Chapter 18 Flashcards

Question

Asterixis

Answer 1

Characteristic sign of acute hepatic failure Nonrhythmic, rapid extension flexion of the head and extremities Seen with arms in extension and dorsiflexied wrists

Answer 2

Associated with cirrhosis though not mutually exclusive Chronic hepatitis B and C, non alcoholic fatty liver disease, alcoholic fatty liver disease

Answer 3

Acute liver failure

Answer 4

Hepatic encephalopathy Bleeding from esophageal varices Bacterial infections

Answer 5

Diffuse transformation of the entire liver into regenerative parenchymal nodules surrounded by fibrous bands and variable degrees of vascular (portosystemic) shunting No single cirrhosis, but rather multiple variable cirrhosis Cirrhosis is no longer considered end stage liver disease because the fibrosis is potentially reversible with increasing numbers of effective treatments for cirrhosis causing conditions

Answer 6

Helps monitor the decline of the patients ont he path to chronic liver failure

Answer 7

Well compensated

Answer 8

Partially compensated

Answer 9

Decompensated

Answer 10

Ductular reactions which increase with advancing stage of disease and are usually most prominent in cirrhoisis

Answer 11

Biopsy specimens with narrow, densely compacted fibrous septa separated by areas of intact hepatic parenchyma

Answer 12

Broad bands of dense scar with dilated lymphatic space, less parenchyma; more likely to progress and lead to end stage disease

Answer 13

Only seen in 40% of patients Jaundice+pruritis Hypoalbuminemia->systemic edema Hyperammonemia Factor hepaticus:mercaptan formation Males hyper-estrogenemia due to impaired metabolism can lead to palmar erythema, spider angiopathy, hypogonadism, and gynecomastia Increased risk of developing hepatocellular carcinoma

Answer 14

Obstructive thrombosis Narrowing of the portal vein before entering the liver Massive splenomegaly with increased splenic blood flow

Answer 15

Severe right heart failure Constrictive pericarditis Hepatic vein outflow obstruction

Answer 16

Usually due to cirrhosis Schistomiasis Massive fatty change Diffuse fibrosis granulomatous disease such as sarcoidosis Diseases effecting the portal microcirculation such as nodular regenerative hyperplasia Increased resistance to portal flow Increased portal venous flow due to hyper dynamic circulation

Answer 17

Contraction of vascular smooth muscle and myofibroblasts Decreased NO production Increased endothelin1, angiotensinogen, eicosanoids production Disruption of blood flow by scarring and formation and parenchymal nodules Remodeling and anastomoses impose arterial pressure on a normally low pressure system Interferes with metabolic exchange of sinusoidal blood and hepatocytes

Answer 18

Splanchnic arterial vasodilation-increased efflux into the portal venous system Due to NO, prostacyclin and TNF

Answer 19

Ascites Portosystemic shunt formation Congestive splenomegaly Hepatic encephalopathy

Answer 20

Excessive fluid in the peritoneal cavity | Detectable with accumulation of 500 ml

Answer 21

Seepage of peritoneal fluid through trans-diaphragmatic lymphatic channels—>hydro-thorax, espicially onthe RIGHT

Answer 22

Fluid is serous, <3mg/dl of protein (albumin) Neutrophils: suggests infection Blood:suggests disseminated intraabdominal cancer

Answer 23

Sinusoidal HTN Precolation of hepatic lymph in peritoneal cavity Splanchnic vasodilation

Answer 24

Hepatic sinusoidal HTN drives fluid into the space of disse which is drained by lymphatics Promoted by hypoalbuminemia->peripheral edema

Answer 25

Beneath the endothelial cells

Answer 26

Fat containing myofibroblastic hepatic stellate cells are found in the space of disse

Answer 27

Normal flow is 800-1000ml; increased to 20L The thoracic duct isn’t ably to keep up and fluid leaks out->peripheral interstitial edema

Answer 28

Causes systemic hypotension which leads to vasoconstriction RAAS activation leads to Na retention (and H2O follows) Increased perfusion pressure of the interstitial capillaries -transudation(protein poor) into the abdominal cavity

Answer 29

Flow is reversed from the portal into the systemic circulation where there are shared capillary bed Esophageal varices: 40% of patients with advanced cirrhosis; rupture can cause massive hematemesis with 30% mortality Falciform ligament and caput Medusa: dilated subcutaneous veins extend from umbilicus to rib margins Rectum: hemorrhoids

Answer 30

Due to long standing congestion Can cause thrombocytopenia(or pancytopenia Due to long standing congestion Can cause thrombocytopenia (or pancytopenia due to hypersplenism)

Answer 31

Hypoxia+dyspnea due to Ventillation/perfusion (V/Q) mismatch from rapid blood through dilated vessels with decreased time for diffusion

Answer 32

Upright position due to gravity

Answer 33

Recumbent position

Answer 34

Dyspnea on excretion and clubbing Pulmonary arterial HTN in liver disease and portal HTN Excessive pulmonary vasoconstriction and vascular remodeling with concomitant portal hypertension

Answer 35

Individuals with stable, well-compensated chronic liver disease develop sudden signs of acute liver failure Commonly have established cirrhosis and extensive vascular shunting Significant amounts of parenchyma have borderline vascular supply and are vulnerable to superimposed insult

Answer 36

Benign, self limited disease Does not cause chronic hepatitis or a carrier state Rarely lethal

Answer 37

Fecal oral via contaminated water Raw or steamed shellfish that get it from human sewage contaminated seawater

Answer 38

Single stranded + RNA

Answer 39

Mild or asymptomatic and rare after childhood

Answer 40

Infection that has a predilection for the liver and can cause a wide spectrum of disease manifestations , with most of the cases leading to asymptomatic chronic disease or clearance

Answer 41

Acute hepatitis with recovery and clearance of virus Non-progressive chronic hepatitis Progressive chronic disease ending in cirrhosis Acute hepatic failure with massive liver necrosis Asymptomatic, ‘healthy’ carrier state Chronically is an important precursor for hepatocelullar carcinoma

Answer 42

High prevalence ares (AFrica, Asia): childbirth Intermediate prevalence: horizontal (breaks in skin/mucus membranes in children with close body contact) Low prevalence: unprotected sex, IV drug use

Answer 43

Partially dsDNA virus Mature virus=spherical double layered “Dane particle” with outer surfac protein+lipid envelope around an electron dense slightly hexagonal core

Answer 44

HBsAg Anti-HBs HBeAg, HBV-DNA and DNA polymerase Anti-HBc

Answer 45

Appears before the symptoms, peaks during the overt disease, and lasts for about 12 weeks *donated blood is screened for HBsAg

Answer 46

Doesn’t rise until the disease is over, about the same time that the HBaAg goes away. The IgG form is what provides the immunity

Answer 47

All appear after HBsAg and indicate there is active viral replication

Answer 48

Indicator of continued viral replication, infectivity, and probably progression to chronic hepatitis

Answer 49

Acute infection has peaked and is on the wave

Answer 50

Appears just before the onset of symptoms and shows up with increased aminotransferase levels (liver damage)

Answer 51

Age at the time of infection Younger age-increased probability of chonicity

Answer 52

Host immune response to the virus is the main determinant of the outcome of the infection Strong response by virus specific CD4 and CD8 interferon (IFN-y)-producing cells is associated with the resolution of acute infection

Answer 53

CD8 cytotoxic T cells attack infected hepatocytes

Answer 54

Difficult due to viral insertion into host DNA Limits the development of an effective immune response Virus persists in the face of rugs that impair its replication

