Chronic Inflammation Lecture PDF

2/3/2025 Chronic Inflammation Lecture 5 Annabel Vila, MD Associate Professor of Pathology 1 Learning Objectives 1. Describe the morphologic patt...

2/3/2025 Chronic Inflammation Lecture 5 Annabel Vila, MD Associate Professor of Pathology 1 Learning Objectives 1. Describe the morphologic patterns of acute inflammation: serous, fibrinous, purulent (suppurative) & abscess, and ulcers. 2. Describe the outcomes of acute inflammation: complete resolution, healing by connective tissue replacement (scarring or fibrosis), and progression to chronic inflammation. 3. Describe the causes and morphologic features of chronic inflammation. 4. Describe the roles of cells and mediators in chronic Inflammation: macrophages, giant cells, lymphocytes, eosinophils, mast cells, and neutrophils. 5. Describe the granulomatous inflammation, immune granuloma, and foreign body granuloma. 6. Briefly describe the main diseases with granulomatous inflammation: Tuberculosis, Leprosy, Syphilis, Sarcoidosis, Cat-scratch disease, and Crohn’s disease. 7. Describe the systemic effects of Inflammation: fever, acute-phase proteins, septic shock, and systemic inflammatory response syndrome (SIRS). 2 Morphologic patterns of acute Inflammation Morphologic patterns of acute Inflammation Purulent (suppurative) inflammation and abscesses Fibrinous inflammation Serous Inflammation Effusion Ulcers 3 1  2/3/2025 Morphologic patterns of acute Inflammation Purulent (suppurative) inflammation and abscesses Production of pus What is pus? An exudate consisting of neutrophils, the liquefied debris of necrotic cells, and edema fluid Infection with bacteria that cause liquefactive tissue necrosis: pyogenic (pus-producing) bacteria Abscesses Localized collection of pus It is often walled off by fibrous tissue and is relatively inaccessible to the circulation 4 Morphologic Patterns of acute inflammation Purulent (suppurative) inflammation and abscesses: Gross Acute appendicitis typically shows hyperemia, mural edema, and serosal purulent exudate (white open arrow) on gross examination 5 Morphologic patterns of acute inflammation Purulent (suppurative) inflammation and abscesses: Microscopy Acute appendicitis secondary to food impaction may show mural abscesses (white open arrow) around partly digested food material (black open arrow) as seen in this example 6 2  2/3/2025 Morphologic patterns of acute Inflammation fibrinous inflammation Location of fibrinous exudate Lining of body cavities, such as the meninges, pericardium, and pleura Pathogenesis ↑ vascular permeability, large molecules such as fibrinogen pass out of the blood, and fibrin is formed and deposited in the extracellular spaces 7 Morphologic patterns of acute Inflammation fibrinous inflammation Microscopy Fibrin appears as an eosinophilic meshwork of threads Fibrinous exudates may be dissolved by fibrinolysis and cleared by macrophages If the fibrin is not removed may stimulate the ingrowth of fibroblast and blood vessels leading to scarring 8 Morphologic Patterns of Acute Inflammation Fibrinous inflammation: microscopy The H&E-stained section shows an extensive deposit of fibrin (black curved arrow) on the pericardial surface and scant fibrovascular proliferation (black open arrow) in an early phase of viral pericarditis 9 3  2/3/2025 Morphologic patterns of acute inflammation fibrinous inflammation: gross Autopsy gross specimen shows the anterior heart surface coated by fibrinous deposits, giving a shaggy irregular appearance (white curved arrow) characteristic of fibrinous pericarditis, which may be seen in viral infections 10 Morphologic patterns of acute inflammation Serous Inflammation Serous Inflammation Exudation of cell-poor fluid into spaces created by injury to surface epithelia or into body cavities lined by the peritoneum, pleura, or pericardium 11 Morphologic patterns of acute inflammation Effusion The fluid is not infected by destructive organisms and does not contain large numbers of leukocytes In body cavities the fluid may be derived from the plasma (as a result of increased vascular permeability) Secretions of mesothelial cells (as a result of local irritation) and accumulation of fluid in these cavities 12 4  2/3/2025 Morphologic patterns of acute inflammation Serous Inflammation: Gross Graphic shows features of pericardial effusion. Pericardial fluid is in the potential space between the serous parietal (white curved arrow) and visceral pericardium or epicardium (white solid arrow) 13 Morphologic