test 2 Flashcards
what does the parathyroid hormone stimulate osteoblasts to secrete?
M-CSF; RANKL
what are the 3 major classes of cartilage
hyaline cartilage
elastic cartilage
fibrocartilage
what does the skeletal system in all vertebrates begin as
cartilage
what are the cell components of cartilage
chondroblasts (cartilage-forming cells)
chondrocytes (cartilage-maintenance cells)
what are the components of the extracellular matrix of cartilage
collagen fibers (mostly type 2 (type 1 in fibrocartilage)) amorphous grous substance
what are the functions of cartilage
compressible resists distortion absorbs shock in joints reduces friction in movable joints necessary for endochondral bone growth involved in bone fracture repair
what is characteristic of cartilage formation
- chondroblasts (lay down cartilage matrix and becomes chondrocytes)
- chondrocytes (maintain cartilage matrix)
- lacunae: pockets within the matrix where the chondroblasts and chondrocytes are found
what is the perichondrium
it surrounds cartilage and is a membrane-like layer
what is the outer and inner layers of the perichondrium consists of
outer fibrous layer: contains fibroblasts
inner chondrogenic layer (cartilage forming layer): gives rise to chondroblasts, which become chondrocytes. Chondrocyte is involved in the production of the collagen and proteoglycans in the matrix. Chondrocytes also secrete chondronectin
what secretes chondronectin
chondrocytes
what is an isogenous group
groups of 2-8 chondroctes occupying the same lacunae. Result of mitotic division. Cells will become separated as they begin to lay down matrix of their own
What are the components of the cartilage matrix
- collagen type 2 (1 in fibrocartilage)
- hyaluronan (hyaluronic acid)
- chondroitin sulfate, keratan sulfate, herparin sulfate
- glycosaminoglycans
- territorial matrix: surrounds each chondrocyte (high glycosaminoglycan content; low collagen content)
- inter-territorial matrix: surrounds territorial matrix (low glycosaminoglycan content; high collagen)
what are characteristics of hyaline cartilage
- most common type
- avascular
- type 2 collagen
- surrounded by perichondrium
- translucent, bluish gray to white
- solid but flexible
- chondrocytes are found in cell groups
- growth patterns: appositional, interstitial
where is hyaline cartilage found
external auditory meatus larynx tracheal cartilage bronchial cartilage fetal long bones articular ends of bones
what are characteristics of elastic cartilage
*specialized by addition of elastic fibers
* surrounded by perichondrium
*yellow color because of presence of elastic fibers
* more opaque, flexible and elastic than hyaline cartilage
*chondrocytes mostly located singly
type 2 collagen + elastic fibers
where is elastic cartilage found
auricle (pinna) of the ear
epiglottis
what are characteristics of fibrocartilage
- increased collagen in matrix
- reduced cellularity compared to hyaline cartilage
- not surrounded by perichondrium
- opaque appearance from fibrous texture
- type I collagen
- single sparse chondrocytes
where is fibrocartilage found
intervertebral discs
pubic symphysis
insertion of some tendons and ligaments
closely associated with dense connective tissue or hyaline cartilage
what is the lucanar rim
Inner layer of the territorial matrix. it consists of loose collagen fibrils
what does the territorial matrix consist of
randomly arranged type 2 collagen fibrils surrounded by proteoglycans
what does Sox 9 do
controls the expression of type 2 collagen and then proteoglycan aggrecan
what type of system is bone tissue based on
canalicular system
how does increase in bone length occur
through appositional growth of hyaline cartilage model
what are the 2 main components of the bone matrix
organic component (osteoid) inorganic component (hydroxyapatite) which makes up 35-65% of the matrix
what are the 3 types of bone
woven bone (occurs during bone development and bone repair) compact bone (also called lamellar bone) spongy bone (also called trabecular or cancellous bone)
what are characteristics of compact bone
- lacks cavities and forms a dense plate
- Haversian lamellae that encircle a central blood vessel forming an osteon
- osteocytes are found between the lamellae located in lacunae & are connected to each other and the Haversian canal via canaliculi
- volkmann’s canals run perpendicular to the haversian cancels
what are characteristics of trabecular (spongy) bone
3D lattice of branching, bony spicules intertwined to form trabeculae surrounding the bone marrow spaces in the long bones and flat bones
what does the endosteum consists of
osteoprogenitor cells & reticular fibers
what are sharpey’s fibers
collagen fibers derived from the outer layer of periosteum, projecting into the outer circumferential lamellar system (connect bone to marrow)
what provides nutrients to osteocytes
a blood vessels within the haversian canal
what is alkaline phosphatase
an ectoenzyme (cell surface enzyme) that hydrolyzes monophosphate esters at high pH
what are osteoprogenitor cells
- stem cells (in adults are described as bone lining cells)
