Epithelium III PDF

Epithelium III By: Dr. Moustafa Al Sawy Dr. Shaimaa Mohamed Amer MBBCH, M.SC. M.D HISTOLOGY MBBCH, M.SC. M.D HISTOLOGY Associate Professor of Histology & Cell Biology Assoc...

Epithelium III By: Dr. Moustafa Al Sawy Dr. Shaimaa Mohamed Amer MBBCH, M.SC. M.D HISTOLOGY MBBCH, M.SC. M.D HISTOLOGY Associate Professor of Histology & Cell Biology Associate Professor of Histology & Cell Biology Certified Medical Educator Intended Learning Outcomes (ILOs): Knowledge : By the end of the lecture , each student will be able to: 1. Define epithelial cell specialization & describe its different types. 2.Differentiate between different types of cell junction. 3.Relate each type of cell specialization to its function.  Epithelial polarity Epithelial cells exhibit different polarity Apical Toward the exterior surface domain Lateral Communicates with adjacent cells domain Basal Rests on the basal lamina anchoring domain the cell to underlying C.T. Specific characteristics are associated with each surface.  Specialization of the cell surface They reflect specific functions Microvilli Stereocilia Apical Cilia Flagella Intercellular junctions Lateral Basement membrane Basal Hemidesmosome Basal & lateral infoldings  A- Apical specializations I-Microvilli E/M: Finger-like extensions of the cytoplasm. Covered by plasma membrane. Each microvillus has actin core that are cross-linked to each other. The basal ends of these microfilaments intermingle with the terminal web.  Terminal web is a dense layer of horizontal filaments in apical cytoplasm beneath the microvillus to give rigidity to the cell apex.  Glycocalyx: filamentous coat (glycoproteins) covering the microvillus & it is PAS positive; called cell coat.  With L/M, microvillus & glycocalyx appear as brush border (striated).  Sites: eg. Absorptive cells of small intestine & cells of proximal renal tubules. Function: increase the surface area of the cell.  II- Stereocilia: -Long branched non-motile irregular microvilli. - In epididymis & inner ear. Functions: 1- Increase the surface area. 2- Facilitate the movements of molecules into & out of the cell.  III- Cilia Elongated, motile structures on the surface of epithelial cells. Sites: Ciliated cell of the trachea which have about 250 cilia in each cell IV- Flagella Present in the human body only in spermatozoa. They are similar in structure to cilia but much longer. EM of cilia & flagella: Each cilium is composed of 1.Basal body (27 microtubules ,9+0) 2.Axoneme (shaft) The axoneme (20 microtubules, 9+2) is formed of outer nine doublets of microtubules surrounding central two singlets The two singlets are surrounded by a central sheath.  Medical Application *Several mutations have been described in the proteins of the cilia & flagella. They are responsible for the Kartagener or immotile cilia syndrome (Primary ciliary dyskinesia). *It is rare autosomal recessive disorder characterized by absent or dysmotile cilia caused by a defect in the microtubules (dynein arm mutations). *The symptoms are immotile spermatozoa, male infertility, & chronic respiratory infections caused by the lack of the cleansing action of cilia in the respiratory tract. N.B. Abnormal cilia also present in the polycystic kidney disorder  Medical Application  Celiac disease, also called gluten-sensitive enteropathy or sprue, is a disorder of the small intestine in which one of the first pathologic changes is loss of the microvilli (brush border) of the absorptive cells (enterocytes).  This is caused by an immune reaction against the wheat protein gluten during its digestion, which produces diffuse enteritis that leading to malabsorption, and eventually to pathologic changes in the intestinal wall.  The malabsorption problems and structural changes are reversible when gluten is removed from the diet. B- Lateral specializations (Intercellular junctions) 1.Tight junction (zonula occludens) 2.Adherens junction (zonula adherens) 3.Desmosomes (macula adherens) 4. The gap junction (communicating junction; nexus) 1.Tight junction (zonula occludens) Site: At the apical parts of the cells. Structure: Formed by fusion (sealing) of the outer cell membranes proteins (claudins and occludins) of two adjacent cells. Functions: 1. Keep fluid from scaping between the cells as in GIT. 2. Form (impermeable barrier) as blood brain barrier. 3. Provide strength and stability to the tissue. 