patterns of acute inflammation Serous pleural effusion: gross A transudate or serous pleural effusion is clear yellow. It is translucent and optically inverts. Transudates are usually signs of cardiac or circulatory disease, not primary lung disease 14 Morphologic patterns of acute inflammation Serous inflammation: Low-power view of a cross-section of a skin blister 15 5  2/3/2025 Morphologic patterns of acute inflammation Serous inflammation Staphylococcal Scalded Skin Syndrome in this infant shows very superficial erosions that began as small blisters in the axillae and neck region. With very gentle pressure, skin peels off (white solid arrow). (Courtesy T. Vandergriff, MD.) 16 Morphologic Patterns of Acute Inflammation Ulcers Definition Local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue Common locations Mucosa of the mouth, stomach, intestines, or genitourinary tract Skin and subcutaneous tissue of the lower extremities in older persons who have circulatory disturbances 17 APHTHOUS ULCERS (CANKER SORES) GROSS Clinical photograph shows aphthous ulcers. Clusters of numerous 1-3 mm ulcers are seen throughout the lower lip. The lesions appear as single or multiple, shallow, hyperemic ulcerations… 18 6  2/3/2025 Morphologic Patterns of Acute Inflammation: Ulcers GROSS Clinical photograph shows Acute Gastric Ulcer perforation in a patient presenting with free air under the diaphragm 19 Morphologic Patterns of Acute Inflammation: Ulcers Hematoxylin & eosin shows an ulcer in the gastric epithelial surface 20 21 7  2/3/2025 Chronic Inflammation Definition and Major morphologic patterns Definition Chronic inflammation can occur when the inciting injury is persistent or recurrent or when the inflammatory reaction is insufficient to completely degrade the agent Major morphologic patterns of Chronic Inflammation Chronic nonspecific inflammation Granulomatous inflammation 22 Cells and Mediators of Chronic Inflammation Role of Macrophages 23 Cells and Mediators of Chronic Inflammation Role of Macrophages 24 8  2/3/2025 Cells and Mediators of Chronic Inflammation Role of Lymphocytes 25 Chronic Inflammation: etiology Etiology Persistent Infections Infectious agents: Mycobacterium tuberculosis and M. leprae… Hypersensitivity diseases Prolonged exposure to potentially toxic agents, either exogenous or endogenous Autoimmune diseases Self (auto) antigens evoke a self-perpetuating immune reaction that results in chronic inflammation and tissue damage Rheumatoid arthritis Multiple sclerosis 26 Chronic Inflammation: etiology Allergic Diseases Chronic inflammation is the result of excessive immune responses against common environmental substances: Asthma Such diseases may show morphologic patterns of mixed acute and chronic inflammation because they are characterized by repeated bouts of inflammation Fibrosis may dominate the late stages Other Diseases Atherosclerosis Cardiovascular Diseases Alzheimer Disease 27 9  2/3/2025 Major morphologic patterns of Chronic Inflammation Chronic nonspecific inflammation Cellular reaction with a preponderance of mononuclear (round) cells (macrophages, lymphocytes, and plasma cells), often with a proliferation of fibroblasts and new vessels Scarring and distortion of tissue architecture are characteristic 28 Major morphologic patterns of Chronic Inflammation Granulomatous inflammation Subtype of chronic inflammation with granuloma formation Granuloma It is a cellular attempt to contain an offending agent that is difficult to eradicate Activation of T lymphocytes leading to macrophage activation Collections of activated macrophages, often with T lymphocytes, and sometimes associated with central necrosis (caseating) 29 Morphologic features of chronic inflammation Granulomatous Inflammation Activated macrophages Epithelioid cells They develop abundant cytoplasm and begin to resemble epithelial cells Multinucleate giant cells some of these activated macrophages may fuse, forming multinucleated giant cells 30 10  2/3/2025 Morphologic features of chronic inflammation Granulomatous Inflammation 31 Morphologic features of chronic inflammation Granulomatous Inflammation 32 Morphologic features of chronic inflammation Granulomatous Inflammation Important point The granulomas are divided into noncaseating and caseating subtypes Noncaseating granulomas Lack of central necrosis Common etiologies: reaction to foreign material, sarcoidosis, Chron disease, and cat scratch disease Caseating granulomas They exhibit central necrosis Common etiologies: Tuberculosis