Pancreas, Gall Bladder, Liver Histology Flashcards
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Liver Function
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Exocrine:
•Synthesis and secretion of bile
Endocrine:
- Synthesis and secretion of plasma protein
- Glucose homeostasis
- Amino Acid Homostasis
- Lipid Metabolism
Other:
- Metabolism of drugs, toxins (alcohol)
- Removal of pathogens from enteric circulation
- Storage of fat soluble vitamins
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Liver Functions - Synthesis and secretion of bile
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- bile salts for emulsification of fats in small intestine
- conjugation and excretion of bilirubin
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Liver Functions - Synthesis and secretion of plasma proteins
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- albumin,
- clotting factors eg. prothrombin,
- carrier proteins eg. transferrin,
- etc.
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Liver Function - Glucose Homeostasis
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- Glycogen synthesis from glucose
- Glycogenolysis - breakdown of glycogen to glucose
- Gluconeogenesis - de novo synthesis of glucose
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Liver Function - Amino Acid Homeostasis
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- Synthesis of non-essential amino acids
- Breakdown of excess amino acids, production of urea
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Liver Function - Lipid Metabolism
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• Synthesis of cholesterol
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Pancreas
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•The pancreas is a mixed exocrine and endocrine gland: the exocrine portion secretes digestive enzymes that are delivered via the main pancreatic duct to the duodenum; the endocrine portion is comprised of the Islets of Langerhans
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Pancreatic Acinar Cells
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- pancreatic acinar cells are large pyramid shaped epithelial cells; the perinuclear cytoplasm is basophilic due to abundant rough ER, and secretory granules are often visible in the apical cytoplasm.
- The acinar cells secrete digestive enzymes and enzyme precursors (= zymogens) including trypsinogen, chymotrypsinogen, procarboxypeptidase, ribonuclease, deoxyribonuclease, triacylglycerol lipase, prophospholipase A2, elastase, and amylase.
- These enzymes are synthesized in inactive forms and are not normally activated until they reach the lumen of the small intestine where they encounter the brush border enzyme enteropeptidase. This enzyme converts trypsinogen to trypsin and trypsin activates the other enzyme precursors.
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Intercalated Duct Cells
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- intercalated duct cells secrete a bicarbonate-rich fluid for neutralizing stomach acid.
- They are low cuboidal epithelial cells with clear cytoplasm
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Secretion Control
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- Although both acinar and duct cells are innervated by parasympathetic and sympathetic fibers, their secretion is mainly controlled by enteroendocrine cells in the duodenum.
- Cholecystokinin stimulates the secretion of digestive enzymes by acinar cells and secretin stimulates the production of a bicarbonate-rich fluid by duct cells.
The excretory ducts of the pancreas are lined with simple cuboidal to columnar epithelial cells. The main pancreatic ducts contain goblet cells.
•In patients with cystic fibrosis, pancreatic acinar and ductal secretion is impaired, ducts become blocked and the pancreatic parenchyma becomes cystic and fibrotic, hence the name of the disease.
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Islets of Langerhans
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- The Islets of Langerhans are clusters of endocrine cells distributed among the exocrine tissue of the pancreas. They are supplied with a well-developed network of fenestrated capillaries. The cells are connected by gap junctions. While they are innervated by parasympathetic and sympathetic fibers, their secretion is regulated mainly by blood glucose levels acting directly on the cells. The Islet cells secrete hormones involved in carbohydrate metabolism.
- alpha cells
- beta cells
- delta cells
PP cells
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Alpha Cells
•secrete glucagon, which stimulates the breakdown of fat and glycogen, thereby increasing blood glucose levels (approx 20% of Islet cells).
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Beta Cells
•secrete insulin, which stimulates uptake of glucose and storage of energy from excess nutrients and thus decreases blood sugar level (approx 70% of Islet cells).
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Delta Cells
•secrete somatostatin, which may inhibit the release of other islet hormones (up to 10% of Islet cells).
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PP Cells
•secrete pancreatic polypeptide; various gastrointestinal effects (approx 2% of Islet cells).
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Liver
•The liver is the largest organ in the body not counting the skin. In humans, it is separated incompletely into lobes covered on their external surfaces by a thin connective tissue capsule, which is a reflection of peritoneum.
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Hepatocyte
* The liver is composed of several cell types that interact with each other, but are adapted to perform specific functions. The principal cell type in the liver is the hepatocyte (also called hepatic parenchymal cell), which accounts for 60 percent of the total cell population and 80 percent of the volume of the organ.
* Hepatocytes are organized into plates that are interconnected to form a continuous 3-dimensional lattice.
* Between the plates of hepatocytes are spaces occupied by hepatic sinusoids, the large-bore fenestrated capillaries of the liver that nourish each hepatocyte on several sides.
