INFLAMMATION

1
??? ???? ?????? ??????
2

• INFLAMMATION
• DRGehan mohamed

3
Learning objectives

• understand the definition of Inflammation.
• List the classification of inflammation.
• Identify the Pathogenesis of Acute Inflammation.
• Recognize the difference between acute and
  chronic inflammation regarding the onset ,causes
  and microscopic picture.
• .

4
Learning objectives

• Outline the mechanism of formation and function
  of the inflammatory fluid exudate

5
Inflammation

• Definition Inflammation is the local vascular,
  lymphatic and cellular reactions of living tissue
  against an irritant.
• Inflammation is a protective mechanism with the
  purpose of
• - localization and removal of the irritant.
• To defend against and to eliminate the injurious
  agent responsible for injury.
• Rid the tissue of the consequences of injury
  (necrotic cells).
• To start healing and repair of injured tissue.

6

• Inflammation is designated by adding the suffix
  itis to the English, Latin or Greek name of the
  organ affected
• Examples
• Appendix ? appendicitis
• Pancreas ? pancreatitis
• Meninges ? meningitis
• Pericardium ? pericarditis
• Liver ? hepatitis
• Joints ? Arthritis

7
CAUSES OF INFLAMMATION (1) Living Irritants
Bacteria and their toxins, viruses, parasites and
fungi. (2) Non Living Irritants include (a)
Physical irritants e.g. excess heat, excess cold
and radiations. (b) Chemical irritants e.g.
concentrated acids, alkalis, organic and
inorganic poisons. (c) Mechanical irritants
e.g. trauma, mechanical friction and foreign
bodies. (3) Antigens Cause allergic
inflammation.
8
Do not confuse inflammation with infection !!!!

• Infection not synonymous with inflammation.
• Infection refers to tissue invasion by an
  infectious organism and usually results in
  inflammation.

9
TYPES OF INFLAMMATION

• (1) Acute Inflammation
• Caused by an irritant of short duration .
• The tissue response is rapid i.e. sudden onset.
• lasts for days to weeks.
• characterized by the presence of fluid exudates,
  fibrin threads and polymorphonuclear leucocytes.

10

• (2) Chronic Inflammation
• Caused by an irritant of prolonged action.
• The tissue response is slow i.e. gradual onset.
• Inflammation lasts for months to years.
• characterized by the presence of macrophages,
  plasma cells, lymphocytes and fibrosis.
• (3) Subacute Inflammation Grades between the
  acute and the chronic types.

11
Acute Inflammation
12
Pathogenesis of Acute Inflammation

• The acute inflammatory reaction consists of
• I. Local tissue damage. II. Local vascular
  reactions. III. Chemical mediators .

13

• I. LOCALTISSUE DAMAGE
• Occurs at the centre of the inflamed area with
  the maximum concentration of the irritant. Local
  death of tissue (necrosis) will result.
• This local damage of cells together with
  inflammatory stimulus trigger the release and
  activation of chemical substances called chemical
  mediators as histamine, serotonin and
  prostaglandins.
• These chemical mediators play an important role
  in promoting the vascular and cellular changes in
  the inflamed area.

14
II. LOCAL VASCULAR REACTIONS
15
(No Transcript)
16
Normal lung microscopy
17
Lung acute inflammation
Dilated blood vessels VASODILATON
Neutrophils
Exudate rich in fibrin
18

• II. LOCAL VASCULAR REACTIONS occur in this
  sequence
• (1)Transient vasoconstriction of the small
  arterioles Caused by the direct effect of the
  irritant on the vascular wall.
• Vasoconstriction is a protective mechanism and
  lasts for seconds to minutes only.

19

• (2) Vasodilatation of the Blood Vessels Occurs
  in the arterioles, venules and capillaries due
  to (a) Direct action of histamine on the
  vascular wall. (b) Local axon reflex.
• The dilatation of the arterioles and capillaries
  will increase the blood flow is called
  hyperaemia. The inflamed area becomes red and
  hot.

20

• (3) Slowing of the Blood Stream
• (Stasis) Caused by
• Increased viscosity of the blood due to formation
  inflammatory fluid exudates. This is the main
  cause of stasis.
• (b) Histamine causes swelling of the vascular
  endothelium which become sticky and offer
  mechanical resistance to the blood.