and fungal infections 33 11  2/3/2025 necrotizing Caseating granuloma Mycobacterium Tuberculosis Typical histologic appearance of pulmonary tuberculosis characterized by necrotizing Caseating granuloma shows peripheral palisading of histiocytes surrounding a necrotic center 34 Pulmonary Tuberculosis Gross appearance of the lung in active pulmonary tuberculosis shows subpleural areas of consolidation with cavitary lesions containing caseous material in the lumen (white solid arrow) 35 Granulomatous Inflammation noncaseating granuloma in Pulmonary Sarcoidosis Immune Granulomas The inciting agent cannot be readily eliminated The inciting agent could be classified as an “ Unknown agent” The inciting agent can induce a persistent T–cell-mediated Sarcoidosis: selected clinical example Unknown etiology Exaggerated helper (CD4 T-Lymphocyte response) Noncaseating Granulomas 36 12  2/3/2025 Granulomatous Inflammation noncaseating granuloma in Pulmonary Sarcoidosis 37 Granulomatous Inflammation: noncaseating granuloma in Pulmonary Sarcoidosis 38 Examples of Diseases With Granulomatous Inflammation Disease Cause Tissue Reaction Tuberculosis Mycobacterium tuberculosis Caseating granuloma (tubercle): focus of activated macrophages (epithelioid cells), rimmed by fibroblasts, lymphocytes, histiocytes, occasional Langhans giant cells; central necrosis with amorphous granular debris; acid-fast bacilli Leprosy Mycobacterium leprae Acid-fast bacilli in macrophages; noncaseating granulomas 39 13  2/3/2025 Examples of Diseases With Granulomatous Inflammation Disease Cause Tissue Reaction Syphilis Treponema pallidum Gumma: microscopic to grossly visible lesion, enclosing wall of histiocytes; plasma 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 recognizable neutrophils; giant cells uncommon Sarcoidosis Unknown etiology Noncaseating granulomas with abundant activated macrophages Crohn disease (inflammatory Immune reaction against Occasional noncaseating bowel disease) intestinal bacteria, possibly self granulomas in the wall of the antigens intestine, with dense chronic inflammatory infiltrate 40 Leprosy LL demonstrates diffuse infiltration with nodules involving the ear lobules and LL nodules involving the face. (Courtesy S. Dogra, MD.) 41 cat-scratch disease due to Bartonella henselae This is an ulcerated papule (black open arrow) at the site of inoculation with regional submandibular lymphadenopathy (white open arrow) in a case of cat scratch disease (CSD) 42 14  2/3/2025 cat-scratch disease due to Bartonella henselae 43 Crohn Disease: Gross This resection specimen contains an ileal stricture with effaced folds and heaped-up, nodular mucosa, which is often described as a "cobblestone" appearance. The mesenteric fat (white solid arrow) 44 Crohn Disease(CD): microscopy High-power magnification of a section from the colon in a patient with CD shows a large, well- formed granuloma (cyan solid arrow) in the muscularis propria. Often containing multinucleated giant cells, they need to be distinguished from foreign body reaction 45 15  2/3/2025 Foreign body granuloma Definition and clinicopathologic features Definition Granulomatous inflammation as a response to traumatically introduced substances Occurs in the dermis, subcutaneous tissue, or soft tissue Examples of foreign bodies Lipids, wood, paraffin, lead, ink (tattoos), silica, insect fragments (e.g., from tick bites) Can be caused by virtually any non-dissolvable material too large for macrophages to carry away 46 Foreign body granuloma: clinical photograph Foreign body granuloma of several months' duration is shown between the toes of a tennis player. A sliver of wood is the site of entry with surrounding erythema (white open arrow) and swelling where granulation tissue is building up 47 Foreign body granuloma: microscopy High-power view shows foreign body granuloma due to a wood splinter (cyan solid arrow). Note how the skin is walling off the foreign body so that it can eventually be extruded. (Courtesy L. Coleman, MD) 48 16  2/3/2025 Systemic Effects of Inflammation Fever cytokines (TNF, IL-1) stimulate production of prostaglandins in hypothalamus Production of acute-phase proteins C-reactive protein Synthesis stimulated by cytokines (IL-6, others) acting on liver cells Leukocytosis cytokines (CSFs) stimulate production of leukocytes from precursors in the bone marrow Septic shock fall in blood pressure, disseminated intravascular coagulation, metabolic abnormalities induced by high levels of TNF and other cytokines 49 17