Subject: Pathology Second Semester A.Y.

2013-2014
Topic: 4.04 Liver Pathology
Lecturer: Dr. Yanez
Date: November 07, 2014

OUTLINE Portal tract contains connective tissues with biliary

I.Normal Liver epithelium, hepatic portal vein and hepatic artery.
II. Patterns of Hepatic Injury
III. Clinical Manifestation of Liver disease Limiting plate:
IV. Cholestasis o Sharply-outlined
V. Hepatic Failure o Boundary of the portal tracts in the liver
VI. Cirrhosis o Delimits the portal system from the hepatocytes
VII. Portal Hypertension
Traditional Classification: The liver lobule is divided into
VIII. Hepatitis A Viral Infection
IX. Hepatitis B Viral Infection centrilobular, periportal, and midzonal areas.
X. Hepatitis C Viral Infection
XI. Hepatitis D Viral Infection NORMAL LIVER HISTOLOGY
XII. Hepatitis E Viral Infection
The liver is primarily made up og the hepatocytes
XIII. Hepatitis G Viral Infection
XIV. Clinicopathologic Syndromes of Hepatitis Portal system contains hepatic artery, portal vein, and bile
XV. Bacterial Infection ducts
XVI. Parasitic Infection Central vein
XVII. Toxic Liver Disease Space of Disse: Space in between the sinusoids
XVIII. Alcoholic Liver Disease
XIX. Hepatic Tumors Kupffer Cells: Macrophages found in the luminal surface;
XX. Malignant Tumors make up the livers phagocytic system
Ito cells: Fat storing cells found un perisinusoidal spaces
References: o Hepatic stellate cells
Robbins 8 ed., Lecture PPT, Lecture Recording
th

o Plays a role in Vit A metabolism

I.NORMAL LIVER
Location: Right upper quadrant of the abdomen
Normal Weight: 14001600 grams
Has a smooth surface
Made up of the left, right, and caudate lobes
Divide into a larger right lobe and a smaller left lobe by the
falciform ligament
Portal Triad: Bile duct, Hepatic artery, Hepatic vein
Figure 1. Normal Anatomy of the Liver
Figure 2. Normal Hepatic Lobule: Fundamental unit of the liver
composed of the central vein, liver cells emanating cords and
trabeculae from the central vein to the peripheral system
o Transformed into fibroblast in case of irritation and
chronic inflammation
o Important in the pathogenesis and the formation of
liver fibrosis (cirrhosis)
LOBULAR MICROANATOMY
Consists of:
o Hepatocytes: Organized into cribriform, anastomosing
sheets or plates extending from portal tracts to the
terminal hepatic veins.
o Canaliculi
o Portal Triad: Arteriole, venule, bile duct branch
The traditional classification has been changed in looking at
the liver as zones:
o Zone 1 or Centriacinar: Liver cells near the portal
hepatocytes; periportal; nearest the afferent blood
supply, surround the portal triads
o Zone 2 or Midzone: Intermediate of midlobular area
o Zone 3 or Periacinar: Central portion; centrilobular;
farthest from the afferent blood supply, surrounds the
central veins
FROM ROBBINS:
Terminology of the hepatic microarchitecture is based on two different
concepts: the hepatic lobule and the hepatic acinus. According to the
lobular model, the liver is divided into 1- to 2-mm diameter hexagonal
lobules oriented around the terminal tributaries of the hepatic vein
(terminal hepatic veins), with portal tracts at the periphery of the
lobule.
The hepatocytes in the vicinity of the terminal hepatic vein are called
centrilobular; those near the portal tract are periportal. In the
acinar model the hepatocytes near the terminal hepatic veins are the
distal apices of roughly triangular acini, whose bases are formed by the
penetrating septal venules from the portal vein extending out from the
portal tracts.

Trans Group: Ramos Family Page 1 of 22

Edited By:
In the acinus the parenchyma is divided into three zones, zone 1
being closest to the vascular supply, zone 3 abutting the terminal
hepatic venule and most remote from the afferent blood supply, and
zone 2 being intermediate. Regardless of the model used, zonation of
the parenchyma is an important concept because of the gradient of
activity displayed by many hepatic enzymes, and the zonal
distribution of certain types of hepatic injury. While the acinar model
best describes the physiologic relationships between hepatocytes and
their vascular supply, the histopathology of the liver is usually
discussed on the basis of a lobular architecture. (Robbins)
Figure 3. Representation of the portal system
Figure 4. New Classification of which the liver is divided into 3 Zones:
Zone 1 (Periportal), Zone 2 (Midzonal), Zone 3 (Pericentral)
II. PATTERNS OF HEPATIC INJURY
The liver is exposed to many injurious stimuli because of the rich
vascular network that supplies it; there are many toxins, drugs,
infectious agents that can go into the liver.
The liver cell is considered to be a stable and labile cell, with a
large functional capacity, and has the ability to regenerate very
quickly
In cases of injury to the liver, there are patterns of predictable
morphologic injury that the liver may present:
o Degeneration and intracellular accumulation (REVERSIBLE)
o Necrosis and apoptosis (IRREVERSIBLE)
o Inflammation: Response to injury
o Repair: Regeneration and fibrosis
DEGENERATION AND INTRACELLULAR ACCUMULATION
Degeneration:
o Ballooning degeneration: Seen in acute viral hepatitis
First acute response
Liver cells become ballooned, swollen, with
clear cytoplasmic granules
Cells can revert back once the injurious stimuli
is removed
o Feathery degeneration: Seen in biliary cirrhosis
Accumulation :
o Iron (siderosis): Frequent transfusions in the patients with
hemolytic diseases, pancytopenia, aplastic anemia; liver
becomes iron-stained.
o Copper (Wilsons disease): Defective genetic abnormality in
copper synthesis
o Fat (steatosis): Alcoholics, diabetes mellitus, malnutrition,
obesity
Figure 5. Swollen and Ballooning Degeneration; important
histologic characteristic of acute viral hepatitis
NECROSIS AND APOPTOSIS
NECROSIS:
Liver cells undergo cell death
Follows different patterns:
1. FOCAL: Groups of hepatocytes in few areas that are
involved in necrosis.
2. MULTIFOCAL: Necrosis in multiple areas ; pattern of
injury in shock states; centroacinar/centrilobular type
3. ZONAL: Affects any of 3 zones of the lobule:
Centrilobular (zone 3): Terminal events of shock,
alcoholic hepatitis
Midzonal: Hepatocytic necrosis, associated with
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 carbon tetrachloride poisoning
Periportal (Zone 1): Viral type of hepatitis
The location of the necrosis gives a clue of the
underlying etiology of the lesion.
4. CONFLUENT (bridging): Connecting portal field to portal
field, portal field to central vein and central vein to central
vein
Necrosis involving large areas of cells distributed in a
certain region of the lobule
Spanning of a bigger area of necrosis from different
parts of the liver lobule.
Necrosis may start from a portal and end up in another
portal tract of another lobule.
More extensive necrosis
Clinical outcome is NOT GOOD
2 subtypes:
o ZONAL: When it affects one of the 3 zones of the Figure 7. Apoptosis
lobule centrilobular, perilobular, midlobular
o BRIDGING: Hallmark of chronic active hepatic
necrosis; necrosis occurs between the portal and
central veins porto-portal, porto-central,
central-central.
5. PANACINAR SUBMASSIVE: Involves all 3 zones
Present with a acute liver failure
HIGH MORTALITY RATE
SUBMASSIVE : Extensive but not completely
encompassing involves all 3 zones
6. PANACINAR MASSIVE: Involvement of all zones of the acini
in all lobules It is fatal