21

• (3) Formation of the Inflammatory Exudates
• The intravascular contents (plasma and cells)
  escape into the interstitial tissue spaces
  forming the inflammatory exudates which consists
  of a fluid component and a cellular component.
• (4) Dilatation of lymphatic vessels
• to accelerate the lymph flow and drains the
  fluid exudates.

22
Terms for abnormal accumulations of fluid

• Edema may be
• - Exudate (pus, serous,.)
• - Transudate

23

• Edema excess amount of fluid in the interstitial
  tissue spaces or body cavities.
• Can be exudate or transudate
• - Exudation the escape of fluid, proteins
  blood cells from the vascular system into the
  interstitial tissue or body cavities.
• Occurs when blood vessels become leaky.
• - Exudate an inflammatory extravascular fluid
  with a high protein concentration, cells/cell
  debris an SG (specific gravity) gt 1020
• Implies significant alteration in permeability
  of small blood vessels in an area of injury.

24

• Pus (purulent exudate) is inflammatory exudate
  rich in neutrophils and debris of dead cells.

25
Exudate microscopy
Neutrophils
Exudate rich in fibrin
26

• Transudate an extravascular fluid with a low
  protein content, few or no cells SG lt 1012
• Results due to imbalance in hydrostatic pressure.
• Occurs when theres organ failure as heart
  failure leading to systemic congestion and
  formation of transudate.

27
Pitting Edema
Laryngeal edema
A
B
28
A-The Inflammatory Fluid Exudates

• Mechanism of formation
• Increased capillary permeability to plasma and
  its proteins caused by histamine (the main
  cause).
• (2) Increased capillary hydrostatic pressure due
  to dilatation of the arterioles and increased
  blood flow. This pushes fluids outside the
  capillaries.

29

• (3) Increased osmotic pressure of the
  interstitial tissue fluid as the large protein
  molecules split into smaller ones in the process
  of tissue necrosis. This acts as a suction force
  from the capillaries.

30

• Characters
• - High protein content, 4-8 gm (the normal
  interstitial tissue fluid contains 1 gm
  protein).
• - High fibrinogen content (turbid clots on
  standing).
• - High specific gravity (above 1018).
• - High cellular content (polymorphs
  macrophages)

31

• Functions
• (1) It dilutes toxins, chemicals and poisons,
  so minimizes their effects.
• (2) Brings antibodies from the blood to the site
  of inflammation.
• (3) Supplies nutrition for the cells and
  carries away waste products.

32

• (4) Fibrinogen forms a fibrin network, which acts
  as a mechanical barrier to the spread of
  infection and as a bridge for leucocytes to reach
  the irritant.

33
Sequence of events in the extravasation of
leukocytes

1. Margination
2. Rolling
3. Adhesion
4. Transmigration (also called diapedesis)
5. Migration toward chemotactic factor chemotaxis

34
Step 1 Margination

• Accumulation of leukocytes along the endothelial
  surface
• Partly mechanical (stacks of RBCs push
  neutrophils to the surface).
• Partly mediated by chemical mediators
• C5a, leukotriene B4 and bacterial products.
• Usually secreted at the site of injury.

35
(No Transcript)
36
Neutrophil Margination
37
Rolling, adhesion and transmigration

• Mediated by binding of complementary adhesion
  molecules on leukocytes and endothelial surfaces

38
Selectins
Integrins
Adhesion molecules
Immunoglobulins
39
(No Transcript)
40
Step-2 Rolling

• Neutrophils weakly bind to the endothelial
  selectins and roll along the surface (Rolling).

41
Rolling
Sialyl-Lewis X
P-Selectin
E-Selectin
42
Step 3 Leukocyte activation

• Neutrophils are stimulated by chemotactic agents
  (chemokines and C5a) to express their integrins.

43
Step-4 Transmigration

• Leukocytes emigration ? pseudopods.
• Interaction of platelet endothelial cell adhesion
  molecule 1 (PECAM-1) on leukocytes and
  endothelial cells mediates transmigration between
  cells.
• Neutrophils release type IV collagenase that
  degrades the Basement membrane.

