Histology PDF - Medical University of Bialystok

HISTOLOGY Alba Becerra MEDICAL UNIVERSITY OF BIALYSTOK First year (2019/2020) LECTURE 1_HISTOLOGY AND ITS METHODS OF STUDY Histology is the study of the tissues of the body and how these tissues are arranged to constitute organs. Four fundamental tissues are recognised:...

HISTOLOGY Alba Becerra MEDICAL UNIVERSITY OF BIALYSTOK First year (2019/2020) LECTURE 1_HISTOLOGY AND ITS METHODS OF STUDY Histology is the study of the tissues of the body and how these tissues are arranged to constitute organs. Four fundamental tissues are recognised: Epithelial tissue. Connective tissue Muscular tissue Nervous tissue Cells are the structural units of all living organisms. Each of the fundamental tissues are formed by several kinds of cells. The human organism presents about 200 different cell types. PREPARATION OF TISSUES FOR STUDY The most common procedure used in histologic research is the preparation of tissue slices that can be examined visually with transmitted light. Because most tissues and organs are too thick for light to pass through, thin translucent sections are cut from them and placed on glass slides for microscopic examination of the internal structures. The ideal microscopic preparation is preserved so that the tissue on the slide has the same structural features it had in the body. FIXATION To preserve tissue structure and prevent degradation by enzymes released from the cells or microorganisms, pieces of organs are placed as soon as possible after removal from the body in solutions of stabilizing or cross-linking compounds called fixatives. Because a fixative must fully diffuse through the tissues to preserve all cells, tissues are usually cut into small fragments before fixation to facilitate penetration. To improve cell preservation in large organs fixatives are often introduced via blood vessels, with vascular perfusion allowing fixation rapidly throughout the tissues. Usually for light microscopy is used formalin: buffered isotonic solution of 37% formaldehyde. For electron microscopy this compound and glutaraldehyde are used EMBEDDING & SECTIONIN To permit thin sectioning fixed tissues are infiltrated and embedded in a material that imparts a firm consistency. Embedding materials include Paraffin, used routinely for light microscopy. Plastic resins, which are adapted for both light and electron microscopy. Before infiltration with such media the fixed tissue must undergo dehydration by having its water extracted gradually by transfers through a series of increasing ethanol solutions, ending in 100% ethanol. The ethanol is then replaced by an organic solvent miscible with both alcohol and the embedding medium, a step referred to as clearing because infiltration with the reagents used here gives the tissue a translucent appearance. STAINING Sections are mounted on glass slides for staining, which is required to reveal specific cellular and tissue components with the microscope. The most commonly used staining method is a combination of the stains hematoxylin and eosin (H&E), which act as basic and acidic dyes, respectively.  Cell substances with a net negative (anionic) charge, such as DNA and RNA, react strongly with hematoxylin and basic stains; such material is said to be “basophilic.” Cationic substances, such as collagen and many cytoplasmic proteins react with eosin and other acidic stains and are said to be “acidophilic.” LECTURE 2_THE CELL CELL THEORY All organisms are composed of cells All cells come only from preexisting cells Cells are the smallest structural and functional unit of organisms Cells carry genetic information in the form of DNA PLASMA MEMBRANE The plasma membrane is a lipid-bilayer structure, visible with electron microscope It looks like two electron-dense layers separated by a lighter central zone - unit membrane It consists of: o Lipids - phospholipids, glycolipids and colesterol o Proteins - peripheral and integral o Carbohydrates - glycoproteins and glycolipids forming a surface coat - glycocalyx Functions: o It envelops the cell, maintains its structural and functional integrity o Plasma membrane functions as selective barrier (regulates the passage of certain material into and out of the cell) o Playing a role in the interactions of the cell with its environment o The role is to keep constant the ion content of cytoplasm MEMBRANE PROTEINS Integral proteins are dissolved in the lipid bilayer Peripheral proteins exhibit looser association with one of the two membrane surfaces Functions: o Attach cytoskeletal filaments to cell membrane o Possess specific enzymatic activity o Transport molecules in or out of cells o Act as receptors (hormone receptors) o Attach cells to extracellular matrix MEMBRANE TRANSPORT Passive transport - without the need for energy, by followings concentration gradient o Simple diffusion o Facilitated diffusion - (ion channel proteins and carrier proteins) Active transport - with energy, usually in the form of ATP o Na+ / K+ pump § 3 Na+ ions are pumped out of the cell and 2 K+ are pumped into the cell § The hydrolysis of a single ATP molecule by the Na+ / K+ ATPase is required to transport five ions o Vesicular transport § Endocytosis - the transfer of material from the extracellular space into the cytoplasm Phagocytosis (cell eating) - the cell engulfs insoluble substances, such as large macromolecules, the vesicles are termed phagosomes Pinocytosol (cell drinking) - the cell engulfs small amounts of fluid § Exocytosis - the transfer of material from the cytoplasm into the intercellular space CYTOSKELETON IT IS COMPOSED OF: Microtubules o Long, flexible, tubular structure o Are the thickest cytoskeletal components o The walls contain subunits - tubulin heterodimers o Each microtubule is polarized o Function: § They sustain cell morphology § Assist in intracellular transport § Form spindle apparatus § Form the core of cilia and flagella § Form centrioles and § basal bodies CENTRIOLES Small, cylindrical structures Composed of two pairs of nine triplet microtubules where the two centrioles are arranged perpendicular to each other Form centrosome, act as nucleation sites of the spindle apparatus, basal bodies – development of cilia and flagella Thin filaments o Microfilaments – the thinnest cytoskeletal elements, more flexible than microtubules o Composed of G – actin monomers, organized in double – stranded helix (two chains of F-actin filaments coiled arround each other) o Have a plus and minus end o Function § They are contractile (must interact with myosin) § Form a thin sheath or network just beneath the plasmalemma § Are involved in all cell shape changes (during endocytosis, exocytosis and cell locomotion) Intermediate filaments o Ropelike structures, form the framework of the cell o Anchor the nucleus in its position o Secure integral membrane proteins to the cytoskeleton o React to extracellular matrix forces o Proteins § Keratins or cytokeratins – more than 20 proteins found in epithelial cells (nails, horns) § Vimentin - a single protein characteristic for mesenchymal cells  § Neurofilaments – consists of three high-molecular polypeptides – neurons § Lamins – framework inside nuclear invelope FUNCTION The protein structures determine the shape of cells Play the role in the movements of organelles and cytoplasmic vesicles Permits cells to adhere to one another NUCLEUS The nucleus contains nuclear envelope, chromatin, one to several nucleoli, variable amount of nucleoplasm. Functions: Contains chromatin a code of DNA – synthesys of cell components and products Indispensable for cellular reproduction Nuclei display wide variations in: Nuclear size – it dependences on amount of cytoplasm in the cell Number per cell – cells may be enucleate, mononucleate, binucleate, multinucleate Nuclear location – central, eccentric, basal Chromatin pattern – amount and distribution varies according to cell type, cellular activity NUCLEAR ENVELOPE It contains an inner and an outer membrane separated by intermembrane space (perinuclear cisterna) External surface – is peppered with ribosomes and shows contiunities with RER Nuclear pores – form where the outer and inner membranas fuse, permitting communication between the cytoplasm and the nucleus CYTOPLASMIC ORGANELLES ROUH ENDOPLASMIC RETICULUM Network of flattened sacs or cisternae, studded with ribosomes RER cisternae are typically parallel, flattened and elongated Abundant in cells specialized for protein secretion Function: o The site, where membrane - packaged proteins, are synthesized (plasma – membrane and lysosomal proteins) o RER monitors retention and degradation of certain proteins SMOOTH ENDOPLASMIC RETICULUM SER – irregular network of membrane – bounded channels, that lacks ribosomes on its surface It looks like as branching anastomosing tubules or vesicles without ribosomes SER is prominent in cells producing steroids, cholesterol, triglyceride Function: o Steroid hormone synthesis o Drug detoxification o Accumulation of calcium ions - muscle contraction and relaxation RIBOSOMES Ribosomes are present free in the cytoplasm,or are attached to RER Spherical particles, that consist of RNA and protein They contain 60S subunit and 40S subunit They are site of protein synthesis for secretion or intracellular use GOLGI COMPLEX Golgi apparatus comprises three major regions: o A stack of 3-10 discrete, slightly curved, flattened cisternnae o Small vesicles peripheral to the stack o A few large condensing vacuoles (concave surface of the stack) The cis face – forming face, cisternae located closest to the RER The trans face – maturing face, cisternae located away from the RER The cisternae located between – medial Golgi Function: o Polysaccharide synthesis – contains glycosyltransferases o Modification of secretory products o Sorting of secretory products o Packaging of secretory products o Concentration and storage of secretory products PROTEASOMES Small, barrel-shaped organelles (contain proteins including proteases) Proteins for destruction are enzymatically tagged with ubiquitin Ubiquitin delivers them to the proteasomes, where they are broken down to small peptides PEROXISOMES Spherical, membrane-limited organelles with oxidative enzymes (catalase and other peroxidases) Function: o They oxidize specific organic substrates o They are responsible for detoxification of substances such as ethanol o They synthesizes bile acids, cholesterol and plasmalogens o They participate in β-oxidation of fatty acids LYSOSOMES Small, dense,membrane-bound structures They contain about 50 acid hydrolases including proteases, nucleases, glycosidases, lipases and phospolipases Lysosomes are sites of