2. OBJECTIVES
Causes of inflammation
Inflammation classifications
– Acute Inflammation
– Chronic Inflammation
Systemic effects of inflammation
3. INFLAMMATION
Latin word, 'inflammare' = to burn
Body's response to injury
DEFINITION:
− Local defence mechanism initiated
by tissue injury
4. INFLAMMATION
Physiological response to tissue damage
& accompanied by a characteristic series
of local changes
– Inflammatory reaction takes place in the
surviving adjacent vascular & connective
tissues
5. INFLAMMATION
Purpose: Protection
⇨to localize & isolate toxic substances
⇨remove/destroy the injurious stimuli
(pathogens) and damaged tissue
⇨initiate the healing and repair process –
remove the cellular debris from the area
6. NOMENCLATURE
Inflammatory lesion are usually indicated
by the suffix ~'itis'
Example:
⇨Appendicitis = inflammation of the appendix
⇨Meningitis = inflammation of the meninges
Some exceptions, example: pneumonia, typhoid
fever
12. ACUTE INFLAMMATION
Immediate & early response to an
injurious agent = protective response!
→Early vascular response and late cell response
Relatively non-specific response
→eliminate dead tissue, protect against local
infection & allows immune system to
response = beneficial
13. ACUTE INFLAMMATION
Relatively short duration
→ lasting for minutes, several hours of a few
days
→ may range from normal to severe
14. ACUTE INFLAMMATION
5 cardinal signs
1)Rubor
2)Calor
3)Tumor
4)Dolor
5)Functio laesa
- latin words
15.
16. ACUTE iNFLAMMATION
1) Rubor
Redness
Due to dilation of small blood vessels within
damaged tissue as it occurs in cellulitis by the
action of mediators
*cellulitis: inflammation spread to the connective tissue
17.
18. ACUTE iNFLAMMATION
2) Calor
Heat
Results from increased blood flow
(hyperemia) due to:
regional vascular dilation
cellular metabolism
19. ACUTE iNFLAMMATION
3) Tumor
Swelling
Due to accumulation of fluid in the
extravascular space = increased vascular
permeability
20.
21. ACUTE iNFLAMMATION
4) Dolor
Pain
Partly results from the stretching &
destruction of tissues due to inflammatory
edema & part from pus under pressure in as
abcess cavity
Some chemicals of acute inflammation are
also known to induce pain
Bradykinins, prostaglandin & serotonin
22. ACUTE iNFLAMMATION
5) Functio leasa
Loss of function
Inflamed area is inhibited by pain while
severe swelling may also physically
immobilize the tissue
25. Steps of acute inflammation
1) Increased blood flow = hyperemia
2) Exudation of fluids & plasma proteins
Exudate: discharge of fluid or substances from cells
or blood vessels onto the skin or organ surface
3) Emigration of leucocytes
26.
27.
28. Capillaries become engorged & dilated with
blood (congestion)
Leakage of fluids and protein into the
tissues = infiltration of leukocytes into the
area of injury
Leukocytes engulf and digest the pathogens
and help remove it from the area
(phagocytosis)
29.
30. 1) Hyperemia
(a) Injured tissues by any agents
(b) Following injury, both the arterioles
supplying the damaged area and local
capillaries dilate
– increasing blood flow to the site
• this causes redness (rubor) & increased
heat (calor) in the affected region
31. 1) Hyperemia
Caused mainly by local released of a
number of chemical mediators from
damaged cells
Mast cells release histamine in response to
tissue injury or infection
32.