Figure 8. Coagulation Necrosis. Outlines of dead liver

cells without details of cytoplasmic organelles and nuclei

Figure 6. Zonal Pattern of Injury. Piecemeal necrosis involves the

area around the portal tract where it eats up or destroys the limiting
plate piece by the surrounding inflammatory cells, indicates chronic
active hepatitis and has a high probability of progression onto liver
cirrhosis

APOPTOSIS:
Programmed cell death
Cells die in a drop out fashion or individually
Cells condense, fragments of dead cells are phagocytosed
by histiocytes Figure 9. Focal Necrosis. Inflammation cells trying to
Very minimal or no inflammatory reaction go around the area of necrosis (around blue arrow); a
COUNCILMAN BODIES: Apoptotic cells in the liver, seen in shadow of former cell is also seen, a subtle hint of a
viral hepatitis remnant of a nucleus, which is already dead. Surrounding
the dead are inflammatory cells. Seen in acute viral
hepatitis

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 Figure 10. Multifocal Necrosis
CONFLUENT NECROSIS
o Necrosis involving large areas of cells distributed in a certain
region of the lobule :
o ZONAL when it affects one of the 3 zones of the lobule:
centrolobular, perilobular, midlobular.
o BRIDGING : Necrosis occurs between the portal and central
veins: porto-portal, porto-central, central-central.
Figure 11. Confluent Necrosis: There are a lot of inflammatory cells
bridging from the central to the portal tract.
PIECEMEAL NECROSIS
Inflammation of the portal tract with necrosis of peri-
portal hepatocytes near the limiting plate
Seen in chronic active hepatitis
Assoc changes:
Necrosis and apoptosis
Ductular proliferation portal tract expansion
The dead hepatic cell is the meal and the ones that eat it
are the surrounding inflammatory cells.
Figure 12. Piecemeal necrosis in chronic alcoholic hepatitis
The portal tract contains inflammatory cells potalitis/
portal triaditis the limiting plate that is the boundary of
the portal tract from the adjoining liver lobule is los.
INFLAMMATION
Associated with influx of acute or chronic inflammatory
cells ( hepatitis ) around liver cell necrosis
type and distribution of inflammation vary according to
the etiologic agent
Ex. Schistosomiasis Eosinophils are prominent
inflammatory response
Acute , chronic, granulomatous
DIFFUSE LOBULAR INFLAMMATION:
o Diffuse mononuclear cell infiltration of the lobule.
o Lymphocytes and monocytes, few neutrophils,
eosinophils and plasma cells maybe present.
KUPFFER CELL HYPERPLASIA
LIVER CELL REGENERATION: Binucleated cells
Figure 13. Lymphocytic Spillover in Acute Hepatitis
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 Figure 14. Diffuse Lobular Inflammation Figure 16. Liver Fibrosis

REGENERATION III. CLINICAL MANIFESTATIONS

1. REPAIR OF LIVER DISEASE
Hepatocyte proliferation Jaundice
Thickening of hepatocyte cords Yellow discoloration of skin/sclerae
Mitosis Hyperbilirubinemia
Multi-nucleation Normal value 1.2 mg/dL (8-24 umol/L)
Parenchymal disorganization > 2.5 mg/dL (50 umol/L)- significant staining/
Bile duct proliferation discoloration can be seen
2. FIBROSIS 2 forms of jaundice:
Indicates irreversible damage 1. Unconjugated hyperbilirubinimia
Cirrhosis Increased Bil 1, forms tight complexes with serum
albumin.
Cannot be excreted in the urine
May diffuse to brain kernicterus

2. Conjugated hyperbilirubinemia
Seen in obstruction of biliary tree
Conjugated bilirubin is water soluble, non-toxic and
loosely bound to albumin
Easily excreted in the urine

A. PATHOPHYSIOLOGY OF JAUNDICE
1. UNCONJUGATED HYPERBILIRUBINEMIA
A. Excessive production of bilirubin
Hemolytic anemia
Ineffective erythropoesis (PA, thalassemia)
Figure 15. Liver Cell Regeneration RBC resorption from internal hge
B. Decreased hepatic uptake
LIVER FIBROSIS Gilberts syndrome
Consequence of chronic liver injury Drug interference w/ membrane carrier sys.
Derangement of the architecture, circulation remodeling, C. Impaired bilirubin conjugation
cirrhosis and portal hypertension Neonatal jaundice: Def. of glucoronyl transfrease
Irreversible change Genetic deficiency of bil UGT activity Crigler
Deposition of collagen regenerating hepatocytic nodules Najjar Syndrome Types 1 and 2
scaring cirrhosis Diffuse hepatocellular disorder
One of the important end response to chronic liver injury is
fibroblastic scarring of the liver cell, whether due to alcohol 2. CONJUGATED HYPERBILIRUBINEMIA
abuse, parasitic or viral infection. A. Decreased hepatocellular excretion/or impaired bile
flow
Ex. Biliary Atresia or obstruction
B. Deficiency in canalicular membrane transporters
Dubin Johnson Syndrome
Autosomal recessive

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 Conjugated hyperbilirubinemia Lab findings show elevated serum alkaline phosphatase and
Brown to black color gamma-glutamyltranspeptidase
Rotor syndrome: Deficiency in canalicular membrane Patients may present with jaundice, pruritus, skin xanthomas,
transport intestinal malabsorption, and deficiency of viatamin A,D,K.

