groups of proteins that form a cylindrical pore in the cell membrane
may open or close with variety of stimuli
receptor proteins
demonstrate high specifirty
external receptor triggers activity inside the cell
ex. neurotransmitter binding to receptor protein
linker proteins
ex. attaches collagen to external surface and connects external collagen to internal actin
maintains integrity of epithelial membrane
desmosome
homophilic binding between structural proteins of neighboring cells
strong attachment
simple diffusion
small lipid soluble or uncharged molecules
follows a concentration gradiet
transport by carrier proteins
mostly small, water soluble molecules
highly selective - binding often causes conformational change
can require energy (active transport) or follow a concentration gradient (passive transport)
transport by channel proteins
small, water soluble molecules
create a hydrophillic passage through cell membrane
regulated by membrane potentials (voltage gated), neurotransmitters (ligand gated) or mechanical stress (mechanically gated)
ligand gated channels
a ligand binds to the outside of a cell and induces ion channels to open
ex. neurotransmitter binding to outside of cell
mechanically gated channels
activated by mechanical stress
ex. hair cells in inner ear when properly affected by vibratiosn through the air and water in ear stretch - open K+ channels
vesicular transport
process involving formation of membrane vesicles and their fusion with membranes (vesicle budding)
maintains integrity of plasma membrane & transport of molecules between cellular compartments
endocytosis, exocytosis
visualization by electron microscopy or immunofluorescence
endocytosis
vesicular transport for substances entering the cell
pinocytosis & phagocytosis
exocytosis
vesicular transport for substances leaving the cell
process by which a vesicle moves from the cytoplasm to the plasma membrane, where it releases its contents
constituitive pathway or regulated secretory pathway
constituitive pathway
continuous delivery of to-be-secreted components via Golgi apparatus
requires no stimulation
present in some form of every cell
difficult to see in microscope
regulated secretory pathway
delivery is triggered by stimulus (hormonal or neuronal)
occurs in specialized cells (eg. endocrine cells, exocrine cells, neurons)
enzymes can be made and stored in vesicles until trigger for release
can usually be seen via microscope
pinocytosis
nonspecific uptake of fluid and small molecules by small vesicles
performed by nearly every cell
constituitive
clathrin-independent
common in endothelial cells
phagocytosis
nonselective uptake of large particles by large vesicles (bacteria or debris)
mainly performed by cells of mononuclear phagocytic system (macrophages, kuppfer cells)
constituitive
receptor-mediated
requires rearrangement of actin cytoskeleton
clathrin independent, actin dependent endocytosis
COP I
coating proteins
retrograde
re-incorporate in to Golgi apparatus
COP II
coating proteins
anterograde
move forward in secretory pathway (either constituitive or regulated secretion)
receptor mediated endocytosis
uptake of specific molecules using cargo receptors
vesicle formation requires assembly of a coated pit involving adaptin, clathrin, and dynamin
clathrin-dependent endocytosis
involved in transport of cargo from the plasma membrane to the early endosomes and from the Golgi apparatus to the early and late endosomes
familial hypercholesterolemia
high levels of cholesterol due to faulty uptake resulting from problem with clathrin coating
receptor mediated endocytosis malfunction
endosomes
membrane bound compartments in the cell formed by endocytotic pathways
early endosomes
pH 6.2 to 6.5
restricted to near cell membrane where they originate
can re-fuse with cell membrane or travel deeper into cell, where they become late endosomes
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
multivesicular bodies
specific vesicles that transport substances between early and late endosomes
lysosomes
digestive organelles
rich in hydrolytic enzymes - proteases, nucleases, glycosidases, lipases, phospholipases
composed of unique membrane resistant to hydrolysis
lysosome membrane mechanisms for resistance to hydrolysis
membrane contains cholesterol and lyso-biphosphatic acid (restricts activity of enzymes)
