Tubular Transport Flashcards
How to determine plasma Na
Plasma Na = total body Na content (mEq)/ECF volume
. It is primary determinant of plasma osmolality
. If body Na content inc. total body water will inc. compensate (thirst and renal conservation of H2O)
Na balance
. Neg. balance: (loss of body Na content) results in dec. in ECF (ECF contraction)
. Positive Na balance: gain in body Na content results in inc. in ECF (ECF expansion)
. Problems w/ balance usually manifest as altered extracellular fluid volume
Hyperaldosteronism
. Elevated aldosterone release from adrenal cortex
. Kidney reabsorbs excess amounts of Na
. Plasma osmolality inc. slightly so H2O consumption (thirst) and water conservation at the kidney inc.
. ECF volume inc.
. Patient becomes hypertensive due to ECF expansion
T/F small adjustments in Na and H2O reabsorption mechanisms result in large changes in Na and H2O excretion
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Transport mechanisms used by kidney
. Solute movement via diffusion (transcellular or paracellular) or facilitated diffusion
. Can also be active transport using ATP
Symport
. Coupled transport of 2 or more solutes in the same direction
. Process can also be called co-transport
Antiport
. Coupled transport of 2+ solutes in the opposite direction
. Also called exchange or exchanger/anti porter
Role of Na/K ATPase in kidneys
. Conc. Gradient for Na to move into the cell from the tubule lumen is maintained by this bringing Na out of cell
Water movement in kidney
. Water movement is passive
. Driven by osmotic pressure gradients caused by reabsorption of Na and other solutes
Solvent drag
. When H2O is reabsorbed the solutes dissolved int he H2O are also carried along
. This is one way solutes (Na, K, Cl, Ca, Mg) can be reabsorbed by the kidney via paracellular route
. H2O moves through the transcellular and paracellular pathways in those tubular segments that are permeable to H2O
Aquaporins
. Aquaporin-1 (AQP-1) is present in prox. Tubule
. Also present in collecting duct as AQP-2 under control of vasopressin
Back leak of Na
. Prox. Tubule junctions are leaky to Na
. Some of reabsorbed Na leaks back into the tubular lumen as the interstitial Na conc. Rises and luminal Na conc. Dec.
. The back-leak reduces the net amount of Na reabsorbed in prox. Tubule and it can change under certain circumstance but always is net reabsorption
Transport maximum
. #sites x rate of transport/site
. Max amount of glucose that can be reabsorbed per min by the kidney
. Usually expressed in mg/min
. Term applies to secretion and reabsorption
. If reabsorption is Tm-limited then if filtered load exceeds Tm, the solute will appear in the urine
T/F if the filtered load is less than the Tm, the urine will be essentially devoid of the solute
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Inhibition of renal Na-glucose transporter for DM II treatment
. SGLT2 inhibitors (dapagliflozin) dec. fasting and peak plasma glucose
. Dec. HbA1c and promotes weight loss
SGLT2
. Low affinity high capacity transporter in early part of prox. Tubule
Renal threshold
. Plasma conc. Of glucose at which glucose 1st appears in urine
Tm-limited secretion
. Transfer from peritubular capillaries to tubule fluid
. If delivery of solute to peritubular capillaries exceeds the Tm secretion rate, then some solute will be returned to circulation via renal v.