B. NEONATAL JAUNDICE A. MORPHOLOGIC FEATURES OF CHOLESTASIS

AKA: Physiologic jaundice of NB Depends on the severity, duration and underlying cause
Transient, mild unconjugated hyperbil as a result of inability Obstruction of the biliary tree induces proliferation of duct
to conjugate and excrete bil in an immature liver - liver does epithelial cells, creating loops and reduplications of ducts and
not fully mature until 2 weeks of age ductules.
Seen in higher incidence among breast fed infants because of Portal tract edema and infiltrates of neutrophils may also be
B-glucuronidase in maternal milk present
2-3 days after birth, babies develop jaundice. Being self-
limiting, just expose the neonate to sunlight, and eventually INTRAHEPATIC EXTRAHEPATIC
the discoloration will subside. Bile plugs Bile plugs
If the jaundice does not subside it may be due to neonatal Ductal proliferation
hepatitis. Bile lakes
Biliary cirrhosis
C. HEREDITARY HYPERBILIRUBINEMIA
Crigler-Najjar Syndrome
o Genetic lack of bil UGT (uridine diphosphate
glucuronosyltransferase ) inc. unconjugated Bil 1
o Type 1: Complete absence of UGT, fatal, death,
secondary to kernicterus within 18 months
o Type 2: Partial defect in conjugation, UGT activity is
greatly reduced, only consequence is extraordinarily
yellow skin
Gilbert Syndrome
o Reduction in hepatic bil glucoridinating activity Bil 1
o Common, mild, benign, fluctuating hyperbiliribunemia
o Absence of hemolysis or liver disease
o Casued by reduction in hepatic bilirubinglucoridinating
activity (30% of normal), not as severe as Vrigler-Najjar
o Unconjugated hyperbilirubinemia
o Maybe detect at times of stress (illness, exercise,
fasting).
Dubin Johnson syndrome
o Hereditary defect in hepatocellular excretion of
bilirubinglucuronides across the canalicular membranes Figure 17. Liver with Jaundice
Conj Hyperbil
o Chronic conjugated hyperbilirubinemia
o Absence of canalicular transport protein for
bilirubinglucoronides (multidrug resistant protein 2)
o Most are asymptomatic except for fluctuating jaundice.
Rotor Syndrome
o Multiple defects in hepatocellular uptake and excretion
of bilirubin pigments.
o Liver is morphologically normal, patients have jaundice
but live normal lives.

IV. CHOLESTASIS
Systemic retention bilirubin and other solutes eliminated in
bile
Stagnation of bile due to impairment of bile flow along its
outflow tract leading to accumulation of bile components in
the blood.
Maybe extrahepatic or intrahepatic obstruction of bile
channels or by defects of hepatocyte bile excretion
Major components of bile
o Bilirubin
o Bile acids

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 Figure 20. Canalicular Cholestasis

Figure 18. Cholestasis. Slowed bile excretion. Intercellular: Drugs,

Viral infection. By means of Ducts: Drugs, Obstruction

B. TYPES OF CHOLESTASIS
CYTOPLASMIC CHOLESTASIS
o Presence of bile throughout the cytoplasm of
hepatocytes
o Hepatocytes take on a fine, foamy appearance
(feathery degeneration)
CANALICULAR CHOLESTASIS
o Presence of bile thrombi in bile canaliculi.
DUCTULAR CHOLESTASIS
o Stagnation of bile in periportal bile ductules
(ducts of Hering). Seen in:
Severe biliary obstruction
Severe necrotizing hepatitis
Septicaemia Figure 21. Ductular Cholestasis
DUCTAL CHOLESTASIS
o Presence of bile casts in portal bile ducts. Rarely C. CLINICAL MANIFESTATION
seen. Xanthelasma
Steatorrhea
Dark urine
Increase alkaline phosphatase and conjugated bilirubin
Pruritus
o Intense itching of skin on a jaundice patient highlights
conjugated type of hyperbilirubinemia
Alcoholic Stool
o Its present reflects obstruction of biliary passages
producing hyperbilirubinemia type 2 (conjugated). The
normal color of the stool is due to the presence of
biliverdin so when it is absent/unable to go to the GO
tract stool looks pale and fatty (looks like a paste of
chalk).

V. HEPATIC FAILURE
Most severe clinical consequence of liver disease
Final pathway of progressive liver injury
Loss 80 90 % of hepatic functional capacity
70 95 % MR
Figure 20. Cytoplasmic Jaundice. Involves the liver cells; bile staining
found within the hepatocytes

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 HEPATIC FAILURE CAUSES transformed into fibrous tissue; the underlying significant
1. Massive hepatic necrosis characteristic is diffused liver parenchymal fibrosis.
Fulminant viral hepatitis Liver cells have the ability to regenerate by complete
Drug induced Hepatitis (acetaminophen, halothane restitution.
anesthetic agent, INH, -anti-TB, CCl4). If there is damage to the reticular framework outcome
2. Chronic Liver Disease: will be repair by scarring & fibrosis with circulatory re-
Most common route of hepatic failure arrangement & cirrhosis.
Chronic hepatitis
Cirrhosis CAUSES
3. Hepatic dysfunction without overt necrosis: Chronic hepatitis infection Hep B , Hep C
Mitochondrial dysfunction characterized by massive Biliary atresia biliary cirrhosis
microvesicular steatosis Schistosoma pipe stem cirrhosis
Reyes Syndrome Chronic alcohol ingestion post alcoholic cirrhosis
o Rare but fatal; occurs unpredictably in children
receiving aspirin for febrile illness. MORPHOLOGIC FEATURES
Acute fatty liver of pregnancy (ALFP) Widespread fibrosis of liver parenchyma
o Seen in pregnant patients who suddenly develop o Most important finding; bridging fibrosis linking portal
liver failure; very high mortality rate; autopsy: no tracts to each other and to central veins
overt necrosis of liver cells, only fatty change. Small regenerative parenchymal nodules (called pseudo-
lobules) form when encircled by fibrosis.
MAJOR CLINICAL FEATURES Disorganization and disruption of parenchymal architecture.
Manifestations are related to the inability of liver cells to function.
1. Jaundice CLASSIFICATION BASED ON ETIOLOGY
2. Hypoalbuminemia: Liver unable to synthesize protein Alcoholic Liver Disease (most common) 60-70%
3. Hyperammonemia Viral Hepatitis (Hep B & C) 10%
4. Fetor hepaticus: Odor related to mercaptan Biliary Diseases
formation/accumulation, described as musty or sweet Primary Hemochromatosis deposits of iron 5%
and sour. Wilsons Disease congenital anomaly; copper Rare
5. Increased liver enzymes accumulation in tissue
Transaminases: AST/SGOT & ALT/SGPT important Alpha1 Antitrypsin Deficiency Rare
markers of liver cell injury & necrosis Cryptogenic/Idiopathic 10-15%
6. Signs of hyperestrogenemia:
Palmar erythema, spider angiomas (vascular anomaly),
gynecomastia, testicular atrophy (more prominent in CLASSIFICATION BASED ON THE SIZE OF THE NODULE
males, estrogen is metabolized/broken down in liver)
Macronodular >3mm Caused by: Post-viral
7. Hepatorenal syndrome/susceptible to multiple organ
hepatitis/Post-necrotic type
failure
Micronodular <3mm Caused by: 1) Alcoholic type
Appearance of acute renal failure in the absence of an
(earlier stages); 2) Biliary type
overt kidney pathology (kidneys fail in sympathy w/
the liver)
Present clinically as anuria or oliguria and azotemia
(high blood urea nitrogen and creatinine)
8. Coagulopathy
Impaired synthesis of clotting factors increase
bleeding (present w/ bleeding disorders)
9. Hepatic encephalopathy
Caused by abnormal neurotransmission in the CNS and
neuromuscular systems (excess ammonia serves as a
false neurotransmitter impairs neuronal function).
Indicate very sever end stage liver failure; one of the
most feared complications Figure 22. Macronodules. Nodules are big, knobby and variable in
Reversible size.
Clinical features:
o Disturbed consciousness (stupor to coma)
o Fluctuating neurologic signs
o Asterexis
o Hyperreflexia

VI. CIRRHOSIS
Chronic liver disease
Liver cirrhosis/fibrosis a state where the liver is

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 Figure 26. Biliary Cirrhosis. Small nodules & very dark green brown
Figure 23. Post Necrotic Cirrhosis. End result of viral hepatitis. discoloration of the liver on top.
Macronodular; may lead to Hepatocellular carcinoma (HCC).

