Cell Biology PDF

The Cell The cell is the functional and morphological unit of living organisms. Unicellular organisms are made up of one cell, while multicellular organisms are made up of several cells grouped together and specialised in certain functions within the organism itself. Eukaryotes Ar...

The Cell The cell is the functional and morphological unit of living organisms. Unicellular organisms are made up of one cell, while multicellular organisms are made up of several cells grouped together and specialised in certain functions within the organism itself. Eukaryotes Are much more evolved and complex cells than prokaryotes. Are larger in size. Have a differentiated nucleus with a more complex DNA and contain numerous organelles. Human Cell - They are differentiated and specialised in certain functions. - We have many different types of cells, each with a particular function. - Cells that resemble each other are grouped together forming tissues, these tissues are organised into organs and systems. Animal eukaryotic cell contents Eukaryotic cells are surrounded by a plasma membrane, inside you can find cytoplasm. Organelles allow it to carry out its functions and the nucleus contains the genetic material. The number of organelles will vary depending on the type of cell. CELL MEMBRANE - The cell membrane is a permeable and selective barrier that separates the external environment from the inside of the cell. - It maintains its integrity, regulates interactions with other cells and controls the movement of substances from the interior to exterior. - Recognises molecules and other cells. Components of Phospholipid Bilayer - Lipids (40-50%): Phospholipids, Glycolipids, Cholesterol - Proteins (60%): Integral or transmembrane and extrinsic or peripheral Phospholipids They consist a polar head (hydrophilic) ands two non-polar (hydrophobic) tails formed by a chain of fatty acids. Phospholipids will form a double layer with non-polar tails on the inside of the membrane and thus leave the polar heads on the outside of the membrane. The tails are joined together by weak covalent bonds allowing movements of molecules through the bilayer. Glycolipids and Cholesterol Glycolipids have two tails of fatty acids linked to a carbohydrate. Glycolipids are located in the membrane between the phospholipids. Cholesterol is located in the spaces between unsaturated tails. Cholesterol helps to regulate fluidity of the membrane and limits the ability of movement. Membrane proteins Are the proteins integrated in the membrane called integral proteins or they can be associated with the membrane by its cytosolic side called extrinsic proteins. Integral proteins can also be called transmembrane as they completely cross the membrane. Transport proteins: joins molecules to take them from one side of the membrane to the other or can also form channels to open up certain stimuli Union proteins: establish cell junctions with other cells and can also fix internal structures of the cell itself. Signal reception: the cells need to receive information from the medium and from other cells in order to control within the multicellular organism. Enzymes: catalyse reactions in the membrane. Protoplasm Is the living substance of the cell and is divided into two compartments: Cytoplasm: is composed of water mainly, where we can find organic and inorganic chemical substances dispersed, also where organelles are found. Carioplasm: material that forms the content of the nucleus. Cell Organelles Ribosomes Small organelles made of rRNA that are responsible for protein synthesis. Each ribosome is formed by a major subunit and a minor subunit. The minor subunit has a binding site for the mRNA and another binding site for the tRNA. The mRNA will bind to the ribosome, which will read the information contained in that mRNA chain. The tRNA will add the amino acid that indicates the mRNA and as the ribosome goes reading the mRNA chain, then amino acids will be added to form a protein. Ribosomes are found in the cytosol. Endomembrane System Endoplasmic reticulum Golgi apparatus Nuclear envelope Endoplasmic Reticulum Is a system of tubules and vesicles whose lumen is called a cistern. There is a smooth Endoplasmic reticulum (SER) and the rough Endoplasmic reticulum (RER) Rough endoplasmic reticulum It is rough as it contains ribosomes. It’s function is protein synthesis. These proteins that are made in the RER can remain the RER membrane and be part of the organelle. Other proteins synthesised in the RER membrane will be stored inside their cisterns. They will come out through vesicles and go to other organelles or outside the cell. Smooth endoplasmic reticulum Formed by a network of anastomosed tubes. Does not contain ribosomes. It’s main functions are lipids synthesis and storage calcium. Golgi apparatus Consists of one or several series of stacked cisterns. Each cistern is dilated and surrounded by vesicles in the process of fusing or detaching from this organelle. The part of the GA closest to the RER and the nucleus is called the cis face. Vesicles from the RER will enter the through cis face. The other side of the GA which is the one facing towards the plasma membrane is called the trans face, this is where the vesicles exit the organelle. Transport control and direction The proteins created and modified in the RER will come out in vesicles and then enter the GA through the cis face. These proteins will then be modified by the GA and released out through the trans face to go to their final destination. Lysosomes Is a spherical shaped cell surrounded by a membrane and full of enzymes. These enzymes are responsible for degrading different types of molecules and to function they need a very high pH. These enzymes must be surrounded by this membrane in order to keep the pH at the right acid level making it suitable for the enzymes to work, also avoids damaging other structures of the cell. Lysosomes destroy macromolecules, cell waste or aged organelles and then this degraded material can be reused by the cell or released from it. Types of lysosomes Primary Lysosome: on a picture can be seen as the lighter circular structure, they are of this colour because they have never intervened in catabolic processes. Secondary Lysosome: on the picture can be seen as the circular structure with some black formed in it, meaning