Acute and Chronic Inflammation (PDF)

Acute and Chronic Inflammation Dr. S. Williams Inflammation – a response to tissue injury A complex biological response of the body to harmful stimuli/agents. Inflammation serves a vital role in the healing process. Inflammation has both protective and curative features. Every stage in the inflammat...

Acute and Chronic Inflammation Dr. S. Williams Inflammation – a response to tissue injury A complex biological response of the body to harmful stimuli/agents. Inflammation serves a vital role in the healing process. Inflammation has both protective and curative features. Every stage in the inflammatory process is necessary as the body responds to tissue injury. The ultimate goal of inflammation is to replace injured tissue with healthy regenerated tissue, a fibrous scar or both. Acute Inflammation Acute Inflammation Tissue damage due to trauma, microbial invasion, or noxious compounds can induce acute inflammation. It starts rapidly, becomes severe in a short time and symptoms may last for a few days for example cellulitis or acute pneumonia. Subacute inflammation is the period between acute and chronic inflammation and may last 2 to 6 weeks. Clinical Signs of Acute Inflammation Heat (Calor), Pain (Dolor), Redness (Rubor) Swelling (Tumor), and Loss of function (Functio laesa) due to protective muscle spasm and pain. Reasons for Classical Signs of Inflammation Redness and heat are due to increased blood flow at body core temperature to the inflamed site; Swelling is caused by accumulation of fluid in interstitial spaces; Pain is due to the release of chemicals such as bradykinin and histamine that stimulate nerve endings. Loss of function has multiple causes [stimulation of nerve ending - pain, swelling]. Acute Inflammation Acute inflammation can be broadly divided into: Vascular phase – involving blood vessels Cellular phase involving immune cells. Acute Inflammation - Vascular Phase First response is vasoconstriction to reduce blood flow. This promotes aggregation of platelets to allow formation of blood clot if a blood vessel is cut. Acute Inflammation - Vascular Phase Vasoconstriction quickly followed by vasodilation occurs first at the arteriole level, progressing to the capillary level, and brings about a net increase in the amount of blood present, causing the redness and heat of inflammation. This increases hydrostatic pressure within the vessel and an increase loss of protein poor [transudate] fluid occurs from the vessel into the injured tissue. Cause swelling. Acute Inflammation - Vascular Phase - Exudation Increased permeability of the vessels occurs next. Endothelial cells lining the lumen of the capillary/venules actively contract and open up their intercellular junctions. This results in the movement of fluid [transudate] then protein rich fluid [exudate] into the [interstitium] tissues. Depending on the severity of the injury, this can last for days. With severe injury all vascular structures may be directly injured and become leaky instantly. Loss of fluid from the vessels result in statis/engorgement of the vessels due to the increase in the concentration of the cells within blood. Increased permeability results in production in transudate and exudate. Characteristics - Transudate and Exudate Due to increased hydrostatic pressure. Low protein content. (clear) Does not coagulate on standing. Low specific gravity ( less than 1.018). No inflammatory cells Can occur early in inflammation TRANSUDATE Due to increased vascular permeability. Rich in protein esp. fibrin (turbed) Coagulates on standing. High specific gravity ( more than 1.018). Contains inflammatory cells (WBC). Occurs late in inflammation EXUDATE Acute Inflammation - Cellular Component Engorgement/Stasis allow leukocytes to marginate (move) along the endothelium of the blood vessel, a process called margination. Glycoproteins [adhesion molecules] on the surface membranes of the leukocytes and on the endothelial cells forms the glue that binds the leukocytes to themselves and to the endothelial cells [endothelial adhesion] of venules and capillaries. Acute Inflammation Cellular Component Next phase – leukocytes actively migrate out of the vessels [extravasation], and into the interstitial spaces – a process called diapedesis. This occurs along a chemical gradient (due to chemical mediators). The process of locomotion is called Chemotaxis. Phagocytosis Phagocytosis Leukocyte Neutrophils Function: To remove or eliminate the injurious stimulus. Release enzymes and toxic substances to kill, inactivate and degrade microbial agents, foreign antigens or necrotic tissue. They also remove injurious substance via phagocytosis and release growth factors necessary for healing/regeneration. First defence against pyrogenic bacteria Macrophages Clean up the debris left behind by the neutrophilic action. Lymphocytes Fights tumor cells and viruses Eosinophils Attacks parasites. Involved in allergic responses Function of the Chemical Mediators of Inflammation (e.g. histamine, cytokines) Vasoconstriction and vasodilatation Modulation of vascular permeability Activation of inflammatory cells Chemotaxis Microbial killing Degradation of tissue Pain and fever In a nut shell …. Acute Inflammation Acute inflammation is typically caused by injuries, like a sprained ankle, or by illnesses, like bacterial infections and common viruses. The acute inflammation process happens quickly and can be severe. Characterized by the increased movement of plasma and leukocytes (such as neutrophils and macrophages) from the blood