I. Necrosis. Virtually any significant insult to the liver may cause hepatocyte necrosis.
In ischemic necrosis, poorly stained mummified hepatocytes remain (coagulative necrosis).
Necrosis of scattered hepatosytes, clumps, or an entire lobule. Isolated necrotic hepatocytes appear as eosinophilic rounded - up, shrunken cells and are called Councilman Bodies or apoptotic bodies).
Alternatively, hepatocytes may osmotically swell and rupture so-called hydropic degeneration.
Necrosis may be limited to scattered cells within the hepatic lobules (focal necrosis) or involve particular regions of the lobule (zonal necrosis), entire lobules (submassive necrosis), or the whole liver (massive necrosis).
Focal necrosis is most characteristic of microbial infections, particularly smoldering forms of viral hepatitis.
Centrilobular necrosis is characteristic of ischemic injury and many drug and toxic chemical reaction.
Midzonal necrosis is a rare pattern, seen in yellow fever. Strictly periportal necrosis is seen primarily in phosphorus poisoning and eclampsia.
Massive necrosis is most commonly caused by severe chemical and drug toxicity or viral hepatitis.
In other conditions, such as typhoid fever, tularemia, brucellosis, and herpes or adenovirus infection, expanding regions of the parenchyma are destroyed (geographic necrosis). With disseminated candidal or bacterial infection, macroscopic abscesses may occur.
II. Degeneration.
Short of outright necrosis, hepatocytes may take on a swollen, edematous appearance (ballooning degeneration) with irregularly clumped cytoplasm and large, clear spaces.
Alternatively, retained biliary material may impart a diffuse foamy swollen appearance to the hepatocyte (cholestasis).
Accumulation of specific substances in viable hepatocytes, such as iron, copper, and viral particles, may be of particular diagnostic value.
III. Inflammation. Inflammation is defined as the influx of acute or chronic inflammatory cells into the liver and is termed hepatitis.
Although inflammation may be secondary to hepatocellular necrosis, lymphocytic attack of viable antigen-expressing liver cells is a common cause of liver damage.
Inflammatory cells may be limited to the site of entry (portal tracts) or spill over into the parenchyma.
In the case of focal hepatocyte necrosis, scavenger macrophages quickly generate scattered clumps of inflammatory cells in an otherwise innocuous parenchyma.
Foreign bodies, organisms, and a variety of drugs may incite a granulomatous reaction.
IV. Regeneration.
The liver has enormous reserve, and regeneration occurs in all but the most fulminant diseases. Regeneration is signified by thickening of the hepatocyte cords (the result of hepatocyte proliferation) and some disorganization of the parenchymal structure.
When massive hepatocellular necrosis occurs and leaves the connective tissue framework intact, almost perfect restitution can occur.
V. Fibrosis.
Fibrous tissue is formed in response to inflammation or direct toxic insult to the liver.
Deposition of collagen has lasting consequences on hepatic patterns of blood flow and perfusion of hepatocytes.
In the initial stages, fibrosis may develop around portal tracts or the central vein or may be deposited directly within the space of Disse.
With continuing fibrosis, the liver is subdivided into nodules of regenerating hepatocytes surrounded by scar tissue, termed cirrhosis.
Classification of the liver diseases
Hepatosis (when degeneration and necrosis inflammation in the hepatocytes prevail).
Hepatitis (when inflammation in the liver prevails).
Cirrhosis (when disregeneration is observed).
Hepatic tumors.
Hepatosis
The term hepatosis is used to describe degeneration and necrosis in the liver caused by infectious, toxic, circulatory or traumatic agents.
Hepatosis may be inherited and acquired. Inherited hepatosis develops in storage diseases or enzymopathy. Acquired hepatosis may be acute and chronic.
The massive necrosis is the most common acute hepatosis.
The steatosis (fat hepatosis) is the most common chronic one.
