Acute Inflammation Flashcards
(52 cards)
1
Q
Define accute inflammation
A
- fundamental response maintaining integrity of organism- dynamic homeostatic mechanism, occurs in higher organisms
- series of protective changes occurring in living tissue as a response to injury
2
Q
Cardinal signs of inflammation
A
- rubor= redness, darkening of skin
- calor = heat
- Tumor= swelling
- Dolor=pain
- loss of function (protective mechanism)
all these explain sequence of pathological events taking place
3
Q
aetiology (causes) of acute inflammation
6 + briefly describe each
A
- micro-organisms - (bacteria, fungi, viruses, parasite); pathogenic organisms cause infection
- mechanical - trauma - injury to tissue- all injuries even sterile (eg surgery)
- chemical (upset stable environment)- acid or alkali (upset pH), bile and urine (irritation when in inappropriate place eg peritoneum)
- physical (extreme conditions)- heat (sunburn), cold (frostbite), ionising radiation
- dead tissue- cell necrosis irritates adjacent tissue
- Hypersensitivity- several classes of reaction
4
Q
process of acute inflammation
more of an overview
A
- series of microscopic events localised to affected tissue
- take place in the microcirculation
- result in the clinical symptoms and signs of acute inflammation - the cardinal signs
5
Q
microcirculation
brief summary, more in cardiovascular block
A
- capillary beds, fed by arteruiles and drained by venules
- extracellular compartment - fluid and molecules within it
- lymphatic channels and drainage
- dynamic balance (hydrostatic and colloid osmotic pressures)
- fast to respond to stimuli
6
Q
steps in acute inflammation (pathogenesis)
A
- changes in vessel radius - flow
- change in the permeability of the vessel wall - exudation
- movement of neutrophils from the vessel to the extravascular compartment
7
Q
what does increased arteriolar radius cause
step 1
A
increased local tissue blood flow - results in abserved redness and heat
8
Q
effect of rapid changes in vessel radius and thus, blood flow
step 1
A
- transient arteriolar constriction - few moments, probably protective
- local arteriolar dilatation; active hyperaemia
- relaxation of vessel smooth muscle - autonomic NS or mediator derived
Called the “Triple Response” - flush, flare, wheal
9
Q
explain the increased permeability of blood vessels during acute inflammation
Go on to describe the effects of increased permeability
step 2
A
- localised vascular response in microvascular bed
- endothelial leak - fluid and protein not held in vessel lumen (imbalance of Starling forces)
- locally produced chemical mediators
Effects:
* net movement of plasma from capillaries to extravascular space - process is exudation (has effect of its own (oedema))
* what is leaked in an exudate (fluid rich in protein - plasma - includes immunoglobulin and fibrinogen)
Further effects:
* fluid loss - increased viscosity (h)
* rate of flow (movement) slows - stasis
* stasis produces a change in flow characteristics in the vessel
key words: exudation, stasis
10
Q
effects of exudation
stage 2
A
- oedema formed (accumulation of fluid in the extravascular space)
- explains swelling of tissue in acute inflammation
- swelling causes pain and reduce function
11
Q
How does normal laminar blood flow pattern compare with flow in inflammation
stage 2/3 (ish kinda just happens)
A
Normal:
* plasma - outside
* erythrocytes - middle
* WBC (neutrophils) - inside
Inflammation:
* WBC - outside (margination of neutrophils)
* erythrocytes - rouleaux formation (stacked up) - inside
* plamsa - everywhere?
12
Q
summarise how blood flow changes in inflammation
stage 2/3 (ish kinda just happens)
A
- neutrophil polymorphonuclear leukocyte is most important cell (neutrophil; polymorph; NPL)
- loss of normal laminar flow
- red cells aggregate in the centre of the lumen
- neutrophils found near endothelium (outside)
13
Q
Phases of emigration of neutrophils
stage 3
A
- margination - neutrophils move to endothelial aspect of lumen
- pavementing - neutrophils adhere to endothelium
- emigration - neutrophils squeeze/contort between endothelial cells - active process - to** extravascular tissues**
14
Q
diapedesis
A
passive movement of (white) blood cells in acute inflammation
15
Q
resolution of acute inflammation - what is the ideal outcome?
