block II (epithelium) Flashcards
From which germ layers does epithelium derive, embryologically?
Ectoderm, mesoderm and endoderm
Does epithelium have large amounts of extracellular matrix?
No, small amount
By what is epithelium composed?
Sheets of contiguous cells bound together by lateral junctional complexes
What is the purpose of the basement membrane in epithelium?
separate epithelium from adjacent connective tissue by a non-cellular layer (basement membrane
are cells in epithelium polarized?
Yes, polarized both functionally and morphologically (Apical, lateral, basal surfaces with different properties)
Does epithelium have a free border?
Yes
What is epithelioid?
A structure of a tissue similar to epithelium but that doe snot contain a free border. (not epithelium)
Describe the vascularity of epithelium
Avascular, if there is blood present, it comes from the connective tissue.
Identify type of epithelium
Small intestine epithelium
Identify type of epithelium
Tracheal epithelium and we can see the basement membrane
mention the function of epithelia
- Cover and line surfaces to provide protection/barrier
- Secretion
- Absorption
- Transport along epithelial surface
- Selectively permeable barrier
- Transcellular transport
- Sensory reception
- Contractility
Provide examples of the function of epithelia that Cover and line surfaces to provide protection / barrier
Skin is an example of an epithelium that provides protection to prevent water loss, to provide protection against abrasion, and protects the body against UV irradiation.
Provide examples of the function of epithelia that serves for Secretion
(both ducts and parenchyma): (e.g. glands- sweat, mucus, enzymes, hormones, stomach, small intestine).
Goblet cells play a key role secreting mucus into the epithelium
Provide examples of the function of epithelia that serves for absorption
small intestine: absorption in lumen.
kidney tubules: protourine to transform into final urine
Provide examples of the function of epithelia that serves for selectively permeable barrier
endothelium provides selectivity by selecting which components can enter or exit
Provide examples of the function of epithelia that serves for transcellular transport
intestinal lining - IgA, endothelium of blood vessel - pinocytosis) In IgA- is transported by vesicles into the lumen for immonulogic factors.
in pinocytocis it move cells by vesicular transport.
Provide examples of the function of epithelia that serves for sensory reception
neuroepithelium - taste buds, retina, inner ear) for sensory stimuli
Provide examples of the function of epithelia that serves for contractility
myoepithelial cells - glands; like sweat glans move secretion by contraction
Provide examples of the function of epithelia that serves for transport along epithelial surface
via cilia - oviduct, trachea) In the trachea for moving mucus along the surface
Identify the tissue and the function
Section through the epidermis of skin; provide protection/barrier
Identify the tissue and the function
Small epithelial cells; goblet cells for secreting mucus into epithelium and absoprtion in lumen and protourine.
Identify the tissue and the function
Tracheal epithelium; move mucus along the surface
Identify the tissue and the function
Micrograph of venule;
selective permeable barrier and transcellular transport
Identify the tissue and the function
Diagram and photomicrograph of a taste bud
and its component cell types ; sensory reception
Identify the tissue and the function
Secretory Portion of eccrine sweat Gland with myoepithelial cells (dark pink); contractility
Epithelia are broadly classified as:
Surface epithelia
Glandular epithelia
specialized epithelia
What are surface epithelia?
Those epithelia which line the general body
surfaces and lumens of organs
What is glandular epithelia?
Those epithelia forming the secretory portion of exocrine and endocrine
glands
What is specialized epithelia?
Epithelial cells specialized as sensory receptors or transducers such as in olfactory and optic systems
identify structure and classification
Specialized epithelia; epithelium lining pancreatic duct
identify structure and classification
Glandular epithelia; pancreatic acinar cells
identify structure and classification
Specialized epithelia; olfactory epithelium
What are goblet cells?
unicellular mucus secreting cells
hOW IS EPITHELIA CLASSIFIED ANATOMICALLY?
- the number of cell layers
- The shape of the surface cells
- Specializations of the apical cell surface
- presence of goblet cells
- Degree of keratinization
How is th eclassification of layers?
simple epithelium if single layer or stratified epithelium if more than one layer
How is the classification of the shape of surface cells?
squamous, cuboidal or columnar
How is the classification of the specializations of the apical cell surface?
microvilli, cilia, stereocilia
How is the classification of the presence of certain cells??
presence of goblet cells - are unicellular mucous
secreting cells
How is the classification of degree of keratinization?
Amount of keratin in stratified squamous epithelial
Identify the classification
simple squamous epithelium
Identify the classification
Simple cuboidal epithelium
identify the classification
Simple columnar epithelium
identify the classification
Stratified squamous epithelium
identify the classification
Stratified cuboidal epithelium
identify the classification
Stratified columnar epithelium
identify the classification
Simple pseudostratified epithelium
identify the classification
Stratified transitional epithelium
What are the functions of simple epithelia?
squamous, simple cuboidal, and simple columnar epithelia are typically involved in absorption and secretion, and translocation of molecules to and from the apical and basal surfaces. The single layer
facilitates increased permeability of the epithelium.
identify
Simple squamous epithelium (blood vessel venule). Allows molecules within the lumen of the cell to pass across thin cells into the connective tissue.
