Histo Block A

ex: H&E staining

• used to localize certain enzymes
• uses marked substrates that bind to a specific enzyme which allows you to visualize organelles

• conventional staining
• enzyme histochemistry
• immunocytochemistry
• hybridization
• autoradiography

• light microscopy
• confocal scanning microscopy
• electron microscopy

• picometer (10^-12 m)
• angstrom (10^-10 m)
• nanometer (10^-9 m)
• micrometer (10^-6 m)

1 angstrom

8-10 nm

~8 um

• removal of tissue from animal
• cutting tissue into this sections
• fixation
• dehydration
• embedding
• sectioning
• mounting and staining

• immersion or perfusion in formalin
• hardens tissue
• stops cellular metabolism
• prevents autolysis
• kills pathogens

• 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)

• tissue cut into ultrathin segments using a microtome
• artifacts from preparation present

• methyl green
• methylene blue
• pyronin G (red)
• toluidine blue

• acid fushsin (red)
• aniline blue
• eosin (red)
• orange G

• the most commonly used staining technique
• counterstain
• both water based stains

• basophilic dye (+ charged)
• affinity for negatively charged molecules (eg nucleic acids)
• will stain DNA, RNA, and ribosomes (rRNA)
• blue in color

• acidophilic dye (- charged)
• affinity for positively charged molecules
• will stain cytoplasm, membranes, SER, and mitochondria, "membranes"
• red/pinkish color

• 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

• Periodic Acid Schiff
• stains carbohydrates and carbohydrate rich molecules a reddish magenta color (glycogen, glycoproteins)
• basement membranes  tend to be high in glycoproteins

• enzyme is localized and stained by binding marker to substrate of that enzyme
• stain will accumulate in areas of enzyme activity

• 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

• 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

fluorescent probe to DNA using nucleic acid probes that bind to complementary DNA segments

• radioactively labeled amino acids/ hormones are incorporated within structures
• visualization determines location and activity of labeled substances

• "father of microbiology"
• early inventor of the microscope
• first looked at cell walls of course

the closest distance that two objects can be distinguished

basic structural unit

basis for histologic characterization of tissues

• cytoplasm & cytoplasmic matrix
• organelles & inclusions
• nucleus

• 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)

• microtubules - cell division and directionality of molecules
• filaments - actin, intermediate (contractility, maintainance of structure)
• centrioles, Basal bodies
• ribosomes - rER or free in cytoplasm

aqueous gel of different components (mostly water) filling most of the cell

• structural components of cytoplasm
• composed of different macromolecules, fibers, fillaments
• surrounded by cell membrane

• "little organs"
• perform specific functions of the cell

ex: fat droplets

• center of genetic activity
• present in all cells EXCEPT mature red blood cells in mammals

• lipid bilayer with amphipathic characteristics
• dynamic structure - participates in many physiological and biochemical processes
• not completely homogenous (eg lipid rafts)
• modified fluid-mosaic model

• one side (exterior) is hydrophilic
• one side (interior) is hydrophobic

• 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)

• 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)

• 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)

• 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

• external face of the cell membrane
• has some integral proteins

• protoplasmic face
• interior face of the cell membrane
• has many (more) integral proteins

• 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)

• largely energy independent
• ex. Na/K pumps

• groups of proteins that form a cylindrical pore in the cell membrane
• may open or close with variety of stimuli

• demonstrate high specifirty
• external receptor triggers activity inside the cell
• ex. neurotransmitter binding to receptor protein

• ex. attaches collagen to external surface and connects external collagen to internal actin
• maintains integrity of epithelial membrane

• homophilic binding between structural proteins of neighboring cells
• strong attachment

• small lipid soluble or uncharged molecules
• follows a concentration gradiet

• mostly small, water soluble molecules
• highly selective - binding often causes conformational change
• can require energy (active transport) or follow a concentration gradient (passive transport)

• 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)

• a ligand binds to the outside of a cell and induces ion channels to open
• ex. neurotransmitter binding to outside of cell

• 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

• 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

• vesicular transport for substances entering the cell
• pinocytosis  & phagocytosis

• 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

• 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

• 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

• nonspecific uptake of fluid and small molecules by small vesicles
• performed by nearly every cell
• constituitive
• clathrin-independent
• common in endothelial cells

• 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

• coating proteins
• retrograde
• re-incorporate in to Golgi apparatus

• coating proteins
• anterograde
• move forward in secretory pathway (either constituitive or regulated secretion)

• 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

• high levels of cholesterol due to faulty uptake resulting from problem with clathrin coating
• receptor mediated endocytosis malfunction

membrane bound compartments in the cell formed by endocytotic pathways

• 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

• pre-lysosomes
• usually near the Golgi apparatus or nucleus
• complex structure with onion-like internal membranes
• pH of 5.5
• mature into lysosomes

specific vesicles that transport substances between early and late endosomes

• digestive organelles
• rich in hydrolytic enzymes - proteases, nucleases, glycosidases, lipases, phospholipases
• composed of unique membrane resistant 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)