lysosome associated membrane proteins
lysosomal membrane glycoproteins
lysosomal integral membrane proteins
transport proteins to transport the final products of digestions to the cytoplasm for further use
proton pumps for acidification (pH 4.7)
pathways for lysosomal degradation
large extracellular particles transported via phagocytosis
small extracellular particules transported via endocytotic pathways
pinocytosis
receptor mediated endocytosis
autophagy
types of autophagy
microautophagy
macroautophagy
chaperone mediated direct transport
protease mediated degradation
microautophagy
non-specific continuous degradation of intracellular proteins via invagination of lysosomal membrane
macroautophagy
entire organelles surrounded by multiple membranes of ER to be degraded by lysosomal enzymes
autophagy
digestion of intracellular particles and organelles
chaperone mediated direct transport
only selective process of lysosomal degradation
involves interaction of the to-be-degraded protein with heat shock chaperone protein (hsc73) and its subsequent transport to lysosome
protease-mediated degradation
degradation of abnormal or short-lived proteins without lysosomal involvement
large ATP-dependent protease complexes in nucleus or cytoplasm
proteins tagged by multiple ubiquitin molecules
decreased degradation leads to accumulation of proteins in cell (Alzheimer's disease)
accelerated degradation of proteins due to overproduction of system proteins (human papilloma virus infections)
lysosomal storage diseases
Gaucher disease
Tay-Sachs disease
Neimann-Pich disease
rough endoplasmic reticulum
region of endoplasmic reticulum associated with ribosomes
membrane often continuous with outer membrane of nuclear envelope
site of protein synthesis (secreted and integral membrane proteins) and post-translational modifications of newly synthesized proteins
very well developed in secretory cells (eg glandular cells, plasma cells)
present in ALL cells
smooth endoplasmic reticulum
structure similar to rER, but lacks ribosomes
tubular appearance
abundant in cells with high lipid metabolism (hepatocytes) and steroid secreting cells (adrenocortical cells and testicular Leydig cells)
principal organelle for detoxification in hepatocytes (ie. modification of pesticides and carcinogens
glycogen metabolism
membrane formation and recycling
golgi apparatus
system of stacked, flattened membrane limited sacs (cisternae) and tubular extensions embedded in network of microtubules
small vesicles transport material between cisternae
golgi apparatus organization
cis-golgi network: closest to rER
medial golgi
trans-golgi network: cisternae farthest away from rER
functions of golgi apparatus
post-translational modification of proteins
sorting
packaging of proteins
four major pathways of protein secretion from golgi apparatus
apical plasma membrane
basolateral plasma membrane
endosomes & lysosomes
apical cytoplasm
apical plasma membrane: protein secretion pathway
proteins have specific sorting signals that direct their transport from TGN to apical membrane
constituitive pathway
basolateral plasma membrane: protein secretion pathway
constituitive pathway
proteins have specific sorting signals that direct their transport from TGN to the basolateral membrane
endosomes & lysosomes: protein secretion pathway
proteins have their specific sorting signal, but may be mistargeted to apical domain and from there are re-directed to lysosomes
apical cytoplasm: protein secretion pathway
proteins stored in secretory vesicles, which mature and fuse with the plasma membrane and release their contents (eg secretory cells of exocrine glands)
regulated pathway
mitochondria
generate energy in the form of ATP
originate from aerobic prokaryote that lived symbiotically within primitive eukaryotic cells - have their own DNA and translational machinery & undergo division (endosymbiotic theory)
present in ALL cells (except RBCs & terminal keratinocytes)
especially numerous in cells requiring high energy usage
shape, number & structure characteristic for specific cell types - histological criteria
high numbers - cytoplasm acidophilic
sense cellular stress: instrumental for cells undergoing apoptosis (programmed cell death)
structural components of mitochondria