2. Adherens junction (zonula adherens) Description: encircles the apical parts of the 2 adjacent cells below the tight junction (Belt like) Structure: 1. The intercellular space between the adjacent cell membranes is 20 nm ( the usual intercellular space). 2. Cadherins adhere the 2 cells together. 3.The cytoplasmic part of cadherins are attached to actin filaments inside the cells. 2. Adherens junction (zonula adherens) Cadherins Calcium-dependent transmembrane proteins responsible for adhesion of cells to other cells. Loss of cadherins is associated with cancer metastasis. 3.Desmosomes (macula adherens) Description: spot like specialization of the cell membrane. * The strongest type of cell junction preventing cells from separation. Structure: 1. Two plaques located opposite each other on the cytoplasmic aspects of the adjacent cell membranes to which Intermediate filaments (keratin) are inserted. 2.Cadherins connect the desmosomal plaques of two cells. 3. The intercellular space is 30 nm.  Junctional Complex Junctional complex; is a several types of junction between adjacent epithelial cells in order to maintain their structural and functional integrity.  Medical Application Pemphigus vulgaris Autoimmune disease characterized by production of antibodies against the desmosomal proteins of the epidermal cells. Affected people develop widespread skin and mucous membrane blistering. 4- The gap junction (communicating junction; nexus) Site: Cardiac & smooth muscles. *There are many intercellular channels connect two adjacent cells. Structure: formed by the interaction of the connexons of two neighboring cells. Connexon: composed of six integral proteins called (connexins) with a central pore. 4- The gap junction (communicating junction; nexus) Function: 1. Allow cells to communicate with each other. 2. Rapid spread of chemical and electrical signals between the cells. 3. Contraction of cardiac muscles, muscle of gut and uterus depends on gap junction. N.B. Local anesthesia depends on block of the gap junctions between the nerve and its receptors.  Medical Application - The enterotoxin secreted by Clostridium bacteria, which causes “food poisoning,” binds claudine Gastric Ulcer molecules of intestinal cells, leading to disruption of tight junctions that causes loss of interstitial fluid through the intestinal lumen (diarrhoea) and intestinal ulcers. - Helicobacter pylori, one of the important cause of gastric ulcers, binds the extracellular domains of tight-junction proteins in cells of the stomach leading to loss of the integrate of this tight junction. - Mutations in various connexin genes have been linked to certain types of deafness and peripheral neuropathy. C- Basal specializations I- Basement membrane II-Hemidesmosome III- Basal & lateral infoldings I. Basement Membrane Site: In the interface between epithelium and connective tissue. Structure: 1.The basal lamina: Synthesis: by epithelial cells. Structure: proteins (collagen type IV+ glycoproteins (laminin)+ proteoglycan (heparan sulphate) 2. The reticular lamina Synthesis: by cells of the connective tissue. Structure : network of reticular fibers (collagen type III) I. Basement Membrane 3. Anchoring fibrils :type VII collagen are responsible for attachment of the basal lamina to the underlying CT. Function 1. Anchoring epithelium to connective tissue 2. Semipermeable filter (nutritional function) 3. Support II. Hemidesmosome Description: attaches cells to the extracellular matrix. Structure: Integrins connect the intracellular cytoskeleton (keratin) with molecules of the basement membrane (laminin, fibronectin, and collagen). IV. Basal & lateral Infoldings Structure: *The basal & lateral membrane of cells is thrown into folds (deep invaginations) *Near these folds numerous mitochondria are located to produce ATP necessary for ion transport. Site: They are present in cells involved in fluid or ion transport, as gut cells and kidney tubules. Function: Increase surface area of plasma membrane.  Case Scenario Your instructor reminds you that epithelial cells have membrane channels that permit ions and small signaling molecules to pass between adjacent cells. Which of the following proteins forms these intercellular (gap) junctions? (A) Cadherins (B) Connexins (C) Netrins (D) Perforins (E) Porins Any Questions?  References: 1.Basic Histology: Text & Atlas. Editor: Luiz Carlos Junqueira, MD, PhD; Jose Carneiro, MD, PhD. 14th Ed, chapter 2. 2.Wheatear’s functional histology. A text & color atlas.15th Ed. 3.AMBOSS platform Thank You