WEEKLY

TUTORIAL
DISCUSSIONS
POST- GRADUATE STUDENTS – DIVISION
OF DENTISTRY
INFLAMMATION
By Beatrice Solok – MDS 1 Oral Medicine
 01
INTRODUCTION

CONTENTS
02 ACUTE INFLAMMATION

03 CHRONIC INFLAMMATION

04 REPAIR AND REGENERATION

 HISTORY 19th Century
Metchnikoff & Cohnheim - Leucocyte
adhesion and transmigration
Wagner

1590
Jansen – first research into
inflammatory process.
Boerhaave, Gaubius et al

AFTER 129 AD
Galen of Pergamon – added loss of
function

38 AD
Aulus Celsus – written description of
4/5 cardinal signs of inflammation

2000 BC
Egyptians first described
abscesses & ulcers
Greek Physician Hippocrates –
first to regard inflammation as a
healing process.
LATIN
“Inflammare” – to set on fire
• Infographic Style

INTRODUCTION

Inflammation
 WHAT IS INFLAMMATION?
• Response of tissues to injury or infection
• Necessary for normal repair and healing.
Ralston, S. et al, 2018

• Host response
• Protective response involving host cells, blood vessels & proteins and other
mediators that is intended to eliminate the initial cause of cell injury, as well
as the necrotic cells and tissues resulting from the original insult and to
initiate the process of repair.
Kumar, V. et al, 2013

• Complex reaction in tissues that consists mainly of responses of blood

vessels and leucocytes.
Warren, P., 2015
 “…without inflammation,
infections would go
unchecked, and wounds
would never heal”.

Starts the wound

healing process
Kumar, V. et al, 2013
 “_itis”
You can Resize without • Suffix = Inflammation
losing quality
You can Change Fill
• Body structure + itis =
Color & inflammation of the structure
Line Color

• Skin – dermatitis
• Appendix – appendicitis
• Larynx – laryngitis
• Dental pulp – pulpitis
FREE • Dental alveolar – alveolitis
PPT • Gingiva – gingivitis
TEMPLATES
www.allppt.com
• Infographic Style
GENERAL
FEATURES
OF
INFLAMMATION
 CARDINAL SIGNS
RUBOR
Redness

FUNCTIO LAESA
Loss of function TUMOR
Swelling

DOLOR CALOR
Pain
Heat/warmth
TWO TYPES OF
INFLAMMATORY
REACTIONS;

1. ACUTE
INFLAMMATION
2. CHRONIC
INFLAMMATION
 ACUTE
INFLAMMATION
 GENERAL FEATURES
• Normally controlled & self-limited.
• Defensive host response to foreign
invaders & necrotic tissues-
capable of causing tissue damage.

• Two main components;

1. Vascular changes
2. Cellular events
 OUTCOMES OF ACUTE
INFLAMMATION
COMPLETE RESOLUTION
• Elimination of stimuli.
• Restoration of injured
site to normal.
01
• Removal of debris and
microbes.

HEALING BY CONNECTIVE
TISSUE REPLACEMENT
(SCARRING & FIRBOSIS
• Occurs after substantial tissue
destruction.
• Involves tissues capable of
regeneration.
• Connective tissue grows into area
of damage or exudate – fibrous
02 03 PROGRESSION OF RESPONSE
TO CHRONIC INFLAMMATION
tissue. • Acute inflammation unresolved;
• Repair tissue. • Persistence of insidious
• Replace damaged cells. agent;
• Scarring in large areas of tissue • Interference with normal
destruction. process of healing..
 STIMULI FOR ACUTE INFLAMMATION
INFECTIONS

01 • Most common.
• Bacterial
• Fungal
TRAUMA
• Parasitic
• Blunt
• Penetrating
• Thermal injury
• Irradiation from chemical agents
02
• Toxicity from environmental
chemicals. TISSUE NECROSIS
03 • Any cause
• Including Ischemia

FOREIGN BODIES
• Can cause traumatic tissue
injury or carry microbes.
04 IMMUNE REACTIONS
• Splinters • Hypersensitivity reactions
• Dirt against environmental
• Sutures
• Crystal deposits 05 substances
• Immune system damages
individual’s own tissues.
• Infographic Style

