Structure & Function Handbook 2024-2025 S1 Theoretical PDF

Cytology The Cell:  Fundamental, functional units of tissues.  Fundamental unit of life  The cell is composed of two basic parts: cytoplasm and nucleus Cytoplasm consists of: 1. Cell organelles 2. Cell inclusions 3. Cytoskeleton 4. Cytos...

Cytology The Cell:  Fundamental, functional units of tissues.  Fundamental unit of life  The cell is composed of two basic parts: cytoplasm and nucleus Cytoplasm consists of: 1. Cell organelles 2. Cell inclusions 3. Cytoskeleton 4. Cytosol Cytoplasmic organelles are classified according to the presence or absence of membranes into: I. Membranous organelles 1-Cell membrane. 2. Mitochondria. 3. RER. 4. SER. 5. Golgi apparatus. 6. Lysosomes. 7. Peroxisomes. 8. Secretory vesicles. II. Non- membranous organelles 1. Ribosomes. 2. Proteasomes 3. Cytoskeleton. 20  The Cell Membrane Definition: The membrane separating the cytoplasm of the cell from surrounding structures is called the Cell membrane or the plasma membrane. It has highly selective permeability properties so that the entry and exit of compounds are regulated. Basic Membrane structure: LM: It is not visualized by LM. EM: Membranes range from 7.5 to 10 nm in thickness and consequently are visible only in the electron microscope. It consists of two densely stained layers separated by a lighter zone; thus creating a trilaminar appearance. EM picture of cell membrane Molecular structure of cell membrane: Membranes are mainly made up of lipids, proteins and small amounts of carbohydrates. 21 Lipids in Cell Membrane: 1-The trilaminar structure of membranes is produced by the arrangement of lipid molecules (predominantly phospholipids) that constitute the basic framework of the membrane. 2-Each phospholipid molecule consists of an enlarged head in which the phosphate portion is located; and of two thin tails. 3-The head end is called the polar end while the tail end is the non-polar end. 4- The head end is soluble in water and is said to be hydrophilic. 5- The tail end is insoluble and is said to be hydrophobic. When such molecules are suspended in an aqueous medium, they arrange themselves so that the hydrophilic ends are in contact with the medium; but the hydrophobic ends are not. 6-The dark staining parts of the membrane (seen by EM) are formed by the heads of the molecules, while the light staining intermediate zone is occupied by the tails, thus giving the membrane its trilaminar appearance. 22 Function of lipids: 1-Prevent passage of water soluble substances and ions. 2-Allow the passage of fat soluble substances and small non polar substances. Proteins in Cell Membrane The proteins are present in the form of irregularly rounded masses. Most of them are embedded within the thickness of the membrane and partly project on one of its surfaces (either outer or inner). However, some proteins occupy the entire thickness of the membrane and may project out of both its surfaces. These are called transmembrane proteins. Functions of protein: 1- Membrane proteins help to maintain the structural integrity of the cell by giving attachment to cytoskeletal filaments. 2- They also help to provide adhesion between cells and extracellular materials. 3- Some proteins play a vital role in transport across the membrane. 4- They form passive channels through which substances can diffuse through the membrane. 5- Other proteins act as receptors for specific hormones or neurotransmitters. 6- Some proteins act as enzymes. Carbohydrates of Cell Membranes In addition to the phospholipids and proteins, carbohydrates are present at the surface of the membrane. They are attached either to the proteins (forming glycoproteins) or to the lipids (forming glycolipids). The carbohydrate layer is specially well developed on the external surface of the plasma membrane forming the cell boundary. This layer is referred to as the cell coat or glycocalyx. Functions of glycocalyx: 1- Special adhesion molecules present in the layer enable the cell to adhere to specific types of cells, or to specific extracellular molecules. 2- In erythrocytes, the glycocalyx contains blood group antigens. 23 Vesicular Transport of cell membrane: Macromolecules normally enter cells by being enclosed within folds of plasma membrane (often after binding specific membrane receptors) which fuse and pinch off internally as cytoplasmic vesicles (or vacuoles) in a general process known as endocytosis. Three major types of endocytosis are recognized: 1. Phagocytosis (―cell eating‖) is the ingestion of particles such as bacteria or dead cell remnants. When a bacterium becomes bound to the surface, it becomes surrounded by extensions of plasmalemma and cytoplasm which project from the cell in a process dependent on cytoskeletal changes. Fusion of the membranous folds encloses the bacterium in an intracellular vacuole called a phagosome, which then merges with a lysosome for degradation of its contents. 