunt (75% of cases in dogs) and/or of severe hepatic insufficiency (for instance consequence of cirrhosis after hepatitis; consequence of severe hepatic lipidosis) Animals affected by congenital PSS present signs of HE before one year of age in around 75% of cases. The form may be congenital or acquired, and accompanied by portal hypertension or by ascites. In subjects with the congenital form, ascites and jaundice are generally absent. This is quite the contrary in the acquired form since these acquired PSS are secondary to a chronic liver disease such as cirrhosis. HE is fairly rare in cats and is usually of the congenital type id there is seldom any presence of extended fibrosis, cirrhosis or even portal hypertension. HE is also found in cats with very severe hepatic lipidosis. Finally, acute liver pathologies may, in rare cases , trigger HE.
Herein lies the interest of regulating intestinal floral using a highly digestible food with moderate fibre content. The more digestible the proteins, the less amonia produced byintestinal bacteria. Moderate quantities of food fibre are useful for animals suffering from hepatic insufficiency. Fermentable fibres like fructo-oligo-saccharides (FOS) and beet pulp are used by intestinal flora. They stimulate the incorporation of ammonia by bacterial proteins , which are then secreted in faeces. is By lowering the pH level in the colon, fermentable fibres also reduce the production and absorption of anunonia and possibly e of other toxins. Non-fermentable fibres may thus prove beneficial in reducing transit time, preventing constipation and toxin e absorption.
Cholangitis is a liver pathology whose inflammatory process C focuses on the bile ducts rather than the hepatocytes.
Cholangio-hepatitis is an inflammation of the bile ducts and associated bile ducts.
Bacterial cholangitis or cholangio-hepatitis occurs when the infection moves up the biliary system and reaches the liver. Any bacteria can be responsible although E.Coli is relatively common.
Necrotic cholecystitis occurs when the bacterial infection damages the walls of the gall bladder, spreading its contents i.e.bile, through the cavity in large quantities. In certain subjects 3 the gall bladder can even burst, This can cause very severe septic Peritonitis.
Finally, emphysematous cholecystitis occurs when the gall e bladder is infected by gas-emitting bacteri
Diseases affecting the liver tissues are far more common n in dogs, Acute hepatitis is characterised morphologically by a set of inflammatory processes, of hepatocellular apoptosis and necrosis that may be accompanied by the regeneration of hepatic oI parenchyma,
Chronic hepatitis is defined as a chronic inflanmation of the liver. It is a disease that encompases a whole set of processes that can affect dogs of all ages. The etiologies of this pathology may be multiple and diverse although n the cause remains indeterminate in the majority of of cases. Additional tests are always necessary. These include biological tests (biochemistry, hematology or even cytology by ascites fluid analysis, for example), imagery (radiography, ultrasound scan) and histopathological tests (biopsy tests etc).
In dogs, the clinical signs may develop at any age, and the disease can last from several weeks to several years. It is characterised morphologically by fibrosis, hepatocellular necrosis, chronic hepatitis by copper intoxication and apoptosis.
The severity of chronic hepatitis depends on the extent of the necrotic and inflammatory process.
The origin of chronic hepatitis with fibrosis is often unknown and may be multifactorial. It may begin with Infectious Canine Hepatitis, for instance; it may occur with inflammations of the pancreas and the gastrointestinal system, the use of corticoids, anticonvulsants or hepatotoxic drugs.
Hence, the etiologies of chronic hepatitis may be infectious (CAV-1 and Parvovirus, Helicobacter Canis and Leptospira are considered as potential agents for certain forms of chronic canine hepatitis) or non infectious (copper accumulation of genetic or non genetic origin, metabolic causes and finally, toxins and toxics).
Fibrosis and cirrhosis may result from any severe or chronic hepatic insult. Because of inflammatory cells during inflammation, hepatocyte necrosis appear and intercellular cells cirrhosis.
