LIVER LIVER GALL BLADDER GALL BLADDER

PANCREASPANCREAS

Department of Histology, Cytology and EmbryologyDepartment of Histology, Cytology and EmbryologyTatiana GlobaTatiana Globa

State University of Medicine and Pharmacy “Nicolae Testemitanu”

The LiverThe Liver Largest gland of the bodyLargest gland of the body

Two principal Two principal lobeslobes: : rightright and and leftleftRight lobe further subdivided: Right lobe further subdivided:

Quadrate lobeQuadrate lobe and and caudate lobecaudate lobe

Is surrounded by a capsule of connective tissue Is surrounded by a capsule of connective tissue (Glisson’s capsule). (Glisson’s capsule).

Functions of the LiverDigestive and Metabolic FunctionsDigestive and Metabolic Functions

synthesis and secretion of bile synthesis and secretion of bile storage of glycogen and lipid reserves storage of glycogen and lipid reserves maintaining normal blood glucose, amino maintaining normal blood glucose, amino

acid and fatty acid concentrations acid and fatty acid concentrations synthesis and release of cholesterol bound synthesis and release of cholesterol bound

to transport proteins to transport proteins inactivation of toxins inactivation of toxins storage of iron reserves storage of iron reserves storage of fat-soluble vitaminsstorage of fat-soluble vitamins

Functions of the LiverNon-Digestive FunctionsNon-Digestive Functions

synthesis of plasma proteins synthesis of plasma proteins synthesis of clotting factors synthesis of clotting factors synthesis of the inactive angiotensinogen synthesis of the inactive angiotensinogen phagocytosis of damaged red blood cells phagocytosis of damaged red blood cells storage of blood storage of blood breakdown of circulating hormones (insulin breakdown of circulating hormones (insulin

and epinephrine) and immunoglobulins and epinephrine) and immunoglobulins inactivation of lipid-soluble drugsinactivation of lipid-soluble drugs

The morpho-functional unit of The morpho-functional unit of the liverthe liver

““classical liver lobule”classical liver lobule”portal lobuleportal lobule liver acinusliver acinus

LIVER LOBULELIVER LOBULE

Hexagonal-shaped liver Hexagonal-shaped liver lobule (classical lobule) is lobule (classical lobule) is the traditional description the traditional description of the liver parenchyma of the liver parenchyma organizationorganization

Composed of hepatocyte Composed of hepatocyte (liver cell) plates(cords) (liver cell) plates(cords) radiating outward from a radiating outward from a central veincentral vein

Between the plates of Between the plates of hepatocytes there are hepatocytes there are sinusoidssinusoids

HasHas a central vein a central vein Portal triads are found at Portal triads are found at

each of the six corners of each of the six corners of each liver lobuleeach liver lobule

Sublobular vein

Central vein

Distributing vein

Plates of hepatocytes

PORTAL TRIADSPORTAL TRIADS

Portal triadsPortal triads (also called (also called portalportal areasareas or or portal portal canalscanals) are located at the corners of liver ) are located at the corners of liver lobuleslobules. . Each Each portal areaportal area contains contains threethree (hence the term (hence the term portal portal triadtriad) more-or-less conspicuous tubular ) more-or-less conspicuous tubular structures all wrapped together in structures all wrapped together in connective connective tissuetissue..

a branch of the a branch of the bile ductbile duct a branch of the a branch of the portalportal veinvein - - interlobular veininterlobular vein a branch of the a branch of the hepatichepatic arteryartery - - interlobular interlobular

arteryartery

HepatocytesHepatocytes are cuboidalare cuboidal cells with one or cells with one or

two large euchromatic nuclei two large euchromatic nuclei and with abundant, grainy and with abundant, grainy cytoplasm that stains well cytoplasm that stains well with both acid and basic dyes with both acid and basic dyes (reflecting the abundance of (reflecting the abundance of various cellular constituents). various cellular constituents).   

