Histology Exam 1

#separator:tab #html:true Histologystudy of the microscopic structure of biological material and the ways in which the individual components are structurally and functionally related. A clear understanding of the fine structure and molecular organization of cells greatly improves comprehension of biochemical and physiological processes CellsSimple vs. Compound Tissue Simple - epithelial (SAME cells repeated) Compound Tissue - Exocrine Pancreas Gland Tissue (VARIETY of cells) Organ"E.g. heart, liver, lungs (consist of a number of cell and tissue types all acting co- operatively)" Organ SystemCirculatory System, Resp system, Digestive Several organs and tissues that may be either close together of dispersed but they co-operate to perform a function Cells (Definition)The individual units which function as the building blocks of most biological materials cells are now classified into one of eight groups based on function not morphology Epithelial TissuesCover surfaces, line body cavities and form solid glands w barriers absorb and secrete tightly bound by cell-cell junctions Support Cellsfibrous support tissue, cartilage and bone organize and maintain body structure. Also produce and interact with the extracellular matrix Contractile Cellsmuscle and contractile cells involved in movement via filamentous proteins organized to create contraction Nerve Cellsbrain, spinal cord and nerves allow direct cell-cell communication via the release of chemical messengers (neurotransmitters) Germ Cellsspermatozoa and ova allow reproduction via possession of half chromosomal content Blood Cellscirculating red and white cells permit oxygen transport and defense Immune Cellslymphoid tissues (nodes and spleen) are involved in recognition and destruction of foreign material Hormone Secreting Cellsvariety of tissues including thyroid and adenoid cells allow indirect cell-cell communication via the secretion of chemical messengers termed hormones Cell Biology- Structure, phys, biochem and genetics - fine structures visualised by light microscopy - specifc cell structures visualised by using antibodies directed against specific protein/subcellular components Anatomy- physical structure of an organism Embryologyorigins of cell sytems and many diseases abnormalities can be connected w final histological developement Pathologylinked to systems histology most disease processes are associated w histological abnormalities Scapelsdirectly accessible tissues e.g. skin, mouth, nose, uterine cervix Needle Biopsysolid organs e.g. CNS, endocrine system, skeletal muscle Endoscopic TubesAlimentary, respiratory and urinary Flexible Cannulaealong blood vessels Wax-embedded sections- Resolution of approximately 0.6 nano m - Cheap, simple and easy, may destroy components - 24 h - Used for routine sampling e.g. PAP smear - Fixation in preservative solution followed by progressive dehydration (using increasing concentrations of alcohol) and embedding of tissue in molten paraffin wax - The tissue can then be cut into sections using a microtome - Wax is removed and section rehydrated through decreasing percentages of alcohol in wate Frozen Sections- Used for immunohistochemistry - Fast (5 minutes) - Used when a rapid decision is needed e.g. when a patient is still on the operating table - frozen water preserves structures better - Sample is first frozen by immersion in liquid nitrogen - Cutting of thin sections (5-10 um) done using a microtome housed in a refrigerated cabinet (cryostat) Other Methods"-Involve usage of harder embedding materials as these provide thinner sections, higher resolution and little tissue shrinkage - Include resin (0.5-2.0 m sections), which is often used in examination of mineralized bone, acrylic (similar methodology to paraffin wax 1-2m sections) and epoxy - (0.5-1 m sections used for electron miscroscopy" Hematoxylin and Eosin (H&E)- Hematoxylin (purple-black) stains nuclei and eosin (red) stains cell components Simple, reliable and inexpensive Van Giesen (EVG)differentiates support cell fibers - Elastic fibers (brown-black) - Collagen fibers (pinkish-red) - Muscle (yellow) Example of a trichrome stain Silver Methods- Certain biological components reduce silver nitrate to silver (black) Demonstrates range of structures esp. reticulin fibers and nerves May-Grunewald-GiemsaSmear preparations of blood and bone marrow cells Toluidene Bluestains nuclei of white blood cells blue Chemical Groups- Periodic acid Schiff (PAS) stain - stains carbohydrates and glycoproteins magenta and is used to delineate basement membranes and neutral mucins of epithelial cells - Sudan black or oil red O - stain lipids Specific Enzymes- Presence determined by adding to incubating solution and examining color change - Used for acid and alkaline phosphatases, dehydrogenases, ATPases and