Pathology Inflammation acute and chronic For Medical students

1. inflammation

2. Furuncle second-degree burn SARS(Severe Acute Respiratory Syndromes)

3. questions
1. What is inflammation?
2. Inflammation is protective or harmful ?

4. Outlines of inflammation
 General Considerations
 Definition; Inflammatory agents; Basic pathological changes of
inflammation; Local and systemic manifestations of Inflammation
 Acute inflammation
 The process of vascular and cellular events in inflammation,
Inflammatory mediators
 The classification and outcomes of acute inflammation
 Chronic inflammation

5. Part 1
General Considerations

6. Definition
Inflammation is a protective response of vascularized
living tissues to local injury due to any agent, leading to
the accumulation of fluid and leukocytes in extravascular
tissues.

7. Purpose of inflammation
• eliminate the initial cause of cell injury
• Remove necrotic cells and tissue
• Initiate the process of repair
• Also a potentially harmful process
– Components of inflammation that are capable
of destroying microbes can also injury bystander
normal tissue.

8. causes
• Physical agents—excessive heat or cold, radiation
• Chemical agents--strong acid/alkali,poisons
• Infective agents--bacteria, viruses
• Immunological agents- cell-mediated and antigen-antibody reaction
• Inert materials --foreign body- splinter, surgical suture
• Ischemic and necrotic tissues
any agents causing local tissue injury can result in inflammation.

9. excessive heat or cold, radiation

10. Cardinal signs of inflamamtion

12. Cardinal signs physiological Actions
1. RUBOR (REDNESS) Increase blood flow
2. TUMOR (SWELLING)
Exudation of fluid
3. CALOR (HEAT) regional increase in blood flow, strong metabolism
4. DOLOR (PAIN)
Stretching of pain receptors and nerves by exudates ＆ mediators
5. FUNCTIO LAESA
(LOSS OF FUCTION)
Pain,
Disruption of tissue structure,
Fibroplasia and metaplasia
Cardinal signs of inflamamtion

13. The arm at the bottom is swollen (edematous) and
reddened (erythematous) compared to the arm at the top.

14. Systemic signs of inflammation
Acute phase reaction
• Fever
• Leukocytosis： 15000-20000/mm3
• synthesis of a variety of proteins
• increased somnolence
• anorexia
• malaise
• accelerated degradation of skeletal muscle proteins

15. Basic morphological changes of inflammation
 Alteration
degeneration, necrosis
 Exudation
hallmark, vascular change, inflammatory mediators )
 Proliferation
parenchymal and stromal cells

16. Basic morphological changes of inflammation
1. Alteration : degeneration, necrosis
• parenchymal cells:
swelling, fatty change, coagulative necrosis, liquefaction necrosis
• stromal cells:
mucoid degeneration, Fibrinoid necrosis

19. Basic morphological changes of inflammation
2. Exudation
The escape of fluid, proteins, and blood cells from vascular
system into the interstitial tissue or body cavities.
inflammatory edema--tissue
inflammatory hydrops--cavity

20. burn blisters pleural effusion

21. alveolar wall
alveolar space
lobar pneumonia

22. Basic morphological changes of inflammation
3. Proliferation
 parenchymal cells
－epithelial cells, glands
 Interstitial cells
--macrophages, endothelial cells, fibroblasts
Limit inflammatory diffusion and repair

23. Alteration, Exudation, Proliferation
1. In one type of inflammatory disease, there is mainly one basic
morphological change.
• viral hepatitis----alteration
• purulent inflammation---exudation
• acute nephritis----proliferation
2. Three basic morphological changes are interchangeable .
3. Alteration is damage course; exudation and proliferation are
anti-injury course.
4. Acute inflammation---alteration, exudation
5. Chronic inflammation---proliferation

