Acute inflammation(pathology)

inflammation

1. Dr. Nausheen Henna
Assistant Professor Pathology
M.Phil; FCPS

2. Inflammation
Beneficial host response to foreign invaders and
necrotic tissue
The main components:
◦Vascular reaction and a cellular response;
Steps of the inflammatory response (5Rs):
Recognition of the injurious agent,
Recruitment of leukocytes,
Removal of the agent,
Regulation (control) of the response, and
Resolution (repair).

3. External manifestations
Cardinal signs:
◦Heat (calor),
◦Redness (rubor),
◦Swelling (tumor),
◦Pain (dolor) and
◦Loss of function (functio laesa).

4. Effect of Inflammation
Either
◦Elimination of the noxious stimulus followed by
decline of the reaction &
◦Repair of the damaged tissue, or
◦Persistent injury resulting in chronic inflammation.

5. ACUTE INFLAMMATION
Acute inflammation is a rapid response to injury or
microbes and other foreign substances that is designed to
deliver leukocytes and plasma proteins to sites of injury.

6. Stimuli for Acute Inflammation
Infections
Trauma
Physical and chemical agents
Tissue necrosis : Ischemia
Foreign bodies
Immune reactions (hypersensitivity reactions)

7. Two major components
◦Vascular changes:
Vasodilatation
Increased vascular permeability
◦Cellular events:
Cellular recruitment and activation.
The principal leukocytes in acute inflammation are neutrophils
(polymorph nuclear leukocytes).

8. Vascular
changes

9. Vascular Changes
Changes in Vascular Caliber and Flow
◦Begin rapidly after infection or injury
Depending on the nature and severity of the original
inflammatory stimulus.
◦Transient vasoconstriction (lasting only for seconds),
◦Arteriolar vasodilation occurs,
Locally increased blood flow &
Engorgement of the down-stream capillary beds.

10. Microvasculature
permeable
RBC become more
concentrated
Slowing of the
circulation
ChemotaxisMargination
Stasis
Protein-rich fluid
moves out EV
tissues
Increasing blood
viscosity

12. Increased vascular permeability
Endothelial cell contraction leading to intercellular gaps in
postcapillary venules
Endothelial injury
Leukocyte-mediated endothelial injury
Increased transcytosis of proteins via an intracellular
vesicular pathway augments venular permeability (VEGF)
Angiogenesis.

14. Endothelial cell contraction
**leading to intercellular gaps in postcapillary venules
Reversible process
Histamine, bradykinin, leukotrienes, and many other chemical
mediators.

15. ◦Occurs rapidly after binding of mediators to specific
receptors, is usually short-lived (15-30 minutes), and is
called the immediate transient response.
◦Changes in the cytoskeleton,
cytokines such as TNF and IL-1.
◦This reaction may take 4 to 6 hours to develop after the
initial trigger and persist for 24 hours or more.

16. Endothelial injury
Vascular leakage by causing endothelial cell necrosis and
detachment.
Direct injury to endothelial cells is usually seen after severe
injuries (e.g., burns and some infections).
Immediate sustained response: leakage begins
immediately after the injury and persists for several hours
(or days) until the damaged vessels are thrombosed or
repaired.

17. Direct injury to endothelial cells may also induce a
delayed prolonged leakage that begins after a delay of 2
to 12 hours, lasts for several hours or even days, and
involves venules and capillaries.
Examples include mild to moderate thermal injury, certain
bacterial toxins, and x- or ultravoilet irradiation
In a thermal burn, leakage results from chemically
mediated endothelial contraction as well as from direct
injury and leukocyte-mediated endothelial damage.

18. Responses of Lymphatic Vessels
In inflammation, lymph flow is increased and helps
Drain edema fluid from the EV space.
Equilibrates with EV fluid.
In severe inflammatory reactions, especially to microbes, the
lymphatics may transport the offending agent.
Lymphangitis &lymphadenitis.
Inflamed LN are often enlarged, because of hyperplasia of the
lymphoid follicles and increased numbers of lymphocytes and
phagocytic cells lining the sinuses of the lymph nodes…. RLH
Red streaks near a skin wound is a telltale sign of an infection in the
wound.

