Notes on Inflammation and Repair

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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.

Additional Reading:

Basic Pathology

1. Cell Injury
2. Inflammation and Repair
3. Immunopathology
4. Water, Electrolyte, Acid-Base, Hemodynamic Disorders
5. Genetic and Developmental Disorders
6. Environmental Pathology
7. Nutritional Disorders
8. Neoplasia
9. Vascular Disorders
10. Heart Disorders
11. Red Blood Cell Disorders
12. White Blood Cell Disorders
13. Lymphoid Tissue Disorders
14. Hemostasis Disorders
15. Blood Banking and Transfusion Disorders
16. Upper and Lower Respiratory Disorders
17. Gastrointestinal Disorders
18. Hepatobiliary and Pancreatic Disorders
19. Kidney Disorders
20. Lower Urinary Tract and Male Reproductive Disorders
21. Female Reproductive and Breast Disorders
22. Endocrine Disorders
23. Musculoskeletal Disorders
24. Skin Disorders
25. Nervous System Disorders
26. Notes on Tissue Regeneration
27. A Table of Bleeding Disorders
28. FAQ on Structure and Function of Red Blood Cells
29. FAQ on Components of Blood
30. Notes on Hemostatic Mechanisms
31. What is Fever?
32. What is Edema?
33. FAQ on Blood Pressure
34. FAQ on principles of fluid and flow dynamics of Blood
35. Causes of Thrombocytopenia
36. Squamous cell carcinoma of head and neck mucosa
37. Four tumors which never metastasize to the brain
38. What is caustic injury?
39. What causes Peripheral Edema?

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