2 nd largest organ of the body Largest gland Location Receives blood from Portal vein Hepatic artery Drains to IVC FUNCTIONS OF LIVER Detoxification of metabolic waste products eg ID: 913472
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Slide1
HISTOLOGY OF LIVER
Slide2LIVER
2
nd
largest organ of the bodyLargest gland Location Receives blood from:Portal vein Hepatic artery Drains to:IVC
Slide3FUNCTIONS OF LIVER
Detoxification of metabolic waste products e.g.
de-
amination of amino acids to produce ureaDestruction of spent RBC’s Synthesis & secretion of bileSynthesis of plasma proteins including albumin & clotting factorsSynthesis of plasma lipoproteins Metabolic functions e.g. glycogen synthesis, gluconeogenesis, storage of glycogen, some vitamins & lipids
Detoxification of various drugs & toxins e.g. alcohol
Slide4STROMA OF LIVER
Connective tissue (
Glisson’s
) capsuleThick at hilumBlood vessels & ducts surrounded by CTReticular fibers surround & supports liver cells & sinosuoids
Slide5HEPATIC LOBULE
Hepatocytes are
epithelial
cellsLobules –structural unit of liver (0.7×2mm)Portal spaces 3-6Lobule has:Portal area /portal triadCentral vein
Slide6PORTAL TRIAD
A branch of:
Portal vein
Largest structureThin walled lined by endotheliumHepatic artery/ arterioleSmallest structureBile ductLined by cuboidal epitheliumLymphaticsDelicate, collapsedNervesLayer of hepatocytes immediately bordering the portal triad is
limiting plate
Slide7HEPATIC LOBULE
Hepatocytes form interconnecting plates –branch & anastomose
Hepatocyte plates one cell thick
Directed from periphery to center forming sponge like pattern of liverSinosuoids
Slide8HEPATIC SINUSOIDS
Dilated veins with INCOMPLETE basement membrane
Supported by reticular fibers
Cells:Endothelial cells- fenestrated without diaphragmKupffer cells (macrophages) present within
sinosuoids
Metabolize aged erythrocytes,
Secrete proteins
Digest bacteria
Slide9PERISINOSOIDAL SPACE (of disse
)
A
subendothelial spacePresent between hepatocytes & sinosuoidsMicrovilli of hepatocytes project into the spaceFat storing (Ito) cells that stores Vit. A present hereSpace continuous with sinusoids
Space drains into
lymphatics
of portal
triad
Slide10Slide11MEDICAL APPLICATION
NORMAL ITO CELLS
:
Vitamin A rich lipid inclusionsUptake ,store , release of retenoidsSynthesis &Secrete ECM proteins and proteoglycansLocal immunityCHRONIC LIVER DISEASE – Ito cells acquire the features of myofibroblasts
Cells found close to damaged hepatocytes
Play a major role in fibrosis
Alcoholic liver disease
Slide12BLOOD SUPPLY
Portal vein-70%
Portal venule- to portal space
Distributing venules-around periphery of lobule into sinosoidsCentral or centrolobular veinHepatic artery -30%Arterioles –lead to sinosoidsDirection of blood flow- from periphery to center of lobuleDifference in properties & functions of peripheral & centrolobular hepatocytes
Slide13HEPATOCYTES
Polyhedral cells 20-30µm
Eosinophilic
Large nucleus /binucleateBile canaliculiGap junctions between hepatocytesHepatocyte surfaces related to:Perisinosoidal spaceAdjacent hepatocyteBile canaliculi
Slide14HEPATOCYTES
Nucleus
Prominent nucleolus
Disperse chromatinPolyploidyCytoplasmGlycogen-lacey appearanceFat-spherical vacoulesRibosomes & RER- basophiliaSERMitochondria-eosinophilicLysosomesGolgi complexPeroxisomes
Slide15FINE STRUCTURE OF HEPATOCYTES
Rough endoplasmic reticulum
– protein synthesis
Smooth endoplasmic reticulum – oxidation, methylationConjugation of bilirubin to gluronate – bilirubin glucoronideSynthesis of bile acidsGolgi apparatus – near nucleusFormation of lysomesSecretion of proteins, glycoproteins, lipoproteins into plasmaLysosomes –turnover & degradation of organelles Mitochondria Peroxisomes –Important for oxidation of excess fatty acid
Breakdown of hydrogen peroxide
Breakdown of purines to uric acid
Synthesis of cholestrol, bile acids & some lipids for myelin
