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State University of Medicine and Pharmacy “Nicolae Testemitanu”




            LIVER
        GALL BLADDER
          PANCREAS

              Department of Histology, Cytology and Embryology
                                                  Tatiana Globa
The Liver
 Largest gland of the body



 Two principal lobes: right and left
   Right lobe further subdivided:
     Quadrate lobe and caudate lobe



 Is surrounded by a capsule of connective tissue
  (Glisson’s capsule).
Functions of the Liver
   Digestive and Metabolic Functions

 synthesis  and secretion of bile
 storage of glycogen and lipid reserves
 maintaining normal blood glucose, amino
  acid and fatty acid concentrations
 synthesis and release of cholesterol bound
  to transport proteins
 inactivation of toxins
 storage of iron reserves
 storage of fat-soluble vitamins
Functions of the Liver
          Non-Digestive Functions

 synthesis  of plasma proteins
 synthesis of clotting factors
 synthesis of the inactive angiotensinogen
 phagocytosis of damaged red blood cells
 storage of blood
 breakdown of circulating hormones (insulin
  and epinephrine) and immunoglobulins
 inactivation of lipid-soluble drugs
The morpho-functional unit of
          the liver

 “classical liver lobule”
 portal lobule
 liver acinus
LIVER LOBULE
           Hexagonal-shaped liver
           lobule (classical lobule) is
           the traditional description
           of the liver parenchyma
           organization
          Composed of hepatocyte
           (liver cell) plates(cords)
           radiating outward from a
           central vein
          Between the plates of
           hepatocytes there are
           sinusoids
          Has a central vein
          Portal triads are found at
           each of the six corners of
           each liver lobule
Sublobular vein




Distributing vein




Central vein



Plates of hepatocytes
PORTAL TRIADS
Portal triads (also called portal areas or portal
canals) are located at the corners of liver lobules.
Each portal area contains three (hence the term
portal triad) more-or-less conspicuous tubular
structures all wrapped together in connective
tissue.
       a branch of the bile duct
       a branch of the portal vein - interlobular vein
       a branch of the hepatic artery - interlobular
        artery
Hepatocytes
        are cuboidal cells with one or
         two large euchromatic nuclei
         and with abundant, grainy
         cytoplasm that stains well
         with both acid and basic dyes
         (reflecting the abundance of
         various cellular constituents).

        they may accumulate
         abundant lipofuscin (yellow-
         brown "wear-and-tear"
         pigment), especially with
         advancing age.
        a typical hepatocyte has two
         surfaces with microvilli
Hepatocyte
 ultrastructure
• all cytoplasmic
  organelles are
  very well
  developed
• cell membrane
  facing a bile
  canaliculus
  and the
  perisinusoidal
  space forms
  microvilli
Hepatocytes are located in flat irregular plates (cords) that are
arranged radially like the spokes of a wheel around a branch of the
hepatic vein, called the central vein or central venule since it really
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
canaliculus. Between the plates of hepatocytes there are sinusoids
capillaries.
Bile canaliculus


Hepatocytes form
2 rows

 Sinusoid




 Space of Disse



 Hepatocytes



 Microvilli
Sinusoids capillaries
   are larger than conventional capillaries and less regular in
    shape. They are lined by thin endothelial cells and lacks a
    basement membrane (is absent over large areas except the
    periphery and center of the hepatic lobule)
   Also residing on the sinusoidal walls are macrophages called
    Kupffer cells. These are phagocytic cells that remove
    particulate material and old red blood cells from circulation.
    Kupffer cells are members of the mononuclear phagocyte
    system.
   Pit cells are attached to the Kupffer’s cells. These cells
    contain granules and they are like large lymphocytes, killer
    cells. They make an anticancer effect.
   The space between the fenestrated endothelium and the cords
    is named the space of Disse.
sinusoid



sinusoid




           Kupffer cell
Perisinusoidal space (space of
   Disse)
It contains
 microvilli of hepatocytes,
 blood plasma,
 processes of the Kupffer’s cells
 lipocytes (adipose cells, commonly called an Ito cells).
   They are located between some hepatocytes. These cells
   have been shown to be the primary storage site for
   vitamin A. They also can produce connective tissue fiber
   in the large amount at the cirrhosis.
 In the fetal liver, the space between blood vessels and
   hepatocytes contains islands of blood-forming cells.
sinusoid




