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Liver and Pancreas

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					        Glands of the
     Gastrointestinal Tract

• Serous and mucous secretions of
  salivary glands, liver and pancreas help
  maintain the optimal environmental
  conditions within the GI tract for
  digestion and absorption of food
  substances.
                 Objectives
• to understand the multifunctional aspects of the
  liver in maintaining circulating levels of amino
  acids and glucose, in digesting food substances,
  in detoxification, and in the immunological
  response.

• to appreciate the how portal circulation assists in
  the function of the liver

• to understand functional roles of the salivary
  glands and pancreas in digesting food substances
                     Outline
• There exists three primary cell types in the liver:
  hepatocytes, Kupffer cells, and endothelial cells.
• There are three types of liver lobules based on
  exocrine function, endocrine function, and blood flow.
• The liver has a portal circulation
• The liver has both endocrine and exocrine functions.
• Liver has the capacity to regenerate.
• Bile produced by the liver is stored and concentrated
  within the gall bladder.
                 The Liver
• the largest gland of the body (about 2% of the
  body weight)
• receives both venous blood through portal
  vein (75%) and arterial blood through hepatic
  artery (25%)
• surrounded by a well defined thin capsule
• functions as exocrine gland because it
  secretes bile and as an endocrine gland
  because it secretes plasma proteins
                           Liver functions
• Metabolic Functions
   – Homeostasis of circulating amino acids, carbohydrates, lipids and vitamins
   – Regulation of serum levels of lipids and hormones by endocytosis
   – Production of urea
• Endocrine Functions
   – Synthesis and secretion of serum proteins
       • Albumin, transferrin, prothrombin, fibrinogen, retinol-binding protein,
         GH-resisting factor, VLDL, LDL, HDL
   – Converts tetraiodothyronine (T4) to triiodothyronine (T3)
   – Converts vitamin D to circulating 25-hydroxycholecalciferol
• Exocrine Functions
   – Production of bile
   – Transport of polymeric IgA
• Detoxification Functions
   – Oxidation (addition of -OH or -COOH groups by cytochrome P450)
   – Conjugation with glycine, taurine, or glucuronic acid
• Phagocytic Functions
   – Foreign organisms
   – Aged red blood cells
• Hemopoiesis (6th week to 7th month embryo)
Venous Portal Circulation
of the Liver




Kierszenbaum, Fig. 17-10
      Lobulation of the Liver

• Portal Lobule: based on excretory function,
  triangle with central veins at corners and a
  portal triad at the center
• Classical Lobule: based on endocrine
  function, hexagon with portal triads at the
  corners and the central vein at the center
• Liver Acinus: based on blood flow, diamond
  shaped with two central veins and two portal
  triads at the apices
Kierszenbaum, Fig. 17-11
                             PT
                                                               PT
             3
                  CV
                                  1                                    CV
                                                          3
     PT                      PT
                                                     CV
                                                                    PT
                   CV

                                                                  CV




Zone 1 cells are the first to receive blood, the first to regenerate and last to die.
         Stem cells present in this zone. Kreb’s cycle activity highest in this zone.

Zone 3 cells are the last to receive blood and the first to die. Pentose shunt
         activity highest and peroxisomes more numerous in this zone. Ethanol
         and acetaminophen cause cell death in Zone 3.
                    Hepatocytes
• Polarized epithelial cells (sometimes binucleated)
   – Basal Surface: Sinusoids
   – Apical surface: Bile canaliculi form a three dimensional network
     between sheets of hepatocytes that empty into the bile duct of the
     portal triad

• Ability to divide upon hepatectomy or injury or toxicity

• Metabolic and Detoxification Functions
   – Homeostasis of amino acids (autophagy) and glucose (glycolysis,
     gluconeogenesis, and glycogenolysis)
   – Regulation of serum lipoproteins by endocytosis

• Endocrine Functions
   – Synthesis and merocrine secretion of serum proteins

• Exocrine Functions
   – Production of bile by ABC transporters
   – Transport of polymeric IgA by transcytosis
                S

H                   Hepatocyte


                S
        H
    S                 Bile
            H         Canaliculi




                       Sinusoidal
    S                  Capillary
Hepatocyte is a Polarized Epithelial Cell
Synthesis and Constitutive Merocrine Secretion
of Plasma Proteins

   –   Albumin
   –   Transferrin
   –   Lipoproteins (VLDL, LDL, HDL)
   –   Prothrombin
   –   Fibrinogen
   –   Alpha1-antitrypsin
   –   Coagulation factors
   –   GH-releasing factor
   –   Retinol-binding protein




                                           Microtubules
                                      IgA
    Basal Surface


                                                                Clathrin
 Secretory
 Component                                                      IgA receptor
                        Actin
                                                                Adaptor

