The Liver The Liver Sometime in December Sometime in December Normal Liver Normal Liver •
• Located in the RUQ of the abdomenLocated in the RUQ of the abdomen
•
• Wt 1500g (2.5% of TBW)Wt 1500g (2.5% of TBW) •
• In surgery, divided into 8 lobes – caudate lobe (1In surgery, divided into 8 lobes – caudate lobe (1stst
lobe), the remaining (2
lobe), the remaining (2ndnd to to 88thth lobe); designated onlobe); designated on
the basis of blood supply the basis of blood supply
•
• Histologically, are composed of hexagonal lobulesHistologically, are composed of hexagonal lobules
o
o In the center: terminal hepatic veinIn the center: terminal hepatic vein o
o In In ththe e pepeririphpheryery: : hehepapatitic c trtracact t (p(porortatal l veveinin,,
hepatic artery & bile duct) hepatic artery & bile duct)
o
o Hepatic plates with thin layer of Hepatic plates with thin layer of endothelial cellsendothelial cells o
o SteStellallate te celcells ls whwhich ich arare e preprecurcursorsors s of of fibfibrourouss
tissue which proliferates in cirrhosis tissue which proliferates in cirrhosis
Patterns of Hepatic Injury
Patterns of Hepatic Injury
A
A.. DDEEGGEENNEERRAATTIIOON N ANAND D IINNTTRRAACCEELLLLUULLAARR ACCUMULATION
ACCUMULATION
•
• SweSwellilling ng (re(reverversibsible)le), , balballoolooninning g ((cluclumpimping ng oo
organelles)
organelles) degenerationdegeneration
•
• Feathery degenerationFeathery degeneration (in (in cholestasischolestasis)) •
• SteatosisSteatosis (there is displacement of nucleus)(there is displacement of nucleus)
o
o MiMicrcrovovesesiciculular ar - - acacutute e fafatttty y lilivever r of of
pregnancy pregnancy
o
o Macrovesicular – diabetic/ Macrovesicular – diabetic/ obese pxobese px o
o Both – alcoholic fatty liverBoth – alcoholic fatty liver
B.
B. NECNECROSROSIS IS ANAND AD APOPPOPTOSTOSISIS
•
• Ischemic coagulative necrosis- poorly stained &Ischemic coagulative necrosis- poorly stained &
mummified, lysed nuclei mummified, lysed nuclei
•
• Apoptotic cell death (Apoptotic cell death (when there is continuouswhen there is continuous
injury)
injury) –sh–shrunrunkeken, n, pykpyknotnotic ic and and intintensenselyely eosinophilic cells obtaining fragmented nuclei eosinophilic cells obtaining fragmented nuclei
•
• LLyyttiic c cceelll l ddeeaatth h ((oouuttccoomme e oof f bbaalloooonniingng
degeneration) degeneration)
•
• Centrilobular – drug and Centrilobular – drug and toxic reactionstoxic reactions •
• Midzonal - rareMidzonal - rare •
• Periportal – eclampsiaPeriportal – eclampsia •
• FoFocalcal/ / spospotty tty – – scascattettered red celcells ls wiwithithin n hephepatiaticc
lobules lobules
•
• Bridging necrosis - contigousBridging necrosis - contigous
C.
C. ININFLFLAMAMMAMATITIONON
•
• HepHepatiatitis tis – – injinjury ury to to the the livliver er assassociociateated d wiwithth
influx of acute and
influx of acute and chronic inflammatory cellschronic inflammatory cells
•
• Viral hepatitisViral hepatitis
o
o quiesquiescent lymphocytcent lymphocyte e may may collcollect ect into theinto the
portal tracts portal tracts
o
o SpSpilill l ovover er the the peperiripoportrtal al paparerencnchyhyma ma asas
activated lymphocytes activated lymphocytes D.
