Path GI III Liver & Biliary Tract (19)

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Path GI III Liver & Biliary Tract (19)
2014-03-10 15:28:35
MBS Pathology
Exam 3
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  1. Jaundice (BILIRUBIN)
    • results from the retention of bile due to an abnormality in the processing of bilirubin
    • manifests as a yellowish staining of the integument, sclerae, deeper tissues, & excretions with bile pigments, due to increased levels of bilirubin in the plasma
  2. Hemolytic Jaundice
    • hemolytic anemia with excessive production of unconjugated bilirubin
    • (hemolytic anemia is the result of genetic defects that lead to enzyme deficiencies or instabilities & is a condition in which RBCs are destroyed & removed from the bloodstream before their normal lifespan is over)
  3. Hepatocellular Jaundice
    • ↓ hepatic uptake of bilirubin is a common cause of jaundice (eg. generalized liver cell injury, hepatitis, some drugs)
    • ↓ bilirubin conjugation; is seen in a number of hereditary syndromes (eg. Crigler-Najjar, Gilbert, etc.)
    • ↓ transport of conjugated bilirubin often involves mutation in the multidrug resistance protein (MRP) family (eg. Dubin-Johnson syndrome)
  4. Obstructive Jaundice
    results from blocked excretion of conjugated bilirubin into the bile (eg. extrahepatic obstruction of the common bile duct)
  5. Cholestasis (BILE)
    • a condition where bile cannot flow from the liver to the duodenum
    • 2 basic types:
    • 1. an obstructive type where there is a mechanical blockage in the duct system (can occur from a gallstone or malignancy)
    • 2. metabolic type where there are disturbances in bile formation (due to genetic defects or acquired as a side effect of medication)
  6. What is there a systemic retention of in Cholestasis?
    • bilirubin & other solutes eliminated in the bile (bile salts & cholesterol)
    • there is ↓ bile flow through the canaliculi & ↓ secretion of H2O, bilirubin, & bile acids by hepatocytes
  7. What causes Intrahepatic & what causes Extrahepatic cholestasis?
    • Intrahepatic is caused by intrinsic liver disease
    • Extrahepatic is caused by obstruction of the large bile ducts
  8. What is the hallmark SIGN of cholestasis?
    • "bile lakes" - the presence of brownish pigment in dilated canaliculi & hepatocytes
    • there's also bile ductular proliferation, edema, bile pigment retention, & inflammatory infiltration in the portal tract
    • Pruritus (itch) develops probably from deposition of bile acids in peripheral tissues, particularly the skin
    • Jaundice
  9. What's one way to test for/diagnose Cholestasis?
    • elevated serum Alkaline Phosphatase is a characteristic finding
    • enzyme normally found in liver hepatocytes - if found in serum → hepatocyte death
  10. Cirrhosis (Nutrition)
    • chronic scarring & fibrosis of the liver
    • blood trying to flow through a cirrhosed liver is met with LOTS of resistance
    • it's IRREVERSIBLE & causes many life-threatening sequelae (pathological conditions)
    • eg. hypoalbuminemia & longer clotting times (prothrombin, ProTime/INR) as a result of the liver losing its ability to synthesize proteins
  11. Cirrhosis
    • the end stage of chronic liver disease defined as the destruction of the normal liver architecture by fibrous septa that encompass regenerative nodules of hepatocytes (as a result of persistent liver cell necrosis)
    • [can cause portal hypertension, esophageal varices, ascites, splenomegaly]
  12. What are the 3 main characteristics of cirrhosis?
    1. Bridging fibrous septa

    2. Parenchymal nodules (encircled by fibrotic bands, usually containing a mix of senescent & replicating (often stem cell-derived) hepatocytes)

    • 3. Disruption of the architecture of the entire liver (diffuse parenchymal cell injury & fibrosis)
    • collagen deposition, vascular architecture disruption, shunting of blood, impairment of exchange
  13. Causes of Cirrhosis
    • Alcoholic liver disease
    • Nonalcoholic fatty liver disease
    • Chronic hepatitis
    • Biliary disease
    • Metabolic disease (Hemochromatosis, Alpha-1-antitrypsin deficiency, Glycogen storage disease)
