Pathology: Inflammation And Wound Healing

Front 1

Define inflammation.

Back 1

Inflammation is a complex response of vascularized living tissue to injury. It is a common response to a variety of provoking agents.

Front 2

What three pieces of laboratory evidence can be used as evidence for inflammatory disease?

Back 2

1. Elevated WBCs
2. Increased erythrocyte sedimentation rate (ESR)
3. Increase in C-reactive protein (CRP)

Front 3

What are the five cardinal signs of inflammation?

Back 3

1. Heat
2. Pain
3. Redness
4. Swelling
5. Loss of function

Front 4

What happens to the blood vessels at the beginning of an inflammatory reaction?

Back 4

There is transient vasoconstriction followed by vasodilation, resulting in hyperemia. Endothelial cells contract, allowing cells and proteins to flow out of the vessels and into the damaged tissue.

Front 5

What is lymphangitis?

Back 5

Lymphangitis is inflammation of the lymphatics.

Front 6

What is lymphadenitis?

Back 6

Lymphadenitis is inflammation of the lymph nodes.

Front 7

Describe an immediate transient inflammatory response.

Back 7

An immediate transient response begins immediately following an injury and phases out within 30-60 minutes. It only affects small to medium-sized post-capillary venules.

Front 8

Describe an immediate sustained inflammatory response.

Back 8

An immediate sustained response occurs in cases of severe tissue injury with endothelial cell sloughing. All levels of microcirculation are affected. There is direct damage to the vascular endothelium, resulting in increased permeability.

Front 9

Describe a delayed prolonged inflammatory response.

Back 9

A delayed prolonged response occurs as a result of thermal, x-ray, or UV injury, as well as with bacterial toxins and delayed hypersensitivity reactions. Sunburn is the classical example. This reaction lasts for hours or days and involves venules and capillaries.

Front 10

What happens during the process of rouleaux formation?

Back 10

Rouleaux formation is aggregation of red blood cells in the center of blood vessels, forcing leukocytes to the periphery.

Front 11

Release of what cytokines by damaged tissue stimulates expression of P- and E-selectins on endothelial cells?

Back 11

TNF-alpha and IL-1 release stimulate expression of P- and E-selectins on endothelial cells.

Front 12

What do endothelial P- and E-selectins bind to on leukocytes to promote emigration from circulation?

Back 12

P- and E-selectins bind to sialylated Lewis-X on the circulating leukocytes.

Front 13

What is margination?

Back 13

Margination is adhesion of molecules on leukocytes to molecules on endothelial cells, causing the leukocytes to roll along the sides of the blood vessels.

Front 14

What molecules are necessary on leukocytes and endothelial cells in order for margination to occur?

Back 14

Leukocytes: sialylated Lewis-X, L-selectin

Endothelial cells: P-selectin, E-selectin

Front 15

What molecules are necessary on leukocytes and endothelial cells in order for pavementing to occur?

Back 15

Leukocytes: integrins

Endothelial cells: ICAM-1, VCAM

Front 16

What is diapedesis?

Back 16

Diapedesis is the transmigration of leukocytes between endothelial cells and out of circulation.

Front 17

What are the primary cells of inflammation before and after the 24 hour mark?

Back 17

Before: neutrophils

After: monocytes/macrophages

Front 18

What chemotactic factors lead extravasated leukocytes to the site of tissue injury?

Back 18

C5a, N-formyl peptides, leukotriene, B4, PAF, interleukins

Front 19

What particles are involved in opsonization?

Back 19

IgG and complement component C3b

Front 20

What is the difference in the mechanisms that PMNs and macrophages use to kill phagocytosed microbes?

Back 20

PMNs use the hydrogen peroxide-myeloperoxidase-halide system (MPO) to target microbes. Macrophages utilize less powerful proteins like lactoferrin and lysozyme/muramidase.

Front 21

What type of cell is deficient in cyclic neutropenia?

Back 21

All granulocytes

Front 22

What are LAD1 and 2?

Back 22

LAD1 is a leukocyte adhesion deficiency resulting from mutations in the beta chain of integrin.

LAD2 is a leukocyte adhesion deficiency resulting from mutations in selectin receptors.