intracellular digestion and turnover of cellular components Types o Primary – small, with electron-dense contents, appear as solid black circles in EMs, enzymes are mostly inactive o Secondary – large, less electron-dense with active enzymes MITOCHONDRIA Large, rod-shaped, membrane enclosed, organelles Each mitochondrion consists of:  o Smooth outer membrane o Inner membrane with many infoldings o Intermembrane space o Matrix (inercristal) space Function: o Synthesis of ATP during oxidative phosphorylation o They participate in apoptosis – procaspases-2,-3 and -9, apoptosis initiation factor (AIF) and cytochromec o They participate in steroidogenesis and thermogenesis The mitochondrial matrix contains circular chromosome of DNA, ribosomes, mRNA, tRNA Small proportion of the mitochondrial proteins is produced locally Most are encoded by nuclear DNA and produced in cytoplasm INCLUSIONS They are nonliving elements of the cell They are freely present i the cytosol They are not membrane bound The major inclusions are: o Glycogen – small granules, energy deposit o Lipids – prominent in adipocytes, adrenal cortex o Melanin – brown pigment located i memrane-limited granules – melanosomes o Lipofuscin – small pigmented body, accumulate with age (neurons, cardiac muscle) LECTURE 3_EPITHELIAL TISSUE AND GLANDS EPITHELIA, FEATURES AND TYPES Epithelial tissue is composed of closely apposed cells interconnected by junctional complexes, with very little intercellular substance Epithelia are avascular Epithelial cells show polarity Basal lamina is present All surfaces have specialized structures Renewal of epithelia cells o Epithelial tissues are labile structures o Renewal rate is variable § Fast in small intestine (every week) § Slow in large gland o Stratified epithelia – mitosis occurs within basal layer o Some functionally complex epithelia – stem cells are present in restricted niches – small intestine – stem cells situated in glands between intestinal villi Origin of epithelia o Ectoderm – epidermis of the skin, sweat and sebaceous glands, lining of the mouth o Endoderm – lining of the digestive and respiratory systems o Mesoderm - lining of the body cavities (mesothelium) o Mesenchyme – lining of the blood and lymphatic vessels (endothelium) Principal functions o Covering, lining and protecting surfaces o Absorption (small intestine) o Secretion (glands) o Detection of sensations (taste) o Selective permeability Clasification of epithelia tissue o Based on the number of cell layers § Simple – one cell layer § Stratified – to or more cell layers o Based on the cell shape § Squamous § Cuboidal § Columnar o Based on function § Covering or lining epithelial § Glandular epithelia SIMPLE SQUAMOUS EPITHELIUM The cells are flat and usually very thin Elongated and flattened nuclei are oriented parallel to the direction of blood flow Function and distribution: o Lining of the blood and lymphatic vessels o Linning body cavities o Lining parietal layer of Bowman’s capsule o Gaseous exchange in the alveoli of the lung o Fluid transport o Lubrication SIMPLE CUBOIDAL EPITHELIUM Cells roughly as thick as they are wide Nuclei are round and located in the center of cell Distribution: o Thyroid follicles o Ovary o Kidney tubules Function o Secretion o Absorption o Protection o SIMPLE COLUMNAR EPITHELIUM Cells taller than they are wide, cylindric cells Nuclei elongated, „hot – dog” shaped, located toward the basal end of the cells Nuclei perpendicular to the basal end of the cells Apical surface covered by numerous microvilli (microvilli and glycocalyx coat form brush border) Funtcion and distribution: o Lining digestive tract, gallbladder, oviducts o Absorption o Secretion o Protection o Transportation PSEUDOSTRATIFIED COLUMNAR EPITHELIUM A single layer of epithelial cells, that only appears stratified All cells rest on basal lamina, but not all reach epithelial surface Their nuclei lie at different levels This type of epithelium is frequently ciliated Function and distribution: o Lining of trachea, bronchi o Transportation o Protection o Secretion, lubrication, absorption STRATIFIED SQUAMOUS EPITHELIUM SQUAMOUS NONKERATINIZED Is formed by multiple layers of cells The basal layer has columnar cells in contact with basement membrane Intermediate layer cells are polyhedral in shape The top surface layers contain flattened live cells with squamous nuclei Function o Protection  o Secretion o Prevents water loss SQUAMOUS KERATINIZED The cells on the basement membrane are columnar (stem cells, dividing, migrating and differentiate) The intermediate layers contain polyhedral cells, which are bound together by desmosomes (stratum spinosum) 3 – 5 layers of flattened, polygonal cells, filled with keratohyalin granules (stratum granulosum) Superficial keratinized layer, 15 – 20 layers of flattened, keratinized structures (dead cells) without nuclei (stratum corneum) Function o Prevent water los o Protectoin TRANSITIONAL EPITHELIUM (RELAXED) Stratified epithelium Lining urinary tract from renal calyces to urethra, function – protection, distensible 4 to 6 cell layers, in the relaxed state – surface cell appears large, dome shaped, often are binucleated Cells located basally are smaller, low columnar or cuboidal cells TRANSITIONAL EPITHELIUM (DISTENED) 2 to 3 cell layers The top dome – shaped cells become flattened squamous cells Specialized regions called plaques are folded into irregular contours – the bladder is empty The plaques disappear – the bladder filling The plaques appear impermeable to fluid and salts STRATIFIED CUBOIDAL EPITHELIUM Usually has only two, occasionally three, layers of cuboidal cells The top layer contains uniform cuboidal cells Basal cells sometimes appear to form an incomplete layer The cells have smooth apical surfaces and centrally located nuclei It forms the ducts of exocrine and sweat glands Function: form a conduit for secretory products of glands STRATIFIED COLUMNAR EPITHELIUM 2 – 3 layers The top layer contains columnar cells Basal cells are cuboidal in shape Lining larger ducts of some exocrine glands, conjuctiva Function: protection EPITHELIA, APICAL SPECIALIZATIONS CILIA Long, highly motile structures The core (axoneme) is composed of microtubules and associated proteins Each cilium is inserted into basal bodies The epithelial cell may contain about 250 cilia (pseudostratified ciliated epithelium) MICROVILLI Immobile, membrane-bound, finger-like projections The core of each microvillus contains a bundle of 25 – 30 actin filaments These filaments insert into the actin filaments of the terminal web Increase absortive surface area Microvilli and glycocalyx form brush or striated border very well visible in light microscope FLAGELA Present only on spermatozoa in human Modified cilia Possess an axoneme and a robust elastic protein complex STEROCILIA Microvilli of unusual lenght Present only in epididymis and on the sensory hair cells of the cochlea (inner ear) Function: o Increase surface to facilitate absorption in the epididymis o Assist the hair cells in signal generation GLYCOCALYX Cell sweet coat Composed of carbohydrates, that form glycolipids or glycoproteins Play a role in cell recognition and attachment to other cells and to extracellular molecules BASAL EPITHELIA SURFACES BASAL LAMINA Visible only with the electron microscope Composed of type – IV collagen, proteoglycan (heparan sulfate), laminin (a glycoprotein that helps bind cells to the basal lamina) and entactin (a glycoprotein associated with laminin) It consists of two zones: o Lamina lucida – lies next to the plasma membrane, the amount of lamina lucida is variable  o Lamina densa – 20 – 100 nm, thick fibrillar network, lies adjacent to the reticular lamina of the deeper connective tissue o Basal lamina and and reticular lamina form basement membrane (visible by light microscope) Functions: o Forms a sievelike barier between the epithelium and connective tissue o Helps maintain cell shape through cellular adhesion o Plays role in diffusion between connective tissue and epithelial cells LAMINA RETICULARIS Consists of types I and II collagens Is synthesized by fibroblasts It is of variable thickness The collagens of lamina reticularis arise from and are continuous with the collagen of connective tissue BASAL PLASMA MEMBRANE INFOLDINGS Present in cells concerned with ion transport Increase plasmalemma surface area Basal membrane infoldings Mitochondria are oriented vertically within the folds The orientation of the mitochondria and the basal membrane infoldings results in a striated appearance along the basal aspecto HEMIDESMOSOMES Are located on the basal plasma membrane Appear to be half of a desmosome Assist in the attachment of the basal plasmalemma to the basal lamina Attach epithelial cells to underlying basal lamina EPITHELIA, LATERAL MEMBRANE SPECIALIZATION Three types of cell junctions form the lateral membranes: o Occluding junctions (zonulae occludentes) o Anchoring junctions (zonulae adherentes, maculae adherentes, hemidesmosomes, actin- linked cell – matrix adhesions) o Communicating junctions (gap junctions) OCCLUDING JUNCTIONS Extend along entire circumference of the cell Are formed by fusion of the outer leaflets of the cells’ plasma membranes Provide an impermeable or selectively permeable Barier that prevents material from traversing an epithelial membrane between adjoining cells ANCHORING JUNCTIONS Zonulae adherentes o Basal to zonulae occludentes o E – cadherins bind to each other in the intercellular space and to actin filaments, intracellularly o Permit epithelial cells to adhere to each other or to the basal lamina of both Maculae adherentes (desmosomes or spot welds) o Small, discreate, disk – shaped adhesive site o Plaques are situated along the lateral surface of adjacent cells o Plaques consisting of plakoglobins and desmoplakins, are anchored by cytokeratins GAP JUNCTION (COMMUNICATING) Permit transcytoplasmic movement of ions and small molecules between adjacent cells Small molecules to pass through the narrow (2-4 nm) wide intercellular space Six connexins form channels - connexons Couple cells metabolically and electrically Present in epithelial tissues and neurons, in cardiac and smooth muscle GLANDS, FEATURES Glandular epithelia are composed of cells specialized to secrete Glandular cells synthesize, store and secrete lipids, proteins or complexes of proteins and carbohydrates FORMATION: Epithelial cells proliferate and penetrate the underlying connective tissue They have or not connection with the surface epithelium Exocrine glands are formed – when the connection is present Endocrine glands are formed – without the connection CLASSIFICATION: Based