Njds Pathology - The Host Response To Injury Ii: Acute Inflammation

Front 1

Origins of acute inflammation

Back 1

1. Infection
2. Mechanical trauma
3. Tissue anoxia
4. Physical agents (e.g. chemical or thermal burns)

Front 2

Transient vasoconstriction

Back 2

1. Affects precapillary arterioles and meta-arterioles
2. Earliest response lasting seconds
3. Regulated by neurogenic and chemical mediatiors (Thromboxin A2)
4. Characterized as temporary decrease blood flow to limit hemorraging
5. Minor clinical significance

Front 3

Vasodilation

Back 3

1. Affect precapillary and metaarterioles
2. Lasts minutes
3. Characterized as increased vascular caliber and opening of inactive capillary beds
4. HYPEREMIA - increased blood flow to affected tissue
5. Actively mediated with bradykinin, histamine, and prostacyclin (thus, ACTIVE HYPEREMIA)
6. TRANSUDATION due to increase hydrosatic forced
7. Clinically seen as erythema (redness) and warmth

Front 4

Immediate transient response

Back 4

1. Immediate transient response
- Leakage is rapid and short-lived
- Due to mild injuries
- Mediated by bradykinin, histamine, prostaglandins, C3a, C5a, substance P, leukotrines, TNF, IL-1
- Venules affected

Front 5

Immiedate sustained response

Back 5

1. Due to direct damage damage to endothelial cell; not elicited by chemical mediators

2. Immediate cell death with rapid leackage until holes are repaired

3. Occurs in sever injuries like burns

4. All levels of microcirculation affected

Front 6

Delayed prolonged response

Back 6

1. Not elicited by chemical mediators

2. Delayed cell death with long-lasting leakage

3. Example is sunburn

4. Venules and capillaries are affected

Front 7

What happens when microvessels become leaky in acute inflammation?

Back 7

1. Exudate - fluid with plasa proteins escape into intersitial tissues

2. Abnormal swelling causes pain from tissue turgor and chemical mediators (PGE3, bradykinin) on nerve endings

3. ↑ Hemoconcentration causing ↑ blood viscosity and stasis (slow blood flow which promotes margination andemigration of leukocytes)

4. Edema (abnormal tissue accumulation of fluid outside of cell) is essentially an exudate

Front 8

Exudate

Back 8

1. Promotes immunologic response
2. Dilutes toxins
3. localize infection (e.g. fibrin)
4. Supplies protective Ab
5. Provides nutrients for cellular elements)

Front 9

Cardinal clinical manifestations of inflammation

Back 9

1. Redness (rubor)
2. Warmth (calore)
3. Swelling from edema (tumor)
4. Pain (dolore)
5. Loss of function (functio laesa)

- These are NOT characteristic of chronic inflammatory processes

- Manifested locally on body surface but not so apparent if on organs

Front 10

Leukocyte margination

Back 10

1. Normally leukocytes limited to central column of laminar blood flow with surrounding sheath of plasma

2. Stasis causes leukocytes to "fall out" of central axis and contact and attach to vascular endothelium

Front 11

Adhesion molecules of leukocyte margination

Back 11

1. SELECTINS - prsent on Leukocytes, Platelets, and Endothelium (L,P,E-selectins)

2. Ig SUPERFAMILY MOLECULES present on endothelium (e.g. ICAM-1, VCAM-1)

3. INTEGRINS present on leukocytes (e.g. α4β7, α4β1)

Front 12

Mechanism of adhesion molecules in leukocyte margination

Back 12

1. Cell adheion molecules in cytoplasm redistributed to cell surface (e.g. by histamine)

2. Adhesion molecule synthesis induced on endothelium and leukocytes by chemical factors (e.g. by IL-1, TNF)

3. Conformational changes of intgrin molecules cause ↑ avidity of binding (e.g. C5a)

Front 13

Leukocyte emigration

Back 13

1. aka TRANSMIGRATION or DIAPEDISIS

2. Cytoplasimic pseudopod extends through endothelial cell junction in ameboid fashion

3. Mediated by PECAM-1

4. Leukocyte secretion of collagenase facilitates emigration

5. Venules in systemic circulation AND capillaries in pulmonary circulation preferred sites for margination/emigration

Front 14

T/F: Macrophages and lymphocytes are considered to be acute inflamatory cells

Back 14

FALSE: Neutrophils are considered to be acute inflammatory cells because they predominate at the injured site in the early phases of acute inflammation.

Later, macrophages and lymphocytes predominate at the injured site during the healing phase

Front 15

Leukocyte chemotaxis

Back 15

1. The process of leukocytes following increasing gradient of CHEMOATTRACTANTS

2. Chemoattractants trigger assemply of contractile elements for cell mobility

3. Examples of chemotactic factors: bacterial products, C5a, leukotriene B4, and chemokines

Front 16

Leukocyte phagocytosis

Back 16

1. Recognition: Opsonization of foreign particle with opsisin like Fc fragment of IgG, C3b, collectins

2. Engulfment: Psuedopods extend to engulf and create phagosome ⇒ + lysosome ⇒ phagolysosome ⇒ + degranulation enzymes ⇒ foreign particle degradation

3. Bacterial killing: Superoxide radicals (HOCL) created; requires MYLOPEROXIDASE + O2 ⇒ HYPOCHLORITE

Front 17

In the absence of myloperoxidase, how else can leukocytes degrade/kill foreign particles?

Back 17

1. Proteins that ↑ bacterial permeability

2. Lysosomes

3. Lactoferrin - against parasites

4. Major basic protein

Front 18

5 outcomes of acute inflammation

Back 18

1. Healing by compete resolution - regeneration of native cells

2. Healing by complete fibrous scarring - involes ORGANIZATION and FIBROPLASIA to replace injured tissue with fibrous CT

3. Healing by repair process - combo of regeneration and fibrous scarring (common outcome)

4. Abcess formation - especially in response to pyogenic organisms

5. Progression in chronic inflammation