Diseases of the Liver

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Diseases of the Liver
Fe A. Bartolome, M.D. Department of Pathology
Laboratory Diagnosis
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• Functions of the Liver
• processing of dietary amino acids, carbohydrates,
  lipids and vitamins
• removal of microbes and toxins in splanchnic
  blood
• synthesis of plasma proteins
• detoxification and excretion into bile of
  endogenous waste products pollutant xenobiotics

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Patterns of Hepatic Injury
Degeneration Intracellular Accumulation

• Degeneration
• mild to moderate ? hepatocyte swelling ?
  reversible
• severe damage ? ballooning degeneration ?
  irregularly clumped organelles and large clear
  spaces
• Accumulations in Viable Hepatocytes
• iron and copper
• triglyceride fat deposits ? STEATOSIS
• microvesicular multiple, tiny (e.g. acute
  fatty liver of pregnancy, alcoholic fatty liver
• macrovesicular single large deposit displacing
  the nucleus (e.g. obesity, diabetes, alcoholism)

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Patterns of Hepatic Injury
Necrosis and Apoptosis

• Types
• Ischemic coagulative necrosis mummified liver
  cells with lysed nuclei
• Apoptotic cell death shrunken, pyknotic
  intensely eosinophilic cells with fragmented
  nuclei
• Lytic necrosis outcome of ballooning
  degeneration ? () shards of cellular debris
• Liquefactive necrosis - abscesses

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Patterns of Hepatic Injury
Necrosis and Apoptosis

• Distribution
• Centrilobular most common immediately around
  terminal hepatic vein
• Mid-zonal and periportal rare
• Degree of involvement
• Focal or spotty limited to scattered cells
  within hepatic lobules
• Interface hepatitis between periportal
  parenchyma inflamed portal tracts
• Bridging necrosis span adjacent lobules
• Submassive necrosis entire lobules
• Massive most of the liver

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Patterns of Hepatic Injury
Inflammation

• Hepatitis
• Influx of acute and chronic inflammatory cells

Regeneration

• Occurs in all but the most fulminant hepatic
  diseases
• Features
• Mitosis
• Thickening of hepatic cords
• Disorganization of parenchymal structure

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Patterns of Hepatic Injury
Fibrosis

• Consequence of inflammation or direct toxic
  insult to liver
• Irreversible
• May eventually subdivide liver into nodules of
  proliferating hepatocytes surrounded by scar
  tissue ? CIRRHOSIS

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Hepatic Failure

• Most severe clinical consequence of liver disease
• May be
• result of sudden and massive hepatic destruction
• end-point of progressive chronic liver disease
• 80 - 90 loss of hepatic functional capacity

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Hepatic Failure

• Morphologic alterations causing liver failure
• Massive hepatic necrosis
• Mechanisms
• (i) direct damage to hepatocytes
• (ii) immune-mediated hepatocyte destruction
• a. drug or toxin-induced
• b. infection viral hepatitis except hep. C
• Chronic liver disease most common cause
• Hepatic dysfunction without over necrosis e.g.
  Reyes syndrome, tetracycline toxicity, acute
  fatty liver of pregnancy

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Hepatic Failure

• Clinical Features
• Jaundice
• Hypoalbuminemia ? peripheral edema
• Hyperammonemia ? cerebral dysfunction
• Fetor hepaticus ? musty or sweet sour body
  odor due to mercaptan formation by action of GI
  bacteria on methionine (sulfur-containing)
• Impaired estrogen metabolism ? hyperestrogenemia
• (a) palmar erythema 2o to local vasodilatation
• (b) spider angiomas central, pulsing, dilated
  arteriole from which small vessels radiate
• (c) hypogonadism gynecomastia in males

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Hepatic Failure

• Clinical Features
• Multi-organ system failure
• respiratory failure with pneumonia, sepsis
  renal failure ? cause of death
• Coagulopathy
• impaired synthesis of factors II, VII, IX and X ?
  () bleeding tendency

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Hepatic Failure

• Complications
• Hepatic encephalopathy
• associated with increased blood ammonia levels
• reversible if underlying hepatic condition can be
  corrected
• features
• (a) change in consciousness
• (b) fluctuating neurologic signs rigidity,
  hyperreflexia, asterixis