. If delivery of solute is less than Tm, then no solute will appear in renal venous blood
Clinical relevance for secretory transporter competition
. Non specific transporters for organic anions (penicillin, PAH, diuretics), cations (H2 blockers, antiarrhythmic, histamine, NE) and molecules with both pos. And neg. charged groups (creatinine) can be transported by either
. Co-administration of drugs that compete for same
Na reabsorption along nephron
. Most filtered Na and H2O reabsorbed in prox. Tubule (67%) then loop of Henle (25%)
. Distal tubule and collecting ducts fine tune excretion (5-7%)
. Electrochemical gradient maintained by Na’K ATPase
Na transport function
. Site of diuretic action in prox tubule
. Site of acid-base regulation
K transport function
. Inside principal cells
. Maintain safe plasma K levels in blood
Cl reabsorption
. Reabsorbed mostly in proximal tubule, somewhat is loop of Henle, and then fine tuning in distal tubule and collecting ducts
. Not same mechanisms as Na
K reabsorption
. Mostly in prox. Tubule
. Some in loop of Henle
. More in late distal tubule/collecting duct than the other solutes
Ca and P reabsorption
. Mostly in prox. Tubule . Ca has some in loop of Henle . P has non in loop of Henle . Some in distal tubule . Fine tuning of Ca in collecting ducts, none of P
Na-H antiport (NHE3)
. Secretion of H ions is important for acid/base regulation
. Results in bicarbonate reabsorption in a 1-for-1 exchange w/ H
Na-solute symport
. Na-glucose
. Na-AA
. Na-other solutes (phosphate, lactate)
T/F glucose and AA are almost completely cleared from tubule fluid by the end of prox. Tubule in normal circumstances
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Late prox. Tubule Na reabsorption
. Little Cl was reabsorbed in early prox. Tubule
. In late tubule Cl is avidly reabsorbed due to passive diffusion of NaCl via paracellular pathway
. Operation of parallel Cl/anion and Na/H antiporters reabsorbed NaCl via secondary active transport
Thick ascending limb (TALH)
. Reabsorption of Na, K, and Cl is linked to activity of basolateral Na/K ATPase
. Apical transporter (Na-K-2Cl symport NKCC)
. Impermeable to H2O
. Positively charged lumen drives passive paracellular reabsorption of cations (Na, K, Ca, Mg)
. Rate of Na transport is load dependent (if Na delivery inc, rate of reabsorption inc.)
Furosemide
. Loop diuretic
. One of the most powerful diuretics
. Used to treat acute pulmonary edema, control edema in CHF or other Na-retaining conditions
. Blocks NKCC symporter
Early distal tubule
. NaCl symporter (NCC) used to reabsorb Na
. Reabsorbs Ca and Pi
. Located in cortex
. Impermeable to water
Thiazides
. Diuretic blocking NaCl symporter in early distal tubule
. Used to treat hypertension and CHF
Late distal tubule and collecting duct
. Reabsorb 5-7% Na
. Has prinicpal cells and intercalated cells
. Principal: reabsorb H2O and Na, secrete K
. Intercalated cell: secrete H or HCO3, reabsorb K, important for acid-base balance
Aldosterone
. Adrenal mineralcorticoid
. AII stimulates release from adrenal cortex
. Stimulates Na reabsorption in TALH, the early distal tubule, and in principal cells of late distal tubule and collecting duct
. Inc. Na/K ATPase protein abundance
. Inc. amount of apical NKCC symporters and NCC transporters
. Influence minor in TALH, primary action in principal cells to stimulate Na reabsorption and K secretion
Aldosterone mechanism
. Classic: alters protein synthesis by interacting w/ nuclear DNA by binding to mineral corticoid receptor (MR), the MR dimerizes and transported to nucleus to affect transcription
. New shorter path: enhance ENaC conductance via stimulation of channel activating protease (CAP1) to quickly inc. # of ENaC in apical membrane via serum glucocorticoid stimulated kinase (SGK1) by slowing rate of removal of ENaC from apical cell membrane
Limiting steps in classic aldosterone pathway
. 11beta-HSD2: metabolizes cortisol into cortisone that has low affinity to MR
. MR
. ENaC
. Na/K ATPase
Aldosterone release stimulated by ___
. AII
. High plasma K
. Lesser extent plasma acidosis
Principal cell epithelial Na Channel (ENaC)
. Used for Na reabsorption
. Tubule lumen is neg. compared to peritubular fluid
. Cl is reabsorbed via paracellular pathway driven by lumen-neg. voltage
. H2O permeability is dependent on action of ADH( vasopressin)
Amiloride
. Diuretic blocking ENaC
Aldosterone receptor antagonists
. Slows Na reabsorption in principal cells
Fractional excretion of Na
. Fraction of the filtered Na load that is excreted
. Helpful in determining whether kidney is retaining or excreting Na w/o obtaining urine collection
. Used in setting of suspected acute kidney injury (AKI) to determine if issue is perfusion of kidney or direct damage to tubules
. Range: 0.1-5% w/ 1% being normal
. Under 1% kidney is retaining Na
. Over 1-2% the kidney is excreting more Na than expected
Acute kidney injury
. Causes: sudden serious drop in blood flow to kidneys, damage from meds, poisons, or infection, or a sudden bloack that stops urine from flowing out of kidneys
. Signs/symptoms: fatigue, big dec. in urine volume, swelling in legs and around eyes, mental status change
FENa under 1% in cases of suspected AKI
. NA tubular reabsorptive function is intact and reacting appropriately to dec. in filtered load of Na
. Likely problem w/ dec. renal perfusion causing renal ischemia and low GFR
. Prerenal failure
FENa over 1% in cases of suspected AKI
. Patient is excreting more Na than expected
. Primary problem w/ kidney (intrarenal) than w/ renal hemodynamics
. Typically acute tubular necrosis
. Prolonged renal ischemia assoc. w/ low perfusion pressure can lead to hypoxic tubular damage
. Tubular damage can be directly from exposure to nephrotoxins (bacterial toxins, heavy metals, certain antibiotics or analgesics)
Pre-Renal causes of AKI
. Hemodynamic derangement like volume depletion, dec. in effective perfusion of kidneys
T/F The amount of water lost from the body affects plasma osmolality
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Regulation of Na content
. Sensed: effective circulating volume
. Sensor: arterial and cardiac baroreceptors
. Effector: AII/aldosterone/SNS/ANP
. Affected: urine Na excretion
. Clinical Dx: bedside exam of ECF volume
Regulation of body fluid Na conc.
