Week 2 - Lecture 1 - Acute Inflammation

Question 1

“wisdom”

Answer 1

all disease processes cause injury
inflammation is a body’s natural response to injury
healing can only occur with an effective inflammatory process

two inflammatory process
1; acute inflammation : expected body response to injury
2: chronic inflammation : altered inflammatory process due to unrelenting injury

Question 2

1st line : no specific barriers

Answer 2

‘walls and moats’

skin & mucous membrane

Question 3

2nd line : non-specific patrols

Answer 3

‘patrolling soldiers’
phagocytic cells
inflammatory response

Question 4

3rd line : true specific

Answer 4

” elite trained units “
immune response
lymphocytes & antibodies

Question 5

First Line of defence

Answer 5

skin and mucous membranes

• physical barrier
• mucus
• protective liquids
  eg. tears with antimicrobial enzymes

Question 6

Second line of defence

Answer 6

inflammatory response

• non-specific
• identical regardless of cause

Question 7

third line of defence

Answer 7

the immune response

• specific response
• depends on the invader
• adaptive
• non adaptive

Question 8

inflammation

Answer 8

reaction of vascularised tissues to injury

inflammatory conditions are named by adding the suffix - itis to the affected organ or system

• appendicitis - inflammation of the appendix
• neuritis : inflammation of a nerve

more description may indicate

• acute / chronic (acute appendicitis )
• what type of exudate was formed

Question 9

what is an exudate

Answer 9

a mass of cells and fluids that accumulates at the site of an injury

Question 10

5 types of exudates

Answer 10

serous 
hemorrhagic 
fibrinous 
membranous/pseudomembranous 
purulent or supportive

Question 11

serous exudate

Answer 11

watery fluid, low in protein content, plasma entering inflammatory site

Question 12

hemorrhagic exudate

Answer 12

severe tissue injury causes damage to blood vessels

significant leakage of RBCs from capillaries

Question 13

Fibrinous exudate

Answer 13

large amount of fibrinogen, sticky meshwork

Question 14

membranous/pseudomembranous exudates

Answer 14

develops on mucous membrane surfaces

necrotic cells enmeshed in fibropurulent exudate

Question 15

purulent or suppurative exudate

Answer 15

contains pus (degraded WBCs, proteins, tissue debris)

Question 16

Inflammation upon injury

Answer 16

Hemostasis occurs (stoppage of bleeding)

• immediately activated upon physical injury
  
  • initial constriction of blood vessel
  • initiation of blood clotting

after a brief period the inflammatory response occurs through vasodilation

Question 17

Acute inflammation

Answer 17

triggered by tissue injury

injury : any form of damage
- cell perspective : deficiency, intoxication, trauma

Question 18

Three goals of inflammation

Answer 18

1. increase blood flow to site (vascular response)
2. increase healing cells at site ( cellular response)
3. remove injured tissue and prepare for tissue repair

Question 19

Vascular response

Answer 19

response required at/near the site of injury

facilitated by chemical mediators (inflammatory mediators)
Induces vasodilation and increases capillary permeability
objective is to get more blood flowing to the injured area
- blood is composed of cells
- active in phagocytosis
- developing immune response
- required for healing
- increased blood flow dilutes harmful substances at the site of injury

Question 20

Structure and function of capillaries

Answer 20

capillaries convey blood into the venules
close proximity / relation to the tissue to which inflammation is a response
capillaries exchange of oxygen, nutrients, waste between blood and tissue
Vessels chiefly participating in inflammatory response : post capillary venues

Question 21

inflammatory response

Answer 21

focused in the vascularised connective tissue present throughout the body

• loose / areolar connective tissue
• most widely distributed connective
• • dermis / skin
• • gastrointestinal tract
• • urinary tract
• • respiratory tract etc

well placed to respond to any breach of surface cover, mechanical injury etc

Question 22

cell derived inflammatory mediators

Answer 22

cell derived

• generated in cell plasma membrane
• made up from proteins within the cells

1. within white blood cells
2. within platelets
3. within endothelial or damaged tissue cells

Question 23

plasma derived inflammatory mediators

Answer 23

continuously circulating
plasma proteins

1. complement system
2. Kinin system
3. clotting system

Question 24

Inflammatory mediators within white blood cells

Answer 24

Mast cells are leukocytes (WBC)
found. in connective tissue of the body
near all blood vessels
strategic placement : rapid response

Question 25

inflammatory mediators within WBCs cont’

Answer 25

other signals are also generated in other WBCs
lymphocytes and monocytes/macrophages release cytokines
- cytokines are large group of proteins
- active in regulating inflammation
- - vasodilation, increased permeability, resolution of inflammation
- different cytokines are released from different cells
- cytokines released by lymphocytes: lymphokines
- cytokines released by monocytes/macrophages : monotones

• interleukins
• growth factor
• interferons
• chemokines

Question 26

inflammatory mediators with platelets

Answer 26

platelets : hemostasis

platelets active in generating and releasing inflammatory mediators

1. increase vasodilation
2. attract white cells
3. help healing of injured tissue by increased vascular permeability (allow cells to get to site)

examples of inflammatory mediates produced by platelets are serotonin and histamine

Question 27

inflammatory mediators within endothelial or injured tissue cells

Answer 27

endothelial cells : single cell thick epithelial lining of blood vessels

normality

• produce anti-platelet, antithrombotic agents
• produce vasodilation, vasoconstriction : maintain blood flow

in inflammation

• platelet-activating factor
  
  • promote clotting
  • promote vasodilation
  • attract white blood cells
• arachidonic acid
• starting conversion point of various inflammatory mediators
  