33. INJURY
Damaged Cells
Nervous
Direct
reaction
effect on
(axon
vessels CHEMICAL reflex)
MEDIATORS
VASCULAR
DILATATION
34. 2) Exudation of Fluids
* Exudation: increased passage of protein-rich fluid
through the vessel wall into the interstitial tissue
Fluid leaving local blood vessels &
entering interstitial space = swelling /
oedema
Caused by
→ Increased permeability of small blood
vessels wall
→ Increased hydrostatic pressure
35. 2) Exudation of Fluids
INCREASED PERMEABILITY
Caused by
→ inflammatory mediators released by
injured cells– prostaglandin, histamine &
serotonin
→ cells that formed the single-layered
venules pull apart from one another
36. 2) Exudation of Fluids
INCREASED PERMEABILITY
The opening of channels that allow the
movement of
→ Excess fluid = leaves blood & enters
tissues
→ Plasma proteins =albumin, globulin etc –
normally retained in bloodstream
reduced osmotic pressure of blood
37.
38.
39. 2) Exudation of Fluids
INCREASED HYDROSTATIC PRESSURE
Increased blood flow into the capillary bed
forces fluid out of the vessels & into the tissues
Some interstitial fluid returns to capillaries but
most of the inflammatory exudates, phagocytes
& cell debris removed in lymph vessels
→ pores of the lymph vessels larger & pressure
inside it is lower than blood capillaries
40. 3) Emigration of Leukocytes
Loss of fluid
→ thicken the blood
→ reduced the flow
→ allowing leukocytes make contact &
adhere to the vessel wall = selectin &
integrins
41. 3) Emigration of Leukocytes
Most important leukocyte = neutrophil
→ Adhere to the blood vessels lining
→ Squeeze between endothelial cells
→ Enters tissue and went to the inflamed
area by chemotaxis
→ Main function: phagocytosis of antigen
42. 3) Emigration of Leukocytes
Macrophages
→ larger and longer lived than neutrophils
→ phagocytose dead/dying tissue, microbes
& other antigenic material and
dead/dying neutrophils
→ predominently in inflamed tissue after
24hours
→ persist in the tissue if the situation is not
resolved = chronic inflammation
43. CHEMOTAXIS
Movement of a motile cell/organism in a direction
corresponding to a gradient of increasing or decreasing
concentration of the particular chemotactic agent
– Chemical attraction of leukocytes to an area of
inflammation
44. PHAGOCYTOSIS
eating
Cell
Macrophages & neutrophils attracted to the
inflammatory & infectious site by chemotaxis
Chemo-attractans released by injured cells & invading
microbes
Phagocytes trap particles either by engulfing them with
their body mass or by extending long psedopodia towards
them
Non-selective = bind, engulf and digest foreign cells or
particles
45.
46. CHEMICAL MEDIATORS
Various chemical mediators have roles in
inflammatory process
They may be circulating in plasma and require
activation or may be secreted by inflammatory cells
Mast cells = histamine
Platelets = serotonin
Many of these mediators have overlapping actions
47. Chemical mediators of
Inflammation
Vasodilating Histamine, serotonin,
chemicals bradykinins, prostaglandin
Chemotactic Fibrin, collagen, mast cell,
factors bacterial peptides
Substances with Complement fragments of
both vasodilating C5a and C3a, interferons,
& chemotactic interleukines and platelet
effects secretion
50. MORPHOLOGY
Involves production of exudates (edema
fluid with high protein concentration,
frquently contain inflammatory cells)
*Transudate?