                                                      Coated
                                                      Vesicle

Apical Surface       Transport
                      Vesicle

                                                          Early Endosome
     Junctional
     Complex


                    Transport of IgA into the intestinal lumen occurs via
                    transcytosis of IgA and its receptor across an
                    epithelium (hepatocyte or intestinal absorptive cell).
Basal Surface      LDL                       LDL receptor




                                             Actin        Recycling Vesicle



                                                Early Endosome



                             Microtubules             Late Endosome


                                                               LH - lysosomal
                                                                    hydrolases
Serum cholesterol is delivered          LH
to the cell by endocytosis of          LH                         LH
LDL and release of cholesterol                 Lysosome      LH
upon degradation of the LDL
within the lysosomes.
                            ABC Transporters and Bile Production




Cholesterol and bile salts, which are synthesized
from cholesterol, are transported into bile by ATP-
dependent transporters where they assist in the
solubilization of food substances. The breakdown         Canaliculi empty into the interlobular bile ducts
of cholesterol into bile salts is the primary mode for   of the portal triad which coalesce to form left
the removal of cholesterol from our body.                and right hepatic ducts. The common hepatic
                                                         duct connects to the cystic duct that leads to
                                                         the gall bladder and the common bile duct that
Kierszenbaum, Fig. 17-22                                 carries bile to the duodenum.
Kupffer
Cell                          S

              H                   Hepatocyte


                              S
                      H
                  S                 Bile
Endothelial               H         Canaliculi
Cell



                                     Sinusoidal
                  S                  Capillary
Discontinuous
Sinusoidal
Capillary

  Space of Disse     S




  Endothelial Cell
          Kupffer Cells

• Traverse the sinusoids

• Differentiate from circulating monocytes

• Phagocytic Functions
   – Foreign organisms (e.g., bacteria and yeast)
   – Aged red blood cells
Bacterium
                   Events of Phagocytosis
                    Pseudopod




                        Actin




                                Phagosome




                                                      Phagolysosome
                                                 LH
                                       LY
     Lysosome
                  LH                             Ly
                LY LH                       LH              LH - lysosomal hydrolases
                                                            LY - lysozyme
            Summary of Key Concepts
• The liver has both endocrine and exocrine functions.

• The liver has a portal circulation that allows the liver to screen the
  blood for pathogens and xenobiotics that may arise from the intestine.

• During liver regeneration, hepatocytes, endothelial cells, and biliary
  epithelial cells are prompted to divide.

• Kupffer cells are derived from monocytes and can phagocytose foreign
  organisms and aged red blood cells.

• IgA is transcytosed from the basolateral surface to the apical surface
  of the hepatocytes and intestinal absorptive cells.

• Endocytosis of LDL by hepatocytes regulates serum LDL levels and
  provides cholesterol for transport into bile and synthesis of bile salts.

• Four ABC (ATP-dependent) transporters present at the apical surface
  participate in the secretion of bile substances.
                    Outline
• The pancreas has both endocrine and exocrine
  functions.
   – Exocrine function: production of 1.5 liters of
     “juice” a day
   – Endocrine function: Islets of Langerhans
     produce insulin, glucagon, and other
     hormones

• Pancreatic acinar and ductal cells are under both
  hormonal and neural control.

• There are three salivary glands: parotid (serous),
  submandibular (serous and mucous), and
  sublingual (mucous).
Pancreas

Islet of Langerhans


Intralobular Duct




Interlobular Duct
                   Pancreas
• Acinar cells synthesize and secrete pancreatic
  juice.

• Juice includes zymogens (proenzymes):
  trypsinogen, chymotrypsinogen,
  procarboxypeptidase and proelastase

• Other enzymes are secreted in the active form:
  ribonuclease, deoxyribonuclease, triacylglycerol
  lipase, phospholipase, and amylase

• Intercalated ducts secrete bicarbonate that assists
  in neutralizing the pH of the chyme.
    Intercalated Duct




Centroacinar cell
Rough Endoplasmic
Reticulum




 Secretory
 Vesicles
Ross, Fig. 16.29
        Pancreatic Duct System

• First portion extends into center of acini, lined
  by centroacinar cells
• Intercalated ducts lined by squamous or
  cuboidal epithelium
• Intralobular ducts, cuboidal epithelium
• Interlobular ducts, columnar epithelium
• Main pancreatic duct or accessory pancreatic
  duct
Centroacinar cell




Acinus




Intercalated Duct




Intralobular Duct
           Hormonal Control
• Cholecystokinin (enteroendocrine cells of the
  duodenum and Islet of Langerhans)
  …stimulates the acinar cells to secrete
  zymogens, less volume enzyme-rich
  extrusion of zymogen granules