<somr breeds show a predisposition (the Bedlington Terrier for example) to abnormal copper accumulation in the liver. Without treatment, the affected dogs develop progressive liver failure and die within several years. Moreover, in an animal iffering from a well established liver disorder, any excess of copper c~ lead to intoxication with positive feed-back on the worsening of parenchymatous lesions.
A Porto-Systemic Shunt (PSS) is a vascular anastomosis (communication) between the portal vein and general venous circulation by "short-circuiting" the liver (the blood of the portal vein normally passes through the liver before entering general circulation).
This shunt may be intra or extra-hepatic.
In Cats, liver disorders include hepatic lipidosis AND inflammatory liver disease with inflammation centered on bile ducts (not hepatocytes). Other entities exist such as toxic hepatitis, portosystemic shunts or hepatic amyloidosis.
Feline hepatic lipidosis (FHL) is a potentially deadly cholestasic syndrome affecting overweight cats. In most cases, disorders causing anorexia or malassimilation/maldigestion are at the origin of the catabolic process preceding the onset of the syndrome. Etio-pathogenic factors create an imbalance between the mobilisation of reserves of peripheral fat toward id the liver AND the hepatic use of fatty acids to produce energy concomitant with the distribution of triglycerides (TG) in the lar body in the form of lipoproteins.
A hepatic deficiency in L-Camitine has also been observed, which may favour the accumulation of lipids in the liver, given that this AA transports FA into the mitochondria to be oxidated to produce energy. It is also responsible for transporting metabolic waste outside the mitochondria, Carnitine is a quarternary amine made up of two essential amino acids, lysine and methionine,
Treatment is as severe as hepatic lipidosis itself, with a high us risk of mortality.It comprises the following elements.
1)Fluidtherapy (rehydrating and electrolyte intake)
2)K+ intake
3)Adequate nutrition (qualitative, quantitative and route ofand intake)
4)L-Camitine (250 mg/day per cat)
5)SAMe (200 mg/d) and vitamin E (20-100 UI/day per os) asiring antioxidants
6)Group B vitamins
7)Vitamin B12 by parenteral route (i.e. other than by digestive ic route) 1 mg by IM route, as deficiencies are common in FHL (with ly absorption disorders from the associated digestive pathologies)
Feline Inflammatory Liver Disease (centered on the bile ducts) is also called CHOLANGITIS COMPLEX
The terminolgy used for describing and classifying feline r, inflammatory liver disease has been variable and inconsistent )I in the past. The WSAVA (World Small Animal Veterinary Association) recently established a new classification helping of to clarify some of the confusion in the histologic criteria for the e terminology of feline inflammatory liver disease.
The cholangitis complex is regarded as the second most s common hepatic disorder in cats in the USA after idiopathic S hepatic lipidosis.
The term triaditis has been used to describe a syndrome of ing concurrent cholangitis, pancreatitis, and IBD.
Neutophilic Cholangitis was previously termed "suppurative" or "exudative cholangitis/cholangiohepatitis" . D The main histological feature is a primarily neutrophilic infiltrate within the bile duct lumen and/or epithelium. Nevertheless, lymphocytes and plasma cells could also be present.
Lnflammatory bowel disease (IBD) has been recognized more yrecently as a coexisting feature in cholangitis. It was diagnosed in 83% of cats with cholangitis in a retrospective pathologic study although the intestinal inflammatory infiltrate was predominantly lymphocytic and plasmacytic in nature,in somecases a neutrophilic element was present,
Lymphocytic Cholangitis (previo usly termed "nonsuppurative cholangitis.cholangiohepatitis" , "lymphocytic cholangiohepatitis, "lymphocytic portal hepatitis" ), the inflammatory infiltrate is predominantly lymphocytic.
Mixed Inflammatory Cholangitis (Infiltrates) are seen in a small propotion of cats, consisting of both neutrophils and lymphocytes on histological findings showing a mixed-cell infiltrate.
