Acute inflammation

Question 1

Define acute inflammation?

Answer 1

inflammation
-fundamental response
-dynamic, homeostatic mechanism
-you find a series of protective changes occurring in living tissue as a response to injury

Question 2

Name the cardinal signs of inflammation?

Answer 2

rubor - redness, darkening
calor - heat
tumor - swelling
dolor - pain
loss of function

Question 3

List the causes of acute inflammation?

Answer 3

-micro-organisms
-trauma
-exposure to chemicals
-physical- extreme conditions
-dead tissue (cell necrosis irritates adjacent tissues)
-hypersensitivity

Question 4

What is the microcirculation?

Answer 4

All over us

It is the capillary beds, fed by arterioles and drained by venules but also the extracellular compartment - fluid and molecules within it.

Also includes the lymphatic channels and lymphatic drainage channels.

Occurs in a dynamic balance- things move but in a way which is balanced

Question 5

What happens in micro circulation?

Answer 5

fluid moves essentially from the vessels into the tissue

Question 6

Pathogenesis of acute inflammation?

Answer 6

changes in vessel radius- alter the amount of flow through the vessel

change in permeability of the vessel wall-endothelium becomes more permissive or less permissive (exudation)

movement of neutrophils from the vessel to the extravascular space

Question 7

Describe what happens with the local changes in vessel radius and blood flow?

Answer 7

1.transient arteriolar constriction
-transient constriction of the feeding arterials
-probably protective
2. local arteriolar dilation
-active hyperaemia
-see more blood in those vessels
-widen radius
3. relaxation of vessel smooth muscle that covers vessel wall

The triple response- goes red, redness about it and then swelling

Question 8

How does increased permeability occur?

Answer 8

-happens in the vessels, in the microvascular bed
-caused by locally produced chemical mediators (small mols from cells) which increase permeability of endothelial cells (lining vessels) and make it leak
-When leaks, leaks fluid. Protein and fluid not held in vessel lumin- escape into adjacent tissue

Question 9

Effects of increased permeability?

Answer 9

net movement of plasma from capillaries to extravascular space (exudation)

what is leaked is an exudate

exudate-exudate - fluid rich in protein - like plasma - includes immunoglobulin and fibrinogen

Question 10

Effects of exudation?

Answer 10

oedema formed

oedema is accumulation of fluid in the extravascular space

explains swelling of tissue in acute inflammation because movement of fluid across membrane

swelling causes pain - reduce function

Question 11

What is a further effect of increased permeability?

Answer 11

fluid loss-increased viscosity
increased viscosity-stasis
got all cells in blood and less plasma holding them up and the rate of flow slows (stasis)

Question 12

What happens to flow in inflammation?

Answer 12

loss of normal laminar flow
red cells aggregate in the centre of the lumen
neutrophils found near endothelium

Question 13

What are the phases of emigration of neutrophils?

Answer 13

margination - neutrophils move to endothelial aspect of lumen
pavementing - neutrophils adhere to endothelium
emigration - neutrophils squeeze between endothelial cells - active process - to extravascular tissues

Question 14

Describe gingivitis?

Answer 14

gums are swollen and inflamed
associated with certain types of acute leukaemias

Question 15

Describe acute pyelonephritis?

Answer 15

tubules inside kidney have blood and pus coming through

Question 16

Describe bacterial endocarditis?

Answer 16

vegetations(mix of fibrin, neutrophils and micro organisms stuck on the atrial surface - of cusp)

Question 17

What happens after acute inflammation?

Answer 17

inciting agent isolated and destroyed
macrophages move in from blood and phagocytose debris; then they leave
epithelial surfaces regenerate (skin heals)
inflammatory exudate filters away
vascular changes return to normal
inflammation resolves

Question 18

What are the benefits of acute inflammation?

Answer 18

rapid response to non-specific insult
cardinal signs and loss of function
transient protection of inflamed area
neutrophils destroy organisms and denature antigen for macrophages to phagocytose
plasma proteins localise process
resolution and return to normal

Question 19

Outcomes of acute inflammation?

Answer 19

resolution
suppuration (pus formation)
organisation (tissue repair)
chronic inflammation( inflammation doesn’t go away- associated with tissue damage)

Question 20

Describe the role of the neutrophil?

