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What is the largest gland of the body?
the Liver
Metabolic funcs: uptake, storage, metabolism & distribution of important nutrients & vitamins; degradation & conjugation of metabolites + potential toxins; iron recycling
Exocrine funcs: production & secretion of bile through bile duct → duodenum
Endocrine: maintaining blood component concentrations, aka synthesis & secretion into the blood of most plasma proteins (albumin, α- & β-globulins)
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Hepatocytes
- liver is highly cellular
- hepatocytes are arranged in plates
- are polygonal & often binucleate
- there's very little CT; only seen around ducts & CT capsule that surrounds the entire organ
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Hepatic Lobules
- functional unit of the liver, are hexagonal in shape
- corners have portal traids: contain 3 main structures, portal vein, hepatic artery, bile duct
- center of classic lobules is a central vein, which receives processed blood that drains into hepatic veins
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Liver Stroma
- V = central vein
- PT = portal triad
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Portal Triad
- upper left: bile duct (stains darkest blue/purple)
- bile is produced/works its way from the center of a lobule OUT toward the bile duct (opposite flow as blood)
middle: portal vein - carries nutrient rich, O 2 poor blood to liver
lower right: hepatic artery - carries nutrient poor, O 2 rich blood to liver
all blood mixes, works its way through a sinusoid on its way to the central vein (not pictured) during which its acted on by surrounding hepatocytes
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- white space in between hepatocytes: Sinusoids, through which blood flows on its way to the central vein
- endothelial cells lining the Sinusoids are DISCONTINUOUS, allowing hepatocytes access to nutrients/toxic substances present in blood
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Central Vein
will go on to join larger veins - called Hepatic Veins - that will eventually go on to join the Inferior Vena Cava
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Perisinusoidal Space (Space of Disse)
- important space between the sinusoid endothelial cell & Hepatocyte (D in picture)
- reticular fibers are present in this space that slows blood flow so hepatocytes can act on materials in blood
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What important cell is in the sinusoids that can wander around?
- Macrophages, aka Kupffer cells
- are luminal compared to to sinusoidal endothelium (exist in the sinusoids) & scavenge whatever they need to
- stain darkly

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Ito / Stellate Cell
- where Vitamin A is stored in the liver
- are abundant
- get activated with liver damage → secrete collagen
- cirrhosis is caused by collagen occlusion of sinusoids (by Ito cells)

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What is the exocrine product of the liver?
- BILE
- is made by hepatocytes & transported between then via a Bile Canaliculus
 - needs to eventually collect @ peripheral portal triad area where it can get dumped into bile duct
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What are the 3 types of liver lobules that can be described?
- 1. Classic
- 2. Portal
- 3. Acinus
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Classic Lobule
- center: central vein
- hexagonal corners: portal tracts
- has metabolic & endocrine functions

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Portal Lobule
- center: bile duct (portal tract)
- triangular corners: central veins
- has exocrine/excretory (waste removal) functions
- exocrine b/c product (bile) secreted toward a 'central' duct

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Liver Acinus
- metabolic unit
- center: incoming blood-signals
- edges: central vein
- by the time blood gets near the CV, it's been depleted of both nutrients & oxygen
- hepatocytes in this region (around CV) are most susceptible to ischemic injury

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Which cells are most likely to die if a toxic substance enters the liver?
zone 1, closest to their entry point (cells around the canal between 2 portal tracts)
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How Bile Gets to the Gall Bladder
- storage organ for bile made by hepatocytes
- bile is transported through hepatocytes via canaliculi until it reaches a bile duct
- L & R hepatic ducts converge to form the common hepatic duct
- if the common bile duct opening into the duodenum is closed, bile goes through the cystic duct into the gall bladder for storage
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What are some distinct features of the Gall Bladder?
no muscularis mucosa or submucosa
it has a simple columnar epithelium (sans goblet cells*) with a lamina propria underneath & a muscularis externa (that contracts to expels bile into duodenum when signaled)
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False Glands
- individual to Gall Bladder that can help with identification
- really just the lumen but looks like 'glands' due to sectional cuts

