Lecture 4 - Acute inflammation Flashcards
what are the main cells that will be seen in acute inflammation ?
neutrophils
what is inflammation
the response of living tissue to injury
we will see immediate acute inflammation
to limit damage prevent infection if possible (local or systemic complications)
it has a vascular and cellular phase
controlled by many mediators
what are the clinical signs of acute inflammation
Rubor - redness
Dolor - pain
Calor - heat
tumor - swelling
loss of function
outline the changes that occur in the surrounding tissue and vessel during acute inflammation
- changes in blood flow
- movement of fluid into tissue - vascular phase
- infiltration of inflammatory cells into tissue - cellular phase
outline the changes in blood flow that occur
- immediate vasoconstriction
- followed by vasodilation - cause of heat and redness
- increase in vascular permeability - causes oedema - cause of swelling
all of this causes red cell stasis
outline the vascular phase
what does this result in ?
starling law - fluid movement controlled by hydrostatic pressure and oncontic pressure - have a go at defining these if you can
normally this fluid flow is balanced, but during aciute inflammation due to vasodilation and increased vascular permeability you get
increased hydrostatic and oncotic pressure out of the vessel
so there is a net movement of fluid out into the tissue
this results in
Increased viscosity of blood - due to more proteins
so reduced flow through the vessel which we call blood stasis
we are forming an exudate
outline the types of interstitial fluid
exudate - occurs in inflammations - protein rich
transudate - not relevant for path pro, or ESA 2
what is the mechanism for increased vascular permeability ?
include the chemical mediators that cause this
– Endothelial contraction (gaps between endothelial
cells)
• Histamine, leukotrienes
– Endothelial cytoskeleton reorganisation
• Cytokines IL-1, TNF
outline the cellular phase
incude recptors needed
infiltration of neutrophils
occurs via
Margination - stasis causes neutrophils to line up at vessel edges
Rolling - intermittent sticking to endothelium
Adhesion - stick in place
done via selectins on endothelium surface joining to intergins on the neutrophils
Emigration (diapedis) - move through into the tissue
how do neutrophils move through the intersitium ?
hint - what chemical is involved
Chemotaxis
movement towatds chemoattracts along a gradient
chemical - Bacterial peptides, C5a, LTB4
outline how neutrophils work
they destory bacteria
first bacteria or opsonised by osponins C3b and Fc sticking to their surface
C3b and Fc receptors on the neutrophil then recognise and bind to these, allowing phagocytosis
they can then kill via two ways
phagosome joins to lysosome to form a phagolysosome where bacteria is digested and then expcytosis
or via respiratory burst - involves production of damaging free radicals such as superoxide
Why is Acute Inflammation Effective? • 1. Vascular phase how does odema formation limit damage ? • 2. Cellular phase how does infiltration limit damage ?
- odema
dilutes toxins
delivers plasma proteins to injury
- fibrin can form and heal wound plus prevent toxin spread
increased lymphatic draining from injured area
delivers antigens to lymph nodes - where T and B lymphocytes are
- antigen present kick starts immune response
- inflammatory cells
• Removal of toxins and pathogenic organisms
• Removal of necrotic tissue
• Release of chemical mediators stimulates and
regulates further inflammation
• Stimulates pain
– Encourages rest and limits risk of further damage
chemical mediators are a vast array of chemicals that contribute to the inflammatory process
you need to know some of these mediators that cause the key steps of acute inflammation
say as many as you can, do not need to get all of them
• Vasodilatation
– Histamine, Serotonin, Prostaglandins, Nitric Oxide
• Increased vascular permeability
– Histamine, Bradykinins, Leukotrienes, C3a and C5a
• Chemotaxis
– C5a, LTB4, TNF-a, IL-1, Bacterial Peptides
• Fever
– Prostaglandins, IL-1, TNF-a, IL-6
• Pain
– Bradykinin, Substance P, Prostaglandins
outline some of the possible complications of acute inflammation
you DO NOT need to get all of these 100%
just make sure you have the jist of it
can be local or systemic
Local Complications
- Swelling – Blockage of nearby tubes and ducts (bile duct/intestines)
- Exudate – Compression of organs
- Loss of fluid – from Burns
- Pain and loss of function
Systemic Complications • Fever – Endogenous pyrogens (prostaglandins, IL-1, TNFa) – Act on hypothalamus to alter baseline temperature control
• NSAIDs– to reduce inflammation
Systemic Complications
• Leucocytosis (increased production of white
cells)
– IL-1 and TNF act on bone marrow to increase
production
– Bacterial infection = more neutrophils
– Viral infection = more lymphocytes
– Clinical use: can measure blood levels of these…
• Acute phase proteins
– Release of proteins from inflammatory cells:
• C-Reactive Protein (commonly used blood marker if it has fallen infection is on way out)
and others
• Cause “acute phase response”
– Malaise, reduced appetite, altered sleep,
tachycardia
• Septic shock – Overwhelming infection – Huge release of chemical mediators – Widespread vasodilatation – Hypotension, tachycardia – Multi-organ failure – Death
what are the possible outcomes post acute inflammation
Complete resolution - exudate drains away, fibrin degredation ect
Continued acute inflammation with chronic
inflammation -> abscess
Chronic inflammation and fibrous repair, with
some tissue regeneration
Death
