Ex: mannitol

can be used to draw water from the tissues and excrete it in the kidneys

20% soln administered as a bolus of 1 g/kg

repeat at 0.25 - 0.5 g/kg every 4-6 hours

effects peak in 1 hr, and last for 4-24 hrs

Beware of rebound

Uses: prophylaxis of acute renal failure, glaucoma, opthalmologic procedures, cerebral edema

Possible side effects: pulmonary edema (esp. in pts w/ cardiac decompensation), HA, NV, convulsions, hypokalemia

K⁺ diuretics that work on the principal cells

Ex: sprionolactone (aldosterone antagonist), triamterene, amiloride (NaCl channel blockers, reduce H⁺ secretion)

↑  lumen negative transepithellial voltage 

↑ NH₃ synthesis

↑ H⁺ pump & Cl^-/CHO₃^- exchanger

Uses: mild edema, hyperaldosteronism, hypokalemia

Side effects: hyperkalemia, metabolic acidosis, impotence, ginecomastic

Ex: furosemide (lasix), bumetanide

inhibition of salt reabsorption (including Mg²⁺) in thick ascending limb Na⁺/K⁺/2 Cl^-

induce a compensatory ↑ in NaCl reabsorption in the distal tubule

Uses: edema (including pulmonary HTN), hyperccalcemia, prophylaxis of ARF

Side effect: hypovolemia, hypokalemia, metabolic alkalosis, Ca²⁺ & Mg²⁺ depletion

Ex: HCTZ, chlorthalidone, metalozone

inhibition of NaCl reabsorption in the early distal tubule 

binds to the Cl^- spot on NaCl transporter

↑ Ca²⁺ reabosption

Uses: edema, HTN, Hypercalciuria/lithiasis, osteporosis, 

Side effects: hypovolemia, hypokalemia, metabolic alkalosis, hyponatermia, hypercalcemia

PO = 2 · plasma [Na⁺] + Glc/18 + BUN/2.8

an ↑ in MAP causes an ↑in GFR

↑ in Na⁺ & Cl^- delivery to macula densa is sensed, causing an ↑ in afferent arteriolar resistance

which normalizes the GFR

short term SNGFR control

The SNS stimulates vasoconstriction in both the a. and e. arterioles (with preference for a.) via α₁ recceptors,

↓ RBF

Prostaglandins (vasodilators) protect against excessive vasoconstriction;

NSAIDS block prostaglandin producction

Angeotensin II constricts both a. and e. arterioles (with preference for e. at low conc.), ↑ GFR

ANP vasodilates both a. and e. arterioles

Dopamine dilates both a. and e. arterioles at low levels (↑RBF)

How is H⁺ is excreted as NH₄⁺ in the: 

1. proximal tubule
2. think ascending limb
3. collecting duct?

1. glutamine → (glutaminase) glutamate + NH₄⁺ glutamate → α-ketogluterate → CO₂ + H₂O → HCO₃^-    NH₄⁺ → NH₃ + H⁺, NH3 can cross the membrane,  H⁺ is reabsorped in exchange for Na⁺
2. NH₄⁺ can take the place of K⁺ on the Na⁺/K⁺/2Cl^- cotransporter (countercurrent multiplication)
3. NH₃ diffuses down gradient into the lumen and combines with H⁺ to make NH₄⁺

1. SNS baroreceptors detect ↓ afferent arteriole P and cause vasoconstriction of the a. arteriole and ↑ Na⁺ reabsorption in the proximal tubule

2. ANP causes vasodilation of a.a. and vasoconstriction of the e.a. ⇒ ↑GFR & ↓ Na⁺ reabsorption

3. Δ's in Starling Forces (hydrostatic and oncotic pressure)

4. RAAS (Na⁺ reabsoption) 

Costanzo p. 287

Myogenic - stretch-activated Ca²⁺ channels respond to stretching with constriction

Tubuloglomerular Feedback - ↑ RBF  & GFR ⇒ ↑ water & solute delivered to macula densa, causing the juxtaglomerular apparatus to secrete a vasocontrictor

Vasocontrictors: angiotensin II, endothelin, stimulation of  α andrenergic receptors of SNS

Vasodillators: prostaglandins, PGE₂, PGI₂, NO, bradykinin, dopamine (low levels), ANP

dilation of cerebral, cardiac, splanchinic, and renal arterioles

constriction of skeletal m. and cutaneous arterioles

Atrial and brain natiuretic peptides and ouabain-like factor (produced by the brain and the adrenal cortex)

↓ Na⁺ reabsorption 

Early Proximal Convoluted Tubule: cotransport w/ Glc, AA, phosphate, lactate, or citrate; exchange w/ H⁺ (stimulated by aldosterone)

Late Proximal Convoluted Tubule: in exchange for H⁺; paracellular absorption with Cl^-

67% of Na⁺ is reabsorbed in the PCT

Thin Descending Limb: permeable to solutes & H₂O (diffusion)

Thick Ascending Limb: Na⁺/K⁺/2Cl^- contransporter

stimulated by aldosterone

blocked by loop diuretics

25 % of Na⁺ is reabsorbed in the TAL

Distal Convoluted Tubule: Na⁺/Cl^- cotransporter

blocked by thiazide diuretics

5% of Na⁺ is reabsorbed in the DCT

Collecting Duct: Na⁺ channels in the principal cells      (K⁺ secretion in exchange for Na⁺ absorption

stimulated by aldosterone

blocked by K⁺ sparing diuretics

3% of Na is reabsorbed in the CT

both creatine and urea are freely filtered across the membrane

nml Creat: 0.5 - 1.5 mEq

nml BUN: 8 - 25 mEq

↑ ratio ⇒ acute injury

smaller ↑ ratio ⇒ chronic failure

Hypovolemia can cause a ↓ in renal perfusion and leave to prenal azotemia 

What are the equations for:

1. filtered load

2. excretion rate

3. reabsoprtion or secretion rate

1. GFR · [P]_x · % of unbound X in plasma

2. V · [U]_x 

3. filtered load - excretion rate

(GFR · [P]_x · % of unbound X in plasma) - (V · [U]_x)

In the cortex and outer medulla, the tubule is permeable to water, but not urea.

After 67% of the water has been reabsorbed in the PCT, the tubule becomes permeable to urea in the TDL of the Loop of Henle (in the inner medulla)

UT1 (urea transporter) synthesis in the inner medullary collection ducts is stimulated by ADH

H⁺ secreted into the lumen combines with HCO₃^- to make H₂CO₃ → (brush border carbonic anhydrase) CO₂ + H₂O

CO₂ can cross the membrane 

H⁺ + CO₂ → (intracellular carbonic anhydrase ) H₂CO₃ 

H₂CO₃ → HCO_3^- + H⁺ 

H⁺ is secreted into  the lumen

HCO_3^- in secreted into the blood stream in exchange for Cl^- or by cotransport with Na⁺