Acute vs Chronic Inflammatory Responses in Humans - Case Study Example

The Similarities and Differences between Acute and Chronic Inflammatory Responses in Humans Name Institution Course Tutor Date Abstract Injuries on cells that are caused by pathogens or trauma trigger inflammatory responses. Mediators of inflammation are released from the injured sites or inactive precursors are activated at the site of inflammation to initiate the inflammatory response. Cytokines are the most involved chemical mediators in inflammatory responses. Cytokines trigger and regulate the release of leukocyte inflammatory cells. The inflammatory cells infiltrate the sites of injury providing mechanisms such as phagocytosis, lysis, and antigen surface reactions that destroy foreign or pathogenic materials. Acute inflammatory responses develop from neutrophilis infiltration which lyses and destroys the foreign components. Cellular repair takes place within a short period of time leading to normal tissue function. Chronic inflammatory responses develop from mononuclear cellular infiltration especially monocytes and lymphocytes after a prolonged exposure of tissue to pathogenic substances. Normal tissue function may not be recovered and fibrosis occurs to heal the injured area leaving a hardened tissue. Introduction Inflammation is a protective response whose goal is to eliminate an underlying cause of cell injury, necrotic cell debris, and initiate the cell repair process (Freire & Van-Dyke 2013). Inflammation is usually activated and regulated by cytokines and other chemical mediators produced by the injured host cells (Freire & Van-Dyke 2013). Leukocyte cells infiltrate into the site of infection or tissue injury to trigger an inflammatory response (Thalhofer et al. 2011). The content describes the differences between acute and chronic inflammatory responses and provides a case study for each type. General Content a. Mediators of inflammation with particular emphasis on inflammatory cytokines and cellular infiltrates Mediators of inflammation can be plasma proteins (antibodies, complement), or other proteins (specialized proresolving mediators/SPM and acute phase reactants) (Serhan et al. 2014). Neuropeptides (substance P), lipids (prostaglandins, PAF), amines (histamines), kinins (bradykinin), gases (Oxygen, Nitric Oxide) and cytokines, chemokines and cellular infiltrates are all mediators of inflammation (Serhan et al. 2014). Cytokines are soluble small-sized proteins produced by leukocytes and also by the epithelium, endothelium and connective tissues (Coondoo 2012). Cytokines regulate the differentiation and activation of immune cells and partly coordinate the inflammatory response (Coondoo 2012). Cytokines include interleukins (IL1, IL2, IL5, IL6, and IL10), TNF (tumor necrosis factor) and interferon (Ploeger, et al. 2009). IL1 for example is produced mainly by monocytes and activates the lymphocytes and other inflammatory cells, IL6 is mainly produced by T-cells and activates the B- and T-cells, and IL2 is produced by T-cells and activates the T-cells, monocytes and NK cells (Ploeger, et al. 2009). Other cytokines produced by T-cells are IL10 which stimulates mass cell replication and IL5 which promotes B-cell proliferation, easinophil maturation and stops macrophage activation (Ludwig & Schmidt 2009). TNF- alpha is mainly produced by monocytes while TNF beta (β) is produced by T-cells and are responsible for the widespread activation of cells, leading to events such as shock, apoptosis, and cachexia (Ploeger, et al. 2009). Alpha forms of interferons are produced by monocytes, beta forms by fibroblasts and gamma forms by T-cells. Interferons provide cell activating, antiviral and tumor suppressant effects (Coondoo 2012). Cellular infiltrates are inflammatory cells consisting of neutrophilis, easinophilis, mast cells, lymphocytes, macrophages and fibroblasts (Freire & Van-Dyke 2013). During an inflammatory response, the cells emigrate and accumulate at the inflamed tissue. The neutrophilis are the first to enter the tissue in early stage inflammation and they release lysosomal enzymes which destroy bacterial cells (Freire & Van-Dyke 2013). Easinophilis are also involved in acute inflammation and respond to allergic reactions and can lyse multicellular parasites (Coondoo 2012). Lymphocyets accumulate in the later stages of the inflammatory process and they are involved in antigen-antibody reactions that mediate and regulate the immune responses (Grivennikov et al. 2010). Monocytes –macrophages- are phagocytic in nature and engulf and lyse foreign pathogens and also worn out and dead cells and tissue debris (Grivennikov et al. 2010). b. Differentiate between acute and chronic inflammatory responses Acute inflammation is triggered by infections from pathogenic microorganisms, tissue