L4: Acute Inflammation Flashcards
What is inflammation?
Response of living tissue to injury
Protective mechanism–> can cause local and systemic complications (sometimes worse than initial thing)
Controlled–> Chemical mediators
What are the characteristic of acute inflammation?
Immediate Short Duration Innate Sterotyped --> same Limits danger
What are the different stages of inflammation?
Vascular phase–> Changes in blood flow, accmulation of exudate
Cellular phase–> Delivery of neutrophils
What can cause inflammation?
Trauma
Hypersensitivity
Microorganism
Other illnesses
What are the cardinal signs of inflammation?
- Rubor–> Redness
- Tumor–> Swelling
- Calor–> Heat
- Dolor–> Pain
- Loss of function (functio laesa)
During the vascular phase what changes in blood flow occur?
Transient vasoconstriction (seconds)
Vasodilation (minutes)–> heat and redness
Increased permeability –> fluid and cells can escape
What controls the movement of fluid?
Starling Law
What does Starling Law state?
Movement of fluid is controlled by the balance of hydrostatic pressure and oncotic pressure
Different to Frank-Starling law of the heart
What is the difference between hydrostatic and oncotic pressure?
Hydrostatic pressure–> pressure exerted on vessel wall by a fluid–> pushes fluid away
Oncotic pressure–> pressure exerted by proteins, in the interstitial fluid–> pulls fluid towards
What happens to the capillaries during inflammation?
Vasodilation–> increased hydrostatic pressure in capillary
Increased vessel permeability–> plasma proteins move into the interstitium–> increased oncotic pressure in interstitium
Fluid movement–> out of vessel into interstitium–> Odema (swelling/tumor)
What happens to the blood when the fluid moves out? What effect does this have on the flow of blood?
Increases viscosity of blood
Reduces the flow through the vessel–> stasis
What are the different types of interstitial fluid? Compare and contrast then?
Exudate–> increased vascular permeability
- -> protein rich fluid (delivers protein to area of injury)
- -> occurs in inflammation
Transudate–> Not related to inflammation
- -> vascular permeability unchanged
- -> fluid movement due to ↑hydrostatic pressure, ↓capillary oncotic pressure
- -> interstitial fluid–> protein free
- -> occurs in–> HF, Hepatic failure, renal failure
How does the vessel wall become permeable?
- Retraction of endothelial cells –> NO, histmaine, leukotrienes
- Direct injury–> burns, toxins, trauma
- Leukocyte dependent injury–> enzymes, toxic O2 species released by inflammatory cells
How is the vascular phase of inflammation effective?
Increased interstitial fluid–> dilutes the toxins
Increased exudate–> delivers proteins
e.g. fibrin–> forms a mesh to limit the spread of toxins–> physical barrier
e.g. immunoglobulins–> adaptive immune response–> targeted destruction of pathogens
Where does the fluid drain to?
Lymph nodes
- -> delivery of antigens to lymphocytes
- -> adaptive immune response activated
What is the main function of the cellular phase?
Immune cells to site of inflammation
What is the main WBC involved in acute inflammation?
Neutrophil
Larger than RBC (just)
Trilobed nucleus
Granulocyte
How do neutrophils escape the circulation?
↑ Viscosity of blood, movement slows Margination--> adhesion to capillary Rolling--> rolls along surface Adhesion-->attached more tightly to capillary Emigration (diapedesis)--> escaping
What adheres the neutrophil to the surface?
Selectins
Integrins
What are selectins?
Expressed on activated endothelial cells
Activated by chemical mediators
Weak bonds–> responsible for rolling
What are integrins?
Neutrophil surface
Change from low affinity to high affinity state
Responsible for adhesion
What makes neutrophils move through the interstitium?
Chemotaxis
Move towards highest concentration of chemoattractant
Chemoattractant: bacterial peptides, Inflammatory mediators
Neutrophil cytoskeleton rearranges to allow movement
What is the role of neutrophils? How do they do it?
To engulf pathogens –> Phagocytosis
- -> phagosome fused with lysosome
- -> produces secondary phagolysosome
- -> release inflammatory mediators–> propagate inflammatory response
How do the neutrophils know what to phagocytose?
Opsonisation– recognition system
- -> proteins bind to surface of pathogen enhancing attachment of phagocytes
- -> Toxin covered in opsonins–> C3b and Fc
- -> receptor for C3b and Fc on neutrophil surface
What are the mechanisms used by neutrophils to kill bacteria?
Oxygen dependent and oxygen independent pathways
What are the features of the oxygen dependent pathway?
Reactive oxygen intermediates (ROS, RNS and free radicals) ROS --> Superoxide anion --> OH• --> H2O2 RNS --> NO --> NO2
What are the features of the oxygen independent pathway?
Enzymatic destruction
- Lysozymes
- Hydrolytic enzymes
- Defensins
What is the draw back to the neutrophil response?