A
- inciting agent isolated & destroyed
- macrophages move in from blood and phagocytose debris; then leave
- epithelial surfaces regenerate/heel
- inflammatory exudate filters away
- vascular changes return to normal
- inflammation resolves
Essentially; everything goes back to normal
16
Q
what are the benefits of acute inflammation
A
- rapid response to non-specific insult
- cardinal signs and loss of function- transient protection of inflamed are
- *neutrophils destroy organisms and denature antigen for macrophages
- plasma proteins localise process
- resolution and return to normal
Essentially; fast, easy to recognise, effecient, localised, returns to normal (no long-term effects)
17
Q
4 (or 5) Outcomes of acute inflammation
A
- Resolution (ideal one)
- Suppuration
- Organisation
- Chronic inflammation
+ dissemination (potentially fatal)
18
Q
Local effects of acute inflammation
A
local edema, redness, tenderness and pain, increased temperature, and restricted function.
19
Q
what does itis mean
A
forming name of inflammatory disease
20
Q
what do neutrophils do
(neutrophil polymorphonuclear leukocytes)
A
- mobile phagocytes - recognise foreign antigen, move towards it - chemotaxis (recognise chemicals), adhere to organism –> vacuole formed
- granules possess oxidants (eg H2O2) and enzymes (eg proteases)
- release granule contents
- phagocytose & destroy foreign antigen
21
Q
consequences of neutrophil action
A
- 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 (not localised)
22
Q
role of plasma proteins in inflammation
A
- fibrinogen (in plasma) - coagulation factor - forms fibrin and clots exudate - localises inflammatory process
- immunoglobulins in plasma specific for antigen - humoural immune response
23
Q
what are the mediators of acute inflamation
don’t need to name directly, just where from
A
- molecules on endothelial cell surface membrane
- molecules released from cells
- molecules in the plasma (–> activated when reach site of infection)
- molecules inside cells
24
Q
what are the collective effects of mediators
brief overview
A
- vasodilatation (inc vessel radius) - and constriction
- increased permeability (dynamic balance)
- cause/enable neutrophil adhesion
- chemotaxis (form part of chemical gradient which neutrophil is attracted to)
- itch and pain
25
cell surface mediations that help neutrophils stick
* adhesion molecules appear on endothelial cells
eg ICAM-1 - help neutrophils stick
* P-selectin - interacts with neutrophil surface
26
List some molecules (**mediators)** released from cells
| 6
* histamine
* 5-hydroxytryptamine (serotonin)
* prostglandins
* cytokines and chemokines
* Nitric oxids (NO)
* Oxygen free radicals
27
histamine as a mediator
* preformed in **mast cells** beside vessels, platelets, basophils
* released as a **result of local injury**; IgE mediated reactions
* causes v**asodilatation, increased permeability**
* acts via H1 receptors on endothelial cells
28
Serotonin (5-hydroxytryptamine) as a mediator
* preformed in platelets
* released when platelets degranulate in coagulation
* **vasoconstriction**
29
prostglandins as mediators
* 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
* latter: effectiveness of non-steroidal anti-inflammatory drugs
* **molecules provide target for treatment**
30
cytokines and chemokines
| moleculer released from cells
* 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
31
nitric oxide as a mediator
* various cells
* smooth muscle relaxation, anti-platelet, regulate leukocyte (lymphocyte) recruitment to inflammatory focus
32
oxygen free radicals as mediators
* released by neutrophils on phagocytosis (when they degranulate)
* amplify other mediator effects
33
does acute inflamation utilise innate or aquired ammunity
Innate only
| (e.g. neutrophils, cytokines but not B/T cells) - I think???
34
molecules inside cells as mediators- signalling
| think patterns...
