Dentistry II - A: Cytology and Histology PDF
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Cebu Doctors' University
Lizzie Regalado
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These notes from Lizzie Regalado cover cytology and histology, focusing on cells, protoplasm, prokaryotic and eukaryotic cells, organelles and inclusion bodies, and the nucleus including chromatin and chromosomes. The notes are for a Dentistry II - A course at Cebu Doctors’ University College of Dentistry.
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DENTISTRY II - A Cebu Doctors’ University | College of Dentistry 1 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry 2 Lizzie Regalado’s Notes...
DENTISTRY II - A Cebu Doctors’ University | College of Dentistry 1 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry 2 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry Cytology Protoplasm LECTURE 01 mass of living matter surrounded by plasma membrane HISTOLOGY → the study of body tissues and its components 2 PROPONENTS: CYTOLOGY → the study of the cell 1. NUCLEUS The Cell Holds the genome consisting of chromosome 2. CYTOPLASM Is the fundamental, structural, and functional unit A complex aqueous gel made of water of all living organisms Cytoplasm Cytosole Is the region outside the nucleus but still inside the plasma membrane Jelly-like portion of the cell with its cellular structures suspended in it Made up of: 70% water 30% lipids, carbohydrates, proteins and inorganic molecules Cytosole plus cellular structure Outside the nucleus but inside the plasma membrane Within the cytoplasm: Types of Cell ORGANELLES Are metabollically active structures PROKARYOTIC CELL Specialized structures with functional Includes bacteria (bacterium) and archaea capabilities (mitochondria, endoplasmic Doesn’t contain a nucleus; instead, DNA can reticulum, golgi apparatus) be found in the cytoplasm INCLUSION BODIES EUKARYOTIC CELL Relatively inert (very slow to move and act) Is found in animals, plants, protists, and fungi Non-metabolically active Have a membrane-bound nucleus where the Transitory (temporary) DNA is stored (vacuoles, cytoskeleton, pigments, crystals, fat droplets, glucogen, granules) Nucleus Largest and most conspicuous part of the cell — contains the genetic material (DNA) Bounded, surrounded, enclosed by the membrane in which consist a pair of unit by the membrane, separated by a space called “perinuclear space” or “cisternae” The outer membrane of nucleus is continuous with the endoplasmic reticulum Four Basic Tissues The inner membrane is a single sac That consist of cells and associated extracellular Nucleus consists of nucleolus, chromatin, nuclear matrix: matrix, and nuclear envelope 1. EPITHELIUM / EPITHELIAL TISSUES The nucleus, specifically the nuclear membrane 2. CONNECTIVE TISSUES exhibits a selective permeability due to its force, 3. MUSCULAR TISSUES which consists of several complex proteins → 4. NERVOUS TISSUES which is to import substances into and export substances out of the nucleus 3 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry The nucleus also possesses chromosomes in the Structures that are abnormal in shape are very eukaryotic cells, which consist of linear DNA macromolecules, which are arranged as double helix. common in patients with cancer The chromosomes are only visible if the cell is 1. Maligmancy → cancer undergoing cell division / mitosis 2. Benign → non-cancerous During cell division, the DNA is highly condensed Two areas : ▶ The main site of pre-ribosome assembly. ▶ It consists of densely packed Pars granulosa clusters of pre ribosomal particles (diameter: 15-20 nm) that are rich in ribonucleoprotein. ▶ Contains a dense, irregular network Pars fibrosa of fine filaments (5 nm in diameter), rRNS genes, and transcription factors Shape of the Nucleus (in a cell) The shape and size of the nucleus depends on the type of cell: Spherical or ellipsoidal (mostly) CHROMATIN Fine purple structure Elongated (columnar epithelial cells) Is a network of slender filamentous threads Lobulated (polymorpho-nuclear leukocytes and intensely stained structures within the nucleus megakaryocytes) Appear as irregular clumps *In the White Blood Cell, the nucleus are nebulations Consist highly folded DNA and structural proteins (nebulated) (histones) Has a strong ability forming haematoxylin, which is why it appears purple or blue Number Site where translation occurs 1 nucleus → Most cells → Liver cells / Comes in two forms: 2 nuclei / bi-nucleated hepatocytes EUCHROMATIN → Bone cells, osteoclast, Transcriptionally active Many / multi-nucleated skeletal muscle cells Synthesizing protein Anucleated (you can’t Uncoiled chromosomes → Mature RBC see a nuclei / nucleus) Lightly stained HETEROCHROMATIN NUCLEOLUS Condensed form of chromosomes Transcriptionally inactive “nucleoli” if plural in form Stain darker with basic dye Structure visible within the nucleus Is usually near the nuclear envelope Is rich in RNA (ribonucleic acid); basophilic (blue) in appearance Site of ribosomal synthesis or transcription Does not possess any membrane around it The size, number and location depends on the functional activity of the cell High content of RNA → it will appear as basophilic or purplish The site of ribosomal RNA (rRNA) transcription and production of ribosomes NUCLEAR MATRIX Nucleolus will disassemble during the prophase of Is within the nucleus; nuclear membrane mitosis and organize into daughter cells when Sponge-like area between the nucleolus and mitosis is completed chromatin Forms the structural scaffolding, which organizes the chromosomes during meiosis and mitosis Also helps regulate gene transcription 4 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry CHROMOSOMES Cells with higher cristae have higher surface area : For ATP synthesis Threadlike structures of DNA and other proteins Reaction release such as histones Kreb cycle human cells have 23 pairs of chromosomes, Citrix acid cycle smallest pair being chromsome #21 Oxidative phosphorylation Electron transport ◸ Clinical Importance ◿ Oxidation reaction Down Syndrome (trisomy 21) ◸ mitochondrial matrix contains : enzymes needed for is a result of improper segregation during cell the redox reaction (oxidation-reduction); work as division reservoirs where calcium is stored temporarily as The most common inborn autosomal chromosome matrix granules, where cellular respiration takes