Notes about inflammation

1. TOPIC 3:
INFLAMMATION

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

7. CAUSES

Physical agents
→Mechanical injuries, alteration of temperature &
pressure, radiation injuries, ultraviolet

Chemical agents
→Organic – microbial toxins & organic poisons
(weedkillers)
→Inorganic – acids, alkaline, drugs

Biological agents/microbes
→Infectious = bacteria, viruses, fungi, protozoa

8. CAUSES

Immunologic disorders
→Hypersensitivity reactions, autoimmunity,
immunodificiency states

Genetic/metabolic disorders
→ Gout, diabetes mellitus

Antigens that stimulate immunological
response

9. CLASSIFICATIONS

10. CLASSIFICATION

Based on duration of the lesion and
histologic appearances

2 classifications
⇨Acute inflammation
⇨Chronic inflammation

11. ACUTE
INFLAMMATION

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

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

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

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

24. Steps of
Acute Inflammation

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

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)

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

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

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

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

49. Morphology of
Acute Inflammation

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

52. BLISTER, “Watery”, i.e., SEROUS

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

54. FIBRINOUS

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

57. PUS
=
PURULENT
ABSCESS
=
POCKET
OF
PUS

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)

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.

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

66. Effects of
Acute Inflammation

67. EFFECTS
2 types of effects
(a) Beneficial effects
(b) Harmful effects

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

70. BENEFICIAL EFFECTS
(c)Fibrin formation:
– Tissue damage is repaired and scars can
form if fibroblasts are involved.

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

76. Course of
Acute Inflammation

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

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

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

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

94. CHRONIC
INFLAMMATION

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

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

111. Causes

Major causes of granulomatious inflammation:
– Bacterial: Tuberculosis, Leprosy, Syphilis, Cat
scratch disease, Yersiniosis
– Fungal: Histoplasmosis, Cryptococcosis,
Coccidioidomycosis, Blastomycosis
– Helminthic: Schistosomiasis
– Protozoal: Leishmaniasis, Toxoplasmosis
– Chlamydia: Lymphogranuloma venerum
– Inorganic material: Berrylliosis
– Idiopathic: Acidosis, Cohn’s disease, Primary
biliary cirrhosis

112. SYSTEMIC EFFECTS
OF INFLAMMATION

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