Overview of Inflammation specially acute.

2. INFLAMMATION
1.Defination
2.Signs
3.Aetiology
4.Types or Classification
5.Mechanism or Pathogenesis:A.Vascular Phenomena or Response, B.Formation of Fluid
Exudate, C.Formation of Cellular Exudte(or Cellular Response),D.Role of Chemical Mediators:(a)cell or Tissue
Derieved ,(b)Plasma Derieved
6.Regulationof Inflammation
7.Systemic Effects of Inflammation
8.Consequences of Defective or Excessive Inflammation
9.Fate of Inflammation: Resolution, Healing, Suppuration, Ch.Inflammation
10.Factors of Variation of Inflammation:Organisms, Host,Type of Exudate,Cellular
Proliferation,Necrosis.
11.Diagnosis or Lab.Investigations of Acute Inflammation

3. INFLAMMATION(contd.)
Defination:Response of living tissues to injury or insult(Response of tissues to sublethal injury).But
Inflammation is best defined in teleologic terms.
Inflammation:is defined as immediate,localised,defensive response or reaction of living,vascularised
tissues to injury consisting of molecular & cellular responses acquired during evolution designed to
either eliminate or limit the spread of injurious agent & usually accompanied by repair or healing of
the damaged tissues.
SIGNS of inflammation:4-Cardinal signs by Celsus(1st.century AD):
1.RUBOR-Redness
2.TUMOR-Swelling
3.CALOR-Heat
4.DOLOR-Pain
To these 5th.sign functio laesa(loss of function)later added by Galen or Virchow
AETIOLOGY of Inflammation:CAUSATIVE Agents of inflammation are:
1.Non Infective: i).Physical or Mechanical like Trauma,Radiation
ii).Thermal:Heat orCold
iii).Chemical:Organic,Inorganic,Poisons,Acid,Alkalies
iv).Immunological:Ab.or Cell Mediated Immunological Injuries
2.INFECTIVE:Microbial Agents like Bacteria,Viruses,Fungi,Parasites,etc.
3.IATROGENIC: Sometimes Inert Foreign Materials like Talc,Sutures ,etc.

5. TYPES OR CLASSIFICATION OF INFIAMMATION
(A)According to TISSUE REACTION:1.Alterative,or 2.Exudative,or 3.Proliferative or Productive
(B)According to AFFECTION of Tissue Elements:1.Parenchymatous,or 2.Interstitial
(C).According to Predominant Exudate:Catarahhal,Serous,Fibrinous or Serofibrinous,Purulent,Haemorrhagic,
(D).According to MODE of ONSET: 1.ACUTE:i).Catarrhal
ii).Serous
iii).Fibrinous or Serofibrinous
iv).Suppurative or Purulent
v).Haemorrhagic
vi).Pseudomembranous
vii).Allergic
l 2.SUB-ACUTE:
3.CHRONIC:i).Ch.Nonspecific
ii).Ch.Specific
iii).Ch.Granulomatous
iv).Ch.Suppurative
v).Ch.Fibrinoid
vi).Ch.Diffuse
(E).AETIOLOGICAL Classification:1.Bacterial,2.Viral,3.Parasitic,4.Allergic or Immunological,etc
(F).According to TISSUES or ORGAN
SInvolved:like:appendicitisEnteritis,Colitis,GastritisOesophagitis,Hapatitis,Cholecystitis,Rhinitis,Tracheitis,Bronchitis,P
neumonitis.Pleuritis,Neuritis,Meningitis,Encephalitis,Conjunctivitis,Otitis,Synnovitis,Osteomyelitis,Myositis,Dermatitis
,etc.

