Histology Flashcards
levels of organization
1) chemical
2) cellular
3) tissue
4) organ
5) system
histology
study of microscopic structures of tissues
tissue
similar cells and cell products that perform a common function
types of tissues
1) nervous: brain, spinal cord, nerves
2) epithelial: lining of GI organs and other hollow orans, skin surface (epidermis)
3) muscle: cardiac, smooth, skeletal
4) connective: fat and other soft padding, bone, tendon (MAJORITY)
hematoxylin & eosin (H&E stains)
- hematoxylin: behaves like base, stains basophilic molecules blue (positive charge attracts negative, ex. phosphate groups on nucleic acids)
- eosin: acidic, stains acidophilic molecules pink (negative charge attracts positive, ex. ionized amino groups on proteins)
- together = purply stain
epithelial tissue
composed of sheets of cells that:
1) cover body surfaces
2) line body cavities
3) form glands
external and internal surfaces
- external: epidermis
- internal: internal passageways, cavities and fluid-filled chambers
endothelium
epithelium lining blood cells
mesothelium
epithelium lining internal body cavities
functions of epithelia
specific to location:
1) physical protection
2) controls permeability: filtration, absorption, excretion
3) provides sensation: extensively innervated
5) produce secretions: mucus, hormones, enzymes
characteristics of epithelia
1) cellularity: densely packed cells bound by specialized cell junctions
2) polarity: apical (free), basal and lateral surfaces with specific functions, attached via basement membrane to underlying connective tissue
3) avascular: nutrients diffuse to epithelial cells from connective tissue
4) innervated
5) regenerates
components of basement membrane
basal lamina (connected to epithelial cells) and reticular lamina (connected to connective tissue)
basement membrane characteristics
- acellular
- molecules (proteins, collagen) that are secreted by basal epithelial cells and CT cells
basement membrane functions
1) support epithelium
2) anchor epithelial tissue to CT
3) semipermeable to restrict passage of large molecules
4) scaffold for repair & regeneration: organizes renewal of epithelium following damage
basement membrane in retina
- healthy retinal microvasculature is dependent on intact BM
- diabetes (hyperglycemia) can alter BM, making it permeable to large molecules
- causes leakage of plasma and lipids = edema, impacts vision
microvilli
- finger-like extensions, core formed by actin
- apical surface
- abundant where absorption and secretion occur, ex. intestines and kidneys
- number/shape correlated with cell’s absorptive capacity (function to increase SA)
- fuzzy appearance on H&E
cilia
- long, motile, core formed by microtubules and associated proteins
- apical surface
- respiratory tract, uterine tube -> where things (mucus, oocyte) need to move
- beat in coordinated fashion to move substances
- easier to define on H&E compared to microvilli
intercellular connections
1) tight junction
2) adherens junction
3) desmosome
4) gap junction
5) hemidesmosome (basal)
tight (occluding) junctions aka zona occludens
- impermeable seal/band
- binds plasma membrane of cells together
- claudin and occludin (transmembrane proteins that form seal)
- function: tight seal to act as permeability barrier, ensures transcellular transport of molecules, prevents passive flow between cells, limits movement of membrane proteins from one surface to the other
- lateral, close to apical side
anchoring junctions
- attach cytoskeletons of adjacent epithelial cells together
- transmembrane proteins essential for mechanical strength and stability
- lateral: adherens junctions, desmosomes
- basal: hemidesmosomes
adherens junction (zonula adherens)
- form adhesion band/belts
- actin microfilaments linked by transmembrane proteins called cadherins
- function to firmly anchor cells, provide strength and distribute shear forces between two cells
desmosomes (macula adherens)
- forms disc-shaped spots, NOT bands
- link intermediate filaments by cadherins
- function to create strong connections, distribute shear forces
- analogy: rivets on jeans
hemidesmosomes
- link intermediate filament network on basal surface to BM by integrins
- function to resist separation from BM
gap junctions
- 6 transmembrane connexins form channels (connexons)
- multiple connexons from adjacent cells align to form junction
- lateral
- function: mediate intercellular communication, permits exchange of small molecules/ions between cells
junctional complex
- cell junctions occur together
- ex. in small intestine
- function: divide plasma membrane into apical and basolateral surfaces, organize into correct spots
