Flashcards in MoD Session 2 Deck (126):
What is acute inflammation?
Response of living tissue to injury
Why is acute inflammation initiated?
To limit tissue damage
What characterises acute inflammation?
How long does acute inflammation last?
Mins to a few days
How does the reaction of acute inflammation to a stimulus vary?
It does not, it is the same irrespective of frequency
What causes the accumulation of fluid exudate and neutrophils in tissues in acute inflammation?
Vascular and cellular reactions
What controls acute inflammation and is derived mostly from plasma cells?
Variety of chemical mediators
Even though acute inflammation is protective, what can it lead to?
What can cause acute inflammation?
Any tissue damage
Microbial infections by pyogenic organisms
Acute phase of hypersensitivity reactions
What are the five cardinal signs of acute inflammation?
Loss of function
Why is function lost in acute inflammation?
To prevent further damage
What are the 3 changes to tissues seen in acute inflammation?
Changes in blood flow
Exudation of fluid into tissues
Infiltration of inflammatory cells
What controls each of the three changes to tissues in acute inflammation?
Mediators for each step
How is blood flow increased in the vascular phase of acute inflammation?
Transient vasoconstriction of arterioles followed by vasodilatation of arterioles then capillaries
What changes do the increase in bloodflow seen in acute inflammation cause?
What are the effects of increasing BV permeability in the vascular phase of acute inflammation?
Exudation of protein-rich fluid into tissues
Slowing of circulation due to thicker blood from fluid loss to tissues
Why is stasis of blood seen in the vascular phase of acute inflammation?
Increased concentration of RBC in small vessels
Increased blood viscosity
What type of granulocyte/polymorphonuclear leucocyte is the primary type of WBCS involved in inflammation?
How is tissue oedema seen histiologically?
Pale neutrophils due to high fluid content
Margination and emigration of neutrophils visible
What determines the exudation of fluid into tissues?
Balance of hydrostatic and colloid osmotic pressure
What two pressure changes cause fluid to move out of the BV?
Increase hydrostatic pressure
Increase oncotic pressure of intersticium
Why does arteriolar dilatation increase hydrostatic pressure?
Lack of resistance to blood flow
What can cause pathological exudation of fluid into tissues?
What mechanisms of vascular leakage can be used?
Leukocyte dependent injury
What causes endothelial contraction?
Histamine and leukotrienes
What mediators are used in cytoskeletal reorganisation?
What is leukocyte dependent injury?
When inflammatory response causes tissue injury itself
What causes damage in leukocyte dependent injury?
Toxic oxygen species
What is transcytosis?
Channels across endothelial cytoplasm not visible by light microscopy
What increases transcytosis?
Vascular endothelial growth factor - VEGF
Why are plasma proteins delivered to the site of injury in the vascular phase of acute inflammation?
Fibrin localises injury and prevents fluid loss
How is delivery of plasma proteins to site of injury in acute inflammation mediated?
How long do chemical mediators take before they mount a response in the vascular phase of acute inflammation?
What mediates the very early steps of acute inflammation and causes its symptoms?
Where is histamine released from?
What stimuli can cause histamine release?
Neutrophils and platelet factors
What action does histamine have?
Acts in receptors in BV wall to cause vascular dilation causing transient increase in vascular permeability and pain
What effect does persistent response have on mediators (which is incompletely understood)?
Histamine thought to interlink w/leukotrienes and bradykinin
What is neutrophil margination?
Neutrophils line up at the edge of the BV along the endothelium
How is neutrophil rolling achieved?
Neutrophils intermittently stick to endothelium whilst rolling
What is the name given to different receptors allowing neutrophils to stick during their infiltration?
What is neutrophil emigration?
Movement through BV wall
How does cell movement alter when blood velocity decreases?
Cells move towards endothelial edge
What do surface ligands bind to in the rolling phase of neutrophils migration?
What do neutrophils bind to in primary adhesion in neutrophil migration?