• large extracellular particles transported via phagocytosis
• small extracellular particules transported via endocytotic pathways
• pinocytosis
• receptor mediated endocytosis
• autophagy

• microautophagy
• macroautophagy
• chaperone mediated direct transport
• protease mediated degradation

non-specific continuous degradation of intracellular proteins via invagination of lysosomal membrane

entire organelles surrounded by multiple membranes of ER to be degraded by lysosomal enzymes

digestion of intracellular particles and organelles

• 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

• 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)

• Gaucher disease
• Tay-Sachs disease
• Neimann-Pich disease

• 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

• 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

• system of stacked, flattened membrane limited sacs (cisternae) and tubular extensions embedded in network of microtubules
• small vesicles transport material between cisternae

• cis-golgi network: closest to rER
• medial golgi
• trans-golgi network: cisternae farthest away from rER

• post-translational modification of proteins
• sorting
• packaging of proteins

• apical plasma membrane
• basolateral plasma membrane
• endosomes & lysosomes
• apical cytoplasm

• proteins have specific sorting signals that direct their transport from TGN to apical membrane
• constituitive pathway

• constituitive pathway
• proteins have specific sorting signals that direct their transport from TGN to the basolateral membrane

proteins have their specific sorting signal, but may be mistargeted to apical domain and from there are re-directed to lysosomes

• 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

• 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) 

• outer mitochondrial membrane
• intermembrane space
• inner mitochondrial membrane
• matrix
• cristae

• in steroid secreting cells - tubular shape
• other cells (mitochondria) - flattened, leaf like structure

increase surface area of inner mitochondrial membrane

• 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

• 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

• 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)

system of connections within cell

• 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

• proteins responsible for transport along microtubule tracks
• dyneins & kinesins

• move towards minus end (from cell periphery to MTOC)
• cytoplasmic dyneins
• axonemal dyneins - cilia & flagella

move towards to plus end (from MTOC to periphery)

• very abundant (up to 20%)
• in nearly all cells
• assemble spontaneously into linear helical array
• polarized structures

• G actin: globular, unpolymerized
• F actin: filamentous, polymerized

• 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

• inability to import proteins into peroxisomes
• peroxisomes lack necessary enzymes
• leads to early death

contains the soluble enzymes of the citric acid cycle and fatty acid beta oxidation, matrix granules (Ca2+, etc.), mitochondrial DNA, ribosomes, and tRNAs

• oxidation reactions of electron transport chain
• synthesis of ATP
• regulates transport of metabolites in and out of matrix

• voltage-dependent anion channels (mitochondrial porins)
• receptors for proteins and polypeptides
• several enzymes (phospholipase A2, monoamine oxidase, acetyl CoA synthase)

• 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

• thin membrane arranged in folds (cristae) to increase surface area
• rich in phospholipid cardiolipin (makes the membrane impermeable to ions)
• site of ATP synthase

regulate rate of actin polymerization and organization

• actin bundling proteins
• actin filament severing proteins
• actin capping proteins
• actin crosslinking proteins
• actin motor proteins

• bundle actin filaments
• parallel arrays - support and rigidity
• fascin
• fimbrin in microvilli

• cut long actin filaments into shorter filaments
• gelsolin

• block further elongation of filaments
• regulate length
• tropomodulin

• spectrin
• adductin
• protein 4.1
• protein 4.9 - cytoskeleton in RBCs

• myosin family
• muscle contraction

• 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

• primary structural role
• non polar
• normally do NOT assemble/dissassemble dynamically
• subunits - very diverse
• NO enzymatic activity

• highly conserved globular domain at N- and C- termini
• highly variable central domain
• all share homologous region required for self assembly

• monomers -> coiled dimers -> staggered tetramers -> fibrils
• additional stabilization - lateral binding of adjacent tetramers

• keratins
• vimentin & vimentin-like filaments
• neurofilaments
• lamins

• >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

• 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

• development of cilia: centrioles become basal bodies
• mitotic spindle organization

• cytoplasmic or nuclear structures containing products of metabolic activity
• non-moving, non-living
• may be surrounded by plasma membrane

• lipofuscin
• hemosiderin
• glycogen
• lipid inclusions (fat droplets)
• crystalline inclusions

• brownish-gold pigment seen in H&E preparations
• conglomerate of lipids, metals and organic molecules
• sign of cellular senescence or stress

• iron storage complex
• indigestible residues of hemoglobin
• easily seen in spleen (site of RBC destruction)

• 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

• fat droplets
• energy for cellular metabolism
• long or short term storage
• normally seen as clear area

• present in many cells, in particular Sertoli and Leydig cells of the testis
• function unclear

• membrane limited compartment
• contains genetic information

• outer mitochondrial space
• intermembrane space
• inner mitochondrial space
• matrix

• 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

• nucleoprotein complex
• DNA
• five basic histone proteins (H1, H2A, H2B, H3, and H4)
• non-histone proteins

• highly condensed DNA clumps
• stains with hematoxylin and basic dyes
• signifies that cell is not actively synthesizing DNA

