Inflammation is the body's protective response to injury or infection. The document discusses the key components of acute and chronic inflammation. Acute inflammation is characterized by rapid onset, short duration, and features like fluid exudation and neutrophil accumulation. Chronic inflammation lasts longer and involves lymphocytes, macrophages and plasma cells. The inflammatory response involves vascular changes like vasodilation and increased permeability, as well as cellular events like leukocyte recruitment and activation through processes such as chemotaxis and phagocytosis. Chemical mediators released include histamine, prostaglandins, leukotrienes and cytokines which regulate the inflammatory response.

1. INFLAMMATIONINFLAMMATION
Dr Sapna MDr Sapna M
Dept pathologyDept pathology
SNIMS,KERALASNIMS,KERALA

2. INFLAMMATIONINFLAMMATION

3. INFLAMMATIONINFLAMMATION
• Protective response intended
to eliminate initial cause of cell
injury , necrotic cells and
tissues resulting from original
insult

4. Introduction:Introduction:
• “Inflame” – to set fire
• Inflammation is “dynamic
response of vascularised
tissue to injury.”

5. -itis-itis
AppendicitisAppendicitis
CellulitisCellulitis
MeningitisMeningitis
PneumonitisPneumonitis
NephritisNephritis
MyocarditisMyocarditis

6. TYPES OF INFLAMMATIONTYPES OF INFLAMMATION
• ACUTE
• CHRONIC

7. Acute Inflammation-FeaturesAcute Inflammation-Features
• Rapid onset
• Short duration( mts. to few days)
• Fluid , plasma protein exudation
• Neutrophil accumulation

9. ChronicChronic Inflammation-FeaturesInflammation-Features
• Onset- insidious
• Longer duration (days to years)
• Lymphocytes ,macrophages ,plasma
cells
• Vascular proliferation & fibrosis
(scarring)

11. HEAT REDNESS SWELLING PAIN LOSS OF
5 Cardinal Signs of Inflammation5 Cardinal Signs of Inflammation

12. 4 cardinal clinical signs of inflammation4 cardinal clinical signs of inflammation
described by Celsus, 1 A.D.:described by Celsus, 1 A.D.:
• Rubor - redness
• Tumor - swelling
• Calor - heat
• Dolor - pain
• Virchow added a fifth--loss of
function(functio laesa)

13. Steps Of Inflammatory ResponseSteps Of Inflammatory Response
• Remembered as five Rs:
• (1) Recognition of injurious agent
• (2) Recruitment of leukocytes
• (3) Removal of agent
• (4) Regulation of response
• (5) Resolution (repair).

14. •ACUTE INFLAMMATION

15. Stimuli for Acute InflammationStimuli for Acute Inflammation
• Infections (b, v, f, p)
• Trauma
• Physical & chemical agents
• Tissue necrosis (MI)
• Foreign bodies
• Immune reactions

16. Acute Inflammation-componentsAcute Inflammation-components

17. Acute Inflammation-componentsAcute Inflammation-components

18. ACUTE INFLAMMATIONACUTE INFLAMMATION
Vascular changes Cellular events
•Vasodilation
Increased vascular permeability.

19. Acute Inflammation-componentsAcute Inflammation-components
• 1.Vascular changes:
• Vasodilation
• ↑ vascular perm.
• 2.Cellular events
• Cellular recruitment & activation

20. VASCULAR CHANGESVASCULAR CHANGES
• 1.Changes In Vascular Caliber And Flow
• Transient vasoconstriction (sec.)
• Arteriolar vasodilation( redness
warmth)

21. • ↑ bld flow & engorgement capillary beds
↓
protein-rich fluid moves into EV
tissues
↓
RBCs conc., ↑ blood viscosity
↓
Stasis
↓
margination of neutrophils

23. ACUTE INFLAMMATIONACUTE INFLAMMATION
• 2. ↑ Vascular Perm.{ mechanisms }
• 1.Endothelial cell contraction
–immediate transient response
:reversible process, by histamine,
bradykinin, leukotrienes ,15-30 min.
2 .Retraction of EC
: TNF and IL-1, 24 hours or more

24. ↑↑ Vascular Permeability{ mechanisms }Vascular Permeability{ mechanisms }
• 3.Endothelial injury
-immediate sustained response , delayed
prolonged leakage
• 4.Leukocyte-mediated endothelial injury
• 5.Increased transcytosis
• 6.Leakage from new blood vessels.

