Histo Block A

  1. conventional staining
    ex: H&E staining
  2. enzyme histochemistry
    • used to localize certain enzymes
    • uses marked substrates that bind to a specific enzyme which allows you to visualize organelles
  3. histology staining techniques
    • conventional staining
    • enzyme histochemistry
    • immunocytochemistry
    • hybridization
    • autoradiography
  4. histology visualization methods
    • light microscopy
    • confocal scanning microscopy
    • electron microscopy
  5. commonly used measurements
    • picometer (10-12 m)
    • angstrom (10-10 m)
    • nanometer (10-9 m)
    • micrometer (10-6 m)
  6. hydrogen atom diameter
    1 angstrom
  7. plasma membrane thickness
    8-10 nm
  8. red blood cell diameter
    ~8 um
  9. tissue preparation
    • removal of tissue from animal
    • cutting tissue into this sections
    • fixation
    • dehydration
    • embedding
    • sectioning
    • mounting and staining
  10. fixation
    • immersion or perfusion in formalin
    • hardens tissue
    • stops cellular metabolism
    • prevents autolysis
    • kills pathogens
  11. embedding
    • dehydration - tissue is run through a series of alcohol baths (causes shrinkage)
    • clearing - xylene or toluene; miscible with paraffin (final embedding material)
    • infiltration/embedding - tissue placed in paraffin (all water in cell has been replaced)
  12. sectioning
    • tissue cut into ultrathin segments using a microtome
    • artifacts from preparation present
  13. basic dyes
    • methyl green
    • methylene blue
    • pyronin G (red)
    • toluidine blue
  14. acidic dyes
    • acid fushsin (red)
    • aniline blue
    • eosin (red)
    • orange G
  15. hematoxylin & eosin (H&E) staining
    • the most commonly used staining technique
    • counterstain
    • both water based stains
  16. hematoxylin
    • basophilic dye (+ charged)
    • affinity for negatively charged molecules (eg nucleic acids)
    • will stain DNA, RNA, and ribosomes (rRNA)
    • blue in color
  17. eosin
    • acidophilic dye (- charged)
    • affinity for positively charged molecules
    • will stain cytoplasm, membranes, SER, and mitochondria, "membranes"
    • red/pinkish color
  18. frozen section
    • use methylene blue
    • sacrifice morphology and resolution to allow quick identification of possible malignant tissue during surgical procedures
    • formalin fixed sections have better resolution & contrast to confirm diagnosis, but take longer
  19. PAS stain
    • Periodic Acid Schiff
    • stains carbohydrates and carbohydrate rich molecules a reddish magenta color (glycogen, glycoproteins)
    • basement membranes  tend to be high in glycoproteins
  20. ATPase histochemistry
    • enzyme is localized and stained by binding marker to substrate of that enzyme
    • stain will accumulate in areas of enzyme activity
  21. direct immunofluorescence
    • antibodies with a fluorescent label directly bind to an antigen (eg. cell surface proteins)
    • 1:1 binding of tagged antibody to antigen
    • produces weak signal
  22. indirect immunofluorescence
    • primary antibodies made for target antigens
    • secondary antibodies with fluorescent label bind to primary antibodies
    • multiple secondary antibodies are able to bind to a primary antibody
    • greater fluorescent signal that is easily visible
  23. fluorescence in situ hybridization
    fluorescent probe to DNA using nucleic acid probes that bind to complementary DNA segments
  24. autoradiography
    • radioactively labeled amino acids/ hormones are incorporated within structures
    • visualization determines location and activity of labeled substances
  25. van Leuwenhoek
    • "father of microbiology"
    • early inventor of the microscope
    • first looked at cell walls of course
  26. resolution
    the closest distance that two objects can be distinguished
  27. cells
    basic structural unit
  28. cell identification
    basis for histologic characterization of tissues
  29. cell components
    • cytoplasm & cytoplasmic matrix
    • organelles & inclusions
    • nucleus
  30. membranous organelles
    • plasma membrane - surrounding the cell
    • transport vesicles
    • endosomes - movement of material into and within cells
    • lysosomes - digestion of waste material, hydrolytic enzymes
    • rough endoplasmic reticulum (rER) - a site of protein synthesis, binds translating ribosomes
    • smooth endoplasmic reticulum (sER) - steroid synthesis, detoxification
    • golgi apparatus - stacked membranes for protein modification
    • mitochondria - production of ATP
    • peroxisomes - oxidative enzymes (peroxidases, catalases)
  31. nonmembranous organelles
    • microtubules - cell division and directionality of molecules
    • filaments - actin, intermediate (contractility, maintainance of structure)
    • centrioles, Basal bodies
    • ribosomes - rER or free in cytoplasm
  32. cytoplasm
    aqueous gel of different components (mostly water) filling most of the cell
  33. cytoplasmic matrix
    • structural components of cytoplasm
    • composed of different macromolecules, fibers, fillaments
    • surrounded by cell membrane
  34. organelles
    • "little organs"
    • perform specific functions of the cell
  35. inclusions
    ex: fat droplets
  36. nucleus
    • center of genetic activity
    • present in all cells EXCEPT mature red blood cells in mammals
  37. plasma membrane
    • lipid bilayer with amphipathic characteristics
    • dynamic structure - participates in many physiological and biochemical processes
    • not completely homogenous (eg lipid rafts)
    • modified fluid-mosaic model
  38. amphipathic
    • one side (exterior) is hydrophilic
    • one side (interior) is hydrophobic
  39. composition of plasma membrane
    • fatty acids: phospholipids, glycolipids
    • cholesterol: stiffening/strengthening of membrane
    • integral membrane proteins: go through membrane
    • peripheral membrane proteins: not embedded in membrane, associate with plasma membrane via strong ionic interactions
    • glycocalyx: surface molecules, establish extracellular microenvironment (often associated with sugar, receptors, etc)
  40. lipid rafts
    • glycosphingolipids with peripheral proteins and carbohydrates - STAY TOGETHER
    • can float around the surface of the cell and to the lateral side of the cell
    • may be inhibited by junctional complex on epithelial cells (structural limitations)
  41. glycocalyx
    • extracellular sugar molecules attached to proteins of cell membranes
    • coats the cell
    • important in cell recognition
    • contains enzymes that may activate other enzymes (intestinal enterokinase activates enzymes secreted by pancreas)
  42. freeze fracture
    • mechanical method that cleaves the lipid bilayer
    • splits open the cell membrane in the hydrophobic layer
    • cells frozen rapidly and hit with a sharp object to peel open the cell membrane
  43. E face
    • external face of the cell membrane
    • has some integral proteins
  44. P face
    • protoplasmic face
    • interior face of the cell membrane
    • has many (more) integral proteins
  45. integral membrane protein functions
    • pumps: transport certain ions, amino acids, sugars
    • channels: allow passage of small ions, molecules, and water
    • receptor proteins: interact with extracellular ligands to introduce intracellular processes
    • linker proteins: anchor the extracellular matrix to the intracellular cytoskeleton (integrins)
    • enzymes: regulate multiple processes at the cell membrane (eg ATPases for ion pumping)
    • structural proteins: maintain cellular architechture (eg tight junctions)
  46. pumps
    • largely energy independent
    • ex. Na/K pumps
  47. channels
    • groups of proteins that form a cylindrical pore in the cell membrane
    • may open or close with variety of stimuli
  48. receptor proteins
    • demonstrate high specifirty
    • external receptor triggers activity inside the cell
    • ex. neurotransmitter binding to receptor protein
  49. linker proteins
    • ex. attaches collagen to external surface and connects external collagen to internal actin
    • maintains integrity of epithelial membrane
  50. desmosome
    • homophilic binding between structural proteins of neighboring cells
    • strong attachment
  51. simple diffusion
    • small lipid soluble or uncharged molecules
    • follows a concentration gradiet
  52. transport by carrier proteins
    • mostly small, water soluble molecules
    • highly selective - binding often causes conformational change
    • can require energy (active transport) or follow a concentration gradient (passive transport)
  53. transport by channel proteins
    • small, water soluble molecules
    • create a hydrophillic passage through cell membrane
    • regulated by membrane potentials (voltage gated), neurotransmitters (ligand gated) or mechanical stress (mechanically gated)
  54. ligand gated channels
    • a ligand binds to the outside of a cell and induces ion channels to open
    • ex. neurotransmitter binding to outside of cell
  55. mechanically gated channels
    • activated by mechanical stress
    • ex. hair cells in inner ear when properly affected by vibratiosn through the air and water in ear stretch - open K+ channels
  56. vesicular transport
    • process involving formation of membrane vesicles and their fusion with membranes (vesicle budding)
    • maintains integrity of plasma membrane & transport of molecules between cellular compartments
    • endocytosis, exocytosis
    • visualization by electron microscopy or immunofluorescence
  57. endocytosis
    • vesicular transport for substances entering the cell
    • pinocytosis  & phagocytosis
  58. exocytosis
    • vesicular transport for substances leaving the cell
    • process by which a vesicle moves from the cytoplasm to the plasma membrane, where it releases its contents
    • constituitive pathway or regulated secretory pathway
  59. constituitive pathway
    • continuous delivery of to-be-secreted components via Golgi apparatus
    • requires no stimulation
    • present in some form of every cell
    • difficult to see in microscope
  60. regulated secretory pathway
    • delivery is triggered by stimulus (hormonal or neuronal)
    • occurs in specialized cells (eg. endocrine cells, exocrine cells, neurons)
    • enzymes can be made and stored in vesicles until trigger for release
    • can usually be seen via microscope
  61. pinocytosis
    • nonspecific uptake of fluid and small molecules by small vesicles
    • performed by nearly every cell
    • constituitive
    • clathrin-independent
    • common in endothelial cells
  62. phagocytosis
    • nonselective uptake of large particles by large vesicles (bacteria or debris)
    • mainly performed by cells of mononuclear phagocytic system (macrophages, kuppfer cells)
    • constituitive
    • receptor-mediated
    • requires rearrangement of actin cytoskeleton
    • clathrin independent, actin dependent endocytosis
  63. COP I
    • coating proteins
    • retrograde
    • re-incorporate in to Golgi apparatus
  64. COP II
    • coating proteins
    • anterograde
    • move forward in secretory pathway (either constituitive or regulated secretion)
  65. receptor mediated endocytosis
    • uptake of specific molecules using cargo receptors
    • vesicle formation requires assembly of a coated pit involving adaptin, clathrin, and dynamin
    • clathrin-dependent endocytosis
    • involved in transport of cargo from the plasma membrane to the early endosomes and from the Golgi apparatus to the early and late endosomes
  66. familial hypercholesterolemia
    • high levels of cholesterol due to faulty uptake resulting from problem with clathrin coating
