Session 2 - Acute inflammation Flashcards
Describe acute inflammation
Two phases in acute inflammation and the end goals of these
How is acute inflammation controlled?
What causes inflammation?
Clinical sings of inflammation?
Describe: Immediate, short duration, innate, stereotyped, limits damage
Two stages: Vascular phase (changes in blood flow, accumulation of exudate), Cellular phase (delivery of neutrophils)
Acute inflammation is controlled by chemical mediatiors
Causes: Traume/foreign body, mirco-organisms, hypersensitivity, other illnesses e.g. necrosis, neoplasia
Clinical signs: Rubor (redness), calor (heat), dolor (pain), tumor (swelling), loss of function
1st step in acute inflammation: Vascular phase
- Vasoconstriction (seconds) - this then gives rise to vasodilation
- Vasodilation (minutes) -> heat and redness (increase in diameter means more blood flows to the area, INCREASES HYDROSTATIC PRESSURE
- Increase vessel permeability -> fluid and cells can escape
Plasma protein moves into interstitium, increased interstitial oncotic pressure
= Fluid movement: NET - OUT of vessel INTO interstituim. ODEMA (swelling/tumor)
The movement of fluid OUT of vessel - increased viscosity of blood, reduced flow through vessel (stasis)
Vascular phase - movement of fluid
- what is the movement of fluid controlled by the balance of…
- explain these two types of pressures
- where do these pressures exist?
- what is the normal state of pressures in a capillary compared to interstitium
- Movement of fluid is controlled by the balance of: Hydrostatic pressure and oncotic pressure
- Hydrostatic pressure: The pressure exerted on a vessel wall fluid (pushes fluid away)
Oncotic pressure: The pressure exerted by proteins (draws fluid towards) - These pressures exist in the vessel AND the interstitium
- Normal state: Equal pressure between hydrostatic pressure and capilllary oncotic pressure = no net movement
Types of interstial fluid - Two types and of interstial fluid
Exudate:
Increased vascular permeability
Protein rich fluid (delivers proteins to areas of injury)
Occurs in inflammation
Transudate:
Vascular permeability unchanged
Fluid movement due to: Increased capillary hydrostatic pressure OR reduced capillary oncotic pressure
Occurs in: heart failure/hepatic failure (liver dysfunction - produce less plasma proteins in blood - reduced capillary oncotic pressure)/renal failure (if kidney filters blood inefficiently - may loose plasma proteins, reducing capillary oncotic pressure)
How does the vessel wall become permeable?
4 ways:
1. Retraction of the epithelial cells: the epithelial cells shrinks, spaces between epithelial cells are larger, allowing passage of proteins, cells, fluid. Due to chemical mediators: Histamine, nitric oxide, leukotrienes
- Direct injury: Epithelial cells are damaged (due to trauma)
How does the vessel wall become permeable - cont.
- Leucocyte dependent injury: Leucocytes become activated in acute inflammation, release enzymes/toxic oxygen species, directly damaging epithelial cells
Overall - how is the vascular phase effective?
- Interstitial fluid (dilutes toxins)
- Exudate (delivers proteins e.g. fibrin - mesh limits spread of toxins, immunoglobulins from adaptive immune responds) - fluid then drains to lymph nodes, delivery antigens and stimulating adpative immune response
Cellular phase:
- What does this involve
- End goal
- Neutrophils:
The neutrophil is the primary white blood cell involved in acute inflammation, it has a trilobed nucleus - End goal of cellular phase - getting neutrophils out into the tissue, so they can deal with infection
4 stages of neutrophil ‘escape’ from the vessel
- Adhesion molecules
- Margination: Movement of neutrophils from the middle of the blood vessel to the edge
- Rolling: Rolling occurs due to weak intermittant bonds between neutrophils and epithelial cells, they occassionally bind to each other, brining about this rolling of neutrophils
- Adhesion: Tight strong bonds form between neutrophils and epithelial (tethering)
- Emigration (diapedesis): Movement of neutropjils out of the blood vessels and into the interstial space between epithelial cells
- *2 major adhesion molecules:**
- Selectins: Expressed on activated endothelial cells, cell activated by chemical mediators, responsible for ROLLING (intermittant binding between neutrophils and epithelial cells)
- Integrins IAN: Found on neutrophil surface, integrins can change from low affinity to high affinity state, responsible for ADHESION
- — when integrins are in high affinity state, then able to tether to the epithelial cells (after the binding has taken place of the neutrophil and the epithelial cells through the selectins, the state of the integrin then changes from low to high affinity state
How do neutrophils move through the interstitium?