D. REREGEGENENERARATITIONON
•
• RegRegenerateneration occurs ion occurs in in all but all but most fulminamost fulminantnt
hepatic disease hepatic disease
•
• Hepatocyte proliferation is Hepatocyte proliferation is marked by:marked by:
o
o MitosesMitoses o
o Thickening of the hepatocyte Thickening of the hepatocyte cordscords o
o DiDisosorrgaganinizzatatiioon n of of the the paparrenenchchymymaall
architecture architecture E
E.. FFIIBBRROOSSIISS
•
• FFiibbrroouus s ttiissssuue e – – foforrmmeed d iin n rreessppoonnsse e ttoo
inflammation or direct toxic insult inflammation or direct toxic insult
•
• Points to generally irreversible hepatic damagePoints to generally irreversible hepatic damage
Hepatic Failure
Hepatic Failure
•
• End pointEnd point
o
o 80-90 % of hepatic functional capacity is eroded80-90 % of hepatic functional capacity is eroded o
o 70-95 % mortality70-95 % mortality
•
• Morphologic alterations that causes hepatic Morphologic alterations that causes hepatic failurefailure
o
o Massive hepatic necrosisMassive hepatic necrosis o
o Chronic liver disease – most common routeChronic liver disease – most common route o
o Hepatic dysfunction without overt necrosisHepatic dysfunction without overt necrosis
•
• Clinical featuresClinical features
o o Jaundice Jaundice o o HypoalbuminemiaHypoalbuminemia o o HyperammonemiaHyperammonemia o
o Fetor hepaticusFetor hepaticus o
o Portosystemic shuntingPortosystemic shunting
o
o HyperestrogenemiaHyperestrogenemia
MR*, Mel, Eisa
•
• Life threateningLife threatening
o
o Susceptible to multiple organ failureSusceptible to multiple organ failure o
o CoagulopathyCoagulopathy
Impaired synthesis of CF II, VII, IX, XImpaired synthesis of CF II, VII, IX, X o
o MaMassssivive e GI GI blbleeeedidingng e.g. e.g. gastgastroesroesophaophagealgeal
varices varices
Further metabolic load on the liverFurther metabolic load on the liver •
• Hepatic encephalopathyHepatic encephalopathy o
o Subtle behavioral changes to confusionSubtle behavioral changes to confusion àà stuporstupor à
àcomacoma
o
o Neurologic signsNeurologic signs
RigidityRigidity HyperreflexiaHyperreflexia AsterixisAsterixis o
o Increase ammonia levelsIncrease ammonia levels
•
• Hepatorenal syndromeHepatorenal syndrome
o
o Functional abnFunctional abn
Na retentionNa retention
Impaired water excretionImpaired water excretion
Decrease renal perfusion and GFRDecrease renal perfusion and GFR
Drop in urine output assoc with rising BUNDrop in urine output assoc with rising BUN
and creatinine and creatinine
Cirrhosis
Cirrhosis
•
• Among top 10 causes of deathAmong top 10 causes of death
•
• CharacteristicsCharacteristics o
o Bridging fibrous septaeBridging fibrous septae
o
o ParenchymParenchymal al nodulesnodules formed by septaeformed by septae
o
o Disruption of the architectureDisruption of the architecture
•
• PathogenesisPathogenesis
o
o Collagen Types I & III are normally inCollagen Types I & III are normally in
Portal tract, central vein, space of Portal tract, central vein, space of DisseDisse o
o Type I & III collagen Type I & III collagen ààdeposited in lobulesdeposited in lobules
o
o New vascular channelsNew vascular channels
o
o Deposition of collagen in Space of DisseDeposition of collagen in Space of Disse (loss of (loss of
hepatic plates and endothelial cells) hepatic plates and endothelial cells)
o
o LosLoss s of of fenesfenestratitrations ons in in sinussinusoidal endothelioidal endothelialal
cells cells
o
o No exchange of solutes between hepatocytes &No exchange of solutes between hepatocytes &
plasma plasma
o
o Impaired secretion of proteinsImpaired secretion of proteins
•
• PerisinusoiPerisinusoidal stellate dal stellate cellscells
o
o Source of fibrosisSource of fibrosis
o
o Vitamin A fat storing cells (normally)Vitamin A fat storing cells (normally)located inlocated in
space of Disse space of Disse
o
o AActctivivatated ed in in cicirrrrhohosisiss (s(stitimumulalated ted inintoto
myofibroblasts) myofibroblasts)
Robust mitotic activityRobust mitotic activity
Shift from resting lipocyte to myofibroblastShift from resting lipocyte to myofibroblast
