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Physio > Tubular Transport > Flashcards

Tubular Transport Flashcards

1
Q

How to determine plasma Na

A

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)

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2
Q

Na balance

A

. 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

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3
Q

Hyperaldosteronism

A

. 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

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4
Q

T/F small adjustments in Na and H2O reabsorption mechanisms result in large changes in Na and H2O excretion

A

T

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5
Q

Transport mechanisms used by kidney

A

. Solute movement via diffusion (transcellular or paracellular) or facilitated diffusion
. Can also be active transport using ATP

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6
Q

Symport

A

. Coupled transport of 2 or more solutes in the same direction
. Process can also be called co-transport

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7
Q

Antiport

A

. Coupled transport of 2+ solutes in the opposite direction

. Also called exchange or exchanger/anti porter

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8
Q

Role of Na/K ATPase in kidneys

A

. Conc. Gradient for Na to move into the cell from the tubule lumen is maintained by this bringing Na out of cell

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9
Q

Water movement in kidney

A

. Water movement is passive

. Driven by osmotic pressure gradients caused by reabsorption of Na and other solutes

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10
Q

Solvent drag

A

. 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

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11
Q

Aquaporins

A

. Aquaporin-1 (AQP-1) is present in prox. Tubule

. Also present in collecting duct as AQP-2 under control of vasopressin

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12
Q

Back leak of Na

A

. 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

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13
Q

Transport maximum

A

. #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

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14
Q

T/F if the filtered load is less than the Tm, the urine will be essentially devoid of the solute

A

T

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15
Q

Inhibition of renal Na-glucose transporter for DM II treatment

A

. SGLT2 inhibitors (dapagliflozin) dec. fasting and peak plasma glucose
. Dec. HbA1c and promotes weight loss

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16
Q

SGLT2

A

. Low affinity high capacity transporter in early part of prox. Tubule

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17
Q

Renal threshold

A

. Plasma conc. Of glucose at which glucose 1st appears in urine

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18
Q

Tm-limited secretion

A

. 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

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19
Q

Clinical relevance for secretory transporter competition

A

. 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

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20
Q

Na reabsorption along nephron

A

. 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

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21
Q

Na transport function

A

. Site of diuretic action in prox tubule

. Site of acid-base regulation

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22
Q

K transport function

A

. Inside principal cells

. Maintain safe plasma K levels in blood

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23
Q

Cl reabsorption

A

. 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

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24
Q

K reabsorption

A

. Mostly in prox. Tubule
. Some in loop of Henle
. More in late distal tubule/collecting duct than the other solutes

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25
Q

Ca and P reabsorption

A 
. 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
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26
Q

Na-H antiport (NHE3)

A

. Secretion of H ions is important for acid/base regulation

. Results in bicarbonate reabsorption in a 1-for-1 exchange w/ H

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27
Q

Na-solute symport

A

. Na-glucose
. Na-AA
. Na-other solutes (phosphate, lactate)

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28
Q

T/F glucose and AA are almost completely cleared from tubule fluid by the end of prox. Tubule in normal circumstances

A

T

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29
Q

Late prox. Tubule Na reabsorption

A

. 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

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30
Q

Thick ascending limb (TALH)

A

. 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.)

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31
Q

Furosemide

A

. 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

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32
Q

Early distal tubule

A

. NaCl symporter (NCC) used to reabsorb Na
. Reabsorbs Ca and Pi
. Located in cortex
. Impermeable to water

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33
Q

Thiazides

A

. Diuretic blocking NaCl symporter in early distal tubule

. Used to treat hypertension and CHF

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34
Q

Late distal tubule and collecting duct

A

. 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

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35
Q

Aldosterone

A

. 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

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36
Q

Aldosterone mechanism

A

. 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

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37
Q

Limiting steps in classic aldosterone pathway

A

. 11beta-HSD2: metabolizes cortisol into cortisone that has low affinity to MR
. MR
. ENaC
. Na/K ATPase

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38
Q

Aldosterone release stimulated by ___

A

. AII
. High plasma K
. Lesser extent plasma acidosis

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39
Q

Principal cell epithelial Na Channel (ENaC)

A

. 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)

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40
Q

Amiloride

A

. Diuretic blocking ENaC

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41
Q

Aldosterone receptor antagonists

A

. Slows Na reabsorption in principal cells

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42
Q

Fractional excretion of Na

A

. 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

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43
Q

Acute kidney injury

A

. 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

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44
Q

FENa under 1% in cases of suspected AKI

A

. 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

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45
Q

FENa over 1% in cases of suspected AKI

A

. 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)

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46
Q

Pre-Renal causes of AKI

A

. Hemodynamic derangement like volume depletion, dec. in effective perfusion of kidneys

47
Q

T/F The amount of water lost from the body affects plasma osmolality

A

T

48
Q

Regulation of Na content

A

. 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

49
Q

Regulation of body fluid Na conc.

A

. Sensed: plasma osmolality
. Sensor: hypothalamic osmoreceptors
. Effector: ADH
. Affected: urine osmolality (H2O output) and thirst (H2O intake)
. Clinical Dx: lab test for plasma osmolality

50
Q

Problems w/ total body water manifest as ___

A

. Altered plasma osmolality that is reflected as alteration in plasma Na conc.

