January 25, 2000 Path 9:00



January 25, 2000 Path 9:00 Scribes: Gill/McIntire

Dr. Oliver

“Take One Down and Pass it Around….” It’s the Liver Cont.!!!

Dr. Oliver began at the Pathology of acute viral hepatitis and followed the slides very closely.

Pathology of Acute Viral Hepatitis

• Under Microscope, you’ll find hepatocyte necrosis; confluent areas of necrosis is called bridging necrosis; indiv hepatocytes that die by apoptosis is are called Councilman bodies (know what it looks like); swelling hepatocytes that die are labeled Ballooning degeneration (these findings are specific for acute hepatocyte injury such as acute viral hepatitis)

• Slide of bridging necrosis

• Slide of Councilman body (see arrow in Fig. 19-19)

• Slide of Ballooning degeneration (Curran’s 11.20 & 11.23 & 11.24)

• Chronic Viral Hepatitis

• Defined by having symptoms of hepatitis that last for more than 6 mo; HAV-rare; HBV- 5-10% in adults; 90% in adults; HCV- majority of pts; HEV- rare; HDV- along with HBV

• It is variable and unpredictable; some pts are asymptomatic and may take many years to become symptomatic

• HBV, HCV can cause extrahepatic disease due to developing immune complex disease such as vasculitis and glomerulonephritis

• Death is due to complications with cirrhosis and possibly Hepatocellular carcinoma

• Pathology of Chronic Viral Hepatitis

• Under microscope you’ll see chronic inflammation in the portal tracts (chronic) and less hepatocyte injury (acute)

• Inflammation cells may breach the limiting plate and expand into the hepatocytes surrounding the portal tract and this is called piecemeal necrosis

• Rarely do you see bridging necrosis

• Impt aspect is Fibrosis b/c it’s slow and leads to necrosis

• Slide of piecemeal necrosis (Curran’s 11.23)

• HCV- get more chronic inflammation, lymphoid aggregates, bile duct damage and steatosis

• HBV- hepatocytes are “ground-glass” looking b/c they’re hypereosinophilic due to virus

• Slide of steatosis

• Slide of the “ground-glass” hepatocytes for HBV

• Autoimmune Hepatitis

• Noninfectious and is a diagnosis of exclusion because there aren’t any good tests or criteria for diagnosis; usually see with rheumatoid arthritis and systemic sclerosis

• Clinically it’s similar to chronic viral hepatitis (mild to severe)

• Primarily affects females as do most autoimmune diseases

• Impt- Will have autoantibodies such as Smooth Muscle Ab (SMA), Anitmitochondrial (AMA) and Antinuclear Ab (ANA)

• Fulminant Hepatitis

• Very rapidly acute that leads to failure and progress to encephalopathy

• Mostly due to viruses and drugs such as acetominophen (Tylenol)

• Have jaundice, encephalopathy, bleeding and renal failure

• Pathologic conditions: Gross- soft, wrinkled due to loss of parenchyma; Microscope- centrilobular necrosis around the central vein and less the portal tracts

• If survive, will have regenerative nodules, shrunken liver, diffuse scarring like cirrhosis (postnecrotic cirrhosis)

• Slides of fulminant hepatitis

• Slides of postnecrotic cirrrhosis that looks similar to cirrhosis except that nodules are more varied

• Liver Abscesses

• Classic cause are amoebas but not here in US; In US it’s bacterial esp post surgical in which bacteria enters portal system

• Can also have bacteria get into bile duct called ascending cholangitis

• See in immunosuppressed, debilitated pts and has a high mortality associated with it; Can only surgically tx by draining and antibiotics

• Slide of ascending cholangitis with lots of neutophils

• Slide of liver abscesses

• Slide of Hydatid cyst (Cannon ball cyst) – no mistakin’ this…looks like a ball of yellow tissue with white egg-looking things ballooning out

• Drug/Toxin-Induced Liver Disease: Results from a) direct hepatotoxicity, b) hepatic metabolism to active toxin, c) immune mechanisms

• Two different mechanisms: 1) dose-related (the more drug, the greater the chance) 2) Unpredictable- idiosyncratic (dose-independent)

• Will see hepatocellular damage (fatty change, acute hepatitis with necrosis, cholestasis), vascular changes and tumor formation. Note Table 19-4…it’s not a tuuumor!

• Alcoholic Liver Disease (a.k.a., what my liver looks like after exams)

• The #1 liver dz in the U.S.

• The first form of alcoholic dz we’ll discuss is fatty liver or steatosis (other things that cause it are obesity, starvation, HCV and Wilson’s disease – anything causing deranged lipid metabolism)

• This is a REVERSIBLE phenomenon , causes hepatomegaly, deranges liver fxn tests and is, generally, asymptomatic

• Gross findings: the liver is BIG, looks soft, yellow and GREEEASSSY (check out Fig 19-25)

• “Under the scope” we see MACROvesicular fatty change (difference between macro and micro is that micro is, yes, tiny, but nucleus is still in center of the cell and “happy”. As more fat droplets plop into the cell, you see a sad (I guess) cell with it’s nucleus pushed aside). This macrovesicular may be centrilobular, but is usually PANlobular. Again, reversible unless you’re progressing to cirrhosis with fibrosis, but steatosis by itself is reversible

• Pathogenesis is not well understood.

