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Def :
It is a local response of living tissue to injurious agent w` consists of a serie of vascular,
lymphatic & local tissue changes. The suffix (itis) is usually added to organs name to
designate its inflammatory nature as tonsillitis & appendicitis.
Aim of inflammation :
1. destroy, dilute, remove or localize injurious agents .
2. prepare tissue for repair .
Failure of inflammatory reaction lead to :
1. spread of infection .
2. no healing of burns & wounds .
Cause of inflammation :
injurious agents w cause inflammation are called irritants.
These may be :
(a) Living irritants : bacteria, viruses, fungi & parasites .
(b) Non living irritants Include :-
Physical irritants : as mechanical trauma, heat, cold, electricity, ionizing radiation.
Chemical irritants : as acids, alkalis.
Necrotic tissue : Irritate adjacent living tissue.
Immune mechanism : (Ag / Ab reaction)
Battleground :
the defense forces of the body meat the irritant in the ground substance of CT .
According to the duration of irritation, it is classified into :-

Acute inflammation Chronic inflammation
Irritant Severe Mild
Onset Sudden Gradual
Duration Short [ days weeks ] Long [ months years ]
Marked Mild
Bl. Vessel Thin dilated congested Thick [ EAO ]
Inflam. cells Macrophage - neutrophil - pus
Macrophage lymphocyte pl. cell
giant cells
Arrangment Diffuse Perivascular or diffuse
Macrophage From blood monocytes From tissue histocutes
Rx. Exudative Proliferative
Fibrosis Absent or mild Marked
Repair Follow Associate
Toxemia Severe Mild
Red hot pain swelling loss
of function
Not present except swelling
Fever present
Leucocytosis present
Normal or decrease
Types Suppurative or non suppurative Specific or non specific

Acute inflammatory cells Chronic inflammatory cells
Plasma cells
Giant cells , fibrocytes
I - Acute inflammation

1\General ch` of acute inflammation :-
- Sudden onset - Severe irritant - Short duration
- Short duration - Severe tissue injury

2\ Morphological changes in acute inflammation :-
1) Vascular changes ...... ( local vascular phenomenon )
2) Exudative changes.
3) Local tissue changes.

1) Vascular changes ...... ( local vascular phenomenon )

Antibodies & WBCs (defense mechanisms) are carried in blood hence the importance of
vascular changes in acute inflammation:-

1- Transient V.C : due to direct effect of irritant on bl. vessel.
2- Permanent V.D : due to chemical mediators.
3- increase Blood flow : increase hydrostatic pressure hotness , redness.
4- Fluid exudates : escape of plasma rich in proteins to interstitial tissue through
High permeability of capillaries.
5- Slowing of blood flow due to :-
a) Increase viscosity due to fluid exudates.
b) Opening of capillary bed.
c) Swelling of endothelial cells project into lumen resist blood flow.
6- Cellular exudates : = change in blood cells :-

Def :
Escape of some leucocytes outside blood vessel towards irritant
guided by chemotactic agents.
Steps = mechanism :
1. Migration of leucocytes = pavementation of endothelium :-
Leucocytes leave axial stream steak to endothelial cells first loosly then
become adherent due to slowing of bl.flow & chemical mediator.
2. Emigration of leucocytes : active process
WBCs move by amoeboid movement through inter-endothelial gaps towards
3. Diapedesis of RBCs : passive process
Some RBCs pushed by blood pressure & follow passage of leucocytes
4. Chemotaxis : directional amoeboid movement of leucocytes on fibrin threads
towards irritant guided by chemotactic agent.
5. Phagocytosis : [ discussed after ] .

2) Exudative phenomenon .. (changes)

vascular changes escape of plasma WBCs from blood vessels into the interstitial
tissue forming ! inflammatory exudate w` consists of.
(A) fluid component (fluid exudate)
(B) cellular component (cellular exudate)

a- fluid exudate

Def :
accumulation of plasma fluid rich in protein in imterstitial spaces due
to acute inflammation process Pathogenesis = aetiology :
1. increase hydrostatic pressure : increase blood flow.
2. increase capillary permeability due to damage of endothelium & widening of inter-
endothelial spaces.
3. increase tissue osmotic pressure due to escape of pl.protein into interstitial spaces.
4. Splitting of large molecules of pl.protein into small ones.

Amount depend on :
- nature of irritant : excess in toxins.
- Site of inflammation : excess in loose area / scanty in solid area.
- State of lymphatics : decrease drainage of fluid exudates its accumulation.

Composition :
contain protein fibrin inflammatory cells.

