Histology: Liver, Pancreas, Gallbladder PDF

I. OVERVIEW HISTOLOGY The liver, gallbladder and pancreas are accessory LIVER, PANCREAS, organs of the...

I. OVERVIEW HISTOLOGY The liver, gallbladder and pancreas are accessory LIVER, PANCREAS, organs of the digestive tract. Accessory organs are located outside of the digestive GALLBLADDER tube. Dr. Suzette S. Labrador The common bile duct from the liver and main pancreatic ducts from the pancreas join to form a single duct. OUTLINE The gallbladder joins the common bile duct via the cystic I. Overview X. Histophysiology of the duct. II. Liver Liver A. Functions of the A. Important Liver Accessory Functions B. Major Aspects of the Intestines in C. Theories on the the Immune System Liver Architecture XI. Pancreas III. Blood Supply XII. Exocrine Pancreas A. Hepatic Portal A. Acinar Tissue Vein B. Duct System B. Hepatic Artery C. Blood vessels, C. Sinusoids Lymphatics, Nerves D. Kupffer Cells XIII. Histophysiology of E. Perisinusoidal Exocrine Pancreas Space XIV. Endocrine Pancreas Figure 1. Visual representation of the Biliary Tree IV. Zonation within the XV. Histophysiology of Liver Lobule Endocrine Pancreas II. LIVER A. Zonation within XVI. Gallbladder the Hepatic A. Mucosa Most important organ but least appreciated organ Acinus B. Lamina Propria Essentially an exocrine gland V. Cytology of C. Epithelium Secreting bile into the intestine Hepatocytes D. Muscularis Externa Also an endocrine gland A. Hepatocytes E. Serosa Blood filter VI. Hepatic Ducts F. Luschka Ducts Weighs 1500 grams (2% of body weight in adults) A. Bile G. Cystic Ducts Located at RUQ of the abdominal cavity B. Bile Canaliculi H. Sphincter of Oddi ○ Not normal if liver is easily palpated (only liver C. Terminal Bile Duct VII. Structure of edge) D. Hepatic Duct Gallbladder ○ If liver is easily palpated it means there is E. Cystic Duct VIII. Blood Vessels, enlargement F. Bile Duct Lymphatics, And Its rounded upper surface conforms to the dome of G. Common Bile Duct Nerves of Gallbladder the diaphragm. H. Extrahepatic Duct XIX. Histophysiology of GLISSON’S CAPSULE System Gallbladder ○ Thin connective tissue VII. Connective Tissue XX. References ○ Blood vessels are on its underside because: Stroma XXI. Appendices It is closer to where it is needed VIII. Lymphatics and For filtering process Nerves For protection of the blood vessels A. Lymphatics B. Nerves IX. Liver Regeneration A. Bile Salts B. Bilirubin C. Function of the Liver Figure 2. Histology of Glisson’s Capsule. Note the Parenchyma 1|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  The biliary tree A. FUNCTIONS OF LIVER 3D arrangement of liver cells and their association with the vascular and biliary system Porta Hepatis ○ Hilum of the liver ○ Where the right and left hepatic ducts leave the organ Metabolic Factory ○ Synthesizes and breaks down a variety of substances ○ Site of glycogenesis, glycogenolysis, and site for synthesis of other proteins A person can survive with ¼ of the liver (liver regenerates) An accessory gland of the GIT but has a diversity of functions Figure 4. Anatomy and Blood Supply of the Human Liver C. THEORIES ON LIVER ARCHITECTURE CLASSICAL LIVER LOBE Figure 3. Aspect that faces contents of the abdominal cavity (L) Flatter Face that is in contact with the diaphragm (R) Formation and secretion of bile ○ Bile is a complex substance required for the emulsification Hydrolysis secreted into the Figure 5. Classic Liver Lobule duodenum via the common bile duct Storage of glycogen (buffer for blood glucose) and Hepatic Lobule: smallest structural unit of the liver triglycerides Connecting tissue septae invaginating from the Synthesis of urea capsule delineate “hepatic lobules” Metabolism of cholesterol and fat Only one 6-sided prism about 2 mm long and 1 mm in Synthesis and endocrine secretion of many plasma diameter proteins including clotting factors At the corner: Portal Triad (bile duct, branches of the Detoxification of many drugs and other poisons hepatic artery, and portal vein) Cleansing of bacteria from blood At the center: Central Vein Processing of several steroid hormones and vitamin D Filled by cords of hepatic parenchymal cells or Volume reservoir for blood hepatocytes Catabolism of hemoglobin from worn-out RBC by Hepatocytes radiate from the central vein and Kupffer cells separated by vascular sinusoids Storage of fat- soluble vitamins (A,D,E,K) In pig liver, lobules appear quite clearly Storage of iron in complexes with protein ferritin Has an enveloping of fibrous connective tissue around each lobule In humans, lobular organization not immediately evident B. MAJOR ASPECT Lobules do not have boundaries Hepatic Vascular System To visualize the lobules: ○ Majority of the liver’s blood supply is “venous ○ Locate the Portal Areas blood” Small patches of CT each containing a For detoxification process duct, a large vein, and a small artery which ○ Receives a dual vascular system marks the corners where lobules come 75% Hepatic Portal Vein together 25% Hepatic