This document summarizes a seminar on inflammation presented by doctors at Adama Hospital Medical College. It begins with a case study of a postpartum woman presenting with abdominal pain, fever, and foul vaginal discharge. The presentation then reviews the definition, cardinal signs, causes, and classification of inflammation. It describes the sequential stages and major components of acute inflammation, including increased blood flow, vascular permeability, leukocyte recruitment, phagocytosis, and tissue injury. The roles of various inflammatory mediators are also summarized.
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SEMINAR ON INFLAMMATION.pptx
1. Adama hospital medical college
Seminar on inflammation
Presenters; Dr. Oda Lamessa(OBGYN R1)
Dr. Birhanu Bacha (OBGYN R1)
Dr. Beshir Birhanu(OBGYN R1)
Moderator ; Dr. Wondimu (MD,Pathologist)
6/25/2023 Inflammation 1
2. case senario
• A 25yrs old para II mother on her 6th post partum day presented with
compliant of lower abdominal pain of 02 days duration which is crampy and
associated with high grade fever, loss of appetite and nausea and foul
smelling vaginal discharge of same days duration .she delivered via SVD 3.3kg
female neonatie with APGAR SCORE OF 8 &9 after 38wk +3 days of GA , 20
hours of gush of fluid per vagina which wetted her underwear ,non offensive
and clear and 16 hours of pushing down pain .
• Otherwise ,she has no history of vaginal bleeding
• Has no hx of frequency ,urgency or dysuria
• Has no hx of failure to pass feces or flatus
• Has no hx of diagnosed chronic illness like DM ,HTN and cardiac illnes
3. PHYSICAL EXAMINATION
GA- ASL (in pain)
– V/S :BP100/70 PR-122 RR-
24 T- 39.2c
– HEENT - Pink conjunctiva NIS
– RS & CVS -NAD
– Abd -
– 18 week sized uterus which
is boggy and tender with
guarding
– Bowel sounds present in all
quadrants
– No sign of fluid collection
• GUS: foul smelling pale red
vaginal discharge
– Cervix closed with
cervical motion
tenderness
• CNS – COTPP
4. Cont.........
• Invetigations
• CBC
– TWBC 21000
– granulocyte 83%
– Hgb 13.3g/d
– HCT 38.4%
Abdominopelvic u/s
– Thickened heterogeneous endometrium with probe
tenderness
– Minimal endometrial fluid collection
– Index; endometritis
Assessment: 6th post partum day
+purpural sepsis 2ry to endometritis
Mgt;
Admitted to Gyn ward and given
Ampicillin 2gm iv Qid,
metronidazole 500mg iv tid,
Gentamycin 80mg iv tid, and
tramadol 50mg iv tid
• *The patient was discharged
improved after 3 days with po
cephalexin and metronidazole
6/25/2023
5. OVERVIEW OF INFLAMMATION:
• Definition:-
– It is a response of vascularized tissues to infections and tissue
damage
– Reaction of blood vessels leads to:
• Accumulation of fluid and leukocytes in extravascular
tissues
• Destroys, dilutes, or eliminate the offending agents
– Initiates the repair process
– Fundamentally a protective response
6/25/2023 Inflammation 5
6. SEQUENTIAL STAPES OF INFLAMMATORY REACTION
1. Recognition of the injurious
agent.
2. Recruitment of leukocytes &
Plasma protein.
3. Removal of the agent.
4. Regulation (control) of the
response.
5. Resolution (repair damaged
tissue ).
6/25/2023 Inflammation 6
7. CARDINAL SIGNS OF INFLAMMATION
1. Heat (calor in Latin)
2. Redness (rubor)
3. Swelling (tumor)
4. Pain (dolor) and
5. loss of function (functio laesa).
6/25/2023 Inflammation 8
8. ?CAUSES OF INFLAMMATION
1. Infections (bacterial, viral, fungal, parasitic) and microbial
toxins.
2. Tissue necrosis( ischemia, trauma and physical and chemical
injury)
3. Foreign bodies (splinters, dirt, sutures)
4. Immune reactions ( hypersensitivity)
6/25/2023 Inflammation 9
9. CLASSIFICATION OF INFLAMMATION
• Inflammation may be of two types:-
– Acute inflammation
– Chronic inflammation
6/25/2023 Inflammation 10
10. ACUTE INFLAMMATION
Rapid in onset response.
