Pathophys Exam 2 (2 Of 3) - Inflammation

Front 1

What are the three aspects of inflammation that Julius Cohnheim observed in the late 1800s that are still considered the main characteristics of inflammation?

Back 1

1. vasodilation, increased blood flow

2. vascular permeability, leaking plasma, inflammatory exudates form

3. white blood cells adhere and emigrate to site of injury

Front 2

What are the two most important physical characteristics of mast cells?

Back 2

cytoplasm contains granules (mediators of inflammation)

receptors: ligands trigger exocytosis of granules

(e.g., allergens, complement fragments, lipopolysaccharide of bacterium wall)

Front 3

What are the four main “things” (name them and explain them) that stimulate the receptors on mast cells and therefore trigger exocytosis and the general activation of the mast cell.

Back 3

1. lipopolysacchride (LPS or "endotoxin") gram- bacteria
2. peptidoglycan: gram+ bacteria
3. complement fragments (C3a, C5a)
4. Allergens (IgE antibodies Fc end stick to Mast cell)

Front 4

Name and explain the function of the white blood cells that are recruited by chemotatic mediators released by the mast cells

Back 4

Monocytes: (macrophages in inflamed tissue)
Purpose: phagocytize, release inflammatory mediators

Neutrophils: Phagocytize (C3b coated bacteria)

APC
B-cells, T-cells, NK cells

Eosinophils: (like mast cells) granules of inflammatory mediators

Front 5

What are the inflammatory mediators released by Mast cells?

and where do they originate from?

Back 5

Granules:
TNF-alpha
chemokines
Histamines

Manufactured from the phospholipid bilayer (AA):
Leukotrienes
prostaglandins
thromboxanes

Front 6

What is (are) the main function(s) of the following inflammatory mediators released by the mast cells:

tumor necrosis factor-alpha (TNF-alpha)

Back 6

TNA-alpha (+feedback):
a) bind with receptors on leukocytes: release more inflammatory factors
b) hypothalmus: cause fever

Front 7

What is (are) the main function(s) of the following inflammatory mediators released by the mast cells:

chemokines

Back 7

Chemokines: chemotactic cytokine (chemoattractant to guide migration of inflammatory cells to damage)

attract mainly: monocyte, neutrophil, eosinophil, Th1, Th2

Front 8

What is (are) the main function(s) of the following inflammatory mediators released by the mast cells:

histamines

Back 8

Histamine: Increase blood flow, increase permeability

(Redness/Swelling associated with inflammation)

Front 9

What are leukotrienes, prostoglandins, and thromboxanes derived from?

Back 9

arachidonic acid (AA)

Front 10

What constituent of the cell membrane does arachidonic acid derivative come from?

Back 10

phospholipids

Front 11

There are two pathways of arachidonic acid metabolism, what are they? What are their products?

Back 11

5-lipoxygenase pathway:
-produce leukotrienes (LT)

Cyclooxygenase (COX) pathway:
-produce prostaglandin H2 (PGH2) --->
-prostaglandins (PG)
-thromboxanes (Tx)

Front 12

What is the general effect of the three potent mediators of inflammation derived from arachidonic acid (AA)?

Back 12

Leukotrienes:
-bronchoconstriction (during asthmatic attacks)

Thromboxanes:
-stimulate aggregation of platelets
-vasoconstriction

Prostoglandins:
(similar to histamines, but like bradykinin)
-stimulate pain receptors
-play a role in coagulation

Front 13

Inflammation is mediated by 3 key plasma protein systems, name them:

How are they similar?

Back 13

1. the complement system
2. hemeostasis
3. kinin system

-Each consists of a series of inactive enzymes (proenzymes)
-The cascade is initiated by activation of the 1st proenzyme

Front 14

What are the complement system's two paths to activation?

Back 14

The classical complement pathway
The alternative complement pathway

Front 15

Which pathway of the complement system is antibody dependent?

Which proteins initiates this pathway?

Back 15

The classical complement pathway:

C1 Complex binds to (specifically) IgM and IgG on a foreign particle

Front 16

Which pathway of the complement system is antibody independent?

Which proteins initiates this pathway?

Back 16

The alternative complement pathway:

C3b fragment (in circulation), binds to pathogen surface (invading micro-organisms)

Front 17

Both complement pathways result in the formation of what complex and what is the effect of this complex?

Back 17

C3-convertase: C3a/C5a + MAC

--------------------------------------------------
C1-complex / C3b fragment --->>
C3-convertase --->>
two anaphylatoxins (C3a and C5a)

C3b+C3-convertase --->> C5b --->> MAC

Front 18

What are the two anaphylatoxins of the complement system?

Back 18

Anphylatoxins:
C3a/C5a

-chemotactic proteins (recruit more inflammatory cells)
-cause degranulation of Mast cells

Front 19

What is the end product of the complement cascade? What is it’s action on the target cell?

Back 19

The membrane attack complex (MAC); it forms a transmembrane channel, which causes osmotic lysis of the target cell

C3-convertase --->> C3a/b
C3b+C3-convertase --->> C5a/b
C5b --->>> MAC

Front 20

What are 2 ways the Complement System is Inhibited?

Back 20

Complement control proteins:

C1-Inhibitors (protease inhibitor)

CD59 (protectin)

Front 21

What is the function/location of CD59 (protectin)?

Back 21

CD59 (protectin)
-on WBC / RBC
-inhibits MAC formation (blocks C9)

Front 22

What is the function of C1-inhibitor? What condition is caused by a hereditary deficiency in C1-inhibitor?

Back 22

C1-Inhibitors (protease inhibitor)
-floating freely in blood stream
-inhibits:
-C1-complex
-clotting/kinin pathways

Hereditary angioedema.

