Flashcards in MoD S3 - Acute inflammation Deck (42):
What is 'Acute inflammation'?
The response of living tissue to injury, initiated to limit the tissue damage
The mechanisms of acute inflammation are innate, immediate and of short duration (minutes to a few days)
What are some of the causes of acute inflammation?
Microbial infections (E.g. Pyogenic organisms)
Hypersensitivity reactions (acute phase)
What are the macroscopic features of acute inflammation?
What are the microscopic hallmarks of acute inflammation?
Rubor - erytherma (redness)
Tumor - oedema (swelling)
Calor - heat
Dolor - pain
Loss of function
Exudate of fluid
Infiltrate of inflammatory cells
What are the major tissue changes present in acute inflammation and how are they controlled?
Changes in blood flow
Exudation of fluid into tissues
Infiltration of inflammatory cells
Inflammatory mediators control each step
Give description of how blood flow changes during acute inflammation
Mention how these changes result in a macroscopic clinical feature of acute inflammation
Transient vasoconstriction of arterioles (only lasts a few seconds)
Then vasodilation of arterioles then capillaries, leading to an increase in blood flow (erythrema)
High concentration of RBCs in small vessels and increased viscosity of blood leads to stasis (serious slowing or cessation of blood flow)
Describe how exudation of fluid into tissues comes about
What macroscopic feature of acute inflammation does this cause?
Increased permeability of blood vessels caused by histamine release in the tissue
Histamine causes endothelial cells to swell and retract, leaving gaps in the endothelium
This, along with arteriolar dilatation leads to exudation of protein rich fluid into tissues (oedema) and a slowing of the circulation
Macroscopically, this causes swelling
What determines fluid flow across a vessel wall?
How does this relate to acute inflammation?
Fluid flow across the vessel wall determined by the balance between hydrostatic and colloid osmotic pressures (Starling's Law)
Increased hydrostatic pressure = increase fluid flow out of the vessel
Increased colloid osmotic pressure = increased fluid flow into the vessel
In acute inflammation:
Arteriolar dilatation leads to increased hydrostatic pressure, fluid moves into the interstitium
Increased permeability of vessels leads to protein loss into interstitium
This leads to protein rich exudate in the tissues (oedema/excess fluid in interstitium)
What is the difference between exudate and transudate?
Which of these leads to oedema?
Exudate is protein rich fluid loss in inflammation
Transudate is fluid loss due to hydrostatic pressure only and is therefore low in protein
Oedema can result from both
Name a major consequence of oedema
Increased lymphatic drainage
What are some other mechanisms of vascular leakage seen in acute inflammation?
Include some of the possible causes for each mechanism
Cytoskeletal reorganisation leading to gaps in the endothelium:
- Cytokines, IL-1 and TNF
- Toxic burns
Leukocyte dependent injury:
- Enzymes from leukocytes
Increased transcytosis across endothelial cells:
what is the most common cell type seen infiltrating into the tissues during acute inflammation?
What other types of cells infiltrate into acutely inflamed tissues?
Describe in basic terms how neutrophils infiltrate into tissues
Hint: 4 stages
Stasis causes neutrophils to line up along the endothelium
Neutrophils roll along the endothelium, sticking intermittently
Then stick more avidly
Neutrophils move through the cell wall
How is it that once neutrophils have adhered to the vessel walls they are able to move into tissues?
Relaxation of endothelial cell junctions
Digestion of the vascular basement membrane
What is a neutrophil? (TOB)
A white blood cell involved in inflammation
List the actions of a neutrophil
Migrate to and infiltrate tissues by chemotaxis
May release toxic metabolites and enzymes that damage the host tissue
What is chemotaxis?
How do neutrophils perform chemotaxis?
Movement along a concentration gradient of chemoattractants
Neutrophils have cell surface receptors that bind to these chemoattractants and allow the neutrophil to direct its migration
Examples of neutrophil chemoattractants include:
- C5a (complement)
- Bacterial peptides
How do neutrophils perform phagocytosis?
Neutrophil must make contact with a cell coated in opsonins (C3b, Antibodies) that it then recognises with cell surface receptors
Cytoskeletal changes allow the neutrophil to internalise the cell forming a phagosome
A lysosome is fused with the phagosome to form a secondary lysosome and digest the internalised cell
By what mechanisms might neutrophils kill internalised cells?
