Pathology Cirrhosis

Macroscopically, the liver may be initially enlarged, but with progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm and the color is often yellow (if associates steatosis). Depending on the size of the nodules there are three macroscopic types: micronodular, macronodular and mi ed cirrhosis. In micronodular form (!aennec"s cirrhosis or portal cirrhosis) regenerating nodules are under # mm. In macronodular cirrhosis (post$necrotic cirrhosis), the nodules are larger than # mm. %he mi ed cirrhosis consists in a variety of nodules with different sizes. Microscopically, cirrhosis is characterized by regeneration nodules, surrounded by fibrous septa. In these nodules, regenerating hepatocytes are disorderly disposed. &ortal tracts, central veins and the radial pattern of hepatocytes are absent. 'ibrous septa are important and may present inflammatory infiltrate (lymphocytes, macrophages) If it is a secondary biliary cirrhosis, biliary ducts are damaged, proliferated or distended $ bile stasis. %hese dilated ducts contain inspissated bile which appear as bile casts or bile thrombi (brown$green, amorphous). (ile retention may be found also in the parenchyma, as the so called )bile la*es). +,-

Micronodular cirrhosis is seen along with moderate fatty change. .ote the regenerative nodule surrounded by fibrous connective tissue e tending between portal regions.

%here are two forms of fatty change : microvesicular and macrovesicular. Microvesicular: .umerous tiny fat vesicles, re/uires fat stain to be appreciated. 0ften, one would be surprised as how enormous fat accumulation is without being seen in 123 sections. %his is a to ic condition causing hepatocellular failure. Macrovesicular: a few large clear vacuoles in the cytoplasm of hepatocytes, pushing the nucleus aside. 4sually, has no effect on the function of the hepatocyte. Macrovesicular: 1epatomegaly is the only sign5 liver function tests are minimally abnormal, if at all. 3 amples include: 6lcohol $ with a combination of macro and microvesicular fatty change, Malnutrition $ in particular protein deficiency, starvation, diabetes, obesity , severe infection or burn, Medication and %o ins, 1ypo imia.

Fatty liver (also *nown as steatorrhoeic hepatosis or steatosis hepatis) is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis. Despite having multiple causes, fatty liver disease ('!D) can be considered a single disease that occurs worldwide in those with e cessive alcohol inta*e and those who are obese (with or without effects of insulin resistance). %he condition is also associated with other diseases that influence fat metabolism+7-. Morphologically it is difficult to distinguish alcoholic '!D from non alcoholic '!D and both show micro$vesicular and macrovesicular fatty changes at different stages.

&athology
'atty change represents the intra$cytoplasmic accumulation of triglyceride (neutral fats). 6t the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus $ microvesicular fatty change. In this stage liver cells are filled with multiple fat droplets that do not displace centrally located nucleus. In the late stages, the size of the vacuoles increases pushing the nucleus to the periphery of the cell giving characteristic signet ring appearance $ macrovesicular fatty change. %hese vesicles are well delineated and optically )empty) because fats dissolve during tissue processing. !arge vacuoles may coalesce, producing fatty cysts $ which are irreversible lesions. +7-. Macrovesicular steatosis is the most common form and is typically associated with alcohol, diabetes, obesity and corticosteroids. 6cute fatty liver of pregnancy and 8eye"s syndrome are e amples of severe liver disease caused by microvesicular fatty change +9-. %he diagnosis of steatosis is made when fat in the liver e ceeds :;7<= by weight +:-+,-+7-.

Defects in fat metabolism is responsible for pathogenesis of '!D which may be due to imbalance in energy consumption and its combustion resulting in lipid storage or can be a conse/uence of peripheral resistance to insulin, whereby the transport of fatty acids from adipose tissue to the liver is increased+>-+7-. Impairment or inhibition of receptor molecules (&&68$?, &&68$@ and A83(&7) that control the enzymes responsible for the o idation and synthesis of fatty acids appears to contribute towards fat accumulation. In addition alcoholism is *nown to damage mitochondria and other cellular structure further impairing cellular energy mechanism. 0n the other hand non alcoholic '!D may begin as e cess of unmetabolised energy in liver cells. 1epatic steatosis is considered reversible and to some e tent nonprogressive if there is cessation or removal of underlying cause. Aevere fatty liver is accompanied by inflammation, a situation that is referred to as steatohepatitis. &rogression to alcoholic steatohepatitis (6A1) or non$ alcoholic steatohepatitis (.6A1) depend on persistence or severity of inciting cause. &athological lesions in both conditions are similar. 1owever, the e tent of inflammatory response varies widely and does not always correlate with degree of fat accumulation. Ateatosis (retention of lipid) and onset of steatohepatitis may represent successive stages in '!D progression +B-. !iver with e tensive inflammation and high degree of steatosis often progresses to more severe forms of the disease +C-. 1epatocyte ballooning and hepatocyte necrosis of varying degree are often present at this stage. !iver cell death and inflammatory responses lead to the activation of stellate cells which play a pivotal role in hepatic fibrosis. %he e tent of fibrosis varies widely. &erisinusoidal fibrosis is most common, especially in adults, and predominates in zone # around the terminal hepatic veins+7<-. %he progression to cirrhosis may be influenced by the amount of fat and degree of steatohepatitis and by a variety of other sensitizing factors. In alcoholic '!D the transition to cirrhosis related to continued alcohol consumption is well documented but the process involved in non$alcoholic '!D is less clear.

Aummary
Mechanism behind lipid accumulation in liver cells. %.': tumor necrosis fator alpha, .': nuclear factor, I8A:insulin receptor substrate, apo(: apolipoprotein (5 M%%&: microsomal triglyceride transfer protein. I created using Dorel draw and used free illustrations from wi*ipedia and wi*icommons. 6 vector graphic version is also available at wi*icommons