types of epithelium
1) surface: continuous sheets of cells classified by number of layers and shape of cells
2) glandular: specialized cells that secrete substances (2 types: endocrine, exocrine)
simple surface epithelia
- one layer of cells all attached to BM
- nuclei at same level
- found in protected areas
stratified surface epithelia
- more than one layer
- areas with mechanical or chemical stresses
pseudostratified surface epithelia
- appears stratified, but all cells attach to BM
- nuclei at different levels
surface epithelia cell shapes
1) squamous: flattened, width > height
2) cuboidal: height = width
3) columnar: nuclei lined up close to BM, height > width
simple squamous
- lines vessels (endothelium) and serous lining of cavities (mesothelium)
- function: regulate passage of substances, material exchange (thin, easy to pass)
serous meaning
epithelial/connective tissue combined -> produces fluid across membrane
simple cuboidal
- surface of ovary, kidney tubules, some glands
- lines surfaces involved in secretion/absorption
simple columnar
- lines small intestine, colon, stomach, gall bladder, uterine tube
- secretion/absorption
- larger cells with more organelles than cuboidal
- nuclei lined up
pseudostratified columnar
- usually has cilia (aka pseudostratified ciliated columnar)
- respiratory tract, ductus deferens, epididymis
- function: secretion and conduit
- ex. mucus secreted in respiratory tract than swept away by cilia
- nuclei not all at same height
stratified squamous
- look to apical layer to identify shape (based on nuclei shape)
- protect against abrasion, water loss, UV and foreign particles
1) keratinized: tough layer of keratin (dead cells, no nuclei), found in skin
2) non-keratinized: lines wet surfaces ex. mouth, esophagus, pharynx, vagina
transitional epithelium
- stratified
- bladder, ureters, urethra
- surfaces that change shape (stretch/relax), allows for stretch/recoil
- relaxed: looks like stratified cuboidal, but apical cells are round and large
stratified cuboidal
generally rare
origin of glandular epithelia
1) simple sheet covering surface
2) invagination (proliferation and downgrowth of cells into CT)
3) disappearance of duct cells for ENDOCRINE glands
exocrine vs endocrine
- exo: secretions travel through ducts to surface, continuous with free surface
- endo: ductless that exist within some covering epithelial, secrete into circulation via diffusion through interstitial fluid
unicellular exocrine glands
- no ducts
- ex. goblet cells
- secrete mucus onto exposed surface to protect apical surface
- analogy: wine glass
multicellular glands
- continuous systems of secreting portion and duct
1) duct: simple (unbranched) or compound (branched)
2) secretory portion: tubular or branched tubular or acinar/alveolar (round, sac-like) - some differentiate between alveolar and acinar: acinar has smaller lumen
exocrine modes of secretion
1) merocrine: exocytosis (most, ex. salivary and pancreas)
2) holocrine: entire vesicle shed into lumen (ex. sebaceous gland)
3) apocrine: pinched off portion of cell secreted (ex. mammary glands)
endocrine glands
- secrete cell product into interstitial fluid
- diffuse into circulation
- ex. hormones
connective tissue vs epithelia
- never exposed to external environment
- highly vascular
basic components of connective tissue
1) specialized cells (few)
2) extracellular fibers
3) ground substance (mostly liquid)
- mostly ECM = 2) and 3)
classification of CTs
- based on composition (liquid ex. blood to solid ex. bone) and amounts of basic components
- also determines function
functions of CT
1) support, surround, interconnect tissue
2) structural framework for body
3) fluid transport
4) protection
5) energy storage
6) defend body from invasion by microorganisms
types of CT
all derived from mesenchymal cells (mesoderm)
1) supportive connective tissue: chondroblasts -> chondrocytes and osteoblasts -> osteocytes
2) fluid connective tissue (ex. blood, lymph)
3) CT proper (“ordinary CT): loose and dense
CT proper jello salad analogy
fruit = cells, sugar = fibers, water = ground substance
CT proper composition
1) specialized cells: fixed/resident or wandering
2) ECM
fixed (resident) cells
- from mesenchymal cells
- formed in and reside in CT
- local maintenance, repair and energy storage -> create favourable environment
wandering cells
- from hematopoietic stem cells, differentiate in bone marrow (blood cells)
- migrate into CT
- increase in number with tissue damage or infections
types of fixed cells
chondrocytes, adipocytes, fibroblasts, osteocytes
fibroblasts
- most common and always present
- spindle-shaped cells
