Renal Physiology (Day 3)

Question 1

Renal control of electrolyte and acid-base balance

Answer 1

Kidneys match electrolyte (Na+, K+, Cl−, bicarbonate, phosphate) excretion to ingestion.

• Control of Na+ levels is important in blood pressure and blood volume.
• Control of K+ levels is important in healthy skeletal and cardiac muscle activity.
• Aldosterone plays role in Na+ and K+ balance.

Question 2

Role of Aldosterone in Na/K Balance

Answer 2

1. About 90% of filtered Na+ and K+ is reabsorbed early in the nephron—not regulated.
2. An assessment of what the body needs is made, and aldosterone controls additional reabsorption of Na+ and secretion of K+ in the distal tubule and collecting duct.

Question 3

Aldosterone Independent Response

Answer 3

Increase in blood K+ triggers increase in the number of K+ channels in the cortical collecting duct. When blood K+ levels drop, these channels are removed.

Question 4

Aldosterone Dependent Response

Answer 4

Increase in blood K+ triggers adrenal cortex to release aldosterone  increases K+ secretion in the distal tubule and collecting duct.

Question 5

Increases in Na absorption drive extra K secretion due to:

Answer 5

1. Potential difference created by Na+ reabsorption driving K+ through K+ channels
2. Stimulation of renin-angiotensin-aldosterone system by water and Na+ in filtrate
3. Increased flow rates bend cilia on the cells of the distal tubule, resulting in activation of K+ channels

Question 6

Control of Aldosterone Secretion

Answer 6

1. A rise in blood K+ directly stimulates production of aldosterone in the adrenal cortex.
2. A fall in blood Na+ indirectly stimulates production of aldosterone via the renin- angiotensin-aldosterone system (juxtaglomerular feedback).

Question 7

Juxtaglomerular Apparatus

Answer 7

located where afferent arteriole contacts distal tubule

Question 8

A decrease in plasma Na results in a fall in blood volume…

Answer 8

1. Sensed by juxtaglomerular apparatus
2. Granular cells secrete renin into the afferent arteriole.
3. This converts angiotensinogen into angiotensin I.
4. Angiotensin-converting enzyme (ACE) converts this into angiotensin II.
5. Ang. II –> aldosterone 
   a) ↑ Na+ reabs/K+ secr by cortical collecting duct,
   b) ↑ blood vol, BP

Question 9

Regulation of Renin Secretion

Answer 9

Low salt levels result in lower blood volume & pressure.

• ↓ pressure in renal artery –> ↓ NaCl & water in renal filtrate
• Juxtaglomerular apparatus senses the changes in filtrate composition –> signals to granular cells in afferent arterioles to secrete renin

Reduced blood volume is detected directly by granular cells in afferent artreriole that act as baroreceptors –> also ↑ renin secretion

Juxtaglomerular cells also stimulated by sympathetic signals triggered by a fall in blood vol/pressure –> also ↑ renin secretion

Question 10

Macula Densa

Answer 10

Part of the distal tubule that forms the juxtaglomerular apparatus

Sensor for tubuloglomerular feedback needed for regulation of glomerular filtration rate

• When there is more Na+ and H2O in the filtrate, a signal is sent to the afferent arteriole to constrict limiting filtration rate.
• Controlled via negative feedback

When there is more Na+ and H2O in the FILTRATE, a signal is sent to the afferent arteriole to inhibit the production of renin.

• This results in less reabsorption of Na+, allowing more to be excreted.
• This helps lower Na+ levels in the blood.

Question 11

Regulation of Renin and Aldosterone Secretion: Decreased blood volume…

Answer 11

increased: renin secretion, Angiotensin II production, Aldosterone secretion

Question 12

Regulation of Renin and Aldosterone Secretion: Increased blood volume

Answer 12

decreased: renin secretion, angiotensin II secretion, aldosterone secretion

Question 13

Regulation of Renin and Aldosterone Secretion: high potassium…

Answer 13

no effect on renin or angiotensin II production
increased

aldosterone secretion

Question 14

Regulation of Renin and Aldosterone Secretion: increased sympathetic nerve activity…

Answer 14

increased: renin secretion, angiotensin II production, aldosterone secretion

Question 15

Atrial Natriuretic Peptide

Answer 15

Increases in blood volume also increase the release of atrial natriuretic peptide hormone from the atria of the heart when atrial walls are stretched.

Stimulates kidneys to excrete more salt and therefore more water

Decreases blood volume and blood pressure

–> opposed to angiotensin II secretion

Question 16

Whatever happens to sodium, the _____ happens to potassium.

Answer 16

opposite

Question 17

Relationship between Na, K, and H

Answer 17

REABSORPTION OF NA stimulates the secretion of other positive ions; K+ and H+ compete:

1. Acidosis stimulates the secretion of H+ and inhibits the secretion of K+ ions; acidosis can lead to hyperkalemia (too much K).
2. Alkalosis stimulates the secretion and excretion of more K+. (not enough H)
3. Primary hyperkalemia stimulates the secretion of K+ and inhibits secretion of H+; can lead to acidosis

Question 18

Acid-Base Regulation

Answer 18

1. Kidneys maintain blood pH by reabsorbing bicarbonate and secreting H+
   - -> urine is thus acidic
2. Proximal tubule uses Na+/H+ pumps to exchange Na+ OUT and H+ IN.
   - Some of the H+ brought in is used for the reabsorption of bicarbonate.
   - Antiport secondary active transport
3. Bicarbonate CANNOT cross the inner tubule membrane so must be converted to CO2 and H2O using carbonic anhydrase.
   - Bicarbonate + H+  –> carbonic acid
   - Carbonic acid (w/ carbonic anhydrase) –> H2O + CO2
   - CO2 can cross into tubule cells, where the reaction reverses and bicarbonate is made again.
   - This diffuses into the interstitial space.
4. Aside from the Na+/H+ pumps in the proximal tubule, the distal tubule has H+ ATPase pumps to increase H+ secretion (these are the ones for which K+ competes)
   - ->SLIDE 71

Question 19

Acidification of the Urine

Answer 19

Apical membrane of
epithelium (i.e. facing tubular lumen) impermeable to HCO3- , so it must be
reabsorbed indirectly

Most secreted H+ in prox. tubule
used for reabsorption of HCO3- (80-90%
of filtered HCO3- reabsorbed here)

Distal tubule: H+ actively
pumped into lumen, excreted in buffered form as H2PO4- & NH4+

Question 20

pH Disturbances (don’t need to know specifics - know what is excreted/absorbed based on certain conditions, ex. excess bicarbonate)

Answer 20

Kidneys can help compensate for respiratory problems

Alkalosis (too much bicarbonate): Less H+ is in glomerular filtrate so less is available to transport bicarbonate into tubule cells –> so LESS bicarbonate is reabsorbed

Acidosis: Proximal tubule can make extra bicarbonate through the metabolism of the amino acid glutamine.

• Extra bicarbonate enters the blood to compensate for acidosis.
• Ammonia stays in urine to buffer H+.

Question 21

Urinary Buffers

Answer 21

Nephrons CANNOT produce urine with a pH below 4.5.

To increase H+ secretion, urine must be buffered.

• Phosphates and ammonia buffer the urine.
• Phosphates enter via filtration.
• Ammonia comes from the deamination of amino acids.