PATHOLOGY

Acute and chronic

Inflammation,
and connective repair

5th& 6th Pathology Lab

 INFLAMMATION

Definition: The inflamation represents the common response of tissues to different

injurious agent.
Terminology: by adding the suffix –itis to the inflammatory place name
Depending on persistence of the agents and of the type of tissue reaction
inflammation could be:
- ACUTE;
- CHRONIC.
ACUTE EXUDATIVE INFLAMATION
- is a rapid response to an injurious agent (hours or days) and implies
three major changes: cellular, humoral and vascular ® formation of
an inflammatory exudate.
CLASSIFICATION OF ACUTE EXUDATIVE
INFLAMATION

Ø SEROUS

Ø FIBRINOUS

Ø PURULENT

Ø CATARRHAL*

Ø HEMORRHAGIC*

* Less common
SEROUS INFLAMMATION
The serous exudate – increased fluid
component (rich in proteins: albumines
and globulinsèwatery appearance).
E.g. Serous alveolitis
-It is the first microscopic stage of acute
lobar pneumonia (days 1-2)
Etiology-Streptococcus pneumoniae
infection.
LM:
üIn the alveolus walls :
§ congestion of parietal-alveolar
capillaries
ü In alveolar lumen: serous exsudate
§ eosinophilic fluid;
§ few neutrophils;
§ variable amount of bacteria.

HE
 FIBRINOUS INFLAMMATION
Fibrinous exudate is rich in fibrin (by
precipitation of fibrinogenè fibrin network).
E.g. Fibrinous alveolitis:
• It is the second microscopic stage of acute
lobar pneumonia (days 3-5)
• Etiology: Streptococcus pneumoniae infection.
LM:
ü In alveolus walls:
• congestion of parieto-alveolar capillaries
ü In alveolar lumen: è fibrinous exudate
ü fibrin network;
§ Few neutrophils;
§ Infectious agent.
Evolution: progression to leukocyte alveolitis

Mallory Stain
FIBRINOUS INFLAMMATION

üIn - Fibrinous pericarditis

ü Etiology: AMI, acute pericardial
rheumatism, uremia, TB, chest
irradiation, autoimmune diseases
Fibrinous exsudate is disposed
ü On the surface of epicardium:
-Intense eosinophilic exudate
forming villi or a network containing
few neutrophils;
üEpicardium:
§ vascular congestion;
§ few neutrophils.
 Fibrinous pericarditis

Is an Acute fibrinous exudative

inflammation

Macroscopy: the pericardium is

• opaque
• thickened, covered with a grayish
exudate
• irregular, villous in appearance
• having “bread and butter " / "cat's
tongue“ appearance
SERO-FIBRINOUS PERICARDITIS

Is an Acute exudative sero-fibrinous

inflammation

Macroscopy:
• thickened, opaque pericardium
• irregular in appearance
• covered with grayish exudate
• sero-citrine liquid in the pericardial
sac
 PSEUDOMEMBRANOUS COLITIS
Is an Acute fibrinous exudative
inflammation

• inflammation of the colon most commonly

caused by Clostridium difficile.
• Predisposing factors: administration of
antibiotics

Macroscopy:
• wall thickened by edema and mucosal
congestion
• white-gray deposits, adherent on the mucosal
surface making the detacment difficult è
“pseudomembranes”
• after their detachment, areas of bleeding
ulceration develop
PURULENT
INFLAMMATION
The purulent exudate is
composed by:

§ neutrophiles;
§ macrophages;
§ eritrocytes;
§ necrotic debris;
§ fibrin;
§ bacteria.

The purulent inflammation can be:

DIFFUSED

LOCALISED
pus smear (MGG)
 PURULENT INFLAMMATION in micro cavities: alveoli

E.g. Leucocytic alveolitis

IIIrd microscopic stage of lobar pneumonia

Microscopy:
• parieto-alveolar capillary
network is still congested;
• alveolar lumen contains a
suppurative exudate composed
of neutrophils-PMNs and
macrophages-Mfs
DIFFUSE PURULENT
INFLAMMATION
In: Purulent Leptomeningitis
• Etiology: meningococcus infection,
etc
LM:
ü The meninges is diffusely thickened
by:
• purulent exudate;
• vascular congestion.
The vessels :
• leukocyte margination and
diapedesis
ü Brain parenchyma:
• Congestion &
• Perineuronal and perivascular
edema

HE HE
Coloraţia
Purulent Leptomeningitis
– leukocyte margination and
diapedesis

HE staining
 ???