on morphology: o Unicellular – are composed of only single cells, secretory material is released directly onto the surface (goblet cell) o Multicellular – are composed of clusters of cells Based on the manner of delivery of their secretory products: o Exocrine glands – possess ducts through which secretory material is delivered onto the body surfaces or into the lumen on organ § Based on the type of secretion the gland produces: Serous – watery (parotid gland) Mucous – viscous (minor salivary gland of the palate) Mixed – serous and mucous (sublingual gland)  § Based on the mechanism by which the secretory material is released from cell: Merocrine – secretory product is released by exocytosis without the loss of cell material (cytoplasm) – pancreatic acinar cells Apocrine - secretory product is released together with part of apical cytoplasm, lipid of mammary gland Holocrine – secretory product is released by disintegration of the entire cell (sebaceous gland) o Endocrine glands – are ductless, secretory material is delivered into the blood stream or lymphatic vessels § Based on the shape of their secretory units: Acinar – alveolar Tubular Tubuloalveolar Based on the distance between the signaling cell and the target cell: o Paracrine – the target cell and signaling cell are near each other o Autocrine – the signaling cell and the target cell are the same – the cell stimulates itself o Endocrine – a great distance between signaling cell and target cell, product enters the blood system SEROUS ACINI Round structures surrounded by basement membrane Pyramidal cells are situated on the basement membrane The lumen is closed or narrow (watery secretory product) Secretory cells have spherical nucleus Basophilic cytoplasm Secretory granules situated in the apical part of cytoplasm MUCOUS TUBULES Oval structures surrounded by basement membrane Cuboidal secretory cells situated on the basement membrane Lumen is large (dense, gellike secretory product) Flattened nuclei at the base of the cell Empty, vacuolated appearance of the apical cytoplasm MIXED GLANDS Contain both mucous secretory portions and serous secretory portions Serous cells form a moon – shaped cap on top of mucous tubul called serous demilune GLANDS, STRUCTURAL CLASSES OF EXOCRINE GLANDS Based on duct shape: simple – glands have no ducts (inestinal glands) or one duct (sweat glands): o Branched – one duct and two secretory portions (stomach) Compound – have branched ducts (pancreas) MYOEPITHELIAL CELLS Stellate or spindle - shape cells present in several exocrine glands Situated between the basal lamina and the basal pole of secretory or duct cells Function is to contract around secretory part and help propel secretory material into the duct GOBLET CELL Unicellular glands Located in epithelial lining small and large inestine, trachea A distinctive goblet shape Are mucus – secreting cells The narrow base (stem) contains organelles, the apical part – numerous mucinogen - containing secretory granules SIMPLE TUBULAR GLAND Straight tubul No duct The secretory cells are goblet cells The secretory material is discharged into the lumen of gland This type of gland is present in large inestine SIMPLE COILED TUBULAR GLAND Secretory portions are formed by coiled tubules Located deep in the dermis Long, excretory duct that is unbranched Sweat glands SIMPLE BRANCHED GLAND Two or more secretory portions They converge onto a single, unbranched duct Mucous cells do not have a goblet shape Stomach SIMPLE BRANCHED ACINAR Secretory portions are branched acini, several secretory acini Short, unbranched duct Sebaceous gland COMPOUND ACINAR GLAND Secretory units are branched acini They drain into a branched duct system Exocrine part of pancreas COMPOUND TUBULAR GLAND The secretory portions are formed by branched tubules Branched ducts Brunner glands COMPOUND TUBULOACINAR GLAND  Three types of secretory units: o Branched tubular o Branched acinar o Branched tubular with demilunes Branched ducts Submandibular gland is the classic example SEBACEOUS GLAND It is the classic example of holocrine secretion Secretory unit – several, branched acini Single excretory duct Stem cells lie on the basal lamina They divide, proliferate, displace toward the middle of acinus They accumulate lipid droplets - transformation into sebum LECTURE 4_BLOOD-HEMOPOIESIS Blood is a unique form of connective tissue. It consists of formed elements, which are suspended in a liquid medium called plasma. There three major cell types: Erythrocytes - 4.2-6.2 million per cubic mm Leukocytes - 5-10 thousand per cubic mm Cell fragments known as platelets - 200-400 thousand per cubic mm PLASMA 90% is water 9% is proteins 1% other solutes Electrolytes (Na+, K+, Ca2+, Mg2+, Cl-, HCO34-, PO43-, SO42-) Nutrients (glucose, lipids, amino acids) Dissolved gases (oxygen, carbon dioxide, nitrogen) Hormones, enzymes Nonprotein nitrogen substances (urea, uric acid, creatine, creatinine, ammonium salts) MAIN PLASMA PROTEINS Albumin - the most abundant plasma protein, small protein, preserves osmotic pressure in the vascular system, helps transport some metabolites Alfa and beta globulinas - made by the liver and other cells, transport metal ions (iron and copper) and lipids Gamma globulins - immunoglobulins, antibodies Fibrinogen - the largest plasma protein, is converted into fibrin during blood clotting SERUM Yellowfish fluid that remains after blood has clotted Similar to plasma but lacks fibrinogen and clotting factors HEMATOCRIT It measures the volume of packed red blood cells per unit volume of blood after centrifugation It is expressed as a percentage Normal values o 40% - 50% in adult men o 35% - 45% in adult women o 35% in children (up to 10 years of age) o 45% - 60% in newborns ERYTHROCYTES Anucleate cells devoid of typical organelles The shape of biconcave disk with a diameter of 7.8 um This shape maximises the cell’s surface area - an important attribute in gas exchange Bind oxygen for delivery to the tissue Bind carbon dioxide for removal freedom the tissues The life span - 120 days, are phagocytosed in spleen, bone marrow, liver  Anisocytosis - the presence of a high percentage of erythrocytes with great variations in size o Erythrocytes with diameters about 7.8 um – normocytes o Erythrocytes with diameters greater than 9 um – macrocytes o Erythrocytes with diameters less than 6 um – mikrocytes Poikilocytosis - it is a condition in which a large population of erythrocytes have varied shapes LEUKOCYTES GRANULOCYTES NEUTROPHILS (45% - 65%) Measure 12-15 um (smaller than eosinophils) Nucleus has 2-5 lobes linked by fine threads of chromatin Specific granules do not stain, resulting in a pale cytoplasm Have a life span of 6 to 7 hours in blood and 1 to 4 in connective tissue Are motile cells, migrate to their site of action The primary function is phagocytosis of bacteria Granules o Primary or azurophilic granules contain elastase, myeloperoxidase, lysozyme o Secondary or specific granules contain alkaline phosphatase, lactoferrin, collagenase, defensis EOSINOPHILS - 2%-5% Measure 12 to 15 um (the largest of granulocytes) Typically bilobed nucleus (appears as glasses) Pale pink cytoplasm with numerous, large, eosinophilic granules (red colour) Azurophilic granules resemble the lysosomes of neutrophils Specific granules have two regions: o Externum - hydrolysis enzymes and cathepsins, peroxidase and histamine o Internal - major basic protein (ECP), eosinophil-derived neurotoxin Life span - few hours in blood, 2 weeks in connective tissue Moderate inflammatory reactions (inactivating histamine and Leuko tríenle C) Kill the parasites (MBP, ECP) Phagocytose and degrade antigen-antibody complexes Eosinophilia: an increase in the number of eosinophils in blood is associated with allergic reactions and parasitic infections BASOPHILS - 0.5%-1% Measure 10 um (the smallest amid granulocytes) Nucleus with 3 lobes, S-shape, often obscured by the specific granules (basophilic, dark blue or purple) Contain a few primary granules Specific granules are large, stain dark blue or purple Contents of granules: histamine, heparin, peroxidase, eosinophil chemotactic factor (ECF) Life span, 1 or 2 years in mice Play a role in immediate (bronchial asthma) and delayed hypersensitivity (allergic skin reaction) Basophilia (an increase in the number of basophils) is observed in acute hypersensitivity reactions, viral infections, chronic inflammatory conditions (rheumatoid arthritis and ulcerative colitis) AGRANULOCYTES MONOCYTES - 4%-8% Measure 20 um (the largest blood cell) Kidney shaped nucleus is eccentrically located Cytoplasm stains pale blue-gray Travel about 20 hours in the bloodstream Enter the peripheral tissue and form macrophages in connective tissue, microclima in the CNS, osteoclasts in bone Are more efficient phagocytic cells than neutrophils LYMPHOCYTES - 28%-42% Have compact, densely stained nucleus Nucleus occupies most of the cell, reducing the cytoplasm to a thin basophilic rim Are divided according to the size: small 6-8 um, medium and large 9-18 um Are divided into two functional groups: o B lymphocytes - important for humoral immunity, differentiate in bone marrow, 15% of lymphocytes o T lymphocytes - important for cell-mediated immunity (rejection of transplanted organ), differentiate in the thymus, 80% of lymphocytes § Types of T-lymphocytes include: T-helper cells, suppressorT-cells, cytotoxic-T- cells o Null cells represent 5% of lymphocytes, natural killer, which attack virus- infected cells, transplanted cells, cancer cells without previous stimulation PLATELETS (THROMBOCYTES) Small cytoplasmic fragments (2-4 um), nonnucleated, dislike fragments 200-400 thousands per cubic mm Derive from the megakaryocyte under the control of thrombopoietin Each platelet has hyalomere (lightly stained peripheral zone) and granulomere (central, darker- staining region) Life span of about 10 days Main function: promote blood clotting and help to prevent blood loss from damaged vessels The cytoplasm of a platelet contains four types of granules: alpha granules, dense core granules, lysosomes and peroxisomes Platelets granules contains: platelet factor IV, Von Willebrand factor, serotonin, platelet-derived growth factor, histamine Thrombocytopenia o It is a disorder marked by a reduced level of circulating platelets (less than 150 thousand per cubic mm) o Spontaneous bleeding - 20 thousand per cubic mm o It can be caused by: § A decrease in the production of platelets § An increase in the destruction of platelets HEMOPOIESIS It is the process of blood cell formation in the bone marrow Prenatal hemopoiesis - blood cells arises from the yolk sac, liver, spleen and bone