place disorder Sequester calcium → granules Occurs at fertilization via non disjunction (improper segregation) leading to this ◸ mitochondrial myopathies : disease (from outside) chromosomal abnormality during meiosis and that affect the mitochondria, resulting to muscle results to three copies of chromosome #21 weakness, cramps and spasms SIGNS Hypotonia in infancy / during pregnancy NUCLEAR ENVELOPE Mental retardation Encloses the nucleaus of interphase cells and Specific facial features features separates nucleus from cytoplasm The frequency of down syndrome is 0.1% of the total number of birth and the risk increases with the advancing age of the mother. Endoplasmic Reticulum Tortorus slender tubules with sacs Complex interconnected network, flattened CELLULAR ORGANELLES membrane — enclosed sacs known as “cisternae” Mitochondrium 1. SMOOTH ER “mitochondria” in plural form Do not have ribosomes attached to it (liver → uses A membrane enclosed or bounded organelle enzymes and G6P) scattered throughout the cytoplasm Lipid and lipoprotein synthesis (ovaries, testis and More mitochondria is visible when a particular cell adrenal glands) requires high energy condensation in a form of Calcium and ion regulations in the muscle cells, ATP (areas like the muscle and heart) which is critical for muscle contraction Basal areas of ion transporting cells have a number Agranular of mitochondria its function depends on the type of cell: Varies to the metabolic activity of a cell and type of LIVER CELL cell For carbohydrate metabolism Size and number vary Makes use of the enzyme G6P or Glucose- Mature RBC → no mitochondrium 6-Phosphate, which converts glycogen to Liver cells → multiple mitochondria (2,500 glucose +) Breaks lipids soluble drugs CP450 Considered a dynamic organelle → shows constant motion, fusion and division in cells 2. ROUGH ER Membrane with porins Has ribosomes on the external surface Fission and division of cells Granular, forming rosettes TWO MEMBRANES Involved in the synthesis and export of proteins ~ Separated by an inter-membrane space and glycoproteins, due to the presence of ribosomes 1. Outer Mitochondrial Membrane Site / area / region of translation, folding, Smooth transport of new proteins (which will then travel to Made of porins, which increases membrane the golgi apparatus) permeability for the passage of molecules and Translation of RNA to amino acids metabolites for ATP synthesis 2. Inner Mitochondrial Membrane Ribosomes Shows transverse shelf-like or tubular folds Small, spherical, electron-dense particles called “cristae” Synthesizes proteins and consist mostly of RNA and associated proteins 5 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry enzymes, leading to cell death when packaged Golgi Apparatus lysosomal enzymes are released. First discovered in neurons by the neurohistologist Camillo Golgi in 1898 Located in the center of the cell, cytocentrum, close 3 KINDS OF LYSOSOME to the nucleus and centrosome 1. Primary Complex array of flattened, slightly curved, closely Newly formed and have homogenous, packed membrane-bound sacs (cisternae) with granular content; no enzymes and no associated vesicles and larger vacuoles digestive material Major role is sorting and packaging secretory 2. Secondary proteins produced in the RER; modify new proteins Larger and more heterogenous in appearance and electron density with remnants of digestive products / material Contains a complete digestive particle It forms when a primary lysosome fuses with a vesicle containing material to be digested 3. Tertiary / Residual Bodies Oldest with complete digestive function Prominent in long-lived cells such as The three functional distinct compartments: nerve and cardiac muscle cells 1. Cis → cisternae nearest the endoplasmic Bizarre looking with abundant debris; reticulum; network of vesicles on the convex side common in cardiac, nerve and muscle 2. Medial → central layers of cisternae; stacks of cells flattened saccules 3. Trans → cisternae farthest from the endoplasmic reticulum; vesicles and vacuoles for distribution and sorting of secretory products ◸ Clinical Importance ◿ Alzheimers Disease A condition where there are structural and functional alternations of the golgi apparatus in some neurons of the brain Characterized as a neurodegenerative disorder, which would lead to progressive dementia, with selective loss of neurons in certain parts of the CNS (Central Nervous System) Histologically, in these patients are fragmentations and marked atrophy of the Golgi Complex, which ◸ Clinical Importance ◿ are accompanied by abnormal protein aggregates consisting of neurofibrillary tangles and senile plaques Tay-Sachs Disease A rare genetic disorder passed from parents to Lysosome child Caused by the absence of an enzyme that helps Membrane bound organelle break down fatty substances called gangliosides, A heterogenous collection of vesicles and vacuoles which build up toxic levels in the brain and spinal derived from Golgi complex vesicles cord and affect the function of nerve cells Contains 50 or more hydrolytic enzymes, most Deficienct of lysosomal enzyme, Hexosaminidase A being glycoproteins that are active at acid pH, and or HEXA stain cytochemically for acid phosphatase; Fatal or deadly genetic disorder lysosomal storage “intracellular digestive system” disease Spherical or irregular in shape The test is done using HEXA during the pre-natal More abundant in phagocytosis → Serve in defense against infection by phagocytes engulfing viruses, bacteria, and other pathogens in bodily defense mechanism In response to cell injury, they aid autolysis of cells → self-destruction by self-produced 6 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry In liver cells → lipid droplets are the main site Peroxisomes of cholesterol synthesis Ubiquitous, membrane-bound organelles which are In Smooth ER → synthesis of cholesterol, prominent in liver cells (hepatocytes) and in lipids and glycoproteins take place proximal tubule cells of the kidney Appears as clear and vacuolated due to lipids are Are spherical to ovoid already discarded to the organic solvent Anabolic and catabolic functions Engaged in an oxidative reaction, therefore contain oxidative enzymes such as catalase and uric oxidase, which act as catalyst, and contain urate oxidase FUNCTIONS: Cellular respiration, fatty acid metabolism, alcohol degradation, transamination, regulation of H2O2, and bile acid metabolism ◸ Clinical Importance ◿ Steatosis Abnormal accumulation of triglycerides, which are stored as lipid droplets and can be seen in patients ◸ Clinical Importance ◿ with atherosclerosis, diabetes syndrome, alcoholic CONDITIONS: liver disease, hepatocellular carcinoma, familial 1. Alzheimers Disease hyper-cholesterolemia — atherosclerotic coronary 2. Hypotania or severe weakness artery or stroke 3. Retinal Degeneration 4. 