Fluid exudates Fluid transudate
Def As before Normal fluid present in tissue but
when increase : cause edema
Aetiology As before Increase capillary pressure
Formation Active Passive
Ptn content 4 - 8 gm% < 4 gm%
Inflam. cells Present Absent
Rich in fibrin , so clot on standing Little , so not clot on standing
> 1018 < 1014

Function :
a) Diluting ! irritant specially chemical & bacterial toxins.
b) It brings antibodies to ! site of inflammation.
c) High fibrinogen content formation of ! fibrin w serves as : 2b & 2p
I - Barrier preventing spread of bacteria.
I I - Act as bridge for inflam. cells & repair cells.
I I I - Surface phagocytosis.
I V - formation of fibrin plugs that obstruct lumphatics to prevent
lymphatic spread of infection.
d) Carries away waste products of Cs & supplies their nutrition.
b- cellular exudate

The WBCs escape outside the circulation by :
(1) Margination (mentioned) (2) Emigration (mentioned)
(3) Chemotaxis (4) Phagocytosis

1- Chemotaxis

* Def :
directional movement of WBCs towards the irritant e` in the area of
acute inflammation.

* chemotactic agents:
1 - Exogenous : bacterial products
2- Endogenous :- Complement system

* Mechanism of action : -
Chemotactic agents bind to receptors on WBCs increase intracellular
contractile proteins
leukocyte movement.

* Characters :
specific : each organism attract specific leucocytes :-
# cocci attract neutrophils
# Bacilli attract monocytes
# Parasite attract eosinophils
2- Phagocytosis

Def :
process by w neutrophils (microphages) & macrophages ingest , destroy organisms,
necrotic debris & foreign particles

phagocytic Cs are :
(1) Macrophages
(2) Neutrophils
(3) Foreign body giant Cs

Mechanism of phagocytosis:
1. Recognition , attachment : - phagocytic cells attach firmly to irritant.
- in case of living irritant , attachment is helped by :-
a- opsonization : fixation of organism to Ab to be phagocytosed.
b- Surface phagocytosis : fixation against fibrin network or tissue surface.

2. Indigestion : when organism is attached to surface of leucocytes surface
pseudopodia emerge fuse together to engulf organism forming phagosome.

3. Digestion : lysosome + phagosome phagolysosome
discharge of lysosomal content to kill organism.

4. Killing : by
- O2 dependent system by O2 metabolites , H2 superoxide.
- O2 independent system by lysosomal enzyme.

Defective phagocytosis

Def :
Group of disease ch` by defect in one or more steps of phagocytosis.
(A) Extrinsic (acquired) defects :
(1) Steroids
(2) Neutropenia
(3) Systemic diseases as diabetes, nephrotic syndrome & advanced malignancy.

(B) Intrinsic defects (congenital) :-
Chronic granulomatous
disease of childhood
Chediak - Higashi syndrome Lazy leukocyte
- Sex linked recessive
- Microphages & macrophages
do not metabolize O2
cant kill some
- Autosomal recessive
Itcomprises :
a - Neutropenia
b - Defective chemotaxis
c - Non destruction of
phagocytosed bacteria,
- It is fatal
defect in
neutrophil motility

3) Local tissue changes

Local tissue change [ necrosis , degeneration ] :-
- Cells in center of inflame. Area are necrosed & surrounding os degenerated.
- Both cells release chemical mediator ++ vascular phenomenon.
- Local transformation of histiocytes to macrophage.

Cardinal signs of acute inflammation: = Naked eye picture (N/E)
(1) Redness :- first sign noted in ! inflamed area . It is d.t V.D of capillaries.
(2) Hotness :- sign of inflammation of body ( ) skin. It is d.t V.D ++ & bl. Flow.
(3) Swelling :- d.t ++ blood flow & accumulation of fluid exudate.
(4) Pain d.t : chemical mediators.
(5) Loss of function : d.t : Pain & tissue destruction.

M/E of acute inflammation :
(1) Dilatation of arterioles, venules & capillaries.
(2) Edema : pale red homogenous material & separate tissue Cs.
(3) Acute inflammatory Cs : neutrophils, macrophages, some RBCs.
(4) Fibrin threads.
Systemic effects of acute inflammation = general changes
(1)Fever :- when infection associated e spread of! organisms into ! blood.
Cause : pyrogens (i.e. fever producing)
A) Exogenous : released from bacteria & fungi.
B) Endogenous: from WBCs as cytokines (specially interleukin 1 = IL-1 & tumor
necrosis factor = TNF). They ++ heat regulating center of hypothalamus
sympathetic nerve stimulation & V.C. of skin vessels,
decrease heat loss fever.
Fever destroy bacteria but also harmful to body

(2) Leucocytosis : Common e bacterial infection.
Cause : ++ WBCs from bone marrow by IL-I & TNF
N.B : in typhoid leucopenia.

