histology and pathology of bone and other connective tissue Flashcards
what does the ECM of hyaline cartilage consist of
- collagen type 2
- aggrecans
- hyaluronic acid
- chondronectin
what are the types of connective tissue
connective tissue proper
cartilage
bone
what is chondronectin
a glycoprotein that binds together the collagen, aggrecans, and integrins together
what are the 2 main aggrecans of hyaline cartilage
chondroitin sulphate
heparin sulphate
where is hyaline cartilage found
ribs, trachea, joints
what is elastic cartilage
modified hyaline cartilage
hyaline cartilage with elastin fibres
where is elastic cartilage found
ears, ear canal, epiglottis and larynx
what is the added benefit of elastic cartilage over hyaline cartilage
flexible, but maintains shape
where is fibrocartilage found
- binds solid joints
- intervertebral discs
- minisci
what is fibrocartilage
mixture of dense fibrous CT made of type 1 collagen, and isolate islands of cartilage
describe the structure of intervertebral discs as you age
initially: fibrocartilage around the periphery (type 1 collagen), surrounding gelatinous nucleus pulposis (type 2 collagen)
as you age: the nucleus pulposis becomes replaced with fibrocartilage until you have a solid disc of fibrocartilage
explain the different parts of a long bone
diaphysis = shaft
metaphysis
epiphysis
where is compact bone found
forms the outside of bone
where is trabecular bone found
in the centre of long bones
what fills the gaps in the trabecular bone
yellow/red marrow and blood vessels
what are special about the blood vessels in the bone
they include sinusoids - Large diameter and can have pores
explain the inner and outer layers of periosteum
outer fibrous (fibroblasts, blood vessels and collagen) inner layer cellular (osteoprogenitor cells)
is the periosteum or endosteum thicker
periosteum
what are sharpey’s fibres
collagen fibres of a tendon that penetrate into the bone for connection, –> the collagen of the tendon and bone become continuous
what are the branches of blood vessels that supply the long bones
epiphyseal artery
metaphyseal artery
nutrient artery (to supply diaphyses)
periosteal arteries
in what two places is there no periosteum on the bones
- articular surface
- where tendon inserts into bone
explain the type of cell of the synovial membrane
- very leaky cells (lack BM, tight junctions, desmosomes) - NOT epithelium
explain the intima of the synovial membrane
2-3 layers thick - mix of fibroblast-like cells and macrophage-like cells
explain the sub-intimal layer of the synovial membrane
fibrous CT
what is synovial fluid
an ultrafiltrate of synovial blood plus proteoglycan
explain the histological structure of dense bone
organised into Haversion systems (organised along the lines of stress)
- centre has the blood vessels
where are osteoprogenitor cells found
in periosteum and endosteum
function of osteoprogenitor cells
can give rise to new osteoblasts to grow or repair bone
what is the origin of osteoprogenitor cells
from mesenchymal stem cells in bone marrow
function of osteoblasts
makes osteoid
what is osteoid
the organic ECM of bone (collagen type 1 and bone matrix proteins)
function of osteocyte
- maintain bone in its vicinity in response to loading
- mechanotransduction (can tell where the stresses are)
loss of osteocytes leads to
bone resorption and release of free calcium
function of osteoclasts
destroys/remodels bone in growth, repair and normal turnover
explain the “look” of osteoclasts
giant multinuclear cells
explain the steps in how osteoclasts destroy bone
- seals itself to bone
- secretes H+, Cl- from H2CO3 breakdown to dissolve CaP
- secretes proteases to destroy to collagen
what molecule is a marker of osteoclast activity
tartrate-resistant acid phosphatase
origin of osteoclasts
related to granulocytes/macrophages
not related to osteoblasts
which hormones affect osteoclast activity
parathyroid hormone - increases activity
calcitonin - decreases activity
(opposite for osteoblasts)
what happens to osteoclasts when not required
they apoptose
during the development of bone.. what two types of bone can be made
membrane bone
endochondral bone
how does membrane bone form
forms directly from mesenchyme
where does membrane bone form
the skull and flat bones of the face, the mandible and clavicles
which bones form by endochondral ossification
weight bearing bones and bones of the extremities
what is the endochondral ossification method of making bone
a cartilage model of the bone is produced and then the cartilage is replaced by bone
what are the 5 steps in endochondral ossification
- bone collar forms around the diaphysis