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Hepatic Failure

• Complications
• Hepatorenal syndrome
• renal failure in patients with chronic liver
  disease
• main renal functional abnormalities
• (a) sodium retention
• (b) impaired free water excretion
• (c) decreased renal perfusion
• (d) decreased GFR
• decreased urine output with rising BUN
  creatinine
• ability to concentrate urine retained ?
  hyperosmolar urine without proteins abnormal
  sediments dec. Na

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Cirrhosis

• Most common cause is alcoholic liver disease
• Key features
• The parenchymal injury consequent fibrosis are
  diffuse.
• The nodularity is part of the diagnosis ?
  reflects balance between regeneration and
  scarring.
• Vascular architecture is re-organized by the
  parenchymal damage and scarring ? formation of
  abnormal interconnections
• Fibrosis is the key feature of progressive liver
  damage.

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Cirrhosis

• Pathogenesis
• Progressive fibrosis re-organization of
  vascular micro-architecture of liver

Collagen deposition (types I III) in the lobule
Loss of fenestration of sinusoidal endothelial
cells
New vascular channels in the septae
Impaired hepatocellular protein secretion
(albumin, clotting factors, lipoproteins)
Shunting of blood around the parenchyma
Create delicate or broad septal tracts
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Cirrhosis

• Main characteristics
• Bridging fibrous septae
• link portal tracts with one another portal
  tracts with terminal hepatic vein
• Parenchymal nodules
• contain proliferating hepatocytes encircled by
  fibrosis
• micronodules - lt 3 mm diameter
• macronodules - gt 3 mm to several cm
• Disruption of architecture of entire liver

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Alcoholic Liver Disease

• Hepatic Steatosis
• Alcoholic fatty liver
• Moderate alcohol intake ? microvesicular
• Chronic alcohol intake ? macrovesicular
• Enlarged, soft, yellow, greasy liver
• Completely reversible

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Alcoholic Liver Disease

• Alcoholic Hepatitis
• Characteristics
• Hepatocyte swelling necrosis ? ballooning due
  to accumulation of fat, water proteins
• Mallory bodies eosinophilic cytoplasmic
  inclusions in degenerating hepatocytes
• Neutrophilic reaction accumulate around
  degenerating hepatocytes
• Fibrosis () activation of sinusoidal stellate
  cells portal tract fibroblasts

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Alcoholic Liver Disease

• Alcoholic cirrhosis
• Final, irreversible 10 15 of alcoholics
• Micronodular with scattered larger nodules ?
  hobnail appearance of liver surface
• Broad expanses of tough, pale scar tissue due to
  ischemic necrosis fibrous obliteration of
  nodules ? Laennec cirrhosis

• Short-term ingestion of up to 80 gm of alcohol
  (8 beers) over one to several days ? FATTY LIVER
• Daily intake of 160 gms or more for 10-20 years
  ? SEVERE INJURY

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Alcoholic Liver Disease

• Alcohol Effects
• Alcohol through action of alcohol DH
  acetaldehyde DH ? excess NADH H ? increased
  lipid biosynthesis
• Impaired assembly secretion of lipoproteins
  increased peripheral fat catabolism ? fatty liver
• Impaired hepatic methionine catabolism ? dec.
  intrahepatic glutathione (GSH) levels ? inc.
  sensitivity to oxidative injury
• Induction of cytochrome P450
• (a) CYP2E1 ? inc. alcohol catabolism in ER
  inc. conversion of other drugs to toxic
  metabolites
• (b) production of reactive O2 species ? damage
  membrane ?hepatocellular dysfunction

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Alcoholic Liver Disease

• Alcohol Effects
• Impaired microtubular and mitochondrial function
• Alcohol ? acetaldehyde ? () lipid peroxidation ?
  disrupt cytoskeletal and membrane function
• Become a major caloric source ? displace other
  nutrients ? () malnutrition and vitamin
  deficiencies
• Lead to chronic gastritis, intestinal mucosal
  damage and pancreatitis ? impaired digestive
  function
• Induce release of bacterial endotoxin into portal
  circulation from gut ? () liver inflammation
• Induce release of endothelins from sinusoidal
  endothelial cells ? () vasoconstriction
  contraction of stellate cells ? dec. hepatic
  sinusoidal perfusion ? regional hypoxia