carried out on frozen sections ImmunocytochemistryThe high specificity of antibodies for their target is used to detect presence of specific cell molecules in tissues - Two types of antibody are used (polyclonal and monoclonal) Polyclonal Antibodies"- Obtained by inoculating purified protein into an animal several times - Each inoculation increases the amount of antibody against that protein i.e. boosts its memory - On harvesting the serum this now contains a mixture of antibodies, many of which are effective against the target - Disadvantage: somewhat “hit and miss” as many antibodies will not recognize target; as a result most tests now employ monoclonal antibodies" Monoclonal Antibodies<div><div>- Produced by inoculating mouse several times intraparentally/ intravenously with purified protein - Using this route ensures mouse will now “process” the protein by taking it to the spleen cells rather than a local lymph node - Mouse is sacrificed and its spleen cells fused with immortal myeloma cells (cancerous white cells) - when fused together the result is a cell that is able to eternally produce antibodies in tissue culture - Advantage: once the spleen: myeloma cell hybrids, called hybridoma, have been identified large amounts of specific antibodies against the target protein can be mass produced<div></div></div></div><div></div> Normal Cell Nuclei- Active cells – large, pale-staining nucleus - Inactive cells – compact, round, intensely staining no nucleoli Normal Cell Cytoskeletonmicrofilaments, intermediate filaments and microtubules Microfilaments"(5 nm) - made of actin (5%) of cell protein these provide mechanical support, stabilization of cell protrusions (e.g. microvilli), communication networks with other cells and motile forces (with myosin)" Intermediate Filaments"(10 nm) - made of six main proteins that vary between cells are anchored to special sites of membrane called desmosomes and hemidesmosomes" Microtubules(25 nm) – are composed of tubulin and organize cell division, transport of molecules around the cell and are important in ciliary function Normal Cell CytoplasmPink = organelles taking up acidic dyes (usually mitochondria or granules) o Purple = active protein production. Stain for RNA o Lipofuscin Lipofuscin"Orange brown wear and tear pigment autophagy of worn out cell components; organelles are wrapped in ER and then fused with a lysosome Most common in long-lived cells e.g. nerve, heart muscle and liver and those of the elderly" Normal Non-Staining AreasStored in cells as non-membrane bound vacuoles (Fat or Mucin) o Clear spaces in cytoplasm (wax sections) or may be stained with dyes (frozen sections) Level 1  - Mild Injury to Cell Components- reversible changes      - swelling of membrane bound organelles      - accumulation of elctrolytes and water -  when stimulus is removed, damage is cleared out by autophagy - damage to desmosome and hemi = roll up in ball to protect cell, recovery = re-expand Level 2 - Severe Injury- Cellular Degeneration - cloudy swelling (ER and Mitochondria) - hydrobic degeneration = water logging, pale cells - fatty changes = fatty acid build up and triglycerides (non-staining areas) Mitochondria Damagelevel of mitochondria damage will determine cell death ApoptosisProgrammed cell death FEW mitochondria normal to eliminate worn out cells NecrosisMANY MITOCHONDRIA pyknosis = nuclear condensation karolysis = nucleus into pieces no cytoplasm definition plasma membrane edges are indistinct Increased Cell Mass- As a consequence of cell division (hyperplasia) - As a consequence of increase in cell size (hypertrophy) - May be normal e.g. hypertrophy of muscle fibers occurs following “working out” and both occur during menstrual cycle - Tissue showing these features may not therefore be abnormal but usually is when combined with abnormal cells Reduction of Cell Mass- Tissue has undergone atrophy - Lost cells are either replaced by adipose or fibrous tissue (maintains size) - May be normal in which case it is termed involution e.g. thymus undergoes conversion to fat with age - Abnormal atrophy may result from o Lack of use (e.g. muscle) o Loss of blood supply (e.g. ischemic atrophy of kidney) o Lipofuscin is usually present Changes in Cell Differentiation"- Cells may adapt to stresses in their environment by altering their appearance (metaplasia = replace one w another) to survive (Fig. 6.6, page 65) o E.g. smokers’ airways, acid reflux in esophagus - Usually epithelial tissue - Removal of stimulus may allow reversion to normal - Non-removal of stimulus may allow progression to neoplasia = abnormal growth uncontrolled" Cellular Atypia and Dysplasia- May be as a result of rapid multiplication to replace damaged cells; if damaging stimulus is removed atypical cells disappear - Dysplasia (proliferation of immature cells) = cancer