Chronic Inflammation Flashcards
List the cell types involved in chronic inflammation.
Lymphocytes - T-cell - B-cell Plasma cells - differentiated B-cell - act with macrophages - immune memory Macrophages Fibroblasts
(granulation tissue
collagen)
List the major causes of chronic inflammation.
Autoimmune disease Lymphocytes, plasma cells, macrophages, fibrosis Material resistant to digestion Exogenous substances Endogenous substances granulomatous inflammation common
Describe the effects of chronic inflammation.
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
clinical findings in chronic inflammation
Often no specific “sore bit”
Malaise (discomfort) 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
causes and components of chronic inflammation
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
outcomes of chronic inflammation:
Organisation
granulation tissue is characteristic of organisation
involves new vessel formation – angiogenesis
results in healing and repair
leads to fibrosis and formation of a scar
Role of angiogenesis 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
Healing and repair involves
- granulation tissue
- scarring and fibrosis
angiogenesis in malignant tumours
- angiogenesis occurs as tumour grows
- potential for therapeutic control
Fibrosis and scarring in atherosclerosis (plaque builds up inside your arteries)
similarities with chronic inflammation
Granulation tissue mechanism and function
- 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
Acute + chronic =
pyogenic granulation tissue
Products of granulation tissue
Fibrous tissue - scar - eg small firm blemish on skin Fibrosis as a problem - adhesions between loops of bowel following peritonitis Chronic inflammation
Endogenous substances in chronic inflammation include
- necrotic tissue, keratin, hair
- cannot easily be phagocytosed
Products of granulation tissue
Fibrous tissue - scar - eg small firm blemish on skin Fibrosis as a problem - adhesions between loops of bowel following peritonitis Chronic inflammation
Material resistant to digestion in chronic inflammation include
- mycobacteria, Brucella, viruses
- cell wall resistant to enzymes
T-cell mechanisms in chronic inflammation
Produce cytokines - attract and hold macrophages - activate macrophages Produce interferons - antiviral effects - attract and stimulate other cells Damage and kill (lyse) other cells and destroy antigen - chemical mechanisms - granule proteins
NK-cell mechanisms
Destroy antigens and cells
- chemical mechanisms - granule proteins
- innate immunity
Macrophage mechanisms
- removes debris
- role in immune system - antigen presenting cell
- monocyte, histiocyte, activated macrophage, epithelioid cell, giant cell
- found in bone marrow, blood tissues
- motile phagocyte move from blood
- long lived
- take over from neutrophils
- contain enzymes eg lysozyme
- produce interferons and other chemicals
- destroy, influence process
Fibroblast mechanisms
- motile cells
- metabolically active
- make and assemble structural proteins
- collagens
- various types
granulomatous inflammation
Characterised by presence of granulomas (granulomata) in tissues and organs
Stimulated by indigestible antigen
- body cannot get rid of it
Many serious infectious and idiopathic (= no known cause) diseases
Diseases important on global scale are granulomatous inflammatory diseases
- global health perspective
granulomas are
- aggregates of epithelioid macrophages in tissue
- may contain giant cells
- may surround dead material
- may be surrounded by lymphocytes
- contain neutrophils, eosinophils
- response to indigestible antigen
- many are type IV hypersensitivity reactions
Describe the adverse effects of tissue scarring.
Nerve pain or numbness if scar tissue forms around nerves.
In certain tissues like muscle there is going to be less flexibility due to the scarring.
Silicone associated
ruptured silicone implants
usually but not always breast
vacuoles contain leaked silicone
describe wound healing
phase of acute inflammation
granulation tissue formation
local angiogenesis – new vessels grow
fibrosis and scar formation
describe fracture healing
modified by situation in bone
have to repair bony structure as well as soft tissue
trauma, fracture, haematoma
bits of dead bone and soft tissue
acute inflammation, organisation, granulation tissue, macrophages remove debris
granulation tissue formation
local angiogenesis – new vessels grow
granulation tissue contains osteoblasts as well as fibroblasts
granulomas are
- aggregates of epithelioid macrophages in tissue
- may contain giant cells
- may surround dead material
- may be surrounded by lymphocytes
- contain neutrophils, eosinophils
- response to indigestible antigen
- many are type IV hypersensitivity reactions
Infectious granulomatous diseases – examples relevant to global health
tuberculosis – Mycobacterium tuberculosis - India, China, Indonesia, leprosy – Mycobacterium leprae - Brazil, Bhutan, India syphilis – Treponema pallidum
Non-infective granulomas - examples
rheumatoid disease - tissue specific auto-immune disease, ? cause
sarcoidosis – classical clinical picture, ? cause
Crohn’s disease – chronic inflammatory bowel disease, ? cause
Giant cells:
Foreign body type
often associated with pyogenic granulation tissue - acutely inflamed - neutrophils, pus - organisation - giant cells eg pilonidal abscess
Healing of larger defects
healing by secondary intention
lots of granulation tissue ingrowth
contraction and scarring
Giant cells:
Warthin-Finkeldy type
rarely see in measles
central cluster of nuclei
Callus formation in bone
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