outer mitochondrial membrane
intermembrane space
inner mitochondrial membrane
matrix
cristae
cristae
in steroid secreting cells - tubular shape
other cells (mitochondria) - flattened, leaf like structure
increase surface area of inner mitochondrial membrane
peroxisomal proteins - imported into peroxisomes by peroxisomal targeting signal
numbers increase in cell related to diet, drugs, hormones
microtubules
non-branching, rigid hollow tubules
one circle composed of 13 alpha & beta-tubulin dimers
dynamic structure - participate in physiological and biochemical processes
formation starts at microtubule-organizing center (MTOC) characterized by the presence of gamma-tubulin
dynamic instability - constant microtubule remodeling linked to pattern of GTP hydrolysis
direction of microtubule growth
minus end: corresponds to orientation of alpha-tubulin; anchored to MTOC
plus end: corresponds to orientation of beta-tubulin; extends to periphery (location of elongation from addition of tubulin molecules)
micro-tubular network
system of connections within cell
microtubule functions
intracellular vesicular transport (secretory vesicles, endosomes, lysosomes)
movement of cilia and flagella
attachment of chromosomes to mitotic spindle and their movement during mitosis and meiosis
cell elongation and movement (migration)
maintence of cell shape
molecular motor proteins
proteins responsible for transport along microtubule tracks
dyneins & kinesins
dyneins
move towards minus end (from cell periphery to MTOC)
cytoplasmic dyneins
axonemal dyneins - cilia & flagella
kinesins
move towards to plus end (from MTOC to periphery)
actin filaments
very abundant (up to 20%)
in nearly all cells
assemble spontaneously into linear helical array
polarized structures
types of actin
G actin: globular, unpolymerized
F actin: filamentous, polymerized
actin polarity
plus end: barbed end, fast growing
minus end: pointed end, slow growing
requires K+, Mg2+, and ATP
growth depends on local concentration of G actin
Zellweger syndrome
inability to import proteins into peroxisomes
peroxisomes lack necessary enzymes
leads to early death
mitochondrial matrix
contains the soluble enzymes of the citric acid cycle and fatty acid beta oxidation, matrix granules (Ca2+, etc.), mitochondrial DNA, ribosomes, and tRNAs
functions of inner mitochondrial membrane
oxidation reactions of electron transport chain
synthesis of ATP
regulates transport of metabolites in and out of matrix
additional stabilization - lateral binding of adjacent tetramers
intermediate filament associated proteins
keratins
vimentin & vimentin-like filaments
neurofilaments
lamins
keratins
>50 different isoforms
do not co-assemble with other types of intermediate filaments (cell and tissue specific)
span cytoplasm of epithelial cells
can connect with keratins of adjacent cells via desmosomes
vimentin
neurofilaments
lamins
centrioles
paired short, rodlike cytoplasmic cylinders
nine microtubule triplets - two pairs aligned at right angles to each other
usually found in proximity of nucleus and Golgi apparatus
MTOC
functions of centrioles
development of cilia: centrioles become basal bodies
mitotic spindle organization
development of cilia
mitotic spindle organization
inclusions
cytoplasmic or nuclear structures containing products of metabolic activity
non-moving, non-living
may be surrounded by plasma membrane
types of inclusions
lipofuscin
hemosiderin
glycogen
lipid inclusions (fat droplets)
crystalline inclusions
lipofuscin
brownish-gold pigment seen in H&E preparations
conglomerate of lipids, metals and organic molecules
sign of cellular senescence or stress
hemosiderin
iron storage complex
indigestible residues of hemoglobin
easily seen in spleen (site of RBC destruction)
glycogen
storage material for glucose
not stained by standard H&E (seen as empty space... result of glycogen wash away during staining in glycogen rich tissue)
high in liver and striated muscle
lipid inclusions
fat droplets
energy for cellular metabolism
long or short term storage
normally seen as clear area
crystalline inclusions
present in many cells, in particular Sertoli and Leydig cells of the testis
function unclear
cell nucleus
membrane limited compartment
contains genetic information
structural components of mitochondria
outer mitochondrial space