precursor - Neoplasia is when this situation progresses to tumor formation Fixing the Damage- Inflammation is always the first response to cell and tissue damage and serves to - Destroy or contain damaging agent - Initiate repair processes - Return damaged tissue to functionality Vascular Dialation- relaxation of smooth muscle of blood vessels, increasing their diameter and allowing immune cells, fluid and proteins to access the area o Also results in swelling of the tissue (edema) Endothelial Activation- allows immune cells and proteins to escape o Increases permeability of blood vessels o Decreases “smoothness” of endothelium, changing it to a “bumpy road” consistency and further slowing speed of blood in area Neutrophil Activation(~75% of white cells; phagocytic) o Cells move more and more slowly in circulation as they become more and more attached to the endothelial surface o Increased ability to squeeze through (diapedesis) vessel wall o Increased killing capacity once inside target tissue Supprative Inflammationusually bacterially-mediated and resulting in formation of necrotic tissue and pus (contains bacteria and neutrophils both live and dead) Fibrous Inflammationusually associated with membrane-lined cavities e.g. around lungs, heart or abdomen and characterized by secretions containing large amounts of sticky protein mats Serous Inflammation<div><div>usually in skin in response to a burn; associated with accumulation of thin, protein and cell-free fluid</div></div> Inflammation Depends On- Level of damage to tissue - Capacity of cells within tissue to divide and replace damage (regeneration) - Type of agent producing damage Inflammation Resolution- Can only occur if framework of tissue is intact and tissue involved has cells able to replace those lost - E.g. skin cells following a burn or peripheral nerves Inflammation Healing- fibrosis (scarring) - Occurs following substantial damage - Dead and damaged tissue is removed by phagocytic macrophages - “Gap” filled in using granulation tissue; consists predominantly of inelastic protein called collagen - Produces scar; fibrous scar - Structural integrity reestablished but not same as original tissue Abscess Formation- Inflammatory response can’t remove cause of damage - Effectively a way of “sending agent to jail” - “Jail” is produced by fibrous tissue and contains pus component Chronic Inflammation- Injurious agent persists over a long period - Immunosuppressed individual - Poor access of immune cells (unable to clear agent) - Usually heals by formation of fibrous tissue (fibrosis Origin of Human Organ SystemsOne day after fertilization, the zygote divides by mitosis to produce a pair of blastomeres, which then divide every 20 hours until a 16- celled morula is formed Morulaattaches to the uterine wall 3-4 days later and cell division continues forming a blastocele (cavity) in the center of the ______; the two cell types present will already have very different finishing points Embryoblast Cellscells inside the blastocele become the embryo Trophoblast Cellscells on the outside of the blastocele will become the chorion (embryonic component of the placenta) Implantation of Embryooccurs at around 5-6 days after fertilization and new capillaries are stimulated in the uterus, by the chorion, to feed the developing embryo Days 7-12trophoblast cells help to develop the blood pools of the placenta whilst the embryoblast cells divide again to produce two distinct layers - Upper cells = embryo and amniotic cavity - Lower cells = yolk sac Two Weeks After Ovulationgastrulation begins; blood and blood vessels of the embryo are formed first and the yolk sac begins to produce hemopoetic, non-nucleated blood cells The embryo now becomes attached by a connecting stalk of cells (later the umbilical cord) to the placenta Day 16true gastrulation begins with the formation of a primitive streak and develops the embryo into a three-layered disk of autoderm, mesoderm and yolk sac Day 16 Autoderm"altered by chemicals secreted by the central mesoderm into ectoderm; this grows very rapidly forming the first true organs of the early nervous system (days 17-19) and thickens into an area termed the neural groove" Day 16 Mesoderm"by ~3 weeks this area condenses into 1-3 pairs of somites on either side of the neural groove; these initially produce the endocardium and the two embryonic heart tubes" Yolk sac"<div><div>embryonic endoderm, which is already producing hemopoetic cells, will later form linings of mucosa and glands</div></div>" Week 2-3"- Primary neurulation begins with ectoderm forming into a neural groove, and associated raised edges termed neural folds - Secondary neurulation produces the spinal cord - Blood vessels and blood cells form (hemopoesis and angiogenesis) - Endocardial cells form into two tubes (early heart)" Week 