26. EXUDATE : INFLAMMATIONEXUDATE : INFLAMMATION

27. • 1.Vascular changes:
• Vasodilation
• Increased vascular permeability.

28. Cellular Events: LeukocyteCellular Events: Leukocyte
Recruitment and ActivationRecruitment and Activation

29. Leukocyte RecruitmentLeukocyte Recruitment
• 4 steps
1. Margination, rolling, and
adhesion
2. Diapedesis (transmigration
across endothelium)
3. Migration toward chemotactic
stimulus - Chemotaxis
4. Phagocytosis

32. Neutrophil MarginationNeutrophil Margination

33. ROLLINGROLLING::
Leukocytes tumble on endothelial
surface, transiently sticking along
the way
• Mediated by SELECTIN family of
adhesion molecules
• 3 members of this family

34. SELECTINSSELECTINS
• E-selectin (CD62E) on EC
• P-selectin (CD62P) EC & platelets
• L-selectin (CD62L) leukocytes
• Selectins bind sialylated
oligosaccharides ( sialyl-Lewis X
on leukocytes)

35. ROLLINGROLLING

36. ADHESION & TRANSMIGRATIONADHESION & TRANSMIGRATION
• Adhesion mediated by integrins
• Activated by chemokines
• TNF and IL-1 activate EC to ↑
expression of ligands for integrins

37. ADHESIONADHESION

38. Ligands For IntegrinsLigands For Integrins
• ICAM-1(intercellular adhesion molecule1)
- binds integrins LFA-1 (CD11a/CD18)
and Mac-1 (CD11b/CD18),
• VCAM-1 (vascular cell adhesion
molecule1)
- bind integrin VLA-4

39. DIAPEDESISDIAPEDESIS

40. DIAPEDESISDIAPEDESIS

41. DIAPEDESISDIAPEDESIS
• Leukocytes migrate thr’u vessel wall by
squeezing between cells at IC junctions
• Mediated by PECAM-1 (platelet
endothelial cell adhesion molecule 1
(CD31) on leukocytes & EC

42. CHEMOTAXISCHEMOTAXIS
• Leukocytes migrate toward sites of
infection or injury along a chemical
gradient
• Chemotactic substances
(1) bacterial products (2) cytokines
(3) C5a (4) LTB4.

43. 6 to 24 hours 24 to 48 hours

44. LEUKOCYTE ACTIVATIONLEUKOCYTE ACTIVATION

45. LEUKOCYTE ACTIVATIONLEUKOCYTE ACTIVATION
• Leukocytes receptors sensing p/o
microbes:
–Toll-like receptors (TLRs) - LPS
–Seven-transmembrane G-protein-
coupled receptors - bacterial
peptides and mediators

46. PHAGOCYTOSISPHAGOCYTOSIS
• 3 steps
• (1) recognition and attachment of
particle to ingesting leukocyte
• (2) engulfment & formation of
phagocytic vacuole
• (3) killing and degradation of ingested
material.

48. (1)(1) Recognition & attachment ofRecognition & attachment of
particle to ingesting leukocyteparticle to ingesting leukocyte
• Opsonins : host proteins that coat
microbes and target them for
phagocytosis (opsonization).
• Leukocytes express receptors for
opsonins

49. OPSONISATION RECEPTORS

50. OPSONINS RECEPTORS FOR
OPSONINS
IgG FcγRI
Breakdown
products of C3
CR1 and 3
Collectins C1q

52. 2.ENGULFMENT2.ENGULFMENT & FORMATION& FORMATION
OF PHAGOCYTIC VACUOLEOF PHAGOCYTIC VACUOLE

56. 3.Killing and Degradation of Microbes3.Killing and Degradation of Microbes
• Important microbicidal substances :
reactive oxygen species (ROS) and
lysosomal enzymes
• ROS
• HOCl• (hypochlorous radical)
•Superoxide radicals
(superoxide,H2O2, and OH•).
• Reactive nitrogen species( NO)

