Pathology – Dr. OliverScribe: Amber

Thursday January 25,2001Proof: Allison

Liver

Dr. Oliver followed his notes very closely so I am just going to include the additional information. He also stated that he will finish the remaining liver slides on the 31st following the breast lectures.

Pediatric Liver Disease:

The most famous one is Reye's syndrome.

  • This is only seen in kids <9 yr. old with a viral illness like chicken pox that were treated with aspirin.
  • This turned out to be great for the makers of Tylenol because it became the DOC. Other NSAIDS and Tylenol don’t cause Reye’s syndrome.
  • The incidence of Reye’s has now decreased since kids no longer take aspirin.
  • Symptoms: starts with vomiting followed by mental changes and hepatomegaly
  • About 75% of them turn out to be okay but the other 25% result in coma, seizures, or death (of those that survive, most have some neurological damage)
  • Labs: necrosis of hepatocytes will cause an increase in ammonia in the blood and other abnormal liver function tests (bilirubin, transaminases)
  • Pathology- microvesicular steatosis, mitochondria damage and cerebral edema
  • When looking at biopsy or autopsy tissue, the liver shows microvesicular steatosis.
  • Slide of microvesicular steatosis- liver with tiny fat vacuoles, nucleus is still intact, looks different than macrovesicular steatosis that is seen in the alcoholic liver.
  • Slide of liver (EM)- mitochondria, disruption of cristae (fragmented and lost)

Neonatal Hepatitis/ Cholestasis

  • Disorders causing conjugated hyperbilirubinemia
  • Look at Table 19-6, p. 877 in Robbins for the different causes
  • 50-60% are idiopathic but 20% are due to extrahepatic biliary atresia (it is important to rule this out because it needs to be treated surgically)
  • Newborns with symptoms of hepatitis, you need to do a good to great biopsy
  • Pathology- look for giant multinucleated hepatocytes, hepatocyte necrosis, lobular disarray, cholestasis, etc.
  • Slide- giant multinucleated hepatocytes, not seen very often, mainly with neonatal hepatitis

Intrahepatic Biliary Tract Disease

  1. Secondary Biliary Cirrhosis
  2. Prolonged obstruction of extrahepatic biliary tree (gallstones)
  3. Reversible initially
  4. Irreversible once it becomes fibrotic (cirrhosis like, hard due to fibrosis)
  5. Pathology-hard, yellow-green, signs of cholestasis (distended bile ducts)
  6. Primary Biliary Cirrhosis (PBC)
  • Not a preexisting cause but it is an autoimmune etiology
  • Formation of immune complexes in biliary epithelium
  • Clinical clue- nondrinker, no viral etiology but is developing cirrhosis, check for antimitochondrial antibodies because they are found in >90% of patients with PBC
  • Chronic, progressive cholestatic disease seen in middle aged women (remember that most autoimmune diseases are seen more in women)
  • Pathology- cholestasis, destruction of bile ducts by non-necrotizing granulomatous inflammation called florid duct lesion, hepatocyte necrosis from portal inflammation called piecemeal necrosis, scarring and eventually ending up with micronodular cirrhosis
  • Slide- portal triad, granuloma (similar to Robbins 19-29)
  • Slide-piecemeal necrosis
  • Slide- liver with cirrhosis, greenish color from cholestasis (Robbins 19-28)
  1. Primary Sclerosing Cholangitis
  • Seen in middle aged patients (important distinction is M:F is 2:1)
  • Famous person that died from this- Walter Payton
  • Etiology- thought to be some kind of autoimmune disease
  • 70% of those with PSC have ulcerative colitis but only 4% of those with ulcerative colitis develop PSC
  • Pathology- bile duct degeneration, “onion skin” concentric periductal fibrosis obliteration and scarring of ducts caused by cholestasis and biliary cirrhosis
  • Slide- ulcerative colitis without PSC (Curran 5.42, p. 97)
  • Slide- onion skin fibrosis with bile duct in the middle (Robbins 19-30)
  • Slide- Xray of dye injected into biliary tract