3-4"- Neural folds migrate towards each other in several places eventually fusing to form a neural tube; at either side are neural crest cells - Eye and ear begin forming - Heart forms and begins beating, septa appear - Cells of first liver and then digestive system form" Week 4-5"- Early skin forms - Brain differentiates into forebrain, midbrain and hindbrain - Heart fills with blood, circulatory system well developed - Respiratory system (lung buds) and lymphatic system initiated - Thyroid and digestive system (stomach, intestines, gallbladder and pancreas) begin to form" Week 5-6"<div><div><div><div>- Ear and eye formation complete; smell is first sense acquired – Mouth and nose begin to form, teeth initiated – Adenohypophyseal pouch (precursor to pituitary) forms – Cartilaginous skeleton forms – Esophagus, trachea, larynx and bronchi form – Semilunar valves of heart form; heart now four chambers – Kidneys form and produce urine – Upper limb formation begins; arms will be made first<div></div></div></div><div></div><div></div></div></div><div><div></div><div></div> </div>" Week 6-8"- Lower jaw forms – Lower limbs form with toes made last; hand differentiates – Muscles wrap around skeleton – Gonadal formation – Intestines migrate into abdomen" Week 8-9"- Primary ossification of cartilage into bone - Genitalia form" Week 10-11"- Brain and digestive system structure completed - Vocal cords form - Liver, pancreas and thyroid all fully functional - Fingernails grow and facial hair develops" Week 12"- Sex organs completed - Lungs allow inhalation and exhalation - Spleen now fully functional - Sweat glands appear - Body hair develops" Week 14toenail growth Week 16eye migration and reflex development Week 18 Egg production by female fetuses, uterine formation Week 20final hardening of skeleton, bones of ear form, true skin Week 32Immune system develops Week 34 Skin develops blood vessels Ectoderm"Outer Epidermis =  hair, nails, sebaceous, glands, olfactory and mouth epithelium*, lens and cornea Neural crest  = PNS, melanocyte, adrenal medulla, teeth dentine, facial cartilage Neural tube =  CNS, neural pituitary and retina" Mesoderm"Chordamesoderm  = Spinal column Paraxial Skeletal muscle, cartilage, bones, skin dermis Intermediate Lateral Plate = Urinogenital system, Heart, blood cells, digestive  respiratory muscles Limb bones Head =  Support tissue and musculature" EndodermDigestive tube, Pancreas, Mucosa Pharynx ,Thyroid, Glands Respiratory tube Lung cell (alveolar) Comparative Embryology- Organ systems may resemble those in other organisms o Experimental evidence with these alternative systems may supply information as to developmental defects TeratologyInvolves genetics, chemicals etc that can induce changes in functioning or appearance of body systems Cell-Cell Communication in Developement- All organ tissues consist of an epithelium plus an associated mesenchyme component e.g. skin = epithelium plus dermis o Their interactions determine their functionality Embryological Origin of Epithelial Cells"Ectoderm forms the skin, lining of mouth, anus and nose Mesoderm forms the kidney epithelium Endoderm forms the mucosal surfaces and glandular linings" Functionality of Epithelia"Cells form a sheet which behaves as if it were a single functional unit. They are maintained as such by cells having close contact with both each other and the underlying basement membrane (extracellular matrix). Adherence is mediated by cell matrix proteins and cell junctions (specialized areas of cell membrane through which cells communicate with each other and the basement membrane)" Occluding Junctions (Tight Junctions)- Impermeable barrier preventing diffusion of molecules between adjacent cells and lateral movement of cell membrane proteins Evident in cells with secretory or absorptive roles (e.g. gut), intramembranous proteins (sealing strands) wrap round neighboring cells Anchoring Junctions"- Provide mechanical stability to groups of epithelial cells. Cell –cell interactions – mediated by adherent junctions (join cells by linking their actin filaments) and desmosomes (bundles of intermediate filaments attached to adjacent cells by desmogleins) Cell - > basement membrane interactions – mediated by focal contacts (join cells’ actin proteins to basement membrane via integrins) and hemidesmosomes (resemble desmosomes and attach to the basement membrane via link proteins)" Communcation Junctions<div>- Circular patches containing several hundred pores that allow cell-cell diffusion of molecules and facilitate communication Important in cardiac and smooth muscle where they pass contraction signals between cells (low levels in other places)<div></div></div><div></div> Epithelial Cell Surface SpecializationsIncreasing surface area Important as there is restricted space for absorption and