• 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

• less condensed DNA
• not evident in the light microscope
• indicates active chromatin in the nucleus

• 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

• condensed X chromosome
• not being used (extra in females)

• 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)

• fibrillar centers
• fibrillar material - pars fibrosa
• granular material - pars granulosa

contain DNA of five chromosomes (13, 14, 15, 21 & 22), RNA polymerase I and transcription factors

• fibrillar material
• contains ribosomal genes actively undergoing transcription, and large amounts of rRNA

• granular material
• site of initial ribosome assembly

network of pars fibrosa and granulosa together

• selectively permeable membranous barrier between nuclear compartment and cytoplasm
• disassembled during cell division
• two 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

• opening in the nuclear membrane
• cytoplasmic ring with protruding protein fibrils
• channels for small molecules
• continuity of nucleoplasm and cytoplasm

• 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)

self regulated sequence of events controlling cell growth and division

• 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

• 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

• prophase
• metaphase
• anaphase
• telophase

• 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

• 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

• pathological process
• when a cell is exposed to unfavorable conditions that cause acute cellular injury
• triggers an intense inflammatory response

• physiological process that eliminates cells from the body which are no longer needed
• no inflammatory response

• balance between proliferation and cell death has to be carefully maintained to avoid disease
• necrosis & apoptosis

• DNA fragmentation
• decrease in cell volume
• loss of mitochondrial function
• membrane blebbing
• formation of apoptotic bodies

• epithelium
• connective tissue
• muscle tissue
• nervous tissue

• 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)

• protection
• absorption
• transportation
• secretion
• receptor function

• endothelium
• mesothelium

epithelial lining of blood vessels

endothelium that lines and covers organs

• 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)

• microvilli
• cilia (motile & non-motile)
• stereocilia

• 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)

• 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)

• 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

• 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)

• autosomal recessive
• Kartagener's syndrome
• Young's syndrome
• about 50% have situs inversus
• also affects sperm & oviducts

• 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

• primary ciliary dyskinesia
• malformation of the radial spokes and dynein arms
• affects ciliary function in the respiratory tracts
• causes chronic respiratory infections

• organs are transposed through the sagittal plane
• occurs in 50% of patients with primary ciliary dyskinesia

• long, immobile microvilli (thinner)
• found in hair cells of the ear & the epididymus
• sense change in the ear

• zonula occludens
• zonula adherens
• macula adherens
• gap junctions

• 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

lateral adhesion between the cells

• desmosome
• spot welds (buttons on a chair)
• composed of intermediate filaments & cadherins
• anchored with intermediate filaments

• held together by connexin
• allow for communication between the cells
• passage of small ions, informational micromolecules, etc.
• prominent in cancer cells

cancer cells

• basement membrane
• basal lamina

• basal lamina + reticular lamina
• attached to reticular cells by hemidesmosomes
• attaches epithelial cells to connective tissue below

intermediate fibers anchor the connection only on one side

• composed of laminins, collagen, proteoglycans & glycoproteins
• integrin receptors specialized for holding the structure in place

• 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

secrete their product into ducts

• ductless
• secrete their product directly into the bloodstream

• goblet cells
• mucus secreting cells
• found in intestines & respiratory tract

• merocrine
• apocrine
• holocrine

• secretory product in membrane bound vesicles
• ex. pancreatic acinar cells

• secretion released in the apical portion of the cell, surrounded by some cytoplasm and plasma membrane
• ex. mammary gland

• the whole cell fills with secretion which is released when cell dies
• ex. sebaceous gland

• secretions activate other cells
• ex. cytokines

• exocrine
• endocrine
• paracrine

• shape of secretory portion: tubular, acnar, or tubuloacinar
• duct: simple or compound

• simple tubular
• simple coiled tubular
• simple branched tubular
• simple acinar

• branched acinar
• compound tubular
• compound acinar
• compound tubuloacinar

• 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

• coiled tubular structure is composed of the secretory portion located deep in the dermis
• typical location - skin
• ex. eccrine sweat 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

• 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

• 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

• coiled secretory portion located deep in the submucosa of the duodenum
• typical location - duodenum
• ex. submucosal glands of Brunner

• alveolar-shaped secretory units formed by pyramind shaped serous-secreting cells
• typical location - pancreas
• ex. excretory portion of pancreas

have both mucous branched tubular and serous branched acinar secretory units; serous endcaps (demilunes)

• number of cell layers: simple, stratified
• shape of cells: squamous, cuboidal, columnar
• special classifications: pseudostratified, transitional

• single layer of squished cells
• lines blood vessels (endothelium) and body cavities
• thin, good for diffusion

• single layer of square cells
• nucleus approximately in center
• found in the kidney (filtration) and in the thyroid (secretion)

• 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)

• 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)

• 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)

• bubbled up dome shaped cells at tome
• found in urinary bladder (distensible property)

• rare
• nuclei are in two distinct rows
• found in largest ducts of exocrine glands (mucus gland duct of tongue) & anorectal junction