Which molecules are used in stable adhesion and aggregation in neutrophil migration?
How are neutrophils found outside BV in neutrophil migration?
Transendothelial migration --> extravasation
How do neutrophils escape from vessels in the cellular phase of acute inflammation?
Relaxation of endothelial cell junctions
Enzymatic digestion of vascular BM
Neutrophils change shape to fit through vessels
How do neutrophils move?
Diapedesis and emigration by chemotaxis
What is chemotaxis?
Movement along a concentration gradient of chemoattractants
What attract receptor-binding ligands causing a rearrangement of the cytoskeleton leading to the production of a pseudopod?
Describe the process of phagocytosis in the cellular phase of acute inflammation.
Contact --> recognition --> internalisation
What is phagocytosis facilitated by?
Non-specific fixed component of antibodies
How are secondary lysosomes formed in phagocytosis?
Cytoskeletal changes occur allowing phagosomes to fuse with lysosomes
What is oedema?
Increase in fluid in intersticium of any cause
What change does oedema cause to the lymphatic system?
What are the two types of oedema?
What causes transudate oedema?
Venous outflow obstruction
Arterial dilation removing resistance
Sluggish flow at venules --> high hydrostatic pressure
What characterises exudate oedema?
High protein content
What mechanism causes exudate oedema?
Leaky membrane --> increase capillary hydrostatic pressure due to arterial dilatation and oncotic pressure
What pathology can cause exudate formation?
Which type of killing mechanism is the most efficient?
What do oxygen dependent killing mechanisms produce?
Which proteins are used in oxygen independent killing mechanisms?
Cationic proteins - defensins
Bactericidal permeability increasing protein (BPI)
How do neutrophils cause host tissue damage?
Migrate to site of injury by chemotaxis --> phagocytose microorganisms --> may release toxic metabolites and enzymes
What molecules are chemical mediators of acute inflammation?
How do cytokines/chemokines mediate acute inflammation?
TNF-alpha and interleukins are produced by WBCs for communication
Which chemical mediators act on neutrophil chemotaxis?
Which chemical mediators of acute inflammation act on phagocytosis?
Which chemical mediators of acute inflammation act to increase blood flow?
Which chemical mediators of acute inflammation act on vascular permeability?
Which proteases mediate acute inflammation?
Complement system - C3a/C5a
Generally plasma proteins produced in liver
How are prostaglandins/leukotrienes formed?
Metabolites of arachidonic acid formed from tissue phospholipids
What does leukotriene B4 do to mediate acute inflammation?
Recruits and activates neutrophils, monocytes and eosinophils
Can prolong inflammation
What is the hallmark of acute inflammation?
Exudate of fluid and infiltration of cells
How does exudation of fluid combat injury in acute inflammation?
Delivers plasma proteins, immunoglobulins, inflammatory mediators and fibrinogen to site of injury
Dilutes toxins, increases lymphatic drainage, delivers microorganisms to phagocytes and antigens to lymph nodes
How does infiltration of cells combat injury in acute inflammation?
Removes pathogenic organisms and necrotic debris
What order do cells infiltrate in acute inflammation?
Neutrophils followed by macrophages
How does vasodilatation combat injury in acute inflammation?
Increases delivery and temperature to give a more efficient response
How does pain and loss of function in acute inflammation help combat injury?
Enforces rest and reduces the chance of further traumatic damage
What are local complications of acute inflammation?
Loss of fluid
Pain and loss of function
How does swelling caused by acute inflammation cause complication?
Blockage of tube e.g. Bile duct, intestine, epiglottis in children
What determines the significance of response in exudate formation in acute inflammation?
At what point does appendix inflammation need rapid treatment?
When perforation of the appendix causes peritonitis which will be fatal if not treated
When can exudate production be dangerous to the heart?
If it causes compression e.g. in cardiac tamponade
What causes circulatory failure due to lack of fluid in vessels from vasodilation and exudation?
