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Hepatocytes are polyhedral in shape, with six or more surfaces, and have a diameter of 20-30 µm.

The eosinophilic nature of the cytoplasm in hepatocytes is mainly due to the large number of mitochondria and some smooth endoplasmic reticulum present in the cells.

Hepatocytes have contact with:

1. The wall of the sinusoids, through the space of Disse.
2. The surfaces of other hepatocytes.

The tubular space formed between two abutting hepatocytes is known as the bile canaliculus.

Bile canaliculi are tubular spaces 1-2 µm in diameter, formed by the plasma membranes of two adjacent hepatocytes. They contain a small number of microvilli and are limited by tight junctions between the cell membranes. Additionally, gap junctions are present for intercellular communication. The canaliculi create a complex anastomosing network that progresses along the liver lobule plates and terminates in the portal spaces.

The organs associated with the digestive tract include the salivary glands, the pancreas, the liver, and the gallbladder.

The three pairs of large salivary glands in humans are the parotid, submandibular (submaxillary), and sublingual glands.

Minor salivary glands secrete 10% of the total volume of saliva and account for approximately 70% of the mucus.

The large salivary glands are surrounded by a capsule of connective tissue that is rich in collagen fibers.

The parenchyma of the large salivary glands consists of secretory end pieces and a branching duct system arranged in lobules, separated by septa of connective tissue originating from the capsule.

The secretory end pieces of large salivary glands contain two types of secretory cells: serous cells and mucous cells, as well as myoepithelial cells which are nonsecretory.

The duct system in large salivary glands modifies and conducts the saliva to the oral cavity.

The main components of a salivary gland include:

1. Serous acinus - clusters of serous cells surrounding a central lumen.
2. Mucous acinus - clusters of mucous cells surrounding a central lumen.
3. Serous demilunes - structures associated with mucous acini.
4. Intercalated ducts - ducts that connect acini to striated ducts.
5. Striated ducts - ducts consisting of stacked cells surrounding a central lumen.
6. Myoepithelial cells - cells that wrap around intercalated ducts and help in the secretion process.

Myoepithelial cells are specialized cells that wrap around the intercalated ducts of salivary glands. Their primary role is to contract and help in the expulsion of saliva from the acini into the ducts, facilitating the secretion process.

Striated ducts are characterized by:

• Stacked cells that surround a central lumen.
• The presence of striations in the cytoplasm, which are indicative of their role in modifying the saliva as it passes through.
• They play a crucial role in the reabsorption of ions and water from the saliva, contributing to the final composition of saliva.

Serous cells are usually pyramidal in shape, with a broad base resting on the basal lamina and a narrow apical surface featuring short, irregular microvilli facing the lumen. They are characterized as polarized protein-secreting cells and form a spherical mass called an acinus with a small lumen in the center.

Adjacent secretory serous cells are joined together by junctional complexes and typically form a spherical mass known as an acinus, which resembles a grape attached to its stem, where the stem corresponds to the duct system.

Mucous cells are usually cuboidal to columnar in shape, with oval nuclei that are pressed toward the bases of the cells.

The glycoproteins, primarily called mucins, are important for the moistening and lubricating functions of saliva, containing 70 - 80% carbohydrate moieties in their structure.

Mucous cells are most often organized as tubules, consisting of cylindrical arrays of secretory cells surrounding a lumen.

In the submandibular and sublingual glands, mucous cells form tubules that are capped at their ends by serous cells, creating structures known as serous demilunes.

Myoepithelial cells surrounding secretory portions are well developed, branched, and usually two to three cells per secretory unit, often referred to as basket cells. In contrast, those associated with intercalated ducts are spindle-shaped and lie parallel to the duct's length.

The main function of myoepithelial cells is to prevent end piece distention during secretion due to increased intraluminal pressure, although their contraction also accelerates saliva secretion.

Myoepithelial cells exhibit characteristics similar to smooth muscle cells, including contractility and the establishment of intercellular junctions such as desmosomes among themselves and with secretory cells.

Intercalated ducts are lined by cuboidal epithelial cells that can divide and differentiate into secretory or ductal cells. They are short ducts that join to form striated ducts.