necrosis from trauma, physical or chemical injury and ischemia, foreign bodies like dirt and hypersensitivity or allergic reactions (Rock et al. 2010). On the other hand, chronic inflammation is caused by persistent injury or infection such as from tuberculosis and ulcers, prolonged exposure to a toxic substance, and autoimmune diseases that result in tissue damage such as rheumatoid arthritis and multiple sclerosis (Maskrey et al. 2011). The onset of acute inflammatory response is fast and takes a few minutes or hours (Thalhofer et al. 2011). On the other hand, chronic inflammatory response is slow and onsets after many days or months (Thalhofer et al. 2011). The cellular infiltrate in acute inflammation mainly comprises neutrophilis, and easinophilis (Rock et al. 2010). On the contrary, the cellular infiltrate in chronic inflammation mostly consists of macrophages and lymphocytes (Sokolove & Lepus 2013). Fibrosis or connective tissue injury in acute inflammatory response is normally mild and self-inhibited (Maskrey et al. 2011). However, that of chronic inflammation is severe and progressive. The localized and systemic signs such as swelling and redness are more prominent in acute inflammatory response than in the chronic inflammation where they are less apparent and possibly subtle (Levy & Serhan 2014). After tissue injury, the acute inflammatory response occurs by mediators, neutrophil recruitment and vascular changes including vasodilation, vascular permeability, and increased adhesion of leukocytes (Thalhofer et al. 2011). The outcome is restoration of normal tissue function through elimination of injurious stimuli, clearance of the mediators and inflammatory cell infiltrates, and replacement of injured cells with new ones (Grivennikov et al. 2010). On the other hand, after persistent injury, chronic inflammatory response entails mononuclear cell infiltrates, angiogenesis, and fibrosis where the scar tissue may lead to loss of tissue function as the injury progresses (Sokolove & Lepus 2013). c. A case study and diagnosis of acute inflammation: in the lung. i. Gross site of inflammation A case is presented where infiltrates are visible in the lower lobe of the right lung. The gross appearance of the inflamed site shows patchy areas of yellowish tan. Consolidation is present only in the affected right lower lobe. Hence, the lobe is filled with liquid and is swollen and hardened (Reynolds et al. 2010). ii. Microscopic appearance The microscopic appearance shows that the alveolar spaces at the site are filled with a discharge containing several neutrophilis and some macrophages (Reynolds et al. 2010). Pink strands of fibrin produced by the coagulation process are present and the alveolar capillaries become congested and filled with red blood cells (Reynolds et al. 2010). iii. Laboratory diagnosis Lobar pneumonia is an acute inflammation of the lung caused by Streptococcus pneumonia (Reynolds et al. 2010). Clinical manifestations that led to the diagnosis include fever, shaking chills, cough, yellowish sputum and rales in the right lung base (Reynolds et al. 2010). The laboratory diagnosis is based on chest X-ray findings that reveals a right lower lobe infiltrate in addition to a sputum culture growing Streptococcus pneumoniae (Reynolds et al. 2010). iv. Treatment options Antibiotic treatment is the mainstay pharmacotherapy for acute lung inflammation caused by bacteria (Reynolds et al. 2010). Treatment options for acute lung inflammation triggered by Streptococcus pneumonia in this case include penicillin G and amoxicillin for penicillin-susceptible strains. Penicillin-resistant strains respond to macrolides, cephalosporins, vancomycin, doxycycline, fluoroquinones, clindamycin and linezolid (Reynolds et al. 2010). d. A case study and diagnosis of acute inflammation: chronic arthritis i. Gross site of inflammation The site of inflammation in the case is the wrist. The gross image at the site of inflammation shows yellowish discharge because of altered synovial fluid (Lyengar et al. 2011). The fingers are swollen and erythematous. The joints have edematous, profuse, hyperplastic synovium coated by feeble and bulging fronds (Lyengar et al. 2011). A decline in osteophytes and new bone formation is evident (Sokolove & Lepus 2013). ii. Microscopic appearance The microscopic appearance shows a dense perivascular cellular infiltrate of T cells, macrophages and plasmatocytes with easoniphilic cytoplasmic inclusions (Lyengar et al. 2011). The lymphoplasmacytic infiltrate shows variable germinal centers, necrobiotic nodules and fibrosis (Lyengar et al. 2011) Fibrin floats in joint spaces forming rice bodies, and there is an increased vascularity and hemosiderin deposit. Osteoclasts are present in bone forming cysts and osteoporosis and pannus formaton