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Major categories of liver function. (4)
metabolic, circulatory, secretion/excretion, storage/filtration
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Metabolic functions of the liver. (3)
carb/fat/protein metabolism, vitamin and mineral metabolism, detoxification and clearance
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How does the liver support glucose homeostasis? (3)
glycogen storage after eating and breakdown during fasting, gluconeogenesis; insulin and glucagon are also affected by liver function
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Why do animals get hypoglycemic in liver failure? (2)
- functional failure: synthetic failure (70% of functional tissue obliterated)--> decreased gluconeogenesis, decreased insulin degradation
- Paraneoplastic to hepatic neoplasia: tumors secrete insulin-like growth factor, driving glucose down
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Liver functions associated with fat metabolism. (6)
cholesterol synthesis, bile acid synthesis, ketogenesis, FA and TG metabolism, lipoprotein synthesis, phospholipid metabolism
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Altered fat metabolism in the liver can lead to... (4)
decreased serum cholesterol (decreased synthetic function) OR increased serum cholesterol (secondary to cholestasis); target cells, hepatic lipidosis
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Protein metabolism functions of the liver. (6)
albumin synthesis, globulin synthesis (ish), coagulation factor synthesis, amino acid regulation, ammonia detoxification, urea synthesis
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Albumin is synthesized in the ___________; it is responsible for...
liver ONLY; maintaining plasma oncotic pressure
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Decreased synthetic function of the liver indicates _____(2)_____.
severity and chronicity
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Is decreased albumin specific for the liver?
No- GI or renal protein-losing -opathies
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What are the 3 mechanisms of bleeding disorders in liver disease?
decreased synthesis of clotting factors, DIC (hypercoagulable: source of AT, plasminogen, and factor clearance), Vit K deficiency
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What are liver functions associated with vitamins/minerals? (3)
fat soluable vitamin storage, water soluble vitamins, storage or iron/copper/zinc/etc
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The liver is responsible for detoxification and clearance of... (5)
pathogens (Kupffer cells), drugs, toxins, hormones, metabolites.
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What are the 2 phases of drug metabolism in the liver?
- Phase I: Oxidation
- Phase II: Conjugation
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How should you handle administration of drugs metabolized by the liver to patients with liver disease?
lower the dose- monitor more closely
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Photosensitivity due to liver disease occurs in ___________.
herbivores
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Biochem markers of decreased synthetic function. (7)
increased ammonia, increase coag factors, decreased glucose, decreased cholesterol, decreased BUN, decreased albumin, increased serum bile acids
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Biochem markers of liver cell necrosis. (2)
increased ALT and AST
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Biochem markers of cholestasis. (6)
increased coag factors, increased bilirubin, bilirubinuria, increase cholesterol, increased serum bile acids, increased ALP and GGT
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Biochem markers of portosystemic shunting. (2)
increased post-prandial bile acids and blood ammonia
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Hepatic blood flow is contributed to by... (2)
hepatic artery, portal blood flow
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The liver is drained by the ____________.
caudal vena cava
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Portal blood drains from... (4)
intestines, stomach, pancreas, spleen
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What is a portosystemic shunt?
vascular communication b/w portal and systemic venous systems, bypassing the liver
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What are potential causes of a single portosystemic shunt?
congenital malformation (no portal hypertension, no abdominal effusion, no hyperbili)
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What are potential causes of multiple portosystemic shunts?
portal hypertension, congenital or acquired (often associated with ascites, other evidence of liver dz)
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What are consequences of portosystemic shunts? (3)
hepatic encephalopathy, urate urolithiasis, hepatic atophy (small liver, evidence of synthetic dysfunction)
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What are causes of hepatic encephalopathy? (3)
portosystemic shunt, loss of critical hepatic mass (massive necrosis, cirrhosis), urea cycle enzyme deficiency
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Describe the pathophysiology of hepatic encephalopathy.
brain is affected by substances (ammonia, synergistic toxins, altered neurotransmitters, oxidative stress, inflammatory mediators) normally metabolized by the liver
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What are clinical signs of portosystemic shunts? (14)
anorexia, lethargy, disorientation, head-pressing, circling/pacing, ataxia, weakness, dull, difficulty training, behavioral changes, blindness, hypersalivation, seizures, coma
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What brain cells are the target of toxins in hepatic encephalopathy?
astrocytes
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Describe ammonia metabolism in the body.
