Week 2 - Lecture 1 - Acute Inflammation Flashcards
“wisdom”
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
1st line : no specific barriers
‘walls and moats’
skin & mucous membrane
2nd line : non-specific patrols
‘patrolling soldiers’
phagocytic cells
inflammatory response
3rd line : true specific
” elite trained units “
immune response
lymphocytes & antibodies
First Line of defence
skin and mucous membranes
- physical barrier
- mucus
- protective liquids
eg. tears with antimicrobial enzymes
Second line of defence
inflammatory response
- non-specific
- identical regardless of cause
third line of defence
the immune response
- specific response
- depends on the invader
- adaptive
- non adaptive
inflammation
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
what is an exudate
a mass of cells and fluids that accumulates at the site of an injury
5 types of exudates
serous hemorrhagic fibrinous membranous/pseudomembranous purulent or supportive
serous exudate
watery fluid, low in protein content, plasma entering inflammatory site
hemorrhagic exudate
severe tissue injury causes damage to blood vessels
significant leakage of RBCs from capillaries
Fibrinous exudate
large amount of fibrinogen, sticky meshwork
membranous/pseudomembranous exudates
develops on mucous membrane surfaces
necrotic cells enmeshed in fibropurulent exudate
purulent or suppurative exudate
contains pus (degraded WBCs, proteins, tissue debris)
Inflammation upon injury
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
Acute inflammation
triggered by tissue injury
injury : any form of damage
- cell perspective : deficiency, intoxication, trauma
Three goals of inflammation
- increase blood flow to site (vascular response)
- increase healing cells at site ( cellular response)
- remove injured tissue and prepare for tissue repair
Vascular response
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
Structure and function of capillaries
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
inflammatory response
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
cell derived inflammatory mediators
cell derived
- generated in cell plasma membrane
- made up from proteins within the cells
- within white blood cells
- within platelets
- within endothelial or damaged tissue cells
plasma derived inflammatory mediators
continuously circulating
plasma proteins
- complement system
- Kinin system
- clotting system
Inflammatory mediators within white blood cells
Mast cells are leukocytes (WBC)
found. in connective tissue of the body
near all blood vessels
strategic placement : rapid response
inflammatory mediators within WBCs cont’
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
inflammatory mediators with platelets
platelets : hemostasis
platelets active in generating and releasing inflammatory mediators
- increase vasodilation
- attract white cells
- 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
inflammatory mediators within endothelial or injured tissue cells
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
inflammatory mediators within plasma
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
cellular response
after vessel dilation : cells are needed for healing
cellular response : regulated by inflammatory mediators
3 essential steps to cellular response
chemotaxis
cellular adherence
cellular migration
what is chemotaxis
moving cells to the site of injury
chemotactic factors are activated
what is cellular adherence
attraction and binding to migration site
regulated by chemotactic factors and receptors that bind leukocytes to the endothelial surface
what is cellular migration
across/ between endothelial cells : diapedesis
Phagocytosis
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
5 cardinal signs of inflammation
redness heat swelling(edema) pain incapacitation (loss of function)
what is lymphadenitis
enlargement and inflammation of the lymph nodes
- result of trying to filter harmful substances
- painful palpable nodes
- not painful palpable : neoplasms
Manifestations of inflammation
systemic manifestations may include
- fever (pyrexia)
- increased circulating leukocytes and plasma proteins
- weight loss
- fatigue
- headache
- lethargy
Fever
controlled hyperthermia
due to infection
- Macrophages release cytokines (also called pyrogens)
cause release of prostaglandins from hypothalamus - prostaglandins reset hypothalamic thermostat higher
- heat producing mechanisms
vasoconstriction, heat loss on body surfaces declines
skin cools, shivering begins to generate heat - core body temperatures reaches new set point
- Natural body defences or antibiotic reverse disease process
cryogens (eg. vasopressin) reset thermostat to lower (normal) level - heat loss mechanisms - temperature falls
Fever from practical point : presence of inflammation (sign of infection)
+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
four successive stages of physiologic behaviours that occur during the development of fever
- a prodrome
- non specific complaints, headache and fatigue, fleeting aches and pains - 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 - a flush
- cutaneous vasodilation, skin becomes warm and flushed - defervescence
- initiation of sweating
laboratory diagnosis for inflammation
two non specific tests for inflammation
- CRP : C-reactive proteins
- 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)
during inflammation
coagulation cascade activated increased level of fibrinogen cells stick together RBCs exposed to inflammatory process : fall faster Elevated ESR : sign of inflammation
Treatment of inflammation
inflammatory response : multiple components
damage to healthy surrounding tissue is common
treatment goal to minimise damage
initial treatment for acute inflammation
reduce blood flow
decrease swelling
block the action of chemical mediators
decrease pain
pharmacologic treatment of inflammation
block inflammatory mediators
-reduce swelling, pain, redness, warmth
non pharmacologic treatment of inflammation
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
Resolution of acute inflammation
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