Artery Represent the stroma of the liver ○ Circulatory system is unlike that seen in any organ 2|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  ○ Look for the Central Vein: Conspicuous, spaces, Space of Disse with no associated CT o The space between the endothelium and the Located roughly midway between cords o Also known as perisinusoidal space portal areas o Significance: facilitate diffusion Mark the centers of lobules o Blood plasma can freely enter the perisinusoidal space through the fenestrated epithelium. Liver lobules are drained by the central vein. Adjoining liver cells form the walls of the bile canaliculi Bile canaliculi via short canals of Hering→ terminal ducts (cholangioles)→ Interlobular bile ducts in the portal triads ducts (cholangioles)→ Interlobular bile ducts in the portal triads Figure 6. Locating the Portal Triad and Central Vein PORTAL LOBULE Triangular in shape Includes sectors of 3 neighboring classical lobules At the Corner: Central Vein At the Center: Portal Triad (bile duct, branches of the hepatic artery and portal vein) Emphasize the “afferent blood supply and bile drainage” by the vessels of the portal triads. Figure 8. Locating the Liver/Hepatic Acini Blood supply radiates from the axial vessels Secondary product drains to a central duct Figure 9. Virtual Depiction of the Theories on Liver Architecture Figure 7. Portal Lobule III. BLOOD SUPPLY LIVER/HEPATIC ACINI Dual vascular supply: Structural and functional unit of the liver ○ Hepatic Portal Vein (75%) Emphasizes the “secretory function of the liver” ○ Hepatic Artery (25%) Acini: smaller units than portal or “classical” liver lobule A. HEPATIC PORTAL VEIN Roughly an ovoid mass of parenchymal cells around each terminal arterioles, venules and bile duct that Brings to the liver all of the poorly oxygenated blood branch laterally from the portal area which has previously passed through the intestine and Central Vein: terminal Hepatic Venule spleen The bulk of the liver consists of epithelial hepatocytes Blood from the 2 sources mingles in the hepatic arranged into cords, separated by vascular sinusoids, where its solutes have direct access to the sinusoids. hepatic cells Hepatocytes are separated from the bloodstream by Blood leaving the organ is carried via the hepatic a thin discontinuous or fenestrated simple squamous veins to the inferior vena cava epithelium, which lines the sinusoids. 3|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  Portal vein→ Interlobar veins → Conducting vein → D. KUPFFER CELLS Interlobular veins A component of the portal triad (Bile duct, Hepatic Discovered by von Kupffer in 1898 Artery, Portal Vein) Function: Engulf bacteria from blood filtration and Makes up 75% of the blood supply RBC for catabolism of hemoglobin Stellate cells in the hepatic sinusoids that could be B. HEPATIC ARTERY selectively stained with gold chloride Contained engulfed erythrocytes and deposits of iron Brings fresh, oxygenated blood from the general containing pigment circulation or aorta Associated with the sinusoids Efferent blood supply Liver macrophages which effectively catch and Carries arterial blood which contains oxygen destroy bacteria which entered the blood in the Hepatic artery → interlobar veins → conducting vein intestine → peribiliary/periductal plexus Recognized and phagocytize effete and damaged Peribiliary/periductal plexus: surround bile ductule RBC Most of the arterial blood reach the sinusoids Can also function as antigen- presenting cells Make up 25% of the blood Derived from circulating monocytes Members of the body’s mononuclear phagocyte C. SINUSOIDS system Situated on the surface of endothelial cells with Facilitates blood processes extending into the lumen Aid in efficient blood flow (blood are mixed with other components) Distensible vascular channels lined with highly fenestrated or “holey” endothelial cells and bounded circumferentially by Hepatocytes Blood flows through the sinusoids and empties into the central vein of each lobule Most of the arterial blood reach the sinusoids through the peribiliary plexus “Sieve plates” Groups of fenestrae Blood from both the portal vein and hepatic artery mixes together in the hepatic sinusoids then passes out of the liver through the hepatic vein Figure 10. Kupffer Cells (Space of Disse) Represents an enormous surface area for exchange of metabolites between the blood and hepatic parenchyma E. PERISINUSOIDAL SPACE 30 sec after injection of dye into the portal vein, it can be found between the wall of sinusoids and the Contains scattered reticular (collagen) fibers and surface of hepatic cells fibroblasts. Hepatocytes are exposed on at least one and usually Typical fibroblast rarely found. on two sides to blood flowing through the sinusoids Contains two cell types: Parenchyma of each lobule can be divided into ○ Fat-forming cells arbitrary zones based on oxygen supply ○ Pit cells Central zone (closest to the central vein) poorest in FAT-FORMING CELLS oxygen Blood flow pattern yield