Front 23

What is the general outcome due to complement deficiencies?

Back 23

increased bacterial infections
-reduced opsonization
-reduced phagocytosis-
-cannot form MAC

Front 24

What are the three basic mechanisms that promote hemostasis (stoppage of bleeding)?

Back 24

vasoconstriction
formation of platelet plug
formation of blood clot (coagulation)

Front 25

What causes platelets to degranulate?

Back 25

when platelets adhere (via vWF) to exposed collagen
(from damaged vessel)


vWF: Von Willebrand factor

Front 26

What are contained in Platelet Cytoplasmic Granules?

Back 26

Serotonin
ADP
Thromboxane A2

Front 27

What is the function of Serotonin (platelet granzyme)?

Back 27

Serotonin is a vasoconstrictor

Front 28

What is the function of ADP (platelet granzyme)?

Back 28

ADP attracts more platelets to the area

Front 29

What is the function of Thromboxane A2 (platelet granzyme)?

Back 29

Thromboxane A2
-promotes platelet aggregation
-degranulation
-vasoconstriction

Front 30

List the two pathways of the final step in hemostasis (blood clot)?

Back 30

intrinsic
extrinsic

Front 31

Although both the intrinsic and extrinsic clotting pathways are initiated by distinct mechanisms, they both converge on what common pathway?

Back 31

Activation of factor X (X to Xa)

Front 32

When considering the extrinsic clotting pathway, what factor is released at the site of injury?

Back 32

The release of tissue factor (TF)

Front 33

What factor is activated by the release of tissue factor (TF)?

Back 33

Tissue factor activates factor VII (VII to VIIa).

Front 34

What factor is activated by factor VIIa

Back 34

Factor VIIa activates factor X (X to Xa)

Front 35

Why is it that the intrinsic pathway is more involved than the extrinsic pathway?

Back 35

It requires many more clotting factors + blood proteins:
-VIII, IX, XI, XII
-prekallikrein (PK) produced by endothelial cells
-plasma protein high-molecular-weight Kininogen (HMWK)
-calcium ions (Ca++)
-phospholipids (PL)

“tighter control”, preventing spontaneous activation

Front 36

In order for activated factor X (Xa) to convert prothrombin to thrombin, it becomes part of the prothrombinase complex. Besides Xa, what are the other components of this complex?

Back 36

prothrombinase complex:
-platelet phospholipids (PL)
-Ca++
-Xa
-Va.

Front 37

Thrombin is involved in two pathways the end in the formation of a stable fibrin clot. One pathway involves the formation of fibrin monomers—what role does thrombin play in this pathway? The second pathway activates what clotting factor and what is the function of this clotting factor?

Back 37

Path 1:
Thrombrin ---> Fibrinogen (removes fibrinopeptides)
--->>> Fibrin monomers (weak clot)

Path 2:
Thrombrin ---> XIII --->>> XIIIa ---> cross-links (covalent bonds)

Results: stable fibrin mesh / fibrin clot

Front 38

Hemophilia A results in the deficiency of what factor?

Back 38

Intrinsic Clotting Pathway:

Factor VIII

Front 39

Hemophilia B results in the deficiency of what factor?

Back 39

Intrinsic Clotting Pathway:

Factor IX

Front 40

Which Hemophilia is most prevalent?

Back 40

Hemophilia A

Hemophilia B is 1/10 of A

Front 41

Which clotting pathway does Hemophilia effect?

Back 41

Intrinsic clotting pathway

Front 42

What is Von Willebrand Disease (VWD)

Back 42

deficiency of vWF (Von Willebrand Factor)

Results:
1) platelets cannot stick to the exposed collagen fibers
2) Von Willebrand factor (vWF) is the carrier protein for clotting factor VIII (becomes inactivated)

Front 43

What are the symptoms of Von Willebrand Disease (VWD)?

Back 43

gums that bleed easily
frequent nosebleeds
easy bruising
heavy bleeding after small cuts and dental work

Females: menorrhagia,

Front 44

What is fibrinolysis?

Back 44

the process whereby the fibrin clot we have just discussed is broken down.

Front 45

What is the main protease of fibrinolysis process?

Back 45

Plasmin

Front 46

In what form (i.e., proenzyme) does Plasmin protease circulate?

Back 46

plasminogen

Plasminogen is in clot;
binds to both fibrinogen and fibrin

Front 47

What two proteases convert the inactive plasminogen to the active form?

Back 47

Urokinase
Tissue plasminogen activator (tPA)

Front 48

At the site of injury, what is the main source of tissue plasminogen activator (tPA)?

Back 48

Vascular endothelial cells

Front 49

What are the three thrombolytic agents?

Back 49

streptokinase
Urokinase
Tissue plasminogen activator (tPA)

Front 50

What do the three thrombolytic agents do?

Back 50

Use of thrombolytic agents:
• Emergency treatment of coronary artery thrombosís in myocardial infarction;
• Emergency treatment of cerebral artery thrombosis in stroke;
• To dissolve deep venous thrombosis that could produce a pulmonary emboli.

Front 51

What is the kinin system?

Back 51

3rd plasma protein system to mediate inflammation

Front 52

What triggers the activation of the kinin system?

Back 52

Hageman factor ---> prekallikrein --->> kallikrein

Front 53

What is the end product when the kinin system is activated?

Back 53

Bradykinin.

Front 54

What are the actions of Bradykinin and what similarity does it have with protoglandins?

Back 54

-Increases vascular permeability (i.e., similar to histamine);

-Causes vasodilation (i.e., similar to histamine);

-WBC chemotactic;

-Stimulates pain receptors (i.e., similar to prostaglandins).