57. Lysosomal enzymesLysosomal enzymes
• Lysosomal acid hydrolases-degrade
dead microorganisms
• Elastase - kill bacteria

58. Defects in Leukocyte FunctionDefects in Leukocyte Function
• Common causes
• BM suppression ( tumors CT,RT)- ↓
leukocyte no.
• Diabetes - abnormal leukocyte
function

59. Defects in leukocyte function:Defects in leukocyte function:
• Margination and adhesion
–Etoh, steroids, AR leukocyte adhesion
deficiency
• Emigration toward a chemotactic stimulus
–drugs
–chemotaxis inhibitors
• Phagocytosis
–Chronic granulomatous disease
(CGD) :phagocyte oxidase generating ROS

60. Defects in leukocyte function:Defects in leukocyte function:
• Myeloperoxidase (MPO) deficiency:
Absent MPO-H2O2 system
• Chédiak-Higashi syndrome :impair
fusion of lysosomes with phagosomes

61. ACUTE INFLAMMATION - THREEACUTE INFLAMMATION - THREE
OUTCOMESOUTCOMES
• Resolution
• Progression to chronic inflammation
• Abscess
• Scarring or fibrosis

62. Acute inflammation
Chronic inflammation
RepairResolution
Abscess
Injury

64. MORPHOLOGIC PATTERNS OFMORPHOLOGIC PATTERNS OF
ACUTE INFLAMMATIONACUTE INFLAMMATION
• SEROUS INFLAMMATION
• Watery, protein-poor fluid .
Serum/secretions of mesothelial cells
• Skin blister
• Fluid in a serous cavity - effusion.

65. SEROUS INFLAMMATIONSEROUS INFLAMMATION

66. FIBRINOUS INFLAMMATIONFIBRINOUS INFLAMMATION
• Severe injuries, ↑ vascular perm. &
fibrinogen pass
• Histology: eosinophilic meshwork
of threads or amorphous coagulum
• Site : Lining of body cavities
• Resolution
• Organization & scarring

68. SUPPURATIVE (PURULENT)SUPPURATIVE (PURULENT)
INFLAMMATIONINFLAMMATION
• Purulent exudate (pus) -
neutrophils, necrotic cells, and
edema fluid
• Staphylococci – pyogenic
• Completely walled off ,replaced by
connective tissue.

69. ABSCESSESABSCESSES
• Focal collections of pus
• Central, large necrotic region
rimmed by neutrophils
(surrounded by vessels and
fibroblastic proliferation )

70. ABSCESSESABSCESSES

71. ABSCESSESABSCESSES

72. ULCERULCER
• Local defect / excavation, surface of an
organ/ tissue prod. by necrosis of cells
& sloughing of inflammatory necrotic
tissue
• Sites (1)mucosa of GIT( Peptic ulcer),
GUT
• (2) Lower extremities, older persons
with circulatory distur.

74. CHEMICAL MEDIATORS OFCHEMICAL MEDIATORS OF
INFLAMMATIONINFLAMMATION
CELL DERIVED

75. CHEMICAL MEDIATORS OFCHEMICAL MEDIATORS OF
INFLAMMATIONINFLAMMATION
PLASMA PROTEIN DERIVED

76. CHEMICAL MEDIATORS OFCHEMICAL MEDIATORS OF
INFLAMMATIONINFLAMMATION
• CELL-DERIVED MEDIATORS
• VASOACTIVE AMINES
• 1.HISTAMINE released by
• (1) physical injury
• (2) immune reactions
• (3) Anaphylatoxins:C3a and C5a
• (4) leukocyte-derived histamine-releasing
proteins
• (5) neuropeptides
• (6) IL-1 and IL-8

