Physiology of the Renin Angiotensin System

Question 1

Where is pro-renin produced?

Answer 1

JGA cells in the afferent arteriole

Question 2

Where is renin stored?

Answer 2

Secretory granules of the JGA

Question 3

What stimulates the release of renin?

Answer 3

Released by JGA in response to:

Decreased BP

Decreased Na⁺ (tubuloglomerular feedback)

Increased sympathetic stimulation (Baroreceptor reflex)

Question 4

What does renin do?

Answer 4

Cleaves angiotensinogen → angiotensin 1

Question 5

Where is angiotensinogen produced?

Answer 5

Liver and Kidney

Question 6

What is responsible for converting angiotensin 1 to angiotensin 2? and where is this enzyme produced?

Answer 6

Angiotensin Converting Enzyme (ACE) produced in the lung

Question 7

What is the action of angiotensin 2?

Answer 7

Vasoconstriction

Increased Na⁺ absorption in proximal convoluted tubule

Increased thirst/ADH/sympathetic stimulation

Aldosterone release by adrenal cortex - increased Na⁺ absorption in distal convoluted tubule

Question 8

What is the tubuloglomerular feedback?

Answer 8

Afferent vasoconstriction

Inhibited in low GFR → ↓Tubular flow rate → ↓Cl^- delivery to macula densa → ↓afferent arteriolar resistance → ↑Renal blood flow → ↑Glomerular pressure

Question 9

How does renal autoregulation act in decreased systemic BP?

Answer 9

↓Systemic BP → ↓Barostretch → Afferent dilation

+ ↑ATII → efferent arteriolar constriction

→ Glomerular pressure

Question 10

How does renal autoregulation react to an increase in GFR?

Answer 10

↑GFR → ↑Tubular flow → ↑Na⁺ and Cl^- delivery to macula densa → afferent vasoconstriction

= Tubuloglomerular feedback

Question 11

What are the actions of ATII?

Answer 11

Vasoconstriction of both afferent and efferent arteriole (efferent more so, overall effect ↑Glomerular pressure)

Sensitises afferent arteriole to ↑TGF effect

Helps release of vasodilatory PGs by glomeruli → prevent excessive constriction in renal circulation

Question 12

What happens to renin levels in single kidney renal artery stenosis?

Answer 12

Ischaemic kidney will release renin → Hypertension

Normal kidney will excrete increasing amounts of salt and water due to pressure diuresis

The hypertension will be maintained by high renin levels released from clamped kidney

Question 13

What happens to renin levels when both kidneys have renal artery stenosis?

Answer 13

Increased renin release

Salt and water retention

Volume dependent HTN lowers renin release

HTN maintained by volume expansion - plasma volume expands due to lack of kidney that can initiate diuresis

Question 14

What does Aliskiren do?

Answer 14

Binds to renin and prevents conversion of angiotensinogen to angiotensin 1

Question 15

What does spironolactone do?

Answer 15

Blocks aldosterone - Potassium sparing diuretic

Question 16

How do the following affect the RAS indirectly?

Diuretics

NSAIDs

Ca Channel blockers

Answer 16

Diuretics - salt and volume depletion → RAS more susceptible to ACE I

NSAIDs - inhibit vasodilatory prostaglandins

Ca Channel blockers - afferent arteriolar dilation → ↑GFR

Question 17

What factors can increase the effect of ACE I on the kidney?

Answer 17

Things that reduce afferent inflow:
Low output cardiac failure

Volume depletion

NSAIDs

Dangerous in bilateral artery stenosis as, glomerular pressure is mediated by efferent arteriolar constriction. ACE I → dramatic drop in GFR

Question 18

What do asymmetrical kidneys on US suggest?