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Alcoholic Liver Disease

• Cause of death
• Hepatic coma
• Massive gastrointestinal hemorrhage
• Intercurrent infection
• Hepatorenal syndrome following alcoholic
  hepatitis
• Hepatocellular carcinoma

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Portal Hypertension

• Causes
• A. Pre-hepatic
• Obstructive thrombosis
• Narrowing of portal vein prior to ramification
  within the liver
• B. Intrahepatic
• Cirrhosis most common
• Schistosomiasis
• Massive fatty change
• Diffuse fibrosing granulomatous disease (TB)
• Diseases affecting portal microcirculation

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Portal Hypertension

• Causes
• C. Post-hepatic
• Severe right-sided heart failure
• Constrictive pericarditis
• Hepatic vein outflow obstruction

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Portal Hypertension

• Clinical consequences
• Ascites
• collection of fluid in peritoneal cavity
• clinically detectable at least 500 ml.
• contents lt 3 gm/dL of protein (albumin),
  glucose, Na, K, mesothelial cells, mononuclear
  wbc
• Pathogenesis
• Sinusoidal HPN ? drive fluid into space of Disse
  ? removed by lymphatics
• Percolation of hepatic lymph into peritoneal
  cavity ? hepatic lymph flow in cirrhosis 20
  L/day
• Intestinal fluid leakage
• Renal retention of Na H2O due to 2O
  hyperaldosteronism ? activation of RAAS

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Portal Hypertension

• Clinical consequences
• Portosystemic Shunts

Inc. portal system pressure
Development of by-passes
Systemic portal circulation share common
capillary beds
Veins around within rectum
Cardio-esophageal junction
Periumbilical abdominal wall
hemorrhoids
Esophageal varices
Caput medusae
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Portal Hypertension

• Clinical consequences
• Splenomegaly
• secondary to long-standing congestion
• lead to hypersplenism
• Hepatic encephalopathy

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Interrelationships Among the Complications of
Cirrhosis
Cirrhosis
Hepatocellular dysfunction
Portal hypertension
Renal Na retention
Hypoalbuminemia
Spontaneous bacterial peritonitis
Ascites
Hepatorenal syndrome
Portosystemic collaterals
Hepatic encephalopathy
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Circulatory Disorders
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Circulatory Disorders
Impaired blood inflow

• Hepatic artery compromise
• thrombus or compression of intrahepatic branch of
  hepatic artery by embolism, neoplasia, sepsis ?
  localized infarct
• Portal vein obstruction
• Extrahepatic
• (a) Banti syndrome subclinical occlusion 20 to
  neonatal umbilical cord sepsis or umbilical vein
  catheterization
• (b) Intra-abdominal sepsis
• (c) Thrombogenic disorders
• (d) Trauma
• (e) Pancreatitis ? splenic vein thrombosis ?
  propagate into portal vein

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Circulatory Disorders
Impaired blood inflow

• Portal vein obstruction
• Intrahepatic
• (a) Acute thrombosis of intrahepatic portal vein
  radicle ? red-blue discoloration ? infarct of
  Zahn
• (b) Invasion by primary or secondary carcinoma

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Circulatory Disorders

• Impaired intrahepatic blood flow
• lead to massive necrosis of hepatocyes ?
  fulminant hepatic failure

• Cirrhosis most common cause
• Sinusoidal occlusion
• (a) Sickle cell disease ? panlobular parenchymal
  necrosis
• (b) DIC ? occlude sinusoids
• (c) Metastatic tumor cells ? fill the sinusoids

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Circulatory Disorders
Impaired intrahepatic blood flow

• Systemic circulatory compromise
• (a) Passive congestion
• R-sided failure congestion of centrolobular
  sinusoids ? atrophy of hepatocytes
• L-sided failure hepatic hypoperfusion
  hypoxia ? ischemic coagulative necrosis
  (centrolobular necrosis)
• Biventricular failure hypoperfusion
  retrograde congestion ? centrolobular
  hemorrhagic necrosis ? nutmeg liver

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Circulatory Disorders
Impaired intrahepatic blood flow

• Systemic circulatory compromise
• (b) Peliosis hepatis
• Primary sinusoidal dilatation
• Associated with exposure to anabolic steroids,
  oral contraceptives and danazol
• Disappear after cessation of drug treatment

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Circulatory Disorders
Hepatic venous outflow obstruction

