Liver, Gallbladder, and Pancreas Flashcards
What makes up the parenchyma of the liver?
Organized plates of hepatocytes, separated by sinusoids (discontinuous capillaries)
What are the two parts of the stroma of the liver?
- Fibrous stroma - Dense irregular CT (Type 1 collagen) forming thin capsule around vessels, ducts, and provides some separation into lobules
- Reticular stroma - Type 3 collagen fibers providing supporting network for hepatocytes and sinusoids.
What is the portal vein’s contribution of blood and what type of blood is it?
75% of liver’s afferent blood. It is rich in nutrients, but relatively poor in oxygen because it comes from capillary bed in intestines.
What is the hepatic artery’s contribution of blood and what type of blood is it?
25% of liver’s afferent blood, rich in oxygen, coming from left ventricle of heart
What is blood flow in the liver, from portal vein / hepatic artery to IVC?
- Portal vein / hepatic artery
- Interlobular branches
- Terminal branches
- Sinusoids / discontinous capillaries
- Central vein
- Sublobular vein
- Hepatic veins
- Inferior vena cava
What is an anatomic or classic lobule? What is at the center? What is at each corner?
A hexagonal shaped lobule containing a radial array of plates of hepatocytes around a central vein.
At each corner: portal triad + connective tissue
What is a portal triad at the corner of the anatomic lobule?
Hepatic artery branch (interlobular), portal vein (interlobular), and bile ductule
What runs on the sides of anatomic lobules?
Between the hexagons, on the sides, are terminal branches of portal veins and hepatic arteries. They empty blood into the sinusoids, where the blood is mixed
What is the direction of bile flow in the anatomic lobule?
Opposite direction of blood.
- Intercellular canaliculi
- Canals of Hering
- Interlobular bile ducts
What is a portal triad + connective tissue called?
Portal canal
This is at the corner of the anatomic lobules
What is a portal lobule centered around? How many adjacent anatomical lobules?
It is centered around a bile ductule and emphasizes the exocrine function of the liver. This means it is the corner of a hexagonal lobule, and thus pulls from three adjacent anatomic lobules (corners are the central veins)
Triangle - 3 adjacent lobules
What is a liver acinus / functional lobule / Rappaport’s lobule centered around?
Delivery of blood to hepatocytes.
It makes a diamond shape from two triangles, with the base of the triangle being a terminal artery, and the apex of each triangle being the central vein of the anatomic lobule
What are the three zones of the liver acinus?
Zone 1: Center of lobule, closest to terminal artery - first to receive oxygen, nutrients, but also toxins
Zone 2: intermediate zone
Zone 3: Cells adjacent to central veins, last to be affected by toxins, but relatively low oxygen levels
What shape are hepatocytes / why are their nuclei weird?
They are large polyhedron cells, with centrally located nuclei. However, sometimes they are binucleate, and may be polyploid (multiple DNA copies)
What is the space between the hepatocytes’ plasma membrane and the sinusoid called? What is in it?
Space of Disse - microvilli from cell wall project into it
What are bile canaliculi?
Intercellular canaliculi formed on lateral surface of hepatocytes with adjacent cell’s plasma membrane. They transport bile?
What type of junction is used to form a bile canaliculi?
Zonula occludens
Occludin and claudin - ZO1-3
How can hepatocytes be identified by SEM?
They have well developed rER, sER, Golgi, lysosomes, and peroxisomes. However, their distinguishing characteristics would probably be the large central nucleus, + GLYCOGEN INCLUSIONS
What is the problem with liver cell regeneration?
They can regenerate, but new cells to not establish proper anatomical relationships with one another
What plasma proteins are released by hepatocytes and where are they released?
Albumin, fibrinogen, and coagulation factors all made in sER.
Released into space of Disse and flow into sinusoid from there
How does the liver detoxify lipid-solubel drugs and steroids?
Processes in smooth ER by transforming nonpolar compounds into polar metabolites, making them water-soluble. Thus, they can be excreted in the kidneys
How do chylomicra reach the liver / what do they do en route?
After being released into capillaries by enterocytes, they undergo lipolysis en route, delivering fatty acids to tissues. The remnants are taken up by hepatocytes and metabolized
What happens to chylomicra in the liver?
