Acute Inflammation Flashcards
What is acute inflammation?
Response of living tissue to injury, innate, immediate and early, short duration
(Initiated to limit tissue damage)
Put simply what happens during acute inflammation?
There are vascular and cellular reactions controlled by chemical mediators whose primary function is to protect the tissue, but there can be complications
Name some causes of acute inflammation?
Infections (bacterial, viral, parasitic) and microbial toxins
Hypersensitive reactions
Physical and Chemicals agents (thermal injury=burns/frostbite, radiation)
Tissue necrosis
Foreign bodies
Trauma (blunt and penetration)
What are the clinical features of acute inflammation?
Rubor (redness) Tumor (swelling) Dolor (pain) Calor (heat) Loss of function
What are the 3 changes in tissue that occur during acute inflammation?
- changes in blood flow (vascular phase)
- exudate of fluid into tissue
- infiltration of inflammatory cells (cellular phase)
(*there are inflammatory mediators of each step)
What are the changes in blood flow that happen during an acute inflammatory response? (4)
- transient vasoconstriction of arterioles
- vasodilation of arterioles (and capillaries)=calor and rubor
- increased permeability of blood vessels=exudate of protein rich fluid into tissues + slowing of circulation (tumor)
- stasis (increased viscosity of blood)
Name a chemical mediator involved in the immediate response during an acute inflammation
Histamine
What role does histamine play in an acute inflammatory response?
- causes vascular (arteriolar) dilation
- causes transient increase in vascular permeability (venular leakage) - histamine causes endothelial cells to contract and pull apart
- causes pain
serotonin has vascular effects similar to histamine
What is histamine?
Chemical mediator-vasoactive amines (another one of which is serotonin)
Stored in granules in mast cells/basophils/platelets -(where serotonin is also stored)
Released in response to many stimuli ie physical damage, immune reactions and complement components
Name some other chemical mediators like histamine involved in the first stages of acute inflammation
Serotonin
Prostaglandins
Leukotrienes
Brandykinins
Why is abundant fluid in the tissue a good thing, what is the function of it?
Excess fluid drains from the tissues into the lymphatic taking with it micro-organisms and antigens which are thus presented to the immune system within the lymph nodes
What are the 3 main types of defensive proteins in the exudate during an acute inflammatory response?
Opsonins
Complement
Antibodies
What do opsonins do?
Coat foreign materials and make them easy to phagocytose
What do complement proteins do?
Assemble locally to produce a bacteria-perforation structure
What do antibodies do?
Bind to the surface of micro-organism and also act as opsonins
Why is the tissue fluid in inflammation called an exudate?
Because it is protein rich
In acute inflammation is there a net flow of fluid in or out of the blood vessels? Why?
Out of vessels
Because arteriolar dilation leads to increase in hydrostatic pressure and increased permeability of vessel walls leads to loss of proteins into interstitium
What is the difference between a transudate and an exudate and what is the significance of this in terms of inflammation?
Transudate- fluid loss due to hydrostatic pressure imbalance only, tissue fluid has low protein content
Exudate- fluid loss in inflammation- tissue fluid has a high protein content
Knowing this we can tell the difference between oedema caused by inflammation (exudate) or something else ie cardiac failure(transudate)
What are the mechanisms of vascular leakage in acute inflammation? What chemical mediators cause these changes?
- Endothelial contraction- histamine, leukotrienes
- Cytoskeleton reorganisation- cytokines IL-1 and TNF
- Direct injury (toxic burns, chemicals)
- Leukocyte dependent injury-toxic oxygen species and enzymes from leucocytes
- Increased transcytosis (process by which fluid moves through cells)- channels across endothelial cytoplasm- VEGF
What are the chemical mediators that induce vascular leakage in acute inflammation?
Histamine (mast cells/basophils/platelets)
Serotonin (mast cells/platelets)
Brandykinin (from plasma precursor)
Complement components- C3a, C4a, C5a (from plasma precursor)
What is the primary type of cells found in acute inflammation?
Neutrophil (presence indicates the invasion of bacteria/parasites/tissue injury)
What are the 6 stages a neutrophil dealing with acute inflammation must complete?
Chemotaxis Activation Margination Diapedesis Recognition-attachment Phagocytosis
What is chemotaxis in acute inflammation?
The process by which a neutrophil is summoned to a place of injury in response to a chemotaxin (bacterial product, injured tissues, substances produced by leucocytes and spilled blood-clotted)
Movement along concentration gradients of chemoattractant
Give an example of a bacterial chemotaxin
Endotoxin
Lipopolysaccharide from the outer membrane of gram negative bacteria
What produces leukotrienes?
Leucocytes
What is ‘activation’ of neutrophils in acute inflammation?
Reorganisation of the cell’s cytoskeleton as a result of Na+ and Ca2+ influx (+swelling)
Cell produces pseudopod.
Cell becomes sticker
What is ‘margination’ of neutrophils in acute inflammation?
