Histology - First Year Cytology PDF

HISTOL06'Y - FIRST Y'EAR.. CHAPTER 2 CYTOLOGY By the end of this chapter, the student should be able to: 1. Recogn ize and interpret drawings and photographs of organelles in animal cells using light and electron microsc...

HISTOL06'Y - FIRST Y'EAR.. CHAPTER 2 CYTOLOGY By the end of this chapter, the student should be able to: 1. Recogn ize and interpret drawings and photographs of organelles in animal cells using light and electron microscope. 2. Compare membranous and non-membranous organelles. 3. Compare organelles and inclusions. 4. Correlate the functions of the different organelles to their structure. 5. Compare and contrast the closely related organelles. 6. Describe the clinical significance of some organelles. 7. List the organelles involved in protein and lipid synthesis. 8. Describe with reference to examples different cellular inclusions. 9. Describe the structure of the different parts of the nucleus and their related functions and clinical significance. 10. Distinguish between euchromatin and heterochromatin The cell Definition: It is the basic structura l & functional unit of the living body. Functions: Absorption, respiration , secretion , excretion , sensation , conduction, contraction, movement,.growth , and reprod uction. Size: Varies from 4 µm (as granular cells of cerebellum) to 150 µm (as ovum). Shape: Rounded, oval, flat, stellate, polygonal, cubical or columnar. Structure: Animal cell is formed of 2 basic components: Cytoplasm & nucleus. The Cytoplasm - It is formed of cytosol , organelles, and inclusions. - Cytosol: Fluid containing carbohydrates, proteins, lipids, minerals, ions and salts, RNA, Metabolites , 02 and Co2. Organelles Inclusions Living Non Living Permanent Temporary Essential Usually not essential Active Inert Have vital functions Result from cell activity  HISTOL06Y - FIRST YEAR 1- Cytoplasmic Organelles They are classified according to presence of limiting membranes into: Membranous organelles Non membranous organelles Covered by membrane Uncovered by membrane Contain enzymes No enzymes ~ Plasma membrane g. Ribosomes ~ Mitochondria ~ Cytoskeleton: ~ Endoplasmic reticulum Microtubules: Golgi apparatus Centrioles, Cilia & flagella ~ Lysosomes Filaments: ~ Peroxisomes Thin and Intermediate A- Membranous Organelles 1- The Plasma Membrane (Plasmalemma) Definition: Limiting membrane that envelopes all the cells. LM: Difficult to be seen because it is very thin (7.5-10 nm). Can be demonstrated when stained with silver (Ag) or PAS stains. EM: Two dark layers separated by an intermediate light layer~ so called trilaminar membrane or unit membrane. Fuzzy material found on the outer surface of plasmalemma only, which represents cell coat (glycocalyx).... - - re'$.- ~ -~ ~ - i· Cell co at_ Two dark lay:r$ · ·... · light layer -· EM picture of plasm lemma I. "' c · t.... y.op asm1c s1 I...;..-d e.. Molecular structure of cell membrane: 1- Lipid: consists of phospholipids and cholesterol: Phospholipid molecules: arranged into 2 layers (lipid bilayer). Phospholipid heads are directed outwards to aquous solutions and tails are directed inwards. Functions: It is permeable to certain substances (selective permeability) and impermeable to ions and polar molecules to perform a barrier between internal and external environment of the cell. ' Cholesterol molecules: present among the hydrophobic fatty acids. Functions: Restrict movement of phospholipid molecules so stabilize cell membrane. Modulate fluidity of membrane preventing it from being too fluid or too rigid. HISTOLOGY - FIRST YEAR 2- Protein: about 50% of total membrane mass, present in two forms: A. Peripheral proteins: Small molecules, loosely attached to both surfaces of cell membrane. A non-continuous layer outside the lipid bilayer. B. Integral proteins (transmembrane proteins): );.;> Embedded in the lipid bilayer. );.;> Two types are present: - Channel proteins for transport of ions & water. - Carrier proteins for transport of small polar molecules as glucose and ions as