(3) Change in plasma protein level :
increase secretion of protein by liver as [ fibrinogen ceruloplasmin
creactive protein ] : - increase ESR.

(4) Others : as tachycardia , hypertension ,


Def :
chemical substance control process of acute inflammation,they include :-
(1) Cellular factors :
(A) Amines : histamine & serotonin are released from mast Cs,
basophils & platelets.
(B) Prostaglandins : released from most Cs.
(C) Leukotrienes : secreted by neutrophils.
(D) lysosomal components : released from neutrophils, macrophages & platelets.

(2) Plasma factors :
(A) Kinin systeme.g. bradykinin formed as follows
(B) Complement system : series of plasma proteins ,present as inactive forms in
plasma (numbered C1 C9). Activation either by :-
(1) Classical pathway : triggered by fixation of C1 to Ag/Ab complex
(2) Alternative pathway : triggered by activation of C3 by Ag/Ab
complex or by certain bacterial endotoxin.
The main active products of complement system are C3a & C5a = anaphylatoxin
w` share in anaphylactic shock.
(C) Coagulation system :- Changes fibrinogen fibrin.
(D) Fibrinolytic system : Dissolves fibrin

Main actions (function) of chemical mediators are:
(1) Vascular dilatation : e.g. by histamine.
(2) ++ Vascular permeability : histamine & kinins
(3) Chemotaxis : leukotrienes , lysosomal components & C5a
(4) Pain : bradykinin.
(5) Fever : IL ,PGs.
(6) Leucocytosis : IL , TNF.

Types of acute inflammation

I - Suppurative inflammation.
II - Non-Suppurative inflammation
I - Acute suppurative inflammation

Def :
Severe acute inflammation characterized by pus formation.
Causes :
Pyogenic (pus forming) bacteria as staphylococcus aureus,
streptococcus hemolyticus, pneumococcus, gonococcus & E-coli.

Def :
Is the fluid formed d.t liquefaction of necrotic tissue & fibrin by proteolytienzymes .
pathogenesis of pus formation : For suppuration to occur 3 factors are required :
1. Tissue necrosis : produced by - powerful toxins of pyogenic bacteria.
- presence of inflammatory edema.
- thrombosis due to slowing of bl.flow & endothelial injury.
There is chemotaxis of large no of neutrophils.
2. Struggleoccur ( ) large no of neutrophil & bateria
death of neutrophils transformed to pus cells.
3. Pus cells produce proteolytic enzyme liquefy (necrotic tissue organism
inflame.cells [ dead, living ] fibrin w` become mixed e` fluid exudates)
forming Pus.
Composition :
- necrotic tissue[ main participate ]
- organism - inflame. cells - fluid exudates
- in old pus : macrophage , cholesterol crystals , fat globules are present.
Characters of pus of staphylococcus aureus :
1. Thick turbid & viscous d.t remnants of tissue destruction especially DNA.
2. Alkaline pH.
3. Yellowish d.t myeloperoxidase of neutrophils. 4. Odorless.
5. Does not clot on standing d.t destruction of fibrinogen by proteolytic enzymes.
Types of suppurative inflammation

I Localized : 1- Abscess 2 - Boil (Furuncle) 3 - Carbuncle.
I I Diffuse : e.g. Cellulitis, suppurative appendicitis... etc.

Def :
A localized suppurative inflammation ! formation of an irregular cavity
containing pus.
Cause :
staphylococcus aureus.
Site :
any where (Common sites are: skin, lung, brain, kidney, liver.... etc.)
Pathogenesis of abscess :
pathogenesis of pus [ as before ]
: co-agulase enzyme divide it into zones :-
early : - central necrotic tissue.
- peripheral area of acute inflame. surround it.
Late : - central necrotic tissue.
- pus cavity surround it.
- area of acute inflammation [ pyogenic membrane ] surround
it e` excess neutrophils.
N/E : cardinal signs of acute inflammation as before( .)
Zones [ early , late ] as before.
M/E : M/E of acute inflammation + acute inflammatory cells
[ mainly neutrophils, pus cells ].
Fate of abscess :
any pus in body must be evacuated because pus can`t be absorped [ ]
- pus can be evacuated either :
1. Surgical method : healing.
2. Spontaneously : complications w` are :
a. local : - ulcer : discontinuity of surface epithelium.
- sinus : blind tract open on surface.
- fistula : tract connect 2 surface epithelium.
- lymphadenitis : inflammation of L.Ns
- lymphangitis : inflammation of lymph vessels.
- phelebitis : inflammation of veins.
b. Systemic : if spread:
- toxemia : toxins in blood.
- pyaemia : circulation of septic emboli in blood e` localization
- septicemia : circulation , multiplication of large No of pathogenic
bacteria & their toxins in blood e`out localization.
c. Chronicity : change to chronic abscess:
N/E :
has thick fibrous wall , smooth lining , covered by some pus w` may
be calcified , surrounded by mild hyperaemic zones.
M/E :
as chronic inflammation [ discussed after ].

