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THE CELL The cell is the basic structural and functional unit of all multicellular organisms, limited to an active cell membrane and consisting of cytoplasm and a nucleus. The cell is open and self reproductive system. The cytoplasm of a cell consists of organelles, inclusions and hyaloplasm. The structure of hyaloplasm includes water, proteins, nucleinic acids, different polysaccharides and a lot of enzymes. PLASMA MEMBRANE OR PLASMALEMMA Each cell is bounded by a cell membrane. The structure of each membrane includes 50-60% proteins, 30-40 % lipids and 5-10% carbohydrates. Cell membrane appears as a trilaminar structure, of two thin, dense lines and light area in the middle. The inner and the outer dense line composed of a single layer of phospholipids, between them settle some proteins. Carbohydrates are present at the surface of the plasma membrane. This layer is referred to as the cell coat or glycocalyx. The plasmalemma and other membranes of a cell carry out some of the important functions: Barrier. Receptor Transport INTERCELLULAR CONNECTIONS 1. Simple contact 2. Zonulae occludentes 3. Zonular adherentes 4. Desmosomes (Maculae adherens) 5. Gap junctions 6. Plasma membrane enfoldings 7. Synapse The cytoplasm contains organelles and inclusions in a cytoplasmic matrix. Organelles constantly present in a cell. Inclusions are changeable ingredients of cytoplasm. Organelles are described as membranous and nonmembranous. The membranous organelles include: -endoplasmic reticulum -mitochondria -Golgi apparatus -lysosomes -peroxisomes 1 The nonmembranous organelles include: -microtubules -filaments (different varieties) -centrioles -ribosomes -cilia -flagella MEMBRANOUS ORGANELLES Endoplasmic reticulum (E. R.) Rough E. R. (rER) Rough E. R. (rER) has ribosomes studding the exterior surface of the membrane. Main functions are: -synthesis of proteins for export from the cell -synthesis of integral proteins of the plasma membrane Smooth E. R. (sER) Smooth E. R. (sER) consists of short anastomosing tubules that are not associated with ribosomes. Main functions are: -detoxification of drugs and conjugation of other noxious substances -metabolism of lipid and glycogen and membrane formation -calcium storage Golgi apparatus Golgi apparatus appears as stacks of flattened membrane limited sacs or cisternae that are closely associated with vesicles. Main functions are: -synthesis of polysaccharides -modification, sorting and packaging of secretory products -concentration and storage of secretory products Lysosomes Lysosomes are spherical, membrane limited vesicles that may contain more than 50 enzymes and function as the cellular digestive system. There are 3 types of lysosomes primary lysosomes are not active secondary lysosomes are active residual body is not active Main functions are: -digestion of extracellular components and of damaged cellular components 2 Peroxisomes (microbodies) Peroxisomes are small membrane-limited spherical bodies that contain oxidative enzymes. Main functions are: -the β oxidation of fatty acids -break down hydrogen peroxide Mitochondria Mitochondria generate the cell’s energy. Each mitochondria is bounded by two unit membranes. The intracristal space contains the mitochondrial matrix. It contains water, solutes, circular DNA and mitochondrial ribosomes. Main functions are: -provide energy for chemical and mechanical work by storing energy generated from cellular metabolites in the high energy bonds of ATP. NON-MEMBRANOUS ORGANELLES Ribosomes and Polyribosomes (Polysomes) Each ribosome is assembled from two ribonucleoprotein subunits, a large and small one. Two types of ribosomes are detected: Free ribosomes Attached ribosomes (form the outer surface of rER) Main functions are: Ribosomes take part in the process of protein synthesis. Microtubules Microtubules are elements of the cytoskeleton and of specialized structures involved in subcellular movements. Microtubules are elongated polymeric structures made up of equal parts of α tubulin and β tubulin. Main functions are: 1. Cell elongation and movement 2. Intracellular transport of secretory granules 3. Movement of chromosomes during mitosis and meiosis 4. Maintenance of cell shape 5. Beating of cilia and flagella Cilia and flagella Cilia and flagella are motile processes with a highly organized microtubule core. This core consists of nine pairs of microtubules surrounding two central tubules. This sheaf of tubules, possessing the characteristic (9×2) +2 pattern is called an axoneme. At the base of each cilium of flagellum is a basal body. 3 Centrioles The formula of centrioles is (9×3) +0. It means 9 pares of microtubules in the periphery and 0 in the center. Each rod-shaped centriole is about 0,2 nm long and consists of nine triplets of microtubules that are oriented parallel to long axis of the organelle. The three microtubules are fused to one another, with adjacent microtubules sharing a common wall. Centrioles and adjacent dense material (centriolar satellites) constitute a general microtubule organizing center in both interphase and mitosis. Filaments There are two basic types of filaments: -microfilaments -intermediate filaments Microfilaments are the thinnest cytoskeletal elements and are more flexible than microtubules. There are two types of microfilaments (myofilaments) present in muscle cells: - microfilaments (thin filaments) of actin - microfilaments (thick filaments) of myosin Actin microfilaments are present in virtually all cell types. Actin filaments are often grouped as bundles close to the plasma membrane. Main functions are: -anchorage and movement of membrane protein -movement of plasma membrane (as in endocytosis, exocytosis and cytokinesis) -formation of the structural core of microvilli on absorptive cells -extension of cell processes -locomotion of cells -contraction in all cells involves interactions of actin and myosin. Intermediate filaments are heterogeneous group of 8-10 nm. Cytoskeletal elements are found in various cell types -cytokeratin -vimentin -desmin -neurofilaments -glial fibrillary acidic protein INCLUSIONS 1. Trophic inclusions are lipids, carbohydrates, glycogen, and proteins. 2. Pigment can be divided into endogenic (melanin, bilirubin) and exogenous. 3. Secretory inclusions are products of life activity of the cells necessary for an organism for example gastric juice. 