Answer 55

Slow progression of disease, reduce liver damage and prevent cirrhosis and cancer

Answer 56

Vaccination and screening of blood donations prevents it

Answer 57

Most cases are self limited and resolve without treatment

Answer 58

In chronic HBV, liver biopsy shows finely granular ground glass hepatocytes packed with HBsAg -cells with endoplasmic reticulum swollen by HBsAg-diagnostic hallmark

Answer 59

Liver biopsy shows finely granular ground glass hepatocytes packed with HBsAg -cells with endoplasmic reticulum swollen by HBsAg

Answer 60

SsRNA virus Genomic instability+antigenic variability=no vaccine Anti-HCV igG antibodies do not confer effective immunity and re infection is possible

Answer 61

More mild than HBV with most acute cases being asymptomatic, but 80-90% of patients develop chronic infection and 20% get cirrhosis Exists as closely related genetic variants inside infected patients

Answer 62

Characteristic repeated bouts of hepatic damage Persistent infection and chronic hepatitis=hallmarks of HCV infection Acute illness is generally asymptomatic chronic HCV infection==persistent elevations in serum aminotransferases -wax and wane, but never normal Cryoglobulinemia is found in 35% of individuals with chronic hepatitis C infection

Answer 63

HCV RNA is detected in blood for 13 weeks during active infection with concurrent increase in aminotransferase levels (will see the increase in ALT/AST chronically)

