05-10-21 - Acute Inflammation Flashcards
What are the causes of acute inflammation?
What causes are the most common?
- Microbial infection (primary cause)
- Hypersensitivity (allergic) reactions (primary cause)
- Physical agents
- Chemical agents
What are the 5 signs of acute inflammation?
What causes them?
Red (rubor)
• Caused by dilation of blood vessels
Hot (calor)
• Peripheral increase in temperature
• Due to increased blood flow (hyperaemia)
Swollen (tumor)
• Due to mainly oedema (swelling caused by fluid build up)
• Some contribution from inflammatory cells
Painful/tendor (dolor)
• Stimulation of nerve endings by pressure and chemical mediators
Loss of function
What are the 2 initial phases of acute inflammation?
- Vascular phase – dilation and increased permeability
- Exudative phase – fluid and cells escape from permeable venules, with the neutrophil polymorph being the most common cell to leak out
How does dilation occur during the vascular phase? What is it caused by?
- Capillary beds that are mainly empty start to contain blood, cells, and fluid
- This is from the release and activation of the pre-capillary sphincters, which leads to the opening of significant numbers of capillary beds
What causes the increased vascular permeability during the vascular phase?
What happens during this process?
Where does it occur?
- The increase in vascular permeability of the vascular phase is produced by chemical mediators, including histamine and bradykinin
- It involves the stimulation of endothelial cells cytoskeleton by chemical mediators, which causes transient intercellular gaps (between the cells) to appear.
- The endothelial cells are not damaged in this process, just moved slightly
- This increase in vascular permeability is confined to post capillary venules
How does the exudate phase occur in venules?
What would occur normally?
What does the exudate contain?
What is a feature of this exudate?
- During the exudate phase, there is an increase in hydrostatic pressure (outwards), which causes fluid and proteins to be pushed out into the localised damaged tissue surrounding the venules.
- In transudate (normal) circumstances, any outflow of fluid is compensated by inflow of fluid (oncotic pressure)
- The exudate has a high protein content including:
- Immunoglobulins – may be important for destruction of invading organisms
- Fibrinogen – this is used to develop fibrin, which is a protein that forms a mesh that impedes blood flow (clot), which can prevent/ mitigate invasion by pathogens
- Fibrin makes extravascular contact, and is found on the surfaces of acutely inflamed organs
- The exudate has a high turn over rate, and is continuously removed by lymphatics
What conditions are exudate and transudate under?
How do they differ?
Exudate – occurs under acute inflammatory process
• Net flow out of fluid release and proteins
• Increased vascular permeability
• High protein content
Transudate – normal circumstances
• No net flow out
• Normal vascular permeability
• Low protein content
What happens to the lymphatic system during acute inflammation?
What is the role of the lymphatic system in acute inflammation?
What are the conditions involving the lymphatic system can be seen due to acute inflammation?
- The lymphatics become dilated during acute inflammation
- The lymphatics drain the fluid from the exudate
- Antigens are carried to the local lymph nodes
- These antigens can then interact with a wide range of immune cells in the lymph nodes, which can then start to generate an immune response
- Lymphangitis – Inflammation of the lymphatic system
- Lymphadenitis – Inflammation of the local lymph node
What is the diagnostic feature of acute inflammation?
What are the 6 tasks neutrophils can perform?
Why might these be harmful?
What must be able to happen to prevent unnecessary damage?
• Neutrophil accumulation in the extracellular space is the diagnostic feature of acute inflammations
Neutrophils can: • Kill organisms • Degrade necrotic tissue • Ingest offending agents • Produce chemical mediators • Produce toxic radicals to kill foreign bodies • Produce tissue damaging enzymes
If the process of acute inflammation goes on for too long, these functions of neutrophils can result in tissue damage, so the reaction must be able to start and stop. The reaction has to be able to be turned on, aswell as off, in order to prevent unnecessary damage
What is the process that involves neutrophils (and other cells in exudate) moving into the inflamed area around venules?
How does this process occur?
- Neutrophils moving out of the vessels into the inflamed area is caused transmigration
- The vessel wall begins to express certain molecules (expressional proteins, like selectins and integrins), which react with the receptors on the neutrophils cell membrane
- This causes the neutrophils to attach to the venule wall with higher affinity, pavement (flatten), and squeeze through the gaps between the endothelial cells, which were formed in the vascular phase
What is chemotaxis?
What are some compounds for the chemotaxis of neutrophils?
- Chemotaxis is the movement of a motile organism in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance.
- Chemotactic compounds include:
- Bacterial products
- Some complement components (system of plasma proteins e.x serum proteins)
- Products of neutrophil activity
What are chemical mediators for in acute inflammation?
What are they made from?
What 5 things do they make happen?
- Chemical mediators spread from the injured tissue out into uninjured areas
- These chemical mediators are derived from cells and extracellular resources e.g. plasma
- The chemical mediaotrs cause:
- Increased vascular permeability
- Vasodilation
- Emigration of neutrophils
- Chemotaxis
- Itching and pain.
Cellular
phase- roles
of
macrophages
Tissue damage activates resting macrophages to produce-
- Chemokines and Interleukin-1 (IL-1) which stimulate adhesion molecules on endothelium and white cells
- Tumour necrosis factor (TNF) which stimulates vascular permeability
- Macrophages (derived from circulating monocytes) role of clearing debris and dead cells
Cellular
phase-
neutrophils
- Migration into tissues
- Recognise bacteria by - formylmethionine at end of surface protein chains
-coating of antibody or complement (C3b) - Phagocytose
- Kill bacteria via lysozyme destroying cell wall and via hydrogen peroxide production
- Very short life-span (8-12 hrs)- then apoptosis so ongoing acute inflammation needs new cells to be attracted in
Cellular phase-
mast
cells/basophils
- Activated by- -tissue damage - complement-derived C3a and C5a - antigens interacting with surface IgE (see white blood
cell lecture) - Produce-
- histamine-vascular dilatation and permeability - leukotrienes- chemotactic for other white blood cells - prostaglandins- vascular dilatation and pain
Plasma mediators of inflammation
- Coagulation pathway resulting in fibrin production to contain infection in a “mesh” (wait for 2002 coagulation lecture)
- Complement system (wait for 2002
innate immunity lecture) - When coagulation factor XII is activated,
bradykinin is produced- vasodilatation
and sensitises pain receptors
Recognising macroscopic appearance of inflammation- depends on site in the body
.
Microscopic appearance
.
Sub- types of
acute inflammation
- Serous
- Membranous
- Suppurative/purulent
- Haemorrhagic
- Fibrinous
- Catarrhal
What are 3 of the harmful effects of acute inflammation?
- Digestion of normal tissues
- Swelling e.g laryngeal oedema (fluid build-up) , brain swelling
- Inappropriate inflammatory response e.g type 1 hypersensitive (allergic reactions)
- The IgE antibody gets stimulated by allergens (such as pollen in hay fever) which causes the degranulation of the mast cell (White blood cell).
What are 3 systemic effects of thermoregulation?
What are symptoms of chronic 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)