24. outcome of inflamamtion

25. CLASSIFICATION OF INFLAMATION
1. Clinical classification
Acute inflammation
--rapidly developing inflamatory
--for short duration (minutes or hours)
Chronic inflammation
--slow and long lasting inflamatory response to injured tissue

26. FEATURES ACUTE CHRONIC
onset Fast: minutes or hours Slow: days
duration Short: days to months Long: months to years
Cellular infiltrate Mainly neutrophils
Monocytes, macrophage,
lyphocytes
Chief pathological event
Exudation of fluid and plasma
proteins
Proliferation of blood vessels
and fibrosis
Tissue injury, fibrosis Usually mild and self limited
Often severe and progressive
Local and systematic
signs
prominent
Less prominent, maybe
subtle

27. CLASSIFICATION OF INFLAMATION
2. Pathological classification
Alteration Inflammation (acute)
Exudation Inflammation (acute)
Proliferation Inflammation (chronic)

28. Inflammatory cells
Polymorphonuclear neutrophils (PMNs)
Functions :
Initial phagocytes
Engulfment
Harmful effect

29. Inflammatory cells
Eosinophils
Increased:
Allergic conditions
Parasitic infections
Skin deseases
Certain malignant
lymphomas

30. Inflammatory cells
Lymphocytes
Roles :
Antibody formation (B lymphocytes)
Cell-mediated immunity (T-lymphocytes)
Inflammations

31. Inflammatory cells
Plasma cells
Eccentric nucleus
Cart-wheel pattern of chromatin
Number increased in the following conditions
• Prolonged infection with immunological
responses (syphilis, rheumatoid arthritis, tuberculosis)
• Hypersensitivity states
• Multiple myeloma

32. Inflammatory cells
Giant cells in inflammation
• Foreign body giant cells (neulei are scattered throughout the
cytoplasm)
• Langhans’ giant cells (nuclei are arranged either around the
periphery in the form of horseshoe or ring, or are clustered at the two
poles of the cell)
• Touton giant cells (lipid content, in xanthoma)
• Aschoff giant cells (rheumatic nodule)

33. Foreign body giant cells

34. Langhans’ giant cells
A giant cell is a mass formed by union several distinct cells(macrophages).
it can arise in response to an infection such as HIV,TB.
Nucleus are ordered arrangement

35. Aschoff giant cells

37. Part 2
acute inflammation

38. Major events of acute inflammation

39. The major local manifestations of
acute inflammation:
(1) vascular dilation;
(2) extravasation of plasma fluid
and protein;
(3) leukocyte emigration and
accumulation in the site of injury

40. Major events of acute inflammation

41. 1. Hemodynamic changes (vascular response)

42. 2. Increased vascular permeability
Depends on the integrity of endothelial cells
E
A. contraction of endothelial cells
(the most common mechanism; venules)
OR retraction of endothelial cells (重构)
B. direct injury to endothelal cells
C. Increased transcytosis
D. leakiness in neovascularisation (newly formed capillaries)
E. endothelial injury mediated by leucocyte

43. 3. Fluid exudation

44. Differences between transudate and exudate
Feature Transudate Exudate
Definition
Filtrate of blood plasma without changes in endothelial
permieability
Oedema of inflamed tissue associated
with increased vascular permeability
Character Non-inflammatory oedema Inflammatory oedema
Protein content
Low(less than 1 gm/dl);mainly albumin, low fibrinogen;
hence no tendency to coagulate
High(2.5-3.5 gm/dl),readily coagulates
due to high content of fibrinogen and
other coagulation factors
Glucose content Same as in plasma Low(less than 60 mg/dl)
Specific gravity Low(less than 1.015) High(more than 1.018)
pH >7.3 <7.3
LDH Low High
Effusion LDH/serum LDH ratio <0.6 >0.6
Cells Few cells, mesothelial cells and cellular debris
Many cells, inflammatory as well as
parenchymal
Examples Oedema in congestive cardiac failure Purulent exudate such as pus

