Lecture B3, B4 Flashcards
Digestive system parts: _____
The digestive tract: Oral cavity, esophagus, stomach, small and large intestine, anus
Associated Glands: salivary glands, liver, pancreas
digestive system comes from which germ layer?
endoderm
endoderm forms ______
foregut, midgut (small intestine), hindgut (colon)
endodermal cells form a _____ which molds into an epithelial tube surrounded by _____. This process requires many different signaling pathways and multiple transcription factor genes encoding proteins involved in ____
-polarized sheet
-mesoderm
-adhesion, the cell cycle and differentiation
Signaling pathways that regulate differentiation of the
different areas of the digestive tract
-Wnt/FGF4,BMP from mesoderm (increases down the digestive tube)
Four main layers of small intestine
- Mucosa (mucous membrane): Epithelial lining, Lamina propria – loose connective tissue, Rich in blood vessels, Thin smooth muscle layer (muscularis mucosae)
- Submucosa, connective tissue, links to underlying muscle layers
- Muscularis: inner layer (circular), outer layer (longitudinal)
- Serosa: outermost layer connective tissue, blood vessels, adipose
Mesentery surrounds the _____ and suspends them from _____
-stomach, small and large intestine
-the abdominal wall
Movement of nutrients from the lumen of small intestine to be absorbed into the bloodstream happens across the _____. Transcellular transport requires: (2)
-epithelial cells
-Membrane transport proteins in the apical surface (active
transport) & the basolateral surface (facilitated diffusion)
the small intestine folds ____ to create _____
-mucosa and submucosa (epithelial lining)
-dense apical fingerlike projections called villi to increase absorptive area
villi are covered by _____ and contain ____
-columnar epithelial cells
-goblet cells and absorptive enterocytes
each villus is connected to _____ which contains ____
-the lamina propria
-the capillary network
enterocyte/absorptive cell has ____ to increase absorption
-dense microvilli (brush border) on apical surface
circular and longitudinal muscle layers of small intestine are responsible for ____
peristalsis
SC of intestine is marked by ____ and differentiates into ___ then into _____
-LGR5+
-TA cells
-enterocytes, goblet cell, tuft cell, enteroendocrine cell, paneth cell
SC of intestine & paneth cells are in _____ and move up the villus when differentiating
-crypts
BMP signalling increases _____
up the villus
WNT signalling increases _____
down the villus (in the crypt)
WNT signalling in villi does what? Notch? BMP? Hh?
-maintains ISCs, Paneth cells
-differentiation of enterocytes
-differentiation of enteroendocrine cells, keeps stem cell from dividing too much
-Sense epithelial integrity
Niche of ISC
-ECM
-Signaling molecules
-Basement membrane
-Physical factors
-Paneth cells support intestinal stem cells (ISCs) via secretion of Wnt, Notch (DLL) and EGF
After injury to intestine, Progenitors and also enterocytes can dedifferentiate into ______
-LGR5+ intestinal stem cells (ISCs) through WNT-mediated niche signals
absorptive intestinal surface forms from ____ signalling (2) + function
-Wnt5 (Highly proliferative during tube elongation -> cells grow in height just prior to villi formation)
-Hh (Villi emergence)
after Hh signalling, cells at tip of villus transition have ______ while cells are inter-villi region remain _____
-simple columnar structure (expanding apical surface)
-pseudostratified
selective absorption of intestine requires _____, giving the gut structure to resist sheer forces in the tube
TJ, AJ, Desmosomes, Hemidesmosomes
what we know about microvilli (3)
-They are dynamic – always recycling actin filaments.
-their structure and the role of actin and actin binding proteins.
-Ezrin plays an important role.
defects in villi formation or structure causes this disease?
