NaCl Regulation Flashcards
TF/Px ratio
-TF (tubular fluid) is urine at any point along the nephron
-P (Plasma) is systemic plasma & considered constant
-TF/Px ratio compares concentration of a substance in TF at any point w/ concentration in the plasma
-if ratio=1.0 then either no reabsorption or reabsorption exactly proportional to water reabsorption
-ex TF/Pna=1 then [Na] in TF equal to [Na] in plasma
-If ratio< 1.0 solute reabsorbed more than h2o
-[plasma]>[TF]
If ratio>1.0 then reabsorption less than reabsorption of H2O
-[TF]>[plasma]
TF/P-inulin
- used as a marker for water reabsorption along the nephron
- Inulin freely filtered but not reabsorbed or secreted
- concentration in TF determined by water in TF
- Fraction of filtered water absorbed- 1-(1/[TF/P]inulin)
[TF/Px]/[TF/P]inulin
- Corrects TF/Px ratio for water reabsorption
- Gives fraction of filtered load remaining at any point
- If 0.3, then 30% of filtered solute remains in TF and 70% has been reabsorbed into blood
Na+ Reabsorption at Proximal Tubule
-Reabsorbs 2/3 filtered Na+ and H2O
-Site of glomerulotubular balance
-Process is isosmotic: Na+ ad H2O exactly proportional
TF/Pna and TF/Posm=1.0
-Early Proximal Tubule
-Reabsorbs Na, H2O, HCO3-, Glu, AA, Phosphate, & lactate
-Na is cotransport w/ Glu, AA, Phophate and lactate
-Cotransport w/ H+ via NHE3: bulk of Na resorbed here
-Directly linked w/ HCO3- resorption
-Carbonic anhydrase inhibitors act here
-inhibiting HCO3- reabsorption
-Diuretic Acetazolamide
-Late Proximal Tubule
-Na+ reabsorbed w/ Cl-
Glomerulotubular balance in proximal tubule
- Maintains constant fractional reabsorption (2/3) of filtered Na+ and H2O
- If GFR increases, filtered load of Na+ increases
- Without a change in reabsorption, Na+ excretion increases
- Na reabsorption increases w/ GFR increase
- Mechanism based on starling forces
- Isosmotic fluid reabsorption from lumen to proximal tubule cell to lateral intercellular space and to peritubular capillary blood
- Starling forces in peritubular capillary govern isosmotic fluid reabsorption
- Fluid reabsorbed increased by increases in πc and decreased by decreases in πc
- Increased GFR & FF cause protein concentration
- πc increases & increases fluid reabsorption
Effects of ECF Volume on Proximal Tubule Reabsorption
- ECF volume contraction increases reabsorption
- increases peritubular capillary [protein] & πc
- Decreases preitubular capillary Pc
- Causes increase in proximal tubule reabsorption
- ECF volume expansion decreases reabsorption
- Decreases peritubular capillary [protein] & πc
- Increases Pc
- Causes decrease in proximal tubule reabsorption
Na+ Reabsorption in Thick ascending Limb of Loop of Henle
-Reabsorbs 25% of filtered Na+
-Contains Na+/K+/2Cl- cotransporter in luminal membrane
-Site of action for loop diuretics
-Furosemide, ethacrynic acid, bumetanide
-Inhibit Na+/K+/Cl- cotransporter
-Impermeable to water: NaCl reabsorbed w/o water
-TF [Na] an TF osmolarity decrease to less than plasma concentrations
TF/Pna and tf/Posm<1.0
-This segment is called the diluting segment
-Lumen positive potential difference
-Some K+ diffuses back into lumen making it positive
Na+ Reabsorption in Early Distal Tubule
- Distal tubule and collecting duct resorb 8% of filtered Na+
- Reabsorbs NaCl by Na/Cl cotransporter
- Site of action for thiazide diuretics
- Impermeable to water
- NaCl reabsorption occurs w/o water, further diluting TF
- Cortical diluting segment
Na+ Reabsorption in Late Distal Tubule and Collecting Duct
- Two Cell Types
1. Principal Cells - Reabsorb Na+ and H2O
- Secrete K+
- Aldosterone increases Na+ reabsorption and K+ secretion
- takes hours for protein synthesis to occur
- 2% of Na+ reabsorption affected by aldosterone
- ADH increases H2O permeability
- Insertion of AQP2 in luminal membrane
- In absence of ADH, virtually impermeable to water
- K+ sparing diuretics decrease K+ secretion
- Spironolactone, triamterene, amiloride
- Alpha intercalated cells
- secrete H+ by H+ ATPase (stim by aldosterone)
- Reabsorb K+ by H+/K+ ATPase
- Spironolactone, triamterene, amiloride
Sodium Reabsorption
- occurs largely by transcellular epithelial transport.