5. Intractable seizure Any impairment of vision or sensorineural hearing Cytoskeleton Slender rod-like filaments 1. Intermediate filaments INCLUSION BODIES 2. Actin filaments Made up of Intermediate, Actin and Microtubules Glycogen MICROTUBULES Inert, transitory, metabolic by products Hollow, semi-rigid cylindrical organelles that Is stored in the cytoplasm of liver cells (hepatocyte) resemble drinking straws in EMs as well as in the skeletal muscle cells They are unbranched and extremely variable in Periodic Acid Schiff (PAS) is a test used to stain to length. visualize glycogen granules They are found in most cells but are especially abundant in neurons, platelets, leukocytes, and ◸ Clinical Importance ◿ dividing cells. Glucose - 6 - Phosphate (G6PD) Main components are cilia, flagella, and centrioles A genetic disorder condition that happens when FUNCTION: provide mechanical strength and your body doesn’t have enough glucose-6- establish cell shape as a major part of the phosphate dehydrogenase enzyme cytoskeleton. Cause organ damage Engages in intracellular transport of organelles. Can be tested through biopsy They have no membrane; the walls of which are composed of proteins which are called tubulin. Lipid Droplets Also called as adipocytes of fat cells which are insoluble in water Are the main storage site of the lipids of the body For thermal regulation; physical pudding such as the butt; shock absorption like the breasts Triglycerides abd esters of cholesterol 7 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry CYTOPLASMIC FILAMENTS Three Components of Phospholipids Non-membranous 1. HEAD Made of phosphate There are six types: Hydrophillic, water-loving, polar part nuclear lamins Intermediate Desmin vimentin 2. BACKBONE filaments neurofilaments Made of glycerol Glial filaments Hydrophobic actin filaments 3. TAIL Made of fatty acids hydrophobic Also called thin filaments or microfilaments Have cytoskeletal and Different particles easily passing through motility functions, specifically: cytokinesis the cell membrane and phagocytosis. Actin ▶ such as gases like They contribute to cell filaments Small & Non-Polar oxygen and carbon movement and interact M dioxide with thick (myosin) filaments. O L ▶ such as water and They are found in microvilli or beneath the E Small & Polar ethanol but at a slower pace plasma membrane C U ▶ such as benzene Large & Non-Polar L but slow at pace Cytoplasmic vesicles are invaginations of the E plasma membrane. ▶ cannot pass such S The vesicles are transported by endocytosis, as glucose and all pinocytosis, and exocytosis. Large & Polar other charged molecules Centrosome A major microtubule-organizing center of a cell Two Types of Protein and the site for generation of new cytoplasmic IN THE CELL MEMBRANE microtubules and the mitotic spindle. 1. Integral Proteins (intrinsic) Non-membrane bound organelle, near the nucleus. Are those that are stuck within the cell Made up of a pair of centrioles; diplosome → membrane and are difficult to remove. oriented at right angles or obliquely to each other. 2. Peripheral Proteins (extrinsic) Each centriole is a short cylinder, each consisting Are those that are attached on the cell of a ring of nine sets of fused microtubule triplets. membrane and can be removed for different They are very prominent in dividing cells. cell processes Abnormality or a defective centrosome are seen in Example→ hormones malignant tumor or cancer cells Lipid bound proteins : channel proteins, carrier Centrioles proteins, glycoproteins are other proteins in the cell membrane Short cylinder Cell membrane is also used for transport of ions Consists of a ring and nine sets of fused microtubule triplets Prominent in dividing cells Different Transport Mechanism In some abnormalities or defective centrosome, Is a particular transport they are seen as malignant tumor cells mechanism that does not PASSIVE require energy. CELL MEMBRANE Example : potassium OR PLASMALEMMA Utilizes the protein channel The structure that protects the cell from FACILITATED and requires energy (ATP). substances that leaves the cell. Semi-permeability property Spreading a molecule from Main building blocks of a cell membrane are the DIFFUSION a high concentration to a phospholipids. low concentration. 8 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry Is movement of water molecules through a CELL CYLE OSMOSIS The lifespan of the cell, also described to be the membrane to make the different seasons of the cell concentration equal. Two Phases / Seasons Endocytosis → movement of larger molecules; uses energy ▶ comprises of the G0 Exocytosis → exits the cell membrane through a phase (quiescence), G1 vesicle (initial cell growth), S phase (DNA synthesis, INTERPHASE CELLULAR MODIFICATIONS duplication of chromosomes), G2 Intercellular Junctions → they are simple (preparation for cell interdigitations to increase adhesiveness division) ▶ active cell division. The Three Types shortest part of the cell cycle. 1. TIGHT (zonula and macula occludens) MITOSIS ▶ The process where one These intercellular junctions will form cell with one nucleus will permeability barriers, to prevent turn into two cells with indiscriminate passage of materials or two nucleus. substances. 2. ANCHORING (macula and zonula adherens) Seen in the epithelial cells in cardiac and smooth muscle cells. Will hold the cells together at focal points. They usually occur between lateral borders of adjacent epithelial cells. 