differences in hepatocyte Also known as stellate cells, interstitial cells, lipocytes appearance and lto cells Fasting- glycogen depleted first on the periphery Presence of multiple lipid droplets in the cytoplasm as Feasting- glycogen deposited first in the periphery a distinguishing feature Can reflect recent nutritional history More common on the center rather than the periphery Blood flows through the sinusoids and empties into Able to store exogenous vitamin A and other lipid the central vein of each lobule soluble vitamins (due to its lipid solubility) Produce extracellular matrix (ECM) components BLOOD SUPPLY (becoming myofibroblasts after liver injury) and Central vein → Sublobular veins → Collecting veins cytokines that help regulate Kupffer cell activity → Hepatic veins → (Porta Hepatis) Inferior Vena Cava 4|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  V. CYTOLOGY OR HEPATOCYTES PIT CELLS Only in rodents; never in humans Small cells with short pseudopodia Are not phagocytic Belong to the immune system IV. ZONATION WITHIN THE LIVER LOBULE Minor differences in hepatic cells in 3 concentric zones within the classical lobule Reflect the differences in degree of metabolic activity of cells Figure 12. Histology of the Liver ○ Zone of permanent function: periphery Rely on aerobic metabolism and more active in protein synthesis A. HEPATOCYTES Oxidative metabolism and Chief functional cells of the liver gluconeogenesis Parenchymal cells of the liver compromising 80% of ○ Zone of variable function: intermediate the mass Mixed complement of enzymes “Metabolic Superstars”: perform an astonishing ○ Zone of permanent repose: around the number of metabolic endocrine and secretory central vein functions Less oxygen and nutrients Polygonal cells joined to one another in anastomosing More involved with detoxification and plated with borders that face either the sinusoids or glycogen metabolism adjacent hepatocytes Glycolysis, lipid & drug metabolism ○ Sinusoidal domain: sides exposed to sinusoids Cells are not intrinsically different ○ Lateral domain: in contact with neighboring “Centrilobular Necrosis”: occurs in disease states hepatocytes attended by hypoxemia ○ Bile canalicular domain: forms the wall of the ○ Zone 1: ellipsoidal area immediately intercellular bile canaliculi surrounding the hepatic arteriole and Sinusoidal and bile canaliculi domains bear sparse terminal portal venule microvilli ○ Zone 2: intermediate Ergastoplasm: present in the cytoplasm; pale, blue ○ Zone 3: cells near the ends of the acinus stained, irregularly shaped areas Nuclei distinctly round (40-60%) with 1 or 2 prominents nucleolus 25% are binucleate Have abundant rough and smooth ER Proteins are synthesized in the ER Liver’s function is for synthesis Contain Golgi organelles forming stacks of Golgi membranes Golgi vesicles numerous in the vicinity of bile canaliculi reflecting transport of bile Active in the synthesis of proteins and lipids; (synthesis and secretion) VLDL; synthesize Glycogen: PAS+ material in Figure 11. Three Concentric Zones surrounding the Hepatic Arteriole and Terminal Portal Venule hepatocytes Contains glycogen granules and vesicles containing VLDL A. ZONATION WITHIN THE HEPATIC ACINUS ○ Glycogen-storage form of CHO that can be drawn on to maintain the normal glucose Phenobarbital administration concentration in the blood ○ Induces hypertrophy confined to cells in Zone 3 Glycogen granules arranged in chrysanthemum-like ○ After 10 days, hypertrophy occurs as well in Zones clusters of electron dense particle 1 and 2 Density varies whether after a meal or during prolonged fast Contain VLDL in electron dense droplets not enclosed in a membrane 5|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  Maybe dramatically increased after consumption of alcohol or hepatotoxic substances C. TERMINAL BILE DUCT Usually begins in cells of Zone 3 Interlobular, intrahepatic ducts Nice to Know! ↓ Brain can only function for 5 minutes without glucose Left and right hepatic duct ↓ Common hepatic ducts or common bile ducts VI. HEPATIC DUCTS ↓ Bile originates as secretion from the basal surface of Cystic duct and bile duct (ductus choledochus) hepatocytes Epithelium: squamous gives way to become low cuboidal D. CYSTIC DUCT Bile collects in a channel called canaliculi Leads to the gallbladder →flow in the periphery of lobules →bile ductules and interlobular bile ducts Lined by columnar epithelium and have a →hepatic duct outside the liver moderately thick wall which includes a thin submucosa, muscularis, and adventitia Lymphocytes are common in submucosa E. BILE DUCT Carries bile to the duodenum Initially lined by squamous cells but give way to low cuboidal cell as the ductules approach the interlobular ducts F. COMMON BILE DUCT More prominent smooth muscles as it approaches Figure 13. Histology of the Liver. Note the location of the ducts. the duodenum Forms a sphincter that regulates flow of bile into the A. BILE duodenum Emulsification of fat Contains organic and inorganic