secretion Microvilli- Finger-like procections (smaller form of a villus) that are found in most epithelial cells but developed in kidney tubule and small bowel (brush border) They also play an important role as stereocilia sensory cells in the ear and in taste bud and olfactory receptor cells Basolateral Folds- Deep folds in surface of cell result in “striped” appearance or striated epithelium found in renal tubular glands, ducts of secretory glands These are often associated with numerous mitochondria that are responsible for pumping ions in and out of the cells Membrane Plaques- Rigid areas of apical cell membrane fold into cell when bladder is empty and unfold to increase surface area when bladder is full; only in bladder epithelium (uroepithelium) New studies have suggested that the presence of these structures is essential to maintain fluid content inside the bladder; animals with defective plaques leak fluid out and lose urea back into the circulation Epithelial cell surface specializations – Moving fluid and cells; Cilia"Hair-like projections 0.25m in diameter with a “9+2” arrangement of microtubules found in respiratory tract, fallopian tube, sperm <img src=""Screen Shot 2023-09-24 at 8.12.38 PM.png"">" Problems With Cilliary Functions - Kartagener's Syndrome"<div>1:32,000 live births Major defect is usually in dynein arm of cilia; since this affects whole of respiratory tract as well as sperm motility and fallopian tube movement patients usually have sterility issues as well as chronic infections As ciliated tissue is also involved in location of the body organs, there may also be situs inversus (where the lungs, heart etc are swapped over) Patients present with chronic nasal, sinus and ear infections from childhood Recurrent nasal symptoms may also be associated with diminished sense of smell and hearing loss can occur if the infections are not treated promptly with antibiotics There is often a series of chronic bronchial infections and poor oxygenation (clubbing of fingers may be seen) <div></div></div><div><div> </div></div>" Types of Epithelial Tissue - Simple Epithelium(single layers of cells) Allow absorption and/ or secretion to occur Simple Squamous"<img src=""Screen Shot 2023-09-24 at 8.15.40 PM.png"" width=""146""> - Consists of “pavement-like” cells Located in blood vessels, lining of the heart and air sacs of the lungs Acts to allow diffusion and osmosis (permeable cells)" Simple Cuboidal"<img src=""Screen Shot 2023-09-24 at 8.16.57 PM.png""> - Consists of cells with central nuclei, which are “cube” shaped Pigmented epithelium lines anterior surface of the lens Forms lining of small ducts of many glands (secretory) " Non-Ciliated Simple Columnar"<img src=""Screen Shot 2023-09-24 at 8.17.47 PM.png""> - Consists of “column-shaped” cells interspersed with goblet cells Also may be thought of as “gastrointestinal epithelium” since it lines the alimentary tract from stomach to anus Found in the major ducts of many glands and in the gallbladder" Ciliated Simple Columnar"<div><div>- Resembles non ciliated; each cell has up to several hundred cilia. Epithelium lines part of the upper airways, some of paranasal sinuses, Fallopian tubes, uterus and in the central canal of the spinal cord Cilia indicate motility, simple means it is involved in absorption and secretion<div></div></div></div><div></div><img src=""Screen Shot 2023-09-24 at 8.19.59 PM.png""> " Types of Epithelial Cells - Complex TissueUnlike “simple” epithelia these prevent diffusion and are protective. Surface cells are true to cell shape, deeper layers tend show distortion Stratified Squamous"- Several layers of cells that appear squamous to cuboidal/ columnar. Keratinized = superficial layer of skin and non-keratinized lines mouth, esophagus and tongue. <img src=""Screen Shot 2023-09-24 at 8.21.28 PM.png"">" Stratified Cuboidal- Usually present as two or more layers of cells; chief location is in the ducts of sweat glands (adult) Stratified Columnar- Cells are columnar to polyhedral in shape. Lines large excretory ducts of some glands, parts of anal mucosa and part of eye conjunctiva Traditional Epithelium"- Appears to consist of a variety of cell types ranging from cuboidal to squamous Also termed “urinary epithelium” <img src=""Screen Shot 2023-09-24 at 8.23.05 PM.png"">" Pseudostratified Ciliated Columnar"<div><div>- Cells appear to have several layers but appearance of stratification is due to nuclei being present at various levels; all cells are attached to the basement membrane but not all reach the outer surface. Also termed “respiratory epithelium”, together with ciliated simple columnar epithelium it lines most of the upper respiratory tract<div></div></div></div><div><img src=""Screen Shot 2023-09-24 at 8.23.46 PM.png""> </div><div></div> " How are support cells organized?Support