3. GAP (or communicating junctions) The site where metabolic, ionic, and electrical communication between adjacent cells will take place. These are specialized sites which are composed of large, tightly packed intercellular channels that connect the cytoplasm of adjacent cells. Each of these junctions have its contact sites which consist of transmembrane proteins. And may vary, it may have occludins, claudins, cadherins which will reinforce the contact site. INTERPHASE Carcinoma → alterations in claudin expression contribute to initiation of many such malignancies G1 Period of growth; organelles formed shown in breast cancers, also in endometrial Synthesis; DNA is a main component cancers. of chromosome doubles through a S process “replication” each chromosome is made up of 2 sister chromatids attached in a centromere. Growth directed more in preparing for G2 mitosis e.g. Assembly of proteins in microtubules (pull chromatids apart) G0 Some cells do not divide e.g. neurons 9 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry MITOSIS 1. Prophase DNA / chromosome condenses; nuclear membrane disintegrates centrioles that migrate to the opposite poles of the cell 2. Metaphase Nuclear membrane disappears; chromosomes line up at the equator of the cell Microtubules / spindle fibers are formed from centrioles 3. Anaphase Shortened microtubules pull apart each sister chromatid which migrates to opposite poles Cleavage furrow starts to develop 4. Telophase Spindle fibers are broken; nuclear envelope starts to reform Chromosomes loosens or uncoil; nucleolus appears Cytokinesis → pinching off of cell membrane resulting to two daughter cells ◸ Clinical Importance ◿ Tumor cells exhibit rapid division than normal cells which responds to Vinca alkaloids (chemotherapeutic agents). Arrest metaphase. Specialization of the Cell Surface 1. MICROVILI are simple, finger-like projections of cell surface that are found on epithelial cells in several sites, such as small intestine and kidney. Their major role is to increase surface area for absorption. They contain a core of actin filaments. 2. STEREOCILLA long, branched microvilli that are on free surfaces of epithelial cells lining parts of the male reproductive tract and inner ear 3. CILIA with the most complex internal structure, are mobile extensions of the cell surface. Their structure is similar to that of flagella, but their beating patterns are different. Found in parts of the respiratory and female reproductive tracts 4. FLAGELLA Found in sperm cells, are longer than cilia. They originate from basal bodies, which are identical to centrioles. 10 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry Epithelium 2. Glandular → number of cell layers a) SIMPLE → one layer b) STRATIFIED → two / many layers LECTURE 02 3. Presence of Surface Specialization a) Ciliated Simple Columnar EPITHELIUM 4. Accumulation Epithelia → plural a) Keratinized Stratified Squamous Epithelium is one of the four basic tissues, with a wide distribution and many functions. It consists of continuous sheets of cells. Epithelium is made almost entirely of contiguous and adhesive cells bound together by intercellular junctions and a small amount of extracellular matrix. Epithelium has tissue polarity and an apical (or free) surface, lateral surfaces between adjacent cells, and a basal surface in contact with an underlying basement membrane. Epithelia lack a direct blood supply and are fed via diffusion from underlying tissues. Unlike other basic tissues, epithelia have a high mitotic index with constant cell renewal—an advantage because cells undergo mechanical stress and trauma. ◸ Clinical Correlation ◿ Disadvantage of having high mitotic index: Susceptible to formation of malignant tumors called Benign and Malignant tumors carcinomas. Epithelial cells have a high mitotic index and are exposed to the surface, which gives pathogens and carcinogens free access to them. Functions: The most common types of cancerous (or Cover exposed body surfaces. It also lines internal malignant) tumors (or neoplasms) in adults cavities, such as those of the digestive, respiratory, originate from epithelial cells; these tumors invade cardiovascular, and genitourinary systems. or metastasize to distant tissues and organs. A selective barrier that protects other tissues, it Neoplasms that grow slowly are benign tumors transports material along its surface uni- or and include papillomas, which arise from surface bidirectionally. epithelium, and adenomas, which originate from Other functions include synthesis, secretion, glandular epithelium. absorption, and, because cells are exposed on free Malignant neoplasms of surface surfaces, sensory reception. epithelium are carcinomas Those originating from glandular Embryonic Origin epithelium are adenocarcinomas. During embryonic development, epithelium Knowing a tumor’s histologic characteristics often invaginates into underlying tissues to proliferate helps determine diagnosis, staging, and treatment. and form secretory glands. Epithelia have diverse embryonic origins and may SIMPLE SQUAMOUS come from ectoderm (eg. skin), mesoderm (eg. kidneys, male and female reproductive organs, EPITHELIUM peritonial cavity, serious cavity, lymph and blood Simple squamous epithelium consists of a single vessels), or endoderm (eg. alimentary tract, liver, layer of flattened cells. pancreas. Respiratory lining, gastric gland). The cells, shaped like scales (Latin squama), are best seen in a surface view and have irregular, serrated outlines that fit together like pieces of a Classifications jigsaw puzzle. 1. Covering and lining → shape of the cells at the surface a) Squamous b) Cuboidal c) Columnar d) Pseudostratified e) Transitional 11 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry Different Names ENDOTHELIUM & MESOTHELIUM Names of this epithelium depend on location: ENDOTHELIUM MESOTHELIUM Simple squamous Consists of simple epithelium of the squamous cells lining of the heart, forming serous blood vessels, and membranes lining lymphatic channels internal body cavities This distinction is important to pathologists because cells behave differently in inflammation and tumor formation ▲ LM of the cortex of the kidney showing part of a renal corpuscle. Simple squamous epithelial cells (arrows) form the parietal layer of Bowman capsule ◸ Clinical Correlation ◿ Malignant Mesothelmia Rare, aggressive tumors called malignant mesotheliomas may arise from parietal and visceral serous membranes of pleural, peritoneal, and pericardial cavities. Pleural mesothelioma — the most common — is usually caused by occupational exposure to asbestos. It has a long latency time (25-40 years) from first contact to onset of symptoms, which include shortness of breath, chest pain, and pleural fluid ▲ Light Micrograph (LM) of the serosa of the urinary bladder.Simple squamous accumulation. epithelial cells make up a mesothelium that covers the bladder and