6 Sodium Homeostasis Flashcards
1
Q
Sodium homeostasis
- Na
- Intracellular Na
- Extracellular Na
- Effect of Na on extracellular fluid volume (ECFV)
A
- Na
- Major extracellular cation
- Main solutes in the extracellular space (along w/ anions)
- Intracellular Na
- Maintained at low levels (10-20 mM) by Na/K ATPase which transports Na out of cells
- Extracellular Na
- Maintained at high levels (140 mM)
- Major determinnat of extracellular fluid volume (ECFV)
- Effect of Na on extracellular fluid volume (ECFV)
- Increase Na content –> increase ECFV
- Decrease Na content –> decrease ECFV
2
Q
Changes in ECFV
- Na excretion regulation
- Hormones that regulate ECFV by altering Na excretion
- Factors that enhance Na reabsorption
- Factors that inhibit Na reabsorption
A
- Na excretion regulation
- Kidney regulates urinary Na excretion
- Na[in] = Na[out] to prevent changes in ECFV
- Rates of Na excretion vary w/ Na intake
- ► no normal values for rates of Na excretion
- Hormones that regulate ECFV by altering Na excretion
- Factors that enhance Na reabsorption
- AII
- Arginine vasopressin (AVP)
- Aldosterone
- Factors that inhibit Na reabsorption: natriuretic factors
- Atrial natriuretic peptide
- Dopamine
- Endothelin
- Ouabain & ouabain analogues
- Factors that enhance Na reabsorption
3
Q
Steady state conditions: Na[in] vs. Na[out]
- Normally
- Abruptly increase Na[in] & maintain it at a high level
- Abruptly decrease Na[in] & maintain it at a low level
- How to estimate Na[in]
A
- Normally
- Na[in] = Na[out]
- ECFV & weight remain constant
- Abruptly increase Na[in] & maintain it at a high level
- Delay (days) until rate of Na[out] increases to match Na[in]
- Positive Na balance (Na retention): increase ECFV, weight, & Na[out]
- Increase Na –> retain salt & water –> expand volume –> kidney excretes Na –> valence –> weight stabilizes
- Abruptly decrease Na[in] & maintain it at a low level
- Delay (days) until rate of Na[out] decreases to match Na[in]
- Negative Na balance: decrease ECFV, weight, & Na[out]
- Decrease Na –> excrete salt & water –> reduce volume –> kidney retains Na –> valence –> weight stabilizes
- How to estimate Na[in]
- Collect urine for 24 hours
- Measure how much Na is in urine (Na[in] = Na[out])
4
Q
Tubular reabsorption of Na
- Glomerulus
- Proximal tubule
- LOH
- Distal convoluted tubule
- Collecting duct
- Earlier vs. later segments of the nephron
A
- Glomerulus
- Filters 1 lb of Na / day
- Proximal tubule
- 65%
- LOH
- 25-30%
- Distal convoluted tubule
- 3-5%
- Collecting duct
- 1-3%
- Earlier vs. later segments of the nephron
- Most Na reabsorption occurs in earlier segments
- Most fine-tuning of Na reabsorption occurs in later segments
5
Q
Mechanisms of Na excretio
- Mechs by which kidney can alter Na excretion
- Total Na excretion
- Na filtration in the glomerulus
A
- Mechs by which kidney can alter Na excretion
- Via changes in filtered load of na
- Via changes in the fraction of filtered Na that’s reabsobed
- Total Na excretion
- = amt filtered - amt reabsorbed
- Na filtration in the glomerulus
- Na is freely filtered at the glomerulus
- Amt of Na filtered = GFR * PNa = 150 L/day * 140 mmols/L = 21,000 mmols/day = 21 moles/day = 0.5 kg (~1 lb)
6
Q
Starling forces: GFR
- Hydrostatic pressure gradient (ΔP)
- Oncotic pressure gradient (Δπ)
- Major determinant of GFR
- Glomerular capillary flow rate
A
- Hydrostatic pressure gradient (ΔP)
- Major force driving filtration across the glomerular capillary
- Tends to be stable throughout the capillary
- Oncotic pressure gradient (Δπ)
- Major force retaining fluid within the glomerular capillary
- Exerted by proteins
- Not stable throughout the capillary
- Filtration –> protein concentration increases –> oncotic pressure increases
- Major force retaining fluid within the glomerular capillary
