*UNIFINISHED* MOD Session 2 Flashcards
What is inflammation?
Response of living tissue to injury to limit the tissue damage
Describe acute inflammation.
Innate, immediate, stereotyped, short duration (minutes, hours, days)
What are the causes of acute inflammation?
Microbial infections e.g. pyogenic organisms Hypersensitivity reactions (acute phase) Physical agents Chemicals Tissue necrosis Foreign bodies Trauma
What are the clinical features of A.I?
Rubor = redness Tumor = swelling Dolor = pain Calor = heat
Loss of function
Describe the changes in blood flow in tissues undergoing A.I?
1) Transient vasoconstriction of arterioles
2) Vasodilation of arterioles and then capillaries (increase blood flow causing heat and redness)
3) Increase permeability of blood vessels (causes exudation of protein-rich fluid into tissues and slowing of circulation causing swelling
4) Concentration of RBCs in small vessels and increased viscosity of blood
Describe the early chemical mediators in A.I (within 30mins)? What does it cause?
1) Histamine released from mast cells, basophils and platelets. (responds to many stimuli e.g. physical damage, C3a, C5a, IL-1 etc.
Causes vascular dilatation, transient increase in vascular permeability and pain
What are the three examples of persistant mediators involved in A.I?
Interleukins, bradykinins and prostaglandins and 5-HT
What two properties of vessels cause fluid infiltrate into tissues?
1) Increased hydrostatic pressure by vasodilation of vessels
2) Increased colloid osmotic pressure of interstitium leaks plasma proteins into the tissue
What is oedema and what does it lead to?
Excess fluid in interstitium which can be exudate or transudate. Leads to increased lymphatic drainage
What is the difference between exudate and transudate?
Exudate - fluid loss in inflammation which is protein-rich
Transudate - fluid loss due to hydrostatic pressure with a low protein content e.g. cardiac failure or venous outflow obstruction
What molecules/situations contribute to vascular permeability and increasing leakage?
1) Endothelial contraction - histamine, leukotrienes
2) Cytoskeletal reorganisation - cytokines, IL-1 and TNF
3) Injury
4) Leukocyte dependent injury (toxic oxygen species and enzymes from leucocytes
5) Incerased transcytosis - channels across endothelial cytoplasm e.g. VEGF
What is the primary WBC involved in acute inflammation?
Neutrophil / Polymorph
How do neutrophils migrate and exert its actions at the site of injury?
1) Respond to chemotatic agents from the site of injury e.g. C5a, LTB4, PAMPs. DAMPs,
2) Produce pseudopods and migrate toward site of injury
3) Marginate at edge of venule and produce a rolling interaction
4) Bind to specific selectins and integrins e.g. ICAM-1 and MAdCAM
5) Produce collagenases which digest the basement membrane allowing extravasation into the tissue.
What are the two killing mechanisms of neutrophils?
1) Oxygen depandent - (efficient) produces superoxide and hydrogen peroxide radicals
2) Oxygen independent - lysozyme and hydrolases, bactericidal permeability increasing protein and defensins (cationic proteins)
What are the metabolites of arachidonic acid?
Prostaglandins / Leukotrienes
What molecules contribute to a) increased blood flow, b) vascular permeability, c) neutrophil chemotaxis, d) phagocytosis ?
a) Histamine and PGLs
b) Histamine and Leukotrienes
c) C5a, LTB4 , bacterial peptides
d) C3b
What are the two hallmarks of acute inflammation?
Exudate of fluid and infiltrate of inflammatory cells
What is the purpose of the exudate in A.I? (3 points)
Delivers plasma proteins to are of injury e.g. Igs, inflammatory mediators and fibrinogen
Dilutes toxins
Increased lymphatic drainage which delivers micro-organisms to phagocytes and antigens to immune system
What is the purpose of the infiltrate of cells in A.I?
Removes pathogenic organisms, necrotic debris
What is the purpose of vasodilatation in A.I?
Increases delivery, increases temperature
What is the purpose of pain and LOF in A.I?
Enforces rest, reduces chance of further traumatic damage
What are the local complications of A.I?
Swelling (blockage of tubes e.g. bile duct, intestine)
Exudate (Compression e.g. cardiac tamponade, serositis)
Loss of fluid e.g. burns
Pain & LOF (especially if prolonged)
What are the systemic effects of A.I for fever and leukocytosis?
Fever : endogenous pyrogens produced : IL-1 and TNFa, PGL2 (NSAIDS inhibit COO thus reducing swelling and PGL2 production e.g. aspirin)
Leukocytosis IL-1 and TNFa produce accelerated release from marrow Macrophages, TLym produces CSFs Bacterial infections - neutrophils Viral infections - Lymphocytes
What are the systemic effects of A.I for acute phase response and proteins?
APR: Decreased appetite, raised pulse rate, altered sleep patterns and changes in plasma concentrations of:
APP: CRP, a1 AT, Haptoglobin, Fibrinogen, Serum amyloid A protein
What is shock?
Clinical syndrome of circulatory failure
What are the pathways after the development of A.I?
1) Complete resolution
2) Continued acute inflammation with chronic inflamm = abcess
3) Chronic inflamm and fibrous repair with tissue regenration
4) Death
How is complete resolution brought about?
Changes gradually reverse
Vascular changes stop
1) Neutrophils no longer marginate (die!)
2) Vessel permeability returns to normal
3) Vessel calibre returns to normal (exudate drains into lymphatics, fibrin degraded by plasmin + proteases)
Give examples of acute inflammation and where it can go wrong.
Bacterial meningitis (vascular thrombosis and reduce cerebral perfusion) Lobar pneumonia (pneumonia affceting large area of lobe of lung), caused by strep pneumoniae Skin blister (pain and profuse exudate which is clear unless infection, few inflamm cells) Abcess (solid tissues, inflamm exudate forces tissue apart, liquefactive necrosis, can cause high pressure = pain, cause tissue damage)
Describe A.I in serous cavities?
Exudate pours into cavity e.g. ascites, pleural effusion, pericardial effusion
Resp or CVS impariment
Localised fibrin depostition
Bread and butter pericarditis
List 5 hereditary disorders of A.I?
1) Hereditary angio-oedema
2) Alpha -1 AT deficiency
3) Inherited complement disorders
4) Defects in neutrophil numbers
5) Defects in neutrophil function
