lecture on inflammation process and its stages.

1. INFLAMMATION

2. Inflammation is a non specific, localized immune reaction of
the organism, which tries to localized the pathogen agent.
Many consider the syndrome a self-defense mechanism.
It consist in vascular, metabolic, cellular changes, triggered
by the entering of pathogen agent in healthy tissues of the
body.

4. Role of tissue and cells in
inflammation
The circulating cells are:
 Neutrophils.
 Monocytes.
 Eosinophils.
 Lymphocytes.
 Basophils.
 Platelets.

5. Sign & Symptoms Of
Inflammation
These are:
 Fever (increase temperature).
 Pain.
 Tissue damage.
 Swelling of tissue.
 Redness of tissue.
 Loss of movements or restricted movement, if
near joints.

6. Types Of Inflammation
Inflammation is divided into
I - Acute inflammation, which occurs over
seconds, minutes, hours, and days.
II - Chronic inflammation, which occurs over
longer times, days & months.

8. Acute Inflammation
 Acute inflammation, begins within seconds
to minutes following the injury of tissues.
 The damage may be purely physical, or it may
involve the activation of an immune
response.

9. Chronic Inflammation
Chronic inflammation is of longer duration and
is associated histologically with the presence
of:
 Lymphocytes and macrophages.
 The proliferation of blood vessels.
 Fibrosis and tissue necrosis.

10. Response Of Inflammation
The main processes are:
I - Increased blood flow.
II - Increased permeability.
III - Migration of neutrophils.
IV - Chemotaxis.
V - Leucocytes recruitment & activation.

11. Response Of Inflammation
The main processes are:
I - Increased blood flow due to dilation of blood
vessels (arterioles) supplying the region.
II - Increased permeability of the capillaries,
allowing fluid and blood proteins to move into
the interstitial spaces

12. Response Of Inflammation
III - Migration of neutrophils (and
perhaps a few macrophages) out of the
venules and into interstitial spaces.

13. Response Of Inflammation
V - Leucocytes recruitment & activation.
 This is the first step is the binding of the
neutrophils to the endothelium of the blood
vessels.
 The binding is due to molecules, called cell
adhesion molecules (CAMs), found on the
surfaces of neutrophils and on endothelial cells
in injured tissue.

14. Response of Inflammation
V - Leucocytes recruitment & activation
(contd.)
The binding of leukocytes occur in two steps:
 In the first step, adhesion molecules called
selectins tightly gather the neutrophil to the
endothelium, so that it begins rolling along the
surface.

15. Response of Inflammation
V - Leucocytes recruitment &
activation (contd).
 In a second step, a much tighter binding
occurs through the interaction of ICAMs on
the endothelial cells with integrins on the
neutrophil.

16. Response of Inflammation
Eosinophils.
However, in some circumstances eosinophils
rather than neutrophils predominate in acute
inflammation.This tends to occur with
parasites (worms), against which neutrophils
have little success.

17. Response of Acute
Inflammation
 Increased Blood Flow, increased
permeability and Edema in Inflammation:
 The increased blood flow & increased
permeability are readily visible within a few
minutes following a scratch that does not
break the skin.

18. Response of Acute
Inflammation
 At first, there is pale red line of scratch.
 Later on there is accumulation of
inflammatory cells lead swelling,
(inflammation).
 Finally, there is accumulation of interstitial
fluid cause edema.

19. Acute Inflammation
(recruitment of neutrophils).

26. Acute Inflammation
(Acute Bronchitis)

27. Acute Inflammation

28. Outcomes
 Resolution
 The complete restoration of the inflamed tissue back to a normal
status. Inflammatory measures such as vasodilation, chemical
production, and leukocyte infiltration cease, and damaged
parenchymal cells regenerate. In situations where limited or short
lived inflammation has occurred this is usually the outcome.
 Fibrosis
 Large amounts of tissue destruction, or damage in tissues unable
to regenerate, can not be regenerated completely by the body.
Fibrous scarring occurs in these areas of damage, forming a scar
composed primarily of collagen. The scar will not contain any
specialized structures, such as parenchymal cells, hence
functional impairment may occur.

