INFLAMMATION
AND
REPAIR
PRACTICAL NO- 4

Definition
Inflammation is a complex reaction of
vascularized connective tissue to any
injury.

CLASSIFICATION
Acute inflammation
Chronic inflammation

Patterns of Inflammation
Acute
* Short duration (minutes-days) with exudation of
fluid & plasma proteins, and emigration of
neutrophils into tissue.
Chronic
* Longer duration (days-months) with tissue
accumulation of lymphocytes, plasma cells, &
macrophages plus variable proliferation of blood
vessels, fibrosis and necrosis.

Inflammation: essential definitions
Exudation = Escape of fluid, proteins, and blood
cells from vessels into tissues
Exudate = Inflammatory fluid, high protein
concentration and sp.gr. > 1.020
Transudate = Watery fluid, low protein concentration
and sp. gr. < 1.012
Oedema = Excess fluid in tissues & excess fluid
in serous cavities lined by mesothelium
(pleural, pericardial, peritoneal)
Pus = Inflammatory exudate rich in
neutrophils and cell debris

Cardinal Signs of Inflammation
Redness : Hyperaemia.
Warm : Hyperaemia.
Pain : Nerve, Chemical
mediators.
Swelling : Exudation
Loss of Function: Pain

Function of inflammatory exudates
1-Dilute the invading microorganism and its
toxins.
2-Bring antibodies through the plasma to the
inflamed area for neutralization.
3-Bring leukocytes that engulf the invading
microorganisms.
4-Bring fibrinogen through the plasma, which is
converted, to fibrin mesh, helping in trapping the
microorganism and localize the infection.
5- Initiate the process of repair

Stimuli For Acute Inflammation
Infections-
* Bacterial, Viral, Parasitic, Microbial toxins
Trauma-
* Blunt and Penetrating
Physical
 Thermal injury.e.g.Burns,Frostbite,Irradiation
Chemical agents-
Tissue Necrosis
Foreign Bodies(Splinters, Dirt, Sutures)
Immune Reaction

Pathogenesis
Vascular events
* Changes in Vascular Flow and Caliber
* Increased Vascular Permeability
Cellular events
* Extravasation of Leukocytes
• In lumen of blood vessel (3 phases):
– Margination
– Rolling
– Adhesion
• Transmigration of leukocytes
• Migration into interstitium toward injury site by
locomotion along a chemical gradient: Chemotaxis
* Phagocytosis

HAEMODYNAMIC CHANGES
Vascular events
Cellular events

Vascular Events
Alteration in vascular flow and caliber
1. Vasoconstriction (Transient)
2. Vasodilatation
3. Slowing
4. Stasis
Increased vascular permeability

Mechanisms vascular permeability
Mechanism Gaps due to
endothelial
contraction
New blood
vessel
formation
Direct injury Leukocyte-
dependent
injury
Increased
transcytosis
Mediators Histamine,
bradykinin,
substance P
VEGF Toxins,
burns,
chemicals
Enzymes
, toxic
oxygen
species
VEGF
Five
proposals,
Fig. 3-4,
Pathologic
Basis of
Disease, 6th
ed, WB
Saunders,
1999.

Cellular Events
Margination, Rolling, and Adhesion to
endothelium
Chemotaxis
Leukocyte activation and phagocytosis

Leukocyte emigration: overview
Fig. 2-6, Pathologic Basis of Disease, 2006.

TRANSUDATE AND
EXUDATE
TRANSUDATE
 Filtrate of blood plasma
without changes in endothelial
permeability.
 Non-inflammatory edema
 <1gm/dl protein
 pH <7.3
 Few cells,mainly mesothelial
 Eg:congestive cardiac failure
EXUDATE
 Edema of inflamed tissue
associated with increased
permeability
 inflammatory edema
 >3.5gm/dl protein
 pH>7.3
 Many cells,inflammatory as
well as parenchymal
 Eg:purulent exudate such as
pus

MORPHOLOGIC PATTERNS
OF ACUTE INFLAMMATION
Serous
Fibrinous
Suppurative or Purulent
Ulcers