Acute abscess Chronic abscess
Same as comparison between acute , chronic inflam. ( ) but
Rough due to fibrin.
Smooth due to fibrosis.
Furuncle (Boil)

Def :
It is small abscess related to hair follicle, sebaceous or sweat gland.
Cause :
Site : mainly hairy parts as face, axilla.
-Multiple neighboring boils are called furunculosis.

Def :
Special type of abscess ch` by intercommunicating suppurative foci opening
on surface e` multiple sinuses.
Cause = aetiology :
1. Staphylococci because it is pyogenic & produce co-agulase enzyme.
2. Thick skin.
3. D.M [ diabetes mellitus ] : common predisposing factor.
Pathogenesis :
1. Pathogenesis of pus
2. Collagen bundles formation.
N/E : 1. site : thick skin . Ex: back of neck ,
2. cardinal signs of acute inflammation :
3. multiple sinuses discharging pus.

M/E : As abscess

As abscess but more likely

Diffuse suppurative inflammation = Cellulitis (phlegmonous inflammation)

Cellulitis : ( )

Def :
acute diffuse suppurative inflammation.

Aetiology :
increase streptococcus haemolytics because it is pyogenic & produce hyaluronidase
enzyme fibrinolycin enzyme.

Pathogenesis :
pathogenesis of pus [ as before ] + no zone formation.

N/E :
1. site : loose C.T Ex : orbit axilla scrotum.
2. Diffuse area w` is congested , edematous , swollen , red , painful &
there is multiple skin scars.

M/E :
Same as abscess. ( )

Complications :

As abscess except : chronicity
No sinus

Abscess Cellulitis

Acute localized suppurative
ch` by pus containing cavity.
Acute diffuse suppurative
Staph. aureus. Streptococcus hemolyticus

1. Pus formation
2. Release of co-agulase enzyme
localize inflammation & divide
it into zones [early , late].

3. Pus is ch` by :
a. thick [large amount of liquefied
b. contain few RBCs.
c. contain few sloughs
- 1 Same
2. Release of hyaluronidase enzyme &
fibrinolysin causing spread of acute
inflam. [no zone formation]

3. Pus is ch` by :
a. thin [ due to fibrinolysin]

b. contain much RBCs.
c. contain much slough.
1. Cardinal signs of acute inflam.
2. Zones:

1. Site : . as before.
2. Diffuse area as before.

Less common More common

II-Acute non- suppurative inflammation

++ RBCs : hemorrhagic inflammation
++ fluid exudate : serous / serofibrinous / Catarrhal
++ necrosis : Necrotizing - membranous - Allergic

Catarrhal inflammation

Def :
Mild acute inflammation of ! M.M characterized by ++ mucous secretion.

Sites :
M.M of R.T or GIT. ! best known example is ! common cold = coryza = Catarrhal rhinitis.

N/E : Mucus membrane is :edematous , congested , swollen and red
& covered e` : 1
serous fluid then mucoserous then mucus.
1.Epithelium may be degenerated , swollen , necrotizing or shedding.
2.Sub-epithelium : M/E of acute inflam. ( ) as before.

Fate :
1) inflammation subsides & regeneration occur.
2) 2ry infection e pyogenic bacteria (exudate becomes muco-purulent).
3) chronic inflammation metaplasia of surface epithelium & fibrosis of
underlying tissue.

Membranous (pseudomembranous) inflammation

Def :
Characterized by formation of membrane formed of fibrin, desquamatedepith & inflam Cs.
Cause :
Bacteria w have a low invasive capacity but grow on ! surface of mucous membrane &
produce exotoxins as : 1. Diphtheria 2 -Shigella (causing bacillary dysentry).
mucous membrane (M.M).
bacteria stick to ! surface of (M.M) releases potent exotoxin. superficial necrosis &
acute inflammation of underlying tissue. As ! exudate passes to ! surface ! fibrinogen in
it clots & encloses ! necrotic epithelium in fibrin network to form ! pseudomembrane
w contains also bacteria, neutrophils & RBCs. Neutrophils accumulate at junction of
living & dead tissue. their digestive enzymes detach ! pseudo membrane leaving a
raw surface.
-Toxemia (as exotoxins are absorbed in ! BI. stream).
N/E : mucuc membrane appear as patches w` are :- ( 8 i )
- multiple. - variable. - irregular.
- grayish yellow in color.
- firmly adherent to underlying tissue.
- slightly raised above surface .
- if removed by force , leave bleeding surface & reform rapidly again.
- later : spontaneously detached.
M/E :
1.Epithelium : replaced by pseudomembrane w` contain :
- fibrin network intangling e`in its meshes [ necrotic tissue,organism , inflam.cells ]
- necrotic tissue.
- organism
- inflam. cells.
2.Sub-epithelium : M/E of acute inflam. ( as before )
Fate: 1) Re-epithelialization 2) Loss of mucosal glands & fibrosis.
Serous inflammation