it has already been part of catabolic processes. Tertiary Lysosome: on a picture can be seen as the darkest circular structure, contains compounds resistant to digestion and remain stored in it Peroxisomes Organelles surrounded by membrane with a spherical shape which contain oxidative enzymes. They intervene in the degradation of fatty acids, where hydrogen peroxide is obtained. Mitochondria Are flexible organelles in the shape of a cane, they contain ATP which is a suitable molecule that stores energy. These organelles are responsible for using oxygen from the wire and glucose to obtain energy for the cells to carry out their functions. Mitochondrias have a smooth outer membrane and another inner membrane that we call cristae, cristae greatly increases the surface of this membrane. In the inner membrane there are protein complexes that form ATP synthase and the electron transport chain, both responsible for the generation of ATP. Inside the internal membrane there is a dense liquid called the matrix, the matrix contains the enzymes of the Krebs cycle. Mitochondria contains DNA that contains specific information of the mitochondria, although this DNA has nothing to do with nuclear DNA. This DNA is more loose and unpacked similar to prokaryotic organisms. Nucleus Is the largest organelle in the cell and is responsible for storing the genetic material such as the DNA and the assembly of ribosomes. It is located in the centre of the cell and is spherical although depending on the function of the cell, its shape, size and position can vary. Most cells have a single nucleus, but in humans you can find some cells with several nuclei such as osteoclasts, and some with none such as erythrocytes. Components of a Nucleus Nuclear envelope made up of external and internal nuclear membrane and nuclear pores. Nucleoplasm which has the nucleolus and chromatin. Nucleoplasm Is the liquid part of the material that fills the nucleus. It is composed of genetic material and the nucleolus. Chromatin Is the complex that forms DNA with proteins called histones for storage. Depending on its activity, it can appear in the shape of heterochromatin or euchromatin. Chromosomes Humans have 46 chromosomes (23 pairs of homologous chromosomes) One chromosome of each pair is inherited from the father and the other from the mother. 22 autosomal chromosomes and 1 sex chromosomes (X or Y) Cells with the complete complement of chromosomes are called diploid. (2n) Cells with only one of each pair of Homologation: haploid (n) Chromosome structure Each identical copy of the DNA will form a chromatid, and two chromatids will join at a point called the centromere which holds them together in order to form the chromosome. The centromere contains a structure called kinetochore, which is where the microtubules of the mitotic spindle will bind during cell division. Cytoskeleton Is a system of tubules and protein filaments that is responsible for maintaining the shape of the cell, the location of the organelles and their movement and also muscle contraction. The cytoskeleton is made up of three components: Microfilaments (movement) Intermediate filaments (structure) Microtubules (shape, transport, cell division) Microfilaments They are formed by a protein called actin that is organised in two chains forming a helix. These actin networks are located next to the plasma membrane and form the structural basis of the cellular cortex. In muscle cells there are actin filaments that are organised in a particular way will be responsible for muscle contraction. These contractile bundles of actin are linked with another protein called myosin, which moves by sliding the actin filaments back. They are responsible for the movements of organelles and vesicles. They form structures such as microvilli. Microvilli Are cellular membranes extending that have dense bundles of cross-linked actin filaments. These structures increase the surface area of the cell so that it has more contact with the environment and helps with absorption. Intermediate filaments Have an intermediate diameter between microfilaments and microtubules. Support the cell maintaining its three dimensional structure. Also support the nucleus and anchor the cytoskeleton to the membrane. Microtubules Are hollow cylinders that are organised from a region near the nucleus called centrosome. There role is to continuously stabilising or depolymerizing, thus suffering change in length depending on the needs of the cell. Provides regidity and maintain the shape of the cell, regulating intracellular movements of organelles. Complex grouping of microtubules 1. Centrioles Are cylindrical structures composed of 9 triples of microtubules. A pair of centrioles is surrounded by a dense matrix called Pericentriolar material and this whole set will form the centrosome. Duplication of a centriole from another centriole When a cell goes through division, the centrioles duplicate, each forming a new daughter centriole perpendicular to the mother centriole. The two pairs of centrioles will be responsible for forming the mitotic spindle necessary for cell division. 2. Cilia They are extensions of the cell membrane with a microtubules cytoskeleton. It’s structure is formed by a central pair of microtubules surrounded by 9 doublets. The basal body is found at the base of the cilium and is formed by 9 triplets of microtubules. Cilia cover the surface of the cell and move substances from the medium. 