Striated ducts are characterized by radial striations that extend from the bases of the cells to the level of the central nuclei. These striations consist of infoldings of the basal plasma membrane with numerous elongated mitochondria aligned parallel to the infolded membranes, indicating their role in ion transport.

Intercalated and striated ducts are called intralobular ducts because they are located within the lobule of the gland.

The initial part of the excretory ducts is lined with pseudostratified or stratified cuboidal epithelium.

The more distal parts of the excretory ducts are lined with stratified columnar epithelium containing a few mucus-secreting cells.

The main duct of each major salivary gland is lined with nonkeratinized-stratified squamous epithelium.

The striated ducts of each lobule converge and drain into ducts located in the connective tissue septae separating the lobules, where they become interlobular, or excretory, ducts.

The capillaries surrounding the secretory end pieces are crucial for the secretion of saliva, as they provide the necessary nutrients and support for the secretory process, which is stimulated by the autonomic nervous system.

Parasympathetic stimulation, often triggered by the smell or taste of food, promotes vasodilation and results in a copious watery secretion of saliva.

Sympathetic stimulation leads to the production of small amounts of viscous saliva, which is rich in organic material.

The parotid gland is a branched acinar gland and its secretory portion is composed exclusively of serous cells.

The secretory granules in the parotid gland are rich in proteins and have a high amylase activity, which is responsible for most of the hydrolysis of ingested carbohydrates.

Amylase activity begins in the mouth and continues for a short time in the stomach, but it decreases considerably when gastric juice acidifies the food.

The lobules of the parotid gland contain intercalated ducts and striated ducts, which are easily observed due to their length.

Plasma cells in large salivary glands secrete IgA, which forms a complex with a secretory component synthesized by the serous acinar, intercalated duct, and striated duct cells. This IgA-rich secretory complex is resistant to enzymatic digestion and serves as an immunological defense mechanism against pathogens in the oral cavity.

The submandibular gland is a branched tubuloacinar gland that contains both mucous and serous cells. The serous cells are the main component of this gland.

In humans, 90% of the end pieces of the submandibular gland are serous acinar, while 10% consist of mucous tubules with serous demilunes.

The cells that form the demilunes in the submandibular gland secrete the enzyme lysozyme, which primarily hydrolyzes the walls of certain bacteria.

Serous cells in the submandibular gland are responsible for the weak amylolytic activity present in the gland and its saliva.

Lactoferrin secreted by acinar and intercalated duct cells binds iron, which is a nutrient necessary for bacterial growth.

In the human submandibular gland, striated ducts are easily observed, while intercalated ducts are very short.

The sublingual gland is a branched tubuloacinar gland that contains predominantly mucous cells and some serous cells. The serous cells are found almost exclusively on the demilunes of mucous tubules.

The serous cells in the sublingual gland secrete lysozyme, which is an enzyme that helps to break down bacterial cell walls.

The intralobular ducts in the sublingual gland are not as well developed as those in other major salivary glands.

Minor salivary glands are nonencapsulated and are distributed throughout the oral mucosa and submucosa. They produce saliva through small groups of secretory units, which is conducted to the oral cavity via short ducts with minimal modification. These glands are typically mucous, with the exception of the small serous glands in the posterior region of the tongue, known as von Ebner's glands. Additionally, lymphocyte aggregates are often found within these glands, which are associated with IgA secretion.

The pancreas is a mixed exocrine-endocrine gland that produces digestive enzymes and hormones. The exocrine portion releases digestive enzymes stored in acini, while the endocrine portion synthesizes hormones in the islets of Langerhans.

The pancreas can be distinguished from the parotid gland histologically by the absence of striated ducts and the presence of islets of Langerhans.

The exocrine portion of the pancreas is classified as a compound acinar gland, similar in structure to the parotid gland.

The islets of Langerhans are clusters of endocrine epithelial cells in the pancreas that synthesize hormones.

The main components of the pancreas include:

1. Main pancreatic duct
2. Common bile duct
3. Capillary
4. Intralobular duct
5. Intercalated duct
6. Islet of Langerhans
7. Centroacinar cells
8. Pancreatic acinar cells
9. Intercellular canaliculi
10. Pancreatic acinus

Pancreatic acinar cells are responsible for:

• Producing digestive enzymes such as amylase, lipase, and proteases.
• Synthesizing and storing these enzymes in zymogen granules until they are needed for digestion.
• Contributing to the secretion of bicarbonate to neutralize stomach acid in the small intestine.