SEROUS INFLAMMATION:
Serous inflammation is marked by the
outpouring of a thin fluid
* e.g. the skin blister resulting from a burn or viral
infection represents a large accumulation of
serous fluid

FIBRINOUS INFLAMMATION
More severe injuries and
More greater vascular permeability,
Larger molecules such as
* fibrinogen pass the vascular barrier, and fibrin
is formed and deposited

FIBRINOUS PERICARDITIS(GROSS)
 Exudation of a protein-
rich fluid into a cavity
leads to a transudate. The
fibrin in this fluid can
form a fibrinous exudate
on the surfaces. Here, the
pericardial cavity has been
opened to reveal a
fibrinous pericarditis with
strands of stringy pale
fibrin between visceral
and parietal pericardium.

FIBRINOUS INFLAMMATION
* A fibrinous exudate is characteristic of
inflammation in the lining of body cavities, such as
the meninges, pericardium and pleura

FIBRINOUS INFLAMMATION
Fibrinous exudates may be removed by
fibrinolysis
But when the fibrin is not removed, it
may stimulate the in-growth of
fibroblasts and blood vessels and thus
lead to scarring (organization)

SUPPURATIVE OR PURULENT
INFLAMMATION
Characterized by the production of large amounts
of pus or purulent exudate consisting of
neutrophils, necrotic cells, and edema fluid
Certain bacteria (e.g., staphylococci) produce this
localized suppuration and are therefore referred
to as pyogenic (pus-producing) bacteria

G 1

Acute Appendicitis(Gross)
Here is acute
appendicitis with
Yellow to tan exudate
and
Hyperemia, including
The peri-appendiceal
fat superiorly, rather
than a smooth,
glistening pale tan
serosal surface.

Acute Appendicitis(Micro)
Here, the mucosa
shows ulceration and
undermining by an
extensive
neutrophilic exudate.

PYOGENIC MENINGITIS(GROSS)
A purulent exudate is
seen beneath the
meninges in the brain
of this patient with
acute meningitis from
Streptococcus
pneumoniae infection.
The exudate obscures
the sulci.

G 55

Pyogenic Meningitis(Micro)
 Microscopically, a
neutrophilic exudate is seen
involving the meninges at
the left, with prominent
dilated vessels.
 There is edema and focal
inflammation in the cortex
to the right.
 This acute meningitis is
typical for bacterial
infection.

G 7

LOBAR PNEUMONIA(MICRO)
At medium power
magnification, numerous
neutrophils fill the alveoli
in this case of acute
bronchopneumonia in a
patient with a high fever.
Pseudomonas aeruginosa
was cultured from
sputum.
Note the dilated
capillaries in the alveolar
walls from vasodilation
with the acute
inflammatory process.

SUPPURATIVE OR PURULENT
INFLAMMATION
Abscesses :
* Localized collections of purulent inflammatory
tissue caused by suppuration buried in a
tissue, an organ, or a confined space

Suppurative inflammation. A, A subcutaneous bacterial
abscess with collections of pus. B, The abscess contains
neutrophils, edema fluid, and cellular debris.

Kidney Abscess(Gross)
In the lower pole of this
kidney is a 1 cm pale
yellow abscess.

G 2

KIDNEY ABSCESS(MICRO)
This is an ascending
bacterial infection
leading to kidney
abscess.
Numerous PMN's are
seen filling renal
tubules across the
center and right of this
picture.

Lung Abscess(Gross)
 Here is lung abscess, in
the upper lobe of this left
lung.
An abscess is a
complication of severe
pneumonia, most
 typically from virulent
organisms such as S.
aureus.

Brain Abscess

G 8
Liver abscess

Localized liquefactive necrosis liver abscess
Removal of the
dead tissue
leaves behind a
scar

Cellulitis
 It is an acute diffuse suppurative inflammation
caused by streptococci, which secrete
hyaluronidase & streptokinase enzymes that
dissolve the ground substances and facilitate the
spread of infection.
Sites:
* Areolar tissue; orbit, pelvis, …
* Lax subcutaneous tissue

Ulcers
An ulcer is a local defect of the surface
of an organ or tissue that is produced by
the sloughing (shedding) of
inflammatory necrotic tissue