19. CELLULAR EVENTS
1.Leukocyte Recruitment
Neutrophils predominate in the early (6-24 hrs)
inflammatory infiltrate and are later replaced by
macrophages in 24- 48 hrs.
1.Leukocyte Activation

21. Leukocyte Recruitment:
Margination, adhesion to endothelium, and rolling along
the vessel wall;
Firm adhesion to the endothelium;
Transmigration between endothelial cells; and migration
in interstitial tissues toward a chemotactic stimulus.
Chemotaxis

22. Histamine,
thrombin & PAF
TNF & IL-1
Collagenase
ß1-integrin& CD44

25. Chemotaxis:
oExo and endo substances
Bacterial products, particularly peptides with N-formylmethionine
termini;
Cytokines (chemokine)
Complement system, particularly C5a; and
Products of the lipoxygenase pathway of arachidonic acid (AA)
metabolism, particularly LTB
4
.

26. Leukocyte Activation
Stimuli for activation
Microbes,
Products of necrotic cells, and
Several mediators.
Leukocytes express on their surface different kinds of
receptors that sense the presence of microbes.

27. Leukocyte Activation
Phagocytosis
Recognition and attachment of the particle to the
ingesting leukocyte;
Engulfment, with subsequent formation of a phagocytic
vacuole; and
Killing and degradation of the ingested material.

28. Fibronectin,
fibrinogen,
MBL, CRP

29. Mannose receptor &
scavenger receptor

31. Bactericidal Mechanism
Oxygen dependent:
Myeloperoxidase
Oxygen independent:
Bactericidal permeability increasing protein (BPI), PL activation
Lysozyme,
Lactoferrin,
Major basic protein,
Defensins,
Neutrophil granules contain many enzymes, such as elastase.
All contribute to microbial killing.

32. Leukocyte induced injury
Regurgitation during feeding
Frustrated phagocytosis
Cytotoxic release

33. Acute Chronic
Acute respiratory distress syndromeArthritis
Acute transplant rejection Asthma
Asthma Atherosclerosis
Glomerulonephritis Chronic lung disease
Reperfusion injury Chronic rejection
Septic shock
Vasculitis
Leukocyte induced injury

34. Defects in leukocyte adhesion
Genetic deficiencies in leukocyte adhesion molecules
(LAD types 1 and 2).
LAD 1 is characterized by recurrent bacterial
infections and impaired wound healing.
LAD 2 is clinically milder than LAD 1 but is also
characterized by recurrent bacterial infections.

35. Defects in phagolysosome function
Chédiak-Higashi syndrome
Autosomal recessive
Characterized by
Neutropenia,
Defective degranulation,

Delayed microbial killing.
The neutrophils (and other leukocytes) have giant granules,
Reduced transfer of lysosomal enzymes to phagocytic vacuoles
in phagocytes (causing susceptibility to infections)

36. Abnormalities in melanocytes (leading to albinism),
Cells of the CNS (associated with nerve defects), and
Platelets (generating bleeding disorders).
The secretion of granule proteins by cytotoxic T cells is also
affected, accounting for part of the immunodeficiency seen in
the disorder.

37. Defects in microbicidal activity
Chronic granulomatous disease:
Recurrent bacterial infection.
Inherited defects in the genes encoding several
components of NADPH oxidase, which generates
superoxide.
The most common variants are an X-linked defect in
one of the plasma membrane-bound components
(gp91phox) and
Autosomal recessive defects in the genes encoding two
of the cytoplasmic components (p47phox and
p67phox).

39. TERMINATION OF THE ACUTE INFLAMMATORY
RESPONSE
Short lived mediators,
Stop signals,
Switch in the production of pro-inflammatory leukotrienes to
anti-inflammatory lipoxins from AA,
Liberation of an anti-inflammatory cytokine,
Transforming growth factor-β (TGF-β), from macrophages and
other cells,
Neural impulses (cholinergic discharge) that inhibit the
production of TNF in macrophages.