Centroacinar cells play a crucial role in:

• Modulating the secretion of pancreatic juices.
• Acting as a conduit for the secretion from the acinar cells to the ducts.
• Participating in the regulation of bicarbonate secretion, which helps to neutralize gastric acid in the duodenum.

Centroacinar cells are nuclei surrounded by pale cytoplasm that constitute the intraacinar portion of the intercalated duct. They are found only in pancreatic acini.

Intercalated ducts are tributaries of larger intralobular ducts, which in turn form larger interlobular ducts lined by columnar epithelium located within the connective tissue septa.

The exocrine pancreatic acinus is composed of several serous cells surrounding a lumen. These cells are highly polarized and are typical protein-secreting cells.

The number of zymogen granules in pancreatic acinar cells varies according to the digestive phase and reaches its maximum in animals that have fasted.

A thin capsule of connective tissue covers the pancreas and sends septa into it, separating the pancreatic lobules.

The rich capillary network in the pancreas is essential for the secretory process.

The exocrine pancreas secretes 1500-3000 mL of isosmotic alkaline fluid per day, containing water, ions, and several proteases.

The majority of the enzymes are stored as proenzymes in the secretory granules of acinar cells and are activated in the lumen of the small intestine after secretion.

The liver is the second-largest organ of the body, weighing about 1-1.5 kg, with the largest organ being the skin.

The liver is situated in the abdominal cavity beneath the diaphragm.

The liver processes and stores nutrients absorbed in the digestive tract for use by other parts of the body, acting as an interface between the digestive system and the blood.

Most of the liver's blood (70-80%) comes from the portal vein, which arises from the stomach, intestines, and spleen, while a smaller percentage (20-30%) is supplied by the hepatic artery.

All materials absorbed via the intestines reach the liver through the portal vein, except for complex lipids (chylomicrons), which are transported mainly by lymph vessels.

The liver's position in the circulatory system is optimal for gathering, transforming, and accumulating metabolites, as well as for neutralizing and eliminating toxic substances.

Bile, an exocrine secretion of the liver, is important for lipid digestion and plays a role in the elimination of toxic substances from the body.

The liver produces important plasma proteins such as albumin, other carrier proteins, coagulation factors, and growth factors.

Glisson's capsule is a thin connective tissue capsule that covers the liver. It becomes thicker at the hilum, where the portal vein and hepatic artery enter the liver, and where the right and left hepatic ducts and lymphatics exit.

The vessels and ducts in the liver are surrounded by connective tissue that extends to their termination in the portal spaces between the liver lobules. This connective tissue forms a delicate reticular fiber network that supports the hepatocytes and sinusoidal endothelial cells of the liver lobules.

The main components of the left lobe of the liver include the falciform ligament, hepatic artery, vena cava, and portal vein.

The structures found in the portal triad of a hepatic lobule include the portal vein, hepatic artery, and bile duct.

The central vein in a liver lobule collects blood from the sinusoids and drains it into the hepatic veins, ultimately leading to the vena cava.

The portal area is significant as it contains the portal triad, which is essential for the blood supply and bile drainage in the liver lobule.

Key features of the microscopic view of a liver lobule include the central vein, liver plates, sinusoids, bile canaliculi, bile duct, portal vein, and hepatic artery.

The basic structural component of the liver is the liver cell, or hepatocyte.

The liver cells, or hepatocytes, grouped in interconnected plates, constitute two-thirds of the mass of the liver.

Liver lobules are structural units of the liver that are polygonal masses of tissue about 0.7 x 2 mm in size.

At the periphery of a liver lobule, there are portal spaces, and in the center, there is a vein called the central or centrolobular vein.

Portal spaces contain connective tissue, bile ducts, lymphatics, nerves, and blood vessels.

The human liver contains three to six portal spaces per lobule.

Each portal space contains a venule (branch of the portal vein), an arteriole (branch of the hepatic artery), a duct (part of the bile duct system), and lymphatic vessels.