Anomalies of the Biliary Tract

  1. Von Meyenburg Complexes:
  2. Most common, clusters of dilated portal bile ducts in the fibrous stroma under the capsule
  3. Polycystic Liver Disease
  • Multiple cysts in the liver lined by biliary epithelium
  1. Congenital hepatic fibrosis (Curran 5.1)
  • More fibrosis: fibrotic portal tracts and fibrous septa
  1. Caroli’s Disease
  • Multiple ducts communicating with the biliary tree

Circulatory Disorders or Vascular Liver Diseases

  1. Liver Infarcts (Robbins 19-33)
  2. Dual blood supply so infarcts are rare and localized unless main hepatic artery thrombosis
  3. Infarcts of Zahn, occlusion of branches of portal vein, secondary atrophy with portal HTN
  4. Portal Vein Obstruction/Thrombosis
  • Extrahepatic (infectious pylephlebitis or inflammation of vein)
  • Intrahepatic (cirrhosis, tumors, ab pain, ascites, esophageal varices)
  • Banti’s syndrome- subclinical occlusion of portal vein causing idiopathic portal hypertension + splenomegaly
  • Slide- infarct of liver, pale wedge shaped infarct
  1. Passive congestion
  • Rt. Sided heart failure causes backflow of blood down inferior vena cava, and liver is the first thing it goes to so you get congestion of liver
  • Nutmeg liver, centrolobular area is where it backs up
  1. Centrilobular Necrosis (Robbins 19-34)
  • Lt. Sided heart failure, shock, vascular insuffiency
  • Centrolobular area is the furthest from the blood supply so it is the most susceptible to infarct
  1. Cardiac Sclerosis (Cirrhosis)
  • Centrolobular liver fibrosis due to chronic CHF
  • Just scarring not true fibrosis
  1. Peliosis Hepatitis
  • Irregular blood filled cystic spaces, usually with no endothelial lining
  • Just pooled blood
  • Associated with ananbolic steroids, oral contraceptives, cat scratch fever
  1. Hepatic Vein Thrombosis (Budd-Chiari Syndrome) Robbins 19-35
  • Acute or chronic
  • Tremendous congestion of the liver, can involve the entire liver
  • Due to: Pregnancy (can cause stasis), postpartum, oral contraceptives (thrombotic), PNH (paroxysmal nocturnal hemoglobinuria), HCC(hepatocellular carcinoma), webs in hepatic veins
  • 30% idiopathic

Pregnancy and Hepatic Disease

  1. Preeclampsia/ Eclampsia (Robbins 19-37)
  2. Hemorrhagic disease, hemorrhage under capsule
  3. HEELP (hemorrhage, elevated liver enzymes and low platelets)
  4. Acute fatty liver of pregnancy
  • Usually 3rd trimester, mild to severe hepatic failure
  • Looks like Reye’s syndrome-microvesicular steatosis
  • If severe enough, termination of pregnancy might be needed to save the woman
  1. Intrahepatic Cholestasis of Pregnancy
  • Benign condition due to estrogen related derangement of bile acid metabolism
  • Mild cholestasis and increased risk of gallstones

Liver and Transplantation

  1. Drug Toxicity
  • Soon after transplant administered
  • Nonspecific cholestasis/ necrosis
  1. Graft vs. Host disease
  • Not from liver transplant but from bone marrow transplant
  • Acute GVH 10-50 days after BM transplant, signs of acute hepatitis
  • Chronic GVH >100 days and limited to portal tracts
  1. Rejection of implanted livers
  • Opposite of GVH- patient’s immune system rejects the graft and fights it
  • Acute-portal inflammation, hepatocyte injury
  • Chronic- vascular problem
  1. Veno-occlusive disease nodular regenerative hyperplasia
  • Follows BM transplant (more common in allografts)
  • Subendothelial deposition of collagen in central vein
  1. Nonimmunologic damage to liver allograft