Hw do neutrophils move through the interstitum?
Chemotaxis (reminder: margination, rolling, adhesion, diapedis, chemotaxis)
- Movement along an increasing chemical gradient of chemoattractants: Bacterial peptides, inflammatory mediators (C5a, LTB4)
Rearrangment of neutrophil cytoskeleton - so neutrophil then can move along chemoattractant concentration gradient
What do neutrophils do?
How do neutrophils recognise what to phagocytose?
How do neutrophils destroy pathogens?
How is the cellular phase effective?
What do neutrophils do? (top pic)
Phagocytosis - Phagosomes fuse with lysosomes, produce secondary phagolysosomes, also release inflmmatory mediators
How do neutrophils recognise what to phagocytose? (bottom pic)
Process is called opsonisation
Toxin covered in C3b and Fc (opsonins)
Receptors for C3b and Fc on neutrophil surface
How do neutrophils destroy pathogens?
- Takes place within the phagolysosome
2 types:
- Oxygen dependent (ROS and RNS - see MEH module)
- Oxygen Independent
How is the cellular phase effective?
Removal: Pathogens, necrotic tissue (this necrotic tissue can stimulate inflammatory response, important to remove this necrotic tissue)
Release (released by neutrophils): Inflammatory mediators
Inflammatory mediators
- role
- oringate from?
Role: 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
- Local
- Systemic
Local complications:
- Swelling - lead to compression of tubes e.g. airways/bile duct/intestines/obstruction
- Exudate - leads to compression of organs e.g. cardiac tamponade (if pericardial lining becomes acutely inflammed, then exudate builds up within the pericardial space, this exerts pressure on the heart)
- Loss of fluid e.g. burns (exudate that builds up can evapourate = severe dehydration)
- Pain - muscular atrophy, psycho-social consequences
Complications of acute inflammation - Systemic
- Fever - some inflammatory mediators are pyrogens e.g. prostaglandins, IL-1, IL-6, TNF-alpha, act on hypothalamus to alter temperature
- NSAIDs - Non-steroidal anti-inflammatory drugs, block cyclo-oxygenase enzymes (involved in the production of prostaglandins)
- Leucocytosis - Increased production of white cells, inflammatory mediators act on bone marrow e.g. IL-1 and TNF-alpha
- – Bacterial = neutrophils
- – Viral = lymphocytes
-
Acute phase response - Malaise, reduced apeptite, altered sleep, tachycardia -> induce rest
e. g. CRP (C-Reactive Protein) - Septic shock - Arises due to: huge release of chemical mediators. Widespread vasodilation, widespread increase of vascular epithelial permeability, hypotension, tachcardia, multi-organ failure, can be fatal
What happens after acute inflammation?
- Complete resolution: Mediators have short half lives (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
- Repair with connective tissue (fibrosis): If there has been substantial tissue destruction
- Progression to chronic inflammation: Prolonged inflammation with repair
Examples of acute inflammation
- Appendicitis: Common causes of appendicitis and then the lumen gets blocked, accumulation of bacteria and exudate, increase the pressure - appendicitis bursts
-
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 (Pia meter, arachnoid mater, dura mater)
Many causative organisms: Group B Streptococcus, E.Coli, Neisseria meningitides
Signs and symptoms: Headache, Neck stiffness, Photophobia, Altered mental state, 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 cavities (exudate pours into serous cavities)