Figure 24. Micronodular. Almost uniform small minute distribution of Figure 27. Cirrhosis of the Liver: Histologic Appearance. Regenerating
degenerative nodules all over the liver parenchyma; small bumpy liver hepatocyte w/ bands of connective tissue that forms
character of liver cells. pseudolobules. The architecture of the central vein and the portal
tract cannot be appreciated it is wiped out.

PATHOPHYSIOLOGY OF CIRRHOSIS
Normal Collagen Pattern:
o Type I & III collagen deposited in the portal tracts and
central veins
o Type IV collagen alongside hepatocytes and space of
Disse
Collagen pattern in cirrhosis
o Type I & III are deposited in lobule, creating broad
fibrous septal tract
o Activation and transformation of Ito cells into
fibroblasts

MECHANISMS OF CIRRHOSIS

Figure 25. Micronodular Cirrhosis w/ Fatty Change. Usually due to

Alcoholic Cirrhosis. (T) gross (B) histo.

Figure 28. Mechanisms of Cirrhosis. There is continuing injury to the

liver cell that causes both inflammation and liver cell necrosis. The
reduction of the reticular framework of the liver cell is contributed by
the continuing necrosis of the liver seen in alcohol abuse and chronic
hepatitis. The net effect of necrosis produces inflammation and

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 hepatocytic regeneration. The hepatocytes that regenerate form activation of vasoconstrictive mechanisms including the RAAS
pseudolobules & the connective tissue fibrosis elaborated by Ito cells and secretion of antidiuretic hormone.
produce bands of connective tissue that span and destroy the normal Increased formation of hepatic lymph to about 20L/day
architecture of the liver cells. exceeding the capacity of the thoracic duct; lymph is rich in
protein and low in TAGs.
CLINICAL MANIFESTATIONS OF CIRRHOSIS Intestinal fluid leakage.
Asymptomatic in early stage
o The liver is able to withstand or be able to function at 2. CONGESTIVE SPLENOMEGALY
about 10-20% remaining capacity. Hypersplenism
Once there is significant destruction of the liver cell of more
than 80%, symptoms can appear in the form of:
o Jaundice
o Chronic Liver Failure
o PORTAL HYPERTENSION
Patient will have ascites, signs of palmar erythema
and sign of varicosities
o Progressive liver failure
o Hepatocellular Carcinoma Figure 29. Slenomegaly with portal hypertension
o Weakness, anorexia
3. PORTO SYSTEMIC SHUNTS
VII. PORTAL HYPERTENSION Cardioesophageal junction esophagealvarices:
One of the important clinical manifestations of liver cirrhosis significant cause of upper gastrointestinal bleeding.
wherein there is increased pressure in the vessels. Many patients with cirrhosis end up dying because
Caused by obstruction of blood flow in the portal system the esophagealvarices ruptured.
Causes of portal hypertension Rectum (varices) hemorrhoids
o Prehepatic: Before entry to the liver. Periumbilical & abdominal wall caput medusa:
Thrombosis of portal vessels. blood vessels appeared to be dilated flowing from
Obstruction of portal vessels. the umbilicus resembling the head of Medusa (Greek
Massive splenomegaly with increased splenic mythology character whose hair is made up of
blood flow. snakes).
o Intrahepatic: Within the liver
Cirrhosis
Schistosomiasis
o Post hepatic: After exiting the liver
Severe right sided heart failure
Constrictive pericarditis
Hepatic vein outflow obstruction

MECHANISM OF PORTAL HYPERTENSION

1. Compression of sinusoids & central veins by fibrosis &
expansile nodules with increase sinusoidal resistance to
Figure 30. (L) Esophageal varices with portal HPN. (R) Caput
portal flow
Medusae with portal HPN. Dilated veins seen on the abdomen of
Contraction of vascular smooth muscle and a patient with cirrhosis of the liver. Looks like snake lesions.
myofibroblasts increases sinusoidal resistance to
blood flow.
Increased portal venous blood flow occurs creating a MAIN CAUSES OF LIVER DISEASE
hyperdynmaic splanchnic circulation mediated by
1. Toxins: Injures the liver
NO, TNF, and prostacyclins.
2. Infections (eg. Bacteria, viruses, parasites)
2. A-V anastomoses within scars
3. Disturbances of vascularity/bile excretion
4. Tumors: Primary and metastatic
CLINICAL MANIFESTATIONS OF PORTAL HYPERTENSION
1. ASCITES INFECTIONS OF THE LIVER
Reflecting the increased portal pressure
Viral Hepatitis
The accumulation of excess fluid in the peritoneal
Other systemic viruses:
cavity.
o Infectious Mononucleosis (caused by EBV)
MECHANISM
o Yellow fever
Increased hydrostatic pressure causes exudation of fluid o Herpes viruses
into the peritoneal cavity o Epstein Barr, Herpes simplex
Decreased plasma oncotic pressure decreased synthesis of o Coxsackie A & B
albumin in the liver o Lassa fever
Renal retention of sodium & water vasodilation triggers o CMV (in newborns or immunocompromised patients)

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 Bacterial, Parasitic, Protozoan Symptomatic WITHOUT jaundice
Clinically important is Viral Hepatitis. These viruses exhibit o Gastro-enteric form
organotropism (predilection for a certain organ); the viral o With fever, mild epigastric pain, diarrhea
antigens have a predilection for liver cells, so they exhibit Symptomatic WITH jaundice (classical)
hepatotropism. Relapsing
o 3.8-6.6%
TYPES OF VIRAL HEPATITIS
A (HAV)Picornavirus
B (HBV)Hepadnavirus
C (HCV)Flavivirus
D (HD.)Variate B
E (HE)Calicivirus
F (?)Picornavirus?
G (HG)Flavivirus
Probably many more viruses will be found to fill up the
alphabet, thanks to the advancements in molecular biology.

