Chronic Inflammation PDF

INFLAMMATION  Chronic Inflammation Performance Objectives At the end of the instruction, the student should be able to : Describe Chronic inflammation based on types, general & systemic features. Describe Chronic Granulomatous inflammation/infection: Syphilis & Tubercu...

INFLAMMATION  Chronic Inflammation Performance Objectives At the end of the instruction, the student should be able to : Describe Chronic inflammation based on types, general & systemic features. Describe Chronic Granulomatous inflammation/infection: Syphilis & Tuberculosis  Chronic Inflammation Chronic inflammation is defined as prolonged process in which tissue destruction and inflammation occur at the same time. Chronic inflammation can be caused by one of the following 3 ways: 1. Chronic inflammation following acute inflammation. When the tissue destruction is extensive, or the bacteria survive and persist in small numbers at the site of acute inflammation e.g. in osteomyelitis, pneumonia terminating in lung abscess. 2. Recurrent attacks of acute inflammation. Repeated bouts of acute inflammation leading to chronicity of the process; e.g. recurrent urinary tract infection leading to chronic pyelonephritis 3. Chronic inflammation starting de novo. Infection with organisms of low pathogenicity is chronic from the beginning e.g. infection with Mycobacterium tuberculosis  Systemic Effects of Chronic Inflammation Chronic inflammation is associated with following systemic features: Fever Anaemia Leucocytosis-lymphocytosis Erythrocyte Sedimentation Rate (ESR) is elevated Amyloidosis: Long-term cases of chronic suppurative inflammation may develop secondary systemic (AA) amyloidosis. General (morphological) characteristics of chronic inflammation 1.Mononuclear cell infiltration (macrophages, T &B lymphocytes, plasma cells) 2.Tissue destruction (induced by injurious agents or by inflammatory cells itself) 3. Healing Phagocytes in chronic inflammation are tissue macrophages epithelioid cells (transformed macrophages ) and sometimes, multinucleated giant cells (formed by fusion of macrophages /epithelioid cells (e.g. Langhan's giant cells).  Macrophages are the dominant cells in chronic inflammation, its functions are: - Phagocytosis - Initiates tissue repair - Secretes inflammatory mediators like TNF, IL1, chemokines etc. - Display antigens to lymphocytes.  TYPES OF CHRONIC INFLAMMATION Conventionally, chronic inflammation is subdivided into 2 types: 1. Chronic non-specific inflammation : reaction leads to formation of granulation tissue and healing by fibrosis , e.g. chronic ulcer chronic suppurative inflammation in which infiltration by polymorphs and abscess formation are additional features e.g. actinomycosis 2. Chronic granulomatous inflammation In this, the injurious agent causes a characteristic histologic tissue response by formation of granulomas e.g. tuberculosis, leprosy, syphilis, actinomycosis, sarcoidosis etc.  Chronic Granulomatous Inflammation Granuloma is defined as a circumscribed, tiny lesion, about 1 mm in diameter, composed predominantly of collection of modified macrophages called epithelioid cells, and rimmed at the periphery by lymphoid cells.  Composition of Granuloma 1. Epithelioid cells: modified macrophages/ histiocytes with epithelial cell-like appearance, and are weakly phagocytic. 2. Multinucleate giant cells: Formed by fusion of epithelioid cells and with 20 or more nuclei. Examples Langhans’ giant cells in tuberculosis with nuclei arranged at the periphery like horseshoe or ring Foreign body giant cells- common in foreign body tissue reactions): Nuclei are clustered at the two poles, or present centrally 3. Lymphoid cells: As granuloma is a cell mediated immune response to antigen, lymphocytes are an integral part. Plasma cells indicative of accelerated humoral immune response are also present in some types of granulomas. 