Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

Anti-Diuretic Hormone (ADH)
/ Vasopressin/ Arginine vasopressin / Argipressin

Renal Physiology
03 April 2017

19:58

9 a
...
peptide
Released in response to low arterial press/ ↑ osmolality:
A
...
Vasoconstriction (blood vessels)
- ↑BP
Action
1) Osmoreceptors detect ↑ osmotic press , Baroreceptors detect ↓BP
2) Send signal to hypothalamic neuron in posterior pituitary
3) -> blood vessels - vasocontriction
& ->kidney - ↑h20 reab
4) ↑blood vol & ↑BP

Sensing BP - Baroreceptors
 Baroreceptors in carotid sinus & aortic arch
 Carotid- sense ↑ & ↓ BP
 Aortic- only sense ↑BP
 Nerve signal -> hypothalamus to ↑/↓ ADH release

ADH in hypothalamus & pituitary
 Synthesised in cell body of neurosecretory cells - hypothalamus
 Stored in secretory vesicles - posterior pituitary
 Osmoreceptor & neurostimuli ↑ ADH secretion

Sensing Osmolality- Osmoreceptors in hypothalamus
• Changes in osmotic pressure of interstitial fluid causes cell body to swell/shrink - osmoreceptors
• Cell shrinking stim ADH release
• Cell swelling blocks ADH release


Mechanism 1- ADH ↑ h2o permeability in DCT & collecting duct

1
...

3
...

5
...

7
...
ADH binds to recep on baso memb of principle cells
2
...
cAMP cascade -> PKA & EPAC activation
4
...
Urea transporter-1 -> apical memb , urea transporter-3 -> basolateral memb
6
...
Receptor linked to G-prot coupled receptor (GPCR)
2
...
Same pway -> urea & water transport

4
...
ADH bind to recept on bas memb
2
...
cAMP cascade -> PKA
4
...
PKA ↑ na-k-cl cotransporter at apical memb
6
...
sinus & a
...
cAMP cascade -> PKA
4
...
PKA ↑ na-k-cl cotransporter at apical memb
6
...
sinus & a
...
Renin released from juxtaglom cells of juxtaglom apparatus
2
...
Angio I cleaved to Angio II by Angiotensin converting enzyme (ACE) - predominantly expressed in
lung cap endothelial cells & vasc tiss

Angiotensinogen -> Angio II - Proteolytic cascade

Angiotensin II
- Stim thirst
1
...
Direct effects to ↑ na absorp & as vasoconstrictor
3
...
Stim ADH secret

Renin release from juxtaglomerular apparatus

Renin

ACE

Active
form

Cellular structure of juxtaglomerular apparatus
- Sensing and signalling for maintenance of renal & systemic BP

Smooth Muscle
 Baroreceptors - stretch receptors
 Paracrine signalling
 Constrict / dilate arterioles
Juxtaglomerular Cells
 Modified smooth musc cells
 Constrict/ dilate arterioles
 Release renin (BP hormone)
Macular Densa
 Modified DCT epithelial cells
 Sense Na in tubular fluid
 Paracrine signalling- vasoconstrictors & vasodilators e
...
adenosine
 Parac signalling reg renin release

Juxtaglomerular cells- signal integration & renin
cAMP sign intergrates sign from
- Afferent arteriole barorec (JGC)
- Systemic baro (sympathetic tone)- catecholamines (adrenaline)
- Tubular flow (paracrine signals) from macula densa (adenosine)
At threshold value renin released

Angiotensin II- Multiple Effects on BP

Mech 1- ↑ symp tone
1) Direct cardiovascular
□ ↑ heart rate
□ Constricts arterioles -↑ resistance & BP
□ ↓ venous capacitance - ↓elasticity
- ↑venous return
- ↑blood flow- more blood per pump
- ↑resistance & BP
2) Neuroendocrine
□ Catecholamines (e
...
adrenaline)
- ↑renin release- feed forward

Neg
...
Aldosterone secreted in response to angiotensin II- adrenal
gland
2
...
Binds & activates mineralocorticoid receptor
4
...

5
...

7
...
cAMP & IP3 secondary sign cascade
B
...
↑ expression na, k pump on basal lateral memb
D
...
Blocks na leak to tubule fluid
F
...
Angiotensin II binds its receptor
2
...
Activating IP3/Ca secondary messenger signalling cascade -> myosin contraction

Mech 5- ↑ ADHV secretion from hypothalamus
Angiotensin II indirectly
a)
b)

↑ h20 reab
↑h2o perm in DCT & collecting duct
↑urea reab in collecting duct
↑ na reab in ascending limb
vasoconstriction

RENIN-ANGIOTENSINOGEN-ANGIOTENSIN SYSTEM SUMMARY
• Renin released in response to low blood and glomerular pressure
(afferent arteriole press, by baroreceptors -> symp response, low
tubular press nacl)
• Renin sets off proteolytic cascade -> angiotensin II & aldosterone
signalling
• Results in ↑ symp tone, ↑ na reab (and II & aldo), vasocontriction & ADH
secretion

Sodium Balance
• Sensory essential & needs to be regulated because
...

2
...

4
...

6
...
Dilates afferent arteriole & constricts efferent arteriole -> ↑ glom press
2
...
Blocks carbonic anhydrase
- ↑ nahco3 excretion
2
...
Blocks na-k-cl cotransporter
- ↑ na excretion
- ↑ k excretion
- ↑ cl excretion
4
...
Antagonises aldosterone receptor
- ↑ na excretion
- ↑ k rentention



---