Central vein lobule

The classic central vein lobule accords with the traditional description of lobular structure (F. Kiernan, 1833 H. Eppinger, 1937 H. Elias, 1949). The hepatic lobule... 

Centrilobular The region of the liver lobule surrounding the central vein. 

Figure 28.1. Comparison of structural liver lobule with functional acinar regions. The liver lobule is centered on the terminal hepatic venule (THV), also called the central vein, and assumes a roughly hexagonal shape with its vertices at the portal triads, which contain the portal vein (PV), hepatic artery (HA), and bile duct (BD). The liver acinus is centered upon the tract of blood vessels that branch from the hepatic artery and portal vein of the portal triads. Hepatocytes within the acinus are grouped within functional zones 1,2, and 3 located at increasing distances from the vascular tracts that interconnect adjacent portal triads.

Figure 2.3. Blood circulation and tissue perfusion in the liver, a Schematic of the blood circulation. Portal vein and liver artery branch out in a parallel fashion. From the terminal branches, the blood enters the tissue and is then eollected into the tributaries of the liver vein, b The liver tissue has a honeyeomb stmcture each hexagon is a liver lobule. The liver artery and portal vein branches are located at the comers in the middle of the lobule, we find the central vein which merges with others to form the liver vein, c Higher power view, showing the sponge-like stmcture of the liver tissue. The blood gains intimate contact with virtually every liver cell - diffusional barriers are absent, and distances extremely short.

Hepatic lobule and hepatic acinus are relatively well-accepted models to describe the structure and functional aspects of the liver. Histologically, the hepatic lobule is a hexagonal region of the liver parenchyma around the central vein. Typically, six portal triads, consisting of branches from the portal vein and hepatic artery as well as bile ductules, border the edge of the lobule. Cords of hepa-tocytes are arranged radially around the central vein and blood sinusoids form between them. The hepatic parenchyma is divided into three zones based on the proximity to... 

S. Minot coined the term sinusoid to describe the blood capillaries leading in a radial fashion to the central vein of the lobule. 

Fig. 2.11 Diagram of the traditional ( classic ) hepatic lobule according to the lobular structure (F. Kiernan, 1833) (s. fig. 1.18) and as stereogram (H. Elias, 1949) the liver cell columns run radially from the limiting plate to the central vein (10) (s. fig. 2.16)...

Fig. 2.12 Hepatic lobules with central vein ( f ) and Glisson s triangles (G). Slight distortion of the lobular architecture...

The portal vein lobule was first recognized in the description of the portal unit given by RP. Mall (1906). It resembles a hexagon. The periportal field constitutes the axis at the centre while the central veins form the limiting points, (s. fig. 2.13) The glandular character of the liver is the main criterion of differentiation of the portal vein lobule. Thus the direction of blood flow is from the centre towards the periphery (centrifugal) and the direction of bile flow from the periphery towards the centre (centripetal). It could also be demonstrated that the lobule periphery is enclosed by basket-like ramifications of the portal vein (= corbicula portalis). (77) This further emphasizes the significance of the hepatic lobule. 

The functional and microcirculatory hepatic unit forms the basis for assessing the hepatic acinus (A. M. Rappaport, 1954). (41-43) The portal vascular bundle, with the terminal branches of the hepatic artery and portal vein diverging fan-shaped after penetrating the lobules, is at the centre of the acinar structure. These vessels represent the central axis for the circular blood supply of the related liver parenchyma. This area is roughly the shape of a rhombus, the outer angles of which are formed by the two central veins of the adjacent lobules while the diagonal... 

Fig. 2.13 Diagram of the classic hepatic lobule (I), the portal vein lobule (II) and the hepatic acinus (III) CV = central vein ( ), P = portal tract ( ). Flow direction venous blood (= blue arrow), arterial blood (= red arrow) and bile (= green arrow), with the microcirculatory acinus zones 1, 2, 3. (cf. W Ekataksin et af, 1992 the microvascular unit is regarded as an area in which all hver cells receive blood from a common terminal vessel)...

