Liver 2 Flashcards
Most common cause of incidental elevation of serum transaminase
NAFLD
Reverses NALFD histologic changes in biopsy proven steatohepatitis
Pioglitazone
stimulator of tf PPAR-y modulating expression of insulin sensitive genes
In children, NAFLD histologic injury is characterized by inflammation and scarring at the rather than neutrophilic infiltrates
portal tract and periportal region
mononuclear infiltrate
Affects children younger 4 years with viral illness
Pernicious vomiting, irritability, lethargy and hepatomegaly
Normal serum trans
Aspirin admin during viral illness
Mitochondrial injury leading to diffuse hepatocellular microvesicular steatosis (mitoch enlargement, electron lucency, disruption of cristae, loss of dense bodies)
Cerebral edema
Skeletal, kidney and heart present with microvascular fatty change
Reye syndrome
Others: tetracycline, valproate, ackee fruit HAART
Prolonged conjugated hyperbilirubinemia lasting beyond first 14d of life
May be extrahepatic or neonatal hepatitis
Jaundice, dark urine, acholic stool
Neonatal cholestasis
Most common alteration in cholestasis of sepsis from microbial product (endotoxemia) is
Canalicular cholestasis
prominent bile plugs in dilated canaliculi in centrilobular region
Cardinal feature of PBC is
non suppurative destruction of small and medium sized intrahepatic bile duct
Autoantibodies directed against several mitochondrial acid dehydrogenase
Immune resp against enzymes targetting intrahepatic ducts
Primary biliary cirrhosis
Destruction of duct, inflammation and scarring with cirrhosis and liver failure
Inc ALP
Tx of PBC with this dramatically improves course greatly slowing progression
Inhibit apoptosis of biliary epicand inhibit immune response
ursodeoxycholic acid
Most revealing in precirrhotic stage with destruction of interlobular bile duct by lympho and plasma cell with or without granuloma termed as
Portal-portal septal fibrosis
Nodular regenerative hyperplasia
Periportal periseptal chronic cholestasis with feathery degeneration
florid duct lesion
PBC
Progressive fibrosis, destruction of extra and intrahepatic bile duct of all sizes
Patchy changes with beading alternating normal and dilated duct
Assoc with IBD:
HLA-DR, ANCA, immunologically mediated
Primary sclerosing cholangitis
Ulcerative colitis
Circumferential fibrosis aka onion skinning
Tombstone scar - button scar tissue
Dx: MRI pf ducts
Biliary intraepithelial neoplasia may be harbinger of cholangiocarcinoma
Inc ALP
Primary sclerosing cholangitis
Full developed cases of hemochromatosis present with
1 cirrhosis all
2 DM 75-80
3 skin pigmentation 75-80
Defect in regulation of iron intestinal absorption leading to accum of 0.5-1 y due to mutations of the gene
Manifests after 20g of iron has accumulated
Hereditary hemochromatosis
HFE on ch6 Interacts with hepcidin by liver to form a web of iron control networks
Downregulates iron absorption in itestine and mac into plasma
Hepcidin
dec in all genetic forms of hemochromatosis
Lipid peroxidation by free rad
Stimulation of collagen
Interaction with DNA
Iron toxicity to cell
Hemosiderin deposits in organs
Golden yellow granules in cytoplasm staining blue with Prussian blue
Absent inflamm but very dark liver
Skin discoloration due to melanin not iron (slate gray)
Pseudogout from calcium dep
Atrophic testes
Liver, pancreas, myocardium, pituitary
Triad of hemochromatosis
Risk for HCC: 200x
Hepatomegaly
Skin pigmentation
DM
loss of libido
impotence
Accumulation of copper in liver, brain, eyes due to mutation of
Wilson disease
ATP7B
Copper is bound to the alpha2 globulin to form ceruloplasmin
But mutation of ATP7B leads to inability to excrete it in bile
apoceruloplasmin
Free radicals
Binding to sulfhydryl groups of cellular proteins
Displacing other metals in hepatic metalloenzyme
Copper toxicity
Mimics fatty liver, moderate steatosis, steatohepatitis Acute hepatitis and chronic hepatitis Cirrhosis Rhodamine stain demonstrates copper Orcein stain for copper assoc protein
Copper 250 ug/g dry weight is diagnostic
Wilson disease
Tx D penicillamine
Zinc salt
Copper affects the of the brain
Copper deposits in eyes as
Basal ganglia putamen atrophy cavitation
Kayser Fleischer ring (green brown deposit in descemet of limbus)
Also hepatolenticular degeneration
Round to oval cytoplasmic globules in hepatocytes
PAS (+)
Diastase-resistant
retaining AAT
Cholestasis with hepatocyte necrosis
Childhood cirrhosis
HCC in 2-3a% of adult
Deficiency in persons with PiZZ genotype causing pulmonary emphysema by accumulated misfolded AAT