they may accumulate they may accumulate abundant abundant lipofuscinlipofuscin (yellow- (yellow-brown "wear-and-tear" brown "wear-and-tear" pigment), especially with pigment), especially with advancing age. advancing age.

aa typical hepatocyte has typical hepatocyte has twotwo surfacessurfaces with microvilli with microvilli

Hepatocyte ultrastructure

• all cytoplasmic organelles are very well developed

• cell membrane facing a bile canaliculus and the perisinusoidal space forms microvilli

HepatocytesHepatocytes are located in flat irregular plates are located in flat irregular plates (cords) (cords) that are that are arranged radially like the spokes of a wheel around a branch of the arranged radially like the spokes of a wheel around a branch of the hepatic vein, called the hepatic vein, called the central veincentral vein or or central venulecentral venule since it really since it really has the structure of a venule. has the structure of a venule. Each hepatic plate contains 2 rows of hepatocytes. Between 2 rows of hepatocytes of the plate there is bile Between 2 rows of hepatocytes of the plate there is bile canaliculus. Between the plates of hepatocytes there are sinusoids canaliculus. Between the plates of hepatocytes there are sinusoids capillaries. capillaries.

Bile canaliculus

Hepatocytes form 2 rows

Sinusoid

Hepatocytes

Space of Disse

Microvilli

Sinusoids Sinusoids capillariescapillaries are larger than conventional capillaries and less regular in are larger than conventional capillaries and less regular in

shape. They are lined by thinshape. They are lined by thin endothelial cellsendothelial cells and and lacks a lacks a basement membranebasement membrane ( (is absent over large areas except the is absent over large areas except the periphery and center of the hepatic lobule)periphery and center of the hepatic lobule)

Also residing on the sinusoidal walls are Also residing on the sinusoidal walls are macrophages called macrophages called Kupffer cellsKupffer cells. These are phagocytic cells that remove . These are phagocytic cells that remove particulate material and old red blood cells from circulation. particulate material and old red blood cells from circulation. Kupffer cells are members of the mononuclear phagocyte Kupffer cells are members of the mononuclear phagocyte systemsystem..

Pit cellsPit cells are attached to the Kupffer’s cells. These cells are attached to the Kupffer’s cells. These cells contain granules and they are like large lymphocytes, killer contain granules and they are like large lymphocytes, killer cells. They make an anticancer effect.cells. They make an anticancer effect.

The space between the The space between the fenestratedfenestrated endotheliumendothelium and the and the cordscords is named the is named the space of Dissespace of Disse. .

Kupffer cell

sinusoid

sinusoid

Perisinusoidal space (space of Perisinusoidal space (space of Disse)Disse)

It contains It contains microvilli of hepatocytes, microvilli of hepatocytes, blood plasma, blood plasma, processes of the Kupffer’s cellsprocesses of the Kupffer’s cells lipocytes (adipose cells, commonly called an Ito cellslipocytes (adipose cells, commonly called an Ito cells). ).

They are located between some hepatocytes. These cells They are located between some hepatocytes. These cells have been shown to be the primary storage site for have been shown to be the primary storage site for vitamin A. They also can produce connective tissue fiber vitamin A. They also can produce connective tissue fiber in the large amount at the cirrhosis. in the large amount at the cirrhosis.

In the fetal liver, the space between blood vessels and In the fetal liver, the space between blood vessels and hepatocytes contains islands of blood-forming cells.hepatocytes contains islands of blood-forming cells.

Ito cell

sinusoid

Lipid inclusions

The blood circulation through the The blood circulation through the liverliver

System of inflowSystem of inflow: the liver receives blood from the : the liver receives blood from the hepatic arteryhepatic artery (supplies oxygen-rich blood to the liver) and (supplies oxygen-rich blood to the liver) and portal vein (portal vein (carries carries venous blood with nutrients from digestive viscera). They branch venous blood with nutrients from digestive viscera). They branch into into lobar, segmental, interlobular, distributing brancheslobar, segmental, interlobular, distributing branches. .