Drug inactivation –by enzyme glucuronyle transferase
Slide16Bile canaliculi
1-2µm diameter
Limited by plasma membrane of hepatocytes
Tight junctionsCanaliculi empty into bile ductules lined by cuboidal cells called cholangiocytesHering’s canalsBile ducts –portal spacesRight & left hepatic ductsDirection of bile flow – opposite
to that of blood
Slide17MEDICAL APPLICATION
DISORDER OF PEROXISOME FUNCTION
Inherited disorder
Mutation of enzymes in peroxisomes.Adrenoleukodystrophy (X-ALD) results from failure to metabolize fatty acids properlyResult:Deterioration of myelin sheath of neurons
Slide18RBC – heme – unconjugated bilirubin + plasma albumin - absrobed by hepatocytes – bilirubin released from albumin – bilirubin + glucoronic acid – bilirubin glucoronide (water soluble) – bile canaliculi
Conjugated bilirubin (bilirubin glucoronide) – urobilinogen – urine
Urobilinogen – stercobilinogen - intestines
Slide19MEDICAL APPLICATION
When bilirubin or bilirubin glucuronide is not excreted properly various diseases characterized by JAUNDICE occur
Neonatal hyperbilirubinemia
– jaundice in newbornUnderdeveloped smooth ERTreatment – blue light exposureUnconjugated bilirubin transformed into water soluble photoisomer that can be excreted by kidneys
Slide20BILE
Exocrine function of liver
Consists of:
Bile acids – emulsify fatsCholesterol Phospholipids Bilirubin Electrolytes
Slide21MEDICAL APPLICATION
Gall stone formation (cholelithiasis)
Causes
Obstructs bile flowJaundice – presence of bilirubin in bloodRupture of tight junctions around bile canaliculi
Slide22MEDICAL APPLICATION
Drugs inactivated by liver can induce increase in smooth ER in hepatocytes e.g. barbiturates
Barbiturates can increase synthesis of glucuronyltransferase synthesis
Use barbiturates in glucuronyltransferase deficiency
Slide23LOBULATION
CLASSIC HEPATIC LOBULE
Central vein at center
Portal triads at peripheryArea near portal triad well supplied by oxygen & nutrientsArea near central vein not well supplied
Slide24Slide25LOBULATION (continued)
PORTAL LOBULE
Triangular area
Three central veinsPortal triad at centerConsists of tissues draining bile into bile duct
Slide26LOBULATION (continued)
LIVER ACINUS
Diamond shaped area
Two portal triads Two closest central veinsBased on nature of blood supply & O2 gradientZONE 1- nearest arteriole- most O2 & nutrients, oxidative metabolismZONE III –near central vein – least O2 & nutrients, glycolysis, lipid formation,ischemic necrosisZONE II – intermediate range
Slide27Slide28COMPARISON
Slide29Slide30LIVER REGENERATION
Has strong capacity for regeration
Compensatory hyperplasia
Original mass of tissue restoredSurgical removal produces similar responseImportant in liver transplantLIVER STEM CELLS (oval cells)Present in initial epitetlium of bile ductules near portal areasCan give rise to hepatocytes & cholangiocytes
Slide31MEDICAL APPLICATION
Continuous or repeated damage to liver cells
Increased amount of CT along with multiplication of hepatocytes
Nodules formed –central mass of disorganized hepatocytes surrounded by CTCirrhosis Causes of cirrhosisEthanol alters hepatic regeneration through unknown mechanism favoring development of cirrhosis
Slide32Slide33EXTRAHEPATIC BILIARY PASSAGES
Simple columnar epithelium
Subepithelial CT:
Elastic fiberLymphoid tissueMucous glands-tubuloalveolar BV, nervesCOMMON BILE DUCTSmooth muscle fibers-isolatedOblique & transverse fibers- near duodenum
Slide34GALL BLADDER
Parts
Three layers
MUCOSAEpithelium- simple columnarStriated borderLamina propria has collagen fibers, muscle fibers, BV, tubuloacinar glands
Slide35GALL BLADDER
Epithelium –absorptive cells
Microvilli
Intercellular spacesMitochondriaApical mucous granules
Slide36GALL BLADDER
MUSCULAR LAYER
Interlacing smooth muscle fibers
Elastic & reticular fibers between musclesPerimuscular layer Adventitia / serosa
Slide37