Pathology Set 2

Front 1

What are the five cardinal signs of inflammation and what causes them?

Back 1

Rubor (redness) - histamine dilated arterioles, calor (heat) - same, tumor (swelling) - histamine increases venule permeability, exudate formed, dolor (pain) - PGE2 sensitizes nerve endings to mediators, functio laesa (loss of function)

Front 2

What vascular events occur in acute inflammation (specifically in the immediate transient response)?

Back 2

Initial arteriolar vasoconstriction, then vasodilation (histamine, NO). Immediate transient response: increased permeability of venules with endothelial gaps (histamine, bradykinin, leukotrienes) - 15-30 minutes. Stasis as hydrostatic pressure increases, transudate -> exudate moves into interstitial space; edema occurs when fluid overwhelms lymphatic ability to remove fluid, blood flow decreases

Front 3

What other vascular events may occur and when do they occur?

Back 3

Immediate sustained: direct endothelial damage like burns, persists for hours/days, arterioles/venules/capillaries all affected. Delayed prolonged: venules and capillaries, delay of 2-12 hours, then lasts for days, sunburns and radiation. Leukocyte-dependent: adhesion of leukocytes to endothelium, increased permeability of pulmonary venules and glomerular capillaries, later response, ARDS and glomerulonephritis

Front 4

What role does the contact system play in inflammation?

Back 4

The contact system is activated by Factor XII (a plasma protein) when something breaks the basement membrane bw a capillary and endothelial tissue. It activates the kinin cascade which release bradykinin (vasodilation), It also activates the clotting cascade (thrombin, plasmin) and the complement cascade. This system begins at the same time as the histamine response.

Front 5

What occurs in the clotting cascade? What do platelets contain?

Back 5

Platelets have dense bodies that contain ADP and 5-hydroxytryptamine (serotonin) which enhance the actions of histamine. PF-3 activates the coagulation cascade (thrombin). Platelets also produce protaglandins and contain alpha granules with proteolytic subtances that enhance vascular permeability.

Front 6

What factors are involved in the complement system?

Back 6

The contact system initiates the complement system. C3a and C5a contribute to anaphylaxis (degranulate mast cells and basophils) and exudation. C5a contributes to neutrophil chemotaxis.

Front 7

What does bradykinin do?

Back 7

Vasodilation of venules, increased vessel permeability, and pain. Released from contact system in kinin cascade.

Front 8

What does nitric oxide do?

Back 8

Vasodilation of arterioles in vascular response to acute inflammation. Released by endothelial cells.

Front 9

What is the difference between an exudate and transudate?

Back 9

Exudate: fluid from an inflammatory response, contains proteins, immunoglobulins, some fibrin and inflammatory cells. Cloudy with high concentration (specific gravity > 1.02). Associated with bacterial infection, pneumonia, cancer (will show malignant cells), pulmonary embolus. Transudate: fluid that occurs due to imbalance between hydrostatic and osmotic pressures. Clear, low concentraion (SG < 1.012), associated with CHF, cirrhosis.

Front 10

What can be used to track the course of an inflammatory process?

Back 10

Lactic dehydrogenase levels: liver, kidneys, striated muscle, heart muscle

Front 11

What cellular events occur in acute inflammation?

Back 11

Leukocytes are attracted and migrate to a site of inflammation, complimentary adhesion molecules on the leukocyte and endothelial cells bind, then they phagocytize and destroy bacteria and tissue debris

Front 12

Explain margination, rolling, adhesion and diapedesis, including the role of integrins and selectins.

Back 12

Margination: RBCs stack up (rouleaux), push PMNs to marginate. Rolling: PMNs loosely bind to selectins (Sialyl-Lewis X) and slow down. Adhesion: PMNs bind firmly to ICAMs and VCAMs (integrins). Diapedesis: PMNs transmigrate through endothelial intercellular junctions into interstitium, form exudate.

Front 13

What is the role of exudate?

Back 13

To provide leukocytes for opsonization, provide Abs and complement and dilute bacterial toxins.

Front 14

What are integrins and what activates them? What activates ICAM and VCAM?

Back 14

Integrins: adhesion molecules, also act as cellular sensors and signaling molecules. Activated by chemokines (C5a, LTB4). ICAM and VCAM on endothelial surfaces activated by IL-1 and TNF (macrophages).

Front 15

What is LTB4?

Back 15

A leukotriene produced by leukocytes involved in chemotaxis. Other leukotrienes are involved in vasoconstriction, bronchoconstriction, and increased vessel permeability.

Front 16

What factors initiate chemotaxis for neutrophils?

Back 16

LTB4 (before), IL-8 (8-ttract) from macrophages, C5a ("500")

Front 17

What is factor XII, the Hageman factor, responsible for?

Back 17

Initiation of clotting cascade, fibrin cascade, complement, bradykinin

Front 18

What is serotonin responsible for and what produces it?

Back 18

Vasodilation, increased vessel permeability (enhance effects of histamine); from mast cells and platelets

Front 19

What factors are responsible for anaphylaxis?

Back 19

C3a and C5a (degranulate mast cells and basophils)

Front 20

What is natalizumab?

Back 20

A recombinant monoclonal antibody against alpha4-integrins. Blocks cellular infiltration of pathogenic T-cells, reducing inflammation. Tx for multiple sclerosis (autoimmune destruction of myelin)

Front 21

What complications occurred with tx with natalizumab?

Back 21

A few pts developed progessive multifocal leukoencephalopathy, secondary to the latent JC virus. Infects oligodendrocytes, demyelinating white matter.

Front 22

What breakdown products set up the gradient in chemotaxis?

Back 22

Bacterial byproducts, components of complement, products of lipoxygenase arachidonic pathways, and cytokines.