Inflammation is a basic pathological topic

Awesome lecture

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2. Learning objectives
At the end of this chapter you will be able to:
1.Define inflammation
2.Contrast the differences between acute & chronic inflammations
3.Know the causes of inflammation
4.Understand the process of inflammation
5.Comprehend the etiopathogenesis of granulomatous
inflammations
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3. Introduction - History
 Egyptian papyrus - 3000 B.C. – clinical features of
inflammation were described.
 Celsus (Roman in 1st century A.D.) for the first time
mentioned the 4 cardinal signs of inflammation.
 Rubor - Tumor - Calor - Dolor
 Virchow (Father of modern pathology) –
 Added functio-laesa( loss of function) later
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4. What is inflammation?

 Literally means – “to set fire”
 Protective response of a vascularized tissue to an
injurious agent.
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5.  Inflammation is a beneficial host response to foreign
invaders and necrotic tissue
 It is itself capable of causing tissue damage.
 The main components of inflammation are a vascular
reaction and a cellular response
 Both are activated by mediators that are derived from plasma
proteins and various cells.
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General Features

6. The steps of the inflammatory response can be
remembered as the five Rs:
1.Recognition of the injurious agent
2.Recruitment of leukocytes
3.Removal of the agent
4.Regulation (control) of the response
5.Resolution (repair)
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7. Nomenclature

Generally speaking the suffix – itis indicates inflammation
of the involved organ
Examples.
 Sinus – sinusitis
 Esophagus – esophagitis
 Liver – hepatitis
 Skin – dermatitis etc…
Exceptions: Lung – pneumonia
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8. Types of inflammation
Acute & chronic
Features Acute Chronic
Onset Immediate Delayed
Duration Few days Wks, months or even yrs
Outcome Healing, abscess formation,
fibrosis & chronic inflammation
Tissue destruction
Primary mediator Vasoactive amines & eicosanoids Cytokines
Causative agents Pathogens Persistent inflammation
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9. Acute inflammation
 It is an immediate & early response to injurious agent.
 Causes include:-
Infections
Trauma
Physical, chemical & thermal radiation
Tissue necrosis
Immune reactions
Foreign bodies
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10. Cardinal signs of inflammation
1.Redness – Rubor
2.Swelling – Tumor
3.Heat – Color
4.Pain – Dolor
5.Loss of function – Fuctio-laesa
 NB. This signs are results of different mechanism & it is more prominent in
acute inflammation.
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11.  Acute inflammation has two major components:
Vascular changes:
Vasodilation
Increased vascular permeability
Cellular events:
 Emigration of the leukocytes from the microcirculation and accumulation in the
focus of injury (cellular recruitment and activation).
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Pathogenesis

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13. Terminology
Exudation – escape of fluid, proteins & blood cells into
the interstitium
There are two types of interstitial fluids
 Exudate
 Transudate
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14. Transudate Vs Exudate
Transudate (non-inflammatory)Exudate (inflammatory)
Specific gravity < 1.012 >1.020
Protein Low High
Vascular permeability Normal Increased
Others Imbalance between hydrostatic
& osmotic pressure
Contains cellular debris
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15. Vascular changes
It occurs in the following sequences
 Vasodilatation - an earliest manifestation first involving the arterioles &
causes increased blood flow.
 Results in heat & redness
Increased vascular permeability
 This leads to escape of protein rich fluid to the extravascular space.

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16. Cellular events
 Inflammation is crucial to deliver leukocytes & antibodies to
the site of injury.
 Leukocytes are crucial for the following activities:
 Ingest offending agents
 Kills bacteria
 Get rid of necrotic tissue & foreign bodies
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17. Leukocyte Recruitment
The sequence of events in the recruitment of leukocytes from the vascular
lumen to the extravascular space
Recruitment consists of
1.Margination along the vessel wall
2.Rolling along the vessel wall
3.Adhesion to the endothelium
4.Transmigration between endothelial cells
5.Migration in interstitial tissues toward a chemotactic stimulus
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19. Chemotactic factors include….
1.Soluble bacterial products
2.Complement components (C5a)
3.Arachidonic acid (AA) metabolite products such as
1. leukotriene B4
4.Chemokines, cytokines
(
IL-8)
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20. Phagocytosis
Is the process of engulfment & internalization by specialized cells.
Three steps in phagocytosis are:
1.Recognition & attachment: Opsonins
(
IgG & C3b) coat target and bind
to leukocytes
2.Engulfment
3.Killing/degradation
O2 dependent: Reactive O2 species in lysosomes
O2 independent: Bactericidal permeability agents, lysozyme, MBP, lactoferrin
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21. Outcomes of Acute Inflammation
1. Resolution
2. Fibrosis
3. Abscess formation
4. Progression to chronic inflammation
 
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Outcomes of Acute Inflammation

