GI: Nelson: Liver and Bilary Tract Path

Which cells convert heme to billirubin

What enzyme conjugates Billirubin?

Type of bilrubin that is excreted in urine when present in the serum at high levels

When is jaundice clinically evident?

Name some causes of unconjugated hyperbilirubinemia

Impaired secretion of bile, or cholestasis, would cause what?

obstructive gallstones, carcinoma of head of pancreas, congenital atresia of extrahepatic bile ducts, PSC may cause what?

Where is the most hypoxic part of the liver?

Path of Gilbert's

Why are liver infarcts rare?

Thrombosis of 2+ hepatic vein branches

What is the classic triad of Budd Chiari?

Most pts with Budd Chiari have an underlying what?

Dx of Budd Chiari is confirmed by what?

Path of Budd Chiari

Central vein sclerosis/thrombosis

Usually occurs in BM transplant pts

associated with toxic effects of pyrrolizidine alkaloids found in certain herbal teas and these patients have clinical symptoms of Budd-Chiari syndrome

Primary sinusoidal dilation (rare)

Association with anabolic steroids, rarely oral contraceptives and danazol; HIV (hepatic infection by Bartonella henselae)

Characteristics of Hep A

Hepatocellular injury due to Hep A is due to what>

Transmission of Hep A

Does Hep A cause a chronic hepatitis?

How is the dx of Hep A made?

Hepatocellular injury in Hep B is due to what?

Transmission of Hep B

indicates ongoing HBV infection, either acute or chronic

: indicates active viral replication; persistence indicates continued infectivity and probable progression to chronic hepatitis (HBV)

: detected at onset of acute hepatitis B; persists for 3-12 months, eventually replaced by IgG anti-HBc

* presence of _______ indicates acute or recent hepatitis B infection

IgG anti-HBc

: indicates recovery and immunity from HBV infection

indicates infection is resolving, even though HBsAg may still be present

Dx of HBV

If patient is HBsAg positive and negative for IgM anti-HBc, what is likely?

Dx of chronic hepatitis requires what?

If chronic hepatitis B present, look for active viral replication by what?

Defective ssRNA virus that causes hepatitis only in the presence of HBV

HDV must be encapsulated by what?

When HDV infects a chronic carrier of HBV

When HDV is transmitted simultaneously with HBV

In US, largely restricted to drug addicts

indicates acute or recent HDV infection

follows IgM anti-HDV, indicates previous infection with HDV, and confers immunity

measures both IgM and IgG anti-HDV, and thus indicates acute or chronic exposure

indicates active viral replication and ongoing infection (HDV)

IgM anti-HBc pos (acute or recent HBV) for HDV

IgM anti-HBc neg (chronic HBV)
for HDV

Characteristics of HCV

How is HCV spread?

Accounts for almost half of all chronic liver disease in the US

Hep virus where Some patients develop extrahepatic autoimmune manifestations/syndromes (cryoglobulinemia, membranoproliferative glomerulonephritis, thyroiditis)

Anti-HCV will develop approx ___ weeks following infection

Characteristics of HEV

Transmission of HEV

Pregnant women have a high mortality rate in this hep virus

Does HEV cause a chronic hep or a carrier state?

Dx of HEV

Def of chronic hep (time)

Massive hepatocellular necrosis, with or without lobular and portal inflammation

MC cause of fulminant hepatitis

Focal random necrosis, inflammatory pattern in Fulminant Hep

Zonal necrosis, non-inflammatory pattern in Fulminant Hep

Infants born to mothers positive for what have a 70-90% chance of acquiring perinatal HBV infection?

female predominance; negative viral markers; elevated serum IgG and gamma globulin levels

Associated with HLA DR3 cells

Increased plasma cells along with lobular inflammation is often a "tip-off"

Type of Cholestasis: canalicular bile stasis, feathery degeneration of hepatocytes

Type of Cholestasis: bile lakes, bile within distended bile ducts, portal tract edema, bile duct proliferation within portal tracts

MCC Cirrhosis

MCC of PHTN

Disorder of middle age females; inflammatory destruction of intrahepatic bile ducts eventually leading to cirrhosis

>90% of pts have circulating ______ antibodies in Primary Biliary Cirrhosis

Elevated alkaline phosphatase and cholesterol, positive for AMA (antimitochondrial antibodies)

What is used to establish dx and to stage the disease of PBC?

