Liver pothology

LIVERLIVER

&&BILIARY TRACTBILIARY TRACT

www.freelivedoctor.com

DUCT

SYSTEM



The IDEAL three-dimensional diagram.


The classical view of liver tissue from a liver biopsy, H&E stained.

PORTAL

“TRIAD”

CENTRAL

VEINwww.freelivedoctor.com


The FIRST part of the lobule, i.e., portal triad is the FIRST to get blood flow, so it is also the FIRST to get the brunt of general toxic effects, and the LAST to get the brunt of ischemic effects.


The LAST part of the lobule, central vein, VICE VERSA!

PATTERNS OF HEPATIC INJURY

• Degeneration:– Balooning, “feathery” degeneration, fat, pigment

• Inflammation: Viral or Toxic– Regeneration– Fibrosis

• Neoplasia: 99% metastatic, 1% primary


BALOONING DEGENERATIONwww.freelivedoctor.com

“FEATHERY” DEGENERATIONwww.freelivedoctor.com

FATTY LIVERwww.freelivedoctor.com

MICROVESICULAR STEATOSIS


MACROVESICULAR STEATOSIS

Obesity

Diabetes

Toxic


“Golden” pigment stained with Prussian Blue stain to make it blue. Hemosiderin? Bile? Melanin?


APOPTOSIS www.freelivedoctor.com

INFLAMMATION

• PORTAL TRIADS

(early)

• SINUSOIDS

(more severe)


MILD TRIADITIS


More severe portal infiltrates with sinusoidal infiltrates also


Hepatic Regeneration

• The LIVER is classically cited as the most “REGENERATIVE” of all the organs!


FIBROSIS• FIBROSIS is the end stage of MOST

chronic liver diseases, and is ONE (of TWO) absolute criteria needed for the diagnosis of cirrhosis.

• What is the other?


CIRRHOSIS• PORTAL-to-PORTAL (bridging)

FIBROSIS

• The “normal” hexagonal “ARCHITECTURE” is replaced by NODULES


CIRRHOSIS• Liver

• Alcoholic

• Biliary (Primary or Secondary)

• Laennec’s

• Advanced

• Post-necrotic

• Micronodular

• Macronodularwww.freelivedoctor.com

ALL CIRRHOSIS IS:• IRREVERSIBLE

• The end stage of ALL chronic liver disease, often many years, often several months

• Associated with a HUGE degree of nodular regeneration, and therefore represents a significant “risk” for primary liver neoplasm, i.e., “Hepatoma”, aka, Hepatocellular Carcinoma


BLIND MAN’s LIVERwww.freelivedoctor.com

Blind Man’s Diagnosiswww.freelivedoctor.com

N

O

FIBROUS

TISSUE


In a normal liver, ther is connective tissue ONLY in the small portal triad area.

IRREGULAR NODULES SEPARATED BY PORTAL-to-PORTAL FIBROUS BANDS


TRICHROMEwww.freelivedoctor.com

CIRRHOSIS, TRICHROME STAINwww.freelivedoctor.com

DEFINITIONS:• CIRRHOSIS is the name of the

disease as demonstrated by the anatomic changes

• LIVER FAILURE is the series and sequence of abnormal pathophysiologic events


“SPIDER” ANGIOMA, CIRRHOSIS


Common Clinical/Pathophysiological Events

• Portal Hypertension WHY? WHERE?• Ascites WHY? (Heart/Renal?)• Splenomegaly WHY? • Jaundice WHY?• “Estrogenic” effects WHY?• Coagulopathies (II, VII, IX, X) WHY?• Encephalopathy WHY?


Hepatic Enzymology• Transaminases (AST/ALT), aka (SGOT/SGPT),

and LDH are “hepatic INTRACELLULAR” enzymes, and are primarilly indicative of hepatocyte damage.

