Inflammation-Acute And Chronic

Front 1

Name the defined events in inflammation

Back 1

1. Recognition of the injurious agent.
2. Recruitment of leukocytes.
3. Removal of the injurious agent.
4. Regulation of the response.
5. Resolution and repair.

Front 2

What is acute inflammation? What is the trademark of this?

Back 2

Acute inflammation refers to a process which develops in a few minutes to hours and typically resolves within a few days. The hallmark cell of acute inflammation is the neutrophil.

Front 3

What are leukocytes?

Back 3

Leukocytes are the white blood cells found within the bloodstream or present in the tissue. They originate in the bone marrow, are released into the blood, and are then recruited to sites of inflammation. The normal numbers of white blood cells in the peripheral blood is listed in table 1. Neutrophils are the predominant cell, followed by lymphocytes. In normal individuals there are relatively few monocytes or eosinophils. Cells newly recruited to the site of inflammation typically come directly from the bloodstream.

Front 4

What are neutrophils?

Back 4

Neutrophils are a major cell mediating acute inflammation. They are short-lived cells, once they have been released into the bloodstream they typically only circulate for less than 24 hours. They survive in tissues for only a few days and do not recirculate back to the blood. In other words, after a neutrophil has left the bloodstream and entered a tissue site, the neutrophil does not re-enter the blood. Once in tissue, they ingest microorganisms or necrotic tissue and die shortly thereafter.

Front 5

What would be considered to be evidence of inflammation? What would not be?

Back 5

When leukocytes or neutrophils are present, you have inflammation. If lympocytes are present, you don't have inflmmation

Front 6

Name the steps in acute inflammation

Back 6

Step 1. Hyperemia – dilatation of blood vessels
Step 2. Increased Vascular Permeability.
Step 3. Emigration, accumulation, activation of leukocytes

Front 7

Vasoactive amines: histamine and serotonin

Back 7

These are usually the first mediators released. Histamine is stored in mast cells, basophils and platelets and is released in response to trauma, heat, or immune reactions. Histamine causes arteriolar dilation and increased vascular permeability. Serotonin is found in pre-formed in platelets and its effects are similar to those of histamine.

Front 8

Arachidonic acid (AA) metabolites

Back 8

These metabolites include prostaglandins, leukotrienes and lipoxins. AA metabolites mediate many steps in inflammation including vasodilatation. Aspirin and other nonsteriodal anti-inflammatory agents (NSAIDs) work by inhibiting the enzyme that produces AA metabolites, cyclooxygenase.

Front 9

Nitric Oxide (NO).

Back 9

NO acts as a smooth muscle relaxant causing vasodilation especially when produced by endothelial cells

Front 10

Platelet activating factor

Back 10

A molecule derived from cell membranes. The name was given since it causes platelet aggregation, in addition to vasoconstriction, bronchoconstriction, and leukocyte activation

Front 11

Bradykinin

Back 11

Kinins are vasoactive peptides derived from plasma proteins, called kininogens. Bradykinin increases vascular permeability and causes contraction of smooth muscle, dilation of blood vessels and pain when injected into the skin.

Front 12

What does a portion of swelling result from?

Back 12

leakage of proteins from the plasma into the tissue interstitium. It's not a hemmorhage since erythrocytes don't escape.

mainly in the post-capillary venules and does not occur across larger arterioles, arteries or veins

Front 13

What's the difference between transudate and exudate?

Back 13

Transudates are low in protein concentration and cell numbers, while an exudate has higher concentrations of proteins and typically contains numerous inflammatory cells.

Front 14

Edema

Back 14

accumulation of fluid within the interstitium of tissues. It can be either a transudate or an exudate. Patients with edema are described as being “wet”. Tissues with edema fluid are described as edematous

Front 15

Effusion

Back 15

accumulation of fluid in a sealed body cavity, such as between the lung and chest wall. This would be called a pleural effusion. An effusion can be directly aspirated through a needle or catheter, whereas edema cannot

Front 16

Purulent exudate

Back 16

large concentration of neutrophils usually due to bacteria that attract neutrophils. The cells result in a cloudy appearance

Front 17

Hemorrhagic exudate

Back 17

one that contains red blood cells due to capillary damage.

Front 18

What are the steps involved in recruitment of leukocytes to tissue?

Back 18

(A) margination, (B) rolling, (C) tight adhesion, (D) migration across vessel wall.

Front 19

What is margination?

Back 19

In order for leukocytes to exit the bloodstream, they must first move to the margin of the bloodstream, and come into contact with the vascular wall.

Front 20

Rolling?

Back 20

The specificity of cellular inflammation is, at least in part, regulated during the rolling phase. The initial adherence of leukocytes to endothelium is weak. Therefore, the leukocytes roll on the endothelial cell layer rather than abruptly stopping.

Front 21

Tight adhesion?

Back 21

Tight adhesion is due to the ability of integrin molecules to rapidly increase their molecular avidity for integrin ligands on the endothelial cell surface. Once tightly adherent, the shear force of the blood is not sufficient to cause the cell to continue to roll.

Front 22

Migration across vessel wall?

Back 22

During this process the leukocyte actually migrates between two endothelial cells. It requires the leukocyte to squeeze between two endothelial cell junctions, allowing those junctions to re-form after passage. Only minutes are typically required for passage of a leukocyte through the vascular wall

Front 23

Migration into the tissue.

Back 23

Inflammatory cells will move toward specific molecules called chemotactic factors. There are several important neutrophil chemotactic agents.

