Chronic Inflammation Flashcards
What is chronic inflammation
Inflammation in which the cell population is especially: lymphocytes, plasma cells and macrophages
Tends to be long term
What does chronic inflammation tend to feature
Tissue or organ damage
Necrosis
Loss of function
Healing and repair (with granulation tissue, scarring and fibrosis)
What could chronic inflammation be due to
Following from ongoing acute inflammation
Arising as primary pathology
What are the clinical presentation of chronic inflammation
Often no specific area which is sore
Malaise (e.g. TB which can affect lung, lymph node, bone, kidney, skin causing a systemic effect)
Weight loss
Loss of function (e.g. autoimmune thyroiditis, a functional gland destruction, Crohn’s disease, a GI tract ulceration and fibrosis causing pain, diarrhoea and gut obstruction and Leprosy which is cutaneous nerve destruction causing loss of sensation)
How does acute inflammation lead to chronic inflammation
It follows on from where there is a large volume of damage and an inability to remove debris. When this fails to resolve the ongoing acute is insult
When chronic inflammation arises as a primary lesion what is seen
No preceding acute phase
Only chronic changes will be seen
What is organisation
An outcome of acute inflammation where granulation tissue is a characteristic which results in healing and repair and can lead to fibrosis and formation of a scar
What is the function of granulation tissue
Patches tissue defects
Replaces dead or necrotic tissue
Contracts and pulls together
What is the mechanism of action of granulation tissue
Capillaries grow into inflammatory mass Plasma proteins access Macrophages from blood and tissue Fibroblasts lay down collagen to repair damaged tissue Collagen replaces inflammatory exudate
What are the products of granulation tissue
Fibrous tissue - scar (small firm blemish on skin)
Fibrosis as a problem - adhesions between loops of bowel following peritonitis
Can progress to chronic inflammation
What cells are involved in primary chronic inflammation
Lymphocytes
Plasma cells
Macrophages
Fibrosis
What is primary chronic inflammation
An autoimmune disease where autoantibodies are directed against own cell and tissue components through autoantigens
It causes damage or destroy organs, tissues, cells and cell components and can result in thyroiditis, rheumatoid disease, pernicious anaemia (chief/parietal cells) and systemic lupus erythematosis (nuclear antigen)
What type of inflammation is common
Granulomatous
What could primary chronic inflammation be due to
Material resistant to digestion (e.g. mycobacteria, Brucella, viruses)
Cell wall resistant to enzymes
Exogenous substances (e.g. sutures, metal and plastic like joint replacements, mineral crystals, glass) which do not provoke an immune response
Endogenous substances (e.g. necrotic tissue, keratin, hair) which cannot be easily phagocytosed
What tissue components are involved in primary chronic inflammation
Granulation tissue
Collagen
What are lymphocytes
Cells which are part of the immune system
Small and round with lots of subtypes and functions
What are the main types of lymphocytes
T cells
B cells
What is the main function of lymphocytes
Immune response
Immune memory
What are plasma cells
Differentiated B cells that assist in antibody production and are intermediate in size
What mechanisms can B cells undertake
Differentiate into plasma cells to produce antibodies
Facilitate an immune response
Act with macrophages for the antigen presenting capacity
Have immune memory
What do T cells do
Produce cytokines
Produce interferons
Damage and kill (lyse) other cells
Destroy antigens
What do cytokines do
Attract and hold macrophages
Activate macrophages
Other cells (e.g. lymphocytes)
Affect permeability
What do interferons do
Antiviral effects
Attract and stimulate other cells
What do NK-cells do
Destroy antigens and cells using chemical mechanisms involving granule proteins
State the features of macrophages
Remove debris
Have a role in the immune system (APC)
Found in the bone marrow and blood tissues
Contain enzymes (e.g. lysozymes)
What can macrophages be
Monocyte Histiocyte Activated macrophage Epithelioid cell Giant cells
What mechanisms are macrophages involved in
The motile phagocyte move from blood and live long
Can take over from neutrophils