Celiac disease
Microvilli are made of _____
- bundles of actin filaments
-Actin binding accessory proteins like Myosin delivers components
-Actin filaments insert into Terminal web or intermediate
filaments
-Formin and other proteins cap F-actin at the top
Microvilli formation during enterocyte differentiation
-Microvilli initially appear as small membrane buds on apical surface
-Protrusions self organize into distinct clusters mediated by adhesion between distal tips
-Distal Tip adhesion promotes packing of bundles together to form an organized structure
-actin filament cores attach to actin binding bundling proteins (fimbrin, villin, espin) and are cross linked to apical membrane by Ezrin
enterocytes absorb _____
lipids, proteins, sugar components
lipid absorption by enterocytes
-Hydrolyzed lipid components enter the cell by passive diffusion
-lipids accumulate in SER then fatty acids are resynthesized as triglycerides
-TGs are processed through the RER and
Golgi and covered in a thin protein layer to form chylomicrons (larger lipid droplet) near the nucleus
-These are exocytosed from the lateral membrane
sugar absorption by enterocytes
-Secrete disaccharidases into the glycocalyx (ECM)
-Hydrolyses disaccharides into monosaccharides
-monosaccharides are actively transported across microvilli and deposited in the underlying capillaries (sodium dependent)
protein absorption by enterocytes
-Secrete peptidases into the glycocalyx (ECM)
-Hydrolyses dipeptides into monopeptides
-monopeptides are actively transported across microvilli and deposited in the underlying capillaries
Goblet cells are essentially _____
a single cell gland (merocrine)
Goblet cells descr.
-Secretory vesicles filled with mucin/mucin2 (glycoproteins)
-interspersed amongst enterocytes
-nuclei and organelle in bottom part of the cell
mucus produced by goblet cells acts to protect and lubricate the ____
- lining of the intestine
Enteroendocrine Cells have varying numbers along _____
-length of small intestine
enteroendocrine cells secrete _____
-various peptide hormones that coordinate food ingestion and nutrient ingestion
Enteroendocrine Cells descr.
-Constricted apical surface with microvilli that contact the intestinal lumens
-Can also have open top in contact with lumen
-has chemoreceptors which determine levels of nutrients and regulate release of peptide factors/enzymes, signal to nerves, smooth muscle
paneth cells function
-Release lysozyme, Phospholipase A, Defensins that Bind and break down walls of microorganisms and
bacteria
-part of Innate Immunity
-regulate microenvironment of small intestine
paneth cells descr.
-Exocrine cells
-eosinophilic secretory granules in apical cytoplasm
Tuft cells descr.
-act as sentinels to alert the innate immune system of the presence of parasites, initiating a T helper cell immune response against them
Functions of Kidney
-regulate balance of water and electrolytes
-excretion metabolic wastes/bioactive substances to bladder through uteters
-secretion of renin (protease the regulates blood pressure)
-secretion of erythropoietin (glycoprotein GF) to increase RBC production
-conversion of vitamin D to active form
-gluconeogenesis during starvation
kidney development comes from 4 key progenitor cell types: ________
-nephron progenitors, ureteric progenitors, endothelial progenitors and stromal progenitors
kidney development steps
- In response to signals from ureter epithelium the
mesenchyme forms a cap around the ureteric tip - Signals from the mesenchyme cause the ureter tip cells to undergo branching morphogenesis to form the collecting ducts and ureter
- Under WNT signaling, cap mesenchyme aggregate and
condense then undergoes a mesenchymal to epidermal
transition to form nephron progenitors (renal vesicle)
Each kidney contains ____ functioning units called ____ which originate in ____
-1 to 4 million
-nephrons
-the cortex
Each nephron contains a ____ and a long simple epithelia _____
- corpuscle
-renal tubule with 3 parts
The renal corpuscle surrounds a tuft of _____
-glomerular capillaries
Renal tubule parts
- proximal convoluted tubule which enters the medulla
- loop of henle which contains thin descending and thick ascending limb
- distal convoluted tubule in cortex with connecting tubules and collecting ducts that empty into the calyx
PCT features? location? major function?
-simple cuboidal epithelium, lots of mitochondria, tall microvilli, basal membrane invaginations
-cortex
-reabsorption of nutrients, water, proteins & secrection of H+, NH4+
Thin limb of loop of henle features? location? major function?
