A liver sinusoid is a type of capillary known as a sinusoid capillary, or discontinuous capillary, similar to a fenestrated capillary, having discontinuous endothelium that serves as a location for mixing of the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein. The liver sinusoid has a larger caliber than other types of capillaries and has a lining of specialised endothelial cells known as the liver sinusoidal endothelial cells, Kupffer cells; the cells have a scavenging function. The LSECs make up around half of the non-parenchymal cells in the liver and are flattened and fenestrated. LSECs have many fenestrae that gives easy communication between the sinusoidal lumen and the space of Disse, they play a part in filtration, in the regulation of blood flow in the sinusoids. The Kuppfer cells can destroy foreign material such as bacteria. Hepatocytes are separated from the sinusoids by the space of Disse. Hepatic stellate cells are present in the space of Disse and are involved in scar formation in response to liver damage.
Defenestration known as capillarisation happens when LSECs are lost rendering the sinusoid as an ordinary capillary. This process precedes fibrosis; the liver sinusoidal. The utility of these cells are of particular interest. One problem to overcome is the reversing of cellular differentiation that has made these cells specialized phenotypically in vitro. UIUC Histology Subject 589 Histology image: 15504loa – Histology Learning System at Boston University - "Liver, Gall Bladder, Pancreas: liver, classic lobule" Histology image: 22103loa – Histology Learning System at Boston University - "Ultrastructure of the Cell: hepatocytes and sinusoids and space of Disse" Histology at anhb.uwa.edu.au
Lobules of liver
A hepatic lobule is a small division of the liver defined at the microscopic. The hepatic lobule is a building block of the liver matter, consisting of a portal triad, hepatocytes arranged in linear cords between a capillary network, a central vein, it should not be confused with the anatomic lobes of the liver, or any of the functional lobe classification systems. The two-dimensional microarchitecture of the liver can be viewed from multiple different perspectives: The term "hepatic lobule", without qualification refers to the classical lobule; the hepatic lobule can be described in terms of metabolic "zones". Each zone is centered on the line connecting two portal triads and extends outwards to the two adjacent central veins; the periportal zone I is nearest to the entering vascular supply and receives the most oxygenated blood, making it least sensitive to ischemic injury while making it susceptible to viral hepatitis. Conversely, the centrilobular zone III has the poorest oxygenation, will be most affected during a time of ischemia.
The portal triad is a functional unit of the liver and consists of three vessels, the interlobular arterie, the interlobular vein and a bile duct. Zones differ by function: zone I hepatocytes are specialized for oxidative liver functions such as gluconeogenesis, β-oxidation of fatty acids and cholesterol synthesis zone III cells are more important for glycolysis and cytochrome P-450-based drug detoxification; this specialization is reflected histologically. Other zonal injury patterns include zone I deposition of hemosiderin in hemochromatosis and zone II necrosis in yellow fever. Bridging fibrosis, a type of fibrosis seen in several types of liver injury, describes fibrosis from the central vein to the portal triad. Histology image: 15401loa – Histology Learning System at Boston University Histology at siumed.edu Histology at okstate.edu Histology at webmd.idv.tw. UIUC Histology Subject 923
Intrahepatic bile ducts
Intrahepatic bile ducts compose the outflow system of exocrine bile product from the liver. They can be divided into: Lobar ducts - stratified columnar epithelium. Interlobar ducts - pseudostratified columnar epithelium. Interlobular bile ducts - simple columnar epithelium. Intralobular bile ducts - simple cuboidal epithelium by hepatocytes Bile canaliculi - two half-canaliculi formed by the hepatocytes facing the perisinusoidal space
Bile or gall is a dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver, stored and concentrated in the gallbladder. After eating, this stored bile is discharged into the duodenum; the composition of hepatic bile is 97% water, 0.7% bile salts, 0.2% bilirubin, 0.51% fats, 200 meq/l inorganic salts. About 400 to 800 ml of bile is produced per day in adult human beings. Bile or gall acts to some extent as a surfactant, helping to emulsify the lipids in food. Bile salt anions are hydrophobic on the other side; the hydrophilic sides are negatively charged, this charge prevents fat droplets coated with bile from re-aggregating into larger fat particles. Ordinarily, the micelles in the duodenum have a diameter around 14–33 μm; the dispersion of food fat into micelles provides a increased surface area for the action of the enzyme pancreatic lipase, which digests the triglycerides, is able to reach the fatty core through gaps between the bile salts.
