Download liver_cirrhosis_ - Cairo University Scholars

Cairo university
Faculty of veterinary medicine
Department of pathology
Research on:
07284:‫الرقم األكاديمي‬
‫ محمود صابر محمد عبد القادر‬/‫ الطالب‬:‫مقدم من‬
CONTENTS
Introduction
Definition & Etiology
Common Symptoms of Cirrhosis
Pathophysiology
PATHOLOGY ,Pathogenesis&
Classification
MORPHOLOGY OF CIRRHOSIS
EVOLUTION OF CIRRHOSIS
ACTIVITY OF CIRRHOSIS
REFERENCES
Introduction
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver
tissue by fibrosis, scar tissue and regenerative nodules (lumps that occur as a result of
a process in which damaged tissue is regenerated), leading to loss of liver function.
Cirrhosis is most commonly caused by alcoholism, hepatitis B and C, and fatty liver
disease but has many other possible causes. Some cases are idiopathic, i.e., of
unknown cause.
Ascites (fluid retention in the abdominal cavity) is the most common complication of
cirrhosis and is associated with a poor quality of life, increased risk of infection, and a
poor long-term outcome. Other potentially life-threatening complications are hepatic
encephalopathy (confusion and coma) and bleeding from esophageal varices. Cirrhosis
is generally irreversible, and treatment usually focuses on preventing progression and
complications. In advanced stages of cirrhosis the only option is a liver transplant.
The word "cirrhosis" derives from Greek κίρῥος, meaning tawny (the orange-yellow
colour of the diseased liver). While the clinical entity was known before, it was René
Laennec who gave it the name "cirrhosis" in his 1819 work in which he also describes
the stethoscope
Normal Liver
CIRRHOSIS
Definition & Etiology
Cirrhosis is a common chronic, progressive and diffusive liver disease, caused by one or
several agents act repeatedly and persistently.
Histologically, cirrhosis is an irreversible alteration of the liver architecture, consisting of
hepatic fibrosis and areas of nodular regeneration
In other words, It is a Diffuse fibrosis of the liver with nodule formation. or Abnormal
response of the liver to any chronic injury
Causes of Cirrhosis:
Chronic viral hepatitis & Prolonged cholestasis (primary biliary cirrhosis, primary
sclerosing cholangitis)& Autoimmune diseases (autoimmune hepatitis)
Drugs and toxins & Alcohol& Certain parasitic infections (such as schistosomiasis)
Normal Liver
CIRRHOSIS
Common Symptoms of Cirrhosis
Jaundice
(Yellow skin or eyes)
Ascites
(Fluid in abdomen)
Hepatomegaly
(Enlarged liver)
Edema
(Swelling of the legs, feet, and back)
Small, red spider-like vessels
Decreased urine output
Pale or clay colored stools
Vomiting blood (portal
hypertension)
Nosebleeds
Fatigue and weakness
Loss of appetite
Weight loss and nausea
Whole body itching (pruritis)
Mental confusion
Redness of the palms of the
hands
Pathophysiology
The liver plays a vital role in synthesis of proteins (e.g.,
albumin, clotting factors and complement),
&detoxification and storage (e.g., vitamin A). In addition,
it participates in the metabolism of lipids and
carbohydrates.
Cirrhosis is often preceded by hepatitis and fatty liver
(steatosis), independent of the cause. If the cause is
removed at this stage, the changes are still fully
reversible
The pathological hallmark of cirrhosis is the development of
scar tissue that replaces normal parenchyma, blocking
the portal flow of blood through the organ and disturbing
normal function. Recent research shows the pivotal role
of stellate cell, a cell type that normally stores vitamin A,
in the development of cirrhosis. Damage to the hepatic
parenchyma leads to activation of the stellate cell, which
becomes contractile (called myofibroblast) and obstructs
blood flow in the circulation. In addition, it secretes TGFβ1, which leads to a fibrotic response and proliferation of
connective tissue. Furthermore, it disturbs the balance
between matrix metalloproteinases and the naturally
occurring inhibitors (TIMP 1 and 2), leading to matrix
breakdown and replacement by connective tissuesecreted matrix.[8]
The fibrous tissue bands (septa) separate hepatocyte
nodules, which eventually replace the entire liver
architecture, leading to decreased blood flow throughout.