Massive necrosis (toxic degeneration of the liver)
Massive necrosis (toxic degeneration of the liver) is acute (rarely chronic) disease characterized by massive necrosis of the hepatocytes with development of the hepatic insufficiency.
Etiology. It is most commonly caused by viral hepatitis, drug or mushroom toxicity.
Morphology
There are 2 stages in this hepatosis.
Stage of yellow degeneration, when liver becomes enlarged, dense and yellow. Then it size increases; it consistency becomes flabby; capsule is shrunken. The cut surface is grey. Microscopically fat degeneration, necrosis and autolysis of hepatocytes are observed.
Stage of red degeneration is characterized by progressive reduction of liver size and mass. Macroscopically the liver is red due to necrosis end autolysis of hepatocytes with appearance of plethoric blood vessels. Jaundice, hyperplasia of lymph nodes and spleen, numerous hemorrhages in the skin and mucous, necrosis of the renal epithelium, degenerative and necrotic changes in pancreas, myocardial, CNS are observed in the patients with massive necrosis of the liver.
Steatosis
It is a chronic disease, which is characterized by increase of fat amount in the cytoplasm of the hepatocytes.
Etiology of steatosis is similar to massive necrosis of the liver. But in this pathologic agent has less toxicity and, as a rule, compensatory and adaptive processes are higher.
Macroscopically the liver is enlarged, flabby. Fat drops are seen on the incision. The color is yellow. This is called “goose” liver.
Microscopically - dust-like, small and large drop in the liver cells are observed.
Viral hepatitis
Viral hepatitis is reserved for infection of the liver caused by a small (but growing) group of viruses having a particular affinity for the liver: Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), and Hepatitis E Virus (HEV).
I. Hepatitis A virus (HAV) causing a fecally spread self-limiting disease. Hepatitis A is responsible for 20-25% of clinical hepatitis in the developing countries of the world. The disease occurs in epidemic form as well as sporadically. The spread is related to close personal contact such as in overcrowding, poor hygiene and sanitation. An incubation period carries on 15-45 days. HAV does not cause chronic hepatitis. The fatality rate associated with HAV is about 0.1%.
II. Hepatitis B virus (HBV), causing a parenterally transmitted disease that may become chronic. An incubation period carries on 4 to 26 weeks. HBV can produce:
Acute hepatitis.
Chronic nonprogressive hepatitis.
Progressive chronic disease ending in cirrhosis.
Fulminant hepatitis with massive liver necrosis.
An asymptomatic carrier state with or without progressive disease.
Further more HBV plays an important role in the development of hepatocellular carcinoma. Transfusion, blood products, dialysis, needle-stick accidents among health care workers, intravenous drug abuse, and homosexual activity constitute primary risk categories for HBV.
III. Hepatitis C virus (HCV), also tenned non-A, non-B (NANB) hepatitis virus involved chiefly in transfusion-related hepatitis. HCV has a high rate of progression to chronic disease and eventual cirrhosis, exceeding 50%.
IV. Delta hepatitis virus (HDV) is acute coinfection by exposure to serum containing both HDV and HBV. Hepatitis may be mild to fulminant, with fulminant disease somewhat more likely than with HBV alone; chronicity rarely develops.
Morphological patterns of Acute Viral Hepatitis
Any one of the hepatotropic viruses can cause acute viral hepatitis. Whatever the agent, the disease is more or less the same and can be divvied into four phases:
An incubation period.
A symptomatic preicteric phase.
A symptomatic icteric phase.
Convalescence.
The morphologic changes in acute viral hepatitis are virtually the same regardless of the causative agent and can be mimicked by drug reactions.
Grossly, the liver is slightly enlarged: more or less green depending on the phase of the acute disease and the degree of jaundice.
Histologically the major findings are:
Hepatocellular injury:
Necrosis of scattered hepatocytes, clumps, or an entire lobule.
Isolated liver cells or small cell clusters appear as eosinophilic rounded-up cells (apoptotic bodies, Councilman’s bodies).
