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Sys Path > Liver 4 (test 1) > Flashcards

Liver 4 (test 1) Flashcards

1
Q

Define metabolic heterogeneity:

A

Drug metabolizing enzymes are concentrated in the centrilobular hepatocytes

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2
Q

Define Biotransformation

A

Conversion of lipid soluble compound into water soluble compound for elimination

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3
Q

Define Bioactivation:

A

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

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4
Q

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

A

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
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5
Q

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

A

Anatomic Metabolic Concentration effect

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6
Q

What are the two types of hepatotoxins?

A

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

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7
Q

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

A

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)
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8
Q

Define Cholangiohepatitis:

A

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

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9
Q

What are 4 factors affecting toxicity?

A
  • 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)
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10
Q

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

A

Microcystin: It disrupts actin filaments=Damages Cytoskeleton

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11
Q

Microcystin toxicitiy results in wha tkind of necrosis?

A

MASSIVE necrosis (Bad juju)

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12
Q

What is Canine Chronic hepatitis?

A

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

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13
Q

How do you definitively diagnosis Canine chronic hepatitis?

A

Requires Biopsy

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14
Q

Chronic canine hepatitis can progess to what?

A

Cirrhosis due to continual injury to the liver

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15
Q

T or F

Cirrhosis is an acute manifestaton of a chronic disease

A

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

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16
Q

What is often the main cause of chronic hepatitis?

A

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

17
Q

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

A

Inherited Copper Toxicosis

18
Q

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

A
  • Infectious Canine Hepatitis Virus
  • Leptospirosis
19
Q

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

A
  • Bedlington Terriers (Copper Toxicosis)
  • Doberman Pinschers (Chonic copper-associated hepatitis)
20
Q

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

A

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
Q

What is the defintion of Cirrhosis?

A

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
Q

T or F

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

A

T: liver enzymes may be normal or only mildly increased

23
Q

What are 2 important consequences of fibrosis and cirrhosis?

A
    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
    1. Portal hypertension: increased resistance to hepatic blood flow due to: fibrosis (compression), abnormal lobular acrchitecture, development of arterioveous anastomoses within the scars
24
Q

What are 3 importanat consequences of portal hypertension?

A
  • Ascites: due to incresased pressure within protal venous system and backflow into abdomen
  • Acquired portosystemic shunts–>hepatic encephalopathy
  • Splenomegaly (diffuse): splenic congestion
25
Q

What is the pathogenesis of acquired Porto-systemic shunts?

A
  • 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
Q

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

A
    1. Chronic, Persistent Stimuli
      * Chronic toxins/drugs
      * chronic canine hepatitis
      * persistent viral infections
      * autoimmune and drug therapy are the most common causes in dogs
    1. Rarely, a single episode of massive necrosis=post-necrotic cirrhosis
27
Q

What type of cirrhosis?

A

Macronodular

28
Q

What type of cirrhosis?

A

Micronodular cirrhosis

29
Q

What can cause passive congestion of the liver?

A

Right sided heart failure (congestive heart failure)

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

30
Q

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

A

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

31
Q

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

A

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

Sys Path (17 decks)

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