• Alkaline Phosphatase (AlkPhos), Gamma-GTP (Gamma-glutamyl transpeptidase), and 5’-Nucleotidase (5’N) are MEMBRANE enzymes and are primarilly indicative of bile stasis/obstruction


Intracellular = DAMAGEAST/ALT/LDH

Membrane = OBSTRUCTIONAlkPhos/GGTP/5’N


JAUNDICE


Bilirubin: (0.3-1.2 mg/dl)

UN-conjugated (indirect)

Conjugated (direct)


JAUNDICE

• Hemolytic (UN-conjugated)

• Obstructive (Conjugated)


JAUNDICE• Excessive production

• Reduced hepatic uptake

• Impaired Conjugation

• Defective Transportation


Neonatal Jaundice

• Neonatal, genetic

– Gilbert Syndrome

– Dubin-Johnson Syndrome

• Neonatal, NON-genetic

– MASSIVE differential diagnosis, i.e., everything


CHOLESTASIS

• Def: Suppression of bile flow• Associated with membrane enzyme

elevations, “primarily”, ie, AP/GGTP/5’N• Familial, drugs, but bottom line is

OBSTRUCTION



Bile accumulations

Bile “plugs”, Bile “lakes”


VIRAL HEPATITIS• A, B, C, D, E• They all look the same, ranging from a few

extra portal triad lymphocytes, to “FULMINANT” hepatitis

• Associated with full recovery (usual), chronic progression over years leading to cirrhosis (not rare), risk of hepatoma (uncommon), or death (uncommon)


VIRAL HEPATITIS

• Jaundice, urine dark, stool chalky

• Viral “prodrome”

• Upper respiratory infection

• All have multiple antigen (virus) and antibody (serology) serum tests

• “Councilman” bodies on biopsy are very very nice to find. Why?


Chiefly Portal Inflammation


FULMINANT HEPATITISwww.freelivedoctor.com

“FULMINANT” Acute Viral Hepatitiswww.freelivedoctor.com

“Councilman” Bodies……Diagnostic? Probably!


Bwww.freelivedoctor.com

CLESS common than B (one fourth)

LESS dangerous than B in the acute phase

MORE likely to go chronic than B

MORE closely linked with hepatoma than B


NON-Viral hepatitides• Staph aureus (toxic shock)• Gram-Negatives (cholangitis)• Parasitic:

– Malaria– Schistosomes– Liver flukes (Fasciola hepatica)

• Ameba (abscesses)

• AUTOIMMUNE• ALCOHOLIC HEPATITIS


DRUGS/TOXINS• Steatosis (ETOH)

• Centrolobular necrosis (TYLENOL)

• Diffuse (massive) necrosis

• Hepatitis

• Fibrosis/Cirrhosis (ETOH)

• Granulomas

• Cholestasis (BCPs, steroids)www.freelivedoctor.com

“Metabolic” Liver Disease

• Steatosis (i.e., “fat”, fatty change, fatty “metamorphosis”)

• Hemochromatosis (vs. hemosiderosis)– Hereditary (Primary)– Iron Overload (Secondary), e.g., hemolysis,

increased Fe intake, chronic liver disease• Wilson Disease (Toxic copper levels)• Alpha-1-antitrypsin (NATURAL protease inhibitor)• Neonatal Cholestasis


PAS positive inclusions with alpha-1-antitrypsin deficiency


INTRAHEPATICBILE DUCTS


Points of Interest• INTRA-hepatic vs. EXTRA-hepatic• PRIMARY biliary cirrhosis is a bona-fide

AUTOIMMUNE disease of the INTRA-hepatic bile ducts

• SECONDARY biliary cirrhosis is caused by chronic obstruction/inflammation/both of the intrahepatic bile ducts

• CHOLANGITIS, or inflammation of the INTRA-hepatic bile ducts, is associated with chronic bacterial (often gram negative rods) infections, or Crohns/Ulcerative colitis (IBD)


CIRCULATORY

Disorders


Points of Interest• Infarcts are rare. WHY?• Passive congestion with “centrolobular” necrosis,

is EXTREMELY COMMON in CHF, and a VERY COMMON cause of cirrhosis, i.e., “cardiac” cirrhosis

• Various semi reliable clinical and anatomic findings are seen with disorders of:– Portal Veins– Hepatic veins/IVC– Hepatic arteries


MISC.• Hepatic Diseases are seen often with

– Pregnancy• PRE-Eclampsia/Eclampsia (HTN, proteinuria,

edema, coagulopathies, DIC)• Fatty Liver• Cholestasis

– Transplant—Bone Marrow or other Organs• Drug Toxicities• GVH


BENIGN LIVER TUMORS

• …..are, in most cases, really regenerative nodules

• Have been historically linked to BCPs

• Can really be neoplasms of blood vessels also


MALIGNANT LIVER TUMORS• 99% are metastatic, i.e., SECONDARY, esp. from portal

drained organs• Just about every malignancy will wind up eventually in the

liver, like the lungs• PRIMARY liver malignancies, i.e., hepatomas, aka

hepatocellular carcinomas, arise in the background of already very serious liver disease chronic hepatitis/cirrhosis, are slow growing, and do NOT metastasize readily