Degenerated hepatocytes may also appear ballooned. Fatty change is unusual except with HCV.
Macrophages may phagocytize the necrotic hepatocytes; and may accumulate clumps of lymphocytes and macrophages.
Confluent necrosis may lead to bridging necrosis connecting portal-to-portal, central-to-central, or portal-to-central regions of adjacent lobules, signifying a more severe form of acute hepatitis.
Inflammation is a characteristic, usually prominent feature of acute hepatitis.
The portal tracts are usually infiltrated with a mixture of inflammatory cells; this infiltrate consists of lymphocytes with a touch of leucocytes and may spill over into the parenchyma, particularly where adjacent hepatocytes have undergone necrosis.
Reactive changes in Kupffer’s cells.
Kupffer cells and sinusoidal lining cells undergo hypertrophy and hyperplasia and are often laden with lipofuscin pigment owing to phagocytosis of hepatocellular debris.
Cholestasis is biliary stasis.
An inconstant finding is bile stasis within the lobule. The bile duct epithelium may proliferate, particularly in cases of HCV hepatitis, forming poorly defined ductular structures (cholangioles).
Regeneration.
In the recovery phase of acute hepatitis, the lobule remains somewhat disorganized because hepatocytes can proliferate faster than normal cord-sinusoid-cord relationships can be established.
Regenerating hepatocytes lack uniformity in size and are pale, the result of diminished numbers of cytoplasmic organelles.
Double and triple nuclei in regenerating cells are commonly observed. Residual clumps of inflammatory cells may persist for some time.
Lobular disarray results from the cellular swelling (ballooning), necrosis, and regeneration of cells producing compression of the vascular sinusoids and loss of the normal, more or less radial array. Disruption of lobular architecture by necrosis is called lobular disarry.
Morphological patterns of Chronic Viral Hepatitis
Symptomatic, biochemical, or serologic evidence of continuing or relapsing hepatic disease for more than 6 months, optimally with histologically documented inflammation and necrosis, is taken to mean chronic hepatitis.
Although the hepatitis viruses are responsible for most cases of chronic hepatitis, there are many other etiologies: Wilson’s disease, alpha-1-antitrypsin deficiency, chronic alcoholism, drugs (isoniazid, alpha-methyldopa, methotrexate), and autoimmunity.
Since 1968, chronic hepatitis has been classified according to the extent of inflammation:
Chronic persistent hepatitis, in which inflammation is confined to the portal tracts.
Chronic active hepatitis, in which portal tract inflammation spills into the parenchyma and surrounds regions of necrotic hepatocytes.
Chronic lobular hepatitis, in which persistent inflammation is confined to the lobule.
It is now apparent that the primary determinant of disease progression, and therefore prognosis, is the etiologic form of hepatitis. Therefore, although histologic information may provide information helpful for patient management, classification of chronic hepatitis strictly by histologic criteria is obsolete and should not be used. This is particularly important because therapy that is effective for one cause of chronic hepatitis may be ineffective, or potentially detrimental, in other forms of the disease.
The likelihood of chronic hepatitis following acute viral infection can be summarized:
HAV: Extremely rare.
HBV: Develops in more than 90% of infected neonates and 5% of infected adults, of whom one-fourth progress to cirrhosis.
HCV: Develops in more than 50% of infected patients, half of whom progresses to cirrhosis.
HDV: Rare in acute HDV/HBV coinfection; a more severe chronic hepatitis is the most frequent outcome of HDV superinfection.
HEV: Does not produce chronic hepatitis.
Chronic hepatitis with HBV, and apparently with HCV, contributes significantly to the development of primary hepatocellular carcinoma.
Morphology
The morphology of chronic hepatitis ranges from exceedingly mild to severe, to eventual cirrhosis.
The diagnosis of chronic persistent hepatitis is confirmed by needle biopsy of the liver, which is invaluable in distinguishing it from more serious form of chronic active hepatitis.
