Yurchenko - Iinflammation

Question 1

What are the three types of infmallation rections?

Answer 1

Acute, chronic, and granulomatous

Question 2

What are the general characteristics of acute infmallation?

Answer 2

Mediated by polymorphic leukocyte so - neutrophils, basophils, eosinophils
It will return back to normal size

Question 3

General characteristics of chronic inflammation?

Answer 3

Longer duration and more severe.
Usually mediated by mononuclear inflammatory cells such as monocytes and macrophages.
Does not return to normal state.

Question 4

General characteristics of granulomatous inflammation?

Answer 4

Inflammatory cells can’t deter destroy inflammatory agents but it tries to sequester it.

Question 5

MEchanism of acute inflammation?

Answer 5

1) mast cells will de granulate and release the histamine which will let blood flow increase.
2) Because of this the arterioles will dilate, leading to the redness
3) The post-capillary Venules will become very leaky, which leads to the edema.
4) Fluid leaves by way of the lymphatic system.
5) After about 12-24 hours, neutrophils begin to get involved and they line the post-capillary Venules and begin to exit them into the interstitial space via diapedesis.
6) They migrate to the bacteria and phagocytize them.
7) After about 48 hours, the mononuclear response then replaces the neutrophil response. They mop up the remaining debris.

Question 6

Red Hepatization vs grey Hepatization

Answer 6

Red - the initial neutrophil (polynuclear) response is red
Grey - the mononuclear (monocytes and macrophages) response will include fibrin which gives off a grey appearance on histology.

Question 7

What is the result of mast cell activation?

Answer 7

1) Histamine release
2) synthesis/release of cytokines
3) synthesis/release of eicosanoids

Question 8

Eicosanoids

Answer 8

Arachidonic acid metabolites

• cell membrane phosphipids will be converted into arachidonic acid via phospholipases
• from arachidonic acid it can go down one of two pathways:::
• – One pathway will make prostaglandins, prostacyclin, and thromboxane
• – the other pathway will make Leukotrienes

Question 9

Inhibitors of the arachidonic acid pathway

Answer 9

Steroids - inhibits phospholipases responsible for the conversion of cell membrane phospholipids –> arachidonic acid
Aspirin - inhibits cyclo-oxygenase, which converts arachidonic acid down the pathway that makes prostaglandins, prostacyclins, and thromboxanes

Question 10

What two barriers need to be crossed in order for liquid to go from the vascular tree out to the interstitium? How?

Answer 10

Endothelium (active transport via pinocytic vesicles) and basal Lamina (Passive diffusion).

Question 11

Types of micro vascular leakage

Answer 11

1) Histamine-type - histamine causes leakage of Venules. Short-lived.
2) Injury-type - much longer lived, associated with injury
3) VEGF-mediated transocytosis - occurs in Venules and is increased by vascular endothelial growth factor (VEGF)

Question 12

Histamine type release

Answer 12

• only in post-capillary Venules
• there is a refractory period
• there is a shape change in the Venule due to the histamine. However, there is no smooth muscle, it is due to the physical change in the endothelial cells.
• the inter-epithelial junctions will undergo a shape change that allows a large amount of fluid to exit.

Question 13

What is the mechanism behind why edema occurs?

Answer 13

When the post-capillary Venule undergoes the shape change, the proteins can begin to leave the Venule and go out into the interstitium.

Question 14

What happens to the viscosity of the blood in acute inflammation? Why?

Answer 14

The viscosity will go way up. This is because we lose all of the protein to the interstitium but the RBCs and WBCs stay in circulation. Therefore it is a high conc of those two because of the less water.
- This is called stasis

Question 15

Leukocyte. Exudation (diapedesis.) molecules involved

Answer 15

selectin - a specific type of lectin found on the vascular endothelial surface. Lectins bind to carbs. In this case, the name of the carb is a Sialyl-Lewis-modified protein. The Sialyl-Lewish-modified proteins are found on the neutrophils. This causes the initial, weak, interaction.
ICAM and VCAM - second set of interactions. They attach to interact with integrins that are found on the neutrophils. This is the firmer attachment.

Question 16

We don’t ways want to have diapedesis occurring, what mechanisms do we have to ensure that it happens in the right time?

Answer 16

1) Usually P-selectin is found in these things called Weibel-Palade bodies, but will come out onto the surface of the endothelium in the presence of histamine and thrombin
2) Expression of new receptors on the endothelial surface in the presence TNF or IL-1
3) “Inside out signaling” in which the integrins on the neutrophil are activated. USually the integrins are bent inwards, but in the presence of chemokines, the subunits will spread out and extend themselves so the signal will happen.

Question 17

What causes selectins to come out onto the surface of the endothelium?
What causes expression of new receptors on the endothelium?
What causes “inside out signaling” on the neutrophil?

Answer 17

Selectins = histamine and thrombin
New receptors = IL-1 and TNF
Inside out = chemokines

Question 18

Neutrophil granules and their contents

Answer 18

Azurophil (primary) - contains lysosomal enzymes, peroxidase, lysozyme, and cationic proteins
Specific (secondary) - alkaline phosphatase, lysozyme, lactoferrin

Question 19

What pathway is important for the proper destruction of microbes in the neutrophils?

Answer 19

Hexose Monophosphate Pathway, there is an increased utilization of this pathway to make the necessary stuff to kill the microbe.

Question 20

Chronic Granulomatous Disease

Answer 20

Usually affects males because one of the subunits is X-linked. There will be a lot of abscesses on the skin, lymph nodes, lung, bones, etc.

• The defect is due to lack of NADH oxidase in the cells, so hydrogen peroxide is not generated.
• Usually susceptible to Catalase producing bacteria.

Question 21

MEchanism of chronic inflammation

Answer 21

1) all of the original steps from acute inflammation still happen, except the process can start with damaged parenchymal cells instead of mast cells
2) New capillaries then begin to form from existing ones (angiogenesis). Fibroblasts begin to migrate into the field as well.
3) abscess is an encapsulated accumulation of pus, which is usually just neutrophils, which are just wreaking havoc on the tissues.

Question 22

Empyema

Answer 22

Accumulation of pus (neutrophils) in an existing body cavity.

Question 23

Mechanism of granulation

Answer 23

Starts off very similar to the other types of inflammation. There is increased capillaries in the field, increased fibroblast accumulation in the interstitium, so there is EM laid down.

• the macrophages then surround the bad material and this can happen for years.
• some of the macrophages can come together to form a giant cell.

Question 24

Fibrosis (scar formation))))

Answer 24

The capillaries begin to recede and the fibroblasts beige in to disappear. But you still have that ECM.

Question 25

WHat is a good example of granulomatous inflammation?

Answer 25

Tuberculosis

Question 26

WHat types of Cells will regenerate and which will Cause scars to form?

Answer 26

If the cells Are permenannt like the cardiac or neuronal cells they will Form scarring. If they are labeled cells they will regenerate.

Question 27

What are the general characteristics of inflammation

Answer 27

Redness, swelling, warmth, pain, loss of function.