Acute and Chronic Inflammation

Question 1

What causes increased blood flow in acute inflammation?

Answer 1

Arteriolar dilation and opening of capillary beds

Question 2

What mediator helps to increase blood flow in acute inflammation?

Answer 2

histamine

Question 3

Increased vascular permeability results in _______.

Answer 3

accumulation of protein-rich extravascular fluid, which forms the exudate

Question 4

How do plasma proteins leave their vessels?

Answer 4

Through widened interendothelial cell junctions of the venules

Question 5

What are the 3 signs of inflammation?

Answer 5

Redness (rubor)
Warmth (calor)
Swelling (tumor)

Question 6

Which leukocytes act first?

Answer 6

neutrophils

Question 7

How do the leukocytes adhere to the endothelium?

Answer 7

Through adhesion molecules

Question 8

How do the leukocytes migrate to the injury site?

Answer 8

Under the influence of chemotactic agents

Question 9

The release of which metabolites cause local pain (dolor)?

Answer 9

Prostaglandins
Neutropeptides
Cytokines

Question 10

What is the order of vascular changes that occurs early after injury?

Answer 10

1) Vasodilation
2) Increased permeability of the microvasculature
3) Stasis

Question 11

What are the effects of vasodilation on the skin?

Answer 11

Increased blood flow causes heat and redness

Question 12

How is vasodilation induced?

Answer 12

By several mediators, notably histamine and nitric oxide on smooth musle

Question 13

What are the effects of stasis on the injury site?

Answer 13

Loss of fluid results in concentration of red cells in small vessels and increased viscosity of the blood

Question 14

What is a hallmark of acute inflammation?

Answer 14

Increased vascular permeability

Question 15

What are the effects of increased vascular permeability?

Answer 15

Escape of a protein-rich fluid (exudate) into the extravascular tissue, which reduces intravascular osmotic pressure and increases the osmotic pressure of the interstitial fluid

Question 16

What causes the outflow of fluid and its accumulation in the interstitial tissue?

Answer 16

Reduced intravascular osmotic pressure

Increased osmotic pressure of interstitial fluid

Increased hydrostatic pressure from increased blood flow

Question 17

What does the net increase of extravascular fluid result in?

Answer 17

Edema

Question 18

In acute inflammation, fluid loss from vessels occurs in 3 phases. What is the immediate response?

Answer 18

Lasting >30 minutes, mediated mainly by the actions of histamine and leukotrienes on endothelium

Question 19

In acute inflammation, fluid loss from vessels occurs in 3 phases. What is the delayed response?

Answer 19

Starting at 2 hours, lasting for 8.

Mediated by kinins, complement products and other factors.

Question 20

In acute inflammation, fluid loss from vessels occurs in 3 phases. What is the prolonged response?

Answer 20

Most noticeable after direct endothelial injury, for example after burns

Question 21

What is extravasation?

Answer 21

Sequence of events in the journey of leukocytes from the vessel lumen to the interstitial tissue

Question 22

What are the 3 general steps of extravasation?

Answer 22

1) Margination, rolling, adhesion to endothelium
2) Trasmigration across the endothelium
3) Migration in interstitial tissues

Question 23

What occurs during margination, rolling and adhesion to the endothelium?

Answer 23

Endothelium is activated to permit it to bind leukocytes, as a prelude to their exit form the blood vessels

Question 24

Describe the activity that occurs in the first 3 days following injury

Answer 24

Day 1 = peak of edema activity
Day 2 = edema subsides, peak of neutrophil activity early and declines, monocyte/macrophage activity begins
Day 3 = mono/macro peaks early, slowly begins to decline

Question 25

What are the 5 mechanisms known to cause vascular leakiness?

