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1. Acute and Chronic Inflammation

2. Acute and Chronic Inflammation
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 General features of inflammation (introduction)
 Acute inflammation
 Chronic inflammation
 Causes
 Systemic effects of inflammation

3. Introduction:
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 “Inflame” – to set fire.
 Inflammation is “dynamic response of vascularized and living
tissue to injury.”.
 Inflammation is a response of vascularized tissues to infections
and damaged tissues that brings cells to injury
 Is a protective, physiologic response.
 Inflammation is intended to
 Contain and isolate injury,
 Destroy invading microorganisms and inactivate toxins, and
 Prepare the tissue for healing and repair

4. Introduction….
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The ultimate goal
 To rid the organism of both the initial cause of cell injury
 E.g., microbes, toxins and the consequences of such injury
 E.g., necrotic cells and tissues
Without inflammation,
 Infections would go unchecked,
 Wounds would never heal, and
 Injured organs might remain permanent festering sores.

5. Introduction…
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 The two main components inflammatory response
 A vascular reaction and
 A cellular response
 Tissues and cells involved in these reactions, include
 The fluid and proteins of plasma
 Circulating cells
 Blood vessels, and
 Cellular and extracellular constituents of connective tissue

6. Introduction…
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 The circulating cells
 Neutrophils
 Monocytes , lymphocytes
 Eosinophils
 Basophils and platelets
 The connective tissue cells are
 The mast cells, which intimately surround blood vessels;
 Fibroblasts;
 Resident macrophages; and lymphocytes.

7.  The extracellular matrix consists[ECM]
 The structural fibrous proteins (collagen, elastin),
 Adhesive glycoproteins (fibronectin, laminin, nonfibrillar
collagen, Tenascin, and others)
 Proteoglycans.

8. Introduction…
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 Inflammation is divided into acute and chronic patterns.
Acute inflammation-is the initial, rapid response to infections and
tissue damage
 Rapid in onset (seconds or minutes)
 Relatively of short duration, lasting for minutes, several
hours, or a few days;
 Main characteristics are the exudation of fluid and plasma
proteins (edema) and the emigration of leukocytes,
predominantly Neutrophils.

9. Chronic inflammation
 Is of longer duration
 Associated histologically with the presence of
lymphocytes and macrophages, the proliferation of blood
vessels, fibrosis, and tissue necrosis.

10. Acute Inflammation
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 It is a rapid response to an injurious agent that serves to deliver
mediators of host defense—leukocytes and plasma proteins—to
the site of injury.
Has three major components:
1. Alterations in vascular caliber (dilation of small vessels) an increase in
blood flow
2. Structural changes in the microvasculature plasma proteins and
leukocytes 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.

11. Fluid changes is vascular flow
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Exudates – Is the escape of fluid, proteins, and blood cells from
the vascular system into the interstitial tissue or body cavities
 An inflammatory extravascular fluid has a high protein concentration,
cellular debris
 A specific gravity above 1.020.
 Vasodilation and stasis, Fluid and protein leakage
 Significant alteration in the normal permeability of small b/vessels in the
area of injury.
 An exudate is formed in inflammation, because vascular
permeability increases as a result of increased inter endothelial
spaces

12. .
Transudate- Is a fluid with low protein content (most of which is
albumin) and little or no cellular material
 a specific gravity of less than 1.012.
 It is essentially an ultrafiltrate of blood plasma that results from osmotic
or hydrostatic imbalance across the vessel wall without an increase in
vascular permeability.
 A Transudate is formed when fluid leaks out because of
increased hydrostatic pressure ( E.g. CHF) or decreased osmotic pressure (
E.g. LD, RD)
Normal, increased hydrostatic pressure and decreased colloid osmotic
pressure of tissues. Therefore, the net flow of fluid across the
vascular bed is almost nil.

13. Edema- is an excess of fluid in the interstitial or serous
cavities
-It can be either an exudate or a Transudate.
Pus- is a purulent exudate
 An inflammatory exudate rich in leukocytes (mostly
Neutrophils), the debris of dead cells and, in many cases,
microbes.