• Hepatic vein thrombosis
• (a) Budd-Chiari Syndrome
• Obstruction of two or more hepatic veins
• Liver enlargement, pain and ascites
• Causes
• i. Myeloproliferative diseases
• ii. Coagulation disorders
• iii.Paroxysmal nocturnal hemoglobinuria
• iv. Hepatocellular carcinoma

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Circulatory Disorders
Hepatic venous outflow obstruction

• Hepatic vein thrombosis
• (b) Inferior vena cava thrombosis
• Involves hepatic portion of IVC
• Obliterative hepatocavopathy
• Veno-occlusive disease (Sinusoidal obstruction
  syndrome)
• occurs primarily in immediate weeks after BM
  transplant
• tender hepatomegaly, ascites, weight gain
  jaundice
• obliterative changes in terminal hepatic vein due
  to sinusoidal damage

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Jaundice and Cholestasis
JAUNDICE

• retention of bilirubin
• functions of bile
• Emulsification of fat
• Elimination of systemic waste products
• Rate of bilirubin production rate of hepatic
  uptake, conjugation and biliary excretion

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Jaundice
Unconjugated Bilirubin Conjugated Bilirubin
Water-insoluble at physiologic pH Water-soluble
Tightly complexed to serum albumin Weak association with albumin
Not excreted in urine even when blood levels high Can be excreted in urine
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Jaundice
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Cholestasis

• retention of bilirubin and other solutes
  eliminated in bile
• Causes
• Hepatocellular dysfunction
• Intrahepatic or extrahepatic biliary obstruction
• Features
• Jaundice
• Pruritus deposition of bile acids in skin
• Skin xanthomas due to hyperlipidemia impaired
  excretion of cholesterol
• Inc. serum alk. phos. released due to detergent
  action of retained bile salts on hepatocyte
  membrane
• Deficiency of fat soluble vitamins (A, D or K)

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Cholestasis

• Morphology
• Accumulation of bile pigment within the hepatic
  parenchyma ? distention of bile ducts and
  ductules
• Bile stasis ? induce proliferation of duct
  epithelial cells ? ductal proliferation
• Portal tract edema periductal neutrophilic
  infiltrates
• Prolonged cholestasis ? focal detergent
  dissolution of hepatocytes ? bile lakes with
  cellular debris pigments
• Portal tract fibrosis

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Infectious Disorders

• Viral hepatitis
• Miliary tuberculosis
• Malaria
• Staphylococcal bacteremia ? 20 to TSS
• Salmonellosis ? typhoid fever
• Candida
• Parasitic helminthic infection

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Viral Hepatitis

• Hepatotropic viruses
• Hepatitis viruses
• Epstein-Barr virus
• Cytomegalovirus
• Yellow fever
• Children immunocompromised ? rubella,
  adenovirus, herpesvirus, enterovirus, CMV

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Hepatitis Viruses
Hepatitis A

• Small, non-enveloped, ssRNA
• Picornavirus genus Hepatovirus
• Serology

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Hepatitis B

• Hepadnaviridae
• present in all physiologic and pathologic body
  fluids ? blood body fluids the primary vehicle
  for transmission
• Incubation period 4 26 weeks
• MOT
• Transfusion
• Blood products
• Dialysis
• Needle stick accidents among health care workers
• IV drug abuse
• Sexual contact
• Vertical transmission lead to carrier state for
  life

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Hepatitis B

• Protein sequences encoded by HBV genome
• HBcAg nucleocapsid core protein remains in
  hepatocytes for assembly of complete virion
• HBeAg secreted into blood
• HBsAg envelope glycoprotein
• DNA polymerase with reverse transcriptase
  activity
• HBx protein necessary for virus replication ?
  acts as transcriptional activator of viral genes
  play a role in development of HCC in HBV-infected
  patients

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Hepatitis B

• Spectrum of illness
• Acute infection with resolution
• Chronic hepatitis ? evolve cirrhosis ? HCC or
  carrier
• Fulminant hepatitis with massive liver necrosis
• Backdrop of hepatitis D infection

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Hepatitis B

• Carrier state () HBsAg in serum for 6 months
  or longer after initial detection
• Serology

