Inflammation-1 Inflammation-1

Dr. Hassan Abdirahman .

Lecturer in Pathology Gollis University , faculty of medicine
Shashi-Sep-12 Shashi-Mar 2000

Inflammation-2

Inflame to set fire. Inflammation is dynamic response of

Inflammation

vascularised tissue to injury. Is a protective response. Response intended to eliminate : The initial cause of cell injury Necrotic cells and Tissues resulting from the original insult Serves to bring defense & healing mechanisms to the site of injury. Shashi-Mar 2000

Inflammation-3

Inflammation accomplishes its protective

mission by: Diluting, Destroying, or Neutralizing harmful agents (e.g., microbes or toxins).

Inflammatory responses are the basis of :-

life-threatening anaphylactic reactions to: Insect bites or Drugs, Rheumatoid arthritis and Atherosclerosis. Shashi-Mar 2000

Inflammation-4

Players in inflammatory response include: Circulating cells

plasma proteins vascular wall cells cells and extracellular matrix of the

surrounding connective tissue An initial inflammatory stimulus triggers the release of chemical mediators from plasma or connective tissue cells.
Shashi-Mar 2000

Inflammation-5

Lewis Triple Response:

Flush: capillary dilatation.
Flare: arteriolar dilatation.

Weal: exudation, edema.

Shashi-Mar 2000

Inflammation-6

Red, Warm & Swollen (Flare, Flush & Weal Lewis)

Triple response

Shashi-Mar 2000

Inflammation-7

The inflammatory response is terminated when: The injurious stimulus is removed

The inflammatory mediators have been:-

Dissipated, Catabolized, or Inhibited Inflammation is divided into two basic patterns: Acute inflammation Chronic inflammation Shashi-Mar 2000

Inflammation-8

Acute Inflammation
It is characterized by : Short duration

lasting from a few minutes up to a few days Fluid and plasma protein exudation Predominantly neutrophilic leukocyte accumulation.

Shashi-Mar 2000

Inflammation-9

This process has two major components : Vascular changes

Vasodilation Increased vascular permeability Cellular events: Cellular recruitment and activation The cascade of events in acute inflammation is integrated by local release of chemical mediators.

Shashi-Mar 2000

Inflammation-10

Inflammation - Mechanism
1. Vaso dilatation 2. Exudation Edema 3. Emigration of cells 4. Chemotaxis
Shashi-Mar 2000

Inflammation-11

Cardinal Signs of Inflammation

Rubor : Redness

Hyperaemia. Dolor : Pain Nerve, Chemical med. Tumor: Swelling Exudation Calor : Warm Hyperaemia. Loss of Function:
Shashi-Mar 2000

Inflammation-12

The vascular changes and cell recruitment

account for: Heat (calor), Redness (rubor),

Swelling (tumor).

Shashi-Mar 2000

Inflammation-13

Vascular Changes
Changes in Vascular Caliber and Flow

Begin relatively quickly after injury

Transient

(seconds) vasoconstriction, then Arteriolar vasodilation .Erythema Warmth The microvasculature becomes more permeable then Protein-rich fluid into the extravascular tissues.
Shashi-Mar 2000

Inflammation-14

Then red blood cells to become effectively

more concentrated: Stasis-blood flow is decrease b/c of high viscosity Margination-leukocytes ( neutrophils) begin to settle out of the flowing blood and accumulate along the vascular endothelial surface.

Shashi-Mar 2000

Inflammation-15

Increased Vascular Permeability

Increased intravascular hydrostatic pressure Transudate-fluid from capillaries. Contains little protein.

Exudate-protein-rich fluid into the interstitium from the capillaries. Edema is resulted b/c of :

Outflow of water and ions into the extravascular tissues: Intravascular osmotic pressure is reduced Osmotic pressure of the interstitial fluid increased is increased.
Shashi-Mar 2000

Inflammation-16

Cellular Events
The sequence of events in the extravasation of

leukocytes from the vascular lumen to the extravascular space is divided into: Margination and rolling, Adhesion and transmigration Migration in interstitial tissues toward a chemotactic stimulus
Shashi-Mar 2000

Inflammation-17

Phagocytosis and Degranulation Phagocytosis consists of three distinct but interrelated steps:

Recognition and attachment of the particle to the ingesting leukocyte Engulfment, with subsequent formation of a phagocytic vacuole. Killing and degradation of the ingested material