Front 23

What is the pathology of chronic granulmatous disease?

Back 23

Chronic granulomatous disease is caused by NADPH oxidase deficiency, which affect bactericidal mechanisms.

Front 24

What is the pathology of Chediak-Higashi syndrome?

Back 24

Chediak-Higashi syndrome is a disorder of PMN granules.

Front 25

What are the two chemical mediators of vasodilation in the triple response?

Back 25

Serotonin and histamine

Front 26

What three types of cells release histamine?

Back 26

Mast cells, basophils, platelets

Front 27

What is the inflammatory triple response?

Back 27

Firm stroking of the skin with a blunt instrument results in:
1. Instant reddening
2. A bright red flare migrating out from the line
3. A wheal (edema) at the site

Front 28

What two pathways use arachidonic acid as a starting material?

Back 28

Cyco-oxygenase (COX) and Lipo-oxygenase (LOX)

Front 29

Name three products of the COX pathway.

Back 29

Prostaglandins, prostacyclin, thromboxane

Front 30

Name the major product of the LOX pathway.

Back 30

Leukotrienes

Front 31

What are the two classes of prostaglandins

What does each do?

Back 31

E class and F class

PGE is a vasodilator, is involved in fever production, and enhances the ability of bradykinin to cause pain.

The F series are antagonistic.

Front 32

What is the role of prostacyclin in inflammation?

What cells make it?

Back 32

Prostacyclin is a vasodilator and increases vessel permeability.

Endothelial cells

Front 33

What is the role of thromboxane A2?

From where is it released?

Back 33

Thromboxane A2 is a vasoconstrictor and platelet aggregator.

It is released by platelets.

Front 34

What pathway does aspirin inhibit?

Back 34

The COX pathway

Front 35

What is the role of leukotrienes in inflammation?

Back 35

Leukotrienes act in chemotaxis, cause transient vasoconstriction, and cause increased vascular permeability.

Front 36

What cell types release platelet activating factor (PAF)?

What is its physiological action?

Back 36

Many!

Neutrophils, eosinophils, platelets, basophils, macrophages, endothelial cells.

At high concentrations, PAF causes vaso- and bronchoconstriction. It is important in asthma. At low concentrations, it induces vasodilation and vascular permeability. In addition, it plays a role in leukocyte adhesion and chemotaxis, as well as stimulating prostaglandin and leukotriene synthesis.

Front 37

What is the role of cationic proteins in inflammation?

Back 37

Cationic proteins act as chemotactic agents for macrophages, increase vascular permeability, and immobilize granulocytes.

Front 38

Describe the difference between the roles of acid proteases and neutral proteases.

Back 38

Acid proteases degrade bacteria and cellular debris within phagolysosomes, while neutral proteases do similar things in the extracellular environment.

Front 39

What role does the enzyme kallikrein play in inflammation?

Which kinin is most important for our purposes?

Back 39

Kallikrein is the enzyme that catalyzes the formation of kinins, which are potent producers of pain. Kallikrein is activated by a fragment of Hageman factor/Factor XII.

Bradykinin is the most important.

Front 40

What is the inflammatory role of C3a and C5a?

Back 40

Both induce release of histamine from basophils, mast cells, and platelets, causing anaphylaxis.

Front 41

What are the four potential outcomes of acute inflammation?

Back 41

1. Complete resolution
2. Healing by scarring
3. Abscess formation
4. Progression to chronic inflammation

Front 42

What cell type predominates in chronic inflammation?

Back 42

Mononuclear cells

Front 43

What is the defining cell type of a granuloma?

Back 43

Epithelioid cells

Front 44

What are the two types of giant cells that may be found in granuloma?

Back 44

Langhans type: nuclei are arranged around the cell periphery

Foreign body type: scattered nuclei

Front 45

What are the two common inclusion body patterns found in giant cells?

Back 45

Asteroid: inclusion has a star-like appearance

Schaumann: concentric lamellae

Front 46

Where are eosinophils frequently observed, besides in allergic reaction and parasitic infection?

To what factors do they respond?

