PHYSIOLOGY: S01L24

Regulation of Extracellular Osmolarity & Sodium Concentration

Dr. Sheila Marie O. Baria | 12-07-2020 | MWF | 7:30-10:00 AM | Lec
OUTLINE ♦ Decreases urine output (concentrated urine)
 Powerful feedback system regulating plasma osmolarity and
I. Osmolarity
sodium concentration
II. Total Body Water ♦ By altering renal water excretion of water independently
III. Mechanisms for Excreting a Dilute Urine of the rate of solute excretion.
IV. Obligatory Urine Volume  When solutes in the body fluids become too concentrated:
V. Requirements for Excreting a Concentrated Urine ♦ Increased ADH (posterior pituitary gland)
VI. Role of Urea ♦ Increase water reabsorption in distal tubule and collecting
VII. Urine Concentrating Mechanisms and Osmolarities of the ducts.
Nephron Segments ♦ Decrease urine volume.
 When ECF osmolarity is reduced due to excess water
VIII. Estimating Plasma Osmolarity
♦ Decreased ADH.
IX. Osmoreceptor-ADH Feedback
♦ Decreased water reabsorption in the distal tubule and
X. Role of Thirst collecting ducts.
XI. Disorders of Water Balance (Hyponatremia & Hypernatremia) ♦ Increased urine volume.
XII. Quiz Review
XIII. References III. MECHANISMS FOR EXCRETING A DILUTE URINE

I. OSMOLARITY

 Total concentration of solutes in the ECF.

 Determined by the number of solutes divided by the volume
of ECF.
 Together with ECF, Na concentration is regulated by EC
amount of water.

II. TOTAL BODY WATER

 Controlled by fluid intake (regulated by factors that control

thirst)
 Renal excretion of water (controlled by factors that influence
GFR and tubular reabsorption)

RENAL WAYS OF EXCRETING WATER

Figure 1. Water Diuresis in humans after ingestion of 1 L water.
 Excess water in the body After water ingestion: (1) Increased Urine Volume, (2) Decreased Urine
♦ Osmolarity is reduced Osmolarity (3) causing an INCREASE diluted urine excretion however total
♦ Kidneys excrete as much as 20L/day of dilute urine (50 amount of solute excreted by kidneys is CONSTANT. This prevents plasma
mOsm/L) osmolarity from decreasing markedly during excess water ingestion.
 Deficit of water
♦ Osmolarity is high  Glomerular filtrate osmolarity is about the same as plasma
♦ Kidneys excrete a concentrated urine (1200 – 1400 (300 mOsm/L).
mOsm/L)  To excrete excess H2O, it is necessary to dilute the filtrate as it
 A dilute or concentrated urine is excreted without a change in passes along the tubule.
the excretion of solutes in the body (Na, K).  Achieved by reabsorbing solutes to a greater extent than
 This ability to regulate H2O excretion independent of solute water which occurs only in certain segments of the tubular
excretion is necessary for survival especially when fluid intake system.
is limited.

ANTIDIURETIC HORMONE (ADH)

 Also known as vasopressin

 Secreted by the posterior pituitary gland
 Alters renal excretion of water independent of the rate of
solute excretion
 Deficit of water
♦ Increase ADH secretion
♦ Allows a large amount of water to be reabsorbed in the
distal & collecting tubule.

"The cure for anything is salt water: sweat, tears, or the sea." -Isek Dinesen 1|8
 TUBULAR FLUID IN DISTAL & COLLECTING TUBULES

 Additional reabsorption of sodium chloride as the dilute fluid

passes into the late distal convoluted tubule, cortical collecting
duct, and collecting tubule.
 Impermeable to water in the absence of ADH.
 Solutes are continually reabsorbed thus creating a very
diluted urine (as low as 50 mOsm/L).
 Failure to reabsorb water & continued reabsorption of solutes
lead to excretion of a large volume of diluted urine.