Short duration.
Main characteristics are the exudation of fluid and plasma
proteins (edema)
Emigration of leukocytes, predominantly neutrophils.
Subsides when the goals is fulfilled
6/25/2023 Inflammation 11
11. MAJOR COMPONENTS OF ACUTE INFLAMMATION
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.
3. Emigration of the leukocytes from the microcirculation
Accumulation in the focus of injury, and their activation to
eliminate the offending agent
6/25/2023 Inflammation 12
12. CHANGES IN VASCULAR FLOW AND CALIBER
• Begin early after injury and consist of the following:
– Earliest manifestation is Vasodilation and may be preceded
by transient vasoconstriction
– Induced by several mediators, notably histamine acting on
vascular smooth muscle
6/25/2023 Inflammation 13
13. – It first involves the arterioles and then leads to the
opening of new capillary beds in the area.
The result is increased blood flow, which is the cause of
heat and redness (erythema) at the site of
inflammation.
14. FORMATION OF EXUDATES AND TRANSUDATES
• Exudation:-
The escape of fluid, proteins,
and blood cells from the
vascular system into
interstitial tissues or body
cavities.
• Transudate:-
Fluid with low protein content,
little or no cellular material,
and low specific gravity.
6/25/2023 Inflammation 15
15. INCREASED VASCULAR PERMEABILITY
– Retraction of endothelial cells :-
results in opening of interendothelial
space
– Occurs rapidly after exposure to a
mediator(within 15 to 30 minutes)
Elicited by histamine, bradykinin,
leukotrienes, and other chemical
mediators.
– Endothelial injury
Resulting in endothelial cell necrosis
and detachment(caused by burns, some
microbial toxin)
6/25/2023 Inflammation 16
16. RESPONSES OF LYMPHATIC VESSELS AND LYMPH NODES
• In addition to blood vessels:-
– It participates in acute inflammation.
– Lymphatics system and lymph nodes filters and polices the
extravascular fluids.
– Lymph flow is increased to help drain edema fluid
– Leukocytes and cell debris, as well as microbes, may find
their way into lymph.
6/25/2023 Inflammation 17
17. • Lymphatic vessels proliferate during inflammatory reactions
to handle the increased load
• The lymphatics may become secondarily inflamed
(lymphangitis), as may the draining lymph nodes
(lymphadenitis).
6/25/2023 Inflammation 18
18. LEUKOCYTE RECRUITMENT TO SITES OF INFLAMMATION
• To perform the key function of eliminating the offending agents.
• Most important leukocytes activated in acute inflammatory
reactions are neutrophils and macrophages.
• Neutrophils: are produced in the bone marrow and rapidly
recruited to sites of inflammation.
6/25/2023 Inflammation 19
19. LEUKOCYTE RECRUITMENT TO SITES
OF INFLAMMATION
• use cytoskeletal rearrangements and enzyme assembly to
mount rapid, transient responses
• Neutrophils predominate in the early inflammatory infiltrate
and are later replaced by monocytes and macrophages.
• Neutrophils predominate during the first 6 to 24 hours
• Monocytes in 24 to 48 hours
20. LEUKOCYTE RECRUITMENT TO SITES
OF INFLAMMATION
• Macrophages: are slower responders.
• - being long-lived, more prolonged responses that often rely
on new gene transcription
• -produce growth factors that aid in repair.
6/25/2023 Inflammation 21
21. LEUKOCYTE EXTRAVASATION
• Extravasation: delivery of leukocytes from the vessel
lumen to the interstitium
– In the lumen: rolling, margination, and adhesion
– Migration across the endothelium (diapedesis)
– Migration in the interstitial tissue (chemotaxis)
6/25/2023 Inflammation 22
23. Sequence of Events - Injury
• Inflammatory reaction in the myocardium after ischemic necrosis (infarction)
6/25/2023 Inflammation 24
24. PHAGOCYTOSIS
• Phagocytosis involves three sequential steps:
1. Recognition and attachment
2. Engulfment, with subsequent formation of a phagocytic
vacuole.
