INFLAMMATION

Response of living tissue to injury, involving neural, vascular and cellular response.

ACUTE INFLAMMATION

It involves the formation of a protein .rich and cellullar exudate and the cardinal signs are calor, dolor, tumour, rubor and function loss

The basic components of the response are

Haemodynamic changes.

Permeability changes

Leucocyte events.

1. Haemodynamic Changes :

• Transient vasoconstriction followed by dilatation.
• Increased blood flow in arterioles.
• More open capillary bed.
• Venous engorgement and congestion.
• Packing of microvasculature by RBC (due to fluid out-pouring)
• Vascular stasis.
• Change in axial flow (resulting in margination of leucocytes)

.2. Permeability Changes:

Causes.

• Increased intravascular hydrostatic pressure.
• Breakdown of tissue proteins into small molecules resulting in
• increased tissue osmotic pressure.
• Increased permeability due to chemical mediators, causing an
• immediate transient response. .
• Sustained response due to direct damage to microcirculation.

3. White Cell Events:

.Margination - due to vascular stasis and change in axial flow.

Pavementing - due to endothelial cells swollen and more sticky.

Leucocytes more adhesive.

Binding by a plasma component

Emigration - of leucocytes by amoeboid movement between endhothe1ial cells and beyond the basement membrane. The passive movement of RBCs through the gaps created during emigration is called diapedesis

Chemotaxis - This is a directional movement, especially of polymorphs and monocytes towards a concentration gradient resulting in aggregation of these cells at the site of inflammation. .Chemotactic agents may be:

• Complement components. (C₃and C₅  fragments and C₅₆₇)
• Bacterial products.
• Immune complexes, especially for monocyte.
• Lymphocytic factor, especially for monocyte.

 Phagocytosis - This includes recognition, engulfment and intracellular degradation. It is aided by .Opsonins., Specific antibodies., Surface provided by fibrin meshwork.

Functions of the fluid and cellular exudate

1. Dilution of toxic agent.

2. Delivers serum factors like antibodies and complement components to site of inflammation.

3. Fibrin formed aids In :

• Limiting inflammation
• Surface phagocytosis
• Framework for repair.

4. Cells of the exudate:

Phagocytose and destroy the foreign agent.

Release lytic enzymes when destroyed, resulting in extracellular killing of organisms- and digestion of debris to enable healing to occur

Surface Defence Mechanisms

1. Skin:

(i) Mechanical barrier of keratin and desquamation.

(ii) Resident commensal organisms

(iii)Acidity of sweat.

(iv) Unsaturated fatty acids of sebum

2. Oropharyngeal

(i)Resident flora

(ii) Saliva, rich in lysozyme, mucin and Immunoglobulins (lgA).

3. Gastrointestinal tract.-

(i) Gastric HCI

(ii) Commensal organisms in Intestine

(iii) Bile salts

(iv) IgA.

(v) Diarrhoeal expulsion of irritants.

4. Respiratory tract:

(i) Trapping in turbinates

(ii) Mucus trapping

(iii) Expulsion by coughing and sneezing.

(iv) Ciliary propulsion.

(V) Lysozymes and antibodies in secretion.

(vi) Phagocytosis by alveolar macrophages.

5. Urinary tract:

(i) Flushing action.

(ii) Acidity

(iii) Phagocytosis by urothelial cells.

6. Vagina.-

(i) Desquamation.

(ii) Acid barrier.

(iii) Doderlein's bacilli (Lactobacilli)

7. Conjunctiva:

Lysozymes and IgA in tears

Immunodeficiency

This may be :- 
- Congenital (Primary)
- Acquired (Secondary)

Features : Complete or near complete lack of T & B lymphoid tissue. Fatal early in life Even with marrow grafting, chances of graft versus host reaction is high.

T Cell Defects :

- Thymic dysplasia
- Digeorge’s syndrome
- Nazelof’s syndrome
- Ataxia teltngiectaisa
- Wiscott Aldrich’s syndrome

These  lessons show predominantly defective cell mediated immunity. But they may also show partial immunoglobulin defects cell mediated immunity. But they may also show partial immunoglobulin defects due to absence og T-B co-operation.

C. Humoral immunity defects.
Bruron type- aggammaglobulinaemia.
- Dysgammaglobulinaemias-variable immunodeficiency’s of one or more classes.

Acquired deficiency

A. Immuno suppression by :
- Irradiation.
- Corticoids.
- Anti metabolites.
- Anti lymphocyte serum.

B. Neaplasia  of lymphoid system :

- Hodgkin's and Non Hodgkin's lymphomas.
- Chronic lymphocytic leukaemia..
- Multime myeloma and other paraproteinaemias (normal immunoglobulins reduced in spite of hyperglobulinaemia).

c. excessive protein loss.
- Nephrotic Syndrome.
- Protein losing enteropathy.

Lymphomas

A. Hodgkin’s disease

1. Characterized by enlarged lymph nodes and the presence of Reed-Sternberg cells (multinucleated giant cells) in lymphoid tissues.

2. Disease spreads from lymph node to lymph node in a contiguous manner.

3. Enlarged cervical lymph nodes are most commonly the first lymphadenopathy observed.

4. The cause is unknown.

5. Occurs before age 30.

6. Prognosis of disease depends largely on the extent of lymph node spread and systemic involvement.

B. Non-Hodgkin’s lymphoma

1. Characterized by tumor formation in the lymph nodes.

2. Tumors do not spread in a contiguous manner.

3. Most often caused by the proliferation of abnormal B cells.

4. Occurs after age 40.

5. Example: Burkitt’s lymphoma

a. Commonly associated with an EpsteinBarr virus (EBV) infection and a genetic mutation resulting from the translocation of the C-myc gene from chromosome 8 to 14.

b. The African type occurs in African children and commonly affects the mandible or maxilla.

c. In the United States, it most commonly affects the abdomen.

d. Histologically, the tumor displays a  characteristic “starry-sky” appearance.

Hematological examination

This is a method by which abnormalities of the cells of the blood and their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.

Paroxysmal nocturnal haemoglobinuria (PNH).

Feature:

• Acquired RBC rnembrane defect rendering it susceptible  to complement lysis.
• Features of intravascular haemolysis.
• Blood picture of haemolysis anemais with pancytopenia.
• Ham’s acid serum test (lysis at 37COin acid pH) + ve