Term
| Describe the mechanism for lipid accumulation in the liver. |
|
Definition
-excess entry of fats into liver
-dec oxidation of FA: due to abnormal hepatocyte function
-impaired secretion of lipoprotein: dec apoprotein synth, dec lipoprotein pdn and export |
|
|
Term
| What are some possible stages of life in which fat transit thru a healthy liver inc thus resulting in a fatty liver? |
|
Definition
-late pregnancy and heavy lactation: esp rums
-neonates ingesting high fat milk |
|
|
Term
| What does a fatty liver look like if it is due to inc of fat through a healthy liver? |
|
Definition
|
|
Term
| What are the two major mechanisms of lipid accumulation |
|
Definition
-dec formation/export of lipoproteins
-dec oxidation of FA w/in hepatocytes |
|
|
Term
| What are th eetwo most common causes of hepatocellular hypoxia? |
|
Definition
-anemia
-passive venous congestion |
|
|
Term
| Which cattle are especially affected by ketosis/bovine faty liver syndrome? |
|
Definition
-obese animals
-often days befire parturition: dairy
-often days after parturition: beef |
|
|
Term
| Describe the pathophysiology behond bovine fatty liver syndrome? |
|
Definition
-continued high E demand leads to excessive fat metabolism and ketone body pn precipitated by anorexia
-lipid accumulates in liver due to: inc mobilization of lipid from adipose & dec lipoprotein export |
|
|
Term
| What is the most common liver lesion in cats? |
|
Definition
| -feline fatty liver syndrome |
|
|
Term
| Which cats are usually affected by feline fatty liver syndrome? |
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Definition
| -typically obsse and anorectic cats: adults after 2-7 days of inappetence |
|
|
Term
| What are the clinical signs of feline fatty liver syndrome? |
|
Definition
-hepatic failure
-icterus
-hepatic encephalopathy: drooling & depression
-vomiting & anorexia
-weakness & wt loss
-jaundice
-hepatomegay
-high mortality if untreated |
|
|
Term
| Which animals are most commonly affected by fattly liver syndrome in puppies? |
|
Definition
| -toy-breed puppies that have been fasting 8-16h |
|
|
Term
| What are the clinical signs fo fatty liver syndrome in puppies? |
|
Definition
| -neuro signs due to hypoglycemia: ataxia, weakness, seizures, coma |
|
|
Term
| Describe the pathophysiology behind fatty liver syndrome in puppies. |
|
Definition
| -insulin levels dec => pup becomes ketotic => hepatic lipidosis |
|
|
Term
| What will the liver look like w/ fatty liver syndrome in puppies? |
|
Definition
| -moderatly enlarged, diffusely pale liver that floats in formalin in severe cases |
|
|
Term
| How do we prevent fatty liver syndrome in puppies? |
|
Definition
| -prevented by high-energy, protein-rich diet w/ frequent feedings |
|
|
Term
| Which animals are most commonly affected by equine hyperlipemia? |
|
Definition
| -ponies and mini horses: pregnant or lactating mares w/ anorexia |
|
|
Term
| What do we see on labs w/ equine hyperlipemia? |
|
Definition
| -inc in plasma triglyceride: lipemia seen in blood/serum |
|
|
Term
| What clinical signs do we see with equine hyperlipemia? |
|
Definition
|
|
Term
| What does the liver look like w/ equine hyperlipemia? |
|
Definition
| -severely fatty liver at necropsy |
|
|
Term
| What is the prognosis of equine hyperlipemia? |
|
Definition
| -usually fatal after about 1 week |
|
|
Term
| What leads to fatty liver in diabetes mellitus? |
|
Definition
-insulin deficiency results in accelerated lipolysis due to reduced glucose uptake by cells
-large load of FA to liver => dec FA oxidation (due to dec glucose and ATP) => dec lipoprotein syth |
|
|
Term
| What frequently complicates fatty livers w/ DM? |
|
Definition
| -exocrine pancreas insufficiency |
|
|
Term
| What commonly induces glycogen accumulation in SA? |
|
Definition
| -glucocorticoids: exogenous or endogenous |
|
|
Term