Answer 64

``` Metabolic syndrome (genotype3) Can give rise toinsulin resistance and non alcoholic fatty liver disease ```

Answer 65

Genotype 2 and 3 have best response to treatment, espicially in patients with IL-28B gene (encodes IFN-y involved in resistance to HCV) polymorphisms -better response to IFN-a and ribavirin Newer regimens may improve prognosis

Answer 66

Leads to portal lymphoid follicle, bile duct reactive changes and lobular regions of microvesicular steatosis Bile duct injury is possible that can histologically mimic primary biliary cirrhosis (easily distinguished clinically) Chronic HCV shows lymphoid aggregates or fully formed lymphoid follicles; fatty change of scattered hepatocytes

Answer 67

External coat antigen surrounds an internal “delta antigen” the only protein produced by the virus

Answer 68

Co-infection Superinfection

Answer 69

HBV must become established first to provide the HBsAg necessary for development of complete HDV virions, resulting in acute hepatitis indistinguishable from acute hepatitis of HBV-only etiology

Answer 70

Self limited | Followed by clearance of both viruses

Answer 71

In IV drug users

Answer 72

Best indicated by detection of IgM against both HDAg and HBcAg

Answer 73

When a chronic carrier of HBV is exposed to a new inoculum of HDV get superinfection 30-50 days later Severe acute hepatitis in a previously unrecognized HBV carrier, or exacerbation of pre existing chronic hepatitis B infection

Answer 74

Active HDV replication and suppression of HBV with high transaminase levels

Answer 75

HDV replication decreases , HBV replication increases, transferase levels fluctuate, and disease progresses to cirrhosis and sometimes hepatocellular carcinoma

Answer 76

HBsAg present in serum, anti HDV persist for months or longer

Answer 77

Western countries: largely restricted to IV drug users and those who have had multiple blood transfusions

Answer 78

HDV RNA is detectable in the blood and liver just before and in the early days of acute symptomatic disease

Answer 79

Enterically transmitter, water borne infection Zoonotic=animal resivoirs(increased risk with exposure to monkeys, cats, pigs, and dogs)

Answer 80

Occurs primarily in young to middle aged adults

Answer 81

Higher mortality rate among pregnant women-almost 20%

Answer 82

Self limiting

Answer 83

Chronic liver disease or persistent fire is in immunocompentent patients

Answer 84

Partially dsDBA

Answer 85

Circular defective SsRNA

Answer 86

Hepatovirus (picornavirus)

Answer 87

HepaDNAvirus

Answer 88

Flaviviridae

Answer 89

Subviral particle in deltavirdae family

Answer 90

Fecal-oral (contaminated H2O)

Answer 91

Parenteral, sexual contact, perinatal

Answer 92

Parenteral, intranasal cocaine

Answer 93

Parenteral

Answer 94

Fecal oral

Answer 95

2-26 weeks (avg 8)

Answer 96

4-26 weeks (avg9)

Answer 97

2-26 weeks (avg 8)

Answer 98

10% coinfection 90-100% superinfection

Answer 99

IgM antibodies

Answer 100

HBsAg, antiHBcAg; PCR for DNA

Answer 101

PCR for DNA, Elisa for Ab

Answer 102

IgM and IgG antibodies; HDV RNA serum; HDAg in liver

Answer 103

Serum IgM and IgG; PCR for HEV RNA

Answer 104

Acute asymptomatic infection with recovery (serologic evidence only) Acute symptomatic hepatitis with recovery (anicteric or interic) Chronic hepatitis Acute liver failure Carrier state

Answer 105

Worldwide, HAV, and HBV infections are frequently subclinical events in childhood verified only in adulthood by the resented of anti-HAV or anti HBV antibodies

Answer 106

Incubation(peak infectivity during last asymptomatic days of incubation period and early days of acute symptoms) Symptomatic pre-icteric phase Symptomatic interic phase Convalescence

Answer 107

With progression to cirrhosis Without progression to cirrhosis

Answer 108

With massive hepatic necrosis With submissive hepatic necrosis

Answer 109

“Healthy carrier’: individual with HBsAg, no HBeAg, andi HBeAg, normal aminotransferases low or undetectable serum HBV DNA, and liver biopsy showing a lack of significant infalmmation and necrosis Inactive carrier Not recognized in the United States

Answer 110

Lymphoplasmactyic (mononuclear) infiltrate Spotty necrosis or lobular hepatitis scattered throughout a lobule Necrosis empty cytoplasm , cell membrane ruptures leads to hepatocyte dropout Collapsed sinusoidal collagen reticulin framework Apoptosis; hepatocytes shrink, become eosinophilic, pyknotic, fragmented Lack of portal inflammation

Answer 111

CONFLUENT NECROSIS of hepatocytes around central veins Cellular debris, collapsed reticulin fibers, congestion +/- hemorrhage Variable inflammation Central portal BRIDGING NECROSIS leads to parenchymal collapse Can lead to massive hepatic necrosis/acute failure Can develop post hepatitis. Cirrhosis with abundant scarring

Answer 112

Mononuclear portal infiltration Mild: inflammatory infiltrates are limited to portal tracts Progressive dise: extension of chronic inflammation from portal tracts with interface hepatitis Linking of orca and portal central regions=bridging necrosis Continued loss of hepatocytes=fibrous septum formation Associated hepatocyte regeneration=cirrhosis

Answer 113

Staphylococcus aureus

Answer 114

Salmonella typhi

Answer 115

Treponema pallidum

Answer 116

Acute infalammation response within the intrahepatic biliary tree due to intrabiliary bacterial microflora during a partial or complete obstruction

Answer 117

Chronic, progressive hepatitis Presence of autoantibodies Therapeutic response to immunosuppression

Answer 118

Viral infection, drug/toxin exposure

Answer 119

Caucasion: DRB1* alleles (HLA association)—genetic predisposition Most frequent in white Northern Europeans Females predominance

Answer 120

2 types based on circulating antibodies

Answer 121

Middle aged older people ANA (anti-nuclear), ASMA (anti-smooth msucle), ANTI-SLA/LP (anti-soluble liver antigen/liver-pancreas antigen), AMA (anti-mitochondrial) antibodies

Answer 122

Children and teenagers Anti-LKM1 (anti-liver kidney microsome-1) antibodies against CYP2D6 ACL1 (anti-liver cytosolic) antibodies

Answer 123

-fibrosis take years to develop in chronic viral hepatitis, does not develop in acute hepatitis Severe necroinfalmmatory activity indicated by interface hepatitis or parenchymal collapse Mononuclear infiltrate: plasma cells Hepatocyte ROSETTES in areas of activity

Answer 124

Severe parenchymal destruction followed rapidly by scarring Fibrosis takes years to develop in chronic viral hepatitis, does not develop in acutehepatitis Severe necroinflammatory activity indicated by interface hepatitis or parenchymal collapse Mononuclear infiltrate: plasma cells Hepatocyte ROSETTES in areas of activity

Answer 125

Initial: severe hepatocyte injury with necrosis but little scarring Chronic: burned out cirrhosis with little necroinflammatory activity; likely due to years of subclinical disease

Answer 126

40% mortality in 6 months Both type 1 and type 2 are likely to lead to liver failure

Answer 127

Plasma cells are prominent and characteristic component of the inflammatory infiltrate in biopsy specimens showing autoimmune hepatitis

Answer 128

Between in adults than in children (delay in diagnosis in pediatric population)

Answer 129

80% of patients respond to immunosuppression for long term survival

Answer 130

Liver transplant with 75% survival at 10 years, recurrent ein 20% of patients

Answer 131

May be immediate or delayed Mild to severe Predictable (intrinsic, dose dependent) or unpredictable (idiosyncratic, multi-factorial) Due to direct toxicity, conversion of a xenobiotic to a toxin or from immune mediated toxicity Recovery usually occurs with removal of the offending agent

Answer 132

Acetaminophen

Answer 133

Due to toxic metabolite produced from the CYP450 breakdown in acinus zone 3 hepatocytes

Answer 134

Closest to the terminal hepatic vein (central vein) and furthest from the portal vein Central vein turns into the hepatic vein

Answer 135

Tries to compensate and become injured

Answer 136

The zone of injury extends into zone 1 (periportal hepatocytes) and this is when you start getting acute hepatic failure

Answer 137

Upregulate CYP450 and make things worse

Answer 138

Cholestasis in patients who are slow to metabolize it to an innocuous byproduct

Answer 139

Fatal immune mediated hepatitis in some patents exposed on multiple occasions

Answer 140

Hepatocellular steatosis or fatty change Alcoholic hepatitis Streatofibrosis up to and including cirrhosis (only in a small fraction) - patterns of scarring typical for all fatty liver diseases including alcohol - cirrhosis develops in only a small fraction of chronic alcoholics

Answer 141

Microvesicular lipid droplets within hepatocytes With chronic use accumulates in microvesicular droplets which displace the nucleus Large, soft, greasy, yellow liver No fibrosis Completely reversible if patients abstains from alcohol

Answer 142

Hepatocyte swelling (fat, H2O, proteins)+necrosis Mallory-denk bodies Neutrophilic reaction to degenerating hepatocytes, espicially those with Mallory dunk bodies

Answer 143

Intracellular eosinophilic aggregates of intermediate filaments (keratin 8 and 18, ubiquitin) in ballooning hepatocytes -hepatocytes are epithelial cells Mallory desk bodies==damaged intermediate filaments(in hepatocytes, cytokeratin)

Answer 144

Alcoholic hepatitis, non alcoholic fatty liver disease, wilson disease, and chronic biliary tract disease

Answer 145

Characteristic finding in alcoholic hepatitis but not specific

Answer 146

Activation of sinusoidal stellate cells+portal fibroblasts=fibrosis (fibrosis begins with sclerosis of central veins (zone3) Scarring in a chicken wire fence pattern Laennec cirrhosis with continuous use due to developing modularity and progressive inter webbing of the scare Liver is large, brown, shrunken and non fatty Closer to cirrhosis =less likely to regress

Answer 147

Fibrosis spreads outward and encircles individual or small clusters of hepatocytes

Answer 148

Classic micro nodular cirrhosis first described for end stage alcoholic liver disease Cirrhosis==chronic liver disease; laennec (aka micro nodular)==chicken-wire==alcoholic steatofibrosis Large bands of fibrous tissue surrounding nodules

Answer 149