The spleen becomes congested, which leads to
hypersplenism and increased sequestration of platelets.
Portal hypertension is responsible for most severe
complications of cirrhosis.
normal
cirrhotic
Micrograph Showing cirrhosis
Trichrome stain
PATHOLOGY ,Pathogenesis& Classification
the first theory as to the pathogenesis of this disorder was advanced by Roessle:
parenchymal degeneration, regeneration and scarring which is now understood
according to the following sequence:
INJURY
DEGENERATION
FIBROSIS
FORMATION OF FIBRO-VASCULAR MEMBRANES
PARENCHYMAL DISSECTION INTO NODULES
REARRANGEMENT OF BLOOD CIRCULATION
CIRRHOSIS
which is considered by most experts as a self-perpetuating irreversible process.
Regenerative nodules may form in the fibrous septa but they are not necessary for
the histological diagnosis of cirrhosis: as nodules alone without fibrosis do not
constitute cirrhosis. In this disease, the nodularity of the liver is mostly the result of
fibrosis dissecting the parenchyma in small uniform acinar or subacinar nodules in
micronodular types and in lobular and plurilobular large non-uniform nodules in
macronodular forms. Regenerative nodules develop in the midst of scars but are a
late phenomenon. They are important, however, for the advancement and neoplastic
transformation of the cirrhosis.
According to World Health Organization :it classified according to:
MORPHOLOGIC: Macronodular & Micronodular & Mixed
HISTOLOGIC: Portal, Post-necrotic, Post Hepatitic, Biliary, Congestive
ETIOLOGIC AGENTS: Genetic, Toxic, Infectious, Biliary, Vascular,
Cryptogenic
MORPHOLOGY OF CIRRHOSIS
GROSS INSPECTION
Grossly, with the naked eye, a cirrhotic liver appears nodular, "hub-nailed", on the
external surface and nodular on the cut surface. Variation in size, color, shape and
consistency is relevant and may help in the identification of the etiology. The liver is
usually indurated shrunken and yellowish-tan but it may be enlarged and yellow as in
alcoholic fatty cirrhosis, rusty as in hemochromatosis or large and green as in biliary
obstruction. It is usually the privilege of the surgeon to inspect the liver in vivo,
therefore he must acquaint himself with the gross changes of cirrhosis and develop
the ability of detecting discolorations of possible neoplastic nodules in order to obtain
adequate samples for histological examination
MICRONDULAR CIRRHOSIS:
Small rather uniform 2m nodules
seperated by thin fibroussepta usually
due to a chemicalagent as alcohol
which diffuseuniformly throught the
liver.
MACRONODULAR CIRRHOSIS:
Larger nodules separated by wider scars
and irregularly distributed throughout the
liver usually due to an infectious agent
such as viral hepatitis which does not
diffuse uniformly throughout the liver
MICROSCOPIC CHANGES
Presence of nodules and fibrous septa with effacement of the lobular architecture.
The nodules are of two types: Dissection type and Hyperplastic Regenerative type
DISSECTION NODULES
contain remnants of portal tracts
and central veins.
are separated by wide scars but
contain thin fibrous septa.
contain dilated sinusoids especially
at their periphery looking like
multiple central veins obviously
produced by the inflow of arterial
blood coming from the
surrounding wide scars.
the portal tracts within large
nodules may be hypoplastic
containing portal venule and
arteriole but no bile ducts giving
the impression of a disappearing
.bile duct disorder.
within wide scars regenerative
.nodules may develop.
HYPOPLASTIC PORTAL
FIELD:
In a dissecting nodule.