Na K pump. );.;> Functions: specific transport of ions and polar molecules. Glycoprotein Molecular structure of cell Integral protein membrane Cholesterol 3- Carbohydrates: at the external surface formed of: A. Glycoproteins: oligosaccharide chains linked to protein molecules. B. Glycolipids: oligosaccharides linked to phospholipid molecules. Cell coat (glycocalyx): ! Formed of molecules of glycoproteins & glycolipids ! On the external surface of cell membrane. ! It includes receptors for drugs, hormones, bacteria and viruses. ! Functions: Adhesion, identification (receptor), protection & cell immunity. Functions of cell membrane: A. Endocytosis: Bulk movement of substance into the cell by forming vesicles; include three types: 1. Phagocytosis (cell eating): Pseudopodia extended from the cell to surround the particle e.g. a bacterium. The membranes of these extensions meet and fuse enclosing the bacterium in an intracellular vacuole called phagosome. The phagosome then fuses with a lysosome for digestion of its contents. Example: WBCs engulfing bacteria.  HISTOLOG)f - FIRST '\'£AR 2. Pinocytosis (cell drinking): Smaller invaginations of cell membrane form and surround extracellular fluid. Pinocytic vesicles then detach off inwardly from the cell membrane. The vesicle usually fuses with a lysosome for digestion of its contents. Example: pinocytosis of colloid in thyroid follicular cell. 3. Receptor mediated endocytosis: Receptors in the form of integral proteins in cell membrane bind to specific substances and aggregate at the site of binding. They associate with other proteins on the cytoplasmic side called clathrin to form a coated pit. The coated pit invaginates and pinches off, forming a coated vesicle containing the specific substances and their receptors internally. Example: uptake of protein hormones as GH by the cell. ' Grawth Hormone Solid particles Extracellular fluid l 0 j Phagosome 0 Pinocytic vesicle Pinocytosis Phagocytosis.___D_iff _e_r_e_n_ t ty _ p_e_ s _o_f _en _d_o_c_y_to_s_i__..I I Receptor mediated endocytosis I B. Exocytosis: Bulk movement of substance from inside to outside of the cell by forming vesicles Cytoplasmic vesicle fuses with cell membrane Release of the contents into extracellular space without affecting continuity of cell membrane. Despite normal level of growth hormone (GH) in blood, lack of GH receptors at cell membrane of target cells, leads to a type of dwarfism. HISTOLOGY' - FIRST Y'EAR 11!11 2-Mitochondria Definition: Membranous organelles, containing enzymes for aerobic respiration and energy production. They are the power-house of the cell. Site: Areas of the most activity of the cell. Number: - More in active cell as liver cell (up to 2000/cell). - Increase in number by simple division. LM: - When abundant they cause cytoplasmic acidophilia. - Appear as rods or granules. - Dark blue with iron Hematoxyline and green with Janus green stain. EM: ;;.. Appear as oval or rounded membranous vesicles. ;;.. surrounded with two unit cristae membranes separated by an inter-membranous space: ;;.. Outer membrane: - smooth contains transmembrane proteins called porins Permeable to small molecules. > Inner membrane: ·Diagram of EM structure of a mitochondrion less permeable (selective). It projects into the matrix forming shelf-like folds called cristae: - Their number corresponds to energy needs. - Increase surface area for attachment of elementary particles, which are globular structures connected to inner membrane by cylindrical stalks. - They represent a protein complex with ATP synthase activity (forms ATP in oxidative phosphorylation). ;;.. Mitochondria/ Matrix: composed of: Oxidative enzymes of citric acid cycle. DNA, mRNA, tRNA and rRNA. Dense granules rich in Ca 2 + that act as catalysts for mitochondrial enzymes. Function: Responsible for energy production (cell respiration): Mitochondria obtain energy from metabolites present in cytoplasm by Krebs cycle (citric acid cycle). Most of this energy is stored as ATP molecules by oxidative phosphorylation and some