into the injured site/tissues. Chronic Inflammation Chronic Inflammation Chronic inflammation is also referred to as slow, long-term inflammation lasting for prolonged periods of several months to years. Generally, the extent and effects of chronic inflammation vary with the cause of the injury and the ability of the body to repair and overcome the damage. Etiology Chronic inflammation can result from failure of eliminating the agent causing an acute inflammation such as infectious organisms including: Mycobacterium tuberculosis, Protozoa, Fungi, and Other parasites that can resist host defenses and remain in the tissue for an extended period. Etiology Chronic inflammation can result from the exposure to a low levels of a an irritant or foreign material that cannot be eliminated by enzymatic breakdown or phagocytosis in the body including substances or industrial chemicals that can be inhaled over a long period, for example, silica dust. Etiology Chronic inflammation can result from the following: Autoimmune disorders, e.g. rheumatoid arthritis (RA), systemic lupus erythematosus (SLE). Recurrent episodes of acute inflammation. Chronic inflammation as an independent response and not a sequel to acute inflammation, e.g. tuberculosis and rheumatoid arthritis. Inflammatory and biochemical inducers are causing oxidative stress and mitochondrial dysfunction such as increased production of free radical molecules, uric acid (urate) crystals, oxidized lipoproteins, and others. Lupus - Lupus is an autoimmune disease that causes pain and inflammation in different parts of the body Pathophysiology Most of the features of acute inflammation continue as the inflammation becomes chronic, including: the expansion of blood vessels (vasodilation), increase in blood flow, capillary permeability and migration of neutrophils into the infected tissue through the capillary wall (diapedesis). Pathophysiology Macrophages, lymphocytes and plasma cells predominate in chronic inflammation, in contrast to the neutrophils that predominate in acute inflammation. Diabetes, cardiovascular disease and chronic obstructive pulmonary disease (COPD) are examples of diseases mediated by chronic inflammation. Obesity, smoking, stress, and poor diet are some of the factors that promote chronic inflammation. Types of Chronic Inflammation - Nonspecific proliferative: Characterized by the presence of non-specific granulation tissue formed by infiltration of mononuclear cells (lymphocytes, macrophages, plasma cells) and proliferation of fibroblasts, connective tissue, vessels, and epithelial cells, for example, an inflammatory polyp-like nasal or cervical polyp and lung abscess. Types of Chronic Inflammation - Granulomatous inflammatory The granulomatous inflammatory response is a special type of chronic inflammation characterized by often focal collections of macrophages, epithelioid cells and multinucleated (Langhans or giant cells giant cells). There are two types: Granuloma formed due to foreign body or T-cell mediated immune response is termed as foreign body granuloma, for example, silicosis. Granuloma formed due to chronic infection is termed as infectious granuloma, for example, tuberculosis and leprosy. Granulomatous inflammatory Granulation tissue can be seen in well healing open wounds – red ‘beefy’ tissue with pin point red dots [new capillaries] and a granular surface composed of newly formed collagen. Leads to the formation of a connective tissue scar. Granulomatous inflammatory Multinucleated (Langhans or giant cells giant cells). Non-necrotizing Granulomas Nonnecrotizing granulomas are made up entirely of immune cells. Necrotizing Granulomas Necrosis is a type of cell death and necrotizing granulomas contain dead cells at their centre. Occurs in tuberculosis Granulomas are seen in: Sarcoidosis – a rare inflammatory disease of unknown aetology affecting especially the lymph bodes and lungs, but also may be other organs. ‘Talc’ granuloma – where particular silicates introduced into the tissue evoke an inflammatory reaction after a latent period [ usually years]. Crohn’s disease – a chronic inflammatory disease affecting the terminal ileum colon. Lymph nodes draining ulcerative areas in which breakdown of lipids is occurring. Lymphangitis Infection of the lymphatic vessels of the skin. Most common bacterium is Streptococcus pyogenes. Bacteria enter into the lymphatic vessels from infected skin lacerations, an area of cellulitis, an infected wound. Several risk factors promote a low-level inflammatory response. These include: Old Age: Increasing age is positively correlated with elevated levels of several inflammatory indicators which may be due to mitochondrial dysfunction or free radical accumulation over time and other agerelated factors like an increase in visceral body fat. Obesity: Many studies have reported that fat tissue is an endocrine organ, secreting multiple adipokines and other inflammatory mediators. Some reports show that the body mass index of an individual is proportional to the amount of pro-inflammatory cytokines secreted. Metabolic syndrome typifies this well. Several risk factors promote a low-level inflammatory response. These include: Diet: Diet rich in saturated fat, trans-fats, or refined sugar is associated with higher production of pro-inflammatory molecules, especially in individuals with diabetes or overweight individuals. Smoking: Cigarette smoking is associated with lowering the production of anti-inflammatory molecules and inducing inflammation. Several risk factors promote a low-level inflammatory