    • Cryptogenic causes
  14. Where is collagen distributed in the normal v. in the cirrhosed liver?
    Normal: interstitial collagens type I & III are concentrated in portal tracts & around central veins; thin strands of type IV are present in the space of Disse

    • Cirrhosed: type I & III collagens are deposited in the SPACE OF DISSE, creating
    • fibrotic septal defects
  15. What is the predominant mechanism of fibrosis in Cirrhosis of the liver?
    • the proliferation of hepatic stellate cells & their activation into highly fibrogenic myofibroblasts
    • pericytes are found in the spaces of Disse, or perisinusoidal spaces (a small area between the sinusoids & hepatocytes)
    • in the normal liver, the perisinusoidal space of Disse contains a delicate framework of ECM components. In liver fibrosis, stellate cells are activated to produce a dense layer of matrix material that's deposited in the perisinusoidal space. Collagen deposition blocks the endothelial fenestrations & prevents the free exchange of materials from the blood. Kuppfer cells also are activated & produces cytokines involved in fibrosis.
  16. Symptoms of Liver Cirrhosis
    • anorexia, weight loss, weakness, debilitation
    • hepatic failure may develop
    • ultimate mechanisms of death:
    • 1. progressive liver failure
    • 2. complication related to portal hypertension
    • 3. development of hepatocellular carcinoma
  17. Major Clinical Consequences of Portal Hypertension (in the setting of cirrhosis)
    • 1. Bleeding from esophageal varices
    • 2. Ascites
    • 3. Splenomegaly
    • in women oligomenorrhea, amenorrhea, & sterility are frequent as a result of hypergonadism
  18. Portal Hypertension
    • increased resistance to blood flow through the liver caused by hepatic fibrosis
    • the resistance leads to high pressures in the Portal vein & Portal system
    • thin veins that aren't built to hold excess blood will attempt to accommodate the backup of blood → varices form
  19. Varices
    • submucosal veins in the esophageal-gastric junctions become dilated and protrude into the lumen as a result of Portal Hypertension
    • can be found anywhere in the GI tract but is much more common in the esophagus & stomach
    • they can burst (stigmata) causing GI bleeding → a life threatening situation
  20. Ascites
    • accumulation of fluid in the peritoneal space
    • due to elevated hydrostatic pressure from Portal Hypertension & from decreased plasma oncotic pressure from hypoalbuminemia
    • without albumin in circulation/blood vessels, fluid will leak out of plasma into the interstitial space → ascites
    • there's renal retention of Na+ & H2O due to secondary hyperaldosteronism
    • treatment: paracentesis (withdraw the fluid), diuretics, & dietary sodium restriction (2 g/day)
  21. Viral Hepatitis
    • an infection of hepatocytes that produces necrosis & inflammation of the liver
    • 95% of viral hepatitis in the industrialized world involve hepatotropic viruses named from A to G