lines the Diagnosis (Dx) : Magnetic Resonance Imaging peritoneal cavity (MRI), Positron Emission Tomography (PET scan), needle biopsy, and electron microscopy are useful Example / Location for diagnosis. (of simple squamous epithelium) Treatment (Txt) is through surgery, radiation, and Simple squamous epithelium in the kidney chemotherapy. constitutes the parietal layer of Bowman capsule and thin loops of Henle; it is also found in the middle and inner ear, and in lungs where it lines Ultrastructure : Intercellular Junction found in this Epithelium: pulmonary alveoli. Desmosome (macula adherens, Anchoring Junction) Tight Junction Gap Junction SIMPLE CUBOIDAL EPITHELIUM Simple cuboidal epithelium consists of one layer of cells whose height roughly equals their width, so in sections perpendicular to the surface, cells resemble small box-like cubes. Cells in horizontal section appear to be a mosaic of polygonal tiles. As in other epithelia, cells rest on a basement ▲ LM of the renal medulla. Simple squamous epithelial cells line hoops of membrane that firmly attaches to underlying Henle. Nuclei (arrows) of the cells bulge into tubule lumina. connective tissue. Each cell has one spherical, centrally placed nucleus. 12 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry Their cytoplasm has more organelles than that of simple squamous epithelial cells, with more SIMPLE COLUMNAR mitochondria and endoplasmic reticulum, which are evidence of high metabolic and functional EPITHELIUM activities. Simple columnar epithelium consists of one layer Choroid plexus of cells that are taller than they are wide and look Capsule of lens, ducts of glands like closely packed, slender columns. Bases of cells rest on a basement membrane; apical surfaces contact a lumen. The ovoid nucleus is centrally or basally placed. The cytoplasm is packed with many organelles. At certain sites, the epithelium may consist of more than one type of cell, with mucus-secreting goblet cells being common; paranasak sinuses In some areas, the epithelium may have cilia (ciliated). Uterus and oviducts Functions: Central canal of the spinal cord This epithelium provides protection, forms conduits for gland ducts, and may be specialized for active secretion and absorption. On the free surface of the ovary, it is ovarian surface epithelium. Example / Location: It also lines renal tubules and small collecting ducts of the kidney, which engage in ion transport. The thyroid— an endocrine gland —contains spherical follicles of these cuboidal cells. The parenchyma of most exocrine glands, such as salivary glands and pancreas, consists of cuboidal to columnar epithelial cells in grape-like clusters called acini. In the eye, cells of pigmented epithelium of the retina and epithelium of the ciliary body are simple Function: This epithelium, widely distributed in the body, is cuboidal and specialized for ion transport and mainly found in sites engaged in protection of wet secretion. surfaces, nutrient absorption, and secretion. Example / Location: It forms major ducts of glands, convoluted tubules of the: Kidney, Inner lining of the digestive tract (stomach) from the cardia to the anus, Small and large intestines, Gallbladder, Small bronchi and large bronchioles of the lungs, and Parts of the male and female (oviducts and uterus) reproductive tracts ▲ LM of a portal triad in the liver. Simple cuboidal epithelium lines a small bile duct. Specialization : Microvilli Free surfaces of cells often bear microvilli—thin, fingerlike cellular projections—for increased Specialization : Microvilli surface area. Free surfaces of these cuboidal cells often have microvilli, which are best seen by electron microscopy. 13 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry ▲ LM of the inner lining of the gallbladder. Simple columnar epithelium lines the lumen. Examples / Location: Striated Border More aptly a type of simple epithelium, it lines many parts of the upper respiratory tract When microvilli are large (1-2 mm high), uniform Nasal cavities, in size, and closely packed, they form a striated Auditory tube, border. Nasopharynx, Larynx, Ultrastructure: Trachea, and Intercellular Junction found in this Epithelium: Large bronchi Lateral cell borders have junctional complexes, which include an apical tight junction, intermediate (adherens) junction, and Specialization : Cilia desmosome. (Ciliated) Mucous goblet cells usually occur in this epithelium, and where they mingle with ciliated PSEUDOSTRATIFIED columnar cells, the tissue is called respiratory epithelium. EPITHELIUM Pseudostratified ciliated columnar epithelium with goblet cells – full name. COLUMNAR Pseudo meaning false The cilia acts as a mucociliary escalator to entrap Also known as the Respiratory Epithelium and rid airways of foreign particles by sweeping, Pseudostratified epithelium consists of more than coordinated ciliary motion. one type of epithelial cell, of varied size and shape. Eustachian tube In sections perpendicular to the surface, the nuclei Part of tympanic membrane usually appear at different levels, so two or three Lacrimal sac layers of crowded nuclei are seen, but all cells are Pseudostratified epithelium lacking goblet cells is in contact with the basal lamina. also found in parts of the male reproductive tract, A basal layer belongs to replacement (stem) cells where some cells have apical nonmotile with mitotic potential for regeneration. stereocilia and mainly lining, secretory, and Large excretory ducts parotid glands and male absorptive roles are performed. urethra. All cells contact an underlying basement membrane, but only some reach the free surface and do not penetrate the whole thickness of the epithelium. These features give the epithelium a false impression of stratification—thus, its name. 14 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry ▲ LM of pseudostratified ciliated columnar (respiratory) epithelium with goblet cells. ▲ LM of nonkeratinized stratified squamous epithelium (LEFT) in the oral cavity and of keratinized stratified squamous epithelium (RIGHT) of skin. STRATIFIED SQUAMOUS ◸ Clinical Correlation ◿ EPITHELIUM Wound Healing After injury by trauma or infection to skin and DESCRIPTION, STRUCTURE, FUNCTION: other soft tissues, the capacity of epithelial cells to is a tough, resilient multilayered epithelium that undergo mitosis and regenerate is clinically mainly protects against abrasion and