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Non-parenchymal Cells
* The sinusoidal space, and non-parenchymal cells associated with sinusoids, comprise the majority of the remaining liver volume. T,
* he non-parenchymal cells include sinusoidal endothelial cells, stellate cells (perisinusoidal; aka fat-storing cells of Ito), and Kupffer cells.
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Kupffer Cell Function
* Phagocytosis of blood-borne particulates such as bacteria from the circulation.
* Secretion of mediators (e.g. inflammatory mediators) that affect the function of adjacent cells.
* Production of beneficial and toxic substances that contribute to host defense as well as liver injury.
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Endothelial Cell Function
These form a leaky barrier between the parenchymal cells and the blood flowing in sinusoids. The endothelial cells are fenestrated and act as a sieve to prevent red blood cells and other cellular components from extravasating in the liver while allowing extensive access of hepatocytes to dissolved substances in the blood.
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Stellate Cell Function
* Storage of Vitamin A and other fat-soluble Vitamins.
* Secretion of the Type III collagen-rich extracellular matrix present in the space of Disse.
* Stellate cells when activated by chronic liver injury synthesize collagen, thus they are important in the development of the large amounts of scar tissue that characterize cirrhosis of the liver.
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Hepatic Portal Vein
•The hepatic portal vein caries 80% of the blood supply going to the liver. The blood it carries is nutrient rich, having come directly from the GI tract where nutrients are absorbed, but it is oxygen poor, since it has just supplied the GI tract, pancreas and spleen with oxygen.
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Hepatic Artery
•The hepatic artery carries about 20% of the blood to the liver, and it supplies the oxygen needs of the liver.
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Porta Hepatis
•Both the hepatic portal vein and the hepatic artery enter the liver at the hilum (also called the porta hepatis). The hepatic duct (carrying bile out of the liver) leaves the liver at this same location.
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Portal Tracts
* Once in the liver, the hepatic artery and hepatic portal vein undergo repeated branching to form ever-smaller vessels that supply all parts of the liver.
* These vessels travel together with bile ducts (see below), as well as autonomic nerves and lymphatics in areas called portal tracts. Note that hepatic artery and portal vein branches are carrying blood into the liver to distribute to sinusoids.
* Bile ducts and lymphatics are carrying bile and lymph respectively out of the liver.
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Hepatic Sinusoids
•The smallest branches of the hepatic artery and hepatic portal vein drain into hepatic sinusoids. These are very large bore fenestrated capillaries that supply the liver parenchyma. Hepatic sinusoids radiate out from portal tracts, and travel alongside hepatocytes.
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Central Veins
* Hepatic sinusoids drain into central veins (aka hepatic venules), which are distributed throughout the liver.
* Central veins are located at the center of polygonal arrays of hepatocytes and sinusoids, and portal tracts carrying hepatic artery and hepatic portal vein branches as well as bile ducts are at the periphery of these polygonal units, which are called liver lobules.
* Because the hepatic veins are so short, surgeons performing liver transplants remove the liver with a short segment of the inferior vena cava, and re-anastomose that vessel, rather than trying to work with the hepatic veins.
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Lymphatic Vessels
•Lymphatic vessels originate as blind-beginning capillaries in the connective tissue of portal tracts. The fluid contained in these lymphatics flows toward the hepatic hilum and eventually into the cisterna chyli, which is a dilated portion of the thoracic duct at its origin in the abdomen.
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Bile Canaliculi
* Bile canaliculi are formed by the apical membranes of adjacent hepatocytes (see below). They are interconnected and form a network of minute intercellular channels, which receive the bile secreted from hepatocytes. The bile canaliculi drain through short bile ductules (cholangioles) partially lined by cuboidal epithelial cells to bile ducts which run in portal tracts.
* Bile ducts drain through left and right hepatic ducts that exit the liver at the hilus. Also contained in the portal tracts are adrenergic, peptidergic, and cholinergic nerves which affect both intra-hepatic blood flow as well as hepatic metabolism.
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Classic Liver Lobule
•The classic liver lobule is a roughly hexagonal unit with a central vein at its center and portal tracts around the periphery.
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Portal Lobule
•The portal lobule is also roughly hexagonal and is understood as having a portal tract at its center and central veins at the periphery. The portal lobule emphasizes the exocrine function of the liver, having bile ducts at the center of the lobule.
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Hepatic Acinus
•The hepatic acinus (dotted line in the diagram above) is a roughly diamond-shaped area based on the vasculature. It has as its center the imaginary line connecting two portal tracts (blood is distributed from portal tract vessels to smaller arterioles along this line, and thence to liver sinusoids). The central veins on either side of this line make the points of the diamond. Within the acinus, hepatocytes nearest the centerline contact blood with the highest oxygen (and blood borne toxicant) content, and those nearest the apices contact deoxygenated blood.
