Pathophysiology of bone Flashcards
Hyaline cartilage (e.g. joints)
Most prevalent
High proportion collagen fibres
Provides smooth surface for joints to glide
Elastic cartilage (e.g. external ear)
More elastic fibres than hyaline
Very flexible
Fibrocartilage (e.g. Invertebrate discs spine)
Parallel rows chondrocytes and collagen fibres
Resists forces of compression and tension.
What happens to cartilage by adulthood?
Replaced by bone with full ossification by adulthood.
2 ways of cartilage growth:
Appositional growth (e.g. epiphyseal plates (ends of the bone) and articular cartilage) Interstitial growth
Appositional growth (e.g. epiphyseal plates (ends of the bone) and articular cartilage)
Miotic division of pre-existing chondrocytes in perichondrium secrete new matrix next to existing cartilage tissue (growth from the outside).
Interstitial growth
Chondrocytes within cartilage divide and secret new matrix, expanding the cartilage (growth from within)
Bone function: (4)
Structural: Support, protect and movement
Mineral storage: Calcium and Phosphate
Lipid storage
Blood cell formation: Haematopoiesis in marrow cavities if long bones
Classification of bone (4)
Long bone (e.g. Humerus, Femur) Short Bone (e.g. Carpal and Tarsal bones) Flat Bone (e.g. Sternum, skull, ribs etc.) Irregular Bone (e.g. Hip bones, vertebrae etc.)z
Long bone (e.g. Humerus, Femur) (3)
Have long shaft and two distinct ends
Classification based on shape not size
Compact bone on exterior with spongy inner bone marrow
Short Bone (e.g. Carpal and Tarsal bones) (2)
Roughly cube-like
Thin compact bone layer surrounding spongy bone mass.
Flat Bone (e.g. Sternum, skull, ribs etc.) (2)
Thin, flattened and usually curved
Parallel layer compact bone with spongy layer between
Irregular Bone (e.g. Hip bones, vertebrae etc.) (3)
Don’t fit into the previous categories
Complicated shapes
Consist of spongy bone with a thin layer of compact
Bone composition:
70% mineral: Ca2+ & PO4- as hydroxyapatite, [Ca5(PO4)3(OH)]
22% protein (95% Type I collagen + 5% proteoglycans)
8% water
Crystals of Ca2+ are deposited in and around the collagen fibres of the extracellular matrix - exceptionally hard and resist compression
Two major types of bone:
Compact Bone Cancellous Bone (spongy)
Where is Compact Bone found?
Found on the outside of the bone
Dense bone tissue on outside of bone.
Enclosed and covered by periosteum (thick fibrous membrane).
Cancellous Bone (spongy) points (4)
Interior of a bone, consisting of fibres and lamellae (reticular structure).
Metabolic Ca2+ regulation
Storage
Stem cells
Function of Cancellous bone (spongy) (3)
Metabolic Ca2+ regulation
Storage
Stem cells (for Haematopoiesis)
Where is Cancellous bone (spongy) found?
Interior of a bone
Cancellous bone (spongy) structure
Consisting of fibres and lamellae (reticular structure).
Compact bone points (3)
Dense bone tissue found on the outside of the bone
Mechanical & protective
Enclosed and covered by periosteum (thick fibrous membrane).
Compact bone structure
Enclosed and covered by periosteum (thick fibrous membrane). The structural unit called osteon
Function of compact bone
Mechanical & protective
4 parts of Long bone
Bone shaft (Diaphysis)
Epiphysis (Head of long bone)
Metaphyses, between diaphysis and epiphysis
Medullary (Marrow) Cavity
Periosteum
On the outside of the bone
Thick fibrous membrane and attachment for muscles and tendons
Blood vessels, nerves, and lymphatic vessels
Endosteum
Thin membrane of connective tissue lining inner surface of (all) bony tissue
Diaphysis (Bone Shaft)
Collar of compact bone surrounds a central medullary or marrow cavity
Long tubular structure
Medullary (Marrow) Cavity
Interior consists largely of spongy bone
Cavity is filled with yellow bone marrow (adipose)
Epiphyses (End of Bone)
Filled with spongy bone
Contains red marrow (myeloid tissue) - Haematopoiesis
Metaphysis
Narrow area containing epiphyseal (growth) plate.
Layer of hyaline cartilage in a growing bone.
Replaced by osseous tissue in fully formed adult bone and epiphyseal plate becomes epiphyseal line.
What happens to epiphyseal plate in adulthood?
Becomes epiphyseal line as the metaphysis is replaced by osseous tissue
What are the epiphysial plates?
Growth plates
What is the osteon?
Basic structural unit of mature compact bone
Osteocytes arranged in concentric lamellae around central perforating canal
What is the osteon made up of?