4. Excretory inclusions are products of life activity of the cells, which should be removed from the cell. 4 NUCLEUS The nucleus is a membrane-limited compartment that contains the genome (genetic information) in eukaryotic cells. The nucleus consists of the following components: chromatin, organized as euchromatin and heterochromatin nucleolus (or nucleoli) -membranous nuclear envelope nucleoplasm Chromatin Chromatin is a complex of DNA, RNA and proteins. There are 2 types of chromatin heterochromatin is densely staining material which is highly condensed and nonactive euchromatin is lightly staining material which is dispersed and active Karyotypes are chromosome pairs sorted according to their morphology. In females, only X chromosome (either of the two) is used by each cell, the inactive X is often visible as a clump of heterochromatin, termed sex chromatin, or the Barr body can be used to identify the sex of a fetus. Nucleolus The nucleolus is the site of ribosomal RNA synthesis and initial ribosomal assembly. The nucleolus is a nonmembranous, intranuclear structure formed by filamentous and granular material. Nucleoplasm Nucleoplasm is the material enclosed by the nuclear envelope exclusive of the chromatin and the nucleolus. Nuclear envelope The nuclear envelope formed by two unit membranes with a perinuclear cisternal space between them serves as a membranous boundary between the nucleoplasm and the cytoplasm of the cell. The nuclear envelope has an array of perforation called nuclear pores. CELL CYCLE The reproduction cycle of a cell is termed the cell cycle. Cell cycle may be described that two principal phases mitosis and interphase. Interphase 1. G1 phase (presynthesis) of interphase is usually a period of cell growth and may last only a few hours in a rapidly dividing cell or may last a lifetime in a nondividing cell. 2. During the S (synthesis) phase DNA of the cell is doubled. The centrioles often self-duplicate during this stage. 5 3. During G2 phase (postsynthesis) the final preparations for cell division occur; these include repair of damaged DNA, synthesis of tubulin for the spindle apparatus and ATP accumulation for the energy-expensive mitosis. Mitosis Mitosis follows the G2 phase and consists of four phases: prophase metaphase anaphase telophase Mitosis is a cell division process that produces two daughter cells with the same chromosome number and DNA content as the original cell. The daughter cells are 2n in DNA content and 2n in chromosome number. 6 EMBRYOLOGY The embryology is a science, which studies lows of formation of an embryos and process of his development. The individual development of living organisms is an ontogenesis. In individual development are two basic stages: 1. Prenatal ontogenesis is development till birth 2. Postnatal ontogenesis is development from birth up to death of an individual Main stages of prenatal period: 1. Fertilization is fusion of a female and male gamete. 2. Cleavage is the series of rapid cell divisions of the zygote with the formation of blastula 3. Gastrulation is the formative process by which the three germ embryonic layers are established in embryos (ectoderm, mesoderm and endoderm). 4. Histogenesis-development of tissues 5. Organogenesis development of organs 6. Systemogenesis development of systems Two types of sex cells are distinguished: 1. Male cell is spermatozoon or sperm 2. Female cell is ovum or ovocyte The spermatozoon The spermatozoon (spermatozoid) is a man’s gamete which produced in testis. The spermatozoid consists of 3 main components: the head (includes nucleus and the acrosomal cap which surrounds the anterior two-thirds of it) the neck (includes two centrioles) the tail (includes axoneme and mitochondrias) The tail is subdivided into: the middle piece the principal piece the end piece Ovums or ovocytes Ovums or ovocytes are formed in female sex glands ovaries during an ovogenesis. They have: a round form volume of cytoplasm and nucleus larger than spermatozoons cortical granules in the periphery of cytoplasm do not have the ability to move actively protein-lipid inclusion of yolk in the cytoplasm primary coated by ovolemme or an initial envelope 7 secondary coated by jelly-like zona pellucida finally coated by corona radiata The human ovocyte is secondary olygolecithal, what means that the amount of a yolk in cytoplasm little, and isolecithal what means that yolk distributed evenly on cytoplasm. FERTILIZATION The fertilization represents penetration of a spermatozoon into an ovum as a result of which it is restored number of chromosomes and the single-celled embryo a zygote is formed. The fertilization consists of 3 phases: In the first distant phase the spermatozoon goes towards to an ovum due to a rheotaxis and chemotaxis. 1. The rheotaxis is spermatozoons locomotion against a current of fluid. 2. Chemotaxis is ability of spermatozoons to move in a direction of the chemicals secreted by an ovum. 3. Capacitation is activation of spermatozoons. The proteins of seed fluid leave from its surface. Capacitation lasts for the man 7 hours. The second phase of fertilization (contact of gametes) begins when a lot of spermatozoons surround ovum. 1. Penetration of corona radiata The sperm uses both chemical and physical means to penetrate the egg’s corona radiate. 2. Penetration of zona pellucida Once inside the corona radiata, the sperm binds to the species-specific receptor on the egg’s glycoprotein coat. 3. Acrosomal reaction The acrosomal reaction is releasing of enzymes stored in the sperm’s acrosome. These enzymes help the sperm “drill through” the zona pellucida. The third phase of fertilization begins by infiltration of sperm cell in an ovum and gametic syngamy. 1. Cortical reaction prevents polyspermy. Cortical granules move to a surface of a plasmatic membrane and their contents secretes in the space environmental ovum. 2. Fusion of pronuclei. In ovoplasma the spermatozoon head turns on 180 degrees, approximated and turns in male pronucleus. The ovum nucleus turns in female pronucleus. The male and female pronuclei fuse and make a synkaryon. The fertilized egg is called zygote (“together”). 