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Liver Functions
**Regulates metabolism of carbs, lipids, and proteins; Secretion of bile and plasma proteins, drug and toxin Detoxification and excretion, & storage of glycogen, fat, iron, and vitamins
1) Detoxification: Zone 1- less subject to metabolite toxins vs. Zone 3- more vulnerable to toxins from metabolites b/c closer to central vein.
2) Regeneration:
3) Excretory Organ: bilirubin, cholesterol
4) Secretory Organ: bile (also recycles bile), IgA from GI tract plasma cells, glucose - glycogen stores, albumin & other plasma proteins, lipoproteins - VLDL
5) Conjugation of bilirubin to soluble product
6) Immune functions: Kupffer cells, IgA (from plasma cells in GALT in GI tract) - rides with bile to small intestine
Hepatocytes
MORPHOLOGY:
-parenchymal cells organized into cellular plates
-1 cell thick bordered by sinusoids
- round nuclei and distinct nucleoli
- abundant in granular and smooth ER (proliferates in response to fat soluble drugs to oxidize and inactivate the drugs)
-peroxisomes with catalase: oxidative enzymes to rid toxins
-lysosomes
-GLYCOGEN GRANULES with some fat droplets: increase after meal and then drops during fasting b/c glucose released
- Gap Junctions - electrotonic coupling: excitability of hepatocytes due to electric current

FUNCTION:
- process the blood that enters from GI and systemic circulation
- produce bile and secrete it into canaliculi (formed by walls of adjacent hepatocytes & tight junctions)
- regenerate for liver re-growth (growth is regulated depending on need by body)
Space of Disse
separates hepatocytes from endothelial lining cells

FUNCTION: site of exchange from blood in sinusoids -> hepatocytes and from hepatoctyes -> blood

CONTENTS:
1) RETICULATE FIBERS that support hepatocytes
2) Ito cells - Fat storing cells: release growth factors for regeneration
3) microvilli that increase SA for absorption
Hepatocyte Necrosis & Fibrosis
- due to chronic liver damage or insults (hepatitis, alcohol consumption -> cirrhosis): CT overwhelms hepatocytes so blood flow to liver blocked
- blocked blood leads to PORTAL HYPERTENSION & LIVER DYSFUNCTION -> Jaundice
PROBLEMS WITH LIVER (ie. bile malabsorption, bilribubin, etc)
Bile absorbed in ILEUM!!

1) buildup of Bilirubin -> can cross BBB
feces unpigmented b/c usually bilirubin byproducts with excretion are brown

2) Diarrhea - bile excretion causes H2O to be excreted
**bile secreted with fatty foods because CCK - green poop
Bile Canaliculi
- enlargement in Extracellular Space between 2 hepatocytes & sealed by tight junctions (no intrinsic structure)
- seen in LM with PTAH or Silver stain that show tight junctions
**VARIES FROM SILVER STAIN OF LIVER BECAUSE BILE CANALICULI ARE FORM CONTINUOUS POLYGONAL BRANCHING SYSTEM WITHIN LOBILE - NEATER SINGLE LOOKING LINES vs SILVER OF SINUSOIDS - MORE ALL AROUND AND CLUMPY: b/c stains space of disse and the hepatocytes

- have microvilli and ATPase (what stains in enzyme cytochemistry)
- converge into transitional canals - Canals of Hering -> Bile ducts (out of liver)
Bile Pathway OUT of liver
- heaptocytes makes Bile -> bile canaliculi -> Canals of Hering (transitional canal - bile ductules) -> Bile Duct (in portal Triad) -> many bile ducts enter Hepatic Duct (exit liver) -> Common Bile duct (Cystic Duct from gall bladder also empties here) -> Pancreatic Duct & Bile Duct JOIN to SPHINCTER OF ODDI -> Duodenum
Bile Duct
- Simple Cuboidal epithelia --> High Columnar Epith. (in hepatic duct)
- part of portal canal (portal triad)
Portal Canal/Portal Triad
1) lympatic tissue

2) portal vein - poorly oxygenated PORTAL blood from GI for detox

3) hepatic artery - oxygenated SYSTEMIC blood TO liver delivering nutritional support for metabolic activity of hepatocytes

4) Bile Duct

**all bundled by DENSE CT; SEPARATED BY INTERLOBULAR CONNECTIVE TISSUE!!!!!!!
Kupffer cells
WHAT:
- part of Mononuclear Macrophage System: MONOCYTES -> MACROPHAGES
- Antigen Presenting Cells - part of Immune System

WHERE:
- lie in sinusoidal lumen

FUNCTION:
**-> MACROPHAGES!
-Macrophages: part of innate (nonspecific) immunity and help initiate specific defence mech (cell-mediated immunity)
-Innate Immunity: phagocyte (engulf and digest material)
- Cell-mediated: stimulate lymphocytes to respond to pathogen
- PHAGOCYTOSE particulate matter and decaying RBC's that pass through sinusoids: takes matter in TO PRESENT TO IMMUNE SYSTEM FOR DEGREDATION
Sinusoids
WHAT: capillaries that carry the MIXED blood through hepatocytes

ARRANGEMENT:
radially around central vein and in continuity with it's lumen --> Sinusoids EMPTY INTO CENTRAL VEIN

FUNCTION: deliver nutrients, toxins, and pathogens absorbed in the intestine directly to hepatoctyes via Space of Disse (also exchange from hepatocytes to blood)

