Inflammation

Question 1

What is acute inflammation?

Answer 1

Rapid non-specific response to cellular injury. Orchestrated when cells release mediators and leukocytes and vascular system responds.

Question 2

What is chronic inflammation?

Answer 2

Persistent inflammatory response. Ongoing inflammation and may arise from acute inflammation. In an attempt to heal damage.

Question 3

Cardinal signs of acute infection? (x5)

Answer 3

Rubor (redness) Calor (Heat) Tumor (swelling) Dolor (pain) Fifth feature that some say, is loss of function.

Question 4

What are the three stages of acute inflammation? Link with the cardinal signs.

Answer 4

1. Increased blood flow (explains why red and hot). 2. Structural change to the microvasculature to allow proteins and leukocytes to leave circulation (swelling). 3. Emigration, accumulation and activation of leukocytes at focus of injury. Action of leukocyte = pain.

Question 5

What are the mediators and what do they do in the acute inflammatory response?

Answer 5

Induced by several mediators including HISTAMINE and nitric oxide which affect smooth muscle and induces vasodilation. CYTOKINES are responsible for endothelial activation and attracting leukocytes to the site.

Question 6

What happens to flow over the site in acute inflammation? (x2 points)

Answer 6

Results in vasodilation which INCREASES FLOW and increased permeability. Leakiness and increased diameter means that flow is slower - leads to stasis (inactivity) over site of inflammation which can be useful for making sure everything is there for dealing with the injury.

Question 7

Where is histamine MAINLY released?

Answer 7

Mast cell is major source of histamine.

Question 8

What is the mechanism for increased vascular permeability? Name of process?

Answer 8

Endothelial cells CONTRACT, so increased interendothelial spacing (holes). Called Immediate Transient Response.

Question 9

What causes vascular leakiness? (x1 for I-T Response, and x3 for other explanations)

Answer 9

Histamine and other chemicals produces immediate transient response. BUT, IT MAY NOT ALWAYS BE ENDOTHELIAL CONTRACTION THAT LEADS TO LEAKINESS… Endothelial cell injury. Leukocyte-mediated cell injury (late stage inflammation). Leukocyte can produce additional signals for leakiness. VEGF increases transfer of materials across cells.

Question 10

What is an exudate?

Answer 10

Materials that have seeped out of blood vessels that shouldn’t have e.g. proteins and cells.

Question 11

Examples of exudate? (x2) [Not needed but helps understanding.]

Answer 11

Blister liquid (quite watery) and pus (lots of cells).

Question 12

What are the main leukocytes in the acute inflammatory response?

Answer 12

Initially, the most important leukocytes are those capable of phagocytosis: NEUTROPHILS and MACROPHAGES. NEUTROPHIL is by far the main one!!! What do leukocytes GENERALLY do and how is their response delivered? Leukocytes recognise microbes and necrotic tissue with receptors and are activated. Kill bacteria and eliminate necrotic material. Also produce multiple factors and mediators that interact with other cells.

Question 13

What are the roles of neutrophils? (x3)

Answer 13

Phagocytosis. Recruit additional cells. Degranulation (secrete enzymes, free radicals, soluble mediators).

Question 14

What makes the acute inflammatory response terminate? (x4)

Answer 14

Mediators and neutrophils have short half-life. Macrophages release anti-inflammatory products. Mast cells and lymphocytes produce anti-inflammatory products like Lipoxins. The cause of the injury is removed.

Question 15

How can an acute infection be identified histologically?

Answer 15

Vessels filled thickly with blood. Dense cloud of neutrophils can be seen. Would also be able to see Eosinophils and mast cells.

1st Photo = neutrophil
2nd photo = eosinophil

Question 16

Causes of chronic inflammation? (x4)

Answer 16

Persistent infection. Prolonged exposure to toxins (endogenous or exogenous), so inflammatory response never has the chance to remove the harmful specimen – which of course is its aim. Autoimmunity. Foreign body may be hard to remove e.g. silica.

Question 17

What is a chronic inflammation characterised by? (x3)

Answer 17

Tissue destruction. Persistent inflammation. Attempts at healing by replacement of damaged tissue with CONNECTIVE tissue. All occur simultaneously.

Question 18

What cells are involved in the chronic inflammatory response? (x3)

Answer 18

Macrophages and T-lymphocytes very important (unlike neutrophils in acute inflammatory response). T-lymphocytes can be cytotoxic. Plasma cells (develop from B-lymphocytes).

Question 19

Where are macrophage names? (x3)

Answer 19

Bone marrow (where they originate) called monoblasts. Circulate in blood - called monocytes. Become macrophages when in tissues.