• CHOLANGIOCARCINOMAS are malignancies if the INTRA-hepatic bile ducts and look MUCH more like adenocarcinomas than do hepatomas


HEPATIC ANGIOMAwww.freelivedoctor.com

HEPATOMA, or HEPATOCELLULAR

CARCINOMAwww.freelivedoctor.com

CHOLANGIOCARCINOMA


EXTRAHEPATICEXTRAHEPATICBILE DUCTSBILE DUCTS

&&GALLBLADGALLBLADDERDER


MAINCONSIDERATIONS

• Anomalies• Stones (Clolesterol/Bilirubin)• (Chole[docho]lithiasis)• Inflammation (Cholecystitis/Cholangitis)• Cysts• Neoplasms


Anomalies

• Congenitally absent Gallbladder

• Duct Duplications

• Bilobed Gallbladder

• Phrygian Cap

• Hypoplasia/Agenesis


Phrygian Cap


CholelithiasisFactors

• Bile supersaturated with cholesterol

• Hypomotility

• Cholesterol “seeds” in bile, i.e., crystals

• Excess mucous in gallbladder


Cholesterolosis of gallbladder mucosawww.freelivedoctor.com

Cholesterolosis of gallbladder mucosa


Cholecystitis• Acute: fever, leukocytosis, RUQ pain• Chronic: Subclinical or pain• Ultrasound can detect stones well• HIDA (biliary) nuclear study can help• Go hand in hand with stones in

gallbladder or ducts• If surgery is required, most is

laparoscopic


Choledochal Cysts

• Dilatations of the common bile duct usually in children.


Adenocarcinoma of the gallbladder


LIVER AND BILIARY TRACTLIVER AND BILIARY TRACT

• 5 generalized disease patterns:a) degeneration and intracellular accumulation

i) moderate swelling is reversibleii) severe swelling (ballooning

degeneration)- “clumped” cytoplasmic

organelles; large clear spacesiii) Fe, Cu, fat accumulation


- “micro-” and “macro-” vesicular steatosis

b) necrosis and apoptosisi) centrilobular necrosis

c) inflammationi) hepatitis

d) regeneratione) fibrosis

i) irreversible damageii) “scar” tissue is referred to as “cirrhosis”


• Hepatic failurea) functional capacity of 80-90%b) 70-80% mortality without liver transplantationc) massive hepatic necrosis

i) drugs, toxins- acetominophen (~40%)- halothane, anti-TB drugs, CCl4, mushroom (Amanita

phalloides)ii) infections/inflammations

- HAV, HBV, unknown


d) chronic liver failurei) most common route

- cirrhosis e) hepatic dysfunction without overt necrosis

i) viable without normal function- Reye syndrome- tetracycline toxicity- acute steatosis of

pregnancy


f) clinical:i) jaundiceii) hypoalbuminemiaiii) impaired estrogen metabolism

- hypogonadism- gynecomastia

iv) MSOF susceptibility v) coagulopathy

- II, VII, IX and X deficiency of clotting factors

vi) death in weeks to months


vii) 2 grave complications:- hepatic encephalopathy

neurotransmission disturbances of CNS and neuromuscular system.

- hepatorenal syndromesevere renal failure without any

intrinsic disorders.1. Na+ retention2. H2O excretion3. RBF4. GFR


• Cirrhosisa) main causes are ETOH and viral hepatitis (in Western World)b) characteristics:

i) diffuse fibrosis- “broad” linking scars

ii) parenchymal nodules- balance between

regeneration and scaring iii) disruption of entire liver architecture

- revasculature (bypass)


c) cirrhosis essentially irreversiblei) main pathogenic processes:

- progressive fibrosis- vascular reorganization (blood shunted around

parenchyma)ii) collagen deposits (via perisinusoidal

satellite cells)- Types I and III

d) may be clinically silente) death: progressive liver failure, portal hypertension, CA