3. Flagela The only human cell that has a flagellum is the sperm. Their main role is to help an organism in movement. Its structure is the same as that of the axonemes. In the main piece of the tail, this structure is surrounded by 9 dense fibres and the middle covered with mitochondir mitochondria providing energy for movement. Part 2 of CELL BIOLOGY: CELL CYCLE The cell cycle is a series of events that occur in the cell to prepare for division into two daughter cells. It is divided into mitosis and interphase, where interphase is the longest stage in which the cell increases its size, its content and replicates its genetic material. Interphase Phase G1: is a period of cellular growth, where the cell regains its size that had decreased when the cell divided into two after mitosis. Synthesis of RNA, enzymes and regulatory proteins necessary for all cell functions. Phase S: stage of DNA synthesis during the cell cycle. The cell duplicates its DNA content. Phase G2: synthesis of RNA and proteins necessary for cell division. Cell division Mitosis: Asexual reproduction and no reduction of genetic material. Meiosis: Sexual reproduction and reduction of genetic material. Mitosis Phases: Prophase, Prometaphase, Metaphase, Anaphase, Telophase, Cytokinesis. Interphase - Chromosomes duplicate, and the copies remain attached to each other. Prophase - In the nucleus chromosomes condense and become visible, spindles start to form. Prometaphase - The nuclear membrane breaks apart, and the spindle starts to interact with the chromosomes. Metaphase The copied chromosomes align, in the middle of the spindle. Anaphase Chromosomes separate into two genetically identical groups and move to opposite ends of the spindle. Telophase - Nuclear membrane form around each of the two sets of chromosomes, the chromosomes begin to spread out and the spindle begins to break down. Cytokinesis The cell splits into two daughter cells, each with the same number of chromosomes as the parent. In humans, such cells have two copies of 23 chromosomes and are called diploid. During telophase a segmentation groove begins to appear in the cytoplasm. This ring contracts until the two daughter cells are separated. Meiosis Is a special type of cell division that gives rise to gametes, the number of chromosomes is reduced from 2n to n. Reducing the number of chromosomes to n, assures that each gamete carries half of chromosomes so that when merged with another gamete, we obtain the number 2n proper to the species. Process 1. In the S phase, the DNA content is doubled as in any division. 2. Prophase I: chromosomes condense and become visible in the nucleus. The homologous chromosomes are paired and fragments of genetic material exchanged, whereby the chromatids no longer have the identical genetic information than in the mother cell. 3. Prometaphase I: the nuclear envelope disappears and the spindle begins to form. The homologs remain together. 4. Metaphase I: The pairs of homologous chromosomes are aligned at the equator of the spindle. 5. Anaphase I: The spindle begins to be disorganised and the microtubules drag a complete chromosome of each pair with it. 6. Telophase I: the two child nuclei are formed with one chromosome of each pair. 7. Meiosis II: begins and will follow the same steps as normal mitosis. At the end of meiosis I, two daughter cells are obtained and in meiosis II each of them gives place two new daughter cells. So at the end of of meiosis we get 4 haploid cells. Cell Death There are two mechanisms by which cells may die: Apoptosis: is a programmed cell death, this means it is a physiological process. This happens for example in cells that are programmed from the embryonic stage for their destruction so that the organism can develop properly. Necrosis: is a process that occurs due to attacks or traumatic injuries. It is no longer a regulated process, and it may damage the organism. Apoptosis Modification of the cell shape and decreases in cell size —> loss of contact with other cells. Condensation of the cytoplasm. No changes in the organelles. Embryonic Development There are cells that during the embryonic development are genetically programmed to undergo apoptosis, as for example those that would form membranes between the fingers and toes. Maintaining body Homeostasis Participates in the continuous remodeling and maturation of all organs and tissues. It helps maintain the balance between proliferation and cell death. Protection against damaged or tutorial cells When intracellular damage occurs and the intervention of the immune system or an inflammatory reaction is not appropriate, apoptosis is activated in an intrinsic manner. For example: Physic agents damage (radiation), Chemical agents damage (toxics), tumoral cells. Necrosis Increase of cell size (the cell swells). Mitochondrial damage. Breakage of the cell membrane Dissolution of the organellles. Tissue damage Topic 3: Epithelial Tissue Epithelial tissue Cover internal and external, line cavities, and form glands. Cells tightly linked together by junctional complexes, there is hardly any extracellular space. Separated from the underlying connected tissue by the basement membrane. Functions Delimitation Protection Diffusion Absorption Filtration Excretion Uptake of stimuli Secretion Polarity Epithelial cells are resting on a surface. They have a basal surface, which attaches to the basement membrane, and apical surface, which faces the lumen of the cavity or the external environment, and a natural surfaces, which face the sides of adjacent cells in the epithelium. Apical membrane specialisations The apical domain of the cell is the one that is directed towards the lumen. It presents abundant ion channels and transport proteins and it is the place where secretion products will be released. In this domain several structures may appear that will be related to the function of the epithelium: microvilli, cilia, stereocilia and keratin. Stereocilia Are extremely long microvilli. They increase the absorption surface, but also help the movement of the medium. They only appear in the male reproductive system and in the inner ear. Keratin Is a protein produced by epithelial cells and is located in the cytoplasm of these cells. It provides rigidity to the cells, making the epithelium more resistant to external damages. Lateral membrane specialisations In the lateral zones of the epithelial cells, we will find structures that intervene in the junctions between cells and that will be responsible for the cohesion of the epithelium: -Zonula occludes or tight junction -Zonula adherens or adherens junction -Desmosomes (adherent macula -Communicating, GAP junctions or nexus Zonula Occludens: tight junction Most apical junction between epithelial cells. Forms a continuous band around the entire perimeter of the cell. Seals completely the space between cells. Does not allow the passage of membrane proteins. Zonula adherens: adherens junction They are located next to the tight junctions. They also form a belt that surrounds the entire perimeter of the cell. The space between membranes is occupied by the extracellular part of membrane proteins called cadherins. These are joined together between cells. The intracellular side of the cadherins