    • receptor mediated endocytosis malfunction
  67. endosomes
    membrane bound compartments in the cell formed by endocytotic pathways
  68. early endosomes
    • pH 6.2 to 6.5
    • restricted to near cell membrane where they originate
    • can re-fuse with cell membrane or travel deeper into cell, where they become late endosomes
  69. late endosomes
    • pre-lysosomes
    • usually near the Golgi apparatus or nucleus
    • complex structure with onion-like internal membranes
    • pH of 5.5
    • mature into lysosomes
  70. multivesicular bodies
    specific vesicles that transport substances between early and late endosomes
  71. lysosomes
    • digestive organelles
    • rich in hydrolytic enzymes - proteases, nucleases, glycosidases, lipases, phospholipases
    • composed of unique membrane resistant to hydrolysis
  72. lysosome membrane mechanisms for resistance to hydrolysis
    • membrane contains cholesterol and lyso-biphosphatic acid (restricts activity of enzymes)
    • lysosome associated membrane proteins
    • lysosomal membrane glycoproteins
    • lysosomal integral membrane proteins
    • transport proteins to transport the final products of digestions to the cytoplasm for further use
    • proton pumps for acidification (pH 4.7)
  73. pathways for lysosomal degradation
    • large extracellular particles transported via phagocytosis
    • small extracellular particules transported via endocytotic pathways
    • pinocytosis
    • receptor mediated endocytosis
    • autophagy
  74. types of autophagy
    • microautophagy
    • macroautophagy
    • chaperone mediated direct transport
    • protease mediated degradation
  75. microautophagy
    non-specific continuous degradation of intracellular proteins via invagination of lysosomal membrane
  76. macroautophagy
    entire organelles surrounded by multiple membranes of ER to be degraded by lysosomal enzymes
  77. autophagy
    digestion of intracellular particles and organelles
  78. chaperone mediated direct transport
    • only selective process of lysosomal degradation
    • involves interaction of the to-be-degraded protein with heat shock chaperone protein (hsc73) and its subsequent transport to lysosome
  79. protease-mediated degradation
    • degradation of abnormal or short-lived proteins without lysosomal involvement
    • large ATP-dependent protease complexes in nucleus or cytoplasm
    • proteins tagged by multiple ubiquitin molecules
    • decreased degradation leads to accumulation of proteins in cell (Alzheimer's disease)
    • accelerated degradation of proteins due to overproduction of system proteins (human papilloma virus infections)
  80. lysosomal storage diseases
    • Gaucher disease
    • Tay-Sachs disease
    • Neimann-Pich disease
  81. rough endoplasmic reticulum
    • region of endoplasmic reticulum associated with ribosomes
    • membrane often continuous with outer membrane of nuclear envelope
    • site of protein synthesis (secreted and integral membrane proteins) and post-translational modifications of newly synthesized proteins
    • very well developed in secretory cells (eg glandular cells, plasma cells)
    • present in ALL cells
  82. smooth endoplasmic reticulum
    • structure similar to rER, but lacks ribosomes
    • tubular appearance
    • abundant in cells with high lipid metabolism (hepatocytes) and steroid secreting cells  (adrenocortical cells and testicular Leydig cells)
    • principal organelle for detoxification in hepatocytes (ie. modification of pesticides and carcinogens
    • glycogen metabolism
    • membrane formation and recycling
  83. golgi apparatus
    • system of stacked, flattened membrane limited sacs (cisternae) and tubular extensions embedded in network of microtubules
    • small vesicles transport material between cisternae
  84. golgi apparatus organization
    • cis-golgi network: closest to rER
    • medial golgi
    • trans-golgi network: cisternae farthest away from rER
  85. functions of golgi apparatus
    • post-translational modification of proteins
    • sorting
    • packaging of proteins
  86. four major pathways of protein secretion from golgi apparatus
    • apical plasma membrane
    • basolateral plasma membrane
    • endosomes & lysosomes
    • apical cytoplasm
  87. apical plasma membrane: protein secretion pathway
    • proteins have specific sorting signals that direct their transport from TGN to apical membrane
    • constituitive pathway
  88. basolateral plasma membrane: protein secretion pathway
    • constituitive pathway
    • proteins have specific sorting signals that direct their transport from TGN to the basolateral membrane
  89. endosomes & lysosomes: protein secretion pathway
    proteins have their specific sorting signal, but may be mistargeted to apical domain and from there are re-directed to lysosomes
  90. apical cytoplasm: protein secretion pathway
    • proteins stored in secretory vesicles, which mature and fuse with the plasma membrane and release their contents (eg secretory cells of exocrine glands)
    • regulated pathway
  91. mitochondria
    • generate energy in the form of ATP
    • originate from aerobic prokaryote that lived symbiotically within primitive eukaryotic cells - have their own DNA and translational machinery & undergo division (endosymbiotic theory)
    • present in ALL cells (except RBCs & terminal keratinocytes)
    • especially numerous in cells requiring high energy usage
    • shape, number & structure characteristic for specific cell types - histological criteria
    • high numbers - cytoplasm acidophilic
    • sense cellular stress: instrumental for cells undergoing apoptosis (programmed cell death) 
  92. structural components of mitochondria
    • outer mitochondrial membrane
    • intermembrane space
    • inner mitochondrial membrane
    • matrix
    • cristae
  93. cristae
    • in steroid secreting cells - tubular shape
    • other cells (mitochondria) - flattened, leaf like structure

    increase surface area of inner mitochondrial membrane
  94. peroxisomes
    • single membrane bounded organelle
    • small (~0.5um diameter)
    • particularly abundant in kidney & liver cells
    • contain oxidative enzymes (eg catalase, peroxidase) - detoxification processes
    • peroxisomal proteins - imported into peroxisomes by peroxisomal targeting signal
    • numbers increase in cell related to diet, drugs, hormones
  95. microtubules
    • non-branching, rigid hollow tubules
    • one circle composed of 13 alpha & beta-tubulin dimers
    • dynamic structure - participate in physiological and biochemical processes
    • formation starts at microtubule-organizing center (MTOC) characterized by the presence of gamma-tubulin
    • dynamic instability - constant microtubule remodeling linked to pattern of GTP hydrolysis
  96. direction of microtubule growth
    • minus end: corresponds to orientation of alpha-tubulin; anchored to MTOC
    • plus end: corresponds to orientation of beta-tubulin; extends to periphery (location of elongation from addition of tubulin molecules)
  97. micro-tubular network
    system of connections within cell
  98. microtubule functions
    • intracellular vesicular transport (secretory vesicles, endosomes, lysosomes)
    • movement of cilia and flagella
    • attachment of chromosomes to mitotic spindle and their movement during mitosis and meiosis
    • cell elongation and movement (migration)
    • maintence of cell shape
  99. molecular motor proteins
    • proteins responsible for transport along microtubule tracks
    • dyneins & kinesins
  100. dyneins
    • move towards minus end (from cell periphery to MTOC)
    • cytoplasmic dyneins
    • axonemal dyneins - cilia & flagella
  101. kinesins
    move towards to plus end (from MTOC to periphery)
  102. actin filaments
    • very abundant (up to 20%)
    • in nearly all cells
    • assemble spontaneously into linear helical array
    • polarized structures
  103. types of actin
    • G actin: globular, unpolymerized
    • F actin: filamentous, polymerized
  104. actin polarity
    • plus end: barbed end, fast growing
    • minus end: pointed end, slow growing
    • requires K+, Mg2+, and ATP
    • growth depends on local concentration of G actin
  105. Zellweger syndrome
    • inability to import proteins into peroxisomes
    • peroxisomes lack necessary enzymes
    • leads to early death
  106. mitochondrial matrix
    contains the soluble enzymes of the citric acid cycle and fatty acid beta oxidation, matrix granules (Ca2+, etc.), mitochondrial DNA, ribosomes, and tRNAs
  107. functions of inner mitochondrial membrane
    • oxidation reactions of electron transport chain
    • synthesis of ATP
    • regulates transport of metabolites in and out of matrix
  108. outer mitochondrial membrane
    • voltage-dependent anion channels (mitochondrial porins)
    • receptors for proteins and polypeptides
    • several enzymes (phospholipase A2, monoamine oxidase, acetyl CoA synthase)
  109. intermembrane space
    • contains enzymes that use ATP generated in inner membrane (creatine kinase, adenylate kinase, cytochrome c)
    • environment is similar to cytoplasmic space in respect to ions and small molecules
  110. inner mitochondrial membrane
    • thin membrane arranged in folds (cristae) to increase surface area
    • rich in phospholipid cardiolipin (makes the membrane impermeable to ions)
    • site of ATP synthase
  111. actin binding proteins
    regulate rate of actin polymerization and organization

    • actin bundling proteins
    • actin filament severing proteins
    • actin capping proteins
    • actin crosslinking proteins
    • actin motor proteins
  112. actin bundling proteins
    • bundle actin filaments
    • parallel arrays - support and rigidity
    • fascin
    • fimbrin in microvilli
  113. actin filament severing proteins
    • cut long actin filaments into shorter filaments
    • gelsolin
  114. actin capping proteins
    • block further elongation of filaments
    • regulate length
    • tropomodulin
  115. actin crosslinking proteins
    • spectrin
    • adductin
    • protein 4.1
    • protein 4.9 - cytoskeleton in RBCs
  116. actin motor proteins
    • myosin family
    • muscle contraction
  117. actin functions
    • anchorage and movement of membrane proteins
    • formation of the structural core of the microvilli
    • locomotion of cells - actin polymerization extends the plasma membrane (lamellipodia)
    • extension of cell processes (filopodia) - small protrusions around the cell
  118. intermediate filaments
    • primary structural role
    • non polar
    • normally do NOT assemble/dissassemble dynamically
    • subunits - very diverse
    • NO enzymatic activity
  119. intermediate filament subunits
    • highly conserved globular domain at N- and C- termini
    • highly variable central domain
    • all share homologous region required for self assembly
  120. formation of intermediate filament
    • monomers -> coiled dimers -> staggered tetramers -> fibrils
    • additional stabilization - lateral binding of adjacent tetramers
  121. intermediate filament associated proteins
    • keratins
    • vimentin & vimentin-like filaments
    • neurofilaments
    • lamins
  122. keratins
    • >50 different isoforms
    • do not co-assemble with other types of intermediate filaments (cell and tissue specific)
    • span cytoplasm of epithelial cells
    • can connect with keratins of adjacent cells via desmosomes
  123. vimentin
  124. neurofilaments
  125. lamins
  126. centrioles
    • paired short, rodlike cytoplasmic cylinders
    • nine microtubule triplets - two pairs aligned at right angles to each other