Microscopically:
There is portal triad characterized by expansion of the portal tract by mononuclear inflammatory cells, consisting of lymphocytes, macrophages, occasional plasma cells, and an occasional rare neutrophiles or eosinophiles.
The lobular architecture of hepatic parenchyma is usually preserved.
There is absence of piecemeal necrosis.
Chronic active (aggressive) hepatitis is defined as a progressive form of chronic necrotising and fibrosing disease involving portal tracts as well as hepatic parenchyma.
Microscopically:
The histologic hallmark of progressive disease is piecemeal necrosis, where by the chronic inflammatory infiltrate spills out from portal tracts into adjacent parenchyma, with associated necrosis of hepatocytes in the limiting plate.
There may be formation of lymphoid follicles.
There may be lobular inflammation with focal necrosis of hepatocytes.
As with acute hepatitis, bridging necrosis may connect adjacent portal-portal, central-central, and portal-central zones.
Although piecemeal and bridging necrosis do not imply inevitable progression of disease, continued loss of hepatocytes results in fibrous septum formation, which, accompanied by hepatocyte regeneration, results in cirrhosis.
The aforementioned features are common to all forms of chronic hepatitis (viral or otherwise). In patients with chronic HCV hepatitis, lymphoid aggregates in portal tracts and mild fatty change are seen in about 50% of cases, and bile duct damage is seen in more than 90%. Conversely, “ground-glass” hepatocytes are sometimes present in chronic HBV hepatitis. Despite use of immuno-histochemical techniques, it is frequently impossible to identify the etiology of chronic hepatitis on tissue samples, so great reliance must be placed on clinical, virologic, and serologic observations.
The clinical features of chronic hepatitis
The clinical features of chronic hepatitis are extremely variable and are not predictive of outcome.
In some patients, the only signs of chronic disease are persistent elevations of serum transaminases, hence the facetious designation “transaminitis”.
The most common symptom is fatigue; less common symptoms are malaise, loss of appetite, and occasional bouts of mild jaundice.
Physical findings are few, if any, the most common being spider angiomas, palmar erythema, mild hepatomegaly, hepatic tenderness, and mild splenomegaly.
Laboratory studies may reveal prolongation of the prothrombin time and, in some instances, hyperglobulinemia, hyperbilirubinemia, and mild elevations in alkaline phosphatase.
Occasionally in cases of HBV, and rarely in HCV, immune-complex diseases may develop secondary to the presence of circulating antibody-antigen complexes, in the form of vasculitis (subcutaneous or visceral, i.e., polyarteritis nodosa) or glomerulonephritis.
The major causes of death are hepatic insuffisiency and hepatic encephalopathy or massive hemorrhage from esophageal varicose and, in those with long-standing HBV (particularly neonatal) or a HCV infection, hepatocellular carcinoma.
Cirrhosis of Liver
Cirrhosis is the final stage of liver disease and is defined by three characteristics:
Fibrosis is present in the form of delicate bands or broad scars replacing multiple adjacent lobules.
The parenchymal architecture of the liver is divided by interconnecting fibrous scars.
Parenchymal nodules are created by regeneration of hepatocytes. The nodules may vary from micronodules (less than 3 mm in diameter) to macronodules (3 mm to several centimeters in diameter).
Several features should be understood:
The parenchymal injury and consequent fibrosis are diffuse, extending throughout the liver; focal injury with scarring does not constitute cirrhosis.
Nodularity is requisite for the diagnosis and reflects the balance between regenerative activity and constrictive scarring.
The fibrosis, once developed, is generally irreversible; some regression has been observed in humans with treated schistosomiasis and hemochromatosis.
Vascular architecture is recognized by parenchymal damage and scarring, with formation of abnormal interconnections between vascular inflow and hepatic vein outflow.
1 ... 8 9 10 11 12 13 14 15 ... 20