3. Killing or degradation of the ingested material .
6/25/2023 Inflammation 25
26. INTRACELLULAR DESTRUCTION OF MICROBES AND DEBRIS
• Killing of microbes & destruction of ingested materials are
accomplished by:-
Reactive oxygen species (ROS)
Reactive nitrogen species, mainly derived from nitric oxide
(NO)
Lysosomal enzymes.
• This is the final step in the elimination of infectious agents &
necrotic cells.
6/25/2023 Inflammation 27
27. Reactive oxygen species (ROS)
• are produced by the rapid assembly and activation of a
multicomponent enzyme, phagocyte oxidase (also called
NADPH oxidase), which oxidizes NADPH
and, in the process, reduces oxygen to the superoxide anion (O2
• )
• In neutrophils, this oxidative reaction is tightly linked to
phagocytosis, and is called the respiratory burst.
6/25/2023 Inflammation 28
28. • ROS are produced within the phagolysosome, where they can act
on ingested particles without damaging the host cell
• O2 • is then converted (H2O2), mostly by spontaneous
dismutation, a process of simultaneous oxidation and reduction
• The enzyme myeloperoxidase (MPO), which, in the presence of a
halide such as Cl− , converts H2O2 to hypochlorite (OCl2 −), a
potent anti-microbial agent
• The H2O2-MPO-halide system is the most efficient bactericidal
system of neutrophils
6/25/2023 Inflammation 29
29. Nitric Oxide
• NO, a soluble gas produced from arginine by the action of
nitric oxide synthase (NOS)
• Expressed when macrophages are activated by cytokines (e.g.,
IFN-γ) or microbial products, and induces the production of
NO
• In macrophages, NO reacts with superoxide (O2 • ) to generate
the highly reactive free radical peroxynitrite (ONOO•)
• - attack and damage the lipids, proteins, and nucleic acids of
microbes and host cell
6/25/2023 Inflammation 30
30. Granule Enzymes and Other Proteins
• Neutrophils and monocytes contain granules packed with
enzymes and anti-microbial proteins that degrade microbes and
dead tissues and may contribute to tissue damage.
• These granules are actively secretory and thus distinct from
classical lysosomes.
• Neutrophils have two main types of granules.
• The smaller specific (or secondary) granules contain lysozyme,
collagenase, gelatinase, lactoferrin, plasminogen activator,
histaminase, and alkaline phosphatase.
6/25/2023 Inflammation 31
31. • The larger azurophil (or primary) granules contain
MPO, bactericidal factors (such as defensins), acid
hydrolases, and a variety of neutral proteases
(elastase, cathepsin G, nonspecific collagenases,
proteinase 3
• Different granule enzymes serve different functions
6/25/2023 Inflammation 32
32. Neutrophil Extracellular Traps
• are extracellular fibrillar networks that concentrate anti-
microbial substances at sites of infection
• - prevent the spread of the microbes by trapping them in the
fibrils.
• - are produced by neutrophils in response to infectious
pathogens (mainly bacteria and fungi) and inflammatory
mediators (e.g., chemokines, cytokines, and complement
proteins).
• In the process of NET formation, the nuclei of the neutrophils
are lost, leading to the death of the cells, sometimes called
NETosis, representing a distinctive form of cell death affecting
neutrophils.
6/25/2023 Inflammation 33
33. Leukocyte-Mediated Tissue Injury
• Leukocytes are important mediators of injury to normal cells and tissues
under several circumstances:
As part of a normal defense reaction against infectious microbes, when
tissues at or near the site of infection suffer collateral damage
When the inflammatory response is inappropriately directed against host
tissues, as in certain autoimmune diseases
When the host “hyper-reacts” against usually harmless environmental
substances, as in allergic diseases, including asthma, and some drug
reactions
6/25/2023 Inflammation 34
34. Mediators of inflammation
Are substances which initiate and regulate inflammatory reactions.
produced:
– locally by cells at the site of inflammation or
– may be circulating in the plasma typically synthesized by
liver.
Cell-derived mediators:
• rapidly released from intracellular granules (e.g. amine) Or
• synthesized de novo (e.g prostaglandins, leukotrienes, cytokines) in
response to a stimulus.
