1.Recognition of Injury

graph TD
    x[Steps of Acute Injury]==> x1[Recognition of Injury];
    x1 ==> x1a[Activation of Neutrophils];
    x1a ==> x1ab[Recruitment of Neutrophils]
    x1ab ==> 2[Neutrophil resonse];
    2 ==> 3|after 2-3 days| 3[Macrophage action];
    3 ==>|either| 4[Healing] & 5[Inflamamtion];

Neutrophils and Edema

Recognition of Injury

1. Cell For microbes

   TLR on Macrophages

2. Intracellular Receptor of Cell damage
3. Fc receptors in Leukocytes
4. Complement Proteins

Mediators Of Acute Inflamamtion

Activate and Mediate Neutrophil and Vascular Permiability

1. Toll Like REceptors On MAcrophages(Microbial Injury)

TLR on Mediation

graph TD
    X[TLR recoganises a Fmet of BActeria] ==> X1[Activation of Nf-KB genes of leukocytes];

1. Aracdonic Acids(Cell wall Injury)

Cell Wall injury

graph TD
    X[cell wall injury] ==>|Phospholipases A| X1[Arachidonic Acid]
    X1 ==>|COX-1 or COX-2| X1a[Prostoglandins];
    X1a ==> X1ab[PGI2,PGE2.PGD2]
    X1 ==>|Lipoxygenase| X1b[Leutrokines];
    X1b ==> X1ba[LTA4,LTB4,LTC4,LTD4]

Prostoglandins	Leukotrines
PGD2.PE2 - Arteriole Vasodilation,increase capillary permeability	LTC4,LTD4,LTE4 - Constriction of Arteriole,Increased Capillary Permiability (Eg:Montelukast a LT Antagonists)
PGE2 - Fever and Pain
PGI2 - Arteriole Dilation , stops Platelet agrregation
TXA2 - Vascular Constriction ,Promote Platelet Aggregation	LTB4 - Neutrophil Chemotaxis

1. Complements(Circulationg Proteins)

   Activation of Complement

   1. Classical Pathway(IgG or IgM)
   2. Alternative Pathway (Microbial products)
   3. MBL(MBL binding to MAnnose of Microbes) > C3a,C5a - mast cell degranulation > C5a - Chemotaxis of Neutrophils > C3b - opsin > MAC - lyse bacteria by holes

2. Mast Cells (PArasitic or Allergic)

   Activation of Mast cells

   1. Tissue Trauma
   2. C3a and C5a
   3. IgE cross-linking > Activation of mast cells releases Histamine, Heparin and Activates Leukotriene secretion (LTB4,LTC4.LTD4,LTE4) > Arteriole Vasodilation and Capillaries Permeability6 by Heparin

3. Hageman Factor

   inactive Pro-inflammatory protein, activated by Collagen and subendothelium kinin system activation,coagulation and Fibrinolytic system activation

Pharmacology of Inflammation

1. NSAID's - irreversibly acetylation of COX-1,2 inhibit Prostaglandin and Leukotriene production
2. Steroid - Inhibit production of Phospholoipase,COX- 1 Enzymes
3. Leukotriene Inhibitors
4. Leukotriene Antagonist - Montelukast

Factors that Recruits Neutrophils

1. C5a(Complement)
2. LTB4(Mastcells,Arachidonic Acid pathway)
3. IL-8
4. Bacterial Products

Sign of Acute Inflammation

1. Redness(rubor) - Increased Arteriole dilation by Histamines,PGI2,PGD2,PGE2 ,bradykinin
2. Warm - increased blood supply (Vasodilation of Arteriole)
3. Swelling(tumor) - Capillary leakage by Histamine,LTC4,LTD4,LTE4, Endothelial damage
4. Pain(dolor) - Bradykinin.PGE2
5. Fever - IL-1,TNF(Hypothalamus - COX-1,2 activity increase PGE2)