2.1 - Acute Inflammation Flashcards
What is inflammation
the response of living tissue to injury
☞ consists of cellular phase (delivery of neutrophils) + vascular phase (changes in blood flow + accumulation of exudate)
☞ acute inflammation is the first line of defence (sep card)
☞ it is controlled by chemical mediators + protective (but can cause local and systemic complications)
Features of acute inflammation
- Immediate
- Short duration
- Innate (everyone has this mechanism built in at birth)
- Stereotyped (same regardless of injury)
- Purpose is to limit damage
- First line of defence
Clinical signs of acute inflammation
- tumor swelling
- dolor pain
- calor heat
- rubor redness
- loss of function ie unable to walk as they normally would
What are the causes of inflammation
- Trauma/foreign bod
- Hypersensitivity (ie allergy)
- Micro-organisms (eg virus, bacteria, fungi etc)
- Other illnesses (ie necrosis or cancer)
What is the vascular phase
Starts immediately after an insult
1. vasoconstriction where blood vessels constrict to prevent blood loss, occurs in seconds
2. vasodilation occurs after minutes. Allows for more blood to flow to organs. Heat + rubor
3. increased permeability where blood vessels become leaky, allowing fluid and cells to escape to interstitium
Starling’s law: movement of fluid controlled by the balance of…
hydrostatic pressure
The pressure exerted on a vessel wall by fluid (pushes fluid away)
oncotic pressure aka colloid osmotic pressure
The pressure exerted by proteins (draws fluid towards)
note: these pressures exist in the vessels + interstitium. This starling’s law is different to the one in CVS
☞ in normal state: the capillary hydrostatic pressure (from plasma) and the capillary oncotic pressure are roughly equal, so fluid is retained within the blood vessel
In acute inflammation, what are the changes to blood flow and blood vessels
vasodilation → more blood flow to the area
Due to increased capillary hydrostatic pressure
increased vessel permeability → leaky blood vessels
Plasma proteins move into interstitium, causing increased interstitial oncotic pressure
☞ as the blood is more concentrated in the vessel, this increases it’s viscosity
☞ as there is less blood, stasis occurs where there is a reduced flow through the vessel
Therefore unequal forces of oncotic pressure + hydrostatic pressure
fluid movement out of vessel and into interstitium ☞ causes oedema (tumor)
Exudate vs transudate
both types of interstitial fluid
exudate
- Increased vascular permeability
- Protein rich fluid (delivers proteins to area of injury)
- Occurs in inflammation
transudate
- Vascular permeability unchanged (so vessels aren’t leaky)
- Fluid movement due to increased capillary hydrostatic pressure + reduced capillary oncotic pressure)
- Occurs in heart / hepatic / renal failure
Why does transudate get released in heart/hepatic/renal failure
- heart due to increased pressure in the blood vessels (pleural effusion often occurs, which is where fluid is trapped around the lungs
- hepatic proteins are made in liver: in renal failure, less proteins are made → reduced oncotic pressure
- renal if in renal failure, proteins are excreted in urine (they shouldn’t be with a functioning kidney!) → reduced oncotic pressure
How does a vessel wall become permeable
- retraction of endothelial cells ie by chemical mediators (histamine, nitric oxide, leukotrienes)
- direct injury eg burns, toxins + direct trauma
- leukocyte dependent injury where leukocytes release enzymes + free radicals
How is the vascular phase effective
increased interstitial fluid
dilutes toxins
exudate
Delivers proteins eg:
- fibrin forms a mesh that acts as a physical barrier, limiting the spread of toxins)
- immunoglobulins from Adaptive immune response (aka antibodies)
fluid drains to lymph nodes
Carrying pathogen parts/foreign particles with it → Delivery of antigens → stimulates adaptive immune response
What are neutrophils
first responder phagocyte
- Part of the innate immune system
- When they are activated, they can undergo phagocytosis
- Primary WBC involved in acute inflammation
- Trilobed nucleus
- Stain purple
How do neutrophils escape vessels
How do neutrophils escape vessels
1. margination thick sticky blood is pushed to edge of vessel
