Acute Inflammation Flashcards
Acute inflammation
What is inflammation - the response of living tissue to injury
Acute inflammation has specific cardinal signs - its immediate, its only a short duration, its innate, its stereotyped and it limits damage
Vascular phase - changes in blood flow - accumulation of exudate
Cellular phase - delivery of neutrophils
What causes inflammation - trauma, microorganisms (infection) and hypersensitivity
Clinical signs of acute inflammation - swelling (tumor), redness (rubor), pain (Dolor), loss of function, heat(Calor) and itching
vascular phase - changes in blood flow and movement of fluid
Vasoconstriction - seconds
Vasodilation - minutes - what and redness
Increased permeability - fluid and cells can escape
Starlings law - Movement of fluid is controlled by the balance of -
Hydrostatic Pressure - The pressure exerted on a vessel wall by fluid
Oncotic pressure - The pressure exerted by proteins
These pressures exist in the vessels and the intersititum
With acute inflammation -
Vasodilatation occurs - Increased capillary hydrostatic pressure
Increased vessel permeability occurs - Plasma proteins move into interstitium Increased interstitial oncotic pressure
Fluid movement - OUT of vessel INTO interstitium OEDEMA (swelling/tumor)
Movement of fluid OUT of vessel - Increased viscosity of blood
Reduced flow through vessel - STASIS
Types of interstitial fluid
Exudate - increased vascular permeability, protein rich fluid (delivers proteins to area of injury), occurs in inflammation
Transudate - vascular permeability uncharged, fluid movement due to (increased capillary hydrosatic pressure and reduced capillary oncotic pressure), occurs in heart failure and hepatic failure (due to reduced proteins (therefore reduced oncotic pressure)), renal failure (proteins lost in the urine )
How does vessel wall become permeable
1) endothelial cell retract, so space between cells gets bigger
2) endothelial cells can become damaged (burns/toxins)
3) Leucocytes become activated - and realease enzymes/ ROS
Why is vascular phase effective ?
Interstitial fluid - dilutes the toxin
Exudate - delivers proteins e.g. Fibrin which forms a mesh around the area of infection limiting its ability to spread / or immunoglobulins
Fluid drains to lymph nodes - delivery of antigens - stimulates adaptive immune response - lymph nodes enlarge as the cells try to replicate to “see if we’ve had this infection before”
Cellular phase
This phase is mainly centred around the neutrophil
It’s the primary white blood cell - involved in acute inflammation
It has a trilobed nucleus
It’s a granulocyte
How do Neutrophils escape vessels ?
At end of vascular phase - blood is thick and sticky
Allows for these cells to migrate to margin of blood vessels, it then forms weak bonds with blood vessel cells (rolling) , it then binds more tightly (adhesion) and then emigrates out of the blood vessel and into the surrounding tissue
Adhesion molecules
Selectins - Expressed on activated endothelial cells
Cells activated by chemical mediators - Responsible for “rolling”
Integrins - Found on neutrophil surface
Change from low affinity to high affinity state - Responsible for “adhesion”
How do neutrophils move through to the interstitium
Chemotaxis - Movement along an increasing chemical gradient of chemoattractants:
Bacterial peptides, inflammatory mediators (C5a, LTB4)
Rearrangement of neutrophil cytoskeleton
What do neutrophils do ?
Phagocytosis - take up bacterium and also phagosomes fuse with lysosomes, produces secondary phagolysosomes and bacteria is broken down
Also release inflammatory mediators
How do Neutrophils recognise what to phagocytose - Opsonisation - toxin covered in C3b and Fc (opsonins)
Receptors for C3b and Fc on neutrophils surface
These then recognise each other and bind to each other - therfore allowing the neutrophil to phagocytose the pathogen
How do Neutrophils destroy pathogens:
Killing mechanisms
Oxygen dependent - ROS intermediates (O. (Superoxide anion), OH. (Hydroxyl radical), H2O2 (hydrogen peroxide))
RNS intermediates - (NO (nitric oxide), NO2 (nitrogen dioxide))
Oxygen independent - Lysosomes, hydrolytic enzymes and defensins
(Activated neutrophils may also cause damage to the host’s tissue
How is the cellular phase effective
Removal - removes pathogens and necrotic tissue
Release - releases inflammatory mediators
Chemical Messengers - Control and co-ordinate the inflammatory response
Varying chemical structures - Overlapping functions
Originate from - Activated inflammatory cells, Platelets, Endothelial Cells, Toxins
Complications of acute inflammation
Can be local and systemic
`Local complications - swelling is good - but if it takes place in a critical anatomical site - i.e. around a tube e.g. epiglottis infection - this can lead to upper airway obstruction
`Exudate around the heart - pericarditis - if exudate builds up in this space, then swelling surrounds the heart and compresses it - so heart cant pump as affectivly
- too much Loss of fluid - due to burns
- Pain - can be too much - can cause atrophy of muscles and psycho-social consequences
Systemic complications -
Fever - Some inflammatory mediators are pyrogens Eg Prostaglandins, IL-1, IL-6, TNF-a
Act on hypothalamus to alter temperature
Therefore you can take NSAIDs - Non-steroidal anti-inflammatory drugs that block cyclo-oxygenase enzymes (involved in the production of prostaglandins)
Acute phase response - Malaise, reduced appetite, altered sleep, tachycardia - Induces rest
Acute Phase Proteins - C-Reactive Protein (common blood test – marker of severity) - Fibrinogen + a1 antitrypsin
Septic shock - Huge release of chemical mediators - Widespread vasodilatation - Hypotension (so cant pump blood to vital organs), - tachycardia - Multi-organ failure - Can be fatal (media attention as its hard to spot
Can have some beneficial events with systemic complications
Leucocytosis Increased production of white cells
Inflammatory mediators act on bone marrow Eg IL-1 and TNF-a
Bacterial = neutrophils Viral = lymphocytes
Therefore can recruit more WBC to the cause
And it can be measured in A+E to see if bacterial/ viral
What happens after acute inflammation
Option 1 - Complete resolution
Mediators have short half lives therefore become Diluted/inactivated/degraded
Vessel calibre and permeability returns to normal
Neutrophils undergo apoptosis and get phagocytosed
Exudate drained via lymphatics
If tissue architecture is preserved, can undergo regeneration
Option 2 – Repair with connective tissue (fibrosis) - If there has been substantial tissue destruction - not 100% functional but body can get by
Option 3 – Progression to chronic inflammation - Prolonged inflammation with repair
Clinical examples
Appendicitis - Blocked lumen - Faecolith (hard type of faeces), which leads to accumulation of bacteria + exudate —> increased pressure —> perforation
Pneumonia - Many causative organisms: Streptococcus pneumoniae Haemophilus influenzae
Signs and symptoms: Shortness of breath, Cough, Sputum, Fever,
Risk factors: Smoking Pre-existing lung condition (Chronic Obstructive Pulmonary Disease/asthma/malignancy)
Bacterial meningitis -
Inflammation of meninges - 3 layers to the meninges (Dura, arachnoid and pia mater)
Many causative organisms: Group B Streptococcus E.Coli Neisseria meningitides
Signs and symptoms: Headache, Neck stiffness, Photophobia, Altered mental state, non blanching rash
Rapidly fatal
Abscess - Accumulation of dead and dying neutrophils
With associated liquefactive necrosis
Can cause compression of surrounding structures:
Pain + Blockage of ducts
Inflammation of Serous Cavitites:
Exudate pours into serous cavities - variety of cases
In the pleural space, peritoneal space and pericardial space