8 CLEAVAGE The zygote undergoes a number of ordinary mitotic divisions that increase the number of cells in the zygote but not its overall size. Each cycle of division takes about 24 hours. The individual cells are known as blastomeres. At the 32-cell stage the embryo is known as a morula, a solid ball consisting of an inner cell mass and an outer cell mass. a) the inner cell mass will become the embryo and fetus b) the outer cell mass will become part of the placenta Blastocyst formation a) Compaction b) Cavitation (formation of the fluid-filled cavity inside the morula) Human cleavage is called: complete asynchronous nearly equal HUMAN IMPLANTATION Implantation is the process of attachment and embedding of the blactocyste into the mucosa layer or endometrium of uterus. Implantation includes two stages: adhesion invasion GASTRULATION Gastrulation is the formative process by which the three germ embryonic layers are established in embryos (ectoderm, mesoderm and endoderm). Human gastrulation includes two main processes: 1. Delamination, which establishes bilaminar disk composed of two layers, the epiblast and hypoblast 2. Migration, which establishes three-laminar embryonic composed of ectoderm, mesoderm and endoderm. These three layers give rise to all tissues and organs of the adult. Gastrulation begins in the same time as implantation. DERIVATIONS OF THE ECTODERM I. Surface ectoderm Give rise to: -Epidermis and its appendages -Enamel of teeth -Lens of eye -Internal ear 9 II. Neural crests Give rise to -Ganglion cells -Pigment cells III. Neural tube DERIVATIONS OF THE MESODERM I. PARAXIAL MESODERM give rise to: Sclerotome gives rise to skeleton (vertebral column) except cranium. Myotome gives rise to striated skeletal muscle (trunk limbs), muscles of head. Dermatome gives rise to dermis and subcutaneous tissue of the skin. II. INTERMEDIARE MESODERM give rise to: Urinary system (pronephros, including ducts. Gonads and accessory glands. mesonephros, metanephros,) III. LATERAL PLATE of MESODERM give rise to: Serous membranes of pleura, pericardium, and peritoneum. Suprarenal gland cortex. Germinal epithelium of gonads. Myocardium, endocardium of heart. e) Connective tissue and muscle of viscera . IV. HEAD MESODERM give rise to: Cranium. Dentin. Connective tissue of head. DERIVATIONS OF THE ENDODERM I. ENDODERM of the GUT give rise to: Epithelium lining gastrointestinal tract (stomach, small intestine, most part of large intestine except caudal portion of rectum). The parenchyma of liver and pancreas. Epithelium lining respiratory tract The reticular stroma of thymus 10 FETAL MEMBRANES Fetal membranes are provisory organs of embryo and fetus, which provide the normal human development during prenatal period. The formations of these fetal membranes take place about during second week Types of fetal membranes: 1. yolk sac 2. allantois 3. amnion 4. chorion 5. placenta 6. umbilical cord YOLK SAC Functions: 1. It functions as primary hemopoietic organ. 2. Yolk sac endoderm is origin for primordial germ cells, which then migrate to the primitive sex cords. 3. Roof of the yolk sac gives rise for the primitive gut. ALLANTOIS Functions: 1. Blood formations occur in its wall. The allantois vessels form the umbilical vessels. 2. Formation of the urachus, which after the birth becomes median umbilical ligament AMNION Functions: 1. The epithelium of an amnion in a region of a placental disk has secretor function. 2. The basic function of epithelium of an extraplacental amnion is resorption of amniotic fluid. AMNIOTIC FLUID Functions: 1. Protective cushion. 2. The fluid absorbs jolts 3. Prevents the adherence of the embryo to the amnion. 4. Allows fetal movements. 5. Amniotic fluid acts as a barrier to infection and contains antibodies. 6. Provides homeostasis of fluid and electrolytes. 7. Assists in the regulation of the fetal body temperature. 11 PLACENTA Placenta is a temporary organ whose formation begins during implantation. It has both embryonic (chorion frondosum or pars fetalis) and maternal (decidua basalis or pars materna) components. Human placenta is hemochorioidal discoidal villous. Functions: 1. Site of the exchange of nutritious substances, waste, gases and electrolytes between maternal and fetal blood. 2. Transmission of the maternal antibodies. 3. Regulation of the myometrium contraction. 4. Production of the hormones (temporary endocrine organ). 5. Placenta has placental barrier which prevents passing of some substances through it. UMBILICAL CORD Functions: 1. The umbilical arteries carry poorly oxygenated blood from embryo to the placenta. 2. The umbilical vein carries well-oxygenated blood from placenta to the embryo. 12 TISSUES Tissues may be defined as aggregates or groups of cells organized to perform one or more functions. There are 4 basic or fundamental tissues: Epithelial tissue (epithelium), which covers body surfaces, lines body cavities, and forms glands Connective tissue, which underlies or surrounds and supports the other three basic tissues, both structurally and functionally Muscular tissue, which is made up of contractile cells and is responsible for movement of the body and its parts Nervous tissue, which gathers, transmits, and integrates information from outside and inside the body to control the activities of the body and its parts EPITHELIAL TISSUE Epithelium- covers body surfaces, lines body cavities and constitutes glands. The cells that make up an epithelium have some principal characteristics. 1. They are closely apposed and adhere to one another by means of special junctions. 2. Epithelium is an avascular tissue. 3. Food and oxygen come into epithelium via diffusion through the basal lamina from underlying connective tissue. 4. Epithelial cells have a polarity (structural and functional asymmetry). 5. Their basal surface is attached to an underlying basement membrane. 6. Epithelia are continuously replaced and renewed. 7. Epithelium creates a selective barrier between the external environment and the underlying connective tissue. CLASSIFICATION OF EPITHELIUM Epithelium is classified by cell arrangement and cell shape not by function. Classification of epithelium is based on the combination of the number of the surface cells. Thus, epithelium is described as: 1. 2. 3. 4. Simple squamous endothelium mesothelium cuboidal columnar pseudostratified 1. 2. 3. 