A1 antitrypsin deficiency
Low serum levels of protein inhibitor AAT bec of a mutation in the allele
PiZZ on ch14 of AAT gene
Portal vein obstruction
Intra or extrahepatic thrombosis
Esophageal varices
Splenomegaly
Intestinal congestion
Impaired blood inflow
Cirrhosis
Sinusoid occlusion
Systemic circulatory compromise
Ascites
Esophageal varices
Hepatomegaly
Elevated trans
Impaired hepatic blood flow
Hepatic vein thrombosis
(Budd-Chiari)
Sinusoidal obstructive syndrome
Ascites Hepatomegaly Abd pain Elevated transaminase Jaundice
Hepatic vein outflow obstruction
Fibrotic partially recanalized vascular channel
Splenomegaly, esophageal v
Subclinical thrombosis of portal vein from neonatal omphalitis or umbilical vein cath
Banti syndrome
Thrombosis of portal vein radicle resulting in sharply demarcated area of red blue discoloration
Infarct of Zahn
No necrosis
Hepatocellular atrophy
Congestion of sinusoid
Hepatoportal sclerosis
Sickle cell disease causes this type of hepatic necrosis
Panlobular parenchymal
DIC causea occlusion of hepatic
sinusoid
Variegated mottled appearance hemorrhage necrosis in centrilobular region alternating with pale midzonal area called
Sharp demarcation of vaible periportal and necrotic pericentral hepatocytes
Nutmeg liver in cirrhosis
Thrombosis of one or more major hepatic vein
Hepatomegaly
Ascites
Abdominal pain
Budd-Chiari syndrome
Budd Chiari rf
Polycythemia vera Pregnancy Postpartum state OCP use PNHG HCC
Swollen red purple
Liver with tense capsule
Severe centrilobular necrosis and congestion
If slow, centrilobular fibrosis
Budd Chiari
Tx: portosystemic shunt
Sinusoidal obstruction syndrome is an outflow problem formerly known as venoocclusive disease from toxic injury to sinusoidal endo
Rf
Bush tea (bec of pyrrolizidine alkaloid)
20-30d post BMT Cyclophosphamide Actinomycin D Mithramycin Total body radiation
Most common hepatic neoplasm are
Metastatic carcinoma from colon, lung, breast
Angiosarcoma of liver is due to exposure to
vinyl chloride
arsenic
Most common benign lesion of the liver
Well circ endothelial cell lined vascular channel and intervening stroma
Red blue soft nodules less than 2cm beneath capsule
cavernous hemangioma
Congenital bile duct hamartoma
Bile duct like structure separated by bland collagenized stroma
No malignant potential but if multiple may indicate fibropolycystic disease of liver
Von Meyenburg complex
Localized well demarcated poorly encap lesion
Hyperplastic hepatocyte nodules with central stellate fibrous scar
Abnormal vascular flow through congenital or acquired anomaly alternating areas of regeneration and atrophy
Incidental finding in women of reproductive age in resp to estrogen
No risk for malig
Focal nodular hyperplasia
Benign neoplasm of women using OCP, regresses on discontinuation
Well demarcated uncapsulated pale yellow tan sheets of cords of cells resembling normal hepatocyte
Absent portal tract but significant neovasc
Significant bec
Mistaken for HCC
Risk of rupture if subcap esp at pregnancy
If B catenin mutated, harbors risk of HCC
Hepatic adenoma
3 types of hepatocellular adenomai
1 mutation of HNF1A or CYP1B1 in women using OCP (little risk for malignancy)
2 activating mutations of B catenin related to anabolic or steroid use in men (ihigh risk of malig transformation)
3 Inflammatory 50% (inc exp of acute phase reactant serum amyloid A and CRP) in obese women with FL express serum amyloid protein
Type of hepatocellular dysplasia characterized by scattered large hepatocyte with pleomorphic multiple nuclei
Markers of molecular change
Large cell change
Smaller than normal hepatocyte with normal but hyperchromatic oval or angulated nuclei, thickened cell plate and high nuclear cytoplasmic ratio
Directly premalignant
Small cell change
Major pathway for HCC
Large size encompassing adjacent hepatic lobules without displacing all of portal tracts
High risk for malignant transformation
Dysplastic nodule
HCC etiologies
HBV infection
HCV infection
Alcoholic cirrhosis
Aflatoxin fr Aspergillus flavus
Others alpha 1 antitrypsin, hemochromatosis, tyrosinemia (most likely)
216 risk if combined
Develops from small cell high grade dysplastic nodule in cirrhotic liver
Arise from both mature hepatocyte and progenitor cell or ductal or oval cells
Nodule vasc by imaging clear indication
Structural and numeric chromosomal abn indicative of genomic instability
Inflamm and regeneration leading to mutation in B catenin and TP53
HCC
HBV and HCV not oncogenic HBV-X is.