binds to actin filaments. Macula adherens: desmosome Junctions of punctual shape distributed randomly in the plasma membrane. Located below the zonules. The cytosolic part of the junction has a junction plate in which intermediate filaments of keratin are attached. Basal membrane specialisations Basement membrane: is a membrane located at the border between epithelia and the underlying connective tissue. It works as an anchor for the epithelium and filters substances that pass from the epithelium to the inside of the body. Folds: are invaginations of the plasma membrane that increase the surface of the cell. Hemidesmosomes Hemidesmosomes They are binding structures that join the cell membrane to the membrane. They appear in the basal cells of the epithelia. In the intracellular part they have a dense plate attached to intermediate filaments just as it appeared in the desmosomes. The extracellular part has proteins called integrins that bind to the basement membrane. Classification of Epithelia Lining epithelia Glandular epithelia or glands Lining epithelia They are classified according to three features: Number of layers of cells: -Simple -Stratified -Pseudostratified Cell shape (surface cells) -Flat -Cuboidal -Columnar Presence of specialisations on apical surface -Microvilli -Cilia and stereocillia Keratin Lining Epithelium Simple squamous epithelium A single layer of thin, flattened cells. Covers pulmonary alveoli, blood and lymphatic vessel and in the meso In addition to lining surfaces, it easily allows the filtration of substance. It covers the pulmonary alveoli, blood and lymphatic vessel and in the mesothelium. Simple cuboidal epithelium A single layer of cuboidal cells, with rounded nucleus in the center of the cell. This epithelium is often associated with absorption, secretion. Appear in the glass ducts, covering the ovary. Simple columnar epithelium A single layer of tall cells, rectangular profile and oval nucleus located more towards the base of the cell. This type of epithelium intervenes in the transport and absorption. Appears largely in the digestive tract, gallbladder and large gland ducts. Stratified squamous epithelium Formed by several layers of cells and only the deepest layer will contact the basement membrane. These basal cells usually have a cuboidal or cylindrical shape and the apical cells are flattened. They cover the lining and also the walls of the mouth, esophagus and vagina. Stratified squamous keratinised epithelium It is a similar to the stratified flat mucosal epithelium, but its apical cells are dead cells filled with keratin. Is resistant to abrasion and is also impermeable to water. Appears mainly in the epidermis of the skin. Stratified cuboidal epithelium It contains multiple layers of cuboidal cells and lines the ducts of some glands. They can be used for absorption and secretion. Stratified columnar epithelium The basal layers are polyhedral or cuboidal and the surface layer is cylindrical. Hardly appears in the organism, only in the conjunctiva of the eye, some large ducts of glands and some regions of the male urethra. In addition to lining, also provides protection and can serve to absorb and secrete. Pseudostratified columnar epithelium Consists of a single layer of cells, but it seems to be stratified. All the cells are in contact with the basement membrane but only some reach the lumen. they are ciliated. Appears mostly in the respiratory tract, but also in ducts of the male reproductive system. Serves for lining and also transport plus secretion. Urothelium Appears only in the urinary tract. Consist of one or several layers of cells and usually has a pseudostratified appearance. They are called umbrella cells because of the way they look. When the organ is filled with urine, the epithelium is more distended, umbrella cells flatten and the epithelium becomes thinner. Glandular epithelia - The glands originate from epithelial cells that leave the surface and penetrate the underlying connective tissue. - These cells will have the same characteristics as the rest of the epithelial cells but they will be specialised in making some product of secretion. The glands can be classified into two main types: - Exocrine: have ducts that communicate with the epithelial surface and release their secretion products to the external environment. - Endocrine: do not have excretory duct. The secretion will be collected by capillaries and distributed throughout the body. Exocrine glands They can be classified according to several criteria: According to the excretory duct -Simple: they only have one duct -Compound: have more than one duct -Branched: a single duct for several secretory units According to the shape of its secretory part: -Tubular: straight, tube shape -Acinar: sac-shaped -Alveolar: rounded shape Type of secretion Merocrine: they release their secretion products by exocytosis, it is the most used mechanism. For example it is seen in the salivary glands. Helocrine: the secretory cell matures and dies releasing the product of secretion. It occurs for example in the sebaceous glands of the skin. Apocrine: release a small portion of cytoplasm with the secretion product inside. Used for lipid in products. It occurs for example in the lipid fraction of milk. Nature of the secretion Mucosae: secrete muggers that together with water form mucin which is the main component of mucus. Ex:goblet cells. Serous: they secrete enzymes. Ex: exocrine pancreas. Mixed: they contain serous and mucous secretion. Ex: major salivary glands. Connective Tissue Connective tissue It’s a support tissue. It serves as a link between the epithelial, muscular and nervous tissue as well as with other connective tissues to keep the whole body integrated. In addition, blood and lymphatic vessels pass through this tissue, contributing to the nutrition and elimination of waste from all tissues. Therefore, the tissue provides structural support, as well as metabolic. It also intervenes in the defence, protection and repair of the body. It is composed of: -Cells -Extracellular matrix Extracellular matrix The ECM is a complex of macromolecules manufactured and secreted by cells into the space between them. In connective tissue we have a large amount of ECM. The ECM has two main components: -Ground substance -Fibers Ground substance Amorphous gelatinous material