progressing to fibrous ankylosis, which ossify to bony ankylosis (Lyengar et al. 2011). iii. Laboratory diagnosis Clinical manifestations of symptoms that aid in diagnosis include painful, swollen, stiff joints in the morning, painful joint movement and musculoskeletal pain, fatigue, and malaise (Sokolove & Lepus 2013). A laboratory diagnosis based on the X-ray of joints shows bone effusions, narrowing of joint space, tendon destruction, radial deviation of wrists from the ligaments and joint capsules, ulnar deviation of digits, and swan neck finger abnormalities (Lyengar et al. 2011). iv. Treatment options Pain caused by chronic arthritis is treated with non-steroidal anti-inflammatory drugs (NSAIDs) (Sokolove & Lepus 2013). Treatment with immunosuppressive drugs is used where tissue injury is caused by autoimmune triggers (Rock et al. 2010). Joint replacement can be done as synovitis tends to lessen (Lyengar et al. 2011). Synovectomy can be considered as the inflamed synovium recurs and the disease severity progresses (Lyengar et al. 2011). Conclusion Inflammation is a response towards an infection or an injury of a tissue. It is mediated by various cellular and chemical factors. Cytokines are produced by the immune body cells and they activate and regulate the inflammatory response process following an infection or injury. Leukocytes including neutrophilis, easonophilis, lymphocytes and macrophages usually infiltrate the site of tissue injury and impart mechanisms to destroy foreign pathogens. An inflammatory response is generated and can be acute or chronic. Acute inflammatory response’s onset is fast, self-limited, characterized by many neutrophilis, and recovery of tissue is achieved in a shorter time period. Chronic inflammatory response’s onset is slow, characterized mainly by macrophages and lymphocytes. Fibrosis forms scar tissue, and progresses over time. Hence, recovery may not be possible leading to loss of function of the tissue. The cases confirm that acute inflammation shows dense neutrophil infiltration while chronic inflammation shows increased mononuclear cell infiltration. List of References: Coondoo, A 2012, ‘The role of cytokines in the pathomechanism of cutaneous disorders. Indian Journal of Dermatology, vol. 57, no. 2, pp. 90–96. http://doi.org/10.4103/0019-5154.94272. Freire, MO, & Van-Dyke, TE 2013, ‘Natural resolution of inflammation’, Periodontology, vol. 63, no.1, pp. 149–164. http://doi.org/10.1111/prd.12034. Grivennikov, SI, Greten, FR, & Karin, M 2010, ‘Immunity, inflammation, and cancer. Cell vol. 140, no. 6, pp. 883–899. http://doi.org/10.1016/j.cell.2010.01.025. Levy, B & Serhan, C 2014, ‘Resolution of acute inflammation in the lung’, Annual Review of Physiology vol.76, pp. 467-492. doi:  10.1146/annurev-physiol-021113-170408. Ludwig, RJ & Schmidt, E 2009, ‘Cytokines in autoimmune bullous skin diseases: Ephinomena or contribution to pathogenesis?’ G Ital Dermatol Venereol, vol. 144, no. 4, pp. 339-349. Lyengar, K, Manickavasagar, T, Nadkarni, J, Mansour, P, & Loh, W 2011, ‘Bilateral recurrent wrist flexor tenosynovitis and rice body formation in a patient with sero-negative rheumatoid arthritis: A case report and review of literature. International Journal of Surgery Case Reports, vol. 2, no. 7, pp. 208–211. http://doi.org/10.1016/j.ijscr.2011.07.001 Maskrey, B, Megson, I, Whifield, P, & Rossi, A 2011, ‘Mechanisms of resolution of inflammation,’ Arteriosclerosis, Thrombosis and Vascular Biology, vol. 31, pp. 1001-1006. doi: 10.1161/ATVBAHA.110.213850. Ploeger, HE, Takken, T, Greef, M, Timmons, B 2009, ‘The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease: A systematic review’, Exercise Immunology Review, vol. 15, pp. 6-41. Reynolds, JH, Mcdonald, G, Alton, H, & Gordon, SB 2010, ‘Pneumonia in the immunocompetent patient’, The British Journal of Radiology, vol. 83, no. 996, pp. 998–1009. http://doi.org/10.1259/bjr/31200593. Rock, KL, Latz, E, Ontiveros, F, & Kono, H 2010, ‘The sterile inflammatory response. Annual Review of Immunology, vol. 28, pp. 321–342. http://doi.org/10.1146/annurev-immunol-030409-101311. Serhan, C, Chiang, N, Dalli, J, & Levy, B 2014, ‘Lipid mediators in the resolution of inflammation,’ Cold Spring Harbor Perspectives of Biology, vol. 7, no. 2. doi: 10.1101/cshperspect.a016311. Sokolove, J & Lepus, CM 2013, ‘Role of inflammation in the pathogenesis of osteoarthritis: Latest findings and interpretations’, Therapeutic Advances in Musculoskeletal Disease, vol. 5, no. 2, pp. 77–94. http://doi.org/10.1177/1759720X12467868. Thalhofer, CJ, Chen, Y, Sudan, B, Love-Homan, L, & Wilson, ME, 2011, ‘Leukocytes infiltrate the skin and draining lymph nodes in response to the protozoan Leishmania infantumchagasi. Infection and Immunity, vol. 79, no. 1, pp. 108–117. http://doi.org/10.1128/IAI.00338-10. Read More