  22. What is the hallmark for acute hepatitis?
    • liver cell death
    • Ballooned Hepatocytes (ballooning degeneration, aka diffuse swelling of the cells)
    • Councilman Bodies (apoptotic liver cells that appear as small, deeply eosinophilic bodies)
    • Scattered necrosis of single or clusters of hepatocytes
    • Intralobular & portal tract infiltration of lymphocytes & macrophages
    • Kupffer cell hyperplasia + hypertrophy Cholestasis
    • Regenerative changes
  23. Chronic Hepatitis
    • a complication of hepatitis B & C + a number of metabolic & immune disorders
    • has ground-glass hepatocytes (cells w/ large granular cytoplasm containing abundant HBsAg)
    • Inflammation: mild necrosis to widespread inflammatory, necrotizing, & fibrosing condition that often leads to Cirrhosis
    • Piecemeal (Periportal) necrosis: limited focal destruction of hepatocytes
    • Bridging Necrosis: the formation of CT septa between adjacent portal tracts
    • Intralobular and portal tract inflammation w/ lymphocytes, macrophages, & PLASMA CELLS
  24. Alcoholic Liver Disease
    • progression: steatosis → hepatitis (inflammation) → cirrhosis
    • spans 3 major morphologic & clinical entities: Fatty Liver, Acute Alcoholic Hepatitis, Cirrhosis
  25. Alcoholic Steatosis
    • fatty deposits in the liver
    • outwardly people are asymptomatic
    • may develop with transient or chronic alcohol use, just depends on if there's a lot consumed
    • fat deposits in liver can be reversed if drinking stops
    • however if alcohol use continues, 20–30% of people develop alcoholic hepatitis or cirrhosis
  26. Acute Alcoholic Hepatitis
    • an acute necrotizing disease associated w/ Intrahepatic collagen deposition
    • there is necrosis of hepatocytes, predominantly in the central zone
    • MALLORY BODIES: cytoplasmic hyaline (keratin intermediate filaments) in hepatocytes
    • collagen deposition, especially around the central vein
  27. Cirrhosis
    • a result of repeated liver injury, fibrosis, & regeneration
    • shows the characteristic diffuse nodularity of the surface induced by the underlying fibrous scarring (greenish tint caused by bile stasis)
  28. How does liver disease often progress regardless of its cause?
    • inflammation → fibrosis → scarring → cirrhosis
    • it takes many years for the liver to develop dysfunction because it can regenerate itself up to a certain point
    • liver disease has different causes however it always progresses the same way
  29. Hepatocellular Carcinoma (HCC)
    • a primary malignant tumor of the liver derived from hepatocytes or their precursors
    • UNCOMMON in US, but very common world-wide
    • most tumors originate in CIRRHOTIC livers (repeated regeneration of cells in Cirrhosis is a hot bed for carcinogenesis)
    • dismal prognosis: patients die of malignant cachexia, tumor rupture w/ catastrophic bleeding into the peritoneal cavity, or Cirrhosis complications
  30. There is a strong association between which infection & HCC?
    • Hepatitus B Viral Infection
    • the genome of HBV becomes integrated into the host DNA of both non-neoplastic & tumor cells
    • HCC is also associated w/ HCV, metabolic conditions (hemochromatosis, cirrhosis, alpha-1-antitrypsin deficiency), & environmental agents (aflatoxin B1)
    • hemochromatosis = excessive iron → free radical formation → damaged cells → carcinogenesis
  31. Appearance of Hepatocellular Carcinoma
    • a soft, hemorrhagic mass in the liver
    • most exhibit a ‘trabecular pattern’ w/ the tumor cells arranged in trabeculae (small beam/rod) that resembles the normal liver
    • pseudoglandular patterned tumor cells are arranged around a lumen & resemble glands
    • have a STRONG propensity for invasion of vascular channels
    • presents as a painful & enlarging mass + PARANEOPLASTIC syndrome
  32. What is a tumor marker of Hepatocellular Carcinoma?
    • Alpha-fetoprotein (AFP)
    • is detectable in the blood
  33. Cholelithiasis (Gall Stones)
    • most gallstones are composed of cholesterol
    • pigmented gallstones are composed of Ca2+ bilirubinate or other Ca2+ salts
    • stones accumulate in gall bladder lumen or extrahepatic biliary tree
  34. Acute Cholecystis (Acute Gall Bladder INFLAMMATION)
    • diffuse inflammation of gall bladder secondary to obstruction by gall stones
    • neutrophils in epithelium & lamina propria
    • [wall is thickened by edema, mucosa is fiery red or purple]
  35. Chronic Cholecystitis (Chronic Gall Bladder INFLAMMATION)
    • thickening of muscular wall, chronic inflammatory cells
    • persistent inflammation of the gallbladder that is almost invariably associated w/ gallstones
    • mucosa may be focally ulcerated & atrophic (or just intact)
    • inflammation may be seen in all layers