ACUTE INFLAMMATION IIACUTE INFLAMMATION IIClinicopathological FeaturesClinicopathological Features

Dr N Williams

Department of Pathology

nadia.williams@uwimona.edu.jm

Lecture OutlineLecture Outline Chemical mediators of acute inflammation

Variations in the acute inflammatory response

The different macroscopic appearances of acute inflammation in tissues

Specific inflammatory lesions

Mechanisms and causes of an abnormal acute inflammatory reaction

CHEMICAL MEDIATORSCHEMICAL MEDIATORS

Exogenous Source Bacterial products

Endogenous Source Cells Plasma Damaged tissues

CHEMICAL MEDIATORSCHEMICAL MEDIATORS

Endogenous chemicals

Components of complement

Arachidonic acid metabolites

Cytokines

CHEMICAL MEDIATORSCHEMICAL MEDIATORS

Vasoactive amines (Active) Histamine* Serotonin

Plasma proteases (Inactive) Kinin (bradykinin) Complement (C3a, C5a)* Plasmin

CHEMICAL MEDIATORSCHEMICAL MEDIATORS

Arachidonic acid Prostaglandins Leukotrienes

Platelet activating factor

Cytokines and chemokines

Nitric oxide

Lysosomal constituents

Oxygen free radicals(reactive oxygen species)

Neuropeptides (Substance P)

Functions of ComplementFunctions of Complement

Inflammation C3a, C5a , >C4a

Vasodilatation (anaphylatoxins) Chemotaxis

Phagocytosis Opsonin

Cell lysis Membrane attack complex

CYTOKINESCYTOKINES

[Polypeptide products of activated cells]

Source Monocytes

Lymphocytes

Non-lymphoid cells

CYTOKINESCYTOKINES

Tumour necrosis factor (TNF)

Interleukin 1 (IL1)

Interferon (IFN)

Chemokines

TNF and IL-1TNF and IL-1

Expression of adhesion molecules on endothelial cells

Induce the secretion of other cytokines and chemical mediators

Induce enzymes for matrix remodelling

Fibroblast activation

Systemic inflammatory response (IL-1>TNF)

Mediators of InflammationMediators of Inflammation Vasodilation

Prostaglandins Nitric oxide

Permeability Vasoactive amines C3a, C5a Bradykinin LT-C4, D4 E4

PAF Substance P

Mediators of InflammationMediators of Inflammation Chemotaxis, leucocyte activation

C5a LTB4 Chemokines Bacterial products

Fever IL-1, IL-6, TNF Prostaglandins

Mediators of InflammationMediators of Inflammation Pain

Prostaglandins Bradykinin

Tissue Damage Lysosomal enzymes Oxygen metabolites Nitric oxide

Systemic Inflammatory Response

Fever Myalgia Arthralgia Anorexia Somnolence Malaise Rigors and chills

SYSTEMIC INFLAMMATORY RESPONSE SYNDROMEHypothalamic – Pituitary – Adrenal Fever

Pyrogens stimulate prostaglandins in vascular and perivascular cells of hypothalamus – reset “thermostat”

Acute Phase Proteins (ESR) C-reactive protein; fibrinogen; serum amyloid A (SSA)

Leucocytosis (neutrophilia with left shift) pulse and blood pressure

Peripheral vasodilatation (glucocorticoids) Shock

The reaction and the outcome of inflammation are dependent on :

The nature of the stimulus

The defense capability of the host/ tissue

Variation in ResponseVariation in Response

Response depends on Factors related to the type of injurious agent

Herpes simplex virus (HSV) blisters Staph aureus abscesses

Factors related to the host and tissues HSV in brain no blisters

Variation in Cellular ComponentVariation in Cellular Component

Typhoid - monocytes Parasites - eosinophils Allergies – eosinophils

Polymorphs in chronic inflammation Chronic Helicobacter pylori gastritis Chronic ulcerative colitis Chronic osteomyelitis Fungal granulomas

Variation in ExudateVariation in Exudate

Serous - Plasma - serosa Fibrinous - Fibrin - serosa Phlegmonous - mucous - mucosa

(Catarrhal) Suppurative - pus - bacteria

(Purulent) Haemorrhagic - RBC - vascular tissue/necrosis

Variation in InflammationVariation in Inflammation Gangrenous

inflammation + necrosis + putrefaction

(putrefying organisms = Clostridium species in gut and soil)

Pseudomembranous

inflammation + necrosis + membrane Diphtheria Clostridium difficile

Specific Inflammatory LesionsSpecific Inflammatory Lesions Pus

Exudate rich in proteins, polymorphs and cellular debris

AbscessLocalized collection of pus in tissue, organ or confines space

Boil (furuncle, carbuncle)

EmpyemaCollection of pus in a cavity

Specific Inflammatory LesionsSpecific Inflammatory Lesions Ulcer

Circumscribed loss of tissue from the surface of an organ with surrounding inflammation

Cellulitis

Diffuse area of oedema Haemolytic streptococcus - hyaluronidase

(spreading factor)

RESOLUTION

Complete restoration of tissues to normal

following acute inflammation.

ORGANIZATIONORGANIZATION

Replacement of the acute inflammatory infiltrate by fibrosis/ scar tissues formation

Sequale of Inflammation

Dependent on :

Amount of tissue damaged

Elimination of the causative agent

DEFECTS IN LEUCOCYTE FUNCTIONDEFECTS IN LEUCOCYTE FUNCTION

Decreased numbers

Defects in leukocyte adhesion

Defects in chemotaxis

Defects in phagocytosis

Defects in microbicidal activity

DEFECTS IN LEUKOCYTE FUNCTIONDEFECTS IN LEUKOCYTE FUNCTION

Congenital Chronic granulomatous disease

Bone marrow failure Drugs Viruses

Diabetes

Cirrhosis

Malnutrition

Sarcoidosis

SummarySummary Acute inflammatory Rxn- mediated by a variety of

exogenous and endogenous chemicals Reaction relates to aetiology and the tissue’s

ability to respond the macroscopic appearances of the exudate – vary

in different tissues Defined specific inflammatory lesions Aim – Resolution Abnormal reaction may be a congenital defect or

acquired in a variety of diseases.