Inflammation and repair (1) Flashcards
Define inflammation
“the vascular and cellular response to injury in cells and tissues”
An inflammatory condition carries the suffix –itis
What are the cardinal signs of inflammation?
Heat and redness = vascular changes (vasodilation) bringing more blood to the affected area.
Swelling = the exudation of fluid into the tissue from the circulatory system.
Pain = the activation of chemical mediators and the swelling of tissues.
Loss of function may be due to a voluntary reluctance to move the injured part (sprains, fractures)
or
the loss of function of an organ due to inflammation (i.e. mastitis leads to a decreased milk production, hepatitis leads to jaundice due to impaired function of hepatocytes)
What is the inflammatory process designed to do?
minimise damage caused by an agent
destroy invading organisms
dilute out toxins
initiate repair
What are the different categories of inflammation?
acute and chronic inflammation, and repair (regeneration)
Define per-acute
couple of hours i.e. nettle sting, insect stings, haemorrhage
Define acute
initiated in 4 – 6 hours – oedema, hyperaemia, +/- cells (role of lymphatics)
Define subacute
days → weeks; ↓vascular ↑cells & repair
Define chronic
stimulus not removed, more obvious repair
Define chronic - active
can have acute stages in a chronic reaction
Define an exudate
the active movement of cells and fluid into the injured area from the circulation
What is the stimulus for exudate?
release of chemical mediators from damaged cells that set up a chain of interacting chemicals
Some chemicals cause vasodilation, whilst others will attract WBCs into the area (chemotaxis)
Chemical mediators are the basis of the exudative response
Where can chemical mediators originate?
Stored in cells and directly released i.e. histamine
Present in plasma and rapid synthesis i.e., bradykinin
Secreted from activated WBCs i.e. leukotrienes; cytokines – interleukins, chemokines
What affects can chemical mediators have?
Enhance blood flow
↑ vascular permeability
Induce emigration of wbcs → site of injury (chemotaxis)
What is the purpose of the exudative response?
Dilutes out irritants (bacterial exotoxins, some chemokines)
Fibrin clot formed → scaffold for repair / cell movement
Gel formation (HA acid & proteoglycans) → cell movement and traps foreign particles
What is the order of actions for inflammation?
the first response is the dilation of small blood vessels in the area of the injury,
followed by an increased permeability of the vessel walls
Plasma and cells (WBCs) can then move out into the injured tissue
Describe vasodilation during acute inflammation
↑ permeability of bvs initially a histamine response (antihistamines) from resident Mast Cells
transient↑ hydrostatic pressure in venules – transudate
then character changes to exudate
Describe the cellular response
Neutrophils are the first WBC to move out of the circulation and into the site of tissue injury
Monocytes are the next; once they reach the tissue spaces they become known as macrophages (histiocytes)
Lymphocytes are the last cell type to arrive; these eventually become plasma cells
Describe granulocytes
neutrophils, eosinophils, and basophils.
termed granulocytes → numerous small granules within their cytoplasm.
staining characteristics give them their name.
neutro = neutral (granules stain very pale pink and blue)
eosino = pink/red staining
baso =blue staining
Describe WBC granules (Lysosomes)
Majority microbicidal
Many different classes
Proteinases important in inflammation and remodelling & repair i.e. collagenase (MMP-8; metallo-matrix proteinase – enzymes that degrade ECM)
Also enzymes that degrade CHO & lipid etc.
(antiproteinases circulate in the blood!)
Describe neutrophils
Neutrophils are the most abundant cell in the granulocytic series
Dead and dying neutrophils are the chief component of pus
Two populations in blood
Marginated pool (primarily in microcirculation)
Circulating pool
In localised area of inflammation ↑ marginated pool (corticosteroids promote loss of adhesiveness → ↓marginated pool)
They have amoeboid activity
What are neutrophils attracted to?
particularly attracted by bacterial infections, necrotic tissue and antigen-antibody complexes that fix complement
What roles can neutrophiles play?
degranulate releasing lysosomal contents → lyse damaged cells and invading micro-organisms, or
phagocytose invading micro-organisms or necrotic cell components.
Describe eosinophils
Eosinophils react in a similar mode to neutrophils;
Connected to surfaces (gut, lung, skin)
Have MMPs in granules; in large numbers can degrade massive quantities of collagen
particularly associated with parasitic infections and allergic reactions
also phagocytic and produce pus, which tends to have a greenish tinge
Describe basophils
Basophils are the least numerous granulocyte, and have similar functions to mast cells.
They are not specifically associated with lesions
Describe mononuclear cells
lymphocytes (plasma cells)
monocytes (macrophages)
epitheliod cells
giant cells
Describe lymphocytes
Lymphocytes are associated with the immune and innate responses and are not phagocytic.
Lymphocytes circulate around both the circulatory system and the lymphatic system, crossing from one to another
Lymphocytes stain with a bluish cytoplasm and have a dark unsegmented staining nucleus
What are the three main types of lymphocytes?
B lymphocytes are associated with the production of humoral antibodies.
T lymphocytes (helper & cytotoxic) are associated with cell-mediated immunity.
Natural killer cells are part of the innate immune system – recognise changes on cell membranes of infected cells
Describe plasma cells
Plasma Cells are formed from B lymphocytes
They produce and store antibody, if they are present in a tissue section it is an indication that a humoral immune response has occurred
Plasma cells are rarely seen in circulating blood.
In tissues they appear with dark blue staining cytoplasm and a dark unsegmented nucleus
Describe macrophages
Macrophages derived from circulating monocytes
main role is the phagocytosis of foreign material & the breakdown of collagen.
also process antigens before presenting them to antibody producing cells
Their presence in tissue often associated with either chronic infection and inflammation, or clearing up the debris (repair)
appearance variable, with both nucleus and cytoplasm varying in size and colour
Name some chemical mediators that macrophages synthesis
Cytokines (IL-1 interleukin; TNFα tumour necrosis factor → acute phase response)
Proteinases
Lipid mediators (PAF, PG, leukotrienes)
NO & O2 radicals (for killing)
Describe epitheliod cells
Formed from macrophages
Tend to lie close together with interdigitating cell membranes, makes it difficult to determine their boundaries.
Describe giant cells
Formed from macrophages
Giant Cells are formed by fusion of macrophages
very large cells multinucleated, shape quite irregular
What do epitheliod and giant cells have in common?
Both types of cell are associated with chronic granulomatous lesions, such as those caused by Mycobacteria spp.
What are the sequence of events in acute inflammation (also name the mechanism)
Transient vasoconstriction (lasts a few seconds)- Neurogenic
Vasodilation (mins-> hours & longer) - histamine
Increase vol. blood flow - vasodilation
Increased vascular permeability - Histamine, leukotrienes
Rate/speed of flow decreases-caused by vasodilation, increase local PCV
Margination of WBCs along bv walls - Decreased rate flow -> WBC adhere to cells of endothelial wall
Exudation-WBCs migrateout into tissues
