L4: Acute Inflammation

Question 1

What is inflammation?

Answer 1

Response of living tissue to injury
Protective mechanism–> can cause local and systemic complications (sometimes worse than initial thing)
Controlled–> Chemical mediators

Question 2

What are the characteristic of acute inflammation?

Answer 2

Immediate
Short Duration 
Innate
Sterotyped --> same
Limits danger

Question 3

What are the different stages of inflammation?

Answer 3

Vascular phase–> Changes in blood flow, accmulation of exudate
Cellular phase–> Delivery of neutrophils

Question 4

What can cause inflammation?

Answer 4

Trauma
Hypersensitivity
Microorganism
Other illnesses

Question 5

What are the cardinal signs of inflammation?

Answer 5

1. Rubor–> Redness
2. Tumor–> Swelling
3. Calor–> Heat
4. Dolor–> Pain
5. Loss of function (functio laesa)

Question 6

During the vascular phase what changes in blood flow occur?

Answer 6

Transient vasoconstriction (seconds)
Vasodilation (minutes)–> heat and redness
Increased permeability –> fluid and cells can escape

Question 7

What controls the movement of fluid?

Answer 7

Starling Law

Question 8

What does Starling Law state?

Answer 8

Movement of fluid is controlled by the balance of hydrostatic pressure and oncotic pressure

Different to Frank-Starling law of the heart

Question 9

What is the difference between hydrostatic and oncotic pressure?

Answer 9

Hydrostatic pressure–> pressure exerted on vessel wall by a fluid–> pushes fluid away
Oncotic pressure–> pressure exerted by proteins, in the interstitial fluid–> pulls fluid towards

Question 10

What happens to the capillaries during inflammation?

Answer 10

Vasodilation–> increased hydrostatic pressure in capillary
Increased vessel permeability–> plasma proteins move into the interstitium–> increased oncotic pressure in interstitium
Fluid movement–> out of vessel into interstitium–> Odema (swelling/tumor)

Question 11

What happens to the blood when the fluid moves out? What effect does this have on the flow of blood?

Answer 11

Increases viscosity of blood

Reduces the flow through the vessel–> stasis

Question 12

What are the different types of interstitial fluid? Compare and contrast then?

Answer 12

Exudate–> increased vascular permeability

• -> protein rich fluid (delivers protein to area of injury)
• -> occurs in inflammation

Transudate–> Not related to inflammation

• -> vascular permeability unchanged
• -> fluid movement due to ↑hydrostatic pressure, ↓capillary oncotic pressure
• -> interstitial fluid–> protein free
• -> occurs in–> HF, Hepatic failure, renal failure

Question 13

How does the vessel wall become permeable?

Answer 13

• Retraction of endothelial cells –> NO, histmaine, leukotrienes
• Direct injury–> burns, toxins, trauma
• Leukocyte dependent injury–> enzymes, toxic O2 species released by inflammatory cells

Question 14

How is the vascular phase of inflammation effective?

Answer 14

Increased interstitial fluid–> dilutes the toxins
Increased exudate–> delivers proteins
e.g. fibrin–> forms a mesh to limit the spread of toxins–> physical barrier
e.g. immunoglobulins–> adaptive immune response–> targeted destruction of pathogens

Question 15

Where does the fluid drain to?

Answer 15

Lymph nodes

• -> delivery of antigens to lymphocytes
• -> adaptive immune response activated

Question 16

What is the main function of the cellular phase?

Answer 16

Immune cells to site of inflammation

Question 17

What is the main WBC involved in acute inflammation?

Answer 17

Neutrophil
Larger than RBC (just)
Trilobed nucleus
Granulocyte

Question 18

How do neutrophils escape the circulation?

Answer 18

↑ Viscosity of blood, movement slows
Margination--> adhesion to capillary 
Rolling--> rolls along surface
Adhesion-->attached more tightly to capillary 
Emigration (diapedesis)--> escaping

Question 19

What adheres the neutrophil to the surface?

Answer 19

Selectins

Integrins

Question 20

What are selectins?

Answer 20

Expressed on activated endothelial cells
Activated by chemical mediators
Weak bonds–> responsible for rolling

Question 21

What are integrins?

Answer 21

Neutrophil surface
Change from low affinity to high affinity state
Responsible for adhesion

Question 22

What makes neutrophils move through the interstitium?

Answer 22

Chemotaxis
Move towards highest concentration of chemoattractant
Chemoattractant: bacterial peptides, Inflammatory mediators
Neutrophil cytoskeleton rearranges to allow movement

Question 23

What is the role of neutrophils? How do they do it?

Answer 23

To engulf pathogens –> Phagocytosis

• -> phagosome fused with lysosome
• -> produces secondary phagolysosome
• -> release inflammatory mediators–> propagate inflammatory response

Question 24

How do the neutrophils know what to phagocytose?

Answer 24

Opsonisation– recognition system

• -> proteins bind to surface of pathogen enhancing attachment of phagocytes
• -> Toxin covered in opsonins–> C3b and Fc
• -> receptor for C3b and Fc on neutrophil surface

Question 25

What are the mechanisms used by neutrophils to kill bacteria?

Answer 25

Oxygen dependent and oxygen independent pathways

Question 26

What are the features of the oxygen dependent pathway?