45. Significance of inflammatory exudation
advantages
 Dilute toxin
 Bring nutrition material and carry out metabolized
product
 Antibodies, complement system
 Fibrins prevent microbe spreading
 Stimulate cell immunity and humoral immunity

46. Significance of inflammatory exudation
disadvantages
 Impair wound healing
 compress and obstruction
Severe exudation in important organs may even cause death
 Organization may cause carnification

47. acute laryngeal edema:
child, asphyxia, allergic reaction

48. pulmonary edema
pleural effusion Organization and conglutination

49. Major events of acute inflammation

50. 1) Recruitment of leukocytes to sites of infection and injury
2) Recognition of microbes and dead tissues
3) Removal of the offending agents
4) Release of leukocyte products and leukocyte-mediated
tissue injury
Significance of Cellular Events

51. 1. Leucocyte exudation
a. Leukocyte margination and rolling
b. Leukocyte adhesion
c. Emigration/Transmigration
d. Chemotaxis
• The most important feature of inflammatory response
• Polymorphonuclear neutrophils (PMNs), monocytes and macrophages

52. a. Leukocyte margination and rolling
 Exudation stasis RBC(clumping)
WBC(Neutrophils) pushed into the
margin of blood vessels, the process
is called “MARGINATION”.
Normal: Central axial stream
 Hemodynamic pressure disrupt the
mild adhesion, leukocytes tumble
slowly along the endothelium, the
process is called “ROLLING”.

53. Leukocyte margination and rolling

54. b. Leukocyte adhesion
CYTOKINES
ENDOTHELIAL CELLS
P&amp;E Selectin
Sialyted sugar
MILD ADHESION
chemokines
leukocytes
Change configuration of
Integrin
ICAM-1
STABLE ADHESION

55. c. Emigration/Transmigration
• Speed: Neutrophils(6-24h)＞Monocyte-macrophages(24-48h)＞
lymphcyte＞eosinophilia＞basophilia
• Span: Neutrophils are death in 24-48h
• Bacteria infection: neutrophils
• Virus infection: Lymphocytes
• Allergic reaction: Eosinophilic leukocytes

56. ameboid movement

57. d. Chemotaxis
 After extravasating from the blood, leukocytes migrate toward sites
of injury along a chemical gradient in a process called Chemotaxis.
Chemotactic Factors
i.e.
Bacteria:
Produce certain
peptides having
(N-formyl-methionine
Amino acid).
Injured cells:
Leukotriene B4 (LT-B4).
Plasma protein:
Complement factor ( C5a).

58. 2. Phagocytosis
• Phagocytosis is defined as the process of engulfment
of solid particulate material by the cells (cell eating).
• There are 2 main types of phagocytic cells:
a) polymorphonuclear neutrophils (PMNs)
b) monocytes and macrophages

59. 2. Process of phagocytosis
 Recognition and attachment stage
 Engulfment stage
 Degranulation stage
 Killing or degradation with
lysosomes

60. 2. Process of phagocytosis
Stages in phagocytosis of a foreign particle.
A, Opsonisation of the particle.
B, Pseudopod engulfing the opsonised particle.
C, Incorporation within the cell (phagocytic vacuole) and degranulation.
D, Phagolysosome formation after fusion of lysosome of the cell.

61. Inflammatory mediator
A large and increasing number of chemical substances
which partake in the processes of acute inflammation.
• Function of chemical mediators:
directing the vascular and cellular events in inflammation
• Cell-derived or Plasma-derived mediators
• Act as a complicated network

62. Role of Mediators in Inflammation
Role in Inflammation Mediators
Vasodilation Prostaglandins, Nitric oxide, Histamine
Increased vascular permeability Histamine and serotonin, C3a and C5a,Bradykinin
Leukotrienes C4, D4, E4, PAF, Substance P
Chemotaxis, leukocyte
recruitment and activation
TNF, IL-1, Chemokines, C3a, C5a, Leukotriene B4
Fever IL-1, TNF, Prostaglandins
Pain Prostaglandins, Bradykinin
Tissue damage Lysosomal enzymes of leukocytes, Reactive oxygen
species
Nitric oxide