35. Major cell types that produce mediators of acute inflammation
are:
• tissue macrophages
• dendritic cells
• mast cells
Plasma-protein-derived mediators
• Typically undergo proteolytic cleavage to acquire their
biologic activities
• produced only in response to various molecules that
stimulate inflammation
36. Most important mediators of acute inflammation are:
• vasoactive amines(histamine & serotonin)
• lipid products (prostaglandins & leukotrienes)
• cytokines (including chemokines) and
• products of complement activation
39. Arachidonic Acid Metabolites
• is a 20-carbonpolyunsaturated fatty acid derived from dietary
sources or by conversion from the essential fatty acid linoleic
acid.
• present in the body mainly in its esterified form
major sources of AA metabolites in inflammation:
• Leukocytes
• mast cells
• endothelial cells and
• platelets
40. AA metabolism proceeds along one of the following major enzymatic pathways:
Cyclooxygenase:
• stimulates the synthesis of prostaglandins and
thromboxanes.
Lipoxygenase:
• responsible for production of leukotrienes and lipoxins
44. Complement system
• combination of plasma proteins that play an important role in
host defense and inflammation.
• C1 to C9 are present in plasma in inactive forms.The critical
step in the generation of biologically active complement
products is the activation of the third component C3.
45. Cleavage of C3 can occur by one of the following three
pathways:
• classical pathway
• alternative pathway
• lectin pathway
48. Morphologic patterns of acute inflammation
Serous inflammation
• characterized by outpouring of a watery relatively protein-
poor fluid
Example: skin blister resulting from a burn or viral infection.
49.
50. Fibrinous inflammation:
• occurs as a consequence of more severe injuries.
• Histologically, appears as an eosinophilic meshwork of
threads or sometimes as an amorphous coagulum.
• characteristic of inflammation in the lining of body cavities,
(meninges, pericardium and pleura).
53. Ulcer
• local defect of the surface of an organ or tissue produced by
necrosis of cells & sloughing of inflammatory necrotic tissue.
54. Outcomes of acute inflammation
• Complete Resolution
• scarring or fibrosis
• Progression to chronic inflammation
55.
56. CHRONIC INFLAMMATION
• a response of prolonged duration (weeks or months) in which
inflammation, tissue injury, and attempts at repair coexist,
in varying combinations.
• Associated with more tissue destruction, the presence of
lymphocytes and macrophages, the proliferation of blood
vessels, and fibrosis.
6/25/2023 Inflammation 57
57. CAUSES OF CHRONIC INFLAMMATION
• Persistent infections by microorganisms that are difficult to
eradicate, such as:-
– Mycobacteria, Certain viruses ,Fungi and Parasites.
• Hypersensitivity diseases;caused by excessive and
inappropriate activation of the immune system .eg MS,RA,
Asthma
• Prolonged exposure to potentially toxic agents, . eg, silicosis
,atheroscerolosis...
6/25/2023 Inflammation 58
58. MORPHOLOGIC FEATURES
• Chronic inflammation is characterized by the following:
– Infiltration with mononuclear cells, which include
macrophages, lymphocytes, and plasma cells.
– Tissue destruction, induced by the persistent offending agent
or by the inflammatory cells.
– Attempts at healing by connective tissue replacement of
damaged tissue, accomplished by angiogenesis and in
particular, fibrosis
6/25/2023 Inflammation 59
59. CELLS AND MEDIATORS OF CHRONIC INFLAMMATION
1. Macrophages
• The dominant cells in most chronic inflammatory reactions by
secreting cytokines and growth factors.
• Professional phagocytes that act as filters for particulate matter,
microbes, and senescent cells.
• As effector cells that eliminate microbes in cellular and humoral
immune responses.
6/25/2023 Inflammation 60
60. ...
• activate other cells (lymphocytes)
• They are found in specific locations in organs such as the liver
(Kupffer cells), spleen and lymph nodes (sinus histiocytes),
central nervous system (microglial cells), and lungs (alveolar
macrophages).
6/25/2023 Inflammation 61
61. macrophages activation
• Two major pathways of macrophage activation:-
1.Classical Path way induced by microbial products such as
endotoxin (TLRs ) and by T cell–derived signals.