Identify
Simple cuboidal epithelium lining of pancreatic duct, plays a role in modification of product in the lumen of the duct and role in passage
Identify
Simple columnar gall bladder; sort prodcut stored in the bladder as well
What is pseduostratified epithelium?
a variation of simple epithelia in which all the cells touch the basement membrane and thus is considered a single layer of cells. However, the cells vary in height so that some of the cells do not touch the apical surface of the epithelium and nuclei
may be at several levels thus making it look stratified.
Identify by classification
tracheal epithelium pseudostratofied.
Name the structure (be specific)
Pseudostratified columnar epithelium with stereocilia
Where can goblet cells be found?
glands present in some simple and pseudostratified epithelia. If present they may be included as part of the classification
identify
(blood vessel) Simple squamous epithelium lining a venule b
Identify
Simple cuboidal epithelium lining a kidney tubule
Identify
Simple columnar epithelium lining a kidney tubule
Simple Columnar Epithelium with Microvilli and Goblet Cells (small intestine)
Simple Columnar Epithelium with Cilia (epithelium of oviduct)
Pseudostratified Columnar Epithelium with Cila and Goblet Cells (Tracheal epithelium)
Pseudostratified Columnar Epithelium with
Stereocilia (Epithelium of epididymus)
Describe stratified epithelia
are not as permeable as simple epithelia, and are less well suited to absorption, secretion or translocation of molecules from one side of the epithelium to the other
Describe function of stratified epithalia
function for protection against abrasion and water loss
Which stratified epithelia are the most common?
Stratified squamous epithelia and stratified cuboidal epithelia are the most common.
Which stratified epithelia is less common?
Stratified columnar is relatively uncommon except for male reproductive system
What is transitional epithelium?
a special stratified epithelium limited to the
urinary system found in the epithelia of the epididymus and vas deferens.
identify
Section through the epidermis of skin (stratified squamous)
Identify
Stratified cuboidal epithelium lining eccrine
sweat gland duct
Which epithelium is also classified by degree of keratinization and what are these classifications?
Stratified squamous epithelia;
Keratinized
Parakeratinized
Non-keratinized
Describe keratinized epithelium and provide example
the epithelial cells near the surface of the epithelium are completely filled with the protein keratin. The squamous cells on the surface of the epithelium are dead and lack nuclei (e.g. Epidermis of skin)
Describe parakeratinized epithelium and provide example
the epithelial cells near the surface of the epithelium are heavily filled with keratin, but still alive and retain their nuclei (e.g. epithelium of hard plate)
Describe non-keratinized epithelium and provide example
the epithelia cells near the surface are minimally filled with keratin, are still alive, and retain their nuclei (e.g. epithelium of esophagus)
With what does the degree of keratinization correlate to?
correlates with the ability of the epithelium to resist abrasion; keratinized epithelium resists abrasion more significantly than parakeratinized epithelium and non-keratinized
Identify keratinization
Keratinized
Identify keratinization
Parakeratinized (hard palate)
Identify keratinization
Non-keratinized (Esophagus)
Identify
Stratified Squamous Epithelium - Non-keratinized (esophagus)
Identify
Stratified Squamous Epithelium - keratinized (epidermis)
Identify
Stratified Squamous Epithelium- Para-keratinized (hard palate)
Which is sometimes referred to as minimally keratinized?
the non-keratinized epithelium because it does have keratin but very minimal
What is transitional epithelium?
Where is it found and by what is characterized for?
specialized stratified epithelium found only in the urinary system.
It is characterized by its ability to change the shape of the cells and the change the number of cell layers to increase the luminal surface area of the epithelium to accommodate the expansion and enlargement of the ureter and bladder when the
volume of urine increases.
Identify
Micrograph of transitional epithelium in bladder relaxed; numbreal shape? (apical)
Identify
Micrograph of transitional epithelium in bladder distended
How are the surfaces of epithelial cells divided?
-Apical domain (free surface)
-Lateral domain (adjacent to other cells)
-Basal domain (attaches to basal lamina)
Identify
small intestine cells
Where is polarization present?
In simple and stratified epithelia
Why is polarization important?
This polarization in the morphology of the epithelial cell and its cell surfaces is extremely important in allowing a separation of many of the epithelial cell’s functions to specific plasma membrane surfaces and domains
mention functions of microvilli and stereocilia in epithelium
May function to increase the surface area of the epithelium for absorption such as in the small intestine (microvilli) and epididymis
(stereocilia)
Stereocilia in the inner ear may also serve a sensory function in the perception of sound waves
mention functions of cilia in epithelium
Motile cilia may function to move substances such as mucus along the epithelia surface such as in the larger passageways of the respiratory tract (trachea, bronchi, bronchioles) and in the oviduct to facilitate passage of the oovte
In the form of primary cilia (monocilia) they also may serve as sensory organelles on many cells in the body and in the case of nodal cilia may be important for determination of left-right symmetry in the developing embryo
identify
Stereocilia male epididymis
identify
tracheal epithelium cilia
identify
Small instestine Microvilli
identify
intestinal Microvilli
identify
Stereocilia
identify
Cilia in trachea
What are the 2 types of specializations in lateral domains?