is liberated as heat to maintain body temperature. ~ Defect in mitochondrial enzymes leads to failure to produce ATP which is needed for all vital activities e.g. in muscle cause muscular weakness  HISTOL061:' ~ FIRST Y'EAR 3- Endoplasmic reticulum Definition: A membranous network that extends from the nucleus to the cell membrane enclosing a series of intercommunicating channels and sacs, called cisternae. Types: according to presence or absence of electron dense particles (ribosomes ) on surface there are two types: Rough and smooth Smooth Endoplasmic Rough Endoplasmic Reticulum Reticulum Site Protein forming cells as plasma cell. Lipid forming cells as liver cells. When abundant -7 LM Localized or diffuse basophilia. acidophilia. - Parallel flattened cisternae contimmus - Anastomosing tubular with outer nuclear envelope. cisternae of various shapes - Covered with electron-dense and size continuous with rER. particles, the ribosomes , bound to EM specific receptors (ribophorins ) on membranes by their large subunit6. - Absence of ribosomes. - Under receptor is a pore that allows newly synthesized proteins to enter and to be stored in rER cisternae. 1. Protein synthesis by attached 1. Phospholipid molecules polyribosomes. synthesis that constitutes cell 2. Segregation of formed proteins. membranes. 3. Initial glycosylation of some proteins 2. Steroid hormones synthesis by addition of monosaccharides. as cortisone & testosterone. c: 0 4. Packing of formed proteins in 3. Breakdown of glycogen to ~ membranous vesicles that bud off glucose in liver cells. c: :::::s LL from cisternae (transfer vesicles) 4. Detoxification of drugs.alcohol to be delivered to Golgi apparatus. & hormones in liver cells. 5. Protection of cytoplasm from 5. Calcium ions (Ca++) release hydrolytic enzymes formed inside it. (pump) in muscle contraction. 6. Intracellular pathway for the formed 6. Acts as an intracellular substances. pathway HISTOLOGY FIRST YEAR ft 4. Golgi apparatus (G.A.) Definition: A membranous organelle, concerned with secretion. Site: Well developed in the secretory cells. LM: Golgi Apparatus ~ Does not appear in H&E stain. In protein forming cells, it can be seen as a pale unstained area near the nucleus called "negative Golgi image". Golgi apparatus in a secretory cell ~With silver stain (Ag), it can be demonstrated as a network of brown granules & fibrils. Its site is either: Apical: Between the nucleus & the upper pole of secretory cells. Perinuclear: Completely surrounds the nucleus as in nerve cells. EM: Secretory vesicle ~ Interconnected parallel flat curved --0 membranous saccules (3-10) arrange above each other forming stacks. ~ Each saccule has a narrow lumen with expanded ends. ~ Filled with low electron-dense material. ~ Each stack has 2 faces: Entry (Cis) face: receives transfer Digram showing the EM of Golgi apparatus vesicles from rER carrying proteins.. Rahma Exit (Trans) face: vesicles that bud off from this face are either: Secretory vesicles that discharge their contents by exocytosis, or Lysosomes. Functions:.--~---------~-·:_·..;.. 4 - Discharge of. secretory 5- Renewal and j products as hormones in maintenance of cell secretorv vesicles. membrane by providing it with integral proteins (f) 3- Formation of from membrane of secretory vesicles secretory vesicles and lysosomes. 2- Chemical modification of proteins & lipids by 1- Packing, addition of carbohydrates concentration & storage of proteins received from rER  HISTOLOGY' - FlRST Y'EAR 5. Lysosome Definition: A membranous organelle contains hydrolytic enzymes e.g. protease & sulfatase, responsible for intracytoplasmic digestion. Origin: - A lysosome is a secretory vesicle that arises from Golgi apparatus (G.A. ) containing hydrolytic (lysosomal) enzymes. - The hydrolytic enzymes are synthesized in rER then carried via transfer vesicles to Golgi apparatus to come out in lysosomes. Number: Abundant in phagocytic cells (macrophages and neutrophils). LM: Lysosomes are not detected by H&E stain. Histochemical stains are used to detect