10-115% of alcoholics develop cirrhosis Females are more susceptible African American>caucasion Iron overload, HBV, HCV=increased severity of liver disease

Answer 150

Homozygous ALDH*2 (asians) has alcohol intolerance Flushing, nausea, lethargy

Answer 151

Impaired lipoprotein assembly and secretion Increased peripheral catabolism of fat-> release of free fatty acids into the circulation Shunting of substrates away from catabolism and towards lipid biosynthesis (due to increased NADH production by enzymes of metabolism) -alcohol dehydrogenase and acetaldehyde dehydrogenase-> increased NADH production

Answer 152

Acetylaldehyde induced lipid peroxidation and protein adduct formation (carcinogen) Induced CYP450-increases conversion of other agents to form potentially toxic metabolites Impaired methionine metabolism Release of bacterial endotoxin (LPS) Release of endothelin1 Decreased perfusion of hepatic sinusoids

Answer 153

Decreases glutathione levels that are normally protective of ROS

Answer 154

Pro inflammatory Estrogen increases gut permeability to endotoxin (LPS)->increased expression of the LPS receptor (CD14, TLR4) in kupffer cells==women are more sensitized to pro inflammatory effects

Answer 155

Chronic disorder of steatosis, hepatitis, progressive fibrosis and deranged perfusion Due to an agent that was initially only marginally harmful

Answer 156

Hepatomegaly Mild increase of serum bilirubin and alkaline phosphatase levels Severe dysfunction Is rare

Answer 157

AST:ALT>2:1 90% 5 year survival with abstinence in patients free of jaundice, ascites, or hematemesis 50-60% 5 year survival in patients that do not discontinue use

Answer 158

Increased bilirubin, alkaline phosphatase and aserum aminotransferase Neutrophilic leukocytosis Nonspecific symptoms: malaise, anorexia, weight loss, abdominal discomfort Follows a bout of heavy drinking

Answer 159

Cessation of alcohol+adequate nutrition may slowly clear disease

Answer 160

Hepatic dysfunction: increased aminotransferase, bilirubin, alkaline phosphatase, hyperproteinemia (globulins, albumin, clotting factors) Anemia May be clinically silent Generally irreversible

Answer 161

Hepatic coma Massive GI hemorrhage Intercurrent infection(predisposed to infection) Hepatorenal syndrome after bout with hepatitis Hepatocellular carcinoma

Answer 162

Non alcoholic fatty liver disease

Answer 163

Spectrum of disorders with hepatic steatosis Patients consume<20g alcohol/week 80gm/day of alcohol is considered the threshold for the development of alcoholic liver disease

Answer 164

Increased incidence due to increased obesity and the association with metabolic syndrome Contributes to progression of other liver disease (HBV, HCV) Increased risk of hepatocellular carcinoma Hispanic>african American>caucasion

Answer 165

Insulin resistance leads to hepatic steatosis Hepatocellular oxidative injury leads to liver cell necrosis and inflammatory reactions

Answer 166

Increased high calorie food intake, high fructose corn syrup, decreased exercise, genetic predisposition

Answer 167

Dysfunctional adipose tissue (endocrine organ), decreased production of adiponectin, increased TNFa, IL6=hepatocyte apopotosis

Answer 168

Oxidative damage to mitochondria and plasma membranes

Answer 169

Oxidative damage Further damaged by decreased autophagy and formation of mallory denk bodies

Answer 170

Scar tissue deposition due to kupffer cells, TNF-a, TGF-b which activates stellate cells (which are also activated through the hedgehog signalling pathway

Answer 171

Hedgehog pathway

Answer 172

Pathological steatosis=involvement of >5% of hepatocytes Overlaps with histology of alcoholic hepatitis, but - mononuclear cells more prominent - portal fibrosis more prominent - mallory denk less common 90% of cryptogenic cirrhosis is not considered “burned out” non alcoholic fatty liver disease

Answer 173

Diffuse steatosis and portal fibrosis Portal+parenchymal infiltrate parenchymal neutrophils

Answer 174

Usually asymptomatic or have nonspecific symptoms with RUQ pain Increase AST, ALT—liver dysfunction D

Answer 175

Liver biopsy

Answer 176

Cardiovascular death

Answer 177

Obesity and diabetes

Answer 178

Pattern will be microvesicular steatosis, with large lipid vacuoles filling hepatocytes

Answer 179

Correct obesity, hyperlipidemia, insulin resistance | -address the underlying metabolic syndrome

Answer 180

One of: diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, or insulin resistance Two of: BP>140/90 TG>1.695 and HDL.9 (male) >.85 (female) or BMI>30 Microalbuminuria: urinary albumin excretion>20 or albumin: Cr>30

Answer 181

Excessive iron absorption deposited in parenchymal organs such as the liver and pancreas followed by heart, joints, and endocrine organs

Answer 182

Hereditary or due to excessive intake (secondary)

Answer 183

Slow progression with symptoms appearing in 4th-5th decades for males, later (if ever) for females due to menstruation until menopause - iron accumulation is lifelong - injury caused be excess iron is slow and progressive

Answer 184

Most common cause is associated with ineffective erythropoiesis (severe thalassemia and myelodysplastic syndrome)-excessive iron from transfusion+increased absorption Transfusions, when given repeatedly over a period of years (ie. patients with chronic hemolytic anemia)->systemic hemosiderosis and parenchymal organ injury Chronic liver disease->loss of hepatocyte mass->impaired hepcdin production_>increased iron uptake from the gut->iron overload

Answer 185

Micronodular cirrhsosis in all patients Diabetes mellitus in 75-80% Abnormal skin pigmentation in 75-80%

Answer 186

Mutation in the HFE gene, whose product is involved in intestinal iron uptake by its effects on hepcidin levels

Answer 187

Intestinal absorption of dietary iron is abnormal Net accumulation of .5-1g/yearmanifests with accumulation 20g One of the msot comon genetic disorders in humans

Answer 188

Lipid peroxidation cia iron-catalyze ROS Stimulation of collagen formation by activation of hepatic stellate cells Interaction of ROS and Fe itself with DNA leads to lethal cell injury and predisposition to hepatocellular carcinoma

Answer 189

If cells not fatally injured

Answer 190

Removal of excess iron promotes recovery of function

Answer 191

Main regulator of iron absorption

Answer 192

Lowers plasma iron levels

Answer 193

Ferroportin

Answer 194

Inflammatory cytokines and iron

Answer 195

Iron defiency, hypoxia, and ineffective erythropoiesis

Answer 196

Iron overload

Answer 197

Hemochromatosis

Answer 198

HFE mutation(C282Y>H63D) Chromosome 6, near an HLA locus

Answer 199

Adult form of hemochromatosis

Answer 200

Inactivation of HEF->inactivation/defiency of hepcidin->hemochromatosis

Answer 201

White population

Answer 202

Low penetrance

Answer 203

Worldwide distribution

Answer 204

Less common

Answer 205

Juvenile hemochromatosis | -more severe form of the disease than the adult variety

Answer 206

Deposition of hemosiderin in liver, seen with Prussian blue stain Golden yellow hemosiderin granules initially form, and fibrous septa slowly develop Leads to small, shrunken liver micronodular cirrhosis Iron is directly hepatotoxic and there is no inflammation Late stages the liver is dark brown black due to iron accumulation

Answer 207

Deposition of hemosiderin, seen with Prussian blue stain Intensely pigmented Diffuse interstitial fibrosis Parenchymal atrophy Hemosiderin in islet and acinar cells

Answer 208

Enlarger with hemosiderin granules in myocardial fibers-> striking brown coloration Delicate interstitial fibrosis

Answer 209

Pigmentation due to increased melanin production causing a gray slate color Some due to hemosiderin deposition in dermal macrophages and fibroblasts Mechanism is unknown

Answer 210

Leads to pseudo gout from calcium pyrophosphate deposition

Answer 211

Small, atrophic testes due to hypothalamic pituitary axis disruption and decreased hormone production

Answer 212

Hepatomegaly, abnormal skin pigmentation (espicially in sub exposed areas), deranged glucose homeostasis or DM due to destruction of pancreatic islet cells and cardiac dysfunction (arrhythmia, cardiomyopathy) Atypical arthritis Hypogonadism

Answer 213

Males over 40

Answer 214

200x increased risk of hepatocellular carcinoma

Answer 215

Not fully bc DNA alterations that occur prior to time of diagnosis and initiation fo treatment

Answer 216

Diagnosible long before irreversible tissue damage occurs Look for iron in the tissues with Prussian blue -Prussian blue stains hepatocellular iron blue Screen for high levels of serum iron and ferritin Screen family members

Answer 217

Diagnosis can be made before irrreversible tissue damage occurs Screen for very high levels of serum iron and ferritin, exclusion of secondary causes or iron overload and liver biopsy if still in doubt

Answer 218

Still accumulate excess iron, but not to a level that causes significant tissue damage

Answer 219

Regulat phlebotomy (blood letting) depletes tissue stores or iron=normal life expectancy

Answer 220

Severe liver disease and extrahepatic hemosiderin deposition of unknown origin

Answer 221

Liver injury occurs in utero; may be due to materanla alloimmune injury to fetal liver Extrahepatic hemosiderin deposition (buccal) has to be documented for proper diagnosis

Answer 222

No treatment, supportive care and possible liver transplant

Answer 223

AR disorder via ATP7B

Answer 224

Impaired shopper excretion into bile and failure to incorporate copper into ceruloplasmin which leads to toxic levels of copper in the liver, kidney and eye (also kidney, bones, joints)

Answer 225

Copper absorption and delivery to the liver is normal but excretion into bile is reduced, it is not incorporated into ceruloplasmin and ceruloplasmin secretion into the blood is inhibited Copper accumulated in the liver cause injury via ROS Non ceruloplasmin bound copper spills into circulation leads to hemolysis and pathology elsewhere

Answer 226

Promotes formation of free radicals by the Fenton reaction Binds to sulfhydral groups of cellular proteins Displaces other metals from hepatic metalloenzymes

Answer 227

