Liver, Gallbladder, and Pancreas Flashcards
what are the extramural organs of the digestive system?
liver and pancreas
what organ is considered the digestive system’s storage organ?
gallbladder
What are the endocrine functions of the liver?
synthesis and release of products into the blood (ie: plasma proteins)
what is the exocrine function of the liver?
production of bile
what is the largest gland in the body?
the liver
what is the parenchyma of the liver?
organized plates of hepatocytes separated by sinusoids
what type of tissue is found in the fibrous stroma of the liver?
type I collagenous tissue
what does the fibrous stroma of the liver do?
forms a thin capsule that surrounds vessels and ducts and provides some separation into lobules
what is the function of the reticular stroma? what type of tissue is found here?
provides a supporting network for the hepatocytes and sinusoids; formed by reticular fibers
What enters that the liver hilus? what exits?
blood vessels enter, bile duct exits
what percent of afferent blood is carried by the portal vein?
75%
what type of blood does the portal vein carry? what is it rich/poor in? where does the blood come from?
carries afferent blood that is rich in nutrients (and some potential toxins) but poor in oxygen;
it comes from the capillary beds of the intestines
What type of blood does the hepatic artery carry? what is it rich/poor in? where does the blood come from
carries afferent blood that is rich in oxygen;
comes from the left ventricle of the heart
what percentage of afferent blood is carried by the hepatic artery?
25%
Describe Hepatic blood flow:
- Portal vein picks up blood from capillaries / hepatic artery gets blood from Left ventricle and carries it to:
- Interloular branches
- sinusoids
- central vein
- sublobular veins
- Hepatic veins
- Inferior vena cava
- Right atrium
How does Bile exit the liver? where is it produced? how does it flow in relation to blood?
Bile is produced by the hepatocytes in the liver and flows out of the liver via a duct system that follows the arterial tree towards the hilus;
bile flows in the opposite direction as blood
Describe the anatomic/classic lobule
hexagonal lobules that contain radial arrays of plates of hepatocytes
what is each anatomic lobule centered around? what borders each corner?
centered around a central vein;
bordered at each corner by a portal canal (portal triad + CT)
What does a portal canal consist of?
portal triad + CT
what does a portal triad consist of?
interlobular branches of portal vein, hepatic artery, and bile duct
Where do the terminal branches of the portal veins and hepatic arteries run?
between lobules;
Where do terminal branches of the portal veins and hepatic arteries empty their blood into?
empty blood into sinusoids where the blood is mixed
Where do the hepatic sinusoid run? where do they carry blood to?
run between the plates of cells; carry blood to central vein (terminal hepatic venule)
what flows through the intercellular canaliculi? where does this substance flow after the intercellular canaliculi?
Bile;
flow: intercellular canaliculi – canals of Hering – interlobular bile ducts
what does the portal lobule center on?
the bile ductule
what does the portal lobule contain?
parts of 3 adjacent anatomic lobules, including any hepatocytes that supply bile to a particular bile ductule in the portal canal
What is a liver acinus? what is it’s main focus? what is another name for the liver acinus?
its a functional lobule that focuses on the delivery of blood to hepatocytes;
aka “Rappaport’s lobule”
is the liver acinus capsulated?
no
What is the liver acinus organized around?
an axis containing the terminal branches of the portal vein and hepatic artery
what does the liver acinus include?
any hepatocytes that are supplied with blood by a particular set of terminal branches that run between the two lobules
Describe how the hepatocytes receive blood in the Rappaport lobule
the cells in the center of the lobule (zone 1) are the first to receive oxygen, nutrients, and toxins; then Zone 2, then Zone 3 which is adjacent to the central vein
Which zone of the rappaport lobule is most prone to hypoxia?
zone 3; it is last to be affected by incoming agents and exposed to relatively low oxygen levels
where is the nuclei located in hepatocytes?
centrally
Are hepatocytes bincucleate? polypoid?
both!
What do hepatocytes border?