* **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**
* **activate** inflammatory response
35
intracellular inflammatory pathways
| probs neet to know but wouldn't bother learning it all
* 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
36
What happens in the plasma during acute infection - (site for **interaction of enzyme cascades**)
* **blood coagulation pathways**:
-clots fibrinogen in **exudate**
-interacts widely with other systems
* **fibrinolysis**:
-breaks down fibrin, helps maintain blood supply
-fibrin breakdown products vasoactive
* kinin system: bradykinin: **pain**
* **complement cascade**:
-ties inflammation with **immune system**
-active components stimulate **increased permeability, chemotaxis, phagocytosis, cell breakdown**
| happen simultaneously
37
What are 3 immediate systemic effects of inflammation
| explain each briefly
* **pyrexia (raised temperature)** - endogenous pyrogens released 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
38
Longer term effects of acute inflammation
| 3
* **lymphadenopathy** (regional lymph node enlargement; "swollen glands") - immune response
* **weight loss** - catabolic process of inflammation
* **anaemia**
39
Outcome of acute inflammation: suppuration
* **pus formation** - dead tissue, organisms, exudate, neutrophils, fibrin, red cells, debris (**abscess**)
* **pyogenic membrane surrounds pus** - **capillary sprouts** (growths giving easier access into infected area), neutrophils, fibroblasts, walls off pus
40
what is an abscess
* **collection of pus** (suppuration) **under pressure**
* single locule (1 blob), multiloculated (many like grapes)
* "points" and discharges
* collapses - healing and repair
41
Explain the process/anatomy leading to pus discharge of an abscess
| (suppuration)
Capillary sprouts grow into pyogenic membrane around abcess cavity. Ingrowth of granulation tissue (pyogenic membrane). Pus is discharged at weakest point, eouthelial surface (outside)
42
what is a multiloculated abscess
pus bursts through pyogebic membrane and forms new cavities
43
empyema
pus in a hollow viscus (e.g. gall bladder/pleural cavity)
44
pyaemia
discharge of pus to bloodstream
45
Outcome of acute inflammation: **organisation**
* **granulation tissue is characteristic**
* healing and repair
* leads to **fibrosis and formation of a scar**
* + **angiogenesis** - new blood vessel formation
| healing + fibrosis
46
granulation tissue
repair kit/pathch for damage
Formed of: new capillaries (angiogenesis) fibroblasts and collagen, macrophages
47
Outcomes of acute inflammation: **dissemination**
* spread to bloodsteam - patient "**septic**"
* bacteraemia - bacteria in blood
* septicaemia - **growth of bacteria in blood**
* toxaemia - toxic products in blood (but not necessarily pathogen/organism)
48
effects of systemic infection
| (sepsis)
* **shock** - inability to perfuse tissues
* clinical picture of early **septic shock**:
-peripheral vasodilatation
-tachycardia - high heart rate
-hypotension - low blood pressure
-often pyrexia (raised body temp; fever)
-sometimes haemorrhagic skin rash
49
Briefly summarise the pathogenesis of septic shock (compensation and then failure)
1. release of chemical mediators into plasma
2. cause vasodilation (loss of systemic vascular resistance)
3. tachycardia - inc heart rate to compensate and **maintain cardiac output**
4. bacterial endotoxin released - **pyrexia**
5. activation of **coagulation** - vasodilation, **haemorrhagic skin rash**
6. compensation **fails** - HR insffucuent to maintain CO
7. reduced perfusion to tissues: **tissue hypoxia** (cell death), locc of cell **tissue and organ function**
8. Haemorrhage
9. Death
50
Summarise the role of neutrophils in acute inflammation
The major role of the neutrophil in acute inflammation is to **phagocytose microorganisms and foreign materials**
51
How can the process of acute inflammation be altered to the detriment of the patient
| not sure if ans true but is LO, so made up this flashcard???
Compensation by inc HR ---> tachycardia... lead to septic shock
52
Endothelial cells
Cells lining blood vessels