A triglyceride is broken down into two fatty acids and a monoglyceride, which are absorbed by the villi on the intestine walls. After being transferred across the intestinal membrane, the fatty acids reform into triglycerides, before being absorbed into the lymphatic system through lacteals. Without bile salts, most of the lipids in food would be excreted in faeces, undigested. Since bile increases the absorption of fats, it is an important part of the absorption of the fat-soluble substances, such as the vitamins A, D, E, K. Besides its digestive function, bile serves as the route of excretion for bilirubin, a byproduct of red blood cells recycled by the liver. Bilirubin derives from hemoglobin by glucuronidation. Bile tends to be alkali on average; the pH of common duct bile is higher than that of the corresponding gallbladder bile. Bile in the gallbladder becomes more acidic the longer a person goes without eating, though resting slows this fall in pH; as an alkali, it has the function of neutralizing excess stomach acid before it enters the duodenum, the first section of the small intestine.
Bile salts act as bactericides, destroying many of the microbes that may be present in the food. In the absence of bile, fats become indigestible and are instead excreted in feces, a condition called steatorrhea. Feces lack their characteristic brown color and instead are white or gray, greasy. Steatorrhea can lead to deficiencies in fat-soluble vitamins. In addition, past the small intestine the gastrointestinal tract and gut flora are not adapted to processing fats, leading to problems in the large intestine; the cholesterol contained in bile will accrete into lumps in the gallbladder, forming gallstones. Cholesterol gallstones are treated through surgical removal of the gallbladder. However, they can sometimes be dissolved by increasing the concentration of certain occurring bile acids, such as chenodeoxycholic acid and ursodeoxycholic acid. On an empty stomach – after repeated vomiting, for example – a person's vomit may be green or dark yellow, bitter; the bitter and greenish component may be bile or normal digestive juices originating in the stomach.
The color of bile is likened to "fresh-cut grass", unlike components in the stomach that look greenish yellow or dark yellow. Bile may be forced into the stomach secondary to a weakened valve, the presence of certain drugs including alcohol, or powerful muscular contractions and duodenal spasms. Biliary obstruction refers to a condition when bile ducts which deliver bile from the gallbladder or liver to the duodenum become obstructed; the blockage of bile might cause a build up of bilirubin in the bloodstream which can result in jaundice. There are several potential causes for biliary obstruction including gallstones, trauma, choledocal cysts, or other benign causes of bile duct narrowing; the most common cause of bile duct obstruction is when gallstone are dislodged from the gallbladder into the cystic duct or common bile duct resulting in a blockage. A blockage of the gallbladder or cystic duct may cause cholecystitis. If the blockage is beyond the confluence of the pancreatic duct, this may cause gallstone pancreatitis.
In some instances of biliary obstruction, the bile may become infected by bacteria resulting in ascending cholangitis. In medical theories prevalent in the West from Classical Antiquity to the Middle Ages, the body's health depended on the equilibrium of four "humors", or vital fluids, two of which related to bile: blood, phlegm, "yellow bile", "black bile"; these "humors" are believed to have its roots in the appearance of a blood sedimentation test made in open air, which exhibits a dark clot at the bottom, a layer of unclotted erythrocytes, a layer of white blood cells and a layer of clear yellow serum. Excesses of black bile and yellow bile were thought to produce depression and aggression and the Greek names for them gave rise to the English words cholera and melancholia. In the former of those senses, the same theories explain the derivation of the English word bilious from bile, the meaning of gall in English as "exasperation" or "impudence", the Latin word cholera, derived from the Greek kholé, passed along in
Round ligament of liver
The round ligament of the liver is a degenerative string of tissue that exists in the free edge of the falciform ligament of the liver. The round ligament divides the left part of the liver into lateral sections; the round ligament represents the remnant of the fetal umbilical vein. The round ligament therefore only exists in placental mammals. Prenatally and for a month or two after birth, the umbilical vein is open, subsequently degenerating to fibrous tissue, the round ligament. In adulthood, small paraumbilical veins remain in the substance of the ligament; these act as an important portacaval anastomosis in severe portal hypertension, resulting in a caput medusae. The umbilical vein/round ligament inserts around the umbilicus and is an important landmark of the inner surface of the anterior abdominal wall. Anatomy photo:38:12-0106 at the SUNY Downstate Medical Center - "Stomach and Liver: The Visceral Surface of the Liver" Anatomy image:7819 at the SUNY Downstate Medical Center Overview at ucc.edu Illustration of Liver Anatomy including ligaments and structures
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 70-85% of the liver's mass; these cells are involved in: Protein synthesis Protein storage Transformation of carbohydrates Synthesis of cholesterol, bile salts and phospholipids Detoxification and excretion of exogenous and endogenous substances Initiation of formation and secretion of bile The typical hepatocyte is cubical with sides of 20-30 µm. The typical volume of a hepatocyte is 3.4 x 10−9 cm3. Smooth endoplasmic reticulum is abundant in hepatocytes, whereas most cells in the body have only small amounts. Hepatocytes display an eosinophilic cytoplasm, reflecting numerous mitochondria, basophilic stippling due to large amounts of rough endoplasmic reticulum and free ribosomes. Brown lipofuscin granules are observed together with irregular unstained areas of cytoplasm; the average life span of the hepatocyte is 5 months. Hepatocyte nuclei are round with prominent nucleoli. Anisokaryosis is common and reflects tetraploidy and other degrees of polyploidy, a normal feature of 30-40% of hepatocytes in the adult human liver.