System of circulationSystem of circulation: the distributing branches of vessels : the distributing branches of vessels contribute blood to the contribute blood to the sinusoids sinusoids which provide the exchange of which provide the exchange of substances between the blood and liver cells. Sinusoids contain the substances between the blood and liver cells. Sinusoids contain the mixed blood. mixed blood.

System of outflowSystem of outflow: sinusoids drain blood from the periphery of : sinusoids drain blood from the periphery of the classical hepatic lobule toward its center, into the the classical hepatic lobule toward its center, into the central veincentral vein. . Outside hepatic lobules central veins drain into the Outside hepatic lobules central veins drain into the sublobularsublobular (intercalated) (intercalated) veinsveins, which join 3-4 together and drain into the , which join 3-4 together and drain into the hepatic veinhepatic vein. It drains into the . It drains into the inferior vena cavainferior vena cava. .

GALL BLADDERGALL BLADDER functionsfunctions

storage of bile storage of bile concentration of bile concentration of bile acidification of bile acidification of bile send bile to the duodenum in response to send bile to the duodenum in response to

cholecystokinin cholecystokinin secreted by from enteroendocrine cells in secreted by from enteroendocrine cells in small intestinesmall intestine

Tunics (layers) of the Gall BladderTunics (layers) of the Gall Bladder TUNICA MUCOSATUNICA MUCOSA:: When the gall bladder is empty, this layer is When the gall bladder is empty, this layer is

extremely folded.  When full, this layer is smoother but still has some extremely folded.  When full, this layer is smoother but still has some short folds.  short folds.  lamina epithelialislamina epithelialis: : composed of simple columnar epithelial cells composed of simple columnar epithelial cells

with numerous microvilli on their luminal surfaces and connected with numerous microvilli on their luminal surfaces and connected by tight junctions near luminal surfaces.   by tight junctions near luminal surfaces.   

lamina proprialamina propria: composed of loose connective tissue rich in : composed of loose connective tissue rich in reticular and elastic fibers to support the large shape changes that reticular and elastic fibers to support the large shape changes that occur in the lamina epithelialisl;  lamina propria may contain occur in the lamina epithelialisl;  lamina propria may contain compoundcompound tubuloalveolar glands. May be mucous or serous. tubuloalveolar glands. May be mucous or serous.

lamina muscularislamina muscularis mucosae: mucosae: not presentnot present

TUNICA SUBMUCOSATUNICA SUBMUCOSA:: present and typical present and typical TUNICA MUSCULARISTUNICA MUSCULARIS:: contains much smooth muscle, poorly contains much smooth muscle, poorly

organizedorganized TUNICA SEROSATUNICA SEROSA:: present and typical present and typical

PancreasPancreas

Exocrine gland (97%)– Exocrine gland (97%)– PROENZYMESPROENZYMES for digestion for digestion of carbohydrates, proteins & fats of carbohydrates, proteins & fats (amylase, trypsin, (amylase, trypsin, lipases)lipases)

Endocrine gland (3%)– Endocrine gland (3%)– INSULININSULIN and and GLUCAGON GLUCAGON (carbohydrate metabolism)(carbohydrate metabolism)

The exocrine pancreas The exocrine pancreas

The exocrine portion of the pancreas is a The exocrine portion of the pancreas is a compound acinar glandcompound acinar gland

It has many small lobules, each of which is It has many small lobules, each of which is surrounded by connective tissue septa surrounded by connective tissue septa through which run blood vessels, nerves, through which run blood vessels, nerves, lymphatics, and interlobular ducts.lymphatics, and interlobular ducts.

Exocrine secretion by the pancreas is Exocrine secretion by the pancreas is controlled by hormones and nerves.  controlled by hormones and nerves. 

The exocrine pancreasThe exocrine pancreas AciniAcini:  The secretory cells of the pancreas are arranged around

a small lumen. 