cells are vital to producing mechanical stability and have the following common features Produce variety of extracellular (EC) matrix materials Mature cells form sparsely cellular tissue in which matrix is the main component e.g. bone Cell adhesion focuses on attachment to matrix rather than other cells Support cells actively secreting matrix have names ending in _____ If support cells are in a quiescent phase they have names ending in _____blast cyte Origins of the support cells<div><div>During embryogenesis a set of mesenchymal cells that are spindle-shaped and differentiate into a “support cell family” of Fibroblasts - secrete EC matrix components of most tissues Myofibroblasts - secrete EC matrix components and have contractile function Adipocytes - store lipids and have cushioning and padding function Chondroblasts - secrete EC matrix components of cartilage Osteoblasts - secrete EC matrix components of bone </div></div> Fibroblasts"<div><div>- In the embryo these are seen as mesenchymic spindle-shaped cells that secrete collagen; later they make a variety of components including collagen, elastic and reticular fibers and fibrocollagenous tissue Fibrocollagenous tissue is described as loose when collagen is thin and widely spaced and dense when fibers are virtually confluent e.g. tendons and ligaments; this tissue is relatively acellular, poorly supplied with blood and heals slowly when damaged<div></div></div></div><div></div> " Fibrocollagenous Tissue Functions"- Supports nerves, blood vessels and lymphatics - Separates functional layers in organs and tissues - loose arrangement and elastic content allow mobility and stretching - Provides support (home) for immune cell population - Forms protective fibrous capsule surrounding most parenchymal organs e.g. liver, kidney and spleen - In response to damage they de-differentiate and produce endothelial cells, myofibroblasts and fibroblasts to repair the damaged area leaving a fibrous scar" Types Of Collagen"In addition there are over 20 types of the protein collagen, which perform a number of roles in the body e.g. providing confluence between tendons/ligaments with cartilage/ bones - Type I is present in all types of cartilage as well as bone and skin - Type II is in hyaline and elastic cartilage and vertebral discs - Type IV is in all basement membranes, forms the lens capsule and meshwork of bone marrow" Myofibroblasts- Resemble fibroblasts by light microscopy but contain actin associated with myosin which allow them to serve a contractile function Not prominent in normal support tissues but involved in repair process following tissue damage Adipocytes"- In the fetus these are mesenchymal cells able to accumulate fat in their cytoplasm first as small vacuoles and later as a single large vacuole (lipoblast) Once formed mature adipocytes are large, polyhedral cells that appear empty unless stained with lipid stains - Adipose tissue acts as shock absorption especially on soles of feet, buttocks and around the orbit of the eye; may also replace damaged tissue and act as food reserve " Chondroblasts and Chondrocytes- Chondroblasts are large, open cells with well-developed nuclei that form cartilage; they then shrink down becoming inactive chondrocytes surrounded by “gaps” (lacunae) Cartilage contains particular glycoproteins that allow resistance to deformation by compressive forces and fibrous collagen that confers mechanical stability Cartilage Growth"results from 2 sites of proliferation - Chondroblast proliferation within established EC matrix (interstitial growth) - Development of new chondroblasts from confining sheet of undifferentiated/fibroblast mesenchyme surrounding cartilage called perichondrium (appositional growth)" Hyaline Cartilagetemporary skeleton in early development (replaced by bone) and support tissue in respiratory passage Fibrocartilageintervertebral discs, tendon attachment to bones and junctions between flat bones of pelvis Elastic Cartilageauricle of ear, external auditory canal walls and epiglottis Osteoblastslarge, cuboidal cells that form bone; they then shrink down into inactive osteocytes surrounded by “gaps” called lacunae Bone"collagen and glycosaminoglycans (osteoid) that bind calcium and inorganic salts that provide strength and allow it to perform a number of functions including mechanical support (ribs), locomotion (long bones), protection (skull), reservoir (mineral salts)" Woven Bonehaphazard organization of collagen fibers and mechanically weak; produced during rapid production:  o Fetal bone is replaced by lamellar bone (temporary) o In adults, following fracture or during disease Lamellar Bone"regular parallel arrangement of collagen (90%) into sheets, which are mechanically strong, due to hydroxyapatite (calcium phosphate) content; virtually all bone in adults o Outer