Chronic inflammation

what is chronic inflammation

Inflammation of prolonged duration (weeks/months/years)

Occurs when:

• The acute inflammatory response fails to remove the stimulus

• There are repeated episodes of acute inflammation

• The stimulus or microbe has unique biochemical characteristics or virulence factors which incite chronic inflammation

Mechanisms:

• Persistent or resistant infections

• Isolation (‘hiding’ from the immune response)

• Unresponsiveness to phagocytosis or enzymatic breakdown (e.g. plant material, grass awns, silica dust, asbestos fibres, some suture materials, surgical prostheses)

• Autoimmunity (response to self antigens promote chronic inflammation) or defects in leukocyte function

• Idiopathic (e.g. granulomatous meningoencephalitis)

Cytokines are a broad category of small, soluble proteins released by cells to regulate immune responses, while chemokines are a specialized subset of cytokines that specifically direct the movement and migration of white blood cells

chronic inflammation - deeper dive

The chronic inflammatory response is maintained by cytokines, chemokines and other inflammatory mediators

Incite:

• Ongoing inflammation mediated by infiltration and activation of

lymphocytes, macrophages, plasma cells and multinucleated giant

cells

• Tissue destruction (necrosis)

• Proliferation of fibroblasts and deposition of collagen

• Angiogenesis and neovascularisation (granulation tissue formation)

• Initiation of wound healing (reepithelialisation and tissue repair)

beneficial and harmful aspects of chronic inflammation

Beneficial:

• ‘Walling off’ the inciting agent or substance

Harmful:

Space occupying lesions (focal, multifocal or diffuse) can be formed resulting in:

• Displacement, replacement or obliteration of the original tissue

• Loss of function

• Clinical significance determined by the size, tissue and position

Dysplasia and malignant transformation of chronically inflamed tissue

subsets of activated macrophages

there are two main types - for a) inflammation and tissue injury - fighters, b)repair - nurses

pic shows the same thing as above, just diff represnataion

you need to memorise the second pic - need to know this

fibrosis - morphology and cells of chronic inflammation

chronic inflammation leads to 3 pathwas

cytokines induce collagen deposition

growth factors

reduced matrix mellasjdajdsjsadh activity

all lead to fibrosis - result of accumulation of mature fibroblasts

starts to shrink when this tissue matures - starts to scar, dries up, depresses

blue part is fibrous connective tissue in the liver

this pic is the liver

abcess formation

Granulomatous inflammation

• Distinct type of chronic inflammation

• Dominated by cells of the monocyte-macrophage system - leading to this granular appearance

• These take the form of macrophages, epithelioid macrophages (activated

macrophages resembling epithelial cells) and multinucleated giant cells (MGCs)

The cells may be:

• Dispersed as sheets at random within the tissue = diffuse or

lepromatous granulomas

• Arranged in discrete masses or nodules = nodular or tuberculoid

granulomas

nodular (tuberculoid granulosomas) - when lymphocytes wrap around foreign substance in body

Develop with a T Helper Lymphocyte Type 1 response

May or may not have a central core of necrotic debris, which can mineralise

• Those with a necrotic core = caseating (Latin caseous = cheese)

• Those without = noncaseating

caseating-a specific type of tissue death (necrosis) where damaged tissue turns into a soft, crumbly, white substance that looks like cheese

Microscopic appearance

• Round to oval

• Numerous macrophages with variable numbers of epithelioid macrophages, MGCs

• Peripheral zone of fibroblasts, lymphocytes and plasma cells

• May form a fibrous capsule

Causes include:

• Mycobacterium bovis and Mycrobacterium tuberculosis

• Deep fungal infections

hsitology shwos the same thing

giant cell has multiple nuclei

fragment is caseous necrosis

dark material is the mineralisation of the caseating core

diffuse (lepromatous) granulomas

• Develop with a T Helper Lymphocyte Type 2 response

• Poorly delineated, forming sheets within the tissue

• Composed of numerous macrophages and few lymphocytes and plasma cells

Causes include:

• Mycobacterium avium subsp. paratuberculosis (Johne’s disease)

• Mycobacterium lapraemurium (Feline leprosy)

Eosinophilic granulomas

fibrinous not fibrous

Characterised by dense infiltration of eosinophils, macrophages and varying

numbers of lymphocytes and plasma cells

All species:

• Eosinophilic (TH2) granulomas secondary to parasitic infections

Cats:

• Eosinophilic plaque, eosinophilic granuloma, and eosinophilic

dermatitis

Dogs:

• Eosinophilic granuloma of the oral cavity of huskies and other breeds

Horses:

• Equine collagenolytic granuloma, axillary nodular necrosis and unilateral papular dermatosis

image shows parasite - the big circular thing

Pyogranulomatous inflammation

• Same cellular constituents as granulomatous inflammation

• Also contains neutrophils, plasma proteins and fibrin (acute inflammatory

response) (pyogranulomatous inflammation)

• Occurs when the inciting stimulus continues to elicit an acute inflammatory

response

• A pyogranuloma is a nodular granuloma with a central area of neutrophils

Lymphoplasmacytic inflammation

• Also termed ‘chronic inflammation’

• Composed of lymphocytes and plasma cells (lymphoplasmacytic) admixed with macrophages

• Sometimes lymphocytes and macrophages predominate over plasma cells (= lymphohistiocytic inflammation)

• Common type of inflammation often seen in the early stages of chronic inflammation

• Also seen in response to specific microbes e.g. viruses

• Seen in response to antigenic inflammation in mucosal surfaces e.g. chronic rhinitis

chronic-active inflammation

Cellular components of chronic inflammation (lymphocytes, plasma cells, macrophages)

• Also constituents of acute inflammation (neutrophils, fibrin, plasma proteins)

Occurs when the inciting cause has not been removed from the exudate of a chronic inflammatory response

• Continues to elicit an acute inflammatory response