15. Stimuli for Acute Inflammation
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 Acute inflammatory reactions are triggered by a variety of
stimuli:
 Infections:- bacterial, viral, parasitic
 Microbial toxins
 Trauma (blunt and penetrating)
 Physical and chemical agents (thermal injury, E.g., Burns or
frostbite; irradiation; some environmental chemicals)
 Tissue necrosis (from any cause)
 Foreign bodies (splinters, dirt, sutures)
 Immune reactions (also called hypersensitivity reactions).

16. A. Vascular Changes
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Changes in Vascular Flow and Caliber ;- It begins early after
injury and develop at varying rates depending on the severity
of the injury.
Vasodilation -is one of the earliest manifestations of acute
inflammation; sometimes, it follows a transient constriction of
arterioles, lasting a few seconds.
 Is the first involves the arterioles and then results in opening of
new capillary beds in the area.

17. VASCULAR CHANGES…
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Vasodilation
 Is induced by the action of several mediators, notably histamine and
nitric oxide, on vascular smooth muscle.
 Is quickly followed by increased permeability of the microvasculature,
with the outpouring of protein-rich fluid into the extravascular
tissues(exudate)
 Is the loss of fluid results in;-concentration of red cells in small vessels
and, increased viscosity of the blood, reflected by the presence of
dilated small vessels packed with red cells and slower blood flow, a

18. Vasodilation..
-As stasis develops, leukocytes, principally Neutrophils,
accumulate along the vascular endothelium.
-stick to the endothelium, and soon afterward they migrate
through the vascular wall into the interstitial tissue.

20. B. Cellular Events: Leukocyte Extravasation and
Phagocytosis
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The sequence of events in the journey of leukocytes from the
vessel lumen to the interstitial tissue, called extravasation, can
be divided into the following steps:
1.In the lumen: margination, rolling, and adhesion to
endothelium.
2.Transmigration across the endothelium (also called
diapedesis).

21. Chemotaxis
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 After extravasation, leukocytes emigrate in tissues toward the
site of injury by a process called chemotaxis, defined most
simply as locomotion oriented along a chemical gradient.
 All granulocytes, monocytes and, to a lesser extent,
lymphocytes respond to chemotactic stimuli with varying rates
of speed.

22. Mechanism :…
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 Both exogenous and endogenous substances can act as
chemo attractants.
 The most common exogenous agents are bacterial
products.

23. Chemotaxis…
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Endogenous chemo attractants, include several chemical
mediators:
1. Components of the complement system, particularly C5a;
2. Products of the lipoxygenase pathway, mainly leukotriene B4 (LTB4); and
3. Cytokines, particularly those of the chemokine family (e.g., IL-8).

24. Cont…
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 The vascular and cellular reactions of both acute and
chronic inflammation are mediated by chemical factors
that are derived from
 Plasma proteins or cells and
 Are produced in response to or activated by the inflammatory
stimulus.
 Such mediators, acting singly, in combinations, or in
sequence, then amplify the inflammatory response and
influence its evolution.

25. Response,when?
The offending agent is eliminated and
The secreted mediators are removed;
Active anti-inflammatory mechanisms are also
involved

26. Chemical Mediators of Inflammation
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 The mediators of inflammation are the substances that
initiate and regulate inflammatory reactions.
 Many mediators have been identified and targeted
therapeutically to limit inflammation.
 Many mediators have been identified, and how they function
in a coordinated manner is still not fully understood.
 Some of the major mediators:

27. Chemical Mediators of Inflammation…
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28. Chemical Mediators of Inflammation…
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29. Leukocyte activation results in the enhancement of the
following functions:
 Phagocytosis of particles
 Intracellular destruction of phagocytosed microbes and dead
cells by
 Oxygen dependent mechanisms with the formation of
ROS or
 Oxygen independent mechanisms using leukocytic
granules

30.  Liberation of substances that destroy extracellular microbes
and dead tissues, which are largely the same as the
substances produced within phagocytic vesicles.
 Production of mediators, including arachidonic acid
metabolites and cytokines, that amplify the inflammatory
reaction, by recruiting and activating more leukocytes

31. Phagocytosis consists of three steps:
1. Recognition and attachment of the particle to the
ingesting leukocyte;
2. Engulfment, with subsequent formation of a phagocytic
vacuole; and
3. killing and degradation of the ingested material.

