chronic inflammation Flashcards
What is chronic inflammation? like what are its characteristics ya know?
- prolonged beyond weeks
- active inflammation, tissue destruction and repair
- persist until stimulus eradicated
- can be injurious
- affect tissue cannot resolve, but undergo healing
what are the 3 causes of chronic inflammation
unresolved acute inflammation, prolonged exposure to toxic agents and immune mediated responses
describe how unresolved acute inflammation leads to chronic inflammation using osteomyelitis
- persistent bone marrow infection
- chronic inflammatory cells stimulate bone resorption and despoit bone tissue
- can be fixed with antibiotics and surgery
describe how prolonged exposure to toxic agents can lead to chronic inflammation in terms of prosthetics
wear particles released from degradation
- granulaomatous inflammation where clustered t cells activate macrophages and transform into epithelial-like cells
describe immune mediated reaction rheumatoid arthritis
- own cells = foreign
- t cells activate macrophages and cytokines
- stimulate synovial cells
- pannus formation = destroy cartilage and lose joint space
what are the main features of chronic inflammation
mononuclear cell infiltration
tissue destruction
attempted healing and replacing damage tissue with ct
what are the systemic effects of chronic inflammation
arthralgia and myalgia fever leukopenia chronic fatigue + mood disorders GI complications
what is the most dominant cell type in chronic inflammation
macrophages
how are macrophages activated
signals from t helper cells (lymphocytes)
what is the function of macrophages
chemical mediators, killing bacteria and cells, remove EV debris, fibrin, foregin particles, granulomatous inflammation
what is the lifespan of macrophages and describe their maturation
in blood (monocyte) = 1 day in tissue = months -> years maturation mediated by growth factors, cytokines, adhesion molecules, cellular interactions
what are the positives and negatives of macrophage activity
positives = increases lysosomal effects and reactive oxygen species which is toxic to microbes. also helps fibroblast proliferation and stimulates angiogenesis negatives = products are responsible for tissue injury and dissolution of EC matrix
what is granulomatous inflammation
a focal collection of macrophages, epitheliods, and multinucleated giant cells that have amassed an indigestible substance
its a protective response that leads to tissue necrsosis because of the secretory cells
what is a mn giant cell and what are the different types
its a fusion of macrophages
langhans = nuclei arranged peripherally
foreign body = indigestible material within the cytoplasm
what are the steps of granulomatous inflammation
injury -> inability to digest agent -> acute failure -> persistent injury -> macrophage recruitment -> giant cell formation -> cell mediated response => granuoma
features of lymphocytes
proliferate bone marrow + tissues long lined some present normally antigen activated release mac act ctokines pos feedback loops
features of plasma cells
humoral
terminally differentiated B cells
1 kind of antibody produced
common lymphoid progenitor
features of fibroblasts
secrete EC matrix components
for immune and wound healing
feature of endothelial cells
angiogenesis
features of eosinophils
IgE mediated reactions
granules are toxic proteins
what are the outcomes of chronic inflammation
if you remove stimulus = repair through fibrosis and scar formation
but healed tissue is not parenchymal tissue
often loses function
if stimulus not removed = poor prognosis, dependant on causative agent
what are the aims of wound healing
remove damaged tissue
fill gap caused by tissue destruction
restore structural continuity and function if possible
what does regenerative healing mean and what are the possibilities for labile, stable and permanent cells
replaced with parenchymal tissue
labile = can regenerate quickly
stable = can regenerate slowly
permanent = cannot regenerate
name the 3 phases of wound healing
reactive, reparative, remodelling
describe the reactive phase of wound healing
haemostasis and vascular spasm
platelet coagulation and clot formation
inflammation, decrase pathogens, cells migration + vasodilation (signs of acute inflam)
describe the reparative phase of wound healing
epithelialisation = grows under the clot, separating clot and underlying tissue = bridge between wound edges granulation = fibroblasts, myofibs (like fibroblasts w/contractile potential), macs, collagen, caps, lymphatic vessels
describe the remodelling phase of wound healing
macrophages, scar formation, realignment of tissue
describe primary intention healing
wound with close edges
fibroblasts and granulation tissue
closure = 1 week
return function with minimal scarring
describe secondary intention healing
wound with far edges healing from bottom up loss cells and tissue inflammation is intense carries lots of necrotic debris and exudate increased granulation tissue fills until the epithelia regenerates increased collagen synthesis wound contraction is frequent scar tissue replaces normal tissue
what is the function of granulation tissue
to protect against microbial invasion and further injury
fills base up with new tissue and vasculature and replaces necrosis until that is replaced with scarring
what are the components of granulation tissue
new, thin blood vessels
fibroblasts, keratinocytes, endothelial cells, inflammatory cells phagocytose dead tissue
what are the sequential changes of granulation tissue
- vascular (new caps, macs, support cells that replace area of tissue damage)
- fibrovascular (fibroblasts, caps, macs)
- fibrous (fibroblasts -> collagen = align and deposit increase contraction)
stages of regenerative healing in a fracture
haematoma -> granulation tissue -> soft calus -> hard callus -> remodelling
describe the haematoma an granulation tissue stage of regenerative healing
happens at time of fracture and severs bv and preiosteum
leads to blood clot
invastion of fibsm macs, oclasts + obblasts
invasion turns the clot into soft fibrous mass of GT
describe the soft callus stage of regenerative fracture healing
angiogenesis
collagen within GT
chondroblasts => patches of firbrocartilage
GT gets stronger but is still malleable
describe the hard callus stage in regenerative fracture healing
oblasts produce bone ring around fracture site
joining ends together
makes sure broken bone is immobilised and prevents reinjury or misalignment
describe remodelling phase of regenerative fracture healing
hard calus = 3-4 months
oclasts dissolve broken bone fragments
oblasts deposit spongy bone
describe the reactive phase of nonregenerative MI healing in terms of hours
6-12 = myocytes die, no macroscopic changes, high eosinophilia
12-24 hours = high eosinophilia + myocyte necrosis
24-72 = high neutrophils infiltrating tissue and removing necrotic myocytes, nuclei fade from cells (karyolsis)
describe the reparative phase of non-regenerative healing in MI
3 days post MI = fibroblasts + endothelial cells infiltrate injury
weeks after = GT
describe remodelling phase of nonregenerative MI healing
6-8 weeks = healed myocaridum
fibs lay collagen
infalm cells drain via lymps
mature scar
local factors taht influence healing
infection mechanical foreign bodies vascular supply size, location, type