Macroscopy: the meninges are:

• thickened, opaque,
• covered with a creamy, yellowish
exudate,
• initially arranged along the blood
vessels,
• then filling the cerebral grooves.
 ACUTE DIFFUSE PURULENT INFLAMMATION
Purulent leptomeningitis

Macroscopy
- leptomeninge is yellowish in color
and thickened by diffuse purulent
infiltration allowing the visualization
of the congested vessels with
difficulty.
 Localized purulent inflammation (microabscess)
In: Renal microabscesses
Ø Etiology: hematogenous infection
spreading
Ø Microscopy:
Ø Interstitial renal microabscesses
(localized purulent exudate):
Ø +/- central microbial colonies
Ø Integre and damaged PMNs
Ø fibrin
Ø necrotic detritus
Ø In renal tubes: PMNs highlighted in
the urine summary as leukocyte
cylinders
Ø Glomeruli: normal looking
HE
??
! Hematogenous dissemination

Macroscopy:
• abscesses are located in the
cortex
• subcapsular, yellowish,
prominent areas
• surrounded by a congested
rim
 Pyoemic renal abscesses

- Is a localized acute purulent

exudative inflammation
! Hematogenous dissemination

Macroscopy
- affected kidneys are swelled
and congested presenting
disseminated micro abscesses
on the renal surface.
- micro abscesses appear as
yellow nodules, 2 mm in
diameter, under tension,
surrounded by an hyperemic
rim.
 ???
• Recent localized purulent
inflammation
• Cause: Lobar pneumonia
complication
Macroscopy:
• softening area of low
consistency
• yellowish in color
Lung abscess (recent)
Pulmonary recent abscess:
Is a recent localized purulent
inflammation
(1) the cavity: contains a
suppurative material and air
content (in case of
communication with air
conducts);
(2) the wall has irregular
borders represented by
suppurate necrotic lung
parenchyma;
Lung abscess (old)

Pulmonary chronic abscess:

(1) the cavity: contains a rest of
suppurative material and air
content (in case of communication
with air conducts);
(2) the wall is a thick and fibrotic
by connective encapsulation.
Liver abscesses: Which types ?

1. Pylephlebitic abscess - dissemination by portal vein

2. Cholangitic abscess - biliary dissemination
3. Pyoemic abscesses - hematogenous dissemination
 Liver abscess

Macroscopy: Pylephlebitic abscess

• portal vein dissemination
• unique, rarely multiple
• large in size
• in the vicinity of the liver hilum
 Liver abscesses

Macroscopy: Cholangitic abscesses:

Ø multiple
Ø smaller dimensions
Ø in the periphery of the liver
parenchyma
Ø the content is green
 CHRONIC INFLAMMATION
Definition: The chronic inflammation represents a long lasting inflammatory
process (weeks, months, years) characterized by:

-Important tissue destruction

-Inflammatory infiltrate formed by lymphocytes, plasma cells, macrophages
-Conective tissue repair

!!! Cell player - macrophage

Types
ØNonspecific: a diffuse or focal inflammatory infiltrate with mononuclear cells.
ØSpecific (granulomatous): the specific lesion is granuloma
§ Infectious - TB granuloma
§ Foreign body granuloma
§ Of unknown etiology – In: sarcoidosis (sarcoid granuloma)
 TUBERCULOUS INFLAMMATION
Chronic specific granulomatous
inflammation of immune type, with
caseous necrosis.
Etiology: Mycobacterium tuberculosis
The characteristic micronodular lesion:
TUBERCULOUS GRANULOMA :
Ø giant multinucleated cells
(Langhans);
Ø epithelioid cells;
Ø specifically sensitized lymphocytes
Ø other cells: activated macrophages,
fibroblasts
Caracteristic features :
- Tendency to fusion;
- Tendency to caseous necrosis.
E.g. TB inflammation located HE
at lymph node and lung
Tuberculous lymphadenitis
Tendency to fusion and caseification