29. Outcomes
 Abscess formation
 A cavity is formed containing pus, an opaque liquid containing
dead white blood cells and bacteria with general debris from
destroyed cells.
 Chronic inflammation
 In acute inflammation, if the injurious agent persists then chronic
inflammation will ensue. This process, marked by inflammation
lasting many days, months or even years, may lead to the
formation of a chronic wound. Chronic inflammation is
characterised by the dominating presence of macrophages in the
injured tissue. These cells are powerful defensive agents of the
body, but the toxins they release (including reactive oxygen
species) are injurious to the organism's own tissues as well as
invading agents. Consequently, chronic inflammation is almost
always accompanied by tissue destruction.

30. Causes of Chronic
inflammation
I - Persistent infection:
 Bacteria.
 Viruses.
 Fungi.
 Parasites

31. Causes of Chronic
inflammation
II - Prolonged exposure to potentially toxic
agents:
 Endogenous, (atherosclerosis).
 Exogenous, ( particulate silica-Silicosis).

32. Chronic inflammation
 Lymphocyte, macrophage, plasma cell
(mononuclear cell) infiltration
 Tissue destruction by inflammatory cells
 Attempts at repair with fibrosis and
angiogenesis (new vessel formation)
 When acute phase cannot be resolved
 Persistent injury or infection (ulcer,TB)
 Prolonged toxic agent exposure (silica)
 Autoimmune disease states (RA, SLE)

33. Morphological Features of
Chronic Inflammation
These are characterized by:
I - Infiltration by mononuclear cells.
II -Tissue destruction.
III - Removal of damaged tissue, (healing).

34. Morphological Features of
Chronic Inflammation
I - Infiltration by mononuclear cells:
The mononuclear cells are become predominant
after 48 hours.
These include:
 Macrophages.
 Lymphocytes.
 Plasma cells.
 Eosinophils.
 Mast cells.

35. Morphological Features of
Chronic Inflammation
II -Tissue destruction
Occur due to:
 Inflammatory cells.
 Persistent infecting material.

36. Granulomatous Inflammation
 Clusters ofT cell-activated macrophages,
which engulf and surround indigestible
foreign bodies (mycobacteria, H. capsulatum,
silica, suture material)
 Resemble squamous cells, therefore called
“epithelioid” granulomas with peripheral
lymphocytes, fibrosis & multinucleated
giant cells.

37. Chronic Granulomatous
Inflammation

38. Lymph Nodes and Lymphatics
 Lymphatics drain tissues
 Flow increased in inflammation
 Antigen to the lymph node
 Toxins, infectious agents also to the node
Lymphadenitis, lymphangitis
Usually contained there, otherwise bacteremia
ensues
Tissue-resident macrophages must then prevent
overwhelming infection

39. Systemic effects
 Fever
 One of the easily recognized cytokine-mediated
(esp. IL-1, IL-6,TNF) acute-phase reactions
including
Anorexia
Skeletal muscle protein degradation
Hypotension
 Leukocytosis
 Elevated white blood cell count

40. Systemic effects (cont’d)
 Bacterial infection (neutrophilia)
 Parasitic infection (eosinophilia)
 Viral infection (lymphocytosis)

42. Neutrophil is the main cell of chronic inflammation
Eosinophilia occurs in parasitic infection
Lymphocytes are dominant in viral infections
Abscess formation is indicator of acute inflammation
Interleukins causes fever
Vasodilatations is the first step in acute inflammation
Acute inflammation always leads to chronic
inflammation
There is no nervous involvement in inflammation

43. TISSUE REPAIR AND
REGENERATION

44. Skin Injuries
 Skin is the body’s first layer of defense
against injury
 Most frequently injured body tissue
 DifferentTypes of Skin Injuries
 Abrasions
 Blisters
 Skin Bruises
 Incision
 Laceration
 Puncture Wound

45. After Tissue Injury…
1. Capillaries become very permeable
 Clotting proteins – form a clot / scab
 Nutrients – healing process
2. Granulation tissue forms
 New capillaries grow into area
 Phagocytes – consume blood clot
 Fibroblasts – collagen fibers (scar tissue)
3. Regeneration and/or fibrosis
 Growth of replacement tissue
 Scab detaches
 Scar (fibrosis) may be visible

