L10-11: Epithelium Flashcards
Characteristics of epithelium
- Cover body’s external and internal surfaces and lines body tubes
- Has apical, lateral and basal domains
- Anchored to basal lamina
- Avascular
- Can be glandular
How is epithelium classified? Discuss
- ) Cell layers: simple, stratified (transitional), pseudostatified
- ) Shape of cells: squamous, cuboidal (uncommon as stratified), columnar (always look at highest cell layer)
- ) Specialization of apical domain or degree of keratinization
Discuss epithelial cell layer types
- ) Simple: one layer with all cells residing on basement membrane
- ) Stratified:
a. ) 2 or more layers
b. ) Transitional epithelium (urothelium = specialized type of stratified) - ) Pseudostratified: all cells (one layer) reside on BM, but nuclei at various levels in tissue section giving it a stratified appearance
Function of simple squamous epithelium
- Blood-brain barrier
- Filtration
- Exchange
Location of simple squamous epithelium
- Blood vessel (known as endothelium)
- Alveolus
- Mesothelium
Function of simple cuboidal epithelium
- Absorption
- Secretion
- Barrier
- Conduit
Location of simple cuboidal epithelium
- Thyroid follicles
- Renal tubules
- Ducts of glands
Function of simple columnar epithelium
- Absorption
- Secretion
- Barrier
Location of nonciliated simple columnar epithelium
- Stomach, intestines
Location of ciliated simple columnar epithelium
- Uterine tubes
Function of pseudostratified ciliated columnar epithelium
- Secretion
- Absorption
- Barrier
- Transport
Location of pseudostratified ciliated columnar epithelium
- Trachea (has thick basement membrane)
- Bronchi
- Ducts of male reproductive system (stereocilia)
Function of stratified squamous epithelium
- Barrier
- Protection
Location of nonkeratinized stratified squamous epithelium
- Esophagus
- Distal anal canal
- Vagina
Location of keratinized stratified squamous epithelium
- Epidermis of skin
Function of transitional epithelium
- Aka urothelium
- Barrier
- Protection
- Distension
Location of transitional/urothelium
- Ureters
- Urinary bladder
- Urethra
List classifications or specializations of the plasmalemma of epithelial cells
- Cilia = motile; monocilia = non-motile = primary cilia; and monocilia = motil = nodal
- Flagella
- Microvilli
- Stereocilia (better term = stereovilli)
What is Kartagenar syndrome?
- Defect in dynein arms lead to immotile cilia and flagella. These individuals are prone to respiratory infections, bronchiectasis and infertility in men.
- Triad seen in these pts: bronchiectasis, situs inversus and chronic sinusitis
What is the molecular composition of motile cilia?
- 9 doublets of microtubules plus central pair of microtubules
- Dynein molecules (are ATPases) that extend from doublets to center
- Base of cilium = basal bodies (9 triplet sets of microtubules)
Function of primary/non-motile monocilium
- Chemosensors, osmoreceptors, mechanoreceptors
- Pivotal role in normal tissue morphogenesis
- Seen in fibroblast and epithelial cells of collecting tubule
Discuss role of primary cilium in development of kidney pathology
- Defect in polycystin 1 / 2 causes defect in calcium signaling at primary cilium
- In normal morphogenesis of kidney epithelial cells, normal polarity of cell occurs in direct of tubule – normal mitotic spindle orientation
- In polycystic kidney disease, morphogenesis of epithelial cells occur in planar orientation and there is expansion of the lumen of the tubule causing cyst development – incorrect mitotic spindle orientation
Defects in primary cilia results in what pathologies?
- Polycystic kidney disease, polydactyly, vision and hearing loss
Discuss role of nodal cilia in embryological development. Discuss defect in this
- These cilia are motile (appearance of non-motile) and located in primitive node
- Their action directs fluid flow in primitive node from right to left and helps establish left/right axis
- Defect = situs inversus and dextrocardia (apex heart to right)
What are microvilli?
- Extensions of apical surface plasma membrane
- Contain proteins (actin microfilaments plus others) that allow for movement by their interaction with terminal web containing myosin II and tropomyosin – separation or bringing together or microvilli
- Increase absorption
What is a brush border? How to stain for this?
- Striated appearance of well-developed microvilli on epithelia
- Contains carbohydrate coat called glycocalyx – PAS (magenta) positive
Where are stereovilli/cilia found?
- Male reproductive ducts – ductus deferens, ductus epididymus and sensory epithelium in inner ear
- Resemble microvilli, with actin filaments, but different protein-protein arrangement
A mother brings her 10 yo son to pediatrician. She is concerned about his chronic respiratory problems and recurring episodes of ear infections. The PEX reveals swollen nasal mucosa, impaired sense of smell and abnormal lung sounds. Nasal biopsy was obtained and sent to pathology and imaging studies were ordered. Cilium at EM level shows that dynein arms are absent. Imaging studies performed indicate maxillary sinus inflammation, bronchiectasis (dilation of bronchi) and situs inversus with dextrocardia.
