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Sodium Physiology Flashcards

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1
Q

What is the principal determinant of ECF volume?

A

Sodium Concentration, [Na+]

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2
Q

How is [Na+], and hence plasma volume, principally regulated?

A

By renal excretion

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3
Q

What is the functional unit for renal excretion?

A

The nephron

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4
Q

What is the site of the ultrafiltration of blood?

A

The glomerulus

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5
Q

What are the characteristics of the ultrafiltrate produced at the glomerulus?

A

It is cell-free and protein-free, with an electrolyte profile resembling plasma

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6
Q

What proportion of fluid filtered at the glomerulus is reabsorbed by the tubules?

A

Over 99% of filtered fluid is recovered by the renal tubules

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7
Q

What is the main mechanism of fluid reabsorption in the renal tubules?

A

Fluid reabsorption is mainly forced by Na+ reabsorption

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8
Q

What is the glomerular filtration rate (GFR) of the average adult?

A

The average adult filters 125ml/min, equivalent to 180L/day

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9
Q

What are the five functional parts of the renal tubule, following the glomerulus?

A
  • Proximal convoluted tubule
  • Loop of Henle
  • Early distal convoluted tubule
  • Late distal tubule
  • Collecting duct

Functionally, the late distal tubule and collecting duct are very similar in their actions

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10
Q

What proportion of sodium is reabsorbed in the proximal tubule?

A

Some 65% of filtered Na+ is reabsorbed in the proximal convoluted tubule

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11
Q

Which pump exists in high density on the basolateral membrane of the proximal tubule, and what exchange does it make?

A

The Na,K-ATPase pump, expelling 3 Na+ ions into the blood in exchange for 2 K+ ions entering the cell

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12
Q

How does the sodium extruded by the basolateral membrane of the proximal tubule enter the cells?

A

Numerous apical membrane cotransporters, driven by the low intracellular [Na+], in turn forced by the Na, K-ATPase pump.

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13
Q

What substances do the apical membrane cotransporters in the proximal tubule reabsorb from the urine along with sodium?

A

Many, including:

  • glucose
  • amino acids
  • phosphate
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14
Q

What is the main apical membrane countertransport responsible for sodium reabsorption in the proximal tubule?

A

The main countertransport is the sodium-hydrogen exchanger (NHE-3)

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15
Q

Which enzyme creates the hydrogen ions required for the sodium-hydrogen exchanger (NHE-3)?

A

Carbonic anhydrase

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16
Q

Which reaction does carbonic anhydrase catalyse?

A

CO2 + H2O ⇒ H2CO3 ⇒ HCO3- + H+

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17
Q

Which other pathway accounts for a large proportion of the transepithelial flux of sodium, water and other dissolved solutes in the proximal tubule?

A

The gaps between cells, known as the ‘shunt’ pathway. This water follows the sodium concentration as the Na, K - ATPase forces flow of sodium into the intravascular compartment.

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18
Q

What is the overall fluid and electrolyte profile absorbed in the proximal convoluted tubule compared to plasma?

A

The proximal tubule reabsorbs largely isotonic fluid as compared to plasma, with similar water and sodium absorbed.

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19
Q

What forces water absorption in the proximal tubule?

A

The flow of water follows the sodium from urine to blood, as forced by the Na, K - ATPase

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20
Q

What are the two routes of water absorption in the proximal tubule?

A

The two routes are:

  1. Shunt transfer between cells
  2. Transfer through cells with aquaporin-1 (AQP-1) water channels
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21
Q

What proportion of sodium is reabsorbed in the loop of Henle?

A

~25%

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22
Q

How much water is reabsorbed in the loop of Henle?

A

No water is reabsorbed in the loop of Henle as it is impermeable to water

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23
Q

What is the principle force for sodium reabsoprtion in the loop of Henle?

A

Again, as in the proximal tubule, the main force is the Na, K ATP-ase on the basolateral membrane

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24
Q

Through what mechanism does the Na+ enter the cell through the apical membrane in the loop of Henle?

A

Sodium enters the cell via the K+, Na+,2Cl- triple cotransporter (NKCC2), which allows electroneutral entry of these ions into the cell