- Major determinant of GFR
- Difference b/n hydrostatic & oncotic pressure over the glomerular capillary
- Increase hydrostatic pressure –> increase filtration
- Increase oncotic pressure –> decrease filtration
- Glomerular capillary flow rate
- Determinant of GFR
- Influences the rate of rise of oncotic pressure during filtration
- Rapid flow rate –> slower rise in oncotic pressure
- Slower flow rate (ex. when AII constricts EffA) –> faster rise in oncotic pressure
7
Q
Tubular reabsorption of filtered Na
- Fate of selected filtered solutes
- Polarity of tubular epithelial cells
A
- Selected filtered solutes
- Removed from the ultrafiltrate by epithelial cells that line the nephron
- Some solutes (ex. Na) pass through the cells by crossing the apical & basolateral plasma membranes
- Some solutes pass b/n cells via a paracellular pathway
- Enter the interstitium
- Taken up by blood vessels
- Removed from the ultrafiltrate by epithelial cells that line the nephron
- Tubular epithelial cells exhibit polarity
- Dif transporters are located on the apical & basolateral sides of the membrane
- Allows epithelial cells to transport solutes in a vectorial/directional manner
- Achieved by chemical & electrical gradients
8
Q
Proximal tubule (PT)
- Na reabsorption
- Transporters that allow Na to enter the cell across the apical plasma membrane
- Transporters that allow Na to exit the cell across the basolateral plasma membrane into the interstitial space
A
- Na reabsorption
- 65% of filtered Na is reabsorbed
- Na croses the apical membrane transcellularly via co-transporters/exchangers
- Na absorption is iso-osmotic
- Na/K ATPase: driving force for Na reabsorption
- Some Na transport occurs w/ Cl via the paracellular pathway in the late PT
- Transporters that allow Na to enter the cell across the apical plasma membrane
- Na/H exchanger
- Na/glucose co-transporter
- Na/amino acid co-transporters
- Na/PO4 co-transporter
- Transporters that allow Na to exit the cell across the basolateral plasma membrane into the interstitial space
- Na/K ATPase
- Na/HCO3 co-transporter
9
Q
Proximal tubule (PT)
- Basolateral Na/HCO3 transporter
- Anion reabsorption
- Cl transport
A
- Basolateral Na/HCO3 transporter
- Na/K ATPase –> negative potential inside the cell
- 3 HCO3 out, 1 Na in
- 90% of filtered HCO3 is reabsorbed in the PT
- Anion reabsorption
- Anions are reabsorbed w/ cations to maintain electroneutrality
- Cl transport
- Paracellular pathway: some Cl is reabsorbed across tight junctions in the latter par to fhte PT
- Transcellular pathway: Cl transport occurs across the apical membrane via anion exchangers
- Cl/formate exchanger
- Cl/HCO3 exchanger
- Cl/oxalate exchanger
10
Q
Proximal tubule (PT)
- Early vs. late paracellular Na transport
- Fate of Na once it reaches interstitial space
- Rate limitng step for Na reabsorption in the PT
- Main factors regulating fluid & Na uptake in the peritubular capillary
A
- Early vs. late paracellular Na transport
- Early: Na reabsorbed w/ HCO3
- Late: Cl conc in tubular lumen > interstitial space –> Cl moves across tight junctions –> (+) lumen potential –> drives Na through tight junction
- Fate of Na once it reaches interstitial space
- Enter pertibular capillaries
- Leak back across tight junctions into tubular lumen
- Rate limitng step for Na reabsorption in the PT
- Uptake of Na into peritubular capillaries by solvent drag (Starling forces)
- Main factors regulating fluid & Na uptake in the peritubular capillary
- Oncotic & hydrostatic pressures
- Increase oncotic or decrease hydrostatic pressure –> increase Na & water reabsorption
- Decrease oncotic or increase hydrostatic pressure –> decrease Na & water reabsorption
11
Q
Na/K ATPase
- General
- Driving force for other solute transport
