CE L3 Therapy rationale

Question 1

Where are endogenous corticoids released from?

Answer 1

Adrenal cortex

Question 2

Mineralocorticoids affect ……

Answer 2

water and electrolyte balance

via aldosterone

Question 3

e.g. of glucocorticoids (2)

Answer 3

hydrocortisone and corticosterone

Question 4

Glucocorticoids affect …….. (2)

Answer 4

• Carbohydrate and protein metabolism

- Anti-inflammatory and immunosuppressive effects

Question 5

Deficiency of corticoids results in ….

Answer 5

Addison’s disease

Question 6

Excessive GC results in ….

Answer 6

Cushings syndrome

Question 7

Excessive MC results in ….

Answer 7

Conns sydrome

Question 8

Where is cortisol released from?

Answer 8

Adrenal glands

Question 9

What causes increase in cortisol release? (2)

via what route?

Answer 9

Stress and proinflammatory cytokines
cause hypothalamus to release CRH
causes pituitary to release ACTH
causes adrenals to release cortisol
(-ve signalling back to pituitary and hypothalamus)

Question 10

What does CRH stand for?

Where does it signal from/to?

Answer 10

Corticotropin releasing hormone

signals from pituitary to hypothalamus

Question 11

What does ACTH stand for?

Where does it signal from/to?

Answer 11

Adrenocorticotropic hormone

signals from the pituitary to the adrenal glands

Question 12

Corticoids act on early or late inflammatory response?

Answer 12

Both

Question 13

Actions of corticoids (3)

Answer 13

decreased extravasation
inhibit cell activation
decreased production of inflammatory mediators

Question 14

GC binds to receptors located where?

Answer 14

cytoplasmic receptors

Question 15

GC-receptor complex goes to ….. and acts as….

Answer 15

nucleus

acts as a transcription factor

Question 16

Transcription factor binds to …. to activate/repress genes?

Answer 16

reponse element

Question 17

GC may repress or activate genes?

Answer 17

Both

Question 18

GC can interact/inhibit binding of other transcription factors such as ….

Answer 18

AP1 and NFKB

Question 19

metabolic s/e

Answer 19

osteoporosis

diabetogenic + increased appetite

Question 20

mineralocorticoid s/e

Answer 20

oedema, CV events

due to Na/H20 retention

Question 21

GC s/e

Answer 21

immunosuppression - infections

supresses HPA axis through feedback

Question 22

The two proinflammatory cytokines involved in proliferation?

Which is also involved in apoptosis?

Answer 22

TNF and IL1

TNF also involved in apoptosis through activation of NFkB

Question 23

When are TNF and IL1 released inappropriately and what happens?

Answer 23

during inflammation

tissue destruction and organ damage

Question 24

What cells produce TNF and IL1

Answer 24

macrophages and monocytes

Question 25

How many forms of IL1 are there? | Where are they synthesised?

Answer 25

2 (alpha and beta) | In the microtubules

Question 26

Where is IL1 beta found

Answer 26

mostly circulating

Question 27

where is IL1 alpha found

Answer 27

cytosolic or membrane bound

Question 28

What enzyme is involved in IL1 synthesis

Answer 28

``` Caspase 1 (also known as IL1 converting enzyme) (ICE inhibitors are anti inflammatory) ```

Question 29

the release of IL1 is facilitated by (2)

Answer 29

ATP and P2X7

Question 30

Effects of IL1

Answer 30

Fever Synth of COX2 and iNOS Increased expression of VCAM and RANKL Bone erosion

Question 31

C5a increases .... RNA

Answer 31

IL1

Question 32

release of IL1 is increased in macrophages/monocytes that are stimulated by....

Answer 32

IFNg

Question 33

CD40L activates ....... in EC and SM cells

Answer 33

ICE

Question 34

IL receptors are part of which superfamily?

Answer 34

Ig

Question 35

Type I IL1 receptors are found on ............ cells | Type II IL1 receptors are found on ............. cells

Answer 35

most cells B cells - decoy receptors (both exist as soluble receptors)

Question 36

Type I IL1 receptors have a signalling domain similar to ........... which leads to activation of .............. (3)..........

Answer 36

Toll like receptors Activation of IRAK, NFKb and AP1