COMPONENTS
OF
INFLAMMATION
 2 MAJOR COMPONENTS

VASCULAR CHANGES
CELLULAR EVENTS
1. Vasodilation
1. Cellular recruitment
2. Increased vascular permeability
2. Activation of leucocytes
3. Activation of endothelial cells
3. Elimination of offending agent
4. Increased adhesion of leucocytes
5. Migration of leucocytes

“The main vascular reactions of acute Principal leucocytes in

inflammation are increased blood flow acute inflammation:
secondary to vasodilation & increased
permeability, both designed to bring blood Neutrophils =
cells and proteins to sites of infection or polymorphonuclear
injury” Robbin’s Basic Pathology leucocytes
 1. Vasodilation
Injury to tissue/skin
• Bacteria – microbes
• Trauma – necrotic tissue - tissue death

Chemical mediators
• Mast cells – histamines
• Macrophages – prostaglandins
• Cytokines

Blood vessels dilate;

• Histamines, prostaglandins – go to blood vessels
• Causing dilation of blood vessel - walls get
bigger/widen
• More blood flows to the area

Histamine – vasodilation – more blood flows

– result in redness (rubor) & heat (calor)
Vascular
Changes
Vasodilation
 Endothelial Line inner wall of blood vessels
Cells Chem mediators go to EC – causes the cells to shrink

Increased EC cells contract – create gaps at the vessel wall

Permeability Gaps – increased ‘leakiness’ – more fluids passes from inside
Permeability vessel to outside (tissue)

Exudates permeates the “gaps” and passes out

Exudate Contain cells and plasma proteins.
When more exudate goes out to tissue – tissue swell ups (tumor)
 Increased Permeability:
THREE RESPONSES
1. Immediate 2. Immediate
transient Sustained
response Response

3. Leucocyte
mediated endothelial
damage
Axons of the Endothelium of capillaries
sympathetic system Endothelial cells
& venules will have
Release of histamine, suffer necrosis in
cytoskeletal
prostaglandins, arterioles, capillaries
reorganization.
leukotrienes = & venules, at the site
Can undergo endothelial
endothelium of infection – direct
apoptosis.
contracts injury.
Happens 2-12 hours after
Occurs in seconds – Occurs within
injury, last for hours or
10 to 15mins seconds, lasts 4 -6
days
hours
Vasoconstriction

Injury to
Delayed
tissue Prolonged
Response
www.free-powerpoint-templates-design.com
Increased
Permeability cont..
Now in tissue around site of injury
Plasma
Proteins Activate kinins – e.g. bradykinin, and
prostaglandins

Tissue swelling + bradykinin + PG – sends

Sensitizing signals to brain
nerves Feeling of pain results

Loss of Exudate + pain = functio laesa

function
CELLULAR
EVENTS

ACUTE INFLAMMATION
2. Cellular Events

RBC – smaller cells,

Exudate – leaks out Inside blood vessel –
aggregate in the
of blood vessel thicker/ viscous
middle of vessel

Neutrophils & larger

WBC pushed to the
Margination periphery -gather to
the side inner walls of
the vessel wall
 Components:
• PMNs – , neutrophils, within first 6 hrs,
• Macrophages – replaces PMNS, 6 to 24 hrs
• Help in recognition & elimination of foreign substance.
• Steps;
• Margination – blood viscous & static, PMNs move
towards endothelial cells, the periphery
• Rolling – reach endothelial cells & start rolling over the
EC
• Binds to EC by agents called Selectins
• Attachment –PMNs attach to EC with the help of
intergrins & adhesion molecules
• Transmigration – PMNs squeezes btwn EC & into the
extravascular space (diapedesis)
• Facilitated by expression of PECAM 1
• Chemotaxis – active movement of cell towards chemical
gradient (enzyme) - neutrophil move towards it
• Phagocytosis – killing bacteria, neutralizing foreign body.
 CELLULAR EVENTS
1.Recognition
2.Binding
• Host cells recognize foreign body and bind to it
• Presence of receptors – opsonin receptor, toll-like
receptor
3.Ingestion – cell expands around foreign body and
PHAGOCYTOSIS engulf it. Forms vesicle
4.Digestion – vesicle contains lysomes, released and
break down bacteria into smaller components
5.Exocytosis – excretion, broken down particles are
released by host cell into extracellular space.
• Systemic changes associated with acute inflammation SYSTEMIC EFFECTS
• aka Systemic Inflammatory Response Syndrome OF INFLAMMATION
(SIRS)
• Important mediators : IL-1, Il-6 and TNF