2.Alternative marophage activation is induced by cytokines (
IL-4 and IL-13) produced by T lymphocytes and other cells.
• Secrete mediators of inflammation (cytokines, chemokines,
and eicosanoids ).
6/25/2023 Inflammation 62
63. mediators of chronic inflammation
2.Lymphocytes
– Microbes and other environmental antigens activate T and
B lymphocytes, which amplify and propagate chronic
inflammation.
– Major function of these lymphocytes is as the
mediators of adaptive immunity but these cells are
often present in chronic inflammation.
6/25/2023 Inflammation 64
64. Cont….
• Dominant population in the chronic inflammation seen in
autoimmune and other hypersensitivity diseases.
• T cells greatly amplify the early inflammatory reaction that is
induced by recognition of microbes and dead cells as part of
the innate immune response.
6/25/2023 Inflammation 65
65. Cont…
• Three subsets of CD4+ T cells that secrete different cytokines and
elicit different types of inflammation.
1. TH1 cells produce the cytokine IFN-γ, which activates
macrophages by the classical pathway.
2. TH2 cells secrete IL-4, IL-5, and IL-13, which recruit and
activate eosinophils and are responsible for the alternative
pathway of macrophage activation.
3. TH17 cells secrete IL-17 and other cytokines, which induce the
secretion of chemokines responsible for recruiting neutrophils
into the reaction
6/25/2023 Inflammation 66
66. Cont….
• Both TH1 and TH17 cells are involved in defense against
many types of bacteria and viruses and in autoimmune
diseases.
• TH2 cells are important in defense against helminthic parasites
and in allergic inflammation.
• Activated B lymphocytes and antibody-producing plasma cells
are often present at sites of chronic inflammation.
6/25/2023 Inflammation 67
67. are abundant in immune reactions mediated by IgE and in
parasitic infections.
– recruitment is driven by adhesion molecules similar to
– those used by neutrophils, and by specific chemokines
– (e.g., eotaxin) derived from leukocytes and epithelial cells
– have granules that contain major basic protein, a highly
cationic protein that is toxic to helminths
6/25/2023 Inflammation 68
A focus of inflammation containing numerous
eosinophils
3 .Eosinophils
68. .4. Mast cells
• are widely distributed in connective tissues and participate in
both acute and chronic inflammatory reactions.
• express on their surface the receptor
(FcεRI) that binds the Fc portion of IgE antibody.
• cells degranulate and release mediators such as histamine
and prostaglandins
• response occurs during allergic reactions to foods, insect
venom,or drugs.
6/25/2023 Inflammation 69
69. 5.neutrophils
• can involve in many forms of chronic inflammation
• induced either by persistent microbes or by cytokines and
other mediators produced by activated macrophages and T
lymphocytes.
• they appear in chronic osteomyelitis.
• are important in the chronic damage induced in lungs by
smoking and other irritant stimuli
6/25/2023 Inflammation 70
70. GRANULOMATOUS INFLAMMATION
• Is a form of chronic inflammation characterized by
collections of activated macrophages, often with T
lymphocytes sometimes with necrosis.
• Granuloma formation is a cellular attempt to contain
an offending agent that is difficult to eradicate.
6/25/2023 Inflammation 71
71. Two types of granulomas
1. Immune granulomas
• persistent T cell mediated immune response
eg. tuberclosis, schistosomiasis
2. Foreign body granulomas
because of inert foriegn bodies (talc ,Sutures and other fibers
which are large enough to perclude phagocytosis)
have no T cell mediated immune response .
6/25/2023 Inflammation 72
73. Systemic effects of inflammation
• Endocrine and metabolic
– Secretion of acute phase proteins by the liver
a .C-reactive protein (CRP), serum amyloid A (SAA)
bind to microbial cell walls, and they may act as opsonins and fix complement
fibrinogen Fibrinogen binds to red cells and causes them
to form stacks (rouleaux) that sediment more rapidly
at unit gravity than do individual red cells.