  • prostaglandins, lipoxins, leukotrienes, thromboxane
• regulate vascular permeability and pain

Question 28

inflammatory mediators within plasma

Answer 28

circulating inflammatory mediators
3 major interrelated system
1. complement - kill foreign cells and attract phagocytic cells
2. clotting - promote blood clotting at the injury site and vascular permeability
3. Kinin - pain signalling

Question 29

cellular response

Answer 29

after vessel dilation : cells are needed for healing

cellular response : regulated by inflammatory mediators

Question 30

3 essential steps to cellular response

Answer 30

chemotaxis
cellular adherence
cellular migration

Question 31

what is chemotaxis

Answer 31

moving cells to the site of injury

chemotactic factors are activated

Question 32

what is cellular adherence

Answer 32

attraction and binding to migration site

regulated by chemotactic factors and receptors that bind leukocytes to the endothelial surface

Question 33

what is cellular migration

Answer 33

across/ between endothelial cells : diapedesis

Question 34

Phagocytosis

Answer 34

inflammatory cells release more inflammatory mediators to attract more neutrophils and macrophages

aggressive process to destroy / phagocytise causative agents

healthy tissue is also damaged

inhibitors proteins of the 3 plasma derived system minimise damage

• complement
• clotting
• kinin

Question 35

5 cardinal signs of inflammation

Answer 35

redness
heat
swelling(edema) 
pain
incapacitation (loss of function)

Question 36

what is lymphadenitis

Answer 36

enlargement and inflammation of the lymph nodes

• result of trying to filter harmful substances
  
  • painful palpable nodes
  • not painful palpable : neoplasms

Question 37

Manifestations of inflammation

Answer 37

systemic manifestations may include

• fever (pyrexia)
• increased circulating leukocytes and plasma proteins
• weight loss
• fatigue
• headache
• lethargy

Question 38

Fever

Answer 38

controlled hyperthermia

due to infection

1. Macrophages release cytokines (also called pyrogens)
   cause release of prostaglandins from hypothalamus
2. prostaglandins reset hypothalamic thermostat higher
3. heat producing mechanisms
   vasoconstriction, heat loss on body surfaces declines
   skin cools, shivering begins to generate heat
4. core body temperatures reaches new set point
5. Natural body defences or antibiotic reverse disease process
   cryogens (eg. vasopressin) reset thermostat to lower (normal) level - heat loss mechanisms - temperature falls

Question 39

Fever from practical point : presence of inflammation (sign of infection)

Answer 39

+survival advantage
+enhanced immune function
+microbial agents growth is inhibited in fever range
- increased demand for oxygen, increased workload for heart
- fever produce confusion, tachycardia
- cell damage above 42.2 degrees celsius
- lead to life threatening changes

Question 40

four successive stages of physiologic behaviours that occur during the development of fever

Answer 40

1. a prodrome
   - non specific complaints, headache and fatigue, fleeting aches and pains
2. a chill, during which the temperature rises
   - uncomfortable chilled sensation, onset of shaking, despite rising of temperature
   - vasoconstriction and piloerection precede the onset of shivering
   - skin is pale, covered with goose bumps
   - urge to put more clothing on, curling up, conserving body heat
   - when body temperature reached new set point, shivering stops
   - sensation of warmth develops
3. a flush
   - cutaneous vasodilation, skin becomes warm and flushed
4. defervescence
   - initiation of sweating

Question 41

laboratory diagnosis for inflammation

Answer 41

two non specific tests for inflammation

1. CRP : C-reactive proteins
2. ESR : erythrocyte sedimentation rate

elevated value indicate inflammation
will not identify source/location

CRP : c reactive protein

• preferred test of acute inflammation
• presence of a specific protein (triggered by plasma protein system during inflammation)

Question 42

during inflammation

Answer 42

coagulation cascade activated 
increased level of fibrinogen 
cells stick together 
RBCs exposed to inflammatory process : fall faster
Elevated ESR : sign of inflammation

Question 43

Treatment of inflammation

Answer 43

inflammatory response : multiple components
damage to healthy surrounding tissue is common
treatment goal to minimise damage

Question 44

initial treatment for acute inflammation

Answer 44

reduce blood flow
decrease swelling
block the action of chemical mediators
decrease pain

Question 45

pharmacologic treatment of inflammation

Answer 45

block inflammatory mediators

-reduce swelling, pain, redness, warmth

Question 46

non pharmacologic treatment of inflammation

Answer 46

initial treatment : RICE
Rest Ice Compression Elevation
Ice/cold : cause vasoconstriction to prevent heat loss
- at the site of injury : reduced formation of exudate
- rule of 10 on and 10 off (mast cells can be damaged)
Heat : helps phagocytosis
sports injury : early on ice, later on heat
limit swelling, help phagocytosis

elevation : blood flow slows, work against gravity
compression : prevents exudates forming by increasing tissue pressure, promotes lymphatic drainage

Question 47

Resolution of acute inflammation

Answer 47

acute inflammatory response is self limited

offending agent is destroyed/removed

• feedback system regulated by 3 plasma protein system
• relevant inflammatory mediators

Deactivate the inflammatory response

tissue is ready to heal, the stage is set

if acute inflammatory response is unsuccessful : chronic inflammation