the hydrolytic (lysosomal) enzymes. EM: ~ 1ry lysosomes: Newly released lysosomes from G.A., appear by EM as homogeneous (moderate electron dense) vesicles. ~ 2ry lysosomes: lysosomes with variable contents, so appear by EM as different heterogeneous vesicles. Types of the 2ry lysosomes according to their content: a. Heterolysosome: Formed by fusion of a primary (1 ry) lysosome with a phagosome to digest solid particles as bacteria or virus. b. Mu ltivesicular body: Formed by fusion of a 1ry lysosome with a pinocytic vesicle to digest fluid particles. c. Autolysosome: Formed by fusion of a 1ry lysosome with autophagic vesicles containing destroyed endogenous substrate as mitochondria. Fate of secondary lysosomes: The digested material diffuses to the cytoplasm through lysosomal membrane while undigested material is retained within vesicles called residual bodies. The residual body may: 1- Discharge the undigested material by exocytosis (cytostool) 2- Accumulate over years in long lived cells as cardiac muscle and nerve cells as lipofuscin granules (age pigments). Functions of lysosomes: 1. Digest nutrients and phagocytosed bacteria and viruses. 2. Maintain cell health by removal of excess or non functional organelles. 3. Postmortem autolysis by digestion of cell after death due to lysosomal rupture. 4. Fertilization by helping the head of sperm to penetrate the ovum. 5. Activation of thyroid hormone by breaking bond between hormone & protein. HISTOL06Y - FIRST Y£AR 11111 1-Heterolysosome Residual 2- Multivesicular body Primary Lysosome 13- Autolysosome I j Types of 2ry lysosomes and residual body Lack of lysosomal enzymes as sulfatases results in intracellular accumulation of sulfated compounds, which interfere with normal function of nerve cells. 6- Peroxisomes (Microbodies) Definition: membranous organelles, contain oxidases and catalase enzymes. Origin: Membranous vesicles bud off the rER. Their peroxisomal enzymes are synthesized in free ribosomes. Number: more in liver & kidney cells and increase Peroxisomes in response to diet and drugs. They divide by simple division (fission ). LM: Can be detected by histochemical method. EM: - Small moderate electron density vesicles. - Spherical to ovoid, bound by a single membrane. Functions: Peroxisom es contain t he Free polysomes following enzymes: 1. Oxidases enzymes ~ Beta oxidation of long- Enzymes chain fatty acids~ produce: a. Energy that comes out as heat and not stored as ATP. b. Hydrogen peroxide which is a toxic product. 2. Catalase enzyme~ breaks down hydrogen peroxide to water and oxygen, thus protecting the cell. N.B. Oxidases are important in liver cells by oxidizing various organic substances to detoxify alcohol and drugs. @ Lack of peroxisomal enzymes affects function of some organs as liver  HISTOL06\1 - FIRST Y'EAR 8. Non-Membranous Organelles 1. Ribosomes Definition. Non membranous particles, formed of rRNA and proteins. Origi rRNA is formed in the nucleolus while proteins are formed in the cytoplasm and pass through nuclear pores. Both unite in the nucleolus to form small and large subunits that pass to the cytoplasm again through nuclear pores and join each other only during protein synthesis. ur b r. Abundant in protein synthesizing cells as plasma cell. LM: When abundant they cause basophilia of the cytoplasm due to the acidity of phosphate group in RNA. The basophilia may be focal, diffuse or localized. )~(_ Diagram r showing different types of Diffuse basophilia Localized basophilia Foool booophilio Niss! granules Embryonic cell Pancreatic cells basophilia in nerve ce ll EM Small electron-dense granules. ~ Each is formed of two subunits, small & large, unite by binding to mRNA. ~ Large subun it has a groove in its center to accommodate polypeptide chain. ~ Two forms: 1. Free: Scattered singly OR as polyribosomes (polysomes) that are linked together by mRNA to appear as rosettes or spiral chains 2. Attached: Bind to outer surface of rER by large subunits at ribophorins. Messenger RNA (mRNA) carries the information for