– Increased production of glucocorticoids
(stress response)
• Fever
Cytokines (TNF, IL-1) stimulate production of PGs in
hypothalamus
74. Systemic effects of inflammation…
• Autonomic
– Redirection of blood flow from skin to deep vascular
beds minimizes heat loss
– Increased pulse and blood pressure
• Behavioral
– Shivering (rigors), chills (search for warmth), anorexia
(loss of appetite), somnolence, and malaise
75. Systemic effects of inflammation…
• Leukocytosis: increased leukocyte count in the blood
– Neutrophilia: bacterial infections
– Lymphocytosis: infectious mononucleosis, mumps,
measles
– Eosinophilia: Parasites, asthma, hay fever
• Leukopenia: reduced leukocyte count
– Typhoid fever, some viruses, rickettsiae, protozoa
76. References;
• 1.ROBBINS AND COTRAN PATHOLOGIC BASIS
OF DISEASE, 10TH EDITION
• 2.ROBBINS BASIC PATHOLOGY ,10TH EDITION
May be potentially harmful
Hypersensitivity reactions to insect bites, drugs, contrast media in radiology
Chronic diseases: arthritis, atherosclerosis
Disfiguring scars, visceral adhesions
Sequence of events in an inflammatory reaction. Macrophages
and other cells in tissues recognize microbes and damaged cells and
liberate mediators, which trigger the vascular and cellular reactions of inflammation.
Recruitment of plasma proteins from the blood is not shown.
RECOGNITION OF MICROBES AND DAMAGED CELLS
The first step in inflammatory responses is the recognition of microbes and necrotic cells by cellular receptors and circulating proteins.
Cellular receptors for microbes. Phagocytes, dendritic cells (cells in epithelia and all tissues whose function is to capture microbes), and many other cells express receptors that detect the presence of infectious pathogens. The best defined of these receptors belong to the family
Sensors of cell damage. All cells have cytosolic receptors that recognize molecules that are liberated or altered as a consequence of cell damage, and are hence appropriately called damage-associated molecular patterns (DAMPs).
Circulating proteins. Several plasma proteins recognize microbes and function to destroy blood-borne microbes and to stimulate inflammation at tissue sites of infection.
The complement system reacts against microbes and produces mediators of inflammation (discussed later). A circulating protein called mannose-binding lectin recognizes microbial sugars and promotes ingestion of microbes and activation of the complement system. Other proteins called collectins also bind to microbes and promote their phagocytosis.
When a microbe enters a tissue or the tissue is injured, the presence of the infection or damage is sensed by resident cells, including macrophages, dendritic cells, mast cells, and other cell types.
These cells secrete molecules (cytokines and other mediators) that induce and regulate the subsequent inflammatory response.
Inflammatory reactions may be triggered by a variety of stimuli:
Infections (bacterial, viral, fungal, parasitic) and microbial toxins are among the most common and medically important causes of inflammation.
Tissue necrosis elicits inflammation regardless of the cause of cell death, which may include ischemia (reduced blood flow, the cause of myocardial infarction), trauma, and physical and chemical injury (e.g., thermal injury, as in burns or frostbite; irradiation; exposure to some environmental chemicals). Several molecules released from necrotic cells are known to trigger inflammation;
3. Foreign bodies (splinters, dirt, sutures) may elicit inflammation by themselves or because they cause traumatic tissue injury or carry microbes. Even some endogenous substances stimulate potentially harmful inflammation if large amounts are deposited in tissues; such substances include urate crystals (in the disease gout), and cholesterol crystals (in atherosclerosis).
4. Immune reactions (also called hypersensitivity) are reactions in which the normally protective immune system damages the individual’s own tissues. The injurious immune responses may be directed against self antigens, causing autoimmune diseases, or may be inappropriate reactions against environmental substances, as in allergies, or against microbes.
It is the initial, rapid response to infections and tissue damage.
It typically develops within minutes or hours and is of short duration, lasting for several hours or a few days.
Its main characteristics are the exudation of fluid and plasma proteins (edema) and the emigration of leukocytes, predominantly neutrophils (also called polymorphonuclear leukocytes).
CHANGES IN VASCULAR FLOW AND CALIBER
Changes in vascular flow and caliber begin early after injury and consist of the following:
Earliest manifestation is Vasodilation is induced by the action of several mediators, notably histamine, on vascular smooth muscle.
It is one of the earliest manifestations of acute inflammation, and may be preceded by transient vasoconstriction.