Fatty acids are esterified to triglycerides by sER. Some of these are stored in fat droplets, most are coated with proteins + cholesterol + phospholipid and are released into blood as VLDL (very low density lipid) particles which are easily used by cells
How is the sER of hepatocytes involved in sugar control?
Glycogen is synthesized and broken down in sER, in the meantime being stored as inclusions in the cytosol
How is iron stored in the liver?
As ferritin or hemosiderin granules in hepatocytes
How is alcohol processed by the liver and why is too much alcohol bad?
Small amounts are metabolized through alcohol dehydrogenase pathway, producing acetaldehyde and acetate.
Large amounts will activate the microsomal ethanol-oxidizing system (MEOS) which produces acetaldehyde and oxygen free radicals which can damage hepatocyte plasma membranes.
Where do hepatocytes synthesize cholesterol, phospholipids, and bile salts? What are the other components of bile?
Smooth ER. Keep in mind that bile salts can sometimes be used from enterocytes which uptook them in the intestines and sent them through the portal vein
Other components: bilirubin + glucuronide, electrolytes, metabolites of drugs, and heavy metals
How is bilirubin, the breakdown product of heme, put in the feces?
Bilirubin is conjugated with glucuronide to make it water-soluble. It is excreted with the bile and is actually the component which makes feces brown
How is bile secreted into intercellular canaliculi?
Via ATP-dependent transports in the canalicular plasma membrane
What is the rate of bile secretion dependent on? Why?
Since it is continuous, it is mainly dependent on the rate of blood flow to the liver
What vitamins do hepatocytes help metabolize?
A, D, and E
The fat soluble ones, minus K?
What are hepatic sinusoids and what two cell types line them?
Discontinous capillaries that lack a continuous basal lamina
- Discontinous endothelial cells
- Kupffer cells - resident phagocytic cells, derived from monocytes
Where are Kupffer cells found, and what is their function?
They span the sinusoidal lumen, and their function is to break down RBCs - this is the reason why you can survive a splenectomy
What are hepatic stellate cells? What is their function?
Also celled lipocytes or cells of Ito, they are located within the space of Disse
- Store lipids
- Store vitamin A
- Produce reticular fibers of the space of Disse and liver parenchyma
What happens in cirrhosis?
Also called fibrosis of liver, hepatic stellate cells undergo transdifferentiation into myofibroblast-like cells and release alot of collagen and extracellular matrix around them, decreasing liver function
What are canals of Hering? What is their epithelium?
Intralobular bile ductules with simple low cuboidal epithelium. They run with terminal arteries and collect from the intercellular canaliculi.
They drain bile into interlobular bile ductules.
What lines the interlobular bile ductules of the portal canal?
Simple cuboidal epithelium. It will become columnar as the ducts increase in size + amount of surrounding connective tissue
What are intrahepatic bile ductules? Where do they drain?
Larger ducts receiving bile from interlobular bile ductules, they have columnar epithelium surrounded by an increasing amount of connective tissue. They will have some smooth muscle in the connective tissue as well as they approach the hilus.
They drain into right and left hepatic ducts, which flow into the common hepatic duct
What layers does the common hepatic duct have?
Four layers: Mucosa, submucosa, muscularis, adventitia
What is the periportal space of Mall? Where does it drain?
The space receiving lymph drainage from the space of Disse. It lies between portal connective tissue and hepatocytes at border of portal canal.
From here, lymph drains into lymphatic vessels within portal canals (not included in portal triad). Lymph parallels bile passageways.
What is the difference in histologic appearance between filled and empty gallbladder?
Filled - smooth inner surface
Empty - Numerous folds or rugae
What defines the epithelium and mucosa in general of the gallbladder wall (in mucosa)?
Simple columnar epithelium with apical microvilli and junctional complexes.
Cells have interdigitations with transport ATPases for pumping ions (Na+, Cl-, and HCO3-), and water absorption.
Lamina propria richly vascularized with fenestrated capillaries
How does the mucosa of the gallbladder wall differ from intestinal mucosa?
- No muscularis mucosa
- No goblet cells in epithelium
- Microvilli not as developed as in enterocytes
- There are deep invaginations of surface epithelium
- There are no mucosal glands
What lies outside the mucosa of the gallbladder?
Muscularis externa - multiple layers of smooth muscle supported by elastic fibers
Serosa / adventitia - connective tissue with blood vessels, nerves, and lymphatics
There is no submucosa in the gallbladder
What are Rokitansky-Aschoff crypts?