intermembrane space
inner mitochondrial space
matrix
cell nucleus components
chromatin: DNA associated with proteins
nucleolus: small area with DNA for ribosomal RNA, RNA and proteins
nuclear envelope: membrane system surrounding nucleus
nucleoplasm: remaining contents of nucleus
chromatin
nucleoprotein complex
DNA
five basic histone proteins (H1, H2A, H2B, H3, and H4)
non-histone proteins
heterogeneous heterochromatin
highly condensed DNA clumps
stains with hematoxylin and basic dyes
signifies that cell is not actively synthesizing DNA
types of heterochromatin
marginal chromatin: at the periphery of the nucleus
karyosomes: discrete bodies in the chromatin spread out through the nucleus
nuclear-associated chromatin: in the nucleolus; responsible for RNA synthesis
euchromatin
less condensed DNA
not evident in the light microscope
indicates active chromatin in the nucleus
different levels of DNA packaging
nucleosome - "beads on a string"
chromatin fibril
loop domains - associated with the chromosome scaffold or nuclear matrix
mitosis/meiosis - DNA is further condensed forming the chromosomes
Barr body
condensed X chromosome
not being used (extra in females)
nucleolus
nucleolus
site of ribosomal RNA synthesis and initial ribosomal assembly
nonmembranous region in the nucleus
stains intensely with hematoxylin and other basic dyes (because of the high amount of nucleolar RNA)
regions of nucleolus
fibrillar centers
fibrillar material - pars fibrosa
granular material - pars granulosa
fibrillar centers
contain DNA of five chromosomes (13, 14, 15, 21 & 22), RNA polymerase I and transcription factors
pars fibrosa
fibrillar material
contains ribosomal genes actively undergoing transcription, and large amounts of rRNA
pars granulosa
granular material
site of initial ribosome assembly
nucleolonema
network of pars fibrosa and granulosa together
nuclear envelope
selectively permeable membranous barrier between nuclear compartment and cytoplasm
disassembled during cell division
two nuclear membranes
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
nuclear pores
opening in the nuclear membrane
cytoplasmic ring with protruding protein fibrils
channels for small molecules
continuity of nucleoplasm and cytoplasm
nuclear pore complex transport
bidirectional
partially assembled ribosomes leave the nucleus
histones, lamins, etc. have to be transported into the nucleus (no translation occurs in the nucleus)
transport via NPC requires the presence of a nuclear localization signal that is recognized by a nuclear import receptor (requires energy in the form of GTP)
cell cycle
self regulated sequence of events controlling cell growth and division
cell cycle phases
G1: gap 1; length varies from cell to cell
S: synthesis phase; DNA replication
G2: gap 2 phase; preparation for division; checks DNA replication
M: mitosis; cell division
checkpoints occur along the well
mitosis
essential process that increases the number of cells
permits the renewal of cell populations
allows wound repair
process of chromosome segregation and nuclear division that produces two daughter cells with the same chromosome number and DNA content as the parent cell
phases of mitosis
prophase
metaphase
anaphase
telophase
meiosis
two sequential nuclear divisions leading to the formation of haploid gametes
necessary to maintain constant number of chromosomes in species
allows exchange of chromosomal material
meiotic phases
prophase I: extended to allow pairing of homologous chromosomes and synaptic recombination
metaphase I: similar to mitotic metaphase only that the chromosomes are aligned at the metaphase plate; chiasmata are cleaved to release the individual chromosomes
anaphase I: similar to mitotic anaphase only that centromeres do not split; leads to the segregation and random assortment of paternal and maternal chromosomes gets resolved
telophase I: division of the cytoplasm
meiosis II: starts right after the completion of meiosis I, there is no S-phase; essentially the same as mitotic division; results in the formation of haploid daughter cells
necrosis
pathological process
when a cell is exposed to unfavorable conditions that cause acute cellular injury
triggers an intense inflammatory response
apoptosis
physiological process that eliminates cells from the body which are no longer needed