The venule contains blood coming from the superior and inferior mesenteric veins and the splenic vein.

The oxygen-rich blood in the arteriole comes from the celiac trunk of the abdominal aorta.

The duct, lined by cuboidal epithelium, carries bile synthesized by the hepatocytes and empties into the hepatic duct.

The liver receives blood from two main sources:

1. Hepatic Artery:

   • Supplies oxygen-rich blood to the liver.
   • Contributes to the liver's metabolic functions.

2. Portal Vein:

   • Carries approximately 75% of the blood from the gastrointestinal tract (GIT).
   • This blood is rich in nutrients, essential for liver function.
   • The pressure in the portal vein is about 8 to 10 mm of Hg.

Additionally, the liver is drained by the Hepatic Veins into the Inferior Vena Cava. The sinusoids within the liver facilitate the exchange of substances between blood and liver cells.

Hepatocytes in the liver lobule are arranged radially, resembling bricks in a wall. These cellular plates extend from the periphery to the center of the lobule, forming a labyrinthine and spongelike structure. The spaces between these plates contain the liver sinusoids, which are irregularly dilated capillaries composed of a discontinuous layer of fenestrated endothelial cells, contributing to their great permeability.

Liver sinusoids are irregularly dilated capillaries found between the plates of hepatocytes. They are composed of a discontinuous layer of fenestrated endothelial cells with fenestrae about 100 nm in diameter, lacking diaphragms and grouped in clusters. Additionally, spaces between the endothelial cells and a discontinuous basal lamina enhance their permeability.

The space of Disse is a subendothelial space that separates endothelial cells from hepatocytes. It allows for the free flow of plasma while preventing the passage of cellular elements, facilitating the exchange of molecules, including macromolecules, between the sinusoidal lumen and hepatocytes.

The microvilli on the basolateral side of hepatocytes enhance the cell's surface area, facilitating endocytic and pinocytic activity, which is crucial for the uptake of substances from the space of Disse.

The fenestrae and discontinuity of the endothelium in the liver allow for the free flow of plasma into the space of Disse while restricting the passage of cellular elements. This structure supports efficient exchange of molecules between the sinusoidal lumen and hepatocytes.

The sinusoid in the liver is surrounded and supported by a delicate sheath of reticular fibers, which provides structural integrity and support to the liver's vascular architecture.

The liver sinusoidal structure consists of three main layers:

1. Top Layer: Composed of Hepatocytes, which are large, rectangular, pink cells with nuclei represented as white circles.

2. Middle Layer: Contains Sinusoidal Endothelial Cells, depicted as elongated pink cavities bounded by elongated blue endothelial cells, also with white circles for nuclei.

3. Bottom Layer: Also consists of Hepatocytes similar to the top layer.

Additionally, Kupffer Cells (green) are present within the sinusoidal lumen, and Stellate Cells are located outside the sinusoidal cavity. Gray spherical shapes are also present in the top and middle layers.

Kupffer cells have several key functions:

1. Metabolize aged erythrocytes
2. Digest hemoglobin
3. Secrete proteins related to immunological processes
4. Destroy bacteria that enter the portal blood from the large intestine

They are primarily located in the periportal region of the liver lobule and are very active in phagocytosis.

Fat-storing cells are also known as stellate or Ito's cells, and they are located in the space of Disse (perisinusoidal space) in the liver.

In a healthy liver, fat-storing cells have several functions, including:

1. Uptake, storage, and release of retinoids
2. Synthesis and secretion of extracellular matrix proteins and proteoglycans
3. Secretion of growth factors and cytokines
4. Regulation of the sinusoidal lumen diameter in response to different regulators.

The primary function of Ito's cells is to store fat in the form of lipid inclusions and to synthesize and secrete extracellular matrix proteins and proteoglycans that contribute to the liver's structural integrity.

Tight junctions between the cell membranes of hepatocytes near the bile canaliculi ensure that the canaliculi remain distinct tubular spaces, while gap junctions facilitate intercellular communication between hepatocytes, allowing for coordinated function and transport of bile.