marrow o Bone marrow participates at 6 month’s gestation and assumes an increasingly larger role thereafter o The liver and spleen cease hemopoiesis at about time of birth Posnatal hemopoiesis o Blood cells and platelets are derived from stem cells located in red bone marrow o This process involves three classes of cells: stem, progenitor and precursor LECTURE 5_CONNECTIVE TISSUE Connective tissue, unlike epithelia is composed mainly of extracellular elements with limited number of cells. The connective tissues include several types of fibrous tissue that vary only in their density and cellularity, as well as the more specialized and recognizable variants - bone, ligaments, tendons, cartilage, and adipose (fat) tissue. Mesoderm gives rise to almost all of connective tissues of the body. The head region contains progenitor cells derived from ectoderm – neural crest cells. The components of the connective tissue CELLS FIBROBLASTS Are the most common cells in connective tissue They synthesize, secrete and maintain all major ECM components Are stellate, with long cytoplasmic processes Contain a large, ovoid, pale – staining nucleus Mitotically active, with abundant RER and Golgi complex FIBROCYTES Less active Smaller and spindle – shaped Dark, elongated nuclei and fewer organelles They may revert to the fibroblast form and participate in tissue repair MACROPHAGES (HISTIOCYTES) Large, stellate cells derived from monocytes (also known as tissue histiocytes) Difficult to detect in H+E stained sections Many lysosomes which aid in digesting phagocytosed materials, irregular nuclei Well developed Golgi complex, RER, SER Maintain connective tissue integrity by removing foreign substances and cell debris MONONUCLEAR PHAGOCYTE SYSTEM Long – living cells Different names in different organs: o Kupffer cells in liver o Microglial cells in CNS o Osteoclasts in bone tissue o Dust cells of the lung PLASMA CELLS Derive from the differentiation of B lymphocytes Synthesize and secrete a single class of immunoglobulin Large, ovoid cells with basophilic cytoplasm (abundant RER) Spherical nucleus, eccentrically located A large pale Golgi complex – golgi zone Characterized by cartwheel (clock-face) nuclei – showing the alternating distribution of the heterochromatin (dark) and euchromatin (light) MAST CELLS Large, oval, round Small, spherical nucleus, centrally located Cytoplasm is filled with basophilic secretory granules: o Histamin o Heparin o Serine proteases o Eosinophil and neutrophil chemotactic factors Originate in the bone marrow There are two populations of mast cells: o Mucosal mast cells (found predominantly in the intestine and lungs) o Connective tissue mast cells Structural and functional characteristics of mast cells depend on the site of differentiation (mucosa or connective tissue) PERICYTES WANDERING CELLS (LEUKOCYTES) Migrate from the blood vessels into connective tissue by diapedesis The following leukocytes are commonly found in connective tissue: o Lymphocytes o Neutrophils  o Eosinophils o Basophils EXTRACELLULAR MATRIX (ECM) FIBERS COLLAGEN FIBERS Collagen is the most abundant protein in human body There are 19 molecular types of collagen The most common collagen types in connective tissue proper are type I and type III Collagen fibers have great tensile strength Bone, skin, tendon, cartilage contain collagen fibers RETICULAR FIBERS Are extremely thin Composed primarily of type III collagen Form delicate silver – staining networks Are present around the parenchymal cells of various organs (liver, endocrine glands) Are abundant in the framework of hematopoietic organs ELASTIC FIBERS Consist of the amorphous protein elastin Stain poorly with standard histological dyes May be stretched up to 150% of their resting length Are coiled, branching, sometimes form loose networks GROUND SUBSTANCE It consists of two glycoconjugate classes: o Proteoglycans § Consist of a core protein to which glycosaminoglycans (GAGs) are attached § Five major classes of GAG, differing in their sugars, exist in connective tissues: hyaluronan, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate o Glycoproteins § Are proteins to which short, branched oligosaccharide chains are bound § Are much smaller than proteoglycans § Examples: § Fibronectin – mediates cell adhesion to the ECM § Laminin – basal lamina component Tissue fluids and salts also are present It is colorless, transparent, gellike material in which the cells and fibers are embedded. INTERSTITIAL FLUID Similar to blood plasma in its content of ions and diffusible substances Contains a small percentage of plasma proteins of low molecular weight CLASSIFICATION OF CONNECTIVE TISSUE EMBRYONIC CONNECTIVE TISSUE Is formed in early embryonic development Is classiefied into two subtypes: o Mesenchyme o Mucous It gives rise to the various connective tissues of the body MESENCHYME CONNECTIVE TISSUE It is found in the embryo and fetus It contains star – shaped mesenchymal cells with pale – staining cytoplasm and small processes The extracellular space contains a viscous ground substance MUCOUS CONNECTIVE TISSUE Exhibits a jellylike matrix with some collagen fibers and stellate – shaped fibroblasts It is the main constituent of the umbilical cord – Wharton jelly It is present in the pulp cavity of young teeth CONNECTIVE TISSUE PROPER LOOSE (AREOLAR) Is characterized by abundant ground substances with numerous connective tissue cells and fewer fibers The most numerous cells – fibroblasts, macrophages and a few mast cells Collagen, elastic and reticular fibers are present It contains moderate amount of ground substance It has delicate consistency, is flexible It is well vascularized It is not very resistant to stress Supports epithelial tissue, surrounds small blood and lymphatic vessels, fills the spaces between muscle and nerve fibers DENSE Regular (collagenous) o Consists of fewer cells and more fibers, with a predominance of type I collagen fibers o Has collagen bundles o Fibroblasts situated linearly in the same orientation o Is present in tendons and ligaments Regular (elastic) o Contains a bundles of thick elastic fibers o With a sparse network of collagen fibers and fibroblasts filling the interstitial space o Is present in the ligamentum flavin of the vertebral columna Irregular o the collagen fibers are arranged in bundles without a definitive orientation, with few elastic and reticular fibers o fibers form a 3-dimensional network o typical examples: capsules of many organs, dermis RETICULAR TISSUE Consists of reticular fibers of type III collagen and specialized fibroblasts called reticular cells Branched reticular fibers form architectural framework for parenchymal organs (lymphoid nodes, spleen, bone marrow) Reticular cells are situated along this framework and partially cover the reticular fibers ADIPOSE Composed of adipocytes, which are predominant There are two types of adipose tissue: o White adipose tissue § Composed of unilocular adipose cells § Each cell contains a single, large droplet of fat in the cytoplasm § The flattened nucleus is displaced to the periphery of the cell § Is found throughout adult human body § Serves as a reserve energy source o Brown adipose tissue § Composed of multilocular adipose cells § The fat is stored in multiple droplets in the cytoplasm § Cells have a central nucleus and relatively large amount of cytoplasm § The brown color is due to large number of mitochondria and rich blood supply § Produce heat in the first months of postnatal life LECTURE 6_BONE & CARTILAGE CARTILAGE, COMPOSITION Cartilage is a form of connective tissue composed of cells and a highly specialized extracellular matrix Cartilage is a skeletal connective tissue characterized by firmness and resiliency CHONDROGENIC CELLS Are located in the perichondrium and differentiate into chondroblasts to participate in appositional growth of cartilage. They are difficult to identify with H + E stain Spindle – shaped, narrow cells Their cytoplasm is sparse with ovoid nucleus (one or more nucleoli) Small Golgi complex, a few mitochondria, some profiles of RER, an abundance free ribosomes CHONDROCYTES Are mature chondroblasts Embedded in the lacunae of the matrix They are present as an isogenous group, two or more chondrocytes arranged in a group that was derived from a single progenitor cell Near periphery are ovoid, deeper are more rounded Display a large nucleus with prominent nucleolus Young – pale-staining cytoplasm, many mitochondria, an elaborate RER, well-developed GA, glycogen Older – display reduced complement of organelles with an abundance of free ribosomes CHONDROBLASTS Young chondrocytes Develop from chondrogenic cells Are able to actively manufacture the matrix of cartilage Contain basophilic cytoplasm with rich network of RER Synthesize and deposit cartilage matrix around themselves Situated in lacunae and are then referred to as „chondrocytes” EXTRACELLULAR MATRIX FIBERS Collagen fibers type II Some may contain type I or elastic fibers GROUND SUBSTANCE Glycosaminoglycans Proteoglycans Glycoproteins CARTILAGE, TYPES HYALINE CARTILAGE The most common type in both fetus and adult, is white and translucent when fresh, with a firm, gel-like consistency Matrix contains thin type II collagen fibrils Their small size and refractive index close to that of ground substance make them difficult to distinguish with the light microscope Most cartilage is covered by perichondrium , except at the articular surfaces of joints Is found in the articular ends of long bones, nose, larynx, trachea, bronchi Covers the smooth surface of joints, providing for free movement and is involved in bone formation and long bone growth ELASTIC CARTILAGE Is yellow when fresh and is more flexible than hyaline Is similar to hyaline cartilage except for its rich network of elastic fibers A perichondrium is present It also contains type II collagen in the matrix Chondrocytes are more abundant and larger than those of hyaline cartilage It contains more isogenous groups, but they have less chondrocytes It provides elastic support In humans occurs in the external ear, the external auditory canals and auditory tubes FIBROCARTILAGE Does not have a perichondrium It contains type II collagen, as do the other two types of cartilage It has thick, coarse bundles of type I collagen fibers, that alternate with parallel groups of columns (or rows) of chondrocytes in the matrix Chondrocytes are smaller and much less numerous than in the other two types Chondrocytes form columns or rows Is found at connections between bones that do not have an articular surface Is found in intervertebral disks, pubic symphysis and insertions of tendons and ligaments