Lec 17/18 - Liver, Pancreas, Gallbladder Flashcards
functions of pancreas, liver, gallbladder
Pancreas: secretes digestive enzymes & hormones
* important for metabolism of ingested nutrients
Liver: synthesizes bile (aids in digestion & absorption of fat)
* important for carbohydrate, lipid & protein metabolism
Gallbladder: stores and concentrates bile
pancreas; what does it produce, what does it look like, surrounded by what, separate from what, what is the duct and what empties
mixed exocrine-endocrine gland
* produces both digestive enzymes and hormones
Grossly:
- elongated retroperitoneal organ
- large head near the duodenum and more narrow body and tail regions that extend to the left
* surrounded by thin capsule of connective tissue
* CT septa extend from capsule to cover large vessels & ducts
* separate the parenchyma into ill-defined lobules
* pancreatic duct extends through the length of the gland
* empties into the duodenum at the hepatopancreatic ampulla
exorine vs endocrine component of pancreas, what they synthesize and secrete and what they are
Exocrine component (acini)
* compound tubuloacinar serous gland
* synthesizes & secretes digestive enzymes into small intestine
Endocrine component (islets)
* diffuse endocrine organ
* synthesizes & secretes insulin and glucagon
pancreas; what does each acinus consist of, surrounded by, staining, what cell type isnt present
- each acinus consists of several serous cells, surrounding a tiny lumen
- each acinus surrounded by basal lamina & supported by delicate layer of reticular connective tissue, rich in capillaries
- acinar cells pyramidal in shape with very eosinophilic apical regions
- no myoepithelial cells in pancreas
pancreatic acinus cells, what they look like and what they do/whats in them
Acinar cells
* polarized, with round basal nuclei
* numerous zymogen granules located apically.
Centroacinar cells
* the initial ductal cells
* appear in the middle of lumen in an H&E stained specimen
* add sodium, bicarbonate & water to secretion
Intercalated ducts
* small ducts with simple cuboidal epithelium
* merge with larger ducts (columnar
epithelium); eventually join pancreatic duct
* secretion by acinar & ductal cells stimulated by hormones (cholecystokinin & secretin, respectively)
* hormones produced by enteroendocrine cells of duodenum
pancreatic acinus; how are zymogen granules released and what do they contain (5)
- zymogen granules released
by exocytosis - contain inactive digestive enzymes:
proteolytic endopeptidases (e.g. trypsinogen)
proteolytic exopeptidases (e.g. pro-aminopeptidase)
amylolytic enzymes (e.g. α-amylase)
lipases
nucleolytic enzymes (e.g. deoxyribonuclease)
pancreatic tissue; how autodigestion is prevented, what is the trypsin activator called and where is it, what is it copackaged with, pH
Pancreas does not get autodigested by its own enzymes because protease activation is restricted to duodenum
* enteropeptidase (trypsin activator) present only in duodenum
* trypsin inhibitor is co-packaged in the secretory granules with Trypsinogen
* pH in the acini and duct system is suboptimal for enzyme activation due to HCO 3- secreted by centroacinar and intercalated duct cells
liver; covered by what, what is the thick part and what do you fine there, blood supply, main digestive function, interphase, synthesis
- covered by a thin capsule and
mesothelium of the peritoneum - capsule thickens at hilum: area where hepatic portal vein & hepatic artery enters organ & common bile duct exits
- liver has complex blood supply: hepatic artery (branch of aorta) portal vein from intestines
- main digestive function is production of bile:
complex substance required for emulsification, hydrolysis & uptake of
fat in the duodenum - acts as major interphase between digestive system and the blood; nutrients
- synthesis of many plasma proteins; detoxification of xenobiotics
how is the parenchyma organized
what occupies the space between hepatocytes
- parenchyma of liver organized as plates of hepatocytes in pillar-like polygonal lobules
- spaces between layers of hepatocytes occupied by vascular components (sinusoids and hepatic capillaries) & bile channels
hepatic lobule; what species are boundaries obvious, what is in the portal triad, blood flow, portal vs hepatic artery