. Sensed: plasma osmolality
. Sensor: hypothalamic osmoreceptors
. Effector: ADH
. Affected: urine osmolality (H2O output) and thirst (H2O intake)
. Clinical Dx: lab test for plasma osmolality
Problems w/ total body water manifest as ___
. Altered plasma osmolality that is reflected as alteration in plasma Na conc.
Problems w/ total body Na content manifest as ____
Altered extracellular fluid volume
Normal plasma osmolality
275-295 mOsm/kgH2O (or mOsm/L)
Diuresis
Excretion of large amount of urine
. Typically urine is hypoosmolar/dilute (can be iso-osmotic)
Antidiuresis
Excretion of small amount of urine
. Typically hyperosmotic/concentrated
Copeptin
. Processing of prohormone into AVP also creates peptide copeptin
. Released into circulation along w/ AVP
. More stable than AVP in plasma samples stored for analysis and is easier to measure in plasma
. Measure this w/in an hour making it a surrogate measure of AVP release
Regulation of AVP release
. Release from posterior pituitary is inc. or suppressed depending on neural signal from hypothalamic osmoreceptors or from signals arising from arterial and atrial baroreceptors
. Inc. H2O absorption in the late distal tubule and collecting ducts and regulates how much H2O leaves in urine
. Non-osmotic stimuli: Nausea, pain and morphine inc. secretion, surgery inc. secretion inc. risk for postoperative hypoatremia
Osmoreceptors
. Neuronal cells in hypothalamus
. Sense changes in plasma osmolality
. Send signals to hypothalamic neurons to suppress or inc. AVP release
. Neural cells synthesize and process the prohormone, and AVP and copeptin are transported to post. Pituitary for storage in nerve terminals
. Release into the circulation occurs when neurons are stimulated by appropriate stimuli
When osmolality is under 280, AVP secretion is ____
Zero
. AVP secretion is very sensitive to small inc. in osmolality above this point
Osmotic regulation of ADH at low plasma osmolality
. Sensed by hypothalamic osmoreceptors (dec. firing rate)
. Reduced stimulation of ADH neurons dec. secretion of ADH
. Dec. plasma ADH
. Reabsorption of H2O in the collecting duct dec. (amount of H2O in the urine inc.)
. Return of plasma osmolality towards normal range
Osmotic regulation of ADH secretion in high plasma osmolality
. Sensed by hypothalamic osmoreceptors (inc. firing rate)
. Enhanced stimulation of ADH neurons inc. secretion of ADH
. Inc. plasma ADH
. Reabsorption of H2O in the collecting duct inc. (amount of H2O in urine dec.)
. Conservation of plasma H2O, return to normal plasma osmolality requires intake of fluids
AVP functions
. Inc. H2O permeability in collecting duct
. AVP dec. urine flow rate and inc. urine osmolality
. Control number of aquaporins in apical membrane
Vasopressin-2 (V2) receptor
. AVP receptor in principal cells
. Receptor inc. cAMP levels which triggers a cascade that causes insertion of more aquaporin protein-2 (AQP2; water channels) into apical membrane
. AVPhas long term regulatory effect by inc. total abundance of aquaporin-2 protein by delaying destruction of protein and inc. production of protein
Effect of AVP on aquaporins
. When AVP dec., the short term effect is that the rate of removal of aquaporins from the apical membrane will exceed rate of insertion, dec. H2O permeability in the cells
. Over time, the total amount of aquaporin-2 protein in the cells will dec.
