INFLAMMATION

For 2nd year BSc comprehensive

nursing students
Dr Adugna E.(MD)
 LEARNING OBJECTIVES

• At the end of this lesson the student will be able to:

1. Define inflammation
2. Contrast the differences between acute &
chronic inflammations
3. know the causes of inflammation
4. Understand the process of inflammation
5. Describe the morphologic patterns of acute
inflammation
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 DEFINITION

It is complex protective reaction of vascularized living tissue

to local injury caused by various endo- and exogenous
stimuli.
• Literally means – “to set fire” in
• Protective response of a vascularized tissue to an injurious
agent.
• Has two main components – vascular & cellular responses.

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 CTD...

• Inflammation is associated with the repair process which

includes parenchymal cell regeneration and scarring.

• Infection is not a synonym of inflammation & vice versa.

The role of inflammation is to

✓ Contain and isolate injury

✓ Destroy invading microorganisms and inactivate toxins

✓ Achieve healing and repair.

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 Inflammation

❖ However, inflammation and repair may be

potentially harmful

• life-threatening hypersensitivity reactions

• Progressive organ damage and scarring

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 NOMENCLATURE

• Generally speaking the • Greek root + -itis

suffix – itis indicates • metritis, not uteritis
inflammation of the
involved organ • nephritis, not renitis
Eg. Sinus – sinusitis • Testis- Orchitis
Esophagus – esophagitis
Liver – hepatitis
Skin – dermatitis
Lung – pneumonia, etc…

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 C ARDINAL SIGNS

• Redness – rubor
• Swelling – tumor
• Heat – color
• Pain – dolor
• Loss of function – fuctio laesa
NB. This signs are results of different mechanism
& it is more prominent in acute inflammation.

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Redness Heat Swelling Pain Loss of
Function

Caused by Increased Caused by Direct injury Increased

dilation of chemical accumulation of nerve pain/ swelling
arterioles/ activity & of blood & fibers,
increased increased damaged pressure of
blood flow blood flow to tissue cells hematoma on
skin surface n. endings
Chemical
irritants –
bradykinin,
histamine,
prostaglandin

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 TYPES OF INFLAMMATION

Acute Chronic

onset immediate delayed

duration few days Wks, months or even yrs

outcome healing, abscess formation, Tissue destruction

fibrosis & chronic
inflammation
primary Vasoactive amines & cytokines
mediator eicosanoids
causative Pathogens Persistent inflammation
agents
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cells Polymorphonuclear Mononuclear
 ACUTE INFLAMMATION

• It is an immediate & early response to injurious agent.

Causes include:-
• Infections
• Trauma
• Physical, chemical & thermal radiation
• Tissue necrosis
• Immune reactions
• Foreign bodies

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 ACUTE INFLAMMATION CTD…

• Acute inflammation has three basic steps

1. Alteration in vascular caliber that leads to an increase in blood

flow (vasodilatation)

2. increased transmembrane permeability- Structural changes

in microvasculature that permits plasma proteins & leukocytes to
leave the circulation

3. Immigration of leukocytes

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 VASCULAR CHANGES

• It occurs in the following sequences

➢ Vasodilatation - an earliest manifestation first involving

the arterioles & causes increased blood flow. Results in heat
& redness

➢Increased vascular permeability

• This leads to escape of protein rich fluid to the

extravascular space. 14
 CELLULAR EVENTS

• Inflammation is crucial to deliver leukocytes & antibodies to

the site of injury.

• Leukocytes are crucial for the following activities:

• Ingest offending agents

• Kills bacteria

• Get rid of necrotic tissue & foreign bodies

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 CTD...

• There are processes so as to deliver these cells to the site

of injury; the process is termed as extravasation.

• It occurs in the following three sequences:

i. Margination, rolling & adhesion to the endothelium

ii. Transmigration – across the endothelium

(diapedesis)

iii. Migration – to the interstitium towards a

chemotactic stimulus.

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 SLOWING CONCENTRATION

Margination Rolling Adhesion

Transmigration
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 PHAGOCYTOSIS

• Is the process of engulfment & internalization by

specialized cells.

• Three steps in phagocytosis:

✓Recognition & attachment

✓Engulfment

✓Killing/degradation.

