Chronic inflammation Is inflammation of prolonged duration weeks

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Chronic inflammation Is inflammation of prolonged duration (weeks to months to years) in which active inflammation, tissue injury, and healing occur together.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Characterized by: 1. Infiltration with macrophages, lymphocytes, and plasma cells 2. Tissue destruction, induced by the products of the inflammatory cells. 2. Repair, involving new vessel proliferation (angiogenesis) and fibrosis.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Examples of Chronic inflammation: 1. Persistent infections by microbes e. g : mycobacteria(TB), viruses and fungi. 2. Autoimmune diseases : immune reactions develop against the individual's own tissues. 3. Allergic diseases, e. g bronchial asthma 4. Prolonged exposure to toxic agents such as inhaled particulate silica (cause silicosis)

Chronic Inflammatory Cells: ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 1. Macrophages In the blood it is called monocytes. when it enter the tissue its name changed e. g: In the liver are called Kupffer cells In the spleen and lymph nodes called sinus histiocytes In the central nervous system called microglial cells In the lungs alveolar macrophages

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 2. Lymphocytes Two types: T and B lymphocytes which migrate into inflammatory sites by action of chemokines. Lymphocytes interact with macrophages to kill the organism

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 3. Eosinophils Found in inflammatory sites around parasitic infections or as part of immune reactions associated with allergies.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 4. Plasma cells: Develop from activated B lymphocytes and produce antibodies directed against antigens in the inflammatory site or against altered tissue components.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Granulomatous Inflammation: Granulomatous inflammation is a distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages that assume an epithelioid appearance.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Example of granulomatous inflammation Disease Cause Tissue Reaction Tuberculosis Mycobacterium tuberculosis 1. Noncaseating tubercle (granuloma prototype): a focus of epithelioid cells, rimmed by fibroblasts, lymphocytes, histiocytes, occasional giant cells 2. Caseating tubercle: central amorphous granular debris, loss of all cellular detail; acid-fast bacilli Leprosy Mycobacterium leprae Acid-fast bacilli in macrophages; noncaseating granulomas Syphilis Treponema pallidum Gumma: microscopic to grossly visible lesion, enclosing wall of histiocytes; plasma cell infiltrate; central cells are necrotic without loss of cellular outline

Gram-negative bacillus Rounded or stellate granuloma containing central granular debris and recognizable neutrophils; giant cells uncommon Sarcoidosis Unknown etiology Noncaseating granulomas with abundant activated macrophages Crohn disease (inflammatory bowel disease) Immune reaction against Occasional noncaseating intestinal bacterial, self- granulomas in wall of antigens intestine, with dense chronic inflammatory ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Cat-scratch disease

SYSTEMIC EFFECTS OF INFLAMMATION ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ The cytokines TNF, IL-1, and IL-6 are the most important mediators of the acute-phase reaction. They are produced by leukocytes (and other cells) in response to infection or in immune reactions and are released systemically

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ TNF induces the production of IL-1, which in turn stimulates the production of IL-6 stimulates the hepatic synthesis of a number of plasma proteins

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ The acute-phase response consists of : 1. Fever: Characterized by an elevation of body temperature, usually by 1° to 4°C. Produced in response to substances called pyrogens that act by stimulating prostaglandin (PG) synthesis in the vascular and perivascular cells of the hypothalamus.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Bacterial products, such as lipopolysaccharide, stimulate leukocytes to release cytokines such as IL-1 and TNF that increase the levels of cyclooxygenases that convert AA into prostaglandins.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ • In the hypothalamus the PGs, especially PGE 2, stimulate the production of neurotransmitters, which function to reset the temperature set point at a higher level

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Note: NSAIDs, including aspirin, reduce fever by inhibiting cyclooxygenase and thus blocking PG synthesis.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 2. Elevated plasma levels of acute-phase proteins: Are plasma proteins, mostly synthesized in the liver, whose concentrations increase in response to inflammatory stimuli. e. g; C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA) protein

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ • Many acute-phase proteins, such as CRP and SAA, bind to microbial cell walls, and they may act as opsonins and fix complement, thus promoting the elimination of the microbes

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Fibrinogen binds to erythrocytes and causes them to form stacks that sediment more rapidly at unit gravity than do individual erythrocytes. This is the basis for measuring the erythrocyte sedimentation rate (ESR).

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 3. Leukocytosis: The leukocyte count up to 15, 000 or 20, 000 cells/μL, Sometimes it may reach extraordinarily high levels, as high as 40, 000 to 100, 000 cells/μL. This elevations are referred to as leukemoid reactions.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ • The leukocytosis occurs because of accelerated release of cells from the bone marrow caused by cytokines, including TNF and IL-1 and is associated with a rise in the number of more immature neutrophils in the blood.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ Most bacterial infections induce an increase in neutrophil count ( neutrophilia). Viral infections, are associated with increased numbers of lymphocytes (lymphocytosis).

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ • Bronchial asthma, hay fever, and parasite infestations all involve an increase in the absolute number of eosinophils (eosinophilia)

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ • Certain infections (typhoid fever and infections caused by some viruses, rickettsiae, and certain protozoa) are associated with a decreased number of circulating white cells (leukopenia).

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 4. Other manifestations of the acute-phase response include: increased heart rate and blood pressure, rigors (shivering), chills (perception of being cold ), anorexia, and malaise

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 6. Chronic inflammation is associated with a wasting syndrome called cachexia, which is mainly the result of TNF-mediated appetite suppression and mobilization of fat stores.

ﺟﺎﻣﻌﺔ ﻛﺮﺭﻱ 7. In severe bacterial infections (sepsis), large amounts of organisms and LPS in the blood stimulate the production of several cytokines, (TNF, IL-12 and IL 1). High levels of TNF cause disseminated intravascular coagulation (DIC), hypoglycemia, and hypotensive shock