• Secretin (enteroendocrine cells of the
  duodenum and Islet of Langerhans)
  …stimulates the intercalated ducts to secrete
  fluid and bicarbonate, neutralizes the pH of
  the chyme
                                 Calcium Regulation of Secretion


                        PI
Cholecystokinin




                     PI kinase



                         PIP2
                  DAG
                                    IP3



                  Phospholipase C

                                                Ca+2
                                                              Microtubules
           Endocrine Pancreas:
           Islets of Langerhans
• 75% beta cells which secrete insulin
   – Stimulates the synthesis of glycogen, protein
     and fatty acids; facilitates the uptake of glucose
     into cells; activates glucokinase in liver cells
• 20% alpha cells which secrete glucagon
   – Effects opposite to those of insulin
• 5% delta cells which secrete somatastain
• Other cells which secrete pancreatic polypeptide,
  vasoactive intestinal peptide, secretin, or motilin
              Salivary Glands
• There exists three salivary glands: sublingual,
  submandibular, and parotid
• Sublingual is predominantly a mucous secreting
  gland, submandibular is a mucous and serous
  secreting gland, and parotid is a serous secreting
  gland.
• These glands produce 1200 ml saliva per day that
  moistens the oral mucosa, buffers the contents of
  the oral cavity, digests carbohydrates, and controls
  bacteria flora.
• Saliva includes amylase, lysozyme, sIgA, urea,
  sodium, potassium, phosphate, carbonate, and
  chloride.
Submandibular
   Gland




  Striated Duct




  Excretory Duct
        Salivary Duct System
• Intercalated ducts lined by low
  columnar/cuboidal epithelium
   – secrete bicarbonate and resorption of
     chloride
• Intralobular (striated) ducts, columnar
  epithelium
   – resorption of sodium and secretion of
     potassium and bicarbonate
• Interlobular excretory ducts, simple cuboidal
  to stratified cuboidal
           Summary of Key Concepts
• Pancreatic acini have serous secreting cells, which secrete inactive
  zymogens, and centroacinar cells.

• Salivary acini are surrounded by myoepithelial cells and composed of
  either mucous or serous secreting cells, which secrete amylase and
  transcytose IgA.

• Pancreas has intercalated (secrete bicarbonate), intralobular, and
  interlobular ducts.

• Salivary glands have intercalated (secretes bicarbonate), striated or
  intralobular (resorbs sodium and secretes potassium and bicarbonate)
  and excretory ducts.

• Cholecystokinin and secretin secreted from enteroendocrine cells of
  the duodenum and Islet of Langerhans stimulate the release of
  zymolases and bicarbonate into the pancreatic juices.
       Laboratory Preview

• Distinguish the parotid, sublingual, and
  submandibular glands.
• Describe the ductal system of salivary glands.
• Understand the lobulation of the liver and how its
  relates to the endocrine and exocrine functions.
• Describe the flow of bile.
• Describe the structure of the gall bladder.
• Understand the flow of pancreatic enzymes from the
  pancreas to the intestine.
Salivary Gland, H&E


     Excretory Duct


       Small Artery




       Striated Ducts
  Striated Duct




  Serous Acinus




  Intercalated Duct


Submandibular
   Gland
Parotid Gland

   Intercalated duct




   Serous Acinus
Sublingual
  Gland

Mucous Acinus




Intralobular Duct
   Liver
Portal Triad:
 Hepatic Artery
 Bile Duct
 Portal Vein




Central Vein
             Liver Circulation
GI, Spleen, Pancreas
 Portal Vein (75%)                       Hepatic Artery (25%)

 Interlobar Vein                          Interlobar Artery
                          Portal Triad
  Interlobular Vein                      Interlobular Artery

                         Sinusoids

                        Central Vein

                       Collecting Vein

                        Hepatic Vein
Liver, H&E


             Portal
             vein


Hepatic
artery




Bile duct
              Central Vein


Lipofuscin

              Hepatocytes




             Liver, H&E
Liver,
toluidine
blue
  Bile
  Canaliculi
               Kupffer
               cell




Endothelial
cells
 Lysosome

                 Nu
Hepatocyte

     RER
                       BC

     Golgi




             M

 Glycogen        RER
Pancreas

Islet of Langerhans


Intralobular Duct




Interlobular Duct
  Pancreas, H&E

   Intercalated Duct




Centroacinar Cells
Gall Bladder, H&E



                    Mucosa


         Gl

               Gl

                    Muscularis
                       Nodule regeneration
Liver cirrhosis, H&E   without central vein




  Portal
  triad




Lymphatic
tissue
Liver cirrhosis, H&E



Mallory
bodies




                       Lipofuscin

				
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posted:2/13/2012
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