the sequence of amino acids for protein synthesis. Transfer RNA (tRNA) picks up the specific amino acids and transports them to ribosome (rRNA) forming polypeptide chain that extends down the groove and is injected into the lumen of rER. I polyribosomes I Diagram Diagram I mRNA I Large of offree ~ subunit ribosomes U 9'. Q attached ribosome IPolypeptid I I Single free I Function of ribosom~: Factories of protein synthesis. -k- Free ribosomes form proteins used within the cell as glycolytic enzymes. *- Attached ribosomes form proteins secreted by cells as enzymes & hormones. HISTOLOGY' - FIRST Y'EAR 2. Cytoskeleton Definition: It is a complex network of microtubules, microfilaments and intermediate filaments , together with some proteins to link them to each other and to cell membrane forming a framework called microtrabecular lattice. Microtubules 13 prtofilaments Alpha tubulin Beta tubulin Protofilament Microtubules {MT) I G actin I I F actin I Micrfilaments I Intermediate filaments  HISTOL06'i - FIRST YEAR Intermediate Microtubules (MT) Microfilaments filaments - Hollow cylinders of fixed diameter with a wall of 13 parallel protofilaments. Fine strands of 2...::J -- Cl.> - Their length varies Filaments formed by chains of globular G by polymerized polymerization of (J actin, coiled around... ::J tubulin molecules, each other to form tetrameric subunits CJ) directed by that differ chemically. filamentous F actin. microtubular organizing center (MTOC) which has gamma tubulin. Diameter 24 nm 5-7 nm 8-10 nm Protein A& ~ tubulin G actin Various proteins subunit Radiating through Beneath Location In cytoplasm, nuclear cytoplasm from plasmalemma in cell envelope MTOC, cilia. Microvilli LM Difficult to be seen except by using immunofluorescent technique 1. Determine the cell 1. Cell shape changes Supportive function shape and cell as endocytosis, 1. Cytokeratin : in cells elongation. exocytosis & of epithelial tissue. 2. Intracellular amoeboid 2. Vimentin : in cells of transport of movements. connective tissue & 2. Intracellular muscular tissue. organelles, transport of 3. Desmin : in cells of vesicles, and organelles & muscular tissue. macromolecules. granules. 4. Neurofilaments: Function 3. Formation of the 3. Cleavage of cell in neurons of mitotic spindle during cell division. nervous tissue. during cell 4. Form microvilli 5. Glial fibrillar acidic division. core to keep their ~rotein {GFAP}: 4. Formation of the shape and change in glial cells of centrioles, cilia their length by nervous tissue. shortening and 6. Lamins: in nuclear and flagella. elongation. envelope. 5. Muscle contraction ~ ! Cancer chemotherapy is used to arrest cell proliferation in tumors by preventing microtubules formation. ! Identification of intermediate filament proteins by immunocytochemical methods is important for diagnosis and treatment of tumors. The cell of origin of the tumor can be recognized. HISTOlOGY1 - FIRST 'YEAR.. STRUCTURES FORMED BY MICROTUBULES (MT) 1) Centrioles ~ Definition: Cylindrical structures composed of MT. ~ LM: Appeared by iron hematoxylin stain as 2 dark bodies near the nucleus. EM: ~ 2 cylindrical structures, perpendicular to each other Surrounded by a matrix of tubulin (centrosome) in the nondividing cells. The wall of each cylinder is formed of 9 bundles of MT, each bundle is formed of 3 MTs (triplets). So, the wall of the centriole is formed of 9 x 3 =27 MTs. Structure of C> ·. ·.-'O. _-- ~·:_· -&~ :-... ""._:h...%. ··.·... ·....... : :..·.. c:::::r;:::c>_ Microtubules In doublet C::X!> ·_-_. ~--.·_.·:··---< ~ :,.. and triplet.. d:?§,. %~1e ·. · (T.S.) Functions: a. Formation of mitotic spindle during 5 phase of interphase of cell cycle, the centrosome duplicates itself. During mitosis it moves to poles of the cell and become organizing centers (MTOC) for MT of the mitotic spindle. b. Share in the formation of cilia and flagella. 