Answer 20

mobile phagocytes
-recognise foreign antigen
-move towards it - chemotaxis
-adhere to organism

granules possess oxidants (eg H2O2) and enzymes (eg proteases)

release granule contents

phagocytose & destroy foreign antigen

Question 21

Why is lung inflammation called pneumonia and not lung-itis?

Answer 21

inflammatory process in pneumonia doesn’t really sit in the lung tissue primarily but in air space within lung

Question 22

Consequences of neutrophil action?

Answer 22

neutophils die when granule contents released
produce a “soup” of fluid, bits of cell, organisms, endogenous proteins - pus
might extend into other tissues, progressing the inflammation

Question 23

Role fibrinogen (plasma protein) in inflammation?

Answer 23

Fibrinogen- coagulation factor
-floats around as blood plasma and under circumstances it coagulates to form fibrin (series of fibrogen mols all bonded together)
-when fibrinogen escapes from vessel due to increased permeability
-becomes in contact with what is around, including enzymes released by neutrophils-which are proteases
-protease chips off a bit of fibrinogen and makes it sticky and it then forms a polymer with other fibrinogen to produce fibrin
-clots the exudate and in doing so, localises the inflammatory process and its less easy for it to leak away into the adjacent lymphatics

Question 24

Role of immunoglobulins in the plasma?

Answer 24

immunoglobulins in plasma specific for antigen - humoural immune response

Question 25

List mediators of acute inflammation and describe functions?

Answer 25

molecules on endothelial cell surface membrane molecules released from cells molecules in the plasma molecules inside cells

Question 26

What are the collective effects of mediators?

Answer 26

vasodilatation- increasing blood flow into area increased permeability- increases leakiness of the endothelium and then thereby increases the permeability of the endothelium to the flow of plasma and its contents across the membrane neutrophil adhesion chemotaxis- attracting neutrophils as transverse the tissue itch and pain

Question 27

Give examples of the cell surface mediators?

Answer 27

adhesion molecules appear on endothelial cells eg ICAM-1 - help neutrophils stick P-selectin - interacts with neutrophil surface

Question 28

Give characteristics of histamine? (mols released from cells)

Answer 28

Histamine (causing vasodilation and increased permeability) -sits in mast cells beside vessels, platelets and in basophils -because of local injury (IgE mediated, histamine is released and has the effects of vasodilation and increased permeability Causes smooth muscle to relax -when histamine is released it acts to H1 receptors on endothelial cells

Question 29

Give characteristics of seratonin (mols released from cells)?

Answer 29

5-hydroxytryptamine (serotonin) (causing vasoconstriction) -found pre formed in platelets -when platelets begin to coagulate, the granules and platelets begin to fall apart and release the content. -causes vasoconstriction

Question 30

Give characteristics of prostglandins (arachidonic acid metabolites via cyclo-oxygenase pathway)?

Answer 30

many cells (endothelium and leukocytes) many promote histamine effects and inhibit inflammatory cells thromboxane A2 promotes platelet aggregation and vasoconstriction – the opposite effect to PGD2, PGE2, etc prostglandins increase effectiveness of non-steroidal anti-inflammatory drugs. Counter acting

Question 31

Give characteristics of cytokines and chemokines? (eg TNFα, IL-1)

Answer 31

small molecules produced by macrophages, lymphocytes, endothelium in response to inflammatory stimuli pro-inflammatory and anti-inflammatory effects different molecules have different effect balance of effects stimulate intracellular pathways and signalling

Question 32

Give characteristics of nitric oxide (molecule released from cells)?

Answer 32

smooth muscle relaxation, anti-platelet, regulate leukocyte recruitment to inflammatory focus

Question 33

Give characteristics of oxygen free radicals?

Answer 33

released by neutrophils on phagocytosis amplify other mediator effects

Question 34

What do molecules inside cells have the role of doing?

Answer 34

pattern associated molecular patterns -microbial antigen -genetically hard wired to recognise -innate and adaptive immunity danger associated molecular patterns -substances released in response to stimulus stimulate pattern recognition receptors on cell membranes to activate inflammatory response

Question 35

Give examples of intracellular inflammatory pathways and their functions?