    • usually found in proximity of nucleus and Golgi apparatus
  127. MTOC
  128. functions of centrioles
    • development of cilia: centrioles become basal bodies
    • mitotic spindle organization
  129. development of cilia
  130. mitotic spindle organization
  131. inclusions
    • cytoplasmic or nuclear structures containing products of metabolic activity
    • non-moving, non-living
    • may be surrounded by plasma membrane
  132. types of inclusions
    • lipofuscin
    • hemosiderin
    • glycogen
    • lipid inclusions (fat droplets)
    • crystalline inclusions
  133. lipofuscin
    • brownish-gold pigment seen in H&E preparations
    • conglomerate of lipids, metals and organic molecules
    • sign of cellular senescence or stress
  134. hemosiderin
    • iron storage complex
    • indigestible residues of hemoglobin
    • easily seen in spleen (site of RBC destruction)
  135. glycogen
    • storage material for glucose
    • not stained by standard H&E (seen as empty space... result of glycogen wash away during staining in glycogen rich tissue)
    • high in liver and striated muscle
  136. lipid inclusions
    • fat droplets
    • energy for cellular metabolism
    • long or short term storage
    • normally seen as clear area
  137. crystalline inclusions
    • present in many cells, in particular Sertoli and Leydig cells of the testis
    • function unclear
  138. cell nucleus
    • membrane limited compartment
    • contains genetic information
  139. structural components of mitochondria
    • outer mitochondrial space
    • intermembrane space
    • inner mitochondrial space
    • matrix
  140. cell nucleus components
    • chromatin: DNA associated with proteins
    • nucleolus: small area with DNA for ribosomal RNA, RNA and proteins
    • nuclear envelope: membrane system surrounding nucleus
    • nucleoplasm: remaining contents of nucleus
  141. chromatin
    • nucleoprotein complex
    • DNA
    • five basic histone proteins (H1, H2A, H2B, H3, and H4)
    • non-histone proteins
  142. heterogeneous heterochromatin
    • highly condensed DNA clumps
    • stains with hematoxylin and basic dyes
    • signifies that cell is not actively synthesizing DNA
  143. types of heterochromatin
    • marginal chromatin: at the periphery of the nucleus
    • karyosomes: discrete bodies in the chromatin spread out through the nucleus
    • nuclear-associated chromatin: in the nucleolus; responsible for RNA synthesis
  144. euchromatin
    • less condensed DNA
    • not evident in the light microscope
    • indicates active chromatin in the nucleus
  145. different levels of DNA packaging
    • nucleosome - "beads on a string"
    • chromatin fibril
    • loop domains - associated with the chromosome scaffold or nuclear matrix
    • mitosis/meiosis - DNA is further condensed forming the chromosomes
  146. Barr body
    • condensed X chromosome
    • not being used (extra in females)
  147. nucleolus
  148. nucleolus
    • site of ribosomal RNA synthesis and initial ribosomal assembly
    • nonmembranous region in the nucleus
    • stains intensely with hematoxylin and other basic dyes (because of the high amount of nucleolar RNA)
  149. regions of nucleolus
    • fibrillar centers
    • fibrillar material - pars fibrosa
    • granular material - pars granulosa
  150. fibrillar centers
    contain DNA of five chromosomes (13, 14, 15, 21 & 22), RNA polymerase I and transcription factors
  151. pars fibrosa
    • fibrillar material
    • contains ribosomal genes actively undergoing transcription, and large amounts of rRNA
  152. pars granulosa
    • granular material
    • site of initial ribosome assembly
  153. nucleolonema
    network of pars fibrosa and granulosa together
  154. nuclear envelope
    • selectively permeable membranous barrier between nuclear compartment and cytoplasm
    • disassembled during cell division
    • two nuclear membranes
  155. nuclear membranes
    • outer membrane: closely resembles membrane of rER (including ribosomes)
    • inner membrane: supported by intermediate filaments (nuclear lamins) forming the nuclear (fibrous) lamina; contains lamin receptors and lamin-associated proteins linking chromosomes to nuclear lamina
  156. nuclear pores
    • opening in the nuclear membrane
    • cytoplasmic ring with protruding protein fibrils
    • channels for small molecules
    • continuity of nucleoplasm and cytoplasm
  157. nuclear pore complex transport
    • bidirectional
    • partially assembled ribosomes leave the nucleus
    • histones, lamins, etc. have to be transported into the nucleus (no translation occurs in the nucleus)
    • transport via NPC requires the presence of a nuclear localization signal that is recognized by a nuclear import receptor (requires energy in the form of GTP)
  158. cell cycle
    self regulated sequence of events controlling cell growth and division
  159. cell cycle phases
    • G1: gap 1; length varies from cell to cell
    • S: synthesis phase; DNA replication
    • G2: gap 2 phase; preparation for division; checks DNA replication
    • M: mitosis; cell division
    • checkpoints occur along the well
  160. mitosis
    • essential process that increases the number of cells
    • permits the renewal of cell populations
    • allows wound repair
    • process of chromosome segregation and nuclear division that produces two daughter cells with the same chromosome number and DNA content as the parent cell
  161. phases of mitosis
    • prophase
    • metaphase
    • anaphase
    • telophase
  162. meiosis
    • two sequential nuclear divisions leading to the formation of haploid gametes
    • necessary to maintain constant number of chromosomes in species
    • allows exchange of chromosomal material
  163. meiotic phases
    • prophase I: extended to allow pairing of homologous chromosomes and synaptic recombination
    • metaphase I: similar to mitotic metaphase only that the chromosomes are aligned at the metaphase plate; chiasmata are cleaved to release the individual chromosomes
    • anaphase I: similar to mitotic anaphase only that centromeres do not split; leads to the segregation and random assortment of paternal and maternal chromosomes gets resolved
    • telophase I: division of the cytoplasm
    • meiosis II: starts right after the completion of meiosis I, there is no S-phase; essentially the same as mitotic division; results in the formation of haploid daughter cells
  164. necrosis
    • pathological process
    • when a cell is exposed to unfavorable conditions that cause acute cellular injury
    • triggers an intense inflammatory response
  165. apoptosis
    • physiological process that eliminates cells from the body which are no longer needed
    • no inflammatory response
  166. cell death
    • balance between proliferation and cell death has to be carefully maintained to avoid disease
    • necrosis & apoptosis
  167. characteristic features of apoptosis
    • DNA fragmentation
    • decrease in cell volume
    • loss of mitochondrial function
    • membrane blebbing
    • formation of apoptotic bodies
  168. tissue types
    • epithelium
    • connective tissue
    • muscle tissue
    • nervous tissue
  169. overview of epithelium
    • avascular
    • relatively thin to absorb nutrients
    • covers surfaces, lines cavities & tubes
    • forms secretory portion of glands
    • specialized cells - receptors for senses
    • tightly adhered to one another
    • cells have polarity (free apical surface and a basal surface)
  170. functions of epithelium
    • protection
    • absorption
    • transportation
    • secretion
    • receptor function
  171. specializations of epithelium
    • endothelium
    • mesothelium
  172. endothelium
    epithelial lining of blood vessels
  173. mesothelium
    endothelium that lines and covers organs
  174. microvilli
    • fingerlike projections of the surface of the cell
    • primary purpose - increase the surface are of the cell
    • pronounced in cells involved in transport (intestinal epithelium & kidney tubules)
    • contains a core of actin filaments
    • actin bundle extends down into apical cytoplasm and forms the terminal web (holds in place)
  175. apical specializations
    • microvilli
    • cilia (motile & non-motile)
    • stereocilia
  176. cilia
    • capable of moving fluid and particles along epithelial surfaces
    • beat in a precise, coordinated & synchronous movement
    • found in trachea & bronchi (move mucus & particles)
    • found in oviduct (move ovum)
  177. composition of cilia
    • made up of microtubules (made of tubulin)
    • 9 + 2 arrangement
    • 9 doublets and 2 central singlets
    • each doublet has a A tubule and B tubule
    • dynein arms connect the microtubules
    • dynein & tubulin serve as motor proteins (dynein - ATPase)
  178. motile cilia
    • movement due to sliding of microtubule doublets along each other
    • dynein generates the sliding forces in axonemes
    • basal bodies anchor the cilia in the apical cell cytoplasm
  179. non-motile cilia
    • AKA primary cilia, monocilia
    • found on a variety of cell types
    • function as the "antenna" of the cell, sensing changes in the environment
    • establish the left-right asymmetry of internal organs
    • 9 + 0 arrangement of microtubules (no central singlets)
  180. primary ciliary dyskinesia
    • autosomal recessive
    • Kartagener's syndrome
    • Young's syndrome
    • about 50% have situs inversus
    • also affects sperm & oviducts
  181. Kartagener's syndrome
    • primary ciliary dyskinesia
    • immotile cilia syndrome
    • structural abnormality results in absence of dynein arms
    • failure of mucociliary transport system to protect the body from bacteria and invading pathogens in respiratory epithelium
  182. Young's syndrome
    • primary ciliary dyskinesia
    • malformation of the radial spokes and dynein arms
    • affects ciliary function in the respiratory tracts
    • causes chronic respiratory infections
  183. situs inversus
    • organs are transposed through the sagittal plane
    • occurs in 50% of patients with primary ciliary dyskinesia
  184. stereocilia
    • long, immobile microvilli (thinner)
    • found in hair cells of the ear & the epididymus
    • sense change in the ear
  185. junctional complex components
    • zonula occludens
    • zonula adherens
    • macula adherens
    • gap junctions
  186. zonula occludens
    • tight junctions
    • prevent movement of water and other molecules between the cells
    • most apical of the junctions
    • acts as seams holding the adjacent cell membranes together
  187. zonula adherens
    lateral adhesion between the cells
  188. macula adherens
    • desmosome
    • spot welds (buttons on a chair)
    • composed of intermediate filaments & cadherins
    • anchored with intermediate filaments
  189. gap junctions
    • held together by connexin
    • allow for communication between the cells
    • passage of small ions, informational micromolecules, etc.
    • prominent in cancer cells
  190. what type of cells have the most gap junctions?
    cancer cells
  191. basal specializations
    • basement membrane
    • basal lamina
  192. basement membrane
    • basal lamina + reticular lamina
    • attached to reticular cells by hemidesmosomes
    • attaches epithelial cells to connective tissue below
  193. hemidesmosomes
    intermediate fibers anchor the connection only on one side
  194. basal lamina
    • composed of laminins, collagen, proteoglycans & glycoproteins
    • integrin receptors specialized for holding the structure in place
  195. epidermolysis bullosa (EB)
    • group of inherited disorders characterized by blister formation in response to mechanical trauma (putting on a diaper, bathing, etc.)