Def :
Acute inflammation characterized by ++ watery fluid exudate.
Skin as in herpes simplex & burn where watery vesicles are seen.
Serofibrinous inflammation

Def :
Acute inflammation characterized by ! formation of ++ fluid exudate rich in fibrinogen
Cause : It occurs e more severe injuries & greater vascular permeability allows ! passage
of fibrinogen molecules.
Site :
(1) inflammation in serous sacs (pleura, pericardium & peritoneum).
(2) lung alveoli (lobar pneumonia).
Pathology :
(1 ) Parietal & visceral layers become red, opaque, rough & thickened.
(2) Fine gray granules = fibrin are seen on both internal surfaces.
(3) Serous fluid collects in ! cavity
(4) According to proportion of serous fluid & fibrin.
If ++ fibrin deposition is of dry type.
If ++ serous fluid collects in ! sac, !wet type.
M/E :
(1) Serosa of ! visceral & parietal layers are swollen or desquamated bare
(2) fluid exudate rich in fibrinogen from ! bare surfaces changes to fibrin
network on both ! visceral & parietal layers entangling acute inflammatory Cs
(3) subserosa shows hyperemia, edema & fibrin network enclosing the
inflammatory Cs.
Fate : repair by organization.
Hemorrhagic inflammation

Def :
Acute inflammation characterized by vascular damage hemorrhage
Cause :
Severe injuries sufficient to cause vascular damage.
Causative bacteria :Small pox, meningococci, strept. hemolyticus & Rickettsia.
Necrotizing inflammation

Def :
It is acute inflammation characterized by extensive tissue necrosis e.g..
(1) Vincents angina & cancrum oris in ! mouth.
(2) Infective gangrene

Allergic inflammation

A type of infam.l in w` inflammatory reaction results from antigen /antibody reaction.

Course of acute inflammation depends on:

a) type of tissue inflamed
b) amount of tissue destroyed (w depends on ! nature & severity of ! irritant).

Fate of acute inflammation
1 - Resolution = complete restoration of tissues to (N)
normal after acute inflammation.
conditions that favor resolution are :
a- Minimal or no cell death.
b- Rapid removal of inflammatory exudate. e.g. Lobar pneumonia.
2- Healing by fibrosis. After tissue destruction:
a - In tissues that can not regenerate.
b - abundant fibrin or necrosis
3- Progression to chronic inflammation
4- spread death.

II Chronic inflammation

Def :
inflammatory process in w lymphocytes, plasma Cs & macrophages predominate +
formation of granulation tissue fibrosis.
Causes :
(1) follows acute inflammation or
(2) Chronic de novo
Types of ch. Inflammation :
1 - non - specific :
Different irritants can produce this reaction so ! etiology cant be
identified from !reaction.
follows acute inflammation e.g. chronic abscess.
2 - specific =granuloma :
Each irritant produces a specific inflammatory reaction & so etiology can be
identified from reaction e.g. tuberculosis, bilharziasis.
General features of chronic inflammation
1) irritant is mild + prolonged action.
2) Onset is gradual & duration is prolonged.
3) Initial tissue necrosis not marked.
4) Vascular phenomenon less marked than acute type. Arterioles show
thickening & narrowing by proliferation of ! subintimal CT = Endarteritis
obliterans. (EAO)
5) Fluid exudate is not marked.
6) Cellular exudate consists of :-
a - lymphocytes : main cell of ch. inflammation, change to plasma cell & secrete
lymphokine .
b - plasma Cs : produces antibodies.
c - macrophages : are phagocytic Cs widely distributed in tissues & Their functions:
- phagocytosis of necrotic debris & bacteria & other irritants
- scavenger Cs in repair
- Formation of epithelioid Cs & giant Cs
d - giant Cs : formed by fusion of macrophages. It may be :
i - Langhans giant cell type: when ! nuclei are peripherally situated
specially in tuberculous lesions.
II - foreign body giant cell type: when ! nuclei are placed
centrally as F.B reaction.
(7) Associated e repair.
M/E of chronic inflammation is :
1. EAO : arterioles show thickness & ( as above )
2. Fibrosis.
3.Chronic inflammatory cells :
- lymphocytes :.
- plasma cells : as above
- macrophage :..
- giant cells , fibrocytes : ..
Chronic non specific inflame :-
M/E : as above.
Chronic specific inflame :-
M/E : as above + specific features that we can recognize organism from it.

