Lesson 2 Flashcards
Give a brief description on acute inflammation
Protective rapid response of living tissue to injury Immediate Short duration Innate Stereotyped = always same result Initiated to limit tissue damage
State some causes of acute inflammation
Microbial infections Hypersensitivity reactions Physical agents Chemicals Tissue necrosis Anything can injure tissue!
What are some key features of acute inflammation?
Vascular and cellular reactions = fluid exudate/neutrophils in tissue
Controlled by a variety of chemical mediators -> from plasma or cells
Protective but can cause complications
What are the five key clinical features of acute inflammation (Latin/english terms)?
RUBOR = redness TUMOR = swelling = oedema CALOR = heat DOLOR = pain FUNCTIO LAESA = loss of function
Describe the changes in tissue during acute inflammation
1 Red & hot = Increased blood flow
2 Exudation of fluid into tissue
3 Infiltration of inflammatory cells
1 & 2 = Vascular phase
3 = Cellular phase
Describe the vascular phase in relation to changes in blood flow
Transient vasoconstriction of arterioles
Followed by vasodilatation of arterioles and then capillaries -> Increased blood flow
Increased vascular permeability -> exudation of protein-rich fluid into tissues and slowing od circulation
Vascular stasis
Describe the vascular phase when related to increased vascular permeability
(1) Hydrostatic pressure
Arteriolar dilatation = hydrostatic pressure increase capillaries relative to pressure interstitial fluid
(2) Osmotic pressure = Increased venular permeability
(1) + (2) = Net flow of protein rich fluid into tissue spaces = oedema
Define Arteriolar dilatation
hydrostatic pressure increase capillaries relative to pressure interstitial fluid
What is Starling’s Law?
movement of fluid across vessel wall governed by balance of forces of hydrostatic + colloid osmotic pressure between intravascular and extravascular space.
Describe the vascular phase in terms of mechanisms on vascular leakage
Endothelial cell contraction = chemical mediators e.g. C5a , NO
Endothelial cell injury
Direct (Trauma, chemicals, microbial toxins)
Indirect (toxic oxygen species/proteolytic enzyme from neutrophils )
Structural re-organization of cytoskeleton
Transcytosis
What is the protein content of transudate?
LOW protein content
What is the protein content of exudate?
HIGH protein content
List the types of exudate?
Purulent ( meningitis )
Haemorrhagic (Malignancies )
Serous (Blister)
Fibrinous (Fibrinous pericarditis)
Describe the cellular phases of acute inflammation
Primary leucocyte = Neutrophil aka. Neutrophil leukocyte, neutrophil polymorph, PMN
WBC involved in acute inflammation
Type of granulocyte
Short-lived , 6-24hrs
Describe neutrophil extravasation
Vascular stasis -> neutrophils to line up along endothelium = MARGINATION
Roll along endothelium = ROLLING
Stick avidly to endothelium = ADHESION
Emigrate through the endothelium = MIGRATION / DIAPEDESIS
Describe the emigration of neutrophils during neutrophil extravasation
ROLLING : Selectins expressed by endothelial cells bind to carbohydrate ligands on neutrophils. Increased by several cytokines secreted by macrophages, mast cells and endothelial cells
ADHESION : Integrins expressed by neutrophils bind to integrin ligands on endothelium
Explain diapedesis
Chemotaxis = movement along concentration gradients of chemoattractant/Chemotaxins
Chemotaxins : C5a, LTB4, cytokines bacterial products, clotted blood
Receptor ligand binding – selectins, integrins
Rearrangement of cytoskeleton
What is the role of neutrophils in acute inflammation
Neutrophils migrate to site of injury by chemotaxis
Phagocytose and kill microorganisms
Eliminate foreign material and necrotic tissue
Produce growth factors for repair
But Activated neutrophils may release toxic metabolites and enzymes causing damage to normal host tissue
What are some chemical mediators?
Modulate the inflammatory response
Short-lived
Endogenous
Every mediator has an inhibitor
What are some chemical mediator groups?
Endogenous (Cell- derived )
Vasoactive amines ( Histamine , serotonin)
Vasoactive peptides ( Bradykinin)
Chemokines and Cytokines (Messengers )
Arachidonic acid metabolites from plasma membrane phospholipids
Nitric oxide
Provide a list of vascular phase chemical mediators
Histamine – Mast cells
Serotonin – platelets
Vasoactive amines
Immediate early response
Response to many injurious stimuli
Cause vascular dilation , INCREASE venular permeability + pain
Provide a examples of some anti-inflammatories
Aspirin / NSAIN e.g naproxen , ibuprofen Antihistamine Corticosteroids Leukotriene antagonists e.g montelukast TNF alpha antagonists e.g .infliximab
What are hallmarks of acute inflammation?
Exudate of fluid
Infiltrate of cells
How do these responses aid to combat injury?
- Exudation of fluid
Delivers plasma proteins, immunoglobulins/inflammatory mediators to area pf injury
Serves to dilute toxins m reducing impact
Oedema elicits increased lymphatic drainage; delivers antigens to immune system as well as microorganisms to phagocytes - Vasodilatation
- Infiltration of inflammatory cells
- Pain and loss of function
What are four main systemic effects of acute inflammation?
- Pyrexia
Bacterial endotoxins
Pyrogenic cytokines - Leukocytosis (Increase WCC)
Macrophages + endothelial cells release colony-stimuklating factord so BM produces more leucocytes - Acute phase response in liver = constitutional symptoms
- Shock = circulatory failure
What are examples of local complications?
Swelling Inappropriate inflammation Exudation of fluid Loss of fluid Prolonged pain and loss of function Digestion of host tissues by harmful enzymes releases by neutrophils
What disorders are a result of acute inflammation?
Hereditary angio-oedema Alpha-1 antitrypsin deficiency Inherited complement deficiencies Defected in neutrophil function Defects in neutrophil number
Give a summary regarding hereditary angiodema
Rare
Autosomal dominant
Deficiency of C1 esterase inhibitor (a component of complement system)
Non-itchy cutaneous angio-oedema + intestinal oedema
FHx sudden death
Give a description on Alpha 1 antitrypsin (A1AT) deficiency
Autosomal recessive Low levels of A1AT A1AT = protease inhibitor which deactivates enzymes released from neutrophils during Inflammation goes unchecked Emphysema + cirrhosis
Give a description on chronic granulomatous disease
Genetic condition
Neutrophil is unable to generate free radical
Superoxide and so it cannot kill the bacteria
Chronic infections from the first year of life
Numerous granulomas and abscesses
