Lecture B5, B6 Flashcards
liver is an organ associated with _____. size?
-the digestive tract
-largest internal organ
functions of liver
-exocrine and endocrine functions
-production of bile
-nutrients absorbed in small intestine are processed in liver before distribution through out the body
Bile function
needed for the emulsification, hydrolysis and uptake of fats in duodenum
75% of the blood entering the liver is _____ and comes from _____
-nutrient rich but oxygen poor
-portal vein (blood from stomach, intestines and spleen)
25% of the blood entering the liver is _____ and comes from _____
-oxygen rich
-hepatic artery
cells of liver
-hepatocytes (majority of cells in the liver)-> functional unit
-cholangiocytes (3-5%)
hepatocytes function
-synthesis and endocrine secretion of albumin, fibrinogen, apolipoproteins, transferrin into blood
-exocrine secretion of bile components
-converts a.a into glucose (gluconeogenesis)
-detox of toxins/drugs
-a.a deamination which make urea
-storage of glucose as glycogen (triglycerides as lipid droplets)
-storage of vitamin A & other fat soluble vitamin
-remove old erythrocytes by Kupffer cells (macrophages)
-storage of iron in ferritin protein
cholangiocytes function
-line bile ducts
-regulate composition and flow of bile
liver formation comes from this germ layer
foregut endoderm
liver formation: budding of ___ from ventral foregut endoderm contains ______
-diverticula
-multipotent progenitor cells
liver formation also involves ____ and ____ signaling in different domains of endoderm
BMP (ventral midline endoderm)
FGF2 (lateral endoderm)
Hepatoblasts expresses ___ leading to formation of liver bud
Hex
In response to FGF2 signaling, _______ induce genes required for hepatic cell fate
-two pioneer transcription factors FoxA (forkhead Box A) and GATA (Zinc Finger)
Hepatoblasts are ______
-bipotental cells (hepatic progenitor cells)
Hepatoblasts + ______ = Hepatocytes
-HGF (hepatic growth factor) signals from surrounding cells
Hepatoblasts + ______ = Cholangiocytes
Gradients of Notch, Wnt, EGF, TGFβ
Hepatocytes descr.
-large cuboidal cells/polyhedral cells
-large round nuclei
Hepatocytes express many TF: ______
-HNF4
-CD133- (prominin 1)
-EpCAM
Cholangiocytes descr.
-cuboidal cells in smaller bile ducts
-columnar cells in larger ducts
Cholangiocytes express many TF: ______
SOX9
CD133+
EpCAM+
Liver is composed of _____ (basic functional units of liver) in which hepatocytes form ______
-small hepatic lobules
-hundreds of irregular plates arranged radially around a small central vein
hepatic sinusoid runs between ______
plates of hepatocytes and drain into central vein
Hepatocytes plates contain the portal triad between the lobules: ______
-venule branch of the portal vein with blood rich in nutrient and low in oxygen
-arteriole branch of hepatic artery that supplies oxygen
-one or two small bile ducts of cuboidal epithelium that are branches of the bile conducting system
In the lives, blood flows past and over each _______
hepatocyte cord “bathed in blood”
hepatocellular structure allows for _____
bidirectional cell to plasma and plasma to cell transport
Hepatocytes has specialized apical and basal surfaces (distinct apical and basal side) to allow ______
-golgi trafficking/secretion, transcytosis (endocytosis then exocytosis in same cell) and receptor mediated endocytosis
Bile secreted from mature hepatocytes is exported sequentially through _____ surrounded by the apical membrane of neighboring hepatocytes, _______ , _________, and, finally, the _____
-bile canaliculi
-intrahepatic bile ducts
-extrahepatic bile ducts
-duodenum
Hepatocytes are highly _____ cells. Basolateral membrane faces the _____
-polarized
-fenestrated sinusoidal endothelial cells
Tight junctions between hepatocytes create ______.