32. Cardinal Signs of Inflammation
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 Rubor : Redness – Hyperaemia.
 Calor : Warm – Hyperaemia.
 Dolor : Pain – Nerve, Chemical med.
 Tumor: Swelling – Exudation
 Loss of Function:

33. Heat Redness Swelling Pain Loss of function
The 5 Cardinal Signs of acute
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34. Morphologic types of acute inflammation
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A. Exudative Inflammation: is excess fluid. E.g TB lung.
B. Suppuration/Purulent Inflammation, abscess– the
collection of large amounts of purulent exudate (pus)
consisting of neutrophils, necrotic cells, and edema fluid.
The most frequent cause of is infection with bacteria that cause
liquefactive tissue necrosis. E.g S.aures
C. Fibrinous Inflammation– occurs as a consequence of more
severe injuries, resulting in greater vascular permeability that
allows large molecules (such as fibrinogen) to pass the
endothelial barrier .
Eg., cancer cells

35. D. Serous Inflammation–characterized by the
outpouring of a watery, relatively protein-poor fluid.
 Serous inflammation is marked by the exudation of
cell poor fluid into spaces created by cell injury or
into body cavities lined by the peritoneum, pleura, or
pericardium.
 Typically, the fluid in serous inflammation is not
infected by destructive organisms and does not
contain large numbers of leukocytes
E. Haemorrhagic – blood vessel damage

36. F. Ulcer --is a local defect, or excavation, of the surface of an
organ or tissue that is produced by necrosis of cells and
sloughing (shedding) of necrotic and inflammatory tissue .
 Ulceration can occur only when tissue necrosis and resultant
inflammation exist on or near a surface.
 Most commonly encountered in
 Mucosa of the mouth, stomach, intestines, or genitourinary
tract &
 Subcutaneous tissues of the lower extremities in older persons
who have circulatory disturbances predisposing affected
tissue to extensive necrosis.

37. Purulent-Inflammation-
Pus ;pneumonia
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38. Outcomes of Acute Inflammation
All acute inflammatory reactions typically have one of three
outcomes
1. Complete resolution:-Clearance of injurious stimuli,
Clearance of mediators and acute inflammatory cells,
Replacement of injured cells , Normal function
2. Healing by connective tissue replacement (scarring, or
fibrosis):- Loss of function
3. Progression of the response to chronic inflammation ;-
Angiogenesis , Mononuclear cell infiltrate, Fibrosis (scar)

40. Chronic Inflammation
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 Although difficult to define precisely, chronic inflammation is
considered to be
 Inflammation of prolonged duration (weeks or months) in which active
inflammation, tissue destruction, and attempts at repair are proceeding
simultaneously.
 It frequently begins insidiously, as a low-grade,
smoldering, often asymptomatic response or may
follow acute inflammation
 Cause of tissue damage in some of the most common
and disabling human diseases, such as
 Rheumatoid arthritis, atherosclerosis, tuberculosis, and
chronic lung diseases.

42. Causes of chronic inflammation
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Chronic inflammation arises in the following settings:
1. Persistent infections by certain microorganisms, such as
tubercle bacilli, Treponema pallidum (the causative organism
of syphilis), and certain viruses, fungi, and parasites. These
organisms are of low toxicity and evoke an immune reaction
called delayed type hypersensitivity.
2. Hypersensitivity disease

43. 3.The inflammatory response sometimes takes a specific pattern
called a granulomatous reaction.
4. Prolonged exposure to potentially toxic agents, either
exogenous or endogenous.
5. Autoimmunity.
 Under certain conditions, immune reactions develop against the individual's
own tissues, leading to autoimmune diseases.