2) Cilia Synthesis stage of interphase Definition: Motile processes with microtubular core covered by plasmalemma. Origin: Centrioles duplicate thousands of times to form basal bodies of cilia that migrate to the apical cytoplasm. A shaft grows up from each basal body. I \\ LM: hair-like striations. IBasal body I EM: Formed of basal body, shaft and rootlets: {ilAaH A.~. 1- Basal body: A centriole is formed of 27 microtubules in 9 triplets, embedded in cytoplasm.  HISTOLOGY - FIRST Y'EAR II· Shaft (axoneme): Finger-like cytoplasmic projection from cell surface covered by plasmalemma. From each triplet, A & B microtubules grow as doublets pushing the cell membrane in front of them. So, the shaft is formed of 9 peripheral doublets and 2 singlet microtubules in the center are formed by polymerization (20 microtubules). Ill· Rootlets: Formed by growth of microtubule C in each triplet of basal body into the cytoplasm (9 MT). They fix the basal body and shaft to cytoplasm. Functions of cilia: a. Repeateq beating motion by bending of adjacent doublets~ moving secretions or particles in one direction as in respiratory & female genital tracts. b. Cilia can modify & act as receptors as in rods & cones of retina. 3) Flagella They are motile projections from the cell, designed to move the cell itself. They have exactly the same structure as the axoneme of the cilium (nine p~riph,eral dou.blets and 2 central singlets), but extremely longer. In human, a flagellum forms tail of the sperm, which helps its movements. Inability of the cilia to move results in bacterial infections on top of accumulated secretions causing chronic respiratory infections. lmmotile flagella cause male infertility STRUCTURES FORMED BY MICROFILAMENTS 1- Microvilli: Finger like projections (shorter than cilia) from cell membrane of some cells. L.M.: Apical striated brush border. E.M.: A core of actin filaments (to maintain its shape), is covered by cell membrane Terminal web and inserted into a terminal web. Function: Increase surface area for more absorption e.g. small intestine. (;IAtt1t A.~. 2- Stereocilia: Non motile solid cilia Not true cilia but long microvilli. L.M. hair like processes from free surface of some cells. E.M. Their core have actin filaments (no microtubules). Function: help absorption in male genital system e.g. epididymis. HISTOLOGY' - FIRST YE_AR IEll 11- Cytoplasmic Inclusions 1) Stored Food 1- Carbohydrates Site: Stored as glycogen granules in liver and muscle cells. L.M.: H&E-+ vacuoles dissolve away during heatin'g. Best's carmine stain ---+ red granules. PAS-+ Magenta red granules. EM: Single granules or rosette-shaped aggregations. Mostly concentrated in areas of cytoplasm rich in sER. Why? J Glycogen stained by Best's Carmine JI Glycogen stained by PAS 2- Fats Site: In fat cells as large globules or in liver cells as small droplets. LM: I Sudan Ill stain I H&E: Fat appears vacuolated as it dissolves in preparation. Sudan Ill stain: Fat appears as orange globule in fat cell. 2) Pigments Definition: Colored particles either produced by the cells or taken from outside. Pigments are materials that possess color of their o'wn nature. Types: A. Endogenous pigments: a. Hemoglobin (Hb): in RBCs, carries gases (0 2& C02). b. Melanin: in skin, to give its color & protects from ultraviolet rays. c. Lipofuscin: in cardiac muscle & nerve cells. They are waste product~ which accumulate with age. B. Exogenous pigments: a. Carbon and Dust particles: taken by dust cells of the lung. b- Carotene pigments: in carrots. c- Tattoo marks : dyes injected under the skin & taken by phagocytic cells.  HISTOLOGY' - FIRST YEAR The Nucleus Definition : The largest component of all cells, except RBCs and platelets (not true cells). Number: Usually one nucleus is present in each cell (mononucleated). Some cells have two nuclei (binucleated) as liver cells. Some have more than two nuclei (multinucleated) as osteoclasts & skeletal muscles. Basal Position of Central Eccentric nuclei in the cells: I Peripheral Shape Rounded of Flat nuclei: Bilobed Multilobed I I Segmented Kidney Staining: Appears basophilic in H&E stained sections due to its content of DNA & RNA. Appearance: May be Pale-stained (vesicular) present in active cells e.g nerve cell& liver cell Darkly-stained (condensed) present in inactive cells e.g small lymphocyte Pale (vesicular) I I Dark (condensed) I HISTOLOG'/ - FIRST YEAR Structure of nucleus: 1. Nuclear membrane (Envelope). 