Bile canaliculi form a complex anastomosing network that runs along the plates of the liver lobule, connecting hepatocytes and ultimately terminating in the portal spaces, thus playing a crucial role in bile transport within the liver's architecture.

Bile flow progresses from the center of the lobule to its periphery, which is opposite to the direction of blood flow.

At the periphery, bile enters the bile ductules, also known as Hering's canals, which are composed of cuboidal cells.

Bile ducts are lined by cuboidal or columnar epithelium and have a distinct connective tissue sheath.

The bile ductules gradually enlarge and fuse to form the right and left hepatic ducts, which subsequently leave the liver.

Hepatocytes have one or two rounded nuclei, each containing one or two nucleoli.

Hepatocytes contain both smooth and rough endoplasmic reticulum. The rough endoplasmic reticulum forms aggregates called basophilic bodies and is involved in synthesizing proteins like blood albumin and fibrinogen. The smooth endoplasmic reticulum is responsible for the inactivation or detoxification of various substances before their excretion from the body.

Basophilic bodies are aggregates of rough endoplasmic reticulum found in hepatocytes, where proteins such as blood albumin and fibrinogen are synthesized on polyribosomes.

Glycogen in hepatocytes serves as a depot for glucose. Its amount varies with the nutritional state of the individual. When blood glucose levels fall below normal, liver glycogen is mobilized to maintain a steady level of blood glucose, which is a primary energy source for the body.

Hepatocytes do not store proteins in their cytoplasm as secretory granules. Instead, they continuously release proteins into the bloodstream, playing a crucial role in maintaining various bodily functions.

Each hepatocyte has approximately 2000 mitochondria.

Hepatocyte lysosomes are important in the turnover and degradation of intracellular organelles.

Peroxisomes in hepatocytes are involved in the oxidation of excess fatty acids and the breakdown of hydrogen peroxide.

Golgi complexes in hepatocytes are responsible for the formation of lysosomes and the secretion of plasma proteins (e.g., albumin), glycoproteins (e.g., transferrin), and lipoproteins (e.g., very low-density lipoproteins).

The main components of bile include:

• Water
• Electrolytes
• Bile acids
• Phospholipids
• Cholesterol
• Lecithin
• Bilirubin

About 90% of bile acids are derived from absorption in the distal intestinal epithelium and are transported by hepatocytes from the blood to bile canaliculi, a process known as enterohepatic recirculation.

About 10% of bile acids are synthesized in the smooth endoplasmic reticulum of the hepatocyte.

The regeneration mechanism in the liver is triggered by the loss of hepatic tissue due to surgical removal or the action of toxic substances, leading to the division of hepatocytes until the original mass of tissue is restored.

In humans, the liver's regeneration capacity is considerably restricted compared to other species, but it remains important for surgical liver transplantation.

Bile produced by hepatocytes flows through the following structures:

1. Bile canaliculi
2. Bile ductules
3. Bile ducts

These structures merge to form the right and left hepatic ducts, which unite to form the common hepatic duct. The common hepatic duct receives the cystic duct from the gallbladder and continues to the duodenum as the common bile duct (ductus choledochus).

The sphincter of Oddi regulates bile flow into the duodenum. It is formed by a thicker layer of smooth muscle in the intramural portion of the common bile duct.

The daily basal secretion of bile is approximately 500 mL.

The gallbladder is a hollow, pear-shaped organ located on the lower surface of the liver. It can store 30-50 mL of bile. Its wall consists of:

1. Mucosa: Composed of simple columnar epithelium and lamina propria, with abundant folds, especially when empty.
2. Smooth Muscle Layer: Facilitates contraction and bile release.
3. Perimuscular Connective Tissue Layer: Provides support.
4. Serous Membrane: Covers the outer surface.

The epithelial cells are rich in mitochondria and can secrete small amounts of mucus, primarily produced by tubuloacinar mucous glands near the cystic duct.

The main function of the gallbladder is to store bile, concentrate it by absorbing its water, and release it when necessary into the digestive tract.

Contraction of the smooth muscle of the gallbladder is induced by cholecystokinin, a hormone produced by enteroendocrine cells in the small intestine.

The release of cholecystokinin is stimulated by the presence of dietary fats in the small intestine.