Flashcards in MOD - Lecture 3 Deck (59):
Name 3 facts of acute inflammation
Evolves over hours or days
How long does chronic inflammation take to evolve?
Weeks, months or years
What suffix is used to indicate inflammation of tissue or organ?
Itis e.g. Appendicitis
Describe acute inflammation
Rapid response that aims to deliver mediators of host defence
Most defensive agents circulate in the blood in active form
When needed, delivered and activated
Leave the blood at site of injury
Why is fluid delivered to site of injury before leucocytes?
Fluid - within seconds
Leuocytes - minutes
As leucocytes can't just pour out of vessels
What causes acute inflammation? (6)
Physical/chemical agents e.g burns, irritation
What are the clinical signs of acute inflammation? (5)
Rubor = redness
Calor = heat
Tumour = swelling
Dollar = pain
Loss of function - enforces rest and reduces chance of further damage
When does pain occur in acute inflammation?
When the specialised nerve endings are stimulated by mediators especially bradykinin
Why does swelling occur in inflammation?
Fluid and leucocytes take up space within the tissue
What forces are involved in Starlings Law equilibrium?
Interstitial free fluid pressure
Plasma colloid osmotic pressure
Interstitial fluid colloid osmotic pressure
Where is histamine stored?
Granules for mast cells, basophils and platelets
Histamine and serotonin are available immediately from preformed supplies
What does histamine produce in acute inflammation?
How does histamine cause fluid leakage?
Causes endothelial cells to contract and pull apart.
This creates gaps through which plasma proteins can pass
How can you reduce pain and swelling?
Describe the mechanism.
What drugs are taken?
Block the production of prostaglandins
By inhibiting the enzyme (cyclo-oxygenase) that produces prostaglandins from arachadonic acid.
What is the effect of bradykinin?
Increased vascular permeability
How does serotonin differ from histamine?
Serotonin produces fibroblasts
In relation to Starlings law, what is the main force driving fluid out of the vessels?
and back into the blood?
Hydrostatic pressure of the blood
Colloidal osmotic pressure of plasma proteins
How does excess fluid drain from the tissues?
Lympathics - excess fluid drawings from the tissues taking with it microorganisms and antigens which are presented to the immune system in the lymph nodes.
Lymph nodes draining a focus of inflammation can themselves become inflamed, swollen and painful. (Lympahedenitis)
What are the three defensive proteins in the exudate?
How do they work?
Opsonins - coat foreign material and make them easy to phagocytose.
Complement - proteins assembled locally to produce bacteria-perforating structure
Antibodies - bind to surface of microorganisms, also act as opsonins.
What is the protein rich and protein poor tissue fluid that develops in inflammation called?
Exudate - protein rich
Transudate - protein poor
Name the chemical mediators that induce vascular leakage?
Histamine & Serotonin (mast cells and platelets)
Bradykinin (formed from plasma precursor)
Complement components - C3a, C4a, C5a (formed form plasma precursors)
What is the primary type of leucocyte found in acute inflammation?
Where are they normally found?
What does their presence in the tissue indicate?
What type of cell are they?
Blood or bone marrow
Invasion by bacteria or some other parasite or tissue injury
End cell - cannot multiply
What is chemotaxis?
Directional movement towards a chemical attractant
E.g. Clotting blood (fresh blood isn't)
Activation of complement fragments C3a, C4a, C5a. All chemotactic - especially C5a.
Leukotriene produced by leucocytes
How does blood clot form? (3)
What enzyme breaks down a clot?
Plasma enzymes activate Thrombin
Thrombin acts on fibrinogen, converting it to fibrin (insoluble protein)
RBC become trapped in insoluble fibrin mesh which forms a clot.
Clots resolve when fibrin is broken down by proteolytic enzyme plasmin
What happens during activation?
Within 5 seconds of chemotaxis binding to cell surface receptors
Calcium and sodium ions rush into the cells
Reorganises its cytoskeleton
Activated cells are more sticky than normal cells
What is margination and what happens during margination?
What happens to the number of selectins and activation of integrins during inflammation?
Leucocytes assume marginal positions in the vessels
Leucocytes stick to the walls of venules
Roll along the wall and become trapped, stop and crawl out of the vessel.
They are trapped when their receptors bind to adhesion molecules
Increase by inflammatory mediators and chemotaxis
What is diapedesis and describe.
Leucocytes dig their way out of vessels as they don't use the endothelial gaps
Produce collagenase to digest basement membrane
Move towards their target by pulling along collagen fibres of other tissue structures.
What substances make it easier for phagocytes to recognise target?
Give two examples
Opsonins - plasma proteins
IgG antibody - not present when bacteria is encountered first time
What happens is opsonins are not present on the molecule to be phagocytosed?
Phagocyte will recognise microbial surface antigens
Phagocyte forms a crater shape around particle to be phagocytosed
Crater forms a cup shape around particle, edges of the cup come together, plasma membranes fuse.
Phagosome digests the particle
Degranulation can occur before particle is completely enclosed and cause some bactericidal enzymes to leak into surrounding tissue = local tissue injury.
What two mechanisms kill organisms that have been phagocytosed?
Oxygen dependent - using free radicals = oxidative burst
Oxygen independent - using enzymes e.g. Proteases, nucleases, phospholipases and lysozyme
What six steps does a neutrophil go through to kill bacteria?
Chemotaxis - summoned to place of injury
Activation - switch to higher metabolism
Margination - stick to endothelial lining
Diapedesis - crawl through endothelium
Recognition/attachment - recognise bacteria and attach
Phagocytosis - engulf bacterium
What is a chemical mediator?