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25
What happens to some of the K+ that enters the cell through the triple cotransporter and the Na, K ATPase in the loop of Henle?
The ROMK specific potassium channel in the apical membrane allows flow of potassium back into the luminal fluid. This allows a continuuing supply of K+ for the triple cotransporter
26
What electrical gradient exists in the lumen relative to the interstitium in the loop of Henle?
A small positive electrical gradient
27
What effect does this electrical gradient in the loop of Henle have?
This forces cations to be absorbed between cells in the shunt pathway, allowing for reabsorption of: * Na+ * K+ * Ca2+ * Mg2+
28
What proportion of Na+ is reabsorbed from the early distal tubule?
~6%
29
What transporter drives the reabsorptive activity in the early distal tubule?
Again, the reabsorptive activity is driven by the Na, K-ATPase in the basolateral membrane, extruding 3 Na+ ions in return for taking up 2 K+ ions from the capillary
30
What is the chief route of Na+ entry into cells in the early distal tubule?
The sodium-choride cotransporter (NCCT) in the apical membrane, which allows for transport of one Na+ ion and one Cl- ion into the cell from the luminal fluid
31
How much water is absorbed by the early distal tubule?
None, as it is impermeable to water. Combined with nil water absorption from the loop of Henle, the luminal fluid leaving the early distal tubule is extremely dilute
32
How much potassium flux occurs in the early distal tubule?
Very little, with no significant potassium pumps in presence
33
How is calcium absorbed in the early distal tubule?
There are two channels of import: 1. Basolateral sodium calcium exchanger, which extrudes one Ca2+ ion in return for absorption of three Na+ ions from the capillary 2. A Ca2+ channel in the apical membrane allowing free flow of Ca2+ ions into the cell
34
What proportion of sodium is reabsorbed by the late distal tubule and collecting duct?
~2-3%
35
What are the two cell types in the late distal tubule and collecting duct?
There are: * Principal Cells * Intercalated Cells
36
What proportion of cells in the late distal tubule and cortical collecting duct are intercalated cells?
Roughly 1/3 of cells
37
How does sodium enter the principal cells in the late distal tubule and collecting ducts?
Through the sodium-specific epithelial apical membrane channel (ENaC)
38
How is the sodium reabsorptive flux in the late distal tubule and collecting duct balanced?
It is balanced by influx of: 1. excretion of potassium and hydrogen ions into the luminal fluid 2. absorption of chloride ions
39
How is potassium excreted in the late distal tubule and collecting duct?
Through the combined action of a basolateral Na,K-ATPase countertransporter and an apical membrane potassium-specific channel (ROMK), passing down the electrochemical gradient maintained by sodium absorption
40
How is Cl- reabsorbed in the late distal tubule and cortical collecting duct?
Largely as 'shunt' between the epithelial cells, down the electrochemical gradient created by sodium reabsorption
41
How is hyrdrogen excretion mediated in the late distal tubule and cortical collecting duct?
H+-ATPase, which extrudes H+ ions, and exists in the apical membrane of intercalated cells
42
How do hydrogen ions accumulate in intercalated cells prior to excretion?
The basolateral membrane contains a Hydrogen-Chloride countertransporter
43
Which hormone controls water permeability of the late distal tubule and cortical collecting duct?
Anti-diuretic hormone (ADH)
44
What is the effect of ADH on the distal tubule and cortical collecting duct?
It increases water reabsorption
45
What hormone affects ion reabsorption in the late distal tubule and cortical collecting duct?
Aldosterone increases absorption of all ions, increasing sodium absorption to a maximum of 2-3% of all filtered sodium
46
What proportion of sodium reabsorption occurs in the medullary collecting duct, and what hormones mediate this?
Less than 1% of filtered sodium is reabsorbed in the medullary collecting duct. This is mediated by the natriuretic peptides (ANP, BNP) which inhibit reabsorption, thereby promoting diuresis
47
What is the overall goal of mechanisms regulating sodium?
Balancing sodium excretion with sodium intake
48
In what two places are the volume receptors present?
1. Cardiac Atria 2. Intrathoracic veins
49
In what three places are pressure receptors present?
1. Aortic Arch 2. Carotid sinus 3. Afferent arteriole of the kidney
50
Does the afferent arteriole lead to or from the glomerulus?
The afferent arteriole leads to the glomerulus
51
What is the juxtaglomerular apparatus?
The juxtaglomerular apparatus is the point where the afferent and efferent arterioles come into close contact with the early distal tubule of the same nephron
52
What hormone is released from the juxtaglomerular apparatus?
Renin is released from the juxtaglomerular apparatus
53
Where is Renin released from?
Renin is released from the juxtaglomerular apparatus
54
What three mechanisms stimulate increased renin secretion?
1. Decreased perfusion pressure in the afferent arteriole 2. Increased sympathetic nerve activity 3. Decreased sodium chloride concentration in the distal tubular fluid
55
What is the overall effect of increased Renin secretion?
Renin increases ECF volume and blood pressure, largely by increasing sodium retention
56
What is the ***direct*** effect of renin?
The direct effect of renin is the cleaving of Angiotensinogen to Angiotensin I
57
Where is Angiotensinogen produced?
The liver
58
What happens once Angiotensin I is produced?
The action of Angiotensin Converting Enzyme (ACE) converts Angiotensin I to Angiotensin II
59
Where in the body does ACE take its effect?
The pulmonary capillary beds
60
What are the three actions of Angiotensin II?
1. Stimulation of Na+ reabsorption in the proximal tubule 2. Aldosterone release 3. Vasoconstriction of small arterioles
61
Where is aldosterone released from?
The Zona Glomerulosa of the adrenal cortex
62
What is the action of Aldosterone?
Aldosterone amplifies sodium retention in the cortical collecting duct
63
What effect does the sympathetic nervous system have on sodium balance?
The sympathetic nervous system promotes sodium retention
64
By what two mechanisms does the sympathetic nervous system promote sodium retention?
1. Afferent arteriolar vasoconstriction with subsequent decreased GFR 2. Direct stimulation of proximal tubular Na+ reabsorption
65
What effect does hypertension and hypervolaemia have on sodium retention?
Numerous humoral mediators lead to increased sodium excretion
66
Through what mechansims does sodium and volume excess lead to natriuresis?
Release of natriuretic peptides (ANP and BNP)
67
What effect does hypovolaemia have on sodium retention?
Hypovolaemia leads to decreased renal perfusion, decreased GFR and increased sodium retention

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