• multiple layers of square cells
• rare
• found in ducts of glands

• 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

• line the peritoneal, pericardial and pleural cavities
• simple squamous epithelium
• no mucus

• epithelium grows in response to wear & tear
• growth may go wrong, resulting in tumors
• ex. epithelial metaplasia, Barrett's esophagus

• conversion of one mature cell type to another mature cell type
• most common - columnar to squamous

• 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

• epithelial metaplasia at junction of stomach and esophagus (chronic acid reflux)
• reprogramming of cells from squamous to columnar
• considered precancerous

• binding, support, compartmentalization
• hydration
• transportation
• defense
• energy storage

• mesenchymal stem cells: primordial stem cells
• fibroblasts: secrete extracellular matrix
• immunce cells: fight infection, involved in inflammation

fibrillar matrix & interfibrillar matrix/ground substance

• collagen: high tensile strength; tough
• elastin: high stretchability; low tensile strength; long & thin
• reticular: thin branched collagen that forms delicate networks

• ground substance
• proteoglycans & glycosaminoglycans
• soak up fluid like a sponge (hyaluronic acid & chondrotin sulfate)

• precursor to other cell types, mesoderm, & C.T.
• connect with adjacent cell processes
• gap junctions
• sparse amount of collagen

• 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

• fetal mesenchyme
• mucous 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

• cells
• fibrillar matrix
• interfibrillar matrix/ground substance

• 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)

• loose connective tissue of mucous membranes (respiratory and alimentary systems)
• contain a large number of immune cells

• loose CT around axons
• made up of collagen fibers

• 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

• abundant in parallel collagen fibers
• poorly vascularized
• makes up ligaments, tendons, aponeuroses, and deep investing fascia of muscles

rows of fibroblasts found between parallel bundles of collagen in tendons (dense regular CT)

• collagen
• elastin
• reticular (type III collagen)

• fascia, tendons, ligaments
• collagen bundle
• collagen fiber
• collagen fibril
• packed collagen molecules
• collagen molecule - triple helix of polypeptide chains
• amino acids (hydrophillic)

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

• 90% of body's collagen
• skin, bone, tendon, fascia, organ capsules

• resistance to tensile force
• regulate other collagen molecules
• ex. type I and II collagen

• developmental collagens
• ex. type X collagen contributes to bone mineralization via hexagonal lattices with fibrillar collagens and FACITs

• interact with the cell membrane and other extracellular matrix proteins
• ex. type XVII collagen interacts with integrins to anchor hemidesmosomes into basal lamina

based on polymerization

• fibrillar collagens
• FACITs
• hexagonal network-forming collagens
• transmembrane collagens
• 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

• proteolytic: matrix metalloprotinases (MMPs), collagenases, gelatinases, and macrophage metalloelastases
• phagocytic: primarily macrophages

• type III collagen
• similar to type I in every way except thinner and have more branching
• found in liver, spleen, and lymph nodes

• 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

• type I collagen (fibrillar class)
• mutation in COL1A1 and/or COL1A2 genes
• abnormal and normal collagen are synthesized

• a variety of gene mutations in type III collagen genes (fibrillar class)
• hyper extensible skin
• easy bruising
• hypermobile joints

• disarrangement of chondrocytes by other collagens
• lack of type IX collagen (FACIT class)
• seriously compromises cartilage development

• type X collagen (hexagonal network forming class)
• mutation in COL10A1 gene
• abnormal hypertrophies chondrocytes and cartilage extends into the metaphysis

• type XVII collagen (transmembrane class)
• blistering due to COL17A1 gene mutation

• composed of two types of molecules - elastin & fibrillin
• stretchable
• synthesized by fibroblasts and smooth muscle cells
• molecules linked together by desmosine & isodesmosine

• sugar & proteins
• glycosaminoglycans (GAGs): most abundant, negatively charged (acidic), hyaluronic acid
• proteoglycans: GAGs covalently bonded to a core protein
• multiadhesive glycoproteins: stabilize ECM

• hyaluronan
• forms a scaffolding for proteoglycans to hang off

• myofibroblasts
• macrophages
• mast cells
• adipocytes
• stem cells
• lymphocytes (T-cells, B-cells, plasma cells)
• granulocytes

• fibroblasts differentiate into contractile & secretory myofibroblasts
• act like a smooth muscle
• F-actin filaments & alpha SMA

• 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

• hypotrophic scar - stria
• hypertrophic scar - keloid

• 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

• hemosiderin: broken down RBCs (rust colored)
• anthracosis: broken down carbon particles (black specks)

• 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

• histamine
• heparin
• serine proteases
• eosinophil chemotatic factor
• neutrophil chemotatic factor

• derived from circulating B-cells
• antibody secreting cells
• lots of rER and Golgi apparati

• 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

• avascular (does not heal well)
• resilient (stress & joint movement)
• key tissue in growing bones

• 3-5% cells
• 15% collagens (80% type II collagen)
• 60-80% intercellular water

• produce and maintain extracellular matrix
• located in lacunae
• isogenous groups: clusters of chondrocytes

