reabsorption
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1
• Na is the most important cation in ECF.
• Is the main determinant of ECF vol.
• Play a major role in the body water & electrolyte
balance.
2
• 99.4% of filtered Na is reabsorbed.
• PCT- 60-70% reabsorbed
• Thick ascending limb of LOH - 25-30%
• DCT- 5-7%
• CD-3%
• Thin descending limb of LH is relatively
impermeable.
3
Mechanism of reabsorption
• Tubular cell – basolateral membrane have large
number of Na+-K+ ATPase
• Pump 3Na+ out of the cell
• Create an electrochemical gradient favourable for
movement of Na into the cell from tubular lumen.
4
In early PCT – 10% Na is reabsorbed
1. Na solute symport / co-transport
eg – Na Glucose co-transport
Na aminoacid co-transport
Na lactate co-transport
Na Pi co-transport
2. Na+- H+ antiport or exchanger accompanied by
HCO3 transport
5
Na+- solute symport
Glucose
Lumen
Glucose
Na+
Na+
ISF
K+
Na+
Amino acid
Amino acid
6
• Na is transported along with solutes – glucose,
amino acids etc
• Then it is pumped out of the cell into the ISF by
Na+-K+ ATPase
• From there into peritubular capillary blood
7
Na+- H+ antiport (exchange / counter
transport)
Renal ISF
Tubular lumen
Na+
CO2+ H2O
K+
H2CO3
HCO3-
HCO3-
+ H+
Na+
H+
8
• Na+ reabsorption is coupled with secretion of H+
into the tubular fluid
• Na+ and HCO3- ( formed in the cell ) --- reabsorbed
into the peritubular capillary
• For each H+ secreted, one Na+ & one HCO3is reabsorbed
9
Reabsorption in late PCT
• Paracellular route –
• Cl- driven Na+ transport
• Transcellular route
• Na+ - H + antiport &
• Cl- - anion antiport
10
11
Paracellular route
Cl- driven Na+ transport
• Fluid reaching late PCT have relatively high
concentration of Cl-.
• Creates a conc gradient for the diffusion of Cl- from
tubular lumen into ISF
12
• The movement of Cl- creates a positivity inside
the lumen
• This causes diffusion of positively charged Na+
along with Cl-
13
Transcellular route
• Occurs via Na+ -H + antiport & Cl- - anion antiport
Anions - HCO3 -,OH-,oxalate, formate etc
14
15
• H+ - Anion complex is formed in the tubular fluid
• It is taken back into the cell
• It dissociates into H+ & anion
• This is transported again into the fluid via the
antiporters
• Na+ leaves the cell via Na+ K+ ATPase pump
• Cl- by K+ Cl_ cotransporter
• Sodium reabsorption in PCT shows
gradient – time transport
• Rate of transport depends on
✓Electrochemical / concentration gradient
✓Duration for which it stays in the tubule
• In PCT, Na reabsorption has NO Tm
Na reabsorption in Loop of Henle
• 25-30%
• Thin descending limb of LOH –
Relatively impermeable to Na+
• Thin ascending limb –
Passive reabsorption of Na+
19
• Thick ascending limb
• 2 mechanisms (transcellular route) - 50%
1.Na+K+2Cl- transport – main mechanism
2.Na+ H+ exchanger as in PCT
Paracellular
reabsorption
Na+
Na+
H+
K+
Cl-
K+
Na+,K+,Ca++, Mg++
K+
Na+
2 ClK+
K+
21
+
+
Na K 2Cl
transport
• Downhill movement of Na+ and Cl− into the cell
• Releases potential energy for the uphill
movement of K+ influx.
• Na+ is pumped into the interstitium by
Na+-K+ ATPase
22
• Cl- moves into the interstitium via Cl- channel
• K+ moves into the interstitium via ROMK
channels
• Then reabsorbed into the peritubular capillary
blood
23
• Significant paracellular reabsorption (50%) of
cations–
Na+, K+, Ca2+, Mg2+etc due to the slight +ve charge
inside the lumen relative to the ISF.
24
Distal convoluted tubule
Mechanism – Na+Cl- cotransporter in early DCT
ISF
lumen
Na+
K+
Na+
Cl-
Cl25
• Across the basolateral membrane, Na+ leaves the
cell via the action of Na + K+ ATPase
• Cl− leaves the cell by diffusion via channels
Reabsorption in Late DCT & CD
ISF
Lumen
K+
Na+
K+
Na+
ENaC
Cl-
27
• Absorption via epithelial Na channels present at
the luminal surface of P cells
• Aldosterone mediated
• It generates a negativity in the lumen
• So small amt of Cl- also move into the cell
through transcellular / paracellular route
28
Regulation of
+
Na reabsorption
29
• Prime determinant of ECF volume
• Kidneys maintain Na+ balance
• Multiple regulatory mechanisms to control the
excretion of sodium.
30
1. Glomerulo tubular balance:
• Intrinsic ability of the tubules to increase their
reabsorption rate in response to increased tubular
load
• When GFR ↑es, rate of proximal tubular reabsorption
of sodium also ↑es
• The percentage of filtered load reabsorbed remains
the same
31
• Tubule reabsorb a constant fraction of the amount
filtered rather than a constant amount
• Helps to prevent overloading of the distal tubular
segments when GFR increases
• The exact mechanism is not identified
• There are certain intrarenal mechanisms
a) When GFR ↑es
protein concentration at the efferent arterioles ↑
peritubular capillary oncotic pressure ↑
favors reabsorption
33
B) When GFR ↑es
↑ed amount of glucose & AA are filtered
↑es the activity of Na+ -solute symporters @PCT
↑es Na+ reabsorption
34
2. Starlings forces b/n peritubular capillary &
renal interstitium
• Peritubular capillary HP - opposes reabsorption
• Colloid osmotic pressure of PT capillary –
favors reabsorption
• ↑ Kf - ↑ reabsorption
35
Peritubular capillary HP
a)arterial pressure
when BP is high
peritubular capillary HP is also high
reabsorption decreases
36
b, Afferent & efferent arteriolar resistance
when they constrict
less amount of blood reaches peritubular capillary
HP ↓
reabsorption increases
Colloid osmotic pressure of PT capillary
a, systemic plasma colloid osmotic pressure
When plasma protein concentration of systemic
blood ↑
↑ colloid osmotic pressure of PT capillary
↑ reabsorption
3. Pressure diuresis & natriuresis
When BP ↑es ( when autoregulatory mech are
impaired as in kidney diseases)
peritubular HP ↑
less Na & water reabsorption
natriuresis & diuresis
40
4, Sympathetic stimulation
1. ↑ Na+ reabsorption from all parts of renal tubules
by activating α adrenergic receptors on the renal
tubular epithelial cells
(low levels of sympathetic activation)
2. Constriction of renal arterioles → ↓ GFR →
↓ sodium and water excretion
(severe sympathetic activation)
41
3. ↑ renin release and angiotensin II formation
• ↑ reabsorption and ↓ renal excretion of Na+
5. Hormones
1. Aldosterone - ↑ sodium reabsorption
P cells of CD & ↑es no: of ENaC
2. Ang II - ↑ Na & Cl reabsorption from PCT, LH & DCT
3. Glucocorticoids -- ↑ reabsorption
43
4. ANP - ↑es Na+ excretion by ↓ing reabsorption
mainly from CD
5. PGE2 – natriuresis
6. Ouabain – inhibits Na+ K+ ATPase pump &
↓ reabsorption