Acute inflammation Flashcards
(36 cards)
What is acute inflammation?
initial rapid response to injury/infection
- takes mins - hours to develop
- short duration (hours - days)
Type of innate immune response
Non-specific, responds to all types of injury
What are the main triggers of acute inflammation?
infections
tissue damage (physical, chemical and mechanical agents/ischaemia)
foreign bodies
What are the main functions of acute inflammation?
- alert the body
- contain infection to prevent it from spreading
- Protect injured site from becoming infected
- eliminate dead cells/tissue
- Healing and repair
Acute inflammation is a physiological response
What are the 5 R’s of acute inflammation?
Recognition Recruitment Removal Regulation (of response) Resolution/Repair
What are the 5 cardinal signs of acute inflammation?
Rubor (redness) Calor (heat) Tumor (swelling) Dolor (pain) Functio laesa (loss of function)
Where does acute inflammation primarily mediate its effect?
locally to site of infection/injury
affecting the capillaries and tissue adjacent initially
(this may have systemic implications)
What systemic changes may be implicated in acute inflammation?
Fever: release of endogenous (IL-6, TNFa) or exogenous pyrogens (microbial toxins)
Neutrophils: G-CSF stimulation of bone marrow. Replenish and release of immature neutrophils = increase in neutrophil count.
Acute phase reactants: CRP, fibrinogen, complement, serum amyloid A protein (SAP)
synthesised in liver, triggered by IL-6, IL-1, TNFa (pro-inflammatory cytokines)
increased fibrinogen -> rouleaux/stacking of RBCs -> increased ESR
What is the mechanism behind elevated ESR in chronic accumulation?
during inflammatory processes, elevated cytokines are released which cause increases in fibrinogen
Fibrinogen deposits on RBCs which causes them to rouleaux
This makes them stickier and heavier, and increases their sedimentation rate. This parameter is known as ESR
ESR has a long duration effect (longer than CRP, which will only be elevated in conditions of acute inflammation)
What are rare consequences of acute inflammation?
Systemic Inflammatory Reaction Syndrome (SIRS)
e.g. sepsis
this is widespread and can cause severe manifestations
SIRS can result in further complications e.g. shock, AKI and multi organ failure
What are the 2 main types of events associated with acute inflammation?
- vascular
- cellular
What vascular events occur in acute inflammation?
- vasodilation (of small vessels)
- Increased blood flow (to injured site)
- increased vessel permeability (fluid leakage results in oedema)
These are driven by release of prostaglandins such as histamine and serotonin
Function of these events is to promote the transport of leukocytes and plasma proteins from the blood to injury site
How does histamine and serotonin affect the endothelium in blood vessels directly?
Causes contraction of the endothelial cells
Exposing gaps between cells where tight junctions normally reside
these gaps are used by immune cells to enter the surround ‘inflamed’ tissue (and also promotes fluid leakage)
What is inflammatory exudate?
produced under inflammatory conditions dues to mediators such as histamine
fluid composed of serum, fibrin and leukocytes
Formed due to increased vessel permeability
How is transudate different from exudate?
transudate formed in non-inflammatory conditions
formed due to increased peripheral pressures (e.g. hypertension) causing fluid to leak out of vessels e.g. lymphoedema
In transudate, the vascular permeability is normal
What are pyrogens?
molecules/mediators that result in an increase in local or systemic temperature
In humans, they usually act at the hypothalamus to initiate a fever
What are the main types of inflammatory exudate?
Serous
Purulent
Fibrinous
Haemorrhagic
What is serous (inflammatory) exudate?
few cells
little or no microbes
fluid derived from plasma or secreted by endothelial cells
found in serous cavities (pleura, peritoneum, pericardium)
skin blisters (burns, viral infections)
What does serous fluid usually refer to?
any body fluid resembling serum
typically pale yellow, transparent and benign in nature
Secretion of serous fluid from cavities is generally termed as an effusion
e.g. pleural effusion
What is purulent (inflammatory) exudate?
= fibrino-purulent
PUS contains many leukocytes (usually neutrophils), dead cells and microbes
pus-producing bacteria (pyrogenic) e.g. staph. A
e.g. in acute appendicitis
e.g. abscess is a collection of (pus) purulent inflammation
What is the long term complications of fibrino-purulent exudate on serous cavities?
This type contains less fluid that other types of exudate
therefore, it is difficult to eliminate
especially in deep structures e.g. pleura
this causes INCREASED FRICTION on epithelial cells
What is fibrinous (inflammatory) exudate?
results in fibrin deposition (from fibrinogen in plasma, increased during acute inflammation in response to IL-6, TNFa)
Forms via large vascular leaks -> fibrinogen exits blood and enters tissue
Present in serous cavities e.g. pleura, meninges
Can lead to chronic scar tissue -> fibrosis -> impaired function
Fibroblasts also may deposits collagen (e.g. stellate cells)
What is haemorrhagic (inflammatory) exudate?
contains RBCs mostly
formed via blood vessel rupture
and trauma
What are the main cellular steps that occur in acute inflammation?
- migration and accumulation of cells e.g. neutrophils
- removal of pathogens + injured/dead cells
- migration and accumulation of monocytes
What are the 5 steps of neutrophil recruitment?
1) Margination and rolling
2) Integrin activation (by chemokines e.g. IL-8)
3) Firm attachment to endothelium (Integrin-ICAMs)
4) Transmigration through endothelium into tissue
5) Chemotaxis to inflamed site (e.g. IL-8 for neutrophils)