Non-inflammatory edema
Caused by cardiac, renal, undernutritional and other
disorders
51. MORPHOLOGY
Different morphologic types of accute
inflammation
i. Serous inflammation - watery
ii. Fibrinous inflammation - haemorrhagic
iii.Suppurative (purulent) inflammation - pus
iv.Catharral inflammation – mucous membrane
v. Pseudomembranous inflammation
53. i. Serous Inflammation
Characterized by an outpouring of a thin
fluid that is derived from either the blood
serum or secretion of mesothelial cells
lining the peritoneal, pleural, and
pericardial cavities
It resolves without reactions
55. ii. Fibrinous Inflammation
More severe injuries
Result in greater vascular permeability that
ultimately leads to exudation of larger
molecules such as fibrinogens through the
vascular barrier
Fibrinous exudate is characteristic of
inflammation in serous body cavities such as
the pericardium (butter and bread appearance)
and pleura
56. ii. Fibrinous Inflammation
Course of fibrous inflammation include:
– Resolution by fibrinolysis
– Scar formation between perietal and
visceral surfaces i.e. the exudates get
organized
– Fibrous strand formation that bridges the
pericardial space
58. iii. Suppurative Inflammation
Characterized by the production of a large
amount of pus
– Pus is a thick creamy liquid, yellowish or
blood stained in colour and composed of
• A large number of living or dead
leukocytes (pus cells)
• Necrotic tissue debris
• Living and dead bacteria
• Edema fluid
59. iii. Suppurative Inflammation
2 types:
A) Abscess formation:
– abscess = a circumscribed accumulation of pus
in a living tissue
– encapsulated by a so-called pyogenic
membrane, which consists of layers of fibrin,
inflammatory cells and granulation tissue
60. iii. Suppurative Inflammation
2 types:
B) Acute diffuse (phlegmonous)
inflammation
– characterized by diffuse spread of the exudate
through tissue spaces
– caused by virulent bacteria (eg. streptococci)
without either localization or marked pus
formation
– example: Cellulitis (in palmar spaces)
61.
62. iv. Catharral Inflammation
Mild and superficial inflammation of the
mucous membrane
Commonly seen in the upper respiratory
tract following viral infections where
mucous secreting glands are present in
large numbers
example: Rhinitis.
63.
64. v. Pseudomembranous Inflammation
Basic elements
– extensive confluent necrosis of the
surface epithelium of an inflamed mucosa
– severe acute inflammation of the
underlying tissues
The fibrinogens in the inflamed tissue
coagulate within the necrotic epithelium
65. v. Pseudomembranous Inflammation
Fibrinogen, necrotic epithelium, neutrophilic
polymorphs, red blood cells, bacteria and tissue
debris form a false (pseudo) membrane = forms
a white or colored layer over the surface of
inflamed mucosa
Example:
– Dipthetric infection of the pharynx or larynx
– Clostridium difficille infection in the large bowel
following certain antibiotic use
68. BENEFICIAL EFFECTS
a) Dilution of toxins:
►concentration of chemical and bacterial
toxins at the site of inflammation reduced by
dilution in the exudate
►removal from the site by the flow of exudates
from the venules through the tissue to the
lymphatic
69. BENEFICIAL EFFECTS
b) Protective antibodies:
►Formation of tissue exudation allows
protective proteins including antibodies at
the site of inflammation
►Thus, antibodies promote microbial
destruction by phagocytosis or complement-
mediated cell lysis = neutralise their toxins
71. BENEFICIAL EFFECTS
d) Promotion of phagocytosis
►Neutrophils & macrophages actively
recruited to the inflamed areas = engulf
biological & non-biological origin
►Phagocyte activity promoted by increasing
temperature (local & systemic)
►Phagocytes may die at the inflamed area if
the material they ingest resist digestion or
excessive = disintegrate & released material
that cause further damage
72. BENEFICIAL EFFECTS
e) Cell nutrition:
►The flow of inflammatory exudates brings
with it glucose, oxygen and other nutrients to
meet the metabolic requirements of the
greatly increased number of cells
►It also removes their solute waste products
via lymphatic channels
73. BENEFICIAL EFFECTS
f) Promotion of immunity:
►Micro-organisms and their toxins are carried
by the exudates, either free or in phagocytes,
along the lymphatics to local lymph nodes
• they stimulate an immune response with
the generation of antibodies and cellular
immune mechanisms of defence
74. HARMFUL EFFECTS
Tissue swelling
⇨Result of the increased blood flow &
exudation
⇨Often accompanies by loss of function
⇨Effects can be harmful = depending on the
site
• Joint = limitation of movement
• Larynx = interference with breathing
75. HARMFUL EFFECTS
Pain
⇨Occurs when local swelling compress
sensory nerve endings
⇨Exacerbated by chemical mediators of the
inflammatory process that potentiate the
sensitivity of the sensory nerve endings
• Bradykinin
• Prostaglandin
77. COURSE OF ACUTE
INFLAMMATION
possible outcomes depend on removal
of inflammatory exudate and replacement
by either regenerated cells or scar tissue
4 possible outcomes
(1) Resolution
(2) Healing by fibrosis
(3) Abscess formation
(4) Chronic inflammation
78. COURSE OF ACUTE
INFLAMMATION
Factors affecting outcome of acute
inflammation
(1) severity of tissue damage
(2) capacity of stem cells to divide
(3) type of agent causing damage
79.