- border on sinusoids with intervening space of disse into which microvilli project
- Bile canaliculi
what are bile canaliculi? what are they formed/sealed by?
channels that are formed by the plasma membrane of adjacent hepatocytes and are sealed off by junctional complexes
what organelles/ inclusions are prominent in hepatocytes?
- rER
- sER
- Golgi
- lysosomes
- peroxisomes
- GLYCOGEN INCLUSION
can hepatocytes regenerate?
yes, but new cells do not establish proper relationships
What are the functions of the hepatocytes?
- Synthesis of plasma proteins (by rER)
- Detoxification of lipid soluble drugs/steroids
- Fat Metabolism
- Glycogen synthesis, storage, and release
- Storage of iron
- Metabolism of alcohol
- Production of bile
- Metabolism of vitamin A,D,E
What plasma proteins are produced by the rER of Hepatocytes?
albumin, fibrinogen, prothrombin, and coagulation factors
where are plasma proteins in the hepatocytes released?
into the space of Disse
How are lipid soluable drugs and steroids detoxified in hepatocytes?
hepatocytes transform nonpolar compounds into polar metabolites that can be eliminated by the kidneys
How are hepatocytes involved in Fat metabolism?
- Chylomicra undergo lipolysis in the circular and deliver fatty acids to tissues, but the remnants are taken up by hepatocytes and metabolized. The fatty acids are esterified to triglycerides by the sER
- some triglycerides are stored as fat droplets; most are coated with a mixture of proteins, cholesterol and phospholipids and are released in the plasma as VLDL (very low density lipid) particles
what organelles/cellular components are involved with glycogen synthesis, storage and release in hepatocytes?
sER and cytosol
What is iron stores as in hepatocytes
ferritin or hemosiderin granules
How is alcohol metabolized in hepatocytes?
through the alcohol dehydrogenase (ADH) pathway, producing acetaldehyde and acetate
what does chronic intake of alcohol active? what does this produce?
activates the microsomal ethanol oxidizing system (MEOS) which produces acetaldehyde and an excess of oxygen radicals. **Reactive oxygen damages hepatocyte plasma membranes
What materials do hepatocytes produce/release that are necessary for the production of bile? what do these material join to form bile?
cholesterol, phospholipids, bile salts, glucuronide conjugated bilirubin from the hepatocytes join electrolytes and metabolites of drugs and heavy metals into bile canaliculi as bile
What in canalicular plasma membrane mediates bile excretion?
specific ATP dependent transporters
What is bile secretion dependent on? is it continuous?
bile secretion is continuous; with the rate dependent primarily on blood flow to the liver
What happens to unused bile salts?
they get reabsorbed by enterocytes and returned to the liver via the portal vein to be reused by hepatocytes
What vitamins are metabolized by the hepatocytes?
A D E
What are hepatic sinusoids?
discontinuous capillaries that lack a continuous basal lamina
What cells form the lining of the sinusoid?
- discontinuous endothelium (endothelial cells with large gaps)
- Kupffer cells
What are Kupffer cells? what are they derived from? what is their function?
“sinusoidal macrophages”
they are resident phagocytic cells that are derived from monocytes and function in the breakdown of aged RBCs
where are Kupffer cells found?
line the hepatic sinusoid; but they may also span the sinusoidal lumen
what is the space of Disse?
perisinusoidal space that surrounds the sinusoid
Where is the space of Disse located?
between the plasma membrane of hepatocytes and basal surfaces of endothelial cells and Kuppfer cells
What does the Space of Disse contain?
- microvillous projections of hepatocytes
- a few reticular fibrers
- Stellate cells
what are the hepatocyte’s stellate cells? where are they located?