- key feature is primary active transport of Na+ via basolateral-membrane Na+,K+-ATPase pumps
- Pumps out of the cells into the interstitial fluid.
- Keeps the intracellular concentrations of Na+ low compared to the luminal concentration
- Proximal Tubule: type 3 sodium hydrogen exchanger (NHE3)
- Thick ascending limb: The bumetanide sensitive Na-K-2Cl cotransporter (NKCC2/BSC1)
- Distal Convoluted Tubulethe thiazide sensitive Na-Cl co-transporter (NCC/TSC)
- Collecting Duct: ENaC sodium channel
Water Reabsorption
- Proximal Tubule: AQP1 found in both the apical and basolateral membranes.
- Collecting Duct: AQP2, -3 and -4 for the passive transport of water through the cell.
- In the collecting duct the antidiuretic hormone (ADH) regulated AQP2 is present in the apical membrane and AQP3 and AQP4 in the basolateral membranes.
Coupling of Water Reabsorption to Sodium Reabsorption
- Movement of Na+ from tubular lumen to interstitial fluid lowers the osmolarity (raises the water concentration) of the luminal fluid.
- Raises the osmolarity (lowers the water concentration) of the interstitial fluid
- The difference in water concentration between lumen and interstitial fluid
- causes net diffusion of water from the lumen across the tubular cells’ plasma membranes and/or tight junctions into the interstitial fluid.
- Water and everything else in interstitial fluid then move by bulk flow into peritubular capillaries
response of ADH to changes in plasma osmolality and blood volume
- Peptide hormone secreted by the posterior pituitary known as antidiuretic hormone (ADH) or vasopressin.
- Controls the level of permeability in the collecting ducts
- ADH stimulates production of cyclic AMP in the epithelial cells of the collecting ducts
- Induces AQP2 insertion into the luminal membrane
- High plasma [ADH]: High H2O permeability of collecting ducts
- Max water reabsorption, and final urine volume is small
- less that 1 percent of the filtered water.
- Absent ADH: Collecting duct water permeability very low
- little water is reabsorbed
- Large volume of water remains in the tubule to be excreted in urine, which is hypo-osmotic
- Increased urine excretion from low ADH is water diuresis
Baroreceptor Control of ADH Secretion
- Decreased extracellular volume triggers increased ADH
- Increased ADH increases water permeability of the collecting ducts (via AQP2 channels)
- More water reabsorbed, less excreted so water is retained in the body to stabilize extracellular volume
- Mediated by neural input to the ADH-secreting cells from baroreceptors
- baroreceptors decrease rate of firing w/ the decreased pressures from low blood volume
- Fewer impulses transmitted from baroreceptors via afferent neurons to the hypothalamus
- Results in increased ADH secretion.
- Conversely, increased cardiovascular pressures cause more firing by the baroreceptors
- results in a decrease in ADH secretion.
Osmoreceptor Control of ADH Secretion
-Changes in total water w/ no change in total Na+
-compensated w/ water excretion w/o altering Na+ excretion
-change in body fluid osmolarity.
-Water gain/loss detected by osmoreceptors in the hypothalamus
-regulate ADH secretion
-receptors responsive to changes in intracellular osmolarity.
Ex: drinking 2 liters
-lowers the body-fluid osmolarity
-reflexly inhibits ADH via hypothalamic osmoreceptors.
-water permeability of collecting ducts becomes very low
-water not reabsorbed
-large volume of hypo-osmotic urine is excreted
-excess water is eliminated.
-Increased osmolarity (e.g., water deprivation)
-ADH secretion is reflexly increased via the osmoreceptors
-water reabsorption by the collecting ducts is increased,
-very small volume of highly concentrated urine is excreted.
