Chronic inflammation Flashcards
(34 cards)
define Chronic inflammation
- inflammation of prolonged duration
- active inflammation ,tissue destruction and attempt at repair occurs simultaneously
- it is insidious (slow)
- often asymptomatic
- results in severe tissue damage and disabling human disease
what causes chronic inflammation 6
- Prolonged / persistent exposure to initial stimuli
- foreign material
- delayed healing
- lowered host resistance
- repeated acute inflammation
List the 2 types of chronic inflammation
- non specific
2. granulomatous
discuss the 3 morphological features of chronic inflammation
- Exudation
* Persistence of acute inflammatory changes with neutrophils ,fibrin ,fluid exudate and pus formation due to prolonged exposure of injurious agent
*results in continued tissue distruction
- Macrophages accumulation and proliferation
* demolition phase - Repair
* Angiogenesis: formation of new blood vessels
* proliferation of fibroblast which lay down collagen
* infiltration by other mononuclear cells eg plasma cells and leukocytes
Discuss the mononuclear infiltration, which is a central process
*Macrophage play a dominant role
Consist of the cells from the bone marrow ,blood monocytes and tissue macrophages
-Tissue macrophages are scattered in the connective tissue or in organs
eg liver = Kupffer cells
How are macrophages activated
There are 2 major pathways of macrophage activation
- Classical
- Alternative
The stimuli that activates ,macrophages by these pathways are and the function of activated cells are different
Discuss the classical pathway that activate macrophages
- Classical macrophage activation is :
- induced by microbial products eg endotoxin which engage TLF and other sensors
- T cell derieved signals and cytokine Interferon gamma gamma in immune responses
- foreign matter eg particular matter
- Classically activated macrophages are called M! produces nitric oxide and Reactive Oxygen Species and upregulate lysosomal enzymes which ,all which enhance the ability to phagocytose enzymes and secrete cytokines that enhance inflammation
- The M1 are capable of injuring normal tissues
Discuss the alternative activation of macrophages
- Induced by cytokines other than Interferon gamma such as IL4 and IL13 produced by lymphocytes and other cells
- These macrophages are called M2 macrophages which function by repairing tissue
- they secrete growth factors that stimulate angiogenesis ,active fibroblast and collagen synthesis
- They are not bactericidal
- cytokines produced may inhibit the classical activation pathway
What is the function of activated macrophages 4
- They ingest and eliminate microbes and dead tissue
- initiate the process of tissue repair and are involved in scar formation and fibrosis
- They secrete mediators of inflammation eg tumor necrosis factor ,il1 and chemokines thus they are central to initiation and propagation of inflammatory reaction
- Macrophages present antigens to T cells and respond to signals from T cells
What are the other cells involved in chronic inflammation
Lymphocytes
*Microbes and foreign antigens activate B and T cells
*Since they are mediators of the adaptive immune system , when they are present , the inflammation tends to be severe and persistent
*T helper cells produce cytokines that promote inflammation and the nature of the inflammation
*Activated b cells and plasma cells are present during chronic inflammation . Antibodies produced maybe against persistent foreign
or self antigens at the inflammatory site or altered tissue
Discuss the macrophage - lymphocyte interaction during chronic inflammation
*lymphocytes
*Macrophages present antigens to Tcells and produce cytokines (IL12) that simulate T cell responses
*Activated T cells secrete cytokines that recruit and activate other macrophages to promotes more antigen presenting and cytokine secretion
this is a bidirectional way and it results in cellular reaction that feu and sustain chronic inflammation
Besides lymphocytes and macrophages , which other cells are involved
Eosinophiles
- Are abundant in immune reactions mediated by IgE and in parasitic reactions
- Have granules that contain basic proteins and cationic proteins that is toxic to parasites and causes lyses pf epithelial cells
Mast cells
* Has receptors that bind to Fc site on IgB antibodies
*During immediate hypersnsitivity ,IgE bound to cells receptors recognize antigens and the cells degranulate and release
mediators such as histamine
*This reaction occurs during allergic reaction
*
Give example of non specific chronic inflammation
- Chronic osteomyelitis
- Chronic bronchitis
- chronic pyelonephritis
- chronic cholecystitis
Discuss chronic osteomyelitis
- occurs in long bones of children and young adults
- Follows acute inflammation in bone
- Due to exudate against bone and compression against blood vessels result in ischemia and necrosis
- Pus is formed which is discharged through the skin via sinuses
- The dead bone acts as a foreign body and organisks continue t grow = sequestrum
- The dead bone maybe broken down by osteoclasts but not completely removed thus there are other attempts at healing and formation of ne bone
- new bone id formed by periosteum which encases the sequestrum known as involucrum
- End result is chronic inflammation of bone or chronic osteomyelitis
Discuss the chronic bronchitis
- Chronic cough with production of sputum for 3 months in at least 2 consecutive years
- Cause ; cigarette irritating the airways and damages the epithelial cells and predispose to infection
- Histology : increase in number and size of mucous producing glands in bronchial wall with increased number of goblet cells in the epithelium
- Hyperaemia and oedema of the submucosa with lymphocytic infiltration later resulting in scaring of bronchial wall
Define granulomatous inflammation
- Granulomatous inflammation is form of chronic inflammation characterized by collections of activated macrophages
- The activated macrophages may developed abundant cytoplasm and begin to resemble epithelial cells and are called epitheliod macrophages
discuss the granulomatous inflammation
- Granuloma formation is a cellular attempt to contain an offending agent that is difficult to eradicate .