Answer 35

NF-κB (nuclear factor kappa-B) pathway MAPK (mitogen-activated protein kinase) Stimulated in inflammation via surface receptors eg toll-like receptors (TLRs) Regulates pro-inflammatory cytokine production and inflammatory cell recruitment JAK-STAT (Janus kinase – signal transducer and activator to transcription) pathway Direct translation of extracellular signal to molecular expression

Question 36

Describe the mechanism of the intracellular signalling pathway?

Answer 36

Microorganism floating around in our blood, releases an unpleasant product. And the unpleasant product works on the cell surface receptor. After this happens, through a number of different pathways, you see activation of NF kappa B or the MAPK pathway. Result is an inflammatory cytokine production occurring (in nucleus)

Question 37

Give the four enzyme cascades in blood plasma and what their function is?

Answer 37

blood coagulation pathways -clots fibrinogen in exudate and interacts widely with other systems fibrinolysis breaks down fibrin, helps maintain blood supply and fibrin breakdown products vasoactive kinin system bradykinin: pain complement cascade ties inflammation with immune system active components stimulate increased permeability, chemotaxis, phagocytosis, cell breakdown

Question 38

What are the general effects of mediators?

Answer 38

mediators have positive and negative effects result is a dynamic balance favours and inhibits acute inflammation relative to need

Question 39

What are the immediate systemic effects of inflammation?

Answer 39

pyrexia - raised temperature endogenous pyrogens from white cells act centrally feel unwell malaise, anorexia, nausea abdominal pain and vomiting in children neutrophilia - raised white cell count bone marrow releases/produces

Question 40

What are the longer term effects of acute inflammation?

Answer 40

lymphadenopathy - regional lymph node enlargement immune response weight loss - catabolic process anaemia

Question 41

Describe suppuration as an outcome of acute inflammation?

Answer 41

pus formation -dead tissue, organisms, exudate, neutrophils, fibrin, red cells, debris pyogenic membrane surrounds pus -capillary sprouts, neutrophils, fibroblasts walls off pus

Question 42

Describe the differences between an abscess and a multiloculated abscess?

Answer 42

instead of pus discharging across epithelial surface, it forms other little abscesses in the tissue itself

Question 43

What is empyema?

Answer 43

Pus in a pleural cavity

Question 44

What is pyaemia?

Answer 44

discharge of pus into bloodstream

Question 45

Describe organisation?

Answer 45

the characteristic tissue reaction of organisation is granulation tissue. Presence of granulation tissue indicates there is a process of healing and repair going on. leads to fibrosis and formation of a scar.

Question 46

What is granulation tissue?

Answer 46

repair kit – for all damage formed of new capillaries - angiogenesis fibroblasts and collagen macrophages

Question 47

What is involved in dissemination/sepsis?

Answer 47

usually has a microbial cause spread to bloodsteam - patient “septic” bacteraemia - bacteria in blood septicaemia - growth of bacteria in blood toxaemia - toxic products in blood

Question 48

What are the equations to work out cardiac output and blood pressure?

Answer 48

Cardiac output CO = SV x HR cardiac output (CO) stroke volume (SV) heart rate (HR) Blood pressure BP = CO x SVR blood pressure (BP) cardiac output (CO) systemic vascular resistance (SVR)

Question 49

Effects of systemic infection?

Answer 49

shock- cannot get enough oxygen delivered to tissues to make them function properly clinical picture of early septic shock- peripheral vasodilatation tachycardia - high heart rate hypotension - low blood pressure often pyrexia sometimes haemorrhagic skin rash

Question 50

Pathogenesis of septic shock?

Answer 50

systemic release of chemical mediators from cells into plasma mediators cause vasodilation causing loss of systemic vascular resistance (SVR) - BP = CO x SVR results in catecholamine release tachycardia (increased heart rate) follows to maintain (CO) because increased heart rate compensates - CO = SV x HR bacterial endotoxin released interleukin-1 released acts on hypothalamus - pyrexia activation of coagulation disseminated intravascular coagulation vasoactive chemical - vasodilatation haemorrhagic skin rash

Question 51

What happens when compensation fails?

Answer 51

raised HR insufficient to maintain cardiac output SVR low; so, BP falls BP = CO x SVR increasing heart rate insufficient (CO = SV x HR) reduced perfusion of tissues tissue hypoxia loss of cell tissue and organ function

Question 52

Outcome of septic shock?