    • mutation of at least ten different genes within cutaneous basement membrane zone
  196. exocrine glands
    secrete their product into ducts
  197. endocrine glands
    • ductless
    • secrete their product directly into the bloodstream
  198. unicellular glands
    • goblet cells
    • mucus secreting cells
    • found in intestines & respiratory tract
  199. mechanisms of exocrine secretion
    • merocrine
    • apocrine
    • holocrine
  200. merocrine secretion
    • secretory product in membrane bound vesicles
    • ex. pancreatic acinar cells
  201. apocrine secretion
    • secretion released in the apical portion of the cell, surrounded by some cytoplasm and plasma membrane
    • ex. mammary gland
  202. holocrine secretion
    • the whole cell fills with secretion which is released when cell dies
    • ex. sebaceous gland
  203. paracrine glands
    • secretions activate other cells
    • ex. cytokines
  204. types of glands
    • exocrine
    • endocrine
    • paracrine
  205. classification of multicellular glands
    • shape of secretory portion: tubular, acnar, or tubuloacinar
    • duct: simple or compound
  206. simple glands
    • simple tubular
    • simple coiled tubular
    • simple branched tubular
    • simple acinar
  207. compound glands
    • branched acinar
    • compound tubular
    • compound acinar
    • compound tubuloacinar
  208. simple tubular gland
    • secretory portion of the gland is a straight tube formed by secretory cells (goblet cells)
    • typical location - large intestine
    • ex. intestinal glands of the colon
  209. simple coiled tubular gland
    • coiled tubular structure is composed of the secretory portion located deep in the dermis
    • typical location - skin
    • ex. eccrine sweat gland
  210. simple branched tubular gland
    • branched tubular glands with wide secretory portions are formed by the secretory cells and produce a viscous mucus secretion
    • typical location - stomach
    • ex. mucus secreting glands of the pylorus
  211. simple acinar gland
    • develop as an outpouching of the transitional epithelium and are formed by a single layer of secretory cells
    • typical location - urethra
    • ex. paraurethral and periurethral glands
  212. branched acinar gland
    • secretory portions formed by mucus secreting cells; short single-duct portion opens directly into lumen
    • typical location - stomach
    • ex. mucus secreting glands of the cardia
  213. compound tubular gland
    • coiled secretory portion located deep in the submucosa of the duodenum
    • typical location - duodenum
    • ex. submucosal glands of Brunner
  214. compound acinar gland
    • alveolar-shaped secretory units formed by pyramind shaped serous-secreting cells
    • typical location - pancreas
    • ex. excretory portion of pancreas
  215. compound tubuloacinar gland
    have both mucous branched tubular and serous branched acinar secretory units; serous endcaps (demilunes)
  216. classification of epithelium
    • number of cell layers: simple, stratified
    • shape of cells: squamous, cuboidal, columnar
    • special classifications: pseudostratified, transitional
  217. simple squamous epithelium
    • single layer of squished cells
    • lines blood vessels (endothelium) and body cavities
    • thin, good for diffusion
  218. simple cuboidal epithelium
    • single layer of square cells
    • nucleus approximately in center
    • found in the kidney (filtration) and in the thyroid (secretion)
  219. simple columnar epithelium
    • single layer of columnar cells
    • nuclei located at base of cell
    • receive nutrients through basement membrane
    • found in the stomach, small intestine & large intestine (absorption and digestion)
  220. pseudostratified epithelium
    • single layer
    • nuclei look like they are in multiple layers, but NOT two distinct rows of nuclei
    • frequently ciliated
    • found in trachea, bronchiole tree, ductus deferens, epididymus (secretion & absorption)
  221. stratified squamous epithelium
    • multiple layers of squished cells
    • get more flat as they move up & flake off
    • 2 types - keratinized (waterproof) and non-keratinized
    • found in epidermis, oral cavity, esophagus & vagina (barrier, protection)
  222. transitional epithelium
    • bubbled up dome shaped cells at tome
    • found in urinary bladder (distensible property)
  223. stratified columnar epithelium
    • rare
    • nuclei are in two distinct rows
    • found in largest ducts of exocrine glands (mucus gland duct of tongue) & anorectal junction
  224. stratified cuboidal epithelium
    • multiple layers of square cells
    • rare
    • found in ducts of glands
  225. mucus membranes
    • line the cavities that connect with the outside of the body
    • consist of epithelium, connective tissue & basement membrane
    • have many goblet cells that secrete mucus
  226. serous membranes
    • line the peritoneal, pericardial and pleural cavities
    • simple squamous epithelium
    • no mucus
  227. abnormal epithelium
    • epithelium grows in response to wear & tear
    • growth may go wrong, resulting in tumors
    • ex. epithelial metaplasia, Barrett's esophagus
  228. epithelial metaplasia
    • conversion of one mature cell type to another mature cell type
    • most common - columnar to squamous
  229. squamous metaplasia
    • reprogramming of cells from columnar to squamous
    • occurs in pseudostratified respiratory epithelium in trachea & bronchi (prolonged exposure to cigarette smoke)
    • occurs in uterine cervix of women (chronic infections)
    • not cancer
  230. Barrett's esophagus
    • epithelial metaplasia at junction of stomach and esophagus (chronic acid reflux)
    • reprogramming of cells from squamous to columnar
    • considered precancerous
  231. function of connective tissue
    • binding, support, compartmentalization
    • hydration
    • transportation
    • defense
    • energy storage
  232. connective tissue cells
    • mesenchymal stem cells: primordial stem cells
    • fibroblasts: secrete extracellular matrix
    • immunce cells: fight infection, involved in inflammation
  233. extracellular matrix
    fibrillar matrix & interfibrillar matrix/ground substance
  234. fibrillar matrix
    • collagen: high tensile strength; tough
    • elastin: high stretchability; low tensile strength; long & thin
    • reticular: thin branched collagen that forms delicate networks
  235. interfibrillar matrix
    • ground substance
    • proteoglycans & glycosaminoglycans
    • soak up fluid like a sponge (hyaluronic acid & chondrotin sulfate)
  236. fetal mesenchyme
    • precursor to other cell types, mesoderm, & C.T.
    • connect with adjacent cell processes
    • gap junctions
    • sparse amount of collagen
  237. mucous connective tissue
    • found in umbilical cord
    • distinct arrangement of collagen type I, III, and V
    • ground substance called Wharton's Jelly (rich on hyaluronic acid)
    • hot area of research in differentiation
  238. embryonic connective tissue
    • fetal mesenchyme
    • mucous connective tissue
  239. types of connective tissue
    • embryonic connective tissue: mesenchyme & mucous CT
    • connective tissue proper: loose CT, dense CT (regular & irregular)
    • specialized connective tissue: cartilage, bone, adipose, blood, hemopoietic tissue, lymphatic tissue
  240. components of connective tissue
    • cells
    • fibrillar matrix
    • interfibrillar matrix/ground substance
  241. loose connective tissue
    • areolar
    • few collagen fibers & elastin fibers
    • abundant ground substance to hold body fluids
    • supports and binds other tissues
    • site of fighting infection (lamina propria & papillary layer of dermis)
  242. lamina propria
    • loose connective tissue of mucous membranes (respiratory and alimentary systems)
    • contain a large number of immune cells
  243. endoneurium
    • loose CT around axons
    • made up of collagen fibers
  244. dense irregular connective tissue
    • much more collagen than loose CT
    • collagen is irregularly arranged
    • resists strong tensions from different directions
    • gives resiliency to the dermis layer of skin
    • makes up fibrous capsules
  245. dense regular connective tissue
    • abundant in parallel collagen fibers
    • poorly vascularized
    • makes up ligaments, tendons, aponeuroses, and deep investing fascia of muscles
  246. tendiniocyte process
    rows of fibroblasts found between parallel bundles of collagen in tendons (dense regular CT)
  247. types of connective tissue fibers
    • collagen
    • elastin
    • reticular (type III collagen)
  248. hierarchy of collagen
    • fascia, tendons, ligaments
    • collagen bundle
    • collagen fiber
    • collagen fibril
    • packed collagen molecules
    • collagen molecule - triple helix of polypeptide chains
    • amino acids (hydrophillic)
  249. FACITs
    Fibril-associated collagens with interrupted triple helixes

    • usually associated on the surface of other collagen fibrils
    • ex. type IX collagen stabilizes network with type II
  250. collagen type I
    • 90% of body's collagen
    • skin, bone, tendon, fascia, organ capsules
  251. fibrillar collagens
    • resistance to tensile force
    • regulate other collagen molecules
    • ex. type I and II collagen
  252. hexagonal network-forming collagens
    • developmental collagens
    • ex. type X collagen contributes to bone mineralization via hexagonal lattices with fibrillar collagens and FACITs
  253. transmembrane collagens
    • interact with the cell membrane and other extracellular matrix proteins
    • ex. type XVII collagen interacts with integrins to anchor hemidesmosomes into basal lamina
  254. classes of collagen
    based on polymerization

    • fibrillar collagens
    • FACITs
    • hexagonal network-forming collagens
    • transmembrane collagens
    • multiplexins & basement-membrane forming collagens
  255. multiplexins & basement-membrane forming collagens
    • interact with the cell membrane and other extracellular matrix proteins
    • ex. type VII collagen secures basal lamina to type II collagen
  256. fiber degradation
    • proteolytic: matrix metalloprotinases (MMPs), collagenases, gelatinases, and macrophage metalloelastases
    • phagocytic: primarily macrophages
  257. reticular fibers
    • type III collagen
    • similar to type I in every way except thinner and have more branching
    • found in liver, spleen, and lymph nodes
  258. collagen disorders
    • osteogenesis imperfecta: type I collagen; fibrillar class
    • ehlers-danlos type IV: type II collagen; fibrillar class
    • multiple epiphyseal dysplasia: type IX collagen; FACIT class
    • schmid metaphysal dysplasia: type X collagen; hexagonal network forming class
    • generalized atrophic benign epidermolysis bullosa: type XVII collagen; transmembrane class
  259. osteogenesis imperfecta
    • type I collagen (fibrillar class)
    • mutation in COL1A1 and/or COL1A2 genes
    • abnormal and normal collagen are synthesized
  260. Ehlers-Danlos Type IV syndrome
    • a variety of gene mutations in type III collagen genes (fibrillar class)
    • hyper extensible skin
    • easy bruising
    • hypermobile joints
  261. multiple epiphyseal dysplasia
    • disarrangement of chondrocytes by other collagens
    • lack of type IX collagen (FACIT class)
    • seriously compromises cartilage development
  262. Schmid metaphysal dysplasia
    • type X collagen (hexagonal network forming class)
    • mutation in COL10A1 gene
    • abnormal hypertrophies chondrocytes and cartilage extends into the metaphysis
  263. generalized atrophic benign epidermolysis bullosa
    • type XVII collagen (transmembrane class)
    • blistering due to COL17A1 gene mutation
  264. elastic fibers
    • composed of two types of molecules - elastin & fibrillin
    • stretchable
    • synthesized by fibroblasts and smooth muscle cells
    • molecules linked together by desmosine & isodesmosine
  265. interfibrillar matrix composition
    • sugar & proteins
    • glycosaminoglycans (GAGs): most abundant, negatively charged (acidic), hyaluronic acid
    • proteoglycans: GAGs covalently bonded to a core protein
    • multiadhesive glycoproteins: stabilize ECM
  266. hyaluronic acid
    • hyaluronan
    • forms a scaffolding for proteoglycans to hang off
  267. other cells found in CT
    • myofibroblasts
    • macrophages
    • mast cells
    • adipocytes
    • stem cells
    • lymphocytes (T-cells, B-cells, plasma cells)
    • granulocytes
  268. myofibroblasts
    • fibroblasts differentiate into contractile & secretory myofibroblasts