1. Fever
• Body temp elevated by 1 -4°C
• Action of PG on the hypothalamus
• NSADIS reduce fever by inhibiting PG synthesis
2. Acute-phase proteins
• Mostly synthesized in the liver
• C-reactive protein, serum amyloid A protein,
Fibrinogen
• aid in destruction of necrotic cell
• Increased levels – reduced availability of iron
• Responsible for anaemia in chronic inflammation
3. Leucocytosis
• Induced by bacterial infections
• >15,000/uL
SYSTEMIC
• Accelerated release of cells from bone EFFECTS OF
marrow –rise in more immature cells in
blood. INFLAMMATION
• Bacterial infections – neutrophilia
• Viral infections – lymphocytosis
• Allergies, parasitic infections – ACUTE-PHASE RESPONSE
eosinophilia
• Typhoid fever, viral infections, ricketsiae,
protozoa - leukopenia
 SYSTEMIC EFFECTS OF INFLAMMATION
ACUTE-PHASE RESPONSE
4. Others
• Increased pulse and BP
• Decreased sweating, because of redirection of blood flow from
cutaneous to deep to minimize heat loss
• Rigors
• Chills
• Anorexia
• Somnolence
• Malaise – action of cytokines on brain cells
• SEPSIS – large amounts of bacteria & their products stimulate enormous
quantities of several cytokines (TNF, IL-1)
• High blood levels of cytokines (clinical triad of septic shock);
• Disseminated intravascular coagulation
• Hypotensive shock
• Metabolic disturbances (insulin resistance, hyperglycaemia)
 Causes of Chronic Inflammation
Persistent Indigestible Material
Persistent Infection
a. Endogenous
• Some organisms are difficult to
i. Necrotic bone. Necrotic
eradicate.
adipose tissue, calcium &
• May persist within cells or tissues. 01 02 uric acids deposits.
• E g mycobacterium tuberculosis
b. Exogenous
• Mycobacterium leprae
i. Silica, asbestos, suture
material
Immune Mediated Reactions
a. Autoimmune reaction 03
b. Organ transplant rejection Following acute inflammation
c. Unregulated immune responses
04 Persistent abscess – formed during
d. Hypersensitivity reactions acute inflam – inability to drain
surgically or spontaneously – Chronic
Repeated episodes of acute Abscess
inflammation 05
Repeated attacks of acute pancreatitis
Repeated attacks of acute cholecystitis
CHRONIC
INFLAMMATION

MORPHOLOGICAL FEATURES
1. Macroscopic features due to tissue
destruction
2. Macroscopic features due to fibrosis
3. Microscopic features
 1. Macroscopic features secondary to
MORPHOLOGICAL tissue destruction
FEATURES

i. Involvement of an epithelial surface –

formation of ulcer. E.g. chronic gastric ulcers
ii. Parenchymal tissue – cavitatory lesions eg in
chronic infection of the TB of lungs
iii. Formation of Chronic abscess – granulation
tissue
iv. Abscess extends into a surface by destructing
tissues in between – sinus formation.
v. Connection of two epithelial surfaces – fistula
formation
 MORPHOLOGICAL FEATURES

2. Macroscopic features due to fibrosis

In hollow organ – thickening Distortion of the organ

of walls
-stricture formation. -Fibrous tissue tends to contract due to the
Eg – pyloric stenosis presence of myofibroblasts
Also formed be malignant tumours -Reduce size of scar
Extensive fibrous contraction – distortion of
the organ,
Eg- distortion of the liver
 MORPHOLOGICAL FEATURES

3. MICROSCOPIC FEATURES
i. Mononuclear cell infiltrations
i. Macrophages and lymphocytes
• Acute inflammation – ii. Eosinophils – in parasitic
Neutrophil infections
• Chronic inflammation ii. Tissue necrosis
- Macrophage
iii. Tissue regeneration
iv. Granulation tissue & fibrosis tissue
v. In granulomatous inflammation –multi
nucleated giant cells – common in TB
ROLE OF
MACROPHAGE IN Macrophage accumulate at
CHRONIC the site of inflammation by;
INFLAMMATION

Proliferation of
Continuous Immobilization at
macrophages at
recruitment from the site of
the site of
blood. inflammation.
inflammation.

