The Liver is the largest organ in the body which plays a central role in fat, carbohydrate and protein metabolism. It contributes significantly to maintaining of hemostasis through its secretory function.
The anatomical and physiological units of the liver are central to the understanding the pathophysiological and biochemical changes seen in a diseased liver. Therefore, the anatomy and physiology of the liver is discussed first and the article culminates in the description of a specific liver disease.
PHYSIOLOGY
The liver has a very large number of important physiological functions which is closely related to its structure: The structural unit of the liver has long been considered to the lobule arranged around a central hepatic venule and with portal tracts at its periphery [Sherwood, 1997].
On the basis of elegant microcirculatory studies, acinus has been defines as an alternative basic structural unit; this is the parenchyma receiving blood from a single terminal portal venule and hepatic arteriole termed together the axial vessels, and passing its bile into a single small duct in the same portal tract. The simple acinus lies between two hepatic venules into which its blood drains [Saxena, 1999].
The simple acinus is subdivided into three zones: the hepatocytes in Periportal zone are those closest to the axial vessels; they receive blood rich in nutrients and oxygen and metabolically more active than cells in the other zones. The two other zones, mid-zone and perivenular, are more peripheral to the axial blood supply; the cells of the perivenular zone are at the microcirculatory periphery of the acinus and are thus the most susceptible to hypoxic damage [Sherwood, 1997].
Functional heterogeneity of hepatocytes is also reflected across the acinar unit with zonal variation in both enzyme distribution and bilirubin secretion. The differences in metabolic activities of the hepatocytes generally depend on their relationship to the axial blood supply, and this influences patterns of pathological damage [Rajasekar, 1999].
It is involved in the intermediary metabolism of proteins, carbohydrates and fats: the glucose level is maintained by the constant interplay between the insulin and glucagon and their effect on liver and muscle enzymes involved in glucose metabolism.
The liver is also a major organ involved in the production of plasma proteins particularly albumin which contributes significantly to the maintenance of plasma oncotic pressure [Sherwood, 1997]. Other plasmas proteins produced are important in the maintenance of hemostasis via the clotting and coagulation pathways; these include clotting factors and fibrinogen. It is also involved in the production of various enzymes such as alkaline and acid phosphatases, amylase, transaminases, levels of which determine the function/dysfunction level of the liver.
Bile is formed and secreted by the liver as well. It is also responsible for the detoxification of endogenously produced waste products or exogenous toxins and drugs, and in the storage of proteins, glycogen, various vitamins and metals [Sherwood, 1997].
Accordingly, the liver is liable to injury from a number of causes, and this will lead to profound metabolic imbalance. These causes of liver injury include biological agents, chemical agents and toxins, tumors, injury from metabolic disturbance and hypoxia [Saxena, 1999]. Understanding these causes and how they impact the liver is crucial to appreciating the onset, progression and clinical presentation of a diseased liver.
Certain viral infections damage the liver severely causing acute hepatitis with extensive necrosis of the liver cells. These include Hepatitis A, B, C, D, and others. Progression to chronic hepatitis is a complication of type B. the liver is vulnerable to Injury from drugs and toxins because it detoxifies several metabolites, drugs and toxic substances. Besides, the liver receives blood from the gastrointestinal tract through the portal system, and is thus exposed to the poisons and toxins absorbed across the gastrointestinal tract.
Prolonged biliary obstruction can cause biliary cirrhosis, and the bile duct is also viable ground for bacterial infection. Specific dietary and enzyme deficiencies have adverse effects on the liver architecture and function. [Jungermann, 1996]
Clinical features of disturbed hepatic function are diverse and varied; this can be considered under the heading of hepatocellular failure and portal hypertension. Hepatocellular failure is said to occur when the total liver function fails below the minimum required to maintain physiological state. It results from loss of a large number of cells, and from impaired hepatocyte function due to interference with blood supply or metabolic function.
Hepatic failure may be acute or chronic. Specific changes which occur with hepatic failure include: Changes in nitrogen metabolism with a rise in the blood level of toxic nitrogenous compounds produced by bacteria in the gut and normally metabolized by the liver cells.
These substances can damage the cells of the central nervous system [Jungermann, 1996]. Jaundice can also result as a result of failure to remove bilirubin from the blood, and to conjugate it and to excrete it in the bile; failure to produce plasma proteins particularly albumin and clotting factors; hormonal disturbances occur which are attributable to interference with the hepatic metabolism of hormones; functional renal failure may occur in a phenomenon called hepatorenal failure.
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