ACUTE INFLAMMATION I & II
Content
1. Causes, clinical aspects, macroscopic appearance and cardinal
signs of acute inflammation.
2. Sequence of events in acute inflammation -early stages of
acute inflammation: changes in vessel caliber, vessel
permeability changes, formation of cellular exudate. Late
stages of acute inflammation: chemotaxis of neutrophils,
chemical mediators of acute inflammation, role of neutrophils,
role of the lymphatics, Exudates, transudate.
3. Sequence of acute inflammation: resolution, suppuration,
organization, progression to chronic inflammation. 1
Learning Outcomes
The student will be able to
1. Define inflammation and list and explain the cardinal
features of acute inflammation
2. List the causes of acute inflammation and outline briefly
the major events in acute inflammation and their underlying
mechanisms.
3. Describe briefly the sequelae of acute inflammation. And
compare and contrast acute and chronic inflammation.
4. Classify inflammation according to morphologic pattern
and describe the morphology. Give the examples of each.
2
Definition
Inflammation is a response of vascularized tissues to
infections and tissue damage that brings cells and molecules
of host defense from the circulation to the sites where they
are needed, to eliminate the offending agents.
Inflammation can be divided into ACUTE and CHRONIC
Feature ACUTE CHRONIC
Onset Fast : minutes or hours Slow : days
Cellular infiltration Mainly neutrophils Monocytes / macrophages
and lymphocytes
Tissue injury, fibrosis Usually mild and self- Often severe and
limited progressive
Local and systemic signs Prominent Less prominent; may be
subtle
3
Inflammation
• A protective response involving host cells, blood vessels, and proteins and other
mediators;
• it is intended to eliminate the initial cause of the cell injury, as well as the
necrotic cells and tissues resulting from the original insult;
and to initiate the process of repair.
Acute inflammation has three major components:
(1) dilation of small vessels, leading to an increase in blood flow,
(2) increased permeability of the microvasculature,
enabling plasma proteins and leukocytes to leave the
circulation, and
(3) emigration of the leukocytes from the
microcirculation, their accumulation in the focus of
injury, and their activation to eliminate the offending
agent.
4
Components of inflammatory responses
• Cells: Granulocytes (Polymorphonuclear leucocytes, Mast cells);
platelets; monocytes/macrophages; lymphocytes; fibroblasts.
• Proteins: complements, pentraxin,
MBL mannose-binding lectin, ficolin; coagulation; kininogens;
proteoglycans.
5
Acute Inflammation
Major components
• 2 major components :
• 1) vascular changes
• (2) cellular events
Stimuli for acute Inflammation
• Infections (eg. bacterial, viral, fungal, parasitic).
• Trauma (blunt and penetrating) and physical &
chemical agents (thermal injury – burns or
frostbites; irradiation; environmental chemicals).
• Tissue necrosis;
• Foreign bodies;suture,splinter dusts
• Immune reaction (hypersensitivity
reactions,autoimmune reaction).
6
Vascular events in acute inflammation
The vascular reaction consist of changes in the flow of blood & permeability
of vessels, both designed to maximize the movement of plasma proteins &
leucocytes out of the circulation & into the site of infection or injury.
Changes in vascular flow and caliber
1. Vasodilation induced by several mediators, histamine
on vascular smooth muscle. This is preceded by
transient vasoconstriction. Vasodilation involved the
arterioles and opening new capillary beds in the area.
This lead to increase blood flow (heat & redness)
2. Vasodilation is quickly followed by increase
permeability of the microvasculature leading
transudate & exudate.
3. The loss of fluid & increase diameter causes slower
blood flow, vascular congestion and localized redness
erythema.
4. As stasis develops, blood leucocytes, mainly
neutrophils accumulate along the vascular endothelium
7
Cellular events in acute Inflammation
The journey of leukocytes from the vessels lumen to the tissue is multistep process
that is mediated and controlled by adhesion molecules & cytokines.
1. Leucocyte Recruitment to Sites of Inflammation
thru multistep processes :
1. Margination and rolling at the periphery of
vessels (this is mediated by selectins),
2. Adhesion : firm attachment to the
endothelial surfaces (mediated by integrins),
and
3. Tr a n s m i g r a t i o n : e x t r a v a s a t i o n o f
leukocytes (diapedesis) occurs at venules of
the systemic vasculature eg pulmonary
circulation.
4. Chemotaxis : movement of leukocytes
towards sites of infection or injury.
1.2 Tissue macrophage produce Cytokines
(TNF, IL-I) that promotes expression of
selectins and integrin on the
endothelium.
1.3 Neutrophils predominate in the early
inflammatory in filtrate ( 6-24 hours) and
later replaced by monocytes
(macrophages) (24-48 hours).
8
Cellular events in Acute Inflammation
2. Leucocyte Effector Mechanism :
i. Leukocytes activation results in
- Phagocytosis of particles.
- Intracellular destruction of phagocytosed microbes and dead cells.
- Liberation of substances that destroy extracellular microbes and dead tissues.