80. (1)Resolution
involves complete restitution of normal
architecture and function
3 main features which potentiate this
sequel are
→ Minimal cell death & tissue damage
→ Rapid elimination of the causal agent
→ Local conditions favouring of fluid & debris
81. (1)Resolution
Inflammatory process is reversed and
→ damaged cells are phagocytosed
→ fibrin strands are broken down by
fibrinolytic enzymes
→ waste material is removed in lymph and
blood vessels
→ repair is complete leaving only a small car
82. (1)Resolution
Arises from damage to parenchyma in
labile/stable tissues
cells replaced by regeneration
normal function restored
Can only occur if the connective tissue
framework of the tissue is intact & the tissue
involved has the capacity to replace any
specialised cells that have been lost
83. (2)Healing by Fibrosis
Occurs when
connective tissue framework damage
tissue lacks the ability to regenerate
specialised cells
1St: dead tissues & acute inflammatory
exudate removed by macrophages
Defect filled by ingrowth of a specialised
vascular connective tissue called granulation
tissue
84. (2)Healing by Fibrosis
granulation tissue - gradually produces
collagen = form a fibrous (collagenous) scar =
repair
loss of some specialised cells & some
architectural distortion by fibrous scar =
structural integrity is re-established
any impairment of function = dependent on the
extent of loss of specialised cells
85. (2)Healing by Fibrosis
Modified forms of repair occur in
► bone after a fracture when new bone is
created
► brain with the formation of an astrocytic
scar
86. (3)Abscess Formation
Takes place when
acute inflammatory reaction fails to
destroy/remove the cause of tissue damage
continues with a component of chronic
inflammation
Most common: infection by pyogenic bacteria
As the acute inflammation progresses, there is
liquefaction of the tissue to form pus
Peripherally, a chronic inflammatory component
& fibrous tissue surrounds the area = localising puss
87. (3)Abscess Formation
If abscess left untreated, it can lead to
sinus formation
fistula formation
88. (3)Abscess Formation
Sinus
tract lined by granulation tissue
leading from a chronically inflamed cavity
to a surface
cause the continuing presence of foreign or
necrotic material
Example: sinus associated with
osteomyelitis & pilonidal sinus
89.
90. A pilonidal dimple is a small pit or sinus in the sacral area
just at the top of the crease between the buttocks - deep
tract, rather than a shallow depression, leading to a sinus
that may contain hair.
During adolescence the pilonidal dimple or tract may
become infected forming a cyst-like structure called a
pilonidal cyst = may require surgical drainage or total
excision to prevent reinfection
91. (3)Abscess Formation
Fistula
tract open at both ends
Abnormal communication b etween two
surfaces is established
2 main types
congenital = development abnormality
acquired = trauma, inflammation or necrosis
92.
