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Principles of Disease 16 > Acute Inflammation > Flashcards

Flashcards in Acute Inflammation Deck (40)
1

Define acute inflammation

Definition: any inflammation that has a fairly rapid onset, quickly becomes severe, and is usually manifested for only a few days, but that may persist for even a few weeks; characterized histologically by edema, hyperemia, and inflitrates of polymorphonuclear leukocytes.

Fundamental response maintaining integrity of organism involving a series of protective changes occurring in living tissue as a response to injury

2

What are the 5 cardinal signs of inflammation?

• Rubor - redness
• Calor - heat
• Tumor - swelling
• Dolor - pain
• Loss of function

All of these explained by the sequence of pathological events taking place

3

What is the aetiology of inflammation?

Microorganisms
Mechanical
Chemical
Physical
Dead tissue
Hypersensitivity

4

What is the microcirculation?

Circulation of blood in smallest vessels e.g.:
• Capillary beds, fed by arterioles and drained by venules
• Extracellular “space” and fluid and molecules within it
• Lymphatic channels and drainage

5

What force controls the flow of fluid over membranes?

Starling forces control flow (fluid flux) across membrane
Q = LpS{(Pc - Pi) - σ(Πp - Πi)}

6

What is the starling equation?

The Starling equation is an equation that illustrates the role of hydrostatic and oncotic forces (the so-called Starling forces) in the movement of fluid across capillary membranes

7

Describe the local changes vessel radius and flow during inflammation and the signs of its occurrence

1. Transient arteriolar constriction - few moments, protective (white)
2. Local arteriolar dilatation - active hyperaemia (local, red)
3. Relaxation of vessel smooth muscle - autonomic NS or mediator derived

Called the “Triple Response” - flush, flare, wheal

8

What is Poiseuille's law?

Poiseuille’s law - flow is proportional to radius to the power of four
• Q = ΔP x Πr4/8ηL
• Increased arteriolar radius causes increased local tissue blood flow
• Radius controls blood flow!

9

What is exudate?

Exudate - fluid rich in protein e.g. plasma which includes immunoglobulin and fibrinogen that seeps out of blood vessels or organs during inflammation

10

Describe the phases of neutrophil emigration

• Margination - neutrophils move to endothelial aspect of lumen
• Pavementing - neutrophils adhere to endothelium
• Emigration - neutrophils squeeze between endothelial cells - active process - to extravascular tissues
• Diapedesis – leukocyte extravasation (not neutrophils, later effector cells)

11

Describe the benefits of acute inflammation reactions

• 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
• Plasma proteins localise process
• Resolution and return to normal

12

What are the 5 possible outcomes of acute inflammation?

Resolution
Suppuration - the process of pus forming
Dissemination
Organisation - replacement with granulation tissue
Chronic inflammation

13

What is the role of neutrophils in inflammation?

• Mobile phagocytes
– Recognise foreign antigen
– Move towards it - chemotaxis
– Adhere to organism
• Granules possess oxidants (e.g. H2O2) and enzymes (e.g. proteases)
• Release granule contents
• Phagocytose and destroy foreign antigen

14

What is pus?

• Neutrophils die when granule contents released
• Produce a “soup” of fluid, bits of cell, organisms, endogenous proteins - pus

15

What helps to localise inflammation?

Fibrinogen in exudate forms fibrin to make a clot

16

What cell surface mediators are useful in inflammation?

ICAM-1 - on endothelial cells, help neutrophils stick
P-selectin - on endothelial cells, interacts with neutrophil surface

17

Describe some useful molecules released during inflammation

• Histamine
• 5-hydroxytryptamine (serotonin)
• Prostaglandins (arachidonic acid metabolites via lipoxygenase pathway)
• Leukotrienes (arachidonic acid metabolites via cyclo-oxygenase pathway)
• Omega-3 polyunsaturated fatty acids
• Platelet-activating factor (PAF)
• Cytokines and chemokines (eg TNFα, IL-1)
• Nitric oxide (NO)
• Oxygen free radicals (H2O2, OH-, O2-)

18

What are the useful effects of histamine?

– Preformed in mast cells beside vessels, platelets, basophils
– Released as a result of local injury; IgE mediated reactions
– Causes vasodilatation, increased permeability
– Acts via H1 receptors on endothelial cells

19

What are the useful effects of serotonin (5-HT)?

– Preformed in platelets
– Released when platelets degranulate in coagulation
– Vasoconstriction

20

What are the useful effects of prostaglandins?

– 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

21

What are the useful effects of leukotrienes?

– Neutrophils especially
– Vasoactive - dynamic effect on vessels to increase permeability and constrict smooth muscle

22

What are the useful effects of omega 3 polyunsaturated fatty acids?

– Decrease synthesis of arachidonic acid derived inflammatory mediators

23

What is the useful effect of platelet activating factor (PAF)?

– Cell membranes of activated inflammatory cells
– Reduces permeability by enhancing platelet degranulation at site of injury

24

What are the useful effects of cytokines and chemokine?

– Small molecules produced by macrophages, lymphocytes, endothelium in response to inflammatory stimuli
– Attract inflammatory cells and activate other immune cells

25

What is the useful effect of nitric oxide (NO)?

– Various cells
– Smooth muscle relaxation, anti-platelet, regulate leukocyte recruitment to inflammatory focus

26

What is the useful effects of oxygen free radicals?

– Released by neutrophils on phagocytosis
– Amplify other mediator effects

(H2O2, OH-, O2-)

27

What 4 enzyme cascades found in plasma are all involved in inflammation?

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

28

What are the immediate systemic effects of inflammation?

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

Can result in septic shock

29

What are some long term effects of inflammation?

• Lymphadenopathy - regional lymph node enlargement
• Weight loss - catabolic process
• Anaemia

30

What surrounds pus?

Pyogenic membrane - a layer of pus cells lining an abscess cavity that have not yet autolyzed. Made up of capillary sprouts, neutrophils, fibroblasts

31

Describe an abscess

• Collection of pus (suppuration) under pressure
• Single locule or multiloculated
• “Points” and discharges, ingrowth of granulation tissue
• Collapses - healing and repair
• In multiloculated abscesses, the pus breaks through the pyogenic membrane to form new cavities within tissues.

32

How do multi-loculated abscesses form?

In multiloculated abscesses, the pus breaks through the pyogenic membrane to form new cavities within tissues.

33

What is empyema?

Empyema - pus in a hollow viscus
– Gall bladder
– Pleural cavity

34

What is pyaemia?

Pyaemia - pus discharge to bloodstream

35

What is granulation tissue made up of?

Formed of:
– New capillaries - angiogenesis
– Fibroblasts and collagen
– Macrophages

36

What are the possible outcomes of dissemination in acute inflammation?

• Spread to bloodsteam - patient “septic”
• Bacteraemia - bacteria in blood
• Septicaemia - growth of bacteria in blood
• Toxaemia - toxic products in blood

37

What is septic shock?

Septic shock is a serious medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism, resulting in the inability to perfuse tissue due to massive exudation.

38

What are the clinical signs of septic shock?

– Peripheral vasodilatation
– Tachycardia - high heart rate
– Hypotension - low blood pressure
– Often pyrexia (fever)
– Sometimes haemorrhagic skin rash

39

What are the possible outcomes of septic shock?

• Rapidly fatal
• Tissue hypoxia - cell death
• Haemorrhage
• Requires urgent intervention and support
– Awareness and early recognition
– Ability of young people to compensate
– Admit to hospital and intensive care

40

List the local effects of acute inflammation

Flush, flare and wheel
Oedema due to exudation