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Inflammation and Repair

Inflammation:
Cardinal signs: redness, heat, swelling, pain.

Acute Inflammation events:


Vasoconstriction, vasodilatation, increased venule permeability, swelling, reduced blood flow. C-reactive protein (CRP) elevated.

Neutrophils:
Primary cells of acute inflammation. Margination, rolling (selectin), adhesion (CD11a:CD18; mediated by C5a and LTB4), diapedesis, chemotaxis phagocytosis.

Leukocyte adhesion deficiency (LAD):


AR disease. Type 1: deficiency of CD11a:CD18. Type 2: deficiency of a selectin that binds neutrophils. Findings: delayed umbilical cord separation, gingivitis, poor wound healing, peripheral blood neutrophilic leukocytosis.

Leukocyte Adhesion Inhibited by:


Catecholamines, corticosteroids, lithium inhibit adhesion.

Role of ICAM and VCAM:


ICAM and VCAM, activated by IL-1 and TNF bind to neutrophils.

Opsonization:
Mediated by IgG and C3b.

Bruton's agammaglobulinemia:
Defective opsonization.

Bacterial killing:
MPO:
neutrophils and macrophages: kill by bleach (HOCl); activated by fever.

NADPH:
oxidative burst.

Glutathione peroxidase:
neutralizes H2O2.

Chronic granulomatous disease:


deficiency of NADPH/respiratory burst; test: NBT.

MPO deficiency:
respiratory burst present.

Types of inflammation:
Purulent (suppurative) inflammation: pus forming organisms; skin abscess. Fibrinous inflammation: fibrin-rich exudate deposition; fibrinous pericarditis. Pseudomembranous inflammation: shaggy membrane of dead tissue; diphtheria toxin.

Chronic inflammation:
Due to infection, autoimmune disease, sterile agents. Monocytes, macrophages, lymphocytes, plasma cells. Granulation tissue; scar tissue. Fibronectin required for adhesion. Granulomatous inflammation seen in TB.

RB, TP53:
Arrest in G1.

BAX:
Activated with excessive DNA damage; cell commits suicide.

Repair by connective tissue:


Occurs in severe or persistent unjury. Steps: neutrophil transmigration, granulation tissue, type III collage production, cross-linking by type I collagen, dense scar tissue production.

Factors that prevent healing:


Infections, metabolic disorders, nutritional deficiencies, glucocorticoid deficiency.

Repair in various tissues:


Liver:
Mild injury: regeneration of hepatocytes. Severe injury: regenerative nodules; increased fibrosis.

Lung:
Type II pneumocytes.

Brain:
Astrocytes, microglial cytes.

Peripheral nerve transaction:


Distal degeneration of axon and myelin sheat / wallerian degeneraton. Proximal axonal degeneration. Macrophages and Schwann cells.

Heart:
No repair mechanisms. Damaged tissue replaced by scar tissue.

Ehlers-Danlos:
Type I/III collagen defects.

Vitamin C deficiency:
Decreased hydroxylation of proline and lysine.

Metals needed for wound repair:


Copper, Zinc.

Glucocorticoids:
Prevent scar formation; decrease tensile strength of collagen.

Inflammation lab findings:


Acute: neutrophilic leukocytosis, left shift, toxic granulation, increased IgM, increased ESR. Chronic: monocytosis, increased IgG, increased ESR.

C-Reactive Peptide:
increased in inflammatory and bacterial infections.

Effects of corticosteroid therapy:


Neutrophilic leukocytosis, lymphopenia, eosinopenia.