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Kidney Lect 6

Sodium Homeostasis

___ is the major extracellular cation. The main solutes in the extracellular space are ___ and its accompanying anions Sodium; sodium
Intracellular sodium concentration is maintained at low levels (10 to 20 mM) by the _____ which constantly extrudes Na from cells Na,K-ATPase
What is the major determinant of extracellular fluid volume (ECFV)? Na present in the extracellular space (Na content); Increased Na content-->increased ECFV Decreased Na content-->decreased ECFV
In order to prevent an increase or decrease in extracellular fluid volume ... the amount of Na excreted daily by the kidneys must equal the amount of sodium ingested daily; this is accompanied by changes in body weight
What is the normal value of Na+ excretion? Rates of Na excretion vary with Na intake. Therefore, there are NO normal values for rates of Na excretion.
Several hormones regulate extracellular fluid volume by altering Na excretion by the kidney; what are the (4) major ones that directly change Na+ levels? 1. Angiotensin II 2. Arginine vasopressin (AVP) 3. Aldosterone 4. “Natriuretic” factors (atrial natriuretic peptide, dopamine, endothelin, ouabain and ouabain analogues)
Under ____ _____ conditions, rates of Na excretion match rates of Na intake. steady state
How does the body respond to a sudden increase in Na+ intake? That is, how fast is the response in sodium output? What about the reverse (how does it respond to drop in Na+ intake? When Na intake abruptly increases and is maintained at a high level, there is a delay (often days) until the rate of Na excretion increases to a level to match Na intake. Since [Na+] increases, ECFV and body weight also increase (VICE VERSA).
How much does sodium does the glomerulus filter out per day? ~0.5 kg (about a pound)
On what sites on the nephron is sodium reabsorbed? 65% is reabsorbed in the proximal tubule, 25-30% in the loop of Henle, 3-5% is reabsorbed in the distal convoluted tubule, and 1-3% is reabsorbed in the collecting duct. (Bulk in proximal, fine tuning in distal)
The mechanisms by which the kidney can alter Na excretion are either ... (2) 1. through changes in the filtered load of Na, 2. through changes in the fraction of filtered Na that is reabsorbed
What are the "sponge" Starling forces that keep plasma water in the glomerular capillary? What are the "pumping" Starling forces that push plasma H2O out of the capillary and into Bowman's space? Pressure (hydraulic) in Bowmnan's space and Plasma oncotic pressure; Pressure in capillary (hydraulic) and Bowman's capsule oncotic pressure
What are the other non-pressure Starling factors that also determine Na+ filtration rates? permeability of the capillary wall and surface area as well as the reflection coefficient of the proteins
What is the MAJOR force that determines GFR? Force driving filtration (the hydrostatic pressure gradient across the glomerular capillary) MINUS force retaining fluid in the glomerular capillary (the oncotic pressure gradient), integrated over the surface area of the glomerular capillar
Describe how the oncotic pressure changes as the fluid moves down from the afferent to efferent arteriole As fluid is filtered, the protein concentration within the glomerular capillary increases (i.e., oncotic pressure).
How is GFR influenced by renal flow rates? Faster flow-->less residence time-->"slower" rise in oncotic pressure (with respect to distance); slower flow rate has the opposite effect
What key morphological feature of renal tubule epithelia allow it to transport Na+ selectively against concentration gradients? Cells are POLAR and basolateral and apical protein makeup differs.
Where is the bulk (65%) of the filtered Na+ reabsorbed? Proximal tubule
Na crosses the apical membrane via co-transporters or exchangers Proximal tubule
Na absorption is isoosmotic in this segment Proximal tubule
The Na,K-ATPase provides the driving force for Na reabsorption Proximal tubule
Some Na transport occurs with chloride via the paracellular pathway in the late ___ ___ Proximal tubule
Na+ enters through the apical side of the proximal tubule membrane via what protein channels? • Na/H exchanger • Na/glucose co-transporter • Na/amino acid co-transporter • Na/PO 4 co-transporter
How does Na+ exit the cell of the proximal tubule epithelium? Na exits the cell by crossing the basolateral membrane into the interstitial space via the Na,K-ATPase and Na/HCO3 co-transporter.
Why does the proximal tubule epithelium pump out HCO3- and Na+? Using the negative potential inside the cell set up by the Na,K-ATPase. 3 HCO3- anions are transported out of the cell along with one Na cation. EMF of the 3 HCO 3-ions co-transport of Na against its chemical gradient.
How does the cell maintain electroneutrality as it reabsorbs Na+? Anions are reabsorbed with cations
How does Cl- enter the proximal tubule cells? The transport of Cl across the apical membrane is facilitated by anion exchanges, including Cl/HCO 3- exchangers, Cl/formate exchangers and Cl/oxalate exchangers.
How does paracellular transport affect Na+ transport throughout the tubule? Early proximal tubule: Na reabsorbed largely with HCO 3-. Late proximal tubule: Cl - concentration in the tubular lumen > in the interstitial space. Cl - moves across tight junctions creating lumen + potential-->drives Na through tight junction.