dehydration. important. It also prevents invasion of pathogens, bacteria, Complex reparative events known as wound and other infectious agents. Its name derives from the shape of the outer layer healing include an inflammatory phase followed of flattened cells. by proliferative and remodeling stages. Epithelial cells from nearby areas replicate, change shape, and migrate across the defect to cover the Types: wound. KERATINZED & NON - KERATINIZED Angiogenesis, whereby new capillaries grow from endothelial cells, also occurs. The basement Keratinized membrane is critical for rapid recovery; if it is In areas exposed to air and subject to abrasion, destroyed, healing is relatively slow. such as epidermis of skin, the surface layer consists of dead cells lacking nuclei and containing plates of the protein keratin, which strengthens Ultrastructure : Keratinocytes and waterproofs the tissue. Keratinocytes → cells of both epithelia, have This keratinized stratified squamous epithelium, many intercellular junctions, which are mostly with a dry, scale-like surface, also lines the desmosomes that connect cells to counteract following: external forces of friction. Outer surface of the tympanic membrane For added strength, an extensive internal Parts of the oral cavity (gingiva and hard cytoskeleton, made mostly of keratin palate) intermediate filaments, internally reinforces Some mucocutaneous junctions (lips and cells. distal anal canal) Desquamation → A process wherein basal cells are mitotically active and continuously divide into Non-Keratinized daughter cells that mature and are pushed toward In other areas covered with fluid and with a moist the surface to die and slough off. surface, superficial squamous cells retain nuclei Keratinized epithelium that makes up the and lack keratin. epidermis of skin is renewed every 15-30 days; This non-keratinized stratified squamous non-keratinized epithelium of the oral cavity has epithelium lines most of: a much more rapid turnover rate. The oral cavity, pharynx, epiglottis, vocal cords, esophagus, anal canal, vagina, parts of the male and female urethra, and cornea. Secretions from closely associated glands lubricate the surface of this epithelium. 15 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry ◸ Clinical Correlation ◿ It also occurs at sites of epithelial transition, interposed between two other types of epithelia. Epithelial Dysplasia Such abrupt epithelial interfaces occur in the Epithelial dysplasia is a premalignant change in epiglottis and rectoanal junction epithelium— an alteration in cell structure encoded These sites are unstable and thus may undergo in the genome plus an abnormal appearance of the malignant change tissue. CERVICAL DYSPLASIA → a precancerous lesion in epithelium of the cervix, is caused by human ◸ Clinical Correlation ◿ papillomavirus (HPV) and is usually found via a Conjunctivitis screening test called the Pap smear. Pink eye or conjunctivitis (inflammation of the ORAL DYSPLASIA → involves increased mitotic conjunctiva), is the most common acute eye activity of oral epithelium with cell shape changes infection in children and loss of stratification of epithelial cells. Is usually caused by bacteria or viruses, allergy or irritation from contact lense use The normally seasonal allergic conjunctivitis leads STRATIFIED CUBOIDAL AND to ocular redness and itching, crusting of eyelids, and photophobia. COLUMNAR EPITHELIUM Bacterial conjunctivitis occurs more often than Both contain two or more layers of tall cells, and the viral form, the most common causativeagents because they are stratified, they are mainly being Haemophilus influenzae and Streptococcus protective and better suited than simple epithelia pneumoniae. to withstand wear and tear. Outbreaks of adenovirus conjunctivitis have This epithelium usually consists of basal cells been linked to contaminated equipment and (cuboidal), intermediate cells (more polyhedral), swimming pools. and superficial cells (columnar). It may often be confused with pseudostratified epithelium. TRANSITIONAL EPITHELIUM (UROTHELIUM) This epithelium has mucus-secreting goblet cells The original term—transitional—is a misnomer; that provide lubrication to the surface. this epithelium was erroneously thought to be intermediate between stratified squamous and stratified columnar epithelium. Its appearance is not static. The basal layer of small cuboidal to columnar cells contacts a thin basement membrane. They serve as precursor stem cells and have a turnover rate of 12-24 weeks. ▲ LM of stratified cuboidal epithelia. ▲ LM of stratified cuboidal epithelia. The most superficial layer in contact with the This epithelium, forms ducts of a This epithelium forms an esophageal lumen consists of relatively large, often binucleate sweat gland. mucous gland. cells. Their free surfaces are convex and they span several cells underneath, so they are called Distribution : umbrella cells. Stratified cuboidal and stratified columnar Electron microscopy shows all cells of this epithelia have limited distribution in the adult; epithelium in contact with the basement they are more common in the embryo and fetus. membrane via long cytoplasmic processes, not Uncommon / seldom found in humans except: unlike cells of pseudostratified epithelium. Fornix of conjunctiva Cavernous urethra Examples / Location : (Ciliated) Stratified cuboidal epithelium, usually two layers of cells, lines ducts of sweat glands and other exocrine glands. Stratified columnar epithelium is in the pharynx and larynx, nasal surface of the soft palate, conjunctiva of the eyelids, major ducts of exocrine glands, and parts of the male urethra. In the urethra and conjunctiva, two to five layers of cells make up the epithelium. 