HE
 HE
Pulmonary tuberculous
inflammation

Ø Tendency to
Fusion &
Caseous
necrosis
 TUBERCULOUS INFLAMMATION
Macroscopic types of tuberculous lesions
I. Nodular lesions (tubercles)
1. simple nodules
2. polycycle tubercles
3. milliary tubercles
4. tuberculoma
II. Diffuse lesions – result by extension of caseous necrosis
in parenchymal organs:
• Pulmonary apical tuberculous infiltrate
• Caseous pneumonia
on serous surfaces:
• tuberculous peritonitis
• tuberculous pleuresia
• tuberculous leptomeningitis
III. Ulcerated lesions – result by elimination of caseous material by various ways
• in the cavitary organs or surfaces develop - ulcerations (skin, intestinum)
• in parenchymal organs (lung) develop - recent and old cavernae
???
I.TUBERCULOUS NODULAR LESIONS IN TUBERCULOSIS
1. Simple nodules: e.g.
ØApical nodules = Assmann focus
ØPrimary affect= Ghon focus

GHON FOCUS
In: Primary TB – first infection ( childhood)

Macroscopy:
Ø TB Primary complex / Ghon complex
Ø Ghon focus
Ø TB lymphadenitis

Ghon focus

Nodular lesion centred by caseous necrosis

 Assmann nodule
1. Simple nodules: e.g.
ØApical nodule = Assmann focus
ØPrimary affect= Ghon focus

Apical Assmann nodule

In: Secondary TB – reinfection
(adulthood)
Macroscopy: calcified apical nodule
• Nodular lesion centred by caseous
necrosis (grayish chessy-like material)
• Deposits of calcium salts=dystrophic
calcification
???

Milliary tubercles in
-systemic miliary tuberculosis (infant organs)
-pulmonary miliary tuberculosis (adult lung)
In: primary TB / secondary TB
 TUBERCULOUS NODULAR LESIONS IN TUBERCULOSIS
2. Milliary tubercles
- are nodular lesions of 1-3 mm in diameter
centered by caseous necrosis (grayish in
color)
- can result by hematogenous dissemination

Milliary tubercles in pulmonary miliary tuberculosis (adult lung)

In: secondary TB
 TUBERCULOUS NODULAR LESIONS IN TUBERCULOSIS
Milliary tubercles
• Hematogenous dissemination in an organism
with a very low immunity
Macroscopy:
• multiple small nodular lesions (2 - 3
mm)=similar to millet seeds in dimension
• grayish in color, well defined, separated by
normal lung
• spread over the entire surface of the affected
organ.
• It affects any organ, often the lungs, liver,
kidneys.
• In: primary TB
Milliary tubercles
In: primary TB
pulmonary miliary tuberculosis (infant lung)
 TUBERCULOUS NODULAR LESIONS IN TUBERCULOSIS
3. Polycycle tubercles
- are nodular lesions
• centred by bronchi
• irregular contour by involvement of
adjacent alveoli
• separated by normal lung parenchyma
- Dissemination along of bronchial tree
- Develops in Tuberculous Bronchopneumonia

Polycycle tubercles
In: secondary TB
Tuberculous Bronchopneumonia
TUBERCULOUS NODULAR LESIONS IN TUBERCULOSIS
Polycycle tubercles

• ! Circumscribed nodular lesions

• Dissemination of bacilli through the

bronchial tree
Macroscopy
• circumscribed lesions - polycycle
tubercles (0.5-1 cm)
• grayish in color
• irregular outlines, centered by a
bronchiole

In: secondary TB

Polycycle tubercles
In: Tuberculous Bronchopneumonia
 II.DIFFUSE LESIONS – In: TB PNEUMONIA