Ab found in 80% of Primary Sclerosing Cholangitis (PSC)

MC sex to develop hemochromatosis

Where is the gene defect of Hereditary (primary) hemochromatosis

Although Fe is usually distributed into hemochromatosis in hepatocytes, what may cause Fe to be deposited in the Kuppfer cells?

Best screening test for hemochromatosis

Clinical triad of hemochromatosis

Autosomal recessive disorder of copper metabolism, resulting in the accumulation of toxic levels of copper in tissues (liver, brain, eye

90 to 95% of plasma copper

Levels of ceruloplasm are what in Wilson's disease

May see a ring of copper deposits at the limbus of the cornea (Kayser-Fleischer ring)

40% of patients present with neuropsychiatric symptoms only

A1AT usually inhibits what?

A1AT is a glycoprotein produced by what?

The pair of A1AT genes are codominantly expressed on what chromo

What type of Alpha-1 Antitryspin def do individuals NOT develop liver disease

Usually occurs in children following a viral infection; 90-95% received salicylates (aspirin)

Reflects hepatocellular DAMAGE

Reflects cholestasis

Refelcts global hepatic synthesis (function)

Why is AST > ALT in ETOH liver disease? (AST:ALT ratio > 2)

If you wonder where an elevated ALP came from, what do you do?

The primary stimulus for ALP production

Test for VIral hep

Testing for Autoimmune Hep

Test for Wilsons

Test for Alpha-1-antrypsin deficiency

Test for hemochromatosis

Test for Primary Biliary Cirrhosis

Ground glass hepatocytes on bx-

Plasma cells on bx-

Lymphocytic/granulomatous cholangitis on bx

Fibrous obliterative cholangitis on bx

Periportal hepatitis with mild steatosis on bx-

Globular hepatocyte inclusions on bx-

What type of steatosis is seen in early stages of alcohol abuse?

Def of Alcoholic Hepatitis

Liver cell swelling (ballooning) and necrosis, Mallory bodies (cytokeratin aggregates)

Fibrosis + nodules

NASH

When cirrhosis is dt biliary disease, what are the different morphological characteristics?

Disorder characterized by progressive, random, uneven fibroinflammatory obliteration of extrahepatic and intrahepatic bile ducts

Cholangiography demonstrates strictures of extrahepatic and intrahepatic bile ducts (beaded appearance on cholangiogram

What labs are elevated in hemochromatosis?

urinary 24 hour copper excretion is increased (DX test) and ceruloplasmin levels are low (DX test)

MC genotype of Alpha-1 antitrypsin deficiency

Possible liver disease is probably related to what in alpha-1 antitrypsin deficiency

Genotype where the defective A1AT protein cannot fold correctly --> hepatocellular secretion is diminished

What type of steatosis do you see in Reye's syndrome?

Sarcoidosis and/or TB may cause what kind of hep?

Alkaline phosphatase may be elevated in cholestasis (liver disease) or _____ disease

Staging of a liver bx is based on what?