- in adults, found in inner portion of periosteum, endosteum, and lining of vascular canals of compact bone
- derived from mesenchyme of the embryonic sometime and possess mitotic potential
- give rise to osteoblasts and bone lining cells
what are osteocytes
derived from osteoblasts and are trapped by the matrix they secete
what are osteoclast cells
- maintain matrix that is already there and play role in uptake and release of phosphates and calcium
- derived from monocyte lineage, which, in turn, is derived form the monocyte precursors in bone marrow
where does the ARF cycle occur
at adult remodeling sites and during development
what does vitamin D3 do for bones
regulates expression of osteoclaclin
what is the parathyroid hormone (PTH) the primary regulator for
bone turnover
what occurs at low and high PTH levels in bone formation
low: bone formation by osteoblasts is stimulated
high: osteoblasts are stimulated to release osteoclasts-differentiation factors
what are the steps for osteoblast regulation of osteoclasts
PTH binds to recepts on osteoblast
osteoblasts stimulated to synthesize MCSF and RANKL
osteoblasts releases M-CSF
M-CSF binds to M-CSF receptor
monocyte is now a macrophage and expresses RANK
RANK BINDS TO RANKL
macrophage becomes a multinucleate immature osteoclast
osteblast secretes protegerin
non-functional osteoclast uncouples form the osteoblast and becomes a functional osteoclast
calcitonin acts to reduce bone resorption
what signals control the aggregation of mesenchymal cells
Wnt, Hedghog, FGF, TGF-beta
what is the mass called when osteoblasts secrete osteiod and trap some of the osteoblasts
blastema
what does osteoid include
collagen 1 and non-collagen proteins
what does the primary ossification center in intramembranous bone become
trabecular
what do numerous trabecular fusing together form
spongy bone
what is the network of cartilage matrix calcified by
the deposition of calcium salts
what are the parts of the epiphyseal plate
reserve zone, proliferative zone, hypertrophic zone, and vascular invasion zone
where does ossification of bone first occur
diaphysis
what is proliferation of bone stimulated by
indian hedgehog
what is the template for long bone
hyaline cartilage
what forms the periosteal collar
osteoprogenitor cells of the perichondrium
what is the metaphysis
part of the diaphysis nearest the epiphysis
describe each zone of endochondral ossificaiton
reserve: primitive hyaline cartilage responsible for the growth in length of the bone as erosion and bone deposition advance into this zone
proliferative: proliferating chondrocytes align as vertical and parallel column
hypertrophic: apoptosis of chondrocytes and calcification of the terroritial matrix
vascular invasion: blood vessels penetrate the transverse calcified septa, and carry osteoprogenitor cells with them
how does bone grow in length
- ossification front invades and destroys the chondrocytes and passes through the site previously occupied by the chondrocytes
- calcification of the cartilage matrix surrounding hypertrophic chondrocytes
- proliferating chondrocytes away from the ossification front increase the length of the cartilage
what are the stages of periosteal bone growth
- new aversion system forms under the periosteum
- ridges fuse and the groove becomes a bony tunnel enclosing the blood vessel
- additional bone lamellae are deposited around the tunnel, which is then converted into the aversion canal containing a blood vessel
- the aversion vessel continues to receive blood through the canals of volkmann extending obliquely across the diaphysis
- when bone reaches full size, and inner circumferential lamellae provide the boundaries of the compact bone consisting of aversion systems, interstitial lamellae are found between aversion systems
what are the steps of compact bone remodeling (within an osteon)
- activation
- resorption
- reversal
- formation
what is a joint
where 2 bones come together
what is a cartilaginous joint (amphiarthroses)
bones are joined by hyaline or fibrocartilage
what are the 2 types of cartilaginous joints
symphysis: joined by fibrocartilage (i.e: intervertebral discs and pubic symphysis)
synchondrosis: joined by hyaline cartilage (idl epiphyseal plates and first sternocostal joint)
what are the types of fibrous joints (synarthroses)
suture: joints between bones of the calvaria
gomphosis (some type of connective tissue holding it in socket): peg-in-the-socket joint such as teeth in alveoli
syndesmosis (bones joined by interposes flat membrane (allow a bit of movement between): idl fibrous membrane between tibia and fibula
what are synovial joints
movable joints exemplified by a connective capsule surrounding a fluid-filled joint space
often reinforced by thickenings of the outer part of the capsule referred to as ligaments
ligaments stabilize the capsule and joint
ligaments control and restrict direction and range of motion
what are the types of synovial joints based on degrees of freedom of movement:
monoaxial (hinge and pivot)
biaxial (condyloid and saddle [sellaris])
triaxial: ball and socket
what are components of the histology of the synovial joint?