 Lipid inclusions   Ito cell
The blood circulation through the
                    liver
   System of inflow: the liver receives blood from the hepatic artery
    (supplies oxygen-rich blood to the liver) and portal vein (carries
    venous blood with nutrients from digestive viscera). They branch
    into lobar, segmental, interlobular, distributing branches.
   System of circulation: the distributing branches of vessels
    contribute blood to the sinusoids which provide the exchange of
    substances between the blood and liver cells. Sinusoids contain the
    mixed blood.
   System of outflow: sinusoids drain blood from the periphery of
    the classical hepatic lobule toward its center, into the central vein.
    Outside hepatic lobules central veins drain into the sublobular
    (intercalated) veins, which join 3-4 together and drain into the
    hepatic vein. It drains into the inferior vena cava.
GALL BLADDER
                functions
 storage  of bile
 concentration of bile
 acidification of bile
 send bile to the duodenum in response to
  cholecystokinin
  secreted by from enteroendocrine cells in
  small intestine
Tunics (layers) of the Gall Bladder
   TUNICA MUCOSA: When the gall bladder is empty, this layer is
    extremely folded. When full, this layer is smoother but still has some
    short folds.
      lamina epithelialis: composed of simple columnar epithelial cells
       with numerous microvilli on their luminal surfaces and connected
       by tight junctions near luminal surfaces.
      lamina propria: composed of loose connective tissue rich in
       reticular and elastic fibers to support the large shape changes that
       occur in the lamina epithelialisl; lamina propria may contain
       compound tubuloalveolar glands. May be mucous or serous.
      lamina muscularis mucosae: not present


   TUNICA SUBMUCOSA: present and typical
   TUNICA MUSCULARIS: contains much smooth muscle, poorly
    organized
   TUNICA SEROSA: present and typical
Pancreas
 Exocrinegland (97%)– PROENZYMES for digestion
 of carbohydrates, proteins & fats (amylase, trypsin,
 lipases)

 Endocrine
          gland (3%)– INSULIN and GLUCAGON
 (carbohydrate metabolism)
The exocrine pancreas
 The  exocrine portion of the pancreas is a
  compound acinar gland
 It has many small lobules, each of which is
  surrounded by connective tissue septa
  through which run blood vessels, nerves,
  lymphatics, and interlobular ducts.
 Exocrine secretion by the pancreas is
  controlled by hormones and nerves.
The exocrine pancreas
   Acini:  The secretory cells of the pancreas are arranged around 
    Acini
    a small lumen. 
   The pancreatic acinar cells are highly active in protein 
    synthesis for export and this high activity is reflected in their 
    bizonal staining properties.  The basal region of these secretory 
             staining
    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.   
Centroacinar
           cell
           These cells
           form the first
           part of the
           intercalated
Zymogen    duct
granules
The exocrine pancreas
   Ducts: The secretory product of the acinar cells is carried out 
    of the pancreas by a duct system as in other exocrine glands.   
   The first part of the duct system is called the  intercalated
    The first part of the duct system is called the  
    duct or intralobular duct.  It is lined with cuboidal epithelial 
    cells that secrete bicarbonate ion into the secretory product.  
    This duct actually extends into the acinar lumen, where its 
    walls consist of the pale staining centroacinar cells. 
    walls consist of the pale staining 
   Intercalated ducts have very little connective tissue around 
    them but they lead into larger interlobular ducts which lie 
    them but they lead into larger 
    within more prominent connective tissue septa. Interlobular 
    ducts are lined with a low  columnar epithelium that may 
    contain goblet cells.  Interlobular ducts empty into the main 
    pancreatic ducts that exit the pancreas.
Pancreatic juice
 trypsin,chymotrypsin and carboxypeptidase
  hydrolyse proteins into smaller peptides or
  amino acids;
 ribonuclease and deoxyribonuclease digest the
  corresponding nucleic acids;
 pancreatic amylase digests carbohydrates;
 pancreatic lipase digests lipids;
 cholesterol esterase breaks down cholesterol
  esters into cholesterol and a fatty acid.
The endocrine pancreas.
   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
• β-cells (75%) which secrete insulin (stimulates the synthesis of 
   -cells
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.
• α-cells (20%) which secrete glucagon (effects opposite to those of 
   -cells
insulin). They are generally located peripherally in the islets. 
• δ-cells (5%) which secrete somatostatin, a locally acting hormone which 
   -cells
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-cells, 
                                                PP-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 – δ1-cells, 
                                                   1-cells
     • secretin, which stimulates the exocrine pancreas, and motilin, which 
     increases GIT motility – EC-cells (enterochomaffin cells).  
                               EC-cells
Islet of Langerhans
Liver pancreas

