chronic inflammation Flashcards
what is the cell population in chronic inflammation
lymphocytes, plasma cells, macrophages
what are the features of chronic inflammatino
tissue or organ damage, necrosis and loss of function (doesnt go back to how it was before)
can follow on from ongoing acute inflammation but also arises as 1y pathology
tends to be long term
leads to scarring and fibrosis
define chronic inflammation
prolonged inflammatory response that involves a progressive change in the type of cells present at the site of inflammation. It is characterized by the simultaneous destruction and repair of the tissue from the inflammatory process.
clinical presentations of chronic inflamamtion
- often no specific sore bit
- non-specific symptoms
- malaise and weight loss
- loss of function as tissue is damaged by chronic inflammation
when does chronic inflammation occur
- arising from acute inflammation: large volume of damage, inability to remove debris, fails to resolve
- arising as a 1y lesion: only see chronic changes
outcomes of acute inflammation (organisation)
granulation tissue
angiogenesis
healing and repair
fibrosis and formation of a scar
angiogenesis
new vessels form capillary buds from existing vessels, VEGF released by hypoxic cells which stimulates proliferation, enzyme secretion aids the process, enable blood supply to enter the damaged tissue
angiogenesis and organisation in thrombosis
limits thrombus propagation
reinstatement of flow
angiogenesis in malignant tumours
angiogenesis occurs as tumour grows
anti VEGF drugs are being used to combat certain tumours as they prevent endothelial growth
granulation tissue mechanism and function (result of acute inflammation)
- capillaries grow into inflammatory mass
- access of plasma proteins
- macrophages from blood (monocytes) and tissue (histiocytes)
- fibroblasts lay down collagen to replace damaged tissue
- collagen replaces inflammatory exudate
- patches tissue defects
- replaces dead or necrotic tissue
- contracts and pulls together
acute and chronic interface
acute inflamamtion –> acute + chronic inflammation (exudate, neutrophils; lymphocytes plasma cells, fibroblasts, fibrosis) –> chronic inflammation
pyogenic granulation tissue
acute + chronic inflamamtion
products of granulation tissue
fibrous tissue - scar
fibrosis as a problem - adhesions between loops of bowel following peritonitis
can progress to chronic inflammation
examples of scars
acne - chronic from acute
cholecystitis - gall bladder, walls become very thick and fibrous with lots of vasculatiry
peptic ulcer - stomach, ulcer in the gastric antrum
osteomyelitis
primary chronic inflammation
- autoimmune disease
- lymphocytes, plasma cells, macrophages, fibrosis
- material resistant to digestion
- exogenous substances
- endogenous substances
- granulomatous inflammation common
primary chronic inflammation - AI disease
adaptive immunity
autoantibodies directed against own cell and tissue components
damage/destroy organs, tissues, cells, cell components
thyroiditis, rheumatoid disease, pernicious anaemia, systemic lupus erythromatosis
primary chronic inflammation - material resistant to digestion
mycobacteria, brucella, viruses
cell wall resistant to enzymes
primary chronic inflammation - exogenous substances
sterile: sutures, metal and plastic, e.g. joint replacements, mineral crystals
dont provoke immune response
primary chronic inflammation - endogenous substances
necrotic tissue, keratin, hair
cannot easily be phagocytosed
rheumatoid disease
swan neck deformity, swellling and dislocation of the joints
rheumatoid nodule - chronic inflammation at extensor surfaces, usually around the elbows
pathogenesis of chronic inflammation
- cells and their roles (lymphocytes, plasma cells, macrophages, fibroblasts)
- tissue components: granular tissue, collagen
role of lymphocytes in chronic inflammation
B cells: differentiate to plasma cells (antibodies), facilitate immune response, act with macrophages (APC), immune memory
T cells: produce cytokines (attract, hold and activate macrophages; influence permability of nearby cells), T cells produce interferons (antiviral effects), damage and kill other cells and destroy antigen
NK cells: destroy antigens and cells
role of plasma cells in chronic inflammation
antibody production
role of macrophages in chronic inflammation
remove tissue debris, APC, monocyte (blood)/histiocyte (tissue); found in bone marrow, blood vessels and tissue
motile phagocytes move from blood, take over from neutrophils, contain lysozymes, produce interferons
role of fibroblasts in chronic inflammation
motile cells, metabolically active, make and assemble structural proteins
granulomatous inflammation
- characterised by presence of granulomas in tissues and organs (generally occur due to indigestible antigens)
- many serious infectious and idiopathic diseases
- NOT THE SAME AS GRANULATION TISSUE
what are granulomas
aggregates of epitheliod macrophages in tissue
ball of cells that may contain giant cells and may surround dead material, they can be surrounded by lymphocytes
contain neutrophils (most dont) and eosinophils
most granulomas are type…
IV hypersensitivity reactions (cell mediated immunity)
giant cells
granulomas compromise epitheliod histiocytes
possibly fusion of macrophages to form larger cells
giant cells can also occur in pyogenic granulation tissue
langhans type giant cells
large cells found in granulomatous conditions. They are formed by the fusion of epithelioid cells (macrophages), and contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery.