Ulceration can occur only when tissue necrosis and
resultant inflammation exist on or near a surface
Epithelial Defect
Fibrinopurulent exudates
Granulation tissue
Fibrosis
Necrotic base

Systemic effects of Inflammation
Acute phase reaction/response
* IL-1 and TNF
* Fever
* Malaise
* Anorexia
Bone marrow
* Leukocytosis
* IL-1 + TNF
Lymphoid organs
Liver
IL-6, IL-1, TNF
Acute phase proteins
* C-reactive protein
* Lipopolysaccharide
binding protein
* Serum amyloid A
* a-2 macroglobulin
* Haptoglobin
* Ceruloplasmin
* fibrinogen

Systemic Effects of Inflammation
Fever
Fever is produced in response to Pyrogens
What are pyrogens?
* act by stimulating prostaglandin synthesis in the
vascular and perivascular cells of the hypothalamus.
 Bacterial products (called exogenous pyrogens),
stimulate leukocytes to release cytokines such as
IL-1 and TNF (called endogenous pyrogens) that
increase the enzymes (cyclooxygenases) that
convert AA into prostaglandins.

Outcomes of acute inflammation
Fig. 3-24, Pathologic Basis of Disease, 6th ed, WB Saunders, 1999.

Chronic inflammation
Chronic inflammation is inflammation of
prolonged duration (weeks or months) in
which inflammation, tissue injury, and
attempts at repair coexist, in varying
combinations.
Types of chronic inflammation
1. Chronic non specific inflammation
2. Chronic specific inflammation: It includes
granulomatous inflammation

Causes of chronic inflammation
Prolonged acute inflammation or repeated bout of
acute inflammation may lead to the presence of
more mononuclear cells and chronic
inflammation.

Causes of chronic inflammation
Persistent infection by microorganisms that are
difficult to eradicate such as mycobacteria, certain
viruses, fungi and parasites. These often evoke
delayed-type hypersensitivity reaction.
Immune-mediated inflammatory diseases: Include
autoimmune diseases & allergic diseases. May
show mixture of acute and chronic inflammation.
Prolonged exposure to potentially toxic agents,
either exogenous (e.g. silicosis) or endogenous
(e.g. atherosclerosis).

CHRONIC INFLAMMATION
Morphologically, characterized by:
Infiltration by mononuclear cells i.e. macrophages,
lymphocytes, and plasma cells.
Tissue destruction.
 Attempts at healing by connective tissue
replacement of damaged tissue accompanied by
angiogenesis and in particular, fibrosis.

Chronic non specific inflammation
 It is seen affecting any organ for a
prolonged period of time.
 It is characterized by diffuse infiltration
with mononuclear inflammatory cells.
 Examples:
1. Chronic nonspecific cervicitis
2. Chronic cholecystitis
3. Chronic osteomyelitis

CHRONIC NONSPECIFIC CERVICITIS

Chronic cholecystitis

Chronic cholecystitis

CHRONIC OSTEOMYELITIS(GROSS)
Gross specimen of
bone shows outer
casing of
necrosed,dead bone
known as sequestrum.
Inner new bone
formation can be
seen,known as
involucrum.

CHRONIC OSTEOMYELITIS
There is fibrosis of
the marrow space
accompanied by
chronic inflammatory
cells.
There can be bone
destruction with
remodeling.

Granulomatous inflammation
Granulomatous inflammation is the
ditinctive pattern of chronic inflammation.
It is caused by organisms which are difficult
to eradicate and induce immune response
known as delayed hypersensitivity.
Immune reactions usually lead to
development of granuloma, which is a
cellular attempt to contain an offending
agent.

GRANULOMA
Granuloma is a focus of chronic inflammation
consisting of a microscopic aggregation of
macrophages that are transformed into epithelium
like cells- epithelioid cells surrounded by a collar
of mononuclear leukocytes, principally
lymphocytes and occasionally plasma cells.
Frequently, epithelioid cells fuse to form giant
cells, having many nuclei arranged either
peripherally (Langhans-type) or haphazardly
(Foreign body-type).
Older granuloma develop an enclosing rim of
fibroblasts and connective tissue.