= lipocytes + cells of Ito
located within the space of Disse
what is the function of the hepatocytes’s stellate cells?
store lipids and vitamin A
produce reticular fibers
What happens to stellate cells during liver cirrhosis?
they undergo trans-differentiation to myofibroblas-like cells and secrete large amounts of collagen and ECM into the space of Disse
Where is bile produced? secreted by? secreted into?
produced and secreted by hepatocytes into bile canaliculi
where do bile canaliculi course?
between hepatocytes within the lobule
Describe the flow of bile
- Produced/secreted by Hepatocytes to
- Bile canaliculi to
- intraloular bile ductules (canal of Hering) to
- interlobular bile ductules (within the portal canal)
- to larger intrahepatic bile ducts to
- R/L hepatic ducts
- to common hepatic duct
what are the canals of Hering (intralobular bile ducts) lined by?
simple low cuboidal epithelium
what are the interlobular bile ductules lined by?
simple cuboidal epithelium as they collect bile, but then they increase in size are lined by columnar epithelium and are surrounded by increasing amounts of CT
what are the larger intrahepatic bile ducts lined by as the hilus is approached?
columnar epithelium and surrounded by dense fibroelastic CT and some smooth muscle
Describe the wall of the common hepatic duct
contains 4 layers: mucosa, submucosa, muscularis, and adventitia
where is most lymph formed in hepatocytes?
from the space of Disse
Describe the lymphatic flow in hepatocytes
lymph drains from the space of Disse to the periportal space of Mall to the lymphatic vessels (within the portal canals) to the larger vessels that parallel the bile passageways and leaves the liver
where is the periportal space of Mall located?
lies between the portal connective tissue and the hepatocytes at the border of the portal canal
What is the gallbladder?
distensible bag connected to the common bile duct via the cystic duct that concentrates and stores up to 50 mL of bile
Describe the surface of the gallbladder (empty and filled)
filled = smooth inner surface empty = numerous folds or rugae
What type of epithelium is found in the mucosa layer of the gall bladder?
simple columnar epithelium with apical microvilli and junctional complexes and lateral interdigitations
what is the function of the lateral interdigitations of the mucosa layer of the gall bladder?
transport ATPase in the membranes pump Na +, Cl-, and HCO3- and water resorption
What are the diverticulae (Rokitansky-Aschoff crypts) of the gall bladder? where are they found?
found in the mucosa layer; the surface epithelium may be invaginated as deeply as the muscular layer forming diverticulae
Describe the Muscularis Externa layer of the Gall bladder
multiple layers of smooth muscle separated by networks of elastic fibers
Describe the serosa/adventitia layer of the gall bladder
broad layer of the CT containing blood vessels nerves and lymphatics
what are the functions of the gall bladder?
- Store Bile
- Concentrate bile by absorption of water
- release bile during meal digestion
what are the layers of the gall bladder wall?
mucosa, muscularis externa, serosa/adventitia
How is bile concentrated in the gall bladder?
through the transepithelial transport of an isotonic fluid from the lumen to the vasculature:
ions (Na+) are pumped into intercellular lateral spaces and water follows
what happens to the interceullar spaces of the gall bladder when the bile is concentrated (active)
the intercellular spaces become distended in the active gallbladder (due to water being pumped into spaces with ions)
What is bile secretion stimulated by?
cholecystokinin (CCK) from the enteroendocrine cells in the duodenom
what does CCK do to the gall bladde?
induces contraction of its musculature and relaxation of the sphincter of oddi (sphincter of hepaticopancreatic ampulla)
How is the gall bladder different from the small I lamina propria?
GB: no mucosal glands
small I: mucosal glands are evident deep in the lamina propria (= intestinal glands = crpyts of Lieberkuhn)
How is the gallbladder different from the small I epithelium?
GB: 1. no goblet cells 2. microvilli not well developed
small I: 1. contain goblet cells 2. well developed microvilli (striated border)
What divide the pancrease into lobules? does it have a capsule?
no distinct capsule; delicate CT divides it into lobules
what cells carry out the exocrine function of the pancreas?
acinar cells
what cells carry out the endocrine function of the pancreas?
islets of Langerhans
What type of gland is involved with the exocrine function of the pancreas?
compound tubuloalveolar exocrine gland with serous alveoli
Describe the morphology and staining of pancreatic acinar cells (and why the areas stain the way they do)
= pyramidal cells that form a spherical acinus surrounding a lumen;
the basal (outer) cytoplasm is basophilic due to lots of rER the inner = eos. due to accumulations of acidophlic zymogen granules in the apical cytoplasm; granules contain a mixture of pancreatic proenzymes
what enzymes are the pancreatic enzymes?
proenzymes including typsinogen + chymotrypsinogen
what is the function of the pancreatic enzymes?
when active they can hydrolyze most food
what is trypsinogen activated by? where?
by enterokinase in the glycocalyx of enterocytes
what is the result of activated trypsinogen?
