Inflammation

1
Inflammation
2
Definition

• Local reaction of vascularized living tissue to
  an injurious agents provided that the stimulus is
  not so severe to cause immediate cells death
  (necrosis)

3
Aim of inflammation

• Elimination of the causative agents and dead
  tissue
• Dilution of toxins
• Prepare the tissues for repair

4
Causes of inflammation

• 1. Living agents bacteria, viruses, parasites,
  fungi, ect.
• 2. Non-living (irritant)
• Physical agents e.g. burn, irradiation, trauma
• Chemical agents e.g. toxins, caustic substances
• 3. Immunologic reaction

5
Types of inflammation

• According to the course
• Acute inflammation
• Chronic inflammation
• Hyperacute inflammation
• Subacute inflammation

6
Acute Chronic

• Sudden onset
• Short duration (minutes to days)
• Characterized by accumulation of inflammatory
  exudate and cells of acute inflammation
  (neutrophil)

• Gradual onset
• Long duration (months to years)
• Characterized by cells of chronic inflammation
  (lymphocytes, macrophages) and evidences of
  repair (vascular proliferation and fibrosis)

7
Cells of inflammation
8
I. Acute inflammation

• The immediate and early response to injury
• Clinical picture
• Local (cardinal) signs
• Systemic manifestations

9
Local (cardinal) signs

• Redness
• Hotness
• Swelling (edema)
• Pain
• Loss of function

10
Systemic effects

• Fever, malaise, loss of appetite
• Leukocytosis increased number of leucocytes
  gt12000/cmm
• Changes in plasma protein levels increase in
  acute phase reactants as C-reactive protein,
  elaboration of certain cytokines (IL-1, IL-6) and
  elevation of ESR (erythrocyte sedimentation rate)

11
Pathogenesis

1. Alteration of vascular caliber and blood flow
   (vascular phenomenon)
2. Cellular events (cellular phenomenon)

12
I. Vascular phenomenon

1. Transient vasoconstriction
2. Vasodilatation
3. Vascular leakage (Increased vascular
   permeability)
4. Slowing of circulation
5. Stasis

13

• 1.Transient vasoconstriction
• Sites arterioles
• Mechanism axon reflex
• Effect localization of the area of inflammation
• 2. Vasodilatation
• Sites arterioles and venules
• Mechanisms
• Chemical mediators (histamine, serotonine)
• Action of toxins and metabolites on
  arterioles
• Effect
• Supply more blood more leucocytes
  and antibodies
• Transudate dilute toxins

14

• Transudate
• Protein poor fluid contains lt1gm/100ml, protein
  formed of albumin
• Low specific gravity lt1020
• Any cause leading to by ?hydrostatic P or?
  osmotic as HF, hypoproteinemia

15

• 3. Vascular leakage
• Endothelial contraction
• Immediate transient
• Histamine, bradykinin
• Junctional retraction
• Delayed transient
• Cytokines as TNF and interleukin
• Endothelial injury
• Direct if the causative agent is severe the
  effect is immediate and sustained
• Leukocyte dependent inducing toxic oxygen species
  and proteolytic enzymes the effect is late

16

• The net result of vascular leakage is the
  formation of inflammatory exudate
• Protein rich fluid containing gt1gm/100ml and
  formed of mixture of low and high molecular
  weight proteins and inflammatory cells
• High specific gravity gt1020
• Induced by vascular leakage
• 4. slowing of blood stream
• 5. stasis

17
Difference Transudate
Exudate

• Protein content
• Types of proteins
• Tendency for coagulation
• Specific gravity
• Mechanisms
• Causes
• Cells

• Low lt1gm Highgt1gm
• Albumin Albumin-globulin-C-Ig
  ,
• proteins of
  coagulation,
• fibrinolytic
  cascades
• -ve ve
  
• lt1020 gt1020
• ?Hydrostatic P ?Vascular permeability
• ?Osmotic P
• HF Inflammation
• Hypoproteinemia
• No or minimal cells Inflammatory cells

18
Mechanisms of cardinal signs of inflammation

• Redness
• Hotness
• Swelling
• Pain irritation of nerve endings
• chemical mediators bradykinin,
  prostaglandins
• Loss of function pain
• swelling
• tissue damage

19
II. Cellular phenomenon

• Margination
• Rolling
• Adhesion
• Migration
• Chemotaxis and activation
• Phagocytosis

20
(No Transcript)
21
Chemotaxis

• Definition
• Unidirectional migragtion of cells towards an
  injuried tissue along a chemical gradient
• Chemotactic agents
• C5a
• prostaglandins, leukotrienes
• soluble bacterial products
• cytokines
• Cells
• All white blood cells
• PNL migrate first, followed by monocytes
  (macrophages)
• Aim
• Accumulation of phagocytic cells
• Activation of these cells by
• modulation of leukocyte adhesive molecules
• activation of oxidative burst by
  degranulation of lysosomal enzymes