63. Classification of inflammation
 Acute inflammation
Alteration Inflammation
Exudation Inflammation
 Chronic inflammation
Proliferation Inflammation

64. Alteration Inflammation
Viral hepatitis (hepatocyte necrosis)
Epidemic Type B Encephalitis (neuronal necrosis)
Poliomyelitis (neuronal necrosis)

65. Viral hepatitis--swelling

66. Viral hepatitis---spot necrosis

67. Epidemic Type B Encephalitis
liquefaction necrosis: reticular softening lesion

68. Classification of Exudation Inflammation
1. Serous Inflammation
2. Fibrinous Inflammaion
3. Suppurative Inflammation
 Phlegmonous Inflammation
 Superficial suppuration and Empyema
 Abscess
4. Hemorrhagic Inflammation
According to the diffierent transudation

69. Serous
Fibrinous
Suppurative
Hemorrhagic
Chronic inflammation

70. 1. Serous Inflammation
Features: accumulation of excessive serous fluid (clear watery fluid)
with variable protein content (plasma)
Location: Mucosa, serosa,body cavities (peritoneal, pleural &
pericardial cavities) , Loose connective tissues,skin
Pathologic changes: Inflammatory edema, blister, hydrops, Catarrh
Outcome: complete resolution

71. second-degree burn a friction blister of the skin

72. right pleural effusion: clear, pale yellow appearance of the fluid

73. 2. Fibrinous Inflammaion
 Causes: More severe injuries can result in greater vascular
permeability. Larger molecules(esp. fibrinogen, then forms
fibrin)come out through the endothelial cells.
 Pathologic changes: Eosinophilic meshwork of threads or sometimes
as an amorphous coagulum.
 Location: Mucosa, serosa, body cavities, Lung

74. 2. Fibrinous Inflammaion
Manifestation:
lung--- lobar pneumonia;
Mucosa: pseudomembrane --dysentery, diphtheria;
rheumatic pericarditis
---Hairy heart/Shaggy heart/cor villosum/trichocardia

75. lobar pneumonia

76. Diphtheria
Pseudo-membranous inflammation
pseudomembrane
pharyngeal diphtheria
diphtheria of trachea

77. Bacillary Dysentery
Fibrinous Inflammation of Intestine

78. Hairy heart/Shaggy heart/cor villosum/trichocardia
serous pericarditis fibrinous pericarditis

79. 2. Fibrinous Inflammaion
Outcome
Absorption: lobar pneumonia
Organization and adherence
-- pericarditis--armored heart
--Pulmonary Carnification
Pseudo-membrane:
--detach—ulcer, bleeding
--trachea diphtheria—asphyxia

80. 3. Suppurative Inflammation
 Features: The presence of large number of neutrophils and
varying degrees of tissue necrosis and pus formation.
Pus—purulent exudation
Purulent cells—degenerated and necrotic neutrophils
 Causes: pyogenic bacteria
 subclass: Superficial Suppuration, Abscess, Phlegmonous
Inflammation

81. Superficial Suppuration and Empyema
 Superficial Suppuration
Location: mucosal or serosa surface
Features: Pus formation, Suppurative Catarrh
e.g. Suppurative meningitis
 Empyema
a collection of pus in a hollow viscus.
e. g. in the gallbladder or fallopian tube, serous cavity

82. Suppurative meningitis
arachnoid
pia mater
subarachnoid space
smaller grooves called sulci, and ridges called gyri.

83. purulent peritonitis

84. purulent exudate in pericardial cavity
Empyema of Fallopian Tube
Empyema

85. Phlegmonous inflammation
Definition: wide-spread purulent inflammation in loose tissue
Locus: skin, muscle and appendix
Causes: hemolytic streptococci
Examples: Phlegmonous appendicitis
Features: large numbers of neutrophils infiltration.
Outcome: heal without sequelae