4. Necrosis: is a feature of some granulomatous conditions e.g. central caseous necrosis of tuberculosis, so called because of cheese-like appearance and consistency of necrosis. 5. Fibrosis: A feature of healing by proliferating fibroblasts at the periphery of granuloma. Multinucleate giant cells Langhan’s  Pathogenesis of Granuloma Formation of granuloma is a type IV granulomatous hypersensitivity reaction It is a defense reaction by the host but eventually causes tissue destruction because of persistence of the poorly digestible antigen e.g. M. tuberculosis, M. leprae, suture material etc. Sequence of events are 1. Engulfment of poorly degradable antigen by macrophages: the cells fail to digest and degrade the antigen, and instead undergo morphologic changes to epithelioid cells. 2. Activation of CD4+ T cells: Macrophages, being antigen-presenting cells, having failed to deal with the antigen, present it to CD4+ T lymphocytes and it gets activated & elaborate lymphokines. Cytokines/ Lymphokines: Various cytokines formed by activated CD4+ T cells and also by activated macrophages perform the following roles: i) IL-1 and IL-2 stimulate proliferation of more T cells. ii) Interferon-γ activates macrophages. iii) TNF-α promotes fibroblast proliferation and activates endothelium to secrete prostaglandins which have role in vascular response in inflammation. iv) Growth factors (transforming growth factor-β, platelet derived growth factor) elaborated by activated macrophages that stimulate fibroblast growth.  EXAMPLES OF GRANULOMATOUS INFLAMMATION: Tuberculosis Aetiology : Mycobacterium tuberculosis. Mode of Transmission: Inhalation (Most common) Ingestion Inoculation of the organisms into skin Transplacental route results in development of congenital tuberculosis in foetus from infected mother and is a rare mode of transmission. Spread of Tuberculosis 1. Local spread. By macrophages carrying the bacilli into the surrounding tissues. 2. Lymphatic spread. lymphoid follicles of pharynx, bronchi, intestines or regional lymph nodes resulting in regional tuberculous lymphadenitis which is typical of childhood infections. 3. Haematogenous spread in tuberculous bacillaemia This produces millet seed-sized lesions in different organs of the body like lungs, liver, kidneys, bones and other tissues and is known as miliary tuberculosis. 4. By the natural passages: i) Lung lesions into pleura (tuberculous pleurisy); ii) Transbronchial spread into the adjacent lung segments; iii) Infected sputum into larynx (tuberculous laryngitis).  Lesions in tuberculosis Primary infection :Tissue reaction to tubercle bacilli in a healthy individual not previously infected; small consolidation in lung (primary focus) with prominent lymphadenopathy. Eg in children Secondary infection (Post -primary infection ) Tissue reaction to tubercle bacilli in an individual who is previously infected/vaccinated (secondary infection); the granulomatous inflammation is much more intense and widespread with caseation/cavitation being more common Immunisation against tuberculosis-Bacille Calmette-Guérin (BCG). Tuberculin (Mantoux) skin test Testing is done by injecting intradermally (0.1 ml of tuberculoprotein, purified protein derivative (PPD) ) on the forearm. Delayed type of hypersensitivity develops in individuals who are having or have been previously infected with tuberculous infection, which is identified as an indurated area (of more than 15 mm) in 72 hours. The test is reported according to the diameter of the indurated area and not the erythema ( redness) False positive test may be seen in atypical mycobacterial infection and previous BCG vaccination False negative test in sarcoidosis, some viral infections, Hodgkin’s disease, severe immunosuppression etc.  