constituted by water and three other components: -Glycosaminoglycans (GAG) -Proteoglycans -Structural glycoproteins Glygosaminoglycans (GAG) GAGs are long chains of disaccharides that repeat themselves. Found in the matrix. The sugars that form these GAG are negatively charged, so they attract positive charges such as the Na+ion. Negative charges cause the GAG chains to repel each other, adding viscosity to the matrix and the water content making the matrix very resistant to compression. Proteoglycans: When GAGs bond to a protein they form a molecule called proteoglycan. Hyaluronic acid can bind numerous proteoglycan molecules forming an aggregate. Structure Glycoproteins: Proteins bound to branched polysaccharides. They have binding sites for various components of the ECM. Anchor the epithelia to the matrix (binding to integrins) Fibers They provide tensile strength and elasticity to the tissue. there are two different types off fibers in the connective tissue: -Collagen -Elastin Collagen fibers Inelastic, hard and firm protein It forms fibers that are very resistant to traction. According to its amino acid sequence, at least 35 different types of collagen Structure of collagen fibers The tropocollagen molecules are assembled spontaneously, always in the head-tail direction and in a regular and staggered manner. These assembled molecules form the collagen microfibrils. When several microfibrils are associated they form a fibril of collagen and several fibrils will already form the collagen fiber. The union between the molecules of tropocollagen, requires the presence of vitamin C. If there is a deficit of this vitamin the chains will become unstable chains and will not be added to form the fibers. Collagen types - Type I: it is the most abundant. It is synthesised by fibroblasts and are also osteoblasts. Very resistant to tension forces. Appears in skin, tendons, and ligaments, organ capsules, bone. - Type II: appears only in the cartilage. It is synthesised by chondroblasts and is very resistant to stress. - Type III: also called reticular fibers. It is synthesised by fibroblasts, smooth muscle cells. Forms networks that support very cellular organs or tissues such as the liver, spleen. - Type IV: it is synthesised by epithelial cells, muscle cells and Schwann cells. - Others: at least 35 different types of collagen. They are minors and serve mainly to establish unions between different parts of the matrix Elastic fibers Made of protein called elastin and also fibrillin. They are thin, long and branched fibers. They have elastic properties and provide elasticity to the tissue Elastin biosynthesis The elastic fibers can be synthesized by fibroblasts and also by smooth muscle cells of the vessels. First, fibrillin molecules are created and will form microfibrils. They microfibrils are grouped to form a hollow cylinder where tropoelastin will be deposited. When the molecules of tropoelastin polymerize and bind to fibrillin, form the elastic fiber. Basement membrane with connective tissue Basal lamina: Manufactured by the epithelium. Consists of structural glycoproteins and integrins fractrions that attach to the epithelium. Next there is a mesh of type IV collagen that joins the reticular lamina and will work as a filter for anything that comes from the epithelium to the connective. Reticular lamina: Synthesized by the connective tissue. Formed mostly by reticular fibers (collagen type III) Fix the basal lamina to the connective. Connective tissue cells In the connective tissue we find two types of cells: Fixed Migratory The fixed cells are cells that have developed in the connective tissue, they always remain in it and is where they perform their functions. The fixed cells of the connective tissue are: Fibroblasts Adipocytes Pericytes Mast cells Macrophages Migratory cells Originate mainly in th bone marrow and circulate in the blood. When receiving a stimulus they leave the bloodstream to go to the connective tissue, where they will develop their specific functions. They are short-lived cells that must be replaced constantly. The migratory cells of the connective tissue are: Leukocytes Plasma cells Mesenchymal cells Undifferentiated, pluripotent cells. Irregular shape with cytoplasmic prolongations. They give rise to most of the fixed cells of the connective tissue. They appear mostly in embryonic tissues. They do not exist in adults, but pericytes will have a similar function. Fibroblasts Main cells of the connective tissue, the most abundant ands most widely distributed cells. Derived from mesenchymal cells. Synthesise most of the connective ECM. When inactive they are called fibrocytes and they are smaller and ovoid. Reticular cells Fibroblasts specialised in segregating reticular fibers. Many extensions. They form a network together with the reticular fibers to support very cellular organs. Myofibroblasts Fibroblasts with contractile properties. Appearance very similar to that of fibroblasts. They participate mainly in wound healing. They also appear in the seminiferous tubules of the testicle. Pericytes Pluripotent cells that derive from mesenchymal. Surround the endothelial cells of the capillaries. Under certain stimuli, they can differentiate to another type of cells, especially fibroblasts, endothelial cells and smooth muscle cells. Mast cells The largest fixed cells of the connective. Ovoid shape with a central spherical nucleus. Contain granules in their cytoplasm whose content will be released in the presence of some antigen. Participate in the immune response. Macrophages Some of them behave like fixed cells, but there are also some that behave like transient cells. They are large, irregular shaped cells. They develop in the bone marrow and circulate in the blood as monocytes. When they reach the tissues they evolve into macrophages. They participate in the elimination of cellular waste and in the protection against invading organisms. Leukocytes They are migratory cells of the connective tissue. Are formed in the bone marrow and circulate in the blood, although they often move to the tissues, especially during inflammation. There are different types of leukocytes: -Neutrophils: granulocytes whose granules are not coloured with the usual dyes. Large and with a multilobed nucleus. They phagocytize bacteria. -Eosinophils: granulocytes whose granules are