Cholangitis Associated with Liver Flukes results in chronic cholangitis and is commonly encountered in cats in endemic areas.
PSS in cats are generally congential. Acquired cases are extremely rare. The reason is that large fibrosis rates, cirrhosis or portal hypertension is very uncomon in Cats. On the other hand, in very sever hepatic lipidosis cases, Hepatic Encephalopathy can appear.It can also occur in very acute and violent occurences of hepatic insufficiency.
Meeting energy and nutritional requirements is an absolute priority, particularly in the case of liver diseases, to prevent the loss of weight and muscle. Substantial weight loss, muscle wasting and hypo-albuminemia are typical signs of malnutrition in animals affected by hepatic insuciency. Anorexia, vomiting, poorer digestion, absorption and metabolism of nutrients, increased protein catabolism and protein synthesis inefficacy explain the poor condition of these animals. By correcting levels of energy, proteins, minerals and vitamins malnutrition can be prevented.
Dogs and cats suffering from hepatic insufficiency have good tolerance to high lipid intake in their diets. Lipids are especially pertinent due to the high energy density and palatability they add to the food The only cases in which lipids could be restricted are those of marked steatorrhea. To put it more simply, providing energy through lipids will reduce protein catabolism (muscle wasting), reduce the size of the ration and of the meal (limiting the risk of vomiting by dividing the daily ration int0 3 meals), optimise palatibility and linut intolerance to carbohydrates.
Next, proteins. An adequate AND highly digestible supply of proteins favours hepatic regeneration. If this is not the case, symptoms of hepatic encepbalopathy may appear or increase. To put it simply, protein energy supply needs to be(NRC 2006)
In the beginning, the food obviously has to be reintroduced gradually, especially in the case of prolonged anorexia (frequent small meals, to attain total energy and protein requirements after 5 to 7 days). Tube feeding may often prove necessary (nasoesophageal or esophagostomy for example).
An adequate supply of energy and proteins is thus indispensable to prevent weight loss. The supply of non-protein calories is important to restrict the use of amino acids in energy metabolism and to reduce the need for ngluconeogenesis. The diet must be energy-concentrated because dogs suffering from liver disease usually have a reduced appetite.
Regarding minerals and vitamins, the main deficiencies are in:
◎ Potassium◎ Vitamin K◎ Zinc◎ Vitamins in the Bgroup
An optimal supply is required of protein, of L-Camitine and c of B-group vitamins,
Proteins are essential for hepatic parenchymal regeneration. As specified above, the aim is to provide the sick animal with the maximum amount of protein without exceeding tolerance before the symptoms of hepatic encephalopathy.
The aim of liver Nutritional suppoty is therefore to limit both hepatocyte necrosis and the production of freee radicals. The problem with latter arises when there is an imbalance between their production and neutralisation. Hepatic lesions progress and the process runs out of control. Antioxidants compensate the physiological production of free radicals, so supplements are recommended for dogs and cats affected by hepatopathies. Antioxidants often act in synergy and are administered as a "cocktail".
Gopper and Zinc. Copper is absorbed by binding with liver proteins. This storage capacity is nevertheless limited and the excess copper is eliminated by bile. Cholestasis will lead to secondary copper retention. In the canine species, chronic hepatitis leads to liver copper accumulation. As we saw earLier, hereditary copper storage disorders have been identified in y certain canine breeds. A low copper diet is therefore highly recommended.
One possible hepatic complication is ascites. In the case of hypoalbuminemia (hypo-proteinemia), there is a drop in oncotic pressure.
Regulating intestinal flora is accomplished by adding highly digestible proteins ~id ensuring food composition that is moderate in soluble (fermentable) fibres and non digestible y oligosaccharides. To reduce NH3 production and absorption, managing this particular aspect requires selecting protein o sources that are highly digestible and finally, by favouring an acid pH in the colon by using non digestible oligosaccharides (FOS, lactulose or lactose) and moderately fermentable fibres (beet pulp).
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