Foundation Module in Medical Histology (PDF)

For Medical Students Histology Dr. Iman Nabil Fou nda t ion Module Foundation Module 1. Cell …………………………….………………………………………...……………1 1.1 Cell Membrane.…………………………………………………….……………..…………..1 1.2 Vesicular trans...

For Medical Students Histology Dr. Iman Nabil Fou nda t ion Module Foundation Module 1. Cell …………………………….………………………………………...……………1 1.1 Cell Membrane.…………………………………………………….……………..…………..1 1.2 Vesicular transport across the cell membrane …………...………..……………………...4 1.3 Cell organelles ……...………………………………………………………….……...………7 1.4 Centrosome …...……………………………………………………….……………………..20 1.5 Cytoplasmic Inclusions …………………………………......……………………………....20 1.6 Nucleus …….………………………………………………...………………………………..22 1.7 Nuclear pore complex …………….…………………………………………………………25 1.8 Nucleolus ……………………...……………………………………..……………………… 26 1.9 Cell Cycle & Cell Division …………...…………………………………..………………..26 1.10 The Human Chromosome. …………………………………………….…………32 1.11 Cell Proliferation & Cell Death.. ………………………………………..……..38 2. Epithelium …..……………………….……………………………………………..45 2.1 Lining Epithelium …….…………………………………………….………………………..46 2.1.1 Simple Epithelium ………………………………………………………………………46 2.1.2 Stratified Epithelium ………...………………………..…………….………………….47 2.2 Glandular Epithelium ………………….………………………………………..………….49 2.3 Special Types of Epithelium ….……………………………….……………………….…..50 2.4 Functions of Epithelium ………………………..…………….…….……….………………50 2.5 Epithelial Cell Polarity …………………………………………….……….………………51 2.6 Basement Membrane...…...……………………...……………………..….………………53 2.7 Lateral Specialization & Intercellular Junctions ………………………..………………53 2.8 Cell Adhesion Molecules (CAMs) ………………..……………………….……………….58 3. Connective Tissue ……………..……………..…………………………………………….59 3.1 Characteristics of CT ………….…….………………………………………………………59 3.2 Structure of CT ……………………………………………………………………………….59 3.2.1 Ground Substances ………………….………………………………………………….59 3.2.2 CT fibers ………………………………………………………………………………….60 3.2.3 CT Cells …………………………………………………………………………………..61 3.3 CT Types …….………………………………………………………………………………..65 3.3.1 Embryonic CT..………………………………………………………………………….65 3.3.2 CT Proper ………………………………………………………………………………..65 4. Skin ……………………….……………………………………………………...……………70 4.1 Epidermis …………………….……………………………………………………………….70 4.2 Dermis ………………………….……………………………………………………………..76 4.3 Hypodermis ……………..……………………………………………………………………77 4.4 Skin appendages, Hair and Nails ………………...……………………………………….78 4.5 Functions of the integumentary system …………………………………………………..85 Chapter 1: Cell (By Prof. Dr. Iman Nabil)  The cell is the functional & structural unit of the body.  A group of cells with similar structure & function will form tissues.  These tissues are grouped to form organs.  A group of organs collect to form the body systems. Plasma membrane = Plasmalemma LM: It cannot be seen by light microscope because it is too thin to be seen but the condensation of the stain on the outer surface of the cell membrane marks its. EM: 1- At Low Magnification: thin dense line 8 - l0 nm in thickness. 2- With Higher Magnification: a trilaminar structure, with an outer (= extracellular leaflet) and an inner (= cytoplasmic leaflet) electron dense lines and a middle electron lucent zone in between. The entire structure is known as the unit membrane. Molecular structure of the Cell membrane: 3 Components: 1-Lipid molecules: a- phospholipids b- cholesterol 2- Protein molecules. 3- Carbohydrate molecules The cell membrane & almost all the membranes surrounding the membranous organelles have the same structure except for minor differences. 1- Lipid Molecules A- Phospholipids: Each phospholipid molecule consists of: 1- One polar hydrophilic head: faces the aqueous media on either side of the membrane. 2- Two long non-polar hydrophobic tails (fatty acids): project towards the center of the membrane facing each other. They form weak non-covalent bonds with each other, holding the bilayer together. Foundation Module Page 1 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Why does the cell membrane appear as a trilaminar structure? Deposition of osmium in the hydrophilic heads Functions of Phospholipid molecules:  Prevent passage of: 1. Water soluble substances. 2. Polar ions.  Allow passages of: 1. Fat soluble substances. 2. Nonpolar substances. B- Cholesterol: They are incorporated within the lipid bilayer. Functions of Cholesterol: 1. Stability of the membrane. 2. Regulation of membrane fluidity in body temperature. 2- Protein Molecules Two Types: A-Integral Membrane Proteins: They are embedded within the lipid bilayer. Most of these proteins traverse the whole thickness of the membrane and are called transmembrane proteins while others are partially embedded within the membrane. There are six functional forms of integral membrane proteins: 1. Pumps: transport ions (Na+, K+) actively across the membrane. 2. Channels: transport substances passively. 3. Receptors: allow binding of specific molecules e.g., hormone. 4. Enzymes: ATP synthase of the inner mitochondrial membrane and some types of digestive enzymes in the small intestine. 5. Linkers: anchor the intracellular cytoskeleton to the extracellular matrix. 6. Structural proteins: form junctions between neighboring cells. B-Peripheral Membrane Proteins: They are not embedded into lipid bilayer, but they are loosely associated with membrane. They are usually located on the cytoplasmic surface of the membrane. Function: form a link between the cell membrane and the cytoplasmic components. Foundation Module Page 2 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 3- Carbohydrate Molecules They are present as glycoproteins and glycolipids of the cell membrane. They are oriented towards the outside of the membrane forming the cell coat or glycocalyx. The cell coat is represented by the "fuzzy" material on the outer surface of the membrane. Functions of cell coat: 1. Cellular recognition e.g. the glycocalyx on the surface of red blood cells determines the four blood groups. 2. Cell-cell adhesion. 3. Receptor: for ligands by the glycoproteins of the cell membrane. Foundation Module Page 3 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Mass transfer of materials through the cell membrane occurs by formation of vesicles. It involves 2 processes: 1- Endocytosis. 2- Exocytosis. 1-Endocytosis  Definition: the uptake of material from the extracellular space.  It is an active process that involves invagination of the membrane to form a vesicle.  3 mechanisms of endocytosis are present in the cell: A-Pinocytosis: Definition: a non-selective process, occurs in nearly all cell types for uptake of fluid containing ions and small protein molecules. Vesicle: pinocytotic vesicles are small and have smooth surface. Site: most evident in the endothelium of blood vessels. B-Receptor- mediated endocytosis:  Definition: a highly selective process resulting in uptake of specific substances by a specific cell that has receptors for these substances e.g. protein hormones. These receptors are concentrated in specialized regions of the plasma membrane called coated pits (coated by clathrin). 1. When a substance binds to its receptor, clathrin-coated pits invaginate and give rise to clathrin-coated vesicles containing this specific substance. 2. Clathrin is lost and recycled leaving uncoated vesicles. C-Phagocytosis:  Definition: ingestion of large solid particles, such as bacteria and cell debris, it is a receptor-mediated endocytosis; however, it does not involve formation of coated pits or vesicles.  Sites: phagocytes e.g. macrophages& neutrophils. 1. Binding of the receptor and foreign body results in extension Foundation Module Page 4 Chapter 1: Cell (By Prof. Dr. Iman Nabil) of pseudopodia that engulf the particle. 2. Fusion of the membrane to internalize the particle into the cytoplasm forming a phagosome. 3. The contents of the phagosome are then digested through lysosome. Types of endocytosis Pinocytosis Receptor mediated Phagocytosis endocytosis 1- Endocytosed Fluid containing ions & small Specific substances Large solid particles e.g. material molecules. (ligand) e.g. hormone. bacteria. 2- Receptors for Nonselective. Present. Present. endocytosed material 3- Shape of the Small& smooth. Coated with clathrin. No coated vesicle but the vesicle membrane fused to form phagosomes. 4- Type of cells Nearly all cell types Specific cell that has Phagocytic cells. especially endothelium of receptor for specific blood vessels. substance. 2- Exocytosis  Definition: the release of cell products into the extracellular space.  During this process, a vesicle moves from the cytoplasm to the cell membrane, fuses with it and discharges its content.  There are 2 types of exocytosis: A-Regulated secretion (stimulus- dependent): 1. The secretory products become stored forming secretory granules. 