Vasodilation first involves the arterioles and then leads to the opening of new capillary beds in the area. The result is increased blood flow, which is the cause of heat and redness (erythema) at the site of inflammation.
Vasodilation is quickly followed by increased permeability of the microvasculature, with the outpouring of protein-rich fluid (an exudate) into the extravascular tissues.
The loss of fluid and increased vessel diameter lead to slower blood flow, concentration of red cells in small vessels, and increased viscosity of the blood. These changes result in stasis of blood flow, engorgement of small vessels jammed with slowly moving red cells.
Reactions of Blood Vessels in Acute Inflammation
The vascular reactions of acute inflammation consist of changes in the flow of blood and the permeability of vessels, both designed to maximize the movement of plasma proteins and leukocytes out of the circulation and into the site of infection or injury.
The escape of fluid,proteins, and blood cells from the vascular system into interstitial tissues or body cavities is known as exudation
transudate is a fluid with low protein content, little or no cellular material, and low specific gravity.
Edema denotes an excess of fluid in the interstitial tissue or serous cavities; it can be either an exudate or a transudate.
Increased Vascular Permeability (Vascular Leakage)
Several mechanisms are responsible for increased vascular permeability in acute inflammation
• Retraction of endothelial cells resulting in opening of interendothelial spaces is the most common mechanism of vascular leakage. It is elicited by histamine, bradykinin, leukotrienes, and other chemical mediators. It occurs rapidly after exposure to the mediator (within 15 to 30 minutes) and is usually short-lived; hence, it is referred to as the immediate transient response, to distinguish it from the delayed prolonged response that follows endothelial injury, described next. The main sites for this rapid increase in vascular permeability are postcapillary venules.
• Endothelial injury, resulting in endothelial cell necrosis and detachment. Direct damage to the endothelium is encountered in severe injuries, for example, in burns, or is induced by the actions of microbes and microbial
toxins that target endothelial cells. Neutrophils that adhere to the endothelium during inflammation may also injure the endothelial cells and thus amplify the reaction. In most instances leakage starts immediately after injury and is sustained for several hours until the damaged vessels are thrombosed or repaired.
Lymphatic vessels proliferate during inflammatory reactions to handle the increased load. The lymphatics may become secondarily inflamed (lymphangitis), as may the draining lymph nodes (lymphadenitis).
Inflamed lymph nodes are often enlarged because of increased cellularity. This constellation of pathologic changes is termed reactive, or inflammatory, lymphadenitis
Lymph flow is increased to help drain edema fluid that accumulates because of increased vascular permeability.
The principal
functions of these cell types differ in subtle but important ways—neutrophils use cytoskeletal rearrangements and enzyme assembly to mount rapid, transient responses, whereas macrophages, being long-lived, make slower but more prolonged responses that often rely on new gene transcription
The leukocytes first roll, then become activated
and adhere to endothelium, then transmigrate across the endothelium, pierce the basement membrane, and move toward chemoattractants emanating from the source of injury. Different molecules play predominant roles at each step of this process: selectins in rolling; chemokines (usually displayed bound to
proteoglycans) in activating the neutrophils to increase avidity of integrins; integrins in firm adhesion; and CD31 (PECAM-1) in transmigration. ICAM-1, Intercellular
adhesion molecule-1; PECAM-1 (CD31), platelet endothelial cell adhesion molecule-1; TNF, tumor necrosis factor.
A) Early (neutrophilic) infiltrates and congested blood vessels. (B) Later (mononuclear) cellular infiltrates. (C) The approximate kinetics of edema and cellular infiltration.
Phagocytosis involves three sequential steps:
Recognition and attachment of the particle to be ingested by the leukocyte.
Engulfment, with subsequent formation of a phagocytic vacuole.
Killing or degradation of the ingested material .
These steps are triggered by:-
Microbes
Necrotic debris, and
Various mediators.