BONE, FEATURES AND COMPONENTS Bone is the main constituent of the adult skeletal system It is skeletal connective tissue, that is specialized for support and protection It has a hard, mineralized, extracellular matrix It is calcified and, hence, is harder and stronger than cartilage Many blood vessels penetrating the tissue Functions o It supports and protects fragile tissue and organs o Serves as a calcium reserve for the body o Provides an environment for blood cell production o Detoxifies certain chemicals in the body o Aids in the movement of the body Surfaces o Periosteum – covers outer surfaces of bone, a double – layered connective tissue coat § Outer of fibrous layer is dense connective tissue  § Inner or osteogenic layer is looser tissue with bone cell precursors o Endosteum – covers internal surfaces of bone, thinner, condensed reticular connective tissue, with a single layer of osteoprogenitor cells and osteoblasts, that lines all internal cavities within bone COMPONENTS: BONE CELLS Osteoprogenitor cells o Are located in the periosteum and can differentiate into osteoblasts o Are mesenchymal stem cells o Spindle-shaped cells with ovoid to elongate nuclei and unremarkable cytoplasm o Sparse RER, poorly developed GA, an abundance free ribosomes o Two types are distinguishable in EMs o One forms osteoblasts, osteoblasts precursors derived from mesenchyme and have sparse RER and Golgi complex o Other forms osteoclasts, osteoclasts precursors derive from blood monocytes, abundant free ribosomes, mitochondria, the term osteoprogenitor cells refers to osteoblast precursors Osteoblasts o The major bone-forming cells o Are cuboidal or low columnar in shape, o Have a well-developed Golgi complex and RER, it correlates with their protein-secreting function o Synthesize and secrete the organic components of bone matrix and participate in bone mineralization Osteocytes o Small with cytoplasmic processes, are unable to divide o Derived from osteoblasts o Are embedded in the bone matrix o Found in cavities in the bone matrix called lacunae (the nucleus and surrounding cytoplasm) o Each has many long, thin processes, that extend into small narrow spaces – canaliculi o Thin processes of osteocytes course through thin channels (canaliculi), that radiate from each lacuna and connect neighbouring lacunae Osteoclasts o Large, multinucleated cells, acidophilic cytoplasm with many lysosomes o Derive from monocytes o Absorb bone matrix o Play an essential role in bone remodeling o Cell surface forming ruffled border - plasma membrane infoldings - many compartments between the cell and the bone surface EXTRACELLULAR MATRIX Organic (noncalcified) matrix, osteoid – type I collagen and ground substance (chondroitin sulfate and keratin sulfate) Inorganic (calcified) matrix – mainly in the form of hydroxyapatite, contains crystalline mineral salts, mostly of calcium and phosphorus BONE, TYPES There are several ways to classify bone tissue: o Primary bone and secondary bone (microscopically) o Long bones, short bones, flat bones and irregular bones (by their shape) o Compact bone and spongy bone (based on gross appearance and density of the bone) COMPACT BONE Has a much higher density and well-organized osteon system It does not have trabeculae and forms external aspect of the bone It is composed of wafer-like thin layers of bone, lamellae, that are arranged in lamellar systems o Lamellar system consists of: § Outer circumferential lamellae – located beneath the periosteum and surrounding the outside of the entire compact bone § Inner circumferential lamellae – located beneath the endosteum and forming innermost layer of compact bone § Interstitial lamellae – located between the osteons § Concentric lamellae – surround the Haversian canal Haversian system o Osteon – basic unit of the compact bone structure. It is composed of: o Haversian canal through which blood vessels pass o Concentric lamellae o Lacunae – each one of which contains an osteocyte o Canaliculi with small, narrow spaces containing osteocyte processes o A cement line, the thin dense, external bony layer, that surrounds each osteon Contains concentrically arranged lamellae surrounding centrally located Haversian canal Volkmann canals run perpendicular to and connect Haversian canals with each other SPONGY BONE Has a much lower density and contains branching bony trabeculae It usually forms the inner part of a bone, also called medullary bone, can be found at the ends of long bones, between the inner and the outer tables of skull There are no haversian systems, but there are irregular arrangements of lamellae These contain lacunae with osteocytes,that are nourished by diffusion from the marrow cavity, which is filled with bone marrow LECTURE 7_MUSCLE TISSUE Muscle tissue develops from mesoderm Muscle cells have their own nomenclature: o Their cell membranes – sarcolemma o Their smooth endoplasmic reticulum – sarcoplasmic reticulum o Their mitochondria – sarcosomes Muscles are classiefied into two types: o Striated, which display alternating light and dark bands § Skeletal, for voluntary movements § Cardiac, for pumping blood o Smooth, which lack such striations REGENERATION Skeletal muscle – mesenchymal satellite cells, small regenerative cells with a single nucleus, lies within the external lamina of each mature muscle fiber Cardiac muscle – lacks satellite cells, have no regenerative capacity Smooth muscle - is capable of a more active regenerative response, cells undergo mitosis and replace the damaged tissue SKELETAL MUSCLE CELLS Are extremely elongated, unbranched cylindrical, Multinucleated, numerous flattened nuclei, located just beneath the sarcolemma The sarcoplasm has little RER or free ribosomes, is filled with long cylindrical filamentous bundles called myofibrils ORGANIZATION A single skeletal muscle is composed of numerous fascicles (small bundles) The muscle as a whole is enveloped in a strong layer of dense connective tissue – epimysium Each fascicle is surrounded by a sheet of less dense connective tissue – perimysium Each muscle fiber is enveloped by a thin layer of delicate connective tissue – endomysium STRIATION Longitudinally sectioned skeletal muscle fibers show cross-striations of alternating light and dark bands The darker bands – A bands (anisotropic) – rotate polarized light strongly The lighter bands – I bands (isotropic) – rotate polarized light only slightly THE SACROMERE The functional unit of contraction in skeletal muscle, that consists of thin actin and thicker myosin filaments A single sarcomere is delineated by 2 Z lines, containing 1 central A band and 2 I bands on either side of the A band A bands – their center is a lighter zone – H band, at the center of an H band is an M line THIN FILAMENTS They are composed of F – actin, tropomyosin, troponin and associated proteins F – actin – a polymer of G – actin monomers forming a double helix Tropomyosin - molecules, that bind head-to-tail, forming filaments located in the grooves of the F – actin hélix Troponin – is associated with each tropomyosin molecule o It contains: § Troponin T – forms the tail, functions in binding the troponin to tropomyosin § Troponin C – possesses four binding sites for calcium § Troponin I – binds to actin, inhibiting interaction of myosin and actin THICK FILAMENTS Contain 250 myosin molecules, forming antiparallel fashion and three associated proteins – myomesin, titin, C protein Myosin consists of two identical heavy chains and two pairs of light chains Myosin heavy chains – contain a long rod-like „tail” and a globular „head” o Tails function in the self-assembly of myosin molecules into bipolar thick filaments o Actin-binding sites of the heads function in contraction TRIADS Specialized complexes consisting of: o A narrow central T tubule consists of invaginations of the sarcolemma at the A-I junction o On either side of each T tubule are situated terminal cisternae (SER) Function: sequester release calcium TYPES OF SKELETAL MUSCLE CELLS RED FIBERS Aerobic (type I), slow, contract slower but are not fatiqued easily Muscle fibers contain abundant mitochondria They contain a large content of myoglobin – red colour of such fibers WHITE FIBERS Anaerobic (type II), fast, They are designed for fast contractility but are easily fatiqued Contain few mitochondria and relatively little myoglobin Rich in glycogen and glycolytic enzymes „white „ colour of such fibers INTERMEDIATE FIBERS Are between red and white fibers They have intermediate content of myoglobin They contain intermediate number of mitochondria Contraction – fast but not easily fatiqued STELLATE CELLS Lie within the external lamina of skeletal muscle cells Small, regenerative cells Possessing a single nucleus Differentiate, fuse with one another and form skeletal muscle cells when the need arises CARDIAC MUSCLE It is also striated muscle but differs from skeletal muscle in many respects Cardiac muscle cells are short, cylindrical, branching They are about 80 µm in length and 15 µm in diameter The cytoplasm contains a single (occasionally two), centrally placed nucleus At either end of the nucleus, the cell possesses glycogen deposits and triglycerides Approximately 50% of the sarcoplasm is occupied by mitochondria There is a copious amount of myoglobin Contract spontaneously and display a rhythmic beat – modified by hormonal and neural stimuli May branch at their ends to form connections with adjacent cells – intercalated disks Thick and thin filaments form poorly defined myofibrils T tubules are larger, than those in skeletal muscle, are lined by external lamina They invaginate at Z disks SER is poorly defined and forms dyads The atrial cardiac muscle cells contain precursor of atrial natriuretic peptide INTERCALATED DISK Specialized transverse junctions between cardiac muscle cells, where they meet end to end They always coincide with the Z lines Function o Bind the cells o Transmit forces of contraction  o Provide areas of low electrical resistance for the rapid spread of excitation throughout the myocardium Structure o The intercalated disk consists of three types of membrane-to-membrane contact o The transverse portion § The predominant type – the fascia adherens, resembles the zonula adherens but is more extensive and less regular § Desmosomes – occur less frequently o The lateral portion § Is well endowed with gap junctions – facilitate the passage of information between cardiac muscle cells, coordinating contraction – the blood is pumped efficiently out of the ventricles and into the aorta and pulmonary trunk SMOOTH MUSCLE Has neither striations or T tubules Is located in the walls of viscera Is not under voluntary