LC These liver-specific antibodies (LCl and LC2) react with a soluble cytosolic antigen in the liver cells (W. Storch, 1975, 1979). This was confirmed by E. Martini et al. in 1982. They are frequently associated with anti-LKM 1 antibodies (60-70%). The hepatocytes around the central vein of the liver lobule are left out of the otherwise homogeneous cytoplasmatic fluorescence. LC 1 antibodies are not present in chronic viral hepatitis C, and thus they are important in differentiating between (LCl-positive) AIH and (LCl-negative) chronic HCV infection. LCl is primarily found in young patients presenting with AIH type 2. Only rarely are LC2 antibodies found in AIH they react with periportal liver cells. (35, 45)... 

Micronodular cirrhosis Monolobular (monoacinar) cirrhosis consists of individual hepatic lobules separated by connective tissue, with the central vein maintained in the interior. In pseudolobular cirrhosis, no elements of the lobular architecture and no central vein can be detected the nodules in this type of cirrhosis are small. The monolobular and pseudolobular forms are classified as micronodular cirrhosis, or Nagayo type C (with node size <0.3 cm). A striking feature is the uniformity of the nodules, (s. figs. 35.4, 35.5)... 

It was previously thought that blood flowed directly from the portal space vessels between plates to hepatocytes to be collected in the central veins. Although it is now clear that the actual flow of blood in these areas is not as previously envisioned, the lobule unit remains conceptually convenient because it exhibits morphologically distinguishable zones, for example, differential deposition of glycogen and fat, referred to as centrilobular, mid-zonal, or periportal. Furthermore, toxic agents of pathological conditions may selectively show their harmful effects in these areas. 

We now know that blood enters the sinusoids of the parenchyma via fine terminal branches of the afferent vessels, which leave the portal spaces at intervals, coursing perpendicular to the central vein and along the sides of the hexagons forming classical lobules. Each fine terminal afferent vessel supplies blood to only sectors of adjacent lobules. The associated mass of parenchymal tissue that they preferentially supply... 

Figure 1 Diagram illustrating the basic anatomical unit of the liver, the liver lobule, showing (1) the radial disposition of the liver cell plates and sinusoids around the central vein, (2) the centripetal flow of blood from branches of fhe hepafic artery and portal vein, and (3) the centrifugal flow of bile (small arrows) fo fhe small bile duct in the portal space. (Reproduced from Bloom W and Fawcett DW (eds.) (1968) A Textbook of Histology, 9th edn. Philadelphia Saunders redrawn and modified from Ham, Textbook of Histology. Philadelphia Lippincott, with permission from Lippincott.)...

Figure 47-2 A low-magnification scanning electron micrograph depicting a portion of a liver lobule from a rat liver. CVJ Central vein PV, porta vein PLV, perilobular venules. fFrom Zakim 0, Boyer TD. Hepatology A textbook of liver disease, 3rd ed. Philadelphia WB Saunders, 1996 9.)...

To understand the possibilities and limitations of liver in vitro systems it is crucial to be aware of the organization principles of this organ. The smallest functional unit of the liver is the lobule (Fig. la). The human liver is composed of approximately one million lobules. Each lobule is supplied by branches of the portal vein which carries blood from the intestine (about 80 % of the liver s blood). Moreover, arterial blood is supplied by branches of the liver artery (about 20 %). The blood enters the lobules in the periphery, passes through microvessels where it is in close contact with hepatocytes, is finally drained off into the central veins, and leaves the liver by the hepatic vein. The oxygen concentration is about 13 % v/v (60-65 mmHg) in the periportal zone and drops to about 4 % v/v (30-35 mmHg) in the central vein [3]. 

A key feature of the liver is the antidromic blood and bile flow system (Fig. lc). Blood enters the lobules in the periphery, passes the sinusoids, and is drained off into the central vein. Bile is secreted by the hepatocytes into the apical bile canaliculi, which form a network organized parallel as well as perpendicular to the sinusoidal vessels. Bile flows to the bile ducts in the periportal field and is finally drained off into the gall bladder and the small intestine. The bile canalicular network is not composed of conventional vessels with endothelial cells. It is formed by the apical membrane of hepatocytes and thereby is a consequence of the polar structure of these cells which have an apical pole (facing the bile canaliculus) and a basolateral side (facing the sinusoid). The direct contact to bile leads to a high vulnerability of hepatocytes. Destruction of the apical hepatocyte membrane may lead to bile acids entering the cell, hepatocyte killing, and inflammation. 

