QUESTIONS

1. What's the difference between hepatic fibrosis & hepatic cirrhosis?
    
2. List all the categories of causes for chronic active hepatitis that you can think of.
    
3. The classical patient profile for a dog with chronic active hepatitis is (choose one ):
   
   male/female
   
   (choose one ):
   
    young/middle aged/aged
    
4. The predominant cells of infiltration in chronic active hepatitis are
   _______________ & _______________.
    
5. In what liver area do the inflammatory cells first show up in CAH?
    
6. What is "Bridging Necrosis"?
    
7. Why can't you just regenerate a new liver in CAH?
    
8. What drug stands out above the others as the grand inflammation arrester in CAH?
    
9. What does colchicine do?
    
10. Penicillamine is a heavy metal chelator but it is used in CAH. What is it supposed to help with here?
     
11. How about Zinc Acetate? How is that supposed to help?
    
    
    
    
     

ANSWERS

1. Fibrosis is the abnormal deposition of collagen in the liver with out a loss of architecture.
   
   Cirrhosis is much worse & here the architecture gets totally distorted.
   
   
   
   
    
2. CAH in dogs can be caused by:
   
   -viruses (like the hepatitis virus - which initiates a perpetuating inflammatory process over years)
   
   - drugs (like phenobarb. In humans, alcohol is the biggie)
   
   -immune-mediated processes (these are not auto-immune processes directed against the liver but other auto-immune processes like SLE or AIHA which invovle general "anti-tissue" antibodies which affect the liver as well as other organs.)
   
   
   
   
    
3. The classical patient is female & middle aged (the average CAH age in the dog is 5-6 years).
   
   
   
   
    
4. The predominant cells are lymphocytes & plasma cells.
   
   
   
   
    
5. Inflammatory cells first infiltrate the portal areas.  As these areas are destroyed, cholestasis sets in.  In response to inflammation, perisinusoidal lipocytes transform into myofibroblasts and begin secreting collagen. This is is helpfulin in  healing injury but in the disease state it is  out of control.   Too much scarring leads to portal hypertension which leads to poor hepatocyte nutrition and poor liver function as blood shunts away from the liver.
   
   
   
    
6. Bridging necrosis = an extension of inflammation from one portal triad to an adjacent one or/and from portal areas through the lobule to the central vein.
   
   
   
   
    
7. Normally hepatocytes live in cords of say 15-20 cells. When these cells die, they are replaced by units only 2 cells thick.  This dramatically reduces the surface area hepatocytes can use to "see" the portal circulation & also leads to the formation of nodules. As normal tissue is killed off, it is not replaced by tissue of an equal amount.  Dead space is filled in with collagen.
   
   
   
   
    
8. I was going to say prednisolone instead of prednisone because the failing liver might not be able to process prednisone into predisolone. (Note: to designate that it has been processed, the liver stamps an "L" on prednisone :) ) but Sharon Center lists both pred & prednisolone in her liver hand out.
   
   
   
   
    
9. Colchicine does several things.  Mostly it is a microtubule poison - no tubules, no collagen formation. It is also supposed to enhance collagenase & interrupt the intracellular transport of collagen.  It may also inhibit leukocyte migration and directly stabilize hepatocyte membranes
   
   
   
   
    
10. Penicillamine interferes with the deposition of collagen by messing up collagen cross-linking & maturation. In other words, lysyl oxidase is inhibited when penicillamine chelates the copper it needs to work.  Lysl what?
    
    Here is how collagen is born:
    
    First, procollagen (a protein strand rich in proline, hydroxyproline and lysine) is made intracellularly.
    
    Next it is hydroxylated and glycosylated to help prepare it for cross linking.
    
    Next it is secreted from the cell where an enzme called ``lysyl oxidase" initiates cross linking. Cross linked collagen can only be degraded by specific collagenases. Improperly cross linked collagen can be degraded by garden variety proteases.
    
    
    
    
     
11. Zinc Acetate inhibits hydroxylation of procollagen by competing w/necessary Fe++ cofactor.   Zinc Acetate may also have lysosome stabilizing properties.