Physiology: Na Handling And Regulation Of Ecf Volume

Front 1

What two major things does [Na] regulate?

Back 1

*Na+ is the major extracellular cation.
*Na+ determines extracellular volume and plasma volume.

Front 2

Simplified schematic of filtration, reabsorption, and excretion in the nephron:

Back 2

Front 3

How much Na is filtered every day?

Back 3

[Serum Na+] X Glomerular Filtration Rate =
140 mEq/L X 160 L/day = 22, 400 mEq/day

Front 4

How much Na gets excreted every day?

Back 4

Front 5

Discuss the actions of the proximal tubule:

Why is it so important?

Back 5

Front 6

What's the Pathway of Reabsorption in the proximal tubule?

Back 6

*Na goes from lumen to the peritubular capillary. It must cross two membranes to get there.

Front 7

How is Na transported across the luminal and basolateral membranes?

Back 7

*Concentration gradient enables it to come in passively on luminal side. It brings some other good stuff with it by co-transport. It also comes in via the H+/Na anti-porter.
*Na/K pump pumps it back out on the basolateral side.

Front 8

With all the Na+ coming into the proximal tubule cell, how is charge maintained?

Back 8

*It must stay electroneutral, so anions get reabsorbed, too.
*Early = Bicarbonate. Note the passive diffusion and rxns that allow this to occur.
*Late = Chloride.

Front 9

With all the reabsorption happening in the proximal tubule, how is osmolality maintained?

Back 9

*Isosmotic filtrate is reabsorbed.
*As solute is removed from the tubular lumen, the osmolality in the lumen falls and water is reabsorbed.
*Water follows sodium!

Front 10

Summary of actions that occur in the proximal tubule:

Back 10

*65%-75% of Na is reclaimed here.
*Glucose, AAs, P by co-transport.
*Na+/H+ by antiport.
*Powered by 2° active transport: Na/K pump.
*Reabsorption across luminal membrane down an electrochemical gradient.
*Na/K pump in basolateral membrane returns reabsorbed Na to blood & provides energy.
*Early in the PT BICARB is the primary anion reabsorbed.
*Late in the PT Cl- is the primary anion reabsorbed.
*H2O is reabsorbed along with Na; filtrate isosmotic to blood is reabsorbed.

Front 11

What actions occur in the Thick ascending loop of Henle?

Back 11

*Powered by 2° active transport (Na/K pump).
*Less Na is reabsorbed (20-30%).
*Along the [gradient], Na brings in K and 2Cl for every Na.
*Clinical correlation: This is where LOOP diuretics work, blocking the Na/K/Cl pump (furosemide/Lasix).

Front 12

What actions occur in the Early Distal Tubule?

Back 12

*5-7% of Na+ is reclaimed here (Na/Cl cotransporter).
*Powered by 2° active transport (Na/K pump).
*Thiazide diuretics act here.

Front 13

What actions occur in the Collecting Duct?

Back 13

*<5% of Na is reclaimed here.
*Epithelial sodium channels (ENaCs) in principal cells have an important regulatory role; they fine-tune Na excretion.

Front 14

What all occurs in the Cortical Collecting Duct?

Back 14

*The number of ENACs determines amount of Na reabsorption. This is the fine-tuning!

Front 15

Sometimes the GFR will increase slightly with random vasoconstriction of the efferent arteriole. How is Glomerulotubular Balance maintained?

Back 15

*If the tubules did not respond by increasing Na reabsorption, Na excretion would increase significantly.

*Let’s say the filtered load of Na is 25,200 mEq/day. A 1% increase in filtration would mean an additional 252 mEq would be filtered.
*Total amount of Na in the ECF is 1960 mEq, making a loss of an extra 252 mEq of Na significant.
*Compensation by the tubules prevents this loss.

*Higher π from plasma proteins upstream encourages compensatory reabsorption downstream.

Front 16

How does the kidney know when to increase or decrease sodium reabsorption (how does it know when you are volume depleted or have volume overload)? 5

Back 16

1) Aortic arch baroreceptors.
2) Carotid sinus baroreceptors.
3) Atrial sensors.
4) JGA's macula densa senses NaCl delivery.
5) Afferent arteriole sensors.

Front 17

So, if the sensory systems detect that there is too much volume or too little volume, how does the body respond? 4 ways.

Back 17

1) Sympathetic Nervous System.
2) Renin-Angiotensin-Aldosterone.
3) Atriopeptin (ANP).
4) Starling Forces.

Front 18

Describe the sympathetic response to a decrease in volume:

Back 18

*The kidney's role is with the renin system to increase reabsorption and increase volume.

Front 19

How does the renin system sense and respond to a decrease in volume?