phenotype phenotype
IInnccrreeaasse e ccaappaacciitty y ffoor r ssyynntthheessiis s oof f
extracellular matrix extracellular matrix
•
• Clinical featuresClinical features
o
o May be clinically silentMay be clinically silent o
o AnorexiaAnorexia o
o Weight lossWeight loss
o
o WeaknessWeakness o
o OsteoporosisOsteoporosis o
o Frank debilitationFrank debilitation
•
• MMecechahaninissm m oof f cicirrrrhohotiticc
deaths deaths
o
o ProgressProgressive liver ive liver failurefailure
o
o Complications related toComplications related to
portal hypertension portal hypertension o o DDeevveellooppmmeennt t oof f hepatocellular hepatocellular carcinoma carcinoma Portal Hypertension Portal Hypertension •
• Increase resistance to bloodIncrease resistance to blood
flow flow
•
• PrPre-he-hepaepatictic, , pospost t hepahepatictic,,
intrahepatic intrahepatic
•
o
o InInc c reresisiststancance e to to poportrtal al flflow ow at at ththe e lelevevel l of of
sinusoids sinusoids
o
o Compression of terminal hepatic veinCompression of terminal hepatic vein o
o Expansile nodulesExpansile nodules
•
• Clinical ConsequencesClinical Consequences o
o Ascites – at least 500 mlAscites – at least 500 ml
o
o Intestinal fluid leakage, renal retention of Na &Intestinal fluid leakage, renal retention of Na &
H20 H20
o
o Portosystemic venous shunts - bypassPortosystemic venous shunts - bypass o
o RReeccttuumm, , ccaarrddiiooeessoopphhaagegeaal l jjxn xn ((665%5%)),,
retroperitoneum retroperitoneum
o
o FFalciform ligament alciform ligament (periumbilical collaterals)(periumbilical collaterals) o
o Congestive splenomegaly – 1,000gCongestive splenomegaly – 1,000g o
o Hepatic encephalopathyHepatic encephalopathy
Jaundice & Cholestasis
Jaundice & Cholestasis
•
• BiBililirurubibin- n- enend d prprododucuct t of of
heme degradation heme degradation
•
• UGT1A1 – a product of UGTUGT1A1 – a product of UGT
1
1 ggeenne e llooccaatteed d oonn chromosome 2q37
chromosome 2q37
•
• Causes of JaundiceCauses of Jaundice
o o Predominantly Predominantly Unconjugated Unconjugated Hyperbilirubinemia Hyperbilirubinemia
ExcExcess ess proproducductiotionn
of bilirubin of bilirubin
Hemolytic anemiasHemolytic anemias
ResResorptiorption on of of bloodblood
ffrroom m iinntteerrnnaall hemorrhage hemorrhage IneffectiveIneffective erythropoiesis erythropoiesis sy
syndndroromemes s (e(e.g.g.,., perni
pernicioucious s anemianemia,a, thalassemia)
thalassemia)
RRededucuceed d hhepepaatiticc
uptake uptake
DrDrug ug ininteterferfererencncee
w
wiitth h mmeemmbbrraannee carrier systems
carrier systems
Some cases of Gilbert syndromeSome cases of Gilbert syndrome
Impaired bilirubin conjugationImpaired bilirubin conjugation
Physiologic jaundice of the newborn (decreasedPhysiologic jaundice of the newborn (decreased
UGT1A1 activity, decreased
UGT1A1 activity, decreased excretioexcretion)n)
Breast milk jaundice (β-glucuronidases in milk)Breast milk jaundice (β-glucuronidases in milk)
GenetGenetic ic deficdeficiency iency of of UGUGT1A1 T1A1 actiactivity vity (Cri(Crigler
gler--Najjar syndrome types I and II)Gilbert syndrome Najjar syndrome types I and II)Gilbert syndrome (mixed etiologies)Diffuse hepatocellular disease (mixed etiologies)Diffuse hepatocellular disease (e.g., viral or
drug-(e.g., viral or drug- induced hepatitis, cirrhosis)induced hepatitis, cirrhosis)
o
o Predominantly Conjugated HyperbilirubinemiaPredominantly Conjugated Hyperbilirubinemia
Deficiency of canalicular membrane transportersDeficiency of canalicular membrane transporters
Dubin-Johnson syndrome,Dubin-Johnson syndrome,
Rotor syndrome)Impaired bile flowRotor syndrome)Impaired bile flow
Alcoholic Liver Disease
Alcoholic Liver Disease
•
• FormsForms
o
o Hepatic steatosisHepatic steatosis o
o Alcoholic hepatitisAlcoholic hepatitis
Hepatocyte swelling & necrosisHepatocyte swelling & necrosis
Mallory bodiesMallory bodies
Neutrophilic reactionNeutrophilic reaction
FibrosisFibrosis
o
o Alcoholic cirrhosisAlcoholic cirrhosis
•
• PathogenesisPathogenesis
Metabolic Liver Diseases
Metabolic Liver Diseases
A.