Fatty change Acute and chronic hepatitis with Mallory denk bodies Eventually leads to cirrhosis +/- necrosis CNS toxicity: basal ganglia atrophy and cavitation Kayser-fleischer rings:green brown copper deposits in descent membrane Can use rhodamine or orcein stains to look for the copper

Answer 228

Elevated Low

Answer 229

Acute or chronic liver disase that presents between 6-40 years Neurological involvement: movement disorders or rigid dystonia (may be confused with parkinsonism)

Answer 230

Basal ganglia Putamen

Answer 231

Poor coordination, chorea, or choreathetosis

Answer 232

Spastic dystonia, mask life fancies, rigidity, and gait disturbances

Answer 233

Land these patients in mental institutions

Answer 234

Copper toxicity to RBC membranes-elevated direct bilirubin

Answer 235

Decreased serum ceruloplasmin Increased hepatic copper content (most sensitive and accurate) - demonstration of hepatic copper content in excess 250 microgram/gram is most helpful - increased urinary copper excretion (most specific screening test)

Answer 236

Long term chelation therapy or zinc based therapy Liver transplant if unmanageable cirrhosis develops;this is curative

Answer 237

AR disorder of protein folding

Answer 238

Wild type 90% of people

Answer 239

Most common clinically relevant genotype

Answer 240

10% of the normal circulating a1-antitrypsin level

Answer 241

Very early with liver disease-a1 antitrypsin defiency is the most commonly diagnosed inherited hepatic disorder in infants and children

Answer 242

Inhibit proteases (neutrophil elastase, cathepsin G, and proteinase 3)

Answer 243

Pulmonary emphysema because activity of destructive proteases is not inhibited Hepatic disease(cholestasis or cirrhosis) because of hepatocellular accumulation of the misfolded protein->ER stress->ER stress (misfolded protein) response->apoptosis

Answer 244

Infants and children

Answer 245

Mutation prevents migration of the protein from the ER to the golgi, leading to accumulation of the protein in the liver All patients with PiZz genotype accumulate protein but only10-25% develop liver disease

Answer 246

Characterized by presence of round to oval cytoplasmic globular inclusions in periportal hepatocytes (*****acidophilic, PAS(+) following diastase digestion of the liver Number of globules does not represent severity of disease Ranges from cholestasis to hepatitis to cirrhosis

Answer 247

Neonatal hepatitis+cholestasis jaundice in 10-20% of affected newborns Adolescence:present with hepatitis , cirrhosis or pulmonary disease (may regres and recur) May be silent until later in life Hepatocellular carcinoma in 2-3% of PiZz adults

Answer 248

Orthotopic liver transplant (cure) In patients with pulmonary disease, the single most preventative measure is avoidance of cigarette smoking

Answer 249

Emulsification of dietary fat in the lumen of the gut through the detergent action of bile salts The elimination of bilirubin, excess cholesterol, xenobiotics, and other waste products that are insufficiently water soluble to be excreted into urine

Answer 250

Complexed onto albumin-unconjugated

Answer 251

Super small amount

Answer 252

No, no matter how high the serum concentration

Answer 253

Into premature infants brain(erythroblastosis fetalis leading to kernicterus)

Answer 254

.3-1.2 mg/dL

Answer 255

>2.5 mg/dL

Answer 256

The ability to conjugate and excrete bilirubin doesn’t occur until about 2 weeks of age It is normal and expected for newborns to go through transient phases of jaundice in the beginning of life Can be exacerbated by breastfeeding due to bilirubin-deconjugate enxymes present in milk

Answer 257

AR complete enzyme defiency No UGT1A1 activity Unconjugated hyperbilirubinemia

Answer 258

Fatal in neonatal period More severe than II

Answer 259

AD, variable penetrance Decreased UGT1A1 activity Unconjugated hyperbilirubinemia

Answer 260

Mild clinical course with only occasional kernicterus

Answer 261

AR decreased UGT1A1 activity Innocuous Unconjugated hyperbilirubinemia

Answer 262

AR Mutated MRP2 Conjugated hyperbilirubinemia Innocuous Impaired excretion of bilirubin glucuronides

Answer 263

Black liver Mutated canalicular MDR protein 2 Pigmented cytoplasmic globules Innocuous

Answer 264

AR Conjugated hyperbilirubinemia

Answer 265

Impaired bile formation and flow->accumulation of bile pigment within the hepatic parenchyma

Answer 266

Jaundice, pruritus, skin xanthomas, malabsorption, vitamin ADEK deficiencies

Answer 267

Characteristic elevated serum y-glutamyl transpeptidase (GGT) and alkaline phosphatase ALT and AST are normal as they indicate there has been loss of hepatocytes integrity

Answer 268

Hepatic parenchyma

Answer 269

Droplets of bile pigment that can be found in hepatocytes with a fine, foamy appearance

Answer 270

Periportal

Answer 271

Extrahepatic cholelithiasis, malignancies of the biliary tree or head of the pancreas, strictures resulting from previous surgical procedures

Answer 272

Biliary atresia, cystic fibrosis,choledochal cysts, and syndromes in which there are insufficient intrahepatic bile ducts

Answer 273

Extrahepatic bile obstruction is treatment with surgery

Answer 274

Biliary atresia, cystic fibrosis, choledochal cysts, and syndromes in which there are insufficient intrahepatic bile ducts

Answer 275

A secondary bacterial infection of the biliary tree that aggravates the inflammatory injury

Answer 276

Subtotal or intermittent obstruction

Answer 277

Enteric bugs like coliforms and enterococci

Answer 278

Fever, RUQ pain, jaundice Also get chills

Answer 279

Influx of periductular neutrophils directly into the bile duct epithelial and lumen

Answer 280

Liver failure

Answer 281

Suppurative cholangitis (most severe; risk of sepsis)

Answer 282

Purple NT bile fills and distended bile ducts Frequently complicated by sepsis (instead of cholestasis)—sepsis is life threatening

Answer 283

Abscess formation, bacterial cholangitis

Answer 284

Ischemia related to hypotension caused by sepsis, espicially when liver is cirrhosis

Answer 285

Most likely to lead to the cholestasis of sepsis Most commmon form of this==canalicular cholestasis - bile plugs within predominantly ventriloquial canaliculi - associated with activation of kupffer cells and mild portal inflammation - hepatocyte necrosis is scant or absent

Answer 286

Dilated canals of hearing and bile duct ulcers at the interface of portal tracts and parenchyma become dilated and contain obvious bile plugs

Answer 287

Due to chronic biliary obstruction and ductular reactions that lead to periportal fibrosis and eventually hepatic scarring and nodule formation There may also be bile infarcts from the detergent effects of the extravasated bile

Answer 288

Disease of intrahepatic gallstone formation that leads to repeated bouts of ascending cholangitis, progressive inflammatory destruction of hepatic parenchyma, and predisposes to biliary neoplasia

Answer 289

Pigmented Ca bilirubinate stones in distended intrahepatic bile ducts Ducts show chronic inflammation, mural fibrosis, and peribiliary gland hyperplasia Biliary dysplasia may also be seen—>may evolve to invasive cholangiocarcinoma

Answer 290

Cholangiocarcinoma by unknown mechanism

Answer 291

Liver injury/inflammation in the neonate Leads to jaundice, dark urine, light or acholic stools, hepatomegaly There may be varying levels of impaired hepatic synthetic function

Answer 292

Prolonged conjugated hyperbilirubinemia in the neonate after 2 weeks (not physiological jaundice of the newborn)

Answer 293

* panlobular giant-cell transformation of hepatocytes - lobular disarray with local liver cell apopotosis and necrosis - hepatocellular and canalicular cholestasis - mild mononuclear infiltration of the portal areas with reactive changes in kupffer cells - extramedullary hematopoiesis

Answer 294

Complete or partial obstruction of the lumen of the extrahepatic biliary tree within the first three months of life

Answer 295

Biliary atresia

Answer 296

Associated with other anomalies resulting from ineffective establishment of laterality of thoracic and abdominal organs during development Due to aberrant intrauterine development of the extrahepatic biliary tree

Answer 297

Most common 80% Destruction of the normal biliary tree shortly after birth Rotavirus, CMV, reovirus, autoimmune are all implicated Genetic basis

Answer 298

Inflammatory and fibrosis stricture of the hepatic or common bile ducts Progressive destruction of the intrahepatic biliary tree

Answer 299

Neonatal cholestasis, but normal weight gain Normal stools change into acholic stools Jaundice lasts longer than 2 weeks

Answer 300

6-12 mg/dL

Answer 301

Leads to cirrhosis in 3-6 months after birth, death by 2

Answer 302

If limited to common duct(typeI) or left/right hepatic ducts(typeII):Kauai procedure Obstruction above the porta hepatitis(typeIII): not correctable (90%) and needs liver transplant -no patent bile ducts amendable to surgical anastomsis

Answer 303

Non-suppurative, inflammatory destruction of small/medium-sized intrahepatic bile ducts -not the large or extrahepatic ducts

Answer 304

Not really

Answer 305

Florid duct

Answer 306

Disease of middle aged women :40-50 year old femmes that live in Northern European countries (England Scotland) or northern US(Minnesota) North south gradient Family member with primary biliary cirrhosis

Answer 307

Anti-mitochondrial antibodies )anti-PDC-E2) Florid duct lesion: interlobular ducts are actively destroyed by lymphoplasmacytic inflammation with or without granulomas Patchy loss of the ducts Feathery degeneration and ballooned, bile stained hepatocytes with mallory denk bodies Hepatocyte loss, regenerative hyperplasia, hepatomegaly Widespread duct loss that leads to cirrhosis and periportal/periseptal cholestasis->end stage Widespread modularity without the surrounding scar tissu seen in cirrhosis (nodular regenerative hyperplasia)->portal HTN

Answer 308

Biopsy (look for florid duct lesion)

Answer 309

Alkaline phosphatase and GGT

Answer 310

Patients may have progressive fatigue and pruritis Secondary symptoms may appear: hyperpigmentatoin, xanthelasmas, steatorrhea, vitamin D malabsorption_>osteomalacia/osteoporosis

Answer 311

Other autoimmune disorders; shorten syndrome (xerostomia, xeropthalmia), sclerosis, thyroiditis, rheumatoid arthritis, raynaud phenomenon, and celiac disease

Answer 312