Binucleate cells are common. Hepatocytes are organised into plates separated by vascular channels, an arrangement supported by a reticulin network; the hepatocyte plates are two cells thick in the chicken. Sinusoids display a fenestrated endothelial cell lining; the endothelial cells have no basement membrane and are separated from the hepatocytes by the space of Disse, which drains lymph into the portal tract lymphatics. Kupffer cells are scattered between endothelial cells. Stellate cells produce extracellular matrix and collagen; the hepatocyte is a cell in the body that manufactures serum albumin and the prothrombin group of clotting factors. It is the main site for the synthesis of lipoproteins, transferrin and glycoproteins. Hepatocytes manufacture their own structural proteins and intracellular enzymes. Synthesis of proteins is by the rough endoplasmic reticulum, both the rough and smooth endoplasmic reticulum are involved in secretion of the proteins formed; the endoplasmic reticulum is involved in conjugation of proteins to lipid and carbohydrate moieties synthesized by, or modified within, the hepatocytes.
The liver forms fatty acids from carbohydrates and synthesizes triglycerides from fatty acids and glycerol. Hepatocytes synthesize apoproteins with which they assemble and export lipoproteins; the liver is the main site in the body for gluconeogenesis, the formation of carbohydrates from precursors such as alanine and oxaloacetate. The liver metabolizes chylomicron remnants, it synthesizes cholesterol from acetate and further synthesizes bile salts. The liver is the sole site of bile salts formation. Hepatocytes have the ability to metabolize and inactivate exogenous compounds such as drugs, insecticides, endogenous compounds such as steroids; the drainage of the intestinal venous blood into the liver requires efficient detoxification of miscellaneous absorbed substances to maintain homeostasis and protect the body against ingested toxins. One of the detoxifying functions of hepatocytes is to modify ammonia into urea for excretion; the most abundant organelle in liver cells is the smooth endoplasmic reticulum.
Primary hepatocytes are used in cell biological and biopharmaceutical research. In vitro model systems based on hepatocytes have been of great help to better understand the role of hepatocytes in physiological processes of the liver. In addition, pharmaceutical industry has relied on the use of hepatocytes in suspension or culture to explore mechanisms of drug metabolism and predict in vivo drug metabolism. For these purposes, hepatocytes are isolated from animal or human whole liver or liver tissue by collagenase digestion, a two-step process. In the first step, the liver is placed in an isotonic solution, in which calcium is removed to disrupt cell-cell tight junctions by the use of a calcium chelating agent. Next, a solution containing collagenase is added to separate the hepatocytes from the liver stroma; this process creates a suspension of hepatocytes, which can be seeded in multi-well plates and cultured for many days or weeks. For optimal results, culture plates should first be coated with an extracellular matrix to promote hepatocyte attachment and maintenance of the hepatic phenotype.
In addition, overlay with an additional layer of extracellular matrix is performed to establish a sandwich culture of hepatocytes. The application of a sandwich configuration supports prolonged maintenance of hepatocytes in culture. Freshly-isolated hepatocytes that are not used can be cryopreserved and stored, they do not proliferate in culture. Hepatocytes are intensely sensitive to damage during the cycles of cryopreservation including freezing and thawing. After the addition of classical cryoprotectants there is still damage done while being cryopreserved. Recent cryopreservation and resuscitatio