histology of liver

7/31/2019 Histology of Liver

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HISTOLOGY OF THE LIVER, GALLBLADDER, AND PANCREASPhysiology/CTSApril 21, 2004

For questions on this topic, contact Susanna R. Keller at [email protected]

Liver and pancreas are the two major glands that are associated with the digestive tract. Theyboth have exocrine and endocrine functions and play important roles in the digestion of foodand in the metabolism of the absorbed nutrients.

Overview of Anatomy

I. The liveris located in the upper right quadrant of the abdominal cavity just beneath thediaphragm. It consists of four lobes. The left and right lobes are the major ones. They areseparated by the falciform ligament. The liver weighs 1500 g and is the largest internalorgan and largest exocrine gland in the human body.

II. The pancreas is located behind the stomach with its head situated in the duodenal loopand its body and tail extending to the hilus of the spleen in the upper left abdominalcavity. It weighs 150 g and is the most important exocrine digestive tissue.

III. The gallbladderis a pear-shaped sac that protrudes from the posterior inferior side of theliver. The serosa covering the gallbladder is continuous with the serosa of the liver and thusattaches the gallbladder to the liver. It serves to store and concentrate the bile producedby the liver.

IV. The bile ducts and pancreatic ducts connect the liver, gallbladder and pancreas with thesmall intestine and carry the exocrine products of the liver and pancreas to their site ofaction in the duodenum. The common hepatic duct drains the bile from the left and righthepatic ducts and joins with the cystic duct from the gallbladder to form the common bileduct. The common bile duct merges with the main pancreatic duct in thehepatopancreatic ampulla that enters the duodenum at the major duodenal papilla.

Liver

I. FunctionsA. Production of bile that acts as a detergent to facilitate the digestion of fatsB. Processing and storage of nutrientsC. Synthesis of blood proteins and coagulation factorsD. Detoxification and inactivation of drugs and toxic substancesE. Participation in iron metabolismF. Production of hormonesG. Phagocytosis of debris and bacteriaH. Storage of Vitamin A

II. Blood Circulation

A. The liver is unusual in that it receives blood from two sources.

1. The major portion (approximately 75%) is supplied by the portal vein thatdrains the blood from the intestinal system (including the pancreas and thespleen) and is rich in nutrients that have been absorbed in the intestine, but ispoor in oxygen.

2. Oxygenated blood is supplied by the hepatic artery.


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3. The blood from the liver drains into the hepatic vein (located at the posteriorside of the liver) that connects to the inferior vena cava.

4. The porta hepatis (located on the backside of the liver) is the entry port forthe blood vessels. It also is the exit port for the common hepatic duct.

III. Organization of the liver lobules (Figure 1)

A. The classic hepatic lobules are hexagon-shaped, about 2 mm in length and 700

m in diameter. In humans they are not well demarcated due to the lack ofconnective tissue septa between adjacent lobules.

B. Branches of the portal vein, the hepatic artery and the bile ducts run embeddedin connective tissue along the longitudinal axis in between adjacent lobules in theportal spaces. There are three to six portal spaces per lobule each containing onebranch of the portal vein, the hepatic artery and a bile duct forming the portaltriad. The branch of the portal vein is characterized by the largest lumen, whereasthe branch of the bile duct can be distinguished by its cuboidal epithelium. Inaddition, lymph vessels are found in the portal spaces.

C. The vessels send distributing branches along the periphery of each lobule. Inletvenules and arterioles branch from these and spill their blood into sinusoids.

The sinusoids drain into the central vein. From the bile canaliculi located inbetween the plates of hepatocytes bile drains into the branches of the bile ducts.

D. The individual lobules function in parallel with one another, not in series. Thus, ifthe vascular supply or drainage for one lobular unit is damaged the adjacent unitswill continue to function.

Figure 1: Schematic drawing of the structure of the liver.From Junqueira et al. Basic Histology 8 th edition.


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E. Liver lobules can be defined as functional units in three different ways (Figure 2).

1. Classic hepatic lobule (as discussed in detail above) hexagonal in shape,borders defined by lines connecting the surrounding portal spaces, center isthe central vein, functionally defined as the territory of drainage by thecentral vein found at its center.

2. Hepatic acinus: diamond-shaped, borders defined by lines that connect thecentral veins of two neighboring classical lobules with two adjacent periportalspaces, functionally defined as the region that is irrigated by the terminal

distributing branch of the portal vein that runs around the periphery ofthe lobule. Based on their proximity to the distributing veins, the cells in thehepatic acinus are subdivided into three zones I-III with the incoming bloodpassing through zone I first and continuing into zone II and III. The gradient forsubstances coming in with the blood (nutrients, oxygen, toxic substances)thus define functional differences among the hepatocytes in the differentzones (Figure 3).