VIII. HEPATITIS A VIRAL INFECTION

a.k.a. Infectious hepatitis
Single stranded RNA virus, measures about 27 nm.
One of the clinically important hepatitis virsues.
Commonly seen in children and young adults.
Route of transmission: oral-fecal route Figure 31. Clinical Profile of Hep A
o Can be found in water and food; close personal contact, It has a short incubation period. During the incubation period, this is
very low risk of blood borne dissemination thats why the start of the gestation of the virus w/n the body and patients have
they are not included in blood screening for blood no clinical symptoms (this is the clinical phase). Then, it goes to
transfusion prodromal phase wherein the clinical manifestations are not specific,
so the px has flu-like symptoms until the icteric (symptomatic) phase;
Short incubation 2 6 wks
usually in acute Hep A wherein the px has jaundice, depicted by
Clinical asymptomatic 90% (may recover spontaneously),
increased levels of bilirubin in the blood and increasing levels of
jaundice 10% and may have symptoms of fever, chills,
transaminase during the symptomatic phase. The px has very high
anorexia and distaste for food.
level of transmaminase because the type of liver cell involvement is
o Does not produce chronic hepatitis, neither cirrhosis nor
diffuse so all the parts of liver lobule are affected. During the clinical
a carrier state.
phase, one can identify the virus in the liver and also in the feces. The
o Does not degenerate into liver cirrhosis with low
shedding of the virus is seen in the prodromal stage where patients
development of HCC.
are very infective. The presence of acute serological marker IgG is
Basically, Hep A is a benign, self-limiting type of hepatitis.
highest during the symptomatic phase and after that the IgG markers
Low MR (0.1%)
continue to increase for life.
No risk of development of HCC
Very low risk of fulminant hepatitis IX. HEPATITIS B VIRAL INFECTION
Probably in childhood, many were exposed and infected with
a.k.a. Serum Hepatitis type of hepatitis that is associated with
Hep A
the transmission of blood.
Markers are related to the detection of antibody to hepatitis.
DNA, ds type of antigen
Serologic Markers:
Long incubation ( 4 26 wks )
o anti IgM HAV: Acute, appears during onset of
Transmission (hepadnaviridae)
symptoms, recent markers for infect (IgM ME
o Parenteral
FIRST!)
o Sexual intercourse, body fluids/secretions
o anti IgG HAV: Marker for past history of exposure
o Vertical transmission: carrier state for life
or experience with the virus, long standing
Most serious cause of hepatocellular carcinoma (HCC) in Phil
protective immunity against re-infection, may
Can cause carrier & chronic state
persist for years.
(protective immunity for re-infection Important Hepatitis serologic markers: HbsAg (so called surface,
bc the antigen is found coating the virion on the surface),
With initial exposure to Hep A, the antibody that usually
HbeAg, Anti HBCAg, HbCAg , anti HbsAg & Anti HbeAg.
develops first is IgM
In the clinical setting of a px with jaundice for about 1-2
Table. Comparison between Hep A and Hep B
weeks, checking for the IgM will be positive BUT the IgG will
Hepatitis A Hepatitis B
be negative because usually increases a month after the
infection. 90% resolve Has many possible outcomes
(carrier, chronic hepatitis, etc)
HAV: CLINICAL FORMS Benign Can lead to cirrhosis and
carcinoma
Asymptomatic
Self-limiting Far worse compared to Hep A
o 73% in children / adults

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Stays in blood for about 2 weeks Remains in the blood throughout for 6 months or longer after initial detection
active phases of the disease o It is an abnormality of serological markers.
o Patient does not have clinical manifestations.
A. PATHOGENESIS o There is a persistence of Hep B surface antigen.
Mechanism of Injury o Implications:
Host response to the virus is the main determinant of Harbors and can transmit the virus
the outcome of infection. Can go to chronic hepatitis
Do not produce direct hepatotoxic damage
Result of immune mediated response by CD8+ D. CARRIER STATE
cytototoxic T-cells to viral antigens expressed by Defined by the presence of HBsAg in the serum for 6
infected hepatocytes months or longer after initial detection

B. HEP B VIRUS: CLINICAL FORMS E. SEROLOGIC INDEX OF CHRONIC REPLICATION OF HBV VIRIONS
Acute hepatitis w/ recovery and clearance Persistence of
Non-progressive chronic hepatitis clinically benign. o HBsAg (> 6 months)
Progressive chronic hepatitis ending in cirrhosis. o HBeAg (detects infectivity)
Fulminant hepatitis w/ massive liver cell necrosis. Presence of HbeAg means patient is
High infective
Backdrop for Hep D virus infection Hep D is a
In Hepatic Phase
parasite, it cannot stand on its own w/o Hep B infection.
o HBV DNA with anti-HBc and anti-HBs
It is a co-infection.
Associated with increased risk of
progressive liver damage

X. HEPATITIS C VIRAL INFECTION

C-Chronic
Caused by single stranded RNA virus
IP : 2 26 weeks
Spread by inoculation (contaminated needles) & blood
transfusion
Most important cause of transfusion assoc hepatitis ( 90
95 % of cases )
low transmission : sexual contact , peri-natal
Clinical 95% asymptomatic, 5% jaundice
Hallmarks of HCV infection: persistent infection & chronic
hepatitis
Causes chronic hepatitis with progression to cirrhosis in
more than 50 % of cases and CA
Clinical feature of chronic HCV infection is episodic
Figure 32. Outcomes of Hep B infections in Adults. elevation of serum transaminases with intervening
normal/near normal periods.
C. POSSIBLE OUTCOMES AFTER AN ACUTE INFECTION Elevated titers of anti-HCV IgG occurring after an active
Subclinical Disease (60-65%) infection do not consistently confer effective immunity
o No clinical symptoms o The virus is inherently unstable, giving rise to
o Has the antigen multiple genotypes and subtypes (known as
o Majority will recover quasispecies).
Acute Hepatitis (20-25%)
o There is liver cell destruction SEROLOGIC MARKERS
o Majority will recover HCV RNA detected in blood from 1 3 weeks
o 1% can have fulminant hepatitis where all liver anti HCV IgG
cells are destroyed anti HCV IgM
Persistent Infection (4%)
o Persistent clinical manifestations
o Elevated transaminase (ALT,AST)
o Has flu-like signs and symptoms of hepatitis
o If persistence is more than 6 months, it becomes
chronic hepatitis which can lead to cirrhosis or
carcinoma.
Carrier state (5-10%)
o Harbors the virus
o No clinical symptoms
o Defined by the presence of HBsAg in the serum

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 Figure 33. Outcomes of Hep C Infection in Adults.
Unlike Hep B, 85% of Hep C infections lead to Chronic Hepatitis and
20% of which can lead to cirrhosis and ultimately carcinoma or death.

XI. HEPATITIS D VIRAL INFECTION

DELTA VIRUS Figure 35. Superinfection.
(Mnemonics: D-virus)
Also called delta agent , hepatitis delta virus SEROLOGIC MARKERS FOR HDV INFECTION
Defective virus: Dependent on HBV superinfection 1. HDV-RNA = blood & liver just before and early acute disease
2. IgM Anti-HDV = recent HDV exposure
Caused by RNA virus that is replicatively defective
3. IgM Anti-HDV + IgM Anti-HbcAg = acute coinfection
Transmission: same as HBV
4. HbsAg + Anti-HDV = superinfection
Infection occurs when encapsulated by HBsAg
Absolutely dependent on the genetic information provided
XII. HEPATITIS E VIRAL INFECTION
by HBV for multiplication
(Mnemonics: E-virus)
Causes Hepatitis only in the presence of HBV
Caused by single stranded RNA virus
Usually causes illness more severe than HBV
Enterically transmitted, water borne infection
Can be acquired as:
Expectant mother: pregnant mother
o Acute co-infection: Get HBV + HDV
Epidemic
simultaneously, but HBV must establish infection
first. Average IP is 6 weeks
o Superinfection: HBV carrier is superinfected with Occur mostly in young to middle aged adult
HDV Most cases are self limited
o Helper independent latent infection: liver Clinical significance: high mortality rate among pregnant
transplant women.
Not associated with chronic hepatitis or carcinoma
Does not lead to chronic liver diseases or persistent viremia