2. As a result of a stimulus (hormonal or neural stimulus), these vesicles move to the surface and fuse with the cell membrane to pour their contents outside the cell. e.g., occurs during release of the digestive enzymes by the pancreas. B-Constitutive secretion: The secretory products leave the cell immediately after their synthesis. These cells lack secretory granules. The secretion is released continuously through secretory vesicles. E.g. occurs during release of antibodies by plasma cells. Foundation Module Page 5 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Types of exocytosis Regulated secretion Constitutive secretion 1- stimulus Stimulus dependent. No stimulus. They released continuously. 2- Secretory product Concentrated & stored inside Leave the cell membrane immediately after their secretory granules. synthesis. No secretory granules. 3- Example of the Digestive enzymes from Antibodies from plasma cell, fibers secreted from released secretion pancreatic cell. fibroblast. Membrane Recycling During the vesicular transport, the cell membrane is maintained; the excess membrane added to the cell membrane by exocytosis is constantly recycled again into the cytoplasmic compartments by endocytosis. Foundation Module Page 6 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Definition: metabolically active structures carrying out specific essential functions. Types: 1. Membranous organelles: nucleus, endoplasmic reticulum, Golgi apparatus, transport vesicles, endosomes, lysosomes, mitochondria, and peroxisomes. 2. Non-membranous organelles: ribosomes, centrosome, and the cytoskeleton. N.B: Haematoxylin and Eosin (H&E):  Haematoxylin is a basic violet stain.  Eosin is an acidic pink stain.  Basophilic structure= A structure that has affinity to stain with basic dyes = acidic in nature……… So it stains violet with haematoxylin.  Acidophilic or eosinophilic structure= A structure that has affinity to stain with acidic dyes = basic in nature………So it stains pink with eosin. 1-Ribosomes Definition: granules of nucleoproteins (ribosomal RNA (rRNA) + proteins). Site: They are present in all cells especially in protein synthesizing cells. Structure: two subunits; small subunit & large subunit. Synthesis: 1. The rRNAs are synthesized inside the nucleolus. 2. Ribosomal-associated proteins are synthesized in the cytoplasm. 3. Ribosomal subunits then leave the nucleus, via the nuclear pores, to enter the cytoplasm. The small and large subunits are present in the cytosol individually and do not form a ribosome until protein synthesis begins. LM: When present in large amounts they cause cytoplasmic basophilia. EM: Ribosomes are small electron dense granules. Foundation Module Page 7 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Types: A-Free ribosomes: 1- Solitary particles: scattered in the cytoplasm. Function: act as a reserve. 2- Aggregated (polysomes): clusters of 10 or more connected by single strand of mRNA. Function of polysomes: responsible for synthesis of cytosolic protein e.g. in dividing cells and growing cells, synthesis of hemoglobin in developing red blood cells and contractile protein in muscle cells. B- Attached ribosomes: these are polysomes that become attached to the outer membrane of the endoplasmic reticulum. Types of Free solitary ribosomes Free aggregated ribosomes Attached ribosomes ribosomes ( polysomes) 1- LM Not seen but in large amount give Not seen but in large amount give cytoplasmic basophilia. cytoplasmic basophilia. 2- EM Small electron dense 10 or more ribosomes connected Small electron dense particles particles. by a single strand of mRNA. attached to rER. 3- Function Reserve. Synthesis of cytosolic proteins Synthesis of secretory proteins, (used within the cell) lysosomal enzymes& membran e proteins. Foundation Module Page 8 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 2-Endoplasmic reticulum The endoplasmic reticulum forms the most extensive membrane system in the cytoplasm. The ER has two types: Rough endoplasmic reticulum (rER). Smooth endoplasmic reticulum (sER). Both types form a single membrane system. 1- Rough Endoplasmic Reticulum (rER): LM: When present in large amounts they cause cytoplasmic basophilia due to their attached ribosomes. EM: 1. It consists of interconnected parallel flattened sacs called cisternae. 2. Its outer surface is studded with ribosomes. 3. It is continuous with the outer membrane of the nuclear envelope. 4. The lumen contains flocculent material that represents newly formed protein. Functions: 1. Synthesis of secretory proteins, lysosomal enzymes and proteins inserted into the cytoplasmic membranes. 2. Post-translational modification of the newly-formed protein e.g.folding, sulfation and initial glycosylation. 3. Transport the newly synthesized protein to the Golgi body by transport vesicles. Sites: Protein synthesizing & secreting cells e.g. liver cells, pancreatic acini, fibroblasts and plasma cells. 2- Smooth Endoplasmic Reticulum (sER) LM: Cells with large amounts of sER exhibit cytoplasmic eosinophilia. EM: 1. It consists of close network of interconnected branching tubules and vesicles. 2. The membranes have smooth surface. 3. The membranes of the sER are continuous with that of rER. Functions: 1. Synthesis of membrane lipids; the phospholipids and cholesterol. 2. Synthesis of steroid hormones. 3. Synthesis of glycogen in liver. 4. Detoxification of toxic substances e.g. alcohol and drugs. Foundation Module Page 9 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 5. Regulation of calcium ions during muscle contraction. Sites: steroid-secreting cells (in the adrenal cortex, testis and ovary), liver cells & muscles. Types of Rough endoplasmic reticulum Smooth endoplasmic reticulum endoplasmic reticulum 1- LM Not seen but in large amount give cytoplasmic Not seen but in large amount give basophilia. cytoplasmic acidophilia. 2- EM Parallel, flattened interconnected tubules. Interconnected branching tubules and Studded with ribosomes. vesicles. No ribosomes. 3- Functions 1- Synthesis of secretory proteins, lysosomal 1- Synthesis of lipid & cholesterol of the enzymes& membrane proteins. cell membrane. 2- Post translational modification of protein. 2- Synthesis of steroid hormones. 3- Transport protein to Golgi. 3- Synthesis of glycogen. 4- Detoxification of toxic substances. 5- Storage of calcium in muscles. 4- Sites Protein secreting cells e.g. liver , fibroblasts. Steroid secreting cells, liver & muscles. Foundation Module Page 10 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 3-Golgi apparatus LM: 1. It is not stained with H&E in routine histological sections. 2. H&E-stained sections of the cells synthesizing protein, its site could be seen as negative Golgi image e.g. plasma cells. 3. It can be seen in histological sections stained with silver stain. EM: 1. It consists of saccules or cisternae called the Golgi stacks. 2. Each stack consists of 4- 6 cisternae (flattened, curved, membrane-bounded, slightly expanded at the ends). 3. The Golgi stack is cup-shaped with a convex surface and a concave surface: a) The cis face (forming face; immature face): Convex in shape. Lies near to the rER. It is the site where the transport vesicles Trans,mature,secretory containing the newly formed proteins from rER enter the Golgi for further processing. b) The trans face (secretory face; mature face): Concave in shape. It is the site where the modified protein is packaged and released from the Golgi in large Cis, immature, forming secretory vesicles. c) The medial compartment: Between the cis & trans compartments. Functions: 1. Post-translational modifications of proteins e.g. addition of sugars. 2. Packaging of different proteins in membrane bounded vesicles. 3. Sorting and targeting of vesicles to the right destination: Formation of lysosomes. Formation of secretory granules for exocytosis. Membrane recycling. Sites: Protein synthesizing and secretory cells. N.B: Cytoplasmic Organelles that participate in the process of Protein synthesis: 1- Ribosomes (factories) 2- Rough endoplasmic reticulum (modification& transport) 3- Golgi apparatus (chemical modification,package,sorting& targeting) Foundation Module Page 11 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 4-Endosomes Definition: are system of vesicles and tubules involved in the endocytotic pathway. Types : A-Early endosomes: Site: at the periphery of the cell as a part in the pathway of the receptor-mediated endocytosis. Content: the receptors-ligands complex. + The membrane of the endosomes pumps H ions into its interior lowers the pH of endosomes to less than 6 uncoupling of the receptors and the ligands. The receptors recycle to the cell membrane and the ligands move to the late endosomes. B-Late endosomes: Site: deep within the cytoplasm near the Golgi complex. They receive: 1. the ligands from early endosomes. 