classically found in TB
large eosinophilic cytoplasm
foreign body type giant cells
often associated with pyogenic granulation tissue acutely inflamed neutrophils, pus organisation giant cells
silicone associated giant cells
ruptured silicone implants
usually but not always breast
vacuoles contain leaked silicone
leads to enlarged lymph node
Warthin-Finkeldy type giant cells
- classic in measles
central cluster of nu
infectious granulomatous diseases - relevant to global health
mycobacterium tuberculosis
mycobacterium leprae
treponema pallidum
mycobacterium tuberculosis:
tuberculosis
caseous necrosis - dead tissue surrounded by macrophages, giant cells, lymphocytes)
mycobacterium leprae
leprosy
treated with mutlidrug therapy, granulomatous inflammation causes peripheral nerve damage
treponema pallidum
(syphilis): sensitive to benzylpenicillin; primary chancre, syphilitic gumma, snail track ulcers
non-infective granulomas - not uncommon in global medicine
rheumatoid disease
sarcoidosis
chron’s disease
rheumatoid disease
tissue specific auto-immune disease, unknown cause
degenerative collagen becomes surrounded by macrophages in rheumatoid nodules
sarcoidosis
disease involving abnormal collections of inflammatory cells that form lumps known as granulomas. The disease usually begins in the lungs, skin, or lymph nodes. unknown cause
chron’s disease
chronic inflammatory bowel disease, unknown cause
wound healing
process of repair after tissue damage
acute injury followed by phase of acute inflammation and granulation tissue formation (try to keep these to a minimum to reduce damage)
local angiogenesis
fibrosis and scar formation
surgical healing
healing by primary intention
minimal gap and blood clot
small amount of granulation tissue
small linear scar
healing of larger defects
healing by secondary intention
larger blood clot filling the gap, much more granulation tissue growing into the clot, contraction due to tighter collagen fibres,
scarring
sequence of events in wound healing
injury, blood clot, acute inflammation, fibrin growth factors and cytokines involved granulation tissue growth angiogenesis phagocytosis of fibrin myofibroblasts move in and lay down collagen contraction of scar re-epithelialisation
favouring wound healing
cleanliness apposition of edges sound nutrition metabolic stability and normality normal inflammatory and coagulation mechanisms local mediators are important
impaired wound healing
leads to infection dirty, open wound, large haematoma poorly nourished abnormal CHO metabolism, diabetes, corticosteroid therapy inhibition of angiogenesis
fracture healing
- repair bony structures as well as soft tissue
- trauma, fracture, haematoma
- dead bone and soft tissue
- acute inflammation, organisation, granulation tissue, macrophages remove debris
granulation tissue contains osteoblasts as well as fibroblasts
callus formation
osteoblasts lay down woven bone
nodules or cartilage present
followed by bone remodelling
bone remodelling
oestoclasts remove dead bone
progressive replacement of woven bone by lamellar bone
reformation of cortical and trabecular bone