A.) Diagnosis
B.) Explain why bronchiectasis is seen
C.) Explain why situs inversus is seen
- A.) Ciliopathy – specifically: Kartagener Syndrome with classic triad
- B.) Cilia defective and non-motile, so mucous remains and bacterial infection occurs leads to chronic inflammation and dilatation of bronchi
- C.) Nodal cilia are defective and are unable to establish movement of fluid in a left-right direction within the primitive node. As a result, no left/right axis symmetry is established
List classifications of junctional complexes
- ) Zonula occludens (tight junction)*
- ) Zonula adherens*
- ) Macula adherens
- ) Focal adhesions
- ) Hemidesmosomes
- ) Gap junctions (nexus)
* Belt-like connection that goes around the entire cell
In what order are apical-lateral junctional complexes found?
- Zonula occludens, zonula adherens and macula adherens
- In order of apical to basal on the lateral domain
Structural characteristics of junctional complex
- Cytoskeletal element (actin or intermediate microfilaments) – if epithelial tissue, intermediate filament = cytokeratin
- Intracellular anchor proteins
- Cell adhesion molecules (TM proteins) = CAMs
Structure of zonula occludens (aka tight junctions)
- Cytoskeletal element = actin
- Intracellular anchor proteins = ZO proteins (1,2,3)
- Cell adhesion molecules = Claudins and occludins
Function of zonula occludens?
- Paracellular pathway permits selective movement
- Prevent cells from separating from one another
- May regulate epithelial proliferation
- Essential for establishing functional polarity (think glucose transporters on apical side with sodium pumps only on basolateral domains)
Discuss functional importance of claudins to occludins
- Claudin to occludin ratio determines permeability between epithelial cells
- High ratio of claudins to occludins = high permeability
- Low ratio of claudins to occludins = low permeability (ie. Blood-brain barrier)
Clinical relevance of zonula occludens
- ) Mutation in gene encoding specific claudin in renal epithelium results in excessive loss of mag ions and severe hypomagnesemia leads to neuromuscular symptoms
- ) Brain CA can lead to loss of claudin 5 causing breach of blood-brain barrier
- ) Loss of claudin 9 shown to cause deafness
- ) Cholera amongst other things attacks ZO proteins causing breach of tight junctions and fluid loss
- ) Occludins are disrupted by H. pylori
Structure of zonula adherens
- Cytoskeletal element = actin
- Intracellular anchor proteins = alpha, beta catenins, alpha actinin and vinculin
- Cell adhesion molecules = E-cadherin
Structure of macula adherens (desmosomes)
- Cytoskeletal element = intermediate filament, mainly cytokeratin in epithelial tissue
- Intracellular anchor proteins = intracellular attachment plaque
- Cell adhesion molecules = desmoglein and desmocollin (cadherin family)
Clinical relevance of macula adherens
- Pemphigus (skin disease): pts develop antibodies against desmoglein 3 of desmogleins. This disrupts desmosomes that connect skin cells to one another producing a blistering of skin
Structure of focal adhesions
- Cytoskeletal element = actin
- Intracellular anchor proteins = vinculin, paxillin, talin
- Cell adhesion molecules = integrin contacts with fibronectin (adhesive glycoprotein)
Function of focal adhesions
- Anchor cell to matrix
Junctional complexes that anchor cells together
- Zonula occludens
- Zonula adherens
- Macula adherens
Junctional complexes that anchor cells to matrix
- Focal adhesions
- Hemidesmosomes
Structure of hemidesmosomes
- Cytoskeletal element = intermediate filament, mainly cytokeratin in epithelial tissue
- Intracellular anchor proteins = intracellular attachment plaque, plectin and BP230
- Cell adhesion molecules = integrin family and type XVII collagen (aka BPAG2 transmembrane protein) interacts with ECM of basal lamina
Clinical relevance of hemidesmosomes
- Bullous pemphigoid: autoantibodies develop against type XVII collagen – BPAG2 = bullous pemphigoid antigen-2. Get separation of epidermis from dermis
Based on the general blueprint for junctional complexes, what component does integrin represent?
A.) Intracellular anchor
B.) Cell adhesion molecule
C.) Cytoskeletal element
- Cell adhesion molecule
Gap junctions (nexus). Structure, function and location?
- Structure: formed by connexon protein structure, which is a hollow cylinder composed of six TM proteins called connexins
- Function: electrical and chemical communication bw cells
- Location: most tissues, esp. cardiac muscle, smooth muscle and hepatocytes
Clinical relevance of nexus/gap junctions
- Female infertility
- Neuropathy
- Deafness
- Congenital cataracts
- Cardiac arrhythmias
What are clue cells?
- stipling appearance on vaginal epithelium that indicate bacterial vaginal infection
- specifically, vaginal epithelial cells are coated with coccobacilli
Describe events that allow CA cells to become metastatic
- ) Changes in junctional complexes/adhesion
- Mutation in E-cadherins
- Decreased number of E-cadherins
- Catenins that are non-functional or absent
- Alteration in integrin numbers or structure - ) Cytoskeleton alteration
- ) ECM altered: proteases digest this barrier (synthesis and release of their own proteases or stimulating other cells to release proteases?)
- ) Enter blood vessels (evade physical forces and leukocytes)
- ) Expression of adhesion molecules: allow CA cells to bind endothelium at distant site and invade/seet into new tissue
- ) Following invasion, replication occurs and they form secondary tumor
What is metaplasia?
- transformation of native epithelium into another epithelial type
