What is the role of inflammation?
•Remove the cause of injury
What are the dominant cells during chronic inflammation?
Lymphocytes, plasma cells and macrophages.
Give examples of primary chronic inflammation.
Infections – TB, leprosy, some viruses
Endogenous materials – have an internal origin eg necrotic adipose tissue, uric acid crystals
Exogenous materials – external origin. Asbestos fibres, sutures, implanted prostheses
Autoimmune – body’s own immune system attacks tissues that are it’s own, e.g rheumatoid arthritis, SLE, pernicious anaemia = autoantibodies to intrinsic factor and gastric parietal cells lead to no B12 absorption and anaemia results.
Primary granulomatous – crohns, sarcoidosis = granulomas (collections of inflammatory cells) collect in organs, often lungs and lymph nodes, viewed as an immune reaction to usually an infection
What is secondary chronic inflammation?
When acute inflammation does not resolve and progresses to chronic.
What are the features of secondary chronic inflammation?
•Most common in supporative (pus forming) acute inflammation
•Pus can form an abscess
•If deep enough the walls thicken
•Granulation and fibrous tissue
•Recurrent acute can lead to chronic e.g cholecystitis = gall bladder inflammation usually due to stones
What are the morphological features of chronic inflammation?
•Infiltration with mononuclear cells (macrophages, lymphocytes, plasma cells)
•Healing by fibrosis
What is the importance of macrophages in chronic inflammation?
•Very important in chronic inflammation
•Increase inflammation, stimulate immune system
•Macrophages already at sight of damage release cytokines which signal to monocytes
•Monocytes enter damaged tissue from endothelium of blood vessel (leukocyte extravasion) = RECRUITMENT
•Macrophages PROLIFERATE locally in damaged tissue
•IMMOBILISATION of macrophages within tissue
How might macrophages cause tissue injury?
Phagocytosis of bacteria and damaged tissue. Proteases are released after they debride damaged tissue. Stimulated by low oxygen content to produce factors that induce angiogenesis, they also induce cells to re-epithelialise the wound and create granulation tissue. Also induse angiogensis factors for blood vessel formation in granulation tissue.
What is a fibroma?
A mass of fibrous tissue to form from one cell line only.
What is granulation tissue?
Is new connective tissue and blood vessels that form on the surface of a wound during healing. Grows up from baase of wound.
Appears light red or dark pink due to capillaries, painless if healthy, soft and moist.
Angiogenesis, fibroblasts develop collagen, inflammatory cells.
What is fibrosis?
•Formation of excess fibrous connective during repair of damaged tissue
•Called fibroma if arises from 1 cell line
•Macrophage induced laying down of connective tissue inc collagen
What are histiocytes?
What is a granuloma?
A granuloma = aggregate (nodule) of epithelioid histiocytes and other cells; lymphocytes and histiocytic giant cells.
What are histiocytic giant cells and why might they form?
•Histiocytic giant cells can form where material is indigestible to macrophages e.g tubercle bacilli which have cell walls resistant to macrophages
•They’re multinucleate giant cells. May have >100 nuclei.
•Develop when 2+ macrophages try to engulf the same particle.
•No known function. Not phagocytic.
•Given different names according to appearance
What are the features of epithieloid histiocytic cells?
Epithelioid histiocytes have large vesicular nuclei and eosinophilic cytoplasm. Arranged in clusters with little phagocytic activity. Secrete angiotensin converting enzyme.
Give an example of a giant histiocytic cell.
Langhans giant cells = horseshoe arrangement of peripheral nuclei, seen in TB often. Foreign body giant cells – large cells with randomly scattered nuclei, seen in relation to foreign body material.
Give examples of common granulomatous diseases.
TB: infectious granulomatous disease caused by mycobacterium tuberculosis. Typically in lungs but can affect other parts (miliary TB). Cough, haemoptysis, night sweats, weight loss.
Leprosy: chronic infection by Mycobacterium leprae. Granulomas of nerve, respiratory tract, skin and eyes. Results in loss of pain sensation and subsequent injuries. Weakness. Poor eyesight. Untreated it is progressive. BODY PARTS DO NOT FALL OFF!
Schistosomiasis = parasitic worms of schistosoma type. Urinary tract and intestines. Pain, bloody diarrhoea, haematuria.
Immunocompromised individuals at greater risk of cryptococcal infection
Silicosis – occupational lung disease from inhaling silica dust, forms scarring and granulomas in upper lobes of lungs, often misdiagnosed as TB as similar.
Sarcoidosis = granulomas form in multiple organs, often lungs and lymph nodes but anywhere can be affected, usually self limiting. Fatigue weight loss joint aches and pains, cough, non specific symptoms. Bilateral hilar lymphadenopathy on CXR.
Crohns = non caseating granulomatous inflammation of bowel, skip lesions, mouth to anus. Diarrhoea, mucus, blood, weight loss, pain.
Describe the granuloma in TB mechinism.
Alveolar macrophages in lung release cytokines to recruit more macrophages. Dendritic cells present antigens to T cells in lymph nodes to mount a T cell response. These 2 events lead to granuloma formation for the purpose of containing infection and eliminating bacteria.
The granuloma contains macrophages, epithelioid cells and langhans giant cells all surrounded by T lymphocytes. TB granulomas are caseous meaning there is necrosis, epithelioid macrophages surround necrotic region that has a T cell rim.
TNF alpha and INF gamma are important in formation and function of granuloma.