2. clathrin- coated vesicles containing lysosomal enzymes from Golgi complex. PH: 5.5. (The enzymes become active at the acidic pH of the late endosome). The lysosomal enzymes in the late endosome begin to degrade the ligands accompanied by further decrease in the internal pH which then "mature" to form lysosomes. Types of Early endosome Late endosome endosomes 1-Site Periphery of cytoplasm. Deep in cytoplasm , near Golgi. 2- Content Receptor ligand complex. 1- Ligands from early endosome. 2- Lysosomal enzymes from Golgi. 3-Function Uncoupling of the receptor Lysosomal enzymes begin to degrade ligands, then the late from ligand. endosome matures to lysosome. 4- pH Less than 6. 5.5. Foundation Module Page 12 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 5-Lysosomes Definition: membrane-bounded organelle containing about 40 types of acid hydrolytic digestive enzymes (proteases, nucleases, phosphatases, and lipases). Function: They are responsible for intracellular digestion of different materials. Synthesis: by a gradual maturation process as by fusion of the clathrin- coated vesicles coming from Golgi complex with late endosomes. Lysosome has a surrounding membrane with unique phospholipids & specialized glycoproteins line the lysosomal membrane from inside that prevents: 1- the leak out of the enzymes to the cytoplasm. 2- protects the membrane from hydrolysis by its own enzymes. If a lysosome leaks its contents, the released enzymes would be inactive because of neutral pH of the cytoplasm. LM: They can be recognized by several histochemical methods used to demonstrate the lysosomal enzymes. EM: Lysosomes are heterogeneous in shape and the appearance of their interior. Some are electron dense, others show electron lucent areas. Site: are abundant in phagocytic cells. Pathways for intracellular digestion by lysosomes: 1. Extracellular small particles: internalized by pinocytosis and receptor-mediated endocytosis early endosome late endosome where the endocytosed materials are degraded by the lysosomal hydrolases. 2. Extracellular large particles: are engulfed in the process of phagocytosis forms a phagosome fuses with a late endosome. 3. Intracellular particles: are removed by a process called autophagy the enclosure of this organelle by membranes from sER forms an autophagosome fuses with a late endosome. The hydrolytic enzymes digest most of the content of the lysosomes. Any indigestible substances remain in lysosomes forming residual bodies. In long-lived cells, accumulated residual bodies indicate cellular aging and are called lipofuscin pigments. Foundation Module Page 13 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 6-Mitochondria Function: Powerhouses of the cell as they are the sites of adenosine triphosphate (ATP) production. Sites: All cells EXCEPT terminal keratocytes & RBCs. H&E stain Structure: LM: When present in large numbers contribute to the cytoplasmic eosinophilia. EM: Silver stain 1. Membrane-bounded organelles. 2. Surrounded by two membranes: outer and inner, which define two mitochondrial compartments: The intermembranous space: between the two membranes. The matrix space: enclosed by the inner membrane. 1-The outer mitochondrial membrane:  It is smooth and porous.  Function: allows passage of small molecules due to the presence of specific transmembrane proteins called porins. 2-The inner mitochondrial membrane: 1- Folded into cristae which increase its surface area; the number of cristae is greater in cells of greater demand for ATP. Types of cristae: Shelf/lamellar-like cristae Tubular cristae  lamellar cristae : most of cells.  tubular cristae: steroid secreting cells. 2- Impermeable to ions and small molecules due to presence of phospholipid called cardiolipin. Function:contains the enzymes of the electron transport system (respiratory chain enzymes) and the ATP synthase (known as elementary particles attached to the cristae and their heads are projecting toward the matrix like a lollypop). 3-Intermembranous space: Contains substances diffusing from the cytoplasm through the outer membrane and ions pumped out of the matrix space through the inner membrane. Foundation Module Page 14 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 4-Matrix space: Surrounded by the inner mitochondrial membrane. Functions: 1. Enzymes involved in mitochondrial functions as citric acid cycle. 2. Mitochondrial DNA and few ribosomes. 3. Matrix granules: store calcium ions, play a role in 2+ mitochondrial regulation of Ca intracellular concentration. The genetic system of mitochondria: The mitochondrial DNA: 1- a circular molecule. 2- limited coding capacity. 3- represents 1% of the total DNA of the cell. Function: Mitochondria can synthesize some of their structural proteins by their own RNAs. Most of the mitochondrial proteins are encoded by the nuclear DNA and are synthesized in the cytoplasm and imported into mitochondria. Mitochondria are self-replicating organelles. How do mitochondria adapt to its function? (E/M) 1.Outer membrane: smooth &porous contains mitochondrial porins allow easy passage of small molecules. 2.Inner membrane is folded into numerous cristae increase surface area for energy production. 3.Inner membrane contains cardiolipin make it highly impermeable to ions & small molecules. 4.Matrix space: contains enzymes for citric acid cycle, mito DNA & ribosomes synthesize some of their structural proteins, also contains matrix granules store Ca thus play an important role in regulation of intracellular Ca concentration. What is your source of mitochondria? Foundation Module Page 15 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 7-Peroxisome Definition: membrane-bounded organelles that contain oxidative enzymes.  Peroxisomes possess no genetic material of their own. A-Structure of Peroxisome: LM: They are not seen by H&E stain. EM: 1. Small, spherical bodies with fine granular electron dense content. 2. Surrounded by a single membrane. B-Functions of peroxisomes: 1. β-oxidation of long chain fatty acids to release energy. However, they differ from mitochondria in that they are unable to store this energy in the form of ATP. This energy is released as heat to maintain body temperature. 2. Generation of hydrogen peroxide, which detoxifies toxic agents. 3. Contain catalase enzyme that converts the excess hydrogen peroxide into water, thus protecting the cell. 4. Detoxification of alcohol in cooperation with the smooth endoplasmic reticulum in the liver. Mitochondria Peroxisome 1- LM -Not seen by H&E except in large amount cause Not seen. cytoplasmic acidophilia. -By special stain (silver stain) appear as brownish granules. 2- EM Double membrane: outer is smooth, and inner is Single membrane enclosed fine granular folded into cristae enclosed matrix space. contents. 3- Function Production of energy & store it in the form of ATP. 1- Produce energy & released it in the form of heat (unable to store it). 2- Produce hydrogen peroxide. 3- convert excess hydrogen peroxide into water. 4- Detoxification of toxic substances. 4- sites All body cells except red blood cells & keratinocytes. Many cells especially liver. 5- Genetic Present Absent material Foundation Module Page 16 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 8-Proteasome Definition & Function: small organelles responsible for proteolysis of malformed endogenous proteins (proteins synthesized within the cell) such as: 1- Excess enzymes & other proteins that become unnecessary after performing their function. 2- Proteins that have been denatured, damaged, malformed. 3- Aberrant proteins of the viruses. The cytoskeleton is a network of structural proteins (non-membranous cell organelles). Types of cytoskeletons: 3 types, depending on their thickness& their structural proteins: 1-Microfilaments. 2-Microtubules. 3-Intermediate filaments. 1-Microfilaments (actin filaments):  Diameter: 7 nm.  LM: can be visualized by using immunohistochemical staining.  EM: thin electron dense filaments.  Structural proteins: monomers of G-actin (globular actin) polymerize to form F-actin (filamentous actin) arranged as a double helix.  They are dynamic structures that can elongate & shorten. Functions of microfilaments: A- Cell motility for:  Cell migration.  Cytoplasmic streaming: during movement of organelles and transport of vesicles.  Cytokinesis: formation of contractile ring during cell division.  Muscle contraction associated with myosin. B-Structural role:  Maintenance of the cell shape.  Formation the core of microvilli. Foundation Module Page 17 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 2-Microtubules: Diameter: 25 nm. LM picture: by using immunohistochemical staining. EM picture: fine tubules. Structural proteins: A. a globular protein dimer called tubulin (each is composed of alpha and beta subunits). B. Chains of tubulin dimers form a protofilament. C. The wall of a microtubule is made up of 13 protofilaments that run longitudinally. Motor proteins associated with microtubules: Kinesin & dynein; they use ATP to provide energy for movement of vesicles and organelles along the microtubules. Microtubules are dynamic structures; can elongate & shorten Functions of microtubules: 1. Transport: of organelles & vesicles in the cytoplasm. 