INFLAMMATION - PDF document

INFLAMMATION By Ajay Kumar What is inflammation? A normal response of living tissues to injury. It prepares the tissue for healing and repair. Ultimate goal is to replace injured tissue. EFFECT OF INFLAMMATION: The four principal effects of inflammation rubor, tumor, calor and dolor Those were described nearly 2,000 years ago by the Roman Aulus Cornelius Celsus, more commonly known as Celsus. Redness (rubor) An acutely inflamed tissue appears red, due to dilatation of small blood vessels with in the damaged area (hyperemia). Swelling (tumor) Swelling results from oedema, the accumulation of fluid in the extravascular space as part of the inflammatory fluid. Heat (calor) Increase in temperature is readily detected in the skin. It is due to incre ased blood flow (hyperemia) through the region, resulting in vascular dilation and the delivery of warm blood to the area. Pain (dolor) Pain results partly from the stretching and distortion of tissues due to inflammatory edema. Loss of function (functio l aesa) Loss of function, a wellknown consequence of inflammation, was added by Virchow (1821 - 1902) to the list of features described in Celsus’ written work. INFLAMMATORY RESPONSES: Leukocytosis White blood cell count increased above the normal range It is not a disorder or a disease, but a sign of illness. IL - 1 and TNF reach the bone marrow and cause accelerated release of leucocytes into the circulation. Endotoxemia Bacteria enter blood stream & release endotoxin WBC react to the presence of bacteria and r elease inflammatory substanceexcessive cytokine production Endotoxemia specifically refers to circulating gram - negative bacterial toxic products (LPS). There are some cell wall products released from gram - positive bacteria that can have a similar toxic effect. Fever Fever is a common systemic response to inflammation The elevation of body temperature is

thought to improve the efficiency of leukocyte killing and may also impair the replication of many invading organisms. Type of Inflammation: Inflam mation is divided into Acute and Chronic type….. Acute inflammation: The inflammation process which starts immediately is called acute inflammation. Cardinal Signs of acute inflammation • Redness (rubor) • Swelling (tumor) • Heat (calor) • Pain (dolor) • L oss of function (functio laesa) Acute inflammation: • Main components: – Vascular changes • Vasodilation • Vascular permeability • Increased adhesion of white blood cells – Cellular events • Cellular r ecruitment and activation of neutrophils (polymorphonuclear leukocytes). 1. Vasodilation: - The reactions of blood vessels - Alterations in vascular caliber (diameter) – Causes decrease in blood pressure 2. Vascular leakage and edema: - The accumulation of fluid and proteins of plasma in the extr avascular tissues (interstitium) 3. Leukocyte emigration to extravascular tissues A. Margination and rolling B. Activation and adhesion C. Transmigration. 1. Vasodilation: • Change in vessel flow – NO, histamineèvascular smooth muscleè vasodilationèincreas ed blood flow (heat & redness) – Stasis: slowed blood flow, hyperviscosity – Margination of circulating leukocytes & endothelial activation • Followed by increased permea bility of the vasculature – Formation of an early transudate (protein - poor filtrate of plasma) gives way to exudate (protein - rich filtrate) into extracellular tissues. Features of chronic inflammation: • Chronic inflammation = long duration • Components: – Lymphocyte, plasma cell, macrophage (mononuclear cell) infiltration. CHRONIC INFLAMM ATION AND CANCER: The normal end result of inflammation is that any damaged tissue or damaged DNA is repaired, the inflammatory res

ponse is quenched, and healing takes place. However, during active inflammation the cellular microenvironment is highly react ive and unstable attributable to the combined effects of the many and abundant reactive oxygen and nitrogen species, cytokines, chemokines, reactive aldehydes, and growth factors that are present. 1.Reactive Oxygen and Nitrogen Species: Most of the literat ure agrees that the sustained generation of free radicals such as the reactive oxygen species hydroxyl radical (OH·) and superoxide (O2·) and the reactive nitrogen species nitric oxide (NO·) and peroxynitrite (ONOO·). 2.Macrophages Macrophages in particula r are important tumor infiltrating cells that affect tumor growth and metastasis. They are found in 2 different polarization states known as M1 and M2. M1 macrophages produce interleukin 12 and promote tumoricidal responses, The mechanisms governing macrophage polarization are unclear. Another inducible enzyme with carcinogenic properties that is active within inflamed and malignant tissues is cyclooxygenase - 2 (COX - 2). The mechanism by which inflammation causes cancer can be modeled as c onsisting of an intrinsic and extrinsic pathway. The intrinsic pathway is activated by oncogene activation and tumor suppressor gene inactivation. An example of this is the inflammatory infiltrate noted in human breast cancer described by Virchow in 1863 . The extrinsic pathway is one of inflammation that increases the risk of cancer at certain anatomical sites such as the colon, pancreas, prostate. Many of the signalling pathways involved in inflammation and normal healing also play a dual role in providing survival and proliferative signals to initiated cells that lead to cancer promotion and progression. The Mitogen Activated Protein Kinase (MAPK) pathway also has a well - recognized dual role in cancer development and in inflammation