Evolution of Tuberculosis Soft tubercle which is the hallmark of tuberculous lesions Hard tubercle - absence of central necrosis  Types of Tuberculosis (Pulmonary) Primary Tuberculosis : Primary complex/ Ghon’s complex or childhood tuberculosis. Primary complex is the lesion produced in the tissue of portal of entry with foci in the draining lymphatic vessels and lymph nodes. Primary complex or Ghon’s complex in lungs consists of 3 components  Types of Tuberculosis (Pulmonary) Contd. B. Secondary Tuberculosis or post-primary or reinfection, or chronic tuberculosis. i) Fibro caseous TB ii) Tuberculous Caseous Pneumonia iii) Miliary TB Spectrum of lesions in the lungs and pleura in all types of pulmonary tuberculosis.  Pulmonary Tuberculosis (Clinical features and Diagnosis) 1. Referable to lungs—such as productive cough, may be with haemoptysis, pleural effusion, dyspnoea, orthopnoea etc. 2. Systemic features—such as fever, night sweats, fatigue, loss of weight and appetite. 3. Chest X-ray may show pleural effusion, nodularity, and miliary or diffuse infiltrates in the lung parenchyma. Causes of death in pulmonary tuberculosis are usually pulmonary insufficiency, pulmonary haemorrhage, sepsis due to disseminated miliary tuberculosis, cor pulmonale or secondary amyloidosis  Diagnosis i) AFB microscopy of diagnostic specimen such as sputum, aspirated material. ii) Mycobacterial culture (traditional method on LJ medium for 4-8 weeks, newer rapid method by HPLC of mycolic acid with result in 2-3 weeks). iii) Molecular methods such as PCR. iv) Chest X-ray (characteristic hilar nodes and other parenchymal changes). v) Positive Mantoux skin test. vi) Complete hemogram (lymphocytosis and raised ERR). vii) Fine needle aspiration cytology of an enlarged peripheral lymph node is quite helpful for confirmation of diagnosis.  Some examples of Extra Pulmonary Tuberculosis: Head and Neck region Scrofula – Tuberculous cervical lymphadenopathy with fistulous tracts to overlying skin. Lupus Vulgaris is the most common clinical type of re-infection cutaneous tuberculosis  Syphilis A venereal disease (STD) caused by treponema pallidum, a coiled spiral filament bacteria. Mode of transmission: sexual intercourse - most common route of infection Intimate person-to-person contact with lesions on lips, tongue or fingers. Transfusion of infected blood Materno-foetal transmission in congenital syphilis if the mother is infected. Two types of serological tests for syphilis: treponemal (specific) and non- treponemal (non specific tests)  Stages of acquired Syphilis Primary syphilis: Lesion called chancre appears on genitals/ site of entry, 2-3 weeks following exposure. It is an indurated lesion with central ulceration accompanied by regional lymphadenitis and heals without formation of scar. Intra orally chancre may appear on the lips and tongue. Chancre is highly infectious - affected LN should be examined for organisms rather than the saliva.  Secondary syphilis: inadequately treated primary syphilis develop highly infective mucocutaneous lesions on mouth & pharynx (mucosal patches), skin rashes, painless lymphadenopathy in 2-3months following exposure. Elevated broad-based verrucal plaques- condylomata lata  Tertiary syphilis: about 2-3years of following first exposure, tertiary lesions appear & are much less infective compared to the other 2 stages. ✓1. Syphilitic gumma. Solitary, localised, rubbery lesion with central necrosis seen in organs like liver (hepar lobatum), testis, bone and brain. Microscopically, gumma shows central coagulative necrosis surrounded by lymphocytes, plasma cells and giant cells. ✓2.Diffuse lesions of tertiary syphilis seen in cardiovascular & nervous system.  Congenital Syphilis Congenital syphilis: develop in a foetus who is exposed to maternal spirochaetemia causing: ✓Still birth -born dead. ✓Child born alive. Showing mucocutaneous lesions and bony lesions. ✓Saddle shaped nose deformity due to collapse of bridge of nose (destruction of nasal cartilage) Huctchinson’s teeth :are small, widely spaced, peg- shaped (notched ) permanent teeth, Mulberry molars High-arched palate Interstitial keratitis Reference Harsh Mohan and Sugandha Mohan. (2017) Essential Pathology for Dental Students. 5th ed. Jaypee Brothers T h a nk Yo u