Chronic Inflammation Flashcards
What is Chronic Inflammation?
Chronic Inflammation is defined as the prolonged duration on which active inflammation, tissue destruction and attempts at repair are proceeding simultaneously.
What are the key cellular distinctions between Acute Inflammation and Chronic Inflammation?
Neutrophils (aka. Polymorphonuclear Cells) are a key indicator of Acute tissue injury and Acute Inflammation. Activated T-Cells and Macrophages are indicative of persistent tissue injury and Necrosis, and thus, Chronic Inflammation.
What kind of diseases can cause Chronic Inflammation?
Persistent Infections (e.g. Tuberculosis), prolonged exposure to toxic agents, both endogenous (e.g. excess endogenous lipids result in atheromatous plaques) and exogenous (e.g. silicosis), and dysregulation of the immune system, causing Autoimmune disease (e.g. Rheumatoid Arthritis).
What are the possible intervening points to relieve the pain-associated symptoms associated with Chronic Inflammation?
Anti-Depressants (counter psychological processes conducive to pain), Anti-Convulsants (counteract neuropathic mechanisms that exacerbate pain), Opioids (affect Neuropathic mechanisms as well as Nociception) and Non-steroidal Anti-Inflammatory Drugs (inhibit visceral and somatic afferent nociceptive signaling) can all act to relieve pain associated with Chronic Inflammation.
What are some of the mechanisms by which Anti-Inflammatory drugs may act to reduce inflammation?
These drugs may act to (i) Decrease the production of inflammatory compounds (e.g. decrease number of cells producing pro-inflammatory cytokines, decrease the production of cytokines for specific cell types, decrease Immunoglobulin synthesis) or (ii) Decrease the sensitivity of cells to pro-inflammatory compounds (e.g. Antibodies that bind to and neutralize TNF-alpha, Chemicals that modify the nuclear responses of pro-inflammatory pathways such as NF-KB pathway).
How do NSAIDs differ from steroid-based Anti-Inflammatory Drugs?
NSAIDs are ideal in that they inhibit the COX enzymes, and thus decrease the amount of Prostanoids produced, which previously had pro-inflammatory effects. However, NSAIDs do not affect the Lipoxygenase pathway, which also brings about deleterious pro-inflammatory products that may exacerbate existing inflammation.
What is the Mechanism of Aspirin, a standard NSAID?
Aspirin is a non-competitive inhibitor of COX. COX is acetylated by Aspirin via donation of its Acetyl group, permanently de-activating the COX enzyme. Thus, more of the COX proteins must be synthesized to restore its endogenous activity.
How do other NSAIDs differ from the mechanism of Aspirin?
Other NSAIDs are competitive inhibitors, such that the degree of inhibition is directly proportional to drug concentration at that time. A consequence of this is that activity of the COX enzymes is restored when drug concentration decreases.
