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63 Cards in this Set
- Front
- Back
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What are the four stimuli of inflammation?
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1. Physicsl (cut, burn)
2. Chemical (acids, chemicals) 3. Microbial (bacterial toxin, parasite, viral) 4. Immunological (normal immune response, hypersensitivity) |
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What are the cardinal signs of acute inflammation?
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Heat
Redness (Erythema) Swelling Pain Loss of function |
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What is the "triple response"?
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This is the term for the 3 of the cardinal signs - heat, redness and swelling
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What is the vascular response to acute inflammation?
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Hyperaemia (more blood in them!)
Sludging of RBCs Blood clotting Margination of leukocytes High endothelial venule (HEV) formation Thickened and raised Exudation (more permeable and dilated) |
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Why is exudate formed?
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There is an altered balance between osmotic pressure and hydrostatic pressure, meaning more fluid and plasma proteins in tissues.
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What causes pain?
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Tissue tension and action of soluble mediators on sensory neurones
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Explain the half lives of inflammatory mediators.
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They have short half lives and are rapidly inactivated
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Give some examples of preformed mediators.
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Histamine (mast cells, basophils)
Serotonin (platelets) |
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Give some examples of newly synthesized mediators.
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Prostaglandins (all leukocytes)
Leukotrienes (all leukocytes) PAF (all leuk) NO (macrophages) Cytokines (all leuk) |
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Give some examples of blood clotting mediators.
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Thrombin (liver)
Fibrinolysin (aka Plasmin, from liver) Kinins (liver) |
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Which mediators induce VASODILATION?
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Histamine
Serotonin Prostaglandins NO |
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Which mediators induce VASCULAR PERMEABILITY?
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Histamine
Serotonin PAF Leukotrienes |
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Which mediators induce PAIN?
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Prostaglandins
Bradykinin |
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How many phases of the TRIPLE RESPONSE are there?
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2 - Immediate Phase and Delayed Phase
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Explain what the IMMEDIATE PHASE of the triple response is due to.
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Histamine in mast cells
Serotonin in granules of platelets Complement Blood clotting factors |
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Explain what the DELAYED PHASE of the triple response is due to.
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Kinins
Prostaglandins Leukotrienes NOTE: This phase may not be visible, due to extent |
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What is the relationship between prostaglandin and paired mediators?
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Prostaglandin LOWERS THE THRESHOLD of sensory pain fibres to other mediators
EX. Bradykinin gives a small pain degree, but added with PGE gives LARGE degree. Same with oedema and itch! |
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What is the definition of a prostaglandin?
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Fatty acids produced from phospholipids in cell membranes
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How is prostaglandin LIKE a hormone and UNLIKE one?
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LIKE
Produced in response to stimuli Act via G-protein linked receptors Rapidly destroyed UNLIKE No stored form Locally acting (paracrine) Can be synthesized by most cells |
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What does PGE stimulate?
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Vasodilation and vascular permeability as well as promoting the sensation of pain
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What is the relationship between PGE and neutrophils?
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PGE recruits neutrophils to damaged areas
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What is PGE produced from?
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Arachidonic Acid is acted on by CYCLOOXYGENASE (COX) to produce PGH2, the parent prostaglandin
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How is Arachadonic acid produced?
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When insult occurs, PHOSPHOLIPASE A2 (PLA2) acts on membrrane phopholipids to split PHOSPHATIDYLCHOLINE (PC) into ARACHIDONATE and PAF
ARACHIDONATE in the "2 series" is ARACHIDONIC ACID |
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What are the different PGEs that can be made?
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PGI2, PGF2, PGE2, PGD2 and Thromboxine A2
NOTE: All cells can make these, except ONLY platelets can make Throm-A2 |
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Explain COX
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There are 2 isoforms.
COX1 is constituitive and involved in 'housekeeping' like maintaining the gut COX2 is inducible and is involved in inflammatory response |
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Serous exudate
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Watery (ex. blister)
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Fibrinous exudate
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Rich in fibrinogen protein (precursor to fibrin); has fluid too
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Catarrhal exudate
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Mucin (ex. mucus membranes)
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Haemorrhagic exudate
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Frank bleeding into tissues
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Suppurative/Purulent exudate
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"Pus", often localized inside an abscess
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Necrotizing exudate
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Cell death, ischaemia, acute venous congestion
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What are the functions of exudate?
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1. Dilute toxins
2. Distribute clotting factors and mediators 3. Opsonization of pathogens by antibodies and complement 4. Continuously drains to lymph vessels |
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What are the three steps of leukocyte adherence?
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Tethering and rolling
Arrest Extravasation |
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What molecules are involved in leukocyte adherence?