2. rolling due to weak bonds between neutrophil + endothelial cells. Selectins are responsible for this (more on sep card)
3. adhesion integrins are responsible for this (more on sep card), and the neutrophil pushes through a small gap in endothelial cells
4. emigration (diapedesis) where they leave the capillary – the flexible cell membrane allows for this
What are the main adhesion molecules involved in neutrophils escaping vessels
selectin
- Expressed on activated endothelial cells
- Cells activated by chemical mediators
- Responsible for ‘rolling’ (prev card)
integrins
- Found on neutrophil surface
- Change from low affinity → high affinity state
- Responsible for ‘adhesion’ (prev card)
How do neutrophils move through the interstitium
chemotaxis
- Move from an area of low chemoattractants to an area of high chemoattractants
- Chemoattractants: eg bacterial peptides, inflammatory mediators (eg C5a and LTB4)
- Rearrangement of neutrophil cytoskeleton (allows them to propel themselves)
Basic principles of phagocytosis
- Neutrophils act as phagocytes
- Pathogen binds to phagocyte by receptor proteins
- Microbe is ‘absorbed’ by phagocyte → forms phagosome
- Lysosome (contains lysozymes) fuses with phagosome
- This forms the phagolysosomes
- The lysozymes digest the pathogen
- Release soluble debris + inflammatory mediators
How do neutrophils recognise what to phagocytose
opsonisation
- Pathogens are flagged by opsonins (aka Fc and C3b)
- Complimentary receptors for opsonins found on neutrophil surface
How do neutrophils destroy pathogens
two main killing mechanisms
oxygen dependent
- Produces reactive oxygen species (eg superoxide, hydroxyl + hydrogen peroxide free radicals)
- Also produces reactive nitrogen intermediates (eg nitric oxide + nitrogen dioxide)
oxygen independent
Lysozymes, hydrolytic enzymes + defensins produced
note that activated neutrophils may also cause damage to host tissue
How is the cellular phase effective
removal of pathogens + necrotic tissue, and release of inflammatory mediators (next card)
What are inflammatory mediators + where do they originate from
chemical messengers that control + co-ordinate the inflammatory response
- Varying chemical structures
- Overlapping functions: different inflammatory mediators do the same thing → this is important for control
originate from
- activated inflammatory cells
- platelets
- endothelial cells
- toxins
What are some examples of inflammatory mediators involved in acute inflammation
- vasodilation histamine, serotonin, prostaglandins, nitric acid
- increased permeability of blood vessels histamine, bradykinin, leukotrienes, C3a + C5a
- chemotaxis C5a, TNF-α, IL-1, bacterial peptides
- fever (pyrogens) prostaglandins, IL-1, IL-6 and TNF-α
- dolor bradykinin, substance P, prostaglandins
Note that: IL stands for interleukin
Complications of acute inflammation
local - specific to one anatomical area
▶︎ swelling: compression of tubes eg airways, bile duct, intestines (eg epiglottis or anaphylactic shock)
▶︎ exudate: can cause compression of organs, such as pleural effusion or cardiac tamponde
▶︎ loss of fluid: if exudate gets to outside world (eg burns)
▶︎ pain: muscle atrophy + psycho-social consequences
systemic - whole body
▶︎ pyrexia / fever: some inflammatory mediators are pyrogens (see card above) that act on the hypothalamus to increase temperature. Need to use NSAIDs to help this (block cyclo-oxygenase enzymes that are involved in the production of prostaglandins)
▶︎ leukocytosis: increased production of WBCs (as inflammatory mediators act on bone marrow)
▶︎ acute phase response: reduced appetite, altered sleep + tachycardia (these induce rest → promote healing)
▶︎ sepsis: huge release of chemical mediators, leading to widespread vasodilation → hypotension + tachycardia (to compensate for hypotension) → multi-organ failure (due to lack of oxygen)
How to differentiate between leukocytosis in bacterial vs viral infection
bacterial = neutrophils will be increased
viral = lymphocytes will be increased
Inflammation marker in blood results
C-reactive protein (CRP)
- Marker of inflammation (but can’t say where inflammation is → no diagnosis)
- Marker of severity (to see progression of disease)
