The liver is the largest internal organ of the human body. The liver weight approximately 1.2 to 1.5 Kg in the adult it is located beneath the diaphragm in the right upper quadrant of the abdomen and is protected by the ribs and held in place by ligamentous attachment. The normal color of the liver is brown and the external surface is smooth (Janelle et al., 2010).
1.1.2 Function of The Liver:
The liver is the largest internal organ of the human body. It is a functionally complex organ that plays a critical biochemical role in the metabolism, digestion, detoxification, and elimination of substances from the body. The liver is involved in a number of excretory, synthetic, and metabolic functions, all of which are essential to life. The liver is unique in the sense that it is a relatively resilient organ that can regenerate cells that have been destroyed by some short-term injury or disease. However, if the liver is damaged repeatedly over a long period of time, it may undergo irreversible changes that permanently interfere with its essential functions (Janelle et al., 2010).
1.1.3 . Liver Anatomy:
22.214.171.124. Gross Anatomy:
The liver is about 2% of bodyweight in the adult. The liver receives its blood supply from two sources (the portal vein, 80%) which drains the spleen and intestines. The remaining (oxygenated blood, 20%) is delivered by the hepatic artery. The portal vein is formed by the union of the splenic and the superior mesenteric veins with the inferior mesenteric vein. These are draining into the splenic vein. The common hepatic artery is a branch of the celiac artery along with the splenic and left gastric arteries. Occasionally, the hepatic artery has accessory and/or replaced vessels supplying the liver these accessory or replaced are a branch of the proximal superior mesenteric artery, while the accessory or replaced left hepatic artery is a branch of the left gastric artery ( Hiatt et al., 2013).
Externally, the liver is divided by the falciform ligament into a larger right lobe and a smaller left lobe. The falciform ligament attaches the liver to the anterior abdominal wall. Its base contains the ligamentum teres, which has a remnant of the vestigial umbilical vein. In cirrhosis, this veinrecanalizes as a result of portal hypertension based on Couinaud classification, the liver is divided into eight independent functional segments. Each segment has its own portal pedicle consists of the hepatic arterial branch, portal branch, and the bile duct with a separate hepatic venous branch that provides outflow. The numbering of segments is in a clockwise manner. Segments II and III, are known as the anterior and posterior segments of the left lobe, respectively. They are known collectively as the left lateral segment of the liver and the topographic left lobe. Segment IV is the medial segment of the left lobe. Segments II to IV make up the functional left lobe of the liver.
The right lobe of the liver is made up of segments V and VIII (the anterior segments, and segments VI and VII (the posterior segments). Segment I, the caudate lobe, is located posteriorly. The outflow of the liver is provided by the three hepatic veins. The right hepatic vein divides the right lobe of the liver into anterior and posterior segments. The middle hepatic vein divides the liver into the left and right lobes which runs in the same plane with the inferior vena cava and the gallbladder fossa. Similarly, the left hepatic vein divides the left liver into medial and lateral segments. The portal vein divides the liver into the upper and lower segments. The segmental liver anatomy is important to radiologists and surgeons, especially in view of the need for an accurate preoperative localization of focal hepatic lesions (Soler et al., 2013).