stained with acid dyes. usually bilobed nucleus. They fight parasites by releasing cytotoxins. -Basophils: granulocytes whose granules are stained with basic dyes. Generally bilobed nucleus. Regulate inflammatory processes. -Monocytes: precursors of macrophages. -Lymphocytes: small, rounded cells with a rounded nucleus that occupies most of the cytoplasm. They are involved in viral infections. Plasma cells They are also migratory cells that come from the blood. Derived from B lymphocytes. Rounded cells and eccentric nucleus, abundant cytoplasm. They secrete antibodies. Classification of connective tissue Embryonic: -Mesenchymal: present in the embryo, contains mesenchymal cells and amorphous ground substance. -Mucoid: loose, amorphous connective, with a gelatinous matrix rich in hyaluronic acid. Found within the umbilical cord and under the skin embryos. Adult: -Loose -Dense -Elastic -Reticular -Adipose Loose connective tissue Abundant ground substance and tissue fluid. Some fixed cells and few fibers arranged loosely and disorderly. Easily vascularised and innervated. Located below the epithelia, in the deep layers of the skin. Dense connective tissue Abundant fibers and a few cells. The collagen fibers are grouped into bundles and give a lot of resistance to stress. When the bundles of fibers are arranged in a disordered manner, they form irregular dense connective tissue. Appears in the dermis, the nerve sheaths. Elastic connective tissue Thick bundles of elastic fibers organized in parallel joined by loose connective tissue. Present in blood vessels, yellow ligament of the spine and suspensory. Reticular connective tissue Association of reticular cells with reticular fibers and macrophages. Present in very cellular organs and tissues: liver, spleen and bone marrow. SPECIALIZED CONNECTIVE TISSUE Adipose tissue Is a connective tissue specialized in storing fat. It’s main cells are adipocytes, which can be of two types: -White or unilocular adipose tissue -Brown or multilocular adipose tissue Adipocytes are cells that are derived from mesenchymal cells and participate in the synthesis and storage of triglycerides. White or unilocular adipocyte They are large spherical cells that become polyhedral when they accumulate in adipose tissue. They store fat constantly in the form of a single drop that displaces all the cytoplasmic content. Have hormone receptors in their membranes that will influence the formation of fat. Brown or multilocular adipocyte Are smaller and more polygonal cells than the white ones. The fat is stored in the form of multiple small drops of fat. The nucleus remains rounded in the center of the cell. White adipose tissue: Composed mainly of white adipocytes. Also presents macrophages, mast cells, and lymphocytes. Scarce ECM. Functions Mechanical protection Thermal isolation Organs trophic support Brown adipose tissue: Composed mainly of brown adipocytes Also presents macrophages, mast cells and lymphocytes. Scarce ECM and fibers. Helps maintain body temperature thanks to the number of mitochondria present in these adipocytes. Cartilaginous tissue Specialized connective tissue Main cells are chondrocytes and occupy small cavities in the matrix called lacunae Does not have blood vessels, cells are nourished by diffusion through the matrix Surrounds almost all the cartilage, there is a sheath of connective tissue called perichondrium, consists of two layers: the outer layers is fibrous and the inner layer is cellular. Formation of cartilage During the embryonic development, the mesenchymal stem cells retract their extensions, round off and group together to form chondrification centers. These cells differentiate into chondroblasts that begin to secrete matrix. When completely surrounded by matrix, they become chondrocytes. Chondrocytes still retain the ability to divide and forms groups of several cells within the same lacuna, which are called an isogenic group. The isogenic group will separate forming individual lacunae and thus grow the cartilage from within. This is called interstitial cartilage growth. Interstitial cartilage growth Apositional cartilage growth The mesenchymal cells that surround the cartilage differentiate into fibroblasts that will originate the connective tissue that forms the perichondrium. - The other fibrous layer of the perichondrium is irregular dense connective tissue. The inner chondrogenic layer contains chondroblasts that can add new layers of cartilage making it grow in thickness. This is what is called apositional growth. Cartilage types Type of cartilage based on differences in fiber composition: Hyaline cartilage - type II collagen. Elastic cartilage - elastic fibers and type II collagen Fibrocartilage - type I and II collagen Hyaline cartilage It is the most abundant. Flexible, semi-translucent, bluish gray colour. Precursor of long bones during embryonic development. Elastic cartilage Same composition as the hyaline cartilage, but also contains abundant elastic fibbers in its matrix. More flexible than hyaline cartilage Yellowish Color and more opaque than hyaline cartilage. Fibrocartilage Intermediate structure between cartilage and dense connective tissue. It’s matrix is formed by type I and II collagen and low concentration of water and proteoglycans Great tensile strength Without perichondrium Found in intervertebral discs, tendons and ligaments insertions in the bone Unit 5: Bones Bones Main constituent of the skeleton. It supports soft tissues. Protects vital organs. Serves as support and lever to the muscles and together with them forms the locomotor system, allows body movements. Is a specialized connective tissue made of cells and matrix. Is the hardest substance in the body, is a dynamic tissue that constantly changes shape depending on the forces that act on it The central cavity in the bones is occupied by bone marrow. The external surface is covert by the periosteum, which consists of an outer layer of dense connective tissue and an inner cellular layer containing osteogenic cells and osteoblasts. The medullary cavity is covered by the endosteum, which is a specialized thin connective tissue containing osteogenic and osteoblasts. Bone Matrix Contains both organic and inorganic components and both responsible for bone consistency and hardness. Inorganic component of the matrix Constitutes around 