6. Mechanisms OR Pathogenesis Of
Acute Inflammation
I.Vascular Phenomenon or Response
II.Formation of Fluid Exudate
III.Formation of Cellular Exudate or
Cellular Response
IV.Role Of Chemical Mediators:
Cell Derieved or Tissue Factors
Plasma Derieved

7. Mechanisms or Pathogenesis of Acute Inflammation
I.Vascular Phenomenon or Responses:Lewis
Tripple Response:Red Line,Flare,Wheal
1.Transient Vasoconstriction:By EC contraction,5
HT(serotonin),ThromboxaneA2,Leucotrines C4,D4,E4.
2.Persistant Vasodilatation & Opening of Dormant
Capillaries(Active Hyperaemia): By EC retraction,
EC injury:Direct
LeucocyteMediated
&
Histamine,NO,PGE2,D2,PGI2
3.Slowing of Blood Flow in Microcirculation(Stasis &
Stagnation)with Disturbance of Axial Flow leading to
Pavementation,Margination,Adhesion(IL17)&Emigration of
Leucocytes(by IL 1,17)

8. Mechanisms or Pathogenesis of ACUTE Inflammation(contd.)
II.FORMATION of FLUID EXUDATE:
1. Vascular Permeability:By Cell Derieved: i)Vasoactive Amines(Histamines,Bradykinines)
toProteins ii)PA F
iii)Prostaglandins(PG)
iv)Leucotrienes C4,D4,E4.
Plasma Derieved:
v)Clotting & FibrinolyticSystem
vi) Kinins
vii)Complements(C2a,C4a,C5a)
2. CapillaryB.P.
3. Breakdown of Large Molecular Tissue Proteins By Lysosomal Enzymes of
Leucocytes,NO,Reactive O2 Species.
4. FLUIDITY of Tissue GroundSubstance By E.C Injury:i)Direct
ii)Leucocyte Mediated like Lysosomal
- Enzymes

9. Mechanisms or Pathogenesis Of Acute Inflammation(Contd.)
III.Formation Of Cellular Exudate OR CellularResponse:
1.Emigration & Exudation ofLeucocyte
2.Phagocytosis
3.Cells of Inflammatory (Cellular) Exudates
1.Emigration & Exudation of Leucocytes:by Chem.Mediators
&Chemokines
Leucocytes Emigration esp.Poly-Neutro. in 2-9 minutes
&Monocytes in 24-48 hours followed by Macrophages
Occurs by:i)Margination & Pavementation
ii)Endothelial Surface Or EC by IL-1,Leucotrienes B4,HETE,PAF
iii)Widening of Inter Endothelial Gaps by Pseudopodia
iv)Passage through gaps by Active Amoeboid Motion by IL-17
v)Passage through Basement Membrane
Followed by Diapedesis of R.B.C.

11. 2.Phagocytosis:is Engulfment of solid particulate Materials by cells(CELL-EATING) by
Microphages(Neutro.) &Macrophages
Consists of:(a)Recognition & Attachmentby Mannose&Scavenger Receptors &Microbes further opsonised by
specific Proteins Opsonins,which are IgG opsonins,C3bopsonins,& Lectins
(b)Engulfment by Pseudopods
(c)Killing & Degradation: by
1)Intracellular Mechanisms:i)OXIDATIVE bactericidal Mechanisms:
By Oxygen Free Radicals:O,OH,H2O2,HOI,HOCl,HOBr,
By Lysosomal Granules of Poly.-Neutrophils & Macrophages
ii) Nonoxidativebactericidal Mechanisms by
Granules:protease,lipase,hydrolases,DNAases,cationic Proteins
NO
2)ExtraCellular Mechanisms:i)Immune Mechanism-Cytolysis-AbMediated
Cell-Mediated
ii)Granules:Degranulation of
Neutro.&Macrophages
cause proteolysis outside the cells
3.Cells of Inflammatory(CELLULAR)Exudate:are
ALL Leucocytes-with Monocytes & Macrophages in Tissues are Histiocytes
& 2-Additional Cells of inflammation are
1. Giant Cells
& 2.Epitheloid Cells
.