no inflammatory response
cell death
balance between proliferation and cell death has to be carefully maintained to avoid disease
necrosis & apoptosis
characteristic features of apoptosis
DNA fragmentation
decrease in cell volume
loss of mitochondrial function
membrane blebbing
formation of apoptotic bodies
tissue types
epithelium
connective tissue
muscle tissue
nervous tissue
overview of epithelium
avascular
relatively thin to absorb nutrients
covers surfaces, lines cavities & tubes
forms secretory portion of glands
specialized cells - receptors for senses
tightly adhered to one another
cells have polarity (free apical surface and a basal surface)
functions of epithelium
protection
absorption
transportation
secretion
receptor function
specializations of epithelium
endothelium
mesothelium
endothelium
epithelial lining of blood vessels
mesothelium
endothelium that lines and covers organs
microvilli
fingerlike projections of the surface of the cell
primary purpose - increase the surface are of the cell
pronounced in cells involved in transport (intestinal epithelium & kidney tubules)
contains a core of actin filaments
actin bundle extends down into apical cytoplasm and forms the terminal web (holds in place)
apical specializations
microvilli
cilia (motile & non-motile)
stereocilia
cilia
capable of moving fluid and particles along epithelial surfaces
beat in a precise, coordinated & synchronous movement
found in trachea & bronchi (move mucus & particles)
found in oviduct (move ovum)
composition of cilia
made up of microtubules (made of tubulin)
9 + 2 arrangement
9 doublets and 2 central singlets
each doublet has a A tubule and B tubule
dynein arms connect the microtubules
dynein & tubulin serve as motor proteins (dynein - ATPase)
motile cilia
movement due to sliding of microtubule doublets along each other
dynein generates the sliding forces in axonemes
basal bodies anchor the cilia in the apical cell cytoplasm
non-motile cilia
AKA primary cilia, monocilia
found on a variety of cell types
function as the "antenna" of the cell, sensing changes in the environment
establish the left-right asymmetry of internal organs
9 + 0 arrangement of microtubules (no central singlets)
primary ciliary dyskinesia
autosomal recessive
Kartagener's syndrome
Young's syndrome
about 50% have situs inversus
also affects sperm & oviducts
Kartagener's syndrome
primary ciliary dyskinesia
immotile cilia syndrome
structural abnormality results in absence of dynein arms
failure of mucociliary transport system to protect the body from bacteria and invading pathogens in respiratory epithelium
Young's syndrome
primary ciliary dyskinesia
malformation of the radial spokes and dynein arms
affects ciliary function in the respiratory tracts
causes chronic respiratory infections
situs inversus
organs are transposed through the sagittal plane
occurs in 50% of patients with primary ciliary dyskinesia
stereocilia
long, immobile microvilli (thinner)
found in hair cells of the ear & the epididymus
sense change in the ear
junctional complex components
zonula occludens
zonula adherens
macula adherens
gap junctions
zonula occludens
tight junctions
prevent movement of water and other molecules between the cells
most apical of the junctions
acts as seams holding the adjacent cell membranes together
zonula adherens
lateral adhesion between the cells
macula adherens
desmosome
spot welds (buttons on a chair)
composed of intermediate filaments & cadherins
anchored with intermediate filaments
gap junctions
held together by connexin
allow for communication between the cells
passage of small ions, informational micromolecules, etc.
prominent in cancer cells
what type of cells have the most gap junctions?
cancer cells
basal specializations
basement membrane
basal lamina
basement membrane
basal lamina + reticular lamina
attached to reticular cells by hemidesmosomes
attaches epithelial cells to connective tissue below
hemidesmosomes
intermediate fibers anchor the connection only on one side
basal lamina
composed of laminins, collagen, proteoglycans & glycoproteins
integrin receptors specialized for holding the structure in place
epidermolysis bullosa (EB)
group of inherited disorders characterized by blister formation in response to mechanical trauma (putting on a diaper, bathing, etc.)