51
Q

Problems w/ total body Na content manifest as ____

A

Altered extracellular fluid volume

52
Q

Normal plasma osmolality

A

275-295 mOsm/kgH2O (or mOsm/L)

53
Q

Diuresis

A

Excretion of large amount of urine

. Typically urine is hypoosmolar/dilute (can be iso-osmotic)

54
Q

Antidiuresis

A

Excretion of small amount of urine

. Typically hyperosmotic/concentrated

55
Q

Copeptin

A

. 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

56
Q

Regulation of AVP release

A

. 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

57
Q

Osmoreceptors

A

. 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

58
Q

When osmolality is under 280, AVP secretion is ____

A

Zero

. AVP secretion is very sensitive to small inc. in osmolality above this point

59
Q

Osmotic regulation of ADH at low plasma osmolality

A

. 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

60
Q

Osmotic regulation of ADH secretion in high plasma osmolality

A

. 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

61
Q

AVP functions

A

. Inc. H2O permeability in collecting duct
. AVP dec. urine flow rate and inc. urine osmolality
. Control number of aquaporins in apical membrane

62
Q

Vasopressin-2 (V2) receptor

A

. 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

63
Q

Effect of AVP on aquaporins

A

. 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.

64
Q

T/F the kidney is capable of disengaging H2O from solute reabsorption

A

. 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

65
Q

Concentration and dilution can occur because ___

A

. 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

66
Q

What creates the medullary interstitial osmotic gradient

A

. 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

67
Q

Dilution (low AVP)

A

. 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

68
Q

Concentration w./ high AVP

A

. 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

69
Q

If transport NaCl out of ascending limb is impaired, the renal urinary concentrating power and urinary deleting power will ___

A

Decrease

70
Q

Urea

A

. 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

71
Q

AVP inc. permeability of urea by ___

A

. 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

72
Q

UT-A2 transporter

A

. 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

73
Q

Protein diet effects on concentrating ability of kidney

A

. Low protein: dec. in urinary concentrating ability

. High protein: mildly enhance maximal conc. Power

74
Q

Vasa recta

A

. 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

75
Q

Why isn’t maximum medullary osmolality 1200 during diuresis?

A

. 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

76
Q

Vasa recta O2 supply to nephron

A

. 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

77
Q

How to tell if urine is iso, hyper, or Hypo-osmolar

A

. 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)

78
Q

Urine volume

A

. 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

79
Q

Free water clearance

A

. 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

80
Q

Oliguria

A

Urine output less than 400 ml/day

81
Q

Anuria

A

Urine output under 50 ml/day

82
Q

Polyuria

A

. Excessive urine volume

. 24 hr volume is over 50 ml/king body weight (or over 3L/day)

83
Q

Major mechanism is which total body K is regulated

A

. Renal excretion of K

84
Q

Regulation of rapid movement of K into cells

A

. 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)

85
Q

Effect of chronic elevated aldosterone on K levels

A

. Results in hypokalemia

. Inc. excretion of K via kidney and uptake of K into cells

86
Q

K reabsorption along nephron

A

. 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

87
Q

What cells secrete and reabsorption K in distal tubule

A

. Secretion: principal cell

. Reabsorption: intercalated cell

88
Q

Dietary intake effect on K excretion

A

. 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

89
Q

Primary physiologic regulators of K secretion

A

. Plasma K and aldosterone maintain normal K balance

. Tubular fluid flow rate and acid-base balance perturb rather than maintain normal K balance

90
Q

Cellular basis of K secretions

A

. 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

91
Q

How aldosterone inc. K secretion

A

. 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

92
Q

Aldosterone effect on ENaC

A

. 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

93
Q

Hyperkalemia rapidly induces K secretion by ___

A

. 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

94
Q

Alkalosis effect on K

A

. 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

95
Q

Acidosis effect on K

A

. 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

96
Q

Effect of tubular flow rate on K balance

A

. Inc. in tubular flow inc. K secretion (diuretics that act on segments preceding collecting ducts)
. Dec. in tubular flow dec. K secretion (hypovolemia)

97
Q

Why does high tubular flow rate inc. K secretion?

A

. 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

98
Q

Why does low tubular flow dec. K secretion

A

. 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

99
Q

Why water diuresis doesn’t inc. K secretion?

A

. 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

100
Q

What occurs when there is a gain of function mutation in ENaC?

A

. Causes excessive Na reabsorption and hypertension
. That paired w/ hypokalemia causes low plasma aldosterone and renin
. Treatment: triamterene/amiloride and a low Na diet

101
Q

Apparent mineralcorticoid excess

A

. 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

102
Q

Pseudohypoaldosteronism type 1

A

. 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

103
Q

What occurs in loss of function in NKCC transporter?

A

. 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.

104
Q

Natriuresis

A

Inc. Na excretion

105
Q

Kaliuresis

A

Inc. K excretion

106
Q

T/F all diuretics work by inhibiting Na reabsorption directly or indirectly

A

T

107
Q

Diuretic-induced natriuresis cycle

A

. 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

108
Q

Proximal tubule diuretics

A

. 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.

109
Q

Osmotic diuretics

A

. 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)

110
Q

Carbonic anhydrase inhibitors

A

. 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
.

111
Q

Loop diuretics

A

. 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

112
Q

Early distal tubule diuretics

A

. 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

113
Q

Principal cell K sparing diuretics

A

. 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

Physio (62 decks)

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