articular cartilage; hyaline cartilage,lacks perichondrium. not lined by synovial membrane
joint capsule: vascular dense CT, lined by synovial membrane, attached to edges of articular cartilage
synovial membrane: highly vascularized, 1-3 layers of synovial cells, no basal lamina
synovial fluid: contains mucin, produced by synovial cells
synovial cells: type A (macrophage-like) and type B (fibroblast-like)
what is the pH range for blood
7.35-7.45
define plasma
blood minus formed elements
define serum
plasma without the blood clotting elements
3 layers of heparinized and centrifuged blood
supernatant (plasma)
buffy coat (leukocytes)
precipitate (sedimented RBC)
define blood clot
fibrin-containing network trapping blood cells
what are the major contents of erythrocytes
lipids, ATP, carbonic anhydrase, hemoglobin
what are the proteins found in erythrocytes
about 50% are integral membrane proteins peripheral proteins (spectrin and actin)
what are the 3 proteins involved in spectrin tetramers
actin, tropomyosin, protein 4.1
what does protein 4.1 do
links the actin-tropomyosin complex to glycophorin
what is adducin
calmodulin-binding protein that stimulates the association of actin with spectrin
what is the major structural protein of RBC
spectrin
define spectrin
tetramer of 2 polypeptide chains (alpha and beta). The ends of the spectrin tetramers associate with short actin filaments, resulting in the spectrin-actin network.
what does ankyrin do
links the spectrin-actin network and the plasma membrane by binding to spectra and a transmembrane protein (band 3)
what are characteristics of neutrophils
- also referred to as polymorphonuclear
- nuclear lobes with connecting strands
- active amoeboid phagocytes
- small, numerous granules
- larger less numerous azurophilic granules
- live for 1-2 days after leaving circulation
what doe the enzymes secreted by neutrophils do
they are capable of destroying certain bacteria by formation of free radicals (superoxide) as well as the release of lysozyme and lactoferrin, which destroy bacterial walls
what are some characteristics of basophils
- lobulated nucleus (bilobed)
- large, membrane-bound basophilic granules
contain: serotonin, heparin, kalikrein - can produce leukotrienes
what do leukotrienes do
increases vascular permeability and slows contraction of smooth muscles
what are characteristics of eosinophils
bilobed nucleus
Major basic protein
peroxidase
cationic protein
respond to allergic diseases and parasitic infections
phagocytize antibody-antigen complexes and parasites
what do major basic proteins do
disrupt parasite membranes
cause basophils to release histamine
what does cationic protein do
neutralizes heparin and is anti-parasitic
what does eosinophil peroxidase do
binds to microorganisms and facilitates their killing by macrophages
what are characteristics of lymphocytes
large round, sometimes slightly indented nucleus; fills most of cell
variation in cell size
B lymphocytes
T lymphocytes
what are B lymphocytes the precursor for
plasma cells
hat are T lymphocytes the precursor for
T lymphocytes
what are characteristics of monocytes
largest leukocytes
eccentrically located, kidney-shaped nucleus
granular cytoplasm due to small lysosomes
precursor of macrophages and osteoclasts
what are characteristics of platelets
enhance aggregation by release of factors, and they promote clot formation, retraction and dissolution
repair damage to endothelium by forming platelet plug
adhesion of platelets involves integrins
platelets release thromboxane which increases platelet aggregation
endothelial cells release prostacyclin which decrease platelet aggregation
what are the 4 types of granules in the cytoplasm of platelets
alpha granules, dense core granules, lysosomes, peroxisomes
define hemostasis
elimination of bleeding
define hematoma
accumulation of blood in tissues
what is the sequence of hemostatic events in small vessels
constriction of smooth muscles around vessels–> constriction of vessels–> slowing of blood–> formation of platelet plug –> blood clotting (coagulation)
what is von willebrand factor
plasma protein, released from weibel-palade bodies in endothelial cells, that facilitates the adherence of platelets to the walls of damaged blood vessels