16 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry Example / Location : Ultrastructure Multilayered transitional epithelium is more aptly Intercellular junctional complexes contain many termed a urothelium, in that it is restricted to tight junctions, which reduce movement of water, lower parts of the urinary tract, where it lines the ions, and solutes between cells. renal pelvis, ureters, urinary bladder, and part of the urethra. BASEMENT MEMBRANE Most epithelia rest on an amorphous extracellular layer where most epithelia rest — the basement membrane — at the boundary between the epithelia and underlying connective tissue. ▲ LM of transitional epithelium in a contracted bladder. EXTERNAL LAMINA Where it surrounds other types of cells such as muscle cells, adipocytes, and Schwann Function : cells, it is called an external lamina. It rapidly adapts to contraction and distention; it BASAL LAMINA changes from a tall epithelium with five to seven With the advent of electron microscopy, cell layers (empty state) to a thinner epithelium the basement membrane has also been with only two or three cell layers (distended state). called the basal lamina. Urothelium acts as a permeability barrier and The two terms are often used interchangeably, protects tissues from noxious effects of urine, but which may cause some confusion, but the basal it can also stretch to accommodate urine volume. lamina is just lamina lucida and lamina densa. ◸ Clinical Correlation ◿ Transitional cell carcinoma Functions : A common malignant neoplasm of the urinary tract A basement membrane supports and cushions is transitional cell carcinoma. epithelia, is a semipermeable sieve or selective It arises from the urothelium of the renal pelvis, filtration barrier, and controls epithelial cell ureter, or bladder and is often fatal unless treated. differentiation in growth and tissue repair. Hematuria (blood in urine) and pain from gradual obstruction to urination are usual presenting symptoms. Its cause is unknown, but risk factors include cigarette smoking and occupational exposure to organic compounds such as benzidine and asbestos. ▲ LM of the basement membrane in a trachea. 17 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry important insights for design of novel therapeutics to minimize or halt metastatic spread. ▲ LM of basement membranes in the cortex of a kidney. Composition : These membranes vary in thickness and contain glycosaminoglycans and proteoglycans (heparan sulfate; perlecan), Glycoproteins (laminin, entactin, and fibronectin), and Collagen LAYERS The lamina lucida is a pale zone (10-50 nm wide) of low density, just next to basal plasma membranes of epithelial cells. An intermediate zone, wider and more electron dense, is the lamina densa. Its thickness (20-300 nm) depends on location. Type IV collagen in both layers is a fine meshwork embedded in an amorphous matrix. The outer layer, the reticular lamina (lamina fibroreticularis), consists mostly of a delicate network of reticular fibers (type III collagen). ◸ Clinical Correlation ◿ Metastasis and Metastatic cascade METASTASIS → “spread” of malignant cells from a primary tumor to distant sites—is the second leading cause of death after cardiovascular disease in North America and poses major challenges in cancer treatment. The sequence of events — known as the METASTATIC CASCADE — begins with detachment of tumor cells from each other by alteration of intercellular adhesion molecules (e.g., cadherins). Tumor cells then develop finger-like protrusions (invadopodia) that perforate and degrade the basement membrane with release of proteolytic enzymes. Tumor cell migration by ameboid movement proceeds via cell receptors (e.g., integrins) and signaling proteins that interact with a cytoskeleton replete with actin and intermediate filaments. Fundamental understanding of such events should provide 18 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry Connective Tissue 3. Acinar → Latin for grape or berry LECTURE 03 4. Mixed → tubuloacinar or tubuloalveolar GLANDS CLASSIFICATION ACCORDING TO Embryonic Origin : STRUCTURE OF DUCT SYSTEM All glands, classified as either exocrine or 1. Simple or Unbranched, as in sweat glands endocrine, develop embryonically from surface 2. Compound or branched, as in most organs (e.g., epithelium; groups of surface cells differentiate, pancreas and liver). proliferate, and penetrate underlying connective tissue. CLASSIFICATION ACCORDING TO TYPE OF SECRETION Main Function : 1. Mucous → when secretions are a viscous Their main function is to synthesize and secrete glycoprotein called mucus; extracellular products. 2. Serous → when secretions are watery and enzyme-rich; Two Types of Glands 3. Seromucous (mixed) → when one gland secretes both types ENDOCRINE GLANDS EXOCRINE GLANDS CLASSIFICATION ACCORDING TO MODE These are ductless and These connect to the release products, called surface by ducts, which OF SECRETION hormones, directly into the take the secretions to the 1. Merocrine → involves release (or exocytosis) of bloodstream. These glands surface or lumen. secretory vesicles from cells by fusion with plasma are arranged in cords or membranes. clumps of cells, close to a 2. Apocrine secretion (most common) → as in complex network of mammary glands, involves release of apical capillaries, for hormone cytoplasm of cells. transport. 3. Holocrine secretion → in sebaceous glands of skin involves disintegration and release of whole cells. Classification of Exocrine Glands Multicellular → (most common) and have secretory units and ducts. SEROUS CELLS Serous cells are polarized and have basal, apical, Unicellular → One secretory cell (e.g., goblet cell) and lateral domains and a basal spherical nucleus. lies between other cells in an epithelium. They rest on an inconspicuous basement membrane, which encloses the whole acinus. Components The epithelial, or functional, component of all Function : glands is parenchyma ; They serve a contractile role by promoting release The parenchyma of most exocrine glands of secretory product into lumina of excretory ducts. consists of secretory units, made of groups of Secretory granules dominate the apical cytoplasm epithelial (secretory) cells around a lumen of serous cells, so it is relatively eosinophilic. that are continuous with an excretory duct system (also lined by epithelial cells). Description of Secretion : Stroma is the main supportive connective tissue Serous cells produce a watery, proteinaceous of the gland secretion, which usually contains enzymes, so their histologic appearance reflects protein synthesis GLANDS MAY BE CLASSIFIED and secretion. ACCORDING TO SHAPE AND EXAMPLES WHERE CELLS OCCUR: ARRANGEMENT ◸ in pure serous glands 1. Tubular → like a test tube Parotid Lacrimal gland 2. Alveolar → Latin for hollow sac or cavity Exocrine pancreas → (the pancreas shows both exocrine and endocrine glands) 19 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry ◸ in mixed seromucous glands connective tissue of the head originates from neutral crest ectoderm such as major and minor salivary glands and in walls of upper