2. Structural role: Formation of the mitotic spindle. Formation of centrioles, cilia & flagella. The microtubule organizing centers: 1. Centriole which forms the mitotic spindle. 2. The basal bodies of cilia and flagella. 3- Intermediate filaments : Diameter:10 nm LM: by using immunohistochemical staining. EM: electron dense filaments thicker than actin filaments. Structural proteins: like woven ropes. Function of intermediate filaments: They are the most stable (not dynamic) types of the cytoskeletons thus they play a structural role. Foundation Module Page 18 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Classification Of Intermediate Filaments: According to their protein composition and their cellular distribution into: A- Cytoplasmic: 1. Keratin: epithelial cells. 2. Vimentin: in the cells of mesenchymal origin e.g., fibroblasts. 3. Desmin: muscle cells. 4. Glial fibrillary acidic protein: neuroglia. 5. Neurofilaments: nerve cells. B- Nuclear: Lamins: lining the inner nuclear envelope. The intermediate filaments (except for the lamins) are located in specific tissue types; they can be used to determine the origin of cancer by immunohistochemical staining. Cytoskeleton Microfilaments Microtubules Intermediate filaments 1- diameter 7 nm. 25 nm. 10 nm. 2- LM Seen only by Seen only by Seen only by immunohistochemistry. immunohistochemistry immunohistochemistry 3- EM Thin electron dense filaments. Fine tubules. Thicker electron dense filaments. 4- Structural Monomers of G actin Tubulin dimer polymerize to Woven ropes. proteins polymerize to form F actin. protofilaments. 13 protofilaments form a microtubule, 5- Functions Dynamic Dynamic. Not dynamic. 1- Muscle contraction. 1- Transport of organelles & Structural support. 2- Contractile ring in cell vesicles. division. 2- Formation of centrioles, 3- Pseudopodia in migration. cilia & flagella. 4- Microvilli. 5- Cytoplasmic streaming. Foundation Module Page 19 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Definition: a non-membranous organelle. EM: 1. It is formed of 2 centrioles, perpendicular to each other. 2. Each centriole is composed of 9 triplets of microtubules (a sum of 27 microtubules). 3. Each triplet is composed of three microtubules (one complete; formed of 13 protofilaments and 2 incomplete; each is formed of 10 protofilaments). Functions of centrosome: 1. It is the microtubule- organizing center. 2. Formation of mitotic spindles. 3. Formation of cilia & flagella. 1- Stored Food: A-Glycogen: Storage form of carbohydrates. Function: source of energy. Sites: mainly in liver & muscle cells. LM:  H&E: not visualized as they dissolve during preparation of the specimen leaving a pale vacuolated cytoplasm.  Periodic acid Schiff: appears magenta red.  Best's carmine: appears bright red. EM: dense granules, larger than ribosomes. In cytoplasm of hepatocytes, glycogen appears as rosette-shaped aggregates B-Lipids: Function: 1. Source of energy. 2. Synthesis of membranes & steroid hormones. Sites: stored in the adipocytes; many other cell types contain few small lipid droplets. LM:  H&E: not visualized because they dissolve during preparation of the specimen leaving a pale vacuolated cytoplasm.  Osmium tetroxide: appear black. EM: grey non- membrane bounded small droplets or large globules. Foundation Module Page 20 Chapter 1: Cell (By Prof. Dr. Iman Nabil) C-Proteins: Site: in protein- synthesizing cells e.g. salivary gland and pancreas. LM: eosinophilic zymogen granules. EM: homogenous electron dense membrane-bounded secretory granules. 2- Pigments: A-Endogenous pigments: 1. Hemoglobin: in red blood cells. 2. Hemosiderin: brownish granules in phagocytic cells of liver and spleen following phagocytosis of old RBCs. 3. Melanin pigment: brown to black granules. 4. Lipofuscin pigment: yellow-brown pigment present in cells with long life span. B- Exogenous pigments: 1. Tattooing: colored pigments are injected into the deep layers of the skin. 2. Dust & smokes: in lung of smokers and people living in polluted areas. Foundation Module Page 21 Chapter 1: Cell (By Prof. Dr. Iman Nabil) It is the largest membranous organelle of the cell. Functions: 1. It contains the chromosomes. 2. Contains the machinery for DNA replication& RNA transcription. Number: 1. Single: most of the cells. 2. Binucleated: liver cells. 3. Multinucleated: skeletal muscle fibers. 4. Absent: RBCs. Components of the Nucleus: 1. The nuclear envelope. 2. The chromatin. 3. The nucleolus. 4. The nucleoplasm (nuclear matrix; sap). I-The Nuclear Envelope: 1. It consists of two parallel membranes; outer & inner separated by the perinuclear cisterna. 2. It is perforated by the nuclear pores which provide a channel between the nucleus and cytoplasm. 1-The outer membrane: It is continuous with the rough endoplasmic reticulum. It is covered with ribosomes on its outer surface. Function: The ribosomes synthesize the transmembrane proteins of the nuclear membranes. 2-The inner membrane: It is supported at its inner surface by the lamins. Functions of the lamin: 1. Supports the nuclear envelope. 2. Influences chromosome distribution and function. 3-The nuclear pores: Definition: They are perforations in the nuclear envelope where the outer and inner nuclear membranes fuse. Distribution: not uniformly distributed. Number: vary according to the cell activity. Function: provide a bidirectional channel through which the nucleus and cytoplasm communicate. Foundation Module Page 22 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Nuclear Pore Complex  II-The Chromatin: It is formed of DNA + histone proteins. DNA is extensively packaged in chromatin as: 1. A segment of the DNA is wrapped two times around eight histone proteins to form a nucleosome. Each nucleosome is separated from the next by a region of linker DNA. 2. Repeating nucleosomes with intervening DNA (linker DNA) form a 10nm fiber (beads on a string). 3. This chain of nucleosomes is packed to form a 30nm fiber. 4. Higher orders of packaging gives the compact structure 700nm seen in the metaphase of the dividing cell known as the chromatid of a chromosome. Types of chromatins: 1- Heterochromatin (condensed chromatin; the inactive chromatin): LM: appears as dense basophilic clumps. EM: appears as condensed filaments or granules distributed in the following sites:  Nucleolar-associated heterochromatin: around the nucleolus.  Peripheral heterochromatin: at the inner nuclear membrane(associated with the nuclear lamin).  Heterochromatin islands: swimming in the nuclear sap. Function: transform into euchromatin when needed. 2- Euchromatin (extended chromatin; the active chromatin) LM: appears as lightly stained basophilic areas. EM: appears as dispersed filaments or granules. Function: It is stretched so, the genetic information in the DNA can be transcribed. The proportion between euchromatin and heterochromatin differs from one cell to another according to its activity. Foundation Module Page 23 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Types of chromatin Heterochromatin Euchromatin 1- LM Dense basophilic clumps. Lightly stained basophilic areas. 2- EM Electron dense filaments or granules distributed in: Dispersed fine filaments or 1- around nucleolus. granules. 2- associated with inner nuclear membrane. 3- swimming in nuclear sap. 3- Function Inactive part acts as a reserve (transformed into Active part (transcribed into RNA). euchromatin when needed). 4- Site Inactive cells. Active cells e.g., dividing cells. Chromosome: During cell division: chromatin is condensed into the chromosomes; formed from two chromatids held together at the centromere. Each chromatid is formed of a single DNA molecule. Karyotyping: The somatic cell contains 46 chromosomes. Karyotyping: is the arrangement of the chromosomes during metaphase into groups of homologous pairs (22 homologous pairs of autosomes and one pair of sex chromosomes). In females (44 autosomes +XX): one X chromosome is heterochromatic (Barr body), it can be identified in neutrophils, attached to the nucleus in the form of a drumstick mass. III-The Nucleolus: Definition: It is a spherical body with no surrounding membrane. Number: single or multiple. Function: it is the site of formation of ribosomal RNA. IV-The Nucleoplasm (nuclear matrix; sap): Definition: It is a colloidal protein solution Function: provides a medium for the rapid diffusion of metabolites. Foundation Module Page 24 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Nuclear Pores: Definition: They are perforations in the nuclear envelope where the outer and inner nuclear membranes fuse. Distribution: not uniformly distributed. Number: vary according to the cell activity. Function: provide a bidirectional channel through which the nucleus and cytoplasm communicate. Nuclear Pore Complex: Definition: non membranous structures(glycoproteins) surround the nuclear pore & embedded in its rim. Structure: A. 3 rings of proteins(nucleoporins) arranged one on top of each other. B. A nuclear basket.  