Junctional complexes
interdigitation (infoldings)
What are the functions of junctional complexes?
to isolate the lumenal contents from the lateral and basal domains and to attach cells together; acts as a seal to prevent things from passing to the cell.
What are the functions of lateral interdigitations (infoldings)?
To increase surface area and they are prevalent in cells involved in electrolyte and ion transport
What are infoldings site of?
Site of most ion and water transfer across epithelia from the lumen to underlying connective tissue; for example water, will enter the membrane and pas through the interdigitations pass the extracellular space into the connective tissue and also the concentration of substances that can be removed by capillaries
Identify the domain
Cell 1
cell 2
lumen
lateral domain of the apical portion of
two adjoining gastric mucosal cells
showing the apical junctional complex
Identify the domain
Lumen, cell 1, cell 2, interdigitation
What are the types of intercellular junctions?
occluding junctions
anchoring junctions
communicating junctions
What are the function of occluding junctions?
occlude the intercellular space (block off)
What are the functions of anchoring functions?
anchor or adhere cells together
What are the functions of communicating junctions?
provide electrical and metabolic communication between adjacent cells
What are the groups of proteins that link cells in the junctions called?
cell adhesion molecules (CAMs)
What do CAMs do?
act to bind cells together or to bind the cells to the extracellular matrix
What are the specific types of intercellular junctions?
- Zonula occludens = tight junctions
- Zonula adherens
- Maculae adherens = desmosome
- Gap junction = nexus
Which intercellular junctions form the apical junctional complex?
The zonula occludens, zonula adherens, and macula adherens
Identify
apical junction complex
Which junctions have clues to the spacial extent?
Zonula – “belt-like”, extending all the way around the cell
*Macula – “spot-like”, limited extent like a spot weld
*Fascia – “sheet-like”, just along one side or end of cell
Which junctions hive clues to the function?
Occludens – to “occlude” or block the intercellular space
* Adherens – involved in mechanical adhesion
What do zonula occludens serves as?
functions to “occlude” the extracellular space
Identify the gap junctions
Nexus (thin section)
Identify the tight junction
Nexus (freexe fracture)
What are the functions of apical occluding junctions?
provide a tight permeability seal between the cells which blocks passage of proteins and other large molecules from the lumen to the intercellular space between the cells (paracellular pathway)
wHAT IS TH EMAJOR OCCLUDING TYPE JUNCTION IN VERTEBRATES?
zonula occludens
Identify
Zonula occlundens thin section
Identify
Pentalaminar appearance of zonula occludens
What is the most apical of the junctions in the epithelial junctional complex?
zonula occludens
How is the strcuture of zonula occludens in thin sections, different from trilaminar plasma membranes?
In thin-sections it appears as a region in which the plasma membranes are fused together giving a pentalaminar appearance with no remaining extracellular space. (dark region at the center)
How does zonula occludens appear in freeze fracture?
it appears as a series of anastomosing strands of particles on the protoplasmic fracture face (P-Face) and corresponding grooves on the extracellular fracture face (E-Face
Identify
Freeze-fracture EM image of the P-face of
zonula occludens showing the anastomosing network of protein strands
Identify
A freeze-fracture replica showing the P-face and E-face appearance of a zonula occludens
Which transmembrane proteins are present in the zonula occludens?
occludins and claudins that form strands of particles in each of the adjacent junctional membranes.
What do occludis and claudins do/
The extracellular domains of the proteins in each junctional membrane interact in the intercellular space to form strands of protein that seal the intercellular space (provide a permeability barrier) between the adjacent cells
WHat other group is present in zonula occludens?
tricellulins, form strands at the corners between the epithelial cells
What is the major protein that maintains the permeability barrier?
occludin
What other proteins maintains the permeability barrier but differs in forming what?
claudin; differs in forming an extracellular aqueous channel allowing water between junctional membranes
What other transmembrane junctional protein is present in zonula occludens? and function.
JAM (Junctional Adherence Molecule). It does not form strands but acts as an attachment site for white blood cells and facilitates their movement through the junction. allowing th eopening of zonula occludens and movement of vesicles
What doe Tricellulin do?
forms vertical strands of protein (green particles in diagram) which seal the corners between cells in a similar way to those formed by occluding and claudin. prevents molecules to pass between corners of cells
tricellulin
What is the finction of zonula occludens?
Functions as a permeability barrier. The strands of the proteins occludin, claudin, and tricellulin seal the extracellular space (paracellular pathway) so that molecules and ions are restricted in moving between the cells by the paracellular route (between cells). Since claudin is also an aqueous channel, water may pass through the junctional seal to at least some extent.
what does the junction of zonula occludens serve to blocK?
The paracellular pathway
Identify structures
zonula occuldens, endothelial cells lining the capillary.
