SODIUM HOMEOSTASIS

Sodium intake = 150 mEq/day Sodium excretion = 150 mEq/day - urine 140 mEq - sweat 5 mEq - stool 5 mEq

1. Sodium together with accompanying anions ( ie. chloride, bicarbonate) determine ECF volume 2. Sodium homeostasis is regulated based on detection of ECF volume and does not depend on actual Na concentration in ECF

SODIUM EXCRETION VIA KIDNEY GLOMERULAR FILTRATION RATE

GFR = Kf [(Pplasma +Bowman space) (PBowman space + plasma )]

At the beginning of the glomerulus

GFR = Kf [(60 + 0) ( 15 + 20 )] = Kf x 25 At the end of the glomerulus GFR = Kf [(60 + 0) ( 15 + 30 )] = Kf x 15 Daily GFR = 150 200 liters

GLOMERULAR FILTRATION RATE REGULATION

INCREASED GFR Kf Glom.Hydrostatic Pressure
Afferent Arteriole Resistance Efferent Arteriole Resistance

DECREASED GFR Decrease Decrease

Increase Decrease

Increase Increase
Decrease Increase

Plasma Oncotic Pressure

Decrease

Increase

GLOMERULAR ARTERIOLE RESISTANCE AND GLOMERULAR PERMEABILITY

AFFERENT ARTERIOLE 1. Myogenic regulation 2. Tubuloglomerular feedback 3. Sympathetic nerves 4. Angiotensin II 5. ADH EFFERENT ARTERIOLE 1. Angiotensin II 2. Sympathetic nerves 3. ADH GLOMERULAR PERMEABILITY COEFFICIENT 1. Angiotensin II 2. Sympathetic nerves 3. ADH 4. Endothelins 5. NO 6. Prostaglandins 7. ANF

AUTOREGULATION OF GLOMERULAR FILTRATION RATE HYPOVOLEMIA

R aff. Art.. R eff. Art.. Kf
Decrease, no change, increase but less then R eff. Art

Increase Decrease

HYPERVOLEMIA
R aff. Art.. R eff. Art.. Kf
Increase No change or decrease Increase

SODIUM REABSORPTION IN NEPHRON

1. Proximal tubules 50-60% 2. Ascending Loop of Henle 25 30% 3. Distal convoluted tubule 3 5% 4. Collecting tubule 1 3%

FRACTIONAL EXCRETION OF SODIUM FENa = sodium clearance/creatinine clearance x 100% FENa = 0.01% - 10%

David H. Ellison

REGULATION OF SODIUM REABSORPTION

1. Proximal tubule Active transport - sympathetic nerves - angiotensin II - peritubular protein - insulin Passive transport - bicarbonates load - carbonic anhydrase activity - nonreabsorbable solutes

REGULATION OF SODIUM REABSORPTION

2. Loop of Henle Passive thin ascending limb - medullary blood flow Active thick ascending limb - NaCl delivery - sympathetic nerve activity 3. Distal convoluted tubule - NaCl delivery 4. Cortical collecting tubule - aldosterone - NaCl delivery (weak effect)

FILTRATION FRACTION OF PLASMA

Filtration fraction of plasma (FFplasma) - volume of plasma which is filtered during one path via the glomeruli - plasma flow = 600 mL/min - glomerular filtration rate = 120 mL/min - FFplasma = 120/600 = 0.2 or 20%

+ 1L isotonic NaCl

+ 1L hypertonic Mannitol

+ 1L isotonic Glucose

ECF vol/osmol ICF vol/osmol Plasma [Na] ADH secretion Renal blood flow GFR Na+ renal excretion Urine volume Urine osmolality

Increase/No change No change/No change No change No change

Increased

No change

Increased

Increased

No change

+ 1L isotonic NaCl

+ 1L hypertonic Mannitol Increase/Increase Decrease/Increase Decrease Increase

+ 1L isotonic Glucose

ECF vol/osmol ICF vol/osmol Plasma [Na] ADH secretion Renal blood flow GFR Na+ renal excretion Urine volume Urine osmolality

Increase/No change No change/No change No change No change

Increase

Increase

No change

No change

Increase

Increase Increase
Increase

Increase

No change

+ 1L isotonic NaCl

+ 1L hypertonic Mannitol Increase/Increase Decrease/Increase Decrease Increase

+ 1L isotonic Glucose Increase/No change Increase/No change Decrease No change

ECF vol/osmol ICF vol/osmol Plasma [Na] ADH secretion Renal blood flow GFR Na+ renal excretion Urine volume Urine osmolality

Increase/No change No change/No change No change No change

Increase

Increase

Increase

No change

No change

No change

Increase

Increase Increase
Increase

Increase

Increase

Increase

No change

No change

HYPONATREMIA [Na] < 135 mEq/L and/or Posm < 280 mOsm/kg H2O
Mild [Na] = 125 135 mEq/L Moderate [Na] = 110 125 mEq/L Severe [Na] < 110 mEq/L ( 50% death) Hyponatremia with hyperosmolality hyperglycemia, mannitol, radiocontrast agents BUT Hyperosmolality with normonatremia not-effective osmoles: urea, ethanol, methanol, ethylene glycol Pseudohyponatremia - with hyperlipidemia - with hyperproteinemia

HYPONATREMIA - PATHOMECHANISMS
1. Water intoxication - excessive water ingestion ( ie.> 10% GFR) - decreased GFR - decreased amount of osmoles in urine 2. Decreased effective circulating blood volume - hypovolemia - congestive heart failure - edematous disorders 3. SIADH - reset threshold for ADH release - ectopic secretion of ADH Water Excess = (Body weight x 0.6) x [(140 Naplasma)/140]

Sumit Kumar & Tomas Berl

HYPERNATREMIA - PATHOMECHANISMS
Na > 145 mEq/L and Plasma osmolality > 295 mOsm/kg H2O HYPERNATREMIA WITH HIGH ADH Excessive NaCl ingestion - infusion of hypertonic NaCl solutions 2. Reset osmostat 3. Loss of hypoosmotic fluids - sweat ( Na + K = 70 mEq/L) - stool (Na + K = 130 mEq/L) - osmotic diuresis ( Na = 60 mEq/L) HYPERNATREMIA WITH LOW ADH 1. Diabetes insipidus central 2. Nephrogenic diabetes insipidus - X-linked congenital disease - decreased synthesis of c-AMP (hypokalemia, hypercalcemia, Li salts - disorders of osmotic gradient in renal medulla