Activated neutrophils can cause damage to host tissue
What are the two outcomes of the cellular phase of acute inflammation?
Removal of pathogens and necrotic tissue
Release of inflammatory mediators
What are inflammatory mediators?
Modulates the inflammatory response in some way
Chemical messengers–> control and coordinate, varying chemical structures, overlapping functions
Where do the chemical mediator originate from?
Activated inflammatory cells
Platelets
Endothelial cells
Toxins
What controls the chemical mediators?
Inhibitors–> stop inflammation from going on endlessly
Short half lives –> seconds to minutes–> effects last minutes to hours
Where do the endogenous mediators come from?
Supplied by plasma, leukocytes, and local tissues
How are the mediators classified?
- Vasoactive amines –> histamine and serotonin
- Vasoactive peptides–> bradykinin (↑ vascular permeability)
- Complement components–> C3a and C5a–> forms membrane attack complex (tube)–> punches holes in bacteria causing them to die
- Clotting and fibrinolytic cascade–> generate inflammatory mediators
- Phospholipid derived mediators –> prostaglandins, thromboxanes and leukotrienes
- Cytokines and chemokines –> IL, TNF, interferons
- Exogenous mediators of inflammation–> in tissue= inflammation, in blood= septic shock
What are the main roles of the inflammatory mediators?
Vasodilatation–> histamine, serotonin, prostagladins, NO
Increased vascular permeability –> histamines, serotonin, prostaglandins
Chemotaxis–> Leukotrienes B4, C5a and C3a, chemokines, and bacterial peptides, TNF-α
Phagocytosis–> C3b complement plasma precursor
Pain –> bradykinin, substance P
Vasoconstriction–> histamine, bradykinins, leukotrienes, C3a and C5a??? look up in workbook
What are the local complications of acute inflammation?
Damage to normal tissues
Swelling–> compression of tubes e.g. airways, bile duct
Exudate–> compression of organs e.g. cardiac temponade
Loss of fluid–> dehydration e.g. burns
Pain and loss of function–> muscle atrophy, psycho-social consequences
What are the systemic complications?
Inflammatory mediators in the blood stream
Fever–> pyrogens (inflammatory mediators)–> acts on hypothalamus to alter temperature
Exogenous sources - NSAIDs- block COX activity - ↓ prostaglandins reduce fever
Leucocytosis–> ↑WBC –> measured in blood
Acute Phase response–> causes discomfort/ unwell (malaise), reduced appetite, altered sleep, tachycardia–> induced rest!!
–> changes in levels of plasma proteins (liver changes pattern of protein synthesis)–> ↑CRP–> marker of inflammation
Septic shock–> huge release of chemical mediators, widespread vasodilatation, increase vascular permeability–> hypotension and tachycardia–> multiorgan failure–> often fatal
What happens after acute inflammation?
1- Complete resolution
2- Repair with connective tissue
3- Progression to chronic inflammation
What is meant by complete resolution?
Mediators–> short half lives- diluted/inactivated/degraded
Vessel calibre and permeability –> normal
Neutrophils undergo apoptosis and get phagocytosed
Exudate –> lymphatics
Regeneration of tissue architecture if preserved
Why would it need repairing with connective tissue? Problem with this?
Extensive damage –> tissue destruction
Leads to fibrosis
What happens if the acute inflammation is unable to kill the pathogen?
Chronic inflammation
Prolonged inflammation with repair
What is appendicitis? Why does it happen?
Inflammation of the appendix
Blocked lumen–> faecolith (hard faeces)
Accumulation of bacteria and exudate–> ↑ pressure–> perforation
What is pneumonia? What causes it? Signs and symptoms? Risk factors?
Common respiratory tract infection
Caused by–> Streptococcus pneumoniae, haemophilus influenza
S and S–> SoB, cough, sputum, fever (accumulation of exudate–>builds up–> prevents gaseous exchange)
Risk factors–> smoking–> destroy mucocillary escalator
Pre-existing lung conditions–> COPD, Astham, Malignancy
What is meningitis? What are the signs and symptoms?
Inflammation of the meninges
Mainly caused by; Neisseria meningitides, E.Coli, Group B Streptococcus
Headache, neck stiffness, photophobia (sensitive to light), atered mental state –> rapidly fatal
What is an abscess?
Accumulation of dead and dying neutrophils
With associated liquefactive necrosis
Can cause compression of the surrounding structures–> pain and blockage of ducts
What happens if you get inflammation of serous caivities?
Exudate pours into the serous cavities
Pleural space–> pleural effusion
Peritoneal space–> ascities (distension of abdomen)
Pericardial space–> pericardial effusion
Can you get disorders of acute inflammation?
Yes but rare
Hereditary angio-oedema
Alpha-1 antitrypsin deficinecy
Chronic granulomatous disease
