Digestive+System+II+-+Associated+Gland

=**Objectives**=


 * 1. List the functions of the liver.**

(1) Vascular functions: Storage and filtration of blood. (2) Secretory/Excretory functions: Vitamin Storage/excretion (A, B12, C, D, E, K), synthesis/secretion of bile. (3) Metabolic functions: protein synthesis (albumin, prothrombin, fibrinogen), lipoprotein and cholesterol synthesis, carbohydrate metabolism (glycogenesis, glycogenolysis, gluconeogenesis), metabolism of lipid-soluble drugs and steroids, urea formation (from ammonium ions).


 * 2. Identify the components of the portal triad. Identify what the function is of each component.**

Portal triad contains the major vessels of the liver in the denser connective tissue between hepatocyte lobules. The triad consists of the hepatic artery, hepatic portal vein, and the bile duct. There is also lymph vessels within the portal triad.

25% of the blood supply of the liver comes from the hepatic arteries, which supply oxygen-rich blood to the hepatocytes.

75% of the blood supply of the liver comes for the hepatic portal vein, which convey nutrient-rich blood with products of digestion for metabolism by hepatocytes.

Bile flows from the periphery to the center of a portal lobule (center of a classic lobule to a corner of the hexagon) into the interlobular bile duct.


 * 3. Describe the models of liver organization including the classic liver lobule, portal lobule, and liver acinus.**

__Classic Liver Lobule__ Described on basis of connective tissue arrangement. Defined by a hexagonal-shaped parenchymal region and bound by portal tracts at each corner of the hexagon with a central vein at its center.

__Portal Lobule__ Descibed in terms of bile flow. Defined as a triangular region of hepatocytes with a central vein at the apices of the triangle and the portal triad (with bile duct) at the center.

__Hepatic Portal Acinus__ Described as the smallest functional unit of the liver. Defined as a diamond-shaped mass of hepatocytes lying between two central veins at the apices of its long axis and two portal tracts at apices of its short axis. The meridian of the diamond is transversed by perterminla branches of a distributing arteriole which supplies blood to the sinusoids.

The hepatic cords are divided into 3 functional zones, with zone 1 closest to the arteriole and receiving the most oxygenated blood and nutrients and least metabolic waste, and zone 3 closest to the central vein with the most poorly oxygenated blood and highest exposure to metabolic waste.


 * 4. Desribe the path of blood flow and bile flow in the liver.**

Within the classic liver lobule, blood flows from the portal triads, centrally toward the central vein via the sinuosids. Bile flows from hepatocytes, peripherally towards the bile ducts in the portal region.

The central vein of each lobule collects blood from all sinusoids in that lobule and empties into the sublobular vein --> collecting vein --> left or right hepatic veins.


 * 5. Describe the histological and functional organization of liver sinusoids including the contribution of Kupffer cells and endothelial cells.**

Liver sinusoids are the discontinuous ducts between individual hepatocytes, leading to the central vein. Its innermost space is lined with sinusoidal lining cells(simple squamos endothelium), which are supported by a delicate network of reticular fibers. The lining cells are riddled with small holes, known as Sieve Plates, that allow the passage of substances less than a half micron into the Space of Disse. The Space of Disse, also known as the perisinusoidal space, is a small gap between the vascular sinusoid and the hepatocytes. This gap allows hepatocytes to directly contact plasma, but not blood cells or platelets. Commonly found inside the Space of Disse are Ito Cells, which are irregular cells with long processes. Their exact function is unclear, but they are thought to store vitamin A. Inside the lumen of the sinusoids are wandering macrophages known as Kupffer cells, derived from the mononuclear phagocyte line. They are specialized to remove damaged RBC's and debris.