A. Non-aNon-alcoholcoholic falic fatty ltty liver diver diseaisease & sse & steatteatosisosis
•
• StStrorong ng asassosoc c wwitith h obobesesitity, y, dydyslslipipididememiaia,,
hyperinsulinemia and insulin resistance hyperinsulinemia and insulin resistance
•
• SmaSmall ll and and larlarge ge vesvesiclicles es of of fat acumulfat acumulate ate inin
hepatocytes hepatocytes
•
• Also an intermediate form of renal damageAlso an intermediate form of renal damage •
• CirrCirrhosis may hosis may occuroccur, , prespresumablumably y the result of the result of
years of subclinical pregression years of subclinical pregression B.
B. HeHemomochrchromomatatososisis
•
• Excessive accumulation of body Excessive accumulation of body ironiron •
• Total body iron 2-6 g normally, 0.5 g is stored in Total body iron 2-6 g normally, 0.5 g is stored in
the liver the liver
•
• May exceed 50 g, 1/3 accumulate in the liverMay exceed 50 g, 1/3 accumulate in the liver •
• Fully developed cases exhibitFully developed cases exhibit
o
o Micronodular cirrhosisMicronodular cirrhosis o
o Diabetes mellitus (75-80 % of Diabetes mellitus (75-80 % of cases)cases) o
o Skin pigmentation (75-80 % of cases)Skin pigmentation (75-80 % of cases)
•
• Hemochromatosis gene – Hemochromatosis gene – 6p21.36p21.3
o
o HFE gene regulates intestinal absorption of HFE gene regulates intestinal absorption of
dietary iron dietary iron
•
• Excessive ironExcessive iron
o
o LipLipid id perperoxoxidaidatiotion n via via iriron on catcatalyalyzed zed frefreee
radical reactions radical reactions
o
o
o InteraInteraction of ction of reacreactive oxygen species andtive oxygen species and
ir
iron on ititseselflfwiwith th DNDNAA àà letlethal hal injinjuryury àà
predisposition to hepatocellular carcinoma predisposition to hepatocellular carcinoma
•
• MorphologyMorphology
o
o Hereditary Hereditary hemochromatosihemochromatosiss
Deposition of hemosiderinDeposition of hemosiderin
CirrhosisCirrhosis
Pancreatic fibrosisPancreatic fibrosis
o
o LiverLiver
GoldGolden en yellyellow ow hemoshemosideriiderin n granulgranules es inin
the cytoplasm in periportal hepatocytes the cytoplasm in periportal hepatocytes
Stain blue with Prussian blueStain blue with Prussian blue
Progressive involvement of Progressive involvement of the lobulethe lobule
Direct hepatotoxinDirect hepatotoxin •
• Hereditary hemochromatosisHereditary hemochromatosis o
o Often in males, evident before 40Often in males, evident before 40 o
o HepatomegalyHepatomegaly
o
o Abdominal painAbdominal pain o
o Skin pigmentationSkin pigmentation o
o Derranged glucose homeostasisDerranged glucose homeostasis o
o Cardiac dysfunctionCardiac dysfunction
C.