Grading of a liver bx is based on what?

may damage both bile ducts and arteries (get "vanishing bile duct syndrome" and obliterative arteritis with ischemic necrosis)

most common benign tumor of the liver

discrete
red-blue hemorrhagic nodules composed of dilated (cavernous) endothelial lined blood filled channels

composed of atrophic biliary epithelium, detached from the biliary tree

congenital intrahepatic biliary dilatations; communicate with the biliary tree; patients may suffer bouts of cholangitis; autosomal recessive inheritance, often associated with varying degrees of Congenital Hepatic Fibrosis

autosomal dominant multi-organ disorder in which the liver exhibits absence of bile ducts in the portal tracts

congenital dilatation of the common bile duct; usually occur in children; may result in biliary obstruction, stones, carcinoma

Both Caroli’s disease and Congenital Hepatic Fibrosis have increased risk of

Well-demarcated tumor composed of a proliferation of all liver parenchymal elements (central veins, hepatocytes, portal triads); sort of like a hamartoma

Lesion characteristically forms a mass with a central fibrous scar with a stellate configuration

Diffuse nonfibrosing nodular hyperplasia of the liver

Diffuse nonfibrosing nodular hyperplasia of the liver

Grossly appear as single or more commonly multiple small white nodules; mimics metastatic carcinoma

disordered collection of ectatic bile ducts in a fibrous stroma

What's more common, primary or mets to liver?

MC mets to liver

In USA, usually occur in patients age > 60 years; rarely occur < 60 years; in areas with high endemic HBV infection, 20-40 years is typical

Aflatoxin B1 produced by Aspergillus flavus puts one at risk for what?

Where does HCC met?

Someone with cirrhosis that suddenly deteriorates rapidly

Elevated serum alpha-fetoprotein may be present

HCC composed of polygonal oncocytic tumor cells in nests and cords separated by lamellar fibrous stroma

No association with cirrhosis or HBV; association with Thorotrast and liver flukes (Opisthorchis sinensis), PSC, Caroli’s disease, Congenital Hepatic Fibrosis, Choledochal cysts

Malignancy composed of immature hepatocytic elements (epithelial or mixed epithelial-immature stroma); in infants!

Malignancy of endothelial cells, resulting in tumor composed of anastomosing vascular channels lined by atypical (malignant) cells

Best way to image a gallstone

Which type of gallstone is more likely to be radiopaque and you can see on an x-ray

RF for pigment stones of the gallbladder

Dystrophic calcification of gallbladder wall can occur, producing "porcelain gallbladder"

Carcinoma of gallbladder is usually associated with what?

Most carcinomas of the GB are of what type?

Tumors of the ampulla of Vater include:

HELLP syndrome in preeclampsia/eclampsia

histologic hallmark of chronic (100 days post transplant) GVHD is ? (BMT)

Do the cysts of Polycistic liver disease communicate with the biliary system?

What does the biliary epithelium look like in a liver cyst?

What pop does congenital hepatic fibrosis normally occur in?

Diff between focal nodular hyperplasia (FNH) and Nodular Regenerative Hyperplasia

Well-demarcated tumor composed of well differentiated hepatocytes (no portal triads or central veins)

Occurs more frequently in females; associated with oral contraceptive use

Microscopic: disordered collection of ectatic bile ducts in a fibrous stroma

MCC HCC in the US

Levels of alpha-fetoprotein >____ are strongly suggestive of HCC

HCC composed of polygonal oncocytic tumor cells in nests and cords separated by lamellar fibrous stroma; thick fibrous bands

Diff between liver amangioma and angiosarcoma?

Name 2 things that are lithogenic for cholelithiasis

subepithelial accumulations of lipid-laden macrophages; grossly see yellow mucosal flecks; due to excessive accumulation of cholesterol from supersaturated bile; no clinical significance

total obstruction of cystic duct or neck of gallbladder results in trapped bile which is resorbed; epithelium secretes mucinous watery fluid and distended gallbladder with atrophic wall is produced

Gross: fungating papillary mass; intraductal nodule; diffuse infiltrative tumor

Microscopic: virtually all are adenocarcinomas (some are well differentiated)

2 types of Cholangiopathic Chronic Liver Disease

2 types of Inflammatory Chronic Liver Disease

2 types of fatty Chronic Liver Disease

2 types of Metabolic Chronic Liver Disease

ANA, anti-SM

AMA