The pancreatic acinar cells are highly active in protein synthesis for export and this high activity is reflected in their bizonal stainingbizonal staining properties.  The basal region of these secretory cells usually stains intensely with hematoxylin reflecting the presence of large amounts of endoplasmic reticulum where the protein is being synthesized on ribosomes – homogen zone. The presence of numerous zymogen granules containing high concentrations of protein is reflected in the intense eosin staining in the apical region of the secretory cells – zymogen zone.  These granules are most abundant during fasting or between meals and least abundant after a meal has been ingested.   

Zymogen granules

Centroacinar cell

These cells form the first part of the intercalated duct

The exocrine pancreasThe exocrine pancreas DuctsDucts: The secretory product of the acinar cells is carried out : The secretory product of the acinar cells is carried out

of the pancreas by a duct system as in other exocrine glands.   of the pancreas by a duct system as in other exocrine glands.   

The first part of the duct system is called the  The first part of the duct system is called the  intercalated duct or intralobular duct..  It is lined with cuboidal epithelial   It is lined with cuboidal epithelial cells that secrete bicarbonate ion into the secretory product.  cells that secrete bicarbonate ion into the secretory product.  This duct actually extends into the acinar lumen, where its This duct actually extends into the acinar lumen, where its walls consist of the pale staining walls consist of the pale staining centroacinar cells..

IIntercalated ductsntercalated ducts have very little connective tissue around have very little connective tissue around them but they lead into larger them but they lead into larger interlobular ducts which lie which lie within more prominent connective tissue septa. Interlobular within more prominent connective tissue septa. Interlobular ducts are lined with a low  columnar epithelium that may ducts are lined with a low  columnar epithelium that may contain goblet cells.  Interlobular ducts empty into the main contain goblet cells.  Interlobular ducts empty into the main pancreatic ducts that exit the pancreas.pancreatic ducts that exit the pancreas.

Pancreatic juicePancreatic juice

trypsin, chymotrypsin and carboxypeptidase trypsin, chymotrypsin and carboxypeptidase hydrolyse proteins into smaller peptides or hydrolyse proteins into smaller peptides or amino acids; amino acids;

ribonuclease and deoxyribonuclease digest the ribonuclease and deoxyribonuclease digest the corresponding nucleic acids; corresponding nucleic acids;

pancreatic amylase digests carbohydrates; pancreatic amylase digests carbohydrates; pancreatic lipase digests lipids; pancreatic lipase digests lipids; cholesterol esterase breaks down cholesterol cholesterol esterase breaks down cholesterol

esters into cholesterol and a fatty acid. esters into cholesterol and a fatty acid.

The endocrine pancreas. The endocrine pancreas.

The The cells of the endocrine portion of the pancreas are arranged either in round-to-oval shaped areas rich in blood vessels known as the islets of Langerhans or they may be scattered throughout the exocrine portions of the pancreas near the acini or ducts. 

Island of Langerhans

• ββ-cells-cells (75%) which secrete insulin (stimulates the synthesis of glycogen, protein and fatty acids; facilitates the uptake of glucose into cells; activates glucokinase in liver cells). They are located in the central part of the island.• αα-cells-cells (20%) which secrete glucagon (effects opposite to those of insulin). They are generally located peripherally in the islets. • δδ-cells-cells (5%) which secrete somatostatin, a locally acting hormone which inhibits α -, β-cells. •a few other endocrine cells, which secrete

• pancreatic polypeptide, which stimulates chief cell in gastric glands, inhibits bile and bicarbonate secretion – PP-cellsPP-cells, • vasoactive intestinal peptide (VIP), which has effects similar to glucagon, but also stimulates the exocrine function of the pancreas and decrease the arterial blood pressure – δδ1-cells1-cells, • secretin, which stimulates the exocrine pancreas, and motilin, which increases GIT motility – EC-cellsEC-cells (enterochomaffin cells).

Islet of Langerhans