T/F the kidney is capable of disengaging H2O from solute reabsorption
. Only this way can the kidney regulate H2O and solute balance separately
. Disengagement is found in the processes of conc. And dilution which occur in loop of Henle through collecting duct system
Concentration and dilution can occur because ___
. Parts of nephron are impermeable to H2O yet transport solute (loop of Henle, early distal tubule)
. Parts of the nephron have H2O permeability that is dependent on the level of AVP (late distal and collecting ducts)
. Medullary interstitium is hyperosmotic and the level toxicity can be altered
What creates the medullary interstitial osmotic gradient
. Solutes that are reabsorbed by thick ascending limb and collecting ducts, particularly NaCl and urea provide the osmoles for the interstitial gradient
. Unique anatomic arrangement of the loop of Henle and collecting ducts also contributes
. Arrangement allows a process (countercurrent multiplication) to occur, creating progressive inc. in osmolality as the loops dips deeper into medulla
Dilution (low AVP)
. Iso-osmolar tubular fluid enters thin descending limb (285 mOsm/kg)
. H2O removed and tubular fluid becomes hyperosmotic (600) at the end of the loop
. In the thin ascending limb, NaCl moves out but H2O can’t leave, dilution starts
. Thick ascending limb, NACC symport removes solutes but water can’t, tubular fluid becomes hypo-osmolar (250 mOsm/kg H2O)
. Distal tubule and cortical collecting duct continue to reabsorb NaCl, in absence of AVP H2O permeability is low, tubular fluid osmolality is 100 mOsm/kg H2O
. Medullary collecting duct, some NaCl is reabsorbed in absence of AVP, H2O permeability is low, final urine can be hypo-osmolar as 50 mOsm/kg H2O w/ minimal amts of NaCl
Concentration w./ high AVP
. Same steps from prox. Tubule to early distal tubule as dilution
. Then if AVP is present, H2O permeability inc. in late distal tubule and collecting ducts
. H2O leaves the tubule, and tubule fluid equilibrates w/ surrounding hyperosmotic medullary interstitial fluid
. At the end of the collecting duct, the urine has osmolality of 1200 or whatever level is in inner medulla
If transport NaCl out of ascending limb is impaired, the renal urinary concentrating power and urinary deleting power will ___
Decrease
Urea
. Byproduct of protein metabolism
. Important solute in the inner medulla interstitial fluid
. Collecting duct is permeable to urea only in the inner medulla, and this permeability inc. w/ AVP
AVP inc. permeability of urea by ___
. Phosphorylating urea transporters (UT-A1) in the apical membrane of the inner medullary collecting duct cells
. Under condition of chronic H2O restriction, AVP stimulates production of additional transporters
. Urea accumulates in interstitium, antidiuresis is maximal about 600 mOsm/kg of total medullary osmolality attributable to NaCl and 600 to urea
. Accumulation of urea in the inner medullary interstitium necessary to reach maximal urinary conc. Power
UT-A2 transporter
. Urea transporter in the thin ascending limb
. Permeability of loop of Henle to urea is considerably less than permeability in the inner medulla
. Recycling of urea in the kidney facilitates the accumulation in the interstitium
Protein diet effects on concentrating ability of kidney
. Low protein: dec. in urinary concentrating ability
. High protein: mildly enhance maximal conc. Power
Vasa recta
. Loop around medullary tubular segments
. Pick up extra H2O and solute deposited in interstitium by tubules
. Solute and H2O are returned to systemic circulation via renal venous system
. If flow inc. a lot the high blood flow will tend to “wash out” the gradient by picking up more solute than normal
. Concentrating ability will be dec. until gradient is reestablished
Why isn’t maximum medullary osmolality 1200 during diuresis?