2. Pinocytosis (―cell drinking‖) involves smaller invaginations of the cell membrane which fuse and entrap extracellular fluid and its dissolved contents. The resulting vesicles called pinocytotic vesicles. 3. Receptor-mediated endocytosis:  Receptors for many substances, such as low-density lipoproteins and protein hormones, are integral membrane proteins at the cell surface.  High-affinity binding of such ligands to their receptors causes these proteins to aggregate in special membrane regions that then invaginate and pinch off internally as vesicles. 24 NB: Movement of large molecules from inside to outside the cell usually involves vesicular transport in the process of exocytosis. In exocytosis a cytoplasmic vesicle containing the molecules to be secreted fuses with the plasma membrane, resulting in the release of its contents into the extracellular space without affecting the integrity of the plasma membrane. Cell organelles Inside the cell membrane the fluid cytoplasm (or cytosol) bathes metabolically active structures called organelles, which may be membranous (endoplasmic reticulum (ER), mitochondria, the Golgi complex, lysosomes and various types of vesicles) or non- membranous (such as ribosomes ,proteasomes and cytoskeleton). 25  1-Ribosomes: Are non-membranous small electron-dense particles, they are composed of rRNA associated different proteins. They are about 20 × 30 nm in size. LM: In stained preparations of cells polyribosomes are intensely basophilic Thus, cytoplasmic regions that stain intensely with hematoxylin and basic dyes, such as methylene and toluidine blue, indicate sites of active protein synthesis. EM: Ribosome has two subunits of different sizes bound to a strand of mRNA. The ribosomes are present in relation to rough endoplasmic reticulum (attached ribosomes). They may also lie free in the cytoplasm (free ribosomes). They may be present singly in which case they are called monosomes; or in groups which are referred to as polyribosomes (or polysomes). Function: 1-Ribosomes play an essential role in protein synthesis. During protein synthesis many ribosomes typically bind the same strand of mRNA to form larger complexes called polyribosomes, or polysomes. 2-Proteins synthesized for use within the cytosol (eg, glycolytic enzymes) or for import into the nucleus and certain other organelles are synthesized on polyribosomes. 3- Polyribosomes attached to membranes of the endoplasmic reticulum (ER) translate mRNAs coding for membrane proteins of the ER, the Golgi apparatus, or the cell membrane, enzymes to be stored in lysosomes and proteins to undergo exocytosis from secretory vesicles. 26  (Clusters of polyribosomes sitting on mRNA) (Attached electron dense ribosomes) 2-Rough Endoplasmic Reticulum  Rough endoplasmic reticulum is an anastomosing network of intercommunicating channels and sacs (cisternae). 27   The name "rough" is due to the presence of ribosomes on its surface LM: R ER in LM can be visualized as masses of material staining with basic dyes. The basophilia of the RER in H&E staining is due to the presence of negatively charged rRNA in the ribosomes attached to it. Visibility of the RER increases in cells that are highly secretory such as Nissl substance in neurons and exocrine pancreatic acinar cells. (L.M of RER) (E.M of RER) EM: The rough appearance of rough ER is due to ribosomes attached to cytoplasmic side of membrane which play an important role in protein synthesis. The lumen of rough ER is continuous with the perinuclear space (between the inner and outer nuclear membranes). 28 Function: The major function of RER is production of membrane associated proteins, proteins of many membranous organelles, and proteins to be secreted by exocytosis. 3-Smooth Endoplasmic Reticulum LM: It cannot be demonstrated by LM best seen with the TEM. EM: It is continuous with the rough endoplasmic reticulum, its membranes lack ribosomes, Unlike the cisternae of RER, SER cisternae are more tubular or saclike, with interconnected channels of various shapes and sizes Function: 1- Smooth endoplasmic reticulum is found in abundance in cells that synthesize phospholipids, cholesterol, and steroid hormones, such as estrogens, testosterone, and corticosteroids. 2- When liver cells are exposed to potentially harmful drugs and chemicals, smooth endoplasmic reticulum proliferates and inactivates or detoxifies the chemicals. 3- Skeletal and cardiac muscle fibers also exhibit an extensive network of smooth endoplasmic reticulum for calcium storage. 