Inflammation Dr. Ahmad Hameed MBBS,DCP, M.Phil
Definition Inflammation is a protective response involving host cells, blood vessels, proteins and other mediators intended to eliminate the initial cause of cell injury, as well as the necrotic cells and tissues resulting from the original insult, and to initiate the process of repair.
Although inflammation helps clear infections and other noxious stimuli and initiates repair, the inflammatory reaction and the subsequent repair process can themselves cause considerable harm.
The cells and molecules of host defense, including leukocytes and plasma proteins, normally circulate in the blood and the goal of the inflammatory reaction is to be bring them to the site of infection or tissue damage.
Features of Acute and Chronic Inflammation FeatureAcuteChronic OnsetFast: minutes or hoursSlow, days Cellular InfiltrateMainly neutrophilsMonocytes/macrophages and lymphocytes Tissue injury, fibrosisUsually mild and self- limited Often severe and progressive Local and systemic signsProminentLess prominent; may be subtle
Inflammation is induced by chemical mediators that are produced by host cells in response to injurious stimuli. Macrophages, dendritic cells, mast cells Also produced from plasma proteins
The components of acute and chronic inflammatory responses and their principal functions.
Cardinal Signs These signs are: rubor (redness) tumor (swelling) calor (heat) dolor (pain) functio laesa, or loss of function Inflammation is normally controlled and self limited
Acute inflamation Two major components VASCULAR CHANGES Vasodilation Increased vascular permeability CELLULAR EVENTS Recruitment Activation, in acute inflammation (neutrophils)
Stimuli for Acute Inflammation CAUSES Infections: bacteria, viruses, parasites Trauma: (blunt and pentrating) Physical and chemical agents Tissue necrosis: myocardial infarct Foreign bodies: Immune reactions:
Recognition of Microbes, Necrotic Cells and Foreign Substances Phagocytes, dentritic cells, epithelial cells express “pattern recognition receptors” Toll like receptors (TLRs) Ten mammalian TLRs Inflammasome Products of dead cell Activates caspase-1 IL-1 IL-1 plays a role in atherosclerosis, obesity associated type 2 diabetes Possibility of treating these diseases by blocking IL-1
Vascular Changes Changes in vascular caliber and flow VASOCONSTRICTION (momentary constriction of small BV). Vascular spasm begins very quickly (30 sec.) after the injury at it last a few minutes. The mechanism of spasm is nervous – through catecholamine liberated from sympathetic nerves endings.
ACTIVE VASODILATION (through catabolism products that act through receptors and directly stimulates vascular dilation – nervous mechanism). Dilation of arterioles and capillaries (redness = rubor); Blood flow increases and gives pulsate sensation; Active hyperemia in skin territory and increased metabolism leads to higher local temperature (heat = calor).
INCREASED VASCULAR PERMEABILITY Blood vessels in the affected area loose their reactivity to nervous and humoral stimuli and passive vasodilation occurs. Progressively fluid move into the tissues cause swelling (tumor), pain, and impaired function. Exudate Transudate Edema
MECHANISMS CONTRIBUTING INCREASED PERMEABILITY Endothelial “gaps” Direct Injury, Leukocyte Injury Transocytosis New Vessels All of them may participate in response to particular stimulus
Endothelial cell contraction leading to intercellular gaps in postcapillary venules Short-lived (15-30) minutes Histamine, bradykinin, leukotrienes, and others Slower and prolonged (6-24) hours TNF, IL-1
Endothelial injury Burns, some infections Venules, capillaries, and arterioles can all be affected Delayed prolonged leakage Thermal injury Bactrical toxins, Ultraviolet irradiation Activated leukocytes release many toxic mediators
Increased trancytosis VEGF Transcytosis occurs through channels formed by fusion of intracellular vesicles Leakage from new blood vessels These vessel sprouts remain leaky until proliferating endothelial cells mature sufficiently to form intercellular junctions. VEGF
Response of lymphatic vessels Increased lymph flow drain edema fluid also transports leukocytes, cell debris and maybe offending agent Offending agent lymphangitis lymphadenitis Clinically: Presence of red streaks near wound indicates infection of wound