Bile produced by hepatocytes is secreted into the bile canaliculi between adjacent hepatic cells. The wall of the canaliculus is formed by the plasma membrane of the hepatocytes, which are held together by tight junctions. Canaliculi arise near central veins and extend to the periphery of the lobules. The direction of bile flow in the canaliculi is centrifugal, whereas that of the blood flow is centripetal. Canaliculi coalesce to form ducts, which are lined by epithelium, and the ducts coalesce to form the right and left hepatic ducts. Outside the liver these ducts form the common hepatic duct. 

Arterial and venous blood from the portal triad passes through the hepatic lobules to the central veins via the hepatic sinusoids. After passing through the hepatic lobules, blood collects in the central veins, which ultimately coalesce into the hepatic veins, which then enter the inferior vena cava. 

The lobes of the liver are divided into smaller lobules with a roughly hexagonal arrangement of hepatocytes around a central vein. At the vertices of the lobules are bile ducts, terminal branches of the hepatic artery, and portal veins—termed the portal triad. Connective stromal tissues extend throughout the liver, providing support for cells and routes for blood vessels, lymphatic vessels, and bile ducts. The hepatocytes form groups of cells around small branches of the portal vein, hepatic arteriole, bile duct, lymph vessel, and nerves this functional unit is called an acinus (plural acini). The acini form part of a larger structure, which can be divided into three zones ... 

The diverse metabolic activities of the liver make it susceptible to solvent induced in-jiuy, particularly from reactive intermediates which damage cellular macromolecules. The microscopic anatomy of the liver provides an explanation for this susceptibility. The basic unit of the liver is the hepatic lobule which consists of a central vein surrounded radially by sinusoids of liver cells (hepatocytes). Portal triads consisting of a hepatic artery, a hepatic vein and a bile canniliculus are located at the periphery. Liver cells closest to the vascular... 

Fig. 344. Uniform distribution of glycogen in the liver lobule (CV = central vein PV = portal vein branch) an unmedicated 465 g old male Wistar rat MR 2000 (No. 2) exsanguinated under ether anaesthesia on March 14, 1977. The tissue was fixed by immersion in Carno/s fluid (ethanol-chloroform-glacial acetic acid) and embedded in Paraplast. Periodic acid-Schiff reaction. Objective Leitz PI 40/0.65. Leitz Orthomat (eyepiece 2X). Film Agfa Pan 25...

On gross examination of a liver section, one recognizes red dots corresponding to the central vein, surrounded by brown polygonal zones made of hepatic cells and alternating with gray areas of the portal spaces. This one-dimensional description of the hepatic lobule does not adequately describe the functional unit, and anatomists and physiologists have coordinated their efforts to reconstitute the functional unit... 

The acinus is that portion of liver supplied by a primary afferent branch of the portal vein and hepatic artery. If we look at a bell-shaped hepatic lobule hanging from and traversed by a branch of the hepatic vein, the portal space runs on its side containing the artery, the vein, and the bile duct (see Figs. 9-21 and 9-22). At some point the vein and the arteriole yield three branches, two lateral and one apical, that are the primary afferent branches. They leave the connective tissue of the portal tract to penetrate in the substance of the lobule, where they further ramify into smaller branches that enter the sinusoid of the lobule. The territory irrigated by these primary afferent arterioles, the acinus, forms a somewhat irregular ovoid mass of tissue inserted between two central veins. The tissue mass is composed mainly of hepatic cells and sinusoids lined by Kupffer s cells. The central zone of the acinus (zone 1) receives the fresh blood supply and may therefore be the first to be injured by toxins in blood. The peripheral zone (zone 3) receives a blood supply partially exhausted in its oxygen and nutrients and is therefore more susceptible to anoxemia. 

Fig. 9-21. Hepatic lobules—longitudinal view around the central vein. Modified after L.G. Whitley from A Companion to Medical Studies . Blackwell Scientific Publications, Oxford and Edinburgh...

---