C. WiWilslson on didiseseasasee
•
• Autosomal recessiveAutosomal recessive •
• Accumulation of toxic levels of copper in manyAccumulation of toxic levels of copper in many
tissues and organs (liver, brain & eye) tissues and organs (liver, brain & eye)
•
• Cerulloplasmin- Cerulloplasmin-o
o Copper +α2 globulin (ER)Copper +α2 globulin (ER)
o
o 90-95 % of plasma copper90-95 % of plasma copper o
o Desialylated, endocytosed by liver, excretedDesialylated, endocytosed by liver, excreted
in the bile in the bile
•
• GeneGene ATP7B, ATP7B, chromosome 13 – encodes 7.5 kBchromosome 13 – encodes 7.5 kB
transc
transcript ript for for transmtransmembranembrane e copper transportcopper transport ATPase
ATPase
•
• 1:200 – frequency of mutated alleles1:200 – frequency of mutated alleles
•
• DeDefefectctivive e bibililiarary y exexcrcretetioion n leleadads s to to cocoppepperr
acc
accumuumulatlation ion in in the the liliverver àà reacreactive tive oxygoxygenen
species
species ààtoxic liver injurytoxic liver injury •
• Liver ChangesLiver Changes
o
o FaFatty change tty change with vacuolated nucleiwith vacuolated nuclei o
o Acute hepatitis likeAcute hepatitis like o
o Chronic hepatitisChronic hepatitis o
o Massive liver necrosisMassive liver necrosis
•
• Brain changesBrain changes
o
o BasBasal al gangangliglia, a, patpaticuicularlarly ly the the putputameamen n isis
affected affected
•
• Eye lesionEye lesion
o
o Kayser Fleischer rings – deposits of copper inKayser Fleischer rings – deposits of copper in
Decemet’s membranes in the cornea Decemet’s membranes in the cornea
•
• Clinical featuresClinical features
o
o Onset is variable, rare before 6 years oldOnset is variable, rare before 6 years old o
o Acute or chronic liver diseaseAcute or chronic liver disease o
o Neuropsychiatric manifestationNeuropsychiatric manifestation
• • Treatment Treatment o o PenicillaminePenicillamine • • DiagnosisDiagnosis o
o Decrease serum ceruloplasminDecrease serum ceruloplasmin o
o Increase hepatic copperIncrease hepatic copper o
o Increase urinary excretion of copperIncrease urinary excretion of copper
D.
D.
α1 antitrypsin deficiencyα1 antitrypsin deficiency•
• Autosomal recessive disorderAutosomal recessive disorder •
• Most commonly diagnosed genetic liver diseaseMost commonly diagnosed genetic liver disease
in children in children
•
• α1 antitrypsin:α1 antitrypsin:
o
o InInhihibibitition on of of prprototeaeasese, , papartrt.. .. elelasastatasese,,
c
catathehepspsin in GG, , anand d prprototeieinanase se 3 3 ((frfroomm neutrophils)
neutrophils)
o
o SmalSmall l 384 384 aminamino o acid plasma acid plasma glycoglycoprotproteinein
synthesized by hepatocytes synthesized by hepatocytes
o
o Gene at chromosome 14Gene at chromosome 14
•
• Pulmonary emphysema & liver diseasePulmonary emphysema & liver disease •
• MorphologyMorphology
o
o Round to oval cytoplasmic inclusionsRound to oval cytoplasmic inclusions o
o Strongly PAS positive and diastase resistantStrongly PAS positive and diastase resistant o
o Neonatal hepatitis, fibrosis, cirrhosisNeonatal hepatitis, fibrosis, cirrhosis
•
• Clinical featuresClinical features
o
o Neonatal hepatitisNeonatal hepatitis o
o May remain silent until cirrhosis occurs laterMay remain silent until cirrhosis occurs later
in life in life
10-20 % of newborns10-20 % of newborns •
• Treatment liver transplantation Treatment liver transplantation
E.
