Session 2 Flashcards
What is acute inflammation?
The response of living tissue to injury
What are some characteristics of acute inflammation?
Innate
Stereotyped
Immediate/Early
Short Duration (mins, hours, days)
Acute inflammation is controlled by…
Chemical mediators
Acute inflammation serves to limit…
The tissue damage
Give 5 causes of acute inflammation
Microbial infections Hypersensitivity reactions Physical agents (e.g. Heat, light, radiation) Chemicals Tissue necrosis
What are 5 clinical features of acute inflammation?
Rubor Tumour Calor Dolor Loss of function
What is rubor?
Redness
What is tumour?
Swelling
What is calor?
Heat
What is dolor?
Pain
Acute inflammation involves which 3 changes in tissues?
Changes in blood flow
Exudation of fluid into tissues
Infiltration of inflammatory cells
Describe the changes in blood flow seen in acute inflammation with regards to the size of the arterial/capillary lumen
Initially vasoconstriction of arterioles
Then vasodilation of arterioles and then capillaries
How long does the initial transient vasoconstriction of arterioles in acute inflammation last for?
First few seconds of acute inflammation
Vasodilation of arterioles and capillaries contributes to which symptoms of acute inflammation?
Calor
Rubor
How is the permeability of blood vessels affected in acute inflammation? What consequences does this have? What happens to the viscosity of the blood as a result of this?
Increased permeability
Exudation of protein rich fluid into tissues and tumour seen
Increased viscosity
Name an immediate early response chemical mediator seen in acute inflammation
Histamine
When does histamine begin its action in acute inflammation? Histamine is produced from which cells?
Immediately (first 30 mins)
Mast cells, basophils and platelets
Name 3 things that histamine causes…
Vascular dilatation
Increase in vascular permeability
Pain
Name some other chemical mediators of acute inflammation?
Leukotrienes, bradykinin
Fluid loss from vessels is determined by ___________ law - the balance of __________ and ___________ __________ pressures.
Starling’s
Hydrostatic
Colloid Osmotic
What effect will increased hydrostatic pressure in a vessel have on fluid flow to tissues?
What effect will increase colloid osmotic pressure in the interstitial have on fluid flow to tissues?
Increased fluid flow out of vessels
Increased fluid flow out of vessels
How does arteriolar dilatation seen in acute inflammation affect hydrostatic pressure in capillaries?
How does increased permeability of vessel walls seen in acute inflammation affect the protein content of the interstitial fluid?
What consequence can both of these factors result in?
Increased
Increased protein content (colloid osmotic pressure)
OEDEMA
The fluid in oedema can be either…
Transudate
Exudate
What is a transudate? What is an exudate?
Give an example of where each is seen.
Fluid in oedema that has the same protein content as plasma
Cardiac failure
Fluid in oedema that has a higher protein content than plasma
Only in inflammation
How does oedema affect lymphatic drainage?
Results in increased lymphatic drainage
Give 5 mechanisms by which vessels can become ‘leaky’
Contraction of endothelial cells Cytoskeletal reorganisation Direct injury - e.g. Sunburn, chemicals Leukocyte dependent injury Increased transcytosis
How does contraction of endothelial cells and cytoskeletal reorganisation result in leaky vessels?
Give an example of a chemical that causes contraction of endothelial cells
Give an example of a chemical that causes cytoskeletal reorganisation
Leads to gaps in the walls of vessels
Histamine, leukotrienes
Cytokines IL-1 and TNF
How does leukocyte dependent injury make blood vessels leaky?
Leukocyte produce toxic oxygen species and enzymes which damage the vessels
Give an example of a chemical that results in increased transcytosis?
VEGF
What is an important protein component of the protein rich exudate seen in acute inflammation?
Fibrin
What is the role of fibrin in the protein rich exudate seen in acute inflammation?
Where is this particularly important?
Forms a sticky meshwork to localise inflammation
Serosal surfaces - e.g. Pleural cavity, pericardium - so whole cavity isn’t filled with fluid
What is another term for a neutrophil? What is the appearance of these cells under the microscope?
Polymorph
Come in multiple shapes with multi-lobed nuclei
What type of blood cell is a neutrophil?
White blood cell - type of granulocyte
What is a granulocyte?
A WBC with secretory granules in its cytoplasm
What is the main inflammatory cell?
Neutrophil
How do neutrophils get from within blood vessels to tissues to combat acute inflammation? (4 step process)
Margination
Rolling
Adhesion
Emigration
Describe the margination process of neutrophils
Stasis causes neutrophils to line up at the edge of blood vessels along the endothelium
What happens to neutrophils after their margination around a blood vessel?
Rolling - roll along the endothelium, sticking to it intermittently
Adhesion - stick more avidly
Emigration of neutrophils into the tissue through the vessel wall
What two things make it possible for the emigration of neutrophils through the blood vessel wall?
Relaxation of inter-endothelial junctions
Digestion of the vascular basement membrane
How doe neutrophils move once inside the tissues?
By chemotaxis
What is chemotaxis?
