Chronic Inflammation Flashcards
Define chronic information
- inflammation in which the cell population is especially: lymphocytes, plasma cells, macrophages
- features tissue or organ damage, (necrosis), loss of function
- healing and repair
-granulation tissue
-scarring and fibrosis - may follow from ongoing acute inflammation**
- but also arises as primary pathology - no acute process
- tends to be long-term
clinical presentations of chronic inflammation
examples also given but remember bold bits
-
malaise and weight loss
-tuberculosis (lung, lymph node, bone, kidney, skin) - systemic effect -
loss of function
-autoimmune thyroiditis (functional gland destruction) - hypothyroidism
-Crohn’s disease (GI tract ulceration and fibrosis) - pain, diarrhoea, gut obstruction
-leprosy (cutaneous nerve destruction) - loss of sensation - No specific sore bit (unlike acute)
when do we see chronic inflammation: what causes it to occur
- arising from acute inflammation
-follows on from acute
-large volume of damage
-inability to remove debris
-fails to resolve - ongoing acute insult - arising as a primary lesion
-no preceding acute phase
-only see chronic changes
angiogenesis
- 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
What outcome of acute inflammation is linked to chronic inflammation
Organisation: granulation tissue, angiogenesis, healing and repair, scar
granulation tissue mechanism of action (process)
- capillaries grow into inflammatory mass
- access of plasma proteins
- macrophages from blood and tissue
- fibroblasts lay down collagen to repair damaged tissue
- collagen replaces inflammatory exudate
- patches tissue defects
- replaces dead or necrotic tissue
- contracts and pulls together
helps us to restore normal function
Describe the overlap/interface between chronic and acute inflammation (briefly)
Mixture:
* exudate, neutrophils
* lymphocytes plasma cells, fibroblasts, fibrosis
pyogenic
pus?
what are the products of granulation tissue
- fibrous tissue - scar, helpful
- fibrosis as a problem (stick bits together when shouldn’t be)
- chronic inflammation
primary chronic inflammation
factor/cause, explanation, example…
-
autoimmune disease
-autoantibodies directed against own cell and tissue components - autoantigens. damage or destroy organs, tissues, cells, cell components (e.g.thyroiditis, rheumatoid disease, pernicious anaemia (chief/parietal cells), systemic lupus erythematosis (nuclear antigen)) - lymphocytes, plasma cells, macrophages, fibrosis - immune response destroys tissue to which it was directed
- material resistant to digestion
- exogenous substances (foreign)
-not provoke immune response - endogenous substances (necrotic tissue, keratin, hair -cannot easily be phagocytosed)
- granulomatous inflammation common
pathogenesis of chronic inflammation: what cells and tissue components are involved?
5 cells, 2 tissue componenets…
Cells: lymphocytes, plasma cells, macrophages, fibroblasts + endothelial cells —> blood clotting/fibrin
Tissue Components: granulation tissue, collagen
B cells meachanism in immune/inflammatory system
essentially; B cell function
- differentiate to plasma cells -antibodies
- facilitate immune response
- act with macrophages
-antigen presenting capacity - immune memory
Role of T cells in immune/inflammatory response
- Produce cytokines* (attract and hold macrophages, activate macrophages, other cells eg lymphocytes, permeability)*
- T-cells produce interferons (antiviral effects, attract and stimulate other cells) helper?
- damage and kill (lyse) other cells and destroy antigen - granule proteins
Summarise NK-cell mechanismsin immune system
Destroy antigens and cells:
* chemical mechanisms - granule proteins
* Innate immunity
Role of macrophages in immune/inflammatory reponse
- removes debris
- role in immune system - antigen presenting cell
- monocyte, histiocyte, activated macrophage, epithelioid cell, giant cell
kills cells, removes dead cells, activates other immune cells
How do macrophages become involved in immune/inflammatory response
- motile phagocyte so moves from blood
- takes over from neutrophils
- containse degrating enzymes (lysosomes) - kill
- produces interferons and other chemicas (destroy/influence process)
interferons - recognise foreign body, signal to othher cells
fibroblast function
Contribute to CT formation
Motile cell that cvcvan make and assemble structural proteins - collagens
Summarise the outcome of chronic inflammation
- ongoing tissue damage/destruction
- insidious loss of function
- cellular and stromal response (granulation tissue, angiogenesis)
- fibrosis and scarring
- granuloma formation
adverse effects of tissue scarring
pain, tightness, itching, or difficulty moving - if internal that can be very bad
effects of chhronic inflammation
(from goole)
Body’s inflammatory response can eventually start damaging healthy cells, tissues, and organs. Over time, this can lead to DNA damage, tissue death, and internal scarring. All of these are linked to the development of several diseases, including: cancer
Major causes of chronic inflammation
- autoimmune disorders
- exposure to toxins
- untreated acute inflammation
explain granulomatous inflammation
- characterised by presence of granulomas (granulomata) in tissues and organs
- stimulated by indigestible antigen
-body cannot get rid of it (important for global health) - many serious infectious and idiopathic (= no known cause) diseases
Granulomas
- aggregates of epithelioid macrophages in tissue
- may contain giant cells
- may surround dead material and be surrounded by lymphocytes
- contain neutrophils, eosinophils
- response to indigestible antigen
what are many granulomas a result from (autoimmunity)
Type IV hypersensitivity reactions
What are giant cells
- granulomas comprise epithelioid histioytes (macrophages)
- fusion of macrophages to form larger cells
- large cytoplasm; multiple nuclei
- not always granuloma for giant cells to be present
what are foreign body types associated with and what is found there
Pyogenic granulation tissue - pus
acutely inflamed, neutrophils (pus), orginisation, giant cells
Foreign body causing inflammation example
silicone: ruptured implants with vacuoles containing leaked silicone
3 infectious granulomatous disease examples
- tuberculosis - Mycobacterium tuberculosis
- leprosy - Mycobacterium leprae
- syphilis - Treponema pallidum
caseous necrosis
dead tissue surrounded by macrophages, giant cells, lymphocytes - granulomas?
Tb common cause
3 non-infective granulomas examples
- rheumatoid disease - tissue specific auto-immune disease
- sarcoidosis - classical clinical picture
- Crohn’s disease - chronic inflammatory bowel disease
Give brief overview of wound healing (from acute inflammation)
Process of repair to tissue damage
* phase of acute inflammation
* granulation tissue formation
* local angiogenesis (new vessel growth)
* fibrosis and scar formation
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
how does surgical wound healing compare to that of larger defects
only small amount of granulation tissue so not much contraction and scarring
factors to favour wound healing
*cleanliness
*apposition of edges (no haematoma)
*sound nutrition
*metabolic stability and normality
*normal inflammatory and coagulation mechanisms
*note local mediators
factors to impair 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 different about fracture healing compared to normal tissue healing
have to repair bony structure as well as soft tissue
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
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
role of angiogenesis in healing and repair
forming new blood vessels from preexisting vessels by invading the wound clot and organizing in to a microvascular network throughout the granulation tissue - provide nutrients and O2 to damaged/healing tissues
factors to impair wound healing and repair
age/weight/sanitation etc.
Nutrients to wound/vasculature
maybe more, is Lo but had to google???