E. NeNeononatatal cal choholeleststasasisis
•
• 1 in 2500 live birth1 in 2500 live birth •
• Major conditions:Major conditions:
o
o Biliary atresiaBiliary atresia o
o Neonatal hepatitisNeonatal hepatitis
•
• Morphologic featuresMorphologic features
o
o Lobular disarrayLobular disarray
o
o GiGiant ant celcell l tratransfnsformormatiation on of of hephepatoatocytcyteses
(unique feature) (unique feature)
o
o Hepatocellular and canalicular cholestasisHepatocellular and canalicular cholestasis o
o Mononuclear infiltration of portal areasMononuclear infiltration of portal areas o
o Reactive changes in Kupffer cellsReactive changes in Kupffer cells o
o Extramedullary hematopoiesisExtramedullary hematopoiesis
Hepatic Disease Assoc with Pregnancy
Hepatic Disease Assoc with Pregnancy
A.
A. PrPreeeeclclamampspsiaia
•
• 7-10 % of pregnancies7-10 % of pregnancies
•
• Maternal Maternal HPN, HPN, proteproteinuriinuria, a, peripperipheral heral edemaedema,,
coagu
coagulatilation on abnorabnormalimalities, ties, varyinvarying g degredegrees es of of DIC
DIC
•
• Eclampsia –if with convulsions and Eclampsia –if with convulsions and hyperreflexiahyperreflexia
•
• HELHELLP LP synsyndrodrome me – – hemhemolyolysissis, , eleelevatvated ed livliverer
enzymes, low platelets enzymes, low platelets
•
• MorphologyMorphology
o
o Normal in size, firm, paleNormal in size, firm, pale o
o Ischemic infarction can be seenIschemic infarction can be seen o
o Fibrin deposits in sinusoidFibrin deposits in sinusoid o
o Hemorrhage in space of DisseHemorrhage in space of Disse
o
o Hepatic hematomaHepatic hematoma ààrupturerupture •
• Treatment Treatment
o
o Termination of pregnancy Termination of pregnancy
B.
B. AcuAcute Fte Fattatty Livy Liver of er of PrePregnagnancyncy
•
• SpeSpectrctrum um frofrom m modmodest est to to subsubcliclinicnical al hephepatiaticc
dysfunction to hepatic failure, coma & death dysfunction to hepatic failure, coma & death
•
• 20-40 % 20-40 % coexistent preeclampsiacoexistent preeclampsia •
• Diagnosis:Diagnosis:
o
o Biopsy – microvesicular steatosisBiopsy – microvesicular steatosis o
o DeDepependnds s on on hihigh gh lleveveel l of of sususspipicciion on &&
confirmation by special stains oil red-O confirmation by special stains oil red-O
Liver Nodules
Liver Nodules
A.
A. FFocal ocal NodNodulaular Hypr Hyperperplaslasiaia
•
• Sponteneous mass lesionSponteneous mass lesion •
• Lighter than surrounding liverLighter than surrounding liver •
• Well demarcateWell demarcated but d but poorly encapsulatedpoorly encapsulated
B.
B. FFocal ocal NodNodulaular Hypr Hyperperplaslasiaia
•
• Sponteneous mass lesionSponteneous mass lesion •
• Lighter than surrounding liverLighter than surrounding liver •
• Well demarcateWell demarcated but d but poorly encapsulatedpoorly encapsulated
Benign Neoplasm
Benign Neoplasm
A.
A. CaCaververnonous hemus hemanangigiomomaa
•
• underneath capsuleunderneath capsule •
• benbenign ign tumtumor or of of blblood ood vesvesselsels, s, comcompoposed sed of of
tortuous vessels tortuous vessels
•
• complication: hemorrhagescomplication: hemorrhages
B.
B. LiLivever cr celell l adadenenomomaa
•
• young women in oral contraceptivesyoung women in oral contraceptives
•
• Morphology:Morphology: o
o Pale, yellow tan, and frequently bile stainedPale, yellow tan, and frequently bile stained
nodules nodules
o
o Well demarcatedWell demarcated o
o Sheets and cords of cells resembling normalSheets and cords of cells resembling normal
hepatocytes hepatocytes
Malignant Tumors
Malignant Tumors
A.