    • act like a smooth muscle
    • F-actin filaments & alpha SMA
  269. wound healing/scar formation
    • cytokines are released to induce a variety of immune cells to migrate to a site of damage
    • fibrin helps blood clot, collagen is produced
    • myofibroblasts differentiate to help close the wound
    • the epithelium repairs itself
  270. types of scars
    • hypotrophic scar - stria
    • hypertrophic scar - keloid
  271. category of damage
    • 1: needle injection, suture cut - little damage & inflammation; little wound contraction & scar tissue
    • 2: scrape, minor cuts - moderate damage & inflammation; moderate scar tissue development
    • 3: infected cuts, abscess - severe damage; abundant granulation of scar tissue
    • 4: burns & bedsores
  272. macrophage
    • hemosiderin: broken down RBCs (rust colored)
    • anthracosis: broken down carbon particles (black specks)
  273. mast cell
    • arise from hemopoietic stem cells in bone marrow
    • bind IgE antibodies
    • degranulation of histamine
    • numerous in skin & mucous membranes
    • NOT present in CNS related tissue
  274. mediators of mast cells
    • histamine
    • heparin
    • serine proteases
    • eosinophil chemotatic factor
    • neutrophil chemotatic factor
  275. plasma cell
    • derived from circulating B-cells
    • antibody secreting cells
    • lots of rER and Golgi apparati
  276. types of cartilage
    • hyaline: glassy; most abundant; provides support through flexibility
    • fibrocartilage: contains lots of collagen; resists strong compression & strong tension
    • elastic: contains elastic fibers; able to tolerate repeated bending
  277. properties of cartilage
    • avascular (does not heal well)
    • resilient (stress & joint movement)
    • key tissue in growing bones
  278. composition of cartilage
    • 3-5% cells
    • 15% collagens (80% type II collagen)
    • 60-80% intercellular water
  279. chondrocytes
    • produce and maintain extracellular matrix
    • located in lacunae
    • isogenous groups: clusters of chondrocytes
  280. location of hyaline cartilage
    • fetal skeletal tissue
    • epiphyseal plates
    • articular surface of synovial joints
    • costal cartilage of rib cage
    • nasal cavity
    • larynx (thyroid, cricoid, arytenoid)
    • tracheal rings
    • plates in bronchi
  281. hyaline cartilage
    • "glassy"
    • perichondrium - where chondrocytes differentiate
    • type II collagen
    • proteoglycans (protein core)
    • glycosaminoglycans (GAGs) - hyaluronan (sugar backbone), chondroitin sulfate, keratin sulfate
    • multiadhesive glycoproteins
    • isogenic groups - dividing chondrocytes
  282. isogenic group
    dividing chondrocytes
  283. perichondrium
    • fibrous membrane surrounding cartilage
    • provides nourishment to the avascular cartilage
    • differentiating chondrocytes
  284. collagen distribution
    • capsular matrix: type VI collagen; immediately surrounding chondrocyte; highest concentration of proteoglycans
    • territorial matrix: type II collagen; surrounds the isogenous groups (most abundant in hyaline cartilage)
    • interterritorial matrix: matrix between groups of chondrocytes
  285. articular cartilage
    • NO perichondrium
    • tight structural zone
    • allows for smooth joint movement
  286. zones of articular cartilage
    • superficial (tangential)
    • intermediate (transitional)
    • deep (radial)
    • calcified
  287. properties of hyaline cartilage
    • provides low friction surface for joints
    • distributes forces to bone
    • resists repetitive stress
    • support structure
  288. location of fibrocartilage
    • intervertebral discs
    • pubic symphysis
    • articular discs (sternoclavicular, temporomandibular joints)
    • menisci (knee joint)
    • triangular fibrocartilage complex (wrist joint)
    • insertion of tendons
  289. fibrocartilage
    • hyaline cartilage + dense connective tissue
    • dense and fibrous
    • type I and type II collagen (variations depending on joint)
    • proteoglycans
    • chondrocytes bunched
    • herring bone appearance
  290. properties of fibrocartilage
    • tensile strength and ability to absorb compressive shock
    • resistant to shearing forces
  291. location of elastic cartilage
    • pinna of external ear
    • external auditory meatus
    • auditory (Eustachian) tube
    • cartilages of larynx (epiglottis, corniculate, cuneiform)
  292. elastic cartilage
    • hyaline cartilage + elastin
    • type II collagen
    • non-collagenous proteins
    • elastin
    • pairs of chondrocytes
  293. properties of elastic cartilage
    • maintains shape of structure but flexible
    • least abundant cartilage of body
  294. growth of cartilage
    • appositional growth
    • interstitial growth
    • division of chondrocytes stops in adolescence
    • calcification of cartilage occurs during normal bone growth and during old age
  295. appositional growth
    • new cartilage forming on surface of existing cartilage
    • cells in the perichondrium secrete matrix against the external face of existing cartilage
    • differentiating perichondrial cells into chondroblasts
  296. interstitial growth
    • new cartilage forming within existing cartilage
    • lacunae-bound chondrocytes inside the cartilage divide and secrete new matrix, expanding the cartilage from within
  297. types of adipose tissue
    • white (unilocular) fat
    • brown (multilocular) fat
  298. white adipose tissue
    • adipocytes store energy in lipid droplets (filled with triglycerides)
    • subcutaneous location provides thermal insulation
    • adipocytes secrete hormones, growth factors, and cytokines
    • contribute to insulin resistances leading to type II diabetes
  299. brown adipose tissue
    • good fat
    • found in new borns
    • found in certain places in adults (back, neck, mediastinum)
    • found in bears (hibernation)
    • highly innervated & under neural control
  300. regulation of adipose tissue
    • leptin
    • resistin
  301. leptin
    • regulates appetite and body energy expenditure
    • signals to the brain about body fat stores
    • increases formation of new vessels (angiogenesis)
    • involved in blood pressure (regulates vascular tone)
    • potent inhibitor of bone formation
  302. resistin
    • increases insulin resistance
    • linked to obesity and type II diabetes
  303. zonula occludens associated proteins
    • occludin
    • claudin
    • JAM (junctional adhesive molecules)
    • ZO1, ZO2, ZO3
  304. zonula adherens associated proteins
    • cadherins
    • actin filaments
    • vinculin
    • alpha-actin
    • catenin
    • E-cadherin
  305. macula adherens associated proteins
    • cadherins (desmocollin & desmoglein)
    • intermediate filaments
  306. gap junction associated proteins
  307. hemidesmosome associated proteins
    • intermediate filaments
    • integrins
  308. focal adhesion associated proteins
    • actin filaments
    • integrins
  309. Epidermolysis Bullosa: possible gene mutation sites
    • intermediate filaments (keratins)
    • anchoring filament proteins
    • anchoring fibril (type VII collagen)
  310. fascia adherens
    • nonepithelial junctional complex
    • cardiac muscle
  311. pemphigus foliaceus
    autoantibody mediated blistering disease in which antibodies against desmoglein 1 (cadherin of desmosomes) cause a loss of adhesion of keratinocytes in the superficial epidermis
  312. bullous pemphigoid
    breakdown of attachment plaque of hemidesmosome
  313. basal infoldings
    • increase membrane surface area
    • mitochondria tend to line up; striated cell surface appearance
    • allow for active transport through ion pumps
  314. lateral infoldings
    • maximize lateral cell contact & adhesion
    • communication
    • transport
  315. what is the embryonic origin of all CT?
    mesenchymal stem cells
  316. descendants of mesenchymal stem cells
    • fibroblasts: fibers
    • chondroblasts: cartilage
    • osteoblasts: bone
  317. fibroblast nuclei appearance
    • heterochromatic: not a lot of transcription going on, condensed DNA, reduced amount of cytoplasm (maintenance activity)
    • euchromatic: very active nuclei during wound healing
  318. mesenchyme
    • embryonic connective tissue that is derived from mesoderm
    • differentiates into mesenchymal stem cells (CT) and hematopoietic stem cells (blood cells, etc)
  319. is it loose or dense CT?
    • loose (areolar) CT: around the epithelium
    • dense CT: found as you migrate away from epithelial structures
  320. collagen fibers: H&E staining
    pink (eosin)
  321. collagen fiber: EM
    see striation of collagen at level of electron microscopy ONLY
  322. type II collagen
    • location -
    • function -
  323. type III collagen
    • location -
    • function -
  324. type IV collagen
    • location -
    • function -
  325. hydroxylation
    • dependent on vitamin C
    • necessary for the formation of hydrogen bonds
    • chaperone proteins prevent collagen aggregation intracellulary
    • keeps collagen soluble in water
  326. multiadhesive glycoproteins
    • fibronectin
    • laminin (NOT lamin - nuclear envelope)
    • associated with basal lamina
  327. osmium tetroxide
    stains FAT black
  328. review of nervous system
    • sensory input (afferent) -> integration in the CNS -> motor output (efferent)
    • afferents are integrated in the CNS to produce either somatomotor (GSE) or visceromotor (GVE) effects
  329. types of nerve tissue cells
    • neurons: basic structural unit of the nervous system
    • neuroglia: supporting cells
  330. neuron
    • the basic structural unit of the nervous system
    • dendrites: receptive field
    • cell body: DNA located in the nucleus; protein synthesis
    • axon: conducting region
    • axon terminal: at effector target; sympathetic boutons will synapse; secretory region releases NTs & causes effects
  331. types of neurons
    • integrative: found mainly in CNS
    • sensory: pseudounipolar neurons & bipolar neurons
    • motor: multipolar & autonomic neurons
  332. autonomic neurons
    • 2 neuron chain
    • innervate smooth muscle, glands & viscera
    • preganglionic & postganglionic neurons
    • sympathetic & parasympathetic nervous systems
  333. cell body
    • perikaryon
    • euchromatic nuclei: associated with neurotransmission; DNA must be transcribed, has to be accessible to RNA machinery to transcribe RNA
    • neurons that have euchromatic DNA are metabolically active
    • nucleolus: site of ribosomal RNA integration with ribosomes
    • Nissl bodies: stack of rER, ribosomes
    • Golgi body: packaging & distribution
    • lysosome: trash
    • mitochondria: energy
    • rough endoplasmic reticulum: production
  334. true or false: neurons are highly metabolic
  335. neuron cell body characteristics
    • euchromatic: DNA is being accessed
    • nucleolus: site of ribosomal RNA assembly
    • Nissl bodies: ribosomes & rough ER
    • protein & NT synthesis - major output!
  336. peripheral ganglia
    • dorsal root ganglia: uniform placement of nucleus in center of cell
    • sympathetic chain ganglia: nucleus polarized to one side; axon hillock (where AP is developed)
  337. dorsal root ganglia
    • cell body comes off axon
    • signal is sent right past the cell body
    • cell has to shuttle NTs and proteins out to periphery/terminal processes
    • not as much of a demand where the neuron is coming into contact with axon
  338. postganglionic sympathetic cell body
    • generation of nerve impulse has to go down only one way
    • cell has to get NTs out in the same direction - nucleus is polarized to one side
    • DNA machinery, rER & golgi bodies in a line - NT production & delivery is efficient
  339. dendrites
    • ex. Purkinje cells
    • located in cerebellum
    • extensive dendritic trees
    • very two dimensional, flat
  340. dendritic modification
    • unencapsulated - free nerve endings
    • encapsultated nerve endings
    • epithelial cell-associated
  341. unencapsultaed - free nerve endings (dendrites)
    peripheral nerve endings go out to every aspect of the skin they innervate
  342. encapsulated nerve endings (dendrites)
    • Pacinian corpuscle: looks like an onion (concentric rings); deeper in subdermis; responds to deep pressure; axons in center
    • Meissner's corpuscle: closely associated with epithelial cell; responds to light touch
  343. epithelial cell-associated dendrites
    • sensation is actually detected by an epithelial cell & sent to a free nerve terminal
    • axon is associated wtih epithelial-derived sensory cell in order to detects chemicals/ movement