mutation of at least ten different genes within cutaneous basement membrane zone
exocrine glands
secrete their product into ducts
endocrine glands
ductless
secrete their product directly into the bloodstream
unicellular glands
goblet cells
mucus secreting cells
found in intestines & respiratory tract
mechanisms of exocrine secretion
merocrine
apocrine
holocrine
merocrine secretion
secretory product in membrane bound vesicles
ex. pancreatic acinar cells
apocrine secretion
secretion released in the apical portion of the cell, surrounded by some cytoplasm and plasma membrane
ex. mammary gland
holocrine secretion
the whole cell fills with secretion which is released when cell dies
ex. sebaceous gland
paracrine glands
secretions activate other cells
ex. cytokines
types of glands
exocrine
endocrine
paracrine
classification of multicellular glands
shape of secretory portion: tubular, acnar, or tubuloacinar
duct: simple or compound
simple glands
simple tubular
simple coiled tubular
simple branched tubular
simple acinar
compound glands
branched acinar
compound tubular
compound acinar
compound tubuloacinar
simple tubular gland
secretory portion of the gland is a straight tube formed by secretory cells (goblet cells)
typical location - large intestine
ex. intestinal glands of the colon
simple coiled tubular gland
coiled tubular structure is composed of the secretory portion located deep in the dermis
typical location - skin
ex. eccrine sweat gland
simple branched tubular gland
branched tubular glands with wide secretory portions are formed by the secretory cells and produce a viscous mucus secretion
typical location - stomach
ex. mucus secreting glands of the pylorus
simple acinar gland
develop as an outpouching of the transitional epithelium and are formed by a single layer of secretory cells
typical location - urethra
ex. paraurethral and periurethral glands
branched acinar gland
secretory portions formed by mucus secreting cells; short single-duct portion opens directly into lumen
typical location - stomach
ex. mucus secreting glands of the cardia
compound tubular gland
coiled secretory portion located deep in the submucosa of the duodenum
typical location - duodenum
ex. submucosal glands of Brunner
compound acinar gland
alveolar-shaped secretory units formed by pyramind shaped serous-secreting cells
typical location - pancreas
ex. excretory portion of pancreas
compound tubuloacinar gland
have both mucous branched tubular and serous branched acinar secretory units; serous endcaps (demilunes)
classification of epithelium
number of cell layers: simple, stratified
shape of cells: squamous, cuboidal, columnar
special classifications: pseudostratified, transitional
simple squamous epithelium
single layer of squished cells
lines blood vessels (endothelium) and body cavities
thin, good for diffusion
simple cuboidal epithelium
single layer of square cells
nucleus approximately in center
found in the kidney (filtration) and in the thyroid (secretion)
simple columnar epithelium
single layer of columnar cells
nuclei located at base of cell
receive nutrients through basement membrane
found in the stomach, small intestine & large intestine (absorption and digestion)
pseudostratified epithelium
single layer
nuclei look like they are in multiple layers, but NOT two distinct rows of nuclei
frequently ciliated
found in trachea, bronchiole tree, ductus deferens, epididymus (secretion & absorption)
stratified squamous epithelium
multiple layers of squished cells
get more flat as they move up & flake off
2 types - keratinized (waterproof) and non-keratinized
found in epidermis, oral cavity, esophagus & vagina (barrier, protection)
transitional epithelium
bubbled up dome shaped cells at tome
found in urinary bladder (distensible property)
stratified columnar epithelium
rare
nuclei are in two distinct rows
found in largest ducts of exocrine glands (mucus gland duct of tongue) & anorectal junction
stratified cuboidal epithelium
multiple layers of square cells
rare
found in ducts of glands
mucus membranes
line the cavities that connect with the outside of the body
consist of epithelium, connective tissue & basement membrane
have many goblet cells that secrete mucus
serous membranes
line the peritoneal, pericardial and pleural cavities
simple squamous epithelium
no mucus
abnormal epithelium
epithelium grows in response to wear & tear
growth may go wrong, resulting in tumors
ex. epithelial metaplasia, Barrett's esophagus
epithelial metaplasia
conversion of one mature cell type to another mature cell type