3 rings are: A- Cytoplasmic ring:  Site: on the rim of the cytoplasmic aspect of the nuclear pore.  Structure: formed of 8 similar protein subunits.  It possesses cytoplasmic filaments that extend into the cytoplasm. B- The spoke ring (middle ring):  Structure: formed of 8 transmembrane proteins that project into the lumen of the nuclear pore as well as into the perinuclear cisternae.  Function: anchor the components of the nuclear pore complex into the rim of the nuclear pore. C- The nuclear ring:  Site: on the rim of the nucleoplasmic aspect.  Structure: formed of 8 similar units, from which arise a filamentous basket –like structure (nuclear basket) protruding into the nucleoplasm& terminating in the terminal ring. Transport across the nuclear pore complex: 1- Small molecules (less than 9 nm in diameter):  Diffuse passively across the nuclear pore.  Bidirectional. 2- Macromolecules (from 9-50 nm as proteins; histone, lamin, RNA proteins):  Transported actively.  In one direction. Foundation Module Page 25 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Definition: It is a spherical body with no surrounding membrane. Number: single or multiple. Function: it is the site of formation of ribosomal RNA. Components of the nucleolus: 1- Fibrillar center (nucleolar organizing center):  Pale areas.  Represent large loop of inactive DNA containing: rRNA genes+ RNA polymerase &transcription factors. 2- Pars fibrosa:  Dense regions.  Represent actively transcribed ribosomal genes+ RNA. 3- Pars granulosa: represent the mature ribosomal subunits. 4- Nucleolar matrix. The Cell Cycle: Definition: it is the alternation between interphase and mitosis. I-Interphase: a longer period: 1- The cell increases in size. 2- Performs its normal functions. 3- Replicates its DNA for preparing itself for division. II-Mitosis: a shorter period during which parent cell gives 2 daughter cells each containing the same number of chromosomes (identical to the parent cell =46 chromosomes). I-Interphase(‫)الطور البينى‬: First gap phase (G1 phase): It is the longest period of the cell cycle between the end of mitosis and the beginning of DNA replication: 1. The RNA and protein synthesis occurs. 2. The cell attains its full size. 3. The cell performs its function. Foundation Module Page 26 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 4. Duplication of centrosomes occurs near the transition between G and S phase. 1 The GO phase: Definition: Differentiation of the cell to carry out specialized function and no longer divide (outside the cycle). GO may be permanent or temporary. DNA synthesis phase (S phase): Replication of DNA, thus the amount of DNA is doubled but not the total chromosomal number. Types of chromosomes: S-Chromosomes made of one DNA molecule (interphase chromosomes = chromatin or chromatids). d-Chromosomes (mitotic chromosomes):are formed during the S phase. Each d-chromosome is formed of two chromatids, linked at the centromere. Each chromatid is made of a DNA molecule. Second gap phase (G2 phase): It starts by the end of the DNA replication and lasts until the beginning of mitosis. 1. Proteins and energy essential to mitosis are stored. 2. Duplication of the centrosome is completed. Foundation Module Page 27 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Cell Division: Mitosis Definition: division of the somatic cell into two daughter cells identical to the mother cell. Function: 1. Growth & development of the organism. 2. Renewal & repair of cells. I-Prophase )‫ (الطور التمهيدي‬: 1. The nucleolus disappears. 2. Condensation of chromatin gives rise to 46 rod-shaped short d-chromosomes. 3. Each pair of centrioles migrates to opposite pole of the cell forming the mitotic spindles. 4. The nuclear envelope breaks up into small vesicles 2-Metaphase )‫(الطور االستوائي‬ 1. The 46 d-chromosomes become maximally condensed. 2. The chromosomes aligned at the equatorial plate of the cell. Each pair of sister chromatid is attached to the mitotic spindles at the kinetochore. 3-Anaphase )‫ (الطور االنفصالي‬: 1. Division of the centromere results in the separation of the sister chromatids. 2. Each 46 chromatids migrate toward the opposite poles of the cell. 3. In late anaphase, a constriction (cleavage furrow) develops at the equatorial plate of the cell. 4-Telophase)‫(الطور النهائى‬ 1. The mitotic spindle disappears. 2. The nucleolus reappears. 3. The chromosomes start uncoiling (46 s-chromosomes). 4. The nuclear envelope is reformed around the new sets of chromosomes. 5. Division of the cytoplasm (cytokinesis): the cleavage furrow becomes deeper due to the formation of a contractile ring of microfilaments until it divides the cytoplasm and its organelles in half resulting into two daughter cells. Foundation Module Page 28 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Regulation of the cell cycle: The cell cycle is regulated by growth factors that control cell proliferation to keep its coordination with the needs of the living organism. Several checkpoints control the transition between the cycle stages. Checkpoints detect external or internal problems and stop the cycle until the problem solved. Checkpoints of the cell cycle: 1. The restriction checkpoint: It occurs in the G phase. 1 It detects the cell size & its interactions with the surrounding environment. Cells that do not receive appropriate growth stimuli do not progress past this point (G 1 phase) and will be die by apoptosis. It is the most important checkpoint in the cell cycle. 2. DNA damage checkpoints: It occurs in G1, S, and G2 phases. It blocks cell cycle progression until repair of the damaged DNA or cell apoptosis occurs. 3. The unreplicated DNA checkpoint: It occurs in the G2 phase. It prevents progression of the cycle into the mitosis before complete synthesis of DNA. 4. The spindle-assembly checkpoint (the metaphase checkpoint): It occurs in mitosis. It prevents entry into anaphase until all chromosomes have attached properly to the mitotic spindle. 5. The chromosome-segregation checkpoint: It occurs in telophase. It prevents the cytokinesis until all of the chromosomes have been correctly separated. Foundation Module Page 29  Chapter 1: Cell (By Prof. Dr. Iman Nabil) Miosis It occurs in germ cells and results in the formation of gametes. It results in formation of 4 daughter cells (each contains 23 s-chromosomes=haploid number). It consists of two successive divisions: without an intervening S phase. I-First meiotic division (reductional division): It is preceded by interphase with an S phase, in which the chromosomes are replicated (46 s chromosomes  46 d chromosomes). 1. Prophase I: A. Pairing of the homologous chromosomes occurs forming tetrads(bivalent). B. Crossing-over occurs between the chromatids of the homologous chromosomes so that each homologous chromosome is no longer solely paternal or maternal but a mixture of both. C. The nucleolus and the nuclear envelope disappear, and the mitotic spindle is formed. 2. Metaphase I: The paired chromosomes arrange themselves at the equatorial plate of the cell. 3. Anaphase I: The centromeres do not divide, instead, each chromosome of homologous pairs moves separately towards the opposite poles of the cell. 4. Telophase I: Cytokinesis occurs results in two daughter cells each containing the haploid number(23d- chromosomes). II-Second meiotic division (equatorial division): It is similar to mitosis but, it is not preceded by S phase. It results in formation of 4 daughter cells, each contains 23 s- chromosomes (haploid number). Foundation Module Page 30 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 46 d chromosomes 23d chromosomes 23 S chromosomes Mitosis Meiosis 1-Types of cells Somatic cells Germ cells of testis & ovaries 2- No of division Single division 2 successive divisions: Meiosis I & Meiosis II. 3- Interphase Preceded by interphase with S Meiosis I preceded by interphase with S phase phase, Meiosis II not preceded by S phase. 3- Prophase No crossing over Meiosis I: Crossing over occurs 4-Metaphase 46 d chromosomes arranged In Meiosis I :23 bivalent arranged at the individually at the equatorial equatorial plane of the cells. plane of the cells. 5- Anaphase Each chromosome divides at In Meiosis I: each chromosome of a centromere into 2 chromatids bivalent moves apart. 