- Driving force for Na uptake across the apical membrane is used to…
- Side benefit
- Mitochondria
A
- General
- Workhorse of the cell
- Pumps 3 Na out for 2 K in
- –> low intracellular Na (chemical gradient)
- –> (-) intracellular charge (electrical gradient)
- Driving force for other solute transport
- Movement of Na across the PT
- Driving force for Na uptake across the apical membrane is used to…
- Reabsorb filtered glucose, aminoa cids, & phosphate in the PT
- Side benefit
- Translocation of Na & other solutes across the membrane –> osmotic driving force for water reabsorption
- Mitochondria
- Large number in PT b/c a lot of ATP is required
12
Q
Loop of henle (LOH)
- Na reabsorption
- Active vs. passive Na transport
A
- Na reabsorption
- 25-35% of filtered Na reabsorption occurs here
- 50% of reabsorbed na travels through the transcellular pathway & 50% through the paracellular pathway
- Na crosses the apical membrane via the Na/K/2Cl co-transporter
- Loop diuretics block Na reabsorption in this segment by blocking the Na/K/2Cl transporter
- Paracellular transport of Ca & Mg occur here
- Active vs. passive Na transport
- No active Na transport across the TnDL & TnAL
- Some passive Na reabsorption occurs across the TnAL
- Na is actively absorbed across the TkAL
- 25-30% of the filtered Na is reabsorbed here
- No active Na transport across the TnDL & TnAL
13
Q
Loop of henle (LOH)
- Na/K/2Cl co-transporter
- Transcellular vs. paracellular pathway in the TkAL
- ROMK (renal outer medullar K channel)
- Na/K ATPase
- Cl channel
A
- Na/K/2Cl co-transporter
- Na: urine –> apical membrane –> TkAL
- Inhibited by loop diuretics (ex. furosemide, bumetanide, torsemide)
- Transcellular vs. paracellular pathway in the TkAL
- 50% transcellular (through cells)
- 50% paracellular (b/n adjacent cells)
- Depends on positive charge build-up in the TkAL
- ROMK (renal outer medullar K channel)
- K: TkAL –> apical plasma membrane –> tubule lumen (urine)
- Creates (+) in the tubule lumen / urine
- (+) charge drives Na, Mg, & Ca: tubular lumen (urine) –> capillary lumen (blood) paracellularly
- Passive process so no energy cost
- Maximizes Na uptake & ATp fuel efficiency
- Na/K ATPase
- 3Na: TkAL –> basolateral membrane –> interstitial space (blood)
- 2K: capillary lumen (blood) –> basolateral membrane –> TkAL
- Cl channel
- Cl: TkAl –> basolateral membrane –> capillary lumen (blood)
14
Q
Distal nephron
- Na reabsorption
- Apical membrane (early)
- Apical membrane principal cells (late)
- Basolateral membrane
- Epithelium
A
- Na reabsorption
- 4-8% of filtered Na is reabsorbed here (final site)
- Apical membrane (early)
- Na/Cl co-transporter
- 1 Na & 1 Cl: tubular lumen (urine) –> distal convoluted tubule
- Acitvated by aldosterone
- Inhibted by thiazide diuretics (used to treat HTN)
- Transcellular transport of Ca & Mg
- 1 Ca & 1 Mg: tubular lumen (urine) –> distal convoluted tubule
- Inhibit Na/Cl co-transporter (ex. w/ thiazides) –> increase Ca/Mg transport
- Na/Cl co-transporter
- Apical membrane principal cells (late): ENaC (epithelial Na channel)
- Na: tubular lumen (urine) –> intracellular
- Actiaved by aldosterone & arginine vasopressin
- Inhibited by K sparing diruetics (amiloride & traimterene), trimethoprim, & by aldosterone antagonists (spironolactone, eplerenone)
- Basolateral membrane: Na/K ATPase
- 3 Na: intracellular space –> interstitium (blood)
- 2 K: interstitium (blood) –> intracellular space
- Epithelium
- High resistance –> minimal back leak of Na paracellularly
15
Q
Other Na transporters: intercalated cells
A
- Acid-base transporting cells in the latter distal nephron
- Reabsorption of filtered Na via an apical Na-dependent Cl/HCO3 exchanger
- Operates in parallel in another apical Cl/HCO3 exchanger (pedrin)
- Little Na/K ATPase so unclear how Na leaves the cell