- connective tissue boundaries obvious in pigs, but not most species
- corners of lobule contain portal triad of:
- bile ductule
- venule (from portal vein)
- arteriole (from hepatic artery
- (lymphatics)
Note: depending on where things branch, a portal ‘triad’ may have more that 3 structures - blood from the stomach, intestines & spleen collects into vessels that ultimately end up at the portal vein
- portal blood O2 poor, nutrient rich, rich in metabolic waste (e.g. bilirubin); potentially rich in xenobiotic toxins
- 75% of blood supply to liver is portal
- remainder of blood supply (25%) from hepatic artery: O2 rich, nutrient poor
- mixes with portal blood in sinusoids & drains to central venule (central vein)
hepatic lobule CT; what type of collagen, provides support for what, blood flow and bile flow
- collagen type III fibers (reticular fibres) run along plates of hepatocytes
- provide support for hepatocytes and for intervening sinusoids
- peripheral portal area contains more connective tissue: site of portal triad
- blood flows from portal area to centre of lobule; bile flows in opposite direction
hepatocytes; size, appearance, main exocrine function, reason for staining
- large cuboidal or polyhedral epithelial cells
- large central nucleus;
eosinophilic, mitochondria- rich cytoplasm - frequently binucleated; about 50 % of them are polyploid
- main exocrine function to produce and secrete bile
hepatocyte function
- hepatocytes (together with other liver cells) contribute to and process blood contents in diverse ways:
- synthesis & secretion into blood of major plasma proteins (albumins, fibrinogen, apolipoproteins, transferrin, etc.)
- conversion of amino acids into glucose (gluconeogenesis)
- breakdown & conjugation of ingested toxins including many drugs (detoxification)
- amino acid deamination for production of urea
- storage of glucose in glycogen granules, & triglycerides in lipid droplets
- storage of iron in complexes with ferritin
- vitamin D and vitamin K conversion
hepatocyte ultrastructure; what is there extensive amounts of, what is stored in the cytoplasm, what is the outside associated with
- cells have extensive amounts of ER (both rough and smooth) & numerous mitochondria
- cytoplasm has stored nutrients (depends on location of hepatocyte in
lobule) - outside (‘lateral’) surfaces of hepatocytes associated with sinusoids: discontinuous endothelial cells with large fenestrations & gaps
how are hepatocytes held together, what is created, what is bile secreted by
- ‘apical’ surfaces of hepatocytes held
together by desmosomes & sealed by tight junctions - small channels created along common edge: bile canaliculi
- bile is secreted by hepatocytes into canaliculi
fate of bile acids, what does bile consist of, bile function, what do bile pigments do
- bile consists of pigments, electrolytes, fatty acids, phospholipids, cholesterol, iron, copper and bilirubin
- bile also contains water, electrolytes and bile acids (lipid emulsifiers)
- bile is released into gut: aids in lipid digestion & absorption
- bile pigments detoxify bilirubin (from hemoglobin breakdown) & carry it into gut for disposal
bile drainage system; what do bile canaliculi join, what cells are in bile canals, what is formed, fusing
- many bile canaliculi join the much larger bile canals which quickly drain into bile ductules
- bile canals and ductules lined by cuboidal or columnar epithelial cells called cholangiocytes
- form a complex network of channels that ends at the lobule periphery (part of portal triad)
- bile ductules fuse into larger bile ducts, then into hepatic ducts & finally into common bile duct: carries bile to gall bladder
organization of sinusoid wall; permeability, waht is the space called
Organization of Sinusoid Wall
* sinusoid wall very permeable; endothelial cells have large fenestrations and cell-cell gaps
* obvious space between basal region of endothelium and surface of hepatocytes: perisinusoidal space (space of Disse;
other liver cells; types, what they look like, function
Kupffer cell (stellate macrophage):
* elongated macrophage found within sinusoid lining
* recognize & phagocytize aged erythrocytes: frees heme & iron for
reuse or storage in ferritin complexes
* remove bacteria/debris present in portal blood
* antigen presentation to immune system