77. HISTAMINEHISTAMINE
• Action: arteriolar dilation , ↑ vascular
perm.
• Inactivated by histaminase
• SEROTONIN (5-hydroxytryptamine)
effects similar to histamine

78. CELL DERIVED –NEWLYCELL DERIVED –NEWLY
SYNTHESISEDSYNTHESISED

79. Arachidonic Acid Metabolites:Arachidonic Acid Metabolites:
((eicosanoidseicosanoids))
• Sources: Leukocytes, mast cells, EC,
platelets
• 2 major enzymatic pathways:
• Cyclooxygenase
• Lipoxygenase
• Cyclooxygenase : prostaglandins and
thromboxanes
• Lipoxygenase: leukotrienes and lipoxins

81. Arachidonic Acid (AA) MetabolitesArachidonic Acid (AA) Metabolites
• CYCLOOXYGENASE PATHWAY
• Products :PGE2, PGD2, PGF2α,
PGI2 (prostacyclin), TXA2
• TXA2: Platelets - thromboxane
synthase ,platelet-aggregating
agent and vasoconstrictor

83. CYCLOOXYGENASE PATHWAYCYCLOOXYGENASE PATHWAY
• PGI2 : EC - prostacyclin synthase ,
vasodilator and inhibitor of platelet
aggregation
• PGD2: mast cells; + PGE2 & PGF2α
causes vasodilation & edema
• PGE2 : pain sensitivity, fever.

85. LIPOXYGENASE PATHWAYLIPOXYGENASE PATHWAY
• 5-Lipoxygenase :AA-metabolizing
enzyme in neutrophils
• 5-HPETE (5-
hydroperoxyeicosatetraenoic acid)
• Reduced to 5-HETE (5-hydroxyeicosa
tetraenoic acid) - chemotactic for
neutrophils
• or converted into leukotrienes

86. Lipoxygenase Pathway- LeukotrieneLipoxygenase Pathway- Leukotriene
• LTA4 gives rise to LTB4 or LTC4
• LTB4: chemotactic agent for
neutrophils
• LTC4 , LTD4 & LTE4: mast cells ,
cause vasoconstriction,
bronchospasm, ↑ vascular perm.

88. LIPOXINSLIPOXINS
• Inhibitors of inflammation
• Endogenous antagonists of
leukotrienes.

89. Principal Inflammatory Actions ofPrincipal Inflammatory Actions of
AA MetabolitesAA Metabolites
• Vasodilation:PGI2 (prostacyclin),
PGE1, PGE2, PGD2
• Vasoconstriction:Thromboxane A2,
leukotrienes C4, D4, E4
• ↑ vascular perm. :Leukotrienes C4,
D4, E4 & PGE2, PGD2
• Chemotaxis, leukocyte adhesion
:Leukotriene B4, 5-HETE

91. Cyclooxygenase enzyme -COXCyclooxygenase enzyme -COX
• Two forms : COX-1 and COX-2
• COX-1 : gastric mucosa, PGs
protective against acid-induced
damage.
• COX inhibitors :Aspirin ,NSAIDs: treat
pain and fever

92. Platelet-Activating FactorPlatelet-Activating Factor
• Stimulate platelets
• Vasoconstriction & bronchoconstriction
• Vasodilation & ↑vascular perm.
• Leukocyte adhesion, chemotaxis,
degranulation, oxidative burst
• Synthesis of mediators , (eicosanoids).

93. CytokinesCytokines
• Polypeptide products .Mediators of
inflammation and immune responses
• Molecularly characterized cytokines -
interleukins
• A/c inflam : TNF, IL-1, chemokines
• C/C inflam: IFN-γ , IL-12.

95. CHEMOKINESCHEMOKINES
• 2 functions : leukocyte recruitment in
inflam. & N anatomic organization of cells
in lymphoid and other tissues
• Four groups
• Two major groups
• CXC :IL-8
• CC chemokines:MCP-1 , MIP-1α,
RANTES (regulated on activation normal
T expressed and secreted) and eotaxin .