29  4-Mitochondria  The number of mitochondria varies from cell to cell being greatest in cells with high metabolic activity (e.g., in secretory cells and sperms).  Mitochondria vary in size, most of them being 0.5–2 μm in length. Mitochondria are large in cells with a high oxidative metabolism.  Mitochondria divide by simple binary division. LM: They are not visible with H&E stain. They need a special supravital stain as Janus green B. They appear as minute rods or spheroid bodies. EM:  The mitochondrion is bounded by a smooth outer membrane within which there is an inner membrane; the two being separated by an intermembranous space.  The inner membrane is highly folded on itself forming incomplete partitions called cristae.  The space bounded by the inner membrane is filled by a granular material called the matrix.  This matrix contains numerous enzymes. It also contains some RNA and deoxyribonucleic acid (DNA).  The matrix contains electron dense granules that bind cations like Ca++ and Mg++ to regulate mitochondrial enzymatic function. 30 Function of mitochondria: 1- It is the power house of the cell. It contains many enzymes including some that play an important part in Kreb‘s cycle. 2- Adenosine triphosphate (ATP) and guanosine triphosphate (GTP) are formed in mitochondria from where they pass to other parts of the cell and provide energy for various cellular functions. 5-Golgi complex: The Golgi apparatus is present in almost all cells. Its size and development vary, depending on the cell function; however, it is most highly developed in secretory cells. LM: In light microscopic preparations suitably treated with silver salts to appear as positive Golgi image. The Golgi complex can be seen as a small structure of irregular shape, usually present near the nucleus; supranuclear, e.g. cells of epididymis or perinuclear, e.g. nerve cells. With ordinary hematoxylin and eosin; negative Golgi image is obvious especially in protein synthetizing cells (plasma cells). 31 EM: Several flattened disc-shape saccules arranged in stacks. The periphery of each saccule is dilated. Golgi apparatus has two faces a. Cis- face (entry) is convex and called cis or immature face b. Trans- face (exit) is concave and called trans or mature face. NB: 1-Transfer vesicles containing the newly synthesized protein arise from RER and are associated with the cis face. 2-Secretory vesicles containing modified protein are associated with the trans face. Function: 1- Modification, concentration and packaging of synthesized proteins into secretory granules. 2- Recycling and redistribution of the cell membrane. 32  6-Secretory vesicles:  The cytoplasm of a cell may contain several types of vesicles. The contents of any such vesicle are separated from the rest of the cytoplasm by a membrane which forms the wall of the vesicle.  Vesicles are formed by budding off from existing areas of membrane.  Some vesicles serve to store material. Others transport material into or out of the cell. 7-Lysosomes:  These membrane bound vesicles contain enzymes that can destroy unwanted material present within a cell. Such material may have been taken into the cell from outside (e.g., bacteria); or may represent organelles that are no longer of use to the cell.  They are abundant in phagocytic cells (e.g.macrophages).  Lysosomal enzymes (e.g. acid phosphatase) are capable of breaking down most biologic macromolecules.  They are active at an acidic pH. LM: In macrophages and neutrophils, lysosomes are slightly larger and visible with the light microscope, especially after histochemical staining. EM: Lysosomes, which are usually spherical, range in diameter from 0.05 to 0.5 μm and seen as a uniformly granular, electron dense appearance. 33 Types and Fate of Lysosomes: 1- Primary Lysosomes: They are newly pinched off vesicles from the Golgi apparatus. The primary lysosomes are small in size. They contain hydrolytic enzymes in the form of granules. 2- Secondary lysosomes: They are formed after combination of primary lysosome with phagosme, pinocytotic vesicle or autophagosome. Types of Secondary lysosomes 1- Heterophagic vacuole: It occurs when the primary lysosome fuses with a phagosome. 2- Multivesicular body: It occurs when the primary lysosome fuses with a pinocytotic vesicle. 3-Autophagic vacuole (Auto-phagosomes, Auto-lysosomes): It occurs when primary lysosomes fuse with the autophagosome (old organelles enclosed in a membrane). Fate of lysosomes: Residual Bodies are those lysosomes in which only indigestible food materials have been left. In some long- lived cells (e.g., neurons, heart muscle) large quantities of fine yellow- brown granules of residual bodies accumulate and are referred to as lipofuscin pigment; "wear-and-tear" pigments. 