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1. Selectin on endothelium aligns with mucin-like molecule on leukocyte
2. Chemoattractant from ednothelium attracted to chemoreceptor on leukocyte 3. Integrin on cell allows compliance with Ig family member on endo |
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What are the two types of Selectin and when are they seen?
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P selectin is seen in the immediate pathway and E selectin is seen in the delayed
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What are the functions of neutrophils in inflammation?
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1. Phagocytosis of pathogens via Ag/Ab complexes, TLR and C3bR
2. Liquification of surrounding tissue by lysosomal enzymes following degranulation 3. Amplification of inflammation by synthesis of PGE, LT and PAF 4. Amplification of inflamm by secreted factors |
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How is monocyte migration different from neutrophil?
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It is much slower, delayed 1-3 days
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What are the functions of macrophages in inflammation?
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1. Phagocytosis of pathogens
2. Secrete toxic factors (NO, H2O2) 3. Secrete IL1, TNFalpha, IL6, which promote leuko adherence, induce acute phase response and fever 4. Secrete colony stimulating factors (CSF) to promote differentiation of immature granulocytes and monocytes |
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What is leukocytosis?
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An increase in concentration of white blood cells in blood
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What is meant by a neutrophil 'shift to the left'?
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Where there is neutropaenia, more neutrophils are released from marrow resulting in neutrophilia...as more and more are seeded to tissues, immature cells start to be released from marrow to keep up with demand.
This is the shift, and the neutrophils are immature and are called 'band neutrophils' |
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How is fever induced? (Pyrexia)
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Il1 and TNF act as endogenous pyrogens (generate heat).
Could also be induced via microbial products acting through TLRs |
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How is fever beneficial?
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1. Decreases microbial replication because of temp
2. Increases phagocytosis and killing by neutrophils and macrophages 3. Increases antigen presentation efficiency |
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What is the acute phase response?
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It occurs in most forms of inflammation, infection and tissue injury.
It is the increased production of several plasma proteins after injury and in disease states by the liver |
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What is anaemia of inflammation?
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The transient reduction of erythrocytes in blood as a result of inflammatory mediators on the liver.
Goal is to reduce the iron in blood that is available for bacteria and microbes |
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What is septic shock?
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Infection-induced syndrome characterized by a generalised inflammatory state.
Characteristics are fever, acute phase response, hypoglycaemia, exudation or haemorrhage, metabolic acidosis and organ dysfunction NOTE: Permeability of gut intestinal flora increases...bad news bears |
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What is RESOLUTION?
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The return to normal is the inflammatory rxn is mild and the cause is eliminated
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What is REPAIR?
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The formation of scar tissue if rxn is extensive
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In resolution, what makes up the built-in termination programme?
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Lipoxins
Resolvins Protectins |
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In resolution, what makes up the 'return to normal' sequence?
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Fibrinolysis - plasmin digests fibrin clots
Phagocytosis - macrophages get dead cells, debris, fibrin in DEMOLITION PHASE Regeneration of tissue |
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What is the DEMOLITION PHASE of resolution?
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When macrophages phagocytose dead cells, debris, fibrin products, etc
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In resolution regeneration, what cells grow?
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The lost tissue is replaced by proliferation of cells of the same type to keep original architecture
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What is resolution regeneration mediated by?
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Wound cytokines secreted from macrophages, including TGFbeta and PDGF
These act as growth factors for endothelials, epithelials, smooth musclem cells and fibroblasts |
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What type of tissue is formed in repair ('organization')?
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Granulation tissue
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What is the original tissue architecture replaced with in REPAIR?
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Avascular fibrous scar tissue with a loss of function
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What is a repair ADHESION?
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Connective tissue between two organs
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What gives rise to suppuration?
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Pyogenic bacteria that resist uptake or destruction
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Why does an abscess cavity form in suppuration?
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Because of the alterations in tissue osmotic pressure induced by exudation and cell death.
Water is drawn into area of pus, enlarging the cavity |
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What is pus?
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Dead and dying neutrophils and bacteria
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Describe formation of granulation tissue in suppuration?
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Tissue forms around abcess cavity and brings in a large number of neutrophils and secretes new connective tissue components.
Also, fibroblast proliferation and formation of new blood vessels |
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What is a pyogenic membrane?
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This forms initially as a thin layer of granulation tissue around an area of suppuration, forming a walled abscess.
This grows to form an abscess capsule. |
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What is the fate of abscesses?
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1. Rupture
2. Healing initiated by granulation tissue - resolution or repair 3. Chronic abscess - cyst or inspissated |
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What aids in progression of acute to chronic inflammation?
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1. Persistent suppuration - failure to kill all microorganisms
2. Foreign body response |
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What does persistent, non-resolving acute inflammation lead to?
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Fibrous scarring or fibrosis...ie, LOSS OF FUNCTION
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