007 Chronic inflammation

Granulomatous Inflammation

A distinctive pattern of chronic inflammatory response in which the predominant cell type is an activated macrophage with a modified (epithelioid) appearance Patterns Irregular organization Discrete lesions - granulomas

Cellular phenomena involved in chronic inflammation include all of the following EXCEPT: Lymphocytes secrete IFN-gamma and other chemokines to attract and activate macrophages Macrophages secrete IL-1, TNF and other chemokines to attract and activate lymphocytes Activated lymphocytes secrete lysozyme and myeloperoxidase to mediate cell killing Activated macrophages produce toxic oxygen metabolites, nitric oxide and other cytotoxic molecules Activated macrophages produce fibrogenic and angiogenic cytokines

Activated lymphocytes secrete lysozyme and myeloperoxidase to mediate cell killing

Mediators

Angiogenesis Basic fibroblast growth factor (bFGF) Vascular endothelial growth factor (VEGF) or vascular permeability factor (VPF) Inflammatory Fibrosis Transforming growth factor beta (TGF-B)

Which of the following promotes rapid healing of a wound by first intention (rapid healing with little scar)? Corticosteroid treatments Daily ingestion of smoothies laced with vitamin C Presence of bacteria or foreign material Rapid removal of surface epithelium Apposition of wound edges with sutures

Apposition of wound edges with sutures

Chronology of Repair

Fibroblast and endothelial cell proliferation (begins as early as 24 hours) Removal of inflammatory exudate (begins around 36 hours) Regeneration or scar formation (organization) (occurs over 3 to 4 weeks)

Featured of Chronic Inflammation

Infiltration with mononuclear cells, including macrophages, lymphocytes, and plasma cells Tissue destruction Attempted repair by connective tissue replacement with proliferation of small blood vessels (angiogenesis) and laying down of collagen (fibrosis)

All of the following are true of granulomatous inflammation EXCEPT: Prominent multinucleated giant cells of macrophage origin Lesions form after failure of acute inflammation to remove inciting agent Lesions rarely exhibit central caseous necrosis Local cell mediated immunity has an important role Typical response to infection by Mycobacterium tuberculosis

Lesions rarely exhibit central caseous necrosis

All of the following are true of granulation tissue EXCEPT: Proliferation of new small blood vessels and conntective tissue matrix with macrophages, lymphocytes and fibroblasts Angiogenesis mediated by basic fibroblast growth factor (bFGF) Angiogenesis mediated by vascular endothelial growth factor (VEGF) Collagen deposition mediated by transforming growth factor beta (TGF-beta) Presence of numerous multinucleated giant cells mediated by interleukin -8 (IL-8)

Presence of numerous multinucleated giant cells mediated by interleukin -8 (IL-8)

Granulation Tissue

Proliferation of new small blood vessels and connective tissue matrix containing macrophages, lymphocytes, and fibroblasts Fibroblasts lay down collagen converting granulation tissue to fibrosis

The end result of injury and inflammation can range from complete restitution of normal structure to massive scarring. Which factor favors repair with "restitutio ad integrum"? Compact, uniform, zonal necrosis involving parenchymal cells and connective tissue stroma Tissue wit parenchymal cells with cell cycle blocks Persistence of inflammatory stimulus Recurrent influx of large numbers of neutrophils Prompt resorption of fibrinous exudate by fibrinolysis and clearing by macrophages

Prompt resorption of fibrinous exudate by fibrinolysis and clearing by macrophages

All of the following are characteristic of chronic inflammation EXCEPT: a. Infiltration by macrophages b. Infiltration by lymphocytes and plasma cells c. Tissue necrosis and destruction d.Attempted repair by connective tissue replacement e.Regeneration of normal parenchyma

Regeneration of normal parenchyma

Repair

Replacement of dead cells and tissue by new, healthy cells derived from the parenchyma or from connective tissue Two distinct processes Regeneration - replacement of dead tissue by parenchymal cells of same type Organization - replacement by connective tissue stroma (scar formation)

Stimulation of Cell Proliferation

Stimulatory hormones and growth factors Hormones - estrogen, progesterone and somatostatin (somatotropin) stimulate growth, erythropoietin - RBCs Humoral growth factors - serum growth factors Macromolecular factors - polypeptide in serum Low molecular wt. factors - cyclic nucleotides, Ca2+, amino acids Proteolytic enzymes - trypsin and thrombin - ↑ fibroblasts Inhibiting factors (chalones) Density-dependent regulation