WHy are JAMz important?
the junction may also act as a preferential pathway for movements of white blood cells from the lumen of blood vessels between the simple squamous epithelial cells into the connective tissue and vice-versa.
WHta is the PDZ-domain proteins?
unique amino acid sequence of occludins, claudins and JAMz, that attracts regulatory and signaling proteins
What are the fucntions of JAMz?
These proteins act to bind complexes of other receptor, regulatory, and cytoskeletal proteins to the junction and may be important for its formation and maintenance
Zonula occludens associated PDZ-proteins include:
ZO-1 - binds actin and is tumor suppressor
ZO-2 - role in epidermal growth factor-receptor signaling
ZO-3 - interacts with ZO-1 & occludin to bind actin
(they can act as a function of opening the junction by binding to actin as necessary)
Clinical conditions resulting from failure of the permeability-barrier maintained by the zonula occludens
Some microbes and toxins can bind to the junctional proteins and destroy the permeability barrier (Review Folder 5.3).
*
For example, the cholera bacterium, some types of E. Coli, some types of salmonella, helicobacter, and the clostridium bacteria have all been shown to destroy the permeability barrier at the zonula occludens. This can result in massive loss of water from the body into the lumen of the intestine or other GI organs resulting in dangerous diarrhea.
Failure of the junction to function properly as a permeability barrier has also been linked to some autoimmune conditions such as celiac disease (gluten may be capable of passing inbetween the zonula occludens to get into the lateral space of the cells into the connective tissue and initiate immune response attacking a protein present in intestinal epithelium, atigenic epitome resulting in destroying of intestinal epithelia)
Clinical Considerations: Zonula occludens as a binding site for viruses
Some viruses can bind to the junctional proteins to disrupt it or use the junction as an entry point into the cell and body.
Examples of viruses which either bind to zonula occludins proteins or require its disruption for entry include:
Hepatitus C virus
Coxsackie B virus
Rotavirus
West Nile virus
Dengue virus
WHat are the apical anchoring junctions?
These junctions provide tight mechanical adhesion between cells
Where is the zonula adherens present?
just basal to the zonula occludens in the epithelial junctional complex.
how does the zonula adherens appears in thin-sections?
region in which the plasma membranes of the epithelial cells are uniformly separated by a 15 - 20 nm intercellular space. A diffuse plaque of density called the “fuzzy” plaque is present on the cytoplasmic surfaces of the membranes. This corresponds to bound actin microfilaments
Identify
EM of zonula adherens with fuzzy plaque
Identify
Zonula adherens high magnification
How many types of zonula adherens are and on what do they differ?
There are 2 different forms of the zonula adherens junction that differ slightly in the type of major cell adhesion molecule (CAM) linking the junctional membranes and the cytoplasmic proteins that link to adjacent actin microfilaments
Which are the proteins in the zonula adherens?
E-cadherins (most comon) and Nectin (less common form)
What is E-cadherin and how does it bind in the extracellular domain?
E-cadherin is the major transmembrane cell adhesion molecule present in the most common form of the zonula adherens junction.. The extracellular domain region of the E-cadherin molecules from adjacent cells bind to each other in the extracellular space. Ca+2 is required for this binding of the E-cadherins
How does E-cadherin bind in the cytoplasmic domain?
On the cytoplasmic side of the membranes, the cytoplasmic domain of E-cadherin binds to the proteins b -catenin and a -catenin, which in turn bind to vinculin and a-actinin which link to the actin cytoskeleton.
Explain Nectin?
In some zonula adherens, another family of proteins called nectins are found. These junctions do not require calcium and bind to a protein called afadin on the cytoplasmic domain.
WHat is Afanin?
prtotein found on the cytoplasmic domain of zonula adheerens alternative class. Afadin (rather than b-catenin and a-catenin) binds to the actin microfilament network. These junctions are weaker than the E-cadherin junctions and are found in regions of frequent tissue turnover
Main functions of zonula adherens
Provides mechanical adhesion between adjacent cells
*
Binds the actin cytoskeleton in adjacent cells together thus providing mechanical strength to the cells
How does fascia adherens differentiate?
fascia adherens junction which links cardiac muscle cells together has a similar structure except that it is a sheet-like junction between the ends of the cardiac cells [key role in contraction of cardiac muscle]
identify
Fascia adherens
Zonula adherens as a binding site for measles virus
In contrast to many other viruses which use binding to or disruption of the zonula occludens junction for entry into the cells, measles virus has been found to use the nectin-afadin protein complex of the zonula adherens for entry into the cell and spreads from epithelial cell to epithelial cell by formation of pores between the cells in the lateral domain. The virus initially in the circulation, enters at the basal-lateral aspect of the cells, and passes between the cells until it reaches the zonula adherens where it binds to the nectin
What is the macula adherens?
Or desmosome; typically present just basal to the zonula adherens in the epithelial junctional complex. It is not always seen since it is spot-like in shape
Why cant macula dherens be seen always in EM?
Due to spot-like it can be missed
How deos macula adherens appear in thin sections?
