Inflammation Flashcards
(36 cards)
1
Q
What are the 2 types of body defence system?
A
Non-specific defence system & Specific defence system
2
Q
What does non-specific defence system comprise of?
A
Mechanical barrier; non-specific phagocytosis; inflammation; interferons
3
Q
What does specific defence system comprise of?
A
Humoral immunity; Cell-mediated immunity
4
Q
What are the 6 types of cellular adaptation?
A
- Atrophy: decrease in size
- Hypertrophy: increase in size
- Hyperplasia: increase in number
- Metaplasia: change in morphology & function
- Dysplasia: increase in number & change in cell type
- Neoplasia (malignancy): new uncontrolled growth
5
Q
What are the causes of cell injury?
A
Ischemia; infection; immune / allergic reaction; direct external damage (e.g. thermal, mechanical, pressure, radiation, electricity); chemical toxins; genetic factors; electrolyte balance; foreign body; nutritional factors
6
Q
What are the 4 phases of acute wound healing?
A
Haemostasis, inflammation, proliferation, remodelling
7
Q
What is the purpose of haemostasis?
A
To form a clot to stop bleeding
8
Q
What are the 2 stages of haemostasis?
A
- Stage 1 (Primary haemostasis) - platelet activation & forming platelet plug
- Stage 2 (Secondary haemostasis) - coagulation cascade & conversion of fibrinogen to fibrin
9
Q
What is the purpose / aim of an inflammation?
A
To eliminate the cause of injury & initiate wound repair process
10
Q
What is released during an inflammation?
A
- Bradykinins & histamine leading to vascular event - capillary dilation & increase permeability (swelling)
- Macrophages & neutrophils leading to cellular event - leaving bloodstream via Chemotaxis to travel to site of injury
11
Q
What are the cardinal signs of inflammation?
A
Redness, swelling, pain, heat
12
Q
What occurs the during cellular event?
A
- Exudation - release of fluid
- Stasis - engorgement of RBC
- Margination - adhesion of accumulated WBC to wall of vessel
- Diapedesis - oozing of WBC outside of blood vessel
- Chemotaxis - migration of WBC to site of injury
13
Q
What are the function of cellular elements in an inflammatory response?
A
- Neutrophils - phagocytosis of microorganisms
- Basophils - release histamine leading to inflammatory response
- Eosinophils - allergic response
- Macrophages - migrate into tissues perform phagocytosis
14
Q
What are the diagnostic test to determine inflammation?
A
- Leukocyte count
- Differential count (can distinguish viral from bacterial infection)
- Plasma protein (increase in fibrinogen & prothrombin)
- C-reactive protein (presence of protein that is normally not in blood)
- Increase ESR (due to elevated plasma protein)
- Cell enzyme (may indicate site of injury due to cell released during inflammation)
15
Q
What are the characteristics of acute inflammation?
A
- Sudden & short duration
- Exudation of fluid & plasma protein
- Migration of leukocytes (neutrophils)
16
Q
What are the characteristics of chronic inflammation?
A
- Period of acute inflammation & continuous tissue destruction
- Less swelling & exudation
- Increase leukocytes, macrophages & fibroblast
- More severe on-going tissue destructions
- More collagen & fibrous scar tissue
17
Q
What are the causes of chronic inflammation?
A
- Persistent acute inflammation
- Persistent infection
- Persistent indigestible material
- Immune mediated reactions (autoimmune, organ transplant rejection, unregulated immune response, hypersensitivity reactions)
18
Q
What are some treatments for inflammation?
A
- Anti-inflammatory (i.e. asprin, NSAIDs, COX-2, GCC)
- Analgesia (i.e. aspirin, panadol, NSIAD, COX-2)
- Anti-pyretic (i.e. aspirin, panadol, NSIAD, COX-2)
19
Q
What are the non-pharmacological management of inflammation?
A
Rest, Ice, Compression, Elevation
20
Q
What are the side effects of Chronic use of NSAIDs?
A
- Coagulopathy - reduced platelet aggregation; longer bleeding time
- Gastrointestinal - ulcer, vomiting of blood, gastritis
- Hepatotoxicity - cholestatic hepatitis, acute hepatitis necrosis
- Haematology effects - leukopenia (low WBC), aplastic anaemia (bone marrow cannot make enough RBC), agranulocytosis (low neutrophils)
- Kidney effects - salt & water retention, oliguria, interstitial nephritis
- Respiratory effects - bronchospasm (sudden constriction of bronchioles)
- Allergy, headache, dermatitis
21
Q
What are the effects of NSAIDS interaction with other drugs?
A
- Reduced efficacy with beta-blockers, ACEi, diuretics
- Increase effect of sulfonylureas, toxicity of aminoglycosides, cyclosporine
- Long term of COXIB increase risk of CV events, thrombosis, MI, stroke
22
Q
What is required for the production of COX-1 & COX-2?
A
Arachidonic Acid through: binding of Phospholipase A2 to Bilayer Phospholipids
23
Q
What does COX-1 & COX-2 generate?