3. Portal lobule: triangular, borders defined by lines connecting the three centralveins that are adjacent to one portal space in the center, functionally definedas the area from which bile flows to one branch of the bile duct.

Figure 2: Schematic drawing illustrating the territories of the classic liver lobule(hexagon), hepatic acinus (diamond), and portal lobule (triangle).From Junqueiraet al. Basic Histology 8th edition.


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Figure 3: Drawing illustrating the heterogeneity of hepatocytes from theperilobular to the centrilobular region (Zones I-III).

From Junqueira et al. Basic Histology 8th

edition.

F. The main cell type constituting 60% of all liver cells is the hepatocyte. It is themost versatile cell type in the human body and carries out all the main liverfunctions:

1. Absorption, Processing and Storage of nutrients transported from theintestine. During a single passage through the lobule 60-100% of mostmetabolites are removed.

2. Secretion. The liver produces most of the proteins found in the blood plasmaincluding albumin, lipoproteins, transferrin, clotting proteins, growth factors(100 g/day).

3. Production of Bile. Hepatocytes continuously synthesize bile acids fromcholic acid, a metabolite of cholesterol.

G. To fulfill their functions the hepatocytes are in close connection with sinusoids andthe bile canaliculi (Figure 4).

H. The sinusoids form an elaborate three-dimensional plexus. They are lined by adiscontinuous layer of fenestrated endothelial cells, that do not have a basallamina (support is provided by a network of loose reticular fibers). Thisarrangement allows the blood plasma to leak through the endothelial cell layer andcome into close contact with the microvilli of the underlying hepatocytes in theSpace of Disse. It thus provides optimal conditions for an extensive metabolic

exchange between the blood plasma and hepatic cells.


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Figure 4: Diagram of the ultrastructure of a hepatocyteFrom Junqueira et al. Basic Histology 8 th edition

I. The bile is secreted into the bile canaliculi that are formed by neighboringhepatocytes between tight junctions. The canaliculi form a belt-like networkaround individual hepatocytes. The bile flows through the canaliculi to theperiphery of the lobule (in opposite direction to blood flow). The canaliculi emptyinto bile ductules that end in the bile ducts at the portal triads. The bile ductscoalesce to form the left and right hepatic ducts that drain into the commonhepatic duct. The bile salts are required for the emulsification and the digestionof fat by the lipases in the small intestine. Through the bile, the liver eliminatescholesterol and blood borne waste products. The metabolic cost of bile productionis high and extra hepatic circulation of bile has evolved to recover 95% of theexported bile.

J. Hepatocytes have both structural and functional characteristics that support theirabsorptive and secretory activities:

1. They are polyhedral cells displaying multiple surfaces per cell. An increase incell surface is provided by the microvilli that protrude into the Space of Disseand line the bile canaliculi.

2. They are metabolically very active and functionally versatile.


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3. They have extensive endoplasmic reticulum that functions in:a. synthesis and export of plasma proteins;b. synthesis and export of cholesterol and phospholipid (as lipoproteins);c. drug detoxification.

4. They possess a large number ofmitochondria for processing absorbedmetabolites:a. oxidative degradation of excess fatty acids;b. deamination of excess amino acids and urea synthesis.

5. They store excess carbohydrate as glycogen that accumulates in granulesassociated with the smooth ER. When needed, glucose can be rapidlymobilized by glycogenolysis to maintain normal blood glucose levels.

K. Two additional cell types are found in association with the sinusoids.

1. The Kupffer cells are macrophages (derived from monocytes) that arepermanent residents within the lumen of the sinusoids. They function in thefiltration of the portal blood through phagocytosis of old red blood cells andbacteria. They also secrete growth factors.

2. The Ito cells (fat-storing cells) are located in the Space of Disse. They store

Vitamin A and synthesize hepatic growth factor. They also are involved in theproduction of the extracellular matrix (collagen).

IV. Supportive Tissue

A. The liver is covered by a thin layer of connective tissue (Glisson's capsule).

B. In the porta hepatis the fibrous tissue thickens and follows as supportive tissuethe blood and lymph vessels and the bile ducts to their termination or origin in theportal spaces between the liver lobules.

C. In the liver lobules the connective tissue continues as a delicate reticular fibrous

network supporting the major cell structures of the lobules, the hepatocytes andthe sinusoidal endothelial cells.

V. Clinical Correlation

A. Liver fibrosis is defined as an excessive accumulation of connective tissue in theliver following repeated or chronic insult (alcohol, viruses, iron or copper overload,cholestasis, hepatic blood congestion) that triggers a "wound-healing" likereaction. Liver fibrosis can progress into liversclerosis and eventually livercirrhosis.