4. Stratified squamous keratinized non keratinized cuboidal columnar transitional 13 GLANDS Glands are composed of epithelial cells specialized to synthesize and secrete a specific product. CLASSIFICATION OF THE GLANDS: Exocrine glands secrete their products into a surface or Endocrine glands body cavities through ducts or tubes. don’t have a duct system. They secrete Exocrine glands are classified as: their products (hormones) into the bloodstream. Multicellular glands are composed Unicellular glands consist of of more than one cell and exhibit single secretory varying degrees of complexity. cell distributed Multicellular glands are classified among other cells as: that are not Compound glands secretory (goblet Simple glands have have branching cell). nonducts branching ducts Simple gland can be branched (two or more secretory portions) or non branched (single secretory portion). Compound glands are always branched. According to the shape of the secretory portion glands can be: tubular alveolar or acinar tubuloalveolar or mixed CLASSIFICATION ACCORDING NATURE OF SECRETION Mucous glands secrete mucinogens, large proteins. Serous glands secrete an enzyme-rich watery fluid. Mixed glands contain acini that produce mucous secretions as well as acini that produce serous secretions. ACCORDING TO THE MODE OF SECRETION: In other words, according to how the secretory cells release their secretion. A) Merocrine glands; Nearly, all exocrine glands are of this type. B) Holocrine glands; A good example of this type is the sebaceous gland of the skin. C) Apocrine glands: Mammary glands and the special types of sweat glands are examples. 14 Blood Blood is a fluid connective tissue. Blood consists of formed elements (cells) and plasma. Functions of a blood 1. Convey nutrients and oxygen to cells. 2. Carry wastes and carbon dioxide away from the cells. 3. Carry hormones and other regulatory agents to and from the cells and tissues of the body. 4. Have a major homeostatic role based on its thermoregulatory and buffering capacity 5. Transport humoral agents and cells that protect the body from infections, foreign proteins and transformed cells, i.e. cancer cells. Plasma Plasma is the liquid intercellular material or matrix. The relative volume of cells and plasma is about 45% and 55%, respectively. This value is called a hematocrit. Plasma consists of 91-92% of water, 7-8% of proteins (fibrinogens, globulins and albumin) and 1-2% of other solutes. The formed elements of blood include. 1. Red blood cells, also called erythrocytes. 2. White blood cells, also called leucocytes 3. Platelets. Red blood cells Erythrocytes, which are anucleate, are packed with the 02 carrying protein hemoglobin (Hb). The normal number of the erythrocytes: for the women is 3,7-4,9×1012/L for the men is 3,9-5,5×1012/L. Poikylocytosis is different shapes of the erythrocytes. There are 2 types of it. Physiological poikylocytosis is when 80% of red blood cells have shape as biconcave disk and 20% other shape. Pathological poikylocytosis is when more than 20% of erythrocytes have other shape. Anisocytosis is different sizes of the erythrocytes. Erythrocytes with diameters greater than 9 μm are called macrocytes, and those with diameters less than 6 μm are called microcytes and with diameter from 7 to 8 μm are called normocytes. A decreased number of erythrocytes in the blood are usually associated with anemia. An increased number of erythrocytes are called erythrocytosis. Erythrocytes are surrounded by a plasmalemma. Erythrocytes contain in their interiors about 33% of hemoglobin, the 02 carrying protein. Main functions are: -the transport of oxygen from the lungs to the tissues of the body -the transport of carbon dioxide from the tissues of the body to the lungs 15 White blood cells Classification Granulocytes Agranulocytes neutrophils eosinophils basophils lymphocytes monocytes 47-72% 0,5-5% 0-1% 19-37% 3-11% segmented banded T B Null (segs) (bands) 90% 55% 1-6% 47-72% 10% The increased number of leucocytes is called leucocytosis. The decreased number of leucocytes is called leucopenia. Granulocytes have two types of granules: specific and azurophilic granules. Agranulocytes do not have specific granules, but they do contain various numbers of azurophilic granules (lysosomes). Neutrophils Neutrophils are so called because of its ability of staining with acidic and basic dyes. The mature neutrophil has three to five lobes of nuclear material joined by thinner nuclear strands. Specific granules are small and most numerous. Example is alkaline phosphatases. In the female, few neutrophils can be seen containing the inactive X chromosome (Bar body) appearing as a drumstick-shaped nuclear appendage. Main functions are: Neutrophils constitute a defense against invasion by microorganisms, especially bacteria. They are active phagocytes of small particles (bacteria). Eosinophils The cell contains a characteristic bilobed nucleus. Eosinophilic specific granules contain histaminases and other hydrolytic enzymes. Main functions are: eosinophils play an important role in the control of local responses in allergic reactions their specific granules contain many enzymes that degrade chemical mediators released by mast cells in association with hypersensitivity reactions eosinophils are thought to play an important role in the defense against certain types of parasites Basophils The nucleus is divided into irregular lobes, but the division usually obscured by the overlying specific granules. Basophilic specific granules contain heparin and histamine. Histamine increases the permeability of the capillaries to white blood cells to allow them to engage pathogens in the infected tissues. 16 Histamine brings on the dilation of small blood vessels. Main functions are: basophils may supplement the function of mast cells in immediate hypersensitivity reactions by migrating into connective tissues basophils have also a very weak phagocytic activity Lymphocytes Lymphocytes are the main functional cells of the lymphatic or immune system. T lymphocytes are T cells, thymus-dependent lymphocytes. T lymphocytes have a long life span, and are involved in cell-mediated immunity. B lymphocytes have variable life spans and are involved in the humoral immunity in the production of the several varieties of circulating antibodies. -B lymphocytes after contact with antigen differentiate into plasma cells which produce antibodies. A null cell is a large lymphocyte without surface markers or membrane-associated proteins from B lymphocytes or a T lymphocytes. -T lymphocytes differentiate into -killer T lymphocytes, -helper T lymphocytes -suppressor T lymphocytes -some B and T cells serve as long lived memory cells, circulating lymphocytes that are primed to respond more rapidly. Main functions are: Lymphocytes are the key cells in the immune system. They recognize foreign antigen and react immunologically to them. Monocytes Monocytes are bone marrow derived agranulocytes. The nucleus is oval, horseshoe- or kidney-shaped. The cytoplasm of the monocyte is basophilic. Main functions are: -monocytes are highly phagocytic cells, but not in the blood stream -they leave vessels and go the connective tissue, transform there into macrophages and take place in the phagocytosis of bacteria Platelets Blood platelets (thrombocytes) are nonnucleated, disk-like cell fragments 2-4 μm in diameter. They range in number from 180-320xl09/L of blood. Platelets derive from large cells in the bone marrow, called megakaryocytes. Human platelets have a life span of about 10 days. Each platelet has a peripheral light blue-stained transparent zone, the hyalomere and a central zone containing purple granules, called the granulomere. Platelet functions: 1. Primary aggregation 17 2. Secondary aggregation. 