In thin-sections it appears as a region in which the plasma membranes are uniformly separated by a 30 nm intercellular space. A distinct dense line (intermediate line) is present between the junctional membranes.
*
A very dense, well defined plaque of density (the desmosomal attachment plaque) is present on the cytoplasmic surfaces of the membranes. Intermediate filaments bind to the dense cytoplasmic attachment plaque
Identify
EM of macula adherens showing the dense
Intracellular desmosomal attachment plaque with
intermediate filaments
which are the major transmembrane cell adhesion molecules (CAM’s) present in the macula adherens?
Desmogleins and desmocollins (members of the cadherin family of proteins)
explain the location of desmogleins and desmocollins in the membrane
The extracellular domains of the desmogleins and desmocollins overlap in the intercellular space to form the intermediate line and their cytoplasmic domains attach to the dense demosomal attachment plaques on the cytoplasmic side of the junctional membranes
WHat is the attachment plaque composed of?
Desmoplakins and plakoglobulins are the major proteins of the desmosomal attachment plaque which is a binding site for the intermediate filaments of the adjacent cells. The plakoglobulins share amino acid sequence similarities to the catenins (attachement point for intermediate filaments).
main fucntion of macula adherens and fascia adherens
The major function of the macula adherens is to provide very strong adhesion between the adjacent cells and to provide strong mechanical strength to the cells and adjacent epithelial cells by linking the intermediate filament cytoskeletons of the cells at the junction.
key point of the macula adherens
It is important to stress that this junction unlike either the zonula occludens or the zonula adherens serves as an attachment point for the intermediate filament cytoskeleton
what are other junctions?
COMMUNICATING JUNCTIONS
Functions of communicating junctions
These junctions function to provide both ionic and metabolic coupling between cells. They allow passage of both ions and small molecules directly between cells
Major type of communicating junctions in vertebrates?
gap junction (Nexus)
Describe nexus
The gap junction is a plaque-like junction (spot-like) that can occur anywhere between the cells of epithelia and other tissues
How does gap junctions(NEXUS) appear in thin sections?
appears as a region in which the plasma membranes of 2 adjacent cells come together and lie parallel with a uniform very narrow 2 nm intercellular gap
How does gap junctions(NEXUS) appear in freeze fracture?
characterized by a plaque of IMP’s of uniform diameter and shape on the PF-fracture face and a similar array of pits on the EF-fracture face
Identify
thin section gap junction nexus
identify
thin section gap junction nexus
identify
thin section gap junction nexus
Identify
freeze fracture gap junction
Identify
freeze fracture gap junction
is THERE distinct density or attachment of filaments on the cytoplasmic surface of the junction?
No, although actin attaches in some cases
What is the major protein in gap junctions?
cONNEXINS
Explain the molecular structure of gap junction?
6 integral transmembrane proteins called connexins form a cylindrical structure called a connexon which has a central aqueous pore 1.5 - 2 nm in diameter
The connexons from the adjacent cells bind in the extracellular space to form an aqueous channel connecting the cytoplasm of the adjacent cells
*
The connexons may be able to open and close
Identify
Atomic force microscope image showing connexons
gap junction in open
identify
Atomic force microscope image showing connexons
gap junction in closed
What are the functions of gap junctions?
Gap junctions function to allow electrical coupling and metabolic coupling of cells by allowing ions and small molecules such as sugars, amino acids, nucleotides, small regulatory molecules to pass from cell to cell THROUGH AQUEOUS CHANNELS
How many connexins have been identified?
21-27
Explain the connexon pathway in terms of passage
When the connexons from adjacent membranes are composed of the same connexin (homotypic interaction), passage through the aqueous pore is similar in both directions, biridectional. If the connexons contain different connexins (heterotypic interaction), passage in one direction may predominate unidirectional.
Clinical Considerations: Diseases Related to Mutations in Connexins
Mutations in members of the connexin family of genes are major pathological factors in several diseases. Currently mutations in 10 of the connexins are responsible or associated with at least 26 different pathologies. Mutations in connexin-26, connexin-32, and connexin-43 are the most common
WHat are the examples of pathologies in mutations of connexins
Mutations in connexin-26 (Cx26) are associated with non-syndromic congenital deafness. Gap junctions containing connexin-26 are found in the inner ear and are involved in recirculation of K+ in the cochlear sensory epithelium. Mutations in connexin-30 and connexin-31 are also associated with deafness
Mutations in connexins-46 and connexin-50 have been associated with inherited cataracts. These connexins are found in gap junctions between the lens cells and lens fibers that are involved in delivering nutrients and metabolites to the cells in the avascular environment of the lens
By what does the basal domain attach to?
basal lamina
describe basal domain
Site of attachment of epithelial cell to underlying basement membrane & connective tissue
*
May have hemidesmosomes and focal adhesion plaques
*
May have basal infoldings and associated mitochondria for ion pumping
*
May be a site of secretion in some epithelial cells (for example endocrine or paracrine secreting cells)
basemrnt membrane =
basal lamina + lamina reticularis
what is the basal lamina?
extracellular matrix secreted by epithelium
What is the lamina reticularis?
extracellular matrix secreted by underlying connective tissue (CT)
identify
Section of colonic glands stained with periodic acid
Schiff reagent (stains carbohydrates) to show basement membrane
Identify
Tracheal epithelium showing very thick basement
membrane below the epithelial cells (cilia)
What is the function of the basement memebrane?