- well developed RER and Golgi complexes
- oval nucleus
- function: produce all CT fibers (collagen, elastin) and ground substance (glycoproteins, proteoglycans)
types of wandering cells
B-lymphocytes -> plasma cells, monocyte -> osteoclasts + macrophages, mast cells, basophils, eosinophils, neutrophils
scar tissue formation
- fibroblasts typically don’t regenerate, but can be stimulated to regenerate CT (ex. damage)
- fill in spaces when tissues cannot be regenerated
adipocytes (fat cells)
- lipid storage
- significant flattening of nucleus due to lipid accumulation
- lots of adipocytes = adipose tissue
- tissue slides look empty because they have to be dehydrated in preparation (no fat)
plasma cells
- derived from B lymphocytes (WBC)
- large egg shaped cell
- small, eccentric nucleus with “clock face” formed by areas of DNA clumps
- sometimes halo around nucleus formed by large Golgi complex
- basophilic cytoplasm rich in RER
- antibody (proteins) producing cells
macrophages
- from monocytes (WBC), mature in tissue spaces
- relatively small and inconspicuous unless they were active in phagocytosis
- specialized names in different organs (microglia in CNS, osteoclasts in bone)
- highly phagocytic, function in ECM turnover, phagocytosis of dead cells, antigen presentation
- ruffled border on electron micrograph, can’t see on H&E
mast cells
- oval, irregular shaped
- central nucleus
- filled with basophilic granules
- numerous near small blood vessels in skin, mesenteries & tissues lining digestive and respiratory tract (areas where sampling occurs)
- function: localized release of bioactive substances (ex. histamine) important in local inflammation, innate immunity and tissue repair
mesenteries
attaches GI tract together
metachromasia
granules in mast cells change the colour of basic dyes from blue to purple, stain dark
sensitization of mast cells
1) antigen (allergen) invades body
2) plasma cell produces large amounts of IgE antibodies against allergen
3) IgE antibodies attach to mast cells in body tissues (and to circulating basophils)
secondary response by mast cells
1) more of antigen invades body
2) antigen combines with IgE attached to mast cells/basophils, triggers degranulation (break down and release of contents), release of histamine and other chemicals
3) histamine causes vasodilation and vessels to become leaky (WBCs and other beneficial things diffuse out); promotes edema; stimulates mucus secretion; smooth muscle contraction
leukocytes (white blood cells)
- from circulating blood cells, migrate into CT where they become functional
- increase in number indicates inflammation
- typically only present for a few days, then undergo apoptosis
- granular
types of fibers
collagen and elastic
collagen
- most abundant protein in body
- strong but flexible, resists shearing and tearing forces
- 3 alpha chain subunits that form fibrils -> fibers -> bundles -> tendon -> muscle
- > 28 different types characterized by interacting alpha chain subunits
main types of collagen
1) most common, ex. deep within skin, tendon, bONE
2) carTWOlage
3) blood vessels (walls), TH-REEticular fibers
4) meshwork in basement membrane (FLOOR)
type 1 collagen
large, wavy appearance
Ehlers-Danlos Syndrome
- defects in synthesizing & processing of collagen
- hyperextensible skin, hypermobile joints/trachea
type 3 collagen (reticular fibers)
- forms stroma (scaffolding) of highly cellular organs (ex. liver, kidney, adrenal glands)
- parenchyma (functional parts of an organ, or of a structure such as a tumour in the body) arranged on stroma
silver stain
common for reticular fibers, stains black
elastic fibers
- sparse networks interspersed with collagen bundles in many organs (that allow for stretch, ex. lungs, large BVs)
- elastin embedded in microfibrils composed of fibrillin
- thinner (often) than collagen
- stretch to 1.5x resting length, then recoil
ground substance function
- resists compression
- allows for passage of molecules between plasma and interstitial fluid (acts as filter)
- anchors cells within tissues
ground substance composition
interstitial fluid (from BVs), glycosaminoglycans (GAGs), proteoglycans, adhesive glycoproteins
GAGs
- unbranched carbohydrate chains
- most linked to core protein
- highly negatively charged and hydrophilic
hyaluronic acid
- a type of GAG
- unbranched, long and large linear carbohydrate chain
- negatively charged, hydrophilic
proteoglycan
- GAGs attached to a core protein
- responsible for gelatinous consistency of ECM
- look like straw cleaner
adhesive glycoproteins
- small proteins
- stabilize and link ECM to cell surfaces
where does interstitial fluid come from?