65% of its dry weight. Made up of minerals, mainly calcium and phosphorous, but also small amounts of bicarbonate, citrate, magnesium and sodium. Calcium and phosphorous are found mainly forming hydroxyapatite crystals which are surrounded by an amorphous ground substance. The association of collagen with hydroxyapatite is what gives hardness to the bone. Organic component of the matrix It constitutes approximately 35% of the dry weight of the bone. Consists mainly of type I collagen that will form large beams. If we eliminate this organic part of the matrix, we will only have minerals, the bone will maintain its shape but will be fragile and break easily. Bone cells Osteogenic cells are found in the periosteum and endosteum. Derived from mesenchymal stem cells, they can divide by mitosis and can differentiate into osteoblasts. Have an elongated shape and an oval nucleus. Osteoblasts Come from osteogenic cells and are also located on the surfaces of bones. Make and release the organic components of the matrix. When cell is completely surrounded by matrix, it will stop producing matrix and the cell will become an osteocyte that is enclosed in a space called lacuna. Osteoblasts have Parathormone (PTH) receptors in their membranes, the hormone makes osteoblasts to activate osteoclasts to degrade the bone. Osteocytes Are the mature bone cells, derived from the osteoblasts that were trapped in their lacunae. They are elongated cells that have these extensions who cross the matrix thanks to very thin channels that we know as calcoforous canaliculi. Thanks to them, the osteocytes establish contact with other cells. Inside the canaliculi there is a fluid that will ease the transport of nutrients to the osteocytes. Osteoclasts Are very large, mobile and multinucleated cells that come from precursors in ther bone marrow, are responsible for bone resorption. In the active osteoclasts we distinguish 4 regions: Basal zone: the furthest from the surface of the bone that contains the nuclei and most organelles. Brush border: microvilli oriented towards the bone surface. Part that participates in reabsorption. Clear zone: zone that surrounds the poeriphery of the brush border. Has no organelles, but many filaments of actin that to join the osteoclast to the bone, sealing the area of the brush border. Vesicular zone: between the basal zone and brush border we find numerous vesicles of endocytosis and exocytosis that will transport the materials off the bone resorption. Bone resorption Process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. When PTH stimulates osteoblast , they activate the osteoclasts that migrate to the bone surfaces and then present their 4 zones. The osteoclasts secretes protons into the subosteoclastic space and acidifies the medium. The acid medium dissolves the inorganic components of the matrix. The osteoclast secretes enzymes that will degrade the organic component. Products of the degradation are endocytosed by the osteoclasts, which is released in the bloodstream Ossification Bone formation during the embryonic development can be carried out in two ways: -Intramembranous -Endochondral No matter the case the same bone is obtained and we call it primary bone. Primary bone is re absorbed and replaced by secondary bone, which continues to be re absorbed throughout life but at a slower rate. Intramembranous ossification Most flat bones are formed by this method. Mesenchymal cells differentiate into osteoblasts and begin to secrete bone matrix forming a network of trabeculae. The region where the bone begins to form is called the primary ossification center The osteoblasts that are trapped in the matrix will become osteocytes. Endochondral ossification Look for video on YouTube Bone growth Chondrociytes of the epiphyseal plate proliferate to maintain the chondrocytes population. As long as cartilage remains, the bone may grow in length. At around 20 years of age, this longitudinal growth stops. Bone remodeling During growth, bone development overcomes resorption. Once the required growth is achieved, the rate of formation and resorption are equalised under normal conditions. The internal structure of an adult’s bone varies continuously to adapt to the forces acting on it, such as weight changes and postural changes. Bone remodeling also occurs to maintain calcium homeostasis. Calcium homeostasis 99% of the body’s calcium in the bones. 1% remaining circulating in the plasma, fundamental: -Muscle contraction -Transmission of the nervous impulse -Blood clotting Lack of calcium in blood: parathyroid secretes PTH, stimulates bone resorption releasing calcium into the bloodstream.;] Excess calcium in blood: thyroid secretes calcitonin that inhibits osteoclasts. Morphological classification of bones Long bones Short bones Flat bones Irregular bones Sesamoid bones In all types of bones we can see a denser part on the outer surface that we call compact bone and another more porous area covering the marrow that we call spongy bone. The axis of the long bones is called the diaphysis and the articular ends are the epiphysis. Between them there is the epiphyseal plate. The whole bone is covered by periosteum. Spongy bone Appears mainly in the interior of the flat, short, irregular bones and in the epiphyses of long bones. Made of trabeculae where the matrix contains bundles of collagen fibers in parallel. The spaces between the trabeculae contain the bone marrow. Compact bone Appears on the surfaces of bone sand diaphysis of long bones. Collagen fibers are organised in concentric sheets around a channel that carries vessels and nerves called the Havers channel. Communicating the Havers channels there are other channels called Volkmann’s ducts and with booth duct systems we ensure the blood supply to the entire bone. Bone repair Watch YouTube video Articulations According to the degree of movement Synarthrosis: without movement or with minimal movement. -Synostosis: bone and bone join directly (skull) -Synchondrosis: between the bones there is hyaline cartilage (ribs-sternum) -Syndesmosis: between the bones there is dense conjunctive (tibia-peroneum) Diathrosis: articulate with a wide range of movements. Diathrosis Most limb articulations are of this type and have very different degrees and types of movements. All of them are covered by hyaline cartilage, the articular