Chronic Inflammation Flashcards
What is chronic inflammation?
Inflammation of prolonged duration
What are the origins of chronic inflammation?
- Progression from irresolved acute inflammation
- Recurrent episodes of acute inflammation
- Denovo process without acute phase (different mechanism)
What is tissue damage caused by if not pathogenic cells?
Inflammatory cells
What are the signs of chronic inflammation like in comparison to acute?
More attentuated, less obvious
What are the cells involved in chronic inflammation? (4)
- Macrophages
- Sometimes lymphocytes
- Mast cells
- Plasma cells
What type of cell is involved in chronic inflammation?
Mononuclear
What differentiates chronic inflammation from acute inflammation?
No neutrophilic response, just mononuclear/lymphocytic response
Give an example of a persistent infection turning from acute response to chronic process
Focus of infection cannot be reached by antibiotics in chronic osteomyelitis
How is osteomyelitis often insiduous?
In acute osteomyelitis the central area of necrosis = surrounded by:
- Possible fibrosis
- Thickened bone formation
Can’t isolate pathogen for effective treatment
What is primary chronic inflammation characterised by? (2)
- All the histological features of a chronic process with mononuclear cells
- Skips neutrophilic response
What are the causes of primary chronic inflammation? (3)
- Persistent infection by organisms with low toxicity
- Prolonged exposure to non degradable toxic agents
- Autoimmune disease
How does persistent infection by organisms with low toxicity trigger primary chronic inflammation?
Immunoresponse called delayed hypersensitivity triggered
What type of response is delayed hypersensitivity?
Intracellular
W hat does delayed hypersensitivity mostly occur in response to?
- Viruses
- Microbacteria e.g TB
What are the 2 types of non degradable toxic agents that prolonged exposure to causes primary chronic inflammation?
- Exogenous
- Endogenous
Give 3 examples of exogenous non degradable toxic agents
- Asbestos
- Silica
- Wood dust
Give an example of endogenous non degradable toxic agents
Plasma lipids found in atherosclerosis
What is autoimmune disease a response to?
Self antigens
Give 2 types of autoimmune disease
- SLE
- Thyroiditis
What are the first cells to populate a site of injury in chronic inflammation (which are progressions of each other)? (3)
- Monocytes
- Macrophages
- Multinucleated giant cells
How long does it take for monocytes, macrophages and multinucleated giant cells to populate a site of injury after damage?
24-48 hours
What are monocytes?
Precursors of macrophages circulating in blood
How long do circulating monocytes survive?
2 days
What are macrophages?
Monocytes that have migrated from the bloodstream into any extravascular tissue
What can macrophages do that monocytes cannot?
- Phagocytise
- When activated: eliminate internalised microorganisms
What property of macrophages allows them to eliminate internalised microorganisms?
Increased lysosomal content
In what ways do macrophages contribute to chronic inflammation? (2)
- Release active products = tissue damage and fibrosis
- Proliferation
How can the presence of cells in inflammation be used to judge the length of time from insult? (3)
- Within 4 hrs: seeing neutrophils
- Longer than 4 hrs: neutrophils and macrophages
- In repair=fibrosis
What accumulation persists in chronic inflammation?
Macrophage accumulation
What are the 3 reasons chronic inflammation macrophage accumulation persists?
- Continuous recruitment from circulation
- Local proliferation
- Peripheral macrophage immobilisation
What are the 2 types of peripheral macrophages that are immobilised?
- Epithelioid histiocytes
- Giant cells
What are the 3 types of giant cell?
- Foreign bodies
- Langhan’s giant cells
- Touton giant cells
What property of a giant cell differentiates it from monocytes/macrophages?
They are multinucleated
Identify the histological pics of different types of giant cells
See notes
What is a giant cell?
A collection of fused macrophages
What type of immune cell is found in chronic inflammation but not acute?
Lymphocytes
What are the 3 types of lymphocyte?
- B lymphocytes
- T lymphocytes
- Natural killer cells/null cell type
What is the purpose of B lymphocytes in chronic inflammation upon activation?
- Increase plasma cells
- Increase IG production
What are the two types of T lymphocytes?
- CD4+ helper T cells
- CD8+ cytotoxic T cells
What is the purpose of CD4+ helper T cells?
Secrete cytokines in immediate cell vicinity regulating other immune cells (e.g B cells/macrophages)
What is the purpose of CD8+ cytotoxic T cells?
Cell mediated immunity
What is the purpose of natural killer cells/null cell type? (2)
- Lyse tumour cells
- Lyse infected cells
What is formed following chronic inflammation and what is it made up of? (3)
Inflammatory infiltrate
- Macrophages
- Lymphocytes
- Plasma cells
What are the possible consequences of chronic inflammation? (4)
- Tissue destruction/necrosis
- Healing due to fibrous tissue replacement
- Chronic non specific inflammation (granulation tissue)
- Chronic granulomatous inflammation
What are the 3 parts of fibrous tissue replacement healing in chronic inflammation? (3)
- Angiogenesis
- Fibroblastic proliferation
- Fibrosis
What is granulation tissue?