components VII. CONNECTIVE TISSUE STROMA ○ Organic components Remarkably little stroma Lecithin Glisson’s capsule Cholesterol ○ Layer of dense connective tissue Bilirubin (breakdown product of Hb) ○ Thickest at the porta hepatis ○ Inorganic Components Origin of collagenous framework a subject of debate Bile salts: facilitate digestion and ○ lto cells, endothelial liver cells absorption of fat in the small intestines ○ Fibrosis in chronic liver disease B. BILE CANALICULI VIII. LYMPHATICS AND NERVES Located midway along the interface between adjoining hepatic cells Form a network within the plates of hepatocytes A. LYMPHATICS Minute channels (0.5-1.5 um in diameter) Produce large volume of lymph for detoxification Confluent with the terminal ductules (Canal of 25-50% of the lymph of the thoracic duct Hering) Contains a large amount of plasma proteins Higher ratio of albumin to globulin compared to plasma Network of lymphatics parallels the branches of the portal vein 6|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  Plasma escaping through the fenestrations move C. FUNCTION OF THE LIVER along the space of Disse counter to the flow of blood Maintain normal concentration of glucose in the blood seeping into tissue spaces in the terminal twigs of the ○ Glycogen portal vein and hepatic artery Absorbed glucose Plasma then enters lymphatic capillaries that Storage form of CHO accompany the blood vessels and ducts of the portal tracts B. NERVES Innervated by efferent autonomic nerves Regularly found in the CT around the portal triads Enzyme Phosphorylase Adrenergic endings can be found in the space of Disse ○ Present in active form Autonomic innervation plays an important role in ○ Activated by epinephrine, glucagon short-term regulation of cell metabolism ○ Release of glucose into the blood IX. LIVER REGENERATION X. HISTOPHYSIOLOGY OF THE LIVER Hepatic parenchyma as a stable cell population Metabolism of Lipids Lifespan of hepatocytes: 150 days ○ Maintenance of normal lipid levels in the Cells in division seldom seen in normal liver ○ circulating blood Exceptional capacity for regeneration ○ Blood lipids: derived from ingested food or Experiments: 2/3 of the liver can be removed and in mobilization of fat reserves in the adipose few days most of it will be replaced (Rapid tissue regeneration) ○ Lipoprotein: VLDL Human liver falls short of that seen in laboratory ○ TG: first generated from fatty acids animals in terms of regenerative capacity. Site of synthesis of plasma proteins ○ Involved in rough ER ○ Produce fibrinogen, thrombin, and factor II A. BILE SALTS (prothrombin) which are essential for blood clotting ○ Bleeding tendencies Emulsifying action on ingested fat that promotes absorption of fatty acids and monoglycerides Absence of bile secretion A. IMPORTANT ACCESSORY FUNCTIONS OF THE ○ Dietary fat not absorbed INTESTINE IN THE IMMUNE SYSTEM ○ Unusually fatty feces (Steatorrhea) IgA B. BILIRUBIN ○ Synthesized by plasma cells in the lamina From destruction of RBCs propria of the gut Toxic greenish pigment coming from the degradation ○ Complexed with secretory component in cells of Hb of senescent erythrocytes that is removed from of intestinal epithelium and secreted into the the circulation by Kupffer cells of the other lumen phagocytes in the spleen ○ Much of IgA in the blood reach the lumen of Taken up by the liver and conjugated with glucuronide the intestine via the hepatobiliary pathway in the ER ○ Secretory component continuously Bilirubin glucuronide excreted into the bile but some synthesized by the liver cells are released into the blood ○ If bile duct is surgically occluded, this will Bilirubin production exceeds the capacity of the liver occur: to excrete it Increase in levels of IgA in the blood Bilirubin uptake and conjugation impaired by liver Decrease to almost one-tenth its disease normal concentration Jaundice: abnormal accumulation of bilirubin in the It is taken up by receptor-mediated endocytosis, a blood number of hormones produced by the endocrine Either conjugated or unconjugated bilirubin may be gland and secretes them into the bile. a probable cause in a patient with jaundice. ○ Metabolism of barbiturates and other lipid soluble drugs Enzymes localized in the smooth ER Induces marked hypertrophy of smooth ER 7|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  Drug tolerance ○ Adaptive response that enhances the ability of A. ACINAR TISSUE the liver cells to eliminate the induced drug Another name for exocrine pancreas ○ Progressive loss of drug effectivity with Compound acinar gland continued use Made up of small lobules bound together by loose Blood filtering function connective tissue ○ Highly vascular Round or elongated and consist of 40-50 pyramidal ○ Receives each minute: 1000 mL blood from the epithelial cells around a narrow lumen portal vein and 350 mL from hepatic artery The size of the lumen is wider during active secretion ○ Blood is exposed to 1.2x107 phagocytic Kupffer Low cuboidal or squamous cell cells/gm