46. Tissue repair = restoration of tissue architecture
and function after an injury
• Occurs in two ways:
– Regeneration of injured tissue
– Replacement by connective tissue (scarring)
• Usually, tissue repair involves both processes.
• Involves cell proliferation, and interaction
between cells and extracellular matrix

48. Continuously dividing (labile) tissues
• Stable tissues
• Permanent tissues

49. Tissue
response to
injury. Repair
after injury
can occur by
regeneration,
which
restores
normal
tissue, or by
healing,
which leads
to scar
formation
and fibrosis.

50. Repair Involves
 Regeneration of injured tissue by parechymal
cells of the same type
 Replacement by connective tissue (fibrosis),
resulting in a scar
 In most cases tissue repair involves both of
these two processes.

51. Repair Involves
 A complete restore is called complete
regeneration
 A repair with connective tissue is called
incomplete regeneration (fibrous repair, scar
repair)

52. Normal cell proliferation and
cell cycle

53. 1- Continuously dividing (labile) tissues
• Cells are continuously proliferating
• Can easily regenerate after injury
• Contain a pool of stem cells
• Examples: bone marrow, skin, GI epithelium

54. 2- Stable tissues
• Cells have limited ability to proliferate
• Limited ability to regenerate (except liver!)
• Normally in G0
, but can proliferate if injured
• Examples: liver, kidney, pancreas

55. 3- Permanent tissues
• Cells can’t proliferate
• Can’t regenerate (so injury always leads
to scar)
• Examples: neurons, cardiac muscle

56. The Extracellular Matrix
 A dynamic, constantly, remodeling,
macromolecular complex
 Interstitial matrix
 Basement membrane (BM)
 Major components
 Collagens
 Elastic fibers
 Fibronectin
 Laminin
 Proteoglycans

57. Major components of the extracellular matrix (ECM), including collagens,
proteoglycans, and adhesive glycoproteins. Both epithelial and mesenchymal
cells (e.g., fibroblasts) interact with ECM via integrins. To simplify the diagram,
many ECM components (e.g., elastin, fibrillin, hyaluronan, syndecan) are not
included.

59. Fibrosis (scar formation)
 Granulation tissue is the initial event in the
repair of an injury, and consists of richly
vascular connective tissue which contains
capillaries, young fibroblasts, and a variable
infiltrate of inflammatory cells
 Do not confuse with GRANULOMA

60. Healing of Skin Wound
 Primary intention: the usual case with a surgical
wound, in which there is a clean wound with
well-apposed edges, and minimal clot formation
 Secondary intention: when wound edges cannot
be apposed, (e.g., following wound infection),
then the wound slowly fills with granulation
tissue from the bottom up. A large scar usually
results.

62. Factors that Influence Wound
Healing
 Type, size, and location of the wound
 Vascular supply (diabetics heal poorly)
 Infection - delays wound healing and leads to
more granulation tissue and scarring
 Movement - wounds over joints do not heal well
due to traction
 Radiation - ionizing radiation is bad, UV is good

63. Factors that Influence Wound
Healing
 Overall nutrition: vitamin and protein
deficiencies lead to poor wound healing,
especially vitamin C, which is involved in
collagen synthesis
 Age: younger is definitely better!
 Hormones - corticosteroids drastically impair
wound healing, because of their profound
effect on inflammatory cells

64. Complications of Wound Healing
 Defective scar formation
 Excessive scar formation (keloid)
 Contraction
 Defective scar formation
 Dehiscence or ulceration is usually due to:
Wound infection (common)
Malnutrition (scurvy - rare)
Hypoxia with ulceration, usually due to
inadequate vascularity in a skin flap (common).

65. Dehiscence

66. A, Keloid. Excess collagen
deposition in the skin forming
a raised scar known as keloid.
B, Note the thick connective
tissue deposition in the
dermis.

67. Scar contracture in a boy after
scald

68. Cirrhosis (gross)