what factor must be present for the fibrin meshwork to form
factor XIII
what occurs during phase 1 of blood clotting
1 activated platelets released
2 endothelial cells release tissue factor, which binds to factor VIIIa to convert X into factor Xa and initiate the common pathway of blood clotting
3 endothelins, stimulate smooth muscle contraction and proliferation of endothelial cells and fibroblasts to accelerate the repair process
what occurs during phase 2 of blood clotting
- fibronectin in plasma binds to activated integrin receptors, and platelets are bridged to each other
5 thrombin acts on fibrinogen to cleave fibropeptides and form a fiber monomer
6 fibrin monomers aggregate to form a soft fibrin clot, factor XIII cross-links fibrin monomers. platelets and fibrin form a hemostatic plug
what occurs during phase 3 of blood clotting
- plasminogen is converted to plasma by tissue plasminogen activator
8 plasmin dissolves the fibrin clot
what typically initiates the intrinsic pathway
injury to the endothelium of the blood vessel exposing collagen fibers
what is thromboplastin
membrane-bound lipoprotein expressed at sites of cell injury; it is derived from the plasma or organelle membranes of damaged cells in the disrupted tissue and enters into the circulating blood
what all does factor XII activate
factor XI
prekallikrein to kallikrein
what does factor XI activate
factor IX
what activates factor X (intrinsic pathway)
factor IX with activated Factor VIII and calcium
what activates factor VIII
thrombin
what leads to the activation of factor VII
thromboplastin
what activates factor X (extrinsic pathway)
activated factor VII and calcium
where are most clotting factors synthesized
liver
what factors need vitamin K present in order to be synthesized
factors VII, IX, X
what activates the homing mechanism
various cytokines released by mast cells, platelets, and damaged tissue cells
where are P-selectins from
weibel-palade bodies
what does the binding of ligands on P-selectins cause
leukocytes to roll along the endothelium
what are sialyl lewis-x antigens
oligosaccharide ligands for P-selectin binding found on leukocyte membranes
where are integrin receptors activated
on leukocyte membrane
what are the 3 general steps of homing and inflammation
1 rolling and attachment
2 adhesion
3 transendothelial migration
what is the major cause of Rh incompatibility
D antigen
what does hemolysis in erythroblastosis fettles result in
- hemolytic anemia which causes hypoxic injury to the heart and liver leading to generalized edema (hydrous fettles)
- jaundice which causes damage to the CNS
- hyperbilirubinemia
define totipotent
cells that can gives rise to all cells of an organism, including embryonic and extra embryonic tissues
define pluripotent
cells that can give rise to all cells of the embryo and subsequently adult tissues
define multipotent
cells that can gives rise to different cell types of a given lineage (adult stem cells)
what are characteristics of embryonic stem cells
- derived from inner cell mass of blastocyst
- pluripotent, differentiate to all cell lineages
- technical and ethical limitations
- may be induced from adult tissues
what are characteristics of adult stem cells
harvested from mature organs/tissues
multipotent
more restricted ability to produce different cell types and to self-renew
what occurs during the 2-8 weeks of gestation (hematopoietic sites)
- islands of hematopoiesis are found in then yolk sac wall
- give rise to nucleated erythrocytes from 2-8 weeks of gestation
- no leukocytes form during this phase
what occurs during 8-28 weeks of gestation (hematopoietic sites)
hematopoiesis first occurs in the liver and then the spleen
normally ceases around the time of birth
what is the stroma
- contains fibroblasts, reticular cells, adipose cells, and endothelial cells
- synthesizes and secretes hematopoietic growth factors
what is the parenchyma
*consists of various lineages of hematopoietic cells in different stages of differentiation
what are sinusoids
- endothelial-lined spaces that connect arterial and venous vessels
- provides access for mature blood cells to move into the circulation
what are hematopoietic cords
bands of parenchyma and stroma lying between the sinusoids