96. Reactive Oxygen Species (ROSReactive Oxygen Species (ROS
• Synthesized via NADPH oxidase
(phagocyte oxidase) pathway
• Action (1) endothelial damage, with
thrombosis & ↑ perm.
• (2) protease activation and
antiprotease inactivation
• (3) direct injury to other cells
• Catalase, SOD, glutathione -↓ toxicity

97. NONO
• Synthesized from l-arginine, molecular
O2, NADPH by enzyme NOS.
• 3 isoforms of NOS
• Type I (nNOS)
• Type II (iNOS) present in macrophages
& EC induced by IL-1, TNF,IFN-γ,
bacterial endotoxin
• Type III (eNOS)

98. Nitric OxideNitric Oxide

99. NO -NO -FunctionsFunctions
• (1) vasodilation (endothelium-derived
relaxation factor)
• (2) antagonism all stages of platelet
activation(a,a,d)
• (3) reduction of leukocyte recruitment
at inflammatory sites
• (4)Microbicidal agent

100. Lysosomal Enzymes of LeukocytesLysosomal Enzymes of Leukocytes
• Acid proteases:acidic pH optima ,
active within phagolysosomes
• Neutral proteases: elastase,
collagenase , cathepsin, active in
ECM
• Cleave C3 & C5 to C3a & C5a
• Generate bradykinin-like peptides
from kininogen.

101. AntiproteasesAntiproteases
• α1-antitrypsin-major inhibitor of
neutrophil elastase
• α2-macroglobulin
• α1-antitrypsin deficiency - lung ,
panacinar emphysema

102. NeuropeptidesNeuropeptides
• Small proteins, such as substance P
• Transmit pain signals
• Regulate vessel tone
• Modulate vascular permeability
• Lung and GIT- Nerve fibers secrete NP

103. PLASMA PROTEIN-DERIVEDPLASMA PROTEIN-DERIVED
MEDIATORSMEDIATORS
• 3 systems
– Complement
– Kinin
– Coagulation

104. ComplementComplement
Immunity and inflammation
• Opsonize particles: phagocytosis and
destruction
• ↑ vascular perm. & vasodilatation
• Leuko. chemotaxis
• Generates MAC (C5b-9)

105. ComplementComplement

106. Critical steps : activation of C3Critical steps : activation of C3
• (1) Classical pathway : fixation of C1
to antig-antib complexes
• (2) Alternative pathway: bacterial
polysaccharides / microbial cell-wall
components, involve properdin and
factors B , D
• (3) Lectin pathway: plasma lectin
binds mannose residues on microbes
, activates early component of CP

107. ComplementComplement
• 3 pathways form C3 convertase :cleaves
C3 to C3a and C3b
• C3b deposits on cell or microbial surface
• Binds to C3 convertase complex to form
C5 convertase
• C5 convertase cleaves C5 → C5a & C5b
• Initiate final stages of assembly of C6 to
C9
• Thrombin : cleave C5

109. ComplementComplement
• 1.Anaphylatoxins: C3a and C5a
↑vascular perm. and vasodilation ,induce
mast cells to release histamine.
• 2.C5a: activates lipoxygenase pathway
• 3.Leukocyte activation, adhesion, and
chemotaxis. C5a
• 4.Phagocytosis: C3b & iC3b act as
opsonins
• 5.Lysis of microbes - MAC

110. Coagulation and Kinin SystemsCoagulation and Kinin Systems
• 4 systems activated by Hageman
factor (factor XIIa)
• (1) Kinin system
• (2) Clotting system
• (3) Fibrinolytic system
• 4) Complement system.

111. Coagulation and Kinin SystemsCoagulation and Kinin Systems

113. Clotting SystemClotting System
• Factor Xa: ↑ vascular perm. and leuk.
Emigration
• Thrombin : leuk. Adhesion
• Fibrinopeptides :↑ vascular perm. and
chemotactic for leuk.