93. (4)Chronic Inflammation
May result following acute inflammation
when an injurious agent persists over a
prolonged period
Causing concomitant tissue destruction,
inflammation, organisation and repair
Some injurious agents induced a chronic
inflammatory type of response from the
outset
95. CHRONIC INFLAMMATION
prolonged inflammatory process
(weeks or months) where an active
inflammation, tissue destruction and
attempts at repair are proceeding
simultaneously
96. Causes
Persistent infections
→Certain microorganisms associated with
intracellular infection = tuberculosis, leprosy,
certain fungi characterictically cause chronic
inflammation
→These organisms have low tosicity and evoke
delayed hypersensitivity reactions
97. Causes
Prolonged exposure to nondegradable
but partially toxic substances
→endogenous lipid components which result
in atherosclerosis
→exogenous substances such as silica,
asbestos
98. Causes
Progression from acute inflammation
→acute inflammation almost always progresses
to chronic inflammation following persistent
suppuration as a result of
• uncollapsed abscess cavities
• foreign body materials (dirt, cloth, wool,
etc)
• sequesterum in osteomylitis
• sinus/fistula from chronic abscesses
99. Causes
Autoimmunity
→autoimmune diseases such as rheumatoid
arthritis and systemic lupus erythematosis are
chronic inflammations from the outset
100. Morphology
Cells of chronic inflammation
– Monocytes & macrophages = main
cells
– T-lymphocytes
– B-lymphocytes & plasma
101. Classification
Classified into 2 types based on histologic
features
1. Non-specific chronic inflammation
2. Specific inflammation
(granulomatous inflammation)
102. Classification
1. Non-specific chronic inflammation
– involves a diffuse accumulation of
macrophages and lymphocytes at
site of injury that is usually
productive with new fibrous tissue
formations
– example: Chronic cholecystitis.
103. Classification
2. Specific inflammation
– Granulomatous inflammation
– characterized by the presence of
granuloma
• granuloma is a microscopic aggregate of
epithelioid cells (modified macrophages)
104. Classification
2. Specific inflammation
– Epithelioid cell
• is an activated macrophage, with a
modified epithelial cell-like appearance
(hence the name epithelioid)
• can fuse with each other & form
multinucleated giant cells – foreign body-
type giant cells & Langhans giant cells
105. Classification
2. Specific inflammation
– granuloma is basically a collection of
epithelioid cells, it also usually
contains multinucleated giant cell &
is usually surrounded by a cuff of
lymphocytes and occasional plasma
cells
106.
107.
108. Pathogenesis
2 types of granuloma
1. Foreign body granuloma
2. Immune granuloma
109. Pathogenesis
1.Foreign body granuloma
– initiated by inert foreign bodies such as
talc, sutures (nonabsorbable), fibers, etc…
– these foreign bodies are large enough to
preclude phagocytosis by a single
macrophage and do not incite an immune
response
110. Pathogenesis
2.Immune granulomas
– antigen presenting cells (macrophages) engulf a
poorly soluble inciting agent
– then, the macrophage processes and presents
part of the antigen and activated lymphocytes
– the activated lymphocytes produce cytokines
that activate another lymphocytes = transform
macrophages into epitheloid & multinucleated
giant cells & maintain the granuloma
– Macrophage inhibitory factor helps to localize
activated macrophages & epitheloid cells
113. Systemic effects of Inflammation
Include
1. Fever
2. Endocrine & metabolic responses
3. Autonomic responses
4. Behavioural responses
5. Leukocytosis
6. Leukopenia
7. Weight loss
114. 1.Fever
most important systemic manifestation of
inflammation. It is coordinated by the
hypothalamus & by cytokines released from
macrophages and other cells
2. Endocrine & metabolic responses
the liver secrets acute phase proteins such as C-
reactive proteins, Serum Amyloid A,
complement and coagulation proteins
Glucocorticoids (increased)
Vasopressin (decreased)
115. 3. Autonomic responses
redirection of blood flow from the cutaneous to
the deep vascular bed
pulse rate and blood pressure (increased)
sweating (decreased)
4. Behavioural responses
Rigor, chills, anoroxia, somnolence and malaise
116. 5. Leukocytosis
also a common feature of inflammation,
especially in bacterial infections
its usual count is 15,000 to 20,000 cells/mm3
most bacterial infections induce neutrophilia
some viral infections such as infectious
mononucleosis, & mumps cause lymphocytosis
parasitic infestations & allergic reactions such
as bronchial ashma & hay fever induce
eosinophilia
117. 6. Leukopenia
Also a feature of thyphoid fever and some
parasitic infections
7. Weight loss
Catabolism of skeletal muscle, adipose tissue
and the liver with resultant negative nitrogen
balance