SUMMARY OF MECHANISM FOR FORMING DILUTE URINE

 Results from the continuous reabsorption of solutes and

Figure 2. Formation of dilute urine when ADH levels are very low. failure of water reabsorption from distal tubules.
 In healthy kidneys, fluid leaving the ascending loop & early
FORMATION OF DILUTE URINE WHEN ADH LEVELS ARE VERY distal tubule is always diluted regardless of the level of ADH.
LOW ♦ Without ADH, urine is further diluted in the late distal
tubule & collecting ducts and a large volume of dilute urine
 In the ascending loop of Henle, fluid becomes very dilute. In is excreted.
the distal & collecting tubules, fluid becomes further diluted
by reabsorption of NaCl and failure of water reabsorption
when ADH levels are low. The failure to reabsorb water and
continuous reabsorption of solutes lead to a large volume of
dilute urine (milliosmoles per L).

TUBULAR FLUID IN PROXIMAL TUBULE

 Water and solutes are reabsorbed in equal proportions.

 Little change in osmolarity occurs.
 Remains isosmotic to the plasma (300 mOsm/L).

TUBULAR FLUID IN DESCENDING LOOP OF HENLE

 Water is reabsorbed by osmosis until it equilibrates with the

surrounding interstitial fluid of the renal medulla which is very
hypertonic (about 2-4 times the osmolarity of original
glomerular filtrate).
 Tubular fluid becomes more concentrated as it flows into the
inner medulla. Figure 3. Mechanisms of urine dilution.

TUBULAR FLUID IN ASCENDING LOOP OF HENLE IV. OBLIGATORY URINE VOLUME

 In the thick segment (THAL = thick ascending loop), active
 Minimum volume of urine that must be excreted to get rid of
reabsorption of Na+, K+ and Cl- occurs.
the body of products of metabolism and ions that are
 Impermeable to water even in the presence of large amounts
ingested.
of ADH
 Dictated by the maximal concentrating ability of the kidney
 Tubular fluid becomes more dilute as it ascends the loop
(1200 mOsm/L).
(hypo-osmotic – can be as low as 100 mOsm/L, about 1/3 that
 A 70-kg man must excrete 600 mOsm of solutes per day.
of plasma until leaving the early distal convoluted tubule).
 If maximal urine concentrating ability is 1200 mOsm/L,
 Hypo-osmolarity of fluid in this segment is independent of the
obligatory urine volume can be calculated as:
presence of ADH.
600 𝑚𝑂𝑠𝑚/𝑑𝑎𝑦
= 0.5 𝐿/𝑑𝑎𝑦
1200 𝑚𝑂𝑠𝑚/𝐿
Nice to know!
 Regardless of whether ADH is present or absent,  This minimal loss of volume in the urine contributes to
fluid leaving the early distal tubular segment is dehydration along with losses from lungs, GIT, and skin when
hypoosmotic, with an osmolarity of only 1/3 the water is not available to drink.
osmolarity of plasma.
WHY DOES DRINKING SEAWATER CAUSE DEHYDRATION?

 The limited ability of the human kidney to concentrate the

urine to a maximal concentration of 1200 mOsm/L explains

"The cure for anything is salt water: sweat, tears, or the sea." -Isek Dinesen 2|8
 why severe dehydration occurs if one attempts to drink
seawater.
 Seawater contains 3.0 to 3.5% NaCl concentration with an
osmolarity between 1000 to 1200 mOsm/L.
 Why then does drinking seawater cause dehydration?
♦ The answer is that the kidney must also excrete other
solutes, especially urea, which contribute about 600
mOsm/L when the urine is maximally concentrated.
♦ Therefore, the maximum concentration of sodium
chloride that can be excreted by the kidneys is about 600
mOsm/L.
♦ Thus, for every liter of seawater drunk, 1.5 liters of urine
volume would be required to rid the body of 1200
milliosmoles of sodium chloride ingested in addition to
600 milliosmoles of other solutes such as urea.
♦ This would result in a net fluid loss of 0.5 liter for every liter
Figure 3. Formation of a concentrated urine when antidiuretic hormone
of seawater drunk, explaining the rapid dehydration that
(ADH) levels are high. Note that the fluid leaving the loop of Henle is
occurs in shipwreck victims who drink seawater.
diluted becomes concentrated as water is absorbed from the distal tubules
and collecting tubules. With high ADH levels, the osmolarity of the urine is
V. REQUIREMENTS FOR EXCRETING A CONCENTRATING about the same as the osmolarity of the renal medullary interstitial fluid in
URINE the papilla, which is about 1200 mOsm/L. (Numerical values are in
milliosmoles per liter.)