12. IV.CHEMICAL-MEDIATORS:Release & Roles:Source & CHEMICALS
Cell or Tissue (Derieved) Factors
Plasma Derieved Factors
 CELL or TISSUE DERIEVED(orTissue Factors):
SOURCE MEDIATORS MAIN-ACTIONS
a)Basophils,Mast Vasoactive Amines(5-HT, VASCULAR-
cells,Platelats : Histamines),NeuropeptideP
VIPetc
b)PLATELSTS:--------------5-HT(Serotonins) PERMEABILITY
c)Inflammatory Cells: 1.Arachidonic Acid Metabolites:
(A) Cyclo-oxygenase Pathway:
(COX): PGs(prostaglandins)-vasodilation
ThromboxaneA2
Resolvin
(B)Lipo-oxygenase Pathway:i.LT(lucotrienes)
2.PAF ii.Lipoxin
3.Cytokines:TNF & IL-1----------------------------------FEVER
4.Lysosomal –Enzymes(Acid&NeutralProtease) Tissue Damage
5.NO & Oxygen Metabolites ------------------------Tissue Damage
PLASMA-DERIEVED-FACTORS:
a)Clotting & Fibrinolytic System-------Fibrin Split Products VASCULAR-
&Fibrinopeptides PERMEABILITY
b)KININ SYSTEM---------------------------Kinin&Bradykinin
c)Complement System-------------------Anaphylatoxins(C3aC4aC5a)

13. Chemical-Mediators(Contd.):According to ACTIONS:
1.Vasoconstriction: ThromboxaneA2,LeukotrienesC4,D4,E4
2.Vasodilatation: Histamine,PGsD2,E2,PGI2 ,NO
3. Vascular Permeability: i)Histamine
ii)SubstanceP(Neuropeptide)
iii)5HT(Serotonin)
iv)Leukotrienes C4,D4,E4.
v)PAF
vi)Bradykinin
4.Chemotaxis,LeucocyteRecruitment&Activation,Adhesion:IL,TNF,Chemokines,
LeukotrieneB4,HETE,C3a,C5a.
5.Fever: Cytokines(IL-1,TNF),PG E2
6.Pain: PGs,Bradykinin,Neuropeptide,Neurokinin,SubstanceP
7.Tissue Damage: Lysosomal Enzymes of Leucocytes,
Reactive O2species,
NO

14. Regulation of Inflammation
Inflammation(Harmful Effects)is regulated in order to resolve by following mechanisms:
1.Acute Phase Reactants (APRs):Synthesised mainly by Liver&also by Macrophases&released into plasma
in order to
Protect the Normal Cells&clear away waste materials &are followings:
i).Certain Cellular Protection Factors: a1-antitrypsin,a1-antichymotrypsin,a2-antiplasmin,
-Plasminogen activator inhibitor.
ii).Coagulation Proteins:Fibrinogen,Plasminogen,von Willebrand factor,FactorVIII.
iii).Transport Proteins: Ceruloplasmin, Haptoglobin.
iv).Immune Proteins: CRP, Serum Amyloid A & P component
v).Stress Proteins: heat shock proteins-HSP, Ubiquitin
vi).Hepcidin :Regulates release of intracellular Iron Stores&increased level associated with
Fe.Deficiency Anemia with Ch.Inflammation
vii).Antioxidants : Ceruloplasmin
N.B.: (a) APRs with Fever,leucocytosis,&othersSystemic menifestations like Pulse,B.P., sweating,rigors,chills,
Anorexia,Somnolence&Malaise,is termed as “Acute Phase Response”
(b) Synthesis of APRs lead to Severe Disease like Ch. & repeated Inflammatory Response
2.CORTICOSTEROIDS:Glucocorticoids-endogenous act as Anti-inflammatory & raised in Inflammation.
3.Free Cytokine Receptors : in Serum corelates Disease Activity Directly.
4.Suppressor T cells :Prohibition of suppressor T cells is seen inhibiting T & B cells function.
5. Anti-inflammatory Chemical Mediators: Prostaglandins PG E2 & PGI2(Prostacyclins) have both
Pro- & Anti- Inflammatory Effects.