of tissue Acinar cell ○ Removes cellular debris, materials and Spherical nucleus has a prominent nucleolus and microorganisms peripheral clumps of heterochromatin ○ Less deeply stained supranuclear Golgi XI. PANCREAS region, enlarges during formation of secretory granules Pinkish-white organ ○ Cytoplasm near the base of the cell is strongly Positioned retroperitoneally on the posterior wall of basophilic due to conc. of ribonucleoproteins the ○ Apical cytoplasm is filled with secretory abdominal cavity at the level of the 2nd & 3rd lumbar granules continuing the precursors of the vertebrae digestive enzymes Measures 20-25 cm in length in adult ○ In basophilic portion, the rough ER occupies Weighs 100-150g about 20% of the cell volume and presents a Has no distinct capsule, but is covered by a thin layer surface area of ~800 um2 of loose connective tissue Formative Stages of Secretory Granules Lobulated with outlines of the larger lobules seen by ○ Due to a few larger vesicles and considering the vacuoles with a homogenous content of low naked eye density 2nd largest gland associated with the alimentary ○ At the concave trans-face of the stacks of tract supranuclear Golgi Consists of 2 portions: Zymogen Granule ○ EXOCRINE PORTION - produces ~1.2L of ○ Most abundant in acinar tissue during fasting pancreatic juice daily (enzyme-rich fluid ○ Contains precursors of digestive enzymes required for the digestion of fats, CHO & ○ Fixed during fasting, reduced after the CHON) copious secretion induced by a meal ○ ENDOCRINE PORTION - secretes hormone ○ Dense membrane-bounded, fill the apical essential for the control of CHO metabolism portion of the cell (insulin, glucagon, etc.) ○ Implies a solid or semisolid consistency at the Accounts for ~1% of the pancreas time of release through the opening formed Consists of cells of islets of Langerhans by fusion of the limiting membrane with the Anatomic Divisions plasmalemma ○ Head: Lodged in the concavity of the C-shaped Secretory Vesicle duodenum ○ Zymogen vesicles fuse with one another and ○ Body another that engages in exocytosis in series ○ Tail ○ Intercommunicating, extends down into the Narrower apical cytoplasm during very active secretion. Extend transversely across the posterior wall of the abdomen to the hilus of the spleen B. DUCT SYSTEM Low cuboidal or squamous cells lining the duct XII. EXOCRINE PANCREAS Unique among compound acinus gland Extend a short distance into the acinus Soft, elongated organ located posterior to the Not merely conduits for the secretory products of the stomach acini The head lies in the duodenal loop Lining epithelium active in transporting water and The tail extends across the abdominal cavity of the bicarbonate ions into the lumen spleen Make a major contribution to the total volume of Secrete digestive enzymes for fat, protein, and pancreatic secretion carbohydrates Bicarbonate ions- neutralize the acidic contents which the stomach empties into the duodenum 8|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  ○ Nervous regulation of pancreatic secretion Centro-acinar Cells less important than its hormonal regulation ○ Pale staining, very low density and paucity of Stimulation of Vagus cytoplasmic organelles ○ Results in exocytosis ○ Continuous with the lining epithelium of ○ Accumulation of secretion in the lumen of slender intercalated ducts acini and small ducts Intercalated Ducts ○ Slender tube drains the acinus ○ Converge to form a larger intralobular duct ○ Low columnar to cuboidal Intralobular Ducts ○ Lined by a low columnar epithelium containing goblet cells ○ Tributaries of interlobular ducts ○ Active in transporting water and bicarbonate ions into the lumen Interlobular Ducts ○ The lining epithelium is the same with intralobular ducts ○ Found in the connective tissue septa between lobules ○ Together with the intralobular, a major contribution to the total volume of secretion Two Main Pancreatic Ducts Figure 14. Histology of the Pancreas ○ Lined by a low columnar with goblet cells and argentaffin cells ○ Enveloped in an substantial layer of XIII. HISTOPHYSIOLOGY OF EXOCRINE PANCREAS connective tissue continuing smooth muscle Accumulation of secretion in the lumen of acini and fibers and mast cells small ducts Ampulla of Vater Produce a great quantity and variety of proteins, ○ Adaptive response that enhances the ability involving their synthesis of the liver cells to eliminate the induced drug Rough Endoplasmic Reticulum is the site of protein ○ Progressive loss of drug effectivity with synthesis continued use Polyribosomes are joined together by binding to a messenger RNA (mRNA) that encodes the information for the sequential assembly of amino C. BLOOD VESSELS, LYMPHATICS, AND NERVES acids into a specific protein Blood Supply Base sequences are translated by transfer RNA ○ Branches of splenic artery (tRNA) into the amino acid sequence of the protein ○ Pancreatic-duodenal branches of hepatic Translation of mRNAs yields a variety of protein arteries products, including