22
Phagocytosis and degraulation

• Definition process by which neutrophils and
  macrophages engulf the offending pathogen,
  foreign bodies and dead tissue
• Steps
• Recognition and attachment
• Engulfment
• Fusion
• Killing and degradation
• The critical function of
• inflammation is the delivery of
• leukocytes to the site of injury

23
Chemical mediators of acute inflammation
pain opsonin chemotaxis ?permeability Vasodilatation Mediators
_ _ _ _ C3a
_ _ _ C5a
_ _ _ _ C3b
_ _ Bradykinin
_ _ _ Histamine
_ _ _ ?Serotonine
_ _ _ _ Lysosomal products
_ Prostaglandins
_ _ _ Leukotreines
_ _ _ O2 radicals
24
Types of acute inflammation

• Suppurative
• Localized
• Diffuse

• Non-suppurative
• Catarrhal
• Serous
• Serofibrinous
• Membranous
• Allergic
• Hemorrhagic
• Gangrenous

25
I. Suppurative inflammation

• Causes Pyogenic organisms staphylococcus
  aureus, streptococcus hemolyticus, gonococci
• Characterized by pus formation
• Thick creamy yellow fluid consists of
  inflammatory exudate, cells (living neutrophils,
  dead neutrophils (pus cells)) and liquifactive
  necrosis

26

• Pathogenesis pyogenic organisms are powerful
  chemotactic for neutrophils with release of their
  proteolytic enzymes inducing liquifactive
  necrosis which together with inflammatory exudate
  and dead neutrophils leading to formation of pus

27
Classification of suppurative purulent-pyogenic)
inflammation

• 1. Localized suppuration
• 2. Diffuse suppuration

28
A. Localized suppuration

• 1. Abscess

29

• 2. Boil furuncle
• 3. Stye

30

• 4. Carbuncle

31
B. Diffuse suppurative inflammation

• 1. Phlegmonous inflammation (acute diffuse
  suppurative inflammation of a hollow organ
• Example phlegmonous appendicitis

32

• 2. Diffuse suppuration in a body cavity

Suppurative meningitis
Suppurative pericarditis
Suppurative peritonitis
33

• 3. Collection of pus in the lumen of an organ
• Example Emyema of gall bladder

34
4. Cellulitis

• Definition diffuse suppurative inflammation
  extending between CT planes
• Cause streptococcus haemolyticus
• Effect secretes
• 1. Streptokinase enzyme fibrinolysis
• 2. Hyaluronidase enzyme break down cement
  substance leading to spread of bacteria and toxins

35
Classification of suppurative inflammation

• 1. Localized suppuration
• Abscess
• Boil (furuncle)
• Stye
• Carbuncle
• 2. Diffuse suppuration
• Phlegmonous inflammation
• diffuse suppuration in a body cavity
• collection of pus in a lumen pf organ
• cellutlitis

36
II. Non-suppurative inflammation

• Catarrhal inflammation
• The mildest form of inflammation
• Characterized by excess mucus
• Sites any mucus surface
• Example common cold
• mild gastritis
• mild colitis

37

• 2. Serous inflammation
• Mild form
• Characterized by excess watery clear fluid, no
  fibrin
• Examples
• serous cavities
• blisters of burn

38

• 3. Serofibrinous and fibrinous inflammation
• Moderate form
• Characterized by exudate rich in fibrin
• Sites
• serous cavities
• joints
• lung alveoli

39

• Gross picture fibrinous exudate gives pink
  yellow mantle bread and butter
  appearance
• MP fibrin network entangling inflammatory cells

40

• 4. Pseudomembranous inflammation
• Severe form
• Characterized by formation of superficial dull
  opaque yellow membrane which when pealed leave
  bleeding surface
• Sites mucus surfaces
• Examples
• diphtheria
• bacillary dysentry

41

• MP membrane formed of necrotic mucosal cells
  bacteria inflammatory cells and exudate

42

• 5. Allergic inflammation
• Mild to severe
• Characterized by exudate rich in eosinophils

43

• 6. Hemorrhagic inflammation
• Severe form
• Characterized by
• vascular damage
• with hemorrhagic
• inflammatory exudate

44

• 7. Gangrenous inflammation
• The severest form
• Characterized by tissue death due to superadded
  putrifaction

45
Classification of non-suppurative inflammation

• Catarrhal
• Serous
• Serofibrinous
• Membranous
• Allergic
• Hemorrhagic
• Gangrenous

46
Fate and complications of acute inflammation

• Fate

Healing
resolution
scarring
47
1. Resolution

• Definition replacement of the lost cells by
  native cells
• Pathogeneis
• Resorption of inflammatory exudate by BV and
  lymphatics
• Removal of cell debris by phagocytosis
• Digestion of fibrin by fibrinolysis

48

• Situations
• Minimal tissue damage
• Rapid elimination of the causative agents
• Tissues capable of regeneration