Caseous pneumonia:
Caseous pneumonia is the result
of replacement of entire lung
lobe by caseous necrosis with
destruction of normal lung
structure (lack of anthracotic
pigment).
 II. DIFFUSE LESIONS – In: Tuberculous peritonitis

Tuberculous peritonitis:
(a) milliary nodules disseminated on peritoneal surface;
(b) fibrinous exudate in the peritoneal cavity;
 II. DIFFUSE LESIONS – In: Tuberculous leptomeningitis

Tuberculous leptomeningitis:
a) milliary nodules disseminated on
meningeal surface;
b) fibrinous exudate covers the
cerebral basis
 III. ULCERATED LESIONS – IN TUBERCULOSIS
TUBERCULOUS CAVITIES OR CAVERNAE
- are cavities resulted by elimination of caseous necrosis by expectoration
TYPES
Recent cavities/caverns:
- loss of substance within lung parenchyma
- thin walls covered by deposits of caseous necrosis
Old cavities/caverns:
- large loss of substance, 1-3 cm in diameter
- thick, smooth, clean walls (fibrotic walls)
- the cavity can be traversed by connective-vascular bridges
 TB recent cavities/caverns – In:
Apical fibro-caseous cavitary tuberculosis
Ulcerated lesions è caverns +
circumscribed nodular lesions (polycyclic
tubercles) ; In: secondary TB
•Apical recent cavities occur by draining
the apical caseous material through a
bronchus and eliminating it externally by
vomiting
• By caseous aspiration can result basal
polycyclic lesions in the lung-free
territories producing tuberculous
bronchopneumonia.
Macroscopy: recent caverns
• The result is one or more incompletely
evacuated cavities, with thin walls, lined
with remnants of caseous material
 TB old cavities/caverns – In:
Advanced fibro-caseous cavitary tuberculosis
Ulcerated lesions è caverns;
In: secondary TB
Macroscopy: TB old caverns
• They are completely evacuated
cavities, with thick fibrotic walls,
with clean internal surface (no
remnants of caseous material)
• In addition: extensive fibrosis
•Perivascular and peribronchial
fibrosis and thickened pleura with
multiple fibrotic adhesions are
identified.
BONE ULCERATIVE LESIONS

???
 TB ULCERATIVE LESIONS
They are ulcers in
cavitary organs or surfaces

E.g. Tuberculous ulceration (ileum – small

intestine):
The ulceration of the ileum intestinal
mucosa, has the long axis perpendicularly to
the longitudinal axis of the small intestine,
and is covered by caseous material.
 HEALING
- is the ability of the body to replace dying cells and to repair damaged tissues
The healing of lesions from inflammatory focus is characterized by 2 types of processes:
• regeneration
• connective repair
REGENERATION: replacement of injured tissue by the same tissue type
• It occurs in injured tissues that kept the capacity of dividing.
REPAIR: replacement of injured tissue by connective tissue
• It occurs in injured tissues that lost capacity of cell division
• Takes place in large tissue destructions: inflammation, necrosis, etc.
The characteristic element of connective repair is:
Granulation tissue (GT) (fibro-vascular tissue of neoformation).
Macroscopy- GT looks like flesh meet granules
Microscopy: GT is composed of new capillaries and fibrous tissue
• GT is involved in processeses of
• Connective organization and
• Connective enncapsulation
 CONNECTIVE REPAIR

Ø Represents the morphological and functional recovery of the injured tissue by

fibrous tissue (in large tissue destructions: inflammation, necrosis)

The characteristic element of connective repair is:

Granulation tissue (connective-vascular tissue).

It could be:
Ø vascular
Ø fibro-vascular
Ø fibrous
 Examples of connective repair

Connective organization

• Replacement of inflammatory exudate by granulation tissue

• Connective organization of a thrombus
• Connective organization of myocardial infarction

Connective encapsulation

Is specific to the large lesions that could not be repaired by connective

organization

At the periphery of these large areas (abscess, hematoma) develop a

connective-vascular tissue that by maturation forms a connective capsule
limiting the affected area by the rest of the tissue.
 LM: Granulation Tissue
• VASCULAR
GRANULATION TISSUE • FIBRO-VASCULAR
(Vascular granulation tissue-VGT) • FIBROUS

Microscopy:
Ø New cappilaries
(with prominent endotelium);

Ø Inflamatory cells (neutrophils,

macrophages, lymfocytes) and eritrocytes.