• Portal Hypertensiona) resistance to portal flow

i) prehepatic- obstructive thrombosis - stenosis

ii) intrahepatic- cirrhosis (most causes of portal

hypertension; compression of HV and resistance from scaring) iii) posthepatic

- right sided heart failure


b) clinical consequencesi) ascitesii) portosystemic shuntsiii) congestive splenomegalyiv) hepatic encephalopathy

1. ascites a) fluid accumulation of fluid in peritoneum b) Starling forces


2. portosystemic shuntsa) shunt flow where portal and systemic share common

circulationi) rectum (hemorrhoids) ii) cardioesophageal junction

- esophageal varices- massive hematemesis

iii) periumbilical and abdominal collaterals- caput medusae


3. Splenomegalya) congestion

i) Starling forces

• Jaundice a) hepatic bile formation (bile salts)

i) emulsify dietary fatsii) eliminate waste products

- primary bilirubin, cholesterol and xenobiotic elimination


b) bilirubin and bile formationi) bilirubin end product of heme degradation

- senescent RBC’s- in spleen, liver and bone marrow- accounts for ~ 0.3 gm/day

ii) most remainder of bilirubin- turnover of hepatic heme

iii) heme biliverdin (via heme oxidase) bilirubin (via biliverdin reductase)


iv) bound to albumin (not soluble)- free may in hemolytic diseases

v) taken up by liver (carrier mediated), conjugated with glucuronic acid

- H2O- secreted into bile- degraded by bacteria to urobilinogens - excreted in feces and urine- reab in ileum and colon


• Bile saltsa) major are cholic acid chenodeoxycholic acid

i) degrade lipids

• Jaundice a) both conjugated and unconjugated may systemically

i) in tissues- yellow color of skin- or sclera (icterus)

b) unconjugatedunconjugated is insoluble, bound to albumin; not excreted in urine


i) small amount may diffuse into brain of infants kernicteruskernicterus

- in hemolytic diseases (erythroblastosis fetalis)

c) conjugated is H2O solublei) can be excreted in urine

d) normal bilirubin = 0.3-1.2 mg/dle) jaundice >2-2.5 mg/dl

i) imbalance between production and clearance


1. excess production2. reduced hepatic uptake3. impaired conjugation4. decreased excretion5. impaired bile flow

f) 1-3 = unconjugated hyperbilirubinemia

g) 4-5 = conjugated hyperbilirubinemia

h) see table 18-3


• specific types of jaundice1) neonatal jaundice

i) conjugation/excretion develops ~ 2 weeks after birthii) almost all newborns develop neonatal jaundice or

physiologic jaundice of the newborna) breast fed jaundice

i) β-glucuronidase - deconjugates bilirubin

glucuronides in gut


2) hereditary hyperbilirubinemia a) genetic deficiency of UGT1A1

i) Crigler-Nijar syndrome typeI- absent UGT1A1- fatal

ii) Crigler-Nijer syndrome typeII- reduced UGT1A1- mild- may develop kernicterus iii) Gilbert syndrome- mild jaundice- innocuous


iv) Dubin-Johnson syndrome- excretion problem- conjugated bilirubin

v) Rotor syndrome- decreased uptake and

excretionvi) see table 18-4


• Cholestasis a) Cholestasis simply means failure of flow of bile. The cause of this failure can arise anywhere in the biliary system, from the liver

cell down to the ampulla of Vater. For clinical purposes it is easiest to think of cholestasis as being either intra- or extrahepaticb) may present with jaundicec) pruritis common presenting signd) skin xanthomas cholesterol


e) classic lab test is Alk. Phos.i) detergent effects of retained bile salts.ii) must verify hepatic in nature

- several isoforms iii) nutritional deficiencies of Vit A, D and K

- malabsorption from gutf) extrahepatic (obstruction)

i) surgery to correctg) intrahepatic not helped with surgery (see table 18-5)


• Causes: (cholestasis)a) intrahepatic

i) Common- Viral hepatitis- Drugs- Alcoholic hepatitis ±

cirrhosis b) extrahepatic

i) Common- Common bile duct stone(s)- Pancreatic/periampullary cancer


ALCOHOLIC LIVER DISEASEALCOHOLIC LIVER DISEASE

• Leading cause of liver disease in Western World

a) ~ 14 million Americans categorized as alcohol abusersi) 200,000 deaths/yr

• 3 overlapping forms of liver disease:a) hepatic steatosisb) alcoholic hepatitisc) cirrhosis


1. hepatic steatosishepatic steatosisa) moderate amounts of ETOH intake small lipid droplets (microvesicular)b) chronic etoh intake large lipid globules (macrovesicular)

i) compressing and displacing nucleus to periphery of hepatocyte

ii) initially centrilobulariii) may involve entire lobe of liver with

progression


Alcoholic liver disease: macrovesicular steatosis, involving most regions of the hepatic lobule. The intracytoplasmic fat is seen as clear vacuoles. Some early fibrosis (stained blue) is present (Masson trichrome).