Process by which leucocytes stick to the endothelial lining, (caused by stasis- slow blood flow)
Become trapped when their receptors bind to adhesion molecules (integrins-adhesion/selectins-for rolling along)
What is ‘diapedesis’ in acute inflammatory responses?
-crawling through the membrane- do not use the endothelial gaps .
Leucocytes produce collagenase which digests the basement membranes
(Also called emigration)
What is ‘recognition-attachment’ of leucocytes in an acute inflammatory response?
Recognising the bacterium and attaching to it- made easier by opsonins (ie IgG antibodies and C3b complement component)
What is ‘phagocytosis’ in acute inflammation?
Engulfing the bacterium
Bacterium is taken into intracellular vacuole- phagosome
Phagosome undergoes degranulation
How does ‘degranulation’ cause local tissue injury?
Early degranulation occurs before the particle in completely enclose and some of the bactericidal enzyme leaks out into the surrounding tissue space, causing local tissue injury
What are the two ways in which phagocytosed molecules can be killed?
- oxygen dependent (using oxygen derived free radicals)= ‘oxygen/replicatory burst’
- oxygen independent (using enzymes eg proteases and lysozymes)
What role does fibrin have in acute inflammation?
Forms a mash work which works to localise inflammation, particularly important when inflammatory reaches a serousal surface
Neutrophils are a type of granulocytes, what is another name for them?
Polymorphs
Polymorphonuclear leucocyte
Name the 3 groups chemical mediators of acute inflammation?
Proteases
Prostaglandins/leukotrienes
Cytokines/chemokines
Name a protease that is a chemical mediator of acute inflammation (3)
- Kinins
- Complement system C3a, C5a
- Coagulation/fibrinolytic system
Name a leucotriene/prostaglandin that is a chemical mediator of acute inflammation
Metabolites of arachidonic acid
Name a cytokines/chemokines that is a chemical mediator of acute inflammation (2)
Interleukins
TNF alpha
Which chemical mediators of acute inflammation cause increased blood flow?
Histamine
Prostaglandins
What chemical mediators of acute inflammation are responsible for vascular permeability?
Histamine
Leukotrienes
What chemical mediators of acute inflammation cause neutrophil chemotaxis?
C5a, LTB4, bacterial peptides
What chemical mediators of acute inflammation cause phagocytosis?
C3b
What are the hallmark features of acute inflammation?
Exudate of [oedema] fluid
And infiltration of [inflammatory] cells
How does exudation of fluid combat acute injury?
- Delivers plasma proteins to area of injury (immunoglobulins, inflammatory mediators, fibrinogen)
- dilutes toxins
- increase lymphatic drainage (delivers micro-organisms to phagocytes and antigens to immune system)
How does infiltration of cells help combat acute injury?
Removes pathogen organisms and necrotic debris
How does vasodilation combat acute injury?
Increases delivery, and increases temperature (which helps cells work more efficiently)
How does pain and loss of function help combat acute injury?
Enforces rest, reduces chance of further traumatic damage
What are the local consequences of acute inflammation?
- Swelling (blockage of tubes eg bile duct, intestine)
- exudate (compression eg cardiac tamponade/ serositis)
- loss of fluid (eg burns)
- pain and loss of function (especially if prolonged)
What are the systematic effects of acute inflammation?
-Fever
L-eukocytosis (an increase in the number of white cells in the blood)
-Acute phase response
What sort of chemical mediators cause fever? And what can be used to treat this?
Prostaglandins (IL-1 and TNF-a)
Aspirin
Describe the process of leukocytosis (including the chemical mediators involved) in acute inflammation.
Prostaglandins (IL-1 and TNF-a) produce an accelerated release of inflammatory cells (macrophages and T lymphocytes) from bone marrow.
The macrophages and T lymphocytes releases ‘colony-stimulating factors’ which induce the production of many more inflammatory cells.
(Eg bacterial infections-neutrophils, viral- lymphocytes)
What is acute phase response in acute inflammation?
Decreased appetite, raised pulse rate, altered sleep patterns and changes in plasma conc of acute phase proteins
Name some acute phase proteins that change conc in acute inflammation
- C-reactive protein (CPR)-good marker for inflammation in the blood
- Alpha-1 antitrypsin
- Haptoglobin
- Fibrinogen
- Serum amyloid A protein
What is the term used for complete circulatory failure?
Shock
( life-threatening medical condition of low blood perfusion to tissues resulting in cellular injury and inadequate tissue function. The typical signs of shock are low blood pressure, rapid heart rate, signs of poor end-organ perfusion (i.e.: low urine output, confusion, or loss of consciousness), and weak pulses.
Dramatic drop in BP due to widespread vasodilation and increase in vascular permeability with resultant fluid exudate )
What are the 4 outcomes of acute inflammation?
1) complete resolution
2) continues acute inflammation with chronic inflammation- abscess (body localises acute inflammation)
3) chronic inflammation and fibrous repair, probably with tissue regeneration
4) death
What is occuring during acute inflammation resolution?