control Is regulated by local factors, hormones, autonomic nervous system Function in contraction and synthesize extracellular matrix macromolecules Classification o Multiunit smooth muscle – in which each cell is innervated individually o Unitary (single-unit) smooth muscle – in which only some of the cells have their own nerve supply LIGHT MICOSCOPY OF SMOOTH MUSCLE Are elongated, fusiform Are generally 200 µm or less in length The single, oval nucleus is located in the center of the cell During contraction, the entire cell twists on itself, the nucleus resembles a corkscrew Have external lamina – it is absent at the sites of gap junction Cells in the micoscopy o Special stains show the slender longitudinal striations – aggregates of myofilaments o Dense bodies act as Z disks are located intracellularly and along the cytoplasmic aspect of the sarcolema STRUCTURE OF SMOOTH MUSCLE CELLS The sarcoplasm contains nucleus, mitochondria, sarcoplasmic reticulum, Golgi apparatus, glycogen deposits Myofilaments are present, they are not associated in the paracrystalline configuration as in striated muscle The thin filaments – similar to those of striated muscle, instead of troponin, caldesmon or calponin The thick filaments – composed of myosin, are each surrounded by as many as 15 thin filaments, the heads of the myosin molecules all point in the same direction CONTRACTILE NONMUSCLE CELLS MYOEPITHELIAL CELLS Arise from ectoderm, can contract to express secretory material from glands into ducts In morphology similar to smooth muscle cells, basket – like shape, several processes Contain actin, myosin, intermediate filaments Present in certain glands MYOFIBROBLASTS Resemble fibroblasts, contain actin and myosin, are capable of contraction Are able to secrete collagen Present in normal tissues but are dominant when tissue undergo repair PERICYTES Smooth muscle – like cells, that surround blood vessels LECTURE 8_NERVE TISSUE The human nervous system is the most complex system in a human body. It is formed by a network of more than 100 million nerve cells – neurons, assisted by many more glial cells. Each neuron has a thousands interconnections with other neurons, forming a very complex system for communication. Neurons are grouped as circuits: Like electronic circuits, neuronal circuits are highly specific combinations of elements that make up systems of various sizes and complexities. A number of Elementary circuits may be combined to form higher-order systems. NERVE CELL (NEURONS) Respond to environmental changes (stimuli) by altering electrical potentials that exits between the inner and outer surfaces of their membranes. cells with this property are called exicable, or irritable. The propagation of the modification of electrical potential is called the action potential or nerve impulse. The action potential is capable of travelling long distances. It transmits information to other neurons, muscles, and glands. CELL BODY The cell body, or perikarion, is the trophic center for the whole nerve cell and is also receptive to stimuli. Is the part of neuron that contains the nucleus and surrounding cytoplasm, exclusive of the cell processes. Most nerve cells have a spherical unusually, large, euchromatic nucleus with a prominent nucleolus. Binuclear nerve cells are seen in symphatetic and sensory ganglia. The chromatin is finely dispersed, reflecting the intense synthetic activity. Contains a highly developed rer organized into aggregates of pararallel cisternae. between the cisternae are numerous polyribosomes. Rer and free ribosomes appears basophilic granular areas called nissl bodies. THE GOLGI COMPLEX Is located only in the cell body and consists o multiple parallel arrays of smooth cisternae arranged around the periphery of the nucleus. MITOCHONDRIA Are scattered throughout the cytoplasm ofthe cell body, and are especially abundant in the axon terminals. NEUROFILAMENTS Intermediate filaments Are abundant in pericarions and cell processes. They form neurofibrils. The neurons also contain microtubules. DENDRITES Multiple elongated processes specialized in receiving stimuli from environment, sensory epitelial cells, or other neurons. Dendrites are usually short and divide like the branches of a tree.  They receive many synapses and are the principal signal reception and processing sites on neurons. Most nerve cells have numerous dendrites, which considerably increase the receptive area of the cell. The arborisation of dendrites makes it possible to receive and integrate a great number of axon terminals from other nerve cells. It has been estimated that up to 200,000 terminations established functional contact with the dendrites of Purkinje cell. Most synapses impinging on neurons are located in dendrite spines – usually mushroom-shaped structures. These spines are the first processing locale for synaptic signals arriving on a neuron. Dendritic spines participate in the plastic changes that underline adaptation, learning & memory. AXON Most neurons have only one axon; a very few have no axon at all. An axon is cylindrical process that varies in length and diameter. Axons of motor cell that innervate the foot muscle – about 100 cm All axons originate from short pyramid-shaped region, the axon hillock. The plasma membrane of the axon is called axolemma, its contents – axoplasm. The portion of the axon between the axon hillock and the point at which myelination begins is called initial segment. Axons have a constant diameter, and branch occasionally, shortly after its departure from the cell body – forming collateral branches. Axoplasm possesses mitochondria, microtubules, neurofilaments and some cisternae of SER. AXONAL TRANSPORT There is a lively bidirectional transport of small and large molecules along the axon. Anterograde flow – continuous transport of macro- molecules and organelles synthesized in the cell body along the axon to its terminals. Retrograde flow – simultaneous with anterograde flow, but in the opposite direction, transport of several molecules, also taken up by endocytosis to the cell body. Motor proteins related to axon flow: o Dynein – a protein with atp-ase activity present in microtubules – anterograde flow o Kinesin – a microtubule-activated atp-ase, promoting anterograde flow of vesicles MOTOR NEURON The neuronal cell body has an unusually large, euchromatic nucleus with a well- developed nucleolus. The perikaryon contains Nissl bodies, which are also found in large dendrites. The myelin sheath is produced by oligo-dendrocytes in the CNS and by Schwann cells in the peripheral nervous system. Motor end-plates, which transmit the nerve impulse to striated skeletal muscle fibers. THE SYNAPSE Presynptic terminal is formed by an axon terminal Synaptic cleft: a thin intercellular space Postsynaptic terminal: a region on the surface of another cell where a new signal is generated. The presynaptic terminal always contains synaptic vesicles with neurotransmitters, and numerous mitochondria. Neurotransmitters are generally sinthesized in the cell body and stores in vesicles in presynaptic region of a synapse. During transmission of nerve impulse they are released into the synaptic cleft by exocytosis. TYPES OF SYNAPSES GLIAL CELLS Glial cells are 10 times abundant in the mammalian brain than neurons. They surround both cell bodies and their axonal and dendrite processes that occupy the interneuronal space. Nerve tissue has only a very small amount of extracelular matrix, so glial cells furnish a microenvironment suitable for neural activity. TYPES OF GLIAL CELLS: OLIGODENDROCYTES: produce the myelin sheath that provides the electrical insulation of neurons in CNS. o Myelin sheath of CNS: The same oligodendrocyte forms myelin sheaths for several (3– 50) nerve fibers. In CNS, processes of other cells sometimes cover the nodes of Ranvier, or there is considerable extracellular space (ES) at that point. SCHWANN CELLS Schwann cells have the same function as oligodendrocytes but are located around axons in the peripheral nervous system. One Shwann cell forms myelin around a segment of one axon, in contrast to the ability of oligodendrocytes to branch and serve more than one neuron and its processes.  Four consecutive phases of myelin formation in peripheral nerve fibers. ASTROCYTES Are star-shaped cells with multiple radiating processes. These cells have bundles of intermediate filaments made of glial fibrillary acid protein (GFAP) that reinforce their structure. Astrocytes bind neurons to capillaries and to pia mater. In addition to their supporting functions astrocytes participate in controlling the ionic and chemical environment of neurons. Some astrocytes develop processes with expanded end-feet that are linked to endotelial cells and are also present at the external surface of CNS, where they make a continuous o Protoplasmic astocytes: with many short-branched processes, are found in grey matter. o Fibrous astrocytes: have few long processes and are located in the white matter. EPENDYMAL CELLS Ependymal cells are low columnar epithelial cell lining the ventricles of the brain and central canal of the spinal cord. In some locations, ependymal cells are ciliated, which facilitates the movement of the spinal fluid. Are low columnar epithelial cell lining the ventricles of the brain and central canal of the spinal cord. MICROGLIA Microglia are small elongated cells with short irregular processes. They have dense, elongated nuclei, with contrast with the spherical nuclei of other glial cells. Microglia, phagocytic cells that represent the mononuclear phagocytic system in nerve tissue, are derived from precursor cells in the bone marrow. When activated, microglia retract their processes and assume the morphologic characteristics of macrophages, becoming phagocytic and acting as antigen-presenting cells. Microglia secrete a number of cytokines and dispose of unwanted cellular debris caused by CNS lesion. LECTURE 9_NERVE SYSTEM When sectioned, the cerebrum, cerebellum and spinal cord show regions of: White matter: the main components is myelinated axons and myelin – producing oligodendrocytes. White matter does not contain neuronal cell bodies. Gray matter: contains neuronal cell bodies, dendrities and the initial unmyelinated portions of axons and glial cells. This is the region abundant in synapses. Gray matter is prevalent at the surface of the cerebrum and cerebellum, forming the cerebral and cerebellar cortex, whereas white matter is present in more central regions Aggregates of neuronal cell bodies forming islands of grey matter embedded in the white matter are called subcortical nuclei. CEREBRAL CORTEX In the cerebral cortex the grey matter