-simple squamous epithelium, few mitochondria
-medulla
-passive reabsorption of Na+ Cl-
Thick limb of loop of henle features? location? major function?
-simple cuboidal epithelium, no microvilli, many mito.
-medulla
-active reabsorption of various electrolytes
DCT features? location? major function?
-simple cuboidal epithelium, basal membrane invaginations, short microvilli
-cortex
-reabsorption of various electrolytes
cells of collecting system + function
-principal cells (most abundant) : regulated secretion of K+
-intercalated cells: reabsorption of K+, regulation of acid-base balance
-transitional cell: between those cell rype
glomerular podocyte descr.
-polarized cells with large central body from which primary processes project into foot processes
CNT descr.
Less extensive basolateral invaginations, fewer
mitochondria
interstitial fibroblast descr.
In cortex and medulla, long processes, produce proteins
(extensive ER)
Distal Convoluted tubule (DCT) divided into _____. Cells have extensive ______
-early (DCT1) and late (DCT2)
-basolateral membrane invaginations and high numbers of mitochondria
Connecting tubule (CNT) is just downstream of ___. Cells have less extensive ______
-DCT
-basolateral membrane invaginations and fewer mitochondria
In chronic kidney disease, ____ of CCD are lost , marked by an increase in ___ signalling that converts _____
-intercalated cells
-NOTCH
-intercalated cells into principal cells
The interconversion of intercalated cells and principal cells via a transitional cell type is regulated by _____
NOTCH signalling
Transcellular transport (def.)
highly regulated transport through cell; both apical and basal membrane
-either passive down a conc gradient or active against conc gradient and needs ATP & transport proteins in membrene
Paracellular transport (def.)
-transport across epithelium between cells
-passive down a conc gradient by diffusion or convection
-not tightly regulated
-unselectibe (based on size and charge of molecule)
-rate limiting barrier is tight junction
combination of different claudins proteins in TJ are essential in _____
-structure and function of renal tubules
glomerular capsule contains ____
capillaries and podocyte cells
blood enters the glomerulus via ____ arterioles
afferent
blood leaves the glomerulus via ____ arterioles
efferent
layer of the capsule is made of podocytes which cover each capillary forming _____
slits between interdigitated processes called pedicles
filtrate is produced in renal corpuscle when _____
blood plasma is forced through filtration slits formed by pedicles under pressure
The glomerular filtration barrier has 3 parts: ______
-The fenestrated capillary endothelium
-The Glomerular basement membrane (GBM)
-The filtration “slit diaphragms”between pedicels.
glomerular filtration barrier is formed by the fusion of ______
-basal lamina of a podocyte and a capillary endothelial
cell (GBM)
capillaries in glomerulus are ____
fenestrated
The _____ of podocytes contains the pedicels (foot processes that bind the GBM)
-basal domain
Endothelial slit fenestrations are _____ wide
-60 to 80 nm
GBM (300-360 nm) is the ECM containing macromolecules such as _____. Formed by fusion both the ____. Functions to separate the _____
-Laminin , collagens, fibronectin
-podocyte and capillary basal laminae
-blood from the capsule space
Filtration slits between the interdigitating pedicles are _____ wide which allows for filtration of the blood and retention of ______
-25 to 30 nm
-plasma proteins
podocyte proteins that contribute to slit structure include ______
nephrin, Neph1, podocin, ZO1, CD adaptor protein a, Fat and Pcadherin
Slit diaphragm formation requires ____
junction proteins
slit diaphragm complex links to ____
intracellular actin cytoskeleton which allows for remodeling of podocyte structure and function
____ forms the structural framework of podocytes
actin cytoskeleton
podocytes sits on GBM through ____
intergrins
______ are podocyte progenitors
-Parietal epithelial cells (PECs)
Parietal epithelial cells express stem cell markers _____ + and transcription factors ____
-CD24, CD133
-Oct4 and BmI-1
PEC are located where? & do what?
-located at urinary pole (renal tubule) which leads to PCT- -divide and produce progenitors that migrate slowly around the capsule and eventually replace lost or damaged podocytes