response. These include: Low Sex Hormones: Studies show that sex hormones like testosterone and estrogen can suppress the production and secretion of several proinflammatory markers and it has been observed that maintaining sex hormone levels reduces the risk of several inflammatory diseases. Stress and Sleep Disorders: Both physical and emotional stress is associated with inflammatory cytokine release. Stress can also cause sleep disorders. Since individuals with irregular sleep schedules are more likely to have chronic inflammation than consistent sleepers, sleep disorders are also considered as one of the independent risk factors for chronic inflammation. Symptoms of Chronic Inflammation Some of the common signs and symptoms that develop during chronic inflammation are listed below. Body pain, arthralgia, myalgia Chronic fatigue and insomnia Depression, anxiety and mood disorders Gastrointestinal complications like constipation, diarrhea, and acid reflux Weight gain or weight loss Frequent infections Measuring Inflammation When inflammation is present in the body, there will be higher levels of substances known as biomarkers. Biomarkers - A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. An example of a biomarker is C-reactive protein (CRP). CRP levels tend to be higher in older adults and those with conditions such as cancer and obisity. Anti-inflammatory Diet Some foods contain nutrients that may help reduce inflammation. They include: Olive Oil High fibre foods Tomatoes Nuts, such as walnuts and almonds Fatty fish, such as salmon and sardines fruit, including blueberries and oranges Herbal supplements eg. ginger and turmeric NOTE: Diet alone will not control inflammation, but making suitable choices may help prevent it from getting worse. Inflammatory Exudates What is an exudate? The inflammation or injury in a tissue result in increased permeability of the blood vessels that results in leakage or secretion of fluid from blood vessels into adjoining tissues; the fluid secreted is known as exudate. Inflammatory Exudates Type Appearance Significance Haemorrhogic/sangui neous Bright red or bloody; presence of RBCs. Small amounts after surgery or trauma. Large amounts indicate haemorrhage. Serosanguineous Blood tinged yellow or pink; presence of RBCs Expected for 48 – 72 hours after surgery or trauma. Can occur with wound dehiscence. Serous Thin clear straw coloured. Contains albumen and immunoglobulins Occurs in the early stages of inflammations. Purulent Thick pus Usually caused by pus forming bacteria (streptococci; staphylococcal) and indicates infection. Catarrhal Thin, usually clear mucous See with inflammation of mucous membranes Fibrinous Thin usually clear; may be yellow or pink, tinged, or cloudy. Occurs with severe inflammation or bacterial infection. Does not resolve easy; Can cause fibrous scaring restriction. Serous exudate: This type appears as a clear or pale yellow, thin, and watery plasma. During the inflammatory stage, serous is a regular part of healing, and small amounts are considered normal. Skin blisters exemplify this pattern of inflammation. Insect Bite - Serous exudate Fibrinous Exudates Fibrinous inflammation is a form of inflammation which is characterised by fibrin deposition. It may be acute, but more often it is a chronic response to more severe infections, and is commonly referred to as pus. It results from the exudation of a high concentration of the plasma protein [fibrinogen] from blood vessels. Fibrinogen is a soluble protein in blood plasma that is converted to fibrin through the action of thrombin during blood clot formation.. Fibrinous Exudates The abdominal cavity is opened at autopsy here to reveal an extensive purulent peritonitis that resulted from rupture of the colon. A thick yellow exudate coats the peritoneal surfaces. What is catarrhal inflammation? An inflammatory process that occurs in mucous membranes Characterized by increased blood flow to the mucosal vessels, edema of the interstitial tissue, enlargement of the secretory epithelial cells, and profuse discharge of mucus and epithelial debris. Catarrh is usually caused by the immune system reacting to an infection or irritation, which causes the lining of nose and throat to become swollen and produce mucus. What infections cause catarrhal exudate? Common cold, Flu, Sinus infections can all lead to catarrh, and. Allergies. People who have allergies may also experience catarrh. Some common allergens include things like - pollen, - dust, and - pet dander. What food allergies can cause catarrhal inflammation? Some of the most frequent Even if you are not food allergies are: allergic to them, some people find that they eggs, experience more phlegm milk, [mucos]when they eat soy, certain foods. fish, Pollution: Exposure to smoke or pollution shellfish, can also cause your body to produce wheat, excessive amounts of mucus to ward off peanuts, and environmental irritants. tree nuts. Catarrhal inflammation Purulent [suppurative] Exudate Purulent or suppurative exudate consists of plasma with both active and dead neutrophils, fibrinogen, and necrotic parenchymal cells. This kind of exudate is consistent with more severe infections, and is commonly referred to as pus. A type of exudate that is distinctively thick and yellowish, grayish or greenish in color, and consisting largely of inflammatory cells and of dead or dying micro-organisms Acne – infected pore Purulent [suppurative] Exudate - Abcess Purulent [supurative] Exudate - Strep. Infection of throat END Excessive Mucous Catarrhal Exudate