34  8-Peroxisomes:  These are similar to lysosomes in that they are membrane bound vesicles containing enzymes. The enzymes in most of them react with other substances to form hydrogen peroxide, which is used to detoxify various substances by oxidizing them.  Hydrogen peroxide resulting from the reactions is bactericidal.  Some peroxisomes contain the enzyme catalase which converts the toxic hydrogen peroxide to water, thus preventing the latter from accumulating in the cell. Peroxisomes are most prominent in cells of the liver and in cells of renal tubules. 35  9-Proteasomes: They are protein complexes which degrade unneeded or damaged proteins by proteolysis; a chemical reaction that breaks peptide bonds. The Cytoskeleton: The cytoplasmic cytoskeleton is a complex array of: (1) Microtubules. (2) Microfilaments (also called actin filaments). (3) Intermediate filaments. 36  1-Microtubules LM : It cannot be demonstrated by LM. EM: Microtubules are about 25 nm in diameter. The basic constituent of microtubules is the protein tubulin (composed of subunits a and b). Chains of tubulin form protofilaments. The wall of a microtubule is made up of thirteen protofilaments that run longitudinally. The tubulin protofilaments are stabilized by microtubule associated proteins (MAPs). Nb: Microtubules can be found in constant stable forms that constitute the centrioles plus in labile forms that are highly dynamic and will frequently grow and shrink at a rapid rate. During this dynamic instability, tubulin subunits will both shorten and elongate to form the mitotic spindles. 37 Function of microtubules: 1- Microtubules are formed in centrioles which constitute a microtubule organizing center (MTOC). 2- As part of the cytoskeleton, they provide stability to the cell. 3- Microtubules facilitate transport within the cell. Some proteins (dynein, kinesin) present in membranes of vesicles and in organelles, attach these to microtubules, and facilitate movement along the tubules. Such transport is especially important in transport along axons. 4- In dividing cells microtubules form the mitotic spindle. 5- Cilia are made up of microtubules (held together by other proteins). 38  Microfilaments (Actin These are about 5 nm in diameter. They are made up of the protein actin. Actin filaments form a meshwork just subjacent to the cell membrane. This meshwork is called the cell cortex (The filaments forming the meshwork are held together by a protein called filamin). The cell cortex helps to maintain the shape of the cell. Cell Meshwork Filamin Intermediate Filaments These are so called as their diameter (10 nm) is intermediate between that of microfilaments (5 nm) and of microtubules (25 nm). The proteins constituting these filaments vary in different types of cells. Types of intermediate filaments: 1. Keratins in skin. 2. Vimentin filaments are characteristic of cells of mesenchymal origin. 3. Desmin is found in smooth muscle. 4. Glial filaments in nervous tissue. 5. Neurofilaments are present in nerve cell body and processes. 39 Function of intermediate filaments: 1- Intermediate filaments link cells together. They do so as they are attached to transmembrane proteins at desmosomes. 2- The filaments also facilitate cell attachment to extracellular elements at hemidesmosomes. 3- In the epithelium of the skin the filaments undergo modification to form keratin. They also form the main constituent of hair and nails. 4- The neurofilaments of neurons are intermediate filaments. Neurofibrils help to maintain the cylindrical shape of axons. 5- The nuclear lamina consists of intermediate filaments; lamins. 40  Desmin The Nucleus: The nucleus is the central, denser, part of the cell. It is the largest cell organelle measuring 4– 10 μm in diameter. LM: 1-In H&E-stained sections, the nucleus stained basophilic. It is usually rounded, oval, flat, bi-lobed, segmented or kidney-shape. 2-The site of nucleus may be central, peripheral or basal. 3- Number of nuclei is usually one (mono-nucleated), some cells are bi-nucleated or multi- nucleated. 4-All cells in the body contain nucleus, except mature red blood cells (RBCs). 41 EM: The Nucleus contains four components: 1- Nuclear membrane 2- Chromatin 3- Nucleolus 4- Nucleoplasm. 1-Nuclear Membrane:  With EM, the nucleus is seen to be surrounded by a double-layered nuclear membrane or nuclear envelope.  The outer nuclear membrane is continuous with endoplasmic reticulum.  The space between the inner and outer membranes is the perinuclear space. This is continuous with the lumen of rough endoplasmic reticulum. 42  Deep to the inner membrane there is a layer containing proteins and a network of filaments this layer is called the nuclear lamina.  