    • ex. taste buds in tongue; hair cells in ear
  344. receptors associated with sensory neurons (dendrites)
    • exteroreceptors: detect outside; not self
    • enteroreceptors: detect inside; self
    • propioceptors: position in space
  345. the axon
    • myelin: insulation of the axon
    • action potential propagation
    • node of Ranvier: gap in myelin surrounding an axon; saltatory conduction increases speed of conduction
  346. node of Ranvier
    • gaps in myelin surrounding an axon
    • high concentration of voltage gated Na+ channels and voltage gated K+ channels
    • key for nerve impulses & development of action potential
  347. nerve
    collection of nerve fascicles (bundles of axons)
  348. nerve fascicle
    axons that have been bundled together
  349. nerve connective tissue elements
    • epineurium: outside lining; separates nerve fascicles (dense irregular CT)
    • perineurium: surrounding individual nerve fascicles; protrudes into nerve fascicles; establishes blood nerve barrier
    • endoneurium: surrounds invidual axons
  350. blood nerve barrier
    • established by perineurium
    • keeps blood & nervous tissue separate
    • perineurium & endothelial cells share basal lamina - allows transfer of oxygen & nutrients
  351. perineurium
    surrounds the nerve fascicle & forms blood nerve barrier
  352. distinguishing between dendrites & axons
    • follow the nerve impulse from start to finish
    • if it has myelin, it is likely an axon
    • if it has receptors, it is likely a dendrite
  353. nerve impulse
    • action potential: all or none wave of depolarization that travels along the neuronal membrane
    • neurons can shift their charge from negative to positive (depolarization) to generate a nerve impulse through manipulation of ions
    • basis of neuronal communication
  354. resting membrane potential of neurons
    • Em = -60V
    • negative charge inside cell
    • [K+] high inside cell, low outside cell
    • [Na+] low inside cell, high outside cell
    • difference in ion concentration along semipermeable membrane
    • chemical force & electrical force oppose each other to maintain this balance
  355. depolarization of neuron
    voltage gated Na+ channels allow positive charge to travel along length of axon
  356. hyperpolarization of neuron
    • opening of voltage gated K+ channels
    • Na/K ATPase activated to restore resting membrane potential
  357. types of conduction
    • continuous conduction: the nerve impulse travels down the neuronal membrane without interuption
    • saltatory (discontinuous) conduction: nerve impulse "jumps" each node of Ranvier until it reaches it's axon terminal (high concentration of voltage gated Na+ & K+ channels at each node)
  358. cellular function of neuron
    • synthesis
    • molecular motor proteins & transport
    • neurotransmitters (in brief)
    • nestin (if dividing... in passing)
    • enzymes (medical biochemistry)
  359. molecular motor proteins
    • kinesins: anterograde transport; from cell body to periphery or axon terminals
    • dyeins: retrograde transport; from periphery or axon terminal to the cell body
  360. kinesins
    • anterograde transport: from cell body to periphery or axon terminals
    • slow or fast transport depends on size & reactivity (larger molecules take longer)
    • shuttles - channel proteins, neurotransmitters (in vesicles), G-protein coupled receptors, organelles
  361. dyeins
    • retrograde  transport: from periphery or axon terminal to cell body
    • common route of toxins & poisons
    • use ATP
    • shuttles - signaling substances, functional proteins, non-functional proteins, damaged organelles, toxins or poisons
  362. retrograde tracer
    • nerve terminals take up lectin (in plants) tagged with red fluorescence
    • transported in retrograde fashion to get in cell bodies
  363. neurons: social network
    • detect stimuli
    • communicate with the use of action potentials & synapses
    • stimulate effector organs, glands, muscle & other neurons
  364. types of synapses
    • axosomatic: axon terminal on cell body (synapse with cell body)
    • axodendritic: axon terminal on dendrites of another neuron (synapse with dendrite)
    • axoaxonic: competing synapses of axons (synapse with axon)
  365. classes of synapses
    • electrical: utilizes connexons
    • chemical: utilizes neurotransmitters
  366. electrical synapse
    • utilize connexons/gap junctions
    • ~12 subunits
    • allows passage of ions from one neuron to the next
    • closure mediated by Ca2+
    • can be unidirectional or bidirectional
  367. chemical synapses
    • utilize neurotransmitters
    • very common
    • signal comes in & causes bouton to depolarize
    • Ca2+ mediates release of synaptic vesicles (release NTs)
  368. neurotransmitter release
    • depolarization of presynaptic element
    • opening of voltage gated Ca2+ channels
    • Ca2+ promotes vesicle release
  369. active zone
    presynaptic terminal of neuron
  370. ligand gated ion channels
    • specific effects on the membrane potential
    • Na+, K+, Cl-
    • ionotropic
  371. G protein coupled receptor
    • second messenger signaling (cAMP, IP3, PKA, etc)
    • produces cellular changes or may modify synthesis of selected proteins or neurotransmitters
    • metabotropic
  372. neurotransmitter receptors
    determine effect of neurotransmitter
  373. methods of removing NTs from synaptic cleft
    • high affinity reuptake: transport proteins take NTs back up at presynaptic membrane
    • degradation: NTs broken down by enzymes; usually at postsynaptic side
  374. controlling reuptake of NTs
    • inhibit reuptake transporters: prolong NT release in synaptic cleft, thus increasing signaling on postsynaptic membrane (crysstal meth & cocaine - catecholamines)
    • NT inactivation/degradation enzymes: catechol O methyltransferase (inactivate catecholamines) & monamine oxidase (destroy catecholamines - depression)
  375. neuroglia
    support cells
  376. PNS support cells
    • schwann cells: secrete myelin
    • satellite cells
  377. CNS support cells
    • astrocytes
    • oligodendrocytes
    • microglia
    • ependymal cells
  378. schwann cell
    • forms myelin around axon in PNS (increases conduction velocity of a nerve impulse)
    • Schmidt Lanterman clefts: where schwann cell cytoplasm will push through myelin & get wrapped around axon
  379. myelination of schwann cell
    • cytoplasm is pushed out in myelinated axons
    • ~80% is just Schwann cell membrane
    • unmyelinated axons have Schwann cell's membrane over it, but cytoplasm hasn't been pushed out
    • membrane is mostly lipid - positively charged link folded cell membrane creating a large distance from the axon (faster nerve impulse!)
  380. Protein O
    transmembrane protein associated with demyelination diseases seen in Multiple Sclerosis & Guillian-Barre Syndrome
  381. myelinated axons: EM
    • membrane is folded tightly on itself
    • SLC: where a little cytoplasm has poked into membrane
  382. unmyelinated axons: EM
    • schwann cells are also found on unmyelinated axons
    • difference is cytoplasm is wrapping around individual neurons (NO FOLDS)
    • neurolemma: schwann cell cytoplasm that wraps around the axon for support
  383. cytoplasmic relationships of schwann cell
    • axon
    • node of Ranvier: little cytoplasm over it, but no folds
    • inner collar: closely related to cytoplasm; just superficial to axon
    • myelin: concentric rings
  384. schmidt-lanterman clefts
    • part of the myelin sheath that contains Schwann cell cytoplasm
    • provides metabolic support for inner lamina of Schwann cell
    • the larger the axon, the more Schmidt-Lanterman clefts
  385. satellite cells
    • found mainly with peripheral ganglia
    • support cell bodies
  386. astrocyte functions
    • regulate NT levels in regions of high neuronal activity
    • regulate capillary blood flow in parts of the brain
    • regulate ionic environment (K+) - potassium batteries
  387. types of astrocytes
    • protoplasmic astrocyte: usually associated with gray matter & has lots of connections with neurons & blood vessels
    • fibrous astrocyte: usually associated with white matter & have few connections with neurons & blood vessels (acts more like CT for CNS, still has some metabolic activity)
  388. clinical relevance of astrocytes
    • ~80% of adult primary brain tumors arise from fibrous astrocytes
    • intermediate filament of importance - glial fibrillary acidic protein (GFAP) is a major marker for diagnosing brain tumors
    • mediation of blood brain barrier
    • involved in potassium spatial buffering
  389. where does blood brain barrier begin?
    • pia mater lines CNS tissue
    • vascular endothelial cells
    • protoplasmic astrocyte foot process will separate these layers
  390. how do the pia & the atrocytes make the blood brain barrier?
    • pia & blood vessels invaginate
    • as you get closer to capillary beds, pia mater thins
    • astrocytes take over - foot process of astrocytes associate with endothelial cells of capillary beds
  391. oligodendrocytes
    • similar to schwann cells - different kinds of myelin proteins
    • found in CNS
    • have few Schmit-lanterman clefts (astrocyte support)
    • nodes of Ranvier are BIGGER
  392. microglia
    • migrate & engulf microorganisms, injured or dead neurons
    • derived from monocytes associated in the immune system
    • the phagocytic macrophages of the CNS
  393. ependymal cells
    • simple epithelium layer that lines ventricles of the brain & spinal canal
    • contain cilia to help circulate CSF
    • contain microvilli to help absorb CSF
  394. response of neurons to injury
    • degeneration
    • regeneration
  395. degeneration
    • Wallwerian: anterograde degeneration of peripheral axon or axon terminal
    • traumatic: retrograde degeneration of proximal axon (toward cell body)
    • chromatolysis: preclude to neuronal death; cell body swells under high metabolic stress
  396. regeneration
    • growth cone: starts at tip of neuron & leads to sprouting
    • sprouting: nerve can grow back (maybe not in correct place)
  397. major factor affecting regeneration
    • presence of myelin
    • macrophages are able to clear it when a nerve is crushed or damaged in PNS
    • microglia are unable to clear it when CNS tissue is damaged
  398. gliosis
    increased production of glial fibrillary acidic protein (GFAP)
  399. contractile cells
    • muscle tissues
    • non-muscle tissues
  400. muscle tissues
    • striated muscle - skeletal & cardiac muscle cells/fibers
    • smooth muscle
  401. other non-muscle contractile cells
    • myoepithelial cells
    • myofibroblasts
    • pericytes
    • perineurium
    • satellite cells
  402. examples of non-muscles cells which contract
    • sweat gland - myoepithelial cells
    • wound healing - myofibroblasts on flexible membrane
  403. striated muscle
    • voluntary/skeletal: axial skeleton, appendicular skeleton
    • involuntary/cardiac: heart, great vessels
    • visceral striated: upper esophagus
  404. smooth muscle
    • vascular smooth: blood vessels
    • visceral smooth: tubular organs
  405. skeletal muscle connective tissue sheaths
    • epimysium: sheath of dense CT surrounding a collection of fascicles that constitute a muscle; main vascular & nerve supply penetrate the epimysium
    • perimysium: surrounds a group of fibers to form a fascicle
    • endomysium: delicate layer of thin reticular (collagen III) fibers with very thin terminal nerve fibers & blood vessels surrounding individual muscles
  406. sarcolemma
    • plasma membrane of muscle cell + basal lamina
    • nucleus is pushed to edge below it
  407. thick sarcolemma
    plasma membrane + external lamina + part of reticular lamina
  408. sarcoplasm
    • muscle cytoplasm
    • filled with bundles of contractile proteins (myofibrils)
  409. myofibril
    • contractile proteins within sarcoplasm
    • composed of myofilaments
  410. cytology of skeletal muscle
    skeletal/voluntary muscles cells are multinucleated
  411. muscle fascicle
    bundle of muscle fibers (composed of myofibrils)
  412. fiber organization of skeletal muscle
    • striations clearly seen - crystalline structure
    • striations are perpindicular to longitudinal axis of muscle fiber & force
    • capillaries lie in the endomysium
    • flattened nuclei are just under sarcolemma
    • fibroblast nuclei: outside of cells
    • cytoplasm filled with contractile proteins
  413. muscle fiber types
    • red (type I)
    • white (type IIa,b)
  414. red fiber
    • Type I