proenzymes and enzymes for ○ Superior mesenteric arteries secretion: Venous Supply o Trypsinogen – hydrolyzes small proteins into ○ Portal veins small peptides or amino acids ○ Splenic veins o Chymotrypsinogen – hydrolyzes small ○ Superior mesenteric veins proteins into small peptides or amino acids Capillary o Procarboxypeptidase – hydrolyzes small ○ In the exocrine pancreas, the walls have a proteins into small peptides or amino acids continuous endothelium o Ribonuclease – split the corresponding ○ In the islet of Langerhans of the endocrine nucleic acid pancreas, it is fenestrated o Deoxyribonuclease – split the corresponding Lymph Capillaries nucleic acid ○ End among the acini o Lipase – hydrolyzes triglycerides into fatty ○ Drains to the pancreaticosplenic lymph nodes acids andmonoglycerides ○ Along the upper border of the gland o Elastase Nerve Supply o Amylase – hydrolyzes starch and glycogen to ○ Vagus nerves glucose and small saccharides ○ Splanchnic nerves via the splenic nerve o Trypsin Inhibitor plexus o Cholesterol esterase – breaks down ○ Small clusters of autonomic ganglion cells cholesterol esters into cholesterol and a fatty acid 9|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  ○ Each islet – 2 to 3T cells To protect the integrity of the gland, enzymes are produced in their inactive form and be activated only Four principle types of cells secrete different after they are secreted in the lumen of the intestine hormones: (to avoid autodigestion). ○ Alpha-Cells (A-cells) Trypsin Secrete glucagon o Most abundant pancreatic enzyme Mainly at the periphery but few are o Synthesized as inactive trypsinogen scattered along the capillaries in its o Cytoplasm of acinar cells contain trypsin interior inhibitor Effects opposite to insulin Acute Pancreatitis Contents are electron dense o Condition where proteolytic enzymes are Typically, smaller than delta cells activated (ave – 300 nm) o Pancreas is rapidly digested by its own ○ β-Cells (B-cells) enzymes Secrete insulin o Often with fatal outcome Predominant cell type occupying its Some proteins are converted into glycoproteins by center (70% of its mass) glycosyltransferase Fairly easy to recognize in EM Acinar cells secrete enzymes for CHON, lipid, and pictures because their contents of CHO digestion their secretory vesicles typically form Secretory activity has a rhythmical cycle with a low one or two crystals basal rate of continuous secretion, increased by Crystals are rectangular or polygonal hormonal stimulation associated with ingestion of ○ δ-Cells (D-cells) food Secrete somatostatin Presence of food in the gastric antrum and passage of ○ F-Cells (PP-cells) acidic products of gastric digestion into the Secrete pancreatic polypeptide, duodenum stimulates the release of: which inhibits the production of ○ Secretin pancreatic enzymes and alkaline (27 amino acids) stimulates the secretions secretion of a fluid containing high Widely scattered, very few in number, concentrations of Bicarbonate and may occur among the acini as Copious alkaline fluid neutralizes the well as in the islets acidic chyme & creates a Other endocrine cells of the islands secrete: neutral/alkaline pH for optimal ○ Pancreatic polypeptide digestive enzyme activity Stimulates chief cell in gastric glands ○ Cholecystokinin Inhibits bile and bicarbonate (33 amino acids) secreted by the secretion mucosa of the duodenum and upper ○ Vasoactive Intestinal Peptide jejunum Effects similar to glucagon Binds to specific receptors in the Stimulates the exocrine function of basolateral membranes of the acinar the pancreas cells, inducing their release of highly ○ Secretin concentrated digestive enzymes Stimulates exocrine pancreas Coordinated action with secretin ○ Motilin results in secretion of a large volume Increase GI motility of enzyme-rich pancreatic juice Less extensive granular endoplasmic reticulum Content of secretory granules is released by exocytosis into the ECF, dispersing to act on XIV. ENDOCRINE PANCREAS neighboring islet cells or enter the blood Axons of sympathetic and parasympathetic nerves Secrete hormones for the control of carbohydrate terminate among the cells of the islets of Langerhans metabolism Segregated in relatively small aggregations of cells, forming the Islets of Langerhans XV. HISTOPHYSIOLOGY OF ENDOCRINE PANCREAS ○ Scattered throughout the gland, but are more numerous in the tail Major product of carbohydrate digestion in the ○ Simply a compact mass of epithelial cells alimentary tract is glucose, which is controlled by the pervaded by a labyrinthine network of hormones secreted by the principal cells capillaries Insulin consists of 21 amino acids alpha-chain and 30 ○ Numerous but constitute only 1-2% of the amino acids beta-chain linked together by two volume of the gland disulfide bonds ○ Arranged in anastomosing cords or plates ○ Cells are polarized toward the capillaries 10|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  ○ Islets of Langerhans become hyalinized/ ○ A much large