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handout: inflammation and repair

as he mentioned last week, even in a normal animal there is a small amt 
of bilirubin - 1-2 micromol/L. if there is accumulation of bilirubin, 
conjugated or unconjugated, up to 17-20, you see clinical jaundice. 
tissue fluid will have a yellow color, CT will be stained yellowish. 
sometimse with unconjugated insoluble bilirubin, will see adipose tissue 
stained yellow. 

if you understand normal handling of bilirubin and hemoglobin, RBC broken 
down by reticuloendothelial cells, unconj bili comes to liver and is 
conjugated, and then it's further broken down, excreted in stool/urine.

say animal has increased breakdown of RBC due to infection, immune 
dysfunction, toxin, whatever. more hemoglobin needs to be processed by RE 
(reticuloendothelial cells) cell, and more bilirubin is formed. so 
there's an increased amt of unconjugated bilirubin coming to the liver. 
the liver can compensate for this, because there are many liver cells. 
liver starts functioning at max capacity, conjugating the bilirubin. but 
at a certain point, it's maxed out, and when it can't conjugate it fast 
enough, it bbacks up in the blood. so in this case, bilirubin 
concentration in blood will be high, animal will be icteric. what kind of 
bilirubin will be accumulating in blood? unconjugated. 

if you do a van den bergh rxn in this case, you would see increased 
indirect bilirubin.

what about urobilin? will it be increased? yes. because liver is working 
at maximum. and stercobilin. 

this is a hemolytic jaundice situation.

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if you have animal with neoplasia eg lymphosarcoma or something, growing 
where duct opens from liver into duodenum - eg, blocks common bile duct, 
causing obstruction.this is an extrahepatic obstruction. you could also 
have biliary adenocarcinoma within the liver, causing intrahepatic 
obstruction. liver is doing it's job, but can't send bile to intestine. 
bile backs up and there's an increase in blood levels of conjugated 
bilirubin. you'd see bile in the bile canaliculi if you sectioned the 
liver. you see a direct van den bergh rxn.
urobilin and stercobilin will be decreased, because bilirubin isn't 
getting out of liver. stool will be very pale, and animal will have 
trouble digesting lipid.
this is called OBSTRUCTIVE jaundice.

now, if normal rbc breakdown, and no obstruction, but liver cells not 
able to conjugate bilirubin due to some congenital defect (missing 
glucoronyl transferase) or because liver is inflamed (hepatitis), then it 
will again back up. unconjugated bilirubin will enter the blood.now, SOME 
of the liver cells may be functioning and able to conjugate bilirubin. 
BUT, liver cells are swollen, which causes obstruction of flow of bile 
through bile canaliculi, so conjugated bili also backs up. so you see a 
rise in conj and unconj bili in the blood. we see increased direct and 
indirect van den bergh rxn.
urobilin and stercobilin are decreased, depending on degree of 
obstruction.

hepatogenus jaundice (?)

if animal had hepatitis, but liver was damaged and is fibrotic, animal 
can conjugate bilirubin but may have obstruction from fibrosis - this 
would cause obstructive jaundice.

hemosiderin: also formed from Hb. when local hemorrhage occurs, mphage 
pick up RBC and make hemosiderin from Hb, it's kind of yellowish brown. 
when we see mphages and hemosiderin, we know hemorrhage has occured. can 
see hemosiderin in and outside cells. this pigment contains iron. is 
membrane bound. when there is alot of generalized hemosiderin deposits 
there is generalized hemosiderosis. in humans, can get that due to iron 
metabolism abnormality, but in animals, usually only see secondary to 
hemorrhage. in heart failure, can see hemosiderin in alveoli (heart 
failure cells). 

hematoidin: crystals outside the cells. this is hemosiderin w/o the iron, 
and is formed outside the cell in anoxic conditions eg hematoma. it's an 
aggregated tissue form of bilirubin. can be hard to tell if is 
hemosiderin or hematoidin histologically. have to stain for iron. take 
K+ferrocyanide and HCl and dip tissue into those reagents, and it forms a 
blue color - prussian blue rxn - if iron is present.

photosensitization rxn:sometimes there is deposition of porphyrin or 
other photodynamic compound. if there is an elevation of a photodynamic 
compound in tissue, exposure of animal to sun will cause dermatitis. 

say a cow eats a lot of green grass...chlorophyll breakdown porduces 
phylloerythrin, a photodynamic compound. in normal animal, that is broken 
down by liver. but if liver is diseased, can't break it down, so it will 
accumulate in blood and tissue fluid. then animal is exposed to sun and 
gets skin inflammation - photosensitization dermatitis. is common in utah 
where high chlorophyll diet is fed as well as toxic stuff that damages 
liver.

high chlorophyll diet, liver damage, and sun cause this problem.
going to lab now.



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