- blood plasma
- hydrostatic pressure pushes fluid out of BVs
- oncotic pressure due to large plasma proteins (cannot pass through walls) pulls fluid in
- usually net absorption and secretion at opposite sides of vessel -> homeostasis
- excess fluid that does not return to blood enters lymphatic vessels, becoming lymph
- lymph vessels run alongside BVs and have lowest hydrostatic pressure
edema
fluid build-up (excess interstitial fluid)
loose (areolar) CT
- several types of cells
- few fibers arranged randomly
- semifluid ground substance
- location: everywhere ex. lamina propria (underneath epithelia) of mucous membranes, around BVs, nerves, organs
- function: support with independent movement of cells and fluid
- most cells are wandering
dense regular CT
- mainly collagen type 1
- regular, parallel arrays of fibers with fibroblasts squished between
- location: tendons, ligaments
- function: strong attachment between structures, withstands tension along one direction (long axis of fibers)
ligament
bone to bone connection
tendon
muscle to bone connection
dense irregular CT
- tightly packed, woven, irregularly arranged
- type 1 collagen
- location: fasciae (tissue beneath skin and around muscles), dermis, pericardium, joint capsules, membrane capsules of various organs
- function: tensive (pulling) strength in many directions
elastic CT
- mostly elastic fibers with fibroblasts in spaces between
- location: lung tissue, elastic artery walls, trachea, some ligaments between vertebrae
- function: support, allows for stretching, accommodates pressure changes on the walls of arteries closest to heart
reticular tissue
- interlacing network of reticular (collagen type 3) fibers and reticular cells (unique fibroblasts found in reticular tissue)
- location: stroma of cellular organs (liver, spleen, lymph nodes, red bone marrow, pancreas)
- function: forms stroma, binds smooth muscle tissue cells, removes blood cells in spleen and microbes in lymph nodes (slow filtration by fiber network)
adipose tissue
- specialized fat storing cells (adipocytes)
- location: found with areolar CT, ex. hypodermis of skin, around organs, joints
- function: reduce heat loss through skin, energy reserve, supports and protects (cushioning)
cartilage
- supporting CT
- dense network of collagen fibers (support) embedded in ECM
- high concentrations of GAGs and proteoglycans, leads to ground tissue with lots of water
- no nerves
- avascular
physical properties of cartilage
- defined by ECM composition
1) firm: tissue can bear mechanical stresses without permanent distortion
2) resilient: resume original shape after deformation (water is fluid)
3) smooth: acts as cushion (ex. for bones)
cartilage function
- provide framework for soft tissues, ex. respiratory tract (trachea) and external ear
- withstand tensile (collagen) and compressive forces (water)
- helps facilitate bone movements (glide past each other), ex. articular cartilage in joints
- development and growth of long bones
types of cartilage
hyaline, fibro-, elastic -> based on characteristics of ECM
chondrocytes
- cartilage cells
- single or in isogenous groups (dividing cells) that are located in lacunae
- synthesize and maintain ECM
perichondrium
- dense CT that surrounds most cartilage, not all
- provide nutrients and gases from vessels that diffuse through cartilage ground substance
- also take waste
two layers of perichondrium
1) outer fibrous: collagen type 1 and fibroblasts (stains darker)
2) inner cellular: chondrogenic cells that differentiate into chondroblasts, responsible for remodelling ability
cartilage ECM composition
- mostly type 2 collagen (a little smaller than type 1)
- ground substance: rich in cartilage specific GAGs linked to core protein, forms proteoglycan monomer called aggrecan
- aggrecan links to hyaluronic acid to create larger aggregates -> attracts lots of water
- ideal for withstanding tensile and compressive forces
hyaline cartilage
- most abundant
- ECM: type 2 collagen, gelatinous (proteoglycans and GAGs)
- function: resist compression, flexible support, reduce friction in articulations
- location: ends of bones (articular cartilage), respiratory passages (nose, larynx, trachea), ribs (costal cartilage), embryonic skeleton
- covered by perichondrium EXCEPT articular cartilage
elastic cartilage
- similar to hyaline, but has additional rich network of elastic fibers (not glassy)
- more abundant, larger chondrocytes compared to hyaline
- function: strength, elasticity, resiliency and maintaining shape
- location: epiglottis, external ear, auditory tubes
- all has perichondrium
fibrocartilage
- thick type 1 collagen fibers that alternate with parallel groups of columns of chondrocytes
- little ground substance
- type 2 collagen also present
- NO perichondrium
- function: resist tension and compression, provide cushioning