Question 20

What are the actions of macrophages? (x4)

Answer 20

Phagocytosis (this would take them down the acute inflammatory response). Amplification of inflammation through cytokine release. This way, they control many other inflammatory cells. Wound repair and fibrosis (chronic). Each cycle of injury initiates another inflammatory response – hence why it is chronic. Anti-inflammatory effects (chronic). Dampen the pathogenic inflammatory response because they aim to repair things simultaneously.

Question 21

What are the differences in outcomes of chronic inflammation when compared with acute infection? (x4)

Answer 21

SCARRING from necrosis more prominent in chronic infection. Formation of granulation tissue (new connective tissue) from attempted repair. No exudate in chronic inflammation. Loss of function much more common in chronic inflammation.

Question 22

What does a chronic infection look like histologically?

Answer 22

Macrophages, lymphocytes and plasma cells will be abundant. Will see a granulation tissue – will look very loose and messy. Lots of cross-sections and fibroblasts.

1st picture is macrophage
2nd picture is lymphocyte
3rd picture is plasma cell

Question 23

How do mediators differ between chronic and acute infections?

Answer 23

Acute – predominantly histamines. Chronic – predominantly cytokines.

Question 24

What is granulomatous inflammation?

Answer 24

Subtype of chronic inflammation. Contains a granuloma. Granuloma is a cluster macrophages, triggered by a STRONG, specific T-lymphocyte reaction. It attempts to eliminate a RESISTANT offending agent, and does so my aggregating together (share nucleus).

Question 25

What causes granulomatous inflammation?

Answer 25

Infections Foreign material Reactions to tumours Immunological diseases.

Question 26

What do granulomatous inflammations look like histologically?

Answer 26

Will see a big swirl of cells. And around that swirl, you will see huge, dense masses that are multi-nucleated. These are the granulomas.

Question 27

What are the long-term sequelae of inflammation? (x3 and x2(x2)).

Answer 27

POSITIVE OUTCOMES: Removal of offending agent. Cessation of the inflammatory response. Healing of the tissue damage with preservation of function – resolution! NEGATIVE OUTCOMES: Excessive tissue damage and scarring, possibly with detrimental effect on adjacent tissue which must pick up the slack. Systemic involvement with multiorgan failure – septic shock where fluid goes into inflammation and lost in circulatory system OR amyloid – abnormal protein build-up which decrease function of the organ they’re deposited in.

Question 28

What are the two ways wounds heal?

Answer 28

Resolution (tissue regeneration of damaged tissue which restores function – as if nothing happened before). Scarring (Results in loss of function).

Question 29

When does scarring occur?

Answer 29

When there’s significant tissue loss and tissue is unable to regenerate. OCCURS MOST USUALLY BECAUSE OF CHRONIC INFLAMMATION.

Question 30

When does resolution occur? (x2)

Answer 30

Tissue contains cells that are capable of regeneration. Little structural damage done.

Question 31

What happens from before inflammation --\> resolution – four stages?

Answer 31

Exudate builds up – white cells, fibrin as it deals with the infectious agent. Red hepatisation – erythrocytes move in --\> makes it feel like liver Erythrocytes break down causing grey hepatisation. Dead cells and bacteria are cleared – resorption of consolidated exudate.

Question 32

What is happens in the process of scarring? (x2)

Answer 32

Fibroblasts – produce collagen. (Collagen – strong scar type collagen.) Remodelling – reorganisation of collagen fibres for maximal tensile strength.

Question 33

How may wound healing be impaired? (x7) NVM SSFM (NeVerMind, SSssssFM)

Answer 33

GENERAL Poor nutrition (needs protein (for structural repairs) and ENERGY). Vitamin deficiency (Vitamin A and C used as cofactors). Mineral deficiency (for same reasons). Suppressed inflammation (steroids, old age). LOCAL Poor local blood supply (peripheral vascular disease). Persistent foreign body (so very difficult to heal). If every time you move, the wound opens again, the healing process with must restart.

Question 34

Complications of repair? (x3)

Answer 34

Keloid formation: Instead of a wound closing up, there is excess collagen deposition. [photo]. Contractures: fibrous scar contracts as part of its maturing process. If this happens across a joint, you can get reduced joint mobility. Impaired organ function: fibrous scars forming in organs will cause loss of functional tissue which can affect function.

Question 35

What is an aneurysm?

Answer 35

An abnormal blood-filled bulge of a blood vessel resulting from weakening of the vessel wall – especially in arteries.