Back 19

*Sense: Receptors (baroreceptors or macula densa).
*Response: Renin cascade!
*Renin comes from afferent arteriole cells (JGA)--> you know the downstream effects.

Front 20

What are the effects of Angiotensin II?

What are the effects of Aldosterone?

Back 20

*Angiotensin II:
1) Vasoconstriction of Efferent Arteriole.
2) Increases proximal tubule Na reabsorption by stimulating Na/H anti-porters.
3) Increases aldosterone levels.

*Aldosterone:
1) Increases Na reabsorption in Collecting Duct by increasing the number of ENAC channels.

Front 21

What are the actions of ANP?

Back 21

1) Dilates blood vessels.
2) Increases Na excretion some by increasing GFR (constricts efferent arteriole, dilates afferent arteriole).
3) Prevents tubular reabsorption some (antagonizes aldosterone and Angiotensin II; not well understood).

Front 22

Describe the role of Starling Forces in the setting of decreased plasma volume:

Back 22

↓ Plasma volume results in higher π (oncotic pressure) in peritubular capillary blood which ↑ Na+ reabsorption.

Front 23

Summarize the proximal tubules's work if you get volume depleted:

Back 23

*BOTH Angiotensin II and NE act to increase the actions of the Na/H anti-porter, which raises Na reabsorption.

Front 24

Summarize Volume regulation in the Loop of Henle and the Early Distal Tubule in the setting of volume depletion:

Back 24

*NOT RESPONSIVE TO NE OR ANGIOTENSIN II.
*Na reabsorption is FLOW-dependent in the loop of Henle and early distal tubule.
*Maintains glomerular tubular balance but DOES NOT provide an effective response to changes in ECF.

Front 25

Summarize Volume regulation in the Cortical Collecting Duct in the setting of volume depletion:

Back 25

*Occurs in Principal Cells (not Intercalated cells).
1) Aldosterone increases Na/K pump activity, which increases the [gradient] into the cell.
2) Aldosterone also increases the number of ENACs.

Front 26

Take home points from this lecture:

Back 26

*Na regulation is one of the kidney’s most important functions. Na determines extracellular volume and plasma volume. Under normal circumstances, daily Na intake = daily Na excretion.

*Since Na is freely filtered in the glomerulus, the majority of filtered Na must be reclaimed by the tubules. Na is reabsorbed across the luminal membrane of tubular cells and returned to the blood via Na/K pumps in the basolateral membrane. These Na/K pumps create an electrochemical gradient that drives reabsorption.

*>95% of the filtered Na has been reabsorbed by the time the filtrate reaches the cortical collecting duct. Nonetheless, the cortical collecting duct plays an important role in Na regulation. Fine adjustments in Na excretion are made in the cortical collecting duct.

*The ability to defend against threats to circulating volume (by moderating Na excretion) is vital to survival. Multiple responses occur to changes in effective circulating volume:
1) Sympathetic nervous system
2) Renin-angiotensin-aldosterone system

*Baroceptors sense a decrease in effective circulating volume and a sympathetic response stimulates proximal tubule Na reabsorption in 2 ways:
1) Direct stimulation of Na/H antiporters.
2) Renin release leading to an increase in angiotensin II which stimulates Na/H antiporters.

*The cells of the macula densa sense a decrease in NaCl delivery when effective circulating volume decreases. Juxtaglomerular cells increase renin release and the renin-angiotensin-aldosterone cascade is activated. Angiotensin II increases Na reabsorption in the proximal tubule. Aldosterone increases Na reabsorption in the cortical collecting duct.

Front 27

A 20-year-old student presents to student health services with NVD X 3 days after eating her roommate’s left over sushi. She complains of weakness and dizziness. Physical exam is notable for Low BP (80/60) and dry mucous membranes.

The patient’s effective circulating volume has:

Increased
Decreased
Not changed

Back 27

Decreased

Front 28

In order to defend circulating volume and maintain organ perfusion which of the following responses will occur?

Vasodilation in the extremities
Bradycardia
The kidney will increase Na+ excretion
The kidney will avidly conserve Na+

Back 28

The kidney will avidly conserve Na+

Front 29

In order to defend circulating volume and maintain organ perfusion which of the following responses will occur?

A-Aldosterone will increase Na+ reabsorption in the cortical collecting duct
B-Angiotensin II will increase Na+ reabsorption in the proximal tubule
C-Renin will increase Na+ secretion throughout the nephron
D-Epinephrine will increase proximal Na+ secretion
E-A and B
F-All of the above

Back 29

E-A and B

Aldosterone will increase Na+ reabsorption in the cortical collecting duct.
Angiotensin II will increase Na+ reabsorption in the proximal tubule.