most common - columnar to squamous
squamous metaplasia
reprogramming of cells from columnar to squamous
occurs in pseudostratified respiratory epithelium in trachea & bronchi (prolonged exposure to cigarette smoke)
occurs in uterine cervix of women (chronic infections)
not cancer
Barrett's esophagus
epithelial metaplasia at junction of stomach and esophagus (chronic acid reflux)
reprogramming of cells from squamous to columnar
considered precancerous
function of connective tissue
binding, support, compartmentalization
hydration
transportation
defense
energy storage
connective tissue cells
mesenchymal stem cells: primordial stem cells
fibroblasts: secrete extracellular matrix
immunce cells: fight infection, involved in inflammation
type I and type II collagen (variations depending on joint)
proteoglycans
chondrocytes bunched
herring bone appearance
properties of fibrocartilage
tensile strength and ability to absorb compressive shock
resistant to shearing forces
location of elastic cartilage
pinna of external ear
external auditory meatus
auditory (Eustachian) tube
cartilages of larynx (epiglottis, corniculate, cuneiform)
elastic cartilage
hyaline cartilage + elastin
type II collagen
non-collagenous proteins
elastin
pairs of chondrocytes
properties of elastic cartilage
maintains shape of structure but flexible
least abundant cartilage of body
growth of cartilage
appositional growth
interstitial growth
division of chondrocytes stops in adolescence
calcification of cartilage occurs during normal bone growth and during old age
appositional growth
new cartilage forming on surface of existing cartilage
cells in the perichondrium secrete matrix against the external face of existing cartilage
differentiating perichondrial cells into chondroblasts
interstitial growth
new cartilage forming within existing cartilage
lacunae-bound chondrocytes inside the cartilage divide and secrete new matrix, expanding the cartilage from within
types of adipose tissue
white (unilocular) fat
brown (multilocular) fat
white adipose tissue
adipocytes store energy in lipid droplets (filled with triglycerides)
subcutaneous location provides thermal insulation
adipocytes secrete hormones, growth factors, and cytokines
contribute to insulin resistances leading to type II diabetes
brown adipose tissue
good fat
found in new borns
found in certain places in adults (back, neck, mediastinum)
found in bears (hibernation)
highly innervated & under neural control
regulation of adipose tissue
leptin
resistin
leptin
regulates appetite and body energy expenditure
signals to the brain about body fat stores
increases formation of new vessels (angiogenesis)
involved in blood pressure (regulates vascular tone)
potent inhibitor of bone formation
resistin
increases insulin resistance
linked to obesity and type II diabetes
zonula occludens associated proteins
occludin
claudin
JAM (junctional adhesive molecules)
ZO1, ZO2, ZO3
zonula adherens associated proteins
cadherins
actin filaments
vinculin
alpha-actin
catenin
E-cadherin
macula adherens associated proteins
cadherins (desmocollin & desmoglein)
intermediate filaments
gap junction associated proteins
connexins
hemidesmosome associated proteins
intermediate filaments
integrins
focal adhesion associated proteins
actin filaments
integrins
Epidermolysis Bullosa: possible gene mutation sites
intermediate filaments (keratins)
anchoring filament proteins
anchoring fibril (type VII collagen)
fascia adherens
nonepithelial junctional complex
cardiac muscle
pemphigus foliaceus
autoantibody mediated blistering disease in which antibodies against desmoglein 1 (cadherin of desmosomes) cause a loss of adhesion of keratinocytes in the superficial epidermis
bullous pemphigoid
breakdown of attachment plaque of hemidesmosome
basal infoldings
increase membrane surface area
mitochondria tend to line up; striated cell surface appearance
allow for active transport through ion pumps
lateral infoldings
maximize lateral cell contact & adhesion
communication
transport
what is the embryonic origin of all CT?
mesenchymal stem cells
descendants of mesenchymal stem cells
fibroblasts: fibers
chondroblasts: cartilage
osteoblasts: bone
fibroblast nuclei appearance
heterochromatic: not a lot of transcription going on, condensed DNA, reduced amount of cytoplasm (maintenance activity)
euchromatic: very active nuclei during wound healing
mesenchyme
embryonic connective tissue that is derived from mesoderm
differentiates into mesenchymal stem cells (CT) and hematopoietic stem cells (blood cells, etc)
is it loose or dense CT?