Early stage-ursodeoxycholic acid to slow progression Late stage-liver transplant (ursodeoxycholic acid is ineffective)

Answer 313

Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts with dilation of preserved segments -see beading on radiographs

Answer 314

Beading seen on radiographs

Answer 315

More likely to affect males 20-40 yo If first degree relative has primary sclerosing cholangitis

Answer 316

IBD(ulcerative colitis) coexists win about 70% of patients with PSC May lead to biliary intraepithelial neoplasia and cholangiocarcinoma with fatal utcomes

Answer 317

PANCAs Atypical perinuclear antineutrophillic cytoplasmic antibodies

Answer 318

Neutrophilic infiltration of the epithelium on a chronic inflammatory backgrounf The inflammation and edema lead to obstruction and scarring that narrow the lumens

Answer 319

Little inflammation with onion skin fibrosis around an atrophic duct lumen that leads to obliteration by a tombstone scar

Answer 320

The liver becomes cholestasis that can lead to primary biliary cirrhosis

Answer 321

Persistent elevation of serum alkaline phosphatase There may be progressive fatigue pruritis and jaundice Acute bouts of ascending cholangitis Typically progresses over 5-17 years leading to cholestasis

Answer 322

Radiology of the larger ducts will show strictures and beading with pruning of the smaller ducts Diagnosis is made by radiologic imaging of the biliary tree

Answer 323

No real treatment | Transplant at end stage

Answer 324

Congenital dilation of the common bile duct

Answer 325

Present most often in kids before 10 years old as jaundice or recurring abdominal pain (symptoms of typical biliary colic) 3-4x more likely in females

Answer 326

Group of different lesions int he liver due to congenital malformations of the biliary tree (ductal plate malformation)

Answer 327

Most are incidental findings, but can also present as hepatosplenomegaly or portal HTN without hepatic dysfunction in late childhood or adolescence

Answer 328

Commonly happens in association with autosomal recessive polycystic renal disease Patients have an increased risk of cholangiocarcinoma

Answer 329

Von meyenburg complexes Caroli disease Congenital hepatic fibrosis

Answer 330

Small bile duct hamartomas that are normal if limited, but indicative of FPD if they are diffuse

Answer 331

Biliary cysts in isolation that lead to clinical symptoms Carli syndrome: biliary cysts that occur with congenital hepatic fibrosis

Answer 332

Portal tracts are enlarged by irregular broad bands of collagenous tissue that form septa to divide the liver into irregular islands - abnormally shaped bile ducts embedded in the fibrous tissue still connected to the biliary tree - may have portal HTN as a result

Answer 333

Clinically significant liver function abnormalities do not always develop Hepatic morphology may be strikingly affected

Answer 334

Liver infarcts are rare due to dual blood supply to the liver Loss of blood supply intrahepatic can lead to localized infarct that is pale or hemorrhagic Transplanted livers are more likely to become infarcted as they only have blood supple from the arterial system

Answer 335

Impaired blood flow to the liver

Answer 336

Portal vein

Answer 337

Physical sinusoidal occlusion

Answer 338

Sickle cell disease Disseminated intravascular coagulation Eclampsia Diffuse intrasinusoidal metastatic tumor

Answer 339

Esophageal varices

Answer 340

Schistosomiasis

Answer 341

Sinusoidal dilation that occurs in any condition in which efflux of hepatic blood is impeded Blood lakes (due to sex hormones, infection)

Answer 342

Passive congestion

Answer 343

Hepatic hypoperfusion and hypoxia->ischemic coagulative necrosis of hepatocytes in the central region of the lobule (centrilobular fibrosis)

Answer 344

Cardiac sclerosis with centrilobular fibrosis Nutmeg liver:hypoperfusion and retrograde congestion

Answer 345

Obstruction of two or more major hepatic veins that leads to hepatomegaly, pain and ascites

Answer 346

High mortality

Answer 347

Liveris swollen red purple, and has a tense capsule There are different areas of preserved or regenerating parenchyma alternating with hemorrhagic collapse Severe centrilobular congestion and necrosis, or fibrosis if slowly developing Affected veins may contain thrombi

Answer 348

Surgery to create a portosystemic venous shunt permits reverse flow throug the portal vein and improves the prognosis (5 year survival>67%)

Answer 349

Obliteration of the terminal hepatic venues by subendothelial swelling and collagen deposition

Answer 350

Jamaican bush tea drinkers 3 weeks after stem cell transplant Cancer patients receiving chemotherapy Toxic injury to the sinusoidal endothelium

Answer 351

Centrilobular congestion, hepatocellular necrosis, and accumulation of hemosiderin macrophages Obliteration of the lumen of the venue is identified with special stains for connective tissue

Answer 352

Histology=gold standard of diagnosis Clinical diagnosis=tender hepatomegaly, ascites, weight gain, jaundice

Answer 353

Hepatic manifestations of systemic circulatory compromise

Answer 354

Graft vs host | Attack the liver

Answer 355

Host vs graft | Attacks the liver

Answer 356

10-50 days

Answer 357

Donor lymphocytes attach the epithelial cells of the liver Hepatitis with necrosis or hepatocytes and bile duct epithelial cells Inflammation of the portal tracts and parenchyma

Answer 358

Portal tract inflammation, selective bile duct destruction, and eventual fibrosis

Answer 359

Cellular Vascular

Answer 360

Characterized by infiltration of a mixed portal inflammatory infiltrate Associated with bile duct injury and endothelitis

Answer 361

Obliteration arteriopathy of small and large arteries leads to ischemic changes int he liver parenchyma Vanishing bile duct syndrome*

Answer 362

Viral hepatitis (most common cause of pregnant jaundice) Hepatic complications that are directly attributable to pregnancy in .1% Preeclampsia and eclampsia

Answer 363

HAV, HBV, HCV, or HBV+HBD HEV infectionruns a more severe course in pregnancy and has a mortality rate of 20%

Answer 364

Maternal HTN, proteinuria, peripheral edema, and coagulation problems

Answer 365

When hyperreflexia and convulsions

Answer 366

Hemolysis Elevated liver enzymes Low platelets (thrombocytopenia)

Answer 367

Periportal sinusoids contain fibrin deposits associated with hemorrhage into the space of disse with associated hemorrhagic necrosis Blood presssure can lead to hematoma and may rupture

Answer 368

Modest to severe elevation of serum aminotransferases and mild elevation of serum bilirubin

Answer 369

Latter half of pregnancy, often int he third trimester

Answer 370

Hepatic dysfunction that can lead to hepatic failure, coma, and death in severe cases

Answer 371

Serum aminotransferase levels

Answer 372

Bleeding, nausea, vomiting, jaundice, and coma

Answer 373

Characteristic diffuse microvesicular steatosis of hepatocytes on biopsy May be lobular disarray with hepatocyte dropout, reticulin collapse, and portal tract inflammation (looks like viral hepatitis)

Answer 374

Can progress very quickly to hepatic failure and death in a few days

Answer 375

Termination of pregnancy

Answer 376

Onset of pruritus, followed by darkening of urine and occasionally light (acholic) stools and jaundice in the 3rd trimester

Answer 377

Serum bilirubin and alkaline phosphatase may be slightly elevated Bile salt levels are greatly increased

Answer 378

Generally a benign condition to mother Incidence of fetal distress, stillbirth, and prematurity is moderately increased

Answer 379

Single or multiple nodules may develop n a non cirrhosis liver either from focal nodular hyperplasia or nodular regenerative hyperplasia

Answer 380

Due to focal or diffuse alterations in hepatic blood obliteration of portal vein radicle and compensatory flow of arterial blood supply

Answer 381

Benign;well demarcated but poorly encapsulated Spontaneous mass lesion that appears in a normal liver

Answer 382

Young to middle aged adults

Answer 383

Tighter than the surrounding liver and is sometimes yellow from steatosis Central grey-white depressed stellate scar (containing vessels with fibromuscular hyperplasia) that fibrous septa radiate outward from

Answer 384

Entire liver is transformed into nodules, looks similar to focal nodular hyperplasia, but there is no fibrosis

Answer 385

Portal HTN

Answer 386

Conditions that affect intrahepatic blood flow like HIV or autoimmune

Answer 387

Usually asymptomatic, only found at autopsy

Answer 388

Plump hepatocytes are surrounded by rims of atrophic hepatocytes

Answer 389

Cavernous hemangiomas

Answer 390

Blood vessels

Answer 391

Red blue nodules located directly under the capsule Vascular channels in a bed of fibrous CT

Answer 392

Found incidentally or after hemorrhage | -might be mistaken radiographically or intraoperatively for metastatic tumors

Answer 393

Benign neoplasm developing from hepatocytes

Answer 394

Intrabdominal bleeding that is a surgical emergency

Answer 395

Oral contraceptive therapy and anabolic steroids (so sex hormones) -HEPATOCELLUAR ADENOMAS WERE UNKNOWN BEFORE THE ADVENT OF ORAL CONTRACEPTIVES

Answer 396

HNF1-a inactivated adenomas B-catenin activated adenomas Inflammatory adenomas

Answer 397

No risk of malignant transformation

Answer 398

Fatty with no atypia Look for NO staining with liver fatty acid binding protein (LFABP)

Answer 399

Use of oral contraceptives and anabolic steroids (so sex hormones)

Answer 400

High degree of dysplasia | Look for glutamine synthetase diffusely and b catenin in the nucleus

Answer 401

NAFLD Mutations in gp130 (IL6, JAK-STAT pathway)

Answer 402

Small, but definite risk of malignant transformation

Answer 403

Characteristically have in addition areas of fibrotic stroma, mononuclear inflammation, ductular reactions, dilated sinusoids, and telangiectatic vessels Over express CRP and serum amyloid A

Answer 404

Hepatoblastoma

Answer 405

Epithelial Mixed epithelial and mesenchymal type

Answer 406

Small polygonal fetal cell or smaller embryonal cells forming acini, tubules, or papillary structures vaguely looking like liver development

Answer 407

Foci of mesenchymal differentiation with osteoporosis, cartilage, or striated muscle

Answer 408