Mediated by
Most important To prevent
Mediated by TGF Migration inhibition
source of migration
β- and PDGF factor – secreted
macrophages; elsewhere;
by T lymphocytes
Macrophage
must be
activated to
perform its
function
Common Clinical Manifestations
CHRONIC INFLAMMATION
1. Ulceration of epithelial surfaces.
2. Sinus & fistula formation.
3. Cavitatory lesions.
4. Loss of function.
5. Wall thickening of hollow organs.
6. Stricture formation.
7. Distortion of the organ.
8. Fibrous adhesion formation –
• formed when 2 inflammatory surfaces come into contact with each other;
• In TB meningitis – adhesions in the sub arachnoid space can affect the CSF flow &
produce hydrocephalus;
• TB pericarditis – constructive pericarditis.
9. End arteritis obliterans – lumen narrows – chronic ischemia & diffuse fibrosis
10. Metaplasia
• if persistent – lead to dysplasia and ultimately malignant proliferation of the
epithelium
Systemic Splenomegaly & Hepatomegaly

Manifestations Lymphadenopathy

Amyloidosis – due to prolonged production of

CHRONIC INFLAMMATION acute phase reactants
Anemia of chronic disease

High ESR

Low-grade long-term fever

Loss of appetite and loss of weight due to

inhibitory effect of TNF
 5 STEPS (5 Rs) OF THE
INFLAMMATORY RESPONSE

Repair

Regulation (control) of the

response
Removal or elimination of
the agent
Recruitment of Leucocytes

Recognition of the injurious

agent or foreign substance Resolution
Regulation
Removal
Recruitment
Recognition
 ACUTE VS CHRONIC • Inflammation of
prolonged duration
(weeks or months) in
ACUTE which inflammation,
tissue injury, & attempts
INFLAMMATION at repair co-exist.
• May follow acute
inflammation.
• May begin insidiously, as

02 low grade, without any

manifestations of an
acute reaction.

• Rapid Onset (typically

within minutes).
• Short duration (hours
– few days).
01
• Edema CHRONIC
• Emigration of
leucocytes.
INFLAMMATION
• Failure to eliminate
leucocytes will initiate
chronic inflammation.
OUTCOMES OF
ACUTE
INFLAMMATION

© Robbins Pathology
RENEWAL, REPAIR AND REGENERATION
REGENERATION
• Complete restitution of lost or damaged
tissue
• Proliferation of lost or damaged tissues to
replace lost structures
• Rare in whole organs and complex
tissues;
• Liver growth after partial resection or
necrosis consist of compensatory
growth rather than true regeneration.
• Tissues with high proliferative
capacity – hematopoietic system,
epithelia of skin and GI tract – as long
as stem cells are not destroyed.
REPAIR
Restores some original structure but can cause
structural derangements.
“patches rather than restore”

Most often consists of a combination of regeneration

& scar formation by deposition of collagen.

Scar formation is the predominant healing process

when ECM is damaged by severe injury

Chronic inflammation that accompanies persistent

injury also stimulates scar formation because of the
local production of cytokines & growth factors that
promote fibroblast proliferation & collagen synthesis.
REPAIR
Fibrosis – extensive deposition of collagen

ECM – extracellular matrix

Essential for wound healing
Provide framework for cell migration
Participate in angiogenesis.
Cells in ECM – fibroblasts, MP – produce
cytokines, GF and chemokines critical for
regeneration and repair.
BASIC FEATURES
Repair by connective tissue deposition;

Migration and Connective

Scar
Inflammation Angiogenesis proliferation tissue
formation
of fibroblasts remodelling

Fibrosis;
• Excessive deposition of connective
tissue
• When inflammation becomes chronic
due to persistence of damage.
CUTANEOUS
WOUND HEALING