6- Cells produced Two daughter cells with diploid Four daughter cells with haploid number number of chromosomes (46 S) of chromosomes (23 S) Daughter cells are genetically Daughter cells are genetically variable. identical Foundation Module Page 31 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Meiosis Meiosis I Meiosis II 1- Preceded Present (the cell enter the Absent (the cell enter the prophase with S phase prophase with 46 d chromosomes). 23 d chromosomes). 2- Prophase Pairing of homologous chromosomes No pairing result in 23 tetrad. No crossing over. Crossing over occurs between each tetrad. 3- Metaphase 23 tetrad arranged at the 23 d chromosomes arranged individually at equatorial plane of the cells. the equatorial plane of the cells. 4- Anaphase No division of the centromere. Centromere splits so each chromatid Each chromosome moves moves independently to the opposite pole independently to the opposite pole of the cell. of the cell. 5- Telophase Cytokinesis results in 2 daughter Cytokinesis results in 4 daughter cells cells each with 23 d chromosomes. each with 23 S chromosomes. Definition: thread-like structures, present in the nucleus. Function: carries the genetic information in the form of genes. Structure of the chromosome: The DNA is packed in the form of chromatin (DNA + histone proteins). DNA is extensively packaged in chromatin as: 1. A segment of the DNA is wrapped two times around eight histone proteins to form a nucleosome. Each nucleosome is separated from the next by a region of linker DNA. 2. Repeating nucleosomes with intervening DNA (linker DNA) form a 10nm fiber (beads on a string). 3. This chain of nucleosomes is packed to form a 30nm fiber. 4. Higher orders of packaging give the compact structure 700nm seen in the metaphase of the dividing cell known as the chromatid of a chromosome. Foundation Module Page 32 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Telomere Definition: a segment of the DNA present at the end of the chromosomes. Functions: 1. Prevent the end of the chromosomes from sticking together. 2. Allow proper dividing of the cells. Each time the cell divides, the telomere gets shorter, until reaching a certain length, the cell stop dividing& become senescent. S-phase Single chromosome Double chromosome Types of microtubules: a. Astral microtubules:  Originate from the MTOCs in the centrosome & radiate from it toward the cell membrane.  Function: necessary for proper orientation of the spindle apparatus within the cell. B.Polar microtubules:  Originate from the MTOCs in the centrosome & begin to polymerize between the centromeres, overlapping each other.  Function: help to push the spindle apparatus apart away from each other. C.Kinetochore microtubules:  Attach to the kinetochore on each side of the centromeres.  Function: pull on the chromosomes and move them. Foundation Module Page 33 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Meiosis, Prophase 1 Leptotene  chromosomes begin to condense appear as long &thin threads. Each chromosome consists of 2 chromatids joined together by a centromere. Zygotene  homologous chromosomes pair up forming 23 bivalents or tetrads. They begin to make connection (synapsis) by synaptonemal complex. Pachytene  chromosomes becoming shorter and thicker. Crossing-over occurs between the chromatids of the homologous chromosomes at sites called chiasmata. Diplotene the synaptonemal complex dissolves, so the 2 homologous chromosomes are separated from each other, but they are connected at the chiasmata. Each chromosome contains some genes inherited from the mother and other genes inherited from the father. Diakinesis  bivalents more condensed & the nuclear membrane and the nucleolus disappear. Size of the chromosome: Meiosis 1) Interphase: long & thin. 2) Division:  Prophase: progressive decrease in its length accompanied by increasing its thickness.  Metaphase: very thick & quiet short (easily recognized). Types of chromosomes: A- According to the amount of the DNA: Single-chromosomes (s-chromosomes): made of one DNA molecule (interphase chromosomes = chromatin or chromatids). Double-chromosomes (d- chromosomes; mitotic chromosomes):are formed during the S phase. Each d-chromosome is formed of two chromatids, linked at the centromere. Each chromatid is made of a DNA molecule. B- According to position of centromere: 1. Metacentric: the centromere in the middle. 2. Submetacentric: the centromere is displaced slightly away from the center. 3. Acrocentric: the centromere is displaced away from the center. 4. Telocentric: the centromere is positioned at the very end of the chromosome. Foundation Module Page 34  Chapter 1: Cell (By Prof. Dr. Iman Nabil) C- Autosomal or sex chromosome: 1- Autosomal chromosomes:  Paired chromosomes with the same length, shape, position of the centromere & genetic information.  Carry the genes for somatic characteristics. 2- Sex chromosomes:  Paired chromosomes differ between males & females.  Carry genes for sex characteristics. X chromosome Y chromosome It is a sex chromosome, that occurs paired in females & It is a sex chromosome, that is single in males. present normally single in males. In female: one X chromosome is inherited from the In male: One chromosome is inherited mother& the other inherited from the father. from the father. In male: one X is inherited from the mother. Contains genes for female sex determination. Contains genes for male sex determination. Bigger in size. Smaller. Contains about 1000 genes. Contains about 50-60 genes. Represents 5 % of the entire human genome. Represents 2 % of the entire human genome. Types of cells in the human body: 1- Somatic cells: contain 46 chromosomes (44 autosomal+ 2 sex chromosomes). 2- Germ cells (Gametes= sperm & ovum): contains 23 chromosomes (haploid number; 22 autosomal+ 1 sex chromosome). Karyotyping: The somatic cell contains 46 chromosomes. Karyotyping: is the arrangement of the chromosomes pf a person during metaphase into groups of homologous pairs:  22 homologous pairs of autosomal chromosomes ; the same in length, position of centromere& genetic information,  One pair of sex chromosomes.  Each pair contains one chromosome originally derived from the mother& the other chromosome derived from the father.  In females (44 autosomes +XX): one X chromosome is heterochromatic (Barr body), it can be identified in neutrophils, attached to the nucleus in the form of a drumstick mass. Foundation Module Page 35  Chapter 1: Cell (By Prof. Dr. Iman Nabil)  Importance: regulates the amount of X-linked gene products being transcribed. How do chromosome abnormalities happen? Chromosome abnormalities usually occur when there is an error in cell division: in mitosis & meiosis: the correct number of chromosomes is supposed to end up in the resulting cells. However, errors in cell division can result in cells with too few or too many copies of a chromosome. Errors can also occur when the DNA are being duplicated. Factors that can increase the risk of chromosome abnormalities are: 1- Maternal Age:  Older women are at higher risk of giving birth to babies with chromosome abnormalities than younger women because they are born with all the eggs they will ever have.  Some researchers believe that errors can crop up in the eggs' genetic material as they age.  Because men produce new sperm throughout their lives, paternal age does not increase risk of chromosome abnormalities. 2- Environment: it is still possible that the environment may play a role in the occurrence of genetic errors. Types of chromosomal abnormalities: 1- Numerical abnormalities (aneuploidy): when a whole chromosome from a pair either missing (monosomy) or extra to the normal pair (trisomy). 2- Structural abnormalities: when part of an individual chromosome is missing, extra, switched to another chromosome, or turned upside down. Structural abnormalities: 1- Deletion: When a chromosome breaks with loss of some genetic materials. 2- Duplication: When a part of the chromosome is duplicated ( 2 copies which means having extragenetic materials) 3- Translocation: When a piece of one chromosome breaks off & attaches to another chromosome. 4- Inversion: When a piece of one chromosome breaks off & turned upside down, and reattached to the same chromosome. As a result, the genetic material is inverted. 5- Rings: when a chromosome breaks in two places and its broken ends fuse together. 