respiratory airways. → These cuboidal, columnar, or pyramidal cells are seen in Components : Like all body tissues, connective or supportive groups of grape-like clusters called secretory acini. Tightly tissues consist of: packed cells with dark-stained cytoplasm surround a small lumen in the acinus. Cells - both fixed and wandering Cells of connective tissue include ◸ Clinical Correlation ◿ fibroblasts, mast cells, macrophages, plasma cells, adipocytes (fat cells), and Tumor Staging and Grading pericytes. In diagnosis of cancers, tumor staging and grading are essential for appropriate treatment and Extracellular matrix (ECM) - composed of prognosis and are also important in identifying fibers embedded in an amorphous ground clinical trials suitable for patients. substance. Staging categories establish the severity and extent of disease, including the size of primary tumor, Functions : regional lymph node involvement, and absence or The many functions of connective tissue depend presence of metastasis. largely on the properties of the ECM, which For tumor grading, samples obtained by various predominates. methods (e.g., excision biopsy, needle aspiration, To provide form, support to organs and connect, cytologic smears examined microscopically). anchor to other parts of the tissue. A medium of exchange of nutrients, oxygen and MUCOUS CELLS waste products between tissues Aids in defense and protection MUCUS, a secretion consisting in part of mucin, Provides cushion or thermoregulation (adipose which contains highly viscous glycoproteins, tissue) protects and lubricates surfaces. Functions : Mucous cells also line the stomach lumen and form small glands in the esophagus and duodenum. Several types of mucin exist, of different chemical compositions, but mucin-producing cells share similar histologic and ultrastructural features. Mucous-Producing Cells : Widely distributed mucus-producing cells are Main Criteria : found either: Amount and type of ECM; Singly, Goblet cells in epithelia of the digestive, Arrangement respiratory, and reproductive tracts, or Kind of Fibers; Grouped, as tubules or acini. Abundance and types of cells. Most notably, they occur in major and minor salivary glands of the oral TYPES OF ADULT CONNECTIVE TISSUE PROPER : Loose (Areolar) Connective Tissue CONNECTIVE TISSUE The most widespread, has the greatest variety of Supportive Tissue cells and fibers. Types : Adult; Specialized, Embryonic It is highly cellular with few fibers and has great flexibility. The composition of connective tissues varies The term areolar refers to small fluid-filled spaces greatly in different parts of the body. On the basis in this tissue. of appearance and related to function, connective Much of the body’s tissue fluid is found within tissue proper can be placed into different loose connective tissue, and excessive categories in the adult and embryo. accumulation of this fluid causes swelling, or edema. Origin Almost all connective tissue, regardless of form, arises embryonically from mesoderm; some 20 Lizzie Regalado’s Notes ヾ( ω `)o DENTISTRY II - A Cebu Doctors’ University | College of Dentistry Dense connective tissue ◸ Clinical Correlation ◿ Has a greater proportion of fibers, fewer cells, and Ehlers-Danlos Syndrome (EDS) less ground substance. Complex collagen synthesis can be impaired by Its division into two subtypes depends on the dietary deficiency of vitamin C (ascorbic acid), orientation of its fibers. producing scurvy, and by errors in critical genes or Dense irregular connective tissue has randomly enzymes, leading to the rare Ehlers-Danlos oriented, interwoven fibers that can respond to syndrome (EDS). stress in many directions. In dense regular connective tissue, fibers are in parallel and can withstand prolonged stress from COLLAGEN one direction. Involves both intracellular and extracellular events known in protein synthesis Three specialized types of connective tissue in Most abundant protein in the body the adult: Enzymatic cleavage by procollagen peptidase Adipose produces tropocollagen molecules that aggregate Reticular to form crossstriated collagen fibrils. Elastic The fibrils then assemble into bundles to form FIBERS TWO TYPES OF EMBRYONIC / FETUS At least 20 genetically distinct types of collagen CONNECTIVE TISSUE exist in this family of extracellular proteins that differ mainly in amino acid composition. Mesenchymal connective tissue occupies spaces between developing organs. Mucous connective tissue is in the umbilical cord Synthesis of Collagen (Wharton’s Jelly). Messenger RNA (mRNA) is synthesized from a template of DNA in the fibroblast nucleus ◸ Clinical Correlation ◿ mRNA molecules enter the cytoplasm and attach to ribosomes of the RER. Fibrosis; Fibrotic Scarring Ribosomes translate the nucleotide sequence of the FIBROSIS → is deposition and overgrowth of mRNA into an amino acid sequence. excess fibrous connective tissue that forms scar A polypeptide chain of a specific sequence of tissue because of injury, infection, allergy, or long- several amino acids is assembled and then term inflammation. detaches from the ribosome to enter the RER FIBROTIC SCARRING → is most common in the cisternae. heart, lung, peritoneum, and kidneys. It differs Hydrox- ylation of proline and lysine residues in from normal development of the stroma of organs the RER requires ascorbic acid (vitamin C) as a and tissues because such scarring may obliterate cofactor. normal architecture, leading to dysfunction and Three alpha chains form a triple helix to form organ failure. procollagen, a precursor to collagen. FIBROLASTS Major Collagen Types : Function is to generate and secrete ground substance Connective tissue proper, bone, TYPE I The main cell type of connective tissue is the most dentin and cementum common cell of loose (areolar) connective tissue TYPE II Hyaline and elastic cartilage and virtually the only cell of dense regular TYPE III Reticular fibers connective tissue such as tendon. In mature connective tissue, these cells are TYPE IV Lamina densa and basal lamina relatively inactive and immobile and are often TYPE V Assisted with Type I and placenta called fibrocytes have one elliptical nucleus, usually euchromatic, with one or more distinct Attaching basal lamina to lamina TYPE VI nucleoli reticulars After injury and during wound repair, they rapidly proliferate and become active fibroblasts to ◸ Elastic Fibers → elasticity is due