sodium reabsorption, diuretics, and diet vivek bhalla, md division of nephrology stanford university...

Sodium Reabsorption, Diuretics,and Diet

Vivek Bhalla, MDDivision of Nephrology

Stanford University School of MedicineSeptember 14th, 2015

Anatomy of the Renal Block

Physiology Pathophysiology UrologyBody Fluids -1 Glomerular Diseases – 3 Histology Lab

GFR, Clearance -1 Acute Kidney Injury – 1 Malignancy – 1

Sodium / Diuretics – 2 1 Chronic Kidney Disease – 3

Potassium – 2 Renal Lab -2 1

Acid – 2 Transplant Pathology-1

Water – 2 Vascular Diseases – 1/2

Steady State - 1 Plumbing- 1/2

Learning Objectives (3)

• To understand how sodium is handled along the nephron

• To learn the 4 major classes of diuretics, their mechanisms of action, their relative potencies, and main side effects

• To understand what is meant by a “low-sodium” diet

Daily Sodium Reabsorption (ancient)

• GFR ≈ 100 mL/min

≈ 150 l/day• [Na] ≈ 140 mEq/L• Filtered load of [Na] ≈ 150

l/day x 140 mEq/L

≈ 21,000 mEq/day• Na excreted ≈ 1 to 50 mEq/day

– (primitive)

Daily Sodium Reabsorption (today)

The average American eats about 150 mmol of NaCl per day.

Many Americans eat much more.

Sodium Reabsorption in Disease States (?)

Sodium retention is prominent in:

heart disease kidney disease

1. no no2. yes no3. no yes4. yes yes

What is a diuretic?

• Diuretic = natriuretic• blocks reabsorption of Na+ and Cl-

by the tubule• increases excretion of Na+ and Cl-

into the urine• presuming that osmolar control is

normal, water will be excreted along with Na+ and Cl, and the ECF volume will decline

Where would Diuretics act?

Classes of Diuretics

• Proximal Tubule

• Thick Ascending limb (of the loop of Henle)

• Distal convoluted tubule

• Collecting duct

• Carbonic anhydrase inhibitors

• “Loop” diuretics

• Thiazide-type diuretics

• Potassium-sparing diuretics

Classes of Diuretics

• Proximal Tubule

• Thick Ascending limb (of the loop of Henle)

• Distal convoluted tubule

• Collecting duct

• Osmotic diuretics (e.g. mannitol)

• Osmotic diuretics (e.g. mannitol)

• Aquaretics (not natiuretics)

Classes of Diuretics

• Where’s the best place to

block sodium reabsorption?

• 1. proximal tubule

• 2. thick ascending limb

• 3. distal tubule

• 4. collecting duct

What will be the side effect of acetazolamide: low serum HCO3- or high serum HCO3

- ?

Carbonic anhydrase

Proximal tubule: carbonic anhydrase inhibitor -- acetazolamide

Thick ascending limb: Na-K-2Cl inhibitor-- furosemide

Na K

Cl

F

Thick ascending limb: Na-K-2Cl inhibitor-- furosemide

Na K

Cl

F

What will the side effects be?

1. low K+, low HCO3-

2. low K+, high HCO3-

3. high K+, low HCO3-

4. high K+, high HCO3-

principal intercalated

Na+

K+H+

HCO3-

Furosemide causes moreNa+ and Cl- to be deliveredto the downstream collectingduct.

More K+ and H+ areexchanged for Na+

in the collecting duct.

More K+ and H+ areexcreted in the urine.

Na+

K+

H+

Aldosterone

Distal convoluted tubule: Na-Cl inhibitor– hydrochlorothiazide

Na T

What will the side effects be?

1. low K+, low HCO3-

2. low K+, high HCO3-

3. high K+, low HCO3-

4. high K+, high HCO3-

Collecting Duct: Na channel inhibition

principal intercalated

Na+

K+H+

HCO3-

Na+

K+

H+

Aldosterone

Spironolactone

AmilorideTriamterene

Osmotic Diuretics

• Act all along the tubule

• Not used for diuresis per se, but important to be aware of

• Mannitol: used commonly in neurologic injury (to minimize cerebral edema)

• Glucose: why poorly controlled diabetics have polyuria

Take Home Points: DiureticsDiuretic Class Site of Action Potency Side Effects Clinical Utility

CA Inhibitors Proximal Tubule Low Low HCO3- Used for contraction alkalosis

Loop TALH High Low K+High HCO3-

Drug of choice in CHF, more advanced renal failure

Thiazide Distal Convoluted Tubule

Medium Low K+High HCO3-

Good for essential HTN, but less effective with GFR < 30 ml/min

Potassium Sparing

Collecting Duct Medium High K+ Great as adjunctive therapy

The ECF volume is increased: do you want to reduce it?

A patient with heart failure comes into your clinic complaining of leg swelling. Physical exam is notable for a blood pressure of 120/70, a pulse of 90, a high central venous pressure, bibasilar rales, and 3+ pitting edema.

Should you give a diuretic to reduce the leg swelling?1. Yes2. No

The ECF volume is increased: do you want to reduce it?

A 5 year old boy is brought in by his mother who says he has gained 25% body weight over a few days and has swollen legs. Physical exam notable for BP 95/65, HR 88, 3+ pitting edema. Labs show Cr 0.6 mg/dL, UA with 3+ protein, albumin 2.0 g/dL.

Should you give a diuretic?1. Yes2. No

Where will diuretics remove fluid from?

1. Plasma2. Interstitial Fluid3. Intracellular Fluid4. All of the above

Where will diuretics remove fluid from?

The ECF volume is increased: do you want to reduce it?

A patient with polycystic kidney disease has a blood pressure of 156/95, a central venous pressure of 7 mmHg, and no edema. Her serum creatinine is 1.8 mg/dL and she currently takes lisinopril 40 mg daily.

Should you give a diuretic?1. Yes2. No

Diuretic Resistance (Refractoriness)?

You give the stuff, and not much comes out.

Diuretic Resistance (Refractoriness)?

• _________________

• _________________

• _________________

• _________________

• _________________

Sodium in our Diet

Sodium in our Diet

• Low-sodium diet

(US recommended daily allowance)

100 meq Na+

= 100 mmol*

23 grams/mol

= 2.3 grams Na+

(not NaCl)

Low Sodium Content in Natural/Raw Foods

Bielamowicz MK, 2011The Sodium Content of Your Food

High Sodium Content in Processed Foods

Bielamowicz MK, 2011The Sodium Content of Your Food

Sauce

Fries

Sources of Dietary Sodium in the American Diet

Sodium in our Diet

Quiznos large turkey club sandwich in NYC

5820 milligrams NaCl

= 5.82 grams /

58 grams / mol

= ~100 meq Na

Sodium in our Diet

Quiznos large turkey club sandwich in NYC

5820 milligrams NaCl

= 5.82 grams /

58 grams / mol

= ~100 meq Na

Learning Objectives (3)

• To understand how sodium is handled along the nephron

• To learn the 4 major classes of diuretics, their mechanisms of action, their relative potencies, and main side effects

• To understand what is meant by a “low-sodium” diet