``` WNT pathway (APC mutation) *patients with familial adenomatous polyposis frequently develop hepatoblastoma ```

Answer 409

Familial adenomatous polyposis and beckwith-wiedemann syndromes

Answer 410

Hepatocellular carcinoma

Answer 411

HBV in Asian countries, HCV in USA (both turn chronic) Alcohol, AFLATOXIN, a1AT, hemochromatosis, NAFLD, wilson disease, adenomas

Answer 412

B catenin activation and p53 inactivation (aflatoxin) are the two most common mutational events May be associated with Il-6/HNF4-a

Answer 413

No atypia, have a higher risk of becoming high grade nodules Shown to be colonial and are probably neoplastic

Answer 414

Signs of atypia, have a great risk of becoming HCC and HCC foci are often found already in nodules

Answer 415

High grade dysplastic nodules

Answer 416

Scattered hepatocytes near portal tracts or septa that are larger than normal hepatocytes with large multiple pleomorphic nuclei Nuclear cytoplasmic ratio is normal Large cell change is a marker of increased risk of hepatocellular carcinoma-considered directly pre malignant in hepatitis B

Answer 417

High nuclear cytoplasmic ration and mild nuclear hyperchromasia/pleomorphism Hepatocytes will commonly form tiny nodules within a single parenchymal lobule Directly premalignant

Answer 418

Large univocal mass Multifocal, widely distributed nodules Diffusely infiltration cancer

Answer 419

By either vascular invasion or direct extension, become more likely once tumors reach 3 cm in size

Answer 420

The larger, primary masss

Answer 421

The most likely route for extrahepatic metastasis, espicially by the venous system

Answer 422

Espicially to the lung, tend to occur late in the disease

Answer 423

Common liver dysfunction symptoms and hepatomegaly

Answer 424

50 Insensitive as a screening test for pre malignant or early lesions

Answer 425

Cachexia, GI or varices bleeding, liver failure, or rarely from tumor rupture and hemorrhage

Answer 426

Die in 2 years

Answer 427

Rare variant of hepatocellular carcinoma

Answer 428

Single large hard scirrhous tumor with fibrous bands coursing through it

Answer 429

Well differentiated cells rich in mitochondria growing in nests or cords separated by parallel lamellae of dense collagen bundles

Answer 430

Second most common primary malignant tumor after HCC Cancer of the biliary tree coming from bile ducts within and outside the liver Adenocarcinoma

Answer 431

Liver flukes (opisthorchis, clonorchis) Chronic inflammation of the large bile ducts HBV, HCV, NAFLD (same as HCC)

