Pathology - Monoarticular joint pain Flashcards
Why did we need bones
Mechanical support Transmission of forces generated by muscle Protection of vital organs Mineral homeostasis Production of blood cells
Trabecular vs cortical bone
T is more metabolically active and makes up 8-% of weight bearing bones, C makes up 80% of long bones exposed to large torsional forces
Methods of bone formation
Intramembranous ossification
Endochondral ossification
Intramembranous ossification
Bone develops directly from sheets of mesenchymal tissue
Begins in utero and continues until adolescence
Why isn’t skull and clavicles fully ossified at birth
Allows passes through birth canal
What are the last bones to ossify
Flat bones of the face
Endochondral ossification
Bone develops by replacing hyaline cartilage – cartilage acts as template
Takes much longer than intramembranous ossification
Which bones form via endochondral ossification
Bones at base of skull and long bones
Haversian systems
Origination of compact bone in parallel systems, run lengthwise down long bones
What do Haversian systems consist of
Lamellae, concentric rings of bone surrounding haversian
Haversian canal
Nerves
Blood vessels
Lymphatic system
How are Haversian systems connected
By Volkmann canals
What are Haversian systems created by
Osteoblasts – secrete matrix and become trapped in lacuna —> osteocytes
Osteon
Packet of bone on which the collagen fibres are aligned
Points of weakness in the bone
Cement lines – collagen poor lines between osteons
Lacunae
Osteocyte canaliculi
Where does vascular insufficiency occur from
Mechanical injury to blood vessels
Thromboembolism blocking vessels
External pressure collapsing vessels
Venous occlusion
Osteonecrosis
Ischaemic necrosis of bone and bone marrow
Causes of osteonecrosis
Trauma or fracture (most common)
Steroids
Siickle cell anaemia
‘The bends’
‘The bends’
Nitrogen released from fatty bone marrow forms a gas
Osteomyelitis
Infection of bone or bone marrow – often in children
Usually bacterial – hematogenous spread
Lytic focus (sequestrum) and surrounding sclerosis (involucrum) on x-ray is v. characteristic
Diagnosis is generally made by blood culture
What is osteomyelitis usually caused by
Staph. aureus
Clinical features of osteomyelitis
Bone pain
Systemic signs of infection e.g fever and leucocytosis
Signs of infl
Rubor - redness Calor - heat Tumor - swelling Dolor - pain Function Laesa - loss of function
Causes of infl
Infections
Tissue necrosis
Foreign bodies
Immune reactions (hypersensitivity)
Why are hypersensitivities difficult to cure
The stimuli for the inflammatory responses cannot always be eliminated
When does acute infl arises
In response to tissue necrosis (to clear necrotic debris) or infection (to eliminate pathogens)
Development of acute infl
Within mins – hrs and lasts for several hrs – few days
What does acute infl allow
Inflammatory cells, plasma proteins and fluid to exit blood vessels and to enter the interstitial space
What is acute infl characterised by
Presence of oedema and neutrophils in tissue
Which external factors can trigger infl
Microbes - virulence factors and PAMPs
Allergens
Irritants
Toxic compounds
Which internal factors can trigger infl
DAMPs – intracellular proteins released when a csm is injured or when a cell dies
Virulence factors
Molecules that help pathogens to colonise tissues and cause infection
PAMPs
Small molecules w/ conserved patterns that are shared amongst many diff pathogens e.g. bacterial wall components like peptidoglycan, lipopolysaccharide and lipoteichoic acid and fungal wall components. May also include viral DNA or RNA – intracellular pathogens.
What are PAMPs and DAMPs recognised by
Pattern Recognition Receptors (PRP) – cell surface receptors on leukocytes (macrophages, dendritic cells, mast cells) that activate them and begin infl process
What do PRP activate
Multiprotein complex (inflammasome) —->I nduces production of IL1 —-> recruits leucocytes —–> inducing infl
5 R’s of infl
Recognition (of the injurious agent) Recruitment (of leucocytes) Removal of the agent Regulation of the response Resolution of the damage
Mediators of infl
Hageman factors (Factor XII) Complement system Mast cells Arachnidonic acid metabolites Toll-like receptors
Factor XII
Inactive pro-inflammatory protein produced by the liver
Contact activation – activated by contact w/ pathogens or artificial surfaces
What does the complement system result in
Formation of C3 convertase —> activates leucocytes using anaphylatoxins, phagocytosis and forms membrane attack complex (causes water to flood in, destroying the pathogen)
Pathways in complement system
Classical
Alternative
Mannose-binding lectin pathway
Classical pathway of complement system
Antigen binds to IgG or IgM —-> Activates C1
Alternative pathway of complement system
Activated by microbial components directly
Mannose-binding lectin pathway
MBL binds to mannose in bacterial surface
Functions of complement system
Formation of anaphylatoxins, opsonisation
Cell lysis (MAC),
Immunoglobulin clearance
What are mast cells activated by
Complement proteins C3a + C5a
Tissue trauma
Crosslinking of cell surface IgE by antigen
Immediate response of mast cels
Via release of preformed histamine granules – causes vasodilation of arterioles and increased vascular permeability
Arichidonic acid metabolite
Steroids – reduce transcription of phospholipase A2
Aspirin and other NSAIDs act as COX inhibitors
Where are toll-like receptors present
Cells of the innate immune system including macrophages and dendritic cells and adaptive immune system
What does toll-like receptor activation up regulate
Nuclear Factor Kappa Beta—–> activates immune response genes producing cytokines which can amplify reaction
Rubor and Calor
Due to vasodilation, causing increased blood flow
Relaxation of arteriolar smooth muscle
What are rubor and calor mediated by
Histamine
Prostaglandins,
Bradykinin
Nitric oxide
What do pyrogens cause
Macrophages to release IL-1 and tumour necrosis factor —-> increases COX activity in hypothalamus
What is tumor caused by
Leakage of fluid from post-capillary venules into interstitial space (exudate)
What is tumour mediated by
Histamine (endothelial cell contraction) and tissue damage (endothelial cell disruption)
Exudate
Extravascular fluid w. high protein conc. and contains cellular debris
Transudate
Fluid w/ low protein content, little to no cellular material and low spp gravity – osmotic/hydrostatic imbalance
Oedema
Excess of fluid in the interstitial tissue or serous cavities, can be exudate or a transudate
Pus
Purulent exudate, rich in neutrophils contains debris of dead cells and in many cases microbes
Neutrophil arrival and function
Margination Rolling Adhesion Transmigration and chemotaxis Phagocytosis Destruction of phagocytosed material Resolution
Margination of neutrophils
Vasodilation slows blood-flow in post-capillary venules, cells marginate from centre of flow to periphery
Rolling of neutrophils
Selectins cause neutrophil to slow down and to roll along the endothelial surface
Adhesion of neutrophils
Uses integrins
Transmigration and chemotaxis of neutrophils
Activation of actin
Destruction of phagocytose material in neutrophils
HOCL generated by oxidative burst in phagolysosomes destroys phagocytosed microbes. O2 dependent killing is the most effective mechanism
Resolution of neutrophils
Neutrophils undergo apoptosis
When do macrophages peak
2 – 3 days after inflammation begins
What sequence does macrophages follow
The margination, rolling, adhesion and transmigration sequence
