Acute and Chronic Inflammation Flashcards
Functions of Inflammation
Defend against and stop aggression. Clean up by products via phagocytosis. Repair damaged tissues.
Two main characteristics of acute inflammation
Interstitial edema and accumulation of neutrophils.
Histological appearance of neutrophils
Multilobar nucleus. More than 3 usually. Lavender cytoplasm and purple nuclei.
Characteristics of chronic inflammation
Many mononuclear cells that include lymphocytes, plasma cells, macrophages. Granulation tissue, angiogenesis, fibrosis.
Histological appearance of plasma cells
Long, have epically located nucleus.
Appearance of lymphocytes
Round nucleus with little cytoplasm.
3 major components of acute inflammation
- Vascular alterations leading to increased blood flow. 2. Microvasculature alterations that allow proteins and neutrophils to leave circulation and produce an inflammatory exudate. 3. Diapedesis and accumulation of neutrophils.
Clinical signs of inflammation
Calor Rubor Tumor Dolor and Functio Laesa
What does vascular permeability do in acute inflammation?
Endothelial cells become leaky, either by direct injury or by chemical mediators. Protein rich fluid escapes into interstitial space (edema).
Why does vascular stasis occur in acute inflammation?
Because vascular dilation and exudation occur. Congestion also occurs to give inflammatory cells maximum time to collect and move into tissue.
Mechanisms of endothelial permeability
Endothelial retraction, where cytoskeleton reorganizes. Also contraction, but not sure about the difference. Direct endothelial injury and neutrophil mediated endothelial injury too.
Cellular events in acute inflammation
Margination, rolling, and adhesion of the leukocytes. Transmigration across endothelium. Migration through interstitial tissue towards chemotactic stimulus.
Selectin
Surface molecule that mediates cell attachment and rolling along endothelial cells. Sialyl Lewis X on cells binds to selectins on endothelium. Promoted by histamine, thrombin. P, E, and L selectin (platelets, endothelial cells, leukocytes).
Integrin
Expressed on endothelial cells. Their affinity is increased by chemokines.
PECAM
Platelet endothelial cell adhesion molecule, facilitates migration.
How do neutrophils know where to go in interstitium?
Follow chemotactic gradient. Usually molecules like leukotrienes, chemokines, complement fragments, which bind to neutrophils, produce secondary messengers, and cause pseudopod movement.
What happens when neutrophil arrives?
Phagocytosis or degranulation
What happens when offending agent is engulfed?
Oxygen dependent killing (myeloperoxidase, which takes hydrogen peroxide and halogenates it). Oxygen independent killing (major basic protein, defensins, lysozyme).
Neutrophil induced tissue injury
Neutrophils can also degranulate, releasing free radicals and lysosomal enzymes into the extracellular space. Can cause chronic inflammation if persistent.
How can acute inflammation resolve?
Macrophages engulf neutrophil and tissue debris causing complete resolution. Abscess can form. Healing and scarring can occur, or progression to chronic inflammation.
Purulent
Exudate with prominent neutrophils
Suppuritive
Purulent exudate with tissue necrosis
Abscess
Localized collection of pus
Fibrinous
Exudate containing fibrin due to leakage of proteins from blood vessels with increased permeability and activation of the coagulation cascade.
Ulcer
Surface defect of an organ secondary to sloughing off of necrotic tissue
Two sources of chemical mediators of inflammation
Cells and blood plasma (synthesized in liver)
Cellular mediators of inflammation
Histamine, prostaglandins, Leukotrienes
Plasma derived mediators of inflammation
Hageman Factor (Kinin system), complement proteins
Histamine Source and Function
Released by mast cells and basophils. Among the first mediators to be released in an inflammatory response. Causes vasodilation and increased vascular permeability.
Arachidonic Acid Metabolites, Function?
Cyclooxygenases (prostaglandins and thromboxanes), and Lipooxygenases (leukotrienes and lipoxins). Short range signaling agents.
How is platelet activating factor released?
From mast cells and other leukocytes. Causes platelet aggregation and other things.
What are the major inflammatory cytokines?
TNF and IL-1. Activate endothelial cells. Also involved in septic shock.
Hageman Factor
AKA clotting factor XII. Initiates the kinin, clotting, finbrinolytic, and complement cascades.
Bradykinin
Generated from Kallikrein. Involved in blood vessel dilation, increased permeability, pain.
Kallikrein effect on Hageman Factor?
Profound amplifier!
Intrinsic Clotting System
Results in the activation of thrombin, which leaves fibrinogen to fibrin. Thrombin also causes increased leukocyte adhesion to endothelium.
Chronic Inflammation
Prolonged duration, active inflammation, tissue destruction, healing, all happening simultaneously
How does chronic inflammation occur?
Persistent acute inflammation, persistent infection, prolonged exposure to toxic substances, autoimmune disease.
Appearance of eosinophils
Bilobed nucleus with eosinophilic granules
Do macrophages appear more in chronic or acute inflammation?
Chronic!
Why does fibrosis occur in chronic inflammation?
Because macrophages induce fibroblast activity.
Appearance of macrophages
Large, kidney shaped nucleus, blue cytoplasm.
Granulomatous Inflammation Appearance
Epithelioid Macrophages surrounded by a collar of leukocytes. Central necrosis. Giant cells in the center.