XIII. HEPATITIS G VIRAL INFECTION

Inappropriately named: NOT hepatotropic and DOES NOT
cause elevation in serum aminotransferases.
o Appears to replicate in the bone marrow and
spleen.
More prevalent than HCV
(3.2% American blood donors vs. 0.5 1.0% HCV infection)
Rare cause of acute hepatitis
No chronic hepatitis noted even with persistence in sera
Nonpathogenic

XIV. CLINICOPATHOLOGIC SYNDROMES IN VIRAL HEPATITIS

1. Asymptomatic infection
o No s/sx
2. Acute symptomatic infection
o Jaundice, flu-like sx, abdominal pain
Figure 34. Coinfection. HBV + HDV
3. Carrier state
4. Chronic viral hepatitis
o Presence of antigen for >6mos; seen in HBV, HCV,
and HDV.
5. Fulminant hepatitis

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 o Rare, liver cells are destroyed, liver failure.

ACUTE ASYMPTOMATIC INFECTION

Infections are subclinical events in childhood that are
incidentally detected in adulthood by the presence of
antibodies to the virus.
Serologic evidence only
Minimal inc of serum transaminases
HAV, HBV, HCV

ACUTE SYMPTOMATIC INFECTION WITH RECOVERY

Four Stages:
1. Incubation Period
o No clinical sx
2. Pre-icteric Phase (Prodromal Phase) Figure 36. Acute Hepatitis. Ballooning is seen as swollen liver cells, 3x
o Nonspecific symptoms such as: Malaise, nausea & its normal size and with cytoplasmic clearing.
vomiting, anorexia, fever, muscle & joint pains,
RUQ pain
In HBV fever, rash, and GN are
present due to circulating immune
complexes (serum sickness)
Lab tests: elevated SGPT
3. Icteric Phase (Diagnostic Phase)
o Jaundice (conj hyper bil), tea colored urine,
acholic stools
o Hepatomegaly
o Lab findings: inc transaminase, inc PT
o Majority in HAV, not seen in 50% of HBV and
majority of HCV
4. Convalescent Period (Recovery phase)
o Symptoms recede, transaminase levels go down, Figure 37. Liver cell appear glassy in appearance. Usually seen in HBV
antigen level go down, increasing titer of antibody infections
specifically IgM.

DIAGNOSIS OF HEPATITIS
Clinical history
Laboratory
Serology
Liver biopsy
Newer Tests: PCR

HISTOLOGY OF ACUTE VIRAL HEPATITIS

Inflammation is the characteristic and predominant feature
of acute viral hepatitis.
Ground glass hepatocytes, sandy eosinophilic nuclei
HBV (Broken/Basagna Baso/Glass HBV)
Ballooning degeneration of hepatocytes and death by Figure 38. Portal and Peri-portal inflammation
apoptosis (Councilmans bodies) acute hepatitis
Liver cell necrosis (drop-out, apoptosis, confluent, bridging)
Focal infiltration of liver by lymphocytes around necrosis
Increased number of lymphocytic inflammation in the
portal tracts may spread to adjacent areas causing
apoptosis of periportal hepatocytes (interface hepatitis)
Fatty change In HCV (Chubby Change HCV)
Mild Cholestasis bile staining.
Hyperplasia of Van Kupffer cells, often laden with
lipofuschin.
Lobular disarray.
Cells in Canal of Hering proliferate forming a ductular
reaction
Bridging necrosis SEVERE CASES Figure 39. Lobular Inflammation. Seen in acute viral hep

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 CARRIERS
Asymptomatic, who harbors virus and thus capable of
transmission
Healthy carriers
o Carriers with chronic disease = patients with no
clinical symptoms and yet have progressive
destruction of the liver
Morphology:
o ground glass appearance HBsAg
o sanded nuclei HBcAg
Diagnosis: in situ hybridization and DNA probes

Figure 40. A mononuclear inflammatory cell infiltrate extends from
portal areas and disrupts the limiting plate of hepatocytes which are
undergoing necrosis, the so called piecemeal necrosis. Piecemeal
necrosis is indicative of a chronic active type of hepatitis that can
progress to cirrhosis
CHRONIC HEPATITIS
DEF: clinical (symptomatic), biochemical or serologic
evidence of continuing or relapsing hepatic disease for
more than 6 months with histologically documented
inflammation and necrosis
May result from any of the viral hepatitis except HAV or
HEV infection
Other causes include: Drugs, alcohol abuse, Wilsons
disease, autoimmune, alpha 1 anti-trypsin deficiency
Most common symptom is fatigue w/ or w/o malaise, loss
of appetite, occasional bouts of mild jaundice
Most common physical findings are spider angiomas,
palmar erythema, mild hepatomegaly, hepatic tenderness
and mild splenomegaly.

Figure 41. Councilmans Bodies

Figure 44. Histologic Difference between Acute and Chronic

Hepatitis. Critical finding in Chronic Hepatitis is the presence of
bridging necrosis with resulting bridging fibrosis. There is also
disruption of liver cell nodule with isolated liver cell necrosis and
Figure 42. Intracellular and Canalicular Cholestasis Bile staining inflammatory infiltrates.

CLASSIFICATION OF CHRONIC HEPATITIs

Liver biopsy may be indicated for px with long history of
elevated transaminases and persistent antigenemia
(presence of antigen in the bloodstream) to check if the px
has persistent or active hepatitis.

1. Chronic persistent hepatitis

o asymptomatic
o inflammation is confined to portal tracts
chronic triaditis or chronic portalitis
o persistently abnormal serum transferases
Figure 43. Confluent Necrosis o absence of liver necrosis
o Cirrhosis does not develop
o Benign form of chronic hepatitis