. Vasa recta blood flow is higher helping to wash out solute
. There isn’t much urea moving out of the collecting duct into the interstitium (due to low AVP) which results in lower medullary osmotic gradient
Vasa recta O2 supply to nephron
. If vasa recta flow dec too much, the medulla will be starved of O2
. NaCl reabsorption by loop of Henle will be impaired and the medullary interstitial osmotic gradient will dissipate over Time
. Concentrating ability will be impaired
How to tell if urine is iso, hyper, or Hypo-osmolar
. Hypo: urine osmolality is less than plasma osmolality (dissolving solute in large amt H2O)
. Iso: urine and plasma osmolality are equal
. Hyper: urine osmolality more than plasma osmolality (dissolving solute in small amt H2O)
Urine volume
. Iso-osmotic urine = free water
. Iso-osmotic: volume of H2O needed to dissolve solute
. Free water: if positive urine is dilute, if neg. it is conc. And if equal it is Iso-osmotic
Free water clearance
. Amount of water that was added to urine to make it dilute or taken out to make it concentrated
. Neg. clearance (-CH2O) is called TcH2O (tubular conservation of water)
. Positive free water clearance (CH2O)
. Pos. When urine dilute
. Ned. When urine is conc.
. 0 when Iso-osmolar
Oliguria
Urine output less than 400 ml/day
Anuria
Urine output under 50 ml/day
Polyuria
. Excessive urine volume
. 24 hr volume is over 50 ml/king body weight (or over 3L/day)
Major mechanism is which total body K is regulated
. Renal excretion of K
Regulation of rapid movement of K into cells
. Insulin: move K into skeletal m. And liver cells w/in minutes by stimulates Na-H ion exchange and Na/K ATPase (infused w/ glucose to rapidly correct hyperkalemia)
. E/NE: stimulate alpha-receptors to release K from cells via insulin inhibition and stimulation of beta-2 receptors promoting uptake of K (Na/K ATPase stimulation)
. Aldosterone: promote K uptake (takes 1 hr rather than minutes)
Effect of chronic elevated aldosterone on K levels
. Results in hypokalemia
. Inc. excretion of K via kidney and uptake of K into cells
K reabsorption along nephron
. 67% in prox. Tubule ( primarily by solvent drag)
. 20% in loop of Henle
. 15-80% load secreted depending on intake in late distal tubule and collecting duct (primary regulation area)
. Excrete 12-80% of filtered load depending on K intake
What cells secrete and reabsorption K in distal tubule
. Secretion: principal cell
. Reabsorption: intercalated cell
Dietary intake effect on K excretion
. Normally excrete 15% of filtered load so in normal intake we secrete K to get to 15% bc 13% of filtered load is sent to distal tubules
. High intake: secretion inc. greatly
. Low intake: reabsorption of K can reduce excretion to 1% of filtered load
Primary physiologic regulators of K secretion
. Plasma K and aldosterone maintain normal K balance
. Tubular fluid flow rate and acid-base balance perturb rather than maintain normal K balance
Cellular basis of K secretions
. Na/K ATPase brings K into cell, then K passively diffuses from cell to tubular fluid through apical K channels (BK and ROMK)
. Rate of movement depends on activity of Na/K ATPase, electrochemical driving force for K movement out of cell, and permeability of apical membrane to K
How aldosterone inc. K secretion
. Inc. # and activity of Na/K ATPases
. Inc. Na reabsorption stimulates Na/K ATPase and slightly depolarizes cell (along w/ neg. luminal voltage) enhances K movement
. Inc. # of apical K channels inc. membrane permeability via activation of SGK1
Aldosterone effect on ENaC
. SHort term: Inc. conductance through existing ENaC and reducing removal of ENaC (inc. # apical ENaC), mediated by cytosolic activation of CAP1 and SGK1
. Long term (hours): new ENaC synthesis
Hyperkalemia rapidly induces K secretion by ___
. Stimulating Na/K ATPase pump inc. cell K
. Stimulating aldosterone release
. Inc. apical membrane K channels inc. overall membrane permeability to K
. Hypokalemia does opposite
Alkalosis effect on K
. Inc. K secretion by stimulating Na/A ATPase
. Inc. permeability to K in apical cell membrane
. Chronic metabolic alkalosis esp. when ECF is depleted is assoc. w/ hypokalemia
Acidosis effect on K
. Acute acidosis (hours) causes dec. in K secretion by inhibition of Na/K ATPase and dec. permeability to K in apical cell membrane
. Chronic acidosis (days) will inc. K secretion bc aldosterone is stimulated
Effect of tubular flow rate on K balance
. Inc. in tubular flow inc. K secretion (diuretics that act on segments preceding collecting ducts)
. Dec. in tubular flow dec. K secretion (hypovolemia)
Why does high tubular flow rate inc. K secretion?
