1. بسم الله الرحمن الرحيم

2. INFLAMMATION DR:Gehan mohamed

3. 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.
*Inflammation is designated by adding the suffix “itis” to the English, Latin or Greek name of the organ affected e.g. tonsillitis, appendicitis, gastritis ... etc.

4. 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.

5. TYPES OF INFLAMMATION Caused by an irritant of short duration .
(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.

6. (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.

7. Acute Inflammation

8. Pathogenesis of Acute Inflammation
The acute inflammatory reaction consists of:
I. Local tissue damage. II. Local vascular reactions. III. Local histiocytes reaction .

9. 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.

10. II. LOCAL VASCULAR REACTIONS
(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.

11. (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.

12. (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.

13. (c) Most of the capillaries in the inflamed area open and blood reaching the arterioles will be distributed among large number of capillaries, so slowing occurs.

14. (4) 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.
(5) Dilatation of lymphatic vessels:
to accelerate the lymph flow and drains the fluid exudates.

15. 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.

16. (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.

17. - High fibrinogen content (turbid & clots on standing).
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)

18. 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.

19. (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.

20. B- The inflammatory cellular exudates
1- Margination of leucocytes: The
polymorphs leave the axial blood stream due to stasis and settle on the endothelial lining of the capillaries.
2- Emigration of leucocytes: The polymorphs push their ways between the swollen endothelial cells through the widened pores by means of pseudopodia to outside the vessels by amoeboid movement.

24. 3- Emigration of blood monocytes: which change in the inflamed area to macrophages together with the tissue histiocytes.
4- Chemotaxis: Is the directed movement of polymorphs and macrophages in the area of inflammation towards the irritant. This is helped by chemical products produced by polymorphs. The inflammatory cells move on fibrin threads.

25. 5- Phagocytosis: It is the ingestion and destruction of bacteria, necrotic debris and foreign particles by phagocytic inflammatory cells (polymorphs and macrophages).

26. III. LOCAL REACTION OF TISSUE HISTIOCYTES
Late in acute inflammation the macrophages replace the polymorphs.
Macrophages are derived from tissue histiocytes and blood monocytes. They phagocytose dead bacteria, necrotic debris, pus cells and fibrin threads cleaning the area of inflammation and preparing the tissue for the repair process.

27. CARDINAL SIGNS AND SYMPTOMS OF ACUTE INFLAMMATION
(1) Redness: Caused by vasodilatation of the capillaries. (2) Hotness: Caused by arteriolar dilatation and increased blood flow. (3) Swelling: Caused by the vascular dilatation and the accumulation of the inflammatory fluid and cellular exudate. (4) Pain: Caused by irritation of the nerve endings by toxins and Pressure of the inflammatory exudate on the sensory nerves. (5) Loss of function: due to destruction of tissues or to avoid Pain.

30. 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.

32. (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.

33. 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.

34. (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.

35. (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.

36. Types of acute inflammation
Suppurative
Localized
Abscess
Furuncle
Carbuncle
Diffuse
Cellulitis
Non-suppurative
Catarrhal
Membranous
Allergic
Fibrinous
Sero-fibrinous
Hemorrhagic
Necrotizing

37. 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.

38. 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.

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

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

41. Complications: Lymphangitis and lymphadenitis
Septicemia, bacteremia and toxemia
Septic thrombophlebitis and payemic abscesses
Chronicity

48. 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.

49. 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.

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

54. 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.

55. 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.

56. 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.

57. 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.

58. 5. Haemorrhagic Inflammation: Characterized by cellular exudate rich in the red blood cells due to vascular damage e.g. smallpox and haemolytic streptococcal infection.

61. 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.

62. 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.

63. (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.

65. 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

66. Differences between acute and
chronic inflammation

67. Chronic inflammation
Acute inflammation
Item
Slow and gradual
Rapid and sudden
Onset
Prolonged
Short
Duration
Slight or absent
Present
Vascular phenomena
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

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

69. Types (1)Infective granuloma (2)Non-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

70. 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

71. Schistosomiasis

72. Schistosomiasis

73. Leishmaniasis

74. Leprosy

75. Leprosy

76. Sarcoidosis