- the cartilage beneath the collar degenerates
- BVs invade, and bring in bone cell progenitors
- a second nucleus of ossification appears in each epiphysis
- zones of ossification grow together, but leave a thin zone of cartilage, the growth plate
what are the 5 zones of the growth plate in bones
resting zone proliferation zone maturation zone hypertrophic zone ossification zone
what is the resting zone of the growth plate in bones
zone of normal hyaline cartilage
what is the proliferation zone of the growth plate in bones
zone of dividing chondrocytes
what is the maturation zone of the growth plate in bones
a zone of mature chondrocytes
what is the hypertrophic zone of the growth plate in bones
a zone of hypertrophic (dying chondrocytes)
what is the ossification zone of the growth plate in bones
zone of bone laid down
when is woven bone made
during development or repair
what is different about woven bone
it is more cellular, has more collagen and has no Haversian systems
how is woven bone made into lamellar bone
remodelled by osteoclasts and osteoblasts
explain the layering of the bone in Haversian canals
the collagen alternate in different directions in each layer and is laid down from outside inside, leaving only a small narrow space around the blood vessel (Haversian canal)
where do osteocytes live
in lacunae within the Haversian systems
how do osteocytes receive/gain nutrients
via their canaliculae
explain the “look” of osteoblasts
amphophilic cytoplasm
perinuclear hoff
(either resting - thin, or active - fat)
are osteoblasts or osteoclasts faster
osteoclasts
how does PTH cause an increased activity of osteoclasts
PTH causes an increase in the expression of RANKL and a decrease in the expression of osteoprotegrin on the osteoclast progenitor–> differentiation to osteoclast
where does the RANKL ligand come from
ligand on osteoblast
receptor on osteoclast
what is the action of osteoprotgrin
blocks the RANK receptor
what are the steps in normal osteoid mineralisation
- osteoblasts secrete collage and secretory vesicles
2. increase in conc of Ca and PO locally causes precipitation around the vesicles
what do the vesicles contain which the osteoblasts secrete
alkaline phosphatase and pyrophosphatase
what are the two types of “incomplete” fractures
greenstick - break only part way through
torus - compression fracture
what is the normal annual bone turnover in adults?
5-10%
what is a comminuted fracture
a fracture where there are more than 2 fragments
what is a butterfly fracture
where the fracture is triangular shaped (3 fragments)
what causes a stress fracture
repeated low force injury to a normal bone
what causes a pathological fracture
a normal amount of force on an abnormal bone
what are the 3 stages of healing bone
inflammatory phase
reparative phase
remodelling phase
what occurs in the inflammatory phase of bone healing
- haematoma formation and granulation tissue (fibrin creates framework, platelets and leukocytes release inflammatory cytokines and bone cells activated to start repair)
- granulation tissue formation
what is the time frame for the inflammatory phase of bone healing
first few days
what are the two subphases of the reparative phase of bone healing
soft callus formation
hard callus formation
at what time frame is the soft callus formation of bone healing
days-weeks
what occurs during the soft callus formation of bone healing
- cartilage formation to hold the fractured ends together
- periosteum repairs itself over the outside due to osteoporgenitor cells
at what time frame is the hard callus formation of bone healing
weeks-months
what occurs during the hard callus formation of bone healing
osteoid formation and ossification (firstly woven bone or endochondral ossification)
at what time frame is the remodelling phase of bone healing
months-years
what occurs during the remodelling phase of bone healing
bone remodelling of woven bone to lamellar bone along the lines of stress
which type of fracture may not need a soft callus to form in the healing process of bone
if the ends are closely apposed
what is the advantage and disadvantage of not having to form a soft callus during bone fracture healing
healing will be faster
but not as strong
what is the goal of fracture management
union of the broken bone to allow healing as fast as possible and without complications
how is ‘union’ of fractures performed
- reduction - minimize the gap
- fixation - minimize the strain or movement (cast)
- minimize any other factors that slow healing
what are the factors that slow fracture healing
- advanced age
- multiple medical comorbidities
- NSAIDs, corticosteroids
- smoking
- poor nutrition