At several points the inner and outer layers of the nuclear membrane fuse leaving gaps called nuclear pores. Each pore is surrounded by dense protein arranged in the form of eight complexes. These proteins and the pore together form the pore complex.  Nuclear pores represent sites at which substances can pass from the nucleus to the cytoplasm and vice versa. The nuclear pore is about 80 nm across. It is partly covered by a diaphragm that allows passage only to particles less than 9 nm in diameter.  A typical nucleus has 3,000–4,000 pores. It is believed that pore complexes actively transport some proteins into the nucleus, and ribosomes out of the nucleus. 2-Chromatin 1- Composed of coiled strands of DNA bound to basic protein (histone) and other proteins. 2- Its basic structural unit is nucleosome; Nucleosome: is composed of a core of histone wrapped by 2 complete turns of DNA string that continue to wrap the next nucleosome (beads on string). 3- Two types of chromatins can be identified, according to the degree of chromosome condensation: heterochromatin and euchromatin. 4- Heterochromatin represents areas where chromatin fibres are tightly coiled on themselves forming ‗solid‘ masses. Heterochromatin appears as coarse, electron-dense material. 5- In contrast, euchromatin represents areas where coiling is not so marked. Euchromatin is visible as finely dispersed granular material in the electron microscope. 43 44  3-Nucleoli: 1- Are larger and more distinct in cells that are metabolically active. 2- It is seen that the nucleoli have a high RNA content. 3- Nucleoli are site where ribosomal RNA is synthesised. The templates for this synthesis are located on the related chromosomes. 4- Ribosomal RNA is at first in the form of long fibres that constitute the fibrous zone of nucleoli. It is then broken up into smaller pieces (ribosomal subunits) that constitute the granular zone. 5- Finally, this RNA leaves the nucleolus, passes through a nuclear pore, and enters the cytoplasm where it takes part in protein synthesis. 45  4-Nucleoplasm: Besides chromatin and nucleolus, the nucleus also contains various small granules, fibres and vesicles (of obscure function). The spaces between the various constituents of the nucleus are filled by a base called the nucleoplasm. Functions of the nucleus: 1- Cellular regulation: houses genetic material, which directs all cellular activities and regulates cellular structure. 2- Production: produces ribosomal subunits in nucleolus and exports them into cytoplasm for assembly into ribosomes. Centrioles and Microtubule-Organizing Centers ( MTOCs): 1-Centrioles, visible in the light microscope, are paired, short, rod-like cytoplasmic cylinders built from nine microtubule triplets. 2-Centrioles are usually found close to the nucleus, often partially surrounded by the Golgi apparatus, and associated with a zone of amorphous, dense pericentriolar material. 46 3-The region of the cell containing the centrioles and pericentriolar material is called the microtubule-organizing center or centrosome. 4-During mitosis, duplicated MTOCs serve as mitotic spindle poles: MTOC is the region where most microtubules are formed, and from which they are then directed to specific destinations within the cell. Therefore, the MTOC controls the number, polarity, direction, orientation, and organization of microtubules formed during the interphase of the cell cycle. Cytoplasmic Inclusions They contain accumulated metabolites or other substances, unlike organelles have little or no metabolic activity themselves. Most inclusions are transitory. Types 1- Lipid droplets, accumulations of lipid filling adipocytes (fat cells) and present in various other cells. 2- Glycogen granules, aggregates of the carbohydrate polymer in which glucose is stored, visible as irregular clumps of periodic acid-Schiff (PAS)—positive or electron- dense material in several cell types, notably liver cells. 47  Lipid Glycogen 3- Pigmented deposits of naturally colored material, including; a- Melanin, dark brown granules which in skin serve to protect cells from ultraviolet radiation. b- lipofuscin, a pale brown granule found in many cells, especially in stable non dividing cells (eg, neurons, cardiac muscle), containing a complex mix of material partly derived from residual bodies after lysosomal digestion. c- Hemosiderin, a dense brown aggregate of denatured ferritin proteins with many atoms of bound iron, prominent in phagocytic cells of the liver and spleen, where it results from phagocytosis of red blood cells. Melanin lipofuscin Hemosiderin 48 4- Crystals: They are present in some cells as sertoli cells and interstitial cells of the testes. Crystals in Sertoli cells 49