B. Liver cirrhosis is marked by an extensive loss of liver cells and disorganization of

the liver lobules. Fibrous tissue surrounds nodules of regenerated remaining livercells.


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Gallbladder

I. FunctionsA. Storage and concentration ofbile: The bile exits the liver through the common hepatic

duct. During periods of fasting, tonic contraction of the sphincter of Oddi keeps themajor duodenal papilla closed. The bile is shunted through the cystic duct into thegallbladder where it is stored until needed for digestion. The gallbladder has a storagecapacity of 40 to 70 ml. The bile is concentrated while stored in the gallbladder by theremoval of H2O and NaCI (600-1000 ml daily).

B. Expulsion ofbile: When a meal is ingested, the sphincter of Oddi relaxes and thesmooth muscle cells in the wall of the gallbladder contract to expel the bile through thecystic and common hepatic duct into the duodenum.

II. Structure of gallbladder wall

A. The wall of the gallbladder consists of a mucosa that is composed of a simplecolumnar epithelium of absorptive cells and a lamina propria, a thin irregular layer ofsmooth muscle cells (responsible for the contraction and expulsion of the stored bile in

response to cholecystokinin), a well developed perimuscular connective tissue layer,and the serosa.

B. The mucosa is extensively folded when the gallbladder is contracted and modestlyfolded when it is relaxed. However, it does not contain villi or tubular glands (crypts).

C. The underlying connective tissue is richly vascularized.

III. Clinical CorrelationCholelithiasis: Formation of gallstones within the gallbladder as a consequence of anabnormal bile composition (in 80% due to an excess of cholesterol).

Pancreas

I. Functions

A. Most (> 80%) of the cells in the pancreas are involved in the exocrine activity of theorgan:

1. The production and export of inactive precursors, known collectively as thezymogens, for twenty major digestive enzymes including proteases, lipases,nucleases, and amylase. The pancreas produces more protein per gram of tissuethan any other organ.

2. The secretion of a bicarbonate-rich alkaline fluid (1200 ml/day in humans) which

functions to neutralize the acidic chyme produced in the stomach. The alkalinizationis necessary for digestive enzyme activity.

B. The remainder of the cells are responsible for the production of hormones(predominantly insulin and glucagon) that are released into the blood stream(endocrine function). They are organized in the islets of Langerhans (for details seeHistology of the Endocrine Glands).


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II. Organization of the exocrine pancreas (Figure 5)

A. The pancreas is a compound acinar gland that is composed ofacini and ducts.

B. The pancreatic acini are the secretory units of the exocrine tissue. They are composedofacinar cells that form a spherical mass around a lumen (acinus).

C. Acinar cells are highly specialized for the synthesis and secretion of zymogens, anddisplay a distinct polarity. They are pyramidal in shape, with the apex facing into thelumen of the acinus. The apical region contains many zymogen-containing granulesthat are poised for secretion. The nucleus is located towards the base.

D. Within the acinus lie the centroacinar cells. They are joined to the acinar cells by tightjunctions.

E. The centroacinar cells form the beginning of the intercalated ducts. The intercalatedducts join with intralobularducts that in turn connect to interlobular(extralobular)ducts.

F. The centroacinar cells and the cells lining the intercalated, intralobular and interlobularducts are responsible for the production of the bicarbonate-rich fluid.

G. The interlobular ducts drain into the main pancreatic duct. The main pancreatic ductruns through the tissue from tail to head to collect the secretory product of the pancreasfrom all its branches. It merges with the common bile duct to form the hepatopancreaticampulla that connects with the duodenum.

III. Supportive Tissue

A. The pancreas is surrounded by a connective tissue capsule that sends septa into thegland and divides the tissue into lobules.

B. The connective tissue between the lobules contains the larger blood vessels thatconnect to capillary networks located in the basal lamina surrounding the pancreaticacini.

C. The basal lamina is supported by a delicate sheath of reticular fibers.


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Figure 5: Schematic drawing of pancreas structureFrom Gartner and Hiatt, Color Textbook of Histology, 2nd edition

IV. Clinical correlation

Cystic fibrosis (CF) is the most common autosomal recessive disorder in the white

population (1:2500 livebirths). It is caused by a defective chloride channel in epithelial cells(CFTR = cystic fibrosis transmembrane conductance regulator).

90% of patients with CF develop pancreatic insufficiency due to a reduction of the volume ofpancreatic fluid with a low concentration of HCO3

-. This leads to an increased viscosity ofthe secretions and the retention of the zymogens in the pancreatic ducts followed by thepremature activation of the enzymes and digestion of the tissue.

Structurally, CF is marked by the destruction of primarily the exocrine portion of thepancreas and its replacement by fibrous tissue. Remaining ducts and acini are dilated andform cyst-like structures filled with secretions.

histology of liver

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