Notice presence of portal
vein, portal artery but no
bile duct.This case was
interpreted as "vanishing
"duct syndrome
REGENERATIVE NODULES
these occur in micro and macro nodular cirrhosis
they arise in the midst of scars favored by the rich
arterial blood of scar tissue
they are round nodules with a fibrous pseudo
capsule with bile ductules due to obstruction of bile
flowthey have embryonal type of cell plates, two
"cells thick, "twinning of cell plates
nuclei are aligned at the sinusoidal pole of the
plates
they often show focal cholestasis
they may undergo dysplastic and malignant
changes
they compress the vessels of the capsule
contributing to the perpetuation of the cirrhosis
THE FIBROUS SEPTA:
Are, with nodules, the other characteristic component of cirrhosis and they are visible even with the
naked eye. They have been termed "fibro-vascular membranes" which provide a diversion of the
blood flow through an alternative route along these fibrous septa instead of through the acinar
sinusoids, thus affecting the physiology of the hepatocytes The fibrous septa are basically
granulation tissue more or less active according to the degree of edema, capillarization,
inflammatory cell infiltration and fibrosis. They reflect the activity of the cirrhotic process
PASSIVE SEPTA
ACTIVE SEPTA
Slender connective tissue
bands containing few chronic
inflammatory cells and sharp
demarcation with parenchymal
liver tissue
Thick connective tissue bands containing
edema, many chronic inflammatory cells
and irregular demarcation with the
parenchymal liver tissue
EVOLUTION OF CIRRHOSIS
The evolution can be assessed on degree of fibrosis and
nodule formation. The following stages can be
identified with some approximation even on a needle
biopsy specimen
1-INCOMPLETE SEPTAL
(Incomplete bridging fibrosis, no nodules(
2- EARLY
(Thin bridging fibrosis with dissecting nodules(
3- MODERATELY ADVANCED
(Thick bridging fibrosis with dissecting nodules(
4-ADVANCED
(Wide septa with regenerative hyperplastic nodules(
INCOMPLETE
SEPTAL CIRRHOSIS:
Presence of very slender
septa radiating from enlarged
fields toward the center of
the lobule. There are
distended efferent vessels
around the septum. This type
of cirrhosis produces only
portal hypertension and no
liver failure. The prognosis is
very good if the portal
hypertension is controlled
EARLY CIRRHOSIS:
Thin fibrous septa with
dissecting nodules. No
regenerative nodules.
Presence of multiple
efferent vessles.
(Reticulim stain by silver
impregnation
ADVANCED
CIRRHOSIS:
Wide scars containing
clusters of
regenerative
hepatocytes. Large
scars may contain
large portal fields
recognizable with a
stain for elastic fibers
ACTIVITY OF CIRRHOSIS
Activity is assessed by extent of cell damage, inflammatory reaction
within the scar tissue, piecemeal necrosis along fibrous septa,
edema of the septa and changes in the parenchymal nodules such
as necrosis and cholestasis. Activity indicates the progression of the
cirrhotic process and is graded as:
INACTIVE
No inflammation and intact limiting plates
around septa which are fibrotic
SLIGHT
Mild inflammation; segmental erosion of limiting
plates
MODERATE
Moderate inflammation and damage of limiting
plates
SEVERE
Marked inflammation, extensive damage of
limiting plates, piecemeal necrosis
and parenchymal damage, i.e.: necrosis,
cholestasis, dysplasia, malignant transformation
COMPLICATIONS OF CIRRHOSIS
About one third of cirrhosis are compensated and, do not produce any clinical symptoms
and are accidentally discovered during a medical examination or an operation or at
autopsy. The rest are decompensated and produce complications mainly due to liver
failure and portal hypertension. They are:
ASCITES
VARICES
Esophageal varices, hemorrhoids
PORTAL VEIN THROMBOSIS
DIGESTIVE HEMORRHAGES
JAUNDICE
HEPATIC ENCEPHALOPATHY
IMPAIRED COAGULATION
ANEMIA
INFECTION
INFARCTION OF NODULES
MALIGNANT CHANGE (HEPATOCELLULAR
CARCINOMA) IN NODULES
MALIGNANT TRANSFORMATION:
of a regenerative nodule. Notice the
capsule, the peripheral zone of the
regenerative nodule and the inner zone
.of hepatocellular carcinoma
HEPATIC
ENCEPHALOPATHY
REFERENCES
Lectures on veterinary pathology (353)
WEB SITES:
www. epcity.com
www.meddean.luc.edu/lumen/MedEd/orfpat
h/cirhosis.htm
www.en.wikipedia.org