The cluster of inflammatory cells marks the site of a necrotic hepatocyte. A Mallory body is present in a second hepatocyte (arrow).


iv) fibrosis with chronic etoh usev) reversible changes with abstinence from etoh

2. alcoholic hepatitisalcoholic hepatitisa) swelling of hepatocytes

i) single or scattered fociii) swelling due to fat and H2Oiii) mild hemosiderin depositsiv) Mallory inclusions

- eosinophilic cytoplasm- not specific (also seen in Wilson

disease, cholestasis


3. alcoholic cirrhosisalcoholic cirrhosisa) irreversible and final form of alcoholic liver diseaseb) nodule formation (micro and macro)c) fibrosisd) deranged vascular perfusion


The characteristic diffuse nodularity of the surface reflects the interplay between nodular regeneration and scarring. The greenish tint of some nodules is due to bile stasis.


The microscopic view shows nodules of varying sizes entrapped in blue-staining fibrous tissue.


• Pathogenesisa) 8 beers or 7 oz. 80 proof etoh/day

i) mild liver changes (reversible)- fatty liver

b) 160 gms/day for 10-20 yrsi) severe injury

c) ~ 15% of alcoholics develop cirrhosisd) women more susceptible e) cirrhosis may develop without any injury such as steatosis or alcoholic hepatitis !


• hepatocellular steatosis:a) shift of fat metabolism from catabolism to fat biosynthesis

i) generates excess NADH + H- alcohol dehydrogenase- acetaldehyde

dehydrogenaseb) impaired biosynthesis and secretion of

lipoproteinsc) increased peripheral catabolism of fat


• etoh-induced impaired metabolism of methionine

a) decreased intrahepatic glutathionei) oxidative injury

• induction of cytochrome P-450 (CYP2E1)

a) toxic drug metabolitesi) e.g., acetaminophen ii) O2 free radicals

• etoh directly affects microtubules and mitochondria and membrane fluidity

• acetaldehyde induces lipid peroxidation


• etho major source of calories in alcoholics

a) nutritional deficienciesi) B12 and folate

• etoh directly causes LPS release into portal circulation

a) activates inflammation within liver

• directly releases endothelinsa) potent vasoconstrictorb) regional hepatic hypoxia


• alcoholic liver disease:a) chronic disease:

i) steatosis- hepatomegaly with increased bilirubin and ALK phosphatase

ii) hepatitis- acute change- malaise, wt loss

iii) progressive fibrosis


iv) cirrhosis- distended abdomen- wasted extremities- caput medusae - LABS:

ALK phos (variable)aminotransferasebilirubinhypoproteinemia(all)anemia

v) vascular derangements


• causes of death:a) hepatic comab) massive GI hemorrhagesc) infectiond) hepatorenal syndromee) CA (3-6%)


METABOLIC LIVER DISEASEMETABOLIC LIVER DISEASE

• nonalcoholic fatty liver disease and steatohepatitis

a) similar to alcoholic liver diseasei) occurs at lower alcohol consumption

b) associated withi) obesityii) type 2 diabetes

c) is a Dx of exclusiond) asymptomatic except for lab values (ALT, AST, etc.)