Concentric rings of calcified matrix = lamella
Centre of each osteon = central canal
What runs through the central canal of the osteon?
Blood vessels, nerves, and lymphatic vessels through perforating (Volkmann’s) canal, to periosteum and endosteum.
What is the lamella of the osteon?
Weight-bearing, column-like matrix tubes composed mainly of collagen
3 Lamellae Types
Concentric Lamellae
Circumferential Lamellae
Interstitial Lamellae
Circumferential Lamellae
Wrapped around the long bone (tree rings) and bind inner osteons together
Interstitial Lamellae
Between osteons made up of concentric lamella. Remnants of old osteons partially digested and remodelled by osteoclast/osteoblast activity
Canaliculi and Lacunae
Osteocytes occupy small cavities or lacunae at the junctions of lamellae
Fine canals called canaliculi connect lacunae to each other and to the central canal
Canaliculi tie all the osteocytes in an osteon together
Where is spongey bone?
Most of tissue in short, flat, and irregularly shaped bones, and epiphysis of long bones
Spongey bone features
Does not have osteons
Honeycomb of matrix spikes = trabeculae
Nourished by blood vessels of periosteum penetrating spongy bone and blood that circulates in the marrow cavities.
Trabeculae features (4)
Contain irregularly arranged lamallae and osteocytes interconnected by canaliculi
Form along lines of stress to provide strength
Spaces provide balance to the dense and heavy compact bone.
Often contains red bone marrow -haematopoiesis.
What are trabeculae?
Honeycomb of matrix spikes in the bone filled with marrow
What is bone marrow?
Space between trabeculae is filled with marrow which is highly vascular
Red bone marrow features?
Supplies nutrients to osteocytes in trabeculae
Forms red and white blood cells (haematopoiesis)
Where is red bone marrow found in adults?
Adults: In diploë of flat bones, and head of femur and humerus
Where is red bone marrow found in infants?
Infants: Medullary cavity and all areas of spongy bone
Yellow bone marrow
Stores fat
4 types of bone cells?
Osteoprogenitor
Osteoblasts
Osteocytes
Osteoclasts
Osteoprogenitor Function (2)
Develop into osteoblasts
Low biochemical activity
Osteoprogenitor Location
Deep layers of the periosteum
Osteoblasts Function (4)
Bone formation (osteogenesis) Secrete type I collagen Regulate mineralisation Differentiate into osteocytes
Osteoblasts Location
Growing portions of bone, including periosteum and endosteum
Osteocytes Function (5)
From osteoblasts Terminally differentiated Maintain bone matrix Occupies lacunae Form gap junctions with neighbouring cells
Osteocytes Location
Entrapped in matrix
Osteoclasts Function (4)
Bone resorption
Secrete acids and digestive enzymes
Dissolve matrix and release minerals (Osteolysis)
Osteoclasts Location
Bone surfaces and at sites of old, injured, or unneeded bone
What is an osteocyte?
Mature bone cell that maintains the bone matrix
What is an osteoblast?
Immature bone cell that secretes organic components of matrix
What is an osteoprogenitor cell?
Mesenchymal stem cell whose divisions produce osteoblasts
What is an osteoclast?
Multinucleate cell that secretes acids and enzymes to dissolve bone matrix (Derived from stem cells producing macrophages)
What is Osteogenesis and ossification?
Process of bone formation
When do bones stop growing?
In adolescence or early adulthood
Which bones can continue to grow throughout life?
Some facial bones such as the nose or lower jaw
Embryonic process leads to the formation of the bony skeleton? (4)
- Human embryo at 6 weeks made from fibrous membranes and hyaline cartilage
- Bone begins to develop and replace most of fibrous or cartilage structures
- Process termed intra-membranous ossification to create membrane bone
- Bone formation by replacing hyaline cartilage structures called endochondral ossification to create an endochondral bone
How does bone grow during youth?
Occurs entirely by interstitial growth of the epiphyseal plates
Bones grow in thickness by appositional growth
What is Intramembranous Ossification?
Results in the formation of most bones of skull and the clavicles (flat bones)
Fibrous connective tissue membranes (from mesenchymal cells) acts as initial supporting structures for ossification, from 8th week of development
Process of Intramembranous Ossification (8)
- Centrally located osteoprogenitor cells cluster and differentiate into osteoblasts, forming ossification centre and bone matrix in fibrous membrane
- Osteoblasts begin to secrete osteoid, mineralised within a few days
- Trapped osteoblasts become osteocytes
- Formation of woven bone and periosteum, with network enclosing blood vessels
- Vascularised mesenchyme forms on external face of bone to become periosteum
- Bone collar of compact bone forms
- Trabeculae in periosteum thicken, forming a collar
- Spongy bone persists internally and its vascular tissue becomes red
5 stages of mechanism of remodelling
Initiation of BMU Activation Resorption Reversal Formation
What is endochondral ossification?