= trypsin, which in turn activates other zymogen (inactive) enzymes
what is secrete from the pancreatic acinar cells?
proenzymes including typsinogen + chymotrypsinogen
also lipase and amylase
Describe the duct system of the acinar cells in the pancrease
- intercalated ducts drain the acini
- which drain into larger intercalated ducts
- which drain into interlobular ducts
What drains the acini of the pancreas?
intercalated ducts
what is the epithelium found in the small intercalated ducts of the pancreas?
low simple cuboidal epithelium
what do the intercalated ducts extend as in the acini?
centroacinar cells
what epithelium is found in the large intercalated ducts of the pancreas?
simple cuboidal
what do the intercalated ducts produce?
a bicarbonate rich water secretion that drains into the extensive duct system (to later intercalated ducts then into interlobular ducts)
what epithelium is found in the interlobular ducts of the pancreas? where are the interlobular ducts located?
simple columnar epithelium; located in the CT septae
what are aciniar cell secretions stimulated by?
Cholecystokinin (CCK): from the enteroendocrine cells
Acetylcholine (ACh) from parasympathetic vagal fibers
what are the duct cells of the pancreas stimulated by? what is their function?
stimulated by SECRETIN to increase bicarbonate transport into the ductal lumen
what are the islets of Langerhans supplied by?
fenestrated capillaries
How do the islets of Langerhans stain (with respect to acini cells)
stain pale (light pink) around darker staining acini
What percent of the islets of langerhans are made up of Beta cells?
60-70%
where are Beta cells located in the islets of Langerhans?
in the center
what inclusion is unique to Beta cells
a crystalloid center that contains insulin
What are the steps of insulin PRODCUTION?
- Preproinsulin is synthesized in the rER
- The signal peptide is cleaved to form proinsulin (still in the rER)
- proinsulin is packaged into secretory vesicles in the golgi; in the vesicles a specific protease cleaves the C peptide from the A and B chains (which are held together by disulfide bonds), resulting in the formation of a mature insulin hormone and C peptide
what holds the A and B chains together in the formation of insulin?
disulfide bonds
What are the steps of insulin secretion?
- Glucose enters the Beta cell through the insulin independent gluoces transporter protein -2 (GLUT-2)
- Glucose undergoes glycolysis and the ATP that results inhibits the ATP-sensitive K+ channel
- This leads to membrane depolarization and opening of the voltage dependent calcium channels
- Resulting increase in cytoplasmic calcium triggers insulin to be released from the vesicles via exocytosis (MEROCRINE SECRETION)
what type of secretion is involved in insulin secretion?
merocrine secretion
What is insulins function in the uptake of glucose by muscle and adipose cells?
it translocates a glucose transporter (GLUT-4) from the golgi apparatus to its site of action in the plasma membrane
what stimulates glycogen synthesis in the liver hepatocytes?
insulin
What is type I diabetes caused by?
destruction of Beta Cells
what is type II diabetes caused by?
a deficiency in insulin receptor mechanisms
What percent of the islets of langerhans are made up of alpha cells?
15-20%
what do alpha cells contain?
larger dense cored granules containing GLUCAGON
when is glucagon released? what is the result of its release?
stimulated by LOW blood glucose; stimulates the metabolic breakdown of glycogen in the liver
What percent of the islets of langerhans are made up of Delta (D) cells?
5-10%
what do Delta cells secrete?
somatostatin and some gastrin
what is the function of somatostatin?
inhibits the release of other pancreatic hormones
What percent of the islets of langerhans are made up of PP cells (F cells)
3-5%
what do PP cells (Fcells) produce? what is its function?
pancreatic polypeptide; it self-reulates pancreatic secretions