ØEosinophilic transudate.

ØRare fibroblasts;

HE
 GRANULATION TISSUE LM: Granulation Tissue
• VASCULAR
(fibro-vascular granulation tissue-FVGT) • FIBRO-VASCULAR
• FIBROUS

Connective organization of
myocardial infarction

Microscopy:

Ø A decreased number of new capillaries

with flat endothelium and large lumen;

Ø A decreased number
of inflammatory cells
(lymphocytes, macrophages).

ØNumerous fibroblasts.

HE
 GRANULATION TISSUE LM: Granulation Tissue
• VASCULAR
(fibro-vascular granulation tissue FVGT) • FIBRO-VASCULAR
• FIBROUS
Eg.Connective Organization of
an occlusive thrombus
In: Occlusive thrombosis – lung venous
vessel
Occlusive thrombus is replaced by a fibro-
vascular granulation tissue
Ødecreased number of new capillaries
• decreased number of inflammatory cells
• numerous fibroblasts

Evolution – blood reflow by:

Ø Thrombus recanalization due to vessel
dilation

HE
 LM: Granulation Tissue
GRANULATION TISSUE • VASCULAR
• FIBRO-VASCULAR
(Fibrous granulation tissue-FGT) • FIBROUS

In: Wall of liver chronic abscess (connective encapsulation)

Microscopy
- External wall layer: FGT
Ø Rare vessels
Ø Numerous fibrocytes;
Ø Collagen fibers.
- Internal wall layer
Ø Fibrin network and
PMNs
The wall is infiltrated by
PMNs= pyogenic
membrane
- The abscess cavity
contains pus

HE
 Connective organization of myocardial infarction
SCAR MYOCARDIAL INFARCTION

ØArea of circumscribed ischemic

necrosis caused by sudden suppression
of coronary circulation (acute ischemia)
in the corresponding territory.
Ø! 99% of cases - complicated
coronary ATS
Ø! 7-8 weeks
Macroscopy :
Øpearly white area
Øirregular margins
Øthin, retracted ventricular wall
 Connective organization of renal infarction
SCAR RENAL INFARCTION

old / healed infarction

• pearly white, stellate, retracted scar

Connective organization of the renal infarction

is the replacement of the area of renal necrosis
with connective-vascular tissue of
neoformation, which by aging becomes a white
fibrous scar.
 Connective organization of spleen infarction
SCAR SPLEEN INFARCTION

old / healed infarction

• pearly white, retracted
scar
Connective organization of the abscesses and pleural exudate

In: pahipleuritis
• Cause: complication of abscess
opening in pleural cavities
Macroscopy:
Old abscess:
• thick, fibrotic smooth walls
• content – free cavity by evacuated
pus within pleural cavities
Pleural symphysis:
• Thick fibrotic pleural layers connected
by a adherences
Connective organization of the pleural exudate
In: Pleural symphysis

Thick fibrotic pleural

layers connected by a
adherences

Pleural symphysis is the result of connective organization of the intrapleural

fibrino-purulent exudate. By replacing of intrapleural exudate with granulation
tissue, the result is fibrotic thickening of the pleural layers and fibrous adherences
between the two pleural layers (pleural symphysis)
 ?? Connective organization lesions
Lung extensive fibrosis occurs in TB:
(a) around cavities - pericavitary
fibrosis;
(b) around bronchi - peribronchial
fibrosis;
(c) around vessels – perivascular
fibrosis (pulmonary
hypertension);
(d) diffused fibrosis in the lung;
(e) pleural fibrosis and adhesive
connections between the two
pleural layers (pleural symphysis).

Pleural symphysis results by connective organization of pleural sero-fibrinous

exudate with formation of adherences between the two pleural layers and fibrous
thickening of them.