44
Transmigration
45
Chemotaxis

• Chemotaxis is the attraction of cells toward a
  chemical mediator that is released in the area of
  inflammation.
• Important chemotactic factors for neutrophils
• Exogenous
• Bacterial products
• Endogenous
• Leukotriene B4 (LT-B4)
• Complement system products C5a
• Alpha Chemokines (IL-8)

46
Phagocytosis

• Engulfment of particulate material (e.g. tissue
  debris, living and dead bacteria, other foreign
  particles) by phagocytic cells.
• Neutrophils and macrophages are the most
  important. Phagocytic cells.
• Phagocytosis Three steps
• Recognition and attachment
• Engulfment
• Killing and degradation of the ingested material

47
Recognition and attachment

• Receptors on leukocytes recognize the particle to
  be ingested.
• Opsonization facilitates phagocytosis
• It Is coating of particulate matter by substances
  referred to as OPSONINS.
• Important opsonins
• IgG
• Complement system product C3b
• Plasma protein Collectins

48
Engulfment

• Triggered by binding of opsonised particle to
  phagocytic receptor.
• Neutrophil sends out cytoplasmic processes
  (pseudopods) that surround the bacteria.
• The bacteria are internalized within a phagosome.
• The phagosome fuses with lysosome to form
  phagolysosome.
• Release of lysosomal contents (degranulation).

49
Intracellular microbial killing

• The final step in Phagocytosis of microbes is
  killing and degradation.
• Mediated within phagocytic cells by
• Oxygen dependent
• Oxygen independent mechanisms
• Usually mediated by lysosomes of the neutrophils
  (lysozyme, defensins, basic proteins, etc.)

50
Oxygen dependent killing

• Killing of bacteria
• By reactive oxygen species (ROS)
• Hypochlorous acid
• After Phagocytosis has occurred, NADPH oxidase
  converts molecular oxygen into a superoxide free
  radical in the presence of NADPH.
• Energy given off in this reaction is called
  respiratory burst.

51
Oxygen independent killing

• Less effective than oxygen dependent killing
• Mediated by substances in leukocyte granules
• Lysozyme
• Lactoferrin
• Major basic proteins
• Bacterial permeability increasing protein (BPI)
• Defensins

52
Degradation

• The dead organism degraded by lysosomal acid
  hydrolases

53
Phagolysosome Formation and degranulation
Opsonins
Engulfment
Attachment
Bacterium
Opsonin receptors
54
Local signs of acute inflammation Mechanism

• Calor Heat
• Histamine dependent vasodilatation.
• Rubor Redness
• Histamine dependent vasodilatation.
• Tumor Swelling
• Histamine dependent increase in vascular
  permeability.
• Dolor Pain
• Caused by irritation of the nerve endings by
  toxins and Pressure of the inflammatory exudate
  on the sensory nerves and release of
  prostaglandin E2 and bradykinin.
• Functio Laesa loss of function
• due to destruction of tissues or to avoid Pain.

55
The 5 Cardinal Signs of Acute
Heat Redness Swelling Pain
Loss Of Func.
56
Five signs of acute inflammation

• Calor (heat)
• Rubor (redness)
• Tumor (swelling)
• Dolor (pain)
• Functio laesa
• (loss of function)

Bee Sting
57
(No Transcript)
58
(No Transcript)
59
General Effects Of Acute Inflammation

• (1) Leucocytosis Increase in the number of
  polymorphonuclear leucocytes in the blood above
  l0000/cm3. Leucocytosis is caused by the
  liberation of leucocytosis promoting factor
  from the injured tissue which stimulates the bone
  marrow to produce more leucocytes.

60
(No Transcript)
61
neutrophils with segmented nucleus
62

• (2) Fever (Pyrexia) Due to the release of
  Pyrogenic substances from the bacteria and dead
  leucocytes. Pyrogenic substances disturb the
  function of the heat regulating centre in the
  hypothalamus causing fever. Fever disturbs the
  vitality of bacteria, but is also harmful to the
  body as it causes loss of fluids and
  electrolytes.
• (3) Toxic effects as anorexia, headache and
  degeneration in parenchymatous organs.

63
FATE OF ACUTE INFLAMMATION

• (1) Resolution
• Means complete restoration of the inflamed area
  to normal. It occurs when tissue damage is
  minimal. The products of inflammation are rapidly
  removed. Resolution is the usual course of acute
  inflammation caused by mild chemical or physical
  irritant, many viral infections and lobar
  pneumonia.

