Renal Physiology 3

Question 1

Where is renin released from?

Answer 1

Juxtaglomerular cells

Question 2

What controls renin release?

Answer 2

The macula densa, detecting low sodium flux

Question 3

What effect does hypotension have on renin release?

Answer 3

Increased renin release

Question 4

What effect do beta blockers have on renin release?

Answer 4

Inhibits renin release

Question 5

How is the renin-angiotensin system activated?

Answer 5

In response to hypotension, and thus a fall in renal blood flow:

• low BP detected by juxtaglomerular apparatus
• JGA secretes renin
• renin stimulates production of angiotension
• angiotension vasoconstricts and also causes aldosterone release from the adrenal cortex
• vasocontriction increases BP
• aldosterone causes sodium and water reabsorption also increasing BP

Question 6

What is the juxtaglomerular apparatus?

Answer 6

It’s the intrarenal baroreceptor.

Composed of the:

• macula dena
• JG cells

Question 7

What is the macula densa? Where is it?

Answer 7

Specialized epithelial cells. They increase renin release in response to low levels of delivered sodium, due to a fall in GFR or increase in PCT reabsorption.

Situated in the wall of the 1st part of the DCT. It abuts the afferent and efferent arterioles.

Question 8

What are the juxtaglomerular cells?

Answer 8

They secrete renin in response to hypovolaemia, increased Na concentration in blood and sympathetic stimulation.

Located in the wall of the afferent arteriole (in the media). Just before the arteriole enters the glomerulus.

Question 9

What is renin?

Answer 9

• A glyocoprotein hormone, synthesised and secreted by the JGA
• formed from pro-renin and pre-pro-renin with a 1/2 life of 80mins

Question 10

What are the actions of renin?

Answer 10

• acts on circulating angiotensinogen, a large liver protein
• cleaves a 10 amino acid peptide, Angiotensin I from angiotensinogen, in the plasma
• Angiotensin I is converted to Angiotensin II in lungs, by angiotensin converting enzyme (ACE)
• ACE is found in the capillary endothelium
• Angiotensin II has multiple effects
• Angiotensin II is converted to angiotensin III in many tissues by aminopeptidase

Question 11

What is renin secretion controlled by?

Answer 11

• renal sympathetic nerves
• intrarenal baroreceptors
• antiontension II

Question 12

What increases renin secretion?

Answer 12

• hypovolaemia
• cardiac failure
• cirrhosis
• renal artery stenosis
• catecholamines acting on beta-1 receptors

Question 13

What is renin secretion decreased by?

Answer 13

• angiotensin II
• vasopressin

Question 14

What are the actions of angiontensin II?

Answer 14

• powerful vasoconstrictor, constricts afferent and efferent arterioles in the kidney
• effect on efferent arteriole is greater, increasing GFR
• causes aldosterone release
• potentiates sympathetic activity
• stimulates thirst by direct effect on hypothalamus
• causes release of vasopressin (ADH)
• acts directly on renal tubules, esp the PCT to cause Na+ and water retention, by stimulation of Na+/H+ antiporters

Question 15

Where is aldosterone produced and secreted by?

Answer 15

It’s a mineralocorticoid. Secreted by the zona glomerulosa of the adrenal cortex in response to:

• reduced renal blood flow (via RAS-angiotensin II)
• stress and trauma via adrenocorticotrophin (ACTH) release
• hyperkalaemia - small changes in plasma K+ are important
• hyponatraemia

Question 16

What are the actions of aldosterone?

Answer 16

• acts on the DCT and renal cortical collecting ducts
• increases Na reabsorption, thus Na and H2O are retained
• potassium and H+ lost in exchange for Na
• (Also increases production of distal nephron transport mechanisms
• works via protein synthesis so effect takes hours)

Question 17

What does the adrenal cortex produce?

Answer 17

Aldosterone (glomerulosa)

Cortisol (fasiculata)

Androgens (reticularis)

Catecholamines (medulla - the rest are all cortex)

Question 18

Where is ADH synthesised?

Answer 18

Hypothalamus

Question 19

Where is ADH secreted from?

Answer 19

Posterior pituitary

Question 20

What does ADH do?

Answer 20

• under control of baro and osmoreceptor reflexes
• inactivated in liver and kidney
• half life of 18 minutes
• causes water retention due to an increase in water permeability of collecting duct membrane
• inserts protein channels for water into luminal membrane via cyclic AMP (aquaporins)
• at high concentrations, can act on arteriolar smooth muscle - reducing renal blood flow and GFR
• also stimulates sodium reabsorption and K+ excretion from collecting ducts

Question 21

What do baroreceptors do?

Answer 21

• can be arterial, venous, cardiac
• detect fall in plasma volume
• afferent firing rate to hypothalamus falls
• ADH release from posterior pituitary increased

Question 22

What do osmoreceptors do?

Answer 22

• osmoreceptors detect changes in plasma osmotic pressure
• fall in plasma osmotic pressure reduces ADH secretion
• rise in plasma osmotic pressure increases ADH secretion

Question 23

What is ANP?

Answer 23

Atrial natriuretic peptide - secreted in response to atrial stretch. Increases renal excretion of sodium and water. Potent vasodilator. Improves renal blood flow.

• afferent arteriolar dilatation and efferent arteriolar constriction - increases net filtration pressure (increased filtration coefficient)
• released from atrial myocytes
• inhibits renin secretion
• inhibits aldosterone release
• direct action on collecting ducts to decrease sodium reabsorption

Question 24

What is the normal GFR of an adult?

Answer 24

125ml/min or 180L/day

Question 25

What is clearance?

Answer 25

The renal clearance of a substance is the **volume of plasma completely cleared of that substance per unit time (ml/min).** Clearance is helped to quantify: * excretory function of the kidney * rate at which blood flows through the kidney * basic functions of the kidney

Question 26

What substances can be used to measure GFR?

Answer 26

Inulin Creatinine

Question 27

What is inulin?

Answer 27

* polysaccharide * molecular weight 5200 daltons * freely filtered, not reabsorbed or secreted * not toxic, metabolised or plasma protein bound * rate of excretion = filtration rate * not endogenous, must be administerd IV

Question 28

What is creatinine?

Answer 28

* a by-product of muscle metabolism * no need for infusion * almost entirely cleared from the body by glomerular filtration * small amount is secreted so the amount excreted slightly exceeds the amount filtered - therefore overestimates GFR * under steady state conditions amount of creatinine excreted = rate of creatinine production

Question 29

How is renal plasma flow estimated?

Answer 29

* if a substance is completely cleared from plasma, clearance should equal renal plasma flow * GFR is only 20% of renal plasma flow * for a substance to be completely cleared from plasma, some secretion must also occur * PAH (Para-aminohippuric acid) is 90% cleared by the kidneys from the plasma * PAH clearance is therefore used to estimate RPF

Question 30

How can renal blood flow be calculated?

Answer 30

You need to know renal plasma flow. You can calculate renal blood flow from this, provided the haematocrit is known. Renal plasma flow = renal blood flow x (1 - haematocrit) RBF = RPF / (1 - hct)

Question 31

What GFR would sodium as an indicator produce?

Answer 31

An **underestimate of GFR** because sodium is reabsorbed so urine concentration would be decreased.

Question 32

What is the calculation for clearance?

Answer 32

Clearance of a substance = renal excretion / plasma concentration