115. FIBRINOLYTIC SYSTEMFIBRINOLYTIC SYSTEM
• FDP : ↑ vascular perm.
• Plasmin :cleaves C3 to C3a causing
vasodilation and ↑ vascular perm.

117. KININ SYSTEMKININ SYSTEM
• Bradykinin :↑ vascular perm, arteriolar
dilation, bronchial smooth muscle
contraction, pain
• Kallikrein: chemotactic activity

118. Role of Mediators in DifferentRole of Mediators in Different
Reactions of InflammationReactions of Inflammation
• 1.Vasodilation:
Prostaglandins, Nitric oxide Histamine
• 2.↑ vascular perm:
Histamine and serotonin
C3a and C5a
Bradykinin
Leukotrienes C4, D4, E4
PAF
Substance P

119. Mediators in InflammationMediators in Inflammation
• 3. Leukocyte recruitment and
activation
TNF, IL-1
Chemokines
C3a, C5a
Leukotriene B4
Bacterial products, e.g., N-formyl
methyl peptides

120. Mediators in InflammationMediators in Inflammation
• 4. Fever
IL-1, TNF, PG
• 5. Pain
PG, Bradykinin, Neuropeptides
• 6. Tissue damage
Lysosomal enzymes , ROS,
Nitric oxide

123. CHRONIC INFLAMMATIONCHRONIC INFLAMMATION
• Prolonged duration .Active
inflammation, tissue injury & healing
simultaneously
• Characterized by
• Infiltration with mononuclear cells
• Tissue destruction
• Repair : angiogenesis and fibrosis

126. Chronic InflammationChronic Inflammation
• Time course:
–> 48 hours (weeks, months, years)
• Cell type
–Mononuclear cells (Macrophages,
Lymphocytes, Plasma cells)

127. Chronic InflammationChronic Inflammation
• Histology :
– L,M,P
– Fibroblasts & small BV
– ↑ CT
– Tissue destruction

129. MACROPHAGESMACROPHAGES
• Derived from circulating
blood monocytes
• SITES:
• Connective tissues
• Liver (Kupffer cells)
• Spleen & LN (sinus
histiocytes)
• CNS( microglial cells)
• Lungs (alveolar
macrophages)
•Mono
nuclear
phagocyte
system
(RES)

130. MACROPHAGESMACROPHAGES
FUNCTION
–Filters: particulate matter,
microbes,senescent cells
–Alert T and B lymphocytes to
injurious stimuli
• Lymphocytes, Plasma Cells,
Eosinophils, and Mast Cells

133. Settings For Chronic InflammationSettings For Chronic Inflammation
• 1.Microbes difficult to eradicate
Mycobacteria, Treponema pallidum ,
viruses and fungi
• 2.Immune-mediated inflammatory
diseases : RA ,IBD, Asthma
• 3.Toxic agents :Silica, atherosclerosis

134. GRANULOMATOUS INFLAMMATIONGRANULOMATOUS INFLAMMATION
• Distinctive pattern of chronic
inflammation
• Characterized by aggregates of
activated macrophages that assume
an epithelioid appearance

135. Diseases with GranulomatousDiseases with Granulomatous
InflammationInflammation
• Tuberculosis :M. tuberculosis
• Noncaseating tubercle : a focus of
epithelioid cells, rimmed by fibroblasts,
lymphocytes, histiocytes, occasional
giant cells
• Caseating tubercle: central amorphous
granular debris, loss of all cellular detail;
acid-fast bacilli

137. LANGHANS GIANT CELLS - HORSE SHOE SHAPE

139. LANGHANS GIANT CELL

141. Granulomatous InflammationGranulomatous Inflammation
• Leprosy
• Mycobacterium leprae
• Acid-fast bacilli in macrophages;
noncaseating granulomas
• Syphilis:Treponema pallidum,
Gumma

142. Granulomatous InflammationGranulomatous Inflammation
• Cat-scratch disease :Gram-negative
bacillus , Rounded or stellate
granuloma
• Sarcoidosis : Unknown etiology
Noncaseating granulomas
• Crohn disease :Immune reaction
against intestinal bacterial, self-
antigens noncaseating granulomas

143. Foreign body granulomas.Foreign body granulomas.

144. EPITHELIOID CELLSEPITHELIOID CELLS
• Elongated, finely granular, pale
eosinophilic cytoplasm
• Nucleus:central, oval or
elongate,small nucleoli ,slipper
shaped
• Indistinct shape , merge to form
aggregates.