Once Na reaches the interstitial space it will either...(2) 1. enter peritubular capillaries 2. leak back across tight junctions into the tubular lumen
What is the rate limiting step for Na+ reabsorption in the proximal tubule? The uptake of Na into peritubular capillaries is the rate-limiting step for Na reabsorption in the proximal tubule. Na enters the peritubular capillary by solvent drag (via Starling forces).
INCREASING oncotic pressure or DECREASING hydrostatic pressure in the peritubular capillary will ____ Na (and water) reabsorption INCREASE
DECREASING oncotic pressure or INCREASING hydrostatic pressure in the peritubular capillary will ___ Na (and water) reabsorption. DECREASE
What drives the reabsorption of glucose, amino acids, and phosphate in the proximal tubule? The sodium gradient produced by Na/K-Atpase
How much Na+ is reabsorbed at the loop of Henle? 25-35% of filtered Na reabsorbed at this site
What percentage of Na+ reabsorbed through the loop of Henle is absorbed transcellularly? Paracelullarly? 50% of the Na absorbed in this segment travels through the transcellular pathway and 50% travels through the paracellular pathway
Na crosses the apical membrane via the ____ Na,K, 2Cl co-transporter
How do loop diuretics work (anatomic site, drug target)? What is their effect? Loop diuretics block Na reabsorption in this segment by blocking the Na, K, 2Cl transporter; block Na+ removal from the urinary space-->increased H2O movement into urinary space-->hydrostatic blood pressure drop
What ions are reabsorbed in the loop of Henle? Paracellular transport of calcium and magnesium occurs in this segment
How much of Na+ reabsorption in the loop of Henle is active? How much is passive? There is no active Na transport across the descending limb and thin ascending limb of Henle’s loop. Some passive Na reabsorption may occur across the thin ascending limb. Na is actively absorbed across the thick ascending limb (~25% to
What ions are transported paracellularly in the loop of Henle? What is the driving force moving them? Paracellular transport of ions depends on the development of a positive charge inside the tubule. This positive charge occurs because K is recycled across the apical plasma membrane via K channels called ROMK (Renal Outer Medullary K channel).
How much Na+ is reabsorbed in the distal nephron? 4 to 8% of filtered sodium is reabsorbed at this site
In the early distal convoluted tubule Na is reabsorbed via the ____ Na, Cl co-transporter
Where does aldosterone act on the distal nephron? The Na, Cl co-transporter is activated by aldosterone; activates ENAC
Where do thiazide diuretics work? The Na, Cl co-transporter in the distal nephron is inhibited by thiazide diuretics
In the late distal convoluted tubule and in the collecting tubule, sodium is reabsorbed via the ___ epithelial sodium channel (ENaC)
How/where do potassium sparing diuretics work? ENaC is inhibited by potassium sparing diuretics (amiloride and triamterene), trimethoprim, and spironolactone.
Amiloride Potassium sparing diuretic; inibits ENAC in distal nephron
Triamterene Potassium sparing diuretic; inibits ENAC in distal nephron
Trimethroprim A component of Bactrim; inibits ENAC in distal nephron
Spironolactone Aldosterone antagonists; inibits ENAC in distal nephron
How is Mg++ and Ca++ reabsorbed in the distal nephron? Transcellularly
Furosemide loop diuretic; inhibit Na,K ATPase
Bumetanide loop diuretic; inhibit Na,K ATPase
Torsemide loop diuretic; inhibit Na,K ATPase
What is the final site of Na+ reabsorption? How much is reabsorbed? Distal nephrone; 4-8%
In the early distal convoluted tubule, Na reabsorption from the lumen is mediated by... The Na,Cl Co-transporter (NCC): an electron neutral symporter that transports 1 Na:1 Cl, and is inhibited by thiazide diuretics. It couples the reabsorption of Na with Cl
How would inhibiting the Na,Cl cotransporter affect absorption of Ca and Mg? It should be noted that when the Na,Cl co-transporter is inhibited (for example by thiazides) that reabsorption of filtered Ca and Mg is increased, in part due to enhanced proximal tubular reabsorption of these cations
In the late distal convoluted tubule and in the principal cells of the collecting tubule, Na exit from the urinary space is mediated by the ___ ENaC (Epithelial Na Channel)
How does Na+ leave the distal nephron intercellular space? Na crosses the basolateral membrane via the Na,K-ATPase, and enters the interstitial space.
an enzyme secreted by juxtaglomerular cells as well as other cell types, cleaves angiotensinogen (or renin substrate), generating Angiotensin I. Ang I is subsequently cleaved by converting enzyme to form Angiotensin II. Renin
What cells secrete Renin? juxtaglomerular cells
What are the effects of Angiotensin II? (low concentrations) selectively constricts the efferent arteriole, reduces renal plasma flow (and glomerular plasma flow) and increases glomerular hydrostatic pressure --> increase the filtration fraction while maintaining GFR (remember, FF = GFR/RPF)
With Ang II, an __ peritubular oncotic pressure and ___ in peritubular hydrostatic pressure lead to an ___ in sodium reabsorption in the proximal nephron increase; decrease; increase
How is renin release regulated? •Amount of solute delivered to the macula densa (which is a function of solute reabsorption in the proximal portions of the nephron) •Stretch of the afferent arteriole •SNS •Prostaglandins - PGE stimulates renin release
How does Angiotensin II effects differ at low to moderate concentrations with high doses? At low to moderate concentrations, angiotensin II also constricts the efferent arteriole. At higher concentrations, Angiotensin II constricts both the afferent and efferent arterioles.