Produced in a focus of inflammation and modulates the inflammatory response
What are the two most common responses to mediators?
What must every mediator have to ensure the inflammatory response is not on-going?
Why is the duration of inflammation also limited?
Mediators have short half lives
What are the seven groups of endogenous mediators?
Vasoactive amines - histamine and serotonin
Vasoactive peptides - bradykinin
Complement components - C3a, C5a, generated from complement forming into tube.
Clotting and Fibrinolytic cascades - generate inflammatory mediators
Mediators derived from phospholipids e.g. Prostaglandins. Leukotriene B4 very powerful chemotactic agent
Cytokines and chemokines - tumour necrosis factor
Exogenous mediators e.g. Endotoxin
What is the difference between a cytokine and chemokines?
Cytokines - polypeptides produced by many cells and act as messengers between cells
Chemokines - a group of cytokines involved in chemotaxis.
Both have local and systemic effects.
What are the five main roles of inflammatory mediators?
Vasoidlation - histamine and serotonin
Increased vascular permeability - histamine and serotonin get (mast cells and platelets) Prostaglandins
Chemotaxis - Leukotriene B4, C5a, C3a, Chemokines
Phagocytosis - C3b
Pain - bradykinin, prostaglandins
What are the local complications of acute inflammation? (4)
Damage to normal tissue - secondary to substances produced by neutrophils
Obstruction of tubes e.g. Fallopian or intestine and compression of vital structures e.g. Fluid accumulation in the brain
Fluid loss - fluid accumulates until a point where it prevents further exudate on. Can continuously leak from a surface wound e.g. Burns
Pain and loss of function
What are the four main systemic effects of acute inflammation?
Why do they occur?
Fever - thermostat of the body is switched higher. Aspirin inhibit cyclo-oxygenase reducing fever
Leucocytosis - Increase in no. Of circulation Leucocytes
Acute Phase Response - change in level of some plasma proteins. Some produced in small amounts e.g. Albumin and others in larger amounts fibrinogen. Sleepiness and lack of appetite are a result of APR
Shock - Blood stream inflammation can occur if bacteria or inflammatory mediators spread around body
Inflammatory mediators enter the blood stream in significant amounts. Effects seen within one day
What is shock?
Inflammatory mediators spread around the body in the blood stream = inflammation throughout body
Dramatic drop in BP due to widespread vasodilation
Increase in vascular permeability - resultant fluid exudation
What is resolution of acute inflammation?
Vascular permeability returns to normal
Neutrophils undergo apoptosis and phagocytosed
Exudate is reabsorbed into venules or drained away in lymphatics
Fibrin is degraded
What happens to tissue in resolution?
If damaged parenchymal cells can regenerate tissue will return to normal
If regeneration cannot occur an extensive fibrous scar will form
What are the four types of exudate?
Pus/abscess - exudate creamy white rich in neutrophils
Haemorrhagic - RBC's make it appear bloody to naked eye. Indicates as well as inflammation significant vascular damage has occurred
Serous - Plasma proteins but few leucocytes suggest there is no infection. Clear - seen in blisters
Fibrinous - Significant deposition of fibrin
How do serous exudates differ from transudates?
Serous - contain plasma proteins. Also differ from plasma as they don't contain fibrinogen
Transudates - don't contain plasma proteins
What are the clinical examples of inflammation?
What are the three disorders of acute inflammation?
Alpha1-anti trypsin deficiency
Chronic granulomatous disease
Describe hereditary angio-oedema
Rare autosomal dominant disorder
Inherited deficiency of C1-esterase inhibitor
Patients have non itchy cutaneous angio-oedema. Recurrent abdo pain
Often a family history of sudden death
Describe alpha1-antitrypsin deficiency.
Autosomal recessive disorder with varying levels of severity
Low levels of alpha-1-antitrypsin = a protease inhibitor which deactivates enzymes released from neutrophils at site of inflammation
Develop emphysema - proteases released by neutrophils in the lungs act unchecked and destroy normal lung tissue
Liver disease - hepatocytes produce abnormal version of protein which is incorrectly folded. Polymerises cannot be exported from ER - hepatocyte damage and eventually cirrhosis
What is chronic granulomatous disease?
Phagocytes unable to generate the free radical superoxide
Bacteria is phagocytosed but phagocytes cannot kill them as they cannot generate an oxygen burst
Results in formation of chronic infections in first year of life
What is a response to injury of living tissue?
What is its purpose?
Inflammation - deliver defensive materials
To protect body from infection
Clear damaged tissue
Initiate tissue repair
What type of respiration do neutrophils use?
Aerobic and anaerboic
How many nuclei do neutrophils have?
What are all inflammatory cells derived from?
Bone marrow precursors
What do macrophages produce?
Interleukin - 1
What would happen to the CRP levels and plasma viscosity in acute inflammation?
CRP - Increase
CRP is an acute phase reactant
Plasma viscosity - increase in acute phase reaction
What are the causative organisms of:
1. Lobar pneumonia
2. Acute appendicitis
3. Bacterial meningitis
4. Ascending cholangitis/ Liver abscess
2. Intestinal worms, foreign bodies trauma
3. Streptococcus. Young adults = Neisseriae meningitidis. Neonate a = Group B streptococci
What is ascending cholangitis?
Bacterial infection on an obstruction of the biliary tree commonly from a gall stone.
Organisms migrate backwards up the bile duct as a result of partial blockage
Symptoms - yellow discolouration of skin, fever, abdo pain
Can be life- threatening
Treatment - IV fluids and antibiotics