• 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

• "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

dividing chondrocytes

• fibrous membrane surrounding cartilage
• provides nourishment to the avascular cartilage
• differentiating chondrocytes

• 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

• NO perichondrium
• tight structural zone
• allows for smooth joint movement

• superficial (tangential)
• intermediate (transitional)
• deep (radial)
• calcified

• provides low friction surface for joints
• distributes forces to bone
• resists repetitive stress
• support structure

• intervertebral discs
• pubic symphysis
• articular discs (sternoclavicular, temporomandibular joints)
• menisci (knee joint)
• triangular fibrocartilage complex (wrist joint)
• insertion of tendons

• hyaline cartilage + dense connective tissue
• dense and fibrous
• type I and type II collagen (variations depending on joint)
• proteoglycans
• chondrocytes bunched
• herring bone appearance

• tensile strength and ability to absorb compressive shock
• resistant to shearing forces

• pinna of external ear
• external auditory meatus
• auditory (Eustachian) tube
• cartilages of larynx (epiglottis, corniculate, cuneiform)

• hyaline cartilage + elastin
• type II collagen
• non-collagenous proteins
• elastin
• pairs of chondrocytes

• maintains shape of structure but flexible
• least abundant cartilage of body

• appositional growth
• interstitial growth
• division of chondrocytes stops in adolescence
• calcification of cartilage occurs during normal bone growth and during old age

• 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

• new cartilage forming within existing cartilage
• lacunae-bound chondrocytes inside the cartilage divide and secrete new matrix, expanding the cartilage from within

• white (unilocular) fat
• brown (multilocular) fat

• 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

• good fat
• found in new borns
• found in certain places in adults (back, neck, mediastinum)
• found in bears (hibernation)
• highly innervated & under neural control

• leptin
• resistin

• 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

• increases insulin resistance
• linked to obesity and type II diabetes

• occludin
• claudin
• JAM (junctional adhesive molecules)
• ZO1, ZO2, ZO3

• cadherins
• actin filaments
• vinculin
• alpha-actin
• catenin
• E-cadherin

• cadherins (desmocollin & desmoglein)
• intermediate filaments

connexins

• intermediate filaments
• integrins

• actin filaments
• integrins

• intermediate filaments (keratins)
• anchoring filament proteins
• anchoring fibril (type VII collagen)

• nonepithelial junctional complex
• cardiac muscle

autoantibody mediated blistering disease in which antibodies against desmoglein 1 (cadherin of desmosomes) cause a loss of adhesion of keratinocytes in the superficial epidermis

breakdown of attachment plaque of hemidesmosome

• increase membrane surface area
• mitochondria tend to line up; striated cell surface appearance
• allow for active transport through ion pumps

• maximize lateral cell contact & adhesion
• communication
• transport

mesenchymal stem cells

• fibroblasts: fibers
• chondroblasts: cartilage
• osteoblasts: bone

• heterochromatic: not a lot of transcription going on, condensed DNA, reduced amount of cytoplasm (maintenance activity)
• euchromatic: very active nuclei during wound healing

• embryonic connective tissue that is derived from mesoderm
• differentiates into mesenchymal stem cells (CT) and hematopoietic stem cells (blood cells, etc)

• loose (areolar) CT: around the epithelium
• dense CT: found as you migrate away from epithelial structures

pink (eosin)

see striation of collagen at level of electron microscopy ONLY

• location -
• function -

• location -
• function -

• location -
• function -

• dependent on vitamin C
• necessary for the formation of hydrogen bonds
• chaperone proteins prevent collagen aggregation intracellulary
• keeps collagen soluble in water

• fibronectin
• laminin (NOT lamin - nuclear envelope)
• associated with basal lamina

stains FAT black

• 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

• neurons: basic structural unit of the nervous system
• neuroglia: supporting cells

• 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

• integrative: found mainly in CNS
• sensory: pseudounipolar neurons & bipolar neurons
• motor: multipolar & autonomic neurons

• 2 neuron chain
• innervate smooth muscle, glands & viscera
• preganglionic & postganglionic neurons
• sympathetic & parasympathetic nervous systems

• 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

TRUE

• euchromatic: DNA is being accessed
• nucleolus: site of ribosomal RNA assembly
• Nissl bodies: ribosomes & rough ER
• protein & NT synthesis - major output!