Defination
Chronic Inflammation- Defined as a
prolong process in which tissue destruction
and inflammation occurs at the same time.
Granuloma-Defined as a circumscribed
,tiny,lesion,about 1mm in diameter
,composed predominantly of collection of
modified macrophages called epitheloid
cells and rimmed at the periphery by
lymphoid cells.

Tuberculosis Mycobacterium
tuberculosis
Caseating granuloma
(tubercle)
Leprosy Mycobacterium leprae AFB in macrophages;
noncaseating granuloma
Syphillis Treponema pallidum Gumma(enclosing wall of
histiocytes; plasma cells)
Cat-scratch disease Gram neg bacillus Round or stellate granuloma
Crohn disease Immune reaction against
intestinal bacteria, self
antigens
Occasional noncaseating
granuloma in the wall of
intestine
Sarcoidosis Unknown etiology Noncaseating granulomas
with abundant activated
macrophages
Inorganic metals
,dusts,silicosis
Foreign body Granuloma with foreign body
type giant cells.

GRANULOMATOUS INFLAMMATION
(GROSS)
Granulomatous
disease can
become quite
extensive.
Here are
numerous
confluent
granulomas in a
case of pulmonary
tuberculosis.

GRANULOMATOUS INFLAMMATION(MICRO,L.P.)
The focal nature of
granulomatous
inflammation is
demonstrated in this
microscopic section of
lung in which
there are scattered
granulomas in the
parenchyma.

GRANULOMATOUS INFLAMMATION (MICRO,L.P.)

G 4
Identify the condition
Describe gross findings

GRANULOMATOUS INFLAMMATION (MICRO,H.P.)

GRANULOMATOUS INFLAMMATION (MICRO,H.P).

Actinomycosis
Causative Agent is Bacterium
Actinomycosis Israeli..
Gross-Painless mass at jaw cervicofacial,
pulmonary, ileocecal region.
The mas has discharging sinuses draining
yellow sulfur granules with centrsl necrotic
area.

ACTINOMYCOSIS(MICRO)
Actinomy
cotic
colony in
dilated
bronchus.

Repair
The injured tissue is replaced through regeneration
of native parenchymal cells, by filling of the
defect with fibrous tissue (scarring) or, most
commonly, by a combination of these two
processes.
Granulation tissue
It is formed during the process of repair.
Grossly, pink & granular soft tissue formed at the
surface of the wounds and is characterized by
proliferation of blood vessels & fibroblasts and
with some degree of inflammatory cells infiltrate .

GRANULATION TISSUE(H.P.)
 At high
magnification,
granulation
tissue has
capillaries,
fibroblasts, and a
variable amount
of inflammatory
cells (mostly
mononuclear).

GRANULATION TISSUE
Healing of
inflammation often
involves in growth of
capillaries and
fibroblasts. This forms
granulation tissue.
Here, an acute
myocardial infarction
is seen healing.

Pathological aspects of repair
Repair will be abnormal in following
conditions:
1. Deficient scar formation: Wound
dehiscence (or rupture) and ulceration.
2. Excessive formation of the repair
components: Hypertrophic scar and
keloid.
3. Formation of contractures.

Cont…
Hypertrophic scar shows excess amount of
collagen deposits.
Keloid is overgrowth of scar tissue beyond
the boundaries of original wound healing. It
shows excessive hyalinisation.

KELOID (GROSS)

KELOID (MICRO)

Definition
• TB (Tuberculosis) is potentially fatal
contagious disease that can affect almost
any part of the body but is mainly an
infection of the lung.
• Tubercle-Round nodule/swelling
• Osis-Condition

Etiology
• Mycobacterium Tuberculosis from the
family Mycobacteiaceae.
• First discovered by Robert KOCH in 1882.
• So called as KOCH BACILLI.
• Although classified as gram positive but its
reaction is weak.