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 INFLAMMATION

❑ The cell type present in the inflammatory response varies with

✓ Stage of the inflammatory lesion
✓ Type of stimulus.
• Neutrophils are predominate in the first 6 to 24 hours,
• Monocytes in the next 24 to 48 hours.
• Neutrophils: acute inflammation
• Eosinophils: parasites hypersensitivity reaction.
• Monocytes(macrophages):granulomatous inflammation
• Lymphocytes: Virus and chronic inflammation
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 MORPHOLOGIC PATTERNS OF
ACUTE INFLAMMATION
1. Serous inflammation
•Is characterized by thin tissue fluid accumulation.
•marked by the exudation of cell poor.
•In the peritoneal, pleural & pericardial cavities it is called an
effusion.
•But it can also occur elsewhere.
E.g. skin burn blisters
•not infected by destructive organisms and does not contain
large numbers of leukocytes

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 2. FIBRINOUS INFLAMMATION

• More severe injuries result in greater vascular

permeability that ultimately leads to exudation of larger
molecules such as fibrinogens.

• Fibrinous exudate is characteristic of inflammation in

the lining body cavities such as the pericardium (butter
& bread appearance) & pleura.

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 3. SUPPURATIVE OR PURULENT
INFLAMMATION

• Is characterized by production of a large amount of pus.

• Pus is a thick creamy liquid, yellowish or blood tingled in

color composed of leukocytes & necrotic cells.

• Abscess refers to a localized collection of pus.

• If the pus accumulates in the serous cavity, it is called

Empyema

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• pus an exudate consisting of neutrophils, the
liquefied debris of necrotic cells, and edema fluid.

• The most frequent cause of purulent (also called

suppurative) inflammation is infection with bacteria
that cause liquefactive tissue necrosis, such as
staphylococci; these pathogens are referred to as
pyogenic (pus-producing) bacteria.

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 OUTCOMES OF ACUTE
INFLAMMATION
1. Complete resolution

- when the injury is limited or short-lived or when there has

been little tissue destruction & the damaged parenchymal
cells can regenerate

2. Healing by connective tissue replacement

(fibrosis/organization)

- occurs after substantial tissue destruction, involves tissues that

are incapable of regeneration or when there is abundant fibrin
exudation. 29
3. Abscess formation – Pyogenic infections may
cause intense neutrophilic infiltration &
liquefaction of tissues.

4. Progression of the tissue response to chronic

inflammation

- occurs when the acute inflammatory response

cannot be resolved due to either persistence of the
injurious agent or some interference with the
normal process of healing.

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 OUTCOMES OF ACUTE
INFLAMMATION

❑Resolution

❑Fibrosis

❑Abscess formation

❑Progression to chronic inflammation

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 CHRONIC INFLAMMATION

• It is an inflammation of prolonged duration wks,

months or yrs.
• The triads of chronic inflammation are:
- active inflammation
- tissue destruction &
- healing which occur simultaneously
• It is not characterized by the cardinal signs of
inflammation rather there is:

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 CTD...

- Infiltration with mononuclear (chronic inflammatory

cells – macrophages, lymphocytes & plasma cells)

- Tissue destruction

- Repair (new blood vessel formation & fibrosis)

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 C AUSES

• Persistent infections : mycobacteria and certain

viruses, fungi, and parasites. These organisms often
evoke an immune reaction called delayed-type hypersensitivity.—pus
formation may ensue.

• Prolonged exposure to potentially toxic agents

- silica

- Toxic plasma lipids --- atherosclerosis---

• Autoimmune diseases like RA (Reumatoid arthritis), multiple sclerosis

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 MEDIATERS IN CHONIC
INFLAMMATION

• Macrophages
• Lymphocytes
• Plasma cells
• Eosinophils- parasitic infestations & allergic
reactions.

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 CLASSIFICATION OF CHRONIC
INFLAMMATION

• Classified in to two types based on histologic features:

1. Nonspecific chronic inflammation

• This involves diffuse accumulation of macrophages &

lymphocytes at sites of injury that is usually productive with
new fibrous tissue formations.

E.g. Chronic cholecystitis

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 Ty p es o f ch ro n ic in f lammation co n t ’….

2. Granulomatous inflammation

• It is a distinctive pattern of chronic inflammatory reaction

characterized by the presence of granuloma.

• A granuloma is focal accumulation of activated

macrophages which develop an epithelial-like (epitheloid)
appearance and surrounded by lymphocytes, plasma cells &
fibroblasts.

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 CTD...

• The epitheloid cells can fuse with each other & form
multinucleated giant cells.

• TB is a prototype of this type of inflammation which forms a

caseous granulomatous lesion.

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 TWO TYPES OF GRANULOMAS
1. Foreign body – which are incited by inert foreign bodies.
• Formed when suture or other fibers preclude phagocytosis.
• No T cell mediated immunity.
• The foreign body can be identified in the center of
granuloma which appears refractile.
2. Immune granuloma – are caused by insoluble particles
typically microbes that are capable of inducing T cell
mediated immune response.
e.g. TB bacilli.