precursor, pre-proinsulin, is fibrotic with destruction of a large portion of assembled on the rough ER where a short AA ß-cells sequence participates in its translocation Hyperinsulinism results from the occurrence of ○ The sequence is removed by cleaving tumors in the islet cells enzymes, yielding proinsulin ○ Patients are at risk for insulin shock ○ Transported to the GA to fuse with a cistern ○ Massive release of insulin leads to fall in blood as vesicles, where conversion to insulin takes glucose (hypoglycemia) place ○ CNS becomes hyperactive (e.g. extreme ○ Vesicles containing insulin, C-peptide, and agitation, tremors, sweating, convulsions) cleaving enzymes lose their clathrin coat, leading to coma concentrate their contents, and give rise to ○ Treatment involves timely administration of secretory granules that are discharged by IV glucose exocytosis Glucagon is secreted by alpha-cells in response to ○ Fuse with primary lysosomes and are hypoglycemia, increasing the degradation of degraded by lysosomal enzymes by glycogen to release glucose or increasing granulolysis/ crinophagy gluconeogenesis by hepatic cells ○ Secretion is stimulated by elevated blood Somatostatin is secreted by ∂–cells in response to glucose after a meal rich in carbohydrate and increased blood glucose, amino acids, or fatty acids gastrointestinal hormones ○ Decreases the rate of insulin and glucagon ○ Binds to receptors that facilitate entry of secretion to diminish the motility of the glucose into their cytoplasm stomach, small intestines, and gallbladder, ○ Activates glucokinase in liver cells slowing nutrient uptake and making the ○ Glucose is incorporated in glycogen in the available over a long period of time liver, which is altered release to maintain ○ Also produced in the hypothalamus to reduce blood glucose levels between meals secretion of growth hormone by the ○ Glucose is used as an energy source in active somatotrophs of the anterior pituitary gland muscle and transiently stored as glycogen in resting muscle XVI. GALLBLADDER ○ Glucose is used in fatty acid and glycerol synthesis in adipose cells Pear-shaped hollow organ Glucose permease is a specific transport protein Occupies a shallow fossa on the interior surface of the present on cell membranes that allow glucose entry liver by conformational changes upon their binding Consists of the body, fundus, and neck that continues ○ Increased by rapid fusion of vesicles with into the cystic duct plasma membranes as insulin binds to its Measure 10 by 4 cm receptors Capacity of 40 to 70 mL ○ Increases 10 times as insulin stimulates Functions adipose cells ○ To store, concentrate, and release into the Diabetes is a consequence of chronic insulin duodenum the bile secreted by the liver deficiency where glucose cannot enter the cells ○ Covered by serosa continuous with threat ○ Polyuria is an excretion of abnormal urine covering the liver except on the hepatic volumes due to excess glucose in the blood surface (hyperglycemia) ○ Wall consists of a subserosal layer of ○ Polydipsia is excessive intake of water due to connective tissue overlying a layer of smooth dehydration with excessive thirst muscle ○ Polyphagia is excessive eating due to the ○ Has a mucosa composed of epithelium and a activation of cells in the hypothalamus that highly vascular lamina propria control appetite Bile leaves the gallbladder via the cystic duct and ○ Rapid weight loss despite increased food enters the duodenum via the common bile duct intake is due to the metabolism of fat and through the major duodenal papilla, a fingerlike muscle protein because of inability to use protrusion of the duodenal wall into the lumen glucose as an energy source The gallbladder is not a gland ○ Ketonuria is the excretion of excess plasma Bile is released into the digestive tract as a result of ketones generated from increased fat hormonal stimulation after a meal metabolism When the gallbladder is empty, the mucosa exhibits ○ Acidosis is due to loss of sodium involved in deep folds. excretion of ketone salts, lowering the The gallbladder is a muscular sac. Its wall consists of buffering capacity of the blood mucosa, muscularis and adventitia or serosa ○ Patients are at risk for comatose and death The wall of gallbladder does not contain a due to metabolic acidosis and dehydration muscularis mucosae or submucosa 11|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM XVII. STRUCTURE OF GALLBLADDER A. MUCOSA The wall consistS of simple columnar epithelium Has many mucosal folds projecting into the lumen Plicated into convoluted folds of varying height that delimit narrow bays and clefts Mucosal folds are tall and closely spaced in the contracted gallbladder Mucosal folds become short and widely spaced when distended Between the mucosal folds are found diverticula or crypts that often form deep indentations in the mucosa In cross section, the diverticula in lamina propria resemble tubular glands There are no glands in gallbladder except in the neck region of the organ Figure 15. Histology of the Gallbladder B. LAMINA PROPRIA D. MUSCULARIS EXTERNA Possesses many capillaries and blood vessels Loose organization of collagenous and elastic fibers Irregular loose network of longitudinal and oblique with lymphatic tissue and blood vessels bundles of smooth muscle cells Provides flexibility to accommodate changes in Spaces between the bundles occupied by collagenous, surface topography elastic fibers, and occasional fibroblast Near the neck are simple tubuloalveolar glands which Dense connective tissue layer rich in collagen, elastic, extends into the muscular layer macrophages, fibroblast, and adipose cells ○ Tubuloalveolar glands Cuboidal epithelium Unstained apical region E. SEROSA Rokitansky-Aschoff sinuses ○ Larger in pocketing of the mucosa Covers the entire unattached bladder surface (diverticulae of the mucosa of the Where the gallbladder is attached to the liver surface, gallbladder) the connective tissue layer is adventitia ○ Mistaken for gland ○ Extend to the lamina propria and muscular layer ○ Continuous with the surface epithelium F. LUSCHKA DUCTS ○ Represent pathological change in the gallbladder wall that permits evagination of Peculiar duct-like structures found on the hepatic the mucosa surface of gall bladder near its neck Aberrant bile ducts formed during embryonic life and persisting in the adult C. EPITHELIUM G. CYSTIC DUCTS Single layer of tall columnar cells with oval nuclei and a faintly eosinophilic cytoplasm Microvilli are shorter and less regular in orientation 3 to 4 cm from the neck of the gallbladder Common hepatic duct (common bile duct) Muscularis of the duodenum: Submucosa Unite to form ampulla of Vater (hepatopancreatic ampulla) 12|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  XVIII. BLOOD VESSELS, LYMPHATICS, AND NERVES H. SPHINCTER OF ODDI OF THE GALLBLADDER Blood supply: Cystic Artery Situated at the wall of the duodenum Venous blood collected by veins that empty into small Encircles the bile and pancreatic ducts veins in the liver Band of smooth muscles Rich supply of lymphatic vessels developed in two Consists of four parts plexuses ○ Sphincter of choledocus ○ Lamina propria Strong circular band of smooth ○ Outer connective tissue layer muscles Receives tributaries from the liver Contraction of this part stops the flow Cholecystitis is associated with hepatitis of bile Nerve supply: branches of the splanchnic and vagus ○ Sphincter pancreaticus nerves Around the pancreatic duct Sensory nerve ending ○ Fasciculus longitudinalis ○ Overdistention of the gallbladder or spasm of Longitudinal bundles of smooth the extrahepatic biliary tract muscles in the space between the ○ Reflex disturbances in the gut ducts Shorten the intramural portion of the ducts, probably facilitate the flow of XIX. HISTOPHYSIOLOGY OF GALLBLADDER bile into the duodenum Store and concentrate the bile that is continually ○ Sphincter ampulla secreted by the liver Meshwork of muscle fibers around ○ Bile is continually produced by liver the ampulla hepatocytes and transported via the A well-developed sphincter ampulla excretory ducts to the gallbladder for storage. may cause reflex of bile into the Here, sodium is actively transported through the pancreatic duct simple columnar epithelium of the gallbladder into the extracellular connective tissue, creating strong osmotic pressure. Water and chloride ions passively flow, producing concentrated bile Release bile in response to hormones signaling the presence of food in the duodenum Cholecystokinin ○ Secreted in response to entry of food in the duodenum ○ Induce rhythmic contraction of the gallbladder wall ○ Sphincter of Oddi relaxes allowing intermittent outflow of bile Concentrated Bile ○ Apical membranes have ion channels that permit free passage of Na+ ions ○ Basolateral membranes contain Na-K pumps that actively transport Na+ into the extracellular space Figure 16. Gallbladder in Chronic Cholecystitis ○ Increased concentration gradient that moves water in the epithelium Importance of the Sphincter of Oddi Functionally capacity assessed clinically by observing o If it is not functioning well, it may cause its ability to concentrate halogen salts of reflux of the bile into the pancreatic duct → phenolphthalein that are radiopaque Pancreatitis Failure to clearly visualize the gallbladder in X-rays will result to no concentrating ability III. REFERENCES ❖ Dr. Suzette S. Labrador’s Video/PowerPoint Presentation ❖ Junquiera’s Basic Histology ❖ SaVi Trans, AliVi Trans & ApSa Trans ❖ Google Photos 13|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM  IV. APPENDICES DUCT OF WIRSUNG DUCT OF SANTORINI Larger ducts Accessory, cranial Begins in the tail to the Duct of and runs through Wirsung the length of the About 6cm in length gland, increasing in diameter as it is joined by interlobular ducts In the head and runs parallel to the common bile duct (ductus choledochus) Table 1.Characteristics of the Two Pancreatic Ducts 14|14 HISTOLOGY: LESSON 20 | CPU-COM | VITA SERVITIUM