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2. Chronic Active Hepatitis
o Serious progressive liver ds with necrosis &
fibrosis
o Morphologic features :
focal, random liver cell necrosis
piecemeal necrosis histologic hallmark
bridging necrosis due to recurrent active
destruction of liver cells leading to cirrhosis
inflammatory infiltrates in the portal tract
Major causes of death:
Cirrhosis may present with s/sx of portal hypertension
Massive hematemesis d/t rupture of esophageal varices
Hepatocellular carcinoma HCC
PATHOLOGY OF CHRONIC HEPATITIS
Liver cell necrosis (bridging, piecemeal) and regeneration
Portal tract inflammation
Portal fibrous deposition
HBV: ground glass hepatocytes
HCV: BD epithelial hyperplasia, lymphoid aggregate,
steatosis
Figure 45. Fatty Change in Viral Hepatitits
Figure 46. Chronic HCV Infection. Portal inflammation and
lymphocyte aggregates are formed.
FULMINANT HEPATITIS
One of the dreaded complications of viral hepatitits
Appearance of s/sx of hepatic failure during the course of
hepatitis
Hepatic insufficiency occurs w/n 2-3 weeks from onset of sx
to hepatic encephalopathy
In HBV infections, the liver undergoes massive apoptosis.
50-65% of the cases is associated with viral hepatitis
25-30% assoc with drugs or chemical injury
o Directly hepatotoxic drug reaction
o Idiosyncratic reaction
Morphology:
Gross:
o Small with wrinkled capsule (d/t significant loss of
liver cells)
o Muddy red, mushy cut surface
o Liver becomes a small limp red organ w/ a too
large capsule.
Figure 47. Gross. Fulminant Hepatitis
Histology
o Diffuse or massive liver cell necrosis
o Collapsed reticulin frame work
Figure 48. Fulminant Hepatitis. Absence of liver cells. Only seen are
inflammatory cells and bile ducts.
Figure 49. Trichrome stain collapse of the liver parenchyma with
viral hepatitis. The blue staining areas are the connective tissue of
many portal tracts that have collapsed together.
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 LABORATORY FINDINGS IN VIRAL HEPATITIS
Alanine aminotransferase (ALT)/Serum Glutamic Pyruvic
Transaminase (SGPT) & Aspartate aminotransferase
(AST)/Serum glutamic-oxaloacetic transaminase (SGOT) are
both markedly elevated (usually >8 fold increase)
Pattern of markedly elevated AST and ALT with mildly
elevated Alkaline Phosphatase and LDH is virtually
diagnostic of acute hepatitis.

Figure 50. Amebic Liver Abscess. The central area of abscess consists
of digested necrotic debris which are rich with cysts and trophozoites
appearing like an anchovy paste.

XV. BACTERIAL INFECTION

Route of transmission:
1. Systemic blood spread the usual route
2. Ascending infection in the portal vessel
3. Ascending spread from bacterial colonization of the biliary
tree
Pyogenic liver abscess
Weils disease (leptospira)
TB, Syphylis (hepar lobatum - tertitary syphilis)

XVI. PARASITIC INFECTION Figure 51. Pyogenic Liver Abscess. Yellow structures correspond to
multiple sites of purulent exudation and necrosis.

Figure 52. Pyogenic Liver Abscess. Purulent necrotic debris with

neutrophilic infiltrates, walled off by zones of granulation tissue and
fibrosis. Seen in ascending cholangitis hence termed as Cholangic
Abscess

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 o Toluene, xylene: Fatty liver, fibrosis.
o Vinyl chloride: Angiosarcoma, fibrosis,

XVIII. ALCOHOLIC LIVER DISEASE (ALD)

Liver injury associated with excess alcohol intake.
Most common form of liver disease in the USA
Lesions:
o Fatty change/ steatosis
o Alcoholic hepatitis
Figure 53. Hepar Lobatum. Not a common finding nowadays d/t o Cirrhosis
decreased incidence of Syphilis. May be asymptomatic or with mild to severe hepatic
inflammation, cirrhosis or encephalopathy.
XVII. TOXIC LIVER DISEASE
A. Drugs and Toxin-Induced Liver Disease A. Morphologic Lesions of ALD
Caused by hepatotoxic drugs Fatty steatosis / Fatty change
Types o Most frequent morphologic abnormality
o Intrinsic: Dose dependent, predictable o Reversible (if one abstains from alcohol)
o Idiosyncratic: Unpredictable (hypersensitivity or o Micro or macrovesicular, initially centrilobular
abnormal drug metabolism) o Liver becomes a large, greasy, soft yellow organ.
Alcoholic hepatitis
Table 2. List of some hepatotoxic drugs o May occur after a bout of heavy drinking.
HEPATOCELLULAR DAMAGE EXAMPLE o Malaise, weight loss, anorexia, upper abdominal
1. Microvesicular fatty Tetracycline, Aspirin, Ethanol discomfort, and tender hepatomegaly.
change o Fatty change, focal liver cell necrosis, infiltrates of
2. Macrovesicular Ethanol, Methotrexate PMNs (neutrophils, also lymphocytes and
3. Centrilobular necrosis CCl4 (Carbon tetrachloride), macrophages)
Acetaminophen, Rifampin, Swelling occurs due to accumulation of fat,
Halothane water and proteins, cholestasis and
4. Diffuse necrosis INH, Methyldopa, Amanita iron/hemosiderin accumulation may also occur.
phalloides o Mallory bodies
Tangled skeins of Cytokeratin (8 and 18) that
5. Hepatitis Methyldopa, INH, Nitrofurantoin
complex with other proteins (ubiquitin)
6. Fibrosis/ Cirrhosis Ethanol, Methotrexate
Appear as eosinophilic clumps in hepatocytes.
7. Granuloma Sulfonamides, Quinidine,
Also present in Non-alcoholic Fatty Liver Disease
Allopurinol, Hydralazine
(NAFLD), Primary Biliary Cirrhosis (PBC),
8. Cholestasis Oral contraceptives,
Wilsons disease, chronic cholestatic syndromes
Chlorpromazine, Erythromycin,
and hepatocellular tumors.
Anabolic steroids
o Fibrosis around central veins and individual liver cells.
o Reversible if one abstains from alcohol inflammation
Some common hepatotoxics and their damage: may wane.
o Aflatoxin B: from moldy foods, rice, corn, cassava, oil. It o Hepatomegaly, mild elevation of serum bilirubin and
causes jaundice, fatty liver, Reye syndrome, alkaline phosphatase.
hepatocellular carcinoma, thromboses, phlebitis, Alcoholic cirrhosis/ Laennecs
phlebosclerosis and veno-occlusive disease. o Typically micronodular
o Amanita phalloides: mushroom poisoning, causes o In late stages, the nodules tend to become larger and
centrolobular and massive necrosis. irregular macronodular (hobnail appearance)
o Benzene from chemical industry, shoe fabrication. It o Liver changes from yellow-tan fatty organ to a brown,
causes steatosis and cirrhosis. shrunken nonfatty organ.
o Beryllium from X-ray tube and fluorescent lamp o Prolonged exposure and great volume of intake
manufacture. It causes necrosis and granulomas. Severe and irreversible change.
o Boron, cadmium from gold melting, nickel, chromium o Laennecs cirrhosis broad expanses of tough pale scar
from plating, copper sulphate. tissue interrupting liver nodules.
o Carbon tetrachloride: Centrolobular necrosis o Centrilobular fibrosis: broad bands of connective tissue
o Cooking oil from adulterated rapeseed from Spain around central vein that coalesce to form macronodules
1981. (micronodules macronodules).
o Kerosene from fuel handling. o End-stage alcoholic cirrhosis closely resembles viral
o Lead: nuclear inclusions, steatosis, hepatitis. hepatitis.
o Pesticides: Steatosis, angiosarcoma.
o Phosphorus from poisons and fire crackers. Fatty liver,
necrosis, fibrosis.
o Pyrrolizidine alkaloids: veno-occlusive disease. From
bush tea with senecio, cereals with crotolaria.