| What does the liver look like due to glycogen accumulation? |
|
Definition
-enlarged, pale tan and friable liver in severe cases
-biopsy reveals zonal hepatocellular swelling and vacuolation |
|
|
Term
| What is hepatic amyloidosis secondary to? |
|
Definition
|
|
Term
| What is hepatic amyloidosis? |
|
Definition
| -amyloid deposited w/in the space of Disse => may lead to liver dysfuction or failure |
|
|
Term
| What are the physiologic effects of hepatic amyloidosis? |
|
Definition
| -hepatomegaly, pallor, and inc fragility |
|
|
Term
| What are the four differentials for an accentuated lobular pattern? |
|
Definition
-passive congestion
-anemia
-hepatotoxin exposure
-lipidosis (zonal) |
|
|
Term
| Describe the hepatic damage due to copper accumulation. |
|
Definition
| -excess copper leads to pdn of reactive oxygen spp => lipid peroxidation => membrane damage |
|
|
Term
| Copper toxicosis occurs due to...? |
|
Definition
-simple dietary excess (sheep): indadequate molybdenum (Mb)
-phytotoins leading to: cholestasis (dec Cu excretion) dec of hepatocyte ability to proliferate (pyrrolizidine alkaloids)
-hereditary disorders => impaired excretion leads to Cu accumulation (dogs) |
|
|
Term
| Describe the pathophysiology of copper toxicosis in ruminants. |
|
Definition
| -copper accumulates in liver => lysis of RBCs => dec PCV => centrilobular necrosis in liver |
|
|
Term
| What do we see on necropsy w/ chronic copper toxicity in sheep? |
|
Definition
-pale + centrilobular degen + gunmetal blue kidneys
-also severe hemoglobinuria |
|
|
Term
| Which breeds of dogs are predisposed to copper accumulation? |
|
Definition
-Bedlinton
-West highland terriers |
|
|
Term
| What are the clinical signs of copper accumulation in dogs? |
|
Definition
-progressive liver failure
-wasting
-lethargy
-vomiting
-ascites
-icterus
-CNS dz uncommon |
|
|
Term
| What lesions do we see due to compper accumulation in dogs? |
|
Definition
-pale, fibrotic, and nodular livers
-hemolysis is NOT significant part of this dz |
|
|
Term
| Describe the pathophysiology of copper accumulation in dogs. |
|
Definition
| -inc hepatic Cu levels assoc w/ chronic hepatitis in several dog breeds: uncertain relationship |
|
|
Term
| What affects do bile pigments have on the liver? |
|
Definition
-green discoloration
-due to cholestasis |
|
|
Term
| What affects does melanin have on the liver? |
|
Definition
-dark brown to black
-endogenous pigment
-esp sheep & some cattle |
|
|
Term
| What affects do liver flukes have on the liver? |
|
Definition
| -dark excreta along migratory tracts |
|
|
Term
| What are the three major routes of infection/injury to the liver? |
|
Definition
-hematogenous
-ascending through the biliary tract
-direct extension or puncture |
|
|
Term
| Via which vessels do infection and injury spread to the liver hematogenously? |
|
Definition
| -hepatic artery or portan vein |
|
|
Term
| Give some examples of infection/injury reaching the liver via direct extension or puncture. |
|
Definition
-thru body wall or puncture by GI FB
-discrete foci of inflammation w/ or w/out necrosis
-may develop into abscesses
-umbilical v in neonates |
|
|
Term
| What are some examples of injuries that hepatocytes are highly susceptible to? |
|
Definition
-injury by toxins, microorganisms, inflammatory cells, metabolic disturbances, etc
-sublethal or lethal injury
-cell welling or lipid accumulation vs necrosis |
|
|
Term
| What are the three general morphological patterns of hepatocellular degeneration or necrosis? |
|
Definition
-random (multifocal)
-zonal: centrilobular, paracentral, midzonal, periportal
-massive |
|
|
Term
| What is the most common pattern of hepatic injury? |
|
Definition
|
|
Term
| What is a random and multifocal pattern of hepatic injury? |
|
Definition
-no predictable location w/in lobules
-discrete pale or less often dark red foci: soze of foci is variable