    • rich in mitochondria - oxidative enzymes
    • thinner than Type II
    • classified as slow twitch
    • ex. postural muscles; deep back muscles
    • function - sustained contraction
  415. white fiber
    • Type IIa,b
    • few mitochondria - glycolytic enzymes
    • larger diameter than Type I
    • classified as fast twitch
    • ex. extraocular muscles
    • function - rapid contraction
  416. true syncytium
    • skeletal muscles
    • form in development as mononucleated small cells from developing mesodermal mesenchyme
    • myoblasts - myotube - strap cell - mature cells
    • myoblasts fuse with adjacent myoblasts to form multinucleated muscle strap cell
  417. cross striation of muscle fibers
    • consist of dark & light bands
    • polarized microscopy
  418. muscle fascicle composition
    • sarcolemma: multiple nuclei lying in close proximity beneath
    • myofibril: banding patterns already visible (arrangement of proteins)
    • mitochondrion: energy
  419. myofibril banding
    • skeletal muscle fiber under phase-contrast light microscopy
    • A band: anisotropic
    • I band: isotropic
    • band shading in electron microscopy similar
  420. sarcomere
    • basic unit of contraction in striated muscle
    • defined as the distance between adjacent Z lines
  421. components of sarcomere
    • A band: anisotropic; overlap region of thick & thin filaments
    • H band: light region that bisects A band; thick fibers arranged in hexagonal pattern
    • I band: isotropic; pattern of 6 thin filaments
    • M line: in middle of H band; interaction of thick & thin filaments (stabilizing lattice)
    • Z line: thin line in middle of I band
  422. sarcoplasmic reticulum
    • non-junctional SR: NOT part of triad
    • junctional SR: contains terminal cisternae (calcium storage)
  423. transverse tubule
    • invagination of sarcolemma that digitizes with parts of SR
    • insert at region of terminal cisternae (where A/I junction occurs)
    • connects outside with inside
    • link between nervous system & contractile apparatus
  424. triad
    • transverse tubule + two terminal cisternae
    • located at A/I junction
  425. calsequestrin
    • bound to calcium in terminal cisternae of skeletal muscle
    • allows calcium to be stored in sarcoplasmic reticulum
  426. molecular basis of contraction
    sliding filament theory
  427. sarcomere function
    muscle contraction
  428. skeletal muscle contraction
    • length of A band always remains the same (length of thick filaments)
    • I & H bands shrink
    • Z lines are drawn toward M
  429. stretched sarcomere
    • thin & think filaments do not interact
    • H & I bands are very wide
  430. contracted sarcomere
    • interdigitation of thin & thick filaments is increased according to degree of contraction
    • H & I bands are very narrow
    • Z line drawn closer to M line
  431. accessory proteins
    • tropomyosin: double helix that forms filaments that run in the groove between the F-actin (thin filament)
    • tropomodulin: binds both actin & tropomyosin; stabilizes
    • troponin complex: three globular subunits; one complex per tropomyosin molecule
  432. troponin complex
    • troponin T: binds to tropomyosin
    • troponin C: binds calcium
    • troponin I: blocks active site on actin filament
  433. thin filament components
    • F-actin
    • tropomyosin
    • tropomodulin
    • troponins
  434. thick filament
    • myosin II
    • tail - two heavy chains
    • head - four light chains; has ATPase activity (ATP binding site); actin binding site
    • bundle of myosin molecules has polarity
  435. alpha-actinin
    • actin binding protein
    • bundles thin filaments into parallel arrays
    • anchors thin filament to Z line
  436. rigor configuration
    • in the absence of ATP, myosin remains tightly bound to actin
    • in death, no ATP is available - rigor mortis
  437. titin
    • anchors thick filament
    • stabilizes M line
  438. nebulin
    spirals around thin filaments; anchors
  439. sliding filament theory
    • stage 1: attachment (rigor configuration)
    • stage 2: release
    • stage 3: bending
    • stage 4: force generation
    • stage 5: reattachment
  440. stage 1: attachment
    • myosin head is tightly bound to one of the globular proteins of thin filament
    • ATP is absent
    • known as rigor configuration
  441. stage 2: release
    • ATP binds to myosin head
    • conformational change occurs in myosin - ATP, myosin head is released from actin
  442. stage 3: bending
    • ATP undergoes hydrolysis
    • conformational change occurs in myosin - ADP & Pi
    • myosin head moves toward Z line
  443. stage 4: force generation
    • myosin head binds weakly to new actin site
    • Pi is released
    • increased myosin affinity for actin
    • head returns to original position generating force
    • ADP released
  444. stage 5: reattachment
    • rigor configuration, cycle can repeat
    • myosin head binds tightly to new actin site
  445. neuromuscular junction
    • voluntary muscles innervated by large nerves
    • nerve's axon (coated with special layers of myelin) comes in & branches to form a bunch of little processes which end on a number of muscle cells
    • loses myelin when comes in contact with muscle cells
    • branches out to form different motor end plates
  446. NMJ: axonal depolarization
    motor neuron: impulse travels from CNS axon that is myelinated (until muscle contact)
  447. motor unit
    single motor neuron & the muscle fibers it innervates
  448. finest motor units
    • fewest muscle fibers/neuron
    • ex. extraocular muscles, intrinsic muscles of hand (lumbricals)
  449. NMJ: motor endplate
    • acetylcholine (ACh) released from motor endplate of presynaptic membrane into synaptic cleft
    • ACh binds to receptor on muscle cell (postsynaptic membrane)
    • Voltage gated Na+ channels open & Na+ rushes into muscle fiber
  450. synaptic cleft
    indentation within muscle fiber with deep protrusions that increase surface area
  451. external lamina
    Schwann cell + nerve fiber + muscle cell fused together
  452. basal lamina
    contains acetylcolinesterase to break down excess ACh
  453. NMJ: excitation-contraction coupling
    • depolarization carried in by T tubules
    • voltage sensitive Ca+ channels change conformation
    • gated Ca+ release channels induce conformational change
    • Ca+ released from SR into sarcoplasm
  454. NMJ
    • 1. motor neuron: impulse travels from CNS down myelinated axon
    • 2. impulse travels down axon & neurotransmitter ACh is released into synaptic cleft; binds to receptor on muscle cell
    • 3. voltage gated Na+ channels open; Na+ rushes into muscle fiber
    • 4. depolarization wave is carried by T Tubules
    • 5. Voltage sensitive gated Ca+ channels change conformation
    • 6. Gated Ca+ release channels induced to change conformation
    • 7. Ca+ released from SR at terminal cisternae into sarcoplasm
    • 8. Ca+ present & binds to troponin to start muscle contraction
  455. proprioception
    muscle spindle response to stretch
  456. innervation of muscle spindles
    • afferent (sensory)
    • efferent (motor)
  457. intrafusal fibers
    modified muscle fibers within spindle apparatus
  458. extrafusal fibers
    normal muscle fibers outside the spindle apparatus
  459. muscle spindles
    • work in conjunction with Golgi tendon organs
    • respond to stretch
    • afferent & efferent innervation
    • intrafusal fibers: within spindle apparatus
    • extrafusal fibers: outside spindle apparatus
    • nuclear bag fiber
    • nuclei chain fiber
  460. Golgi tendon organ
    • innervated by afferent (sensory) nerves ONLY
    • respond to contraction
    • counteract the action of muscle spindles
    • located at junction between muscle fibers & tendon
  461. cardiac muscle fibers
    • short 15-80um cells
    • branches, mono, or binucleated fibers (in adults)
    • connected by intercalated disks
    • innervated by autonomics
  462. functional syncytium
    • cardiac myocardium
    • not cellular (fused) as with skeletal muscle cells; but function as a unit
  463. intercalated disk
    • specialized stair-case like junction
    • can form terminal junctions as well as side connections
    • termination of cardiac muscle fibers
  464. cardiocyte features
    • huge myofibrils
    • nucleus in center of myofibrils (mono or binucleated)
    • reduced SR
    • no terminal cisternae
    • large diameter T tubes anchor at Z line
    • diad: 1 T tube + 1 SR
  465. ANF
    • atrial natriuretic factor
    • contained in secretory granules from atrial cardiac myocytes
    • regulates blood pressure & salt content
    • functions with renin-angiotensin system
  466. intercalated disc complex
    • stepwise junctional complex unique to heart
    • macula adherens: spotlike junction
    • fascia adherens: tight connections
    • gap junctions: primarily seen as longitudinal component
    • transverse components - macula adherens & fascia adherens
  467. smooth muscle
    • found in all tubular organs
    • fusiform cells: nucleus in middle with spindle state
    • no defined sarcomere
    • caveolae: small vesicles associated with plasma membrane that serves as Ca2+ storage (NO T system)
    • cytoplasmic Ca2+ bound to calmodulin
    • dense bodies: anchor intermediate filaments and myofibrils
    • NO striations
    • epimysium, perimysium, and endomysium not well defined
    • communicate via gap junctions
  468. dense bodies
    • anchor intermediate filaments & myofibrils in smooth muscle
    • similar to Z line of skeletal muscles
    • composed of alpha actinin
  469. relaxed smooth muscle
    • actin sites closed
    • myosin tail coiled on itself
  470. active smooth muscle
    • myosin light chains are phosphorylated via myosin light chain kinase
    • myosin tail released
    • actin binding sites open
  471. smooth vs skeletal muscle thick filament (myosin)
    • skeletal: bipolar thick filament
    • smooth: side-polar thick filament
  472. smooth muscle contraction
    • inactive: actin sites closed; myosin tail coiled
    • in presence of Ca2+, calmodulin myosin light chain kinase is activated
    • active: myosin light chains are phosphorylated; myosin tail is released; actin binding sites open
  473. pulmonary circulation
    • right side
    • receives blood through Superior & Inferior Vena Cava
    • moves blood from heart to lungs
    • usually smaller than systemic
  474. systemic circulation
    • left side
    • receives blood from lungs, moves it throughout the body (arterial system)
    • usually larger
  475. function of circulatory system
    • transport nutrients & waste
    • acid/base regulation
    • immune response
    • water balance
  476. average adult fluid volume
    • 3.5L plasma
    • 2.0L RBCs
    • 10.5L interstitial fluid

    ~16L circulating fluid
  477. vascular fluid distribution
    • 65% peripheral veins
    • 20% heart/lungs
    • 10% peripheral arteries
    • 5% capillaries
    • veins predominant as capacitance vessels
    • while capillaries contain the least amount of fluids, they are the major site of exchange
  478. circulatory site of exchange
    • capillaries
    • thinnest walls, greatest area
  479. layers of all vessels in macrocirculation
    • tunics
    • tunica intima: innermost layer
    • tunica media: "in the middle"
    • tunica adventitia: outermost layer
  480. tunica intima
    • innermost layer of circulatory vessel
    • lined by single layer of endothelium
    • smooth muscle cells may be present
    • some connective tissue
    • may be subendothelium as well
  481. tunica media
    • 'in the middle'
    • smooth muscle: secretion of elastin & collagen
    • connective tissue
    • diagnostic layer
  482. tunica adventitia
    • outermost layer
    • connective tissue & many types of cells
    • vaso vasorum: blood vessels that supply blood to blood vessels (ex. coronary arteries)
    • nervi vascularis: nerve supply to blood vessels (ex. tenth nerve)
  483. pinocytosis
    transportation of water or water-soluble products across the cell
  484. receptor mediated endocytosis
    transport process involving ligand, receptor complexes, clathrin coated vesicles
  485. channels
    hole/tunnels through cells for transportation of large macromolecules & cells
  486. continuous capillaries
    • 4-10um in diameter (~size of RBCs)
    • endothelium: different types of cells that complement each other
    • pinocytotic vesicles NOT fenestrations
    • marginal folds: form tight continuous seal
  487. pericytes
    • stem cells associated with basal lamina
    • can differentiate into endothelium, muscle, etc...