Def :
Chronic specific inflammatory reaction in w` the histiocytes play a predominant
role. It starts as tiny granules w fuse to form tumor - like mass grossly

Types :
1. I nfective granuloma : a - Bacteria : e.g. tuberculosis (TB), leprosy & syphilis ($)
b - Virus : lymphogranuloma inguinale
c - Parasites : e.g. bilharziasis (B)
d - Fungi : Actinomycosis
2. Non infective granuloma:
a - Allergic granuloma : as Rheumatic fever, Rheumatoid arthritis
& crohns disease.
b - Foreign body granuloma : around foreign bodies as beryllium,
catgut, talc powder.
foreign body giant Cs are a prominent feature.
c - Granulomas of unknown cause : as sarcoidosis.

Microscopic picture :

(1) Specific to each irritant .! irritant may be seen inside or outside phagocytic Cs.
(2) Vascular change may not be apparent.
(3) Macrophages, epithelioid Cs & Fb giant Cs are ! main Cs of a granuloma.
(4) Lymphocytes & plasma Cs.
(5) Fibrosis.


Def :
# replacement of damaged tissue by a healthy one.
# occurs when body defense & treatment destroy the irritant.
# macrophages then clean the area (scavenger Cs)

Types of repair :
1. Healing = repair
2. Regeneration : replacement of damaged tissue by same kind of tissue.
3. Fibrosis : replacement of damaged tissue by fibrous tissue.
4.Organization : replacement of non-living tissue by fibrous tissue.
ex : thrombus [non-living tissue] can be transformed to be fibrous tissue [ living ].
5. Resolution : type of repair w` occur e`out cell proliferation.
- occur only by absorption if no necrosis.

1 - Regeneration

Def :
replacement of the damaged tissue by a healthy tissue of the same kind.
So regeneration depend on :-
1. Extent of damage only in stable cells:
a. if small : regeneration.
b. if large : fibrosis.

2. Stage of framework :
a. if injury to parenchyma only : regeneration.
b. if injury to parenchyma + stroma [framework] : fibrosis.
3. Type of cells :

Labile cells Stable Permanent

Cells in continuous
state of proliferation
Cells e` limited capacity of
Cells e` no ability to
ex. 1. cells of epithelial
2. bone marrow cells
3. lymphoid tissue
1. parenchematous cells of all
2. mesenchymal cells as
& chondroblast
1. nerve cells
2. skeletal ms. cells
Repair By regeneration
- if small damage : regeneration
- if large damage : fibrosis
By fibrosis [ gliosis
only in nerve cells ]

examples :
I - Regeneration of skin :
Epidermal Cs (labile Cs) regeneration
Dermis fibrosis e absent skin appendages
(hair follicles, sebaceous & sweet glands.)
II - Regeneration of liver Cs :
1 - mild damage + intact fibrous framework e.g. mild viral hepatitis regeneration
2 - severe damage + destroyed fibrous framework e.g. severe viral
hepatitis, cirrhosis (loss of ! (N) liver architecture).
III - Repair of kidneys :
1 - tubulear damage : a - intact b.m as in tubular necrosis Regeneration
b - destroyed b.m as in infarction Fibrosis.
2 - glomerular damage Fibrosis.
IV - Repair of muscles : skeletal, cardiac & smooth muscles fibrosis.
V - Repair of bone fracture :-
1. for normal bony union : 2 bony end must be fixed against each other.
2. at site of fracture : there is Hge, necrotic tissue w` are cleaned
by astrocytes ,macrophage.
3. provisional = procallus formation :
Def .
modified type of granulation tissue formed during process of bone healing.
Formed by : invasion of heamatoma at site of fracture by capillaries , fibroblast ,
osteoblast w` lay down osteoid tissue.

Types :
a. External callus : w` encircle broken end from outside.
b. Internal callus : w` encircle broken end from inside.
c. Intermediate callus: w` directly unite broken ends.

4. permanent bone formation [ final remodeling ] :
- external & internal callus : removed by osteoclast.
- intermediate callus undergo ossification , calcification : form lamellar bone
- bone marrow : regenerate.
- final remodeling is completed in about one year.
5.complication = anomalies :
- non union due to soft tissue interposition ( ) bony ends. Ex:muscle
- malunion due to imperfect reduction.
- delayed union due to : infection ischemia old age.
- fibrous union due to poor immobilization of bones.
VI- Repair in nervous system:
A) In CNS :
1. nerve cells repair by gliosis as it is permanent cells.
2. mechanism: destruction of any part of neuron then
astrocytes proliferate & produce gliosis.