Hepatocytes express _____
-canaliculus that surrounds each hepatocyte
-Ecadherin, but CD133-
Cholangiocyte (Bile ductal cells) form specifically around _____ & has high expression of ______
-portal vein
-Neural Cadherin and Ecadherin, CD133+
Canals of Hering provide the continuum between _____ and it is also the _______
-the hepatocyte canaliculus and the small bile ducts
-hepatic stem cell niche
Cholangiocytes are ______ closer to Canal of Hering and are considered _____
-less differentiated
-progenitor cells (repair and regeneration)
As we get farther from canal of hering ducts become _____
larger (larger cholangiocyte) & more differentiated with
distinct apical and basal domains
______ occurs in small and large bile ducts and determines the _______ across cholangiocytes
-Active biliary epithelial transport of electrolytes and solutes
-absorption or secretion of water
cholangiocytes has a _____ that acts as antennae like organelles to monitor _____
-primary cilium
-bile composition and flow
In hepatocytes, intracellular trafficking is specific to apical (____) and basolateral (______) membranes
-apical transporters/ATP binding cassette proteins
-GPI terminated proteins, basolateral targeted proteins
Hepatocytes arranged in ____ to fill the space between the central vein and portal vein => forms ____
- cords (plates)
-zones where specific functions runs in parallel
Zone 1 of hepatic lobule + functions
-aka peripheral zone
-closest to portal triad
-glycogenesis, fatty acids oxidation, urea synthesis, cholesterol synthesis occurs
Zone 2 of hepatic lobule + functions
-aka intermediate zone
-Sinusoidal capillaries carry oxygenated blood past hepatocyte to CV. Bile is secretion from the heptaocytes into the canicular channels and transported to IHBD.
Zone 3 of hepatic lobule + functions
-aka pericentral zone
-closest to CV
-glycolysis, lipogenesis, glutamine synthesis and bile acid
synthesis
cells in zone 1 are called _____
periportal
cells in zone 3 are called _____
pericentral
zones of lobule are ____ and are dependent on ____. This allows for ____
-dynamic
-gradient of Wnt, Hh signalling and hormones
-regeneration
oxygen gradient between zones
-highest in zone 1
-lowest in zone 3
Zonation of hepatic lobule is set up and regulated by ____
Wnt signalling and B-catenin
in hepatic lobule, B-catenin competes with ____ for ______
-Hnf4 (hepatocyte nuclear factor)
-binding of targets in the nucleus with Tcf/Lef
When zoning hepatic lobule for lipogenesis, ______
Hh signalling is also important
Hepatocytes in different zones appear ___ but _____
-homogenous but are different in terms of metabolic activity
WNT signalling in the zones
zone 3 (highest)
zone 1 (lowest)
Liver is unique as it is highly ____; Hepatocytes are the first to _____ during regeneration and produce ______ for other cell types
-regenerative
-enter the cell cycle
-mitogenic signals
Liver injury responses can be divided into two
groups: _____
1) activates facultative stem cells (not normally a SC - condition dependent) => hepatoycte form duct-like oval cells that have properties of both cells types
2) one that does not involve stem cells - just relgular tissue homeostasis
Facultative stem cells are activated if ______. Marked by _____
-injury severe enough or hepatocytes destroyed
-CD133, EpCAM, Sox9
Pancreas is an _____ organ
endocrine and exocrine
Pancreas produces and secretes ____
digestive enzymes and hormones
pancreas descr.
-elongated retroperitoneal organ, with a large head near the duodenum and more narrow body and tail regions that extend to the left
exocrine cells of pancreas (______) produce ______
-acinar cells
-digestive enzymes, which are secreted into tiny ducts that feed into the pancreatic duct
endocrine cells of pancreas (______) secrete ______
-islets of langerhans (clusters of cells)
-hormones such as insulin and glucagon directly into a capillary network, which also joins the
pancreatic duct.
pancreas is from this embryonic germ layer?