has 6 layers of cells with different forms and sizes. The majority of cerebral neurones are pyramid-shaped cells. THE CEREBELLUM The cerebellar cortex has 3 layers: An outer molecular layer A central layer of large Purkinje cells with highly developed dendrites occupy most of the molecular layer An inner granular layer is formed by very small neurons, which are compactly disposed THE SPINAL CORD In cross sections of the spinal cord, white matter is peripheral and grey matter is central, assuming the shape of an H. o In the horizontal bar of this H is an opening the central canal, which is remnant of the lumen of the embryonic neural tube, lines with an ependymal cells. o The grey matter of the legs of the H forms anterior and posterior horns o Anterior horns contain motor neurons whose axons make up the ventral roots of the spinal nerves o Posterior horns receive sensory fibers from neurons in the spinal ganglia (dorsal roots) MENINGES DURA MATTER The dura mater is the external layer and is composed of dense connective tissue continuous with the periosteum of the skull The dura mater that envelops the spinal cord is separated from the periosteum of the vertebrae by the epidural space, which contains thin walls vein, loose connective tissue, and adipose tissue The dura mater is separated from the arachnoid by the thin subdural space. The internal surface of the dura mater and its external surface of the spinal cord is covered by simple squamous epithelium of mesenchymal origin. ARACHNOID Has two components: o A layer in contact with dura mater o System of trabeculae connecting the layer with the pia mater Subarachnoid space – form by the cavities between trabeculae and filled with cerebrospinal fluid. This space form a hydraulic cushion that protects the CNS from trauma. This space communicates with the ventricles of the brain. The arachnoid is composed of connective tissue devoid of blood vessels. The simple squamous epithelium covers its surfaces. PIA MATTER The pia mater is a loose connective tissue containing many blood vessels. The pia mater is not in contact with nerve cells or fibers. Between the pia mater and the neural elements is a thin layer of neuroglial processes, adhering to the pia mater and forming a physical barrier at the periphery of the CNS. This barrier separates the CNS from the cerebrospinal fluid. The pia mater, covered by squamous mesenchymal cells follows all the irregularities of the surface of the CNS and penetrates to some extent along with the blood vessels. BLOOD VESSELS Blood vessels penetrate the CNS through tunnels covered by pia matter - the perivascular spaces. The pia matter disappears before the blood vessels are transformed into capillaries. In the CNS the blood capillaries are completely covered by expansions of the neuroglial cell processes. Blood-brain barrier o The blood-brain barrier is a functional barrier that prevents the passage of some substances, such as antibiotics from the blood to nerve tissue. o Occluding junctions, which provide the continuity between the endothelial cells of these capiliaries, represent the main structural component of the barrier. o The cytoplasm of these endothelial cells does not have the fenestrations found in many other locations, and very few pinocytic vesicles. o The expansions of neuroglial cell processes that envelop the capillaries are partly responsable for their low permeability. CHOROID PLEXUS The choroid plexus consists of invaginated folds of pia mater rich in dilated fenestrated capilaries It is found in the roofs of III and IV vetricles and in part in the walls of the lateral ventricles. The choroid plexus is composed of loose connective tissue of the pia mater, covered by a simple cuboidal or low columnar epithelium made of ion-transporting cells.  The main function is to elaborate cerebrospinal fluid, which is important for the metabolism and the protection of CNS, and completely fills: o The ventricles o Central canal o Subarachnoid space o Perivascular space. CEREBROSPINAL FLUID Cerebrospinal fluid is: o Clear o Has a low density (1.004 – 1.008 g/ml) o A few desquamated cells o 2-5 lymphocytes Cerebrospinal fluid is continuously produced and circulates through the ventricles, from which it passes into the subarachnoid space, where is absorbed into the venous circulation. PERIPHERAL NERVOUS SYSTEM Nerve fibers consist of axons enveloped by a special sheath derived from cell of ectodermal origin. In peripheral nerve fibers, the sheath cell is the schwann cell In central nerve fibers the sheath cell is the oligodendrocyte UNMYELINATED NERVE FIBERS Axons of a small diameter In the peripheral system all are enveloped within simple clefts of the schwann cells Schwann cell can sheat many unmyelinated axons Unmyelinated nerve fibers do not have nodes of ranvier, because abutting schwann cells are united to form a continuous sheath. In the brain and spinal cord, numerous unmyelinated axonal processes run free among the other neuronal ad glial processes MYELINATED NERVE FIBERS Progressively thicker axons are generally sheated by increasingly numerous concentric wrappings of the enveloping cell The plasmolemma of the covering shwann cell winds and wraps around the axon and form myelin. Myelin consists of many layers of modified cell membranes, with a higher proportion of lipids in comparison to other cell membranes. The myelin sheath shows gaps along its path called the nodes of Ranvier. Interdigitating processes of schwann cells partially cover the node. In the cns the processes of the oligodendrocytes form the myelin sheath. The different branches of one oligodendrocyte can envelop segments of several axons. NERVES In the peripheral nervous system, the nerve fibers are grouped in bundles to form the nerves. Nerves have an external fibrous coat of dense connective tissue called EPINEURIUM, which also fills the space between the bundles of nerve fibers. Each bundle is surrounded by the perineurium, a sleeve formed by layers of flattened epithelium like cells.  Within the perineurium sheath run the Schwann cell-sheated axons and their enveloping connective tissue, the endoneurium – consists of a thin layer of reticular fibers produced by Schwann cells. Afferent fibers carry the information to the CNS, while efferent fibers carry the information from the CNS to the effector organs GANGLIA Ganglia are ovoid structures containing neuronal cell bodies and glial cells supported by connective tissue with one nerve entering and one exiting each ganglion. The direction of the nerve impulse determines whether the ganglion is sensory or an autonomic. Sensory ganglia: o Cranial ganglia – associated with cranial nerves o Spinal ganglia – associated with the dorsal root of the spinal nerves, comprise large neuronal cell bodies (pseudounipolar cells) surrounded by abundant small glial cells called satellite cells. Autonomic ganglia – appear as bulbous dilatations in autonomic nerves, when located within certain organs are called-intramural gangia, devoid of connective tissue capsules. LECTURE 10_CIRCULATORY SYSTEM The circulatory system pumps and directs blood cells and substances to all tissues of the body. It includes both the blood and lymphatic vascular system. The cardiovascular system consists of the following structures: Heart: propels blood through the system. Arteries: vessels of efferent from the heart, become smaller as the branch into the various organs, carry blood to the tissues. Capillaries: the smallest vessels, sites of O2, CO2, nutrient and waste product exchange between blood and tissue. Capillaries in almost every organ form a complex network of thin, anatomizing tubules, microvasculature. Veins: result from the convergence of venues into a system of venues into a system of larger channels, which they carry the blood to be pumped again. HEART Cardiac muscles in the four chambers of the heart wall contracts rhythmically. The right and left ventricles propel blood to the pulmonary and systemic circulation, respectively. The right and left atria receive blood from body and the pulmonary veins, respectively. Three major layers: Endocardium, thin inner layer endothelium and supporting connective tissue, a middle myoelastic layer of smooth muscles fibers and connective tissue. And a deep layer of connective tissue, subendocardial layer. The thickest layer, myocardium, cardiac muscle with its fibers arranged spirally around each heart chamber. The myocardium is much thicker in the walls of the ventricles, particularly the left. Epicardium is simple squamous mesothelium, supported by a layer of loose connective tissue containing blood vessels and nerves. The epicardium is the parietal layer lining the pericardium. Helping coordinate the heartbeat as electrical insulation between atria and ventricles. Within the subendocardial layer and adjacent myocardium, modified cardiac muscle cells make up the impulse conducting system of the heart. This system consists of two nodes of specialized myocardial tissue in the right atrium: the SA node (pacemaker) and AV node, followed by the AV bundle. And subendocardial conducting network. Both the parasympathetic and sympathetic neural components innervate the heart. Ganglion is nerve cell and nerve fibers are present in the regions close to the SA and AV nodes. Stimulation does the parasympathetic division (CN X) slows the heartbeats, whereas stimulation of the sympathetic nerve accelerates activity of the pacemaker (SA node). TISSUES OF THE VASCULAR WALL Wall of all blood vessels, contains connective tissue in addition to the endothelial lining. Smooth muscle fibers occur in the walls of all vessels larger than capillaries. In arterioles and small arteries, the smooth muscle cells are connected by more gap junctions and permit vasoconstriction and vasodilation. The endothelium is specialized epithelium that acts as semipermeable barrier between twelve major internal compartments: the blood and the interstitial fluid. Vascular endothelial cells are squamous, polygonal and elongated with long axis in the direction of blood flow. Endothelial cells have several other functions: The endothelium presents a non thrombogenic surface on which blood will not clot and actively secreted agents that control local clot formation. The cell regulate local vascular toner and blood flow by secreting various factors that stimulate smooth muscles contraction (ACE) or relaxation (NO or prostacyclin). Endothelium has several roles in inflammation and local immune responses. In venues endothelial cells induce specific white blood cells to stop. Endothelial cells also secrete various factors, interleukins that affect the activity of local white