Granuloma PDF

Granuloma B e t h a n D a v i e s -J o n e s b .w. d a v i e s -j o n e s @ b a n g o r. a c . u k Learning Outcomes • Discuss the formation of effusions, how they can be collected and analysed. • Discuss the purpose of a post -mortem examination. • Describe the process of granuloma formation...

Granuloma B e t h a n D a v i e s -J o n e s b .w. d a v i e s -j o n e s @ b a n g o r. a c . u k Learning Outcomes • Discuss the formation of effusions, how they can be collected and analysed. • Discuss the purpose of a post -mortem examination. • Describe the process of granuloma formation and its role in the immune response to pathogens. • Differentiate between the types of granulomas, including infectious and non -infectious. • Evaluate the diagnostic and treatment options and identify future research directions. “Our Patient” A 68 -year -old male presented with weight loss over a 4 -month period and the recent onset of fever and chills at night . Admission chest x -ray revealed an irregular opacity of the right lung with pleural effusion. Pleural fluid • Pleural space normally contains 5 -10 ml of clear fluid, which lubricates the apposing surfaces of the visceral and the parietal pleura during respiratory movements. • The formation of the fluid results from hydrostatic and osmotic pressures. • Fluid accumulation due to pathology present - usually due to infection and/or cancer. • Effusions are either classified as exudates or transudates. • Fluid or air that accumulates in the pleural space will reduce lung expansion and lead to respiratory compromise and hypoxia Effusions TRANSUDATE • Low protein • Low specific gravity • Low cellular content • Caused by an imbalance of hydrostatic and oncotic pressure • Associated with kidney, heart or liver failure, or hypoalbuminemia EXUDATE • H igh protein content • High specific gravity • C aused by the increased permeability of capillaries, which can occur when the serous membranes are damaged by a disease process • Metastatic malignancy, infections, connective tissue diseases (e.g. SLE, rheumatoid disease), and inflammatory conditions (e.g. pancreatitis). Thoracocentesis • Thoracocentesis was performed, • Thoracocentesis is done to try and find the cause of a pleural effusion; it may also be done to help you to breathe easier. • Cytologic examination of the pleural fluid revealed cancer cells (poorly differentiated adenocarcinoma). • Abdominal CT scan revealed hepatomegaly and diffuse lymphadenopathy. Abdominal CT • Hepatomegaly is an enlarged liver. • Non -specific clinical finding • Causes include infection, hepatic tumours, or metabolic disorder • Lymphadenopathy sometimes raises fears about serious illness, however it is usually a result of benign infectious causes Clinical progression The patient was treated with multiple broad -spectrum antibiotics, but his fever did not respond. His hospital course was also notable for electrolyte imbalances, including hypercalcemia and hyponatremia. Despite supportive care, the patient died on the fourth hospital day, and an autopsy (post -mortem examination) was performed. What is an autopsy (post - mortem examination)? Coroners post -mortem • Carried out because the cause of death is unknown, or following a sudden, violent or unexpected death • To decide whether a legal investigation (inquest) is needed Hospital post -mortem • Or to find out more about an illness or the cause of death, or to further medical research and understanding Ensure you engage with this lecture on Blackboard. Given by Dr Suzy Lishman, Consultant Histopathologist at Peterborough City Hospital. Carcinoma (right lung) Cancer cells surrounding blood vessels and bronchi have spread into the lung tissue. The gross appearance of cancer is not the focus of the current case and will be discussed further in MSE -3019. T he effects of a debilitating disease such as cancer on the body’s ability to control infectious disease need to be considered. Caseous necrosis (left lung) A large central area of caseous necrosis is seen as granular pink, structureless material with complete destruction of the lung parenchyma. The caseous material is surrounded by a cellular zone that contains epithelioid cells and giant cells. At the periphery (lower magnification image), some alveolar spaces can be seen. A large multinucleated giant cell is clearly visible. The cells with dark round nuclei are lymphocytes. Granulomatous Inflammation FOREIGN BODY GRANULOMAS • Caused by relatively inert foreign bodies. • Foreign body granulomas form around materials such as talc, sutures, or other fibres that are large enough to not be phagocytosed. • Absence of inflammatory or immune response. • The foreign material can usually be identified in the centre of the granuloma, particularly if viewed with polarized light. IMMUNE GRANULOMAS • Caused by a variety of agents that are capable of inducing a persistent T cell – mediated immune response. • Immune response produces granulomas usually when the inciting agent is difficult to eradicate, e.g. persistent microbe or a self antigen. • Macrophages activate T cells to produce cytokines, which activates other T cells, perpetuating the response. Other diseases with granulomatous inflammation Disease Cause Tissue Reaction Leprosy Mycobacterium leprae Acid -fast bacilli in macrophages; noncaseating granulomas Syphilis Treponema pallidum Gumma: microscopic to grossly visible lesion, enclosing wall of histiocytes; plasms cell infiltrate; central cells are necrotic without loss of cellular outline Cat -scratch disease Gram -negative bacillus Rounded or stellate granuloma containing central granular debris and neutrophils; giant cells uncommon Sarcoidosis Unknown aetiology Noncaseating granulomas with abundant activated macrophages Crohn disease (IBS) Immune reaction against intestinal bacteria Occasional noncaseating granulomas in the wall of the intestine, with dense chronic inflammatory infiltrate Acid - fast stain (ZN ) Reddish rods are acid -fast bacteria (Mycobacterium tuberculosis ) seen within an area of caseous necrosis. Why do you think this patient developed tuberculosis? Can this explain the other clinical features in this patient? Adrenal gland, granulomatous inflammation What’s the difference between granulation tissue and granulomatous inflammation? Granulation tissue contains new small blood vessels, fibroblasts, and mononuclear cells in an oedematous extracellular matrix; it is part of the repair response. A granuloma is a circumscribed collection of epithelioid cells, usually surrounded by lymphocytes; it is a particular form of chronic inflammation. Do granulomas in different organs look different? Granulomas look similar regardless of the organ. Granulomatous inflammation of testis with caseous necrosis is shown. The pink granular caseous material also contains some bluish nuclear debris. No normal -looking testis tissue can be identified in these images. Lymph node from patient with sarcoidosis • Each of these clusters of pink cells is a granuloma composed of interlacing epithelioid cells and giant cells. Note the absence of caseous necrosis. • Although granulomas in sarcoidosis do not have caseous necrosis, early lesions in tuberculosis may also have noncaseating granulomas. • It is essential to look for specific organisms to establish a cause of the granulomatous process. Complications? Granulomas can cause complications due to chronic inflammation and tissue damage. C omplications include tissue damage, obstruction of fluid or air flow, systemic complications in granulomatous diseases, secondary infections, and malignancy. It's crucial to monitor and manage granulomas to prevent further complications, and people with conditions that can lead to granuloma formation should work closely with their healthcare provider to manage their symptoms and prevent complications. Treatment Treatment depends on the underlying cause and the severity of symptoms . Treatment options include managing the underlying condition, using corticosteroids to reduce inflammation and suppress the immune response, using immunomodulators to modify the immune response, and surgery in cases where the granuloma is causing significant tissue damage or obstructing vital organs. Treatment of granulomas requires a personalized approach Future research directions • Granuloma formation mechanisms • Biomarkers • Personalised medicine • Alternative therapies • Prevention