cortical/ compact zone; rigid shell resists deformation o Inner trabecular zone; mesh containing bone marrow cells" When does ossification begin?within 1 ½ months of conception Intramembranous Ossification"- Condensation from sheets of mesenchymal cells, which act as bone-forming membranes of flat bones e.g. skull - Mesenchymal cells transform into osteoprogenitors (osteoblasts), which deposit osteoid in small islands - This is mineralized into bone and remodeled to produce sheets" Endochondrial ossification- Transformation of existing cartilage into bone - Permits elongation and thickening of bone during fetal development and throughout childhood until bone growth ceases Phases of Endochondrial Ossification- Chondrocytes enlarge and deposit fibrillar glycoproteins allowing mineralization to form bone o Invasion of cartilage by blood vessels o Death of chondrocytes allowing space for bone marrow o Differentiation of mesenchyme around cartilage into osteoblasts Osteoclastsremodeling and changes to bone - use parathormone and inhibited by calcitonin Extracellular Matrix"Consists of interaction between proteins and glycosaminoglycans producing a mesh-like structure providing a binding/ interaction site for parenchymal and support cells (basement membrane)" Important Components of Extracellular Matrix"- Chondrocytes will not survive and differentiate if not surrounded by matrix - Proteins within the matrix may induce specific gene expression leading to formation of liver, testis and mammary gland - Migration of mesenchymal cells involves their interaction with the protein fibronectin, their adhesion in specific locations involves binding to another protein laminin (present in all basement membranes)" Glycosaminoglycans- Negatively charged - Retain sodium ions and water - Able to easily link to proteins forming proteoglycans; this capacity allows the generation of a molecular sieve providing a permeability barrier to the parenchymal tissue Basement membrane- In blood vessels it prevents leakage of large proteins - In kidney it prevents protein loss from filtered blood during urine production - In lung it allows gaseous exchange - May also control cell organization and differentiation and play a role in spread of cancer Tenascin"- Non-fibrillar protein - Expressed only in embryonic tissue and believed to be important to glial cell migration in developing nervous system especially optical locations - Synthesized by neural crest cells and glial cells - Function in the nervous system is probably related to promoting cell motility and establishing selective barriers to neurite outgrowth - Over expression is seen in gliomas but the connection between these events is unclear" FibronectinFibrillar protein involved in early phases of mesoderm migration during gastrulation - Death of the embryo by day 8 o No notochord or somites are made as the protein is necessary for the organization of the precursor cells o Red blood cells are made but no vessels o Neural crest cells become kinked and abnormal o No skeletal muscle or heart muscle is produced Fibrilin"- Fibrillar protein thought to be involved in restricting bone length - Composed of microfibrils found as part of elastic fibers, renal glomeruli, suspensory fibers of leg; prominent in skin, lung and blood vessels" Osteogenesis ImperfectaBrittle bone syndrome Defect in type I collagen; this protein constitutes 30% of the body’s weight A number of types of disease exist; some are lethal in utero (type II) and in some cases babies may undergo fractures whilst still in the womb (types III and IV) Type I is the mildest with patients having o No overall height, long bone or teeth issues o High tolerance to pain despite frequent fractures o Often blue sclera (eye) o Deafness by age 40 (50%) Ehlers Danlos Syndrome- Autosomal dominant inheritance pattern for most forms except the severe Joint hypermobility, skin fragility (easy scarring and with a hyperextensible, soft, doughy consistency) Collagen defect affecting a variety of structural collagens but commonly affects types I, III or V collagen or tenascin expression (cf OI) Type III collagen is an integral protein in skin, blood vessels and intestines with type V collagen present on or near the basement membranes of most cell Marfan's Syndrome<div><div>- Autosomal dominant mutations in fibrillin Increased height, long limbs and digits with laxity (arachnodactyly) Patients may also exhibit sunken chest and flat feet due to laxity of elastic fibers in these locations Scoliosis (spine curvature) is a major problem Mitral valve defects also frequently present (lack of sufficient cusps, chordae tendinae abnormal) Aortic problems (may lead to aneurisms) Loose lenses and myopia<div></div></div></div><div><div> </div></div>

Histology Exam 1

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