Answer 25

``` 1) Histamines, bradykinins leukotrienes 2) Cytokine mediators 3) Direct endothelial cell damage 4) Margination pile-up and damage 5) VEFG mediators ```

Question 26

How do histamine, bradykinins, and leukotrienes cause vascular leakiness?

Answer 26

Through an early, brief immediate transient response in the form of endothelial cell contraction that widens intracellular gaps of venules (NOT arterioles, capillaries)

Question 27

How long does the effect of the histamines, bradykinins, and leukotrienes last?

Answer 27

15-30 minutes

Question 28

How do cytokine mediators cause vascular leakiness?

Answer 28

They induce endothelial cell junction retraction through cyoskeleton reorganization

Question 29

When do cytokine mediators take effect? How long do they last?

Answer 29

4-6 hours post injury, lasting 24 hours or more

Question 30

What are the cytokine mediators?

Answer 30

TNF, IL-1

Question 31

What type of damage can occur from direct cell damage?

Answer 31

Necrosis, detachment

Question 32

What is the immediate sustained response?

Answer 32

When cell damage occurs and they are leaky until they are repaired

Question 33

What is delayed prolonged leakage?

Answer 33

Damage from thermal or UV, or bacterial toxins

Question 34

How does pile-up cause damage?

Answer 34

Through activation and release of toxic oxygen radicals and proteolytic enzymes (leukocyte-dependenet endothelial cell injury)

Question 35

How do VEFG mediators create leakiness?

Answer 35

Through increased transcytosis via intracellular vesicles which travel from the luminal to basement membrane surface of the endothelial cell

Question 36

How do leukocytes leave the vasculature?

Answer 36

1) Margination and rolling 2) Adhesion and transmigration 3) Chemotaxis and activation

Question 37

Once the leukocytes leave the vasculature, what do they participate in?

Answer 37

Phagocytosis and degranulation | Leukocyte-induced tissue injury

Question 38

Why does margination take place?

Answer 38

There is increased vascular permeability, so fluid leaves the vessel causing leukocytes to settle out of the central flow column and "marginate" along the endothelial surface

Question 39

Explain rolling.

Answer 39

Endothelial cells and leukocytes have surface adhesion molecules that briefly stick and release, causing them to roll along the endothelium until it comes to a stop as mutual adhesion reaches a peak

Question 40

What is early rolling adhesion mediated by?

Answer 40

Selectin Family

Question 41

E-Selectin

Answer 41

endothelium

Question 42

P-Selectin

Answer 42

Platelets, endothelium

Question 43

L-Selectin

Answer 43

Leukocytes

Question 44

What do E,P,L-Selectin do?

Answer 44

Bind other surface molecules that are upregulated on endothelium by cytokines at injury sites

Question 45

What are the endothelial adhesion molecules?

Answer 45

ICAM-1, VCAM-1

Question 46

What are the leukocyte adhesion molecules?

Answer 46

LFA-1, Mac-1, VLA-4

Question 47

Which adhesion molecules bind together?

Answer 47

``` ICAM-1 = LFA-1, Mac-1 VCAM-1 = VLA-4 ```

Question 48

What is the normal state of the adhesion molecules?

Answer 48

Normally down-regulated or in an inactive conformation, inflammation alters this

Question 49

What is the other name of transmigration?

Answer 49

Diapedesis

Question 50

When does transmigration occur?

Answer 50

After firm adhesion within the systemic venules and pulmonary capillaries

Question 51

What mediator causes the firm adhesion?

Answer 51

PECAM-1 (CD31)

Question 52

Once the leukocyte is firmly adhered, what must it do?

Answer 52

Cross the basement membrane via collagenases, integrins

Question 53

Which are most abundant in the early inflammatory resposne?

Answer 53

PMNs

Question 54

What is the chemical gradient that leukocytes follow to the site of injury?

Answer 54

- soluble bacterial products - complement components - cytokines - LTB4

Question 55

What happens when chemotactic agents bind to the surface receptors?

Answer 55

Calcium mobilization and assembly of cytoskeletal contractile elements

Question 56

Once leukocytes reach the site of injury, what do they do?

Answer 56

1. recognize and attach 2. engulf 3. kill

Question 57

What is suppurative or purulent inflammation characterized by?

Answer 57

Production of large amounts of pus or purulent exudate consisting of neutrophils, necrotic cells and edema fluid

Question 58

What is serous inflammation characterized by?

Answer 58

Outpouring of a thin fluid that, depending on the size of injury, is derived from either the plasma or the secretions of mesothelial cells lining the peritoneal, pleural, and pericardial cavities

Question 59

What is fibrinous inflammation characterized by?

Answer 59

More severe injuries and the resulting greater vascular permeability, larger molecules such as fibrinogen pass the vascular barrier and fibrin is formed and deposited in the extracellular space

Question 60

What is an ulcer characterized by?

Answer 60

A local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) or inflammatory necrotic tissue

Question 61

What is chronic inflammation characterized by?

Answer 61

- infiltration with mononuclear cells - tissue destruction - attempts at healing by connective tissue replacement of damaged tissue

Question 62

How do leukocytes undergo activation?

Answer 62

- prepare AA metabolites from phospholipids - prepare for degranulation and release of lysosomal enzymes (oxidative burst) - regulate leukocyte adhesion molecule affinity as needed

Question 63

What are the pseudopods that help bind them to the ECM during chemotaxis?

Answer 63

adhesion molecules (integrins)