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Flashcards in Liver 4 (test 1) Deck (31):
1

Define metabolic heterogeneity:

Drug metabolizing enzymes are concentrated in the centrilobular hepatocytes

2

Define Biotransformation

Conversion of lipid soluble compound into water soluble compound for elimination

3

Define Bioactivation:

Conversion of an inert molecule into a reactive, possibly TOXIC, molecule

4

If one of the liver's primary functions is detoxification, why do so many toxins/toxicants cause hepatic lesions?

3 reasons so many toxins cause hepatic lesions:

  • 1] ANATOMIC: Toxicants that are ingested and absorbed from the alimentary tract are first carried to the liver via the portal circulation
  • 2] METABOLIC: Many harmless compounds are actually converted to toxic metabolites by the enzyme machinery (e.g. CYP450) that is designed to excrete chemicals. e.g. CCl4, pyrrolizidine alkaloids, etc,
  • 3] CONCENTRATION EFFECT:Some toxicants are concentrated in bile for excretion e.g. copper

5

What are the 3 reasons that toxins can cause hepatic lesions?

Anatomic Metabolic Concentration effect

6

What are the two types of hepatotoxins?

1] PREDICTABLE = will cause lesions in all exposed animals in a dose dependent fashion

2] IDIOSYNCRATIC = doses safe for almost all animals except a few e.g. carprofen, mebendazole, halothane reflects some aberration in the animal’s drug metabolizing abilities – NOT usually immune mediated or hypersensitivity

7

What are the factors that determine whether a hepatotoxin is predictable, or idiosyncratic?

FACTORS:

  • a) competition for detoxification pathways
  • b) drug binding in plasma (bound vs. unbound)
  • c) effects of other drugs or toxins on drug metabolism system
  • d) GENETICS ! (e.g. defects in specific pathways)

8

Define Cholangiohepatitis:

Involves neutorpils or mixed inflamation centerted on the biliary tree with secondary hepatocyte involvement 

9

What are 4 factors affecting toxicity?

 

  • competition for detoxification pathways
  • drug binding in plasma (bound vs. unbound)
  • effects of other drugs or toxins on drug metabolism system
  • GENTETICS! (e.g. defects in specific pathways) 

10

What is the toxin that causes disease with Blue-green algae toxicity? What does the toxin do in order to cause disease?

Microcystin: It disrupts actin filaments=Damages Cytoskeleton 

11

Microcystin toxicitiy results in wha tkind of necrosis?

MASSIVE necrosis (Bad juju) 

12

What is Canine Chronic hepatitis? 

It is Chronic inflammation, some degree of ongoing necrosis, regeneration and fibrosis 

13

How do you definitively diagnosis Canine chronic hepatitis?

Requires Biopsy 

14

Chronic canine hepatitis can progess to what?

Cirrhosis due to continual injury to the liver

15

T or F

Cirrhosis is an acute manifestaton of a chronic disease

 

True: this is how you get cirrhosis. Clinical signs often don't manifest until much later after disease has progessed due to the liver's extreme reserve capacity

16

What is often the main cause of chronic hepatitis?

It is often idiopathic, meaning we don't know why it just occurs..

17

What is a known cause of chronic hepatitis in Bedlington terriers?

Inherited Copper Toxicosis 

18

What are two known agents to cause chronic hepatitis, even though they may rarely mainifest in this way?

  • Infectious Canine Hepatitis Virus
  • Leptospirosis 

19

What are two Breeds that are genetically susceptible to chronic hepatitis?

  • Bedlington Terriers (Copper Toxicosis)
  • Doberman Pinschers (Chonic copper-associated hepatitis) 

20

What is this a picture of? and why might it look this way? (This is from a female doberman pinscher)

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This is a very cirrhotic liver with what appears to be regenerative nodules

- Macronodular Cirrhosis, secondary to chronic copper associated hepatitis in a Dobie

 

Chronic Hepatitis resulting in cirrhosis would also work.  

21

What is the defintion of Cirrhosis?

A diffuse process characterized by: 

-fibrosis (collagen deposition) and conversion of normal lobular architecture into structurally abnormal nodules (regeneration) 

-Leads to a decrease in liver size due to scarring 

-it is the end result of chronic hepatitis resulting from a number of chronic, progressive disorders=end stage liver

22

T or F

A cirrhotic liver may or may not cause an increase in liver enzymes 

T: liver enzymes may be normal or only mildly increased 

23

What are 2 important consequences of fibrosis and cirrhosis?

  • 1. liver failure: sinusoidal fenestrations lost, the transfer of macromolecules between the hepatocytes and blood is impaired. Decrease ability to carry out its synthetic, catabolic, and excretory roles
  • 2. Portal hypertension: increased resistance to hepatic blood flow due to: fibrosis (compression), abnormal lobular acrchitecture, development of arterioveous anastomoses within the scars 

24

What are 3 importanat consequences of portal hypertension?

  • Ascites: due to incresased pressure within protal venous system and backflow into abdomen 
  • Acquired portosystemic shunts-->hepatic encephalopathy
  • Splenomegaly (diffuse): splenic congestion 

25

What is the pathogenesis of acquired Porto-systemic shunts?

  • Fibrosis impedes hepatic blood flow and produces portal hypertension
  • Due to this increase in portal blood pressure, blood seeks the path of least resistance 
  • may shunt around the liver OR directly through the liver via shared capillary beds 
  • Typically causes many SMALL shunts, not a single large vessel 
  • shunting of blood and bile acids around (acquried extrahepatic shunts and through (acquired intrahepatic shunts) the diseased liver 

26

What are 2 causes of cirrhosis, which is most common?

  • 1. Chronic, Persistent Stimuli
    • Chronic toxins/drugs
    • chronic canine hepatitis
    • persistent viral infections
    • autoimmune and drug therapy are the most common causes in dogs 
  • 2. Rarely, a single episode of massive necrosis=post-necrotic cirrhosis

27

What type of cirrhosis?

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Macronodular 

28

What type of cirrhosis?

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Micronodular cirrhosis 

29

What can cause passive congestion of the liver?

Right sided heart failure (congestive heart failure) 

-cardiomyopathy, endocardidits, heartworm disease (caval syndrome) etc. 

30

What will an acute outflow disturbances cause the liver to look like?

Enlarged, congested with prominent central veins, distended centrilobular sinusoids atrophy of centrilobar hepatocytes

31

What type of liver lesion is this called and what is it associated with?

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NUTMEG Liver caused by chonic passive outflow disturbance (centriolobar necrosis)