Leukocytes ingest offending agents (phagocytosis), kill microbes, and degrade necrotic tissue and foreign antigens
(A) Phagocytosis of a particle (e.g., a bacterium) involves binding to receptors on the leukocyte
membrane, engulfment, and fusion of the phagocytic vacuoles with lysosomes. This is followed by destruction of ingested particles within the phagolysosomes
by lysosomal enzymes and by reactive oxygen and nitrogen species. (B) In activated phagocytes, cytoplasmic components of the phagocyte oxidase enzyme
assemble in the membrane of the phagosome to form the active enzyme, which catalyzes the conversion of oxygen into superoxide (O2
− ) and H2O2. Myeloperoxidase,
present in the granules of neutrophils, converts H2O2 to hypochlorite. (C) Microbicidal reactive oxygen species (ROS) and nitric oxide (NO) kill
ingested microbes. During phagocytosis, granule contents may be released into extracellular tissues (not shown). iNOS, Inducible NO synthase; MPO, myeloperoxidase;
ROS, reactive oxygen species.
The killing and degradation of microbes and elimination of dead-cell debris within neutrophils and macrophages occur most efficiently after their activation.
-participates in microbial killing
-In some infections that are difficult to eradicate, such as tuberculosis and certain viral diseases such as hepatitis
It is the initial response fails to clear the stimulus and the reaction progresses to a protracted type.
These organisms often
evoke an immune reaction called delayed-type hypersen_x0002_sitivity (Chapter 5). The inflammatory response some_x0002_times takes a specific pattern called granulomatous
inflammation (discussed later). In other cases, unresolved
acute inflammation evolves into chronic inflammation,
such as when an acute bacterial infection of the lung
progresses to a chronic lung abscess.
Prolonged exposure to potentially toxic agents, either
exogenous or endogenous. An example of an exogenous
agent is particulate silica, a nondegradable inanimate
material that, when inhaled for prolonged periods,
results in an inflammatory lung disease called silicosis
(Chapter 13). Atherosclerosis (Chapter 10) is a chronic
inflammatory process affecting the arterial wall that is
thought to be induced, at least in part, by excessive
production and tissue deposition of endogenous cholesterol
and other lipids.. In allergic diseases, chronic inflamma_x0002_tion is the result of excessive immune responses against
common environmental substances, as in bronchial
asthma. Because these autoimmune and allergic reac_x0002_tions are triggered against antigens that are normally
harmless, the reactions serve no useful purpose and
only cause disease
Attempts at healing by connective tissue replacement of damaged tissue, accomplished by angiogenesis (proliferation of small blood vessels) and, in particular, fibrosis
contrast to acute inflammation, which is manifested by
vascular changes, edema, and predominantly neutrophilic
infiltration, chronic inflammation is characterized by the
following:
• Infiltration with mononuclear cells, which include
macrophages, lymphocytes, and plasma cells (Fig. 3.17) • Tissue destruction, induced by the persistent offending
agent or by the inflammatory cells
• Attempts at healing by connective tissue replacement
of damaged tissue, accomplished by angiogenesis (prolif_x0002_eration of small blood vessels) and, in particular,
fibrosis
from bm hsc monocyte activinated macrophages
proginator yoc sac fetal liver to resident tissue .
mononuclear phagocyte system instead of reticuol endo.sysapc phago opsonised mic
why activated
to sec
Neutrophils also are important
in the chronic damage induced in lungs by smoking
and other irritant stimuli. This pattern of
inflammation has been called acute on chronic.
The activated macro_x0002_phages may develop abundant cytoplasm and begin to
resemble epithelial cells, and are called epithelioid cells.
Some activated macrophages may fuse, forming multinu_x0002_cleate giant cells. Granuloma formation is a cellular attempt
to contain an offending agent that is difficult to eradicate.
In this attempt there is often strong activation of T lympho_x0002_cytes leading to macrophage activation, which can cause
injury to normal tissues.Two types of granulomas
Immune granulomas are caused by a variety of agents that are capable of inducing a persistent T cell–mediated immune response.
Foreign body granulomas are seen in response to relatively inert foreign bodies, in the absence of T cell– mediated immune responses.
activ th1 ifr g . activate mac tuberculoma
th2 schs
In the setting of persistent T cell responses to certain microbes (e.g., M. tuberculosis, Treponema pallidum, or fungi), T cell derived cytokines are responsible for chronic macrophage activation and granuloma formation.
Granulomas may also develop in some immune-mediated inflammatory diseases, notably Crohn disease, which is one type of inflammatory bowel disease
