Pathology - Monoarticular joint pain Flashcards by Jasmine Sappor

Why did we need bones

Mechanical support 
Transmission of forces generated by muscle 
Protection of vital organs 
Mineral homeostasis 
Production of blood cells

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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

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Methods of bone formation

Intramembranous ossification

Endochondral ossification

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Intramembranous ossification

Bone develops directly from sheets of mesenchymal tissue

Begins in utero and continues until adolescence

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Why isn’t skull and clavicles fully ossified at birth

Allows passes through birth canal

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What are the last bones to ossify

Flat bones of the face

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Endochondral ossification

Bone develops by replacing hyaline cartilage – cartilage acts as template
Takes much longer than intramembranous ossification

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Which bones form via endochondral ossification

Bones at base of skull and long bones

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Haversian systems

Origination of compact bone in parallel systems, run lengthwise down long bones

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What do Haversian systems consist of

Lamellae, concentric rings of bone surrounding haversian

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Haversian canal

Nerves
Blood vessels
Lymphatic system

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How are Haversian systems connected

By Volkmann canals

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What are Haversian systems created by

Osteoblasts – secrete matrix and become trapped in lacuna —> osteocytes

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Osteon

Packet of bone on which the collagen fibres are aligned

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Points of weakness in the bone

Cement lines – collagen poor lines between osteons
Lacunae
Osteocyte canaliculi

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Where does vascular insufficiency occur from

Mechanical injury to blood vessels
Thromboembolism blocking vessels
External pressure collapsing vessels
Venous occlusion

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Osteonecrosis

Ischaemic necrosis of bone and bone marrow

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Causes of osteonecrosis

Trauma or fracture (most common)
Steroids
Siickle cell anaemia
‘The bends’

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‘The bends’

Nitrogen released from fatty bone marrow forms a gas

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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

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What is osteomyelitis usually caused by

Staph. aureus

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Clinical features of osteomyelitis

Bone pain

Systemic signs of infection e.g fever and leucocytosis

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Signs of infl

Rubor - redness 
Calor - heat 
Tumor - swelling 
Dolor - pain 
Function Laesa - loss of function

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Causes of infl

Infections
Tissue necrosis
Foreign bodies
Immune reactions (hypersensitivity)

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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