contributes to inflammation and inc cell turnover
Unifocal
Multifocal with variable size
Diffusely infiltrative
Yellow white punctuated with strong propensity for vascular invasion
Better diff variant of globules of bile found within cytoplasm of cells and pseudocanaliculi
HCC
Clinical variant of hcc in young male and female adults
No association with cirrhosis or risk factors
Single tumor with fibrous band coursing through it resembling focal nodular hyperplasia
Better prog
Fibrolamellar carcinoma
Rapid inc in liver size
Sudden worsening of ascites
Bloody ascites, fever, pain
Marker:
HCC
Alpha fetoprotein
False positive in yolk sac and cirrhosis hepatitis pregnancy and massive necrosis
Radio screening at 6 mo interval look for early dysplastic nodules or small HCC
Broad spec tyrosine kinase inhibitor giving benefit to those with advanced disease
Sorafenib
Right-sided cardiac decompensation leads to passive congestion of the liver
Left-sided cardiac failure or shock may lead to hepatic hypoperfusion and hypoxia causing centrilobular necrosis
Chronic Passive Congestion
Distinctive centrilobular fibrosis
Cardiac sclerosis
Cardiac cirrhosis
Loss of inhibution of proteases released from neutrophils lead to panacinar emphysema
Alpha-1 Antitrypsin Deficiency
Accumulation of abnormal alpha-1 leads to
Liver disease
Panlobular giant cell transformation of hepatocytes
Lobular disarray with focal apoptosis and necrosis
Prolonged conjugated hyperbilirubinemia in neonates
2 major etiologies:
cholangiopathies like biliary atresia
neonatal hepatitis
Neonatal cholestasis
Fine foamy appearance due to droplets of bile pigment that accumulates within hepatocytes
feathery degeneration
Neonatal cholestasis
Cholestatic hepatocytes
Dilated canalicular spaces
Apoptotic cells
Kupffer cells with regurgitated bile pigments
Intrahepatic cholestasis
Bile duct proliferation
Edema, bile pigment retention
Swollen and degenerating hepatocytes
Extrahepatic cholestasis
Viral hepatitis transmitted via oral fecal routes
Hep A
Hep E
Vowels hit the bowels
Most common blood transfusion hepatitis
Hep C
Placental barrier, blood and sexually transmitted
Hep B
Only DNA hepadna
Infectious particle:
Sand nuclei
Hep B
Dane
Empty cytoplasm with scattered remnants of cytoplasmic organelles
Ballooning degeneration
Eosinophilic globules
Councilman bodies
Connecting portal-to-portal, central-to-central, or portal-to-central regions of adjacent lobules
Bridging necrosis
Hepatocyte apoptosis
Continued interface hepatitis
Bridging necrosis
Chronic hepatitis
Hallmark of chronic hepatitis
deposition of fibrous tissue
bridging fibrosis
Hepatocytes with finely granular cytoplasm
Chronic Hep B infection
Ground glass hepatocytes
Lymphoid aggregates
Macrovesicular steatosis
Chronic hepatitis C infection
Hepatic insufficiency that:
progresses from onset of symptom to hepatic encephalopathy within 2 to 3 weeks
occurs in individuals who do not have chronic liver disease
Fulminant hepatitis
Massive loss of liver mass
Liver is transformed into a limp, red organ covered by a large wrinkled capsule
Muddy red, mushy appearance
Fulminant hepatitis
Hepatitis B
Pipestem fibrosis
Schistosomiasis
Bilharziasis
Result of sudden and massive hepatic destruction (fulminant hepatic failure)
End stage of progressive chronic damage to liver
Transplantation offers the best hope for survival
Hepatic failures
Acute liver illness that is associated with encephalopathy within 6 months after the initial diagnosis
Acute liver failure
Within 2 weeks of onset of jaundice
Fulminent liver failure
Within 3 months of onset of jaundice
Sub-fulminant liver failure
Caused by massive hepatic necrosis, most often induced by drugs or toxins
Acute liver failure
Drug accounting for almost 50% of cases
Acetaminophen
Jaundice
Hypoalbuminemia
Hyperammonemia (encephalopathy)
Fetor hepaticus
Hepatic failure
Musty or sweet and sour body odor
Formation of mercaptans by the action of intestinal bacteria on methionine