URINE SPECIFIC GRAVITY

WHAT IS THE PROCESS BY WHICH RENAL MEDULLARY
 Provide rapid estimate of urine solute concentration.
INTERSTITIUM BECOMES HYPEROSMOTIC?
 The higher the urine concentration, the higher the urine
 This process involves the operation of the countercurrent
specific gravity.
mechanism.
 Linearly increases with increasing urine osmolarity.
 Depends on the special anatomical arrangement of the loops
 It is the measure of the weight of solutes in each volume of
of Henle and the vasa recta (the specialized peritubular
urine determined by size and number of solute molecules
capillaries of the renal medulla.
♦ Expressed in grams/mL
♦ 25% of human nephrons are juxtamedullary nephrons
♦ Ranges from 1.002 to 1.028
with loops of Henle and vasa recta that go deeply into the
♦ Rises by 0.001 for every 35 to 40 mOsm/L increase in urine
medulla before returning to the cortex.
osmolarity
♦ Critical role of the collecting ducts in this mechanism:
 Altered by glucose, radiocontrast media, and antibiotics
Carry urine through the hyperosmotic renal medulla
before it is excreted.
REQUIREMENTS FOR EXCRETING A CONCENTRATED URINE

 High Level of ADH Countercurrent Mechanism Producing a Hyperosmotic Renal

♦ Increases water permeability of distal tubules and Medullary Interstitium
collecting ducts, allowing water reabsorption
 Interstitial fluid osmolarity in all parts of the body is 300
 High Osmolarity of the Renal Medullary Interstitial Fluid
mOsm/L, similar to plasma osmolarity.
♦ Provides osmotic gradient necessary for water
 Interstitial fluid osmolarity of renal medulla is much higher –
reabsorption to occur in presence of high levels of ADH
1200 to 1400 mOsm/L (in the pelvic tip of the medulla).
 The renal medullary interstitium surrounding the collecting
♦ This means it has accumulated large solutes in great excess
ducts are normally hyperosmotic.
of water.
 The presence of high ADH levels move water from the
 Once high solute concentration is achieved, it is maintained by
collecting tubules via osmosis to the interstitium.
balance inflow and outflow of solutes & water in medulla.
 The water is carried away by the vasa recta back into the
blood.
 Thus, urine concentrating ability is limited by the ADH levels FACTORS THAT CONTRIBUTE TO BUILDUP OF SOLUTE
and by the degree of hyperosmolarity of the renal medulla. CONCENTRATION

 Active transport of Na+ and co-transport of K+, Cl- and other

ions out of the thick portion of the ascending limb of the loop
of Henle into the medullary interstitium.
 Active transport of ions from the collecting ducts into the
medullary interstitium.
 Facilitated diffusion of large amounts of urea from the inner
medullary collecting ducts into the medullary interstitium, far
less than solute reabsorption into the medullary interstitium.
 Diffusion of only small amounts of water from medullary
collecting tubules into the interstitium, far less than the
reabsorption of solutes into the medullary interstitium.

"The cure for anything is salt water: sweat, tears, or the sea." -Isek Dinesen 3|8