blood cells during inflammation. Under various conditions endothelial cells secrete serious growth factors, including proteins promoting proliferation of specific white blood cell lineages amend cells that make up the vascular wall. Vascular endothelial growth factor (VEGF) stimulate formation of the vascular system from embryonic mesenchyme (vasculogenesis) and promote capillary sprouting and outgrowth from small existing vessels (angiogenesis) during normal growth , during tissue repair and regeneration. Collagen fibers are found in the subepithelial layer (endocardium), between the smooth muscle layers and in the outer covering. Elastic fibers provide the resiliency required for the vascular wall to expand under pressure. Elastin is a major component in large arteries where. TUNICA INTIMA Consists of the endothelium and a thin subendothelial layer of loose connective tissue sometimes containing smooth muscle fibers. In arteries the intimate includes a thin layer, the internal elastic lamina composed of elastin, with holes allowing better diffusion of substances from blood deeper into the wall. TUNICA MEDIA Consists of concentric layers of helically arranged smooth muscle cells. Interposed are variable amounts of elastic fibers and elastic lamellae, reticular fibers and proteoglycans, all of which are produced by the smooth muscle cells. In arteries the media may also have an extra elastic lamina separating it from the outermost tunic. TUNICA ADVENTITIA Is connective tissue principally of type i collagen and elastic fibers. Is continuous with and bound to the stroma of the organ through which the blood vessels runs. The vasa vasorum are required to provide metabolites to cells in those tunics in larger vessels because the wall is too thick to be nourished solely by diffusion from the blood in the lumen. The adventitia of larger vessels also contains a network of unmyelinated autonomic nerve fibers, the vasomotor nerves, which release the vasoconstrictor norepinephrine. The density of this innervation is greater in arteries than in veins. VASCULATURE ELASTIC ARTERIES aorta, pulmonary artery and their larger branches, the conducting arteries. The most prominent feature is the thick tunica media in which elastic lamellae alternate with layers of smooth muscle fibers. The tunica intima is well developed, with smooth muscle cells in subendothelial connective tissue. Between the intimate and the media is the internal elastic lamina, is more well-defined than the elastic laminae of the media. The adventitia is much more thinner than the media. ARTERIAL SENSORY STRUCTURES Carotid sinuses are slight dilations of the bilateral internal carotid arteries where they branch from the (elastic) common carotid arteries; they act as important baroreceptors monitoring arterial blood pressure. The brain’s vasomotor centers process these afferent impulses and adjust vasoconstriction, maintaining normal blood pressure. These structures are part of the autonomic nervous system called paraganglia with rich capillary networks. The capillaries are closely surrounded by large, neural crest-derived glomus cells filled with dense- core vesicles containing dopamine, acetylcholine, and other neurotransmitters, which are supported by smaller satellite cells. MUSCULAR ARTERIES Distribute blood to the organs and help regulate blood pressure by contracting or relaxing the smooth muscle in the media. The intima has a thin subendothelial layer and a prominent internal elastic lamina. The media may contain up to 40 layers of large smooth muscle cells interspersed with a variable number of elastic lamellae. The external elastic lamina is present only in the larger muscular arteries. The adventitia connective tissue contains lymphatic vessels capillaries, vasa vasorum and nerves, all of which may penetrate to the outer part of the media. ARTERIOLES Muscular arteries branch repeatedly into smaller and smaller arteries. The smallest arteries branch as arterioles. Have only one or two smooth muscle layers; these indicate the beginning of an organ’s microvasculature where exchanges between blood and tissue fluid occur. The subendothelial layer is very thin, elastic laminae are absent, and the media consists of the circulatory arranged smooth muscle cells. In both small arteries and arterioles the adventitia is very thin and inconspicuous. At the ends of arterioles the smooth muscle fibers act as sphincters and produce periodic blood flow into capillaries.  Muscle tone normally keeps arterioles partially closed. Resisting blood flow, which makes these vessels the major determinants of systemic blood pressure. CAPILLARY BEDS Capillaries permit and regulate metabolic exchange between blood and surrounding tissues. These smallest blood vessels always function in networks called capillaries beds. The density of the capillary bed is related to the metabolic activity of the tissues, tissues with high metabolic rates, such as the kidney, liver and cardiac and skeletal muscle, have abundant capillaries. Capillaries branch from the metarterioles, which are encircled by scattered smooth muscle cells, and converge into the thoroughfare channels, which lack muscle. Capillaries are composed of the simple layer of endothelial cells rolled up as a tube surrounded by basement membrane. The average diameter of capillaries varies from 4 to 10 μm. TYPES OF CAPILLARIES CONTINUOUS CAPILLARIES, well-regulated metabolic exchange across the cells. The most common and is found in muscle, connective tissue, lungs, exocrine glands and nervous tissue. FENESTRATED CAPILLARIES the endothelial cells are penetrated by small circular openings. Some fenestrations are covered by very thin diaphragms of proteoglycans. Are found in organs with rapid interchange of substances, such as the kidneys, intestine, choroid plexus, and endocrine glands. DISCONTINUOUS CAPILLARIES sinusoids, maximal exchange of macromolecules as well as allow easier movement of cells between tissues and blood. The endothelium has large perforations and irregular intercellular clefts. Sinusoidal capillaries of this type are found on the liver, spleen, some endocrine organs, and bone marrow. CELLS OF CAPILLARIES ENDOTHELIAL CELLS Simple squamous epithelial cells of mesenchymal origin, elliptical nucleus bulges out into the lumen, cytoplasm contains AG, RER, free ribosomes and few mitochondria, large number of pinocytotic vesicles PERICYTES Small, mesenchymal cells scattered along capillaries, long primary processes are located along the long axis of the capillary and from which secondary processes arise to wrap around the capillary. VENULES The transition from capillaries to venules occurs gradually. Postcapillary venules are similar to capillaries with pericytes but larger. Postcapillary venules converge into larger collecting venules that have more distinct contractile cells. Increasing size venules become surrounded by a tunica media with two or three smooth muscle layers and are muscular venules. VEINS Veins carry blood back to the heart from microvasculature all over the body. Most vends are classifies as small or medium veins, with diameters of 10 mm or less. The tunica intima is usually thin, the media has a small bundles of smooth muscle cells and delicate elastic fibers, and the collagenous adventitial layer is thick and well developed. The big trunks, are the large veins. These have well-developed intimal layers, but thin media with alternating smooth muscle and connective tissue. The tunica adventitia is thicker than the media in large veins. Both the media and adventitia contain elastic fibers, and an internal elastic lamina. Important feature of large and medium veins are valves, consists of thin, paired folds of the tunica intima projecting across the lumen, rich in elastic fibers and covered on both sides by endothelium. LECTURE 11_ENDOCRINE SYSTEM The endocrine system produces various secretion called hormones that serves to regulate the activities of various cells, tissues and organs in the body. Those hormones are classified into: Proteins and polypeptides – insulin, glucagon, FSH Amino – acid derivatives – thyroxine, epinephrine, norepinephrine Steroid and fatty acid derivatives – testosterone, progesterone Endocrine glands are aggregates of epithelioid cells that are embedded in connective tissue. Endocrine cells are typically epithelial, at least in origin, and aggregated as cords or clusters. Hormones, like neurotransmitters, are frequently hydrophilic molecules such as proteins. THE PITUITARY GLAND (HYPOPHYSIS) It’s formed in the embryo partly from the neuroectoderm (posterior pituitary) and partly from the developing oral cavity (anterior pituitary). Endocrine and neuroendocrine control of other endocrine glands. Regulatory feedback system. ADENOHYPOPHYSIS (ANTERIOR PITUITARY) PARS DISTALIS 75% of the adenohypophysis and has a thin brows capsule. Main components are cords of weel-stained endocrine cells intersected with fenestrated capillaries and supporting reticular connective tissue. Two broad groups of cells in the pars distalis with different staining: chromophils and chromophobes. Chromophils (poorly stained) are secretory cells in which hormone is stored in cytoplasmic granules. o Basophils: dark blue or purple (granule content) o Acidophils: pale pink, eosinophilic Secrete two different glycoproteins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). PARS INTERMEDIA Located between the pars anterior and the pars nervosa Not well developed in human Contains colloid-filled cysts, pouch and clusters of basophils producing pro-opiomelanocortin PARS TUBERALIS A smaller funnel-shaped region surrounding the infundibulum of the neurohypophysis. Most of the cells of the pars tubercles are gonadotrophs. (GnRH/LH/FSH) CELLS ACIDOPHILS The most abundant cells of pars distalis Pinkish – staining cells with acidic dyes Produce:  o growth hormone (somatotropin) – the cells are called somatotrophs o prolactin – the cells are called mammotrophs BASOPHILS More abundant in the core of the pars distalis Purple – staining cells with basic dyes Three subtypes are represented: o corticotrophs – which secrete adrenocorticotropic hormone – ACTH o thyrotrophs – which secrete thyrotropin – TSH o gonadotrophs – which produce follicle stimulating hormone and luteinizing hormone FSH and LH CHROMOPHOBES Possess little cytoplasm Possess few secretory granules and do not take up histologic stains They are probably chromophils that have released the contents of their secretory granules They may be stem cells The most prominent cells are folliculostellate cells – function is unknown NEUROHYPOPHYSIS (POSTERIOR PITUITARY) Consists of the pars nervo