3. Blood coagulation 4. Clot retraction. 5. Clot removal. Hematopoiesis Mature blood cells have a short life span, and consequently the population must be continuously replaced with the progeny of stem cells, produced in the hematopoietic organs. In the adult, red blood cells, granulocytes, monocytes and platelets are formed both in the red bone marrow, lymphocytes are formed both in the marrow and in the lymphatic tissues. Hematopoiesis in embryonic and fetal life The first phase of hematopoiesis occurs in “blood islands” in the wall of the yolk sac. In the second or hepatic phase, hemopoietic centers appear in the liver and lymphatic tissues. The third phase involves the bone marrow (and other lymphatic tissues). After birth, hemopoiesis occurs in the red bone marrow and in lymphatic tissues as in adult. Pluripotential hematopoietic stem cells It is believed that all blood cells arise from a single type of stem cell in the bone marrow. Because this cell can produce all blood cell types, it is called a pluripotential stem cell. These cells proliferate and form one cell lineage that will become lymphocytes (lymphoid cell) and another lineage that will form the myeloid cells that develop in bone marrow (granulocytes, monocytes, erythrocytes and megakaryocytes). These unipotential or bipotential progenitor cells generate precursor cell (blasts). 18 Connective tissue Connective tissue consists of cells and an extracellular matrix that includes extracellular fibers, ground substance and tissue fluid. Classification of connective tissue Classification is based on the composition and organization of the cellular and extracellular components and on special functions. Connective tissue proper -loose connective tissue -dense connective tissue dense irregular connective tissue (examples: tendons, ligaments, aponeuroses) Specialized connective tissue -adipose tissue -blood -bone dense regular connective -cartilage tissue (example: -lymphatic tissue derma of the skin) -hemopoietic tissue Embryonic connective tissue Mesenchyme Mucous connective tissue Connective tissue (C.T.) with special properties 1. Reticular С.Т.: In this type of С.Т., the reticular fibers are dominating. It is formed of branching and anastomosing network of reticular fibers and reticular cells. Location in the body: reticular tissue serves as the stroma for hemopoietic tissue (red bone marrow) and lymphatic organs (spleen, lymph node). 2. Mucoid С.Т.: It is a type of C.T. proper in which the mucoid amorphous component of the intercellular substance is dominating, with mucoid cells and some few collagenous fibers. Location in the body: in Wharton’s jelly of the umbilical cord and bulb of the tooth. 3. Pigmented С.Т.: It is a type of C.T. proper in which the pigment cells are dominating. Location in the body: in the uveal tract of the eye ball (the choroid, the ciliary body and iris). 19 4. Adipose C.T.: It is a type of C.T. proper, in which the fat cells are dominating. There are two types of adipose C.T. a) White adipose С.Т. which is characterized by containing unilocular adipose cells. Functions: energy storage, insulation of heat, supportive pads of fat for other organs and gives the body its characteristic contour Location in the body: subcutaneous adipose C.T., mammary glands of the adult females. b) Brown adipose C.T. which is characterized by containing multilocular adipose cells. Functions: thermoregulation Location in the body: the mediastinum, perinephric fat and around the aorta. Connective tissue fibers Each of the fiber types is produced by the fibroblast and is composed of protein formed by long peptide chains. There are 3 types of fibers: -collagen fibers -reticular fibers -elastic fibers Collagen fibers Collagen fibers are the most numerous fibers in connective tissue. Characteristic of collagen fibers: 1. Fresh collagen fibers are colorless strands. 2. Collagen fibers are inelastic 3. Collagen fibers have a tensile strength greater than that of steel. 4. Collagen fibers consist of closely packed thick fibrils, the collagen fibrils. 5. The collagen fibrils consist of tropocollagen. 6. Collagen fibers lie parallel to each other, forming collagen bundles. Reticular fibers Characteristic of reticular fibers: 1. Reticular fibers consist of collagen fibrils. 2. Fibrils do not bundle to form thick fibers. 3. The reticular fiber is composed of type III collagen. 4. The reticular fiber has a thread-like appearance. 5. Reticular fibers are arranged in a mesh-like pattern or network. 20 Elastic fibers Characteristic of elastic fibers: 1. Elastic fibers are typically thinner than collagen fibers. 2. Elastic fibers are arranged in a branching pattern to form a three dimensional network. 3. Elastic fibers provide tissues with the ability to respond to stretch and distension. 4. Elastic fibers are composed of two structural components, elastin and microfibrils. 5. In mature fibers, the microfibrils are located with elastic fiber and at the periphery of the fiber. Ground substance Ground substance is the component that occupies the space between the cells and fibers. Ground substance is a viscous, clear substance that has a slippery feel. It has high water content and consists largely of proteoglycans and hyaluronic acid. Function: Permit diffusion of oxygen and nutrients between the microvasculature and adjacent tissues. Connective tissue cells The types of cells found in loose connective tissue as well as their relative numbers reflect the tissues functional activity. Connective tissue cells can be categorized as: -fibroblasts -the myofibroblasts -macrophages -adipose cells -mast cells -plasma cells -pericytes -undifferentiated mesenchymal cells Fibroblasts The fibroblasts are the principal and most common cells in connective tissue. Active cell is called fibroblast. Quiescent cell is called fibrocyte. Fibroblast contains rough endoplasmic reticulum, which synthesis procolagen and elastin, and Golgi complex, which synthesis GAG (glycosaminoglycan) of the intercellular ground substance. The fibrocyte has an acidophilic cytoplasm with a small amount of rough endoplasmic reticulum. 