• hemochromatosis a) excessive accumulation of body iron. Deposited mainly in:

i) liverii) pancreas

b) results mainly from genetic defects causing:i) excess iron absorptionii) parenteral administration

- transfusionsc) hereditary hemochromatosis

i) homozygous recessive


d) acquired hemochromatosisi) “secondary” hemochromatosisii) see table 18-9

• Total body irona) 2-6 gms (normal)

i) 0.5 gms in liver- 98% in hepatocytes

b) hemochromatosisi) > 50 gms

- > 33% stored in liver


• clinical (hemochromatosis)a) micronodular cirrhosis in all patientsb) diabetes mellitus in ~ 80%c) skin pigmentation in ~ 80%d) lifelong accumulation

i) appearing in 5th to 6th decadese) hemochromatosis gene 6 (p21.3)

i) regulated dietary iron absorptionii) causes 1gm/day accumulation

f) S&S after 20 gm accumulation


g) excess iron is directly toxici) lipid peroxidation

- via Fe-induced free radicalii) stimulation of collagen formationiii) O2 free radicals and iron interact with

DNA lethal injury

- predisposing to hepatocellular CA

iv) removing excess iron is Tx in cells not irreversible damaged


h) most common 2o hemochromatosisi) hemolytic anemias associated with ineffective erythropoiesis

i) most common sites for hemosiderin deposition (decreasing order)i) liverii) pancreasiii) myocardiumiv) pituitary glandv) adrenalsvi) thyroid, parathyroidvii) joints and skin


• Wilson diseasea) accumulation of toxic levels of Cu++

in liver, brain and eye b) 40-60% Cu++ absorbed in stomach and duodenum (~ 2-5 gms)

i) transported to liver on albuminii) resecreted into blood as

ceruloplasmin (90-95% of plasma copper)c) Cu++ excreted in bile (after normal aging process of proteins - albumin) 40-150 mg total body Cu++


d) gene for Wilson disease 13e) when excretion is defective

i) Cu++ spills over into blood- urinary excretion

ii) causes direct toxic effects- hemolysis- organ dysfunction

f) rare before 6 yrs.


g) most common presentationi) acute/chronic liver diseaseii) neuropsychiatric (behavioral) iii) Dx urine Cu++, serum

ceruloplasmin, hepatic Cu++

iv) plasma Cu++ NOT useful !!v) “Kayser-Fleischner” rings

- green to brown deposits in cornea

h) D-penicillamine Tx (Cu++ chelator)


• - 1 antitrypsin deficiencya) autosomal recessiveb) important protease inhibitor

i) primarily elastase, cathepsin G and proteinase 3

- released from neutrophils during inflammation

c) formed on chromosome 14i) “Pi” protein inhibitorii) most important variant is PiZZ

- only 10% of normal - 1AT


d) Most commonly diagnosed genetic liver disease in infants and childrene) clinical:

i) neonatal hepatitis with cholestatic jaundice 10-20%

ii) older children hepatitis or cirrhosis

iii) adults emphysema


• neonatal cholestasisa) see table 18-10b) idiopathic neonatal hepatitis and biliary atresia share similar clinical S&S

i) need to Dx for adequate Tx


Intrahepatic biliary tract diseaseIntrahepatic biliary tract disease 11oo and 2 and 2oo biliary cirrhosis biliary cirrhosis

• 1o sclerosing cholangitis

• see table 18-11

• 11oo biliary cirrhosis biliary cirrhosisa) destruction of intrahepatic biliary tree

i) portal inflammation and scaringii) cirrhosis and liver failure

b) chronic, progressive and often fatal


c) major features are:i) nonsuppurative inflammationii) destruction of medium sized bile ducts

d) mainly in middle aged women (6:1)i) peak between 40-50 yrs

e) initial presentation is pruritis i) jaundice late in courseii) hepatomegaly is typicaliii) xanthomas due to cholesterol f) antimitochondrial Ab in > 90%

i) against PDH complex E2 subunit


g) clinical:i) autoimmune diseaseii) sicca complex

- dry eyes and mouthiii) etiology remains unclear

- lack of “trigger(s)”iv) causes of death:

- liver failure - portal hypertension and variceal bleeding- infection


• 22oo biliary cirrhosis biliary cirrhosisa) prolonged obstruction of extrahepatic bile treeb) most common causes

i) cholelithiasis (gallstones)ii) malignancies of biliary tree or head of pancreas

iii) strictures- following previous surgery

c) obstructions in childreni) atresiaii) cystic fibrosis and cyst


d) secondary inflammation can cause periportal fibrosis hepatic scaring and nodule formation 2o biliary cirrhosis