TUBERCULOSIS
Genus Mycobacterium
waxy cell wall composed of mycolic acid
Acid Fast

METHODS FOR
DEMONSTRATION
Ziehl Neelson’s stain 20% Sulphuric acid
Culture in LJ medium-6 weeks
Sputum,bronchial washings,urine,fluid
analysis-microscopic & culture
PCR
IgG antibodies

TB flourishes wherever there there is
poverty, crowding & chronic deblitating
disease.
DISEASES INCREASING RISK
* Diabetes mellitus - Hodgkins lymphoma
* malnutrition - immunosupression
* chronic lung & renal disease

Development of Monocytes/Macrophages

< 3 weeks

Lung, Ghon complex - In the radiograph and in the photograph, a
calcified, well-circumscribed nodule in the left lung represents an old
healed focus of primary tuberculosis; these are characteristically
peripheral in location. In addition, other calcified nodules can be seen in
the radiograph in the left hilar region -This is a former focus of infection
by TB in draining lymph nodes.
•CALCIFIED
LYMPHNODE
•SUBPLEURAL
NODULE

•Caseous
necrosis
•Zone of
epitheloid
cells
Lung, left, caseous necrosis - Low power
There is a large central area of caseous necrosis, which is seen as
granular pink structureless material with complete destruction of the lung
parenchyma. The caseous material is surrounded by a cellular zone that
contains epithelioid cells and giant cells. These cells are seen at a higher
magnification in the next image. At the periphery, some alveolar spaces
can be seen.

In this higher magnification of the lung lesion, caseous necrosis is seen
as pink granular structureless material that has destroyed the lung
alveoli. Epithelioid cells surrounding the caseous material are
elongated cells with indistinct cell boundaries. Individual epithelioid
cells are difficult to see in this lesion. A large multinucleated giant cell
is clearly visible. The cells with dark round nuclei are lymphocytes.

Testis, granulomatous inflammation - High power Granulomatous
inflammation with caseous necrosis.
•Caseous
necrosis
•Epitheloid
histiocytes

Lymph node, noncaseating granulomas - Low power. This image is of a
lymph node from a patient with sarcoidosis and is provided here for
comparison with the caseating granulomas of tuberculosis. Each of these
clusters of pink cells is a granuloma composed of interlacing epithelioid
cells and giant cells. Note the absence of caseous necrosis. While
granulomas in sarcoidosis do not have caseous necrosis, it should be
remembered that early lesions in tuberculosis may also have
noncaseating granulomas. .
•GRANULOMA
•GIANT CELL

- Lung, left, acid-fast stain - High power Reddish rods = acid-fast
bacteria (Mycobacterium tuberculosis) seen within an area of caseous
necrosis

Lung, tuberculosis, secondary (reactivation) - The cavities in the upper
lobes are the pathologic and radiographic findings in secondary, or
reactivation, tuberculosis. The major bronchi have been opened to reveal
mucosal hyperemia, which indicates congestion or inflammation of the
bronchial mucosa. In addition, patchy consolidation is present in the
upper lobe; this may represent either superimposed bronchopneumonia
or progressive
•CYSTIC CAVITIES
•PATCHY
CONSOLIDATION

Spleen, miliary tuberculosis - Gross, cut surface This cut surface of the
spleen shows multiple light tan areas of caseous necrosis, which look
like multiple small abscesses grossly. Miliary tuberculosis may occur in
patients after either primary or secondary (reactivation) tuberculosis

PRIMARY TB
Ghon focus-lung lesion
Ghon complex-lung+LN
Ranke complex-detected on X-ray

SECONDARY TB
Fibrocalcification
Miliary TB
Progressive pulmonary TB
Endobronchial,endotracheal,laryngeal TB
Systemic miliary TB
Isolated organ TB
Lymphadenitis,intestinal TB

EXTRAPULMONARY TB
Often due to reactivation or re-infection.
REACTIVATION:
Common
Represents breakdown of immunity
REINFECTION:
Due to partial immunity.
Load of bacteria to cause this must be relatively large.