B) In PNS:
1. Cutting of nerve : 2 types of degeneration affect both segments
of cut nerve:-
A - Nissel = retrograde degeneration:
- nucleus: eccentric , small , dark stained.
- nissel granules : disappear.
- cells : absorb H2O So become swollen.
- dendrites : disappear.
B - Wallarian degeneration :
- axon : fragmented.
- myelin sheath : break down to myelin droplet.

*Both are absorbed by macrophage*
2.Regeneration = Recovering:-
- nucleus : central in position.
- nissel granules : regenerate.
- cells : normal size.
- axon : grow from proximal segment in rate 1-3 ml / day.
- myelin sheath : reformed by proliferation of schwan cells on both sides.

Complication of repair in PNS :stump [ traumatic] neuroma:

Def :
Whitish painful mass composed of nerve axons , fibers at cut end of nerve
due to non-aproximation of two end together.

2- Healing by fibrosis

Granulation tissue :
transitional tissue = repair tissue following acute inflammation or associates chronic
inflammation and followed by fibrosis & consist of capillaries and fibroblast.

- Structure (M/E) : it is formed of :
1 - Many new capillaries lined by swollen endothelial cells
without a basement membrane.
2 - Fibroblast cells appear between ! capillaries.
3 - The ground substance between the capillaries and around fibroblasts shows
homogenous, pale pink exudate
collagen fibers (type III) transforms to bundles (type I).
Mixed acute and chronic inflammatory cells.

- Mechanism of formation = pathogenesis :
1\ Macrophage clean the area.
2\ Capillary proliferation : in 4 steps:-
o budding.
o Solid cords.
o Canalization.
o Establishment of circulation
3\ Fibroblast activation : fibrocytes are activated to fibroblasts w` migrate to area.

Characters (N/E):
1 -red granular & velvety. 2-moist 3- fragile bleeds easily
4-Resistant to infection (contain fluid exudate w contains macrophages).
5 -high absorptive power (as it is vascular)
6-Not sensitive (as it is devoid of nerves)

- Fate :
ends in formation of scar(fibrous tissue):-
1 - Fibroblasts produce ! ground substance & 15 types of collagen fibers (I,II,III
etc.( d.t transformation from one type to another). ! Cs & fiber lie in all directions.
2 - Collagen compresses & obliterate ! capillaries.
3 - Fibroblasts contract (termed myofibroblasts as they develop actin filaments in
their cytoplasm. so ! lesion gets smaller.
4 - Fibroblasts change to fibrocytes.
5 - Fibrocytes & collagen fibers are remodeled.
6 - Finally avascular fibrous tissue (a scar) is produced.

Healing of wounds . ( Example of fibrosis )

1ry union = 1st intension 2ry union

Occur in
Surgical wound ch` by :-
- clean.
- minimal tissue loss.
- edge are
approximated together
- haematoma is
Infected wound ch` by :-
- infected.
- excess tissue loss.
- gapping edge.
- haematoma is marked.
Inflam. Rx.
Minimal Excessive
Fluid exudates
Minimal Excessive
Granulation tissue
Minimal Excessive
Tissue destruction
Minimal Excessive
Mechanism of repair
Epidermis cover 1st. Granulation tissue cover 1st .
Wound contraction
Les marked More marked
Time consumed
Short Prolonged
Scar left
Thin , linear Thick , irregular
Rare More common
Healing of wound

1\ Healing by primary union = 1st intension:-
- type of wound :
clean non - gapping wound.
- mechanism :
Day 1 gab is filled e` clotted blood covered by scab of dry
clotted blood on surface.
Day 2 at both edges : epidermal regeneration occur e` formation of basement
membrane & pass across blood clot.
- neutrophil invade wound gab.
Day 3 macrophage replace neutrophils & start phagocytosis.
Day 4,5 - granulation tissue fill gab.
- collagen fibrils start to appear.
2nd week - collagen increase accompany by capillaries disappearance.
- scab separate.
4th week mature scar formed of regenerated epidermis , lost skin
appendage e` dense collagen bundles in dermis.

2\ Healing by 2ry union = 2ry intension :
- type of wound :infected gabbing wound.
- mechanism :
similar to mechanism of 1ry union except differ in following :-
a. excess necrotic tissue ,inflam. ,exudates that must be removed
so taking long period.
b. epidermal regeneration occur but don`t cover gab except after removal of
necrotic tissue & filling gab by granulation tissue.
c. large G.T [ granulation tissue ] : so big scar is formed.
d. wound contraction is major difference done by myofibroblasts.