- open fracture with poor blood supply
- multiple traumatic injuries
- local infetion
what are the complications of bone fracture
- non-union
- delayed union
- mal-union
- infection
- osteonecrosis/AVN
most upper limb fractures in adults repair completely in …
6-8 weeks
most lower limb fractures in adults repair completely in…
12-16 weeks
what is mal-union
healing of a bone in anunacceptable position
what are the potential problems of mal-union
- disability
- post-traumatic osteoarthritis
- cosmetic
what is the most common cause of osteomyelitis
staph aureus
what are the common sites of osteonecrosis after fracture
neck of femur (blood supply is via neck)
scaphoid (blood supply is via distal end)
why can osteonecrosis occur after bone fracture
because fractures can interrupt the blood supply and leave part of the bone ischaemic
what is osteoporosis
reduced mass of otherwise normal bone
how can menopause lead to osteoporosis
decreased serum oestrogen and increased IL-1, IL-6 and TNF levels leads to increased expression of RANK and RANKL –> increased osteoclast activity
how can aging lead to osteoporosis
- decreased replicative activity of osteoprogenitor cells
- decreased synthetic activity of osteoblasts
- decreased biological activity of matrix-bound growth factors
- reduced physical activity
what causes Paget’s disease
large, overactive osteoclasts and osteoblasts that produce more bone
what is the result of Paget’s disease
- thick soft cortex
- coarse trabeculae
- easily fractured
- can compress nerves
what are the 3 stages of Paget’s disease
osteolytic - osteoclasts
mixed - osteoclasts and osteoblasts
osteosclerotic - osteoblasts
what are the primary and secondary causes of hyperparathyroidism
primary - parathyroid hyperplasia or tumour
secondary - prolonged hypocalcaemia or hyperphosphataemia
what are the effects of hyperparathyroidism
- increased osteoclastic activity (RANK-L) with associated compensatory increase in osteoblastic activity
- -> dissecting osteitis
- -> osteitis fibros cystica
what histological features do you see in dissecting osteitis
osteoclasts in trabeculae
what do you see in osteitis fibrosa cystica
microfractures and granulation tissue
what are the presenting symptoms of bony mets
- pathological fractures
- hypercalcaemia
- bone marrow failure
- bone pain
how do the malignant cells influence bone
they produce RANK-L an PTHrP
they dont influence bone directly
which primary tumours can lead to bony metastases
breast lung thyroid kidney prostate bowel
what are the disorders of bone metabolism
hypocalcaemia hypercalcaemia hypophosphataemia hyperphosphataemia osteoporosis
what causes hyperphosphataemia
renal failure
what percentage of trabecular bone and cortical bone is remodelled per year
trabecular - 25%
cortical - 3%
which bones in particular are affected by bone remodelling
femoral neck and vertebral bodies (trabecular bone)
what things affect bone remodelling
ageing
physical factors (exercise, loaing)
hormones (oestrogen)
drugs
what causes the expression of RANKL by osteoblasts
active vitamin D (calcitriol) and PTH
what are the components of synovium
- macrophage like cells
- fibroblast like cells
- blood vessels and lymphatics
from what is synovial fluid derived
- a transudate of plasma from synovial capillaries
- hyaluronic acid produced by synovial cells
what is in the ECM of hyaline cartilage
- collagen type 2
- hyaluronic acid produced by chondrocytes
- proteoglycans - aggrecan
- glycosaminoglycans such as chondroitin sulphate
- water
what is in the Haversian canal
blood vessels, nerves, lymphatics and connective tissue
what structures link the lacunae of Haversian systems
canaliculi
what are the 2 main types of ossification
endochondral
intramembranous
what causes osteophytes in a joint with OA
calcification of periarticular cartilage and synovium
what causes subchondral cysts in a joint with OA
synovial fluid entering bone through microfractures
what causes subchondral sclerosis in a joint with OA
thickening of subchondral bone and trabeculae
what causes a loss of joint space in a joint with OA
fibrillation and sloughing of articular cartilage
what is the precursor protein of the amyloid deposition that occurs in rheumatoid arthritis
serum amyloid associated protein
what other diseases are associated with serum amyloid associated protein
TB
IBD
bronchiectasis
chronic osteomyelitis
which cytokines are involved in fracture healing and what do they do
TGF-b, PGDF, FGF - activate osteoprogenitor cells in the periosteum and activate OB and OC
what does the haematoma provide during fracture healing
- stops the bleeding
- provides a framework for fibroblasts and inflammatory cells