126.96.36.199. Microscopic Anatomy:
The liver is divided into microscopic units called lobules. The lobules are the functional units of the liver; they are responsible for all metabolic and excretory functions performed by the liver. Each lobule is roughly a six-sided structure with a centrally located vein (called the central vein) with portal triads at each of the corners. Each portal triad contains a hepatic artery, a portal vein, and a bile duct surrounded by connective tissue. The liver contains two major cell types: hepatocytes and kupffer cells. The hepatocytes, making up approximately 80% of the volume of the organ, are large cells that radiate outward from the central vein in plates to the periphery of the lobule. These cells perform the major functions associated with the liver and are responsible for the regenerative properties of the liver. Kupffer cells are macrophages that line the sinusoids of the liver and act as active phagocytes capable of engulfing bacteria, debris, toxins, and other substances flowing through the sinusoids. (Janelle et al., 2010)
Friedman, 2008 showed that the repetitive injury in the liver stimulates an inflammatory response, which attempts to clear the instigating factor, for example a virally infected hepatocyte, and then heal the injury through fibrogenesis to maintain hepatic integrity. Liver fibrogenesis occurs in the context of a chronic inflammatory response, which leads to myofibroblast proliferation, increased production of extracellular matrix (ECM) and parenchymal cell proliferation as part of a process of scar formation and regeneration that replaces hepatocytes lost through necrosis or apoptosis. In the wound healing response, increased ECM deposition occurs which is a normal appropriate response. The constituents of this matrix include basement membrane and interstitial collagens, proteoglycans, elastin and matrix glycoproteins such as fibronectin and laminin. In normal liver fibril forming collagens are physiological. Types 1, 3 and 5 are found in the capsule, around large vessels and in the portal areas Types 3 and 4 collagens with fibronectin accumulate early in liver injury in the space of Disse and over time greater amounts of type 1 and 4 collagen together with elastin and laminin re deposited as the injury becomes sustained and chronic. Although all 4 types of collagen are increased by 3-10 folds, the proportion of type 1 collagen in chronic liver disease increases the most. The maturity of the fibrosis can therefore be assessed using knowledge of the different types of ECM deposited together with the amount of crosslinking observed. Recently it was shown that elastin accumulation in liver injury occurs not only as a result of increased synthesis but also as a failure of matrix metalloproteinase-12 (MMP)-12 derived degradation (Pellicoro et al., 2012).
1.2.2. The Mechanisms of Fibrogenesis:
Liver fibrogenesis is characterized by cellular activation of hepatic Stellate cells (HSCs) and its mediators. HSCs have dominated studies exploring mechanisms of liver fibrosis over the last two decades. HSCs are resident vitamin A-storing cells in the perisinusoidal space of Disse between the sinusoidal endothelium and hepatocytes. Following hepatic injury, HSCs become activated into a myofibroblast-like phenotype that is contractile, proliferative and fibrogenic. Collagen and other ECM components are deposited which result in a fibrous scar eventually leading to cirrhosis and liver failure. Liver fibrosis is a dynamic process, resulting from the equilibrium between fibrogenesis and altered matrix degradation, and may be reversible prior to the establishment of advanced architectural (Lee et al., 2011).
Changes to the liver HSC represent the final common pathway of the wound healing response of the liver. Activation consists of two major phases, initiation (also called preinflammatory stage) and perpetuation, followed by a resolution phase if the injury subsides (Friedman, 1993).
Following alcohol consumption, cholestasis and iron overload, reactive oxygen species (ROS) and lipid peroxidation products are generated in large amounts leading to Kupffer cell activation. Activated Kupffer cells, infiltrating circulating monocytes, activated and aggregated platelets, and damaged hepatocytes are sources of platelet-derived growth factor (PDGF) and transforming growth factor-b1 (TGF-b1), which both trigger the initiation of intracellular signaling cascades after binding to HSC surface receptors. Activated HSC lose vitamin A droplets and increase expression of cytoskeletous proteins such as desmin and ?-smooth muscle actin, which are associated with augmented contractile activity, as well as generate ECM, which includes type I and III collagen (Kawada, 2011). In addition, augmented production of the tissue inhibitor of matrix metalloproteinase (TIMP) hampers ECM degradation of and stimulates their accumulation in case of inflammation liver. Activated HSC, also known as myofibroblast (MFB) are contractile and their capacity to generate contractile force mediates the liver’s injury response through modulation of sinusoidal blood flow and scar contracture. Metalloproteinases-1 (MMP-1) is a key collagenase. However, MMP activity also strictly regulates its binding partner TIMP. Because HSC are able to generate both TIMP-1 and -2, a local balance between MMP and TIMP plays an important role in fostering the resolution of the fibrotic process (Benyon and Arthur, 2001).