23. Effects of acute inflammation
1. Beneficial Effects
 Dilution of toxins
 Protective abs
 Fibrin formation

 Plasma mediator system provisions
 Promotion of immunity

24. Effects of acute inflammation cont.…
2. Harmful effects
 Tissue destruction
 Swelling
 Inappropriate response

25. Morphologic patterns of Acute
inflammation
There are different morphologic types of acute inflammation:
1
.
Serous inflammation
 Is characterized by thin tissue fluid accumulation
 In the peritoneal, pleural & pericardial cavities it is called an effusion.
 But it can also occur elsewhere.
 E.g. skin burn blisters
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27. 2 .Fibrinous inflammation
 More severe injuries result in greater vascular permeability that
ultimately leads to exudation of larger molecules such as fibrinogens.
 Fibrinous exudate is characteristic of inflammation in serosal body
cavities such as the pericardium (butter & bread appearance) &
pleura.
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29. 3 .Suppurative/purulent inflammation
 Is characterized by production of a large amount of pus.
 Pus is a thick creamy liquid, yellowish or blood tingled in color composed of
leukocytes & necrotic cells.
 Abscess refers to a localized collection of pus.
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30. 4 .Ulcers
Are local erosions of epithelial surfaces produced by sloughing of
inflamed necrotic tissues.
E.g. gastric ulcers
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31. Chronic inflammation

It is an inflammation of prolonged duration weeks, months or
years.
 The triads of chronic inflammation are:
 Active inflammation
 Tissue destruction
 Healing which occur simultaneously
It is not characterized by the cardinal signs of inflammation rather
there is:
Infiltration with mononuclear (chronic inflammatory) cells – macrophages,
lymphocytes & plasma cells
Tissue destruction
Repair (new blood vessel formation & fibrosis)
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32. Cont....
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33. Causes
1.Persistent infections
2.Prolonged exposure to potentially toxic agents
 Silica
 Toxic plasma lipids → atherosclerosis
3.Autoimmune diseases like RA
(
Rheumatoid arthritis)
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34. Chronic inflammatory cells & mediators
 Monocytes & macrophages are the primary cells in chronic inflammation.

1. Macrophages
 Play a central role in chronic inflammation.
 They are tissue cells derived from monocytes after immigration from
blood stream
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35. Other cells in chronic inflammation
1.T- lymphocytes-
Are primarily involved in cellular immunity
They are the key regulator & effector cells of the immune system.
 
2
.
B- lymphocytes & Plasma cells
Produce antibody directed either against persistent antigen in the
inflammatory site or against altered tissue components.
3. Mast cells & eosinophiles
Appear predominantly in response to parasitic infestations & allergic
reactions
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Other cells in chronic inflammation:

37. Classification of chronic inflammation
 Classified in to two types based on histologic features:

1
.
Nonspecific chronic inflammation
This involves diffuse accumulation of macrophages & lymphocytes at sites
of injury that is usually productive with new fibrous tissue formations.
 E.g. Chronic cholecystitis
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38. 2 .Granulomatous inflammation
 It is a distinctive pattern of chronic inflammatory reaction characterized
by the presence of granuloma.
 A granuloma is focal accumulation of activated macrophages which
develop an epithelial-like (epithelioid) appearance and surrounded by
lymphocytes, plasma cells & fibroblasts.
 The epithelioid cells can fuse with each other & form multinucleated
giant cells.
 TB is a prototype of this type of inflammation which forms a caseous
granulomatous lesion.
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39. Two types of granulomas
1.Foreign body:-
Which are incited by inert foreign bodies.
Formed when suture or other fibers preclude phagocytosis.
The foreign body can be identified in the center of granuloma
which appears refractile.

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40. Cont.…
2. Immune granuloma:-
 Are caused by insoluble particles typically microbes that are capable of
inducing cell mediated immune response.
E.g. TB bacilli
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41. Pathological conditions associated with
granuloma formation
1.Bacteria:- TB, leprosy, T. pallidum, cat scratch disease
2.Parasite:- Schistosomiasis, onchocerciasis
3.Fungus:- Histoplasma, Cryptococcus
4.Inorganic metals or dusts:- Silicosis, pneumoconiosis
5.Foreign bodies
6.Unknown:- Sarcoidosis 41

42. Systemic effects of inflammation
 Systemic changes associated with inflammation are collectively
called acute phase response.
 In severe cases it is known as systemic inflammatory response
syndrome (SIRS).
 These represent responses to cytokines produced either by
bacterial products or by other inflammatory stimuli.
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43. Cont.…
 Acute phase response consists of several clinical & pathological
changes:
 Fever
 Acute phase proteins
 Leukocytosis
 Other manifestations:-
Increased pulse & blood pressure, decreased sweating,
rigors, chills, anorexia
,
somnolence & malaise
.
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44. Systemic effects of inflammation
1.Fever
2.Endocrine & metabolic responses
3.Autonomic responses
4.Behavioral responses
5.Leukocytosis
6.Leucopenia
7.Weight loss
8.Sepsis

45. Leukocytosis
 Increase in white cell count
 Leukocyte count
 Typically increases to 15,000 or 20,000 cells per μL (normal = 4000 to
11,000 cells per μL)
 May climb as high as 40,000 to 100,000 cells per μL, a so-called
leukemoid reaction.
 Leukocytosis initially results from the release of cells from the
bone marrow (caused by IL-1 and TNF)
 Is associated with an increased number of relatively immature
neutrophils in the blood ("left-shift").

46.  Most bacterial infections induce a relatively selective increase in polymorphonuclear
cells (neutrophilia),
 Parasitic infections (as well as allergic responses) characteristically induce
eosinophilia.
 Certain viruses, such as infectious mononucleosis mumps, and rubella, engender
selective increases in lymphocytes (lymphocytosis).
 Typhoid fever are associated with a decreased number of circulating white cells
(leukopenia).
 Leukopenia is also encountered in infections that overwhelm patients debilitated by,
for example, disseminated cancer.
Leukocytosis cont.…

47. Weight loss
Due to IL-1 & TNF-a
Increase catabolism in skeletal muscle adipose & liver.

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