Produce interferons and other chemicals to destroy or influence processes
What are fibroblasts
Motile cells which are metabolically active and can make and assemble structural proteins (e.g. collagens various types)
What is granulomatous inflammation characterised by
The presence of granulomas (granulomata) in tissues and organs
What stimulates granulomatous inflammation
Indigestible antigen (body cannot get rid of it) which causes many serious infectious and idiopathic (= no known cause) diseases
What are granulomas
Aggregates of epithelioid macrophages (epithelioid histioytes) in tissue
Describe the features of granulomas
May contain giant cells
May surround dead material
May be surrounded by lymphocytes
Contain neutrophils, eosinophils (only specific types)
Response to indigestible antigen
Many are type IV Hypersensitivity reactions
What are giant cells
They are formed from the fusion of macrophages
They have a large cytoplasm with multiple nuclei (several types)
Where are the langhans type classically found
TB
Describe the features of langhans
Peripheral rim of nuclei
Large eosinophilic cytoplasm
When a foreign body enters the body what type of tissue is it associated with
Pyogenic granulation tissue Presents as: Acutely inflamed Neutrophils, pus Organisation Giant cells e.g. pilonidal abscess
Where is the nuclei in the warthin-finkeldy type
Central cluster of nuclei
Give examples of infectious granulomatous diseases that are relevant to global health
Tuberculosis – Mycobacterium tuberculosis
Leprosy – Mycobacterium leprae
Syphilis – Treponema pallidum
What is caseous nercrosis
Dead tissue surrounded by macrophages, giant cells, lymphocytes
Which drugs can be used to treat a patient with leprosy
Dapsone, rifampicin and clofazimine
This combination kills the pathogen
Give example of non-infective granulomas
Rheumatoid disease
Sarcoidosis
Crohn’s disease
What is rheumatoid disease
A tissue specific auto-immune disease
What is crohn’s disease
Chronic inflammatory bowel disease
How does wound healing occur
There is a: Phase of acute inflammation Granulation tissue formation Local angiogenesis – new vessels grow Fibrosis and scar formation
How does surgical wound healing occur
Healing by primary intention
Minimal gap from blood clot
Small amount of granulation tissue
Small linear scar
How do larger defects heal
Healing by secondary intention
Lots of granulation tissue ingrowth
Contraction and scarring
Give an example when healing by primary intention occurs
Surgical wound healing
Give an example when healing by secondary intention occurs
For larger defects
Describe the sequence of events which occur for secondary intention 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 helps a wound to heal
Cleanliness Apposition of edges (no haematoma) Sound nutrition Metabolic stability and normality Normal inflammatory and coagulation mechanisms Note local mediators
What prevents a wound from healing
Dirty, gaping wound, large haematoma
Poorly nourished, lack of vitamins C, A
Abnormal carbohydrate metabolism, diabetes, corticosteroid therapy
Inhibition of angiogenesis
What are the features of fracture healing
It’s the same principles as healing at any site
Modified by situation in bone
Have to repair bony structure as well as soft tissue
Describe the sequence of events which occur 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
How do calluses form
Osteoblasts lay down woven bone
Nodules of cartilage present
Followed by bone remodelling
How does bone remodelling occur
Osteoclasts remove dead bone
Progressive replacement of woven bone by lamellar bone
Reformation of cortical and trabecular bone
Describe the process of angiogenesis
New vessels form from capillary buds
Vascular Endothelial Growth Factor (VEGF) released by hypoxic cells stimulates proliferation
Enzyme secretion aids process
Enable blood supply to enter damaged tissue
What does angiogensis and organisation in thrombosis do
Limits thrombus propagation
Reinstatement of flow
What does angiogenesis in malignant tumours have the potential for
Potential for therapeutic control
What does chronic inflammation have similarities with
Fibrosis and scarring in atherosclerosis
Name types of giant cells
Foreign body
Langhans
Silicone associated
Warthin-Finkeldy
What is wound healing
Its a process of repair of tissue damage