21 Functions: Fibroblasts are responsible for the synthesis of fibers and intercellular ground substance. Myofibroblasts The myofibroblast displays properties of both fibroblast and smooth muscle cell. These cells have the morphologic characteristics of fibroblasts but contain increased amounts of actin microfilaments and myosin. Function: Their activity is responsible for wound closure after tissue injury, a process called wound contraction. Macrophages Macrophages are phagocytic cells derived from connective tissue macrophages, also known as tissue histiocytes; contain a large Golgi, rough and smooth endoplasmic reticulum, mitochondria, secretory vesicles and lysosomes. Functions: phagocytosis in immune reactions presenting lymphocytes with concentrated antigens Mast cells Mast cells are oval to round connective tissue cells, whose cytoplasm is filled with basophilic granules. Mast cell granules include four substances: -histamine -slow reacting substance of anaphylaxis (SRS-A) -eosinophil chemotactic factor of anaphylaxis (ECF-A) -heparin Functions: Histamine and SRS-A increase the permeability of small blood vessels thereby causing edema in the surrounding tissue. Heparin is an anticoagulant. The secretions of mast cell granules can result in immediate hypersensivity reactions, allergy and anaphylaxis. The ECF-A stimulates eosinophils to migrate to the sites where mast cells have released their agents and counteract the effects of the histamine and SRS-A. Adipose cells The adipose cell is a connective tissue cell specialized to store neutral fat. When they accumulate in very large numbers, they are called adipose tissue. Plasma cells Plasma cells are antibody-producing cells derived from B lymphocytes. Their average life is 10-20 days. Plasma cells are large, ovoid cells. The cytoplasm displays strong basophilia due to the presence of an extensive rough endoplasmic reticulum. 22 Pericytes The pericytes is a cell that serves as an undifferentiated mesenchymal cell. Pericytes, also called adventitial cells and perivascular cells, are found around capillaries and venules. Cartilage Cartilage is a form of connective tissue composed of cells called chondrocytes and a highly specialized extracellular matrix, composed of fibers and ground substance. Characteristic of the cartilage: avascular have lacunae (matrix cavities in which are located chondrocytes) have perichondrium (sheath of dense connective tissue that surrounds cartilage in most places) 80% of cartilage consists of water 10-15% of organic substances 5-8% of nonorganic salts. There are three different kinds of cartilage: -hyaline cartilage, characterized by a homogeneous amorphous matrix -elastic cartilage whose matrix contains elastic fibers and elastic lamellae -fibro cartilage, whose matrix contains large bundles of type I collagen Hyaline cartilage Location in the body: in the articular surfaces of the movable joints, in the walls of larger respiratory passages (nose, larynx, trachea, bronchi) in the ventral ends of ribs, where they articulate with sternum in the epiphyseal plate Characteristic of the cartilage The matrix consists of two components: collagen fibrils and ground substance Hyaline cartilage matrix does calcify Water constitute from 60% to 78% of the net weight of hyaline cartilage 40% of the dry weight of hyaline cartilage consists of collagen embedded in a gel of proteoglycans and structural glycoproteins. The ground substance of hyaline cartilage contains three kinds of glycosaminoglycans 23 The cartilage matrix which surrounding each chondrocyte is called the territorial or capsular matrix The cartilage matrix which located between the capsules is called the interterritorial matrix Except in the articular cartilage of joints, all hyaline cartilage is covered by perichondrium Groups of eight chondrocytes originating from mitotic divisions of a single chondrocyte are called isogenous. Chondrocytes fill the lacunae completely Elastic cartilage Location in the body: in the external ear in the walls of the external auditory canal the auditory (Eustachian) tube in the epiglottis in the larynx Characteristic of the cartilage Possesses a perichondrium The matrix of elastic cartilage does not calcify Contains elastic fibers in addition to collagen type II fibrils Fibro cartilage Location in the body: in the intervertebral discs the symphysis pubis the articular discs of the sternoclavicular the articular discs of temporomandibular joints the meniscus of the knee joint certain places where tendons attach to bones Characteristic of the cartilage Consists of chondrocytes and their territorial matrix in combination with dense connective tissue The chondrocytes are very often arranged in long rows There is no identifiable perichondrium in fibro cartilage 24 Bone Bone is a connective tissue characterized by a mineralized matrix. Characteristic of the bone Bone consists of extracellular matrix and three cell types: osteocytes, osteoblasts and osteoclasts Bone matrix consists of type I collagen and ground substance containing proteoglycans and noncollagenous glycoproteins The association of hydroapatite with collagen fibers is responsible for the hardness and resistance of bone tissue Within the bone matrix are spaces called lacunae, each of which contains a bone cell, the osteocyte The osteocyte extends numerous processes into little tunnels called canaliculi Bone cells Osteoblasts Characteristic: Cuboidal or polygonal shape The cytoplasm of contains an abundant rough endoplasmic reticulum, Golgi complex and free ribosomes Some osteoblasts are gradually surrounded by newly formed matrix and become osteocytes Functions: Synthesis of the unmineralized bone matrix Calcification of the matrix Osteocytes Characteristic: The osteocyte, the mature bone cell, is enclosed by bone matrix Each osteocyte occupies a space or lacunae Shape of the cells is lenticular The osteocytes contact, by means of gap junctions, processes of neighboring cells Function: Osteocytes are responsible for maintaining the bone matrix. Osteoclast Characteristic: It is large multinucleated cell The cytoplasm