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Liver pancreas

  • 1. State University of Medicine and Pharmacy “Nicolae Testemitanu” LIVER GALL BLADDER PANCREAS Department of Histology, Cytology and Embryology Tatiana Globa
  • 2. The Liver  Largest gland of the body  Two principal lobes: right and left  Right lobe further subdivided: Quadrate lobe and caudate lobe  Is surrounded by a capsule of connective tissue (Glisson’s capsule).
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  • 4. Functions of the Liver Digestive and Metabolic Functions  synthesis and secretion of bile  storage of glycogen and lipid reserves  maintaining normal blood glucose, amino acid and fatty acid concentrations  synthesis and release of cholesterol bound to transport proteins  inactivation of toxins  storage of iron reserves  storage of fat-soluble vitamins
  • 5. Functions of the Liver Non-Digestive Functions  synthesis of plasma proteins  synthesis of clotting factors  synthesis of the inactive angiotensinogen  phagocytosis of damaged red blood cells  storage of blood  breakdown of circulating hormones (insulin and epinephrine) and immunoglobulins  inactivation of lipid-soluble drugs
  • 6. The morpho-functional unit of the liver  “classical liver lobule”  portal lobule  liver acinus
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  • 8. LIVER LOBULE Hexagonal-shaped liver lobule (classical lobule) is the traditional description of the liver parenchyma organization  Composed of hepatocyte (liver cell) plates(cords) radiating outward from a central vein  Between the plates of hepatocytes there are sinusoids  Has a central vein  Portal triads are found at each of the six corners of each liver lobule
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  • 11. Sublobular vein Distributing vein Central vein Plates of hepatocytes
  • 12. PORTAL TRIADS Portal triads (also called portal areas or portal canals) are located at the corners of liver lobules. Each portal area contains three (hence the term portal triad) more-or-less conspicuous tubular structures all wrapped together in connective tissue.  a branch of the bile duct  a branch of the portal vein - interlobular vein  a branch of the hepatic artery - interlobular artery
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  • 14. Hepatocytes  are cuboidal cells with one or two large euchromatic nuclei and with abundant, grainy cytoplasm that stains well with both acid and basic dyes (reflecting the abundance of various cellular constituents).  they may accumulate abundant lipofuscin (yellow- brown "wear-and-tear" pigment), especially with advancing age.  a typical hepatocyte has two surfaces with microvilli
  • 15. Hepatocyte ultrastructure • all cytoplasmic organelles are very well developed • cell membrane facing a bile canaliculus and the perisinusoidal space forms microvilli
  • 16. Hepatocytes are located in flat irregular plates (cords) that are arranged radially like the spokes of a wheel around a branch of the hepatic vein, called the central vein or central venule since it really 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 canaliculus. Between the plates of hepatocytes there are sinusoids capillaries.
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  • 18. Bile canaliculus Hepatocytes form 2 rows Sinusoid Space of Disse Hepatocytes Microvilli
  • 19. Sinusoids capillaries  are larger than conventional capillaries and less regular in shape. They are lined by thin endothelial cells and lacks a basement membrane (is absent over large areas except the periphery and center of the hepatic lobule)  Also residing on the sinusoidal walls are macrophages called Kupffer cells. These are phagocytic cells that remove particulate material and old red blood cells from circulation. Kupffer cells are members of the mononuclear phagocyte system.  Pit cells are attached to the Kupffer’s cells. These cells contain granules and they are like large lymphocytes, killer cells. They make an anticancer effect.  The space between the fenestrated endothelium and the cords is named the space of Disse.
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  • 22. sinusoid sinusoid Kupffer cell
  • 23. Perisinusoidal space (space of Disse) It contains  microvilli of hepatocytes,  blood plasma,  processes of the Kupffer’s cells  lipocytes (adipose cells, commonly called an Ito cells). They are located between some hepatocytes. These cells have been shown to be the primary storage site for vitamin A. They also can produce connective tissue fiber in the large amount at the cirrhosis.  In the fetal liver, the space between blood vessels and hepatocytes contains islands of blood-forming cells.