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Hepatitis C

• Most common chronic blood-borne infection ?
  accounts for 50 of all patients with chronic
  liver disease in the US
• Flaviviridae family genus Hepacivirus
• HCV RNA polymerase with poor fidelity ?
  inherently unstable ? () genomic instability
  antigenic variability within one individual ?
  evade IFN-mediated anti-viral response ? repeated
  bouts of hepatic damage
• Persistent infection and chronic hepatitis are
  the hallmarks of HCV infection
• MOT 1. inoculations 4. sexual transmission
• 2. blood transfusions 5. perinatal
• 3. hemodialysis

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Hepatitis C

• potential outcomes

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Hepatitis C

• serology

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Hepatitis D

• hepatitis delta virus
• replication defective ? cause infection only
  when encapsulated by HBsAg
• co-infection vs. superinfection

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Hepatitis D

• serology

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Hepatitis G

• Flavivirus similar to HCV
• MOT
• Contaminated blood or blood products
• Sexual contact
• 75 cleared from plasma 25 chronic
• Site of replication mononuclear cells ? not
  hepatotropic ? no increase in serum transaminases
• No pathologic effect
• Commonly co-infects patients with HIV ? protects
  against HIV disease

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Hepatitis

• Clinicopathologic Syndromes
• Acute asymptomatic infection with recovery
• Minimal serum transaminase elevation
• Common in HCV-infected patients
• Acute symptomatic infection with recovery
• 4 phases
• (a) Incubation period
• (b) Pre-icteric phase non-specific S/Sx
• (c) Icteric phase conjugated
  hyperbilirubinemia
• (d) Convalescence

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Hepatitis

• Clinicopathologic Syndromes
• Chronic hepatitis
• Asymptomatic, biochemical or serologic evidence
  of continuing or relapsing hepatic disease for
  more than 6 months, with histologically
  documented inflammation and necrosis
• Fulminant hepatic failure
• Hepatic insufficiency progresses from onset of
  symptoms to hepatic encephalopathy within 2 3
  wks
• Extrahepatic complications
• (a) coagulopathy bleeding
• (b) cardiac instability (e) electrolyte
  acid imbalance
• (c) renal failure (f) sepsis
• (d) ARDS

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Hepatitis

• Morphology

• Acute Hepatitis
• Ballooning degeneration ? ground- glass
  hepatocytes
• Periportal necrosis with inflammatory infiltrates
• Lobular disarray
• 2 patterns of hepatocyte death
• cytolysis 20 to rupture of cell membrane
• apoptosis due to anti-viral cytotoxic T cells
• severe acute hepatitis ? () bridging necrosis

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Hepatitis

• Morphology

• Chronic Hepatitis
• periportal lymphoid aggregates
• Periportal necrosis fibrosis
• Bridging necrosis fibrosis
• Hallmark of irreversible liver damage is
  deposition of fibrous tissue

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Liver Abscess

• common in developing countries
• usually pyogenic ? multiple, small abscesses
• parasitic usually solitary ? amebic
  echinococcal
• reach liver via
• Portal vein
• Arterial supply
• Ascending infection in biliary tract ? ascending
  cholangitis
• Direct invasion from nearby source
• Penetrating injury
• Clinical RUQ pain, fever, tender hepatomegaly

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Autoimmune Hepatitis

• chronic form of hepatitis indolent or severe
• Features
• Female preponderance young or post-menopausal
• (-) viral serologic markers
• Inc. serum IgG and ?-globulin
• Inc. serum titers of autoantibodies, including
  ANA (antinuclear Ab) SMA (anti-smooth muscle Ab)
  anti-LKM1 (anti-liver/kidney microsomes Ab)
  (-) AMA (anti-mitochondrial Ab)
• Subgroups
• Type 1 () ANA and/or SMA most common
• Type 2 () anti-LKM1 younger patients

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Drug Toxin-Induced Hepatic Disease

• Mechanism of injury
• Direct toxicity
• Hepatic conversion of a xenobiotic to an actual
  toxin
• Immune mechanisms ? drug or metabolite acts as
  hapten
• Types of injury
• Hepatocyte necrosis
• Cholestasis
• Insidious liver dysfunction
• Reye syndrome children given ASA extensive
  accumulation of fat droplets within hepatocytes
  (microvesicular steatosis)

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Hepatic Disease Associated with Pregnancy

• Pre-eclampsia
• Subclinical hepatic disease a primary
  manifestation ? part of HELLP syndrome ?
  hemolysis, elevated liver enzymes, low platelet
• Morphology
• fibrin deposition in periportal sinusoids
• hemorrhage into space of Disse
• periportal hepatocellular coagulative necrosis