 * 6. Describe the bile canaliculi and their function.**

Bile canaliculi form a ring around hepatocytes and connect with those of adjacent hepatocutes, forming a complex branched network that converges on the portal area of the liver. Ultimately, they are responsible for collecting bile and transporting it to the hepatic ducts. Bile canaliculi empty into Bile Ductules (canals of herring), which then lead to the Portal Bile Ducts, which then fuse with the Hepatic Bile Ducts. Bile Ductules and Ducts are lined by cuboidal epithelial cells. Histologically, the portal bile ducts are easy to recognize because they look like a small circular string of pearls.

Hepatocytes are polygon-shaped cells that grow in cords towards a central vein in layers 1-2 cells thick called plates. The part of the hepatocyte that borders other hepatocytes is known as the Lateral Domain, whereas the part bordering the sinusoid(s) is the Sinusoidal Domain.
 * 7. Describe the general ultrastructure of the hepatocyte.**

The Lateral Domains contain the Bile Canaliculi, the initial portion of the bile duct system, comprised of invaginations in the hepatocyte membranes(these DO NOT have their own membrane lining!) and the junction of those membranes.

The Sinusoidal Domain contains the sinusoids, but they are not in direct contact with the hepatocytes-- instead, they are separated by the Perisinusoidal Space of Disse. The hepatocytes extend microvilli into the Space of Disse to increase their surface area for absorption-- they also display high levels of Na/K-ATPase and adenylate cyclase activity, facilitating membrane transport.

On the cellular level, hepatocytes have a large RER and Golgi, due to its role in enzyme synthesis and packaging. Hepatocytes also have a large Smooth Endoplasmic Reticulum to assist them with metabolism of lipid-soluble compounds.


 * 8. Identity the endocrine and exocrine portions of the pancreas.**

The endocrine portion of the pancreas are the islets of Langerhans, multihormonal micro-organs in the form of ovoid groups of clear endocrine cells scattered throughout the exocrine pancreas and are most numerous in the tail region of the pancreas.

The exocrine portion of the pancrease are the pancreatic acini. Acini are oval-shapped secretory units composed of 40-50 pyramindal-shaped acinar cells which form the scretory component and 3-4 centrally located low cuboidal centroacinar cells, with form the beginnings of the duct system, the intercalated ducts.

Intercalated ducts (simple cuboidal-columnar cells) --> Intralobular ducts --> interlobular ducts (low cuboidal-columnar cells) --> main pancreatic duct --> duodenum


 * 9. Describe the histological organization of the islets of Langerhans. List the function of the various cell types.**

The endocrine portion of the pancreas are the islets of Langerhans, multihormonal micro-organs in the form of ovoid groups of clear endocrine cells scattered throughout the exocrine pancreas and are most numerous in the tail region of the pancreas.

Cell types and their functions will be addressed in a future lecture.


 * 10. Describe the histological organization of the gall bladder and correlate the function to the morphology of this organ.**

The gallbladder is hollow, pear-shaped, and approximately 4 inches long. It's attached to the posteroinferior surface of the liver. Its primary function is to store, concentrate(5-10x), and release bile(into the duodenum). It consists of a blind pouch, attached to the cystic duct via the gallbladder neck.

It consists of 5 layers: - Columnar Epithelium made up of Brush cells(specialized for water extraction) and Clear Cells - Lamina Propria, consisting of loose vascularized connective tissue (no muscularis interna!) - Muscularis Externa, which is composed of mixed-orientation smooth muscle fibers - Perimuscular connective tissue (slightly more dense than the LP) - A thin Serosa made of simple squamous epithelium

The gallbladder can release up to 1200ml of bile a day into the duodenum via its contribution to the Bile Duct. It responds by contracting its smooth muscle layer in the presence of CCK(Cholecystokinin), a hormone produced by the EC cells of the small intestine in response to peristalsis. The sphincter choledochus(at major duodenal papilla) is relaxed in response to CCK release, allowing bile to enter the duodenum.

Clinical Correlation: The overconcentration of bile salts can lead to the precipitation of solid masses in the gallbladder known as Gallstones. Masses small enough to pass through the ducts will not cause pathology, however, masses can become as big as 1-3cm and obstruct the cystic or hepatic ducts.**