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 PATHOLOGICAL CONDITIONS ASSOCIATED
WITH GRANULOMA FORMATION

• Bacteria:- TB, leprosy, T.pallidum, cat scratch disease

• Parasite:- schistosomiasis, onchocerciasis

• Fungus:- histoplasma, Cryptococcus

• Inorganic metals or dusts:- silicosis, pneumoconiosis

• Foreign bodies

• Unknown:- sarcoidosis
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WOUND HEALING
 OUTLINES

• Process of wound healing

• Patterns of wound healing

• Complications of cutaneous wound healing

• Fracture healing

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 PROCESS OF HEALING

• The healing process involves two distinct processes:

1. Regeneration

• Proliferation of cells that survive the injury and retain the capacity
to proliferate, and differentiation of cells derived from tissue stem
cells.

e.g. in the rapidly dividing epithelia of the skin and intestines,

hematopoietic system

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2. Repair (healing) by scaring – the replacement loss of
tissue by granulation tissue which matures to form scar
tissue.

• E.g. In skin, superficial wounds heal by regeneration but

deep wounds (dermis) heal by scar formation.

• Fibrosis - the extensive deposition of collagen that occurs

in the lungs, liver, kidney and other organs as a
consequence of chronic inflammation.
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 TYPES OF CELLS

• Based on their proliferative capacity there are three types of

cells:
1. labile cells
• These are cells which have a continuous turn over by
programmed division of stem cells.
• They are found in the surface epithelium of the GI tract,
urinary tract, oral cavity, vagina, and cervix, uterus, and
fallopian tubes,
• cells of lymphoid & haemopoietic systems are further
examples of labile cells.
• The chances of regeneration are excellent.

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 CTD...
• 2. Stable cells
• not proliferating, but they are capable of dividing in
response to injury or loss of tissue mass.
• include the parenchyma of most solid organs, such as
liver, kidney, and pancreas. Endothelial cells, fibroblasts,
and smooth muscle cells.
• 3. Permanent cells
• terminally differentiated nonproliferative cells.
• Example – adult neurons, striated muscle cells, myocytes & cells of
the lens
• Injury to these tissues is irreversible and results in a scar, because
the cells cannot regenerate.

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 REGENERATION

❖The importance of regeneration in the replacement of injured tissues

varies in different types of tissues and with the severity of injury.

✓In epithelia of the intestinal tract and skin, injured cells are rapidly
replaced by proliferation of residual cells and differentiation of
cells derived from tissue stem cells.

✓in parenchymal organs whose cells are capable of proliferation, but

with the exception of the liver, this is usually a limited process.
Pancreas, adrenal, thyroid, and lung have some regenerative capacity.

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• Regeneration of the liver occurs by two major mechanisms:

✓proliferation of remaining hepatocytes and

✓repopulation from progenitor cells; occur In situations in which

the proliferative capacity of hepatocytes is impaired, such as
after chronic liver injury, infection or inflammation.

• Which mechanism plays the dominant role depends on the

nature of the injury.

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 REPAIR BY SCARRING

• repair by replacement of the injured cells with connective tissue,

leading to the formation of a scar, or by a combination of regeneration
of some residual cells and scar formation.

• happen if the tissue injury is severe or chronic and results in damage

to parenchymal cells and epithelia as well as to the connective tissue
framework, or if nondividing cells are injured.

• In contrast to regeneration, which involves the restitution of tissue

components, scar formation is a response that “patches” rather than
restores the tissue.
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 STEPS IN SC AR FORMATION
• Repair by connective tissue deposition consists of a series of
sequential steps that follow tissue injury.
1. haemostatic plug comprised of platelets is formed, stops
bleeding , occurs within minutes after injury,.
2. Inflammation
Macrophages are the central cellular players in the repair
process.

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 SCAR FORMATION CONT…

• 3.Cell proliferation takes up to 10 days.

✓Epithelial cells migrate over the wound to cover it.

✓Endothelial and other vascular cells proliferate to form

new blood vessels(angiogenesis).

✓Fibroblasts- lay down collagen fibers (begins 3 – 5 days after

injury) form the scar.

➢The combination of proliferating fibroblasts, loose

connective tissue, new blood vessels and scattered
chronic inflammatory cells, forms a type of tissue that
is unique to healing wounds and is called granulation
tissue.
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 SC AR FORMATION CONT…

4. Remodelling. The balance b/n ECM synthesis & degradation

results in remodelling of the connective tissue framework.