Figure 4. Summary of tubule characteristics – urine concentration.
0, minimal level of active transport or permeability
+, moderate level of active transport or permeability
++, high level of active transport or permeability
+ADH, permeability to water or urea is increased by ADH
SOLUTE TRAPPING IN THE RENAL MEDULLA
 Special Characteristics of Loop of Henle:
♦ Most important cause of high medullary osmolarity
 Active transport of Na+ and co-transport of K+, Cl- and other
ions from the thick ascending Loop of Henle into the
interstitium.
 Capable of establishing 200 mOsm/L concentration gradient
between tubular lumen and interstitial fluid.
 Descending limb of Loop of Henle is very permeable to water
and tubular fluid osmolarity quickly becomes equal to the
renal medullary osmolarity.
 Tubular fluid osmolarity rises as it flows to the tip of the loop.
STEPS IN CAUSING HYPEROSMOTIC RENAL MEDULLA
1. Assume loops are filled with fluid with 300 mOsm/L, same
as in the proximal tubule fluid.
2. Active pump of the thick ascending limb on the loop of
Henle is turned on, reducing concentration inside the tubule
and raising interstitial concentration until a 200-mOsm/L
concentration gradient is reached (maximum limit because
paracellular back diffusion of ions counterbalances the
transport of ions out of the lumen).
3. Osmosis of water from the descending limb of the loop of
Henle occurs until tubular fluid and interstitial fluid osmolarity
equilibrates. Interstitial fluid osmolarity is then maintained at
400 mOsm/L because of the continued transport of ions of the
thick ascending loop of Henle.
4. Additional flow of fluid into the loop from the proximal
tubule pushes the previously hyperosmotic fluid in the
descending limb to flow into the ascending limb.
There, the pump actively transports the ions out to the
interstitium, leaving water in the tubule until the 200
mOsm/L gradient is reached.
5. Again, water from the descending limb, equilibrates with
the hyperosmotic medullary interstitial fluid.
6. As the hyperosmotic tubular fluid in the descending limb
flows into the ascending limb, this allows more solute buildup
in the medullary interstitium.
"The cure for anything is salt water: sweat, tears, or the sea." -Isek Dinesen
 These steps are repeated over and over, with the net effect of
adding more and more solute to the medulla in excess of
water.
 With sufficient time, this process gradually traps solutes in the
medulla and multiplies the concentration gradient established
by the active pumping of ions out of the thick ascending loop
of Henle, eventually raising the interstitial fluid osmolarity to
1200 to 1400 mOsm/L.
COUNTERCURRENT MULTIPLIER
 Multiplication of the gradient established by the active pump
in the thick ascending loop of Henle, raising the medullary
interstitial osmolarity to as high as 1200 to 1400 mosm/L.
 The repetitive reabsorption of sodium chloride by the thick
ascending loop of Henle and continued inflow of new sodium
chloride from the proximal tubule into the loop of Henle.
 The sodium chloride reabsorbed from the ascending loop of
Henle keeps adding to the newly arrived sodium chloride, thus
"multiplying" its concentration in the medullary interstitium.
Figure 5. Countercurrent multiplier system in the loop of Henle for
producing a hyperosmotic renal medulla. (Numerical values are in
milliosmoles per liter.)
VI. ROLE OF UREA
ROLE OF UREA IN HYPEROSMOTIC RENAL MEDULLARY
INTERSTITIUM AND TO CONCENTRATED URINE
 Urea contributes about 40% (500 mOsm/L) of the renal
medullary interstitium osmolarity.
♦ When the kidney is forming a maximally concentrated
urine.
 Passively reabsorbed from the inner medullary collecting ducts