what are the 2 kinds of multi potential precursor cells in hematopoietic stem cells
myeloid (give rise to all blood cell lines except lymphocytes)
lymphoid (give rise to lymphocytes)
what is the series for Granulocyte-macrophage CFU
*monoblast–> promonocyte–> monocyte–> macrophage
or
* myeloblast–> promyelocyte–> myelocyte–> metamyelocyte–> band cell–> neutrophil
how are monocytes recognized
by the indented nucleus
what is a macrophage called that is in bone
osteoclast
what is a macrophage called that is in skin
langerhans cells
what is a macrophage called in the liver
kupffer cell
what is the series for eosinophil and basophil CFUs
myeloblast–> promyelocyte–> myelocyte–> metomyelocyte–> band cell–> eosinophil or basphil (which becomes mast cell)
what is the series for megakaryocytic CFU
megakaryoblast–> megokaryocyte–> platelets
what is the series for erythroid CFU
proerythroblast–> basophilic erythroblast–> polychromatophilic erythroblast–> orthochromatic erythroblast–> reticulocyte–> erythrocyte
what are characteristics of colony-stimulating factors
GM-CSF: produced by endothelial cells, T cells, fibroblasts, monocytes, stimulates granulocytopoiesis and monocytopoiesis, ameliorates neutropenia associated with chemotherapy or radiation therapy
G-CSF: produced by endothelial cells/fibroblasts/macrophages, directs CFU-G to proliferate and differentiate into myeloblasts, may be used following chemotherapy or radiation therapy
monocyte-colony stimulating factor: commits CFU-GM to monocytic pathway
what does erythropoietin do
- directions CFU-E to proliferate and differentiate into pro erythroblasts
- produced in kidney response to decrease in oxygen saturation
what does thrombopoietin do
*directs formation of megokarytoblasts
* produced in proximal convoluted tubules of kidney
produced in parenchymal cells and sinusoidal endothelial cells of liver
no therapeutic use
what doe cytokines do
mediate positive and negative affects on cellular quiescence apoptosis, proliferation, and differentiation
engage specific receptors and activate a variate of signaling pathways
what do chemokines do
regulate blood cell trafficking and homing sites of need
may serve as positive and negative growth regulators
bind to guanine protein-coupled transmembrane receptors
what are characteristics of type 1 myofibers
*intense staining for oxidative enzymes
* rich in NADH transferase, myoglobin, ATPase
*posses many mitochondria
*primarily utilize oxidative phosphorylation
produce slow and continuous contraction
dark/red fibers
what are characteristics of type 2a myofibers
intermediate staining
use aerobic and anaerobic respiration
contract more rapidly than type 1
resistance to fatigue
what are characteristics of type 2Bmyofibers
light staining primarily anaerobic contract quickly fatigue quickly white/light fibers
how do the cells of cardiac muscle communicate
gap junctions (intercalated discs)
what does the perimysium consist of
fibroblasts and type 1 collagen fibers
what does the endomysium consist of
basal lamina and reticular collagen fibers
what does the basal lamina of the endomysium secreted by and do
secreted by muscle cells
anchors muscle fibers to each other
helps to distribute the force of contraction
how are sarcomeres separated
by transverse disks called Z bands/discs
what does creatine kinase do
catalyzes a reversible reaction generating creatine and ATP from the hydrolysis of creatine phosphate
what does create phosphate derive from and do
derives from mitochondria
shuttles phosphate groups between mitochondria and the myofibril
what are characteristics of the thick myofilaments
myosinL dimeric protein with long tails and 2 heads at one end
each head has actin binding region, atp-binding region, light-chain binding region
2 pairs of light chains: similar to calmodulin but have lost ability to bind calcium
what provides the driving force for movement
myosin II
what are characteristics of thin myofilaments
F actin: polymer of G actin, each filament consists of 2 polymers wound in alpha-helix, plus end inserts on Z-disc
what are the actin associated molecules
troponin:
tropomyosin: sits in the groove between 2 actin strand on actin filament
what are the types of troponin and what do they do