86. Acute phlegmonous appendicitis
mucosal layer
submucosa
muscularis
serosa

87. Acute phlegmonous appendicitis

88. Acute phlegmonous appendicitis

89. Abscess
 Definition: Focal localized collections of purulent inflammatory
tissues caused by suppuration buried in a tissue, an organ, or a
confined space.
 Locus--skin, lung, brain, liver, kidney
 Reason: a deep seeding of pyogenic bacteria into a tissue
Staphylococcus aureus
 Features: a cystic space from the resolved liquefactive necrosis.

90. Abscess of Lung

91. Abscess of Liver

92. Abscess of Skin
Furuncle：the localized suppurative
inflammation of haircyst, sebaceous
gland & surrounding tissues.
Carbuncle：Fusion of quite a few
furuncles.

93. 4. Hemorrhagic Inflammation
Inflammation associated with conspicuous haemorrhage
as a result of vascular damage.
In some instances:
epidemic hemorrhagic fever
Leptospirosis
Plague
anthrax
anthrax bacillus meningitis

94. outcome of acute Inflammation
 Resolution
 Progression to chronic inflammation
 Dissemination
 Local spread
 Lymphatic spread
 Hematogenous spread

95. Events in the complete
resolution of inflammation
 Return to normal vascular
permeability
 Removal of fluid and protein
 Macrophage pinocytosis
 Phagocytosis by neutrophils
 Necrotic debris by macrophages
 Eventual exodus by
macrophages

96. Local spreading
Ulcer cavity Sinus Fistula
gastric ulcer cavitary pulmonary tuberculosis

97. Dissemination
 Local spreading
 Lymphatic spreading：
lymphnoditis
lymphangitis
 Blood spreading
Bacteremia: organisms→ blood
Toxemia: toxin→ blood
Septicemia: ①+②
Pyaemia: pyogenic organisms

98. primary pulmonary tuberculosis
primary lesion
lymphnoditis
lymphangitis

99. outcome of acute Inflammation

100. Part 3
chronic inflammation

101. Causes of chronic inflammation
 Chronic inflammation following acute inflammation
 Recurrent attacks of acute inflammation
 Chronic inflammation starting de nove

102. General features of chronic inflammtion
• inflammatory cells infiltration
Mononuclear cells :Macrophages(MOs)/ Histiocytes
others : Lymphocytes, Plasma cells and Eosinophils
• Tissue destruction or necrosis
• Proliferative changes
Proliferation of small blood vessels (revascularization).
Increase the connective tissue(fibrosis)

103. Maturation of mononuclear phagocytes

104. MOs functions
1. Produce toxic, biologically active substances such as
oxygen metabolites.
2. Cause influx of other cells such as other macrophages
and lymphocytes.
3. Cause fibroblast proliferation and collagen deposition.
4. Phagocytosis.

105. chronic inflammation
 Characterized by cellular proliferation
 parenchymal cell proliferation
 mesenchymal cell proliferation
 lymphoid tissue proliferation
 granulomatous inflammation
 proliferation of macrophage and its derivatives

106. Types of Chronic inflammation
 Chronic non-specific inflammation
Inflammatory pseudotumor
Inflammatory polyp
 Chronic granulomatous inflammation

107. Inflammatory pseudotumor
 Tumor-like proliferation of local
tissues (parenchymal, stromal,
even inflammatory cells) resulting
from chronic inflammation
 It is not a real tumor
 Occur in the orbit, lung, liver and
spleen

108. Inflammatory polyp
 composed of mucosal glands,
granulation tissue, and
inflammatory cells.
 Commonly seen in nasal,
cervical & colorectal
mucosa.
polyp of vocal cord
cervical polyp