• Slide of macrovesicular steatosis: (Curran’s 11.12 and Fig 19-23) This can happen after ONE night of binge drinking!

• Next on the list is alcoholic hepatitis: Follows bouts of HEAVY drinking. Is NOT asymptomatic. See notes for these. Acutely, presents with RUQ pain. 10-20% mortality rate with each episode. These pts. will actually risk having these bouts with each night of binge drinking. 1/3 get cirrhosis.

• Histo: looks like acute viral hepatitis. There are clues to steer you towards alcoholic dz. Usually, there’s centrilobular necrosis. A big clue is Mallory bodies. These are seen elsewhere: Hepatocellular carcinoma (HCC), Wilson’s and primary biliary cirrhosis (PBC). One thing not on this slide is that they often have steatosis. PMN infiltrate in lobules between hepatocytes and especially around the dead ones. See notes for rest.

• Slide of Mallory body (19-24). Slide of trichrome stain to show fibrosis around central vein.

• #3 on the list is chronic alcoholic liver dz, which usually takes the form of cirrhosis. Once a pt. gets this, there’s nothing to tell you how h/she got there. Most have portal HTN and that’s how they die. Esophageal varices and others seen in the notes. Some call it Laennec’s, “but I don’t see anything specific about that.”

• These three don’t always go together. You can have fatty liver, go to hepatitis and never get cirrhosis, make it all the way to cirrhosis and never get hepatitis, etc, etc, etc

• Pathogenesis of Alcoholic Liver Dz: cytP450 induced, free radical damage, direct toxicity, acetaldehyde (break down product of EtOH) can induce lipid peroxidation, which leads to more free radical damage…see notes

• Inborn Errors of Metabolism: #1 Hemochromatosis: the accumulation and storage of iron in organs (esp. the liver and pancreas). There’s primary and secondary forms:

• Primary: iron has a direct toxic effect on hepatocytes. Therefore, we see micronodular cirrhosis. To establish this diagnosis, do a Prussian Blue stain. One of the best ways though is to quantitate the iron in a tissue biopsy sample…. “it’s more specific”

• With iron accumulating in the pancreatic Islets, you get “bronze diabetes” because you can get hemosiderin depositing in skin macrophages (Slide of woman with this, “I guess she’s hyperpigmented”. Thus, another TRIAD…hyperpigmented, diabetes and cirrhosis. Can get cardiac failure. Note the other complications in the notes. Histo slides of heart, pancreas and liver stained with Prussian blue (Fig 19-26).

• See notes for genetic info. TIBC = total iron binding capacity. Tx: penicillamine to chelate

• #2 Wilson’s Disease: Hepato(liver – duh)lenticular(basal ganglia of brain) degeneration

• Deposit copper in brain, liver and eye mostly. Defective ceruloplasmin which is a copper transport protein. It takes copper to the liver to be excreted in the bile. Yet, here pts can’t get rid of the copper in the liver and it accumulates.

• Morphology: see notes. There are special stains, which “I’ve never used.” Again, the best is to measure the copper per dry weight of liver tissue like in hemochromatosis.

• Slide of a histo special stain (“I don’t know which one”) where you can see copper in regenerative nodules in cirrhosis.

• Basal ganglia can be injured with accumulation.

• Kayser-Fleischer Rings in cornea (I’ll call it a “buzzword”. I like that word…buzzword): Slide of this: basically, it’s an eyeball with a brown ring around the iris…pretty weird. Also, you can see scleral icterus. So, this person already has substantial liver disease.

• If you did lab tests for Wilson’s, you’d see a DECREASE in serum ceruloplasmin and you’d have an INCREASE in urinary excretion of copper. Penicillamine to chelate. Transplant may be warranted if you progress to cirrhosis.

• #3 Alpha 1 – Antitrypsin Deficiency: probably the #1 primary protease inhibitor we have

• Once again, check out the notes.

• PiMM is designated “normal” for the gene while PiZZ is the homozygous recessive that’s at the greatest risk

• What do you do without this???? Well, you get PANLOBULAR/ACINAR (call it what you wish) emphysema, cholestasis progressing to cirrhosis, neonatal liver dz.

• What we like to see are (not a buzzword, but a “buzzslide”, if you will) alpha 1 – AT GLOBULES in the hepatocyte cytoplasm. Histo buzzslide of this: use PAS stain (19-27)

Well folks, that’s it for this scribe. Until we meet again, or should I say until your highlighter meets my next exciting scribe (I know there’s so much great info here), good luck on exams and please, please avoid the macrovesicular fatty liver! Let’s keep it to micro for awhile. At least wait until Step 1 is over and done with!!!!!! 4 months, 4 months, 4 months………….

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