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Hepatic Disease Associated with Pregnancy

• Acute fatty liver of pregnancy (AFLP)
• sub-clinical hepatic dysfunction to hepatic
  failure, coma and death
• 3rd trimester with multiple metabolic defects
• diagnosis depends on
• high index of suspicion
• characteristic microvesicular steatosis
  demonstrated on frozen tissue sections OR with
  stain (oil red-O or Sudan black)
• Treatment termination of pregnancy

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Hepatic Disease Associated with Pregnancy

• Intrahepatic cholestasis of pregnancy
• Characteristics
• onset of pruritus in 3rd trimester
• darkening of urine with occ. light stools
• jaundice conjugated hyperbilirubinemia
• Mechanism altered hormonal state biliary
  secretion defects ? cholestasis
• Increased incidence of fetal distress, stillbirth
  and prematurity

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Nodules Tumors
Nodular Hyperplasia

• non-cirrhotic liver nodules
• types
• Focal nodular hyperplasia
• spontaneous mass lesion female preponderance
• Morphology
• central stellate scar with large arterial vessels
  exhibiting fibromuscular hyperplasia ? ()
  narrowed lumen
• Intense lymphocytic infiltration
• bile duct proliferation

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Nodules Tumors
Nodular Hyperplasia

• Nodular regenerative hyperplasia
• () development of portal HPN
• Associated with conditions affecting intrahepatic
  blood flow ? renal transplant, BM transplant,
  vasculitic conditions
• Morphology plump hepatocytes surrounded by
  atrophic cells no fibrosis

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Nodules Tumors
Benign Neoplasms

• Cavernous hemangioma
• Most common blood vessel tumor
• Soft nodules lt 2 cm diameter immediately beneath
  the capsule
• Clinical significance mistaken for metastatic
  tumors ? blind percutaneous biopsies not done

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Nodules Tumors
Benign Neoplasms

• Liver cell adenomas
• Cell of origin hepatocytes
• Young women on oral contraceptives ? regress on
  discontinuance of use
• Clinical significance
• Present as intrahepatic mass ? mistaken for HCC
• If subcapsular ? () rupture ? intraperitoneal
  hemorrhage
• May harbor HCC rare
• Morphology cords of hepatocytes with clear
  cytoplasm (w/ glycogen), absent portal tracts
  prominent arterial vessels and draining veins

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Nodules Tumors
Malignant Tumors

• Primary tumors uncommon ? often involved in
  metastatic spread

• Hepatoblastoma
• rare most common liver tumor of young children
• fatal if not resected
• () activation of Wnt/ß-catenin signaling pathway
  ? stabilize mutations of ß-catenin
• Angiosarcoma
• rare malignant endothelial neoplasm
• associated with exposure to vinyl chloride,
  arsenic or Thorotrast
• highly aggressive, metastatic, fatal

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Nodules Tumors

• Cholangiocarcinoma
• malignancy of biliary tract
• risk factors
• Primary sclerosing cholangitis
• Congenital fibropolycystic diseases of biliary
  system
• Previous exposure to Thorotrast
• Chronic liver fluke infection (O. sinensis)
• Morphology resemble sclerosing adenocarcinoma ?
  well-defined glandular tubular structures
  separated by dense collagenous stroma

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Nodules Tumors

• Hepatocellular Carcinoma
• male preponderance 20 40 y/o
• Risk factors
• Viral infection chronic HBV HCV infection ?
  no cirrhosis
• Chronic alcoholism () cirrhosis
• Food contaminants aflatoxin from Aspergillus
  flavus ? bind covalently with cellular DNA ? ()
  p53 mutation
• gt85 occur in countries with high rates of
  chronic HBV and HCV infections

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Hepatocellular Carcinoma

• Infection with HBV/HCV and HCC
• Viral DNA integrated into host cell genome ? ()
  genomic instability ? insertional mutagenesis
• Chronic liver cell injury accompanying
  regenerative hyperplasia ? () spontaneous
  mutations
• HBx protein encoded by HBV ? activate host cell
  proto-oncogenes and disrupt cell cycle control
• HCV core protein with oncogenic potential