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Rokitansky-Aschoff Sinuses
- lumen diverticula that penetrate into muscularis externa area
- sacs with fluid in them; a lot is associated with gall stone development

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CCK (Cholecystokinin)
compound made in the duodenum & jejunum that stimulates muscle contraction (muscularis externa) of the gallbladder
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Secretin
- stimulates bicarbonate secretion from bile duct cells themselves
- (helps neutralize chyme in the SI)
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What concentrates the bile when its stored in the gall bladder
- the gall bladder epithelium
- when there are white space between the basolateral spaces of the epithelium, its actively concentrating the bile
- does so by pumping Na+ into spaces, causing water from lumen to enter the spaces (dilating them)

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Cholelithiasis (Gall Stones)
- formation of concretions (calculi/stones) in gallbladder or bile ducts
- major component cholesterol
- factors: female, obesity, Western diet, family history
- are the most common cause of pancreatitis, cholesystitis (when stone blocks duct, any time there's a solution in stasis, can lead to inflammation)
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Pancreas
- large, lobulated gland with exocrine & endocrine function
- exocrine secretions are transported through ducts
- endocrine secretions are secreted through fenestrated capillaries directly into the blood stream
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Acini → Ducts
- grape-like functional units whose ~45 secretory cells synthesize pancreatic enzymes
- each acinar cell has zymogens made in the basal RER, glycosylated & packaged in the Golgi, stored in the apical cytoplasm until hormones signal for their release via exocytosis into intralobular ducts
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What are a few enzymes/zymogens that originate from the pancreas acini?
- 1. protein degrading enzymes (trypsinogen, carboxypeptidases,
- elastase)
- 2. carbohydrate degrading enzymes (amylase)
- 3. nucleic acid degrading enzymes (ribonuclease, deoxyribonuclease)
- zymogens are activated by trypsinogen, which itself is activated by enterokinase in the small intestine
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Intra v. Interlobular Ducts
 - LEFT = intra/intercalated: diluting the concentrated enzymes (clear in H&E); exist within lobules
- are much smaller
- RIGHT = inter ducts: transporting diluted enzymes through a system of ducts; exist embedded in CT between lobules
- interlobular ducts have simple cuboidal epithelium
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Cholecystokinin
- peptide hormone released from enteroendocrine cells in duodenum that:
- causes the release of zymogen granules from the acinar cells (pancreas)
- causes emptying of the gall bladder
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Secretin
- peptide hormone released from enteroendocrine cells in duodenum that:
- causes the intralobular ducts to secrete a bicarbonate-rich solution that dilutes released zymogens (pancreas)
- stimulates the cells of the bile duct to release an aqueous solution that dilutes the concentrated bile
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Islets → Capillaries
compact clusters of epithelial cells richly vascularized with fenestrated capillaries (into which the cells secrete their hormones)
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What are the 3 main cells in a pancreas islet?
- 1. beta cells: most, secrete insulin (cellular uptake of glucose from blood)
- 2. alpha cells: secrete glucagon (cellular release of glucose into the blood)
- 3. delta cells: produce somatostatin (modulates secretion of insulin & glucagon)
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Locate the Acini & Islets
- magenta cells = acini: zymogens secreted through ducts via exocrine mechanism
- light pink clumps = islets: hormones secreted through capillaries via endocrine mechanism
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Centroacinar Cell
- Intralobular duct cell located in the middle of an acinus
- looks lighter than the surrounding acinus cells

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Cystic Fibrosis CFTR (cystic fibrosis transmembrane conductance regulator) Channel
- in addition to transborting Cl-, CFTR also moves bicarbonate
- with a mutated channel ductal bicarbonate secretion is reduced
- the enzyme solution produced = too viscous
- this causes a backup of enzymes release from pancreas → inflammation, scarring
- ducts fill & form cysts (disease name)
- glycocalyx in SI is inefficient due to reduced enzyme adsorption -malabsorption results
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