Inflammation Flashcards
Acute
minutes to a few days
Main causes of acute inflammation
Allergic reaction/ hypersensitivity.
Infections
Physical injury
Chemical injury
What happens in the vascular phase of acute inflammation ?
Small vessels dilate, Vascular endothelium cells contract thus making spaces between them
What happens in the exudative phase of inflammation ?
Fluid and protein leaking through capillary walls and cells through venules.
Exudate meaning
Leaky/dilated blood vessels so protein and cells in fluid.
Transudate meaning
Passive outflow of fluid when balance of osmotic and hydrostatic pressure change.
Transudate vs Exudate
Transudate has low protein content, few cells.
Exudate has high protein content, may contain some white & red blood cells.
Chemokines and IL-1
Stimulate adhesion molecules on endothelium and white cells
Tumour necrosis factor
Stimulates vascular permeability
Macrophages role
Have the role of clearing debris and dead cells
What is the role of neutrophils during inflammation ?
Migration into tissues
Recognise bacteria by
- formylmethionine at end of surface protein chains
-coating of antibody or complement (C3b)
Phagocytosis is carried out.
Kill bacteria via lysozyme destroying cell wall and via hydrogen peroxide production
Apoptosis
What is the lifespan of neutrophils ?
8-12 hours (short lifespan)
How are basophils/mast cells activated ?
By tissue damage
Or antigens interacting with surface IgE
What do mast cells produce ?
Histamine
Leukotrienes
Prostaglandins
Histamines role
Vascular dilation and permeability
Leukotrienes role
Act as a chemoattractant for other white blood cells
Prostaglandins function
Vascular dilation and pain
What does the coagulation pathway result in ?
Fibrin production to contain infection in a ‘mesh’.
When coagulation factor 12 is activated, bradykinin is produced - vasodilation and sensitises pain receptors.
Abscess
Pus enclosed by fibrin and connective tissue
Pus
Inflammatory exudate rich in neutrophils, organisms and dead tissue
Empyema
Pus enclosed in an existing body cavity eg gall bladder, pleura etc.
What are some beneficial effects of acute inflammation ?
Dilution of toxins
Effector cells and antibodies (and antibiotics) get to the area
Fibrin helps to “wall-off” further spread of infection
Antigens get carried to local and regional lymph nodes- prevents systemic spread and allows antibodies to be made
What are some harmful effects of acute inflammation ?
Destruction of normal tissues eg colo-vesical fistula.
Swelling within a confined space eg brain.
SEPSIS
Cytokine storm
Systemic effects of acute inflammation
Monocyte/macrophage derived TNF and IL-1 cause re-setting of temperature control at hypothalamus
Results of systemic effects of acute inflammation
Production of Granulocyte colony stimulating factor (G-CSF)- increase production and release of neutrophils from marrow
Rise in “acute phase proteins” eg C-reactive protein (CRP)- assists complement binding to microbes
Rise in immunoglobulins (later in acute inflammation)
Chronic
Goes on for a long time. e.g. months, years
What happens in chronic inflammation ?
Tissue damage, inflammation, healing going on at same time
What types of cells are involved in chronic inflammation ?
macrophages, lymphocytes, plasma cells rather than neutrophils
Chronic vs Acute inflammation
Chronic inflammation goes on for a long time, whereas acute inflammation is resolved quickly.
Factors promoting resolution of acute inflammation
Minimal cell death and tissue loss
An organ with good regenerative capacity
Rapid destruction of the causative agent
Rapid removal of fluid and debris by good blood supply
Good nutrition and immune function
As part of resolution of acute inflammation, what is the damaged/dead tissue organised into ?
Granulation Tissue
Role of macrophages
Digests debris
What does granulation tissue contain ?
Macrophages
Fibroblasts
New blood vessels
Role of fibroblasts
Provide scaffolding for repair
Role of new blood vessels
Allow nutrients for regeneration of tissues
What is the end result of using granulation tissue ?
Healing, often with some scarring.
Primary chronic inflammation examples
Leprosy
TB
Asbestosis
Inflammatory Bowel disease
Rheumatoid arthritis
Examples of progression from acute to chronic
Osteomyelitis, foreign body
Causes of chronic inflammation processing from acute inflammation - osteomyelitis
Poor blood supply, pus can’t drain away, pools under periosteum, portion of bone dies which stimulates chronic inflammation
What are some consequences of chronic inflammation ?
Fevers, weight loss, malaise.
Fibrosis and hence distortion of tissues.
Amyloid deposition.
Reduced growth in children.
Anaemia of chronic disease.
What can macrophages produce which is bad ?
Peroxynitrite and TNF which cause DNA damage.
Via a multi-hit mechanism, accumulated DNA damage and hence mutations leads to cancer
What makes TB cells difficult to kill ?
Waxy coating on cell walls
What is the hallmark of chronic inflammation ?
Macrophages
What do macrophages produce that can cause DNA damage ?
peroxynitrite and TNF
What does accumulated DNA damage lead to ?
Mutations
Cancer
What increases the risk of gastric cancer ?
Helicobacter pylori infection
What increases the risk of cervical cancer ?
Papilloma virus
What increases the risk of liver cancer ?
Hepatitis B and C
What increases the risk of bowel cancer ?
Chronic inflammatory bowel disease