A. HeHepapatotoblblasastotomama
•
• Arise from embryonic cells of the liver Arise from embryonic cells of the liver •
• Most common liver cell tumor of young Most common liver cell tumor of young childrenchildren •
• FFatal within few years atal within few years if not if not resectedresected •
• MorphologyMorphology
o
o Epithelial typeEpithelial type o
o Mixed epithelial and mesenchymal typeMixed epithelial and mesenchymal type
B.
B. AnAngigiososararcocomama
•
• Tumor of adults Tumor of adults •
• Associated with vinyl chloride exposure, arsenicAssociated with vinyl chloride exposure, arsenic
or thorotrast or thorotrast
•
• Poor prognosisPoor prognosis •
• Vascularized tissueVascularized tissue
C.
C. HepHepatoatocelcellullular ar carcarcincinomaoma
•
• Malignant tumor of Malignant tumor of •
• 85 % of cases of HCC occur in countries with85 % of cases of HCC occur in countries with
high rates of chronic hepatitis B
high rates of chronic hepatitis B virus infectionvirus infection
•
• Cirrhosis is present in 85-90 % of Cirrhosis is present in 85-90 % of patientspatients •
• Etiologic associations:Etiologic associations:
o
o Viral infectionViral infection o
o Chronic alcoholismChronic alcoholism o
o Food contaminants (aflatoxin)Food contaminants (aflatoxin)
•
• Morphology Morphology
o
o Pale tan to Pale tan to yellow liver with nodulesyellow liver with nodules
•
• Factors implicating HBV & HCV in HCCFactors implicating HBV & HCV in HCC
o
o RReeppeeaatteed d ccyyccllees s oof f cceelll l ddeeaatth h aanndd
regeneration regeneration
o
o HeHepapatotocycyte te dydyspsplalasisia a reresusult lt frfrom om popoinintt
mutation in selected cellular genes mutation in selected cellular genes
o
o Damage DNA repair mechanismDamage DNA repair mechanism o
o GeGenonomimic c ininststababililitity y is is momore re lilikekely ly in in ththee
presence of integrated HBV DNA, (giving rise presence of integrated HBV DNA, (giving rise deletions, translocations, and duplications). deletions, translocations, and duplications).
o
o X-protein, that is a transcriptional activatorX-protein, that is a transcriptional activator
of many genes and is present in most tumors of many genes and is present in most tumors with integrated HBV DNA.
with integrated HBV DNA.
D.
D. ChChololanangigiococararcicinonomama
•
• Cells are similar to biliary tract epitheliumCells are similar to biliary tract epithelium •
• Malignancy of the biliary treeMalignancy of the biliary tree •
• Risk factors:Risk factors:
o
o Exposure to thorotrastExposure to thorotrast o
o
o ConCongengenitaital l fibfibroropolpolycyycystistic c disdiseasease e of of thethe
biliary system biliary system
o
o Opisthorchis sinensis – in the orientOpisthorchis sinensis – in the orient
E.
E. MeMetataststatatic ic TTumumororss
• • Breast CABreast CA • • Lung CALung CA • • Colon CAColon CA •
• LeukemiLeukemia and a and lymphomaslymphomas
Quiz Quiz 1 – 3
1 – 3 Patterns of Hepatic InjuryPatterns of Hepatic Injury 4 Cells that are the cause
4 Cells that are the cause of fibrosis – stellate cellsof fibrosis – stellate cells 5 Excess iron –
5 Excess iron – hemochromatosishemochromatosis 6 Accumulation of Cu – Wilson Dse 6 Accumulation of Cu – Wilson Dse
7 Benign tumor in women on OCPs – liver cell adenoma 7 Benign tumor in women on OCPs – liver cell adenoma 8 – 9 S/Sx of portal hypertension – ascites, portocaval 8 – 9 S/Sx of portal hypertension – ascites, portocaval shunts etc
shunts etc
Madami pa ata kaming utang na trans… Paunti unti na Madami pa ata kaming utang na trans… Paunti unti na llaang ng aakkoong ng mmag ag uuuuplploaoad.d. TThhaannkks s fofor r tthhee
understanding understanding
Haay, sarap magbakasyon (pag may life ka other than Haay, sarap magbakasyon (pag may life ka other than acads!) :-p