Complication of wound healing

1 - More common e` 2ry union.
2 -
Cosmotic deformities : due to excess scarring .
Functional troubles : due to contraction of scar around joints.
Keloid : disscused later
Squamous cell carcinoma may develop but rarely.
Epidermal cyst = implantation cyst:
Cyst filled e` keratin due to proliferation of epidermal cells that may be
trapped e`in depth of wound during epithelial regeneration.
Chronic ulcer , fistula , sinus : due to improper healing caused by either :-
- persistent infection that destroy G.T
- excess deposition of collagenat edge of wound e`out filling wound e` enough

3- Healing by organization

replacement of non-living tissue by fibrous tissue.
Ex: thrombus [non-living tissue] can be transformed to be fibrous tissue [ living ].
- Healing of sero-fibrinous inflammation of a serous sac:
1 - serous component of ! inflammatory exudate is absorbed.
2 - fibrin & cellular exudate change to a structurless mass removed by
3 - Granulation tissue arises from ! subserosal layer & covers both surfaces.
4 - serosal Cs at ! edges of! bare area proliferate & cover ! granulating surface.
Later on ! granulation tissue matures to fibrous tissue.

Effects: according to extent of fibrosis :-
+ (l) Formation of white patch in serous membrane.
++ (2) Band adhesions ( ) ! two layers of ! serous membrane.
+++ (3) Complete adhesion ( ) ! two layers of ! serous membrane.

Q: discuss serofibrinous inflam. & how can it heal ?
Answer : as before as above + mechanism of formation of G.T


Too less cellular proliferation :
1- ulcer 2- sinus 3- fistula 4- stretching of a weak scar incisional hernia.
B-Too much cellular proliferation & fibrosis
1. +++ granulation tissue protrudes above ! level of adjacent skin & block
2. +++ scaring keloid: more common in young Negroes

imbalance ( )collagen synthesis & destruction by collagenase.
N/E : firm raised scar e claw- like processes.
ME: Dense hyalinized collagen bundles parallel to ! surface.


a- Spreads progressively & then stop.
b -may recur after removal.
3- fibrosis (according to ! site)
a -scar in ! skin disfiguring
b- scar in tubular structure stricture of bowel, ureter ....etc.
c -scarring of heart valves stenosis or incompetence.
d -scarring of arterial wall aneurysm
e- fibrosis in ! liver may cirrhosis.
f- fibrous adhesion in peritoneum
g- fibrous ankylosis of joints.
h- cerebral scar cerebral irritation & epilepsy.
4 - painful Scar as in stump neuroma.
5 - epithelium may dip down into ! underlying tissue forming implantation dermoid
6-squamous cell carcinoma rarely develops in a scar.

A- Local factors:
1 infection 2- foreign body 3- ischemia 4 -severe damage (++ necrosis)
B- General (systemic) factors:
1 - Age: repair is more rapid & adequate in young age.
2 - Nutrition
a- decrease protein particularly sulfur containing AA as methionin
needed for collagen synthesis decrease repair.
b- decrease vitamin:
i - vit C deficiency defective formation of collagen & bone
ii- vit D deficiency failure of calcification of bone
c- decrease metals: 1 - zinc deficiency : necessary for collagen synthesis.
2 - Ca++ deficiency: required for CT & bone
3 - Hormones: e.g. cortisol decrease repair.
4 - Systemic disease: e.g. diabetes mellitus ++ susceptibility
to infection delay repair.
5 - Physical agents: e.g. ionizing radiation decrease repair.
6 - Chemicals & drugs e.g. cytotoxic drugs decrease repair.

Control of repair

1 -Contact inhibition: direct contact ( ) similar Cs suppress both division & motility.
In wounds d.t absence of contact inhibition, Cs can migrate to cover ! wound

2 - Chemical mediators: Cell growth is controlled by growth stimulation & inhibition.
a-Chalones (Inhibiting factors): formed by living Cs & -- mitosis in !
neighboring Cs of ! same type.
-Tissue destruction lack of chalones locally, so adjacent living Cs can proliferate.
b-Trephones (Growth factors): stimulate mitosis of! dividing Cs. they contain:-
I - Epidermal growth factor (EGF): ++ mitosis in epithelial Cs & fibroblasts.
Ii - Platelet-derived growth factor (PDGF): ++ mitosis in fibroblasts & smooth ms.
Iii - Fibroblast growth factor (FGF): ++ mitosis in fibroblast & ++ vascularization
Iv - Transforming growth factor- a (TGF-a)- ++ mitosis in epithelial Cs.
v -TGF-B & Tumor necrosis factor (TNF) ++ collagen synthesis.

3 -Collagen synthesis & destruction: net collagen accumulation depends on both
collagen synthesis (by growth factors) & degradation (by collagenases).

4 - Extracellular matrix proteins :consists of structural proteins + adhesive proteins.
- Collagen := structural protein, forming most components of basement membrane.
- Fibronectin: = adhesive protein, w binds ! cell membrane e other proteins as
collagen & fibrin. It is important in cell attachment & movement of Cs.