L26- acute inflammation

Question 1

what is the function of acute inflammation

Answer 1

eliminate offending agents

Question 2

how is acute inflammation initiated

Answer 2

injurt

Question 3

the difference between acute and chronic inflammation

Answer 3

ACUTE: lasts 2-3 days up to 2-3 weeks, resolves rapidly, presence of neutrophils and macrophages
CHRONIC: prolonged inflammation >3weeks, presence of immune mediated leukocytes T/B Cells, characterised by constant healing an damage of tissue

Question 4

list 5 R steps involved in AI

Answer 4

Recognition
Recruitment
Removal
Regulation
Repair

Question 5

what is recognition

Answer 5

First step of acute inflammation
Involves recognising the noxious agent that is initiating stimulus

Question 6

what is recruitment

Answer 6

2nd step of acute inflammation
Involves the recruitment of leukocytes and plasma proteins to the site via teh vasculature

Question 7

What is removal

Answer 7

3rd step of acute inflammation
Involves the removal of the stimulus via phagocytic cells

Question 8

what is regulation

Answer 8

4th step of acute inflammation
Involves the termination or slowing down of the inflammatory response

Question 9

what is repair

Answer 9

Final step of AI
consists of a series of events that hela damages tissue

Question 10

What are the inducers of inflammation

Answer 10

Infection, Trauma, chemical agents, radiation, tissue necrosis, hypersensitivity

Question 11

the consequences of acute inflammation

Answer 11

acute respiratory distress, asthma, Glomerulonephritis, septic shock

Question 12

the consequences of chronic inflammation

Answer 12

arthritis, asthma, atherosclerosis, pulmonary fibrosis

Question 13

clinical signs of acute inflammation

Answer 13

Heat (Colar) - VC/VD, Redness (Rubor) - VC/VD, Loss of function, Swelling (tumor) - ^ VSC perm, Pain (Dolor) - soluble mediators

Question 14

key processes of the vascular response in AI

Answer 14

1. Venule vasoconstriction
   (neurogenic; decreased outflow)
2. Arteriole vasodilation
   (neurogenic; increased inflow)
3. Blood thickening (stasis)
4. Increased vascular permeability
   (increased interstitial fluid)
5. Endothelial activation
   (transmigration)

Question 15

what is leukocyte extravasation

Answer 15

it is the process of leukocytes moving from the blood vessels into the tissue

Question 16

what are the key steps in leukocyte extravasation

Answer 16

they roll along and adhere to the endothelium, gaps in the endothelium allow them to move outward chemotaxis signals in tissue

Question 17

what are chemotaxis signals

Answer 17

o chemokine family (e.g., IL-8)
o complement components (e.g., C5a)
o arachidonic acid metabolites (e.g.,
leukotriene B 4)
o bind to specific 7-transmembrane G protein– coupled receptors on the surface of leukocytes

Question 18

where are cellular receptors for microbes located

Answer 18

plasma membrane (for extracellular microbes), endosomes (for ingested microbes), cytosol (for intracellular microbes)

Question 19

what is the role of PAMPS and DAMPS in recognising and initiating inflammation

Answer 19

Pathogen-associated-molecular-pattern are signals released by pathogens that are recognised by Pattern recognition receptors

Damage-associated molecular patterns are signals released when cells are damaged and are recognised by PRR

Question 20

what is exudates

Answer 20

high internal pressure forces fluid out of the vessel and into tissues - high protein and high fluid amounts are leaving the cell - exudate is the fluid

Question 21

what is transudate (oedema)

Answer 21

identified by the leaving of fluid from the vessel due to high osmotic pressure and a lack of endothelial cell separation low amounts of proteins and cells exit - related to disease and not inflammation

Question 22

what are the major groups of soluble mediators from cells

Answer 22

Arachidonic Acid Metabolites
Vasoactive Amines
Cytokines & Chemokines

Question 23

how is each mediator activated

Answer 23

Leukocytes (AAM)
Mast cells and granules (VA)
Lymphocytes and MACs (CC)

Question 24

what/how are mediators released

Answer 24

via cell membranes
preformed in granules
newly synthesised

Question 25

examples of arachidonic acid metabolites

Answer 25

thromboxane, prostaglandins, leukotrienes, lipoxins, resolvins

Question 26

examples of vasoactive amines

Answer 26

histamine, serotonin

Question 27

examples of cytokines and chemokines

Answer 27

IL-1b, IL-6, TNFa

Question 28

what causes the degranulation of serotonin and histamine

Answer 28

Type I hypersensitivity, trauma, heat, cold, complement fragments (anaphylatoxins), cytokines (IL-1, IL-8), Neuropeptides

Question 29

what are the clinical effects of the release of serotonin and histamine

Answer 29

Vasodilation, smooth muscle contraction, vascular permeability, pain (serotonin), eosinophil chemotaxis (histamine)

Question 30

where do soluble receptor mediator originate

Answer 30

in cells or in the liver (factor 12)

Question 31

what are the possible outcomes of inflammation

Answer 31

1. Complete resolution 2. Healing via fibrosis 3. Progression to chronic inflammation 4. Abscesses & ulcers

Question 32

explain the release and metabolism of arachidonic acid

Answer 32

phospholipase 2 --> membrane phospholipids --> arachidonic acid --> lipoxygenase --> leukotrienes cyclooxygenase --> prostaglandins, thromboxanes