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Space of Disse
•connective tissue space between hepatocytes and endothelial cells
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Basal Surface of Hepatocytes
* The fundamental relationships of apical, basal and lateral plasma membranes are the same in hepatocytes as in other epithelial cells, but instead of one basal surface each hepatocyte has several, each of which faces a sinusoid. The hepatocytes do not produce a basal lamina, and the basal surfaces have microvilli to increase surface area for exchange with blood plasma.
* The basal plasma membranes have microvilli that extend into the Space of Disse (connective tissue space between hepatocytes and endothelial cells) to increase surface area for exchange of materials between hepatocytes and blood plasma.
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Apical Surface of Hepatocytes
•The apical surface is present as a very narrow band that runs around the hepatocyte where it faces adjacent hepatocytes, and forms a tiny channel called a bile canaliculus. Bile canaliculi form a network of channels that carry bile secretion (exocrine secretion) of hepatocytes. The apical surfaces also form microvilli to increase surface area for secretion.
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Lateral Surface of Hepatocytes
* The lateral surfaces flank the bile canaliculus on either side and form junctions with adjacent hepatocytes, including tight junctions that seal the bile canaliculus (connected to the outside world) from the basal compartment, which faces the sinusoids.
* These tight junctions are critical in that they prevent leakage of plasma into bile as well as backflow of bile from canaliculi into the blood. Lateral membranes also form gap junctions, which facilitate communication between hepatocytes.
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Hepatocyte Anatomy
* hepatocytes are polyhedral cells and are organized into anastomotic sheets.
* They have one or sometimes two nuclei and their cytoplasm contains numerous mitochondria as well as a prominent Golgi apparatus, rough endoplasmic reticulum, and smooth endoplasmic reticulum with associated rosettes of glycogen particles.
* They contain numerous endosomes, lysosomes, and peroxisomes.
* Fat droplets also may be present within hepatocytes, and these may increase greatly in number with acute liver injury (the basis of fatty liver)
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Hepatocyte Heterogeneity
* Within hepatic lobules, hepatocytes exhibit heterogeneity along the portal venous-central venous axis. For example, periportal hepatocytes are exposed to higher levels of oxygen and extrahepatic hormones than centrilobular (pericentral) hepatocytes.
* In addition, expression levels of critical hepatocyte enzymes differ in periportal vs centrilobular hepatocytes. This results in an intralobular metabolic zonation with different cellular functions represented in different zones within each lobule.
* Mixed function oxidation and glucuronidation are mainly centrilobular functions while sulfation is principally a periportal function.
* This zonation of enzymatic functions also is reflected ultrastructurally in differences in mitochondria and smooth endoplasmic reticulum between different zones.
* As a result of this zonation as well as the portal-central oxygen gradient, many toxic and pathologic events in the liver also preferentially affect periportal or centrilobular zones. An example of a toxin eliciting periportal injury is allyl alcohol, while carbon tetrachloride and acetaminophen elicit centrilobular injury.
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Anatomy of Endothelial Cells
•The endothelial cells are highly fenestrated and lack a supporting basal lamina. The fenestrae are organized in clusters known as sieve plates. As a result, there is continuity between the plasma in the sinusoid lumen and the perisinusoidal space (of Disse). The sinusoidal endothelial cells contain numerous endosomes and scavenge a number of substances including breakdown products of connective tissue.
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Anatomy of Stellate Cells
* Stellate cells lie external to the endothelium in the Space of Disse. They are pericytes, which frequently contain lipid droplets that are a storage site for fat-soluble vitamins, especially Vitamin A.
* Multiple cytoplasmic projections of these cells surround and embrace the abluminal (away from the lumen) surfaces of the endothelial cells. During chronic liver injury, stellate cells become activated and deposit Type I collagen in the space of Disse.
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Anatomy of Kupffer Cells
•Kupffer cells are attached to the luminal surfaces of the endothelium. These are highly phagocytic, specialized fixed macrophages of the liver and contain numerous lysosomes and phagosomes. Kupffer cells are involved in a number of host defense mechanisms and immune functions.
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Gall Bladder
* The gall bladder is a pear-shaped hollow organ that collects bile secreted by the liver, stores and concentrates it, and then discharges the bile into the duodenum as required for digestive processes.
* The gall bladder lumen is lined by a simple columnar epithelium. In the undistended, collapsed organ the mucosa, consisting of the epithelium and underlying lamina propria, is thrown into folds.
* External to the lamina propria is a muscularis composed of smooth muscle whose fibers are oriented obliquely and longitudinally.
* The outer layer of the gall bladder is a serosa. It is a relatively thick layer containing many blood vessels, which carry fluid recovered from bile by the absorptive gall bladder epithelium.