Back 46

Ulcerative colitis and asthma

Chemotactic agents of mast cells (LT B4, eosinophil chemotactic factor of anaphylaxis) and lymphokines

Front 47

What cytokine is necessary for granuloma formation?

Back 47

TNF-alpha

Front 48

What two circumstances are necessary for granuloma formation?

Back 48

1. Presence of indigestible matter
2. Cell-mediated immunity to the inciting agent

Front 49

What type of necrosis occurs in the middle of a granuloma?

Back 49

Caseous necrosis

Front 50

What type of necrosis is observed with syphilis?

Back 50

Gummatous necrosis

Front 51

Define healing and name the two major types.

Back 51

Healing is the replacement of lost or destroyed tissue with viable tissue.

The two main types are regeneration and repair.

Front 52

Give examples of labile cells.

Back 52

Surface epithelia, mucosal lining of excretory ducts, transitional cells of the urinary tract, hematopoietic cells

Front 53

Give examples of stable cells.

Back 53

Liver, kidney, vascular endothelium

Front 54

Give examples of permanent cells.

Back 54

Neurons, cardiac and skeletal muscle

Front 55

What is necessary for total regeneration of tissues made up of stable and labile cells?

Back 55

Preservation of the basement membrane and as much stroma and ECM as possible.

Front 56

What components are always present in an LM view of granulation tissue?

Back 56

New small blood vessels, fibroblasts, mast cells, macrophages

Front 57

Describe the major differences between healing by first intention and healing by secondary intention.

Back 57

Healing by first intention occurs in a clean wound with minimal difference between the edges. Healing by second intention occurs when there is a large defect between edges of the wound and when there is excessive tissue loss. Healing takes much longer. Scarring is expected in this case because of extensive loss of parenchyma.

Front 58

Describe the major events in the timeline of wound healing by first intention.

Back 58

Day 1: Clot forms and dehydrates to a scab. Basal epithelial cells and resident fibroblasts proliferate.

Day 2: Epithelial cells migrate and meet beneath scab and dissolve the bottom of the scab.

Day 3: Macrophages clean up debris and granulation tissue fills incision. Collagen types I and III are at wound margins.

Day 4: Fibroblasts produce profollagen and fibronectin in wound site.

Day 5: Granulation tissue is highly vascularized. Surface epithelium is keratinized.

Day 7: Maximal collagen synthesis. Inter-cellular connections appear.

Day 9: Abundant ECM. Fibroblasts stop producing collagen.

Days 7-14: New vessels, leukocytes, and edema disappear. Wound contraction occurs.

Months-years: Collagen type III is replaced with type I

Front 59

Under what circumstances does organization occur? What happens?

Back 59

Organization occurs when granulation tissue grows into a wound, covering an inflammatory exudate, area of necrotic tissue, or thrombus. The exudate/necrotic tissue/thrombus is turned into a fibrous mass.

Front 60

What signaling factor is likely the key link between inflammation and healing?

Back 60

TGF-beta

Front 61

What cells release TGF-beta?

What does TGF-beta act on?

Back 61

Activated platelets and stimulated macrophages release TGF-beta.

TGF-beta is a chemotactic factor for fibroblasts and macrophages, blocker of plasminogen inhibitor, enhancer of angiogenesis, stimulator of fibroblasts, inhibitor of collagen production, and inducer of myofibroblast formation.

Front 62

What might be in a gel seeded onto a hard-to-heal wound?

Back 62

RGD tripeptides (to form a foothold for integrins)

Front 63

What is dehiscence?

Back 63

Wound rupture

Front 64

In what two settings might chronic inflammation be observed?

Back 64

1. Following acute inflammation

2. As a low-grade "smoldering" inflammation such as arthritis, with no evidence of acute inflammation

Front 65

What four mediators of inflammation are released from eosinophils?

Back 65

1. Eosinophil cationic protein (ECP)- stimlates HA synthesis and inhibits T-cell proliferation

2. Eosinophilic peroxidase (EPO)- mediates cytotoxicity

3. Eosinophil-derived neurotoxin- ribonuclease

4. Major basic protein- destroys epithelium

Front 66

Define organization.

Back 66

Organization is the conversion of dead tissue or inert material into granulation tissue.