Chronic inflammation and repair Flashcards
How long does chronic inflammation last?
Weeks - years
Describe histological features of chronic inflammation
- Mononuclear cells infiltrate - macrophages (may include giant cells and epithelioid cells), lymphocytes
- Absence of PMNs and pus (although PMNs present in repeated and longstanding acute inflammation
- little oedema
- angiogenesis
- collagen deposition (with time) that may become excessive
What two types of chronic inflammation are there?
- toxic and innate-immune triggered
2. Adaptive immune-triggered
Describe toxic and innate immune-triggered chronic inflammation
- Toxic, non-antigenic, particles activate and kill macrophage - stimulates further recruitment and death of macrophages - mediators released by macrophages cause persistent repair reaction leading to fibrosis and loss of
function - SILICOSIS - Repeatedacute inflammation lead to fibrosis and scarring - CHRONIC CHOLEOCYSTITIS
- Prolonged acute inflammation (eg. presence of foreign body, necrotic tissue or CHRONIC OSTEOMYELITIS)
Describe adaptive immune-triggered chronic inflammation
- CD4 + T-cell mediated immune response to persistent antigens
- Infective – eg. tuberculosis, leprosy, chronic viral hepatitis, peptic ulcer
- Autoimmune – eg. rheumatoid arthritis, thyroiditis, insulin-dependent diabetes, MS
What is chronic osteomyelitis?
This is a chronic inflammatory process of the bone, secondary to infection with pyogenic organisms:
Staphylococcus aureus and occasionally Enterobacter or Streptococcus species
- Risk factors include recent trauma/surgery, diabetes, IV drug abuse, and immune-suppression
- Pathogenesis – can be thought of as long-standing acute inflammation in sites of poor vascular access
Stimuli are the same as in acute inflammation
Macrophages predominate, but PMNs are still present
- Treatment is with prolonged antibiotics, following surgical debridement and bone graft/amputation if
necessary
Describe silicosis
Simple chronic silicosis results from long term exposure (>20 years) to low
amounts of silica dust
- Macrophages are presented with silica and phaogyctose it, but silica is
impervious to the hydrolytic enzymes so causes lysosomal disruption; the
enzymes lead to cell death and the release of cytokines (especially IL1-) and
growth factors which cause macrophage recruitment (continuing the cycle) and
fibroblast recruitment which leads to collagen deposition, and resultant fibrosis
and respiratory failure
- Nodules of chronic inflammation and scarring provoked by the silica dust form in the lungs and chest
lymph nodes; chronic cough and breathlessness lea to cyanosis
- Similar story with asbestos, but accompanying mesothelial tumours
Describe cholecystitis
Inflammation of gallbladder
usually caused by gallstones
Describe cirrhosis
Since early 1970s, 8-fold increase in men and 7-fold increase in
women in the incidence of alcoholic-related cirrhosis of the liver –
important cause of illness and death
- Ballooning necrosis of hepatocytes, neutrophilic infiltration,
megamitochondria – liver takes on a micronodular appearance
- Alcoholic hepatits persists and progresses to cirrhosis if heavy
alcohol use continues, but if it ceases the alcoholic hepatitis
resolves slowly over weeks to months (sometimes without
permanent sequelae but often with residual cirrhosis that limits regeneration)
- May lead to portal hypertension, which causes caput medusae (important clinical sign) and
oesophageal varices (dilation of submucosal veins in oesophagus, easily eroded leading to massive
gastrointestinal haemorrhage)
Describe TB
Primary infection:
Often occurs in childhood; airborne (previously unpasteurised milk)
Pathogenesis revealed by X-rays and histology
Infection develops in periphery of lung – Ghon focus; hilar lymph nodes may also be infected –
calcification often seen on chest X-rays. Ghon focus and lymph node involvement = primary cortex
Most infections heal without clinical disease – many people give positive Mantoux (BCG) tests with
no clinical history of TB, as exposed in childhood
However, a small proportion of infected individuals cannot contain the infection – leads to
widespread dissemination (if by bloodstream, may go anywhere – military TB, TB meningitis); but
if infection is contained the bacteria remain, perhaps indefinitely
- Secondary infection:
Secondary TB is rare in ‘healthy’ individuals
Bacteria cultured from secondary TB are genetically-identical to those causing primary infection
Re-activation of TB infection is seen in drug addicts and alcoholics – reasons unclear
Re-activation common in HIV-infected individuals in sub-Saharan Africa – highlights importance of
CD4+ T cells in containing TB within granulomata, as HIV depletes T cells?
Re-activation also seen in patients treated with anti-TNF drugs – highlights importance of TNF in
host suppression of TB infection
- Pathogenesis
Tubercle bacteria don’t have direct virulence mechanisms – don’t secrete exotoxins, no endotoxin
Infection can be associated with massive tissue destruction, and histology shows classic hallmarks
of chronic inflammation (abundant macrophages, lymphocytes, fibroblasts, collagen deposition)
Granulomata – small nodules seen in inflammatory disease (eg. TB, sarcoidosis, Crohn’s)
Each granuloma is a group of epithelioid macrophages (highly-secretory cells with abundant
rough ER) surrounded by a lymphocyte cuff
Granulomata can contain macrophage giant cells
(MGCs) which are the result of macrophage fusion
(eg. Langhans cells in TB granulomata)
TB granulomata can be associated by extensive
necrotic cell death – may be caseating necrosis
Describe RA
Rheumatoid arthritis is a chronic, systemic,
inflammatory disease with a strong
autoimmune component; its primary target is
the synovial tissues
- When the disease is unchecked, it leads to
substantial disability and premature death
What is granulation tissue?
New connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process
Which cells govern formation of ECM?
Created and modified by fibroblasts
Network of type III collagen which is later replaced by stronger long-stranded type I collage
Which cells govern opeation of the immune system in tissue repair?
Macrophages and neutrophils phagocytose old or damaged tissue and protect healing tissue from infection
Which cells govern angiogenesis in tissue repair?
Endothelial cells branch from older vessels and anastomose