(IMCD) into the interstitium.
MECHANISM FOR REABSORPTION OF UREA INTO THE RENAL
MEDULLA
 As water flows into the ascending limb, into the distal and
cortical collecting tubule, little urea reabsorption occurs due
to impermeability of these tubules.
 With ADH and consequent water reabsorption to the
interstitium, urea concentration inside the tubules increases.
 As the fluid reaches the inner medullary collecting duct
(permeable to urea) further water reabsorption takes place,
causing an even higher concentration of urea in the tubular
fluid.
4|8
  Simultaneous reabsorption of water and urea out of the inner
medullary collecting ducts maintains a high urea concentration
in the tubular fluid.
 Urea recirculation
♦ Occurs from the collecting ducts to the loop of Henle
♦ Provides an additional mechanism for forming a
hyperosmotic renal medulla
 Malnutrition
♦ Associated with a low urea concentration in the inner
medullary interstitium.
♦ Impaired urine concentrating ability.
 Diffusion of urea is facilitated by urea transporters
♦ UT-AI
◦ Activated by ADH
◦ Increase transport of urea out of the IMCD
COUNTERCURRENT EXCHANGE IN THE VASA RECTA
 2 Special features of the renal medullary blood flow to
preserve its hyperosmolarity.
♦ Low medullary blood flow
◦ 1 to 2% of the renal blood flow.
◦ Minimizes solute loss but sufficient to supply metabolic
needs.
♦ Vasa recta serve as countercurrent exchangers
◦ To minimize solute washout from the interstitium.
◦ Vasa recta like other capillaries is highly permeable to
solutes in the blood except protein.
◦ Has a U-shaped configuration.
Steps Involved
 Plasma flowing from the descending limb of the vasa recta
becomes hyperosmotic.
♦ Water diffusion out of the blood.
♦ Solute diffusion from the renal interstitium into the blood.
 In the ascending limb of the vasa recta, solutes diffuse back
into the interstitium and water diffuses back into the vasa
recta. The U-shaped capillary prevents the loss of solutes from
the interstitium.
Counter Current Exchanger
 The vasa recta do not create the medullary hypersosmolarity,
but preserves it by the diffusion of fluid and solutes into and
out of the medullary interstitium and the blood.
 Though it minimizes solute loss from the interstitium, it
maintains its reabsorptive capacity through bulk flow due to
the colloid osmotic and hydrostatic pressures that favor
reabsorption in these capillaries.
 Even with maximal levels of ADH, urine concentrating ability
of the kidneys will be reduced without medullary interstitial
hyperosmolarity.
 Drugs that can increase medullary blood flow can reduce urine
concentrating ability.
 Large increases in BP can increase medullary blood flow to a
greater extent than other regions in the kidney and tend to
wash out the hyperosmotic interstitium, thereby reducing
urine-concentrating ability.
"The cure for anything is salt water: sweat, tears, or the sea." -Isek Dinesen
VII. URINE CONCENTRATING MECHANISMS AND
OSMOLARITIES OF THE NEPHRON SEGMENTS
PROXIMAL TUBULE
 Highly permeable to water.
 65% of filtered electrolytes reabsorbed here.
 Osmolarity is the same as plasma (300 mOsm/L).
DESCENDING LOOP OF HENLE
 Highly permeable to water, less permeable to electrolytes.
 Osmolarity gradually increases until it equalizes with the
surrounding interstitial fluid; may reach to 1200 mOsm/L.
THIN ASCENDING LOOP
 Impermeable to water.
 More permeable to NaCl.
 Some passive diffusion of NaCl in to the interstitium.
 The tubular fluid becomes more dilute as it flows to the thick
segment.
 Urea from the medullary interstitium (from the inner
medullary collecting duct) diffuses back into this segment.