Invaginations of the epithelium which may go as deep as the muscularis externa layer
What is the function of gallbladder?
- Stores up to 50 mL of bile,
- Concentrates bile by absorption of water by same mechanism as intestines (sodium follows), (intercellular spaces become distended in active gallbladder)
- Releases bile during meal digestion in response to CCK
What produces CCK and what does it induce?
Cholecystokinin is produced by enteroendocrine cells in the duodenum, inducing contraction of gall bladder musculature and relaxation of sphincter of Oddi
What is the sphincter of Oddi?
The sphincter opening the hepatopancreatic ampulla into the duodenum
Does the pancreas have a capsule? How are the lobules divided?
It has no distinct capsule, delicate connective tissue divides the lobules.
What type of gland is the exocrine pancreas?
Compound tubuloalveolar exocrine gland with serous alveoli
What are pancreatic acinar cells and what are their cellular characteristics?
Pyramidal cells that form a spherical acinus surrounding a lumen for exocrine pancreas.
- Basal cytoplasm is basophilic due to rough ER
- Apical cytoplasm is acidophilic due to zymogen granules (pancreatic proenzymes)
What are the four main pancreatic enzymes released by pancreatic acinar cells?
Proenzymes: 1. Trypsinogen 2. Chymotrypsinogen Enzymes: 3. Lipase 4. Alpha-amylase
They hydrolyze the foods we eat
How is trypsinogen activated and what is its function?
Activated by enterokinase in the glycocalyx of enterocytes. It can activate other zymogens like chymotrypsinogen.
What are centroacinar cells?
Lightly staining cells of the intercalated ducts which can be found in the center of pancreatic acini. They do not have a secretory function
What is the duct progression of the exocrine pancreas - name + epithelium
Acini drain into:
- Intercalated duct - simple low cuboidal
- Intralobular intercalated duct - simple cuboidal
- Interlobular ducts - simple columnar + connective tissue
- Main duct
What stimulates the acinar cells of the pancreas to release produce?
- Cholecystokinin release from enteroendocrine cells in duodenum
- Acetylcholine - from parasympathetic fibers from vagus
What is the special function of pancreatic ducts and what enhances this function?
They produce a bicarbonate rich watery secretion
Enhanced by secretin, produced by enteroendocrine cells in duodenum, responding to too low of pH
What are islets of Langerhans and where are they found? How do they stain?
The functional unit of the endocrine pancrea. Found among acini of exocrine pancreas, supplied by fenestrated capillaries and surrounded by delicate connective tissue.
They are pale-staining by H&E
What are the four types of cells in the islets of Langerhans? What is their relative abundance?
- Alpha cells - 15-20%
- Beta cells - 60-70%
- Delta cells - 5-10%
- PP cells (F cells) - 3-5%
What is the function of pancreatic Beta cells?
Produce and release insulin, they have crystalloid centers which contain it
How is insulin produced?
- Preproinsulin is released in rough ER
- Signal peptide is cleaved to form proinsulin in rough ER
- Packaged into secretory vesicles in Golgi
- Within these vesicles, a protease cleaves C peptide from A and B chains which become held together by disulfide bonds.
Mature / activate insulin + C peptide will be found in this vesicle
How is insulin released?
- Glucose diffuses into beta cell via GLUT-2 transporter (insulin-independent)
- Glucose undergoes glycolysis, increasing cellular ATP.
- ATP surge inhibits action of an ATP-dependent potassium transporter, depolarizing the membrane
- Depolarization triggers Ca+2 channel to open, resultant influx triggers insulin release by exocytosis
- Insulin is released by merocrine secretion
What are the two functions of insulin?
- Causes translocation of glucose transporter (GLUT-4) from Golgi apparatus to plasma membrane of muscle and adipose cells, allowing them to uptake it.
- Stimulates glycogen synthesis in liver hepatocytes
What do Alpha cells produce and what is the function of their product?
Larger, dense granules are produced here containing glucagon
Glucagon: stimulates breakdown of glycogen in liver in response to low blood glucosa
What do Delta cells produce and what is the function of their product?
- Somatostatin - inhibits release of other pancreatic hormones
- Gastrin - increase parietal cell production of HCl (only small amount of this)
What do PP or F cells produce and what is the function of their product?
Pancreatic polypeptide - self-regulation of other pancreatic secretions, not well understood