loose (areolar) CT: around the epithelium
dense CT: found as you migrate away from epithelial structures
collagen fibers: H&E staining
pink (eosin)
collagen fiber: EM
see striation of collagen at level of electron microscopy ONLY
perineurium & endothelial cells share basal lamina - allows transfer of oxygen & nutrients
perineurium
surrounds the nerve fascicle & forms blood nerve barrier
distinguishing between dendrites & axons
follow the nerve impulse from start to finish
if it has myelin, it is likely an axon
if it has receptors, it is likely a dendrite
nerve impulse
action potential: all or none wave of depolarization that travels along the neuronal membrane
neurons can shift their charge from negative to positive (depolarization) to generate a nerve impulse through manipulation of ions
basis of neuronal communication
resting membrane potential of neurons
Em = -60V
negative charge inside cell
[K+] high inside cell, low outside cell
[Na+] low inside cell, high outside cell
difference in ion concentration along semipermeable membrane
chemical force & electrical force oppose each other to maintain this balance
depolarization of neuron
voltage gated Na+ channels allow positive charge to travel along length of axon
hyperpolarization of neuron
opening of voltage gated K+ channels
Na/K ATPase activated to restore resting membrane potential
types of conduction
continuous conduction: the nerve impulse travels down the neuronal membrane without interuption
saltatory (discontinuous) conduction: nerve impulse "jumps" each node of Ranvier until it reaches it's axon terminal (high concentration of voltage gated Na+ & K+ channels at each node)
cellular function of neuron
synthesis
molecular motor proteins & transport
neurotransmitters (in brief)
nestin (if dividing... in passing)
enzymes (medical biochemistry)
molecular motor proteins
kinesins: anterograde transport; from cell body to periphery or axon terminals
dyeins: retrograde transport; from periphery or axon terminal to the cell body
kinesins
anterograde transport: from cell body to periphery or axon terminals
slow or fast transport depends on size & reactivity (larger molecules take longer)
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)
clinical relevance of astrocytes
~80% of adult primary brain tumors arise from fibrous astrocytes
intermediate filament of importance - glial fibrillary acidic protein (GFAP) is a major marker for diagnosing brain tumors
mediation of blood brain barrier
involved in potassium spatial buffering
where does blood brain barrier begin?
pia mater lines CNS tissue
vascular endothelial cells
protoplasmic astrocyte foot process will separate these layers
how do the pia & the atrocytes make the blood brain barrier?
pia & blood vessels invaginate
as you get closer to capillary beds, pia mater thins
astrocytes take over - foot process of astrocytes associate with endothelial cells of capillary beds
oligodendrocytes
similar to schwann cells - different kinds of myelin proteins
found in CNS
have few Schmit-lanterman clefts (astrocyte support)
nodes of Ranvier are BIGGER
microglia
migrate & engulf microorganisms, injured or dead neurons
derived from monocytes associated in the immune system
the phagocytic macrophages of the CNS
ependymal cells
simple epithelium layer that lines ventricles of the brain & spinal canal
contain cilia to help circulate CSF
contain microvilli to help absorb CSF
response of neurons to injury
degeneration
regeneration
degeneration
Wallwerian: anterograde degeneration of peripheral axon or axon terminal
traumatic: retrograde degeneration of proximal axon (toward cell body)
chromatolysis: preclude to neuronal death; cell body swells under high metabolic stress
regeneration
growth cone: starts at tip of neuron & leads to sprouting
sprouting: nerve can grow back (maybe not in correct place)
major factor affecting regeneration
presence of myelin
macrophages are able to clear it when a nerve is crushed or damaged in PNS
microglia are unable to clear it when CNS tissue is damaged
gliosis
increased production of glial fibrillary acidic protein (GFAP)