Hint: 2 types of mechanism
O2 dependent mechanisms:
- Produces superoxide and H2O2
- H2O2-myeloperoxidase-halide system (produces HOCl)
O2 independent mechanisms:
- Lysozyme and hydrolases
- Bactericidal permeability increasing protein (BPI)
- Cationic proteins (Defensins)
List some of the chemical mediators of inflammation according to the process they mediate
Increased vascular permeability:
How does exudation of fluid into tissue combat injury?
Delivers plasma proteins to area of injury
Increases lymphatic drainage delivers microorganisms to phagocytes and antigens in the immune system
How does infiltration of inflammatory cells help combat injury?
Removes pathogenic organisms and necrotic debris
How does vasodilatation help combat injury?
Increases delivery of blood to the area and increases temperature
How does pain and loss of function help combat injury?
Reduces chance of further traumatic damage
What are the possible local complications of acute inflammation?
Swelling can cause the blockage of tubes, for example in the bile duct or intestine
Exudate into tissues can cause compression (as in cardiac tamponade) and serositis
Can lead to loss of fluid (E.g. In burns)
Can lead to pain and loss of function, especially when prolonged
List the systemic effects of acute inflammation
Acute phase response
Spread of microorganisms and toxins that can lead to shock
Why does acute inflammation lead to fever?
What can be done to reduce the fever?
Endogenous pyrogens produced:
Note: Pyrogens are compounds that cause fever
Prostaglandins also produced, therefore aspirin reduces fever
What is leukocytosis?
Why does acute inflammation lead to leukocytosis?
Leukocytosis is a white blood cell count of above normal range, a sign of inflammatory response
IL-1 and TNF-alpha produce an accelerated release of WBCs from the marrow
Macrophages produced as T-lymphocytes produce M-CSF (Macrophage colony stimulating factor)
In bacterial infections, neutrophils are produced
In viral infections, lymphocytes are produced
What is the acute phase response and what does it cause?
A class of proteins whose concentrations increase or decrease in response to inflammation
Raised pulse rate
Altered sleep patterns
Changes in plasma protein concentrations
List some proteins involved with the acute phase response
C-reactive protein (CRP)
Serum amyloid A protein
List the possible consequences of acute inflammation
Continued acute inflammation with chronic inflammation = abscess
Chronic inflammation and fibrous repair, probably with tissue regeneration
In complete resolution of inflammation, what morphological changes are seen?
Changes gradually reverse
Vascular changes stop:
- Neutrophils no longer marginate
- Vessel permeability returns to normal
- Vessel calibre returns to normal
What is the result of the morphological changes seen during resolution of inflammation?
Exudate drains to lymphatics
Fibrin is degraded by plasmin and other proteases
Neutrophils die, break up and are carried away or phagocytosed
Damaged tissue might be able to regenerate
What determines whether tissue will be able to fully regenerate after acute inflammation?
If tissue architectures is damaged, full resolution is not possible
If intact, full resolution possible
By what mechanisms is acute inflammation resolved?
For each mechanism, give an example of an inflammatory mediator that is inactivated by it
All mediators of inflammation have short half lives and may be inactivated by:
- Degradation (E.g. Heparinase)
- Inhibitors may bind (E.g. Anti-proteases)
- May be unstable (E.g. Some arachidonic acid derivatives)
- Dilution in exudate (E.g. Fibrin degradation products)
- Specific inhibitors of inflammatory change (E.g. Lipoxin)
What is meningitis and what are two common features?
Acute inflammation of the meninges
- Vascular thrombosis
- Reduce cerebral perfusion
What might be observed in the alveoli during lobar pneumonia?
What does this cause and what is the causative organism?
Can lead to:
- Shortness of breath/difficulty breathing
- Worsening fever, prostration and hypoxaemia over a few days
Infection by streptococcus pneumoniae
What are the possible causes of a skin blister?
What are the predominant features?
How is it resolved?
Heat, sunlight, chemical
- Pain and profuse exudate
- Collection of exudate in tissue strips off epithelium
- Exudate clear due to relatively few inflammatory cells unless bacterial infection develops
Complete resolution or scarring can occur
What is an abscess?
What might an abscess cause?
Inflammatory response in solid tissues where the exudate forces tissues apart
Liquefactive necrosis then occurs in the centre
High pressure, therfore can cause pain
Can cause tissue damage and squash adjacent structures
What happens during acute inflammation of serous cavities?
Give some examples
Exudate pours into the serous cavity
Pleural or pericardial effusion
What is bread an butter pericarditis?
Pericarditis with fibrin deposition in the pericardium that results in a 'bread and butter' appearance
Give a few examples of disorders of acute inflammation
Alpha-1 anti-trypsin deficiency
Inherited complement deficiencies
Defects of neutrophil function or number