. Epithelial tubular cells have primary cilium mechanosensor, that affects Ca permeability
. When flow inc. primary cilium bends, inc. Ca entry, inc. number of open K channels (BK)
. Inc. flow accompanied by inc. Na delivery which stimulates inc. Na reabsorption stimulated K secretion
Why does low tubular flow dec. K secretion
. Reduced cilium stimulation reduces apical K permeability
. Dec. [Na]/low Na delivery rate slows reabsorption via ENaC which reduces electrochemical gradient for K secretion
. Low flow rate (shock, renal failure) assompanied w/ hyperkalemia
Why water diuresis doesn’t inc. K secretion?
. Low AVP dec. stimulators effect on K secretion
. High tubular flow stimulates K secretion
. Contradictory effects cancel out and urinary K excretion does not change
What occurs when there is a gain of function mutation in ENaC?
. Causes excessive Na reabsorption and hypertension
. That paired w/ hypokalemia causes low plasma aldosterone and renin
. Treatment: triamterene/amiloride and a low Na diet
Apparent mineralcorticoid excess
. Aldosterone acts on mineralcorticoid receptors (MR) in cytosol of distal nephron cells
. Cortisol can bind to MR but has 11-beta-HSD 2 enzyme that converts it into inactive cortisone and prevents cortisol from acting like aldosterone
. Licorice blocks 11-beta-HSD2 activity so excessive licorice can lead to syndrome that mimics elevated aldosterone levels
. Inc. Na reabsorption and K secretion in collecting duct
. Low renin, low aldosterone hypertension w/ hypokalemia
Pseudohypoaldosteronism type 1
. Loss of function in ENaC
. Looks like aldosterone is absent when it is really elevated due to ensuing volume contraction and hypotension
. Inc. Na excretion causes hypotension
. Stil presents w/ hyperkalemia
What occurs in loss of function in NKCC transporter?
. Na wasting syndrome.
. Inc. Na excretion along w/ concentrating (and dilution) defect causes dec. effective circulating volume
. This stimulates RAAS to inc. Na reabsorption (still has excessive net Na loss)
. Causes inappropriate K secrete
. Leads to hypokalemia.
Natriuresis
Inc. Na excretion
Kaliuresis
Inc. K excretion
T/F all diuretics work by inhibiting Na reabsorption directly or indirectly
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Diuretic-induced natriuresis cycle
. Self limited
. giving diuretic causes neg. Na and H2O balance
. Several days pass w/ this
. New steady state Na and H2O balance reached as compensatory mechanisms reduce Na excretion
. ECF is now reduced even at new steady state
Proximal tubule diuretics
. Osmotic
. Carbonic anhydride inhibitors
. 5-10% of the filtered load of Na is excreted w/ diuretics
. The % lower expected because the loop of Henle will inc. its Na reabsorptive rate when the delivery of Na is inc.
Osmotic diuretics
. Unreabsorbable solutes that reduce osmotic driving force for H2O reabsorption going into paracellular and transcellular routes
. Primary diuretic action in prox. Tubule and thin descending limb
. Osmotic diuretics dec. net Na reabsorption via a dec. in solvent drag (when H2O movement drags ions along w/ it)
. Mannitol is classic drug
. If glucose exceeds Tm, the excess glucose left in tube fluid acts like this (why DM patients have polyuria)
Carbonic anhydrase inhibitors
. Acetazolamide
. Inhibit enzyme that provides H for Na/H antiporter
. Dec. Na reabsorption in prox. Tubule
. Actions also reduces the kidney’s ability to acidity the urine and reduce the kidney’s ability to conserve filtered bicarbonate
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Loop diuretics
. Furosemide
. Inhibit NGCC symport in thick ascending limb
. Impair ability of the kidney to maximally concentrate and maximally dilute the urine
. Potent, up to 25% filtered load Na excreted w/ drugs, collecting duct can’t limit reabsorption that much
Early distal tubule diuretics
. Thiazides
. 1st-line drugs for primary hypertension
. Block Na/Cl symport
. Reduce max diluting capacity of kidney
. 5-10% of filtered load of Na is excreted
Principal cell K sparing diuretics
. Aldosterone receptor antagonists (spironolactone)
. ENaC blockers (amiloride)
. K secretion dec. when Na reabsorption slows down
. Other diuretics are K wasting bc inc. in tubular flow and [Na] stimulates collecting duct to inc. K secretion
. Sparing diuretics don’t impair the maximal concentrating or diluting power of th kidney