A
- COX-1 (present in most tissues): Prostaglandin I2 (gastric protection) & Thrombin A2 (platelet function)
- COX-2: Prostaglandin E2 (fever, pain, inflammation)
24
Q
What are the pharmacological effects of NSAIDs?
A
- Anti-inflammatory - due to decrease synthesis of PG (PG plays a role in V.D)
- Anti-pyretic - due to inhibition of COX-2 in hypothalamus leading to reduced PG (IL-1 stimulates PG in Hypo. -> increase temperature)
- Analgesia - due to inhibition of PG synthesis (PG synthesis sensitise nociceptors which lead to inflammation)
25
What are the pharmacological effects of GCC?
- Inhibits NFkB - inhibit production of inflammatory mediators
- Inhibits Phospholipase A2 & COX enzymes - reduce production of PG, thromboxane
- increase transcription of anti-inflammatory proteins
26
What are the mechanism of anti-inflammatory actions?
- ASA (aspirin) - irreversible inhibits COX-1 & COX-2; weakly selective to COX-1
- Acetaminophen (panadol) - exact mechanisms unknown; selective inhibition to COX-2
- NSAIDS - competitive inhibitor to COX-1 & COX-2; ibuprofen & naproxen are weakly selective to COX-1
- GCC - inhibits NFkB; increase transcription of anti-inflammatory proteins IL-1 receptor antagonist, IL-10
- COX-2 - competitive inhibitor of COX-2 at therapeutic dose
27
What are the common synthetic GCCs (produced by adrenal glands)?
- Cortisone - short acting corticosteroids; T1/2 = 6-12 hrs; converted into Cortisol/ Hydrocortisone in the liver
- Prednisone - intermediate acting drug; T1/2 = 12-36 hrs; converted into Prednisolone in the liver; 5x more potent then Cortisol
- Dexamethasone - long acting drug; T1/2 = 36-72 hrs; 25x more potent than Cortisol
- Betamethasone - long acting corticosteroid; T1/2 = 36-72 hrs; used topically to manage inflammatory skin condition
28
What are the other effects of corticosteroid
- decrease immunity
- decrease inflammation
- decrease Ca2+ absorption
- decrease serotonin
- increase blood sugar
- retains Na+
- regulate metabolism
29
What are the 2 processes of proliferation?
1. Formation of granulation tissue
- compose of proliferating capillaries, fibroblast & residual inflammatory cells
- cells are metabolically active with Angiogenesis & proliferating fibroblast
2. Collagen synthesis & laydown of fibroblast
- starts within 3-5 days of injury & continues for weeks depending of size of injury
- collagen mass increase; cellular & vascular events decrease
30
What are the key building blocks of tissue healing?
-Fibronectins & Proteoglycans - lay the foundation & forms a scaffold that provides tensile strength
- Elastin - cross linking to fibrils; provides elasticity to tissues
- Collagen - provide structural support & tensile strength; key determinant of structural stability
31
What occurs at the stage of remodelling?
Parallel process of synthesis & degradation
- synthesis of collagen & extracellular metric protein
- degradation by Matrix Metalloproteinases (Type III & Type I collagen)
32
What are the 3 determinants of "complete" healing?
The involved tissue; extent of tissue injury & nature of injury (chronic vs acute/ persistent)
33
What are the 3 'R's of healing?
- Resolution - minimal tissue damage; able to regain original structure; intact extracellular matrix framework
- Regeneration - occurs in cells capable of mitosis (replication); damages tissue replaced by proliferating nearby cells; new tissues are functional; no fibrosis / scarring
- Replacement - tissue unable to generate; functional tissues replaced by connective tissues (except brain); lead to loss of function
34
What are the types of healing according to regenerative ability?
Labile tissues
- stem / undifferentiated cells
- capable of division & replace the damaged tissue
- Eg. epithelial cells (skin, GI); haemopoietic tissues
Stable tissues
- low proliferative activity
- can undergo division if stimulated
- Eg. Parenchymal tissues (liver, kidney, pancreas)
Permanent tissues
- cannot proliferate; left the cell cycle
- Eg. skeletal & cardiac muscle; nervous tissue
35
What are the factors that affect healing?
Promote healing
- youth
- good nutrition
- adequate Hb
- clean, undisturbed wound
Delay healing
- advanced age
- poor nutrition, dehydration
- anemia
- circulatory problems
- chronic disease / co-morbidities
- infection / foreign materials
- chemotherapy treatment
- prolonged GCC
36
What is the difference between Necrosis & Apoptosis?
Necrosis
- Cells enlarge in size
- Nucleus goes through Pyknosis (clumping) -> Karyorrhexis (fragmentation) -> Karyolysis (dissolution)
- Plasma membrane is disrupted
- Cellular content goes through enzymatic digestion
- Frequent inflammation
- Caused by pathologic factors (e.g. inflammation)
Apoptosis
- Cells reduce in size
- Nucleus are fragmented into nucleosome-size fragments
- Plasma membrane are intact
- Cellular content are packaged into apoptatic body
- No inflammation
- Caused by physiologic factors; can be pathologic