cartilage. Between them there is a capsule, filled with synovial fluid and sealed in a fibrous layer and a synovial layer. Synovial fluid nourishes chondrocytes of the articular cartilage and also lubricates the joint. Blood Blood Is a dark, viscous and slightly alkaline shiny liquid that circulates within the circulatory system. is a specialized connective tissue composed of blood cels and a liquid matrix, plasma Serves as mode of transport for substances: -Transports nutrients to the digestive system to the whole body. -Transports hormones and other signaling molecules between cells. -Helps regulate body temperature and osmotic balance of tissues. Plasma Is a yellowish liquid in which cells, platelets, organic compounds and electrolytes are dissolved or suspended. Composed 90% by water, 9% proteins and 1% are nutrients and respiratory gases. Erythrocytes (red blood cells) - They have no nucleus or organelles. Have numerous enzymes that will participate in obtaining ATP to cover the energy needs of the erythrocyte. - Have a lifespan of about 120 days. - Have a biconcave disc shape, which gives them a high surface-volume Ratio: provides a large surface to facilitate gas exchange, adaptation to pass through narrow capillaries without breaking Transport of O2 and CO2 - Erythrocytes are full of haemoglobin, gives red color to erythrocytes and blood in general. - In the lungs, where there will be abundant O2, the hemoglobin will bind 4 molecules of O2 forming oxyhemoglobin. - When it reaches tissue, where there is little O2 and abundant CO2, the O2 is released and ther hemoglobin will bind CO2 forming carbaminhemoglobin. Leukocytes (white blood cells) - Are larger than erythrocytes, much less numerous, have nuclei and organelles. - Perform immune function. - These cells are classified into two large groups: Granulocytes cells: present specific granules in their cytoplasm. (Neutrophils(55-70%), Eosinophils (1-4%), Basophils (0.2-1.2%)) Agranulocytes: do not present specific granules. (Monocytes (2-8%) and Lymphocytes (17-45%)) Neutrophils Most numerous leukocytes. Have a multilobed nucleus and specific granules that do not stain with usual dyes. Granules contain enzymes that help the neutrophil in its antibacterial functions. Are attracted by chemotactic substances to the places of infection, where they will bind to selections to leave the blood vessels where they circulate. Once in the tissue,these cells phagocytize bacteria and release hydrolytic enzymes and leukotrienes, which will initiate the inflammatory process. Once bacteria are eliminated, neutrophils die since they little capacity to regenerate its enzymes and lysosomes. The accumulation of leukocytes and dead bacteria with tissue fluid form pus. Eosinophils Have a bilobed nucleus and specific granules that are stained with acid dyes. Histamine, leukotrienes or eosinophil chemotactic factor attract them to the site of the allergic, inflammatory or parasitic infection. Eosinophils degrade antigen-antibody complexes by moderating the inflammatory or allergic response. Basophils Have an S-shaped nucleus that is usually masked by specific granules that are stained with basic dyes, as well as the nucleus. In their membrane they have IgE receptors. In the first exposure to an antigen, IgE specific for that antigen is synthesised and bound to the basophil membrane. In a second exposure, the antigen binds directly to the IgE of the basophil membrane, which will release the content of its granules. An inflammatory response is initiated, neutrophils and eosinophils are attracted, histamine produces vasodilation, increased capillary permeability and heparin makes blood flow better. Monocytes Are the largest blood cells, its nucleus is large, eccentric and kidney-shaped. Remain in the blood fore a few days and then migrate to tissues where they differentiate into macrophages. Lymphocytes Are the smallest leukocytes, are rounded with a round nucleus and scarce cytoplasm There are three types of lymphocytes: T,B and NK (natural killer) cells. T lymphocytes are formed in the Bon marrow, then migrate to the thymus to mature and acquire immune competence. B lymphocytes and NK cells are formed in the bone marrow and go directly to the tissues where they will act. Up on contact with a specific antigen, T and B lymphocytes poliferate and give rise to two populations: -Memory lymphocytes: do not participate in the immune response but remain in the body as memory cells, upon second exposure to that specific antigen, they can generate a response quickly. -Effector cells: those that perform the immune response. Platelets Are the smallest formed elements of the blood. Are disc-shaped fragments of another larger formed in the bone marrow. Have no nucleus, but many granules. The zone of the platelet that is lighter is called hyalomere whereas the central one, that is where granules are, is darker and is called granulomere. There are 3 types of granules in the platelets: -alpha granules: more abundant, they contain fibrinogen, coagulation factors. -dense granules: they contain Ca2+, ATP and ADP. -lambda granules: lysosomes Clotting process Platelets participate in hemostasis, which is a set of physiological processes that aim to prevent extravasating of blood, repair damaged vessels and keep the blood fluid. The endothelium of the vessels secretes prostacyclines, which inhibit platelet aggregation, and thrombomodulin that blocks coagulation. The added platelets form a plug that blocks the bleeding, the coagulation factors will then activate each other in what is known as the coagulation cascade. Whose final step activates fibrinogen giving rise to fibrin, which forms a denser and more stable clot. When the vessel is repaired, the endothelial cells release enzymes that initiate thrombus removal. Hematopoiesis Process of blood cells formation, since all of them have a limited life and must be renewed continuously. Begins in the second week of embryonic development and will first occur in the liver and spleen. After 6 mont of development, when the skeletal system develops, it will occur in the bone marrow. These cells will give rise to multi potential stem cells that will be either common lymphoid progenitors,which give rise to all types of lymphocytes. Or common myeloid progenitors which give rise to erythrocytes, granulocytes, monocytes.