Selective efferent arteriolar constriction has two major effects: 1. Increase in hydrostatic pressure in the glomerular capillary. 2. Decrease in renal plasma flow.
With angiotensin II low-moderate levels, the net result on GFR is ___. Why is that? The net result is that moderate efferent arteriolar constriction results in little change in GFR. Increase in Hydrostatic pressure (favors GFR increase) and decrease in RPF --> increase in oncotic pressure increase rate (decreases GFR)-->BALANCE
Angiotensin II ___ oncotic pressure and ____ hydrostatic pressure in the peritubular capillary. increases; reduces
Increased oncotic pressure and reduced hydrostatic pressure in the peritubular capillary results in... increased proximal tubular reabsorption of Na and water.
Angiotensin II also stimulates Na/H exchange in the proximal tubule, contributing to ____ Na reabsorption. increased
Arginine vasopressin is secreted in response to... osmotic stimuli or non-osmotic stimuli such as volume depletion or reduced “effective” arteriolar volume
For the purposes of sodium handling, vasopressin ...(2) 1) activates the Na,K,2Cl co- transporter in the thick ascending limb, and therefore increases sodium transport into the cell, facilitating Na reabsorption. 2) also activates epithelial Na channels (ENaC) in the collecting tubule.
The effect of vasopressin Arginine vasopressin increases sodium reabsorption in the tick ascending limb of Henle’s loop, by increasing the activity of the apical Na,K,2Cl-co- transporter.
Aldosterone is secreted in response to...(2) angiotensin II and increased plasma K
Aldosterone increases Na reabsorption by...(2) activating the Na-Cl co-transporter, ENaC, and by increasing basolateral Na,K,ATPase activity in the distal nephron.
Aldosterone acts on cells in ... the distal convoluted tubule and collecting tubule (to increase Na reabsorption)
The thiazide- sensitive Na,Cl co-transporter and Na,K- ATPase in the distal convoluted tubule, and the amiloride-sensitive epithelial Na channel (ENaC) and Na,K-ATPase in the collecting tubule, are activated by _____ aldosterone
What are the intracellular effects of aldosterone? 1) modest effects on ENaC messenger RNA (increases expression of the alpha subunit) 2) regulates ENaC via post-translational mechanisms (e.g. move channels from intracellular pool to apical plasma membrane + increase the open probability of chann
How does aldosterone affect K+ and H+ levels in the distal nephron? Aldosterone also increases K+ and H+ secretion in the distal nephron.
____ is a small peptide synthesized and secreted by atrial myocytes in response to stretch Atrial natriuretic peptide (ANP)
ANP effects on: GFR; Na reabsorption hormone both increases GFR and inhibits Na reabsorption in the inner medullary collecting tubule due to an inhibition of the Na/K-ATPase, thereby increasing urinary Na excretion.
An analog of ____ that inhibits Na,K-ATPase is secreted by the hypothalamus. In addition, recent studies suggest that adrenal glands synthesize ____. ouabain
What does ouabain target? inhibits Na,K-ATPase; Inhibition of Na,K- ATPase will increase renal Na excretion.
How does Dopamine affect kidney function? Dopamine increases urinary Na excretion, in part by inhibiting the Na/H exchanger and by inhibiting the Na/K- ATPase in the proximal tubule. Dopamine also inhibits Na reabsorption in more distal nephron segments.
Endothelin Endothelin increases urinary Na excretion by inhibiting ENaC.
Prostacyclin and PGE 2 enhance secretion of... renin secretion by the juxtaglomerular apparatus
How do renal prostaglandins promote urinary Na+ excretion? Renal prostaglandins (e.g., PGE 2 ) also promote urinary Na excretion by inhibiting Na reasbsorption in the thick ascending limb and the cortical collecting duct
Activation of the sympathetic nervous system enhances ___ secretion leading to an increase in the generation of angiotensin II and secretion of ____. renin; aldosterone
The sympathetic nervous system (α-adrenergic receptors) also directly enhances renal... Na reabsorption, primarily in the proximal tubule
ANP causes... Sodium wasting by inhibiting basolateral NaK-ATPase in IMCD-->salt wasting by preventing flow down concentration gradient through epithelial Na Channel (ENaC)
ANP's effects are similar to ... Ouabain and ouabain like factors (both inhibit NaKAtpase)
Created by: karkis77



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