THICK ASCENDING LOOP
 Impermeable to water
 Active transport of electrolytes
 Tubular fluid becomes dilute
DISTAL TUBULES AND COLLECTING DUCTS
 Early Distal Tubule
♦ Same properties as the thick ascending loop
 Late Distal Tubule/Cortical Collecting Tubule
♦ Osmolarity dependent on the levels of ADH
♦ Urea is not permeant, resulting in increased urea
concentration as water is reabsorbed.
♦ Highly permeable to water.
 Inner Medullary Collecting Duct
♦ Tubular fluid concentration depends on ADH and
medullary interstitial osmolarity established by the
countercurrent mechanism
POINTS TO CONSIDER
 The kidney can excrete a highly concentrated urine that
contains little sodium.
♦ Hyperosmolarity of this urine is due to high concentration
of other solutes such as urea.
♦ E.g., dehydration with low sodium intake, stimulates
formation of angiotensin II and aldosterone, causes avid
reabsorption from tubules leaving concentrated urea and
solutes.
 Large quantities of dilute urine can be excreted without
sodium excretion (due to ADH).
♦ Accomplished by decrease in ADH secretions → reduces
water reabsorption in distal tubular segments.
 The obligatory volume is dictated by the max concentrating
ability of the kidney, and the amount of solutes to be excreted.
5|8
VIII. ESTIMATING PLASMA OSMOLARITY
 Na+ and its associate anions (bicarbonate and Cl) account for
about 94% of solutes in the ECF.
 Posm = 2.1 x plasma Na+ concentration.
 To be exact, and if there is a renal disease, the contributions
of urea and glucose are included (about 3 to 5 % more).
 Systems that regulate Na+ concentration and ECF osmolarity:
♦ Osmoreceptor–ADH system
♦ Thirst mechanism
ANTIDIURETIC HORMONE
IX. OSMORECEPTOR-ADH FEEDBACK
FEEDBACK MECHANISM OPERATES AS FOLLOWS:
 Osmolarity (plasma sodium concentration) increases above
normal because of water deficit:
♦ Increase in ECF or in plasma Na+ causes the osmoreceptor
cells in the anterior hypothalamus to shrink.
♦ Shrinkage sends additional signal to the cells of the
supraoptic nuclei to send signals down the pituitary stalk
to the posterior pituitary.
♦ Stimulate release of ADH which is stored in the secretory
granules in the nerve endings.
♦ Increased water permeability of the late distal, cortical,
and inner medullary collecting ducts.
♦ Increased water permeability causes water reabsorption
and decrease urine output.
 The opposite sequence of events occurs when the
extracellular fluid becomes too diluted (hypo-osmotic).
♦ For example, with excess water ingestion and a decrease
in extracellular fluid osmolarity, less ADH is formed, the
renal tubules decrease their permeability for water, less
water is reabsorbed, and a large volume of dilute urine is
formed.
♦ This in turn concentrates the body fluids and returns
plasma osmolarity toward normal.
 ADH is synthesized in the supraoptic (5/6 of ADH) and
paraventricular nuclei (1/6 of ADH) of the hypothalamus
 Released from the posterior pituitary (storage)
 Calcium entry in the nerve endings increase to affect
membrane permeability when hypothalamic nuclei are
stimulated – ADH release
 AV3V – anteroventral region of the 3rd venticle
♦ Subfonical organ – upper part
♦ Organum vasculosum of the lamina terminalis – inferior
part
♦ Median preoptic nucleus – multiple nerve connections
 Osmoreceptors
♦ Located in the vicinity of A3V3 and supraoptic nuclei
♦ Neuronal cells excited by changes in ECF osmolarity
 ADH release is controlled by cardiovascular reflexes:
♦ Arterial baroreceptor reflex
♦ Cardiopulmonary reflexes
 In addition to increased osmolarity, other stimuli which
increases ADH secretion include:
♦ Decreased arterial pressure
♦ Decreased blood volume