COMPOSITION:
3 cell types lined with Space of Disse to separate endothelium from hepatocytes
1) ENDOTHELIAL CELLS - no basal lamina, Fenestrations/Discontinuous for MAX absorption; Flat nuclei
2) KUPFFER CELLS
3) ITO CELLS
SINUSOIDS AND HEPATOCYTES LINED RADIALLY AROUND CENTRAL VEIN!!
Blood Flow through Liver
*Portal System (portal Vein) or Systemic System: (Hepatic Artery)

GI tract/Systemic-> portal vein/hepatic artery -> sinusoids -> central vein ->> many central veins empty into Sublobular Veins (thick CT, no accessory organs) -> many sublobular veins empty into Collecting Veins -> Hepatic vein -> Vena Cava
Portal Veins
-carry blood from GI- contains material to be 'cleansed' by liver Kupffer cells
- part of Portal Triad: TERMINAL PORTAL VEINS: connect adjacent hepatocytes, center of HEPATIC ACINUS
Hepatic Acinus (Liver acinus)
FUNCTION: flow of BLOOD between hepatocytes

MORPHOLOGY:
- DIAMOND SHAPED: Portal triad on 2 corners connected by Terminal Portal vein and central Vein on other 2 corners
- centered on terminal portal vein (blood flow between 2 portal triads)
- 3 Zones
Portal Lobule:
FUNCTION: flow of BILE through liver
-hepatocytes within triangle make BIle that enters bile duct in center

MORPHOLOGY:
TRIANGULAR: 3 corners are central veins and Center is Bile duct
Classic Lobule:
hexagonal radiating arrangement of hepatocytes
- center is Central Vein
- corners are Portal Triads

NO FUNCTION! just STRUCTURAL LOBULE
Liver Organization:
LOBULES: Basic Structural Unit of Liver that has plates of hepatocytes radiating from central vessel
- Composed of 100,000 classic lobules
- LIVER IS THE LARGEST ORGAN IN THE BODY, BUT IT IS ONLY 1-2 CELLS THICK B/C FORMED BY HEPATIC PLATES (MADE UP OF A BUNCH OF HEPATOCYTES) THAT ARE SEPARATED BY SINUSOID
Functional Gradient of Liver Acinus
ZONE 1: highest concentration of nutrients (o2) and highest concentration of toxins, lowest concentration of metabolite toxins; nearest to terminal portal Vein

ZONE 2

ZONE 3: lowest concentration of Toxins, highest concentration of metabolite toxins, Lowest concentration of Nutrients (low o2- vulnerable to apoxia); closest to central vein
Blood Vessels of the Liver: (ones we viewed in lab: not including collecting vein and hepatic vein)
1) Sinusoids: radially arranged around central vein, one cell thick

NOT SURROUNDED BY CT:
2) Central Vein: epithelial lining directly in contact with hepatocytes

SURROUNDED BY CT:
3) Sublobular Portal Veins: where central vein empties; no accompanying structures; THICK CT
4) Portal vein: thin walled, large vessel; part of Portal Triad/Canal

5) Hepatic Artery: thick wall, small vessel
Glisson's capsule:
fibroelastic hepatic capsule that covers external surface of liver
Gall Bladder
FUNCTION:
- store bile from liver and concentrate it by absorbing H20 and electrolytes
- releases bile in response to CCK that was released due to FA/peptides in duodenum

MORPHOLOGY:
MUCOSA:
-1 epithelial cell type: narrow columnar --> no goblet, mucus cells w/ short microvilli!(distinguishes from small intestine)
- lamina propria with Loose CT
- NO MUSCULARIS MUCOSA/SUBMUCOSA


- MUSCULARIS EXTERNA: interlacing loose smooth muscle
- SEROSA: where it's free from Liver
-ADVENTITIA: connects with liver wall (shares wall with liver)
Pancreas: Morphology - acinar cells and duct cells
1) ENDOCRINE: islets of Langerhans - basal granules that secret into capillary plexus of the Islets
2) EXOCRINE:
- ACINAR cells: eosinophilic apical granules - zymogen granules
- Centroacinar cells: continuous from intercalated ducts
- ALL INTERCALATED - no striated ducts --> intralobular ducts -> interlobular ducts -> pancreatic duct -> sphincter of Oddi (join with Common bile duct from liver & gall bladder)-> duodenum
Pancreas: Function

- ENDOCRINE

- EXOCRINE (& affects by CCK & Secretin)
ENDOCRINE
1) Beta cells - insulin
2) Alpha cells - glucagon
3) D cells: somatostatin

EXOCRINE: Enzyme & Alkaline Fluid Release AFFECTED BY ENDOCRINE HORMONES!!
ACINAR cells:
FA/peptides -> AcH -> CCK: enzyme release AND bile secretion from gall bladder

*INACTIVE FORMS:
- Proteases: ie) Trypsinogen - activated by enterokinase from Enteroctyes in small intestine
- Pro-Phospholipase A2
- Pro-Elastase

*ACTIVE FORM
-Glycolytic Enzymes: Amylase - breakdown Starch
-Nucleotidases (RNA/DNA breakdown)
- Pancreatic Lipase
- Cholesterol breakdown: cholesterol esterase

DUCT CELLS:
low pH in duodenum -> VIP -> SECRETIN -> duct cell secretion of alkaline fluid, mediated by cAMP levels
**secretin augments CCK stimulated enzyme rich secretions but ENZYME SECRETION IS INDEPENDENT OF ALKALINE FLUID RELEASE
BILE CANALICULI versus SINUSOIDS
Bile Canaliculi: in BETWEEN 2 hepaotcytes - enlargement of extracellular space
-need close resolution to see

vs.

Sinusoids: can see from far resolution
- MANY HEPATOCYTES AROUND IT!