Shashi-Mar 2000

Inflammation-18

Chemical Mediators of Inflammation

Mediators may be

circulating in the plasma (typically synthesized by the liver), or produced locally by cells at the site of inflammation ( histamine )

Most mediators induce their effects by

binding to specific receptors on target cells. Mediator function is generally tightly regulated.
Shashi-Mar 2000

Inflammation-19

Outcomes of Acute Inflammation

Consequences of acute inflammation are

modified by: The nature and intensity of the injury The site and tissue affected, and The ability of the host to mount a response.
Acute inflammation generally has one of

three outcomes:1-Resolution. 2-Scarring or fibrosis 3-Progression to chronic inflammation

Shashi-Mar 2000

Inflammation-20

CHRONIC INFLAMMATION

It can be considered to be inflammation of

prolonged duration (weeks to months to years). Steps in chronic inflammation. Active inflammation, Tissue injury, and Healing proceed simultaneously. In contrast to acute inflammation, which is distinguished by:vascular changes, edema and largely neutrophilic infiltrate,

Shashi-Mar 2000

Inflammation-21

Chronic inflammation is characterized by the :

Infiltration with mononuclear cells: Macrophages Lymphocytes Plasma cells

Tissue destruction, largely directed by the inflammatory cells Repair, involving new vessel proliferation (angiogenesis) and fibrosis.

Shashi-Mar 2000

Inflammation-22

Cause of Chronic inflammation

Viral infections

Persistent microbial infections

Prolonged exposure to potentially toxic

agents Autoimmune diseases

Shashi-Mar 2000

Inflammation-23

Gastric Ulcer:

Shashi-Mar 2000

Inflammation-24

Laryngitis:

Shashi-Mar 2000

Inflammation-25

Mouth Aphthus ulcer

Shashi-Mar 2000

Inflammation-26

Acute Enteritis:

Shashi-Mar 2000

Inflammation-27

Pneumonia

Shashi-Mar 2000

Inflammation-28

Mechanism of Inflammation:

Shashi-Mar 2000

Inflammation-29

Shashi-Mar 2000

Inflammation-30

Neutrophil Margination

Shashi-Mar 2000

Inflammation-31

Vascular changes

Shashi-Mar 2000

Inflammation-32

Pneumonia - Exudation

Shashi-Mar 2000

Inflammation-33

Chemical substances synthesised or released which

Chemical Mediators:

mediate the changes in inflammation. Histamine by mast cells - vasodilatation. Prostaglandins Cause pain & fever. Bradykinin - Causes pain.

Shashi-Mar 2000

Inflammation-34

Acute: Exudative Inflammation: excess fluid. TB lung. Suppuration/Purulent Bacterial - neutrophils Fibrinous pneumonia fibrin Serous excess clear fluid Heart, lung Haemorrhagic b.v.damage - anthrax. Chronic inflammation: with healing. Grannulomatous clusters of epitheloid* cells eg. TB, Fungus, Foreign body.

Morphologic types

Shashi-Mar 2000

Inflammation-35

Never let the competition define you. Instead, you have to define yourself based on a point of view you care deeply about.
Tom Chappel

Shashi-Mar 2000

Inflammation-36

Inflammation Outcome
Fibrosis/Scar Resolution Injury Acute Inflammation Abscess Chronic Inflammation Fungus Virus Cancers T.B. etc.

Ulcer
Fistula Sinus

Shashi-Mar 2000

Inflammation-37

Chronic Inflammation:

Shashi-Mar 2000

Inflammation-38

Edema

Shashi-Mar 2000

Inflammation-39

Serous Inflammation - Effusion

Shashi-Mar 2000

Inflammation-40

Serous Inflammation - Effusion

Shashi-Mar 2000

Inflammation-41

Fibrinous Inflammation

Shashi-Mar 2000

Inflammation-42

Purulent - Inflammation - PUS

Shashi-Mar 2000

Inflammation-43

Purulent Inflammation PUS

Shashi-Mar 2000

Inflammation-44

Purulent Inflammation PUS

Shashi-Mar 2000

Inflammation-45

Chronic Inflammation:
Lung Abscess

Shashi-Mar 2000

Inflammation-46

Granuloma:

Shashi-Mar 2000

Inflammation-47

Acute Vs Chronic
Flush, Flare & Weal Little signs -

Fibrosis, Acute inflammatory Chronic cells - Neutrophils inflammatory cells Vascular damage Lymphocytes More exudation Neo-vascularisation Little or no fibrosis No/less exudation Prominent fibrosis
Shashi-Mar 2000

Inflammation-48

"People who soar, are those who refuse to sit back and wish things would change."
Charles R. Swindoll Author and Pastor

Shashi-Mar 2000

Inflammation-49

The 5 Cardinal Signs of

Heat

Redness Swelling

Pain Loss Of Func.

