3 - Acute Inflammation Flashcards
What is inflammation?
The response of living tissue to injury
What are the characteristics of acute inflammation?
- Eary transient response to cell injury in live vascular tissue, e.g cannot have inflammation in cartilage
What causes inflammation?
- Physical trauma
- Physical and Chemical agents
- TIssue necrosis
- Immune reactions
- Foreign bodies
- Infections and toxins
- Hypersensitivity
What are the clinical signs of acute inflammation?
What are the two different phases in acute inflammation?
1. Vascular - to form exudate via changing blood flow and fluid entering tissue
2. Cellular - response to get cells to the scene
What is the first stage of inflammation?
Vascuar phase - changes in blood flow
1. Initial vasoconstriction (s)
2. Vasodilataton (mins) (heat and redness)
3. Permeability increase so oedema
4. Red cell stasis due to more viscous blood
How does vasodilatation occur?
Due to vasoactive mediators like histamine, which is a vasoactive amine
What are vasoactive amines?
Group of chemical mediators that are involved in early inflammation, e.g histamine and serotonin. They are stored in granules of basophils, mast cells and platelets (serotonin), and released in response to stimuli like damage
Cause: Increased venular permeability, pain, arteriolar dilatation
How does fluid move from in the blood into the interstitium?
- Vasodilatation increases the hydrostatic pressure in the capillary as blood flow increases, forcing out
- Increased vessel permeability leads to leakage of proteins so increased interstitial oncotic pressure
STARLINGS LAW
Why does inflammation lead to stasis?
Fluid is leaving the capillary so decreased fluid in capillary, increased haematocrit so increased viscosity and decreased flow through vessel
What are the different types of interstital fluid?
Exudate: In inflammation due to increased vascular permeability
Transudate: Low protein fluid due to increase hydrostatic pressure or decreased oncotic pressure, e.g heart failure, hepatic failure or renal failure (excretion of plasma proteins)
How can there be increased vascular permeability?
- Endothelial contraction: histamines, leukotrienes, bradykinin
- Direct injury: burns
- Leucocyte dependent injury: respiratory bursy
- Endothelial skeleton reorganisation: cytokines, TNF
What will a tissue sample look like under the microscope during acute inflammation?
Lots of neutrophils
What does it mean if neutrophils are found in the tissues?
Normally only in blood/bone marrow so in tissue indicates infection by parasite, bacteria etc
How do neutrophils get from the blood to killing bacteria in the tissues?
- Chemotaxis
- Activation
- Margination
- Diapedesis/Emigration
- Recognition-attachment to bacteria
- Phagocytosis
What is chemotaxis and what are some chemotaxins?
Directional movement towards a chemotaxin, up a concentration gradient.
Chemotaxins:
- Leucocytes: LTB4
- Bacterial peptides/Endotoxins
- Complement release fragments especially C5a
- Clotted blood due to thrombin and FDP’s
How does activation of neutrophils occur?
Chemokine binds to receptor on neutrophil causing massive influx of Na and Ca so it swells and reorganises it’s cytoskeleton into triangle towards stimulus. Puts out pseudopodia and cell becomes stickier
How does a neutrophil adhere to endothelial cells?
Selectins: On endothelial surface, upregulated with chemotaxins
Integrins: On neutrophil surface and bind to selectins. Binding of PAF receptor increases affinity of integrins by activating them
How does diapedisis occur?
Leucocytes produce collagenase to break down basement membrane of endothelial cells so they can fit in. Once in tissue, move along collagen fibres
What is opsonisation and how does it aid phagocytosis?
Plasma proteins that cover targets making it easier for phagocytes to recognise them e.g IgG antibody (reinfection) and C3b fragment of complement
If no opsonins phagocyte recognising surface antigens
What are the two pathways that a neutrophil can kill a bacteria by?
What is degranulation?
Cells granules move towards phagosome and release bactericidal substances into it. Occurs before membrane fully closes so some can leak out and damage host cell.
How does oedema limit damage?
- Dilute toxins
- Deliver plasma proteins to injury site, e.g immunoglobulins and fibrin
- Increased lymphatic drainage in area so antigens more likely to reach lymph nodes
How do inflammatory cells limit damage?
- Removal of toxins and pathogenic organisms
- Release of chemical mediators
- Removal of necrotic tissue
- Stimulare pain to encourage rest
Where are chemical mediators released from?
- Endothelial cells
- Exotoxins
- Activated inflammatory cells
- Platelets
- Some in the blood in inactive state
What are some of the roles of chemical mediators?
- Vasodilatation: histamine, serotonin, prostaglandins, NO
- Increased vascular permeability: hitamine, bradykinin, leukotrienes, C3a and C5a
- Pain: prostaglandin, bradykinin, substance P
- Chemotaxis: C5a, LTB4, TNF, IL-1, bacterial peptides
- Fever: IL-1, IL-6, TNFa, prostaglandin
What can different chemicsl mediators be classified as?
- Vasoactive amines
- Vasoactive peptides
- Endotoxins
- Complement components
- Clotting cascades
- Cytokines/chemokines
- Mediators from phospholipids
What chemical mediator can lead to sepsis?