  • 25. The blood circulation through the liver  System of inflow: the liver receives blood from the hepatic artery (supplies oxygen-rich blood to the liver) and portal vein (carries venous blood with nutrients from digestive viscera). They branch into lobar, segmental, interlobular, distributing branches.  System of circulation: the distributing branches of vessels contribute blood to the sinusoids which provide the exchange of substances between the blood and liver cells. Sinusoids contain the mixed blood.  System of outflow: sinusoids drain blood from the periphery of the classical hepatic lobule toward its center, into the central vein. Outside hepatic lobules central veins drain into the sublobular (intercalated) veins, which join 3-4 together and drain into the hepatic vein. It drains into the inferior vena cava.
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  • 27. GALL BLADDER functions  storage of bile  concentration of bile  acidification of bile  send bile to the duodenum in response to cholecystokinin secreted by from enteroendocrine cells in small intestine
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  • 29. Tunics (layers) of the Gall Bladder  TUNICA MUCOSA: When the gall bladder is empty, this layer is extremely folded. When full, this layer is smoother but still has some short folds.  lamina epithelialis: composed of simple columnar epithelial cells with numerous microvilli on their luminal surfaces and connected by tight junctions near luminal surfaces.  lamina propria: composed of loose connective tissue rich in reticular and elastic fibers to support the large shape changes that occur in the lamina epithelialisl; lamina propria may contain compound tubuloalveolar glands. May be mucous or serous.  lamina muscularis mucosae: not present  TUNICA SUBMUCOSA: present and typical  TUNICA MUSCULARIS: contains much smooth muscle, poorly organized  TUNICA SEROSA: present and typical
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  • 33. Pancreas  Exocrinegland (97%)– PROENZYMES for digestion of carbohydrates, proteins & fats (amylase, trypsin, lipases)  Endocrine gland (3%)– INSULIN and GLUCAGON (carbohydrate metabolism)
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  • 35. The exocrine pancreas  The exocrine portion of the pancreas is a compound acinar gland  It has many small lobules, each of which is surrounded by connective tissue septa through which run blood vessels, nerves, lymphatics, and interlobular ducts.  Exocrine secretion by the pancreas is controlled by hormones and nerves.
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  • 38. The exocrine pancreas  Acini:  The secretory cells of the pancreas are arranged around  Acini a small lumen.   The pancreatic acinar cells are highly active in protein  synthesis for export and this high activity is reflected in their  bizonal staining properties.  The basal region of these secretory  staining 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.   
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  • 40. Centroacinar cell These cells form the first part of the intercalated Zymogen duct granules
  • 41. The exocrine pancreas  Ducts: The secretory product of the acinar cells is carried out  of the pancreas by a duct system as in other exocrine glands.     The first part of the duct system is called the  intercalated The first part of the duct system is called the   duct or intralobular duct.  It is lined with cuboidal epithelial  cells that secrete bicarbonate ion into the secretory product.   This duct actually extends into the acinar lumen, where its  walls consist of the pale staining centroacinar cells.  walls consist of the pale staining   Intercalated ducts have very little connective tissue around  them but they lead into larger interlobular ducts which lie  them but they lead into larger  within more prominent connective tissue septa. Interlobular  ducts are lined with a low  columnar epithelium that may  contain goblet cells.  Interlobular ducts empty into the main  pancreatic ducts that exit the pancreas.
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  • 44. Pancreatic juice  trypsin,chymotrypsin and carboxypeptidase hydrolyse proteins into smaller peptides or amino acids;  ribonuclease and deoxyribonuclease digest the corresponding nucleic acids;  pancreatic amylase digests carbohydrates;  pancreatic lipase digests lipids;  cholesterol esterase breaks down cholesterol esters into cholesterol and a fatty acid.
  • 45. The endocrine pancreas.  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.
  • 46. Island of Langerhans • β-cells (75%) which secrete insulin (stimulates the synthesis of  -cells 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. • α-cells (20%) which secrete glucagon (effects opposite to those of  -cells insulin). They are generally located peripherally in the islets.  • δ-cells (5%) which secrete somatostatin, a locally acting hormone which  -cells 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-cells,  PP-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 – δ1-cells,  1-cells • secretin, which stimulates the exocrine pancreas, and motilin, which  increases GIT motility – EC-cells (enterochomaffin cells).   EC-cells