Shashi-Mar 2000

Inflammation-50 Inflammation-50

Dr. Venkatesh M. Shashidhar.

Associate Professor of Pathology Fiji School of Medicine
Shashi-Sep-12 Shashi-Mar 2000

Inflammation-51

Stages of Healing:
Hemorrhage
Inflammation Granulation tissue (soft callus) Scar Fibrosis (hard callus) Remodeling & Wound strength

Shashi-Mar 2000

Inflammation-52

Repair
Regeneration of injured tissue by parenchymal cells of

the same type Replacement by connective tissue In other words

Regeneration Scar

Shashi-Mar 2000

Inflammation-53

Proliferative Potential
Labile cells - continuously dividing Epidermis, mucosal epithelium, GI tract epithelium etc Stable cells - low level of replication Hepatocytes, renal tubular epithelium, pancreatic acini Permanent cells - never divide Nerve cells, cardiac myocytes, skeletal mm

Shashi-Mar 2000

Inflammation-54

Polypeptide growth factors

Most Important Mediators affecting Cell Growth
Present in serum or produced locally Exert pleiotropic effects; proliferation, cell migration,

differentiation, tissue remodeling Regulate growth of cells by controlling expression of genes that regulate cell proliferation

Shashi-Mar 2000

Inflammation-55

Repair by connective tissue

Occurs when repair by parenchymal regeneration

alone cannot be accomplished Involves production of Granulation Tissue replacement of parenchymal cells with proliferating fibroblasts and vascular endothelial cells

Shashi-Mar 2000

Components of the process of fibrosis

Inflammation-56

Angiogenesis - New vessels budding from old Fibrosis, consisting of emigration and proliferation of

fibroblasts and deposition of ECM Scar remodeling, tightly regulated by proteases and protease inhibitors

Shashi-Mar 2000

Inflammation-57

Wound healing
Induction of acute inflammatory response by an initial

injury Parenchymal cell regeneration Migration and proliferation of parenchymal and connective tissue cells

Shashi-Mar 2000

Inflammation-58

Wound healing (contd)

Synthesis of ECM proteins Remodeling of parenchymal elements to restore tissue

function Remodeling of connective tissue to achieve wound strength

Shashi-Mar 2000

Inflammation-59

Healing by First Intention Focal Disruption of Basement Membrane and loss of only a few epithelial cells e.g. Surgical Incision

Shashi-Mar 2000

Inflammation-60

Healing by Second Intention Larger injury, abscess, infarction Process is similar but Results in much larger Scar and then CONTRACTION

Shashi-Mar 2000

Inflammation-61

Wound Strength
After sutures are removed at one week, wound

strength is only 10% of unwounded skin (Walker Law) By 3-4 months, wound strength is about 80% of unwounded skin (Walkers Law)

Shashi-Mar 2000

Inflammation-62

Granulation tissue

Shashi-Mar 2000

Inflammation-63

Healing Skin wound

Shashi-Mar 2000

Inflammation-64

Healing - Skin Scar

Shashi-Mar 2000

Inflammation-65

Factors affecting Healing:

Systemic Age Nutrition Vitamin def. Immune status Other diseases Local Infection Size or extent. apposition Blood supply Mobility Foreign body
Shashi-Mar 2000

Inflammation-66

Summary:
Healing Proliferation & Differentiation.
Labile, Stabe & Permanent cells Stages of Healing: 1-2-3-4. Healing by First or Second intention. Skin wound healing - bone healing. Factors affecting healing Local / Systemic

Shashi-Mar 2000

"Each time you are honest and conduct yourself with honesty, a success force will drive you toward greater success. Each time you lie, even with a little white lie, there are strong forces pushing you toward failure."
Joseph Sugarman Author and Marketing Specialist