Liver 2 Flashcards by Denisse Tiangco

Most common cause of incidental elevation of serum transaminase

NAFLD

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Reverses NALFD histologic changes in biopsy proven steatohepatitis

Pioglitazone

stimulator of tf PPAR-y modulating expression of insulin sensitive genes

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In children, NAFLD histologic injury is characterized by inflammation and scarring at the rather than neutrophilic infiltrates

portal tract and periportal region

mononuclear infiltrate

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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

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Prolonged conjugated hyperbilirubinemia lasting beyond first 14d of life

May be extrahepatic or neonatal hepatitis

Jaundice, dark urine, acholic stool

Neonatal cholestasis

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Most common alteration in cholestasis of sepsis from microbial product (endotoxemia) is

Canalicular cholestasis

prominent bile plugs in dilated canaliculi in centrilobular region

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Cardinal feature of PBC is

non suppurative destruction of small and medium sized intrahepatic bile duct

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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

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Tx of PBC with this dramatically improves course greatly slowing progression
Inhibit apoptosis of biliary epicand inhibit immune response

ursodeoxycholic acid

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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

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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

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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

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Full developed cases of hemochromatosis present with

1 cirrhosis all
2 DM 75-80
3 skin pigmentation 75-80

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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

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Downregulates iron absorption in itestine and mac into plasma

Hepcidin

dec in all genetic forms of hemochromatosis

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Lipid peroxidation by free rad
Stimulation of collagen
Interaction with DNA

Iron toxicity to cell

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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

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Triad of hemochromatosis

Risk for HCC: 200x

Hepatomegaly
Skin pigmentation
DM

loss of libido
impotence

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Accumulation of copper in liver, brain, eyes due to mutation of

Wilson disease

ATP7B

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Copper is bound to the alpha2 globulin to form ceruloplasmin

But mutation of ATP7B leads to inability to excrete it in bile

apoceruloplasmin

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Free radicals
Binding to sulfhydryl groups of cellular proteins
Displacing other metals in hepatic metalloenzyme

Copper toxicity

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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

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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

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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

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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