Answer 432

Perihilar tumors (klaskin tumors) located at the junction of the hepatic ducts (most common) Common bile duct, posterior to the duodenum

Answer 433

Only 10% of tumors

Answer 434

Biliary intraepithelial neoplasia (low to high grade: Bi1IN-1,2,3) 3 is the highest grade and has the highest risk of malignant transformation

Answer 435

Form grey nodules in the bile duct wall that can be diffuse to papillary Generally small lesions at the time of diagnosis

Answer 436

Track along the intrahepatic portal tract system that creates a branching tumor within a portion of the liver

Answer 437

Moderately well Glandular/tubular Epithelial

Answer 438

Median time to death is 6 months for intrahepatic, but overall for any location is 14% 2 year survival

Answer 439

Present as obstruction to bile flow or symptomatic liver mass

Answer 440

Biliary obstruction , cholangitis, and RUQ pain

Answer 441

Suggest an origin from a multipotent stem cell

Answer 442

May occur as in situation lesion or as invasive cholangiocarcinoma

Answer 443

Has historic association with vinyl chloride, arsenic, or thorotrast

Answer 444

Middle aged men

Answer 445

HBV, HCV, HIV< PBC

Answer 446

Most are diffuse large B cell lymphomas, then MALTomas

Answer 447

Young adult males

Answer 448

Hepatic and splenic sinusoids as well as the marrow

Answer 449

Metastases

Answer 450

Colon, breast, lung, pancreas

Answer 451

Appear as multiple nodular metastases that replace most of the parenchyma and lead to hepatomegaly, but can also appear as just a single nodule Usually clinically silent until late stage

Answer 452

A fundus that is folded inwards, creating a phrygian cap

Answer 453

Cholelithiasis

Answer 454

Stones of either cholesterol or pigment (bilirubin) that collect in the gallbladder

Answer 455

Diet Infections

Answer 456

Middle to older age female Obesity, metabolic syndrome Estrogen exposure (OC, pregnancy) Native Americans Gallbladder stasis ABCG8 variant (ABC transport)

Answer 457

Collect when their concentration increases above the capacity of the bile-precipitate out of bile Can happen when there is too much cholesterol, crystal nucleation, mucus secretion, or hypomotility Cholesterol stones are more common in the US and western countries-probably do to diet

Answer 458

Stones of unconjugated bilirubin and inorganic calcium salts Can happen when there are elevated levels of unconjugated bilirubin in the bile - chronic hemolytic anemia - severe ideal dysfunction or bypass - bacterial contamination of the biliary tract leading to release of beta-glucuronidases(e coli, ascaris, lumbricoides, liver fluke c sinensis) Arise primarily in te setting of bacterial infections of the biliary tree and parasitic infestations

Answer 459

In gallbladder Pure cholesterol stones look pale yellow, finely granular, hard, crystalline palisade - stones composed largely of cholesterol are radiolucent - sufficient calcium carbonate renders 10-20% of them radiopaque - BECOME MORE BLACK and are more lamellated when they are mixed with other substances

Answer 460

Black stones are found in sterile bile ducts and are made up mostly of bilirubin, salts, and mucin. Appear friable with speculated and molded contours 50-70% of black stones are radioopaque due to calcium salts Brown stones are found in infected large bile ducts ; composition is the same, but also have some cholesterol mixed in and are found in ducts with infections. Soap like, greasy, soft, laminated -radiolucent because they contain calcium soaps

Answer 461

Usually asymptomatic Biliary colic=excruciating constant pain Pain in RUQ that radiates to the right upper shoulder or the back, which is worse after a fatty meal***

Answer 462

Small stones (gravel) are more dangerous Gallstones ileus/bouveret syndrome: when a large stone erodes directly into an adjacent loop of small bowel and generates intestinal obstruction

Answer 463

Acute cholecystitis

Answer 464

From chemical irritation and inflammation from a stone - absence of bacterial infection (though one may develop later in the course) - 90% of the time caused by obstruction of the neck or cystic duck by a stone - most common reason for an emergency cholecystectomy

Answer 465

May occur in severely ill patients - accounts for the other 10% - frequently develops in diabetic patients who have symptomatic gallstones - though to result from ischemia (cystic artery=end artery) - primary bacterial infection 9salmonella typhi and staphylococci) - incidence of gangrene and perforation is much higher in acalculous that’s in calculous

Answer 466

Sepsis with hypotension and multisystem organ failure, inspired, major trauma and burns, diabetes, infections

Answer 467

Gallbladder is enlarged and tense, may be green-black, bright red, or blotchy Serosa covering is typically covered in a fibrous exudate In calculous cholecystitis, the stone is blocking the exit and causes the lumen to fill with cloudy or turbid material that may contain fibrin

Answer 468

When the exudate is virtually pure pus

Answer 469

Wall is thickened, edematous, and hyperemic

Answer 470

Wall is green-black and necrotic (gangrenous cholecystitis)

Answer 471

When the gallbladder is invaded by gas forming organisms (clostridium and coliforms)

Answer 472

When the gallbladder is invaded by gas forming organisms

Answer 473

Most patients have experienced pain before the acute attack The acute attack: progressice pain in the RUQ or epigastric that lasts longer than 6 hours Mild fever, anorexia, tachycardia, sweating, nausea, and vomiting

Answer 474

Slightly elevated

Answer 475

Obstruction of the common bile duct

Answer 476

25% will need surgery, other patients will recover in 10 days

Answer 477

Gangrene Perforation

Answer 478

Chronic inflammation of the gallbladder that is due to stones in 90% of the time Can be due to repeated acute attacks, but many times is not At risk population is the same as that for cholelithiasis

Answer 479

Serosa may be dulled to subserosal/subepithelial fibrosis Wall is variably thickened, has a grey white appearance Reactive proliferative may lead to fusion of the mucosal folds and give rise to buried crypts of epithelial in the gallbladder

Answer 480

Outpouching of the mucosal epithelium through the wall | -diverticulum of the gallbladder

Answer 481

Rare calcification of the wall that increases the risk of developing cholangiocarcinoma

Answer 482

Very thick wall and the gallbladder is shrunken, nodular with foci of necrosis and hemorrhage that was triggered by rupture of R-A sinuses. Leads to foam (xanthoastrocytoma) cells

Answer 483

Atrophic, chronically obstructed, often dilated gallbladder that may contain only clear secretions

Answer 484

Recurring acute symptoms with intolerance for fatty foods Beware of bacterial secondary infections, perforation, fistula, and obstruction

Answer 485

Adenocarcinoma of the gallbladder

Answer 486

Women Chile, Bolivia, northern India, south western ethnic US population HAVING GALLSTONES

Answer 487

Biggest risk factor is having gallstones, 1-2% of stone patients get cancer 95% of gallbladder cancers arise in the setting of gallstones Though that chronic inflammation is reason cancer comes

Answer 488

Poorly defined area of mural thickening and induration | More common

Answer 489

Grows intot he lumen (and invades the underlying wall)

Answer 490

Infiltrating

Answer 491

Fistula penetration into other viscera

Answer 492

Cystic duct, adjacent bile ducts, portal hepatic lymph nodes, peritoneum, GI tract and lungs

Answer 493

At surgery when he gallbladder is though to have stones

Answer 494

Same as those for cholelithiasis: abdominal pain, jaundice, anorexia, nausea, vomiting

Answer 495

5 years survival is <10%

Answer 496

ERBB2 (Her-2/neu)

Chapter 18 Flashcards

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