I: inhibits binding between actin and myosin
C: binds calcium ions
T: binds to tropomyosin
define T tubules
extensions of the sarcolemma that extend down into the sarcoplasm (located at the A-I junctions)
what do T tubules do
provide electrochemical coupling myofiber contraction by transferring the AP of the sarcolemma into Ca++ release from the cisternae
what does A-beta-crystallin do
heat shock protein that protects desmin from mechanical stress
what does dystrophin do
links the alpha-actinin/desmin complex to cytoplasmic side of sarcolemma. anchors actin to sarcolemma and reinforces sarcolemma during muscle contraction
what does dystroglycan complex do
links dystrophin and laminin-2
what does alpha-actinin do
attaches thin filaments to Z line
what does Titin do
extends from the Z-disk to the middle of H band and connects ends of thick filaments to Z line. Provides myosin with elasticity and centers thick filaments in sarcomere
what does the desmin intermediate filaments do
framework of desmin filaments which surrounds the Z line and extends into each sarcomere.
Links myofibrils laterally and to the sarcolemma
what does plectin do
binds desmin filaments
what does nebulin do
extends from Z disc to end of actin filament
serves as template to regulate length of actin filament
what does dystrophin do
links actin filaments to transmembrane proteins of muscle cell plasma membranes
what does muscular dystrophy result in
X-linked inherited disease that results in progressive degeneration of skeletal muscle
what do mutations of desmin, plectin and alpha-B-crystallin cause
fragility of the myofibrils and their destruction after continuous stress
what is the function of satellite cells
attach to myotubes before basal lamina is laid down and function as stem cells.
give rise to myogenic precursor cells: replace damaged muscle by proliferating, fusing, and differentiating into skeletal muscle fibers
what are the components of neuromuscular spindle
extrafusal fibers, intrafusal fibers, alpha motor neurons, gamma motor neurons, gamma motor fibers, primary and secondary afferent fibers
what do gamma efferent (motor) fibers do
derived from neurons in the spinal cord, innervate the contractile region of the intrafusal fibers of the spindle. The axon terminates in motor end plates
compare smooth and cardiac muscle
nucleation: both mono
nucleus location: both central
T tubules: smooth doesn’t have it, cardiac does
communication: both via gap junctions
arrangement: smooth is non-sarcomeric, cardiac is sarcomeric
compare T tubules of cardiac and skeletal
cardiac: each T tubules interact with one cistern and forms diad
skeletal: each T tubule interacts with 2 cistern and forms triad
where are the diads located in cardiac muscle
at the Level of the Z lines
what is the composition of the intercalated discs of cardiac muscle
macula adherens: link intermediate filaments of adjoining cardiac muscles
fascia adherents: anchor actin filaments of sarcomeres
gap junctions
what is located in the transverse or longitudinal component of the intercalated disc
transverse: macula adherens and fascia adherens
longitudinal: gap junctions
where are the triad of skeletal muscle found
at the A-I junction
what secretes ANP
cardiac muscle cells in atria
what do ANPs do
regulate fluid electrolyte balance
relax vascular smooth muscle (reduces blood volume and pressure)
what is the release of ANP stimulated by and result in
stimulated by atrial stretch
results in cleavage of prohormone
how is ANP stored
as prohormone in secretory vesicles
where is the meshwork of actin and myosin bundles of smooth muscle cells found
throughout cytoplasm except in nuclear area
describe the dense bodies of cardiac muscle
anchor actin filaments to each other and to cell membrane
contain alpha-actinin
interconnected by a specific type of desmin
communicate force of contraction to cytoskeleton and cell membrane
found in cytoplasm and in the cell membrane
what do the pinocytotic vesicles of smooth muscle cells do
transport calcium ions from extracellular fluids to sarcoplasmic reticulum
what does cave-in do
binds to cholesterol in the lipid rafts and initiates the formation of caveolae
define lipid raft
region or domain of a membrane enriched in cholesterol and sphingolipids