147. • Lymphocytes secrete cytokines →
macrophage activation
• Multinucleated giant cells
• Hypoxia and free-radical injury leads to
caseous necrosis
• Healing of granulomas accompanied
by fibrosis

148. SYSTEMIC EFFECTS OFSYSTEMIC EFFECTS OF
INFLAMMATIONINFLAMMATION
• ACUTE-PHASE REACTION/ SYSTEMIC
INFLAMMATORY RESPONSE
SYNDROME.
• TNF, IL-1, and IL- 6

149. Clinical And Pathologic ChangesClinical And Pathologic Changes
-APR-APR
• 1.Fever- pyrogens –stimulate PG
synthesis in hypothalamus

150. LPS(EX .P)
LUECOCYTES(IL-1 &TNF)
ENDO.P
AA
PG(PGE2)
STIMULATE NEUROTRANSMITTERS
RESET TEMP.
↑ CYCLOOXYGENASE

151. 2.Acute-phase proteins2.Acute-phase proteins
• 2.Synthesized in liver
• Up-regulated by IL-6
• I) CRP II) Fibrinogen III)Serum amyloid A
(SAA) protein.
• Fibrinogen cause rouleaux- ↑ ESR
• CRP: ↑ risk of MI or stroke in pts. with
atherosclerotic vascular disease

152. 3. Leukocytosis
• TNF & IL-1-release cells from BM .
Shift to left
• CSFs - ↑ output of leukocytes from BM
• Neutrophilia , lymphocytosis ,
eosinophilia , leukopenia

153. Other manifestationsOther manifestations
• ↑ heart rate and BP
• ↓ sweating
• Rigors (shivering)
• Chills
• Anorexia, somnolence & malaise:
cytokines on brain cells
• Chronic inflammation: wasting syndrome
called cachexia, TNF- mediated appetite
suppression & mobilization of fat stores

154. SEPTIC SHOCKSEPTIC SHOCK
• High levels of TNF cause DIC,
hypoglycemia, and hypotensive
shock.

156. 1.A 65-year-old woman had fever the past day.
On physical examination her temperature is 39 C
and blood pressure 90/50 mm Hg with heart rate
of 106/minute. A blood culture is positive for
Escherichia coli. Her central line pressure falls
markedly. She goes into hypovolemic shock as a
result of the widespread inappropriate release of a
chemical mediator derived from macrophages.
Which of the following mediators is most likely to
produce these findings?
A Nitric oxide
B Bradykinin
C Histamine
D Prostacyclin
E Complement C3a

157. 2.The major difference between a
transudate and an exudate is
(A) transudate has proteins whereas
exudate is essentially devoid of proteins
(B) both these are only seen during acute
inflammatory processes
(C) both are associated with a Suppurative
or Purulent inflammatory process
(D) transudate is associated with serous
inflammation whereas exudate is
associated with fibrinous inflammation

158. 3.Granulomatous Inflammation is
associated with which of the following
a. distinct acute inflammatory
process
b. distinct chronic inflammatory
process
c. persistent B-cell response to
certain microbes
d. IgM mediated response

159. 4.Which of the following is/are considered
an anaphylatoxins(s)
(A) lipoxins
(B) leukotrines
(C) C3a
(D) IL-1 and TNF

160. 5.What is the most common form of
increased vascular permeability
associated with acute inflammation
(A) direct endothelial injury
(B) endothelial cell retraction
(C) endothelial cell contraction
(D) leukocyte-dependent endothelial
damage

161. 6.Endothelial cell contraction &
retraction occur in
a) Postcapillary venules
b) Capillaries
c) Arterioles
d) All of the above