Sodium balance, blood pressure and renal haemodynamics

Question 1

How is blood pressure regulated in the short and long term?

Answer 1

Short term: cardiac output (TPR) and fluid shifts from the ICF to the plasma

Long term: kidneys and thirst

Question 2

Which region of the kidney recieves the majority of blood flow?

Answer 2

Cortex - 90%

permits a high GFR

Question 3

Where is the majority of sodium found in the body?

Answer 3

In the ECF.

Cl-, HCO3- and Na+ largely deermine the osmolality of the ECF.

The Na+ content of the ECF determines the amount of water (volume) of the ECF. Osmotic potential of Na+ causes water to be drawn into the ECF

Question 4

What is relationship between the ECF and bp?

Answer 4

Low ECF reduced blood volume which reduces arterial bp.

ECF volume controls BP
ECF osmolarity maintains cell volume

Question 5

Effect of GFR on Na+ balance

Answer 5

Changes in GFR affect tubular reabsorption
If GFR rises then the tubules reabsorb less well and Na+ excretion increases

If the GFR falls then the tubules are able to reabsorb more Na+ and excretion falls.

Large losses of Na+ are prevented by glomerulartubular balance. The tubules increase the rate of reabsorption when GFR is increased and decrease reabsorption when GFR falls.

Question 6

Name four physiological functions of salt (Na+)

Answer 6

Principle cation in ECF (Na+)

Maintenance of ECF volume/osmotic pressure

Acid base balance

Nerve/muscle conduction

Sodium dependant cellular transport pump mechanisms e.g. Na/ATP pumps

Question 7

Effect of RAAS system on Na+ balance

Answer 7

Renin: proteolytic enzyme produced by granular cells in the JGA in response to low arterial blood flow. It converts angiotensinogen made by the liver into angiotensin I.

ACE converts Angiotensin I into angiotensin II as the blood travels through the lungs.

Angiotensin II stimulates:
production of aldosterone (increases Na+
tubular reabsorption of Na+ by PCT
thirst and release of ADH from posterior pituitary (more H2O)

Also a potent vasoconstrictor, and increases bp

Question 8

Three main stimuli for renin relese

Answer 8

1. Decrease in pressure in afferent arteriole.
2. Sympathetic stimulation via b2R on the granular cells
3. Decrease in luminal NaCl at the macula densa (due to low GFR)
4. Decrease in efferent arteriole blood volume

Question 9

Effect of hydrostatic pressure on Na+ balance

Answer 9

An increase in bp rapidly causes Na+/H+ exchangers to be removed from the apical membrane of the PCT. Basolateral cell Na+/K+-ATPase is also decreased. These changes result in reduced tubular reabsorption of Na+ and enhanced excretion.

Question 10

How does aldosterone affect Na+ reabsorption?

Answer 10

Aldosterone induces expression and activity of SGK (serum and glucocorticoid regulated kinase) which causes increased expression and translocation of ENaC to membrane

Na+/K+ATPase activity also increased by aldosterone

Increases Na+ reabsorption

Question 11

Addison’s disease

Answer 11

Results from the desctuction of the adrenal glnd by infection or AI disease. All three zones of the adrenal cortex are involved, so there is inadequate secretion of glucocorticoids and mineralocorticoids.

Low mineralocorticoids leads to decreased renal K+ secretion and reduced Na+ retention, causing hypotension and dehydration.

Low glucocorticoids results in abnormal glucose metabolism, leading to weight loss and anorexia.

Question 12

Liddle’s syndrome

Answer 12

Autosomal dominant disorder.

Defect causes increased opening and number of ENaC channels in principal sells, resulting in excess reabsorption of sodium and loss of potassium from the renal tubule

Known as pseudohyperaldosteronism because patients have hypertension, low renin activity, metabolic alkalosis due to hypokalemia but patients have normal/low aldosterone levels.

Question 13

How does ANP affect Na+ balance?

Answer 13

ANP is released in response to atrial stretch (volume expansion)

Acts on the kidneys to increase GFR and inhibits Na+ reabsorption in collecting ducts (inhibits Na+K+-ATPase and Na+ channels)

inhibits renin and aldosterone secretion (lowers Na+ reabsorption)

inhibits ADH release

vasodilates afferent arterioles, increasing GFR and lowering bp

Question 14

How does sympathetic stimulation reduce renal Na+ excretion

Answer 14

Produces a decline in GFR and renal blood flow, leading to decreased filtered Na+ and hydrostatic pressure in the peritubular capillaries, which reduces excretion.

Has a direct stimulatory effect on Na+ reabsorption by renal tubules

Activates RAAS system by increasing renin release, which increases tubular Na+ reabsorption.

Question 15

What are osmotic diuretics?

Answer 15

Solutes excreted in the urine that increase the urinary excretion of Na+, K+, salts and water. e.g. urea, glucose

High concentration of unreabsorbed solute in the tubule lumen alters the concentration gradient so Na+ leaks back into the tubule lumen. Less is reabsorbed and more is excreted.

Question 16

How is the ECF volume regulated?

Answer 16

Arterial baroreceptors in the carotid sinus, aortic arch and the kidneys sense the volume in the arterial system.

Decrease in arterial stretch produces reflex activation of sympathetic fibres to the kidneys, which decreases GFR, causing renin release, promoting Na+ retention.

Reduced renal perfusion has the same effect.

Question 17

Why are the kidneys sensitive to ischaemic damage?

Answer 17

The kidneys use about 8% of resting O2 but they receive much more than they need. Renal extraction of O2 is low and a large fraction of the blood is shunted to the veins before it enters the capillaries, so O2 tension in the tissue is not hgih.

Most renal O2 is used for Na+ reabsorption

Question 18

What is the relationship between O2 consumption and Na+ reabsorption in the kidney

Answer 18

Most O2 in the kidney is used for Na+ reabsorption. Consumption is proportional to reabsorption.

Question 19

What happens to GFR when bp changes?

Answer 19

Renal blood flow is kept at a constant level despite changes in bp, GFR is also autoregulated.

When the bp is raised/lowered vessels upstream of the glomerulus constrict/dilate to maintain a constant glomerular blood flow and capillary pressure.

Question 20

How do the afferent and efferent arterioles respond to changes in GFR?

Answer 20

If BP falls: Dilating the afferent arteriole and/or constricting the efferent arteriole will increase GFR.

If bp rises: Constricting the afferent arteriole and/or dilating the efferent arteriole will reduce GFR

Question 21

What are the two mechanisms for renal autoregulation?

Answer 21

Myogenic: vasoactive agents made by endothelial cells act on smooth muscle cells

Tubuloglomerular: GFR in individual nephrons regulated in response to [solutes] and flow

Question 22

Mechanism of myogenic renal autoregulation

Answer 22

Increase in pressure stretches the blood vessel walls and opens cation channels in smooth muscle cells. This causes membrane depolarisation, opening VG-Ca2+ channels, producing vasoconstriction. This increases resistance to flow.

Question 23

Mechanism of tubuloglomerular renal autoregulation

Answer 23

Raid response (20-60secs) lowers bp:
 Increased bp increases GFR, so there is increase NaCl delivery to the macula densa. This increases NaCl reabsoption and ATP release from the macula densa. ATP is metabolised to adenosine which causes vasoconstriction in the afferent arteriole so blood flow and GFR are reduced. 

Slow response (5-10mins)raises bp: Decrease in luminal NaCl leads to increases PGE2, and causes renin synthesis and release. Alsosterone release increases NaCl and water reabsorption so fluid volume and bp increase