The process where cartilage is replaces by bone. Spongy bone is formed.
Method for the formation of most bones, especially long bone.
Where does endochondral ossification occur?
Hyaline cartilage shaft
Endochondral ossification process (7)
- The perichondrium becomes infiltrated by blood vessels. This causes an increase in nutrition, which enables the osteoprogenitor cells to differentiate into osteoblasts.
- The osteoblasts then begin to secrete the osteoid against the hyaline cartilage.
- The cartilage at the centre of the diaphysis then begins the calcify. The calcification process blocks the nutrients causing the chondrocytes in the area to die. This causes the matrix to diaphysis and cavities start to develop in that area.
- The bone is then stabilised by growth around the collar. Growth occurs at the epiphysis – end of the long bones.
- Due to this the internal cavities are infiltrated by the periosteal bud, and the spongy bone being to form.
- The periosteal bud contains arteries, veins, lymphatics and nerve fibres to support osteoblasts and osteoclasts.
- Then we end up with ossification at the epiphyseal plates. This means hyaline cartilage remains only at the epiphyseal plates.
Endochondral ossification process short (3)
- Formation of bone collar around hyaline cartilage model.
- Cavitaion of hyaline cartilage within the cartilage model (deteriorating cartilage matrix)
- Invasion of internal cavities by the periosteal bud and spongy bone formation.
How often is the epiphysis and shaft replaced?
Epiphysis replaced every 5-6 months while the shaft is replaced more slowly
Long bone is accompanied by almost continuous remodelling in order to…
Maintain proper proportions
Why does remodelling occur at different rates within different areas of the same bone?
Remodelling can be dependent on where the stress and tension is within that bone.
What is bone remodelling?
It is the cycle of bone resorption and bone formation driven by sequential evolution of events over 3-6 month period.
Bone removal then replacement at each site. (Resorption followed by formation at the same rate).
Bone remodelling function
Allows bone to respond to physical loads (stresses) and repair micro damage.
Participates in plasma calcium control
Random remodelling turns over bone to prevent accumulation of brittle material
Bone resorbing cells?
Osteoclasts
Bone forming cells?
Osteocytes and osteoblasts
What is BMU?
Basic multicellular units formed by bone resorbing and bone forming cells. The BMU function at discrete sites in highly coordinated sequence of cellular activity.
How do bone become weak?
More breakdown than building. The osteoblasts (forming) and osteoclasts (resorbing) not working at them same rate.
What can increase bone formation?
Exercise can cause osteocytes to build bone. This is due to the increased stress and muscle tension.
Initiation of BMU
Response of osteocytes in response to loading or microdamage
Signalled (or at least influenced) by local hormones, cytokines and growth factors
Activation
Quiescent bone surface becomes populated with osteoclast precursors
Osteoblasts and osteoclasts are continuously recruited, at “cutting” edge
Resorption
Osteoclasts mature and remove a finite quantum of mineralised bone
Causes release of IGF, FGF, etc., which recruits osteoblasts
Reversal
Osteoclast activity and numbers decline and are replaced by osteoprogenitor cells
Formation
Osteoprogenitor cells become osteoblasts, secrete type I collagen (osteoid) from basal
surfaces onto resorbed surface, which undergoes mineralisation
Bone resorption involves
Resorption bays: grooves formed by osteoclasts when breaking matrix
Involves osteoclast secretion of lysosomal enzymes that digest organic matrix and acids that convert calcium salts into soluble forms
Dissolved matrix is transcytoses across the osteoclast cell where it is secreted into the interstitial fluid and then into the blood
Bone resorption process (5)
A)
-Osteoclast adheres to bone through integrin αvβ3, creating sealing zone,
-Secretes HCl and proteases (cathepsin K, MMP-9 & -13)
-Carbonic anhydrase converts CO2 to H+ & HCO3−
B)
-Integrin engagement results in signals that target
acidifying vesicles (= proton pump complex).
-Fusion of vesicles with the plasma membrane generates
polarised cell capable of secreting acid and proteases
required for bone resorption.
How is HCI in bone resorption generated?
HCl generated by combined actions of a vacuolar H+
ATPase, coupled Cl- channel and basolateral chloride-
bicarbonate exchanger.
Septic Arthritis
Infections/bacterial
Secondary infection
Invasion of the joints resulting in inflammation
Post traumatic arthritis
Secondary to physical injury
The trauma causes inflammation to joint. Inflammation may go or become chronic.