• The connective tissue that has been deposited by fibroblasts is

reorganized to produce the stable fibrous scar.

• This process begins 2 to 3 weeks after injury and may

continue for months or years.

✓ Wound contraction- is a mechanical reduction in the size of

the defect.

• The wound is reduced ≈ by 70-80% of its original size.

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 SKIN WOUND HEALING

❖Two types of wound healing (by first intention & healing

by second intention)
✓described depending on the amount of tissue damage.
✓essentially the same process varying only in amount.
✓Whether a wound heals by primary or secondary union
is determined by the nature of the wound, rather than
by the healing process itself !!

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 Healing by First Intention

• Occurs in wounds that close easily.

• Epithelial regeneration predominates over fibrosis.
• Healing is fast, with minimal scarring/infection
• Examples:
• Paper cuts
• Well-approximated surgical incisions.

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 Healing by Second Intention
 Occurs in larger wounds that have gaps between wound margins
 Fibrosis predominates over epithelial regeneration
 Healing is slower, with more inflammation and granulation tissue
formation, and more scarring
 Examples:
 Infarction
 Large burns and ulcers
 Large devitalized tissue
✓ Regeneration of parenchymal tissues can not completely
restore original architecture.

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Second intention healing has:

 More inflammation
 More granulation tissue
 Wound contraction

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 WOUND STRENGTH

• Wound healing is initially largely dependent on

suturing.
• When the sutures are removed (typically at 1
week), wound strength is only about 10% of the
normal.
• At the end of 3 months 70- 80% of normal.

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 FACTORS THAT INFLUENCE
HEALING

❖1. Local factors

✓ Type, size & location of the wound
• stable and labile cells- Complete repair.
• wounds on the face heal fast(rich vascularization)
• small injuries heal faster
✓Mechanical stress- pressure areas long time.
✓ Foreign bodies
✓Infection-is the single most important cause of delay in
healing
• persistent tissue injury and inflammation.
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 2.SYSTEMIC FOCTORS

✓Nutrition - vitamin C, proteins

✓Circulatory status.
✓Metabolic status – diabetes mellitus
✓ E.g-poorly controlled DM →delayed wound healing
✓Hormones – steroids/glucocorticoids
E.g.- corticosteroids -impair wound healing
-ed collagen synthesis
-anti-inflammatory effect..... result in weak scars
diminish fibrosis

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 COMPLICATIONS IN CUTANEOUS
WOUND HEALING

1. Infection
2. Deficient scar formation
Complications:
A. wound dehiscence
B. incisional hernias
✓dehiscence occurs in 0.5-5% of abdominal surgeries
• can be due to:-inappropriate surgical techniques, stress,
increased pressure or infection.
C. ulceration- varicose, DM, leprosy, 30 syphilis (spinal
involvement)
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 3.EXCESSIVE SCARRING

• Excessive formation of the components of the repair process

can give rise to hypertrophic scars and keloids.

• failure in 'maturation arrest' or block in the healing process.

➢hypertrophic scar- often grow rapidly and contain abundant

myofibroblasts, but they tend to regress over several months.

• Thermal and traumatic injury

➢Keloid- If the scar tissue grows beyond the boundaries of the

original wound and does not regress.
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4. Excessive contraction

• exaggeration of contraction →contracture (cicatrisation)

• results in severe deformity

• Palms, soles, and anterior thorax are prone for contracture

• follows burn injuries

• it can occur in hollow viscera → stricture

E.g-urethra, esophagus

• palmar contracture-Dupuytren contracture

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Fracture
Repair

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 Step 1:
A. Immediately after the fracture, extensive bleeding
occurs. Over a period of several hours, a large
blood clot, or fracture hematoma, develops.

B. Bone cells at the site become deprived of nutrients

and die. The site becomes swollen, painful, and
inflamed.

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• Step 2:

A. Granulation tissue is formed as the hematoma is infiltrated by

capillaries and macrophages, which begin to clean up the
debris.

B. Some fibroblasts produce collagen fibers that span the break ,

while others differentiate into chondroblasts and begin secreting
cartilage matrix.

C. Osteoblasts begin forming spongy bone.

❖ This entire structure is known as a fibro cartilaginous callus

and it splints the broken bone.
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Step 3:
A. Bone trabeculae increase in number fibro cartilaginous callus

bony callus of spongy bone

• Typically takes about 6-8 weeks for this to occur.
Step 4:
A. During the next several months, the bony callus is continually
remodeled.
B. Osteoclasts work to remove the temporary supportive
structures
Osteoblasts rebuild the compact bone and reconstruct the bone so
it returns to its original shape/structure.

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Thank you!!!

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