• 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)

• 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

• 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

• ex. Purkinje cells
• located in cerebellum
• extensive dendritic trees
• very two dimensional, flat

• unencapsulated - free nerve endings
• encapsultated nerve endings
• epithelial cell-associated

peripheral nerve endings go out to every aspect of the skin they innervate

• 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

• 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

• exteroreceptors: detect outside; not self
• enteroreceptors: detect inside; self
• propioceptors: position in space

• myelin: insulation of the axon
• action potential propagation
• node of Ranvier: gap in myelin surrounding an axon; saltatory conduction increases speed of conduction

• 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

collection of nerve fascicles (bundles of axons)

axons that have been bundled together

• 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

• established by perineurium
• keeps blood & nervous tissue separate
• perineurium & endothelial cells share basal lamina - allows transfer of oxygen & nutrients

surrounds the nerve fascicle & forms blood nerve barrier

• 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

• 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

• 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

voltage gated Na+ channels allow positive charge to travel along length of axon

• opening of voltage gated K+ channels
• Na/K ATPase activated to restore resting membrane potential

• 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)

• synthesis
• molecular motor proteins & transport
• neurotransmitters (in brief)
• nestin (if dividing... in passing)
• enzymes (medical biochemistry)

• kinesins: anterograde transport; from cell body to periphery or axon terminals
• dyeins: retrograde transport; from periphery or axon terminal to the cell body

• 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

• 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

• nerve terminals take up lectin (in plants) tagged with red fluorescence
• transported in retrograde fashion to get in cell bodies

• detect stimuli
• communicate with the use of action potentials & synapses
• stimulate effector organs, glands, muscle & other neurons

• 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)

• electrical: utilizes connexons
• chemical: utilizes neurotransmitters

• 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

• utilize neurotransmitters
• very common
• signal comes in & causes bouton to depolarize
• Ca²⁺ mediates release of synaptic vesicles (release NTs)

• depolarization of presynaptic element
• opening of voltage gated Ca²⁺ channels
• Ca²⁺ promotes vesicle release

presynaptic terminal of neuron

• specific effects on the membrane potential
• Na+, K+, Cl-
• ionotropic

• second messenger signaling (cAMP, IP3, PKA, etc)
• produces cellular changes or may modify synthesis of selected proteins or neurotransmitters
• metabotropic

determine effect of neurotransmitter

• high affinity reuptake: transport proteins take NTs back up at presynaptic membrane
• degradation: NTs broken down by enzymes; usually at postsynaptic side

• 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)

support cells

• schwann cells: secrete myelin
• satellite cells

• astrocytes
• oligodendrocytes
• microglia
• ependymal cells

• 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

• 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!)

transmembrane protein associated with demyelination diseases seen in Multiple Sclerosis & Guillian-Barre Syndrome

• membrane is folded tightly on itself
• SLC: where a little cytoplasm has poked into membrane

• 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

• axon
• node of Ranvier: little cytoplasm over it, but no folds
• inner collar: closely related to cytoplasm; just superficial to axon
• myelin: concentric rings

• 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

• found mainly with peripheral ganglia
• support cell bodies

• regulate NT levels in regions of high neuronal activity
• regulate capillary blood flow in parts of the brain
• regulate ionic environment (K+) - potassium batteries

• 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)

• ~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

• pia mater lines CNS tissue
• vascular endothelial cells
• protoplasmic astrocyte foot process will separate these layers

• 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

• similar to schwann cells - different kinds of myelin proteins
• found in CNS
• have few Schmit-lanterman clefts (astrocyte support)
• nodes of Ranvier are BIGGER

• migrate & engulf microorganisms, injured or dead neurons
• derived from monocytes associated in the immune system
• the phagocytic macrophages of the CNS

• simple epithelium layer that lines ventricles of the brain & spinal canal
• contain cilia to help circulate CSF
• contain microvilli to help absorb CSF

• degeneration
• regeneration

• 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

• growth cone: starts at tip of neuron & leads to sprouting
• sprouting: nerve can grow back (maybe not in correct place)

• 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

increased production of glial fibrillary acidic protein (GFAP)

• muscle tissues
• non-muscle tissues

• striated muscle - skeletal & cardiac muscle cells/fibers
• smooth muscle

• myoepithelial cells
• myofibroblasts
• pericytes
• perineurium
• satellite cells

• sweat gland - myoepithelial cells
• wound healing - myofibroblasts on flexible membrane

• voluntary/skeletal: axial skeleton, appendicular skeleton
• involuntary/cardiac: heart, great vessels
• visceral striated: upper esophagus

• vascular smooth: blood vessels
• visceral smooth: tubular organs

• 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

• plasma membrane of muscle cell + basal lamina
• nucleus is pushed to edge below it

plasma membrane + external lamina + part of reticular lamina

• muscle cytoplasm
• filled with bundles of contractile proteins (myofibrils)

• contractile proteins within sarcoplasm
• composed of myofilaments

skeletal/voluntary muscles cells are multinucleated

bundle of muscle fibers (composed of myofibrils)

• 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

• red (type I)
• white (type IIa,b)

• Type I
• rich in mitochondria - oxidative enzymes
• thinner than Type II
• classified as slow twitch
• ex. postural muscles; deep back muscles
• function - sustained contraction

• Type IIa,b
• few mitochondria - glycolytic enzymes
• larger diameter than Type I
• classified as fast twitch
• ex. extraocular muscles
• function - rapid contraction

• 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

• consist of dark & light bands
• polarized microscopy

• sarcolemma: multiple nuclei lying in close proximity beneath
• myofibril: banding patterns already visible (arrangement of proteins)
• mitochondrion: energy