- In this attempt there is often activation of T - lymphocytes leading to macrophage activation ,which can cause injury to normal tissues .
- Some activated macrophages may fuse ,forming multinucleate giant cells .
Types of granuloma
Two types of granuloma
- Foreign body granuloma
* Are incited by relatively inert foreign bodies, in the absence of T cell mediated immune responses
*Typically, form around such as talc (associated with IV drug abuse ) ,sutures , or other fibers that are large enough to preclude phagocytosis by a macrophage often
- immune granulomas
* Induced by a variety of agents that are capable of inducing persistent T cell mediated
* This type of response produces granulomas when the stimulating agent is difficult to eradicate such as a persistent microbe
* In such responses macrophages stimulate surrounding cells to produce cytokines eg IL2 ,which activates other T cells which secrete interferon gamma which activates macrophages
What causes a granulomas inflammation
- It is seen in specific pathogenic states and it is important to be able to recognize this kind of inflammation because only a few conditions can simulate the reaction
- TB is a prototype of a granulomatous disease caused by infection and should be excluded as the cause when granulomas are identified
list the causes and tissue reaction of granulomatous infection
- Mycobacterium(TB)=Causing granuloma
- Myobacterium laprae (leprosy) =acid fast in macrophage and non-ceasing granuloma
- Treponema pallidum(syphilis) =visiable lesions ,enclosing wall of hoistocytes ,plasma cell infiltates
- Gram- neg bacillus (Cat scratches )= rounded granuloma containing central granular debris and recognizable neutrophils
- Unknown aetiology (sarcoidosis) =Non-caseating granulomas with abundant activated macrophages
Discuss granuloma inflammation in TB
l*Aetiology
Mycobacterium
*Portals of entry
+Inhalation > pulmonary disease
+Ingestion > Tonsillar or gastrointestinal disease
+Inoculation > Subcutaneous tissue
*Basic pathology
Granulomatous inflammation and caseous necrosis
Pulmonary tuberculosis
- Primary infection- so called TB
- The primary complex (ghon compleex)
- sequelae
- healing
- local spread in lungs
- lymphatic spread > hilar nodes > thoracic duct >Right heart > lungs
- Hematogenous spread > veins more easily breached than arteries
- Post -Primary Infection /secondary TB
* Re-activation :organsms arise from previous infection
* Re-infection :occuring in
Sequelae of primary pulmonary TB
- Healing
* this occurs in most cases
* Fibrosis and dystrophic calcification
* But may contain visible bacilli for a long time
2.Dissemination (progressive primary TB)
*Local in lungs
*Blood - spread via
+Pulmonary artery > extensive lung involvement
+Pulmonary vein
> bacteremia
> Miliary sub - acute spread
>organ tuberculosis
2.Progressive primary TB
- So called hematogenous ( Blood /lymphatic spread )
* Mediastinal lymph nodes > thoracic duct >subclavian vein
* Bacteremia > lungs and /or rest of the body
*Rupture of caseous material into vessel > usually from a lymph node
+Pulmonary artery > extensive involvement of using
+released into bloodstream
-incidental bacteraemia
-miliary tuberculosis
-organ tuberculosis