• 11oo sclerosing cholangitis sclerosing cholangitis a) inflammation b) obliterative fibrosis

i) intra- and extrahepatic bile ductsii) dilation of preserved segments


c) 1o seen in association with inflammatory bowel disease

i) UC- ~75% coexistence

ii) only ~4% of patients with UC have have coexistence of 1o sclerosing cholangitis

d) etiology unknowni) association with IBD

e) liver transplant is Tx


Circulatory disordersCirculatory disorders

• pre, intra and post hepatic circulatory disorders

• impaired blood flow into liverimpaired blood flow into liver 1- 1- hepatic arteryhepatic artery

a) infarcts are rare ! Localized infarcts due to:i) thrombosisii) compressive neoplasmsiii) emboliiv) sepsis


b) loss of hepatic artery flow does not always cause infarcti) sufficient collateralsii) exception is transplanted liver (thrombosis causes infarct)

2 – 2 – portal veinportal vein a) abdominal pain

b) ascitesc) similar to portal hypertension

i) esophageal varices- prone to rupture


d) extrahepatic portal vein obstruction:i) Banti syndrome

- neonatal umbilical sepsis- umbilical catheterization

ii) peritonitis- pylephlebitis

iii) thrombogenic disordersiv) traumav) pancreatitis

- splenic vein thrombosis to portal vein


e) portal vein thrombus NO infarcti) red-blue discolorization which is well demarcated

- “infarct of Zahn”ii) severe hepatocellular atrophy

f) neoplastic obstruction 3 – intrahepatic3 – intrahepatic

a) most common cause is cirrhosismost common cause is cirrhosisb) sickle cell diseasec) DIC

i) eclampsia of pregnancyd) obstructive neoplasms


e) passive congestion and centrilobular necrosisi) CHF (R-sided)

- cardiac cirrhosisii) CHF (L-sided)

- ischemic damage- centrilobular necrosis- “nutmeg” liver

f) peliosis hepatisi) 1o sinusoidal dilation (rare)ii) usually exposure to anabolic steroids


4 – hepatic vein obstruction4 – hepatic vein obstruction

a) single vein obstructioni) is silent

b) 2 or more major hepatic veins(“Budd-Chiari syndromeBudd-Chiari syndrome”)i) hepatomegalyii) painiii) ascitesiv) intrahepatic BP


c) venous thrombosis associated with i) myeloproliferative disordersii) inherited disorders of coagulationiii) PNHiv) hepatocellular CA

d) BC pills and pregnancyi) with underlying thrombotic disorders

e) if untreated mortality is highf) veno-occlusive disease

i) following bone marrow trans.


Hepatic Disease Associated With PregnancyHepatic Disease Associated With Pregnancy

• Preeclampsia a) ~ 10 % of pregnancies

i) hypertensionii) proteinuriaiii) peripheral edemaiv) coagulopathy (DIC)

• Eclampsia a) same as preeclampsia with

i) seizures and hyperreflexia


• Clinical (HELLPHELLP syndrome)a) hemolysisb) hepatic enzymesc) platelets

• Acute Fatty Liver a) may be similar presentation to pre- or eclampsia

i) Tx is termination of pregnancyb) fetus (rare) causing hepatic failure in mother


NeoplasmsNeoplasms

• Benigna) cavernous hemangiomas

i) most common- no percutaneous biopsy- do not mistake for

metastatic tumorsb) liver cell adenomas

i) develop from hepatocytesii) young women (BC pills)


• Malignanciesa) most often metastatic site (lungs also !)b) 1o CA of liver are rare in USA and Western Europe

i) hepatoblastoma- most common in children

ii) angiosarcoma - same as in other parts

vinyl chloride, arsenicc) most arise from hepatocytes

i) hepatocellular CA (HCC)


d) less common from bile ducti) cholangiocarcinoma

• Hepatocellular Carcinoma (HCC)a) Asian (~ 75% of all HCC)b) > 85% of HCC occur in countries with high rates of chronic HBVc) when HBV is not prevalent, ~ 90 % of HCC occur in patients with cirrhosis

• Pathogenesis: 3 main etiologies1) viral (HBV, HCV); 2) chronic etoh;3) food contamination (aflatoxins)


• Clinicala) -fetoprotein in ~ 75%b) palpable irregular massc) metastasis 1st to lung then to other partsd) death from:

i) cachexiaii) variceal bleedingiii) liver failure with comaiv) rupture of tumor with fatal hemorrhage


• Metastatic tumorsa) more common than 1o tumors

i) multiple nodular metastases ii) hepatomegaly


Liver pothology

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