15. SYSTEMIC EFFECTS OF INFLAMMATION
1.FEVER
2.LEUCOCYTOSIS
3.ACUTE PHASE RESPONSE: is Acute Phase Reactants (APRs)with Systemic Menifestations like Fever,Leucocytosis,
PulseRate&B.P., Sweating,Rigors(Shivering),Chills,Anorexia,Somnolence & Anorexia.
4.Severe Bacterial Infection (SEPSIS): leading to Septic SHOCK,Cardiac Failure,DIC,,Hypoglucemia
5.Lymphangitis & LYMPHADENITIS:is important in Localised Inflammation.
Consequences Of DEFECTIVE & EXCESSIVE Inflammation
Defective Inflammation: results in increased susceptibility to Infection &Delayed Wound Healing.
Excessive Inflammation : causes Allergies,Autoimmune Diseases,Cancer,Atheroslerosis,IHD,some
Neurodegenerative Diseases like Alzheimer, Prolonged Inflammation & accompanying Fibrosis also cause
pathologic changes in Ch.Infectious,Metabolic & other Diseases.
FATE OF ACUTE INFLAMMATION:are
1.RESOLUTION
2.Healing :by: i)Regeneration
ii)Scarring or Fibrosis
3.SUPPURATION
4.Chronic Inflammation

17. Factors Determining Variation in Inflammatory Response
The Morphologic Variation in Inflammatory Responses depend Upon a Number of Factors&Processes :
1.MICROBES(organism) FACTORS:like i).Type of Infection&Injury,ii).Virulence,iii).Dose,
iv)Portal Of Entry,V)Product of Organism.
2. HOST FACTORS: i).General Health, ii). Immmune State,iii).Site & Type of Tissue-
-Involved ,iv)Systemic Diseases, iv).Congenital Neutrophil-
-Defects,vi).Leucopenia,vii).Local Factors
3.TYPE of EXUDATION:i).Serous(watery like serum),ii).Catarrhal(mucous like),
iii)Fibrinous, iv)Purulent(Suppurative),v)Haemorrhagic etc.
4.CELLULAR PROLIFERATION:a).No Significant cellular proliferation-e.g.,Acute Bacterial-
Infection except Typhoid Fever-intestinal lymphoid hyperplasia
b).Significant cellular proliferation:i).Viral Infection,
ii)RPGN(kidney),v).Ch.Inflammation –Macrophage&
Fibroblast Proliferatio
5. NECROSIS: e.g.,i).Gas Gangrene-Extensive Necrosis.
ii). inAcute Appendicitis-Necrosis due to vascular obstruction.
iii). in Ch.Inflammation-like T.B.-characteristic caseous necrosis.

18. Diagnosis or Lab.Investigation of ACUTE-Inflammation
1.TLC+DLC: Leucocytosis with Neutrophilia,but Leucopenia in Viral,esp.measles,
hepatitis,influenza
2.ACUTE PHASE PROTEINS : like CRP,ESR,Fibrinogen,a1antitrypsin,C3,4.
3.EXAM.of Inlammatory EXUDATE :
i) Sp.Gravity(>1.8),ii) Protein(>3gm./dL), iii)Neutrophils
4.Biopsy&MICROSCOPIC EXAM.OfTissues:M/Efeaturesincludei)Hyperaemia,
ii)Oedema,iii)Fibrins,iv).Neutrophils.
5.OTHER Diagnostic Tests: are
(a).Microbiologic Exam.-i)Morphology Study of smear by Staining
ii).Isolation of Microbes by Culture
iii).Biochemical,iv)Serological&Ag.detection
(b).Immunological Tests for serum Ab.&Ag.for diagnosis of Microbes,esp.,IgM&Auto-
-immune Dis.,SKIN-Tests –ve in Early orAcute process
(c).Molecular Methods.- P C R,Hybridization etc,.

19. Acute Inflammation

21. Acute Inflammation

22. Acute Inflammation

23. Acute Inflammation
(with pus)

24. Acute Inflammation
(Acute Bronchitis)

26. Acute Inflammation

27. Acute Inflammation