  488. fenestrated capillaries
    • fenestrations: "little window"; clusters of openness
    • may have "window panes"/ membrane or not
  489. sinusoidal capillaries
    • incomplete or absent basal lamina
    • CT fibers
    • HUGE - fit RBS in them
  490. functions of continuous capillaries
    • gas exchange
    • have occluding junctions
    • found in brain, muscle, blood
    • serves as blood organ barriers
  491. function of fenestrated capillaries
    • filtration
    • found in endocrine organs/glands, kidney
  492. function of sinusoidal capillaries
    • passage of large molecules (ex. RBC in spleen)
    • found in liver, spleen, bone marrow
  493. precapillary sphincters
    • muscles that can close/open metarterioles
    • control blood flow through thoroughfare channel
  494. thoroughfare channel
    link from metarteriole directly to venule bypassing capillary bed
  495. ateriovenous shunt
    • completely bypasses microcirculation
    • shunts arterial blood directly to venial side
  496. portal systems
    • blood perfuses two separate and distand capillary beds without passing through the heart
    • involve arterial links or venous links
  497. arterial portal system
    • afferent arteriole - capillary network - efferent arteriole - capillary - venule
    • ex. glomerulus of kidney
  498. venous portal
    • arteriole - capillary - vein - capillary/sinusoid - vein
    • ex. hepatic portal system
  499. features of large elastic arteries
    • thin layer of tunica intima
    • MOST prominent layer - tunica media; alternating layers of smooth muscle cells & elastic tissue; "ham & cheese"
    • tunica adventitia - contains many cell types
  500. fetures of muscular arteries
    • tunica intima + internal elastic lamina
    • tunica media - mostly smooth muscle cells (thickest layer)
    • external elastic lamina
    • tunica adventitia - visible fibroblasts & unmyelinated nerves
  501. features of arterioles
    • tunica intima - 1 cell thick; very thin internal elastic lamina
    • tunica media - 1-2 layers of smooth muscle
    • tunica adventitia - thin ill-defined sheath of CT
  502. site of greatest peripheral resistance
  503. function of endothelium in cardiovascular system
    • endothelial cells secrete a number of products
    • endothelial cells are connected by a junctional complex which creates compartments
    • endothelial cells are specialized for a number of functions
  504. features of muscular venules
    • tunica intima - one layer of endothelial cells & pericyte
    • tunica media - one to two layers of smooth muscle cells
    • tunica adventitia - connective tissue with some elastic fibers
    • 50-100um
  505. features of small muscular veins
    • tunica intima - endothelium
    • tunica media - 2 to 3 layers of smooth muscles
    • tunica adventitia - CT; thicker than T. media
    • 0.1-1.0mm
  506. features of medium muscular veins
    • tunica intima - endothelium; maybe smooth muscle; internal elastic lamina
    • tunica media - smooth muscle cells
    • tunica adventitia - bundles of smooth longitudinal smooth muscles; thick; blends with interstitial tissue
    • 1-10mm
  507. features of large muscular veins
    • tunica intima - endothelium, internal elastic lamina
    • tunica media - 2 to 15 layers of smooth muscle cells
    • tunica adventita - HUGE smooth muscle cells in longitudinal bundles
  508. varicosities
    • failure of valves due to weakening of muscular tunics
    • varicose veins in legs
    • esophageal varices
    • epidydmal varices
  509. features of lympathic capillaries
    • begin as blind sac (lacteals in GI)
    • tunica intima - single epithelium
    • tunica media - one to 4 layers smooth muscle cells
    • tunica adventitia - anchoring fibrils, reduced CT
  510. lacteals
    • located within core of villus in intestine
    • contain loose CT filled with lymph & a few WBCs
  511. valves
    • skeletal muscle contraction propels lymphatic system
    • shape of valve leaflets prevents backflow
  512. function of lymphatics
    • lymphatic vessels are more permeable that blood caps
    • collect excess protein rich tissue fluid
    • important in removing excess interstitial fluid & proteins
    • loss due to surgery, injury, or disease lead to edema (excess interstitial fluid)
  513. layers of the heart
    • epicardium: visceral pericardium
    • myocardium: muscle of the heart
    • endocardium: inner endothelial lining
  514. epicardium
    • thin mesothelium (specialized cuboidal epithelium)
    • subendothelial fat & coronary arteries
    • secretes pericardial fluid
  515. atrial cardiocytes
    • weak contraction
    • secrete ANF to help decrease blood pressure
  516. ventricular cardiocytes
    • contraction
    • highly developed intercalated disks
  517. myocardium
    • muscle of the heart
    • analogous to tunica media
    • atrial & ventricular cardiocytes
  518. endocardium
    • inner endothelial lining
    • analogous to tunica intima
    • consists of three compartments - endothelial, subendothelial, subendocardium
  519. ventricular endocardium compartments
    • endothelial: contains endothelium, CT
    • subendothelial: contains smooth muscle cells, CT
    • subendocardium: site where conductive fibers (Purkinje cells) pass into myocardium
  520. Purkinje fibers
    • modified cardiac muscle cells
    • contain glycogen
    • poorly organized myofibrils
    • no striations or intercalated discs
  521. lung lagniappe
    • surface area - 80m2
    • entire blood volume (5 liters) passes through lungs eaach minute
    • lungs inspire about 10,000 liters air/day
    • gas exchange occurs in about 0.25 sec
    • 10% of lung composed of solid tissue
    • 90% blood & air
    • lungs weight 300-400 grams
  522. respiratory system
    • extensive branching system
    • extends from the vestibile of the nasal cavity to the alveoli of the paired lungs
  523. functions of respiratory system
    • air conditioning - warms & moistens
    • air filtration
    • gas exchange
    • facilitates speech, smell, hormone, and immune functions
  524. parts of respiratory system
    • conducting portion: nasal cavitities, pharynx, larynx, trachea, bronchi & bronchioles (transport, filter, & condition)
    • respiratory portion: respiratory bronchioles, alveolar ducts, sacs, & alveoli (gas exchange)
  525. nasal cavity
    • paired chamber separated by nasal septum
    • communicates: external environment & nasopharynx, paranasal sinuses, nasolacrimal duct
  526. parts of the nasal cavity
    • vestibule: transition zone
    • olfactory region: mucosa for smell
    • respiratory region: characteristic mucosa of respiratory region
  527. olfactory epithelium
    • olfactory receptor cells: bipolar neurons
    • sustentacular cells: columnar support cells
    • basal cells: stem cells
    • brush cells: general sensation
    • NO goblet cells
    • Bowman's glands: serous secretions
  528. respiratory epithelium
    • ciliated psuedostratified columnar
    • ciliated cells: tall columnar; not covered by microvilli
    • brush cells: microvillus receptor cells (general perception)
    • small granule cells: enterendocrine cells
    • basal cells: stem cells
    • Goblet cells: mucous cells
  529. ciliated cells
    • most numerous cell type
    • extend through full thickness of epithelium
    • apical surface covered with 200-300 cilia
    • cilia contain 9+2 arrangement microtubules (MOVEMENT - dyeins & kinesins)
    • cells function as the mucociliary escalator
    • responsible for removing mucous from lungs
  530. Goblet cells
    • mucous cells
    • interspersed among ciliated cells
    • extend the full thickness of epithelium
    • accumulate mucinogen granules
    • lack cilia on apical surface
    • number of mucous cells increases during chronic irritation of air passages
  531. brush cells
    • columnar cells with microvilli
    • basal surface in synaptic contact with afferent nerve endings
    • sensory receptor cell
  532. small granule cells
    • enteroendocrine cells that secrete polypeptide hormones
    • sparingly dispersed along basal lamina
    • though to regulate vascular and airway diameter
  533. basal cells
    • reserve stem cell population
    • nuclei line up along basal lamina
    • give rise to all cell types
  534. structures involved in particle elimination
    • vestibile region of nasal cavity (vibrissae)
    • nasal conchae or turbinates (nasal cavities)
    • goblet and ciliated cells
  535. function of particle elimination
    • vestibular vibrissae collect particles
    • turbinates increase surface area
    • mucosa captures particles & cilia propel to pharynx - mucociliary escalator
  536. larynx
    • air passageway between oropharynx & trachea
    • organ for sound production
    • ventricular folds & vocal folds
  537. structure of larynx
    • complex structure
    • hyaline & elastic cartilages: epiglottis, thyroid, cricoid, arytenoid, cuneiform, corniculate
    • ligaments & ligamentous membranes: conus elasticus & quadrangular membrane
    • numerous skeletal muscles
  538. luminal folds
    • ventricular folds: "false vocal cords"; paired folds superior to laryngeal ventricle; contain mixed mucoserous glands
    • vocal folds: "true"; paired folds inferior to laryngeal ventricle; contain a supporting ligament & vocalis muscle
    • abrasive region changes epithelium
  539. trachea
    • flexible air tube
    • numerous C-shaped hyaline cartilage rings (16-20)
    • bifurcates into 2 main (primary) bronchi - around T4/T5 vertebral level
  540. layers of tracheal wall
    • mucosa: respiratory epithelium & thick basement membrane & lamina propria
    • submucosa: seroumucous glands & lymphatic tissue (BALT - bronchial associated lymphatic tissue & MALT - mucosal associated lymphatic tissue)
    • cartilaginous layer: C-shaped hyaline cartilage & trachealis muscle "bridge"
    • adventitia: CT layer binds tracheal parts together, contains blood vessels & nerves
  541. extrapulmonary bronchi
    • same general respiratory epithelium & histology as trachea
    • thick basement membrane
    • cartilaginous rings
    • submucosal glands
    • BALT - bronchial associated lymphatic tissue
    • full ring of muscle (circumferential layer)
  542. intrapulmonary bronchi
    • divide into lobar (secondary) bronchi
    • secondary branch into segmental (tertiarty) bronchi
    • cartilaginous rings replaced by plates
    • circumferential smooth muscle
  543. bronchi diameter decreases...
    • increase in smooth muscle
    • decrease in cartilaginous plates
    • ciliated simple columnar epithelium
    • loss of submucosal glands
  544. layers of bronchi
    • mucosa: ciliated psuedostratified columnar epithelium; cell height decreases with diameter; decreased basal membrane & lamina propria
    • muscularis: continuous circumferential layer of smooth muscle; loosely organized in smaller bronchi; helps regulate diameter of airway
    • submucosa: loose CT & mucoserous glands
    • cartilage layer
    • adventitia
  545. bronchioles
    • diameter - 1mm
    • branches of segmental bronchi
    • larger have respiratory epithelium
    • NO submucosal glands or cartilage plates
    • simple ciliated columnar in smaller bronchioles
    • reduced goblet cells
  546. olfactory transduction pathway
    • non-motile cilia
    • second messenger pathways depolarize cells of olfactory receptors (usually use Ca2+)
  547. terminal bronchioles
    • branches of bronchioles
    • no goblet cells
    • simple ciliated columnar OR cuboidal epithelium
    • smooth muscle reduced
    • clara cells present in terminal bronchioles
  548. Clara cells
    • non-ciliated dome cells
    • secretes surface-active agent - decreases surface tension in alveoli
    • secretes Clara cell secretory protein (CC16) - protein marker for damage to lungs (COPD, smoker, etc see increase in CC16 serum levels)
  549. terminal portion of respiratory tract
    • terminal bronchiole
    • respiratory bronchiole
    • alveolar duct
    • alveolar sac
    • alveoli
  550. respiratory bronchioles
    • transition zone between the conduction to the gas exchange portions
    • outpocketing of alveoli along wall
    • initial segments - mixture of ciliated cuboidal epithelium & Clara cells
    • distal segments - only a few Clara cells, NO ciliated cells
    • NO goblet cells
    • smooth muscle is patchy
  551. alveolar ducts
    • elongated air ways with almost no walls
    • made of alveoli
    • knoblike smooth muscle within intralveolar septa
  552. alveolar sacs
    • space within small cluster of alveoli
    • terminal portions of alveolar ducts
  553. alveoli
    site of gas exchange
  554. cells of alveolar septum
    • type I alveolar cells
    • type II alveolar cells
    • capillary endothelium
    • fibroblast
  555. type I alveolar cells
    • type II pneumocytes
    • line 95% of alveoli surface
    • highly flattened squamous cells
  556. type II alveolar cells
    • type II pneumocyte or septal cells
    • cuboid shape
    • lines 5% alveolar surface
    • gives rise to type I alveolar cells
    • secretes surfactant: phospholipid decreases surface tension
    • approximately the same number of pneumocytes as type I
    • found at septal junctions
  557. capillary endothelium
    highly flattened squamous cells
  558. fibroblast
    produce connective tissue components
  559. air-blood barrier
    • alveolar septum
    • cells & cell products (gases) must diffuse between alveoli & capillaries
    • components - surfactant, type I alveolar cell, capillary endothelium, basal lamina of both cells (fused)
  560. alveolar macrophages
    • phagocytic cell derived from blood monocytes
    • dust cells: single macrophages containing dust particles from inspired air
    • foreign body giant cell: several macrophages that fuse together to encapsulate large particles
    • unique - function in the septum & in the air of alveoli spaces
    • can remain in septum filled with phagocytosed material
  561. cystic fibrosis
    • autosomal recessive disease
    • mutation of CFTR (cystic fibrosis transmembrane conductance regulator)
    • chloride channels that are responsible for mucus hydration due to increased absorption of sodium
    • abnormally thick mucus
    • increased infections, bronchiole thickening, degeneration of alveoli
  562. overview of epithelial changes in respiratory system
    • ciliated pseudostratified columnar epithelium: from trachea to main bronchi
    • ciliated simple column epithelium: in bronchioles
    • ciliated simple cuboidal epithelium: in terminal bronchioles
    • simple squamous epithelium: in alveoli
Card Set
Histo Block A
Histology Block A