*Separates the epithelium & connective tissue (each organ =unique molecularly)
*Anchors and stabilizes epithelial cells to CT
*Influences cell polarity
*Functions in filtration of molecules to & from epithelium & CT
*Influences epithelial cell proliferation
*Guides cell migration and regeneration
What are the regions of the basal lamina?
Lamina lucida and lamina densa
identify
EM of two adjoining epithelial cells with their basal laminas
identify
lamina lucida and lamina densa components
What is the lamina lucida?
(adjacent to plasma membrane)-Light staining region in EM.
Contains the extracellular domain of the integrins (transmembrane proteins – laminin and fibronectin receptor proteins) + laminin
What is the lamina densa?
(adjacent to underlying CT)-dark staining region of basal lamina in EM.
The major protein is collagen type IV. In addition it contains extracellular glycoproteins (laminin, fibronectin & nidogen/entactin), sulfated proteoglycans (perlecan)
WHat do laminin and type IV collagen do?
can polymerize into sheet like macromolecular structures that comprise the basal lamina
How does laminin polymerize?
polymerizes in a calcium-dependent process at the basal plasma membrane in association with laminin receptor proteins (Integrins of the CAM family) which bind the laminin polymer sheet to the plasma membrane
How does collagen type IV polymerize?
polymerizes into a sheet-like collagen suprastructure below the laminin polymer sheet and is crosslinked to it by nidogen/entactin (sulfated glycoprotein) and perlecan (proteoglycan)
Identify
showing the attachment of the basal lamina to the
underlying lamina reticularis collagen fibers by type VII collagen anchoring
fibrils and fibrillin microfibrils
what other multiadhesive glycoproteins are present in the basal lamina?
fibronectin and other sulfated proteoglycans are present in the lamina densa.
What is the lamina reticularis? and what proteins act in its attachment to the lamina densa
The lamina densa attaches to the lamina reticularis (an underlying network of reticular fibers and elastic fibers) by type VII collagen anchoring fibrils and fibrillin microfibrils
WHat are the two types of specialized junctions that can attch the cell to the underlying connective tissue and what is the reason?
Focal adhesions and hemidesmosomes; providing additional strength to the cell binding to the connective tissue
WHat are focal adhesions?
specialized membrane contacts that connect the actin cytoskeleton to the basal lamina & underlying CT
WHat are the functions of focal adhesions?
Play an important role in dynamic changes in cell shape and movement;
Formation & dismantling of adhesions is important for control of cell migration (wound healing, embryogenesis)
Important for detection of contractile forces or mechanical changes in the extracellular matrix (ECM )and conversion of these to biochemical signals = mechanosensitivity role
What are hemidesmosomes?
specialized membrane contacts that connect the intermediate filament cytoskeleton to the basal lamina & underlying CT
What are the functions of hemidesmosomes?
Provide a very strong attachment of epithelial cell to the CT and resist shear or abrasive forces to the epithelial cell
Explain the cytoplasmic molecular structure of focal adhesions
The cytoplasmic domains of the transmembrane integrins bind to the cytoplasmic proteins talin, paxilli, vinculin, and a-actinin which bind to actin cytoskeleton
*
The extracellular domains of the integrins bind to fibronectin in the lamina densa of the basal lamina and thus to the underlying CT
identify
Fluorescent micrograph showing labeled focal
adhesion junctions (orange) and attaching actin stress fibers inserting at focal adhesions
(green)
WHat happens if there is a change in the attachment of the focal adhesion?
Changes in this attachment of the actin cytoskeleton to the underlying CT may be related to changes in the cell occurring during transformation and cancer
identify
hemidesmosomal junctions (arrows) at the basal plasma membrane of an epithelial cells. Note the intermediate filaments binding to the hemidesmosomes
explain the cytoplasmic structure of hemidesmosomes and its proteins
The cytoplasmic attachment plaque contains the proteins plectin, BP230, and erbin which mediate attachment of the intermediate filaments to the cytoplasmic domains of the transmembrane proteins α6β4 integrin (yellow) and collagen type XVII (brown) [extracellular proteins]
explain the extracellular structure of hemidesmosomes and its proteins
The extracellular domains of the α6β4 integrin transmembrane proteins interact with the basal lamina proteins laminin-332 (green) or perlecan (on collagen IV) providing a connection of the junctional plasma membrane and cell to the extracellular matrix
Clinical Consideration of hemidesmosomes
Bulbous Pemphigoid;
group of skin blistering diseases (such as bulbous pemhigoid) which result from autoimmune reactions against the proteins of the hemidesmosome such as collagen XVII. This results in the autoimmune destruction of the hemidesmosome allowing separation of the basal layer of the epidermis from the underlying connective tissue of the dermis thus allowing for the formation of massive blistering of the skin.