109. chronic cervicitis

110. Chronic bronchitis

111. Chronic granulomatous inflammation
Granuloma is defined as a circumscribed, tiny lesion, composed
predominantly of collection of modified macrophages, and
rimmed at the periphery by lymphoid cells.
• Special type of chronic inflammation
• Distinctive pattern (granuloma--small nodular )
• Aggregation of activated macrophages (derived cell)
• Diameter 0.5-2mm

112. Activated Macrophages in Granulomas
 Special type of Macrophage
 Epithelioid cells: Tuberculosis, Sarcoidosis, Crohn disease,
Leprosy
 Typhoid cells Typhoid fever
 Aschoff cells Rheumatic fever
 Multinuclear giant cells
 Langhans cells : Tuberculosis
 Foreign body giant cells: Foreign body granuloma

113. the cells derived from macrophage
atherosclerosis—foamy cell Rheumatism—Aschoff cell

114. the cells derived from macrophage
Tuberculosis-- epithelioid cell
-- a squamous cell-like appearance
typhoid fever--typhoid cell

115. causes of granulomas
 Infective granuloma
Bacteria—tubercle bacillus，mycogerms leprea
treponema—syphilis
fungi ---pulmonary histoplasmosis
parasite---Liver Schistosomiasis
 Foreign body’s granuloma
 Agnogenic: sarcoidosis

116. Two factors necessary for granuloma formation
 Presence of indigestible organisms or particles
(Tb-- tubercle bacillus, mineral oil, etc)
 Cell mediated immunity (T cells)

117. Injury
Failure to digest agent
Weak acute inflammatory response
Persistence of injurious agent
T cell-mediated immune
response
Poorly digestible agent
Activation of CD+ T cells
Monocyte chemotactic factor
Accumulation of tissue macrophages
Macrophages activated by IFN-γ
Transformed to epithlioid cells, giant cells
Granuloma
THE MECHANISM
OF EVOLUTION OF
GRANULOMA

118. Granulomatous Inflammation
 Tuberculosis Tubercle
 Leprosy Tuberculoid granuloma
 Syphilis Gumma (syphiloma)
 Typhoid Fever Typhoid nodule (typhoid granuloma)
 Sarcoidosis Noncaseating Epithelioid granuloma
 Crohn Disease Noncaseating Epithelioid granuloma
 Rheumatic fever Aschoff body
 Cat-scratch disease

119. Pulmonary Tuberculosis
granuloma

120. Tuberculosis

121. Tuberculosis
• Central focus:
Caseous necrosis
• Surrounding:
Epithelioid cells
Langhans gaint cells
• Rim:
Lymphocytes
Fibroblasts

122. Caseous necrosis
Epithelioid cells

123. Langhans gaint cells
Lymphocytes
Nucleus are ordered arrangement

124. rheumatic myocarditis

125. rheumatic myocarditis
longitudinal section: caterpillar-likecross section: owl-eye

126. Foreign body’s granuloma
Features: foreign bodies
Foreign body giant cells: seen in association with
particulate insoluble material. Nuclei scattered
throughout cytoplasm.

127. Two foreign body giant cells are seen just to the right of center where
there is a bluish strand of suture material from a previous operation

128. Here is a foreign body type giant cell at the upper left of center
adjacent to a segment of vegetable material aspirated into the lung

129. Outcome of chronic inflammation
 Resolution/regeneration/restitution of normal structure.
 Repair/organization/healing by connective tissue/ fibrosis/
scarring.
 It can continue indefinitely--some disease processes are capable
of continuing indefinitely such as rheumatoid arthritis.

130. Resolution
Definition: Resolution is the return of tissue to its normal state.
Factors necessary for resolution:
• Removal of the offending agent
• Regenerative ability if cells have been destroyed
• Intact stromal framework

131. Causes and outcomes of acute and chronic inflammation

132. objective