Summary: Episode 49: The original recording is very long for this topic because it covers, inflammatory mediators, phagocytosis and opsonization, complement and arachadonic acid, and cluster designations.<br> Listen to the podcast here…<br> I. Acute Inflammation<br> <br><br> <br> A. Cardinal signs of inflammation<br> In the scenario with a bee sting: you will see redness (Tubor). The king of vasodilators is histamine and it vasodilates the arterioles. Therefore, histamine is responsible for the redness of acute inflammation (i.e., bee sting), and is working on arterioles. Now if we felt the area, it will be warm (Calor = heat), this is due to vasodilating the arterioles, which is caused by histamine. For example in endotoxic and septic shock, the skin is warm b/c you are vasodilated. Tumor is a raised structure caused by histamine. Histamine can lead to increased vessel permeability in the venules; is arterial thicker than venules? Yes. The venules are very thin; they basically have an endothelial cell with a basement membrane, all you have to is drill a hole through the BM and you are out. Therefore, increased vessel permeability occurs at the venule level, not the arterial level.<br> Histamine contracts the endothelial cells, and leaves the BM bare, leading to increased vessel permeability, producing an exudate, and swelling of tissue, hence tumor of acute inflammation. The area may hurt (Dolor = pain) but histamine does not have anything to do with this. Bradykinin is part of the kininogen system between factor 11 and Hageman factor 12. So when you activate the intrinsic pathway, you automatically activate the kininogen system. When you activate factor 12 (Hageman factor), it will activate 11 and the whole kininogen system. The end product is bradykinin. ACE inhibits the degredation of bradykinin, therefore complicating the clinical condition with angioedema. Also inhibit metabolism of bradykinin, which increases vessel permeability, producing the angioedema (swelling of the tissues). How bradykinin produces cough is not really understood. Bradykinin and PGE2 cause pain (dolor) and is the only one out of the four Latin terms of acute inflammation that is not due to histamine release.<br> B. Steps involved in Acute inflammation <br> (this the normal sequence in acute inflammation): <br> 1. Emigration:<br> Includes margination, pavementing, rolling, adhesion, and transmigration Neutrophils in circulation start to become sticky b/c of adhesion molecule synthesis. Endothelial cells begin to synthesize adhesion molecules. Eventually, neutrophils will stick to endothelial cells, these steps are called pavementing or margination. Then neutrophils look for bare basement membrane on the venules and then they drill a hole through it via type 4 collagenase. Cancer cells also have type 4 collagenase, that’s how they metastasize. Cancer cells attach to endothelial via adhesion molecules, usually against laminin in BM, and they have collagensae to get through the BM, therefore, cancer cells are pretty much like a neutrophil when invading tissue.<br> 2. Chemotaxis:<br> When they pass BM of small venules, they emigrate but they have to know what direction to go. They get directions in a process called directed chemotaxis. C5a and LT-B4 (leukotriene B4) are the chemotactic agents. These chemotactic agents are also involved in making adhesion molecules on neutrophils). Therefore, they make adhesion molecules AND give direction by acting like chemotactic agents.<br> 3. Phagocytosis via opsonization:<br> a) Example: in an acute inflammation with staph aureus, the bacteria are being processed by opsonins, which immobilize the particles on the surface of the phagocyte. The two main opsonins are IgG and C3b. They help with phagocytosis.<br> b) Example of an opsonization defect: Brutons agammaglobinemia: an x-linked recessive dz, where all the immunoglobulins are missing, including IgG. Therefore,