Movement along concentration gradients of chemoattractants
Give 3 examples of chemotaxins for neutrophils? How do they work?
C5a
LTB4
Bacterial peptides
They bind to receptors on the neutrophils, resulting in rearrangement of cytoskeleton, production of pseudopod and movement.
What do neutrophils do once in the tissue?
Primarily phagocytosis
How are microorganisms recognised by neutrophils for phagocytosis?
Through the action of opsonins
Give an example of an opsonin
C3B
Fc (fixed component of antibodies)
Internalisation of a microorganism during phagocytosis is a result of what changes in the cell?
Changes to the cell cytoskeleton
How is a secondary lysosome formed?
Fusion of phagosome with lysosome
Phagocytosis can take place in neutrophils by which two mechanisms?
Oxygen dependent
Oxygen independent
How does the oxygen dependent mechanism of phagocytosis in neutrophils work?
Produces superoxide and hydrogen peroxide
Produces HOCl*
How does the oxygen independent mechanism of phagocytosis in neutrophils work?
Enzymes such as lysozyme and hydrolases
Bactericidal permeability increasing protein (BPI)
Cationic proteins
What are some chemical mediators of acute inflammation, excluding neutrophils?
Proteases
Prostaglandins
Leukotrienes
Cytokines
Where are proteases produced?
In the liver
Prostaglandins and leukotrienes are both metabolites of…
Arachidonic acid
Which cells produce chemokines/cytokines? Give an example of a cytokine/chemical?
WBCs
Interleukins, TNF-a
What chemical mediators result in increased blood flow in vessels?
Histamine
Prostaglandins
Which chemical mediators result in increased vascular permeability?
Histamine
Leukotrienes
Which chemical mediators are important in neutrophil chemotaxis?
C5a, LTB4, bacterial peptides
What are some important chemicals for opsonisation?
C3B, Fc
How does exudation of fluid combat injury? (3)
Delivers plasma proteins (e.g. Inflammatory mediators) to area of injury
Dilutes toxins
Increases lymphatic drainage
How does increased lymphatic drainage as a result of exudation of fluid combat injury?
It delivers microorganisms to phagocytes and antigens to the immune system
How does infiltration of cells in acute inflammation combat injury?
Removes pathogenic organisms and necrotic debris
How does vasodilation in acute inflammation help combat injury?
Increases delivery to the area and increases temperature
How does pain and loss of function in acute inflammation combat injury?
Enforces rest and reduces chance of further traumatic damage
What complications can result due to the swelling seen in acute inflammation?
Blockage of tubes - e.g. Bile ducts/small intestine
What complications can result due to the exudate seen in acute inflammation?
Compression - e.g. Cardiac tamponade
In what instances of acute inflammation is fluid lost from the body?
Burns
What are some systemic consequences of acute inflammation?
Fever Leukocytosis Acute phase response Changes in plasma concentration of acute phase proteins Shock
What causes fever in acute inflammation?
Production of endogenous pyrogens e.g. IL-1 and TNF-a
Give an example of an endogenous pyrogen?
Which household drug can be given to reduce fever?
IL-1, TNF-a, prostaglandins
Aspirin
What is leukocytosis?
A high WBC level in FBC
Bacterial infections are associated particularly with which types of WBC?
Viral infections are more associated with…
Neutrophils
Lymphocytes
What causes the leukocytosis commonly seen in acute inflammation?
IL-1 and TNF-a which produce an accelerated release of WBCs from marrow
What are features of the acute phase response?
Decreased appetite
Raised pulse rate
Altered sleep patterns
Give an example of two acute phase proteins whose concentration changes in acute inflammation?
CRP
Fibrinogen
What is shock? What causes it?
A clinical syndrome of systemic circulatory failure
The spread of microorganisms and toxins in the body
What are 4 different outcomes after the development of acute inflammation?
Complete resolution
Continued acute inflammations with chronic inflammation
Chronic inflammation and fibrous repair
Death
What happens to the exudate in resolution from acute inflammation? What happens to vessel permeability? What happens to fibrin produced? What happens to the neutrophils?
Drains into lymphatics
Returns to normal
Degraded by plasmin
Die, break up and carried away or phagocytosed
Describe the half-life of mediators of acute inflammation?
Short half lives
Bacterial meningitis can cause vascular __________ and reduce cerebral ____________
What part of the body does it affect?
Thrombosis
Perfusion
Meninges of the brain
What is the causative organism for lobar pneumonia? List some symptoms. Can it be resolved?
Streptococcus pneumoniae
Worsening fever, dry cough, hypoxaemia, breathlessness
Yes completely if treated
Why does the exudate seen in skin blisters appear relatively clear? What can cause skin blisters?
Inflammatory cell levels are low
Heat, sunlight, chemicals
What are two other terms for an autopsy? Name three types of autopsy.
Post-mortem
Necropsy
Medicolegal
Forensic
Consent
For which type of autopsies is no consent required?
Medicolegal
Forensic
Name 4 parts of the body that are common causes of sudden death.
Head
Heart
Blood vessels
Lungs
What is involved in an autopsy? (3)
History
External examination
Internal examination