Regulation of ADH Secretion

 INCREASES ADH SECRETION

♦ Increased plasma osmolarity
♦ Decreased blood volume
♦ Decreased blood pressure
♦ Nausea (most powerful stimuli)
♦ Hypoxia
♦ Drugs:
◦ Morphine
◦ Nicotine
◦ Cyclophosphamide

 DECREASES ADH SECRETION

♦ Decreased plasma osmolarity
♦ Increased blood volume
♦ Increased blood pressure
♦ Drugs:
◦ Alcohol
◦ Clonidine
◦ Haloperidol

X. ROLE OF THIRST
Figure 6. Osmoreceptor-antidiuretic hormone (ADH) feedback mechanism
for regulating extracellular fluid osmolarity in response to a water deficit.  Adequate fluid intake is necessary to counterbalance
whatever fluid loss does occur through sweating and breathing
 Thus, water is conserved in the body while sodium and other and through the gastrointestinal tract.
solutes continue to be excreted in the urine. This causes  Fluid intake is regulated by the thirst mechanism, which,
dilution of the solutes in the extracellular fluid, thereby together with the osmoreceptor-ADH mechanism, maintains
correcting the initial excessively concentrated extracellular precise control of extracellular fluid osmolarity and sodium
fluid. concentration.

"The cure for anything is salt water: sweat, tears, or the sea." -Isek Dinesen 6|8
THIRST CENTER XI. DISORDERS OF WATER BALANCE (HYPONATREMIA &
HYPERNATREMIA)
 Anteroventral region of the third ventricle and anterolateral 

portion of the preoptic nucleus.
 Act as osmoreceptors to activate the thirst mechanism. HYPONATREMIA
 Increased osmolarity of the CSF in the 3rd ventricle stimulate
 Increased plasma osmolality (hypertonic hyponatremia)
thirst.
♦ Glucose
♦ Mannitol
CONTROL OF THIRST ♦ Glycine
♦ Sorbitol
 INCREASES THIRST ♦ Gamma globulin
♦ Increased ECF osmolarity (most important)
♦ Increased angiotensin II (2nd important)  Normal plasma osmolality (pseudohyponatremia)
♦ Decreased ECF blood volume (3rd important) ♦ Lipids (as in DM)
♦ Decreased blood pressure ♦ Protein (as in MM)
♦ Dryness of the mouth  Low plasma osmolality (hypotonic hyponatremia)
♦ Urine osmolality < 100 mOsm/kg
 DECREASES THIRST ◦ Primary polydipsia
♦ Decreased osmolarity ◦ Beer potomania
♦ Decreased angiotensin II ◦ Malnutrition
♦ Increased blood volume ◦ Reset osmostat (pregnancy, psychosis, malnutrition,
♦ Increased blood pressure quadriplegia)
♦ Gastric distention
Urine Osmolality > 100 mOsm/kg
 When the sodium concentration increases only about 2 mEq/L
above normal, the thirst mechanism is activated, causing a  ECF increased (hypervolemic hyponatremia) (edema)
desire to drink water. This is called the threshold for drinking. ♦ Urinary sodium >20mmol/L
◦ Acute or chronic renal failure
ROLE OF ANGIOTENSIN II AND ALDOSTERONE IN ♦ Urinary sodium <20mmol/L
CONTROLLING EXTRACELLULAR FLUID OSMOLARITY AND ◦ Cardiac failure
◦ Cirrhosis
SODIUM CONCENTRATION
◦ Nephrotic syndrome
 Low sodium intake, increased levels of hormones to stimulate  Euvolemic Hyponatremia
sodium reabsorption  prevents sodium loss ♦ Urinary sodium > 20mmol/L
 High sodium intake, decrease hormone formation  excrete ◦ SIADH
large amounts of sodium ◦ Hypothyroid
 Important role in regulation of ECF sodium concentration ◦ Stress
 Increase in sodium amount also increase ECF by increasing ◦ Aldosterone insufficiency
water reabsorption ◦ Cortisol insufficiency
 Two reasons why Ang II and aldosterone do not have main ◦ Glucocorticoid deficiency
effect on sodium concentrations. ◦ Drugs
♦ They increase both sodium and water reabsorption by the
renal tubules which cause increase in extracellular fluid Causes Disorders
volume and sodium quantity but little change in sodium Malignancy Small cell lung disease (most common), CNS
(ectopic ADH) disease, leukemia, Hodgkin’s disease, duodenal
concentration.
cancer, pancreatic cancer
♦ As long as the ADH-thirst mechanism is functional,
Pulmonary Infection, acute respiratory failure, mechanical
tendency toward increased plasma Na concentration is
ventilation
compensated by increased water intake or increased
Miscellaneous Pain, nausea (power simulator of ADH), HIV,
plasma ADH secretion.
general post op state
Pharmacologic Drugs Cyclophosphamide, vincristine, vinblastine,
SALT-APPETITE MECHANISM FOR CONTROLLING ECF SODIUM (enhances or mimics NSAIDs, tricyclics and related agents,
CONCENTRATION AND VOLUME ADH) selective serotonin reuptake inhibitors,
chlorpropamide, nicotine, bromocriptine,
 Two primary stimuli believed to excite salt appetite: oxytocin, DDVAP
♦ Decreased ECF Na+ concentration. Table 1. Common causes of SIADH.
♦ Decreased blood volume or blood pressure associated
with circulatory insufficiency.  ECF decreased (hypovolemic hyponatremia)
 Neuronal mechanism is analogous to that of thirst mechanism. ♦ Urinary sodium < 20mmol/L – extrarenal loss
 Circulatory reflexes elicited by low BP or decreased blood ◦ Vomiting
volume affect both thirst and salt appetite at the same time. ◦ Diarrhea
◦ Sweating
◦ Third spacing of fluids (burns, pancreatitis, trauma)
♦ Urinary sodium > 20mmol/L – renal loss
◦ Diuretics