- location: pubic symphysis, intervertebral discs, menisci of knee, entheses (tendon and ligament attachment to bone)
interstitial growth of cartilage
1) condensation of embryonic mesenchyme; cell projections retract as cells clump together
2) differentiation into chondroblasts
3) chondroblasts separate from one another as they produce ECM (swells with H2O), they become isolated in lacunae
4) multiplication of chondroblasts within matrix gives rise to isogenous groups, isolated chondroblasts become quiescent and maintain matrix as chondrocytes
chondroblast vs chondrocytes
- blast: actively building ECM
- cyte: maintaining
- cytes can be stimulated to revert to chondroblasts
appositional growth of cartilage
- mesenchymal cells at surface of developing cartilage differentiate into fibroblasts
- fibroblasts secrete type 1 collagen, form outer fibrous layer of perichondrium (therefore, cartilage with no perichondrium cannot have appositional growth)
- inner cellular layer has mesenchymal cells that differentiate into chondroblasts, these secrete matrix onto surface of newly forming chondrocytes
bone
- supporting CT
- hard, mineralized ECM containing osteocytes
- matrix is solid, but porous: microscopic extensions through channels allow for diffusion of metabolites and gases, communication
- richly innervated and vascular
- two layers: endosteum (inside) and periosteum, both are involved in remodeling and repair
function of bone
1) protect internal organs
2) body movement
3) support soft tissue, provide attachment for muscles
4) mineral/fat storage
5) produce blood cells (hematopoiesis)
bone cells
- 2% of body mass
- multipotential mesenchymal cells from bone marrow -> osteoprogenitor cells -> osteoblasts -> osteocytes
- WBCs -> osteoclasts
osteoblasts
- bone building cells located on inner and outer surface of bone matrix
- typically form a single layer of cuboidal cells, nucleus often located to one side
- communicate via gap junctions (with other osteoblasts and osteocytes)
- function: produce bone matrix (collagen + organic components, called osteoid, later calcifies)
- become osteocytes once surrounded by ECM
osteocytes
- mature bone cells, do not divide
- trapped in lacunae
- extend processes through canaliculi
- function: maintain surrounding bone tissue (nutrient, gas, water exchange), sense mechanical stress, organize remodeling accordingly
osteoclasts
- large, multinuclear, derived from combination of several monocytes
- ruffled border with phagocytic activity
- concentrated in endosteum
- function: secrete lysosomal enzymes and acids for osteolysis
osteoblast/clast homeostasis
- if disrupted, leads to complications ex. osteoporosis
bone ECM composition
- organic matter (osteoid) = 1/3: 95% collagen type 1, glycoproteins and proteoglycans -> tensile strength and flexibility
- inorganic matter = 2/3: osteoid mineralized in the process of matrix formation by inorganic matter, mostly calcium and phosphate hydroxyapatite crystals -> compressional strength
bone classifications
based on shape:
1) long: L>W, not necessarily large
2) flat
3) irregular: ex. holes, projections
4) short: somewhat cuboidal
- sesamoid: type of short bone that is within a tendon (largest is patella)
long bone characteristics
- shaft (diaphysis)
- 2 ends (epiphyses)
- metaphysis from diaphysis to epiphyseal lines/plates (at both ends)
- medullary cavity filled with marrow
- external surface lined by periosteum (except at ends with articular cartilage)
- internal surface lined by endosteum
proximal vs distal
proximal closer to core of body
bone marrow
fat storage and blood cell development
compact (cortical, dense) vs spongy (travecular) bone
same matrix make-up, different 3D arrangement
compact bone structure
- osteon: functional unit, runs parallel to diaphysis
- each osteon consists of:
1) central canal: blood supply, in the middle
2) concentric lamellae: bone matrix strengthened by alternating orientation of collage fibers in adjacent lamellae, wraps around central canal
3) osteocytes: located in lacunae between adjacent lamellae
4) canaliculi: channels that connect lacunae, joining osteocytes and central canal
other lamellae in compact bone
1) external circumferential: wraps everything
2) interstitial lamellae: between osteons, fragments of older osteons
3) internal circumferential lamellae: wraps internal spongy bone
*these are not specifically part of the osteon
spongy bone structure
- no osetons
- tissue arranged in trabeculae (“beams”) oriented along lines of stress (resists compression from many directions)
- trabeculae composed of:
1) parallel lamellae (matrix)
2) osteocytes between - canaliculi open at surface of trabeculae, gases and nutrients diffuse through tissue to exchange with BVs in red marrow
- red marrow in spaces between trabeculae