contains numerous mitochondria and lysosomes, Golgi complex and rough endoplasmic reticulum There are 2 parts of the cell which are directly in contact with the bone: 25 a central region called the ruffled border a ring like perimeter of cytoplasm, the clear zone (demarcates the limits of the bone area being resorbed) Function: Bone resorption Organic components of the bone matrix is digested by collagenase Non organic components of the bone matrix is dissolved by carbonic acid Classification of bone tissue compact (dense) spongy (cancellous) General structure of bones The fibrous connective tissue capsule, which covers the outer surface of the bone, is called the periosteum. Bone cavities are lined by endosteum a layer of connective tissue cells containing osteoprogenitor cells, which differentiate into osteoblasts. Mature bone is composed of structural and functional units called osteons (haversian systems). The Haversian canals communicate with the marrow cavity, the periosteum, and one another through transverse or oblique Volkmann’s canals. The osteon consist of concentric lamellae of bone matrix surrounding a central canal, the osteonal canal (Haversian canal) that contains the vascular and nerve supply of the osteon. Inner circumferential lamellae are located around the marrow cavity Outer circumferential lamellae are located beneath the periosteum. Between the two circumferential systems are numerous haversian systems, including parallel lamellae called interstitial lamellae. HISTOGENESIS AND GROWTH OF HYALINE CARTILAGE Formation of the cartilage Cartilage arises from mesenchyme. I. In areas where cartilage develops, excluding the head, mesenchymal cells aggregate and form a mass of rounded, closely apposed cells, which begin to secrete cartilage matrix and are then referred to as chondroblasts. II. When they have become completely surrounded by matrix material, the cells are then called chondrocytes. III. During this process the mesenchymal tissue immediately surrounding the chondrogenic blastema gives rise to perichondrium. 26 Cartilage is capable of two kinds of growth, appositional and interstitial. Appositional growth, the process that forms new cartilage at the surface of preexisting cartilage (from the inner portion of the surrounding perichondrium) Interstitial growth, the process that forms new cartilage within the cartilage mass (from division of chondrocytes within their lacunae) Hyaline cartilage when calcified is generally replaced by bone. Bone formation The Development of a Bone Is Traditionally Classified as Endochondral or Intramembranous In intramembranous ossification, bone is formed by differentiation of mesenchymal cells into osteoblasts. Endochondral ossification, also, begins with the proliferation and aggregation of mesenchymal cells at the site of the future bone. However, the mesenchymal cells differentiate into chondroblasts that, in turn, produce cartilage matrix. The bones of the extremities and those parts of the axial skeleton that bear weight (e.g., vertebrae) develop by endochondral ossification. The flat bones of the skull and face, the mandible, and the clavicle develop by intramembranous ossification. Growth of Endochondral Bone Endochondral bone growth begins in the second trimester of fetal life and continues into early adulthood. The continued growth of long bones is dependent on the presence of epiphyseal cartilage throughout the growth period. 27 Muscle tissue Muscle tissue is responsible for movements of the body and for changes in the size and shape of its internal organs. Classification of muscle tissue Striated muscle a. skeletal muscle b. visceral striated c. cardiac muscle Smooth muscle Skeletal muscle Skeletal muscle tissue is the major muscle component of the body. In a skeletal muscle, each muscle cell, more commonly called a muscle fiber, consists of a multinucleated syncytium. Plasma membrane of the muscle fiber is called the sarcolemma. A skeletal muscle consists of striated muscle fibers held together by connective tissue. Endomysium is the delicate layer of reticular fibers that immediately surrounds individual muscle fibers. Perimysium is a thicker connective tissue layer that surrounds a group of fibers to form a bundle or fascicle. Epimysium is the sheath of dense connective tissue that surrounds the collection of fascicles that constitute the muscle. Skeletal muscle fibers There are 3 types of the skeletal muscle fibers. I. Red fibers are small fibers with large amounts of myoglobin (an oxygenbinding protein that closely resembles hemoglobin) and cytochromes and many mitochondria. Red fibers make up slow-twitch motor units. They have a great resistance to fatigue. II. White fibers are large fibers with less myoglobin and cytochromes and fewer mitochondria. White fibers make up fast twitch motor units, fatigue rapidly. III. Intermediate fibers are of intermediate size and have pigment contents and mitochondrial numbers between the two extremes of red and white fibers. Myofibrils and myofilaments The structural and functional subunit of the muscle fiber is the myofibril. Myofibrils give the muscle fiber a stippled appearance. Myofibrils are 28 composed of bundles of myofilaments. Myofilaments interaction is responsible for muscle cell contraction. Two types of myofilaments are associated with cell contraction. They are -thin filaments, composed primarily of the protein actin -thick filaments, composed of the protein myosin. The functional unit of the myofibril is the sarcomere, the segment of the myofibril between two Z discs. The short formula of the sarcomere is: Z (T) + ½ I + A + ½ I + Z (T) Where the Z line, is a dense zone that bisects the I band. The I band is called isotropic band and contains only thin filaments. The A band is called anisotropic band and contains both thin and thick filaments. Contractile mechanism (for skeletal muscle) When a muscle contracts, each sarcomere shortens and becomes thicker, but the myofilaments remain the same length. The thin filaments slide past the thick filaments during contraction. Calcium must be available for the reaction between actin and myosin. After contraction, the Ca must be removed. This rapid delivery and removal of Ca is accomplished by the combined work of the sarcoplasmic reticulum and a transverse tubular system or T system derived from the plasma membrane. The sarcoplasmic reticulum serves as reservoir and regulator of the Ca. Ca stimulates binding of myosin and actin. The complex of T tubule