• skeletal muscle fiber under phase-contrast light microscopy
• A band: anisotropic
• I band: isotropic
• band shading in electron microscopy similar

• basic unit of contraction in striated muscle
• defined as the distance between adjacent Z lines

• 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

• non-junctional SR: NOT part of triad
• junctional SR: contains terminal cisternae (calcium storage)

• 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

• transverse tubule + two terminal cisternae
• located at A/I junction

• bound to calcium in terminal cisternae of skeletal muscle
• allows calcium to be stored in sarcoplasmic reticulum

sliding filament theory

muscle contraction

• length of A band always remains the same (length of thick filaments)
• I & H bands shrink
• Z lines are drawn toward M

• thin & think filaments do not interact
• H & I bands are very wide

• 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

• 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

• troponin T: binds to tropomyosin
• troponin C: binds calcium
• troponin I: blocks active site on actin filament

• F-actin
• tropomyosin
• tropomodulin
• troponins

• 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

• actin binding protein
• bundles thin filaments into parallel arrays
• anchors thin filament to Z line

• in the absence of ATP, myosin remains tightly bound to actin
• in death, no ATP is available - rigor mortis

• anchors thick filament
• stabilizes M line

spirals around thin filaments; anchors

• stage 1: attachment (rigor configuration)
• stage 2: release
• stage 3: bending
• stage 4: force generation
• stage 5: reattachment

• myosin head is tightly bound to one of the globular proteins of thin filament
• ATP is absent
• known as rigor configuration

• ATP binds to myosin head
• conformational change occurs in myosin - ATP, myosin head is released from actin

• ATP undergoes hydrolysis
• conformational change occurs in myosin - ADP & Pi
• myosin head moves toward Z line

• 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

• rigor configuration, cycle can repeat
• myosin head binds tightly to new actin site

• 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

motor neuron: impulse travels from CNS axon that is myelinated (until muscle contact)

single motor neuron & the muscle fibers it innervates

• fewest muscle fibers/neuron
• ex. extraocular muscles, intrinsic muscles of hand (lumbricals)

• 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

indentation within muscle fiber with deep protrusions that increase surface area

Schwann cell + nerve fiber + muscle cell fused together

contains acetylcolinesterase to break down excess ACh

• 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

• 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

muscle spindle response to stretch

• afferent (sensory)
• efferent (motor)

modified muscle fibers within spindle apparatus

normal muscle fibers outside the spindle apparatus

• 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

• innervated by afferent (sensory) nerves ONLY
• respond to contraction
• counteract the action of muscle spindles
• located at junction between muscle fibers & tendon

• short 15-80um cells
• branches, mono, or binucleated fibers (in adults)
• connected by intercalated disks
• innervated by autonomics

• cardiac myocardium
• not cellular (fused) as with skeletal muscle cells; but function as a unit

• specialized stair-case like junction
• can form terminal junctions as well as side connections
• termination of cardiac muscle fibers

• 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

• atrial natriuretic factor
• contained in secretory granules from atrial cardiac myocytes
• regulates blood pressure & salt content
• functions with renin-angiotensin system

• 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

• 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

• anchor intermediate filaments & myofibrils in smooth muscle
• similar to Z line of skeletal muscles
• composed of alpha actinin

• actin sites closed
• myosin tail coiled on itself

• myosin light chains are phosphorylated via myosin light chain kinase
• myosin tail released
• actin binding sites open

• skeletal: bipolar thick filament
• smooth: side-polar thick filament

• 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

• right side
• receives blood through Superior & Inferior Vena Cava
• moves blood from heart to lungs
• usually smaller than systemic

• left side
• receives blood from lungs, moves it throughout the body (arterial system)
• usually larger

• transport nutrients & waste
• acid/base regulation
• immune response
• water balance

• 3.5L plasma
• 2.0L RBCs
• 10.5L interstitial fluid

~16L circulating fluid

• 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

• capillaries
• thinnest walls, greatest area

• tunics
• tunica intima: innermost layer
• tunica media: "in the middle"
• tunica adventitia: outermost layer

• 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

• 'in the middle'
• smooth muscle: secretion of elastin & collagen
• connective tissue
• diagnostic layer

• 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)

transportation of water or water-soluble products across the cell

transport process involving ligand, receptor complexes, clathrin coated vesicles

hole/tunnels through cells for transportation of large macromolecules & cells

• 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

• stem cells associated with basal lamina
• can differentiate into endothelium, muscle, etc...