When endotoxins are released into blood, not tissue, so multiple inflammation pathways triggered at once
What are some local complications of inflammation?
- Swelling causing blockage of ducts and tubes
- Exudate compressing organs
- Loss of fluid e.g in burns
- Pain and loss of function leading to muscle atrophy
What are some systemic complications of acute inflammation?
- Fever: prostaglandins, IL-1, TNFa
- Leucocytosis: IL-1 and TNF act on bone marrow. viral more lymphocytes, bacterial more neutrophils
- Acute Phase Response: change in levels of plasma proteins and liver changes synthesis rate and released proteins, e.g CRP, a1 antitrypsin. Lead to sleepiness and lack of appetite
- Shock: Drop in blood pressure due to widespread vasodilation and vascular permeability. Can be fatal. When mediators in blood so all over body
What is the acute phase response?
When acute phase proteins are released leading to tachycardia, sleepiness, reduced appetite and malaise
Why does septic shock often cause fatal consequences?
- Overwhelming infection due to huge release of mediators
- Widespread vasodilatation
- Tachycardia and hypotension
- Multiple organ failure as cannot perfuse organs
How does resolution of acute inflammation occur?
- Chemical mediators have short half life so break down
- Neutrophils apoptosis
- Vascular permeability back to normal
- Fibrin degraded
- Exudate is drained into the lymphatics
- Tissue repairs itself or forms a fibrous scar
What are the different types of exudate?
- Pus: rich in neutrophils, bacterial infections
- Haemorrhagic: contains enough red blood cells to appear bloody, destructive infections and malignant tumour
- Serous: Clear and seen in blisters, contain protein but not many leucocytes and fibrinogen. Exudate in serous cavity
- Fibrinous: Contains lots of fibrin but no red blood cells, serosal surfaces can no longer slide over one another
What are some clinical examples of acute inflammation?
- Appendicitis: blocked lumen
- Pneumonia
- Bacterial Meningitis
- Abscess
What happens pathologically in appendicitis and why is it a medical emergency?
- Loses all structure
- Can rupture and can spill into peritoneum causing inflammation and widespread infection
What are the causes and signs of pneumonia and what are the reasons behind the symptoms?
- Bacterial infection e.g streptococcus pneumoniae and haemophilius influenzae
- Shortness of breath, fever, cough, sputum, chest pain as pleural lining damaged
What are the signs and causes of bacterial meningitis?
- Inflammation of the meninges
- Causes: Group B streptococcus, E.Coli, Neisseria meningitides
- Signs: stiff neck, fever, photophobia, altered mental state, non-blanching rash
What is an abscess?
An accumulation of dead and dying neutrophils with liquifactive necrosis
- Causes compression of surrounding areas so pain and blockages
What are some disorders of acute inflammation?
Chronic Granulomatous Disease: Cannot produce superoxide so prone to chronic infections. Abscesses and numerous granulomas
A1-AntiTrypsin Deficiency: Autosomal recessive. Normally deactivates enzymes released by neutrophils. Leads to emphysema and liver disease
Hereditary angio-oedema - Autosomal dominant where deficiency of C1-esterase inhibitor which is part of complement system. Patients have attacks of cutaneous angio-oedema, abdominal pain due to intestinal oedema and family history f sudden death
What defensive proteins are found in the exudate?
- Opsonins: to coat foreign material so can be recognised
- Complements: proteins assembled local to produce bacteria perforating structuring
- Antibodies: act as opsonins
What is this picture displaying and what is happening?
- Appendicitis
- Enlarged due to exudate and oedema
- Fibrinopurulant exudate
Why is there heat in acute inflammation?
In peripheries blood is rushing from the core, which is a higher temperature
What are some examples of opsonins?
- CRP
- Tail of antibody
- Some complement proteins
Where does exudate come from in the vascular system?
- FROM THE VENULES NOT CAPILLARIES
- Fluid normally runs on sides of blood vessel and cells in the middle during laminar flow but not when venules are leaky
What type of drug is aspirin?
- Antiplatelet
- Antipyretic as COX inhibitor, inhibits cyclooxidase
- Stops chemical mediators, particularly prostaglandin, being produced from cell membranes, stopping parts of inflammatory response
What is septicemic shock?
- Shock is when there is a low b.p so hypoperfusion of tissues
- Septicemia is when infeciton is in the blood so vasodilatation is generalised over body, so large amounts of fluid loss, leading to drop in blood pressure
What is anaphylactic shock?
An immune response causing wide spread mast cell degradation so histamine released all over body
Why does appendicitis lead to perotinitis?
- Neutrophil accumulation and necrosis in appendix leading to perforation so bacteria gets out into the peritoneum
What are the four stages of lobar pneumonia?
Extra cells accumulate in the alveoli so no scarring as no invasion of the interstitium
What are the basics of the following diseases:
- Chronic granulomatous disease?
- Inherited angio-oedema?
- Deficiency of NADPH oxidase so no superoxide and respiratory burst
- Autosomal dominant, C1 esterase inhibitor issue so complement cannot be stopped from abnormal activation. an be random due to pregnancy, food, surgery, stress etc causing swelling under skin or mucous membranes