Answer 26

``` Reactive oxygen intermediates (ROS, RNS and free radicals) ROS --> Superoxide anion --> OH• --> H2O2 RNS --> NO --> NO2 ```

Question 27

What are the features of the oxygen independent pathway?

Answer 27

Enzymatic destruction - Lysozymes - Hydrolytic enzymes - Defensins

Question 28

What is the draw back to the neutrophil response?

Answer 28

Activated neutrophils can cause damage to host tissue

Question 29

What are the two outcomes of the cellular phase of acute inflammation?

Answer 29

Removal of pathogens and necrotic tissue | Release of inflammatory mediators

Question 30

What are inflammatory mediators?

Answer 30

Modulates the inflammatory response in some way | Chemical messengers--> control and coordinate, varying chemical structures, overlapping functions

Question 31

Where do the chemical mediator originate from?

Answer 31

Activated inflammatory cells Platelets Endothelial cells Toxins

Question 32

What controls the chemical mediators?

Answer 32

Inhibitors--> stop inflammation from going on endlessly | Short half lives --> seconds to minutes--> effects last minutes to hours

Question 33

Where do the endogenous mediators come from?

Answer 33

Supplied by plasma, leukocytes, and local tissues

Question 34

How are the mediators classified?

Answer 34

- Vasoactive amines --> histamine and serotonin - Vasoactive peptides--> bradykinin (↑ vascular permeability) - Complement components--> C3a and C5a--> forms membrane attack complex (tube)--> punches holes in bacteria causing them to die - Clotting and fibrinolytic cascade--> generate inflammatory mediators - Phospholipid derived mediators --> prostaglandins, thromboxanes and leukotrienes - Cytokines and chemokines --> IL, TNF, interferons - Exogenous mediators of inflammation--> in tissue= inflammation, in blood= septic shock

Question 35

What are the main roles of the inflammatory mediators?

Answer 35

Vasodilatation--> histamine, serotonin, prostagladins, NO Increased vascular permeability --> histamines, serotonin, prostaglandins Chemotaxis--> Leukotrienes B4, C5a and C3a, chemokines, and bacterial peptides, TNF-α Phagocytosis--> C3b complement plasma precursor Pain --> bradykinin, substance P Vasoconstriction--> histamine, bradykinins, leukotrienes, C3a and C5a??? look up in workbook

Question 36

What are the local complications of acute inflammation?

Answer 36

Damage to normal tissues Swelling--> compression of tubes e.g. airways, bile duct Exudate--> compression of organs e.g. cardiac temponade Loss of fluid--> dehydration e.g. burns Pain and loss of function--> muscle atrophy, psycho-social consequences

Question 37

What are the systemic complications?

Answer 37

Inflammatory mediators in the blood stream Fever--> pyrogens (inflammatory mediators)--> acts on hypothalamus to alter temperature Exogenous sources - NSAIDs- block COX activity - ↓ prostaglandins reduce fever Leucocytosis--> ↑WBC --> measured in blood Acute Phase response--> causes discomfort/ unwell (malaise), reduced appetite, altered sleep, tachycardia--> induced rest!! --> changes in levels of plasma proteins (liver changes pattern of protein synthesis)--> ↑CRP--> marker of inflammation Septic shock--> huge release of chemical mediators, widespread vasodilatation, increase vascular permeability--> hypotension and tachycardia--> multiorgan failure--> often fatal

Question 38

What happens after acute inflammation?

Answer 38

1- Complete resolution 2- Repair with connective tissue 3- Progression to chronic inflammation

Question 39

What is meant by complete resolution?

Answer 39

Mediators--> short half lives- diluted/inactivated/degraded Vessel calibre and permeability --> normal Neutrophils undergo apoptosis and get phagocytosed Exudate --> lymphatics Regeneration of tissue architecture if preserved

Question 40

Why would it need repairing with connective tissue? Problem with this?

Answer 40

Extensive damage --> tissue destruction | Leads to fibrosis

Question 41

What happens if the acute inflammation is unable to kill the pathogen?

Answer 41

Chronic inflammation | Prolonged inflammation with repair

Question 42

What is appendicitis? Why does it happen?

Answer 42

Inflammation of the appendix Blocked lumen--> faecolith (hard faeces) Accumulation of bacteria and exudate--> ↑ pressure--> perforation

Question 43

What is pneumonia? What causes it? Signs and symptoms? Risk factors?

Answer 43

Common respiratory tract infection Caused by--> Streptococcus pneumoniae, haemophilus influenza S and S--> SoB, cough, sputum, fever (accumulation of exudate-->builds up--> prevents gaseous exchange) Risk factors--> smoking--> destroy mucocillary escalator Pre-existing lung conditions--> COPD, Astham, Malignancy

Question 44

What is meningitis? What are the signs and symptoms?

Answer 44

Inflammation of the meninges Mainly caused by; Neisseria meningitides, E.Coli, Group B Streptococcus Headache, neck stiffness, photophobia (sensitive to light), atered mental state --> rapidly fatal

Question 45

What is an abscess?

Answer 45

Accumulation of dead and dying neutrophils With associated liquefactive necrosis Can cause compression of the surrounding structures--> pain and blockage of ducts

Question 46

What happens if you get inflammation of serous caivities?

Answer 46

Exudate pours into the serous cavities Pleural space--> pleural effusion Peritoneal space--> ascities (distension of abdomen) Pericardial space--> pericardial effusion

Question 47

Can you get disorders of acute inflammation?

Answer 47

Yes but rare Hereditary angio-oedema Alpha-1 antitrypsin deficinecy Chronic granulomatous disease