Front 24

Name and describe the systemic consquences of inflammation

Back 24

Fever. Fever is caused by a collection of substances collectively called pyrogens. Pyrogens are molecules produced by the body. Therefore, the bacteria do not directly cause the fever, it is the body's response to the infection which causes fever. Pyrogens stimulate prostaglandin synthesis in the hypothalamic thermoregulatory centers, thus altering the “thermostat” controlling body temperature.

Leukocytosis. Is the term for increased number of leukocytes in the peripheral blood. During acute inflammation, the number of circulating neutrophils typically increases.

Tachycardia. Increased heart rate duuring acute inflammation.

Tachypnea. In a similar manner, the respiratory rate will increase.

Acute phase reactants. These will be discussed in chronic inflammation.

Front 25

What's the ideal outcome of acute inflammation?

Back 25

complete resolution

Front 26

Name and describe the cells of chronic inflammation

Back 26

1. macrophages/monocytes - components of the mononuclear phagocytic system. They originate in the bone marrow, moved into the bloodstream after maturation and become monocytes. These monocytes then migrate to the tissue to become fixed cells where they are given specific names.

2. Lymphocytes - T cells and B cells. Plasma cells which secrete immunoglobulins are also derived from B lymphocytes

3. Eosinophils - the principal effector cell of antibody-dependent cellular cytotoxicity against helminths, as these cells express high levels of the IgE Fc receptor. Eosinophils are also found at local sites of inflammation in individuals with allergies

4. Basophils and mast cells are related cell types which become activated following the binding of antigen to surface-bound IgE. Basophils are found in blood whereas mast cells are found within tissues. Other stimuli, such as fragments of complement, certain drugs and chemicals, as well as certain physical stimuli (cold, heat, sunlight) can also activate these cel

Front 27

What type of cell dervied mediators are typically found in chronic inflammation, in general?

Back 27

Newly synthesized mediators may be produced for long periods of time, even years. Consequently, they may be a part of both acute and chronic inflammation. Effective strategies for reducing the impact of these could include preventing their synthesis, such as cyclooxygenase inhibitors, or preventing them from binding to their receptors

Front 28

During chronic inflammation, what does the liver keep producing?

Back 28

acute phase proteins, never slowing down. Consequently, there are increased concentrations of several proteins, termed acute phase proteins, which may be used as biomarkers for the level of inflammation. These proteins are rapidly increased during acute inflammation, but they stay chronically elevated unless the inflammation subsides. Acute phase proteins, also known as acute phase reactants are present in the blood. These molecules, synthesized primarily by the liver, are induced by the cytokine interleukin six (IL-6). Acute phase reactants may be measured clinically as an index of inflammation.

Front 29

Name 2 lab tests which may be used as biomarkers for the level of inflammation.

Back 29

Two laboratory tests used to measure inflammation are C reactive protein or the erythrocyte sedimentation rate.

Front 30

Name 4 causes of chronic inflammation

Back 30

1. prolonged exposure to tissue injury, or potentially toxic agents
2. immune mediated diseases
3. allergic disease
4. persistent infections

Front 31

What is the predominant feature in granulomatous inflammation?

Back 31

The granuloma is a small, microscopic focus of chronic inflammation. The characteristic cell of the granuloma is a macrophage which has been transformed into a cell termed an epithelioid macrophage. The epithelioid macrophage is a large cell with abundant, pale, pink cytoplasm. These cells are typically clustered in the center of the granuloma. Surrounding these macrophages is a collar of lymphocytes

Front 32

Name 4 causes of granulomatous inflammation

Back 32

1. Certain bacterial infections, most notably infections associated with mycobacteria, resulting in diseases such as tuberculosis and leprosy.
2. Certain fungal and parasitic infections, such as histoplasmosis and schistosomiasis.
3. Foreign bodies, i.e. suture threads, asbestos, talcum powder (once used for surgical gloves)
4. Unknown causes associated with specific diseases, such as sarcoidosis and Crohn’s disease.

Front 33

1) what do glucocoriticoids inhibit?
2) COX-1 and COX-2 inhibits?

Back 33

1) phospholipases that make arachidonic acid
2) cyclooxygenase (create prostaglandins)

Front 34

During the rolling phase, how do endothelial cells and neutrophils interact?

Back 34

On endothelial cells, proteins from selectin family (E + P selectins) interact w/ heavily glycosylated proteins (PSGL-1) at surface of neutrophil

Front 35

What reduces the velocity of rolling neutrophils?

Back 35

active up regulation of P selectin in inflamed endothelial cells

Front 36

What is secreted by endothelial cells, and remains bound to heparan sulfate proteoglycan?

Back 36

IL-8

Front 37

What does the binding of IL-8 to neutrophil stimulate?

Back 37

Binding of IL-8 to neutrophil chemokine receptors stimulates neutrophils and triggers an intracellular cascade of signaling reactions intiated by G proteins associated w/ chemokine receptors

Front 38

How does integrin become activated?

Back 38

cascade of signaling events inside neutrophil activates integrin. its extracellular domains adopt in an extended conformation

Front 39

What enables neutrophils to bind strongly?

Back 39

ICAM. It also results in a reorganization of neutrophil cytoskeleton + a dramatic change in cell morphology

Front 40

What is transendothelial migration?

Back 40

complete mirgration of neutrophil through vessel wall into surrounding CT

Front 41

In lymphoid tissues, what interacts with L-selectin on the leukocytes?

Back 41

CD-34. A glycoprotein at the surface of endothelial cells.

Front 42

What are homing receptors?

Back 42

These direct the migration of lympcyte subsets to particular sites (lympoid tissues, or inflamed endothelium)

Front 43

What do monocytes interact w/ on endothelial cells during rolling?

2) what do monocytes differentiate into after extravasation

Back 43

P selectins.
2) develop into macrophages