Fetor hepaticus
Protosystemic shunting
Caput medusae
Esophageal varcies
Hemorrhoids
Impaired estrogen metabolism
Palmar erythema
Spider angioma
Hypogonadism and gynecomastia
Hepatic failure
Associated with elevated ammonia levels
Promote generalized brain edema
Hepatic encephalopathy
Drug for hepatic encephalopathy
Lactulose
Delta waves slowing on EEG
hepatic and uremic encephalopathy
Fluctuating neurologic signs include rigidity, hyperreflexia, and asterixis
Nonrhythmic, rapid extension-flexion movements of head and extremities
Hepatic encephalopathy
Appearance of renal failure in individuals with severe chronic liver disease
Drop in urine output, associated with rising blood urea nitrogen and creatine
Treatment of choice: liver transplantation
Hepatorenal syndrome
Chronic liver disease
Hypoxemia
Intra-pulmonary vascular dilations
Only curative treatment is liver transplantation
Hepatopulmonary syndrome
Key mediator in hepatopulmonary syndrome
Nitric oxide
Etiology of liver abscess usually caused by bacteria
Pyogenic liver abscess
Neutrophilic infiltrate
Liquefactive necrosis
Pyogenic liver abscess
Usually caused by echinococcal and amebic infections
Nonpyogenic liver abscess
Eosinophilic infiltrate
Laminated cystic wall with hooklet in echinococcosis
Anchovy paste-like material
Nonpyogenic liver abscess
Water lily sign
Camalote sign
Hydatid infection
Detachment of endocyst membrane which results in floating membranes within pericyst that mimic appearance of water lily
Chronic and progressive hepatitis of unknown etiology
Pathogenesis: T cell-mediated autoimmunity
(+) for anti-smooth muscle antibodies
Autoimmune hepatitis
Progressive alcohol consumption is the leading cause of liver disease
Three distinctive forms:
Hepatic steatosis (fatty liver disease)
alcoholic hepatitis
cirrhosis
Alcoholic liver disease
Mallory bodies
Alcoholic liver disease
Small lipid droplets accumulate in hepatocyte steatosis
microvascular steatosis
Large, clear lipid globules displace the nucleus to periphery
Completely reversible
Hepatic steatosis
Eosinophilic cytoplasmic clumps in hepatocytes
Mallory bodies
Prominent activation of sinusoidal stellate cells and portal tract fibroblasts
Sinusoidal prevenular fibrosis
Alcoholic hepatitis
Scattered larger nodules create a hobnail appearance on the surgsce of the liver
Macronodular cirrhosis
Alcoholic cirrhosis
Brown, shrunken, nonfatty liver
Alcoholic cirrhosis
Broad expanses of tough, pale scar tissue created by ischemic necrosis and fibrous obliteration of nodules
Laennec cirrhosis
Alcoholic cirrhosis
Uniform micronodules created by regenerative activity of entrapped parenchymal hepatocytes
Micronodular cirrhosis
Alcoholic cirrhosis
Hepatic steatosis in individuals who:
do not consume alcohol
do so in very small quantities (<20 g/week)
Most common cause of CLD in the United States
Nonalcoholic fatty liver disease (NAFLD)
Simple hepatic steatosis
Non-alcoholic steatohepatitis (NASH)
NAFLD
Steatosis
Mallory bodies
Hepatocyte death (ballooning degeneration and apoptosis)
Sinusoidal fibrosis
Steatohepatitis (NASH)
Benign neoplasms developing from hepatocytes
Most frequently occurs in young women who have used oral contraceptives
Hepatic adenoma
Chronic viral infection (HBV, HCV)
Chronic alcoholism
Non-alcoholic steatohepatitis (NASH)
Food contaminants (primarily aflotoxins)
Hepatocellular carcinoma
Pallor
Green hue
Strong propensity for invasion of vascular structures
Hepatocellular carcinoma
Large, hard “scirrhous” tumor with fibrous bands
Separated by parallel lamellae of dense collagen bundles
Better prognosis
Fibrolamellar carcinoma
Malignancy of the biliary tree, arising from bile ducts within and outside of the liver
Cholangiocarcinoma
Primary sclerosing cholangitis
HCV infection
Previous exposure to Thorotrast
Clonorchis/Opistorchis infection
Classified into intrahepatic and extrahepatic forms
Cholangiocarcinoma
Perihilar extrahepatic form of cholangiocarcinoma is called
Klatskin’s tumor