What are basal infoldings?
specialization of epithelium found in basal domain
What are basal infoldings?
*
Increase the basal surface area
*
Are often associated with elongated mitochondria that provide energy
Function: active ion transport
[active pumping of Na+, and water follows passively]
This can operate as a mechanism by which the epithelial cell can concentrate or modify the contents of the fluid compartment found at the apical or luminal surface of the epithelial cell
identify
Basal infoldings with associated mitochondria
to provide energy for ion pumping
What is the turnover rate of epithelial cells?
Epithelia cells are among the most actively dividing cells in the body. The turnover rate of epithelia for replacement of the cells by new cells by cell division of stem cells is generally high ranging from approximately 4 -6 days in epithelia of the GI tract to longer than 40 days or more in skin and some other organs
What is metaplasia?
Metaplasia is the conversion of one type epithelium to another type which occurs under some conditions of stress to the epithelium such as excess abrasion or chronic infections
What is the most common metaplasia?
columnar to squamous metaplasia in which columnar epithelia are converted to a squamous epithelium as frequently seen in the respiratory epithelium of smokers or in the lining epithelium of the cervix in women with chronic infections
What can occur in Barrett esophagus?
Squamous to columnar metaplasia where gastric reflux causes the stratified squamous epithelium of the esophagus to change to a simple columnar epithelium with goblet cells in response to the acid
identify
Micrograph showing squamous metaplasia of the epithelium of the uterine
cervix
Is metaplasia reversible?
Metaplasia is reversible and considered to be within the normal range of differentiation of a tissue and thus is not cancer. However, note that this plasticity and changes in the epithelium may be a prelude to cancerous changes.
what is carcinoma? (epithelial cancer)
Carcinoma refers to a malignant neoplasm of epithelial origin or cancer of the internal or external lining of the body
what are adenocarcinomas?
adenomas) are a subtype of the carcinomas which occur in glandular tissue of organs like the colon, prostate, and breast
Carcinomas, malignancies of epithelial tissue, account for how much % and what are some examples?
80-90% of cancer cases in adults
Ovarian epithelial carcinoma- cancer of the ovary
Acinar adenocarcinoma- a major type of cancer of the prostate and lungs
Basal cellcarcinoma- a form ofskin cancer
Squamous cell carcinoma- a form of skin cancer
Gastric adenocarcinoma- stomach cancer
Renal cell carcinoma- kidney cancer
Clinical Considerations: The Epithelial-Mesenchymal Transition (EMT)
During embryological movement epithelial cells undergo a process called the epithelial-mesenchymal transition in which the epithelial cells undergo a change to a more mesenchymal-like cell morphology. A key feature of this process is that the intermediate filament composition changes from cytokeratin-containing intermediate filaments to vimentin-containing intermediate filaments and the breakdown of desmosomal and hemidesmosomal junctions. The cells then assume a more mesenchymal – fibroblast-like morphology, express new cell adhesion molecules, new focal adhesion junctions and become motile.
The clinical significance of this is the finding that epithelial cells becoming cancerous typically recapitulate this epithelial-mesenchymal transition to become motile and metastatic. Evidence has been shown for example that vimentin expression is required for the invasive behavior and metastasis of both prostate and breast cancer cells
What are glands?
Single epithelia cells or multicellular aggregates of epithelial cells (and their CT) specialized for the synthesis and release of a product needed by the body
WHat are the origins of glands?
Multicellular glands originate as surface epithelial cells which penetrate into underlying CT and specialize for the secretion of the product as well as forming ducts
larger glands can be divided into?
Parenchyma: secretory units & ducts = functional units
[epithelial origin]
-
Stroma: supporting CT (may form capsule & septa)
[connective tissue origin]
what happens with the product of glands in a unicelular or multicellular gland?
manufactured intracellularly then secreted either to the duct (for exocrine glands) or into CT or blood vessels (for endocrine glands)
identify
Light micrograph of parotid salivary gland showing serous secreting acini, intralobular ducts and the connective tissue stroma between the secretory acini and ducts
Multicellular glands based upon presence or absence of a duct can be divided into:
Exocrine glands and endocrine glands
Describe exocrine glands
These glands have a duct or duct system to convey the released product out of the gland. For example salivary glands, liver, pancreas.
Describe endocrine glands
These glands are ductless and release their product into the CT. For example: adrenal gland, thyroid gland, parathyroid gland and pituitary gland
identify
Micrograph of exocrine pancreas and diagram of the compound nature of the gland
identify
Low magnification image of endocrine adrenal gland
Exocrine glands are classified according to:
- cell number
- duct arrangement
- shape of secretory units
- type of secretion
- secretory mechanism (mode of secretion)
by cell number how can exocrine glands be classified?
Unicellular (goblet cells)
*
Multicellular: e.g. sweat glands,gastric glands, salivary glands, colonic glands, pancreas, liver
identify
Goblet Cells in Intestinal Epithelium –Unicellular gland (exocrine)
identify
Exocrine Pancreas – Multicellular gland secretory acini
Duct arrangement and secretory unit shape of exocrine glands?
