Lec 17/18 - Liver, Pancreas, Gallbladder

Question 1

functions of pancreas, liver, gallbladder

Answer 1

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

Question 2

pancreas; what does it produce, what does it look like, surrounded by what, separate from what, what is the duct and what empties

Answer 2

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

Question 3

exorine vs endocrine component of pancreas, what they synthesize and secrete and what they are

Answer 3

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

Question 4

pancreas; what does each acinus consist of, surrounded by, staining, what cell type isnt present

Answer 4

• 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

Question 5

pancreatic acinus cells, what they look like and what they do/whats in them

Answer 5

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

Question 6

pancreatic acinus; how are zymogen granules released and what do they contain (5)

Answer 6

• 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)

Question 7

pancreatic tissue; how autodigestion is prevented, what is the trypsin activator called and where is it, what is it copackaged with, pH

Answer 7

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

Question 8

liver; covered by what, what is the thick part and what do you fine there, blood supply, main digestive function, interphase, synthesis

Answer 8

• 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

Question 9

how is the parenchyma organized

what occupies the space between hepatocytes

Answer 9

• 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

Question 10

hepatic lobule; what species are boundaries obvious, what is in the portal triad, blood flow, portal vs hepatic artery

Answer 10

• 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)

Question 11

hepatic lobule CT; what type of collagen, provides support for what, blood flow and bile flow

Answer 11

• 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

Question 12

hepatocytes; size, appearance, main exocrine function, reason for staining

Answer 12

• 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

Question 13

hepatocyte function

Answer 13

• 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

Question 14

hepatocyte ultrastructure; what is there extensive amounts of, what is stored in the cytoplasm, what is the outside associated with

Answer 14

• 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

Question 15

how are hepatocytes held together, what is created, what is bile secreted by

Answer 15

• ‘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

Question 16

fate of bile acids, what does bile consist of, bile function, what do bile pigments do

Answer 16

• 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

Question 17

bile drainage system; what do bile canaliculi join, what cells are in bile canals, what is formed, fusing

Answer 17

• 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

Question 18

organization of sinusoid wall; permeability, waht is the space called

Answer 18

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;

Question 19

other liver cells; types, what they look like, function

Answer 19

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

Question 20

liver lobule arrangements

Answer 20

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

Question 21

liver damage and regeneration; capacity, proliferation, cells, chromic damage, poor blood perfusion

Answer 21

~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

Question 22

gallbladder; shape, how is it formed, emptying, release

Answer 22

• 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

Question 23

gallbladder histo; folds, epithelium, whats not present, ruminant feature, orientation, what is it covered by

Answer 23

• 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)

Question 24

gallbladder ultrastructure; epithelium, complexes, mitochondira, apical regions, pumps

Answer 24

• 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

Question 25

gallbladder pathology; excess concentration leads to what, supersaturation, hypomotility, what do gallstones lead to, what can it affect

Answer 25

• 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