Presentation on theme: "CHRONIC (AND GRANULOMATOUS) INFLAMMATION"— Presentation transcript:
1CHRONIC (AND GRANULOMATOUS) INFLAMMATION Leicester Warwick Medical SchoolMechanisms of DiseaseCHRONIC (AND GRANULOMATOUS) INFLAMMATIONDr Peter FurnessDepartment of Pathology
2Chronic (and Granulomatous) Inflammation Mechanisms of Disease: Session 3Dr Peter Furness
3SUMMARY OF MAIN POINTS OF ACUTE INFLAMMATION Rapid response of living tissue to any injury.Naked eye (Macroscopic): Redness, swelling, heat, pain & loss of function.Microscopic: Vascular dilatation, exudate leaks into tissues, neutrophils emigrate.Changes controlled by many short-lived chemical mediators. Some can be manipulated by drugs.Neutrophils: Fast acting, short-lived phagocytes, engulf & degrade bacteria, dead tissue etc.Phagocytosis enhanced by opsonisation of particles, e.g. antibody or complement on surface.Bacterial killing largely oxygen dependent.Defects in the system lead to severe susceptibility to infection.
5CHRONIC INFLAMMATION May ‘take over’ from acute inflammation if damage is too severe to be resolved within a few days.May arise de novo in some circumstancese.g. some autoimmune conditions, some chronic infectionsi.e. chronic low-level irritationMay develop alongside acute inflammationin more severe persistent irritationWhat is chronic inflammation?Characterised by the microscopic appearances.Most important characteristic is the type of cell present.
7MacrophagesDerived from blood monocytes. Various levels of ‘activation’.Functions:Phagocytosis and destruction of debris & bacteriaProcessing and presentation of antigen to immune system.Control of other cells by cytokine releaseSynthesis; not only cytokines, but also complement components, blood clotting factors, proteases, ....
9LymphocytesSometimes called ‘chronic inflammatory cells’ (but note they are a normal component of some tissues)Functions:Complex, mainly immunological.B lymphocytes differentiate to produce antibodies.T lymphocytes involved in control & some cytotoxic functions. (See Immunology teaching)
10Other cells involved in chronic inflammation Plasma cells:Differentiated antibody-producing B lymphocytes. Implies considerable chronicity.Eosinophils:Allergic reactions, metazoal infestations, some tumours.Fibroblasts / Myofibroblasts:Recruited by macrophages; make collagen. See next lecture.
12‘Giant’ CellsMultinucleate cells made by fusion of macrophages. Several types.Morphology of most chronic inflammatory reactions is non-specific, BUT proportions of each cell type may vary in different conditions.For example:Rheumatoid arthritis: Mainly plasma cells.Chronic gastritis: Mainly lymphocytes.Leishmaniasis (a protozoal infection): Mainly macrophages.Giant cell type may be a help to diagnosis.
22TUBERCULOSIS Caused by Mycobacteria especially M. tuberculosis. Difficult & slow to culture.Nature of organism: see microbiologistsn.b. wall lipids (Mycosides).Produces no toxins or lytic enzymesCauses disease by persistence and induction of cell-mediated immunity.
24Caseous necrosis‘Epithelioid’ macrophagesLanghans’ type giant cell
25Patterns of disease: Primary: Non-sensitized individual Secondary: Previously exposed individual
26PRIMARY TUBERCULOSIS Initial infection, mid-zones of lung: GHON FOCUS Spread to hilar lymph nodes: GHON COMPLEX
27Outcome:Usually heals with some scarring & persistent bacteria in lung.Other possibility:Progressive primary tuberculosis.1) Massive hilar lymph nodes2) Tuberculous bronchopneumonia3) ‘Miliary’ tuberculosis
28SECONDARY TUBERCULOSIS Re-activation or re-infection?PATTERN OF DISEASE IMMENSELY VARIABLEUsually starts in apex of lung.
29Outcomes: 1) Arrest, fibrosis, scaring. 2) Erosion into bronchus bronchopneumoniaT.B. in G.I.T.3) Erosion into pleura & tuberculous empyema4) Erosion into blood stream Many bugs: MILIARY TUBERCULOSIS Few bugs: SINGLE ORGAN TUBERCULOSISOrgans: Cervical lymph nodes, Meninges & brain, Kidney, Adrenals, Bone, Fallopian tube, Epididymis, etc.