Page 55 - Concise Pathology for Exam Preparation ( PDFDrive )

40 SECTION I General Pathology

• Plasma-derived mediators are mainly produced in the liver; circulate in precursor form
and must be activated.
• Cell-derived mediators are synthesized de novo or are preformed and stored in intracel-
lular granules and need to be secreted.
• Production of active mediators is triggered by microbial products or by host proteins,
such as proteins of the complement, kinin and coagulation systems that are themselves
activated by microbes and damaged tissue.
• Most mediators act by binding to specific receptors on target cells; one mediator can
stimulate release of other mediators.
• Once activated and released from the cells, most of these mediators are short-lived.
• The various mechanisms underlying their action include
• Receptor–ligand interactions
• Direct enzymatic activity
• Oxidative damage

Q. Enumerate the steps involved in generation of arachidonic acid
metabolites.
Ans. Steps involved in generation of arachidonic acid metabolites and their role in inflammation
are summarized in Flowchart 2.5.

Cell membrane phospholipids
Phospholipases Inhibited by steroids

Arachidonic acid Inhibited
by aspirin,
Lipoxygenase Cyclooxygenase indomethacin,
COX 1 and
2 inhibitors
5HETE 5HPETE Prostaglandin G2
Free radical generation
Leukotriene B4 Leukotriene A4 Prostaglandin H2

Leukotriene C4 Prostacyclin I2 Thromboxane A2
• Vasoconstriction • Vasodilatation • Vasoconstriction
• Bronchospasm Leukotriene D4 • Inhibits platelet • Promotes platelet

• ↑ Permeability aggregation aggregation
Leukotriene E4

Lipoxin A4 Lipoxin B4

PGD2 PGE2 PGF2α
• Vasodilatation • Vasodilatation
• Bronchodilatation • Broncho-
• Increased vascular constriction
permeability
HETE – Hydroxyeicosatetraenoic acid
HPETE – Hydroperoxyeicosatetraenoic acid
FLOWCHART 2.5. Generation of arachidonic acid metabolites and their role in inflammation.

• There are two types of cyclooxygenases–COX-1 and COX-2. COX-1 are responsible for
the production of prostaglandins which are involved in both inflammation and homoeo-
stasis (fluid and electrolyte balance and cytoprotection of gastrointestinal tract or GIT),
whereas COX-2 generate prostaglandins that are only involved in inflammation. The
role of COX-2 inhibitors has therefore been explored as anti-inflammatory agents. It has

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