-single-cell necrosis or aggregates of necrotic hepatocytes |
|
|
Term
| Which insults typically cause random and multifocal patterns of hepatic injury? |
|
Definition
| -infectiou agents spread in the blood |
|
|
Term
| What does a liver with a zonal pattern look like? |
|
Definition
-typically pale and slightly enlarged s/ rounded margins
-inc friability and enhanced lobular pattern |
|
|
Term
| What insults typically cause zonal patterns? |
|
Definition
| -toxic, hypoxic, or metabolic dz |
|
|
Term
| What are the 2 most common causes of hepatocellular hypoxia? |
|
Definition
-anemia
-passive hepatic congestion |
|
|
Term
| Within which region of hepatic lobule are hepatocytes first injured by hypoxia? |
|
Definition
| -centrilobular (periacinar or zone 3) |
|
|
Term
| Name a metabolic dz that may result in an enhanced lobular pattern due to hepatocellular accumulation of lipids? |
|
Definition
-DM
-ketosis/bovine fatty liver
-pregnancy toxemia
-feline hepatic lipidosis |
|
|
Term
| Is centrilobular hepatic necrosis common or rare? Describe that region. |
|
Definition
-common
-receives least oxygenated blood and has greatest enzymatic activity (mixed-function oxidases) |
|
|
Term
| What causs centrilobular necrosis? |
|
Definition
-anemia
-passive congestion
-biotransformed toxins |
|
|
Term
| What is massive hepatic necrosis? What does it cause? |
|
Definition
-necrosis of entire lobule or acinus
-results in collapse and post-necrotic scarring: no cells left for lobules to regen form |
|
|
Term
| What are the typical causes of massive necrosis? |
|
Definition
-toxins
-acute vascular accidents
-nutritional origin |
|
|
Term
| Describe the regenerative capacity of the liver. |
|
Definition
| -large, regen possible after removal of up to 70% of hepatic mass |
|
|
Term
| Regen of normal hepatic architecture requires what? |
|
Definition
| -requires retention of fibrous framework |
|
|
Term
| How does the liver regen in response to injury? |
|
Definition
-mature hepatocytes proliferate to replace lost cells
-oval cells: stem cells for hepatocytes and bile duct epi |
|
|
Term
| What happens to liver regen with susteined or repetitive injury? |
|
Definition
-becomes nodular: due to constricting bands of fibrosis
-hepatic mass may be regenerated but function may not be adequate |
|
|
Term
| why does fibrosis occur in the liver? |
|
Definition
-common manifestation of chronic or repetitive hepatic injury
-combined w/ regen, is responsible for nodularity of chronically diseased livers |
|
|
Term
| What does the effect of fibrosis on hepatic function depend on? |
|
Definition
-reversibility: immature collagen may be degraded
-site of collagen deposition: alteration of blood flow and may interfere w/ vascular distension |
|
|
Term
| How does the site of collagen deposition alter blood flow through the liver? |
|
Definition
-causes bypass of parenchyma
-altered lobular architecture
-collagen in space of Disse => get backed up fluid |
|
|
Term
| What effects are caused by severe firbrosis in the liver? |
|
Definition
| -can interfere w/ vascular distension => to portal hypertension |
|
|
Term
| What is bile duct hyperplasia? |
|
Definition
-non-specific response to a variety of insults
-especially in dz obstructing normal bile drainage or portal inflammation
-usually seen in long-standing injury
-can occur swiftly, especially in young animals |
|
|
Term
| What is bile duct hyperplasia associated w/ in horses? In small rums? |
|
Definition
-pyrizzolidine alkaloids
-aflatoxins |
|
|
Term
| What is cirrhosis? Describe it. |
|
Definition
-end-stage liver
-nodular regen, disorganization of hepatic architecture |
|
|
Term
| Describe the pathophysiology that leads to end-stage liver. |
|
Definition
| -cell death + inflammation => nodular regen + fibrosis => end-stage liver |
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