44. Morphologic features
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 Chronic inflammation is characterized by:
 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
proliferation of small blood vessels (angiogenesis)
and, in particular, fibrosis.

45. Morphologic features….
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1.Non specific chronic inflammation
2. Specific – granulomatous chronic
inflammation.

46. Morphologic features…
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Granulomatous inflammation
 It is a distinctive pattern of chronic inflammatory reaction
characterized by focal accumulations of activated
macrophages, which often develop an epithelial-like
(epithelioid) appearance.
 Encountered in a limited number of immunologically
mediated, infectious and some non-infectious conditions.
 Tuberculosis is the prototype of the granulomatous diseases,
sarcoidosis, leprosy, brucellosis, syphilis, some mycotic
infections….

47. Granulomatous inflammation …
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A Granuloma- is a focus of chronic inflammation consisting of a
microscopic aggregation of macrophages that are transformed
into epithelium-like cells surrounded by a collar of mononuclear
leukocytes, principally lymphocytes and occasionally plasma
cells.

48. Granuloma:
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 H and E stained tissue section,
 the epithelioid cells have a pale pink granular cytoplasm with indistinct
cell boundaries, often appearing to merge into one another.

49. Caseating granulomas

50. Conditions for formation of granulomas
There are two types of granulomas, which differ in their
pathogenesis
 Presence of indigestible foreign body (material ) derived
from bacteria or other sources
 Cell-mediated immune reaction against the injurious agent
(type IV hypersensitivity reaction)=> interferon gamma
transforms, macrophage into epithelioid cells

51. Chronic
Inflammation:
Lung Abscess
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52. Systemic Effects of Inflammation
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 Fever :- Caracterized by an elevation of body temperature,
usually by 1° to 4°C,
 Is one of the most prominent manifestations of the acute
phase response, especially when inflammation is associated
with infection.
 Acute-phase proteins are plasma proteins, mostly synthesized
in the liver, whose plasma concentrations may increase several
hundred-fold as part of the response to inflammatory stimuli.
 ESR
 Fibrinogen

53. Systemic Effects of Inflammation,,,,,
 Leukocytosis is a common feature of inflammatory
reactions, especially those induced by bacterial
infection.
 The leukocyte count usually climbs to 15,000 or 20,000
cells/mL, but sometimes it may reach extraordinarily
high levels of 40,000 to 100,000 cells/mL.
 Neutropilia-------- Acute infection (bacterial)
 Lymphocytosis-------------chronic infections ( viral)
 Monocytosis------------ ‘’
 Eosinophilia------------parasites, allergy
 Leucopenia (occasional)

54. Cont…
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Other manifestations of the acute phase response
include
 Increased pulse and blood pressure;
 Decreased sweating, mainly because of redirection of blood
flow from cutaneous to deep vascular beds, to minimize heat
loss through the skin;
 Rigors (shivering), chills (search for warmth), anorexia,
somnolence, and malaise, probably because of the actions of
cytokines on brain cells.
 In severe bacterial infections (sepsis)

55. Consequences of Inflammation
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The clinical and pathological consequences of too
much or too little inflammation.
 Defective inflammation typically results in
 Increased susceptibility to infections and
 Delayed healing of wounds and tissue damage.

56. Consequences of Inflammation…
 Excessive inflammation is the basis of many
categories of human disease.
 Allergies, in which individuals mount unregulated immune
responses against commonly encountered environmental
antigens,
 Autoimmune diseases, in which immune responses develop
against normally tolerated self-antigens.
 Abscess formation
Fistula
Sinus
sepsis

57. Acute Vs Chronic
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 Flush, Flare & Weal
 Acute inflammatory cells -
Neutrophils
 Vascular damage
 More exudation
 Little or no fibrosis
 Little signs
 Chronic inflammatory cells –
Lymphocytes,macrophages
 Neo-vascularization
 No/less exudation; abcess.
 Prominent fibrosis

58. Outcomes of inflammation
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