Question 33

what are the classes of of AI drugs

Answer 33

Non-steroidal anti inflammatory Steroids

Question 34

what are the 5 mechanisms of action of glucocorticoids

Answer 34

1. genomic mechanisms 2. non genomic mechanisms 3. suppression of pro inflamm pathways 4. modulation of immune cells 5. apoptosis induction

Question 35

how do glucocorticoids modulate genes

Answer 35

Interaction with glucocorticoid receptors → nucleus Upregulation of anti-inflammatory genes: inhibits phospholipase A2 → ↓ synthesis of pro-inflammatory eicosanoids Downregulation of pro-inflammatory genes: Suppresses transcription factors (e.g., NF-κB & AP-1) → ↓ of proinflammatory cytokines (e.g., interleukins, TNF-α)

Question 36

how do glucocorticoids reduce inflammation using Non-Genomic Mechanisms

Answer 36

Membrane stabilisation: stabilise lysosomal & cell membranes, stops release of inflammatory mediators Reduction in immune cell trafficking: ↓ adhesion molecule expression → ↓ leukocyte migration to site of inflammation

Question 37

how do glucocorticoids reduce inflammation using Suppression of Pro-inflammatory Pathways

Answer 37

Inhibition of cyclooxygenase-2 (COX-2): ↓ prostaglandin synthesis, mitigating pain, swelling, and redness Blocking phospholipase A2: induces lipocortin-1 to inhibit the release of arachidonic acid

Question 38

how do glucocorticoids reduce inflammation by Modulation of Immune Cells

Answer 38

T lmphocytes: suppresses activation and proliferation of T cells Macrophages/DCs: ↓ antigen presentation and cytokine production Neutrophils: ↓ migration into tissues

Question 39

how do glucocorticoids reduce inflammation by inducing apoptosis

Answer 39

↑ apoptosis of eosinophils, lymphocytes, and other inflammatory cells → ↓ accumulation at inflamed sites

Question 40

what are the side effects of glucocorticoids

Answer 40

Endocrine and metabolic effects (e.g., adrenal suppression, hyperglycemia, growth suppression Musculoskeletal effects (e.g., osteoporosis, muscle weakness) Immune system effects (e.g., immunosuppression, delayed wound healing) Gastrointestinal effects (e.g., hypertension, oedema) Neuropsychiatric effects (e.g., mood changes, insomnia) Dermatologic effects (e.g., skin thinning, acne, hirsutism) Opthalmological effects (e.g., cataracts, glaucoma)

Question 41

what are the primary mechanisms of action of NSAIDs

Answer 41

1. Inhibition of Cyclooxygenase (COX) Enzymes 2. Reduction of Prostaglandin Synthesis

Question 42

how do NSAIDs reduce inflammation by inhibiting COX

Answer 42

COX enzymes convert arachidonic acid to prostaglandins and thromboxanes

Question 43

Types of COX enzymes and functions

Answer 43

COX-1 and COX-2. COX-1 is constitutively expressed and important for physiological functions. COX-2 is inducibly active at inflammation sites

Question 44

how do NSAIDs reduce inflammation by inhibiting prostaglandins synthesis

Answer 44

Reduces inflammation - ↓prostaglandins (e.g., PGE2, PGI2) at injury site → ↓ vasodilation and vascular permeability Pain - ↓ prostaglandin levels → ↓ sensitization of nociceptive neurons, alleviating pain Heat - ↓PGE2 synthesis in hypothalamus resets the body’s thermostat, reducing fever

Question 45

NSAIDs side effects

Answer 45

Inhibition of thromboxane A2 - promotes platelet aggregation, particularly aspirin, irreversibly inhibit COX-1 in platelets, reducing clot formation Renal effects:↓ renal perfusion → fluid retention or acute kidney injury Gastrointestinal effects ↑risk of ulcers and bleeding Dyspepsia (indigestion) Cardiovascular effects : increased risk of thrombosis, hypertension Allergic reaction - Aspirin-exacerbated respiratory disease (e.g., asthma) Neurological side effects - headaches & dizziness General effects - fatigue and malaise, swelling (due to fluid retention)

Question 46

NSAID classes

Answer 46

1. Nonselective COX inhibitors (traditional NSAIDs) 2. Preferential COX-2 inhibitors 3. Selectve COX-2 inhibitors 4. Analgesis-antipyratics with poor anti-inflammatory action

Question 47

what are 4 drugs of non-selective COX inhibitors and their subclasses

Answer 47

aspirin - salicylate ibuprofen - propionic acid derivative diclofenac - Aryl-acetic acid derivative indomethacin - indole derivative

Question 48

what class of NSAIDs does meloxicam belong to

Answer 48

preferential COX-2 inhibitors

Question 49

what class of NSAIDs does celecoxib belong to

Answer 49

selective COX-2 inhibitor

Question 50

What medications are analgesis-antipyratics with poor anti-inflammatory action

Answer 50

paracetamol - para aminophenol derivative metamizole - Pyrazolone derivative