and two terminal cisternae is called the triad. Cardiac muscle It consists of long fibers that appear to branch and anastomose with neighboring fibers. Unlike skeletal muscle fibers, the fibers of cardiac muscle are formed by individual, mononucleated cardiac muscle cells (with central location of the nucleus) that are joined to one another in linear array. Cardiac muscle fibers exhibit densely staining cross-bands, called intercalated discs that cross the fibers in a linear fashion. More about cardiac muscle you are going to study in cardiovascular system. Smooth muscle Location in the body: alimentary canal blood vessels genitourinary tract respiratory tract other hollow and tubular organs 29 Structure: Smooth muscle generally occurs as bundles of elongate fusiform cells which also called fibers The cytoplasm of the smooth muscle contains actin and myosin The nuclei of smooth muscle cells are located in the center The cytoplasmic organelles are concentrated at each end of the nucleus The rest of the cytoplasm is seen to be filled with actin filaments interspersed with intermediate filaments Smooth muscle cells have no T system Contractile mechanism (for smooth muscle) There are 2 types of contraction: Peristaltic movements are slow, prolonged contraction in a wave-like manner, in the gastrointestinal tract and the male genital tract Extrusive movements are throughout contraction in the urinary bladder, the gall bladder and the uterus. Smooth muscle has spontaneous contractile activity. 30 Nervous tissue Nervous tissue consists of two principal types of cells: nerve cells (neurons) and supporting cells. The neuron or nerve cell is the functional unit of the nervous system. Neurons do not divide. They must last for a lifetime. All neurons have a cell body and processes, the axon and dendrites. Cell body (perycaryon) The cell body of the neuron has the characteristics of a protein-secreting cell. Cell body contains a large euchromatic nucleus, inclusions, Nissl bodies which are rough endoplasmic reticulum (rER). The perikaryon also contains numerous mitochondria, a large perinuclear Golgi apparatus, lysosomes, microtubules, neurofilaments, vesicles and inclusions. Difference between dendrites and axons Dendrites are neuronal processes that receive stimuli from other nerve cells or from the environment. Axon transmit stimuli to other neurons or to effector cells Dendrites have a greater diameter than axons Axons are longer processes compare to dendrites Dendrites are unmyelinated Axons can be myelinated and unmyelinated Dendrites form extensive arborizations called dendritic trees Axon is only one for each neuron Dendrites have Nissl bodies, free ribosomes and the Golgi complex Axon doesn’t have Nissl bodies, free ribosomes and the Golgi complex 1. 2. 3. 4. Classification of neurons on the basis of the number of processes Multipolar neurons have only one axon and two or more dendrites. Bipolar neurons have one axon and one dendrite. Unipolar neurons have one axon. Pseudounipolar have one process the axon that divides close to the cell body into two long processes. Classification of neurons according to their function sensory neurons which convey impulses from receptors to the central nervous system (CNS) motor neurons which convey impulses from the CNS or from ganglia to effector cells interneurons or central neurons, form a communicating and integrating network between the sensory and motor neurons 31 Synapses Neurons communicate with other neurons and effector cells by means of synapses that facilitate transmission of impulses from one neuron to another Classification of the synapses axodendritic, occurring between axons and dendrites axosomatic, occurring between axons and the cell body axoaxonic, occurring between axons and axons dendrodendritic, occurring between dendrites and dendrites Structure of the synapse 1. Presynaptic membrane (component) is formed by an axon terminal, from which neurotransmitter is released. 2. Synaptic cleft is a thin intercellular space, that neurotransmitter must cross 3. Postsynaptic membrane (component) has receptor sites on the plasma membrane with which the neurotransmitter interacts. The release of neurotransmitter by the presynaptic component can cause either excitation or inhibition at the postsynaptic membrane. The most common transmitters are acetylcholine and norepinephrine. Neuroglia Within the CNS, the supporting cells are designated neuroglia or glial cells. The neuroglia is divided into macroglia and microglia. The macroglia consists of next cell types: 1. Olygodendrocytes are irregular branching cells. They are present in the white and gray matter of the CNS. Functions: formation of the myelin sheath in the CNS insulators of the nerve fiber supportive function for the nerve cells nutritive function for the nerve cells 2. Astrocytes are star-shaped cells with long numerous processes. There are two types of astrocytes: fibrous (present in the white matter of the CNS) and protoplasmic (present in the gray matter of the CNS). Functions: physical support for the neurons of the CNS metabolic support for the neurons of the CNS repair and healing of the nervous system may share in the formation of the blood-brain barrier 3. Ependymal cells are low columnar epithelial cells lining the ventricles of the brain and central canal of the spinal cord. Function: produce cerebrospinal fluid by transport and secretion of materials derived from adjacent capillary loops 32 4. Schwann cells have the same function as olygodendrocytes but are located around axons in the peripheral neuron system. The microglia is originated from the blood monocytes. Microglia has small spindle-shaped cells. The branching processes arise from each pole of the cell. Function: It is a phagocytic and immunological cell that plays a protective defense function in the CNS. They are called the police man of the CNS. Axons in the peripheral nervous system may be described as myelinated or unmyelinated. Myelinated have myelinated sheath (lipid rich layer) have a smaller diameter of axons than unmyelinated one the myelin is absent between adjacent olygodendrocytes such areas are known as node of Ranvier the nerve impulse is jumped from node to node because of it conduct impulses more rapidly Unmyelinated surrounded by unmyelinated sheath every sheath is formed by olygodendrocytes and axon lies in the fold of its plasmalemma a single olygodendrocytes can form folds of several axons conduct impulses more slowly 33