64

• (2) Regression and Healing
• The body defense overcomes the irritant. Part of
  the necrotic tissue, dead cells and fibrin are
  removed by the macrophages. The rest gets
  liquefied.
• The liquefied part together with the fluid
  exudates are drained by the lymphatics and veins.
  Next healing occurs by fibrosis.

65

• (3) Progression and Spread
• The bacteria overcome the defense mechanism and
  inflammation spreads directly, by lymphatics and
  by blood causing toxaemia, bacteraemia,
  septicaemia or pyaemia.
• (4) Chronicity
• The causative agent is partially overcomed, but
  the body is unable to get rid of it completely.
  It remains as a weak irritant acting on the
  tissue for a long time.

66
Types of acute inflammation

• Suppurative
• Localized
• Abscess
• Furuncle
• Carbuncle
• Diffuse
• Cellulitis

• Non-suppurative
• Catarrhal
• Membranous
• Allergic
• Fibrinous
• Sero-fibrinous
• Hemorrhagic
• Necrotizing

67
I. SUPPURATIVE INFLAMMATION (Pyogenic or Septic)

• Definition Severe acute inflammation
  characterized by pus formation
• Causes Pyogenic microorganisms as staphylococcus
  aureus, pneumococcus, gonococcus and bacillus
  coli.

68
Abscess

• Definition Localized suppurative inflammation
  resulting in the formation of an irregular cavity
  filled with pus
• Etiology Caused mainly by staphylococcus aureus
  which produce coagulase enzyme that helps fibrin
  formation and localize the infection.

69

• Sites
• Commonly the abscess occurs in in the
  subcutaneous tissue and in any organ as the lung,
  brain, liver, breast.

70

• Characters
• the abscess shows three zones. (a) Central zone
  of necrosis.(b) Midzone containing pus.(c)
  Peripheral zone of inflamed tissue called
  pyogenic membrane.

71

• Complications
• Lymphangitis and lymphadenitis
• Septicemia, bacteremia and toxemia
• Septic thrombophlebitis and payemic abscesses
• Chronicity

72
(No Transcript)
73
(No Transcript)
74
(No Transcript)
75
(No Transcript)
76
(No Transcript)
77
(No Transcript)
78
Cellulitis

• Definition Acute diffuse suppurative
  inflammation.
• Cause Streptococcus haemolyticus. The organism
  produces two enzymes (1) Fibrinolysin
  (streptokinase) Dissolves fibrin. (2)
  Hyaluronidase (spreading factor) Dissolves
  hyaluronic acid of ground substance helping
  spread of bacteria and its toxins.

79

• Sites Loose connective tissue as subcutaneous
  tissue, scrotum, upper respiratory tract and wall
  of the appendix.
• Characters
• (1) Failure of localization because of absence of
  fibrin. (2) Extensive necrosis.(3) Pus is thin
  in consistency and may contain many red cells
  i.e. sanguinous.

80

• Complications
• (1) Acute lymphangitis and lymphadenitis.
• (2) Septic thrombophlebitis causing pyaemic
  abscesses.
• (3) Septicaemia.

81
(No Transcript)
82
(No Transcript)
83
(No Transcript)
84
II. NON-SUPPURATIVE INFLAMMATION

• 1. Catarrhal Inflammation Mild acute
  inflammation of the mucous membranes of the
  respiratory and GIT characterized by excess mucus
  secretion e.g. catarrhal rhinitis (common cold),
  bronchitis, ... etc.

85

• 2. Membranous Inflammation (Pseudomembranous)
• Severe acute inflammation characterized by the
  formation of a pseudomembrane on the affected
  surface formed of necrotic cells, fibrin threads,
  leucocytes and the causative organism e.g.
  diphtheria and bacillary dysentery.

86

• Pathogenesis
• The bacteria remain on the mucosal surface and
  produce powerful exotoxin which causes patchy
  mucosal necrosis. The exotoxin diffuses through
  the necrotic mucosa to the submucosa causing
  acute inflammation. The exotoxin is absorbed in
  the blood stream causing severe toxaemia.
• A yellowish white slightly elevated
  pseudomembrane is formed on the surface. The
  membrane is adherent and its removal leaves a
  bleeding surface with the formation of another
  membrane.