Failure of initial inflammatory reaction to localise cause leading to acute phase response and subsequent spread of micro-organisms and toxins
What are systemic effects of acute inflammation?
Acute phase response
What causes fever in acute inflammation?
Endogenous pyrogens IL-1, TNF-alpha, and prostaglandins turn up thermostat in hypothalamus
How does acute inflammation cause leukocytosis?
IL-1 and TNF-alpha stimulate WBC release --> macrophages and T-lymphocytes produce CSF
How are viral and bacterial leukocytosis differentiated?
Bacterial = neutrophils
Viral = lymphocytes
What is the acute phase response?
Altered sleep patterns
Changes in plasma concentration of: CRP, alpha 1-antitrypsin, haptoglobin, fibrinogen, serum amyloid A protein
What are the four acute inflammation sequelae?
Continued acute inflammation w/chronic inflammation causing abcess - effectively walled off and needs extra input to overcome
Chronic inflammation and fibrous repair probably w/tissue regeneration
What happens to changes that have occurred gradually during acute inflammation?
What takes place during resolution of acute inflammation?
Vascular changes stop
Neutrophils no longer marginate
Vessel permeability returns to normal
Vessel calibre returns to normal
What happens to exudate formed by acute inflammation upon resolution?
Drains into lympahtics
What thrombolytic process occurs during resolution of acute inflammation?
Fibrin degraded by plasmin and proteases
What happens to neutrophils upon resolution of acute inflammation?
Die --> break up --> carried away/phagocytosed
What must happen for damaged tissue to be regenerated in resolution of acute inflammation?
Tissue architecture not destroyed
Which acute inflammation resolution mechanisms may be unstable?
Some arachidonic acid derivatives, esp. prostaglandins
Which inhibitors may bind to allow resolution of acute inflammation?
Which specific inhibitors of acute inflammatory changes are used in acute inflammation resolution?
What may inactivate mechanisms to resolve acute inflammation?
Degradation e.g. by heparhase
What common feature do all mediators of acute inflammation resolution share?
Short half life
What mechanism of acute inflammation resolution may be diluted in the exudate?
Fibrin degradation products
Give four clinical examples of acute inflammation.
Why can bacterial meningitis cause vascular thrombosis and reduce cerebral perfusion?
All BV to the brain transverse meninges so can be compromised by inflammation
What accumulates in bacterial meningitis?
What causes lobar pneumonia?
Streptococcus pneumoniae (pneumococcus) causes alveoli to contain exudate instead of air
What are the S/S of lobar pneumonia?
Hypoxaemia over a few days
What is prostration?
No energy to get up
What can cause a skin blister?
What are the predominant features of a skin blister?
Pain due to high sensory function
Profuse exudate which can lead to large loss of fluid
What causes the overlying epithelium in a skin blister to strip off?
Collection of fluid
In what circumstance would the exudate of a skin blister not appear clear?
If bacterial infection develops due to few inflammatory cells
What are the sequelae of skin blisters?
Where are abscesses usually found?
In solid tissues
How do abscesses form?
Inflammatory exudate forces tissues apart w/liquefactive necrosis in the centre forming pus
Why do abscesses cause lots of pain?
They can cause high pressure
What can abscesses do to surrounding tissue?
Squash adjacent structures
What alternative treatment can be better than antibiotics in some cases when treating an abscess?
How does acute inflammation in serous cavities cause ascites, pleural or pericardial effusion?
Exudate pours into the cavity
What can acute inflammation in serous cavities cause?
Respiratory of cardiac impairment
Localised fibrin deposition --> 'bread and butter' pericarditis
Why are disorders of acute inflammation rare?
Give four examples of acute inflammation disorders.
Hereditary angio-oedema (angioneurotic oedema)
Alpha-1 antitrypsin deficiency
Inherited complement deficiencies
Defects in neutrophil function or numbers
What does hereditary angio-oedema predispose patients to?