LIVER

x the largest and heaviest gland ( 1.5 kgs or 3 lbs) x fresh specimen: dark red or reddish brown due to its rich blood supply x location: beneath the diaphragm, just behind the right costal arch x receives all materials absorbed from the intestinal tract x both exocrine and endocrine x bile produced is partly secretion and partly excretion

x parenchymal cell: hepatocyte

I. Stroma Glissons Capsule

- thin fibroconnective tissue covering the liver - covered by peritoneum except at the bare area (superior & posterior surfaces) - arising from the capsule is the fibroconnective tissue skeleton made of collagenous fibers and some fibroblast, within the liver substance

Porta hepatis

- transverse fissure on the inferior surface of the liver, where the portal vein, the hepatic artery, the hepatic ducts and lymphatic vessels enter.

II. Blood supply a. Portal vein - brings nutrient-rich blood from the intestinal tract, pancreas and spleen; 7080% of the livers blood b. Hepatic artery - supplies O2- rich blood from the abdominal aorta; 20-30% of the livers blood c. Hepatic vein - union of several sublobular veins from

III. Liver lobules 1. Classic liver lobule (hepatic lobule) - structural unit of the liver - polygonal mass made of liver plates or cords radiating like spokes from the central vein with the portal canals at its corners a. central veins - smallest radicles of the hepatic veins at the center of a hepatic lobule - sinusoids drain into the central vein then into the sublobular vein which join

b. portal area (3-6 per lobule) - portal canal or portal triad - contains the portal vein, hepatic artery, bile duct and lymph vessels c. liver sinusoids - blood vessels found in between liver cords/plates whose basal lamina is incomplete due to fenestrations and gaps - diameter is 9-12um (>capillaries) - flow of blood is from the periphery to the central vein; near its termination is a sphincteric mechanism that controls blood flow - lined by endothelial type & Kupffer cells

Endothelial" type cells - small, elongated with dark-staining nucleus & cytoplasmic processes - has few organelles but numerous micropinocytotic vesicles - fenestrations in the attenuated cytoplasm & gaps between cells Kupffer cells - phagocytic (stellate) cells of Kupffer - 15% of hepatocytes - actively phagocytic, with larger, paler nucleus and extensive cytoplasm; on endothelial lining of the sinusoids

- numerous in the periportal area where they are most active - in time of need, its number is increased by differentiation of the endothelial cells Functions of Kupffer cells: 1) remove debris & cellular fragments 2) metabolize aged RBCs 3) digest Hb to form bilirubin 4) secrete CHON for immunologic processes 5) destroy bacteria in the portal blood

d. Space of Disse (perisinusoidal space) - interstitial space between liver cells and sinusoidal endothelial cells - for active metabolic exchange between the liver and blood; may play an important role in lymph production - contain reticular & collagen fibers to maintain the architecture of sinusoids, & short microvilli of hepatocytes to provide large surface area for absorption & secretion - also contains mesenchymal cells which

- AKA of the mesenchymal cells: 1) pericyte 4) Itos cell 2) lipocyte 5) fat-storing cell 3) extravascular reticular cells Functions of Itos cells: 1) uptake, storage & release of retinoids 2) synthesis & secretion of CHONs and proteoglycans 3) secretion of cytokines 4) regulation of the sinusoidal lumen diameter in response to regulators, e.g. prostaglandins, thromboxane A

5) probably responsible for formation of reticular and collagen fibers 6) in fetal liver, this may be the stem cell for hemopoiesis

2. Portal lobule - a triangular area whose 3 apices are neighboring central veins and whose center is the portal canal - consists of structures draining bile into the bile duct of that portal area

3. Hepatic acinus of Rappaport

- functional unit of the liver - a diamond shaped-area encompassing triangular sections of 2 adjacent liver lobules (central veins are its apices); divided by the portal canal branches transversely between the 2 lobules

IV. Liver parenchymal cells

- hepatocytes - large, polygonal cells( 20-35um) with 1 or 2 centrally located nuclei

- arranged as branching perforated plates or cords between which are sinusoidal spaces; the plates/cords extend from the periphery of the classical lobule to the central vein in a radial fashion - contain basophilic bodies which are aggregates of rough ER in the cytoplasm (where several CHONs, e.g. albumin & fibrinogen, are synthesized) - smooth ERs in the hepatocytes are responsible for the processes needed for inactivation or detoxification of substances, as oxidation, methylation and conjugation

- up to 50 Golgi complex per cell; its functions include lysosome formation, secretion of plasma CHON, lipoChON and glycoCHON - small but numerous mitochondria are scattered in the cytoplasm (associated with glycogen storage) hepatocyte lysosome - important in the turnover and degradation of intracellular organelles peroxisomes or microbodies - enzyme-containing organelles are abundant; its functions are: 1) oxidation of excess fatty acids

3) breakdown of excess purines to uric acid 4) participates in the synthesis of cholesterol, bile acids, & some lipids used to make myelin liver glycogen - depot for glucose; mobilized if the blood glucose level falls below (N) Hepatocyte surfaces: 1. Surface facing the space of Disse - with microvilli to increase surface for transfer of materials between hepatocytes and blood

2. Surface closely applied to surface of adjacent liver cell 3. Surface partially separated from an adjacent cell to form a bile canaliculus Limiting plate or Limiting hepatocytes - sheet of smaller modified hepatocytes (1cell thick) lying against the periportal connective tissue; perforated by blood vessels & branches of the bile ducts Space of Moll - separates the limiting plate from the connective tissue of the portal area

V. Bile Flow ( exocrine function) Bile canaliculus - 1st portion of the bile duct system which are small tunnel-like expansions of the intercellular spaces between adjacent liver cells without any lining epithelium
Bile ductule or canal of Herring - junction found between bile canaliculi and bile ducts, near the periphery of a hepatic lobule -liver cells are replaced gradually by smaller, lighter cells-ductule cells- with distinct basal lamina - lumen of the ductule eventually joins that

Bile duct - intermediate-sized vessel at the portal area lined by cuboidal epithelium; receives bile from the canal of Hering - nearer the porta hepatis, they enlarge, now lined by columnar epithelium, and fuse to form the hepatic ducts Bile from hepatocytes Bile canaliculi Bile ductule Bile duct Left & right hepatic Ducts

VI. REGENERATION - liver shows remarkable degree of regeneration after injury - hepatocytes are capable of both hypertrophy and hyperplasia - bile ducts actively proliferate - after continuous or repeated damage to hepatocytes for a period of time, the multiplication of cells is followed by a marked increase in the amount of connective tissue (cirrhosis)
VII. FUNCTIONS - the liver is a detoxifying gland; thus, is susceptible to damage from absorbed toxic

Functions of the liver: 1. Secretory- synthesizes bile, CHO, CHON,etc. 2. Excretory- releases waste & even harmful substances for ultimate evacuation 3. Exocrine- releases bile through the duct system 4. Endocrine- releases plasma proteins, etc, directly into the circulation 5. Metabolite storage- stores glucose in the form of glycogen; lipid in the form of triglucerides 6. Vitamin storage- vitamin A is stored

8. Glycogenolysis- in fasting state, hepatocytes respond to glucose- poor blood by breaking down glycogen & releasing it as glucose 9. Amino acid deamination- results in the production of urea (transported thru the blood to the kidney, where it is excreted) 10. Detoxification- inactivates various drugs, noxious chemicals & toxins, by enzymes such as oxidase system thru the process of oxidation, methylation or conjugation