Chronic Inflammation Flashcards
Define chronic inflammaiton
Inflammation in which cell population is especially
Lymphocytes
Plasma cells
Macrophages
What are the features of chronic inflmmation?
Tissue or organ damage, necrosis, loss of function
What are the features of healling and repair in chronic inflammation?
Granulation tissue, scarring and fibrosis
What is granulation tissue?
Vascularized tissue that forms as chronic inflammation evolves.
Characterized by presence and proliferation of fibroblasts, keratinocytes, endothelial cells, new thin-walled capillaries, and inflammatory cell infiltration of the extracellular matrix.
What can cause chronic inflammation?
May follow from acute inflammation
Arises as primary pathology
What are the clinical findings in chronic inflammation?
No specific sore area
Malaise and weight loss
Loss of function
What is an example of loss of function due to chronic inflammation?
Crohn’s disease (GI tract ulceration and fibrosis) – pain, diarrhoea, gut obstruction
What is characteristic of organisation in acute inflammation?
Granulation tissue - healing and repair, leads to fibrosis and formation of a scar
What is the granulation tissue mechanism?
Capillaries grow into an inflammatory mass
Access of plasma proteins
Macrophages from blood and tissue
Fibroblasts lay down collagen to repair damaged tissue
Collagen replaces inflammatory exudate
What is the function of granulation?
Patches tissue defects
Replaces dead or necrotic tissue
Contracts and pulls together
What are the products of granulation tissue?
Fibrous tissue - scar
Can progress to chronic inflammation
What is the most likely cause of primary chronic inflammation?
Autoimmune disease
How does Autoimmune disease result in chronic inflammation?
Autoantibodies directed against own cell and tissue components - autoantigens
They damage or destroy organs, tissues, cells, cel components
What types of cells does primary chronic inflammation use?
Lymphocytes, plasma cells, macrophages, fibrosis
What are the other common methods of triggering a chronic inflammatory response?
Material resistant to digestion : mycobacteria, Brucella, viruses, this is because their cell wall is resistant to enzymes
Exogenous substances:
sutures, metal and plastic eg joint replacements, mineral crystals, glass
Endogenous substances: Necrotic tissue, keratin, hair, none of which can easily be phagocytosed
Granulomatous inflammation is common
What are lymphocytes responsible for?
B cells and T cells
Immune response
Immune memory
What is a plasma cell?
Differentiated B cells, differentiated to produce antibodies
What do NK cells do?
Destroy antigens and cells, granule proteins like T cells
Which is longer lived, macrophages or neutrophils?
Macrophages, they take over from neutrophils
What might macrophages produce?
Interferons and other chemicals, used to destroy
What are fibroblasts?
Motile cells which are metabollically active, they make and assemble structural proteins, including collagens
Where do fibroblasts originate from?
From the embryonic mesoderm tissue, and they are not terminally differentiated.
What is the outcome of chronic inflammation?
Ongoing tissue damage and destruction,
insidious loss of function
Granulation tissue, angiogenesis
Scarring and fibrosis
Granuloma formation
What is angiogenesis?
Angiogenesis is the formation of new blood vessels.
How does angiogenesis play a role in granulation tissue?
New vessels form- capillary buds
Vascular Endothelial Growth Factor (VEGF) released by hypoxic cells stimulates proliferation
Enzyme secretion aids process
Enable blood supply to enter damaged tissue
Discuss angiogenesis and organisation in thrombosis
Limits thrombus propagation
Reinstatement of flow
Discuss angiogenesis in malignant tumours
Angiogenesis occurs as tumour grows
Potential for therapeutic control
What is granulomatous inflammation always characterised by?
Granulomas (granulomata) in tissues and organs
How is Granulomatous inflammation stimulated?
Stimulated by indigestible antigen, body cannot get rid of it
What are idiopathic diseases?
Diseases which we don’t know why they happened.
How are granulomas formed?
Aggregates of epithelioid macrophages in tissue
What is epitheliod?
Looks like epithelial
What might granulomas surround?
Giant cells, dead material
What might granulomas be surrounded by?
Lymphocytes
What do granulomas contain?
Neutrophils, eosinophils
Granulomas are formed as a result of?
Response to indigestible antigen
Many are type 4 hypersensitivity reactions
What do giant cells consist of?
A giant cell is a mass formed by the union of several distinct cells (usually macrophages)
Describe the structure of a giant cell
Large cytoplasm; multiple nuclei
- several types
Are there always granuloma for giant cells to be present?
No
Name a type of giant cell
Langhans type
What is a Langhans type giant cell classically found in?
TB
Describe the structure of Langhans type
Peripheral rim of nuclei
Large eosinophilic cytoplasm
What is the giant cell often associated with pyogenic granulation tissue?
Foreign body type
Acutely inflamed neutrophils, pus
organisation
giant cells
What type of giant cell might you see with a ruptured silicone implant? e.g breast implant
Silicone associated giant cells
Vacuoles contain leaked silicone
Name some Infectious granulomatous diseases
Tuberculosis (Mycobacterium tuberculosis),
Leprosy Mycobacterium leprae
Syphilis
Describe Caseous necrosis
Cell death in which the tissue maintains a cheese-like appearance. Dead tissue appears as a soft and white proteinaceous dead cell mass.
Dead tissue surrounded by macrophages, giant cells, lymphocytes
Give examples of Non-infective granulomas
Rheumatoid disease - tissue specific auto-immune disease
Sarcoidosis - Development of granulomas within organs of the body
Crohn’s disease – chronic inflammatory bowel disease
What are the common processes in chronic inflammation?
Acute inflammation
Granulation tissue formation
Local angiogenesis - new vessels grow
Fibrosis and scar formation
What is surgical wound healing?
Healing by primary intention
What are the goals of surgical wound healing?
Minimal gap, small amount of granulation tissue, small linear scar
What is healing of larger defects?
Healing by secondary intention
Describe the granulation tissue ingrowth in larger defects
Lots of it
Contraction and scarring
What is the sequence of events in wound healing?
- injury, blood clot, acute inflammation, fibrin
- many growth factors and cytokines involved
-granulation tissue growth - angiogenesis
- phagocytosis of fibrin
- myofibroblasts move in and lay down collagen
- contraction of scar
- re-epithelialisation
What conditions favour wound healing?
Cleanliness
Apposition of edges (no haematoma)
Sound nutrition
Metabolic stability and normality
Normal inflammatory and coagulation mechanisms
Note local mediators
What conditions result in impaired wound healing?
Dirty, gaping wound, large haematoma
Poorly nourished, lack of vitamins C, A
Abnormal CHO metabolism, diabetes, corticosteroid therapy
Inhibition of angiogenesis
What is the sequence of events in fracture healing?
Trauma, fracture, haematoma
Bits of dead bone and soft tissue
Acute inflammation, organisation, granulation tissue, macrophages remove debris
Granulation tissue contains osteoblasts as well as fibroblasts
What are the stages of callus formation?
Osteoblasts lay down woven bone
Nodules of cartilage present
Followed by bone remodelling:
osteoclasts remove dead bone
progressive replacement of woven bone by lamellar bone
reformation of cortical and trabecular bone
What stimulates proliferation of vessels?
Vascular endothelial growth factor, released by hypoxic cells, stimulates proliferation
What aids the process of angiogenesis?
Enzyme secretion
What is the benefit of angiogenesis?
Allows blood supply to enter damaged tissue