6- Insertions: when a segment of one chromosome is translocated and inserted into another non- homologous chromosome (inter-chromosomal insertion), or into a different region of the same chromosome (intra-chromosomal insertion) Most chromosome abnormalities occur as an accident in the egg or sperm. In these cases, the abnormality is present in every cell of the body. Foundation Module Page 36 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Some abnormalities, however, happen after conception; then some cells have the abnormality and some do not. Chromosome abnormalities can be inherited from a parent or be "de novo" (new to the individual). This is why, when a child is found to have an abnormality, chromosome studies are often performed on the parents. Foundation Module Page 37 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Difference between cell proliferation and cell differentiation: Cell differentiation Cell proliferation It is the process by which unspecialized cells acquire specialized structural and/or functional features that Increase in the number of cells by division. characterize the specialized cells. Cell proliferation & differentiation: Early development: Rapid proliferation of embryonic cells, which then differentiate to produce the many specialized types of cells that makeup the organs. As cells differentiate: The rate of proliferation decreases, and many cells are arrested in the GO stage. Cell proliferation is balanced with cell death to maintain a constant number of cells. Classification of the body cells according to their ability of proliferation: 1-Static cell population (non-dividing, permanent): They leave the cell cycle to perform specialized function (GO stage), e.g. cardiac muscle fibers& neurons. 2-Stable cell population(quiescent): They are considered to be in Go stage, but they may be stimulated to divide by signals e.g. smooth muscle fibers and the cells of the liver. Foundation Module Page 38 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 3-Labile cell population:  They are continuously renewing cells e.g. cells have short life span as blood cells, epithelial cells of the skin &epithelial cells lining the digestive tract  They are replaced by proliferation of the stem cells. Stem Cells Definition: undifferentiated (unspecialized) cells that can proliferate & differentiate to give specialized cells. Stem cell properties: 1- Self-renewal: the ability of the cell to go through numerous cycles of cell division while maintaining the undifferentiated state. 2- Potency: the capacity to differentiate into different cell types. Types of stem cells: Foundation Module Page 39 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 1-Totipotent stem cells: They have the potential to generate all types of cells and construct a complete organism. They are derived from the cells produced by the first few divisions of the fertilized ovum (morula cells). 2-Pluripotent stem cells: They can differentiate into the derivatives of the three germ layers =ectoderm, endoderm, and mesoderm. They are derived from the inner cell mass of the blastocyst. 3-Multipotent stem cells: They can produce cells of a closely related family e.g. hematopoietic stem cells that can differentiate into red blood cells, white blood cells and platelets. 4-Unipotent cells: They can produce a single type of mature cell but still have the property of self-renewal which distinguishes them from non-stem cells e.g. stem cells in the skin epidermis. Potential sources of stem cells for clinical application: 1- Embryonic stem cells: They are pluripotent stem cells derived from inner cell mass of blastocyst. Advantage: They can specialize and become any type of body cells. Disadvantage: ethical restriction. 2- Adult stem cells: Most of them are multipotent. 3-Amniotic fluid stem cells: They are multipotent. Foundation Module Page 40 Chapter 1: Cell (By Prof. Dr. Iman Nabil) 4-Umbilical cord blood stem cells: They are pluripotent. Definition: Stem cells produced after alteration of the genes of adult somatic cells (dedifferentiation) to give them the properties of the embryonic stem cells. Foundation Module Page 41  Chapter 1: Cell (By Prof. Dr. Iman Nabil) 1- Necrosis = accidental cell death: Causes: It is a pathological process due to e.g. hypoxia, radiation or pathogens such as viruses. Morphological features: 1- Damage of the cell membrane with cell swelling& rupture. 2- Breakdown of cell organelles. 3- Denaturation or coagulation of cytoplasmic proteins. 4- Inflammation with extensive damage of the surrounding tissue. 2- Apoptosis = programmed cell death: It is a physiological process controlled by several genes (loss of mitochondrial function initiates several reactions that lead to cell death). What makes a cell decide to commit suicide? I-During embryonic development: Removal of excess cells that have no function e.g. during morphogenesis and for determination of organ size. Foundation Module Page 42 Chapter 1: Cell (By Prof. Dr. Iman Nabil) II-In adult: 1- Hormone-dependent:  Involution of the endometrium during the menstrual cycle.  Regression of lactating mammary gland after weaning.  Regression of prostate in old males 2- Elimination of cells during cell cycle when their DNA damage is not repaired. 3- Maintaining a constant number of cells in proliferating cell populations, e.g. intestinal epithelium. Morphological features of apoptosis: 1- Loss of microvilli and intercellular junctions. 2- Shrinkage of the cell with membrane blebing. 3- Breakdown of DNA with hypercondensation of chromatin and its collapse against the nuclear periphery. 4- Change of cell membrane characters without loss of its integrity. 5- Cell organelles remain apparently normal but become clumped inside the cytoplasm. 6- Fragmentation of the cell into apoptotic bodies that contain fragments of the nucleus, mitochondria, and other organelles. 7- The apoptotic bodies are removed by the phagocytic cells. Necrosis Apoptosis 1- Type Pathological. Physiological. 2- Cell membrane Damage with loss of its Change of some characters without loss of its integrity. integrity. 3- Organelles Broken down. Intact. 4- Proteins Denatured or Broken down of DNA with hypercondensation coagulated. of chromatin. 5- Apoptotic bodies Absent Present 6- inflammation Present Absent Foundation Module Page 43 Chapter 1: Cell (By Prof. Dr. Iman Nabil) Foundation Module Page 44 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) Basic tissues: A group of similar cells specialized to perform a common function. These tissues exist in associations forming body organs. They are 4: Connective tissue Muscular tissue Epithelial tissue Nervous tissue Epithelium Characteristics of Epithelium: 2-Held by intercellular junctions 1-Close ly aggregated cells 3-Lying on basement membrane 4- Avascular, nourished by Diffusion, but \ rich in sensory nerve endings Classification of Epithelium: Lining/ covering Glandular Special types Foundation Module Page 45 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) I- Lining Epithelium Classification of covering epithelia Number of layers Shape of cells Nucleus Flattened Simple: only one Squamous '* layer. Central Cuboidal rounded j f. ‘Stratified: more than one layer. Columnar ||11|jjJ Oval& basal 1- Simple Squamous: Side view: Flat cells & Flattened nucleus. Surface view: polygonal. Sites: , 1- Filtration: Bowman s capsule of kidney. * r 2- Diffusion: alveoli of lung. 3- Smooth passage: endothelium of blood vessels and lymph vessels. 4- Allows free mobility: mesothelium. 2- Simple cuboidal: Shape: cubical cells with central rounded nuclei. Sites: Kidney tubules & Thyroid follicles (ion exchange). 3- Simple columnar: Non ciliated Shape: columnar cells, the nuclei are oval & basal ciliated Foundation Module Page 46 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) Types & Sites: 1- Non ciliated: Secretion & absorption (stomach, small intestine, gall bladder). 2-Ciliated: Secretion (uterus, fallopian tube). 4- Pseudostratified columnar epithelium: 1- Crowded cells, all cells lie in contact with the basement membrane, but they do not all reach the surface. 2- The cells that reach the surface are tall columnar cell, while the other cells which do not reach the surface are short and triangular. 3- Several layers of nuclei, each lies at the widest portion of the cell, giving false appearance of stratification. iepididymis 1 Types & Sites: 1- Non ciliated: male genital tract. 2- Ciliated: most of respiratory system (pseudostratified ciliated columnar epithelium with goblet cells). It is classified according to the shape of the most superficial layer of cells. 1- Stratified squamous: Squamous Function: protection. Polygonal Structure: cuboidal/low columnar 1- Basal layer: low columnar; cuboidal cells. 2- Intermediate layers: Polygonal cells. 3- Superficial layer: Squamous cells. Types: 1- Keratinized: The superficial cells are filled with keratin (skin). 2- Non keratinized: In wet surfaces subjected to wear & tear (cornea, esophagus, mouth cavity & vagina). Foundation Module Page 47 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) 2-Stratified cuboidal:  Uncommon type.  Two layers of cuboidal cells. Ducts of sweat glands 3-Stratified columnar: Structure of human eye  Uncommon type.  The superficial cells are columnar in shape. Cornea Conjuctival fornix 2- Transitional Epithelium: Change its shape and number of layers, according to the functional state of the organ, e.g. urinary bladder& ureter. Empty bladder 1. A basal layer: low columnar cells. 