MODE OF SPREAD OF EXTRA PULMONARY TB
Primary
focus
Bacteria invade pulmonary
vein in vicinity
Bacteria try to
invade systemic
circulation
Impaired Phagocyte
Function
M
E
T
A
S
T
A
S
I
S
Kidney
Adrenals
Fallopian tubes
Epididymis
Bones & Joints
Tendon Sheaths

Tuberculous Lymphadenitis
Commonest form of extra pulmonary TB.
Cervical lymphadenopathy most common.
Nodes are firm and often matted due to periadenitis.
Common cause of pyrexia of unknown origin

Stages Of Cervical Lymphadenitis
 Enlargement
 Matting
 Cold Abscess Formation
 Burst abscess in deep fascia
(Collar Stud Abscess)
 Sinus Formation.
(1)
(2)
(3)
(4)
(5)

CNS Tuberculosis
 Organisms reach brain via blood.
 Common in HIV patients
1) TB Meningitis
2) Tubercular Abscess (Tuberculoma)

Tuberculoma

Abdominal TB
 It may be Primary or secondary.
 Swallowing of sputum in patients with active
tuberculosis causes sec. TB
 Most common site - Terminal Ileum
 Types Of Intestinal TB:
1. Ulcerative
2. Hyperplastic
3. TB Peritonitis
4. TB Lymphadenitis

Tuberculous Ulcer

TB Bones and Joints
Occurs secondary to lypho-haematogenous
dissemination from primary focus and later
reactivation.
Most commonly involves Spine (Pott’s Spine)
Tuberculous arthritis and Ankylosis.

Potts Spine

Renal TB

Lupus Vulgaris

MILIARY TB
Haematogenous spread
Millet sized casseous necrosis 2-3mm foci
Involvement of multiple organs
Rapid spread and detioration occurs in a
short period of time

MAC COMPLEX
Mycobacterium avium intracellulare
complex
More common in soil,water,dust and
domestic animals
More seen in AIDS with CD4
lymphocytes<60 cells/mm3
Abundant acid fast bacilli seen within
macrophages involve LN,lung,liver,spleen
Granulomas,lymphocytes, tissue destruction
is rare

CLINICAL FEATURES
Malaise,fever,anorexia,weight loss
Low grade ,intermittent with night sweats
Haemoptysis and cough
Pleuritic pain

LEPROSY & SYPHILIS

Modified Ridley & Jopling’s
classification of leprosy
TT – Tuberculoid polar
BT – Borderline tuberculoid
BB – Mid borderline
BL – Borderlinne lepromatous
LL – Lepromatous polar

Lepromin Test
Used for classifying leprosy on basis of
immune response
Early reaction: induration within 24 to 48
hrs
Delayed granulomatous lesion: After 3 to 4
wks
Pts with tuberculoid leprosy give positive
lepromin test and lepromatous leprosy pts
are negative

Tuberculoid (TT): well defined infiltrated lesion

Borderline tuberculoid (BT) : Note loss of hair and a satellite
lesion.

Borderline (BB)Large tuberculoid type and small
lepromatous type lesions.

Borderline(BB): Close up of a typical BB lesion with
‘inverted saucer’ appearance.

Borderline (BB) in reaction : the lesions are oedematous and scaly

Borderline lepromatous(BL):multiple illdefined and
some ‘BB’ type lesions

Trophic ulcer on anaesthetic foot.

Neuritic leprosy: bilateral ulnar neerve palsy: no skin
lesions

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Lepromatous leprosy

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Foamy macrophages/ lepra cells in lepromatous leprosy

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Acid fast stain shows organisms (arrows) in a perineural
inflammatory infiltrate.

Syphilis
Primary syphilis (2 to 4 wks) : Chancre
Secondary syphilis (2 to 3 months):
Mucocutaneous lesions and painless
lymphadenopathy
Tertiary syphilis (2 to 3 yrs):
Syphilitic gumma
Diffuse lesions – cardiovascular and
neurosyphilis

Syphilitic aneurysm
Ascending aorta
Arch
Location

Syphilitic Aortitis - VDRL
Gross
 Tree bark appearance
 Cor osteal narrowing
 Aortic root dilatation
 AV – commissural
widening, shortening
of cusps/ bowing/
thickening of cusps
 Jet lesion of AI

Syphilitic Aortitis
Microscopy
 Endarteritis/Periarteritis
 Lymphoplasmacytic infiltrate
 Neovascularisation of media
 Periadventitial scarring
 Secondary intimal thickening/
atherosclerosis

Periarteritis

Endarteritis

Periadventitial scarring

Syphilitic aortitis

Syphilitic gumma of liver

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