• fenestrations: "little window"; clusters of openness
• may have "window panes"/ membrane or not

• incomplete or absent basal lamina
• CT fibers
• HUGE - fit RBS in them

• gas exchange
• have occluding junctions
• found in brain, muscle, blood
• serves as blood organ barriers

• filtration
• found in endocrine organs/glands, kidney

• passage of large molecules (ex. RBC in spleen)
• found in liver, spleen, bone marrow

• muscles that can close/open metarterioles
• control blood flow through thoroughfare channel

link from metarteriole directly to venule bypassing capillary bed

• completely bypasses microcirculation
• shunts arterial blood directly to venial side

• blood perfuses two separate and distand capillary beds without passing through the heart
• involve arterial links or venous links

• afferent arteriole - capillary network - efferent arteriole - capillary - venule
• ex. glomerulus of kidney

• arteriole - capillary - vein - capillary/sinusoid - vein
• ex. hepatic portal system

• 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

• tunica intima + internal elastic lamina
• tunica media - mostly smooth muscle cells (thickest layer)
• external elastic lamina
• tunica adventitia - visible fibroblasts & unmyelinated nerves

• 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

arterioles

• 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

• 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

• tunica intima - endothelium
• tunica media - 2 to 3 layers of smooth muscles
• tunica adventitia - CT; thicker than T. media
• 0.1-1.0mm

• 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

• 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

• failure of valves due to weakening of muscular tunics
• varicose veins in legs
• esophageal varices
• epidydmal varices

• 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

• located within core of villus in intestine
• contain loose CT filled with lymph & a few WBCs

• skeletal muscle contraction propels lymphatic system
• shape of valve leaflets prevents backflow

• 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)

• epicardium: visceral pericardium
• myocardium: muscle of the heart
• endocardium: inner endothelial lining

• thin mesothelium (specialized cuboidal epithelium)
• subendothelial fat & coronary arteries
• secretes pericardial fluid

• weak contraction
• secrete ANF to help decrease blood pressure

• contraction
• highly developed intercalated disks

• muscle of the heart
• analogous to tunica media
• atrial & ventricular cardiocytes

• inner endothelial lining
• analogous to tunica intima
• consists of three compartments - endothelial, subendothelial, subendocardium

• endothelial: contains endothelium, CT
• subendothelial: contains smooth muscle cells, CT
• subendocardium: site where conductive fibers (Purkinje cells) pass into myocardium

• modified cardiac muscle cells
• contain glycogen
• poorly organized myofibrils
• no striations or intercalated discs

• 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

• extensive branching system
• extends from the vestibile of the nasal cavity to the alveoli of the paired lungs

• air conditioning - warms & moistens
• air filtration
• gas exchange
• facilitates speech, smell, hormone, and immune functions

• conducting portion: nasal cavitities, pharynx, larynx, trachea, bronchi & bronchioles (transport, filter, & condition)
• respiratory portion: respiratory bronchioles, alveolar ducts, sacs, & alveoli (gas exchange)

• paired chamber separated by nasal septum
• communicates: external environment & nasopharynx, paranasal sinuses, nasolacrimal duct

• vestibule: transition zone
• olfactory region: mucosa for smell
• respiratory region: characteristic mucosa of respiratory region

• 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

• 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

• 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

• 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

• columnar cells with microvilli
• basal surface in synaptic contact with afferent nerve endings
• sensory receptor cell

• enteroendocrine cells that secrete polypeptide hormones
• sparingly dispersed along basal lamina
• though to regulate vascular and airway diameter

• reserve stem cell population
• nuclei line up along basal lamina
• give rise to all cell types

• vestibile region of nasal cavity (vibrissae)
• nasal conchae or turbinates (nasal cavities)
• goblet and ciliated cells

• vestibular vibrissae collect particles
• turbinates increase surface area
• mucosa captures particles & cilia propel to pharynx - mucociliary escalator

• air passageway between oropharynx & trachea
• organ for sound production
• ventricular folds & vocal folds

• complex structure
• hyaline & elastic cartilages: epiglottis, thyroid, cricoid, arytenoid, cuneiform, corniculate
• ligaments & ligamentous membranes: conus elasticus & quadrangular membrane
• numerous skeletal muscles

• 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

• flexible air tube
• numerous C-shaped hyaline cartilage rings (16-20)
• bifurcates into 2 main (primary) bronchi - around T4/T5 vertebral level

• 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

• 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)

• divide into lobar (secondary) bronchi
• secondary branch into segmental (tertiarty) bronchi
• cartilaginous rings replaced by plates
• circumferential smooth muscle

• increase in smooth muscle
• decrease in cartilaginous plates
• ciliated simple columnar epithelium
• loss of submucosal glands

• 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

• 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

• non-motile cilia
• second messenger pathways depolarize cells of olfactory receptors (usually use Ca²⁺)

• branches of bronchioles
• no goblet cells
• simple ciliated columnar OR cuboidal epithelium
• smooth muscle reduced
• clara cells present in terminal bronchioles

• 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)

• terminal bronchiole
• respiratory bronchiole
• alveolar duct
• alveolar sac
• alveoli

• 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

• elongated air ways with almost no walls
• made of alveoli
• knoblike smooth muscle within intralveolar septa

• space within small cluster of alveoli
• terminal portions of alveolar ducts

site of gas exchange

• type I alveolar cells
• type II alveolar cells
• capillary endothelium
• fibroblast

• type II pneumocytes
• line 95% of alveoli surface
• highly flattened squamous 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

highly flattened squamous cells

produce connective tissue components

• 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)

• 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

• 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

• 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