Inflammation

Question 1

What are the 5 key aspects of inflammation?

Answer 1

Heat
Swelling
Redness
Pain
Loss of function

Question 2

What is the immune process behind inflammation?

Answer 2

Mast cells/macrophages detect pathogen
Release inflammatory mediators - cause vasodilation
Polymorphonuclear cells activated - release proteases with anti-microbial activity and mediators that recruit leukocytes
Endothelial cells activated - express cellular adhesion molecules - leukocytes in blood adhere at site of inflammation
Neutrophils leave vasculature - migrate to stimulus site - kill/phagocytose pathogens
Monocytes enter site - differentiate to macrophages - phagocytose microbes and release mediators
T-cells activated if response unsuccessful - response repeated - chronic inflammation - can damage host cells

Question 3

Name 6 groups of inflammatory mediators and their effects

Answer 3

NO - heat and redness - increases blood flow
Histamine - heat, redness, and swelling - increases blood flow and vascular permeability
Bradykinin - heat, redness, swelling, and pain
Lipases, proteases, free radicals - loss of function
Prostaglandins - heat, pain, and swelling
Cytokines - pro-inflammatory/anti-inflammatory - change gene expression in target cell via binding to CS receptors

Question 4

What is the process of IgE activation of mast cells?

Answer 4

Antigen binds to B-lymphocyte in blood
B-lymphocyte releases IgE
IgE binds to mast cells - degranulation - histamine release

Question 5

Which histamine receptor is involved in allergic reactions and what is its mechanism?

Answer 5

H1

Via Gq - increases Ca2+

Question 6

Which histamine receptor is involved in gastric acid secretion and what is its mechanism?

Answer 6

H2

Via Gs - increases cAMP

Question 7

Through which receptor does histamine stimulate C fibres?

Answer 7

H1

Question 8

Name an H1 antagonist

Answer 8

Diphrenhydramine

Question 9

Name an H2 antagonist

Answer 9

Ranitidine

Question 10

What is the key difference between old and new antihistamines?

Answer 10

Old cross BBB - cause dizziness, drowsiness, tinnitus

New do not

Question 11

How is bradykinin synthesised in plasma?

Answer 11

Factor XIIa + prekallikrein -> plasma kallikrein

Plasma kallikrein + HMV kininogen -> bradykinin

Question 12

How is bradykinin synthesised in glands, pancreas, kidneys, and neutrophils?

Answer 12

LMV kininogen -> kallidin

Kallidin -> aminopeptidase + bradykinin

Question 13

What are the classes of bradykinin receptors, what receptor type are they, and what is their key difference?

Answer 13

GPCRs
B1 - no internalisation - resistant to desensitisation
B2 - internalisation - desensitise

Question 14

What breaks down bradykinin?

Answer 14

Peptidase

Question 15

What causes angioedema?

Answer 15

Drug-induced - ACE inhibitors prevent bradykinin breakdown - swelling
Hereditary - C1 inhibitor missing - no bradykinin regulation - swelling

Question 16

Which enzyme converts arachidonic acid to prostaglandins?

Answer 16

Cyclooxygenase

Question 17

How do NSAIDs work?

Answer 17

Inhibit cyclooxygenase

Question 18

What are the types of cyclooxygenase and what are their actions?

Answer 18

COX-1 - constitutive - gastric protection

COX-2 - induced at inflammation site - causes inflammation and cardiovascular protection

Question 19

What is the key difference between new and old NSAIDs?

Answer 19

Old non-selective - cause GI tract ulcers

New selective for COX-2 - no GI tract ulcers - inhibits cardiovascular protective role - cardiovascular side effects

Question 20

What is the mechanism of glucocorticoids in the HPA axis?

Answer 20

Hypothalamus releases corticotropin releasing factor (CRF) - onto anterior pituitary
Anterior pituitary releases adrenocorticotrophic hormone (ACTH) onto adrenal cortex
Adrenal cortex releases glucocorticoids - inhibit hypothalamus

Question 21

What is the role of glucocorticoids?

Answer 21

Inhibit inflammatory mediators - anti-inflammatory

Question 22

What are the individual inhibitory actions of glucocorticoids?

Answer 22

Neutrophil migration
Neutrophil and macrophage activation
T-lymphocyte activation and clonal expansion

Question 23

What is Cushing’s syndrome and what is its treatment?

Answer 23

Excessive ACTH - adrenal cortex produces excess cortisol
Glucocorticoids as treatment - inhibit ACTH production - adrenal glands shrink - withdrawing treatment prevents adrenaline production - adrenaline crisis - must be weaned off treatment

Question 24

What are biologics?

Answer 24

Biomolecules that target inflammatory mediators

Question 25

Name a cytokine and describe its roles

Answer 25

Tumour necrosis factor (TNF) alpha

Causes fever, activates macrophages