"The cure for anything is salt water: sweat, tears, or the sea." -Isek Dinesen 7|8
 ◦ Na losing nephropathy ♦ Inner medullary collecting tubule
◦ Osmotic diuresis ♦ Cortical collecting tubule
◦ Intrinsic renal disease ♦ Thick ascending limb of loop of henle
◦ Post obstructive diuresis
◦ Addison’s disease 6. In the steps involved in hyperosmotic renal medulla, active
pump of thick ascending limb is turned on, reducing the
HYPERNATREMIA concentration inside the tubule and raising the interstitial
 concentration until how many mOsm is reached?
 Hypervolemic hypernatremia ♦ 100
♦ Hypertonic saline administration, primary ♦ 200
hyperaldosteronism ♦ 300
 Hypovolemic hypernatremia ♦ 400
♦ Increased urine volume
◦ Osmotic diuresis (high urine osmolality)
◦ Central or nephrogenic diabetes insipidus (low urine
osmolality) 7. What preserves the hyperosmolarity of renal interstitium?
♦ Decreased urine volume ♦ Distal tubule
◦ Insensible losses ♦ Thick ascending limb
◦ Osmotic diarrhea ♦ Vasa recta
♦ Lack of access to water ♦ Cortical collecting tubules
 Euvolemia (Hypernatremia associated with normal body Na +)
♦ Renal losses 8. In which segment is tubular fluid very diluted (100mOsm/L)?
◦ Diabetes insipidus ♦ Proximal tubule
◦ Hypodipsia ♦ Descending limb of loop of Henle
♦ Extrarenal losses ♦ Thick ascending loop of Henle
◦ Insensible losses (respiratory, dermal) ♦ Distal and cortical collecting tubule
♦ Urinary sodium varies
9. True of osmoreceptor-ADH feedback system, EXCEPT?
XII. QUIZ REVIEW ♦ Decrease in ECF/ decrease in plasma Na causes the
osmoreceptor cells in the anterior hypothalamus to
1. True of ADH except: shrink.
♦ Vasopressin ♦ Shrinkage and additional signal to the cells of the
♦ Secreted by posterior pituitary gland supraoptic nuclei to send signals down the pituitary stalk
♦ Regulation of extracellular osmolarity and sodium to the posterior pituitary
concentration ♦ Stimulate release of ADH
♦ Magnesium entry in the nerve endings increase to effect ♦ Increase water permeability of the late distal, cortical and
ADH release. (calcium) inner medullary collecting ducts

2. Active reabsorption of Na, K, Cl 10. Potent stimulus for ADH release

♦ Proximal tubule ♦ Hypoxia
♦ Descending limb of loop of henle ♦ Nicotine
♦ Ascending limb of loop of henle ♦ Nausea
♦ Distal and collecting tubule ♦ Decrease in blood pressure

3. Determinants of concentrating ability except

IX. REFERENCES
♦ Distal delivery
♦ Active NaCl transport in distal tubule
 Guyton and Hall Textbook of Medical Physiology, 13th Edition
♦ Fluid delivery to medullary collecting duct
 Doc Baria’s PowerPoint Presentation and Side Notes
♦ Collecting duct water permeability
 SaVi Trans
4. Factors contributing to the build-up of solute concentration in
the renal medulla
♦ Active transport of sodium ions and co-transport of
potassium, chloride and other ions out of the thick
ascending limb of loop of Henle into the medullary
interstitium.
♦ Passive transport of ions from the collecting ducts into the
medullary interstitium.
♦ Active transport of large amounts of urea from the inner
medullary collecting ducts into the medullary interstitium.
♦ Diffusion of large amounts of water from the medullary
interstitium.

5. ADH act on the following except:

♦ Distal tubule

"The cure for anything is salt water: sweat, tears, or the sea." -Isek Dinesen 8|8