Inflammation and repair (1)

Question 1

Define inflammation

Answer 1

“the vascular and cellular response to injury in cells and tissues”

An inflammatory condition carries the suffix –itis

Question 2

What are the cardinal signs of inflammation?

Answer 2

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)

Question 3

What is the inflammatory process designed to do?

Answer 3

minimise damage caused by an agent

destroy invading organisms

dilute out toxins

initiate repair

Question 4

What are the different categories of inflammation?

Answer 4

acute and chronic inflammation, and repair (regeneration)

Question 5

Define per-acute

Answer 5

couple of hours i.e. nettle sting, insect stings, haemorrhage

Question 6

Define acute

Answer 6

initiated in 4 – 6 hours – oedema, hyperaemia, +/- cells (role of lymphatics)

Question 7

Define subacute

Answer 7

days → weeks; ↓vascular ↑cells & repair

Question 8

Define chronic

Answer 8

stimulus not removed, more obvious repair

Question 9

Define chronic - active

Answer 9

can have acute stages in a chronic reaction

Question 10

Define an exudate

Answer 10

the active movement of cells and fluid into the injured area from the circulation

Question 11

What is the stimulus for exudate?

Answer 11

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

Question 12

Where can chemical mediators originate?

Answer 12

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

Question 13

What affects can chemical mediators have?

Answer 13

Enhance blood flow

↑ vascular permeability

Induce emigration of wbcs → site of injury (chemotaxis)

Question 14

What is the purpose of the exudative response?

Answer 14

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

Question 15

What is the order of actions for inflammation?

Answer 15

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

Question 16

Describe vasodilation during acute inflammation

Answer 16

↑ permeability of bvs initially a histamine response (antihistamines) from resident Mast Cells

transient↑ hydrostatic pressure in venules – transudate

then character changes to exudate

Question 17

Describe the cellular response

Answer 17

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

Question 18

Describe granulocytes

Answer 18

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

Question 19

Describe WBC granules (Lysosomes)

Answer 19

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!)

Question 20

Describe neutrophils

Answer 20

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

Question 21

What are neutrophils attracted to?

Answer 21

particularly attracted by bacterial infections, necrotic tissue and antigen-antibody complexes that fix complement

Question 22

What roles can neutrophiles play?

Answer 22

degranulate releasing lysosomal contents → lyse damaged cells and invading micro-organisms, or

phagocytose invading micro-organisms or necrotic cell components.

Question 23

Describe eosinophils

Answer 23

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

Question 24

Describe basophils

Answer 24

Basophils are the least numerous granulocyte, and have similar functions to mast cells.

They are not specifically associated with lesions

Question 25

Describe mononuclear cells

Answer 25

lymphocytes (plasma cells) monocytes (macrophages) epitheliod cells giant cells

Question 26

Describe lymphocytes

Answer 26

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

Question 27

What are the three main types of lymphocytes?

Answer 27

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

Question 28

Describe plasma cells

Answer 28

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

Question 29

Describe macrophages

Answer 29

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

Question 30

Name some chemical mediators that macrophages synthesis

Answer 30

Cytokines (IL-1 interleukin; TNFα tumour necrosis factor → acute phase response) Proteinases Lipid mediators (PAF, PG, leukotrienes) NO & O2 radicals (for killing)

Question 31

Describe epitheliod cells

Answer 31

Formed from macrophages Tend to lie close together with interdigitating cell membranes, makes it difficult to determine their boundaries.

Question 32

Describe giant cells

Answer 32

Formed from macrophages Giant Cells are formed by fusion of macrophages very large cells multinucleated, shape quite irregular

Question 33

What do epitheliod and giant cells have in common?

Answer 33

Both types of cell are associated with chronic granulomatous lesions, such as those caused by Mycobacteria spp.

Question 34

What are the sequence of events in acute inflammation (also name the mechanism)

Answer 34

``` 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