Simple – single unbranched duct
Compound- branched duct system
Name the simple classification?
- Simple tubular
- Simple alveolar (acinar)
- Simple tubuloalveolar
- Simple branched tubular or alveolar (multiple secretory units with single duct)
Name the compound classification
- Compound tubular
- Compound alveolar
(acinar) - Compound tubuloalveolar
identify
Simple tubular
identify
simple coiled tubular
identify
simple branched tubular
identify
Simple acinar
identify
branched acinar
identify
compound tubular
identify
compound acinar
identify
compound tubuloalveolar/acinar
identify
simple tubular of mucosal glands of colon
identify
Simple Branched Acinar (cardiac stomach
identify
Simple Coiled Tubular (Sweat gland)
where are large exocrine glands found?
salivary glands, liver, and pancreas are classified as compound glands which are characterized by a branched duct system.
how are secretory acini typically arranged in exocrine secreting compound glands?
arranged into larger anatomical structures called lobules which are separated by septa of connective tissue.
How are lobules drained in exocrine compound glands?
drained by a branched system of intralobular ducts of different sizes
Identify
Low magnification light micrograph of parotid salivary
Gland showing secretory acini (inset) their arrangement and their
arrangement into lobules separated by connective tissue septa
and ducts
What is the interlobular duct?
Groups of lobules are drained by still larger ducts called interlobular ducts which are present in the connective tissue septa between the lobules
what are lobes?
The lobules in turn may be grouped to form even larger anatomical arrangements known as lobes which are drained by still larger ducts known as lobar ducts or excretory ducts
Which cells are in the intercalated duct?
simple cuboidal epithelium
where does the secretory acinus typically drains?
two types of intralobular ducts: 1) intercalated ducts and 2) striated ducts or intralobular collecting ducts)
What is the extralobular duct?
(interlobular ducts and lobar ducts) which join to form the main excretory duct
identify
compound acinar (pancreas)
which duts are considered to be examples of interlobular ducts present within the lobule itself?
intercalated duct and intralobular duct
identify
Compound Acinar (parotid salivary gland. striated ducts and in intercalated ducts [branched ducts bc there are two duct systems]
identify
Compound Tubuloacinar (submandibular salivary gland) [serous and mocus secreting]
what are the main types of secretions in exocrine glands?
serous
mucous
mixed
describe serous secretion
an aqueous ionic or protein secretion. The cells may stain light or dark and are typically pyramidal in shape with centrally-located nuclei
describe mucous secretion
A glycoprotein rich solution that is typically very viscous. Cells are typically very pale staining with nuclei flattened along base of cell
describe mixed secretion
The secretion is a mixture of serous and mucous secretions
identify
Micrograph of parotid gland showing serous secreting acini
identify
Hard palate showing mucuous secreting
glands
identify
Submandibular gland showing mixed serous secreting And mucous secreting secretory units
identify
light micrograph showing both serous and mucous glands in tongue
What are the modes of secretion of exocrine glands?
merocrine
apocrine
holocrine
Describe merocrine
(most common mode) only product released. e.g. eccrine sweat gland
Describe apocrine
thin layer plasma membrane also secreted
(e.g. lactating mammary, ciliary & ceruminous glands)
Describe holocrine
whole cell secreted (dead or live) (e.g. sebaceous gland)
identify
merocrine
identify
apocrine
identify
holocrine
What are myoepithelial cells?
many glands such as eccrine sweat glands, the salivary glands and some sero-mucous glands of the respiratory tract are surrounded by epithelial cells specialized to have contractile properties.
what is the fucntion of myoepithelial cells?
can contract forcing the secretion out of the gland and along the duct.
identify
Eccrine sweat gland in skin
Eccrine sweat gland in skin showing myoepithelial cells (dark pink) surrounding the secretory unit
Identify
EM of eccrine sweat gland showing myoepithelial cells`
describe endocrine cells
Endocrine glands are ductless. The secretion is released at the base of cell into the CT. The secretion may enter the blood vessels or diffuse to nearby cells
whata re the action of the secretion of endocrine glands?
endocrine
paracrine
autocrine
What is endocrine secretion?
if the secretion is transported by the blood and effects a distant target
What is paracrine secretion?
if the secretion acts on nearby cells by diffusion through the CT (local effect)
What is autocrine secretion?
if the secretion acts on the cell itself or other cells of that type (feedback mechanism)
identify
endocrine
identify
paracrine
identify
autocrine
identify
Thyroid – Follicular Arrangement of Cells [thyroglobulin]
identify
Adrenal Gland – Strands of Cells
What is the diffuse neuroendocrine system? (DNES)
Single endocrine cells interspersed in epithelium. DNES cells are of different origin (neural crest) than epithelium
IDENTIFY
Stomach Gastric Glands neuroendocrine cells. SOMETIMES REFERRED AS AMINOPRECURSOR CELLS, secrete acid and pepcin