Changes gradually reverse:
-vascular changes:
Neutrophils no longer marginate, vessel permeability returns to normal, vessel calibre (diameter) returns to normal
-exudate drains to lymphatic
-fibrin is degraded by plasmid and other proteases
-neutrophils undergo apoptosis and are phagocytosed
(Some damaged tissue might not be able to regenerate)
In acute inflammation resolution, why might complete resolution not be possible?
If tissue architecture has been destroyed
How are chemical mediators involved in acute inflammation ‘turned off’ during resolution?
- all mediators have short half lives
- may be inactivated by degradation eg heparinise
- inhibitors may bind eg various anti-proteases, lipoxins, endothelin
- may be unstable eg some arachidonic acid derivatives
- may be diluted in exudate eg fibrin degradation products
How might an inhibitor such as lipoxins work to resolved an acute inflammatory response?
Work to reverse the actions of the pro-inflammatory mediators, dampen and reverse the inflammatory response, and initiate tissue repair.
What is bacterial meningitis?
Acute inflammation in meninges, can cause vascular thrombosis and reduce cerebral perfusion
There is damage to vessels during vascular exudate
What is lobar pneumonia?
What organism is responsible? And what is the clinical course?
Affects a large and continues area of the lobe of a lung
Looks pink under microscope (due to large amount of fibrin)
There is an increased numbers of neutrophils and fibrin
Exudate enters and solidifies and consolidates
Caused by streptococcus peumoniae (pneumococcus)
Get a worsening fever, prostration, hypoxaemia over a few days. Dry could and breathlessness
(If untreated, can still completely resolve)
Discuss what is happening in a skin blister:
Causes
Features
Resolution?
Causes: heat, sunlight, chemical (burns)
Features: pain and profuse (very plentiful/ abundant) exudate - very painful due to all the pain receptors in the skin and it is very easy to become dehydrated because water is easily lost from the skin
The collection of the fluid strips off the overlying epithelium,
Relatively few Inflammatory cells- exudate is clear UNLESS bacterial infection develops
Resolution: can be resolved completely but can also be left with scarring
Discuss an abscess: Where? What happens? What kind of necrosis? Clinical features? Resolution? When is it most likely to occur?
Where: Occurs in solid tissues
What happens: Inflammatory exudate forces tissues apart
Necrosis: Liquefactive necrosis in centre
Clinical features High pressure therefore pain
Resolution: May cause tissue damage and squash adjacent structures
When: if the organism is pus forming
Name an organ that you might get an abscess in?
Liver
What happens during acute inflammation of serous cavities? What does this cause and why?
Exudate pours into cavity
Ascites, pleural/pericardial effusion = respiratory or cardiac impairment=localised fibrin deposition
In an attempt to try and contain the inflammation
What is pericarditis?
What it is sometimes called?
Bread and butter pericarditis
Symptoms: cardiac tamponade=light headedness, blurred vision, palpitations, nausea
Fever
Weakness
Shortness of breath
Sudden onset of sharp chest pain
(Also felt in shoulders, neck or back)
Better sitting up, and breathing lightly
Most often a viral infection (can be bacterial ie TB)
Myocardium has a lot of fibrin (scar tissue) -shows pink under microscope
Name some rare disorders of acute inflammation, why are these rare?
- hereditary angiotensin-oedema (swelling in the throat)- attacks of non-itchy cutaneous angiotensin-oedema and recurrent abdominal pain due to intestinal oedema
- alpha-1 antitrypsin deficiency (protects tissues from enzymes of inflammatory cells- especially neutrophil elastase- none of this enzyme results in the damage of tissues by inflammatory cells ie alveoli=emphysema as parenchymal tissue is damaged + liver disease= build up of incorrectly folded proteins in hepatocytes’ ER-cirrhosis)
- chronic granulomatous disease- phagocytes unable to generate superoxide- cant break down phagocysed microorganism (no oxygen burst)= numerous granulomas occur- affect skin, lymph nodes (lungs, liver and bones)
- inherited complement deficiencies
- defects in neutrophil function
- defect in neutrophil numbers
Rare because of natural selection
What produces chemical mediators of the acute inflammatory response?
Plasma, leucocytes and local tissues
What. Is the function of complement in acute inflammation?
Forms a tube which punches holes in bacteria causing them to die
Name an exogenous mediator of inflammation
Endotoxins produced by gram negative bacteria
What are the main roles of inflammatory mediators? (5)
- Vasodilation
- Increased vascular permeability
- Chemotaxis
- Phagocytosis
- Pain
Name the types of exudate (4)
Pus/abscess-typical of infections by chemotactic bacteria
Haemorrhagic-inflammation AND significant vascular damage has occurred. Seen in destructive infections and when the exudate is a result of infiltration by a malignant tumour
Serous- plasma proteins, clear with no leucocytes=no infection by microorganism (not the same as a seroma)
Fribrinous-deposition of fibrin (blood clot without RBC). Can stop serosal surfaces from sliding over each other=rubbing sound
What is the dominant cell type in acute inflammation ?
Neutrophils