2. Intermediate layers: polygonal cells,tend to be pear-shaped near surface. 3. The surface layer: large cuboidal (dome-shaped cells; umbrella cells). Full bladder 1- Superficial: large, flattened cells. 2- Basal: cuboidal cells. How does the transitional epithelium adapt to its function? 1- Decrease of number of layers. 2- Flattened cells Increase surface area Foundation Module Page 48 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) Hroineiatxxi o> catis arm mi downgrowth into the subjacent Epithelium II- Glandular Epithelium connective tissue V V Bn full lamina. Connective tivs ua — -  Function: fluid secretion.  Origin: from the covering epithelium Follicular endocrine gland tormaiion Types Of Glandular Epithelium: 1-According to number of cells: 1. Unicellular glands: consist of one cell e.g., goblet cells present in the small intestine and the respiratory tract. 2. Multicellular glands: consist of groups of cells e.g., most glands of the body. Acinus *- W l Rollauod 2-According to the presence or absence of a duct system: ** * *** (lamite 1- Exocrine glands: in which the secretion is carried by ducts e.g., At * fCin> salivary glands. 2- Endocrine glands or ductless glands: in which the secretion is released into the blood vessels e.g., thyroid gland and suprarenal gland. 3- Mixocrine (mixed exocrine and endocrine) glands: contain the two types e.g., pancreas. 3-According to the mode of secretion (the secretory mechanism): &nctolory vcmtclo |M«roc rlna Qo4ul coiftpl«M « 11011 [ «—T ( Nucl»u» 1- Merocrine glands: the secretory granules are discharged by O) Apocrlna Pinched Of MII 0ft portion > lisa nialiti exocytosis through the cell membrane without losing any part of < lotion the cell e.g., pancreas& salivary glands. O ) Holoorln * KO (toll (kna 2- Apocrine glands: the secretion is discharged together with the apical parts of the cytoplasm e.g., mammary gland. Uisinleqrolinq cell and ill released 3- Holocrine glands: the secretion is discharged with the whole cell [oidwilj leading to its complete destruction e.g., sebaceous gland. Hotoctine 4-According to the nature of secretion: Mitotic divisions lo replace cells 1- Serous glands: secrete a watery secretion e.g., parotid salivary gland. 2- Mucous glands: secrete mucous e.g., goblet cells and sublingual salivary gland. 3- Mixed glands: secrete both mucous and serous secretions e.g., submandibular salivary gland. 4- Glands with special secretions: ceruminous glands which secrete ear wax 'tA* ** ) ' and sebaceous glands which secrete a fatty secretion (sebum). 5-According to the shape of the secretory portion: ecretory V] ortion 1- Tubular: the secretory units are tubular in shape. m 2- Alveolar (acinar): the secretory units are rounded. —— 3- Tubuloalveolar (tubuloacinar): the secretory units have both tubular and 1 icintmy ducts alveolar parts. Sac ratoi acinar ala Foundation Module Page 49 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) 6-According to the branching of the ducts and branching of the secretory portion: iBludu) 9lqmii tubular Cooifoand taiMilar 1- Simple glands: have only one unbranched duct and one secretory unit. 9\ \n\ fix3 Example * sbnBlQ lenitaejn Stomach (gastric) Exmpie glands C.o«rrji-:s:‘nui ! «:« 2- Simple branched glands: have one unbranched duct and branched secretory units. 3-Compound glands: have branched duct system& branched secretory units. i$¥9lqrniS Simple branched III- Special Types of Epithelium iGloevIc alveolar Mnpound alveolar ComptKind i ui iuue 1- Neuroepithelium: Palatino Tons Ungual Tonsil The epithelial cells act as nerve receptors. Foliate Papillai Sites: 1- The taste buds of the tongue. 2- The organ of Corti in the ear. 3- The retina of the eye. 2- Germinal epithelium: The epithelium carrying the function of reproduction. Sites: in the testis and ovary. 3- Myoepithelial cells: Definition: modified stellate epithelial cells which surround the secretory units (the acini) and the ducts of the glands. Structure: contain myosin and actin myofilaments. Function: they are able to contract and squeeze the secretion from the glands. Sites: 1- Salivary gland. 2- Mammary gland. Functions of Epithelium: 1- Protection (stratified) 2- Absorption (simple) 3- Filtration (simple) 4- Gas diffusion (simple) 5- Secretion (glandular) 6- Contraction (special) 7- Reproduction (special) 8- Perception (special) Foundation Module Page 50 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) Epithelial Cell Polarity Definition: The epithelial cell has an apical, basal, and lateral surfaces, each surface exhibits special structural modifications to carry out specific functions. I- Apical Madificatians;: 1-Microvilli: Definition: non-motile, finger like cytoplasmic projections arise from the apical surface of epithelial cells. Structure: a core of actin filaments. Function: increase the surface area for absorption. Sites: The cells of the intestine and kidney tubules. 2-Stereocilia: Definition: long, branching microvilli. Function: increase the surface area for absorption. Site: the non-ciliated pseudostratified columnar epithelium of the male genital ducts e.g. the epididymis. 3-Cilia ‫الأهداب‬and flagella: Definition: motile cytoplasmic projections that extend from the cell surface.  Cilia: are hair-like processes that are longer than microvilli.  Flagella: resemble cilia in structure but they are much longer and are single for each cell e.g., flagellum of the sperm.  Structure: each cilium is formed of: 1- The basal body: replicate of the centrioles (9 triplets of microtubules) from which the shaft arises. The basal body is present in the apical cytoplasm. 2- The shaft (axoneme): extends from the cell surface. It contains 9 peripheral doublets of microtubules + a central pair of singlet microtubules (9x2+2=20 microtubules). 3- Rootlets: extend from underneath the basal body, in the form of radiating microtubules anchoring the cilium into the cytoplasm. N.B: The immotile cilia syndrome: Primary ciliary dyskinesia Classification and external resources Abnormal proteins of cilia or flagella resulting from mutation.  Male infertility: due to immotile sperm.  Chronic respiratory infection : caused by lack of cleaning action of cilia in the epithelium of respiratory tract. Normal cilia (A ) and cilia representative of Kartageneds syndrome ( 8) Foundation Module Page 51 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) Apical modifications Microvilli Stereocilia Cilia 1- Motility Non motile Non motile Motile. 2- Length Shorter. longer Longer. 3- Shape Finger like Branching microvilli. Hair like cytoplasmic projections. cytoplasmic projections. 4- Structure Core of actin Core of actin filaments. Consists of basal body, shaft & rootlets, filaments. all formed of microtubules. 5- Function Increase surface area Increase surface area Move a layer of fluid. for absorption. for absorption. 6- Most common Intestinal cells & Male genital tracts e.g. Respiratory tract. sites kidney tubules. epididymis. II- Basal iyiadifrie;atiatfii:; 1-Basal infoldings: Definition: the basal cell membrane is thrown into folds. Function: increase the surface area for ions transport. Site: kidney tubules 2-Basement membrane: Lamina lucida Site: in the interface between epithelium and connective tissue. Structure: C - termmalVIl domain - 70 mV ) Tight junction 1. the basal lamina: formed of adhesive Brush border (luminal Collagen fiber: mei ihi.me ) » lyM land ID ’ glycoprotein. fibril Anchoring COMMA l > M VI MUSCLE 2. the reticular lamina: formed of fine network of collagen fibrils. basal lamina connective tissue , Some non-epithelial cells are invested‫ مغلفة‬by a basal lamina like material called external lamina e.g., muscle fibers, Schwann cell ‫خلية موجودة فى الجهاز‬ ‫العصبىى الط رفى مس ئولة عن تكوين غالف الميالين حول الليفة ا لعصيبة‬ and adipocytes (the i W 31 ' external lamina protects the fat cells from mechanical stress ‫)الضغط الح ركى‬. muscle cell plasma membrane It is not called basal lamina because these cells have no basal surface. glomerular basement Figure ! membrane Functions of Basement Membrane: l I endothelial filtration slits 1. Structural attachment: attachment of the epithelial cells to the cell with with slit diaphragm fenestrae i underlying connective tissue. — ! 2. Filtration: regulates exchanges of macromolecules between the epithelium and the surrounding tissues. mrion ^ foot processes ofpodocytes (blue and green) invasive 3. Tissue scaffold: it directs the migration of epithelial In situ cancer cancer cells (re-epithelization) during wound repair. It acts as Dysplasia i barrier against passage of malignant cells. 3-Basal cell-to-matrix adhesions: Hemidesmosomes Hyperplasia Foundation Module Page 52 Chapter 2: Epithelium (By Prof. Dr. Iman Nabil) Basement Membrane keratnocyte Basal !UT to Desmosome Hemidftsmosomas Site: in the interface between epithelium and connective '