49
2. Scarring

• Definition replacement of lost tissue by fibrous
  tissue
• Situations
• Excess tissue destruction
• Excess exudation
• Tissues not capable of regeneration
• Suppurative inflammation

50
Complications of acute inflammation

1. Progression to chronic inflammation
2. Complications related to healing
3. Superadded suppuration
4. Spread

51
1. Progression to chronic inflammation

• Causes
• Persistence of the injurious agent
• Interference in the normal process of healing

52
2. Complications related to healing

• I. Complications related to excess fibrous
  formation
• A. Adhesions
• Adhesive pericarditis
• Constrictive pericarditis

53

• B. Sinus
• Blind ended tract from a cavity to a surface

54

• C. Fistula
• Track between 2 surfaces that opens on both ends

55

• D. Keloid
• Excess scar formation

56

• II. Ulcer formation
• Definition local defect or excavation of the
  surface epithelium
• Mechanism sloughing of inflammatory necrotic
  surface

57

• 3. Superadded suppuration
• 4. Spread
• Direct spread to adjacent organs
• Natural passages tonsilitis leads to upper
  respiratory tract infection
• Lymphatic spread leading to reactive lymphangitis
  and lymphadenitis of draining lymph nodes

58

• Blood spread
• Bacteremia transient presence of bacteria
  without toxins in blood
• Viremia presence of circulating virus
• Toxemia presence of circulating toxins
• Septicemia circulation virulent,
  multiplying microorganisms and their toxins
• Pyemia circulating septic emboli

59
Complications of acute inflammation

• 1. Progress to chronic
• 2. Complications related to healing
• Excess scar formation
• Adhesion (adhesive pericarditis and constrictive
  pericarditis
• Sinus
• Fistula
• Keloid
• Ulcer
• 3. Superadded infection
• 4. Spread

60
Effects of acute inflammation
harmful
beneficial
61
Beneficial effects

• Dilution of toxins by inflammatory exudate and
  allow them to be carried by lymphatics
• Entry of antibodies ? vascular permeability
  allow entrance of Abs to extracellular space
• Ab Ag complement activation
• C5-9
  C3b
• Neutralization of toxins

62

• 3. Delivery of nutrients and oxygen
• 4. Drug transport
• 5. Fibrin formation
• Impede the movement of micro-organisms
• trap them then enhance phagocytosis
• 6. Stimulation of immune response
• Drainage of inflammatory exudate allow
  particulate and soluble Ags to reach LNs thus
  stimulate immune response

63
Harmful effects of inflammation

• 1. Digestion of normal tissues
• Collagenases and proteases may digest normal
  tissue leading to their destruction especially BV
  vascular damage e.g.
  glomerulonephritis
• 2. Swelling
• May be harmful specially in certain sites as
• Epiglottis airway obstruction especially
  in children death
• Cranial cavity ? intra-cranial pressure

64

• 3. Inappropriate inflammatory response
• Allergic inflammatory response may be life
  threatening as type I hypersensitivity reaction
  (anaphylactic shock)

65
Chronic inflammation

• Definition an inflammation of prolonged duration
  in which
• Proceeding
  simultaneously

tisue destruction
Active inflammation
healing
66

• Causes
• 1. Following acute inflammation
• Persistence of the injurious agent
• Interference in the normal process of healing
• 2. De novo
• Intracellular microbes which are of low toxicity
  but evoke immunological reaction e.g. T.B
  bacilli and some viruses
• Immune reaction particularly auto-immune diseases
  
• Prolonged exposure to non-degradable but
  potentially toxic substances e.g. silica,
  asbestos

67
Histologic features

• Mononuclear inflammatory cells
• Tissue destruction
• Fibrosis and angiogenesis

68
Types of chronic inflammation
Chronic specific inflammation
(granulomatous inflammation)
Chronic non-specific inflammation
69
Granulomatous inflammation(Granuloma)

• Distinctive pattern of chronic inflammation
  characterized by formation of aggregates of
  activated macrophages (epithelioid cells) around
  material that has not been eliminated

70
Differences between acute and chronic
inflammation
Chronic Acute
Long (weeks months) Short (days) 1. Duration
insidious acute 2. Onset
specific Non-specific 3. Specificity
Lymphocytes, macrophages, plasma cells and fibroblasts Neutrophils macrophages 4. Cells
71
Chronic Acute
angiogenesis Vasodilatation, ? vascular permeability 5. Vascular changes
-- 6. Exudation and edema
-- 7. Cardinal signs
Usually ve Usually -ve except in suppurative inflammation 8. Tissue necrosis
72
Chronic Acute
ve Usually -ve 9. Fibrosis
Low-grade fever Weight loss anemia High fever 10. Systemic manifestations
Frequently none Variable leukocyte changes ? plasma immunoglobulis ? neutrophils Lymphocytosis in viral infection 11. Changes in peripheral blood
73
Thank you