Lecture 22 - Sodium

Question 1

describe the importance of sodium in the human body

Answer 1

• sodium (salt) is critical for life
• required for normal blood volume, blood pressure, organ perfusion

Question 2

describe how human’s relationship with sodium has changed over time

Answer 2

• early humans probably evolved in a very low sodium environment; salt was scarce
• human kidneys are designed to retain sodium to maintain blood volume
• in modern times, we eat too much salt, leading to problems like high blood pressure

Question 3

compare recommended sodium intake to the average in North America

Answer 3

recommended = 70 mmol/day
average in North America = 150 mmol/day

Question 4

seven ways in which you lose sodium

Answer 4

• excessive sweating (Na+ = 35 mmil/L)
• diarrhoea (Na+ = 100-120 mmol/L)
• vomiting (gastric fluid Na+ = 10mM)
• osmotic diuresis (common in diabetes)-hyperglycaemia
• diuretics
• blood loss
• decreased intake

Question 5

how do you gain sodium?

Answer 5

• primarily from diet
• processed food: bread, cakes, biscuits
• fast food: fries, hamburgers, Chinese take-out

Question 6

state the levels of sodium handling by each of the main nephron segments

Answer 6

• proximal tubule (70%)
• loop of Henle (20-30%)
• distal tubule (5-10%)
• collecting duct (1-3%)

Question 7

overall stats about filtration of sodium

Answer 7

filtered volume: 150L
[Na]: 140mMol/L
filtered Na: 21,000 mmol, <1% goes into the bladder

Question 8

what are the sensors for volume in the extracellular space?

Answer 8

• arterial baroreceptors (in the carotid body and aortic arch)
• afferent arteriole (kidney)
• atrial stretch receptors (heart)

Question 9

describe the role of the arterial baroreceptors

Answer 9

1. the greater the wall tension (volume and pressure), the greater the frequency of baroreceptor firing to the brainstem
2. decreased sympathetic nervous system outflow from the cardio regulatory centre of medulla
3. this leads to decreased renin production, decreasing the renin angiotensin system

Question 10

renin angiotensin system

Answer 10

angiotensinogen –(renin)–> angiotensin I –(ACE)–> angiotensin II binds to AT1, causing vasoconstriction, aldosterone and ADH release

Question 11

describe the role of the afferent arteriole (kidney)

Answer 11

contains baroreceptors and can release renin via the juxtaglomerular cells

Question 12

three locations of baroreceptors that influence renin production

Answer 12

• arch of the aorta (SNS)
• carotid body (SNS)
• afferent arteriole

Question 13

three methods of regulation of renin secretion

Answer 13

• arterial blood pressure (afferent arteriolar stretch, macula dense): low pressure = increased renin
• sympathetic nervous system (baroreceptors): increased SNS activity = increased renin
• low sodium intake = increased renin

Question 14

how does angiotensin II affect sodium handling by the kidney?

Answer 14

angiotensin II affects sodium transporter activity

Question 15

impact of angiotensin II on the proximal tube

Answer 15

acts to increase the activity of the sodium-hydrogen exchanger (NHE3)

Question 16

impact of angiotensin II on the distal convoluted tubule

Answer 16

acts to increase the activity of the sodium chloride co-transporter (NCC)

Question 17

what is meant by the hemodynamic effects of angiotensin II?

Answer 17

angiotensin II has hemodynamic effects in the renal microcirculation that enhance proximal tubule reabsorption

Question 18

what impact does angiotensin II have on reabsorption in the peritubular capillaries?

Answer 18

angiotensin II increases the filtration fraction and increases the oncotic pressure in the peritubular capillaries

Question 19

what is the impact of angiotensin II on aldosterone production? what downstream effects does this have?

Answer 19

• angiotensin II increases aldosterone production by the glomerulosa cells of the adrenal cortex
• aldosterone increases the number and open probability of Na⁺ channels (ENaC), increasing Na⁺ reabsorption

Question 20

describe the process by which aldosterone impacts the collecting duct

Answer 20

1. aldosterone combines with a cytoplasmic receptor
2. hormone-receptor complex initiates transcription in the nucleus
3. translation and protein synthesis makes new proteins channels and pumps
4. aldosterone-induced proteins modulate existing channels and pumps
5. result is increased Na+ reabsorption and K+ secretion

Question 21

what is the physiological impact of eating too much sodium or sitting in a hot tub/pool for a long time?

Answer 21

• water pressure pushes on your skin and transmits pressure to the interstitial space
• this changes starling forces, driving water and sodium from the interstitial spaces to the vascular compartment
• the body responds by increasing urine and sodium excretion

Question 22

importance of the cardiac atria as volume receptors

Answer 22

atrial myocytes secrete a hormone in response to atrial stretch

Question 23

who discovered the importance of the cardiac atria as volume receptors

Answer 23

discovered in Canada about 1980 (de Bold and Sonnenberg)

Question 24

describe hormone release by the heart following increased vascular volume

Answer 24

1. increased vascular volume
2. increased stretch of atrial myocytes
3. increased ANP released
4. increases GFR and reduces sodium reabsorption in the collecting duct

Question 25

describe the mechanism by which ANP acts on medullary collecting duct cells

Answer 25

ANP binds to NPR-A on collecting duct cells → ↑ cGMP → PKG activation → inhibition of ENaC → increased Na⁺ excretion.

Question 26

describe an experiment that was done to determine how accurately the kidney maintains ECF volume

Answer 26

- take people on a constant sodium intake, then suddenly increase dietary sodium - when sodium intake increases, sodium excretion does not increase immediately, so ECF volume increases - it takes several days for sodium excretion to increase - after a few days, sodium intake = excretion, a new steady state at expanded ECF volume