87

• 3. Fibrinous Inflammation Characterized by an
  exudate rich in fibrinogen e.g. lobar pneumonia.
• 4. Serofibrinous Inflammation It involves
  serous sacs as pleura, peritoneum and
  pericardium. Characterized by excess serous
  exudates in the sac and deposition of fibrin on
  the surface.

88

• 5. Haemorrhagic InflammationCharacterized by
  cellular exudate rich in the red blood cells due
  to vascular damage e.g. smallpox and haemolytic
  streptococcal infection.

89
(No Transcript)
90
(No Transcript)
91

• 6. Necrotizing Inflammation Acute inflammation
  characterized by marked tissue necrosis.
• 7. Allergic Inflammation
• as urticaria. It is an antigen antibody reaction
  characterized by abundant fluid exudates and
  eosinophils.

92
Clinical case
93
Clinical case

• An 18-year-old female presents to the emergency
  room with
• Severe abdominal pain, progressive over the last
  3 days.
• Sexually active with several partners.
• Inconsistent use of birth control.
• Physical examination
• Marked lower abdominal/pelvic tenderness and
• A purulent vaginal discharge.
• Febrile (390C).
• CBC WBC count of 20,000/µL with 82 neutrophils
  and 10 bands and metamyelocytes.

94
Tubo-ovarian mass
Fallopian tube
Uterus
ovary
95
Fallopian tube- Medium power
Lumen
Mucosa
96
Fallopian tube- High power
97
Diagnosis ???

• Acute salpingitis !!!
• (acute inflammation of fallopian tubes)

98
Fallobian tube infiltrated by neutophils(acute
salpingitis)
99
CHRONIC INFLAMMATION
100
CHRONIC INFLAMMATION

• Chronic inflammation is characterized by the
  following (1) The irritant is mild and has a
  prolonged action. (2) Chronic inflammation may
  follow acute inflammation or starts as slowly
  progressing chronic disease as in tuberculosis
  and syphilis. (3) The tissue response is gradual
  and prolonged.

101

• (4) The small arteries and arterioles show
  thickening and narrowing called end arteritis
  obliterans. (5) The inflammatory fluid exudates
  is scanty. (6) The inflammatory cellular
  exudates consists of lymphocytes, plasma cells,
  macrophages and foreign-body giant cells.

102
(No Transcript)
103
Types of Chronic inflammation

• (1) Chronic non-specific inflammation Different
  irritants produce inflammatory reactions of the
  same microscopic picture e.g. chronic abscess and
  chronic tonsillitis.
• (2) Chronic specific inflammation
• Each irritant or organism produces a
  characteristic microscopic picture called
  granuloma e.g. tuberculosis, bilharziasis and
  leprosy

104

• Differences between acute
  and
• chronic inflammation

105
Chronic inflammation Acute inflammation Item
Slow and gradual Rapid and sudden Onset
Prolonged Short Duration
Slight or absent Present Vascular phenomena
Slight or absent Present Cardinal signs
-Plasma cells, lymphocytes, macrophages, giant cells, fibroblasts -Few thick walled narrow lumen(end arteritis oblitrans) -Polymorphs, pus cells, macrophages -Numerous, thin walled, dilated and filled with blood Mic. Changes Cells Blood vessels
106
Granuloma

• Definition
• Chronic specific inflammation characterized by
  focal accumulation of large number of chronic
  inflammatory cells to form tumor like mass .

107

• Types
• (1)Infective granuloma
• Bacterial as TB, leprosy syphilis
• Parasitic as bilharziasis leishmaniasis
• Mycotic (fungus) as madura foot, actinomycosis
• Viral as granuloma inguinale
• (2)Non-infective granuloma
• As silicosis, asbestosis and foreign-body
  granuloma.
• (3) Unknown cause
• sarcoidosis, crohns disease

108
Histopathology of granuloma

• A- Macrophages main bulk of granuloma, made of
  tissue histiocytes, blood monocytes and foreign
  body giant cells
• B- Other inflammatory cells as lymphocytes,
  plasma cells, eosinophils.
• C- Granulation tissue
• D- Fibrous tissue
• E- Specific organism or foreign body

109
Schistosomiasis
110
Schistosomiasis
111
Leishmaniasis
112
Leprosy
113
Leprosy
114
Sarcoidosis
115
(No Transcript)
116
granuloma