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 Figure 55. (L) Fatty Change. Greasy, yellow. (R) Fatty steatosis.
Vesicles and macrovesicles (fatty acid in liver cell)
Figure 54. Alcoholic liver progression

B. Pathogenesis
o Exposure to alcohol causes steatosis, dysfunction of
mitochondrial and cellular membranes, hypoxia and
oxidative stress.
o Factors influencing the development and severity of alcoholic
liver disease:
o Genetics
o Ethnic differences
o Gender women are more susceptible. Estrogen
increases gut permeability to endotoxins, thus
increasing production of pro-inflammatory cytokines
and chemokines.
o Co-morbid conditions iron overload and infections
with HBV and HCV have increased risk.
o Injury is related to the amount of alcohol intake
o Ingestion of up to 80 gm/ ethanol (8 beers) mild, Figure 56. (L) Alcoholic Hepatitis. Liver cell necrosis. Transaminase
reversible hepatic changes is Fatty liver increased, thus patient has jaundice.
o Daily intake of 80 gms or more significant risk for
severe hepatic injury
o Daily ingestion of 160 gms or more for 10-20 yrs.
associated with severe injury
o Thus, moderate the intake of alcohol. Give the liver a
chance to rest!
o Effects of Alcohol
o Increase mobilization of lipid from adipose tissue stores
excessive entry of FFA into the liver
o Increased the esterification of FA to triglycerides
o Decreased FA oxidation
o Decreased formation and secretion of lipoprotein
o Malnutrition and vitamin deficiency (Ex. Thiamine)
Alcoholics do not eat properly, they just drink beer.
o Bacterial endotoxins evokes inflammation and induces
release of vasoconstricting endothelins activates the
Ito cells to contract decreased sinusoidal perfusion Figure 57. Alcoholic Hepatitis. Diagnostic cell = Mallory cell = pink
hyaline bodies inside cytoplasm of liver cells. Neutrophils surround
liver cells.

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 Figure 60. Hemangioma

o HEPATIC ADENOMA
o Related to use of oral contraceptives.
Figure 58. Alcoholic Hepatitis. Mallory Bodies (Alcoholic Hyaline o Tendency to rupture and cause fatal hemorrhage
Bodies) especially if located under the Glissons capsule.
o Histologically consists of normal appearing liver cells
w/o portal tracts & bile ducts.
Benign proliferation of well differentiated
hepatocytes
Abundant glycogen may form large cells with
clear cytoplasm
Solitary arterial vessels and veins are present
Steatosis is present
o Grossly appears as a solitary, may or may not be
encapsulated, nodule.

Figure 59. (L) Micronodular cirrhosis w/ fatty change. Looks

shrunken, dense fibrosis thus its firm appearance. (R) Alcoholic
Centrolobular Cirrhosis. Fibrosis starts in Centrilobular portion.

QUESTION. Why do Mallory Bodies occur in Alcoholic Liver

Disease?
There is destruction of cells before they become necrotic,
thus there are cytoplasmic condensations of protein that
appear as pink coagulum in the cell. The cell is not dead but it is
about to die. Protein denaturation (pink substance) occurs as
evidence of beginning destruction of liver cells before they die.
These are Mallory Bodies.

QUESTION. How is this different from Councilman Bodies?

Councilman Bodies: The counterpart of Mallory Bodies in Viral
Hepatitis is the ground-glass Hepatocyte. They appear pink and
sandy.
Mallory Bodies: Pink and shiny.

XIX. HEPATIC TUMORS

o BENIGN TUMOR: Hemangioma
o Vascular tumor discrete red-blue soft nodules, usually
less than 2cm diameter. Figure 61. Hepatic Adenoma. Note the solitary, encapsulated nodule
o Histologically appear as vascular channels in a bed of in gross specimen. Note the mature-looking hepatocytes
fibrous connective tissue. microscopically.
o Most common benign tumor of the liver.
o Usually located underneath the Glissons capsule. XX. MALIGNANT TUMORS
o Danger of rupture hemorrhage. More common

A. PRIMARY CARCINOMA
I.HEPATOCELLULAR CARCINOMA (HCC)

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 Frequent complication of cirrhosis cirrhosis. Area can be resected. One can live with this liver. (B)
Rare in the US & Europe Multinodular.
Common in the Far East & Africa
Elevated -fetoprotein is found in 50% of HCC cases.
Associated with aflatoxin B, viral hepatitis
o Aflatoxin B- a mycotic toxin secreted by Aspergillus;
common in decaying grains and peanuts.
o High incidence of Viral hepatitis B and C.

Morphology
GROSS
3 Forms of HCC
1. Solitary discrete,
usually large,
amenable for surgical
resection.
2. Multiple widely
distributed involving
several parts of a
lobule.
3. Diffuse cant be
surgically resected,
sometimes involves
the entire liver.
All 3 forms may cause LIVER
ENLARGEMENT.
HCC cells are usually paler than
normal liver tissue; may be
green if cells are well
differentiated and bile
producing.
HISTOLOGY
Malignant cell that
resembles the liver cells
2 patterns:
o Trabeculae cord-
like pattern that
resembles liver
plates
o Acinar
pseudoglandular
appearance prognosis. Liver is a single, large, scirrhous tumor with fibrous
Bile production if cells are
well differentiated
Aggressive with a high
tendency for invasion of
blood vessels (may spread
via hepatic vascular system
to IVC and right heart)
Figure 63. Hepatocellular CA. This recapitulates the appearance of
liver cells with vascular sinusoids and polygonal shape except that
nuclei are bigger, scarier and angry looking.
HCC Variant: Fibrolamellar CA
Patients have no underlying chronic liver disease; good
bands coursing through. Composed of well differentiated
polygonal nests or cords, separated by parallel lamellae of dense
collagen.
II.CHOLANGIOCARCINOMA (CCA)
Associated with parasitic, biliary atresia.
Originate from biliary tree within and outside the liver:
o Intrahepatic tree-like tumorous mass, resemble
adenocarcinomas.
o Extrahepatic small, gray, firm nodules within bile duct
wall; diffusely infiltrative; papillary or polypoid; may or
may not secrete mucin; with abundant fibrous stroma
and epithelial proliferation.

Figure 64. Cholangiocarcinoma. Intrahepatic. Tumor grows

in solid masses.

Figure 65. Adenocarcinoma. Due to irregular duct-forming

Figure 62. Hepatocellular Carcinoma. (T) Nodules with corresponding structures.

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 B. METASTATIC or SECONDARY TUMORS
Account for the majority of hepatic malignancies
Common primary sites include: GIT, breasts & lung
o The liver is a very vascular organ & it becomes a seat to
hematogenous seeding of cancers elsewhere.
o Distinct organotropism for liver metastasis.
Gross characterized by multiple nodules with umbilication

Figure 66. Metastatic Adenocarcinoma. Microscopically,

metastatic infiltrating ductal carcinoma from breast is seen
on the right, with normal liver parenchyma on the left.

Figure 67. Metastatic liver cell carcinoma. Note the serrated

edges of the tumor and the prominent central necrosis seen
in the larger nodules. Metastases are usually multiple
throughout the liver.

Figure 68. Metastatic adenocarcinoma

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