acute inflammation

Question 1

Define acute inflammation

Answer 1

Fundamental response maintaining integrity of organism
- dynamic homeostatic mechanism
- higher organisms
Series of protective changes occurring in living tissue as a response to injury

Question 2

Cardinal signs of inflammation

Answer 2

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

Question 3

Aetiology of inflammation

Answer 3

Micro organisms - 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

Question 4

Processes of acute inflammation

Answer 4

Series of microscopic events
Localised to affected tissue
Take place in microcirculation
Result in clinical symptoms and signs of acute inflammation - cardinal signs

Question 5

What is microcirculation?

Answer 5

Capillary beds, fed by arterioles and drained by venules
Extracellular space and fluid and molecules within it
Lymphatic channels and drainage
Starling forces control flow across membrane
Dynamic balance - hydrostatic and colloid osmotic pressures
Compartments and physical constants

Question 6

Pathogenesis

Answer 6

Changes in vessel radius
Change in permeability of the vessel wall - exudation
Movement of neutrophils from the vessel to the extravascular space

Question 7

Local changes in vessel radius and blood flow

Answer 7

Transient arteriolar constriction - few moments, probably protective
Local arteriolar dilatation - active hyperaemia
Relaxation of vessek smooth muscle - autonomic NS or mediator derived
“Triple response” - flush, flare, wheal

Question 8

What is an exudate?

Answer 8

fluid rich in protein - plasma - includes immunoglobulin and fibrinogen

Question 9

Effects of exudation

Answer 9

oedema

Question 10

What is oedema?

Answer 10

accumulation of fluid in the extravascular space

swelling - causes pain, reduces function

Question 11

Explain flow in inflammation

Answer 11

neutrophil polymorphonuclear leukocyte is most important cell

loss of laminar flow
red cells aggregate in centre of lumen - rouleaux formation
neutrophils found near endothelium - margination

Question 12

Phases of emigration of neutrophils

Answer 12

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 13

What is diapedesis?

Answer 13

passage of blood cells through intact walls of capillaries typically accompanying inflammation

Question 14

Resolution of acute inflammation - ideal outcome

Answer 14

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

Question 15

Benefits of acute inflammation

Answer 15

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

Question 16

Outcomes of acute inflammation

Answer 16

resolution
suppuration
organisation
dissemination
chronic inflammation

Question 17

examples of conditions

Answer 17

appendicitis
pleural inflammation
bacterial endocarditis
acute pyelonephritis
gingivitis

Question 18

Neutrophils - function

Answer 18

They are mobile phagocytes which recognise foreign antigens and move towards them, this is called chemotaxis. Then adhere to organisms.

granules possess oxidants (egH2O2) and enzymes (eg proteases)

release granule contents

phagocytose and destroy foreign antigen

Question 19

Consequences of neutrophil action

Answer 19

neutrophils 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 20

What is the role of plasma proteins in inflammation?

Answer 20

fibrinogen - coagulation factor - forms fibrin and clots exudate - localises inflammatory process

immunoglobulins in plasma specific antigen - humoral immune response

Question 21

Mediators of acute inflammation

Answer 21

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

Question 22

What are the collective effects of mediators?

Answer 22

vasodilation
increased permeability
neutrophil adhesion
chemotaxis
itch and pain

Question 23

What are cell surface mediators?

Answer 23

adhesion molecules appear on endothelial cells
eg ICAM-1 help neutrophils stick

P-selectin interacts with neutrophil surface

Question 24

Give examples of molecules released from cells

Answer 24

histamine
- preformed in mast cells beside vessels, platelets, basophils
- released as a result of local injury; IgE mediated reactions
- causes vasodilation, increased permeability
- acts via H1 receptors on endothelial cells
5-hydroxytryptamine (serotonin)
- preformed in platelets
- released when platelets degranulate in coagulation
- vasoconstriction

Question 25

other common molecules released from cells

Answer 25

prostaglandins

cytokines and chemokines

nitric oxide

oxygen free radicals

Question 26

What are intracellular inflammation pathways?

Answer 26

NF-kB - nuclear factor kappa-B pathway

MAPK - mitogen-activated protein kinase

• stimulated in inflammation via surface receptors eg toll-like receptors
• 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 27

Plasma - interaction of 4 enzyme cascades

Answer 27

blood coagulation pathways
fibrinolysis
kinin system
complement cascade

Question 28

Blood coagulation pathways

Answer 28

clots fibrinogen in exudate

interacts widely with other systems

Question 29

Fibrinolysis

Answer 29

breaks down fibrin, helps maintain blood supply

fibrin breakdown products vasoactive

Question 30

Kinin system

Answer 30

bradykinin: pain

Question 31

Complement cascade

Answer 31

ties inflammation with immune system

active components stimulate increased permeability, chemotaxis, phagocytosis, cell breakdown

Question 32

immediate systemic effects of inflammation

Answer 32

pyrexia

feel unwell - malaise, anorexia, nausea, abdominal pain and vomiting in children

neutrophilia - raised white blood cell count - bone marrow releases/produces

Question 33

Longer term effects of acute inflammation

Answer 33

lymphadenopathy - regional lymph node enlargement - immune response

weight loss - catabolic process

anaemia

Question 34

Suppuration - outcome of inflammation

Answer 34

pus formation - dead tissue, organisms, exudate, neutrophils, fibrin, RBCs, debris

pyogenic membrane surrounds pus - capillary sprouts, neutrophils, fibroblasts
- walls of pus

Question 35

What is an abscess?

Answer 35

collection of pus (suppuration) under pressure
single locule, multiloculated
“points” and discharges
collapses - healing and repair

Question 36

organisation outcome

Answer 36

granulation tissue characteristic
healing and repair
leads to fibrosis and formation of a scar

Question 37

What is granulation tissue?

Answer 37

“universal patch” - repair kit - for all damage

formed of

• new capillaries - angiogenesis
• fibroblasts and collagen
• macrophages

Question 38

Dissemination outcome

Answer 38

spread to bloodstream - patient “septic”

bacteraemia - bacteria in blood
septicaemia - growth of bacteria in blood
toxaemia - toxic products in blood

Question 39

Pathogenesis of septic shock

Answer 39

systemic release of chemical mediators from cells into plasma

• mediators cause vasodilation causing loss of systemic vascular resistance
• results in catecholamine release
• tachycardia (increased HR) follows to maintain CO because increased HR 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 40

When HR is insufficient to maintain CO

Answer 40

SVR low; therefore BP falls

• BP = CO x SVR
• increasing HR insufficient (CO = SV x HR)

reduced perfusion of tissues

• tissue hypoxia
• loss of cell tissue and organ function