NH3 produced in colon by bacterial action on dietary protein--> absorbed from colon--> portal blood--> NH3 carried to liver--> converted to urea (BUN) in hepatocytes--> NH3 low in peripheral blood
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What are supporting points for the hypothesis that ammonia toxicity causes hepatic encephalopathy? (4)What is the argument against it?
- For: NH3 is neurotoxic and increased NH3 causes CNS signs, PSS dogs are usually worse after a meal, NH3 causes type II astrocytosis, NH3 modulates neurotransmitters
- Against: poor correlation b/w blood NH3 levels and signs
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What are the general principals of treating hepatic encephalopathy? (4)
correct precipitating events, restrict dietary protein, decrease colon NH3 absorption, alter intestinal bacteria
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What are potential precipitating events of hepatic encephalopathy? (8)
high protein meal, GI bleeding, blood transfusion, constipation, dehydration, azotemia, infection, alkalosis/ hypokalemia
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What drugs are usually used to treat the precipitating events of hepatic encephalopathy? (6)
corticosteroids, NSAIDs, tranquilizers, anticonvulsants, anesthetics, diruretics
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What dietary changes are usually recommended for patients with hepatic encephalopathy/PSS?
lower protein- avoid red meat or organ meat-based diets; soy based diets are best, chicken or egg based diets are second best
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How can you alter intestinal bacterial to reduce NH3 absorption from the colon in hepatic encephalopathy?
antimicrobials
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What are the mechanisms of increased resistance and portal hypertension? (3 groups)
- Post-hepatic: CVC and heart, mass/CHF, pericardial effusion
- Intrahepatic: cirrhosis, hypoplastic portal system
- Pre-hepatic: portal vein obstruction (thrombus, mass)
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What are consequences of portal hypertension? (4)
ascites, hepatomegaly, acquired PSS, gastric ulcers
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You tap the abdomen of an animal with abdominal effusion; what conclusion can you draw if the fluid has high protein content? Low protein content?
- High protein: ascites- intrahepatic obstruction and portal hypertension
- Low protein: pre-hepatic obstruction and portal hypertension
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What mechanisms of liver disease can lead to GI ulceration? (3)
decreased mucosal blood flow, decreased gastric epithelial turnover (d/t negative nitrogen balance, hypoalbuminemia), +/- increased gastric acid secretion
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What are the components of bile? (5)
bile salts, bilirubin, cholesterol, electrolytes, water, others
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What is cholestasis?
increased amounts of substances (bile acids,bilirubin, cholesterol) in the blood that are normally excreted in bile
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What substances are increased in the blood with cholestasis? (3)
bile acids, bilirubin, cholesterol
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What are the different mechanisms of cholestasis? (2)
extrahepatic (mechanical- gallbladder, common bile duct, main bile duct), intrahepatic (functional)
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Briefly describe normal bilirubin metabolism.
senescent RBCs are sent to the liver through the portal vasculature (unconjugated bili)--> hepatocytes conjugate it (conjugated bili)--> delivered to gallbladder and dumped to intestines through bile duct--> excreted in feces/urine
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What is unique about bilirubinemia in horses?
they get fasting hyperbili- icterus of anorexia
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What are the functions of Vit K?
activation of clotting factors in hepatocytes
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Fats and fat-soluble vitamins require _____________ for absorption.
micelle formation
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How does liver disease lead to Vit K deficiency?
intestinal malabsorption of Vit K because of lack of bile acids for proper micelle formation [cholestatic disorders- mechanical biliary obstruction, severe intrahepatic cholestasis]
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What route of administration is essential to treat Vit K deficiency due to biliary obstruction?
parenteral b/c dietary deficiency is not the problem....the animal can't absorb it from the intestines
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If an animal has hyperbilirubinemia, should you test their bile acids?
No- you already know that bile acid flow is going to be blocked- waste of time and money
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