Vascularised fibrous tissue replacing fibrin clot
What does granulation tissue contain? (5)
- Loose connective tissue
- Lots of fluid
- Lots of blood vessels (angiogenesis)
- Fibroblasts
- Macrophages
Why does granulation tissue contain macrophages?
To clear debris
What is granulation tissue normally part of?
The repair process for existing defects
When can granulation tissue cause issues? (2)
- Too large
- Issues with healing process
What is a granuloma?
Mass collection of mononuclear macrophages/granulation tissue
What is a granuloma a type of?
Inflammation
What are the two types of granuloma?
- Necrotising (caseating)
- Non necrotising
Name a condition with non necrotising granulomas
Sarcoidosis
Name a condition with necrotising granulomas
TB
What is a useful purpose of a granuloma?
Destroying/isolating pathogens/foreign material
What negative effects can a granuloma have?
Tissue destruction
Why do necrotising granulomas cause problems?
Tissue necrosis means macrophage can’t access granulomas
What pathogen is TB caused by?
Mycobacterium tuberculosis (MT)
What are the two types of Mycobacterium tuberculosis?
- MT Hominis
- MT Bovis
How many individuals are affected by TB in the world?
1.7 billion
How many new cases of TB are there every year?
8 million
How many TB deaths are there every year?
1.6 million
What is the only disease that causes more deaths than TB every year?
HIV
What disease is TB often associated with in epidemics?
HIV
What defines a TB infection?
Presence of mycobacterium
Does TB necessarily lead to clinical manifestation?
No
What is the 1st stage of TB pathogenesis?
Primary tuberculosis
How long does the 1st stage of primary tuberculosis last?
0-3 weeks
What occurs in the 1st stage of primary tuberculosis?
MT enters macrophages by endocytosis mediated by macrophage receptors
What are the features of the 1st stage of primary tuberculosis? (4)
- Asymptomatic initially
- Fever
- Malaise
- Primary complex
What is there a delayed hypersensitivity to in primary tuberculosis?
MT antigens
What test detects the delayed hypersensitivity to MT antigens in primary tuberculosis?
Tuberculin - Mantoux skin test
What is the primary complex at the TB infection site caused by?
Local lymph node that has become fibrotic and calcified
How long does the second stage of primary tuberculosis last?
4-6 weeks
What occurs in the second stage of primary tuberculosis?
- T helpers 1 response activates macrophages to become bactericidal
- Phagolysome complex contains infection
- Granuloma formation
What type of T helper is involved in primary tuberculosis?
T helper 1
What forms a phagolysosome complex in the second stage of primary tuberculosis?
T helpers 1 releasing IFN-gamma stimulating macrophages to form it
How do T helpers 1 stimulate granuloma formation in the second stage of primary tuberculosis?
Conversion of macrophages into epithelioid histiocytes/giant cells
What are epithelioid histiocytes?
Activated macrophages resembling epithelial cells
What are the first 2 steps of TB?
- Primary infection
- Primary complex
What 3 ways can a primary complex progress in TB?
- Healed lesion (scar)
- Progressive primary TB
- Latent lesions (dormant)
What is a TB primary complex? (2)
- Localised caesation
- Tiny granuloma fibroclacific nodule at infection site
What type of TB can progressive primary TB become?
Milary TB
What is milary TB?
Potentially fatal TB form from massive lymphohematogenous dissemination of MT
What can latent dormant lesions progress to if reactivated?
Secondary TB
What occurs in secondary TB? (4)
- Initial lesions starts regrowing again
- Small nodule progresses to caverna (large cystic lesion)
- Leads to widespread caviating granulomatous inflammations
- Localised caseating destructive lesions
What can secondary TB progress to? (2)
- Progressive secondary tubculosis
- Then malary TB
What do patients with unhealed primary TB have?
Widespread multiple small granuloma scabs
List the 3 markers of inflammation
- ESR blood test
- CRP blood test (C-reactive protein)
- Plasma viscosity (PV)
What needs to be disposed after TB and why? (2)
- Myobacterium
- Macrophages
=indigestable
What can be used to tell the stage of inflammation?
The type of WBC present
What does ESR blood test stand for?
Erythrocyte sedimentation rate
What does the ESR blood test measure?
The rate at which red blood cells separate from plasma and fall to bottom of test tube
What causes an increased ESR? (3)
- Increased proteins e.g fibrinogen covering red cells due to more inflammation
- Proteins stick to each other
- Cause RBCs to fall more quickly
What is the disadvantage of the ESR blood test?
Not specific for acute inflammation
What is a CRP blood test also known as?
Acute phase protein
What is the advantage of a CRP blood test compared to an ESR blood test and why?
Very specific - measures level of 1 specific protein, ESR = many proteins
What does CRP increase in response to?
When IL6 is released and activates complement cascade
Why does increased plasma viscosity indicate inflammation?
Loss of fluid in inflammation
What are the disadvantages to the PV test? (2)
- More difficult to perform
- Not widely used
PV is more specific and sensitive than ESR or CRP when monitoring the activity of which condition?
Rhuematoid arthritis