foregut endoderm
foregut endoderm + SHH+ = _____
intestine
foregut endoderm + SHH- = ____
pancreatic bud
pancreatic bud + NOTCH+ = _____
exocrine glands
pancreatic bud + NOTCH-/Ngn3 = _____
endocrine glands
pancreas formation: thickening of endoderm leads to _____. Then invagination of dorsal and ventral bud forms ____, part of which then forms _______
-proliferation of pancreatic progenitors
-tubes
-acinar, ducts, and endocrine cells
pancreas: Early endoderm specified and then undergoes extensive morphogenesis and transforms from a _______ to a _____ back to a _____. Branches emerge via ______ as opposed to extension of the bud. During this morphogenesis the epithelium form into distinct _____
-monolayer epithelial sheet
-stratified epithelial bud
-monolayer as it forms a tubular tree
-remodeling of the epithelium
-tip and truck regions
Pancreatic epithelium multipotent progenitor cels gives rise to _____ lineages; MPCs proliferate to make more tips and _____
-endocrine, exocrine and ductal
-bipotent trunk cells
Bipotent progenitor + low NOTCH + Ngn3 =
endocrine progenitors
Bipotent progenitor + high NOTCH =
ductal cells
ductal cells of pancreas expresses _____
Sox9, Hnf1B
mature iselts of pancreas are ____
vascularized and innverted
acinar cells expresses ____
PTF1-L complex
______ are the functional units of the pancreas and eroduce and secrete _____
-The secretory acini (exocrine)
-digestive enzymes
Acini (rounded secretory unit) are surrounded by ______ that is supported by a ____
-a basal lamina
-delicate sheath of reticular fibers with a rich capillary network
Pancreatic islets (Islets of Langerhans (endocrine) function of the pancreas involves _____
-primarily smaller cells located in variously sized clusters
Acini make up ____ of the pancreas.
-85-90%
Each acinus consists of ____
-several serous cells surrounding a very small lumen
serous cells of acinus descr.
-apical and basal side
-apini are pyramid-shaped cells oriented radially around a small lumen
-Apical zymogen granules (protein secreting)
-Round and basally located nuclei.
Each acinus is drained by a _____ . Initial cells of duct that extend into the lumen are the _____. This duct then merges with ______
-short intercalated duct (squamous or low cuboidal)
-centroacinar cells
-intralobular and larger
interlobular ducts
The centroacinar and intercalated duct cells secrete _____-
.
HCO3 − rich fluid that hydrates, flushes, and alkalinizes the enzymatic secretion of the acini
Acinar cells have abundant number of ____ and zymogen granules that can make _____
-RER (synthesis) and golgi (concentrating step)
-20 different digestive enzymes
Islets of the pancreas make up ____ of the
pancreas
- 1 to 2 %
Pancreatic islets are _____ embedded in the _____ . Clusters of _____ cells.
-clumped masses of pale-staining endocrine cells
-exocrine acinar tissue of the pancreas
-100 to 1000
The cells of islets are _____, and more lightly stained than the surrounding _____, arranged in ______
-polygonal or rounded, smaller
-acinar cells
-cords separated by fenestrated capillaries
α or A cells of islets does what?
secrete primarily glucagon and are usually located
peripherally
β or B cells of islets does what?
produce insulin (L. insula, island), are the most
numerous, and are located centrally.
δ or D cells of islets does what?
secreting somatostatin, are scattered and much less abundant
PP cells of islets does what?
secretes pancreatic polypeptide
pancreatic islet cell types
-α or A cells
-β or B cells
-δ or D cells
-PP cells
Glucagon, insulin and somatostatin act in a paracrine manner to ______
-affect hormone release in islet cells and nearby acinar cells
Epithelial cells usually organize their sensory and secretory functions to their ______ surface respectively
-apical and basolateral
B-islet cells localize their sensory and secretory functions to the ______ (displays ____)
-same location at the edges where two cells faces meet at a sharp angle) and vertices
-high levels of F-actin/E-cadherin
current evidence shows that pancreas does not have ___
SC pop’n
If injury to pancreas is severe enough differentiated cells can _____
-dedifferentiate and in some cases become more stem cell like and participate in injury repair