- Production of mediators (including arachidonic acid metabolites and
cytokines)
9
Phagocytosis involves
3 sequential steps
1. Recognition and
attachment of the
particle to be
ingested by the
leucocyte
2. Engulfment, with
subsequent
formation of a
phagocytic vacuole
3. Killing or
degradation of the
ingested material
10
11
Chemical Mediators of Inflammation
Cell derived
Plasma protein-derived
12
Actions of the Principal Mediators of Inflammation
13
The roles of cytokines in acute inflammation. The cytokines (TNF,
IL-I, and IL6) are the key mediators of leukocytes recruitment in
local inflammatory response and also play important roles in the
systemic reactions of inflammation.
14
Transformation of transudate and exudates
15
Principal Inflammatory
Actions of Arachidonic
Acid Metabolites
(Eicosanoids)
Role of Mediators in
Different Reactions
of Inflammation
16
Injurious attacks
stimuli
Host cell
Cardinal signs of inflammation
Heat (calor)
Redness (rubor) Chemical mediators
induced from the injured cell
Swelling
(tumor)
Inflamed cell
Pain (dolor)
Loss of function
(function laesa)
17
Cardinal signs of inflammation
Heat (calor)
Swelling (tumor)
Redness (rubor)
Pain (dolor)
Loss of function (function laesa)
18
Inflammation is normally controlled and self-limited
• General features of Inflammation :
• Defensive host response to foreign invaders and necrotic tissue, but itself
capable of causing tissue damage.
• The main components of inflammation : vascular reaction and a cellular
response; both are activated by mediators derived from plasma proteins and
various cells.
• Cardinal signs of inflammation : heat (calor), redness (rubor), swelling
(tumor), pain (dolor) and loss of function (functio laesa).
• 5 Rs steps : (1) recognition of the injurious agents, (2) recruitment of
leukocytes, (3) removal of the agents, (4) regulation (control) of the
response, and (5) resolution (repair).
• Outcome of inflammation : either elimination of the noxious stimulus,
followed by decline of the reaction and repair of the damaged tissue, or
persistent injury resulting in chronic inflammation
19
Differences between Transudate and Exudate
20
SUMMARY :
Sequence of events in Acute Inflammation
• The vascular changes are increased blood flow secondary to
arteriolar and capillary bed dilation (erythema and warmth).
• Increased vascular permeability (due to widening of interendothelial
cell junctions of the venules or direct endothelial cell injury), results
in an exudate of protein-rich extravascular fluid (tissue edema).
• The leukocytes (predominantly neutrophils) adhere to the
endothelium via adhesion molecules, leave the microvasculature and
migrate to the site of the injury under the influence of chemotactic
agents.
• Phagocytosis, kills and degrades the offending agent.
21
SUMMARY :
Sequence of events in Acute Inflammation
• Genetic and acquired defects in leukocyte functions give rise to
recurrent infections eg acquired (bone marrow suppression –
tumour (leukemia), radiation and chemotherapy, diabetes
mellitus, sepsis malnutrition; genetic – leukocyte adhesion
deficiency 1 and 2, chronic granulomatous disease,
myeloperoxidase deficiency, Chediak-Higashi syndrome.
• The outcome of acute inflammation : removal of the exudate
with restoration of normal tissue architecture (resolution);
transition to chronic inflammation; or scarring (due to
excessive destruction of the tissues)
22
Outcomes of Acute Inflammation – 3
outcomes
1. Resolution : regeneration and repair,
2. Chronic inflammation may follow if the offending agent is not removed,
3. Scarring : tissue repair.
23
24
Morphologic Patterns of Acute Inflammation
(morphologic patterns are associated with etiology
and clinical situations)
• Serous inflammation
Skin blister
Epidermis is separated Serous effusion
From the dermis
Serous inflammation is characterized by the outpouring of a watery, relatively protein-poor
fluid that, depending on the site of injury, derives either from the plasma or from the
secretions of mesothelial cell lining the peritoneal, pleural and pericardial cavities.
25
Morphologic patterns of acute inflammation
Serous inflammation
Purulent inflammation due to
Streptococcal infection of the throat
Fibrinuous pericarditis = also known
as bread and butter pericarditis.
26
Fibrinous Inflammation
i. Fibrinous inflammation occurs as a consequence of more severe injuries, resulting in greater
vascular permeability that allows large molecules (eg fibrinogen) to pass the endothelial
barrier.
ii. Histologically : accumulated extravascular fibrin appears as an eosinophilic meshwork of
threads or sometimes as an amorphous coagulum (fig 2-19).
iii. Eg. Inflammation lining the meninges, pericardium, and the pleura.
27
Morphologic Patterns of Acute Inflammation
(morphologic patterns are associated with etiology
and clinical situations)
Suppurative (purulent) inflammation and abscess formation.
These are manifested by the collection of large amounts of purulent exudate
(pus) consisting of neutrophils, necrotic cells and edema fluid. Eg
staphylococci infection.
28
Ulcer : local defect / excavation of the surface of an organ / tissue that is produced
by necrosis of cells and sloughing (shedding) of necrotic and inflammatory tissue. Eg
mucosa of the mouth, stomach, intestines, or genitourinary tract.
A : chronic duodenal ulcer
B : x-section of a duodenal ulcer crater with an
acute inflammatory exudate in the base.
B
29
After leucocyte leave the vasculature, their migration in tissue to
the site of infection or injury is mediated by which of the following
substances acting as a chemotactic factor?
A. Bradykinin
B. Chemokines
C. Histamine
D. prostaglandins 30
