These drugs inhibit

so less collagen is secreted by

Matrix metalloproteinases are also

- degrade extracellular matrix components e.g. collagen, generated by fibroblasts

Diabetes results in

wound healing, particularly in

limbs, which can result in ulcers, gangrene, and can lead to amputations. This is due to increased blood glucose - narrowing of arteries due to impaired

signalling. This limits flow so also limits the recruitment and activation of

so infection can persist.

.Clean, uninfected wound, approximated by surgical sutures. Wounding causes rapid activation of

pathways, which results in clots forming. The clots serve to stop bleeding, scaffold migrating cells and prevent infiltration by

agents. In the inflammatory phase,

infiltration clears debris and are then replaced by

when the neutrophils are phagocytosed. Epithelial cells migrate and proliferate and meet at the midline, depositing

molecules. Granulation forms at 3-5 days: fibroblast mediated collagen deposition and

are evident. Also see interspaced macrophages.

At 2 weeks, there is continued collagen depositon: oedema and

infiltration decreases. Remodelling begins using matrix

At 4 weeks: devoid of leukocytes and covered by essentially normal epidermis. Scar blanches and

strength increases over time. Function of tissue is restored.

Extensive tissue loss. Fibrin clot is

with increased exudate and necrotic debris. Paired with more intense

and greater chance of secondary inflammatory mediated injury. Much larger amounts of

tissue are formed: matrix protein deposit mediated by fibroblasts and increased angiogenesis.

Formation of fibrous scar takes about 2 weeks: provisional matrix contains fibrin, plasma protein and the

collagen is replaced by a matrix composed of

collagen. At 4 weeks: granulation tissue remodelled to a pale scar composed of acellular and

connective tissue devoid of inflammatory infiltration. Covered by intact epidermis.

Identical to classical pathway, apart from initiation is done by

and ficolins binds to bacterial surfaces with mannose-containing polysaccharides. MBL and ficolins form complexes with

proteases and recognise the mannose-containing carbohydrates. Associated with the MBL molecule are 2 proteases:

When MBL binds, these are activated and the formation of MBL/MASP-1/MASP-2 attracts other MASPs and leads to the cleavage of

and C2. C4a is released into the microenvironment and C4b binds to the membrane.

binds with C4b to form the

complex - a C3 convertase. C3b binds to form a

complex which is a

convertase. The generation of this complex is the end of the lectin pathway)

C-reactive protein can bind to bacterial and

cell envelopes and can opsonise. It works by the

complement pathway and is a non-specific marker form infection and inflammation. Normal CRP is

mg/L. It is now used to decide whether to prescribe antibiotics in pneumonia and LRTIs;

no antibiotics if CRP is

mg/L; delayed prescription if CRP is 20 to

mg/L; antibiotics if CRP is

mg/L

Innate immunity is immediate and is within 0-

hours. It is the recognition of invaders by pre-formed

and broadly specific effectors.

Early induced innate immunity is immediate and occurs between 4 and

hours. This is the recognition of a pathogen associated with a molecular pattern. Get

and recruitment of

cells.

Adaptive immunity is after

hours. It occurs when the innate immune system fails to eliminate the infection.