THREE
PHASES;
• INFLAMMATION
• PROLIFERATION
• MATURATION
 • Healing of a clean, uninfected surgical incision approximated by
surgical sutures.
• Occurs when dermal edges are close together.
• 4 steps;
1.Hemostasis: -
• Platelets 7 cytokines form a haematoma,
• leading to vasoconstriction and limiting blood loss.
• proximity of wound edges allows for easy clot formation,
HEALING BY preventing infection by forming a scab.
2.Inflammation:
PRIMARY • Cellular inflammatory responses remove cell debris & pathogens
3.Proliferation:
INTENTION • Inflammatory cell-released cytokines drive fibroblast
proliferation and the formation of granulation tissue.
• Angiogenesis is promoted by growth mediators (such as VEGF),
allowing further maturation of the granulation tissue.
Healing by primary intention usually results
in minimal scarring and a complete return to • Collagen production by fibroblasts facilitates wound closure after
approx a week.
function.
4.Remodelling:
• Collagen fibres are deposited within the wound, providing strength.
• Subsequently, fibroblasts undergo apoptosis.
 large defects on skin surface
extensive loss of cells and tissue
Excisional wounds;
wound edge are not opposed – need for
healing from bottom of wound upwards.

A large fibrin mesh forms within the

Haemostasis: wound, filling the gap left by the
unopposed edges.

An intense inflammatory
Inflammation: response ensues, removing cell debris
and pathogens present in the wound.

HEALING BY Proliferation:
Similar to healing by primary
intention, cytokines released by
inflammatory cells drive fibroblast
proliferation.

SECONDARY formation of granulation tissue.

Collagen fibres are deposited within the

INTENTION Remodelling: wound, providing strength.

fibroblasts undergo apoptosis.

Healing by secondary intention is typically slower than

primary intention.

more scarring and loss of skin appendages.

common in wounds with open edges, where the sides cannot

be easily approximated
SCAR FORMATION
 Factors influencing scar formation include
PRIMARY TYPES genetics, age, bacterial colonization, skin
tension, inflammation, and underlying skin
OF SCARS diseases. While complete prevention of
scarring is not possible in full-thickness
wounds, adequate wound care can minimize
• Cicatrix: scarring and improve outcomes.
• flat or slightly raised, often with a pink or reddish WedMd
color.
• Proper wound care can increase the chances of a
flat scar rather than a raised one.
• considered normal scarring.
• Hypertrophic:
• raised and firm
• potentially causing pain or restricting movement.
• frequently form from wounds on the chest, upper
back, or shoulder.
• Keloid:
• scars grow larger than the original wound.
• can appear up to a year after the injury
• may be itchy or painful.
 WOUND
CONTRACTION
• Crucial aspect of the wound healing process;

1. Initiation:
• Approximately a week after
wounding, fibroblasts differentiate into myofibroblasts.
• key role in wound contraction.
2. Peak Contraction:
• In full-thickness wounds, contraction peaks between 5 to
15 days post-wounding.
• myofibroblasts actively work to decrease the wound size.
3. Duration:
• Contraction can persist for several weeks, even after the
wound is completely re-epithelialized.
4. Mechanism:
• Myofibroblasts grip the wound edges and contract.
• contraction helps close the wound and reduce the deficit
that needs to be filled with connective tissue.
 CONNECTIVE TISSUE
REMODELLING
• dynamic process that involves several cellular players –
• growth factors, cytokines, chemokines, and the turnover of the extracellular
matrix (ECM);
• Inflammatory Phase:
• Following injury, the body responds with inflammation.
• Acute inflammation
• Chronic inflammation
• Repair Phase:
• After the initial bleeding phase, the repair phase begins.
• Fibroblasts play a crucial role in rebuilding the damaged tissue structure.
• Granulation tissue forms, and angiogenesis (new blood vessel formation)
occurs.
• Collagen production helps bridge the wound gap, leading to scar tissue
formation.
• Remodelling Phase:
• The final form of the tissue emerges during the remodelling phase.
• Myofibroblasts, which differentiate from fibroblasts, contribute to wound
contraction.
• Collagen fibres are restructured, and capillaries regress.
• Goal -restore anatomical structure & normal function to the damaged tissue.
FACTORS
Systemic Factors; Local Factors;
AFFECTING
WOUND
HEALING 1. Nutrition 1. Infection
2. Metabolic status 2. Mechanical factors
3. Circulatory status 3. Foreign body
4. Hormones 4. Size, location & type
of wound
THANK YOU