2. Chromatin material. 3. Nucleolus. lm.an Jcuhk 4. Nuclear sap. Peripheral heterochromatin Diagram for Structure of Nucleus 1- Nuclear Membrane {Nuclear Envelope) LM: Basophilic line by chromatin on its inner side & ribosomes on its outer side. EM: Double walled membrane formed of two parallel unit membranes separated by a perinuclear space, interrupted at intervals by nuclear pores. i Outer nuclear membrane: It is rough & granular due to attached polyribosomes and is continuous with rER cisternae. * Inner nuclear membrane: It is fibrillar due to attached chromatin threads (peripheral chromatin). It is associated with nuclear lamina formed mainly of Lamins for stabilization of nuclear envelope. Nuclear pore complexes: circular openings at intervals, where inner and outer membranes fuse. They are formed of 30 nucleoporin proteins which form an octagonal ring. Nucleoporin filaments extend into cytoplasm and nucleus. Cytoplasmic filaments I Transporter protein Cytoplasmic ring.·.. ·.. Nuclear ring I Diagram for nuclear pore complex Function: Transport of proteins to the nucleus & export of RNA & ribosomal subunits to the cytoplasm through transporter protein.  HISTOl.06.Y'-FIRST Y'£AR 2- Chromatin Definition: · In nondividing nuclei chromatin is the chromosomal material in uncoiled state. It represents the genetic material, formed of nucleoproteins (Double-stranded DNA + Histones &nonhistone protein ). It is found in 2 forms: Euchromatin Heterochromatin Extended {uncoiled) chromatin Coiled inactive chromatin Contains active genes Contains inactive genes Predominates in metabolically Predominates in metabolically active cells as protein forming cell inactive cells e.g. small lymphocyte L.M: fine threads ---t pale L.M: coarse clumps ---t dark basophilic {vesicular) nucleus basophilic (condensed) nucleus with clear nucleolus with unclear nucleolus E.M: Appears as electron lucent E.M: It appears as electron dense Sites of heterochromatin: a) Peri~heral chromatin : attached to inner surface of nuclear membrane. b) Chromatin islands : aggregated clumps scattered in the nuclear sap. c) Nucleolus-associated chromatin : condensed around the nucleolus. Vesicular Nucleus Condensed Nucleus Functions of chromatin: 1- Carries genetic information. 2- Formation of RNA (mRNA, rRNA& tRNA). 3- Directs & controls protein synthesis. ® Chromosomal alterations are associated with tumors and genetic diseases. HISTOLOG~ - FIRST Y'£AR 3. Nucleolus LM: Rounded, deeply basophilic mass rich ~it~~ in nucleic acids. Surrounded with chromatin. Usually one or two in each nucleus. EM: - Spongy appearance, not limited by. membrane. - It has dark and light areas: A. The dark areas are formed of: o Pars amorpha (nucleolar organizer): filaments of DNA, which are parts of chromosomes carrying the genes encoding rRNA. o Pars fibrosa (fibrillar component): strands ofnewly formed rRNA. o Pars granulosa (granular component): granules of mature rRNA. Both pars granulosa and fibrosa are called "nucleolonema". B. The light areas: formed of the nucleolar sap. Functions of the Nucleolus: Formation of ribosomal RNA & ribosomal subunits (rRNA +proteins), which pass through nuclear pores to cytoplasm. Large nucleoli are found in rapidly growing malignant cells. 4- Nuclear Sap Definition: A colloidal solution that fills the spaces between chromatin material and nucleolus. Constituents: Formed of nucleoproteins, enzymes, sugars , calcium, potassium & phosphorous ions. Functions of Nuclear Sap: Provides a medium for transport of RNA through nuclear pores to cytoplasm for protein synthesis. Functions of the Nucleus 1. Carries all the genetic information and hereditary factors. 2. Controls all the cell functions including protein synthesis. 3. Responsible for the formation of RNA. 4. Directs cell division.