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Hepatocellular Carcinoma

• Morphology
• Gross
• Unifocal large mass
• Multifocal
• Diffusely infiltrative

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Hepatocellular Carcinoma

• Morphology
• Microscopic
• Well differentiated ? trabecular pattern or
  acinar, pseudoglandular pattern
• Poorly differentiated ? pleiomorphic with
  anaplastic giant cells

bile
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Hepatocellular Carcinoma

• Clinical features
• upper abdominal pain or fullness
• malaise, fatigue, weight loss
• hepatomegaly with irregularity or nodularity
• Laboratory
• increased tumor markers serum AFP and serum
  CEA ? not conclusive ? false () in
  non-neoplastic conditions (e.g. cirrhosis,
  chronic hepatitis, massive liver necrosis, fetal
  neural defects such as anencephaly)

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GALLSTONES (CHOLELITHIASIS)

• Cholesterol stones
• a. Composition mostly cholesterol monohydrate
• b. Risk factors
• Female gender
• Obesity
• Pregnancy
• Oral contraceptive HRT
• Incidence increases with age

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GALLSTONES (CHOLELITHIASIS)

• 2. Pigmented bilirubinate stones
• a. Composition calcium salts B1
• b. Risk factors
• Chronic hemolytic anemias
• Cirrhosis
• Bacteria (ascending cholangitis)
• Parasites ? Ascaris or Clonorchis sinensis

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GALLSTONES (CHOLELITHIASIS)

• Clinical features of gallstones
• Presentation
• Frequently asymptomatic
• Biliary colic RUQ pain due to impacted stones
• Diagnosis ultrasound
• Complications
• a. cholecystitis
• b. choledocholithiasis calculi within biliary
  tract
• c. biliary tract obstruction
• d. pancreatitis
• e. cholangitis

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INFLAMMATORY CONDITIONS OF GALL BLADDER

• Acute cholecystitis
• Acute inflammation of the GB, usually caused by
  cystic duct obstruction by gallstones
• Presentation
• 1. biliary colic
• 2. RUQ tenderness on palpation
• 3. nausea and vomiting
• 4. low-grade fever and leukocytosis
• Complications
• 1. gangrene of GB 3. fistula formation
• 2. perforation and peritonitis 4. gallstone ileus

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INFLAMMATORY CONDITIONS OF GALL BLADDER

• Chronic cholecystitis
• Ongoing chronic inflammation of the GB usually
  caused by gallstones
• Micro chronic inflammation Rokitansky-Aschoff
  sinuses
• Late complication calcification of the
  gallbladder (porcelain gallbladder ? high
  association with carcinoma

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INFLAMMATORY CONDITIONS OF GALL BLADDER

• Ascending cholangitis
• Bacterial infection of the bile ducts ascending
  up to the liver, usually associated with
  obstruction of bile flow
• Presentation biliary colic, jaundice, high fever
  and chills
• Organisms gram negative enteric bacteria

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MISCELLANEOUS CONDITIONS OF GALL BLADDER

• Cholesterolosis
• Gross yellow speckling of the red-tan mucosa ?
  strawberry GB
• Micro collections of lipid-laden macrophages
  within the lamina propria
• No clinical significance

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MISCELLANEOUS CONDITIONS OF GALL BLADDER

• Hydrops of the gallbladder (mucocele)
• Chronic obstruction of the cystic duct ?
  resorption of normal GB contents ? enlargement of
  GB by the production of large amounts of clear
  fluid (hydrops) or mucous secretions (mucocele)

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BILIARY TRACT CANCER

• Cancer of the gallbladder
• Clinical presentation
• Frequently asymptomatic
• Cholecystitis
• Enlarged palpable GB (Courvoisier law)
• Biliary tract obstruction (uncommon)
• X-ray may have calcified GB (porcelain GB)
• Micro adenocarcinoma
• Prognosis poor ? 5-yr survival 1

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BILIARY TRACT CANCER

• Bile duct cancer
• Bile duct CA carcinoma of the extrahepatic bile
  ducts
• Cholangiocarcinoma CA of intrahepatic bile
  ducts
• Klatskin tumor CA of the bifurcation of the R
  L hepatic bile ducts
• Risk factors
• a. Asia Clonorchis (Opistorchis) sinensis
• b. Primary sclerosing cholangitis
• Presentation biliary tract obstruction
• Prognosis poor