Ito (hepatic stellate) cells:
* modified pericyte with small lipid droplets found within perisinusoidal space
* store vitamin A & other fat soluble vitamins
* produce ECM components (role in fibrosis) and cytokines that regulate
Kupffer cell activity
liver lobule arrangements
classic hepatic lobule
* area drained by one central venule/vein
* circumscribed by connective tissue connecting portal triads (arrowheads)
* blood flows towards central venule; bile flows towards portal triads
~centrilobar zone: region closes to lobule middle- sees blood last
~periportal zone: region at periphery of lobule- sees blood first
portal lobule
* area draining bile into one portal triad
* hepatocytes from 3 ‘classic’ lobules all contribute bile to one ‘portal lobule
hepatic acinus
* reflects flow of oxygenated/nutrient rich blood
* blood from each portal area supplies cells in two or more classic lobules
* major activity of hepatocyte is determined by its location along the
oxygen/nutrient gradient
* zone I cells get most O 2 & nutrients; also most toxins
* zone III cells get lowest O 2 & nutrients; fewer toxins
* cells show metabolic activity reflective of location in acinus:
~zone 1 cells have highest metabolic
rate: highest glycogen storage/
utilization
~zone 3 cells 1 st to die of ischemia;
last to give up energy stores; most
lipid accumulation
liver damage and regeneration; capacity, proliferation, cells, chromic damage, poor blood perfusion
~liver has superior regeneration capacity: cell and tissue damage
triggers mitosis of remaining healthy hepatocytes: compensatory hyperplasia
- proliferation restores normal architecture & function
- liver also contains stem cells (oval cells) which generate both
hepatocytes and cholangiocytes - chronic damage/infection can lead to fibrosis/scar tissue: cirrosis
interferes with exchange between blood and hepatocytes
leads to systemic disease (clotting disorders, edema, jaundice, etc.) - poor blood perfusion of liver can induce centrilobular necrosis
(cardiac cirrosis)
hepatocytes in acinar Zone III most affected- undergo ischemic
necrosis with little fibrosis or regeneration
gallbladder; shape, how is it formed, emptying, release
- hollow, pear shaped organ attached
to lower surface of liver (lacking in
some species) - bile ducts in liver gradually merge to
form common hepatic duct that joins
cystic duct from gallbladder and
continues as common bile duct - common bile duct empties together
with main pancreatic duct into
duodenum - bile concentrates during storage due to selective uptake of water
- in response to fatty acids in duodenum lumen, cholecystokinin
released from enteroendocrine cells: gall bladder contraction
gallbladder histo; folds, epithelium, whats not present, ruminant feature, orientation, what is it covered by
- wall is highly folded mucosa
(accommodates volume changes): folds can resemble glands! - simple columnar epithelium &
lamina propria-submucosa of
loose connective tissue; no
muscularis mucosae - may be glands in CT: ruminants
- relatively thick muscularis; smooth
muscle cells oriented in all directions - covered by external adventitia
(against the liver), or serosa (where
exposed to abdominal cavity)
gallbladder ultrastructure; epithelium, complexes, mitochondira, apical regions, pumps
- epithelium columnar with abundant, short microvilli
- well developed apical junctional
complexes create barrier between luminal space & intercellular compartment - mitochondria localized to apical
and basal cytoplasm; complex
lateral folds - cells contain Na+/K + ATPase in
lateral membranes: water resorption - apical regions of cells contain mucus granules; more with damage or inflammation
gallbladder pathology; excess concentration leads to what, supersaturation, hypomotility, what do gallstones lead to, what can it affect
- excessive concentration of bile (mostly due to excessive production
of bile salts) can lead to formation of choleliths (gallstones) - most are bile supersaturated with cholesterol; can also have ‘pigment’ gallstones from excess billirubin
- hypomotility of gallbladder and subsequent bile stasis also can lead to cholelith formation
- gallstones can lodge in neck of gallbladder leading to painful
inflammation (cholecystitis) - can affect pancreas or liver; can cause perforation
